Spirit Bear
------ Neuro_echopraxia.txt ------
The imitation of gestures (echopraxia) and mimicking of use of objects in the environment (utilization behavior) are seen after lesions to the lateral orbitofrontal cortex.
Source:
RITE 2009
------ Rett_gene.txt ------
Rett syndrome MECP2 X chromosome (twisting hands) (peds)
Source:
nowyouknowneuro
------ Neuro_Balintsyndrome.txt ------
Balint's syndrome is composed of the triad of optic ataxia (the inability to reach for an object under visual guidance), simultanagnosia (the inability to view multiple objects at once), and ocular apraxia (the inability to voluntarily direct gaze to a specific target). It usually results from bilateral damage to the parietal-occipital region secondary to separate infarctions. However, cases have been reported following head trauma as well as neoplastic disease.
Source:
RITE 2017
------ Neuro_NeuroOphthalmology_verticalsaccadesandhorizontalsaccades.txt ------
Vertical saccades are initiated by activating the connection between the frontal eye fields and the rostral interstitial nucleus of the MLF (riMLF). Horizontal saccades are initiated by a signal from the frontal eye fields to the ipsilateral superior colliculus and the contralateral paramedian pontine reticular formation.
Source:
RITE 2017
------ CerebrovascularDisease_NAPMSAH.txt ------
Pts with non aneurysmal perimesenphalic subarachnoid hemmorhages should still get TCD monitioring for vasospasm but they tend to do well
Source:
yacoub
------ Neuro_NervesandNeuropathy_C6_Dermatome.txt ------
The C6 dermatome includes the thumb
Source:
me
------ NervesandNeuropathy_CharcotMarieTooth.txt ------
The history and examination are consistent with type 1 Charcot-Marie-Tooth disease (CMT1), the most common form of CMT disease. CMT1 is an inherited autosomal dominant sensory and motor peripheral neuropathy with hypertrophic demyelinating pathology. The most commonly present genetic alterations are either duplications or point mutations on the PMP22 gene. Nerve conduction slowing with velocities less than 30 m/s is characteristic. The other gene alterations listed are associated with CMT2, an axonal CMT variant typically manifesting nerve conduction velocities faster than 40 m/s.
Source:
RITE 2017
------ .DS_Store ------
Bud1%
@ @ @ @
E%DSDB` @ @ @
------ DementiaNeurodegenerativeProcesses_alzheimersdifferential_symptomotology.txt ------
Alzheimer disease is characterized by amnestic memory loss, transcortical aphasia, and visuospatial deficits. Patients with dementia with Lewy bodies typically have Parkinsonism. Pick disease and frontotemporal dementia typically do well with calculations and constructions. Progressive posterior cortical atrophy has severe visuospatial deficits but not as significant memory problems.
Source:
RITE 2017
------ NervesandNeuropathy_posteriorcord_brachialplexus.txt ------
The posterior cord of the brachial plexus gives off the thoracodorsal and subscapular nerves and terminates by splitting into the axillary and radial nerves. Any muscles innervated by these branches may be weakened with a lesion in the posterior cord of the plexus.
Source:
RITE 2017
------ SpinalCord_MultipleSclerosisRelatedDisorders_transverse_myelitis.txt ------
nmo and mog, aquaporin 4
Source:
test
------ DementiaNeurodegenerativeProcesses_Lewybody.txt ------
Lewy body is an alphasynucleopathy frequently characterized by hallucincations and parkinsonisms
Source:
Dr. Cheponis (less colorful)
------ DementiaNeurodegenerativeProcesses_MSA.txt ------
Pleomorphic neuronal inclusions and neurites may be seen in MSA and are shown here. However, the hallmark neuropathologic feature of MSA is the glial cytoplasmic inclusion, or GCI, which is immunoreactive for alpha-synuclein. Although GCIs may show reactivity for other markers, it is the reactivity of widespread GCIs for filamentous alpha-synuclein that pathologically defines MSA by current diagnostic criteria. Beta-amyloid
is found in Alzheimer’s pathology, and tau in progressive supranuclear palsy and corticobasal degeneration. TDP-43, tau, and FUS are all seen in types of frontotemporal dementia.
Source:
2021
------ CerebrovascularDisease_Headache_RCVS.txt ------
Multiple thunderclap headaches over days raises concern for RCVS, vessel imaging should be pursued
Source:
colin
------ SpinalCord_Neuroinfectious_spinalepiduralabcess.txt ------
This patient has a disc space infection with an associated epidural abscess. The triad of back pain, fever, and neurologic deficit is the classic triad of this disorder. Most occur in the thoracolumbar region. Age, diabetes and the history of an invasive procedure (coronary angiogram) are the risk factors in this patient. Most disc space infections are from staphylococcus aureus.
References:
Darouiche RO. Spinal epidural abscess. N Engl J Med 2006;355(19):2012.
Source:
RITE 2017
------ Neuro_Headache_encephalocele.txt ------
Positional nasal drainage, clear transparent fluid. CSF rhinorrhea. Test fluid for beta-2-transferrin
Source:
Dr. Szewka
------ NeuroOncology_Neuroinfectious_differentiating_cerebralabcess_recurrenttumor.txt ------
Cerebral abscess can be distinguished from recurrent tumor based on differences in diffusion weighted imaging and ADC maps. Both demonstrate a ring-enhancing mass with surrounding T2 hyperintensity representing brain edema. Abscesses are characterized by marked hyperintensity on DWI in the cavity and corresponding hypointensity on ADC imaging. The opposite pattern is seen with recurrent tumor.
Source:
RITE 2017
------ Movement_Disorders_Neuroimaging_Neurological_Diseases__Diagnostics_and_Criteria_Gross_Anatomy_parkinsons.txt ------
parkinsons is associated with loss of dopaminergic cells within the basal ganglia
Source:
colin
------ SpinalCord_NeurologySystemicDisease_subacutepyramidalanddorsalcolumn.txt ------
This patient has subacute syndrome of pyramidal tract and dorsal column impairment due to copper deficiency. Alpha-tocopherol transfer protein gene mutation would present typically in childhood with gradual onset. A complete blood count might be abnormal, but not diagnostic. MRI of the spine might show increased T2 signal in the dorsal columns in several acquired nutritional deficiencies, but may be normal. Copper deficiency should be considered in patients with myelopathy following gastric surgery, or after zinc overdose.
Source:
RITE 2017
------ CerebrovascularDisease_epiduralhemorrhage.txt ------
An epidural hemorrhage is most commonly caused by trauma and can involve the middle meningeal artery. It is characterized by a lucid period and a delay prior to symptomatic development of a blood collection. In this patient, extensive bleeding in the left hemisphere led to right-sided long tract signs and uncal herniation.
Source:
RITE 2017
------ Guillan_Barre_funfact.txt ------
1) Guillan barre can be a presenting symptom of HIV 2) pertussis can cause guillan barre
Source:
Walsh
------ MillerFisherSyndrome_symptomtriad.txt ------
Ataxia, Areflexia, Ophthalmoplegia (triad of symptoms)
Source:
Clauser
------ DementiaNeurodegenerativeProcesses_MovementDisorders_NervesandNeuropathy_adultonset_polyglucosanbodydisease.txt ------
Adult-onset polyglucosan body disease is a disorder typically presenting in the fifth to seventh decades of life. Patients present with gait difficulties with lower and upper motor neuron involvement and peripheral neuropathy, with sensory deficits predominantly in the lower extremities, neurogenic bladder, and dementia. The combination of lower and upper motor neuron signs with leukoencephalopathy should lead the clinician to suspect this entity.
Source:
RITE 2017
------ DementiaNeurodegenerativeProcesses_Autonomics_MovementDisorders_MSA.txt ------
Rationale: The arrows indicate glial cytoplasmic inclusions of alpha- synuclein in a patient with parkinsonism, ataxia, and autonomic failure. These findings are diagnostic of multiple-system atrophy (MSA). MSA is typically a sporadic disease characterized by parkinsonism, ataxia, and
a spectrum of findings consistent with autonomic failure (eg, urinary incontinence, erectile dysfunction, and orthostatic hypotension).
Source:
RITE 2021
------ NervesandNeuropathy_lateralcord_brachialplexus.txt ------
Weakness involving the median nerve (pronator teres, flexor carpi radialis, pronation and wrist flexion) along with musculocutaneous nerve (elbow flexion, biceps) could reflect a lesion of the lateral cord of the brachial plexus
Source:
Nowyouknow
------ NervesandNeuropathy_L5vsSciatic_tensorfascialatae.txt ------
Some of the muscles with contributions from the L5 myotome include the tibialis anterior, tibialis posterior, peroneus longus, tensor fascia latae (TFL), gluteus medius, semitendinosus and semimembranosus, and the biceps femoris (long and short head). The sciatic nerve innervates all of the hamstring muscles and all muscles below the knee via the peroneal and tibial nerve branches. Of the choices, only the tensor fascia latae could be weak with an L5 but spared with a sciatic mononeuropathy.
Source:
RITE 2017
------ DementiaNeurodegenerativeProcesses_CJD.txt ------
The patient's presentation is strongly suggestive of Creutzfeldt-Jakob disease (CJD). The otherwise unremarkable MRI and normal routine CSF parameters are consistent with CJD. Diffusion-weighted MRI demonstrates restricted diffusion in the cortical mantle and basal ganglia, characteristic of this disorder. Of the biomarkers listed, total CSF tau is the most specific and sensitive, followed by neuron-specific enolase and 14-3-3 protein.
References:
Hamlin C, Puoti G, Berri S, Sting E, Harris C, Cohen M, Spear C, Bizzi A, Debanne SM, Rowland DY. A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease. Neurology. 2012 79(6):547-52.
Source:
RITE 2017
------ PediatricNeurology_Developmental_Lissencephaly.txt ------
Lissencephaly, which is characterized by a reduction in the number of gyri and sulci, is one of the disorders of neuronal migration. Other neuronal migration disorders include polymicrogyria, schizencephaly, and focal cortical dysplasia.
Source:
RITE 2017
------ CerebrovascularDisease_transcorticalmotoraphasia.txt ------
A transcortical motor aphasia is a nonfluent aphasia with preserved naming and repetition, differentiating it from a Broca aphasia, which has impairment of spontaneous speech, naming, and repetition. The most common neurologic symptom is a right hemiparesis that predominately affects the leg. The lesion producing a transcortical motor aphasia lies in the left frontal lobe and is usually caused by a stroke of the anterior cerebral artery. Sensory loss is usually absent or restricted to the right leg and visual field deficits are usually absent.
Source:
RITE 2017
------ Sleep_DementiaNeurodegenerativeProcesses_REMBehaviorDisorder_alphasynucleopathy.txt ------
This individual has REM behavior disorder (RBD). It is estimated to be a harbinger of an alpha-synucleinopathy in over 50% of individuals with RBD (especially for Parkinson disease, dementia with Lewy bodies and multiple systems atrophy). Alzheimer disease (AD) is associated with sleep-wake disturbances, but the latter is not a known risk factor for AD. ALS is associated with sleep related breathing disorders, but the latter are not known risk factors for ALS. Nocturnal seizures with complex behaviors can simulate RBD. They are generally focal seizures and arise out of NREM sleep. The prevalence of progression to generalized seizures is unknown. Obstructive sleep apnea is a well documented risk factor for stroke.
Source:
RITE 2017
------ DementiaNeurodegenerativeProcesses_Clininical_Parkinsoniansyndromes.txt ------
Progressive supranuclear palsy is a neurodegenerative disorder that begins with falls and is characterized by vertical gaze palsy, rigidity, dysarthria, cognitive decline and parkinsonian features. Pathologic features include tau positive inclusions that are most commonly found in the basal ganglia. Idiopathic Parkinson disease typically presents with bradykinesia, rigidity and resting tremors. Lewy Body Dementia has parkinsonian features but also has prominent fluctuations in cognition and visual hallucinations. Corticobasal degeneration is a progressive asymmetric movement disorder that presents with abnormalities in one limb or on one side of the body. Multiple system atrophy has parkinsonian features as well but also has dysautonomia, pyramidal signs or cerebellar symptoms.
References:
Williams,David and Litvan, Irene. Parkinsonian Syndromes. Continuum 2013;19:1189-1212
Jankovic JJ, Tolosa E. Parkinson's disease and movement disorders. 4th ed. Philadelphia: Lippincott, Williams and Wilkins, 2002.
Source:
RITE 2017
------ CerebrovascularDisease_DxandTx_CerebralVenousThrombosis.txt ------
INTRODUCTION
Cerebral venous thrombosis (CVT) is estimated to account for less than 1% of all strokes.1,2 Unlike arterial strokes, CVT tends to affect young patients with a female predominance, is often nonapoplectic in onset, and has a wide spectrum of clinical presentations.3 These and other features make CVT a challenging disease to diagnose without an understanding of its evolving epidemiology, clinical features, associated conditions, and the neuroimaging findings typically needed to confirm the diagnosis.
ANATOMY AND PATHOPHYSIOLOGY
The condition of CVT includes clots in both the large dural sinuses and cortical veins.4 The most prominent superficial sinus is the superior sagittal sinus, which drains into the transverse (lateral) sinuses and then out of the skull via the sigmoid sinuses into the internal jugular veins on each side. The superior sagittal sinus is the most frequent CVT location.5 The largest of the many tributary cortical veins that drain into the superior and transverse sinuses are the bilateral veins of Trolard (veins draped vertically over the parietal lobe, which drain into the superior sagittal sinus) and Labbé (veins situated horizontally over the temporal lobe, which drain into the transverse sinus). The deep venous system includes the straight sinus, vein of Galen, inferior sagittal sinus, internal cerebral veins that drain the thalami, and basal veins of Rosenthal (figure 7-16).7 It is thought that venous clots often originate in dural sinuses and then propagate to smaller veins resulting in venous infarction, increased intracranial pressure, or both.4
EPIDEMIOLOGY
Recent population-based studies have shown a higher incidence of CVT than previously reported. The latest annual CVT incidence ranges from 1.32 to 2 per 100,000 adults based primarily on data from high-income countries.1,2,8-10 Rising CVT incidence over time is likely partially due to better disease ascertainment with increasing availability of neuroimaging, although it is also possible that changes in the prevalence of known, emerging, or as yet unknown CVT-predisposing conditions may be a contributing factor.11 In one of the recent studies using US data from two states, 0.66% of all stroke admissions from 2005 to 2016 were for CVT, with an estimated annual CVT incidence of 1.4 to 2 per 100,000 people.1 In this study, the authors found that the proportion of stroke admissions due to CVT had increased by 70%, from 0.47% in 2005 to 0.80% in 2016, with the largest increases in CVT incidence noted among men and older women. Epidemiologic data from lower- and middle-income countries are lacking and represent an important area for future CVT research.1
Rates of CVT among women of reproductive age are consistently 3 times higher than those for similarly aged men.2,8,12,13 The incidence of CVT among women age 18 to 44 years in the aforementioned US study remained virtually unchanged over the study time period at 2.9 to 3.3 cases per 100,000 people.1 Higher CVT rates among young women are consistent with known sex-specific factors (eg, oral contraceptive use, pregnancy, and the puerperium) associated with CVT.12 To date, racial differences in CVT incidence have been underexplored. Data from a 2020 study suggest that the incidence of CVT may be disproportionately higher in Black people compared with people of other races in the United States.1 Prevalence rates of systemic venous thromboembolism, deep venous thrombosis, and pulmonary embolism are generally higher in African Americans compared to other racial and ethnic groups, but the reasons for these differences as well as whether or not they are similar in patients with CVT require additional study.14
ASSOCIATED CONDITIONS
Conditions associated with CVT can be classified as either predisposing (eg, genetic prothrombotic diseases, antiphospholipid syndrome, cancer) or precipitating (eg, oral contraceptives, infections). In 80% of patients with CVT at least one associated condition is found, and in nearly half of patients with CVT more than a single condition is identified.5 Thus, the identification of one condition known to be associated with CVT should not deter clinicians from looking for additional conditions, particularly inherited thrombophilias.15 Indeed, the American Heart Association/American Stroke Association (AHA/ASA) CVT guidelines note that testing for prothrombotic conditions, including protein C, protein S, or antithrombin deficiencies antiphospholipid syndrome, and prothrombin G20210A and factor V Leiden mutations, can be beneficial for the management of patients with a first CVT (class 2a; level of evidence B).16 The more recently published European Stroke Organization (ESO) guidelines, however, note that good clinical practice includes performing thrombophilia testing in patients with a high probability of carrying severe thrombophilia (eg, those with a personal or family history of venous thrombosis, or those with CVT without a transient or permanent risk factor) to prevent recurrence based on the existing low-quality evidence surrounding thrombophilia testing.17 Conditions associated with CVT have been previously detailed in a comprehensive meta-analysis of case-control and cohort studies from 201818; table 7-118-25 summarizes and expands upon these findings. In the future, genetic and lifestyle data may identify additional conditions associated with CVT and, perhaps, facilitate precision medicine in this space. For example, a recent genome-wide association study using genetic data from 11 European and 1 US research center identified a locus on chromosome 9 that was strongly associated with a nearly threefold increased CVT susceptibility.26 The single-nucleotide polymorphisms with the largest associations were in the coding regions of the ABO blood type gene and, after determining the blood group distribution of cases and controls, these researchers found that a non-O blood group was more prevalent in CVT cases.26
COVID-19 AND CEREBRAL VENOUS THROMBOSIS
The COVID-19 pandemic has led to the identification of additional conditions associated with CVT.
COVID-19 Infection
Infection as a precipitant of CVT (pyogenic CVT) has been well described.27,28 Data from a 2021 study suggest that a rare but demonstrable association between CVT and COVID-19 infection exists, although the underlying mechanism of this association is uncertain.29 Several thromboembolic pathways have been implicated in the pathophysiology of COVID-19 infection and cerebrovascular disease as well as systemic venous thromboembolism that may also play a role in CVT formation.30,31 The true prevalence of CVT in patients with COVID-19 infection is not known. A recent systematic review of existing case reports and retrospective cohort studies using data from 34,331 patients hospitalized with COVID-19 estimated the frequency of CVT at 0.08%. Signs, symptoms, and diagnosis of CVT followed the onset of respiratory or systemic COVID-19 symptoms by 1 to 8 weeks in nearly all 54 patients with CVT included in this study.32 Patients with CVT were often noted to have altered mental status, with thrombosis of the deep cerebral venous system or involvement of multiple sinuses.32 Only one of the identified patients with CVT and COVID-19 had an isolated headache which may reflect the fact that patients with CVT without severe neurologic deficits were underdiagnosed during the pandemic (ie, selection bias) or that, among patients with active COVID-19 infection, CVT is clinically more severe.33 Inpatient mortality was reported in nearly half of patients with CVT and COVID-19 infection, much higher than that of patients with CVT without COVID-19.34 It is unclear if this high mortality rate is related to neurologic complications, care quality, or the severity of COVID-19 infection itself.32 Based on these limited data, in patients with neurologic symptoms and COVID-19 infection, a high index of suspicion for CVT should be encouraged, and treatment of CVT should be initiated as soon as possible.
COVID-19 Vaccination
Another CVT precipitant was identified during postauthorization surveillance of people who had received COVID-19 vaccines using adenoviral vectors (human Ad26.COV2.S and chimpanzee ChAdOx1 nCov-19) to encode the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In February 2021, reports emerged of patients with thrombocytopenia and venous thromboembolism in unusual locations following administration of the ChAdOx1 nCov-19 vaccine. Within months, three independent descriptions were published of 39 people with thrombosis, frequently CVT, and thrombocytopenia that developed 5 to 24 days after initial vaccination with ChAdOx1 nCov-19.35-37 Shortly thereafter, 12 women aged 18 to 60 years who presented with CVT and thrombocytopenia 6 to 15 days postvaccination with Ad26.COV2.S were reported.38 To date, no independent predictors for CVT development postvaccine have been identified, although vaccine recipients with CVT and thrombocytopenia were often younger than age 60 years and were women who lacked prothrombotic risk factors.39 In a comprehensive study using data from postauthorization safety reports and official data from 30 European countries and the United Kingdom, the calculated risk of CVT with thrombocytopenia within 28 days of the first ChAdOx1 nCov-19 dose was 4.4 (95% confidence interval, 3.9 to 4.9) per million doses and 0.7 (95% confidence interval, 0.2 to 2.4) after Ad26.COV2.S vaccination. In this analysis, the risk of CVT with thrombocytopenia after ChAdOx1 nCov-19 vaccination was highest among people aged 18 to 24 years (7.3 per million first doses) and lowest in those aged 70 years or older (0.2 per million doses).40 On a population level, these absolute numbers are small and, although data collection is ongoing as vaccination continues, findings continue to overwhelmingly support the safety and efficacy of vaccination with respect to reducing COVID-19 risk and reducing death due to COVID-19.39,41 Additionally, the prevalence of CVT among hospitalized patients with COVID-19, as noted above, is far higher (60-fold to 230-fold) than that of people who received adenovirus-based COVID-19 vaccines.4,29,42 However, given the link between adenoviral vector–based vaccines and CVT, mRNA vaccines (BNT162b2 and mRNA-1273) may be preferred for certain patient subgroups (eg, younger) since the risk of CVT with thrombocytopenia following administration of mRNA vaccines is nearly zero.40
The entity implicated in these rare but potentially devastating cases of CVT and thrombocytopenia following adenovirus-based COVID-19 vaccine administration is now called vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome. VITT is one of three rare but pathophysiologically related hypercoagulable states associated with thrombosis, low platelet counts, and disseminated intravascular coagulation. The other two hypercoagulable states are heparin-induced thrombocytopenia (HIT), which occurs after heparin exposure and autoimmune heparin-induced thrombocytopenia (aHIT), which refers to a condition where antibodies activate platelets in the absence of heparin.4 These three hypercoagulable states (VITT, HIT, and aHIT) are all mediated by platelet-activating antibodies to platelet factor 4 (PF4). In HIT, exposure to unfractionated heparin, a polyanion, causes complexes of PF4 and heparin to form, resulting in the development of IgG autoantibodies against this complex and eventually leading to platelet activation, aggregation, and release of procoagulant molecules. Similarly, in VITT, autoantibodies are thought to be generated from a not-yet-identified polyanion in the adenoviral vaccines or expressed by the cells infected by the vaccine that binds to PF4.43 Why the cerebral veins and sinuses, as opposed to other sites, are a frequent location of thromboses in VITT, occurring in approximately half of patients with VITT at presentation, is not well understood44; rates of CVT in VITT differ substantially from rates of CVT in HIT (1.6%) and aHIT (2.5%).45,46 Prior to the COVID-19 era, thrombocytopenia at CVT presentation was very uncommon.47
In a multicenter UK cohort study, patients with VITT-associated CVT had similar presenting features to those with non–VITT-associated CVT, including 84% presenting with headache.48 Those with VITT-associated CVT had more intracranial veins thrombosed, more frequent extracranial thromboses, and higher rates of death or dependency as compared to other patients with CVT despite aggressive treatment.48 Fortunately, mortality for patients with VITT-associated CVT has significantly decreased from nearly 50% in March 2021 to around 22% for cases diagnosed thereafter, likely due to the beneficial effect of earlier recognition and improved treatments, especially the avoidance of heparin anticoagulation to treat CVT in VITT.49 Therefore, in patients with CVT with symptom onset within 4 to 42 days of having received a COVID-19 vaccine using adenoviral vectors, following an algorithmic approach to evaluate and treat VITT is advised (figure 7-243,50).43,50,51
CLINICAL PRESENTATION OF CEREBRAL VENOUS THROMBOSIS
The signs and symptoms of CVT are diverse and may mimic other neurologic disorders, complicating diagnosis. Symptoms of CVT reflect the location of the vein or sinus affected and, in some cases, multiple locations may be affected simultaneously. Presentations of CVT can be roughly divided into four syndromes: (1) isolated headache or increased intracranial pressure, (2) focal neurologic presentations, (3) subacute encephalopathy, and (4) cavernous sinus syndrome with multiple cranial neuropathies.5 In ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis), a multicenter registry, the median time from CVT symptom onset to diagnosis was 7 days (interquartile range 3 to 16 days), suggesting considerable diagnostic delay.52 More recently, a multicenter retrospective US study found that a probable CVT misdiagnosis occurred in 3.6% of patients who presented emergently mostly with headache symptoms.53 Detecting CVT in patients with isolated headache presentations, particularly those with a prior headache history, remains a significant clinical challenge.54,55
Headaches are present in approximately 90% of patients with CVT.5,28,56 Failure of blood to drain properly from the brain can lead to increased intracranial pressure manifesting with headache, vomiting, and papilledema with or without visual loss or sixth nerve paresis. When any combination of these features without other neurologic signs is present, the syndrome is referred to as isolated intracranial hypertension and is estimated to occur in nearly one-third of patients with CVT.5,57 Up to one-quarter of patients with CVT can present with isolated headache without any additional stigmata of raised intracranial pressure.56,58 Headache presentations in CVT are notoriously diverse. Among patients with new headache, obtaining a detailed neurologic examination, assessing for features known to be associated with CVT, and including secondary causes of headache in the differential may help to improve diagnostic accuracy in CVT. The International Classification of Headache Disorders, 3rd Edition, explicitly notes that headaches attributed to CVT have no specific characteristics. Evidence of a causal relationship between CVT and headache per the International Classification of Headache Disorders, 3rd Edition, simply requires that the headache developed in close temporal relation to the CVT and either headache has significantly worsened in parallel with clinical or radiological signs of extension of the CVT or headache has significantly improved or resolved after improvement of the CVT.59 Some key clinical features of CVT-associated headache include being exacerbated by Valsalva maneuver and recumbency, subacute onset of pain, and more often diffuse than unilateral headache location.60 However, acute presentations consistent with migraine or thunderclap headache may also occur.58 The transverse sinus is frequently a site of thrombosis among patients with CVT and isolated headache.58,61 Interestingly, a prospective study from 2020 where all patients with CVT were treated with anticoagulation acutely found no significant difference in the frequency of headache of any type or headache with features of intracranial hypertension in patients achieving full recanalization as compared with those who did not fully recanalize.62 The relationship between venous recanalization and CVT-associated headache as well as the mechanism by which CVT causes headache pain require further investigation.
Alternatively, patients with CVT may present with focal deficits, seizures, or both. Symptoms depend on the area of the brain affected. Common focal symptoms in CVT include hemiparesis, aphasia, and loss of vision.5 A key feature of focal neurologic deficits due to CVT is that they are frequently progressive in contrast with arterial strokes, which tend to be maximal at onset.63 The duration of CVT symptoms prior to presentation was greater than 48 hours in 53% of patients in the VENOST study,56 another large CVT registry, and, in ISCVT, symptom onset of between 48 hours and 30 days was seen in slightly more than half of patients.5 Another feature that may distinguish the focal deficits of CVT from those of more commonly encountered arterial strokes is their bilateral nature, particularly when the superior sagittal sinus is affected.28,52 Seizures, both generalized and focal, are far more common in CVT than with arterial cerebrovascular events, occurring in nearly 40% of patients with CVT at initial presentation.52
Finally, patients with thrombosis of the deep venous system may develop a subacute encephalopathy with confusion and lethargy or experience a rapid neurologic deterioration progressing to coma due to edema of bilateral thalami, basal ganglia, or other deep structures typically drained by these veins.64,65 Approximately 10% of patients with CVT have thrombosis of the deep cerebral venous system.52,64 Timely neurologic imaging is an essential component of the diagnostic evaluation for patients who present in coma to distinguish deep cerebral vein thrombosis from other neurologic causes. Cortical vein thrombosis is thought to be even more rare than deep venous system thrombosis, occurring in only 116 patients in the published literature.66 However, since most of the published cases of isolated cortical vein thrombosis have associated venous infarct, underreporting and potentially underdiagnosis of nonsevere isolated cortical vein thrombosis cases may occur.
RADIOGRAPHIC FINDINGS
Given the broad spectrum of presentations seen in CVT, recognizing the presence of CVT on clinical grounds requires a high degree of suspicion. Radiologic studies are crucial to establish the definitive diagnosis of CVT. In the emergency setting, CT is often the imaging test of choice for patients presenting with acute focal neurologic symptoms. However, ruling out CVT is difficult to do using CT alone.67 Both direct visualization of a thrombus in a cerebral vein or sinus, often called the “dense clot sign” or “cord sign,” as well as visualization of a filling defect within a dural sinus after contrast administration, the “empty delta sign,” have high specificity but low sensitivity.68 Intracerebral hemorrhage, which is well seen on head CT, is present in approximately one-third of patients with CVT.5 Increased suspicion for hemorrhagic venous infarcts from CVT should occur when multiple intraparenchymal hemorrhages are present; infarcts are ill-defined or in a nonarterial territory; or involve the bilateral thalami or bilateral basal ganglia, or are juxtacortical (case 7-1).69,70
Advanced imaging is generally required to diagnose and rule out CVT with certainty, and noninvasive imaging is typically favored over cerebral angiography, which is the gold standard.72 CT venography, a contrast-enhanced helical CT examination performed with a time-optimized contrast bolus, allows direct visualization of a thrombosed cerebral vein, and is a fairly reliable alternative to angiography with high sensitivity but low specificity.73 Magnetic resonance venography (MRV) can also be used to detect CVT without ionizing radiation exposure. Both CT venography and contrast-enhanced MRV are superior to time-of-flight MRV techniques since complex flow can produce artifacts in the latter. Contrast-enhanced MRV allows for a direct assessment of luminal filling similar to that of CT venography, with comparable sensitivity and specificity to CT venography.74,75 Contrast-enhanced brain MRI provides detailed information about the brain parenchyma and is probably more accurate for diagnosing CVT than noncontrast-enhanced MRV sequences.68 On brain MRI, the most common finding is visualization of the thrombus in the T1-weighted images. However, the timing of the CVT is an important consideration for thrombosis visualization on MRI: in the acute phase (first 5 days after CVT) thrombus is isointense on T1-weighted images and hypointense on T2*-weighted images; from 5 to 15 days the thrombus becomes hyperintense on T1-weighted and T2*-weighted images; finally, after 15 days it becomes homogeneous and hypointense in all image sequences. T2*-weighted and susceptibility-weighted imaging sequences can be useful to assist in the diagnosis of isolated cortical venous thrombosis on brain MRI.16,76
Using MRI black-blood thrombus imaging, a noncontrast-enhanced T1-weighted imaging method that allows for direct visualization of the thrombus itself, to detect CVT has very high sensitivity and excellent specificity compared to combined CT and MRI modalities in small studies.77,78 Since a similar native contrast thrombus MRI technique is highly accurate for the diagnosis of new and recurrent lower-extremity deep venous thrombosis,79,80 black-blood thrombus imaging may be of value for CVT detection if current findings are supported by additional data.68 An interesting radiographic finding seen on brain MRI, the brush sign, has recently been described in CVT. This sign is an abnormal hypointensity of the subependymal and deep medullary veins in paramagnetic-sensitive MRI brain sequences that has been reported in patients with CVT, particularly those with thrombosis of the deep venous system (figure 7-481). The deep medullary veins are small-caliber vessels located adjacent to the atrium and posterior body of the lateral ventricle, draining the white matter of the cerebral hemispheres to the subependymal veins of the lateral ventricles. The brush sign was associated with higher thrombus load as well as ipsilateral parenchymal lesions in one small study; this sign may be a marker of CVT severity and should prompt close monitoring during the acute phase.81
TREATMENT
Medical, endovascular, and surgical treatments can be used to treat CVT.
Acute Anticoagulation
Anticoagulation remains the first-line treatment of choice for CVT in the acute setting, even when concurrent intracerebral hemorrhage is present.16,17,82 Both the AHA/ASA and the ESO guidelines recommend initiation of parenteral anticoagulation with unfractionated or low-molecular-weight heparin (LMWH) prior to transitioning to oral anticoagulants for CVT treatment.16,17 The ESO guidelines have a weak recommendation for LMWH over unfractionated heparin based on a meta-analysis suggesting a nonsignificant trend toward improved functional outcomes and mortality with LMWH without a difference in rates of bleeding.17,83 This trend is in keeping with an analysis from ISCVT that suggested LMWH might be safer and perhaps more efficacious than unfractionated heparin.84
The clot in the venous system is the primary target of acute anticoagulation. In a systematic review including data from 694 patients with CVT, vessel recanalization occurred in roughly 85% at follow-up. This study found a significant increase in the chance of favorable outcome (defined as a modified Rankin Scale [mRS] score of 0 to 1) in patients with CVT with recanalization.85 New data suggest that vessel recanalization occurs early once anticoagulation is initiated. In a prospective study of 68 patients with CVT all treated acutely with anticoagulation who were imaged 0, 8, and 90 days from diagnosis, 43 (68%) had partial recanalization and 4 (6%) had full recanalization at day 8.62 At 90 days, 41% had partial recanalization and 54% had full vessel recanalization. Patients with early recanalization were at a lower risk of enlargement of nonhemorrhagic lesions and showed early regression of venous infarcts. These findings support the widely accepted hypothesis that recanalization improves regional perfusion.62 An additional important aspect of early anticoagulation initiation in CVT is prevention of other dangerous venous thromboembolisms in patients with CVT, particularly pulmonary embolisms, at index hospitalization.86
Duration of Anticoagulation
The duration of anticoagulation following CVT has not been studied in any randomized controlled trials; current recommendations are based on extrapolation from venous thromboembolism data.16,17 This extrapolation from venous thromboembolism to the CVT population, who are younger and likelier to have had a provoked event, has been challenged. EXCOA-CVT (EXtending oral antiCOAgulation treatment after acute Cerebral Vein Thrombosis) is a cluster randomized trial designed to evaluate the efficacy and safety of anticoagulation with vitamin K antagonists for 3 to 6 versus 12 months after CVT to clarify the optimal duration of this therapy.87 Current AHA/ASA guidelines note that for patients with provoked CVT (associated with a transient risk factor) a 3- to 6-month duration of anticoagulation is reasonable but that for patients with unprovoked CVT anticoagulation may be continued for 6 to 12 months.16 Patients who have recurrent venous thrombosis or an associated prothrombotic condition with a high thrombotic risk may need permanent anticoagulation; specific recommendations for the prevention of recurrent venous thromboembolic events should be followed in those conditions.17
Use of Direct Oral Anticoagulants
Since the noninferiority of direct oral anticoagulants to prevent systemic venous thromboembolism as compared to vitamin K antagonists has been shown,88 a great deal of interest has been expressed in using these newer agents to reduce the risk of venous thromboembolism after CVT. Direct oral anticoagulants have a favorable safety profile, predictable pharmacokinetics, and are easier to administer than vitamin K antagonists.89 Some support for the use of direct oral anticoagulants after CVT comes from recent clinical trials. RESPECT-CVT (Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate with Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis) was a prospective, randomized, open-label trial to evaluate the efficacy and safety of dabigatran compared to dose-adjusted vitamin K antagonists to prevent recurrent venous thromboembolism.90 In this trial, 120 adult patients with CVT were randomized in a 1:1 fashion to dose-adjusted warfarin to maintain an international normalized ratio (INR) of 2 to 3 or dabigatran 150 mg twice a day for 24 weeks. Patients were eligible for inclusion if they were stable after 5 to 15 days of treatment with therapeutic heparin, able to swallow, did not have CVT associated with either CNS infection or major trauma, and did not have any surgical treatments planned. At the end of the study, no recurrent venous thromboembolisms were observed in either treatment group, but three major bleeding events occurred. These major bleeding events involved one patient with intestinal bleeding in the dabigatran group and two patients with intracranial (subdural) hemorrhages in the vitamin K antagonists group. The two treatment groups had nearly identical rates of CVT recanalization on imaging. While RESPECT-CVT could not detect a statistically significant difference between the two treatments for recurrent venous thromboembolism, it did suggest that dabigatran is a reasonable option to prevent recurrent venous thromboembolism after CVT.
The safety and efficacy of rivaroxaban in CVT has also been studied. EINSTEIN-Jr (Oral Rivaroxaban in Children With Venous Thrombosis), a multicenter, parallel-group, open-label, randomized study, compared rivaroxaban to dose-adjusted vitamin K antagonists in children (aged 0 to 17 years) with venous thromboembolism; a prespecified substudy of patients enrolled with CVT was published in 2020.91 The main trial assigned patients in a 2:1 fashion to body weight–adjusted rivaroxaban in a 20 mg equivalent dose or standard anticoagulation. Of the 114 children with confirmed CVT, symptomatic recurrent venous thromboembolism occurred in none of the 73 children in the rivaroxaban group versus one (2.4%) of the 41 children in the standard anticoagulation group. Clinically relevant, nonmajor extracranial bleeding was observed in five rivaroxaban recipients (6.8%) and one child (2.4%) in the standard anticoagulation arm had a major bleeding event (subdural). No new venous infarcts occurred in either group and repeat imaging demonstrated a similar effect on clot resolution with rivaroxaban as compared to vitamin K antagonists.91 Although it is challenging to apply the findings from a pediatric trial (particularly one that was not powered for hypothesis testing) to an adult population, the CVT substudy of EINSTEIN-Jr supports the overall trend that direct oral anticoagulants are effective after CVT. Currently, SECRET (Study of Rivaroxaban for CeREbral Venous Thrombosis), an open-label, randomized, controlled, phase II clinical trial designed to evaluate the safety of rivaroxaban in adults, is ongoing.92 Another trial called RWCVT (Rivaroxaban versus Warfarin in CVT Treatment) has completed enrollment but has not yet published results. An ongoing international observational study, DOAC-CVT (Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis, NCT04660747), may also inform future practice.
Many practitioners have already started using direct oral anticoagulants to treat CVT based on existing data. A systematic review of direct oral anticoagulant use in CVT found a substantial increase in observational cohorts and case series that included patients with CVT treated with apixaban, dabigatran, edoxaban, or rivaroxaban since 2019. The observational cohorts included in the systematic review reported a similar risk of death in direct oral anticoagulant versus standard therapy arms and noted that favorable outcomes (mRS 0 to 2) were more likely in direct oral anticoagulant–treated patients with CVT.93 ACTION-CVT (Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis), a large multicenter retrospective study, provides additional reassurance to those who use direct oral anticoagulants after the acute phase of CVT. The ACTION-CVT study included 845 patients with CVT across 27 centers in four countries. It found that direct oral anticoagulant treatment was associated with a similar rate of recurrent venous thromboembolism (5.26 versus 5.87 per 100 patient years), a lower risk of major hemorrhage (2.44 versus 4.70 per 100 patient years), and similar rates of death and recanalization as with vitamin K antagonists.94 In ACTION-CVT, two-thirds of patients on direct oral anticoagulants were treated with apixaban. Although ACTION-CVT and other retrospective treatment studies are prone to confounding by indication, no major safety issues have been found with the use of direct oral anticoagulants as opposed to vitamin K antagonists in clinical practice.95 It is important to note that patients with antiphospholipid antibody syndrome should not be treated with direct oral anticoagulants based on two randomized trials showing an increase in arterial thrombotic events when these patients were treated with rivaroxaban instead of warfarin.96,97 Additionally, pregnant patients with CVT should likely be continued on LMWH rather than any other agent due to potential teratogenicity.98
Endovascular Therapy
Endovascular therapy, defined as mechanical thrombectomy with or without thrombolysis, has long been used to rapidly recanalize occluded sinuses in patients with severe CVT who worsen despite anticoagulation or who cannot receive anticoagulation. The results of the TO-ACT (Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis) trial were recently published.99 This multicenter, open-label, blinded-endpoint, randomized trial was designed to assess the safety and efficacy of endovascular therapy. Patients with CVT were randomized 1:1 to receive either endovascular therapy with anticoagulation or anticoagulation alone. Adult patients with radiologically confirmed CVT who had one or more prespecified features associated with poor outcome (mental status disorder, coma state, intracerebral hemorrhage, or thrombosis of the deep venous system) were included in the study. TO-ACT was halted after the first interim analysis for futility. A total of 67 patients were randomized into TO-ACT, accounting for approximately 16% of patients with CVT (67 of 420) seen at the sites during the study period. The number of patients with a favorable functional outcome (mRS 0 to 2) at 12 months was very similar between treatment groups (85% versus 82%). The mortality rates at 6 and 12 months were numerically higher in the endovascular therapy group than the medical management group but did not reach statistical significance. Because of the small sample size, TO-ACT is somewhat difficult to interpret. It remains possible that improved methods of patient selection or different endovascular techniques (in TO-ACT, more modern stent retrievers and aspiration catheters were not used) may increase the frequency of favorable outcomes after CVT. Indeed, symptomatic hemorrhage was higher in the medical arm (9% versus 3%) in TO-ACT, suggesting that EVT may be effective in reducing the risk of further bleeding. Retrospective data, however, have suggested that the role of endovascular therapy in CVT is limited. Using data from the Nationwide Inpatient Sample from 2004 to 2014, researchers found that 3% of identified patients with CVT were treated with endovascular therapy. These researchers found that endovascular therapy was independently associated with an increased risk of death (odds ratio 1.96) after adjustment to account for measured confounders.100 Further data as to the role of endovascular therapy in select patients with CVT are likely needed before treatment recommendations can be made.
Treatment of Vaccine-Induced Immune Thrombotic Thrombocytopenia–Associated Cerebral Venous Thrombosis
Early recognition, diagnosis, and treatment of VITT has led to favorable patient outcomes.101 As in HIT, therapeutic anticoagulation with nonheparin anticoagulants is the primary treatment for VITT with or without CVT. Based on data from patients with aHIT, administration of IV immunoglobulin (IVIg) as soon as VITT is diagnosed or under consideration is recommended by both the American Society of Hematology (ASH) and the AHA/ASA at a recommend dose of 1 g/kg for two days.50,51 In patients with severe VITT (extensive thrombosis with platelets <50 × 103/μL) or resistant VITT (continued thrombosis despite medical therapy), treatment with IVIg as a sole immunotherapy might not be enough because of the high antibody burden.43 Although the 2020 AHA/ASA guidelines for VITT-associated CVT do not address plasma exchange as a treatment modality, the ASH notes that plasma exchange can be considered if thrombosis continues despite nonheparin anticoagulation and IVIg.102 Aspirin should not be used in patients with VITT. Platelet transfusions should be avoided with careful risk and benefit assessments made in patients with bleeding, who require surgical intervention, or both.51 Some cases of VITT-associated CVT with extensive clot burden treated with endovascular therapy have been reported with mostly favorable outcomes.103 Given the rarity of thrombocytopenia and CVT, all care should be individualized for each patient.
Decompressive Surgery
Herniation attributable to unilateral mass effect produced by large edematous venous infarctions or parenchymal hemorrhages is the major cause of acute death in CVT.104 Although the vast majority of patients with CVT have a favorable outcome, about 4% develop cerebral edema severe enough to cause brain herniation. In these instances, decompressive craniectomy, hematoma evacuation, or both have been used to prevent death.5 Although a potential disadvantage of craniectomy is that it precludes anticoagulation for the immediate postoperative period, support for decompressive surgery exists. In a retrospective study that included a systematic review of the literature, a total of 69 patients with CVT were identified.105 Of those, only 12 (17%) had a poor outcome (mRS 5 to 6) at a median of 12 months of follow-up. Nearly one-third of patients who were comatose prior to surgery recovered completely at follow-up.105 An updated systematic review published in 2019 identified 169 patients with CVT who were treated with decompressive surgery, mostly from low- to middle-income countries, and similarly found a low mortality rate of 16% at follow-up.106 Despite the low quality of evidence, the ESO guidelines now strongly recommend using decompressive surgery for patients with acute CVT and parenchymal lesions with impending herniation to prevent death as a randomized controlled trial is unlikely for ethical and feasibility reasons.17
Chemical Prophylaxis
Whether individuals with a history of CVT would benefit from targeted prophylaxis in scenarios associated with increased venous thromboembolism risk is uncertain and represents an important area for future research. Pregnant women have been the focus of some research regarding the use of chemical prophylaxis to prevent venous thromboembolism or CVT recurrence.107 In a small retrospective study of 63 women who became pregnant after their diagnosis of CVT and were treated with LMWH for the entire gestational period, two (3%) had venous thromboembolisms and none had bleeding complications.108 In an update of a systematic review published in 2017 that included a total of 393 patients, an analysis stratified according to antithrombotic prophylaxis showed a trend toward lower rates of recurrent CVT and extracerebral venous thromboembolism in patients receiving antithrombotic prophylaxis with heparin.109,110 Although limited, based on these and other data both AHA/ASA and the ESO recommend LMWH prophylaxis in pregnant patients with a previous history of CVT.16,17 The optimal dose of LMWH in pregnant women with moderate to high risk of recurrence of venous thromboembolism is the subject of substantial debate with an ongoing open-label randomized controlled trial comparing two different doses of LMWH in pregnant patients with a history of venous thromboembolism.111
CLINICAL OUTCOMES
In general, CVT has a favorable outcome with an in-hospital mortality rate ranging from 1% to 4% and from 8% to 10% during long-term follow-up.2,5,10,13,104,112,113 Mortality rates after CVT have been declining. One systematic review found an inverse correlation between mortality and the calendar year in which patients with CVT were recruited into a particular study.114 The frequency of presenting with focal neurologic deficits and coma also decreased significantly over time. Possible explanations are improvements in treatment, a shift in risk factors, and the identification of less severe cases by improved diagnostic methods.114 Most studies reporting outcomes after CVT have reported mRS scores at follow-up which may not accurately capture the morbidity that follows CVT. A single-center study of 161 patients with CVT in Finland found that even though 82% of patients had an mRS of 0 to 1 at 6 months, as many as 68% of patients reported residual symptoms which frequently included neuropsychological difficulties and headache.115 Older, smaller-cohort studies have identified cognitive impairments, headaches, and seizures after CVT, frequently resulting in unemployment.116-118 Future research detailing functional outcome after CVT and evaluating interventions to improve patients’ ability to return to the workforce is warranted.
CONCLUSION
The epidemiology of CVT is changing, including more frequent detection among older patients and increased reported incidence rates. The presentation of CVT can be subtle and usually differs from that of other cerebrovascular diseases, making detection of CVT on advanced neuroimaging an essential component of diagnosis. The use of direct oral anticoagulants to treat CVT is an important advance that has recently been shown to be safe and effective, and evidence supports a shift toward their use in clinical practice. To date, the rates of CVT as a complication of adenovirus-based COVID-19 vaccination are very low (<5 per million vaccine doses) and essentially zero with mRNA-based vaccines, with the benefits of COVID-19 vaccination far outweighing the risk of VITT.
Source:
Continuum Cerebrovascular April 2023 Vol 29 No 2
------ NervesandNeuropathy_TarsalTunnel.txt ------
After exiting the tarsal tunnel, the tibial nerve will divide into the medial and lateral plantar nerves. These nerves relay sensation from the plantar skin of the foot. Another branch of the tibial nerve is the calcaneal nerve which innervates the skin over the heel.
Source:
RITE 2017
------ Headache_Neuroimaging_lowpressureheadache.txt ------
This patient has a spontaneous low-pressure headache that is likely due to a dural tear that occurred during her fall. Characteristic features include improvement in the headache while lying down. The radiographic appearance of diffuse dural enhancement is typical.
References:
Mokri B. Spontaneous cerebrospinal fluid leaks: from intracranial hypotension to cerebrospinal fluid hypovolemia-evolution of a concept. Mayo Clin Proc 1999;74:1113-1123.
Source:
RITE 2017
------ HIV_meningitis.txt ------
crytococcal meningitis in pt with HIV, diagnosed after first time seizure (T cell count < 200) low glucose, elevated protein
Source:
nowyouknow neuro
------ Neuroinfectious_NeurologySystemicDisease_infectiousencephalitisdifferential_symptomotology.txt ------
Symptoms of herpes simplex encephalitis include anosmia, olfactory and gustatory hallucinations, and personality changes that can involve bizarre and psychotic behaviors. Symptoms of rabies encephalitis include agitation, restlessness and hydrophobia. Symptoms of neurosyphilis personality change, poor judgement, delusions of grandeur, poor self-care. Symptoms of cryptococcal meningitis include headache, memory impairment and confusion. Symptoms of Lyme disease include irritability, depression, poor concentration and memory impairment.
Source:
------ Autonomics_Neuroinfectious_NeurologySystemicDisease_neurosarcoid.txt ------
Rationale: Bilateral hilar adenopathy, bilateral cranial nerve palsies, and encephalopathy due to a basilar meningoencephalitis are typical of neurosarcoid. Progressive multifocal leukoencephalopathy due to the JC virus, herpes simplex virus encephalitis, and HIV dementia all are characterized by white matter or cortical lesions on MRI. The case is inconsistent with strokes due to cardiac thrombi.
Source:
RITE 2021
------ CerebrovascularDisease_Neuropathy_cnpalsy.txt ------
cn palsies can be caused by aneurysm
Source:
sunny
------ Pompe_disease.txt ------
Alglucosidase alfa is an FDA-approved treatment for late- onset (age >8 years) (noninfantile) Pompe disease, a rare genetic disorder that occurs in an estimated 1 in every 40,000 to 300,000 births. Principal signs and symptoms are cardiac and skeletal muscle weakness that progresses to respiratory weakness and death from respiratory failure.
A mutation of the GAA gene prevents the body from making an enzyme, or making enough of the enzyme, necessary for lysosomal degradation of muscle glycogen. Without the enzyme action, glycogen builds up in the lysosomes.Alglucosidase alfa is an FDA-approved treatment for late- onset (age >8 years) (noninfantile) Pompe disease, a rare genetic disorder that occurs in an estimated 1 in every 40,000 to 300,000 births. Principal signs and symptoms are cardiac and skeletal muscle weakness that progresses to respiratory weakness and death from respiratory failure.
A mutation of the GAA gene prevents the body from making an enzyme, or making enough of the enzyme, necessary for lysosomal degradation of muscle glycogen. Without the enzyme action, glycogen builds up in the lysosomes.Alglucosidase alfa is believed to work by replacing the deficient GAA, thereby reducing the accumulated glycogen in cardiac and skeletal muscle cells. Multiple brands of alglucosidase alfa are available,
with some directed at the treatment of infants and children with Pompe disease because younger patients generally have a much more aggressive form of the disease.
------ Neuro_MuscleNeuromuscularJunction_NervesandNeuropathy_Kennedysdisease_spinalbulbarmuscularatrophy.txt ------
Spinal bulbar muscular atrophy (Kennedy disease) is characterized by lower motor neuron findings, especially affecting cranial musculature associated with decreased libido and gynecomastia. Female carriers are asymptomatic. Muscle biopsy shows nondiagnostic neuropathic changes. Testicular biopsy shows diminished spermatozoids with abnormal motility and mild elevation of FSH and LH. Diagnosis is by DNA analysis which shows expanded CAG repeats translated into polyglutamine repeats.
Source:
RITE 2017
------ CerebrovascularDisease_GerstmanSyndrome.txt ------
A lesion to the angular gyrus of the dominant parietal lobe can cause Gerstmann syndrome, which is characterized by the dyscalculia, finger agnosia, dysgraphia, and right-left confusion. The angular artery, a branch of the middle cerebral artery supplies this part of the cortex.
Source:
RITE 2017
------ CerebrovascularDisease_gertmannsyndrome_presentation.txt ------
This patient is presenting with the sudden onset of the inability to balance her checkbook suggesting she has trouble with calculations. Her exam is indicative of mild finger agnosia and dysgraphia. This constellation of symptoms is part of the Gerstmann syndrome that has been localized to left angular gyrus.
Source:
RITE 2017
------ Neuro_CranialNerves_vagusnervelesion.txt ------
A unilateral lesion of the vagus nerve produces ipsilateral paralysis of the soft palate, pharynx and larynx. The glossopharyngeal nerve does supply the stylopharyngeus muscle which elevates the pharynx during talking, swallowing, and gagging. A lesion of IX, however, would not be expected to cause complete unilateral vocal cord paresis. The other nerves do not innervate the palate or laryngeal muscles. The nucleus tractus solitarius processes visceral afferent information carried by cranial nerves.
Source:
RITE 2017
------ PediatricNeurology_Neuroimaging_CerebrovascularDisease_nonaccidental_trauma.txt ------
Rationale: This patient’s CT scans show extensive bilateral edema with intracranial hemorrhage. Coronal suture is widely spread, and a skull fracture is visible. In a 2-month-old infant, the most likely etiology is nonaccidental trauma. The most common presentations of nonaccidental trauma are decreased responsiveness, respiratory difficulty, and seizures.
Reference: Swaiman AF, Ashwal S, Ferriero DM, et al (eds). Swaiman’s Pediatric Neurology. Principles and Practice. 6th ed. Philadelphia: Elsevier, 2017.
Source:
RITE 2021
------ NeuroOphthalmology_homonymoushemianopia.txt ------
Homonymous hemianopsia results from lesions occuring in the visual radiations or occipital cortex. As the occipital cortex is approached the visual field defects become increasingly congruent. In addition, occipital cortex lesions characteristically produce macular sparing.
Source:
RITE 2009
------ NervesandNeuropathy_Neuroimaging_femeroalneuropathy_retroperitonealpain.txt ------
A femoral neuropathy or high lumbar plexus lesion, associated with retroperitoneal pain in a patient with coagulopathy, suggests a retroperitoneal hemorrhage. Imaging is required to confirm the diagnosis.
Source:
RITE 2017
------ DementiaNeurodegenerativeProcesses_primaryprogressiveaphasia.txt ------
Primary progressive aphasia (PPA) is a frontotemporal dementia (frontotemporal degeneration, FTD) that is characterized initially by word-finding trouble, difficulty with naming, and comprehension. These language features are typically a dominant component of the disease in the first 2 years. Patients can later develop dysfunction in other domains, and late stage PPA patients may not appear that different from patients with other late stage dementias.
Source:
RITE 2017
------ MultipleSclerosisRelatedDisorders_areapostremasyndrome_nmo.txt ------
An area postrema syndrome, characterized by intractable hiccups, nausea, and vomiting, occurs in up to 43 % of patients with Neuromyelitis Optica Spectrum Disorder.
Source:
RITE 2017
------ Epilepsy_Neuroinfectious_herpessimplexencephelitis.txt ------
Rationale: The EEG shows periodic lateralizing epileptiform discharges in the left temporal leads. The clinical presentation, EEG findings, and CSF abnormalities are typical of herpes simplex encephalitis. The treatment of choice is IV acyclovir.
Source:
RITE 2021
------ Pregnancy_NEUROLOGIC_COMPLICATIONS_OF_OBSTETRIC_ANESTHESIA.txt ------
ABSTRACT
PURPOSE OF REVIEW
The advantages of neuraxial anesthesia over general anesthesia in the obstetric population are well established. Some neurologic conditions have the potential to lower the safety threshold for administration of neuraxial anesthesia, whereas others require special consideration before using general anesthesia. The aim of this article is to help neurologists determine when neuraxial anesthesia can be safely administered and when it is inadvisable.
RECENT FINDINGS
Neuraxial anesthesia can usually be given safely in most pregnant patients with neurologic disease. Patients with mass lesions causing increased intracranial pressure or spinal tumors at the site of neuraxial needle placement and patients on anticoagulant medication are the exceptions. Post–dural puncture headaches and obstetric nerve injuries are the most common complications of neuraxial anesthesia and resolve in most patients. Other complications, including epidural hematoma, meningitis, and epidural abscess, are rare but devastating.
SUMMARY
This article provides a review of neurologic diseases that may affect the decision-making process for anesthesia during delivery. It discusses the neurologic complications that can occur because of obstetric anesthesia and how to recognize them and describes obstetric nerve injuries and how to distinguish these relatively benign injuries from more serious complications.
KEY POINTS
Women with multiple sclerosis who are pregnant often have less frequent exacerbations than women with multiple sclerosis who are not pregnant. Flare-ups increase in the postpartum period.
Neuraxial anesthesia may be given safely in women with multiple sclerosis.
Studies show that the use of neuraxial anesthesia poses no risk to women with Chiari malformation type I in the absence of increased intracranial pressure. Spinal and epidural anesthesia may be given safely in pregnant women with syringomyelia.
Although elevated intracranial hypertension due to a mass lesion is a contraindication to neuraxial anesthesia because of the risk of herniation, it is safe in patients with idiopathic intracranial hypertension and may be therapeutic in these patients.
General anesthesia should be avoided, if possible, in patients with idiopathic intracranial hypertension because of the risk of increased intracranial pressure during intubation. Obesity puts these patients at increased risk for difficult intubation and aspiration.
Epidural and spinal anesthesia is preferable in pregnant women with myasthenia gravis. When general anesthesia is used, extubation can be challenging. If general anesthesia is used, depolarizing agents (including succinylcholine) should be avoided because of the risk of neuromuscular blockade.
Meningiomas, schwannomas, and gliomas may all have accelerated growth in pregnancy. If increased intracranial pressure is demonstrated, neuraxial anesthesia should be avoided because of the risk of herniation.
General anesthesia presents risk in pregnant women with brain tumors. An increase in intracranial pressure can occur during induction and intubation.
In most pregnant women with brain tumors without mass effect and increased intracranial pressure, neuraxial anesthesia can be safely administered. A case-by-case assessment of these patients is indicated.
In patients with neurofibromatosis, the presence of lumbar tumors can increase the risk of epidural hematoma during spinal and epidural needle placement. Pregnant women with neurofibromatosis should undergo noncontrast MRI of the lumbar spine before undergoing neuraxial anesthesia.
Patients with Guillain-Barré syndrome are at no increased risk with the use of neuraxial anesthesia but should be monitored carefully for the development of hypotension due to autonomic dysfunction and exaggerated vasovagal response. If general anesthesia is used, succinylcholine is contraindicated because of the potential for life-threatening hyperkalemia.
Most women with lumboperitoneal shunts are able to undergo neuraxial anesthesia; however, imaging may be needed before delivery to ascertain the position of the shunt. Spinal anesthesia may be unpredictable and of shorter duration if local anesthetic leaks via the shunt into the peritoneal cavity, which can lead to an inadequate block.
In pregnant women with myotonic dystrophy, delivery may be difficult because of uterine smooth muscle abnormality, which can affect all stages of labor. The second stage of labor may be prolonged because of skeletal muscle weakness.
General anesthesia should be avoided in patients with myotonic dystrophy, if possible, as they are at high risk for aspiration because of pharyngeal muscle weakness and gastric immotility. Triggers for myotonia should be avoided, including hypothermia and shivering. Respiratory complications can occur in the postoperative period, and opioid use should be minimized.
Intubation may be difficult in patients with spinal muscular atrophy as many have limited jaw opening because of mandibular joint ankylosis and cervical immobility. Depolarizing neuromuscular blockers have a prolonged effect on patients with spinal muscular atrophy even after reversal and should be avoided. Neuraxial anesthesia is preferable to general anesthesia but may not be feasible in some patients with severe scoliosis. Imaging before placement of epidural or spinal anesthesia can be helpful.
Post–dural puncture headache is the most common complication of neuraxial anesthesia. It may be associated with hyperacusis, double vision, photophobia, and nausea. It can be distinguished from migraine and other types of headaches by its postural nature.
Treatment of post–dural puncture headache starts with conservative management, including bed rest, adequate hydration, and analgesics. Although some clinicians advocate the use of caffeine, this has not been supported by the literature.
If conservative management of post–dural puncture headache fails, an epidural blood patch can be placed. A blood patch done less than 24 hours after the dural puncture has a high failure rate. An epidural blood patch performed after 24 hours after dural puncture has a success rate of 70% to 97%.
A rare consequence of intracranial hypotension from dural puncture is the development of a subdural hematoma.
Spinal epidural hematoma should be suspected in patients who experience anesthesia persisting for greater than the expected duration, unusual back pain, persistent motor weakness, sensory loss, and sphincter dysfunction.
Risk factors for spinal epidural hematoma include intrinsic or iatrogenic clotting dysfunction and spinal tumors.
Early diagnosis and management of a spinal epidural hematoma is essential to prevent permanent neurologic injury.
Direct conus and cord injury can result if the lower end of the spinal cord is not accurately determined before needle placement. Placement of neuraxial block, especially spinal anesthesia, at the level below the second lumbar vertebra reduces the risk.
Cauda equina syndrome manifests as burning low back pain, sphincter dysfunction, lower extremity weakness, and saddle anesthesia. It can develop because of neurotoxicity caused by pooling of local anesthetic.
Skin flora is the most common source of infection in women who develop spinal epidural abscess, and Staphylococcus aureus is the most common underlying organism. The risk of developing an abscess increases with prolonged duration of epidural catheterization. Urgent MRI with gadolinium should be done to confirm the diagnosis.
Microbial contamination from the mouth and nose of the practitioner are the most common source of meningitis as a complication of neuraxial anesthesia. The most common causative organism is Streptococcus viridans. Confirmation is obtained with CSF analysis, and treatment is aggressive antimicrobial therapy.
A total spinal block will occur if a large volume of local anesthetic intended for the epidural space is injected into the subarachnoid space. It can produce anesthesia involving the entire spinal cord, nerve roots, and brainstem. Cranial nerve findings, including pupillary dilatation, may occur. It can lead to respiratory insufficiency and profound hypotension and bradycardia. Treatment is supportive.
Seizures may occur when local anesthetic is accidentally injected intravascularly. Systemic toxicity is more likely to occur after obstetric epidural anesthesia than spinal anesthesia because larger volumes of local anesthetics are used.
Source:
Continuum 2022
------ MultipleSclerosisRelatedDisorders_MSpregnancy_relapseandtreating.txt ------
The risk of MS relapses during pregnancy, and the postpartum period, is proportionate to the rate of relapses in the year prior to pregnancy. Since there were 2 relapses in the prior year she remains at higher risk for relapses if she conceives within the next year. This supports the recommendation to continue her MS modulating therapy. Beta-inteferon, natalizumab and dimethylfumarate are classified as FDA category C for pregnancy. Each are associated with either embryolethality or teratogenicity in animal studies, although this has not been proven in humans. At this time glaterimer acetate is considered the safest agent to use during pregnancy and lactation. Ideally this individual should be transitioned to GA 1-2 months prior to conception.
Source:
RITE 2017
------ Epilepsy_functionaldisorders.txt ------
The patient presents with neurologically unexplained symptoms. Neither the history, neurologic examination or testing conform to a known neurologic disorder or pattern of neurologic pathology. The diagnosis of a functional disorder is supported by the dissociative non-epileptic seizures that are triggered by panic attacks, and the giveaway weakness on neurologic examination. Neuropsychologic testing can help to document positive findings supporting the diagnosis of a functional disorder (conversion disorder in this case). Pursuing additional testing, such as any of the other answers listed, is not necessary or appropriate, and may reinforce the patient’s perception of a serious underlying neurologic or medical disorder.
Source:
RITE 2017
------ Epilepsy_AUTOIMMUNE-ASSOCIATED_SEIZURES.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article focuses on the seizure manifestations and presentations of autoimmune-associated epilepsy and acute symptomatic seizures in autoimmune encephalitis. It discusses the specificity of the various central nervous system autoantibodies and clarifies when their presence can be considered indicative of an immune etiology. Finally, current recommendations regarding patient selection for autoimmune antibody evaluation are reviewed, and an approach to immunotherapy is provided.
RECENT FINDINGS
Although autoimmune seizures are caused by a heterogeneous group of autoantibodies, key features reported in the literature should alert clinicians to the possible diagnosis. In particular, seizure characteristics including frequency, timing, duration, and symptomatology can provide vital clues to help differentiate autoimmune-associated seizures from other causes of epilepsy. Diagnostic certainty also requires an understanding and integration of the spectrum of clinical and paraclinical presentations, and several scoring systems have been developed that may be useful to aid the identification of autoimmune seizures.
SUMMARY
Seizures due to autoimmune etiology are increasingly encountered in clinical practice. It is critical that clinicians recognize immune seizure etiologies early in their course given they are often responsive to immunotherapy but are usually resistant to antiseizure medications. Currently, however, it is unfortunately not uncommon for autoimmune-associated seizure disorders to remain undiagnosed, resulting in missed opportunities to administer effective therapies. Efforts to better understand autoimmune seizure manifestations and treatment strategies are ongoing.
KEY POINTS
Immune seizure etiologies are often responsive to immunotherapy but are usually resistant to antiseizure medications.
The term autoimmune-associated epilepsy is now proposed to describe a clinical presentation with an enduring predisposition to unprovoked seizures with evidence of an immune etiology, whereas acute symptomatic seizures secondary to autoimmune encephalitis is recommended for seizures that occur as a symptom of active autoimmune encephalitis.
Not all neural antibodies are considered definitively pathogenic, so clinicians must have an understanding of the pathogenic significance of each antibody to ensure accurate diagnostic and treatment decisions are made.
Seizures in adults with autoimmune encephalitis are reported to occur at a higher frequency and with shorter duration than seizures due to other etiologies.
Anti-LGI1 encephalitis most commonly presents with focal seizures. Patients are typically between the ages of 40 and 80 years. It is somewhat more common in men than women. Hyponatremia is relatively common. Faciobrachial dystonic seizures are the most characteristic seizure type in this disorder, although they are absent in more than half of cases.
EEG may show no ictal findings even during focal seizures in anti-LGI1 encephalitis.
Certain seizure manifestations can provide clues about an autoimmune etiology.
Although seizures are common in anti–N-methyl-d-aspartate (NMDA) receptor encephalitis, affecting approximately 70% of cases, it is less common for them to be the presenting symptom in adults. Seizures are most common in children and young men.
EEG changes in anti–NMDA receptor encephalitis typically progress in parallel with the severity of the clinical illness, and a higher degree of abnormality on EEG can correlate with a poorer prognosis.
A characteristic EEG finding in anti–NMDA receptor encephalitis is the “extreme delta brush” pattern, present in up to 30% of cases.
Although anti–leucine-rich glioma inactivated protein 1 (LGI1) and anti–NMDA receptor encephalitis are most commonly associated with seizures, many other autoimmune encephalitides can also cause seizures.
Autoimmune encephalitis can occur in the absence of detectable neural autoantibodies, and if the pretest probability is high, then the diagnosis of seronegative autoimmune limbic encephalitis should be considered.
Examples of autoimmune-associated epilepsy include the persistence of seizures after resolution of the active phase of encephalitis; chronic unresolving encephalitis including Rasmussen encephalitis; and in patients with epilepsy with compelling evidence of a CNS autoimmune condition where no alternative etiology for the epilepsy is identified.
Rasmussen encephalitis is a rare neuroinflammatory disorder resulting in chronic focal seizures, emanating from one hemisphere, progressive hemiparesis, other lateralized cortical deficits, and cognitive impairment.
Immunotherapy can lead to seizure freedom when due to autoimmune etiologies; consideration of these disorders should be given in the setting of drug-resistant seizures, especially those of recent onset and intractability from inception.
Diagnostic accuracy requires an understanding and integration of the spectrum of clinical and paraclinical presentations, and several scoring systems have been developed that may be useful in aiding the identification of autoimmune seizures.
If used alone, antiseizure medications are rarely effective in the setting of symptomatic seizures secondary to autoimmune encephalitis. They also may not be required after resolution of the acute illness, so cessation should be considered after 6 months or a greater period of sustained seizure freedom.
Immunotherapy is the mainstay of treatment for autoimmune seizure etiologies and should be administered early in the course of the illness. Eighty percent to 90% of patients may achieve seizure freedom depending on the specific etiology, and it may lead to improvements in cognitive and functional outcomes.
ARTICLE 6: WOMEN’S ISSUES IN EPILEPSY
Esther Bui, MD, FRCP(C). Continuum (Minneap Minn). April 2022; 28 (2 Epilepsy):399–427.
ABSTRACT
PURPOSE OF REVIEW
Issues pertaining to women with epilepsy have advanced with a better understanding of multidirectional influences among hormones, seizures, and antiseizure medications, as well as pregnancy-related concerns around fertility, seizure destabilization, and antiseizure medication–associated teratogenicity. This article highlights important developments in this field and reviews best practices in the management of women with epilepsy.
RECENT FINDINGS
Important external hormonal influences may impact women with epilepsy particularly in the context of gender-affirming medications, hormonal replacement therapy, and fertility therapies. Fertility for women with epilepsy is influenced by multiple variables; however, in the absence of preexisting fertility issues, epilepsy per se is not associated with significantly impaired fertility. Once women with epilepsy are pregnant, the majority have a stable course. Antiseizure medication use in pregnancy is associated with major congenital malformations 2 to 5 times that of the general population and is highest with high-dose (≥1500 mg or greater total daily) valproate. Carefully considered changes in drug choice and dose may mitigate these risks. Therapeutic drug monitoring plays an important role in pregnancy care, and under expert supervision, women with epilepsy in pregnancy have similar seizure risks as women with epilepsy who are not pregnant. As women with epilepsy age, bone health and menopause may further be impacted by seizures and antiseizure medications.
SUMMARY
The care of women with epilepsy is a multifaceted discipline that recognizes the life-long impact of sex and gender influences on epilepsy care.
KEY POINTS
Gender-affirming medications may interact with antiseizure medications, and antiseizure medications may have unwanted esthetic side effects and significant drug-drug interactions.
Women with epilepsy without preexisting infertility have as good of a chance for conceiving as do women without epilepsy.
Seizure exacerbation may occur with hormonal therapies used in assisted reproductive technology; however, women with epilepsy have a similar chance at successful assisted reproductive technology treatment as women without epilepsy irrespective of concurrent antiseizure medication use.
The intrauterine device, either hormonal based or copper based, continues to be the top-recommended contraceptive choice for women with epilepsy taking enzyme-inducing antiseizure medications or lamotrigine.
Up to two-thirds of women with epilepsy remain seizure free in pregnancy. The best predictor of seizure frequency during pregnancy is the 9 to 12 months of seizure frequency before conceiving.
Under specialized epilepsy care, women with epilepsy in pregnancy have similar rates of seizures as women with epilepsy who are not pregnant, but women with epilepsy in pregnancy require higher rates of antiseizure medication dose adjustments.
The risk of major congenital malformations is drug and dose dependent. When these factors are combined, some risks may be near comparable, for example, high-dose carbamazepine (>700 mg total daily) and low-dose valproate (≤650 mg total daily).
Different antiseizure medications are associated with different malformation types, and fetal assessment as well as neonatal examination should be tailored to these risks.
Data on major congenital malformation risk of newer antiseizure medications continue to be insufficient because of the limited numbers of reported exposure, with most on polytherapy.
Polytherapy that includes either valproate or topiramate as a component infers the highest risk of major congenital malformations among different polytherapy combinations.
The risk of major congenital malformations with antiseizure medication exposure is highest with high-dose (≥1500 mg total daily) valproate. The risks may be lowered with low-dose valproate combined with another antiseizure medication.
Genetic factors are important additional influences for the risk of major congenital malformations. A paternal and maternal history should be acquired to fully characterize the risks.
Decisions to withdraw or avoid valproate should be specific to the individual woman, her seizure type, and physical as well as psychosocial impact of potential seizure recurrence.
Preconception folic acid 0.4 mg to 5 mg daily is recommended for women with epilepsy of reproductive potential, although some recent concerns have been raised about supratherapeutic (>5 mg daily) folic acid supplementation.
Antiseizure medication clearance and metabolism are differentially impacted at specific stages in pregnancy. When these serum drug levels decrease by more than 35% of preconception levels, seizures may recur.
Regular therapeutic drug monitoring should be considered in pregnancy, when available, especially with drugs recognized to have pregnancy-related altered pharmacokinetics such as lamotrigine, levetiracetam, oxcarbazepine, topiramate, and zonisamide.
Maternal mortality is elevated 5 to 11 times for women with epilepsy compared with the general population, although in absolute numbers, these occurrences remain rare.
If dose increases have been made during pregnancy, tapering antiseizure medication doses should be planned within the first few weeks postpartum, especially with lamotrigine.
Breastfeeding is generally safe and beneficial for women with epilepsy who are taking antiseizure medications and for their babies.
Antiseizure medications are associated with osteoporosis. Vitamin D and calcium supplementation and a baseline bone mineral density are recommended especially with chronic antiseizure medication use.
Hormonal replacement therapy may exacerbate seizures in a dose-dependent way. If necessary, simplified estrogen with natural progesterone could be considered.
Source:
Continuum Epilepsy 2022
------ Epilepsy_NEUROPSYCHIATRIC_AND_COGNITIVE_COMORBIDITIES_IN_EPILEPSY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses psychiatric and cognitive comorbidities of epilepsy over the lifespan and illustrates opportunities to improve the quality of care of children and adults with epilepsy.
RECENT FINDINGS
One in 3 people with epilepsy have a lifetime history of psychiatric disorders, and they represent an important prognostic marker of epilepsy. Contributors are diverse and display a complex relationship. Cognitive comorbidities are also common among those living with epilepsy and are increasingly recognized as a reflection of changes to underlying brain networks. Among the cognitive comorbidities, intellectual disability and dementia are common and can complicate the diagnostic process when cognitive and/or behavioral features resemble seizures.
SUMMARY
Comorbidities require consideration from the first point of contact with a patient because they can determine the presentation of symptoms, responsiveness to treatment, and the patient’s day-to-day functioning and quality of life. In epilepsy, psychiatric and cognitive comorbidities may prove a greater source of disability for the patient and family than the seizures themselves, and in the case of essential comorbidities, they are regarded as core to the disorder in terms of etiology, diagnosis, and treatment.
KEY POINTS
Psychiatric disorders occur more commonly in epilepsy than in the general population and are increasingly recognized as a major source of disability in epilepsy.
The etiology of psychiatric disorders in epilepsy is complex and can include both biological and psychosocial factors, including altered functioning of brain networks, stigma, social limitations, and distress.
The relationship between epilepsy and psychiatric disorders is bidirectional, including depression, psychogenic nonepileptic seizures, attention deficit hyperactivity disorder, autism spectrum disorder, and schizophrenia.
Consideration of psychiatric comorbidities is clinically relevant for neurologists because comorbid psychiatric conditions have been associated with poorer treatment outcomes, as well as increased health care utilization and increased mortality.
Barriers to diagnosis and treatment can include a lack of training of neurologists and psychiatrists in the psychiatric aspects of neurologic disorders and a lack of clinical resource allocation to support a multidisciplinary approach, as well as broader stigma and cultural barriers to mental health support.
Some useful tools to screen for psychiatric conditions in epilepsy include the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Epilepsy Anxiety Survey Instrument (EASI), the brief Epilepsy Anxiety Survey Instrument, the Beck Depression Inventory II (BDI-II), Patient Health Questionnaire 9 (PHQ-9), the Hospital Anxiety and Depression Scale (HADS), and the Generalized Anxiety Disorder Scale (GAD-7).
Diagnosis of psychiatric conditions in epilepsy involves careful consideration of the timing of symptom onset and progression to determine the presence of postictal symptoms and/or possible contribution of antiseizure medications.
Further research is needed to examine the efficacy of treatment approaches for psychiatric disorders in epilepsy, but first-line treatment involves psychoeducation and psychological interventions.
Choice of medication for psychiatric conditions should include consideration of metabolic, extrapyramidal cardiovascular, and hormonal side effects and interactions with antiseizure medications, including the possibility of amplifying side effects of antiseizure medications.
Cognitive comorbidities are common among people living with epilepsy and can range from generalized cognitive impairment to relatively circumscribed deficits.
The International Classification of Cognitive Disorders in Epilepsy seeks to advance the understanding of the essential cognitive comorbidities of epilepsy.
Cognitive difficulties may extend beyond intellectual functions, such as attention and memory, and may include difficulties with emotional expression and regulation.
Several specific childhood epilepsy syndromes typically involve significant developmental delay and/or intellectual disability. Many of these syndromes represent rare genetic epilepsy syndromes.
An epileptic encephalopathy has been defined by the International League Against Epilepsy as “a condition in which the epileptiform abnormalities themselves are believed to contribute to the progressive disturbance in cerebral function.”
The recognition of a bidirectional relationship between epilepsy and dementia is growing, with an increased risk of dementia among people living with epilepsy and an increased risk of seizures in dementia.
Increased risk of seizures has been identified across several different dementia syndromes, including Alzheimer disease, frontotemporal dementia, and dementia with Lewy bodies.
Risk factors for seizures in dementia include poor cardiovascular health, raised inflammatory markers, decreased physical fitness, and decreased social interaction.
Subjective cognitive concerns are not always correlated with objective cognitive performance and may be influenced by mood, lack of insight, and other psychological factors.
Different cognitive screening measures may include the Montreal Cognitive Assessment (MoCA) or the Mini-Mental State Examination (MMSE). However, cognitive comorbidity can only be properly diagnosed following a comprehensive workup that includes formal neurologic, neuropsychological, and/or neuropsychiatric assessment.
Consideration of a patient’s cognitive functioning is crucial in the workup to epilepsy surgery. This is important not only in considering the possible cognitive risks of surgery but also in how clinicians discuss the surgery with patients and their family members and obtain informed consent. Cognitive aids, such as written and/or simplified information, may be helpful for some patients.
Consideration of psychiatric well-being is important not only for patients’ general well-being but also for their subjective cognitive functioning, because the reduced physical and social activity that may be prompted by low mood can be detrimental to cognition.
Source:
Continuum Epilepsy 2022
------ MovementDisorders_DIAGNOSING_COMMON_MOVEMENT_DISORDERS_IN_CHILDREN.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article is designed to help the clinician identify the most common pediatric movement disorders and recognize benign versus pathologic movements in infancy and childhood, with a particular focus on treatable conditions and those that should not be missed.
RECENT FINDINGS
As telehealth has become more prevalent as a means of providing health care services, the challenges of obtaining relevant examination findings during telehealth encounters for assessment of children with movement disorders have become evident.
SUMMARY
Although many children who present with a chief complaint of “abnormal movements” are found to have a benign, self-resolving etiology, it is critical that neurologists accurately recognize benign versus pathologic movements in children to ensure appropriate diagnosis and intervention.
KEY POINTS
Developmental control of voluntary movement begins at the head and neck and progresses to the trunk and then the extremities (rostrocaudal gradient).
Coordinated movement involves the whole brain, not just the basal ganglia and motor cortices but also the brainstem, limbic system, cerebellum, frontal lobes, and nonmotor pathways.
Voluntary movement involves an intricate balance of “stop and go” signaling, with dopamine playing the role of fine motor modulator.
Understanding phases of movement (motor planning, initiation, and execution) can help to better identify abnormal movements.
The clinician should ask the child about their movements: what, where, when, with whom, wax/wane, worsening, why (Why do you think you have these movements?) (What do you want help with?).
The clinician should pay careful attention to developmental milestones and watch for signs of subtle delay when evaluating a child for movement disorders.
The clinician should dig deep on family history; encourage parents to ask their families about their own childhood movements when evaluating a child presenting with a movement disorder.
Understand both the manifestation and functional impact of movements in multiple environments when evaluating a child presenting with a movement disorder.
Ask about and normalize worry to further explore the role of anxiety when evaluating a child presenting with a movement disorder.
Understanding of developmental milestones is key to recognizing normal versus abnormal movements.
Observation is an essential skill for the pediatric movement examination.
Making the examination fun and using play to elicit movement patterns is key to an efficient and thorough movement examination in children.
Tone is dynamic. Accurate and thorough understanding of tone demands examination in multiple states (at rest, with activity, while asleep).
Many abnormal movements in children are benign and will resolve with development.
Tics and stereotypies are the most common benign movement disorders in childhood.
Benign motor stereotypies typically do not require intervention.
Urge and suppressibility are key features of tics.
Nonpharmacologic interventions for tics include comprehensive behavioral intervention for tics.
Movement disorders in children can present with phenomenology similar to that in adults and may be categorized as chorea, dystonia, myoclonus, tremor, ataxia, spasticity, and parkinsonism.
Unlike adults, children often present with a mixed movement disorder; thus, discerning the primary phenomenology can be challenging but remains the foundation of accurate and timely diagnosis and treatment.
Sydenham chorea is a common cause of treatable acute-onset chorea in children. Early recognition and diagnosis allow for appropriate intervention with steroids for symptom management.
Symptom severity in Sydenham chorea is highly variable, but children commonly present with complaints of new clumsiness (dropping items, falling), gait instability, irritability, poor coordination, and possible changes in speech and behavior.
Sydenham chorea is a form of rheumatic disease; thus, screening and monitoring for associated cardiac involvement are imperative.
Genetic causes for chorea should be considered in any child with new-onset subacute progressive chorea, especially if accompanied by other neurologic or psychiatric features.
For the child with spasticity and dystonia, surgical intervention must be considered carefully, as certain interventions for spasticity (in particular, selective dorsal rhizotomy) may improve the spasticity but “unmask” concurrent dystonia, resulting in worsened motor function.
Surgical candidates should be evaluated by a multidisciplinary review board including specialists in neurology, neurosurgery, and physical, occupational, and speech therapy, as well as undergo a thorough psychosocial evaluation.
Surgical intervention with pallidal deep brain stimulation should not be delayed for children with medication-refractory progressive dystonia.
It is always prudent to trial levodopa for any child with dystonia to rule out a treatable dopa-responsive dystonia.
Examples of benign physiologic myoclonus include hiccups, exercise- or anxiety-induced myoclonus, benign neonatal sleep myoclonus, or hypnic jerks in older children.
The most common causes of tremor in children are the primary tremors: developmental tremor, enhanced physiologic tremor, and essential tremor.
The clinician should obtain a thorough family history and examination of accompanying family members at the time of neurologic examination for tremor.
Toxic ingestion is at the top of the differential diagnosis for acute ataxia.
Clinical distinction between spasticity, dystonia, and rigidity is essential for accurate diagnosis and appropriate treatment of the hypertonic child.
Although spastic cerebral palsy is the most common type, many children with cerebral palsy present with a mixed movement disorder.
Key principles regarding the diagnosis of cerebral palsy are as follows: (1) Cerebral palsy is a clinical description and not an etiology. (2) Cerebral palsy is a permanent disability. (3) Cerebral palsy is a nonprogressive brain process, but the physical manifestations of the disorder are not necessarily static.
Botulinum toxin injections for focal spasticity are approved by the US Food and Drug Administration for children 2 years old and older and may be used in isolation or in conjunction with oral medications.
Recognition of spasticity and distinction from dystonia and rigidity is particularly important when considering possible etiologies as well as appropriate therapeutic interventions for cerebral palsy.
Some surgical procedures targeting spasticity, such as selective dorsal rhizotomy, may actually worsen a patient’s function if their dystonia is mistaken for spasticity.
Parkinsonism in infants may be difficult to identify as such and should be considered for any infant with hypotonia and reduced movement of undetermined etiology.
Early and accurate diagnosis of functional movement disorders avoids excessive medical testing and treatment and delayed diagnosis and enables implementation of appropriate interventions.
Diurnal fluctuation of symptoms may point to an underlying neurometabolic disorder.
Potentially life-threatening drug-induced movement disorders include acute dystonic reaction, neuroleptic malignant syndrome, and serotonin syndrome.
It is prudent to consider referral for pediatric deep brain stimulation for any child with medication-refractory dystonia, chorea, or tremor.
Source:
Continuum 2022
------ Headache_AcuteMigraineManagement_pregnantpatient.txt ------
1.During pregnancy acute migraine headache management is appropriate. Of those listed, Promethazine is the recommended first line agent during pregnancy. Although ibuprofen can be used for headache management in pregnancy, it is not advisable in the 3rd trimester. Sumatriptan is probably safe but not recommended as a first line agent. Ergotamine can trigger miscarriages and should not be used. 2.Valproic acid is associated with 5-14% known risk of major fetal malformations including neural tube defects. Topiramate has been associated with facial and oral clefts. 3. Amitriptyline can be safely used for migraine prophylaxis during pregnancy. 4.Although there is an increased risk of augmentation with levodopa compared to dopamine agonists, it is the preferred agent during pregnancy. Dopamine agonists have been reported to cause fetal malformations and intrauterine growth retardation in animals 5.Both CYP 450 enzyme inducers (eg, PHT and CBZ) and inhibitors (VPA) have been shown to impair bone health. TPM has not been shown to be deleterious to bone health.
Source:
RITE 2017
------ Sleep_Circadian_Rhythm_Sleep-Wake_Disorders.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides an overview of circadian physiology and discusses common presentations and treatment strategies for the circadian rhythm sleep-wake disorders.
RECENT FINDINGS
Circadian rhythms are present throughout the body, and appreciation for the role that circadian dysregulation plays in overall health is increasing, with mounting associations between circadian disruption and cardiometabolic disease risk.
SUMMARY
It is important to recognize the ubiquitous role that circadian rhythms play throughout the brain and body. An understanding of circadian neurophysiology will provide insight into the means by which patients with a variety of neuropathologies at the level of the retina, optic nerve, or hypothalamus may also be at risk for circadian dysfunction.
KEY POINTS
In mammals, circadian rhythms are coordinated by the suprachiasmatic nucleus located in the anterior hypothalamus, directly above the optic chiasm.
The daily rhythmic activity within the suprachiasmatic nucleus is regulated by a complex transcription-translation feedback loop containing positive and negative elements.
Light exposure in the early biological evening causes delays of circadian timing, whereas light exposure during the late biological evening advances circadian timing.
Melatonin administration in the early evening results in advances in circadian timing, whereas morning melatonin administration delays the circadian clock.
Delayed sleep-wake phase disorder is characterized by a delay in sleep-wake timing with respect to the time that the individual desires or is required to be awake and asleep, resulting in a combination of difficulty awakening, daytime sleepiness, and difficulty falling asleep.
There appear to be at least two forms of delayed sleep-wake phase disorder. The first type includes those who experience a delay in both sleep-wake behaviors and circadian biomarkers such as melatonin, often referred to as circadian delayed sleep-wake phase disorder. Patients with the second type experience a delay in their sleep-wake behaviors, but melatonin timing is not delayed, referred to as noncircadian or motivated delayed sleep-wake phase disorder.
The first genetic mutation associated with familial delayed sleep-wake phase disorder was recently identified: a mutation in the CRY1 gene is associated with a lengthening of the circadian period.
Overall, greater sensitivity to evening delaying signals, decreased exposure to morning advancing signals, and a longer intrinsic period all likely contribute in varying degrees to the development of delayed sleep-wake phase disorder.
Treatment of circadian delayed sleep-wake phase disorder primarily focuses on the use of timed exposure to light and melatonin, with a goal of advancing sleep-wake timing.
Advanced sleep-wake phase disorder is characterized by a significant advance in sleep-wake timing, often presenting with reports of either early morning awakenings or early evening sleepiness.
The primary recommendation for the treatment of advanced sleep-wake phase disorder is the use of evening bright light to delay circadian rhythms.
Irregular sleep-wake rhythm disorder is characterized by multiple irregular bouts of sleep and wake, without a clear circadian rhythm.
Non–24-hour sleep-wake rhythm disorder is characterized by a sleep-wake schedule that is typically slightly longer than 24 hours and can be seen in blind individuals who lack light perception, as well as in some sighted individuals.
Shift work disorder results when individuals develop sleep-wake symptoms that are specifically related to being required to work during times that they would normally be sleeping.
The health consequences of shift work disorder can be quite significant and extend beyond just the sleep symptoms. The overall risk appears to increase with greater duration of exposure (>5 years) and exposure to rotating shift work at a younger age.
The wake-promoting agents modafinil and armodafinil have been approved by the US Food and Drug Administration for the treatment of sleepiness associated with shift work disorder.
Jet lag disorder occurs as a result of rapidly crossing multiple time zones, resulting in a temporary mismatch between an individual’s biological time and the environmental light-dark cycle.
It is important to keep circadian rhythm sleep-wake disorders in mind, particularly in neurologic patients who may have impaired light input through the retina and optic nerves, neurodegeneration at the level of the suprachiasmatic nucleus, or pathology of the melatonin-producing pineal gland.
Source:
Continuum Sleep 2020
------ MovementDisorders_DIAGNOSIS_AND_TREATMENT_OF_ESSENTIAL_TREMOR.txt ------
ABSTRACT
PURPOSE OF REVIEW
Essential tremor is a chronic, progressive syndrome that primarily presents with an action tremor involving the arms and hands. This article reviews the history and physical examination features pertinent for diagnosis, differential diagnoses, and treatments and approaches for optimal control of symptoms.
RECENT FINDINGS
Essential tremor is a syndrome with symptoms extending beyond tremor to involve disturbances in gait, speech, cognition, and mood. Although the new guidelines on the definition and biaxial classification scheme have provided clarity, some tremor experts have critiqued the recently coined term essential tremor plus. For treatment, new orthotic devices and peripheral stimulation devices are now available in addition to pharmacologic and surgical options.
SUMMARY
Essential tremor has a rich clinical phenomenology with many subtleties and nuances. A detailed history with open-ended questions and focused questions encompassing medical history, social history, and family history is key for establishing the diagnosis. The presence of bilateral action tremor for 3 years and absence of isolated head and voice tremor and absence of task- and position-dependent tremor are necessary for diagnosis. Dystonic tremor, Parkinson disease tremor, physiologic tremor, and drug-induced tremor are common differential diagnoses. Differentiating these tremor disorders from essential tremor based on phenomenology and physical examination alone could be challenging; thus, clinicians should seek additional clues from a detailed history. Treatment could begin with noninvasive and nonpharmacologic therapies, especially in mild cases. As the severity increases, they can advance stepwise to include pharmacotherapies and surgical interventions. With the growing recognition that essential tremor is not a monosymptomatic disorder, management should involve a multidisciplinary team. Furthermore, treatment selection should be based on shared decision making between patients and providers that gives due consideration to severity of symptoms, level of functional disability, impact on social interactions, patient preferences, and patient expectations.
KEY POINTS
The involuntary movements of essential tremor are both rhythmic and oscillatory.
Tremor syndrome classification is biaxial, first based on clinical phenotyping and second based on underlying etiologies.
Essential tremor is among the most prevalent movement disorders.
Isolated tremor syndrome of bilateral upper limb action tremor present for at least 3 years is a requirement for the diagnosis of essential tremor.
Patients with early-onset essential tremor commonly report at least one affected first-degree family member.
Essential tremor is a syndrome with symptoms in many patients extending beyond tremor to involve disturbances in gait, speech, mood, and cognition.
Essential tremor with a resting component or accompanied by soft signs of dystonic posturing or parkinsonism is labeled as essential tremor plus; currently, no evidence has been found that essential tremor plus is biologically distinct from essential tremor.
Dystonic head tremor commonly affects women in their fifth decade and includes headaches, neck pain, posturing, and isolated head tremor.
Isolated head tremor, voice tremor, and task- or position-specific tremor should not be diagnosed as essential tremor.
Unlike essential tremor, dystonic head tremor often persists when the patient is examined while lying down.
The tremor in dystonia may be neither rhythmic nor oscillatory.
Arm tremor in dystonia is frequently unilateral and asymmetric.
Unlike essential tremor, dystonic arm tremor may not reveal a clear axis during the spiral-drawing task.
Based on physical examination alone, dystonic tremor may not be distinguishable from essential tremor; history must be given consideration.
Unlike essential tremor, resting tremor in Parkinson disease increases in amplitude with walking and mental calculation and is generally asymmetric.
Unlike essential tremor, arm tremor in Parkinson disease reveals a reemergent quality (a tremor that occurs after a finite latency period from the time the patient assumes a horizontal posture of the arm to the onset of the wrist and/or finger tremor).
In contrast to essential tremor, the jaw tremor of Parkinson disease is more often noted when the patient’s mouth is closed and relaxed rather than while the patient is speaking.
Head tremor is not a feature of enhanced physiologic tremor or drug-induced action tremor.
Holmes tremor has resting, postural, and kinetic components.
Fragile X-associated tremor/ataxia syndrome has a prominent intentional component.
Wilson disease has prominent wing-beating postural tremor.
Functional tremor is abrupt in onset and distractible, suggestible, and entrainable.
Management of essential tremor requires a multidisciplinary team, and treatment selection requires shared decision making between patients and providers.
Adaptive tools, orthotic devices, limb cooling, and peripheral stimulation devices are useful nonpharmacologic therapies for essential tremor.
If the tremor is severity does not reduce despite multiple medication trials, surgical intervention may be warranted.
Source:
Continuum 2022
------ CerebrovascularDisease_MECHANICAL_THROMBECTOMY_FOR_ACUTE_ISCHEMIC_STROKE.txt ------
ABSTRACT
OBJECTIVE
Endovascular stroke therapy has greatly improved the ability to treat the deadliest and most disabling form of acute ischemic stroke. This article summarizes some of the recent innovations in this field and discusses likely future developments.
LATEST DEVELOPMENTS
At present, there is robust activity to improve all facets of care for patients with large vessel occlusion stroke, including better prehospital routing, more efficient in-hospital screening, expanding indications for thrombectomy eligibility, innovating novel thrombectomy devices, and improving the effects of recanalization on clinical outcomes. In addition, the integration of endovascular stroke therapy (EVT)—an emergent and frequently off-hours procedure that requires a specialized team of nurses, technologists, and physicians—into acute stroke care has transformed referral patterns, hospital accreditation pathways, and physician practices. The eligibility for the procedure will potentially continue to grow to include patients screened without advanced imaging, larger core infarcts, and more distal occlusions.
ESSENTIAL POINTS
In this review, we discuss the current state of EVT and its implications for practice, and present three cases that highlight some of the directions in which the field is moving.
KEY POINTS
Endovascular therapy has become the consensus approach for appropriately selected patients and can produce dramatic improvements in clinical outcomes for patients with large vessel occlusion.
Several endovascular therapy trials published in 2015 established the treatment as clearly beneficial compared to medical management.
Because neurologists are frequently the frontline evaluators of patients with large vessel occlusion acute ischemic stroke and serve as the gatekeepers for the procedure, they must have a basic understanding of the risks, benefits, and technical aspects of endovascular stroke therapy.
Despite this growth in endovascular stroke therapy performance, a large proportion of patients receive their acute ischemic stroke care at hospitals not capable of performing endovascular stroke therapy.
The challenge of how to balance the availability of sufficient daytime neurointerventional elective work with the need for additional physicians to sustainably cover the call burden remains unsolved.
One of the lingering obstacles to endovascular treatment access remains the absence of a uniformly accepted neurointerventional accreditation system for training and certification.
The efficacy of endovascular stroke therapy for large vessel occlusion acute ischemic stroke is highly time sensitive and bringing appropriate patients directly to endovascular stroke therapy–performing centers may accelerate treatment times and possibly improve clinical outcomes.
Given the known adverse effects on clinical outcomes with delays in IV thrombolysis, accurate large vessel occlusion detection in the field to ensure that non–large vessel occlusion patients do not suffer from delays in IV recombinant tissue plasminogen activator (rtPA) is now of heightened importance.
As clinical experience with endovascular stroke therapy has grown, the need for CTP to screen patients has been called into question.
Two ongoing randomized clinical trials—MR CLEAN LATE and RESILIENT Extend—are evaluating the efficacy of endovascular stroke therapy in late-window patients without relying on CTP.
The consensus remains to treat with IV rtPA in all eligible patients, including those with large vessel occlusion acute ischemic stroke for whom endovascular stroke therapy may be needed.
Two studies, both performed in China, demonstrated superiority of endovascular stroke therapy over medical management alone in patients with basilar artery large vessel occlusion acute ischemic stroke, in both the early time window (<12 hours from last known well in ATTENTION) and late time window (6 to 24 hours from last known well in BAOCHE).
The natural history for patients with large vessel occlusion acute ischemic stroke presenting in the late treatment window is poor, with over 80% having substantial disability.
One of the interpretations of the large effect sizes seen in DAWN and DEFUSE 3 is a need to shift from time-based selection paradigms to an imaging-based one.
Some of the key questions to ask regarding the results of large core trials will be the extent of clinical improvement and the proportion of patients who achieve good quality of life, rather than slightly less but still severe disability.
Improvement in device technology was likely an important factor in the success of the 2015 thrombectomy trials.
The goal of endovascular stroke therapy procedures has become achieving complete reperfusion (thrombolysis in cerebral infarction grade 3) with a single pass, termed the first pass effect. This bar has become the new standard by which device performance can be measured.
Intracranial atherosclerotic disease can lead to large vessel occlusion acute ischemic stroke through several different mechanisms, including artery-to-artery distal embolization, in situ parent vessel occlusion, occlusion of a perforator branch adjacent to the intracranial atherosclerotic disease plaque, or hypoperfusion related to high-grade stenosis.
Despite the greater than 90% substantial recanalization rates that can be achieved with modern endovascular stroke therapy, about 50% of patients still do not achieve functional independence after treatment.
While its results will need to be replicated, the CHOICE trial provides one of the first treatment approaches for microvascular dysfunction.
Source:
END
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------ Sleep_Insomnia.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides updated information regarding the diagnosis and treatment of chronic insomnia disorder. In addition to discussing the latest recommendations regarding pharmacotherapeutic options for insomnia, this article also discusses the increased use of nonpharmacologic treatment approaches, including cognitive-behavioral therapy intervention, integrative medicine, mindfulness and meditation, and other therapeutic options in clinical practice.
RECENT FINDINGS
Insomnia is one of the most common sleep disorders in patients with other neurologic disorders. The definition and criteria for insomnia were updated with the release of the International Classification of Sleep Disorders, Third Edition. The American Academy of Sleep Medicine has updated clinical practice guidelines for the pharmacologic treatment of chronic insomnia in adults. New diagnostic and therapeutic options (eg, pharmacologic and behavioral therapies, at-home devices) have emerged to optimize and personalize the evaluation and management of sleep disorders such as insomnia. Although some of these devices and treatment options are still in the early stages of development, several are currently in clinical trials or will soon be available.
SUMMARY
This article emphasizes complexities related to the evaluation and management of patients with chronic insomnia disorder and describes alternative therapeutic options for patients with this common sleep disorder.
KEY POINTS
Insomnia can be a symptom of another medical disorder (eg, chronic pain, sleep apnea, anxiety, and depression) or its own disorder (ie, chronic insomnia disorder).
Many individuals may have chronic insufficient sleep but do not report any daytime consequences and, therefore, do not qualify for an insomnia diagnosis due to the absence of a related functional impairment.
The typical person has a circadian rhythm set to go to bed at 11:00 pm and awaken at 7:00 am.
While it remains important for individuals to get enough sleep (ie, 7 to 9 hours each night), it is just as important, and for some individuals even more important, that the timing of their sleep-wake schedule is consistent.
Patients with circadian rhythm sleep-wake disorders experience insomnia or excessive sleepiness, but they can experience both depending on the nature of their circadian rhythm misalignment.
Chronic insomnia disorder remains a clinical diagnosis based on meeting the diagnostic criteria and does not require polysomnography.
Cognitive-behavioral therapy for insomnia, a structured and personalized nonpharmacologic program, generally conducted by a sleep behavioral psychologist who guides individuals to modify their cognitive processes and sleep behaviors in an effort to improve their sleep, remains the gold standard therapy for insomnia.
The American Academy of Sleep Medicine and the American College of Physicians both recommend cognitive-behavioral therapy for insomnia as the first-line treatment for chronic insomnia disorder.
Online cognitive-behavioral therapy for insomnia has been shown to improve insomnia severity, sleep efficiency, subjective sleep quality, wake after sleep onset, sleep-onset latency, total sleep time, and the number of awakenings from sleep.
Medications to treat chronic insomnia may sometimes be used, ideally in a short-term manner.
Mindfulness meditation alone has shown significant improvement in sleep efficacy.
Pranic healing is a type of biofield therapy modality that uses a standardized process; it is intended to complement allopathic medicine and not replace it.
Autonomous sensory meridian response is a sensory-type strategy in which individuals experience a tinglinglike sensation typically across the scalp and back of the neck in response to specific triggering of audio and visual stimuli to induce states of relaxation.
While more research is needed to assess its clinical benefits, cranial electrical stimulation is one example of a clinical tool that is increasingly being considered as a potential treatment option for insomnia.
Source:
Continuum Sleep 2020
------ Neuroimaging_THE_RIGHT_IMAGING_PROTOCOL_FOR_THE_RIGHT_PATIENT.txt ------
ABSTRACT
OBJECTIVE
This article provides a high-level overview of the challenge of choosing the right imaging approach for an individual patient. It also presents a generalizable approach that can be applied to practice regardless of specific imaging technologies.
ESSENTIAL POINTS
This article constitutes an introduction to the in-depth, topic-focused analyses in the rest of this issue. It examines the broad principles that guide placing a patient on the right diagnostic trajectory, illustrated with real-life examples of current protocol recommendations and cases of advanced imaging techniques, as well as some thought experiments. Thinking about diagnostic imaging strictly in terms of imaging protocols is often inefficient because these protocols can be vague and have numerous variations. Broadly defined protocols may be sufficient, but their successful use often depends largely on the particular circumstances, with special emphasis on the relationship between neurologists and radiologists.
KEY POINTS
The American College of Radiology Appropriateness Criteria provide a good starting point for finding the right imaging modality. The American College of Radiology does not prescribe disease-specific protocols.
Imaging protocols are not generally applicable laws but rather rules that may be adapted to the circumstances.
Communication is key for two main reasons: (1) the default imaging approach may need to be changed based on relevant clinical data, and (2) communication can facilitate focused examinations and reporting.
Even if MRI would be the method of choice, in urgent cases CT may be preferred.
One should always follow the “as low as reasonably achievable” principle with studies that use ionizing radiation.
Providing MRI safety information for patients with implants improves safety.
Contrast agents do not automatically make a scan more informative, and clinical gain versus safety risks should always be considered.
Disease-specific imaging protocols are mostly born out of necessity and refer to a distinct way of manipulating conventional image acquisition or reconstruction in order to produce specific views that highlight pathologic features of the disease. Real disease-specific imaging operates with biomarkers.
Imaging technologies advance, causing clinical protocols to change. A powerful future technology could rewrite prevailing practices regarding what is considered “right” imaging, or even eliminate the question entirely. This will depend on many factors, an important one being the inertia of the medical industry and practices.
MRI protocol optimization is the process of creating a disease-specific protocol via iterative customization of imaging sequences. It can provide significant added value, but the process can be lengthy and resource-intensive. The optimization must be driven by clinical outcome and achieved through a systematic approach.
Source:
Continuum 2023
------ CerebrovascularDisease_DIAGNOSIS_AND_MANAGEMENT_OF_LARGE_ARTERY_ATHEROSCLEROSIS.txt ------
ABSTRACT
OBJECTIVE
Ischemic stroke due to large vessel atherosclerosis is a significant cause of stroke globally. With the aging population, the number of people with atherosclerotic stroke will increase in the coming decades. This article reviews the recent developments in the assessment and treatment of extracranial and intracranial atherosclerotic disease.
LATEST DEVELOPMENTS
More intensive dual antiplatelet therapy can now be recommended for patients with transient ischemic attack or stroke. More stringent blood pressure and lipid control is also advised. The need for carotid revascularization will likely decrease in the coming decades because of advances in multimodal medical therapy; in particular, the role of revascularization for treating asymptomatic carotid stenosis is controversial. Patients with symptomatic intracranial stenosis should receive intensive medical therapy. Interest in high-resolution carotid plaque imaging is growing.
ESSENTIAL POINTS
The prevention of stroke due to large vessel atherosclerosis has improved owing to advances in medical therapies. The role of carotid revascularization is unclear for many patient subgroups.
KEY POINTS
Clinical trials that compared carotid endarterectomy versus medical therapy for the treatment of patients with carotid stenosis are more than 25 years old and some consider these data to be obsolete.
In previous trials, several subgroups of symptomatic patients had enhanced benefit from carotid endarterectomy.
Beyond the periprocedural period, long-term rates of stroke appear similar between patients treated with carotid endarterectomy and carotid artery stenting.
Timing of revascularization and patient age should be considered in selecting between carotid endarterectomy and carotid artery stenting.
Transcarotid artery revascularization is an emerging revascularization technique, but randomized studies are lacking.
It is unclear if carotid revascularization is useful for asymptomatic carotid stenosis.
For asymptomatic carotid stenosis, men derive greater benefit from revascularization compared with women.
Microemboli detection using transcranial Doppler can be useful for risk stratification in patients with asymptomatic carotid stenosis.
There is not an established role for proximal vertebral artery stenosis stenting.
From a global perspective, intracranial atherosclerosis is a leading cause of stroke.
Intracranial atherosclerosis needs to be distinguished from recanalized emboli and vasculopathies.
Intensive medical therapy is essential in the management of patients with intracranial atherosclerosis.
Intracranial stenosis has a high stroke recurrence rate.
Stenting is not recommended as a first-line treatment for patients with intracranial atherosclerotic disease.
Nonstenotic plaques with complex features are potentially linked with otherwise cryptogenic strokes.
Source:
Continuum April 23
------ Epilepsy_SEIZURES_AND_EPILEPSY_IN_CHILDHOOD.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article highlights basic concepts of seizures and epilepsy in pediatric patients, as well as basic treatment principles for this age group.
RECENT FINDINGS
Epilepsy is the most common neurologic disorder in childhood. Accurate diagnosis is key; in older children, epileptic seizures need to be differentiated from various paroxysmal nonepileptic events, whereas in neonates, the majority of seizures are subclinical (electroencephalographic). Antiseizure medications remain the first-line treatment, but ketogenic diet and epilepsy surgery have also shown positive outcomes and can decrease drug burden. Genetic causes account for approximately 30% of cases, and the recognition of electroclinical syndromes is being replaced by the concept of genetic spectrums. Precision medicine therapies are promising, but wide application in daily practice still has a long way to go. Early access to specialist centers and optimal treatments positively affects prognosis and future neurodevelopment.
SUMMARY
Although novel findings from all fields of research are being incorporated into everyday clinical practice, a better quality of life for children with seizures and epilepsy and their families is the ultimate priority.
KEY POINTS
Epilepsy affects 0.5% to 1% of children, and its prevalence is highest during infancy.
Seizures need to be differentiated from several paroxysmal nonepileptic events (eg, seizure mimics in infancy, paroxysmal nonepileptic seizures in older children). Parental mobile videos and video-EEG records are useful screening tools.
Seizures can be classified according to their onset or their ictal symptomatology.
Etiology has been included as an essential part of the operational definition of epilepsy. An underlying cause can be identified in two-thirds of children with epilepsy (genetic in one-third, structural in one-third).
Neonatal seizures affect 2 to 3 per 1000 births, and they are mainly subclinical (electroencephalographic-only); hypoxic-ischemic encephalopathy is the most frequent cause.
A diagnosis of epilepsy is clinical with a medical history and description of the event being the principal diagnostic tools.
Although several well-known epilepsy syndromes have been associated with seizures in the setting of fever, the majority of febrile seizures (simple or complex) have a favorable and self-limiting course, but recurrences are frequent. The total risk of epilepsy after a previous simple febrile seizure is 2%.
Although well-described electroclinical syndromes with age-related expression are known, they still represent parts of different spectrums and can also share underlying genetic mechanisms.
The term developmental and epileptic encephalopathy was first introduced in 2017 and highlights the fact that the epileptic activity contributes to the neurodevelopmental compromise beyond what might be expected from the underlying pathology alone but also that the underlying cause independently impacts neurodevelopment beyond what might be expected from the epilepsy.
Children with epilepsy (even those with self-limited types) exhibit a wide range of comorbidities, which are often more deleterious than seizures themselves.
Several epilepsy syndromes with childhood onset have a very good prognosis, but early-life onset epilepsies usually have poor outcomes.
Sudden unexpected death in epilepsy (SUDEP) is a significant cause of death in pediatric epilepsy; incidence is similar in children and adults.
Treatment with antiseizure medications leads to seizure freedom in almost two-thirds of cases, and ketogenic diet and epilepsy surgery represent valid therapeutic options for children with drug-resistant epilepsy. Precision medicine treatments are also available for patients with specific genetic epilepsies.
Beyond seizure control, clinicians need to consider the full spectrum of needs of children with epilepsy. Early referral for optimal therapeutic choices in appropriate centers is justified to enable appropriate management and optimize the natural course of the disease.
Source:
Continuum Epilepsy 2022
------ CerebrovascularDisease_DIAGNOSIS_AND_MANAGEMENT_OF_CARDIOEMBOLIC_STROKE.txt ------
ABSTRACT
OBJECTIVE
Cardioembolic stroke accounts for nearly 30% of ischemic strokes. Prompt diagnosis of the underlying mechanism may improve secondary prevention strategies. This article reviews recent randomized trials, observational studies, case reports, and guidelines on the diagnosis and treatment of cardioembolic stroke.
LATEST DEVELOPMENTS
Several pathologies can lead to cardioembolic stroke, including atrial fibrillation, aortic arch atheroma, patent foramen ovale, left ventricular dysfunction, and many others. Secondary stroke prevention strategies differ across these heterogeneous mechanisms. In addition to medical treatment advances such as the use of direct oral anticoagulants in patients with atrial fibrillation, surgical treatments such as closure of patent foramen ovale have been shown to reduce the risk of recurrent stroke in select patients. Furthermore, left atrial appendage occlusion is a promising strategy for patients with atrial fibrillation who are candidates for short-term oral anticoagulation therapy but not long-term oral anticoagulation therapy.
ESSENTIAL POINTS
A thorough diagnostic evaluation is essential to determine cardioembolic causes of stroke. In addition to risk factor management and lifestyle modifications, identification and targeting of the underlying cardioembolic stroke mechanisms will lead to improved stroke prevention strategies in patients with cardioembolic stroke.
KEY POINTS
Direct oral anticoagulants are at least as effective as warfarin in stroke prevention in atrial fibrillation and have lower risk of intracranial hemorrhage.
There is growing evidence to support left atrial appendage occlusion as an alternative to oral anticoagulation in patients with atrial fibrillation.
In patients with acute cardioembolic stroke treated with oral anticoagulants, treatment is generally started without bridging with heparin or low-molecular-weight heparin.
In patients with atrial fibrillation and ischemic stroke despite anticoagulation a full diagnostic evaluation is important to rule out alternative mechanisms such as small vessel disease or large artery atherosclerosis that are not necessarily related to the atrial fibrillation and thus do not signify anticoagulation failure.
In addition to atrial biomarkers, certain left atrial appendage biomarkers may indicate an increased risk of atrial thromboembolism.
Patent foramen ovale (PFO) is a congenital septal defect that is present in nearly 25% of the population and is associated with a right-to-left shunt, which is more prominent during Valsalva maneuvers.
Evidence suggests that transcranial doppler is superior to transthoracic echocardiography in diagnosing a right-to-left cardiac shunt.
Transesophageal echocardiography provides the best views of the septum and thus is best at visualizing the PFO and associated abnormalities such as atrial septal aneurysm.
In patients with cryptogenic stroke in the setting of a PFO, medical and in certain cases surgical management are recommended for secondary stroke prevention.
In the absence of another indication for anticoagulation, antiplatelet therapy may be reasonable for secondary stroke prevention in patients with ischemic stroke in the setting of a PFO.
Atheromas of the aortic arch, particularly when large or mobile, have been suggested to cause ischemic stroke by artery-to-artery embolism.
The secondary prevention of ischemic stroke in the setting of aortic arch atherosclerosis consists of risk factor modification, high-intensity statin therapy, and antiplatelet therapy.
Spontaneous aortic dissections can be seen in patients with Marfan syndrome, familial thoracic aortic aneurysm or dissection, bicuspid aortic valve, Loeys-Dietz aneurysm syndrome, and vascular Ehlers-Danlos syndrome (Ehlers-Danlos syndrome type IV).
In patients with systolic heart failure, studies have shown an increased ischemic stroke risk with low left ventricular ejection fraction.
In patients with ischemic stroke and low ejection fraction, prolonged cardiac rhythm monitoring is important to look for atrial fibrillation which would lead to anticoagulation therapy.
In the setting of a low ejection fraction and evidence of a left ventricular thrombus with or without ischemic stroke, patients should receive at least 3 months of anticoagulation with warfarin and until repeat cardiac imaging shows resolution of the thrombus.
Clinical trials are needed to test the safety and efficacy of direct oral anticoagulants when compared to aspirin in patients with left ventricular dysfunction, particularly those with low ejection fraction and with an ischemic stroke.
There is an increased ischemic stroke risk in patients with an acute myocardial infarction, and this risk is particularly high in the first 12 weeks after myocardial infarction.
In patients with myocardial infarction and left ventricular thrombus with or without ischemic stroke, anticoagulation treatment should be initiated for at least 3 months pending resolution of the thrombus on follow-up cardiac imaging.
Valvular pathologies that are associated with increased stroke risk are prosthetic heart valves, rheumatic heart disease, and both infective and noninfective endocarditis.
In patients with an ischemic stroke in the setting of a bioprosthetic valve, a diagnostic evaluation is needed to exclude valve failure, thrombosis, or infection as an etiology.
Direct oral anticoagulants are not recommended in patients with mechanical heart valves.
Ischemic stroke risk in patients with rheumatic mitral disease has been suggested to be linked to atrial fibrillation, particularly since studies demonstrating such associations did not involve cardiac monitoring.
In patients with marantic endocarditis in the setting of cancer, treatment entails management of the underlying malignancy as well as antithrombotic therapy.
In patients with ischemic stroke in the setting of Libman-Sacks endocarditis, guidelines suggest anticoagulation with heparin or low-molecular-weight heparin instead of oral anticoagulation if deemed safe, but these suggestions lack high-level supporting evidence.
Left-sided cardiac tumors such as atrial myxomas and fibroelastomas are very rare causes of ischemic stroke.
While the optimal stroke prevention strategy for patients with ischemic stroke and left sided cardiac tumors is unknown, in addition to antithrombotic treatment, surgical tumor resection is a reasonable approach.
Source:
Continuum April 23
------ MuscleNeuromuscularJunction_DIAGNOSIS_AND_MANAGEMENT_OF_MYASTHENIA_GRAVIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews updated diagnostic procedures and currently available treatment modalities for myasthenia gravis (MG).
RECENT FINDINGS
Patients with MG can be classified based on antibody status and their clinical presentation; treatment responses may differ based on disease subtypes. Improved diagnostic methods and recognition of new antigenic targets such as lipoprotein-related protein 4 have led to improved diagnostic efficiencies. Corticosteroids remain the first-line immunotherapy, but there is a trend toward minimizing their use at high doses and for long durations. Oral immunosuppressants such as mycophenolate mofetil, azathioprine, and tacrolimus remain useful. An international, multicenter randomized trial comparing thymectomy plus prednisone with prednisone alone demonstrated that thymectomy improves clinical outcomes in selected patients with nonthymomatous MG. Eculizumab, efgartigimod, and ravulizumab have recently been approved by the US Food and Drug Administration (FDA) for adult patients with generalized MG who are acetylcholine receptor–antibody positive. These drugs take advantage of novel mechanisms of action and expand treatment options for patients with MG. Data on rituximab suggest that it can be a good option, especially for patients with MG who are positive for antibodies against muscle-specific tyrosine kinase (MuSK). The number of clinical trials and drugs in development for MG is steadily increasing.
SUMMARY
The diagnosis of MG can generally be made from the patient’s history, a neurologic examination, and laboratory and electrodiagnostic testing. Carefully selected treatment improves outcomes in MG. Additional treatment options for MG will likely be available in the near future.
KEY POINTS
Patients with myasthenia gravis (MG) develop characteristic muscle weakness that worsens with activity and fatigue. MG has a predilection to affect ocular, bulbar, neck, respiratory, and proximal limb muscles more than others.
Two-thirds of patients with MG develop a combination of diplopia and eyelid ptosis. Up to 75% of these patients will progress to generalized MG within the first 2 to 3 years of developing symptoms.
Classification of patients based on age, autoantibody status, and ocular versus generalized MG is essential to guide the diagnostic workup and treatment decisions.
Evaluation of patients with suspected generalized MG relies on a combination of clinical history, clinical examination, bedside maneuvers, serum autoantibody testing, and electrodiagnostic testing.
The MG Core Exam can be used to evaluate and follow patients in the clinic and through video telemedicine.
In patients with ptosis, the ice pack test carries a sensitivity of 80% to 95% and a specificity of 79% to 97%.
Anti-acetylcholine receptor–binding antibody can be elevated in about 75% to 90% of patients with generalized MG. At low titers, false positives can be observed in patients with other autoimmune disorders.
Antibodies against muscle-specific tyrosine kinase, lipoprotein-related protein 4, and clustered acetylcholine receptors can be detected in a large portion of patients with generalized MG without anti-acetylcholine receptor–binding antibodies.
Slow-rate repetitive nerve stimulation and single-fiber EMG can be used to confirm a diagnosis of MG in those who do not have measurable autoantibodies.
Confirming the diagnosis of ocular MG relies on bedside testing and electrodiagnostics in many patients because of the low sensitivity of antibody testing when symptoms are restricted to ocular muscles.
Slow-rate repetitive nerve stimulation has high specificity but low sensitivity in ocular MG.
Single-fiber EMG has a high sensitivity in ocular MG. However, single-fiber EMG has the possibility of false-positive testing in ocular MG due to lower specificity (75% to 90%).
The specificity of single-fiber EMG can be improved by combining it with an ice pack test for patients with ocular symptoms.
Treatment of MG varies according to many patient characteristics and practical considerations and should be individualized.
Patient education on typical MG symptoms, course, prognosis, and treatment is important for treatment success.
Physical exercise is beneficial to patients with MG and can be modified based on tolerability.
Fatigue in MG is multifactorial, and isolated perception of fatigue may not require medication escalation.
Isolated perception of dyspnea at rest or with exertion does not indicate myasthenic crisis and rarely needs treatment escalation.
Medications listed as “use with caution” in MG can be tolerated by patients with mild disease and may be given to patients with significant weakness under careful monitoring if no alternatives exist.
Immune checkpoint inhibitors may cause a combination of MG, myositis, and myocarditis, and an aggressive treatment strategy for these complications is needed.
Pyridostigmine is used alone in ocular and mild MG or in combination with immunosuppressants in severe cases and can be minimized or stopped after patients improve on immunotherapy.
Prednisone remains the first-line immunotherapy for MG, and the starting dosage may vary depending on disease severity. A higher dosage may not be necessary for mild disease.
Prednisone tapering should be slow, with a target goal of 5.0 to 7.5 mg/d at approximately 1 year.
Selection of corticosteroid-sparing agents depends on many factors, including patient preference and providers’ familiarity.
The tapering of corticosteroid-sparing agents in MG should be slow to avoid a relapse.
For maintenance therapy of MG, patients can be kept on a stable low-dose corticosteroid, a low-dose corticosteroid-sparing agent, or a combination of both.
Rituximab can be an option for refractory and new-onset MG, and the incidence of progressive multifocal leukoencephalopathy appears rare.
Eculizumab and ravulizumab have a quick onset of action, and their efficacy is long lasting, but cost is a limiting factor.
Efgartigimod has a quick onset of action and is well tolerated, but data on optimal long-term treatment are lacking.
Plasma exchange and IV immunoglobulin can be used for acute exacerbation or as a maintenance therapy. Subcutaneous immunoglobulin has potential as maintenance immunotherapy in MG.
Patients with impending myasthenic crisis should be monitored closely. The decision on extubation of intubated patients with MG should be made conservatively.
Thymectomy should be considered for early-onset acetylcholine receptor antibody–positive MG, and endoscopic approaches can be used for most patients with MG.
If ptosis or extraocular dysmotility in MG does not reverse with maximal treatment after 2 years, surgical options could be considered in selected cases.
Fast-acting treatment of MG symptoms using plasma exchange or IV immunoglobulin may spare the use of high-dose corticosteroid therapy.
Rituximab is particularly effective for anti–muscle-specific tyrosine kinase MG.
Newer agents to treat MG are being developed and investigated at a rapid pace.
Source:
Continuum 2022
------ Neuro_erefat.txt ------
test124
Source:
erefat
------ CerebrovascularDisease_MANAGEMENT_OF_UNRUPTURED_INTRACRANIAL_ANEURYSMS_AND_BRAIN_ARTERIOVENOUS_MALFORMATIONS.txt ------
ABSTRACT
OBJECTIVE
Managing a patient with an unruptured brain aneurysm or brain arteriovenous malformation (AVM) can lead to uncertainty about preventive treatment. While the bleeding risks are low, the morbidity or mortality associated with a hemorrhagic event is not insignificant. The objective of this article is to review the natural history of these vascular entities, the risk factors for hemorrhage, preventive treatment options, and the risks of treatment.
LATEST DEVELOPMENTS
Randomized trials to inform preventive treatment strategies for unruptured intracranial aneurysms and brain AVMs are ongoing. Higher angiographic obliteration rates of unruptured intracranial aneurysms have been reported with the flow-diversion technique compared with alternative standard techniques. One randomized trial for unruptured brain AVMs showed a higher rate of morbidity and mortality in patients who underwent interventional treatment compared with observation.
ESSENTIAL POINTS
The decision to treat a patient with a brain aneurysm should consider patient factors, the patient’s life expectancy, aneurysm anatomical factors, and treatment risks. Patients with unruptured brain AVMs should be observed in light of recent clinical trial data or enrolled in an ongoing clinical trial.
KEY POINTS
An estimated 3% of the population has an unruptured intracranial aneurysm.
The risk of rupture for an asymptomatic unruptured intracranial aneurysm is estimated at 0.3% to 1% per year.
The risk of aneurysm rupture increases with aneurysm size, a family history of aneurysm, and prior subarachnoid hemorrhage from another aneurysm.
An aneurysm that is documented to have growth on serial imaging carries a higher risk of rupture than an aneurysm that has not been documented to grow.
ISAT (International Subarachnoid Aneurysm Trial) demonstrated better outcomes among patients with ruptured aneurysms who underwent coiling compared to those who underwent surgical clipping.
Endovascular techniques that are commonly used in the treatment of brain aneurysms include coiling, balloon remodeling, stent-assisted coiling, intrasaccular flow disruption, and flow diversion.
Higher angiographic obliteration rates of unruptured intracranial aneurysms have been reported with flow diversion compared to alternative standard techniques.
Ischemic complications related to flow diversion are estimated to occur in up to 9.8% of cases.
There are no completed randomized trials to inform treatment of unruptured aneurysms, but several are ongoing.
The decision to treat an intracranial aneurysm is based on the natural history of risk of rupture, patient and aneurysmal anatomical factors, and the risk of repair.
The risk of an asymptomatic, unruptured brain arteriovenous malformation (AVM) rupture is estimated at 1.3% per year.
Age and prior AVM hemorrhage are risk factors for future AVM hemorrhage.
Conservative management, endovascular embolization, radiation, and operative resection are four modalities that can be considered in the treatment of a patient with brain AVM with a multidisciplinary team; the modalities can be performed either in isolation or in combination.
A randomized trial demonstrated that, overall, patients with unruptured AVMs who were conservatively managed had better outcomes than patients who underwent intervention mostly with endovascular embolization.
Source:
Continuum April 23
------ DementiaNeurodegenerativeProcesses_GENETICS_OF_ALZHEIMER_DISEASE.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses the spectrum of genetic risk in familial and sporadic forms of early- and late-onset Alzheimer disease (AD). Recent work illuminating the complex genetic architecture of AD is discussed in the context of high and low risk and what is known in different populations.
RECENT FINDINGS
A small proportion of AD is autosomal dominant familial AD caused by variants in PSEN1, PSEN2, or APP, although more recently described rare genetic changes can also increase risk substantially over the general population, with odds ratios estimated at 2 to 4. APOE remains the strongest genetic risk factor for late-onset AD, and understanding the biology of APOE has yielded mechanistic insights and leads for therapeutic interventions. Genome-wide studies enabled by rapidly developing technologic advances in sequencing have identified numerous risk factors that have a low impact on risk but are widely shared throughout the population and involve a repertoire of cell pathways, again shining light on potential paths to intervention. Population studies aimed at defining and stratifying genetic AD risk have been informative, although they are not yet widely applicable clinically because the studies were not performed in people with diverse ancestry and ethnicity and thus population-wide data are lacking.
SUMMARY
The value of genetic information to practitioners in the clinic is distinct from information sought by researchers looking to identify novel therapeutic targets. It is possible to envision a future in which genetic stratification joins other biomarkers to facilitate therapeutic choices and inform prognosis. Genetics already has transformed our understanding of AD pathogenesis and will, no doubt, continue to reveal the complexity of brain biology in health and disease.
KEY POINTS
Rare single-gene causes of Alzheimer disease (AD) exist, although even sporadic AD likely has important genetic contributions.
Early-onset autosomal dominant familial AD can be caused by variants in the PSEN1, PSEN2, and APP genes.
PSEN1 variants are the most common autosomal dominant form of AD.
Individuals with Down syndrome have three copies of the APP gene and can also present with AD-type dementia and neuropathology.
Significant clinical overlap exists between PSEN-related AD and sporadic AD, although patients with PSEN-related AD may develop spasticity, movement disorders, and cerebellar signs.
APOE is the strongest known genetic risk factor for typical late-onset AD.
APOE has three isoforms, APOE ε2, APOE ε3, and APOE ε4, and APOE ε3 is the most common allele.
APOE ε4 confers the highest risk for AD.
APOE ε4 associated risk varies between populations of different ancestries.
Genome-wide association studies identify associations between a disease trait and a common genetic variant.
Polygenic risk scores are generated based on aggregated risk as estimated through studies such as genome-wide association studies. However, since most genome-wide association studies have been conducted in the non-Hispanic White populations, polygenic risk scores are not appropriate for use in the clinic.
Common variants identified by genome-wide association studies each confer low risk.
Rare variants confer risk in a range between common variants and autosomal dominant AD.
Variants in the TREM2 gene are a risk factor for AD.
Variants in SORL1 are found in sporadic and familial AD.
Some gene variants may be protective against AD.
Genetic testing should start with a dementia panel, although beyond a panel, yield is very low.
Genetic counseling is strongly recommended for genetic testing, particularly in the at-risk asymptomatic individual.
Genetic counselors are clinicians trained in molecular and clinical genetics. They provide education to patients deciding whether to pursue genetic testing in precounseling visits and counseling when disclosing results.
Individuals who do not want to undergo genetic testing immediately but want to have that option available to family members after their death may consider DNA banking for future testing.
APOE genotyping is useful in clinical trials and research, although it has limited utility in the clinic.
Our understanding of AD will be massively strengthened as the cohorts being studied are broadened, moving us closer to tailored AD therapies.
Source:
Continuum 2022
------ Epilepsy_GENETIC_EPILEPSY_SYNDROMES.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews the clinical features, typical EEG findings, treatment, prognosis, and underlying molecular etiologies of the more common genetic epilepsy syndromes. Genetic generalized epilepsy, self-limited focal epilepsy of childhood, self-limited neonatal and infantile epilepsy, select developmental and epileptic encephalopathies, progressive myoclonus epilepsies, sleep-related hypermotor epilepsy, photosensitive occipital lobe epilepsy, and focal epilepsy with auditory features are discussed. Also reviewed are two familial epilepsy syndromes: genetic epilepsy with febrile seizures plus and familial focal epilepsy with variable foci.
RECENT FINDINGS
Recent years have seen considerable advances in our understanding of the genetic factors underlying genetic epilepsy syndromes. New therapies are emerging for some of these conditions; in some cases, these precision medicine approaches may dramatically improve the prognosis.
SUMMARY
Many recognizable genetic epilepsy syndromes exist, the identification of which is a crucial skill for neurologists, particularly those who work with children. Proper diagnosis of the electroclinical syndrome allows for appropriate treatment choices and counseling regarding prognosis and possible comorbidities.
KEY POINTS
Genetic epilepsy syndromes may follow Mendelian patterns or may exhibit complex inheritance, likely related to both polygenic and epigenetic factors.
Overall, the genetic generalized epilepsy syndromes are characterized by normal background activity and interictal generalized epileptiform discharges on EEG; brain imaging is also almost always normal. Genetic testing is usually negative, as the vast majority of cases are thought to occur through complex inheritance.
In childhood absence epilepsy, the defining seizure type is a typical absence seizure, involving a sudden, brief loss of awareness (usually 4 to 30 seconds) followed by an almost immediate return to baseline (ie, no significant postictal state). Patients typically stare blankly and may have subtle automatisms, most commonly oral.
Typical absence seizures can often be provoked by hyperventilation; asking the patient to hyperventilate for at least 3 minutes provides a useful method to evaluate seizure control in the clinic. During seizures, EEG shows an abrupt onset of generalized rhythmic spike-wave discharges at approximately 3 Hz.
Children with absence seizures starting before the age of 4 years are considered to have early-onset absence epilepsy; 10% of these patients have glucose transporter type 1 (GLUT1) deficiency due to pathogenic SLC2A1 variants.
Age of onset of juvenile myoclonic epilepsy is typically between 12 and 18 years. The prototypic seizure type is myoclonic jerks that are most prominent in the mornings, although patients may also experience generalized tonic-clonic or absence seizures. Seizures are often provoked by sleep deprivation, flashing lights, or alcohol intake.
Interictal EEG of JME typically shows normal background activity with generalized 4- to 6-Hz spike-wave and polyspike-wave fragments.
Although the majority of patients with JME have seizures controlled with medication, the rate of long-term epilepsy remission is very low.
Sodium channel inhibitors should be avoided in patients with juvenile myoclonic epilepsy, if possible, as there is the potential to exacerbate myoclonic seizures.
Juvenile absence epilepsy bears many similarities to JME, with one of the main differentiating factors being the lack of myoclonic seizures.
The ictal EEG of juvenile absence epilepsy during absences shows a faster rhythmic spike-wave signature of 4 to 5 Hz.
Roughly 50% to 80% of patients with juvenile absence epilepsy will also experience generalized tonic-clonic seizures.
The seizure control prognosis is poor in juvenile absence epilepsy, with less than half of patients seizure free on medications after 2 years and nearly all having seizure recurrence if medication weaning is attempted.
Epilepsy with generalized tonic-clonic seizures alone is a genetic generalized epilepsy in which generalized tonic-clonic seizures are the only seizure type.
Epilepsy with eyelid myoclonias is a childhood-onset genetic generalized epilepsy classically involving a triad of (1) characteristic brief eye-fluttering seizures (eyelid myoclonia), (2) eye closure–induced seizures/epileptiform abnormalities on EEG, and (3) photosensitivity.
Children with childhood epilepsy with centrotemporal spikes first present with seizures typically between 7 and 10 years of age (range, 1 to 14 years), often from sleep. The seizure symptomatology is focal aware or focal impaired awareness, involving prominent hemifacial jerking or dystonia, facial paresthesia, drooling, and mumbling, and occasionally progressing to bilateral tonic-clonic convulsions. EEG shows focal monomorphic medium-high amplitude spikes and spike-wave discharges over one or both centrotemporal regions, having a characteristic morphology and horizontal dipole.
Decisions on whether to initiate antiseizure medication in childhood epilepsy with centrotemporal spikes should be made on a child-by-child basis, taking into consideration frequency and duration of seizures, if seizures have progressed to bilateral tonic-clonic, as well as parent/caregiver concerns.
In Panayiotopoulos syndrome, seizure onset is usually between 3 and 6 years of age (range, 1 to 14 years). Seizures may be focal aware or focal impaired awareness, usually occurring from sleep, with the most notable feature being prominent autonomic symptoms. Vomiting, pallor, flushing, mydriasis/miosis, and temperature changes are among the autonomic signs that may be seen. Lateral head and eye deviation may occur late in seizures, and progression to bilateral tonic-clonic seizures is possible.
Status epilepticus is common in Panayiotopoulos syndrome, with nearly half of patients having seizures lasting longer than 30 minutes.
Interictal EEG in patients with Panayiotopoulos syndrome shows focal spikes and spike-wave discharges, which are often abundant, over one or both occipital regions.
Patients with Gastaut syndrome have focal aware seizures, although awareness may become impaired late in events. The symptomatology mostly involves visual hallucinations usually lasting 1 to 3 minutes. These are most typically elementary visual phenomena such as multicolored circles, but about 10% of patients can have complex hallucinations, such as faces or figures. Ictal blindness lasting several minutes is also commonly reported.
EEG in patients with Gastaut syndrome shows focal occipital spikes and spike-wave discharges as in Panayiotopoulos syndrome, and fixation-off sensitivity (the appearance of epileptiform abnormalities with removal of visual fixation, often by eye closure) often occurs.
Children with Gastaut syndrome may be misdiagnosed with migraines or psychiatric disorders as they present with visual hallucinations, sometimes with associated headache.
In self-limited familial neonatal epilepsy, seizures begin in the neonatal period, usually on the second or third day of life. Seizures may involve any or all of tonic posturing, apnea, vocalization, eye deviation, change in skin color, and unilateral or bilateral clonic movements. Duration is typically brief, usually less than 30 seconds.
Affected children with self-limited neonatal epilepsy have spontaneous resolution of seizures, occurring by 6 weeks in two-thirds of cases and by 6 months in 94% of cases.
Self-limited infantile epilepsy is usually defined as seizures occurring in otherwise healthy and typically developing children, usually between the ages of 3 and 20 months.
Patients with self-limited infantile epilepsy have focal impaired awareness seizure, often with hemiclonic movements, head and eye deviation, or facial/limb automatisms. Seizures usually occur in clusters of up to 8 to 10 per day over 1 to 3 days.
Dravet syndrome first presents around 6 months of age, usually with febrile seizures that are often hemiclonic and prolonged. Patients subsequently develop afebrile seizure types that most commonly include any or all of generalized tonic-clonic, focal impaired awareness, atypical absences, and myoclonic seizures.
Early mortality risk is high in Dravet syndrome, with death most commonly occurring due to sudden unexpected death in epilepsy (SUDEP), drowning, or massive cerebral edema following prolonged seizures.
Myoclonic-atonic epilepsy is considered a developmental and epileptic encephalopathy, although the developmental course can be quite variable.
Epilepsy of infancy with migrating focal seizures has a very characteristic seizure symptomatology involving focal seizures with interhemispheric migration that can be diagnosed either by clinical observation or EEG or both.
The progressive myoclonus epilepsies are a clinically and genetically heterogeneous group of disorders that share the common features of myoclonic seizures and progressive neurologic decline. Age of onset is typically in childhood or adolescence, and patients may have additional seizure types including focal, atypical absence, atonic, and generalized tonic-clonic.
Sleep-related hypermotor epilepsy is a form of focal epilepsy involving seizures that usually occur exclusively from sleep. Seizures usually arise from the frontal lobe; however, extrafrontal onset with spread to the frontal regions can produce the same phenotype.
The seizure symptomatology in sleep-related hypermotor epilepsy typically involves hypermotor behaviors such as violent thrashing and writhing, often with vocalization and emotional facial expression.
In photosensitive occipital lobe epilepsy, the classic seizure symptomatology is of a colorful visual aura that may evolve into lateral head and eye version; the patient may maintain awareness throughout.
Epilepsy with auditory features is an epilepsy syndrome characterized by focal aware seizures localized to the lateral temporal region. Patients experience seizures involving simple or complex auditory hallucinations, and 86% of patients have focal-to-bilateral tonic-clonic seizures.
Genetic epilepsy with febrile seizures plus is a familial syndrome in which members of the same family have different phenotypes, the most common being febrile seizures and febrile seizures plus (febrile seizures outside the usual age range or bilateral tonic-clonic seizures occurring with and without fever).
Source:
Continuum Epilepsy 2022
------ DementiaNeurodegenerativeProcesses_THE_VALUE_OF_NEUROIMAGING_IN_DEMENTIA_DIAGNOSIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses neuroimaging in dementia diagnosis, with a focus on new applications of MRI and positron emission tomography (PET).
RECENT FINDINGS
Although the historical use of MRI in dementia diagnosis has been supportive to exclude structural etiologies, recent innovations allow for quantification of atrophy patterns that improve sensitivity for supporting the diagnosis of dementia causes. Neuronuclear approaches allow for localization of specific amyloid and tau neuropathology on PET and are available for clinical use, in addition to dopamine transporter scans in dementia with Lewy bodies and metabolic studies with fludeoxyglucose PET (FDG-PET).
SUMMARY
Using computerized software programs for MRI analysis and cross-sectional and longitudinal evaluations of hippocampal, ventricular, and lobar volumes improves sensitivity in support of the diagnosis of Alzheimer disease and frontotemporal dementia. MRI protocol requirements for such quantification are three-dimensional T1-weighted volumetric imaging protocols, which may need to be specifically requested. Fluid-attenuated inversion recovery (FLAIR) and 3.0T susceptibility-weighted imaging (SWI) sequences are useful for the detection of white matter hyperintensities as well as microhemorrhages in vascular dementia and cerebral amyloid angiopathy. PET studies for amyloid and/or tau pathology can add additional specificity to the diagnosis but currently remain largely inaccessible outside of research settings because of prohibitive cost constraints in most of the world. Dopamine transporter PET scans can help identify Lewy body dementia and are thus of potential clinical value.
KEY POINTS
Brain MRI is the first-line neuroimaging as recommended by the American Academy of Neurology, National Institute on Aging, and American College of Radiology imaging guidelines for dementia, although CT is also recommended as an alternative.
The minimum elements of a dedicated dementia MRI protocol should include a high-resolution T1-weighted imaging sequence to allow for quantitative analysis of specific brain atrophy patterns.
For volumetric acquisitions, the three-dimensional T1-weighted scan is used; this scan has different designations but is most commonly called either a magnetization prepared rapid gradient echo (MPRAGE) sequence or a spoiled gradient recalled acquisition (SPGR) sequence, depending on manufacturer.
If specific conditions for use of MRI in patients with medical devices are documented by the device manufacturer, the conditions can be evaluated on mrisafety.com.
When evaluating brain MRIs from a neuroradiologic perspective, is it important to consider whether the dementia under evaluation is chronically progressive or rapidly progressive.
Brain atrophy related to neurodegenerative dementing diseases is progressive in nature and worsens over time.
A decline in regional brain volume even within a statistically normal comparative range can be compatible with progressive brain atrophy in the setting of neurodegenerative disease.
The relatively recent amyloid, tau, neurodegeneration (A/T/N) framework for AD research may offer some insights into the diagnostic imaging evaluation of dementia.
The amyloid, tau, neurodegeneration (A/T/N) framework is being examined in research settings, but in clinical practice, physicians caring for patients with dementia are most likely to monitor the N (neurodegeneration) component using brain MRI and/or fludeoxyglucose positron emission tomography (FDG-PET).
The current US Food and Drug Administration–cleared amyloid positron emission tomography tracers are florbetapir, florbetaben, and flutemetamol.
Although visual analysis is the current standard in amyloid positron emission tomography image interpretation, standardized uptake value ratios with a reference region such as the cerebellum can generate high diagnostic accuracy.
The distribution of FDG-PET changes can suggest other neurodegenerative conditions, especially when postprocessed with z score maps.
As the imaging abnormalities seen on FDG-PET can substantially overlap across different types of neurodegeneration, the use of more specific amyloid and tau biomarker studies will remain important to utilize as clinical practice evolves.
Much interest exists in the development of fluid and, in particular, plasma biomarkers for the detection of AD, which have been shown to predict brain amyloidosis on PET.
The role of chronic hypertensive vascular disease as an etiologic factor for cognitive decline is best evaluated on fluid-attenuated inversion recovery images.
The distribution of white matter hyperintensities in the setting of chronic small vessel ischemic changes is typically in periventricular or subcortical regions or in the deep white matter, and the location of these lesions in older people supports the underlying small vessel ischemic etiology and can independently predict brain atrophy.
In cerebral amyloid angiopathy, cerebral microhemorrhages relate to amyloid-β deposition and insoluble amyloid fibrils within the walls of leptomeningeal and cortical arterioles.
Brain MRI is essential for the recently approved anti-amyloid therapy with aducanumab to monitor for the complications of amyloid related imaging abnormalities with hemorrhage and superficial siderosis (ARIA-H) or with vasogenic edema with or without sulcal effusion (ARIA-E).
On imaging, a biomarker suggestive of dementia with Lewy bodies is ioflupane I 123, which labels the dopamine transporter in the nigrostriatal dopaminergic pathway on PET or single-photo emission computed tomography (SPECT).
The callosal angle is drawn at the posterior commissure; it is typically abnormal in the setting of normal pressure hydrocephalus when it is between 50 and 80 degrees and typically normal when it is between 100 and 120 degrees.
Source:
Continuum 2022
------ MultipleSclerosisDemyelinating_MYELIN_OLIGODENDROCYTE_GLYCOPROTEIN_ASSOCIATED_DISORDERS.txt ------
ABSTRACT
PURPOSE OF REVIEW
Anti–myelin oligodendrocyte glycoprotein (MOG) autoantibodies have become a recognized cause of a pathophysiologically distinct group of central nervous system (CNS) autoimmune diseases. MOG-associated disorders can easily be confused with other CNS diseases such as multiple sclerosis or neuromyelitis optica, but they have a distinct clinical phenotype and prognosis.
RECENT FINDINGS
Most patients with MOG-associated disorders exhibit optic neuritis, myelitis, or acute disseminated encephalomyelitis (ADEM) alone, sequentially, or in combination; the disease may be either monophasic or relapsing. Recent case reports have continued to expand the clinical spectrum of disease, and increasingly larger cohort studies have helped clarify its pathophysiology and natural history.
SUMMARY
Anti–MOG-associated disorders comprise a substantial subset of patients previously thought to have other seronegative CNS diseases. Accurate diagnosis is important because the relapse patterns and prognosis for MOG-associated disorders are unique. Immunotherapy appears to successfully mitigate the disease, although not all agents are equally effective. The emerging large-scale data describing the clinical spectrum and natural history of MOG-associated disorders will be foundational for future therapeutic trials.
Key Points
Myelin oligodendrocyte glycoprotein (MOG)-associated disorders represent a unique subset of central nervous system demyelinating diseases that is pathophysiologically distinct from multiple sclerosis and aquaporin-4–positive neuromyelitis optica.
The evolution of more advanced laboratory techniques was foundational to the identification of MOG-associated disorders as a distinct disease entity. Live cell–based assays are the gold standard for detecting anti-MOG autoantibodies.
MOG-associated disorders have a bimodal distribution, with children representing about one-third of cases and a second peak occurring in young/midadulthood. Males and females appear equally at risk.
MOG-associated disordersmay be monophasic or relapsing; the clinical course is not yet possible to predict at the time of the incident event.
MOG-associated disordersmay arise in a postinfectious setting, but they are not strongly associated with any single organism.
MOG-associated disorders do not overlap with multiple sclerosis or aquaporin-4–positive neuromyelitis optica. They may rarely overlap with antibody-mediated autoimmune encephalitis.
MOG-associated disorders have pathologic findings that are distinct from multiple sclerosis and aquaporin-4–positive neuromyelitis optica.
MOG autoantibody titers frequently fluctuate over time and are higher during exacerbations compared with during remission.
Patients with MOG autoantibodies and a congruent clinical phenotype should be diagnosed with MOG-associated disease, regardless of whether they also meet clinical criteria for a different neuroimmune disease. Identification of specific autoantibodies takes diagnostic precedence over clinical diagnoses of exclusion.
MOG-associated disorders occupy a broad clinical spectrum, with themost common phenotypes being optic neuritis, myelitis, and acute disseminated encephalomyelitis (ADEM).
Optic neuritis and myelitis associated withMOG-associated disorders often have unique clinical, laboratory, or radiologic features that distinguish them from other central nervous system autoimmune diseases.
MOG-associated disorders can overlap the clinical spectrum of neuromyelitis optica, but MOG autoantibodies and aquaporin-4 autoantibodies do not colocalize within an individual.
“Atypical” MOG-associated disorder presentations are still emerging, and this diagnosis should be considered when patients present with unusual central nervous system pathology.
MOG-associated disorders are rarely associated with subclinical radiologic activity, although emergence of asymptomatic MRI lesions has not been associated with future clinical relapses. Routine MRI screening of asymptomatic patients is typically unnecessary.
MOG autoantibodies should be tested in the serum. High titers are both sensitive and specific, but low titers may represent false positives. Clinical correlation is important.
MOG-associated disorders can be associated with a significant CSF lymphocytic pleocytosis in a subset of patients.
High-dose steroids, IVIg, and/or plasma exchange may be effective for treating MOG-associated disorder relapses. Thismay be followed by an oral steroid taper lasting up to 3 months because relapses often cluster temporally.
Steroid-sparing immunomodulators including azathioprine, mycophenolate mofetil, rituximab, and IVIg appear effective for treating relapsing MOG-associated disorders, but most patients continue to have some level of breakthrough disease.
Most patients withMOG-associated disorders recoverwell fromthe incident attack, but significant disability may accumulate with subsequent relapses.
MOG-associated myelitis is the clinical phenotype most strongly associated with permanent disability.
Source:
Continuum 2022
------ Neuro_Tourettes.txt ------
Pimozide and haloperidol are approved and the most effective treatments of Tourette's disorder.
Source:
RITE 2017
------ MultipleSclerosisDemyelinating_APPROACH_TO_SYMPTOM_MANAGEMENT_IN_MULTIPLE_SCLEROSIS_WITH_A_FOCUS_ON_WELLNESS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article describes an approach to symptom management in people with multiple sclerosis (MS), emphasizing healthy lifestyles and evidence-based treatments.
RECENT FINDINGS
Growing evidence supports healthy nutrition, exercise, and emotional well-being (wellness) as foundational for MS symptom management. A stepped approach starts with healthy lifestyle practices and adds nonpharmacologic, pharmacologic, and procedural-based therapies balancing levels of evidence, risks, and potential benefits. The growing availability of cannabis and widespread use of dietary supplements in self-management of MS symptoms raise both therapeutic promises and challenges.
SUMMARY
Wellness approaches for MS symptom management foster self-reliance and should be reinforced early and often. Recognition of symptom clusters and medical comorbidities helps limit polypharmacy.
Key Points
Symptomatic management supports the day-to-day experience of people living with multiple sclerosis (MS) to maximize function, independence, and quality of life over the course of this chronic disease.
Ongoing challenges inMS symptom management include the paucity of clinical trial evidence for commonly used symptomatic treatments, difficulties in comparing relative efficacies of nonpharmacologic to pharmacologic treatments, and finding time-efficient methods to monitor MS symptoms over time.
Although people with MS with greater disease duration report more symptoms, not all symptoms become more prevalent over time.
Symptomatic treatment for an individual may evolve variably and in a nonlinear fashion over time.
Of wellness topics, diet, exercise, and mood management are of special interest to people with MS.
Education and support of healthy lifestyle habits are the foundation of MS symptom management.
The approach to symptom management in this article emphasizes choosing best-evidence pharmacologic and nonpharmacologic practices to minimize systemic side effects.
A critical stepwhen evaluating a report of MS symptoms is determining if they are due to new central nervous system inflammation (termed exacerbation or relapse), are due to a general medical illness causing acute worsening of baseline MS symptoms (pseudoexacerbation), or represent expected progression of chronic symptoms.
Because urinary tract infections are common culprits for pseudoexacerbations, a urine dipstick with reflex culture is the minimum evaluation for all patients with acute or worsening MS symptoms.
Treatment of the underlying medical or psychological triggers of pseudoexacerbations may be sufficient to relieve the worsening MS symptoms without the need for additional symptomatic therapy.
When needed, symptomatic therapy for pseudoexacerbations should be prescribed for shorter periods with the expectation that the need for extra support will diminish as the underlying trigger resolves.
Augmenting the review of symptoms with targeted questions and patient-reported outcome measures is useful in screening and following invisible symptoms over time.
Awareness of symptom clusters helps identify underlying etiologies for optimalmultifactorial treatment that avoids polypharmacy.
As MS symptoms can fluctuate in severity and impact over the lifespan, the impact of aging and comorbid disease may also fluctuate in unpredictable ways. Therefore, MS symptom management treatments require periodic reevaluations for both benefits and risks.
For many patients, education regarding the origin, prevalence, and natural history of their MS symptoms is sufficient for symptom management, particularly early in the disease course or when symptoms are mild.
Commonalities across the interventional diets include increased fruits and vegetables, reduced processed foods and refined sugars, and (when included in the diet) whole grains over refined ones.
Registered dietitians are important members of the MS treatment team. Nutritional counseling is a key resource.
Growing evidence supports that exercise reduces MS fatigue, improves biometric data, and, encouragingly, may even improve cognitive performance in people with MS.
Updated exercise recommendations now include the full spectrum of MS-related disability and add more kinds of exercise and physical activity. Recommended weekly time spent exercising increased from 120 to 150 minutes.
Receiving verbal recommendations about healthy lifestyles directly fromtrusted physicians ismore effective at promoting behavioral change than receiving printed material only.
Nonpharmacologic symptomatic treatments for MS have advantages of avoiding systemic side effects that often exacerbate other MS symptoms.
Given their relatively low risks and high acceptability among people with MS, nonsystemic integrative techniques should be considered. Cost, insurance limits, availability, and frequency of visits can be barriers to their use.
When oral agents are used for MS symptom management, those with the highest evidence should be prioritized.
Based on studies in the United Kingdom, two American Academy of Neurology (AAN) systematic reviews concluded that high-quality evidence supports that cannabinoids reduce patient-reported spasticity in MS, although this effect is modest.
The greatest concern with the use of cannabinoids is cognitive impairment.
Although often listed at the end of treatment options, suggesting they are a “last resort” for MS symptom management, high-evidence and low-risk medical procedures may prove a more favorable risk-benefit evaluation as they avoid the systemic effects of oral medications.
When referring patients for onabotulinumtoxinA, it is important to clearly communicate goals of minimizing oral agents.
Based on study results, providers should have tempered expectations when prescribing amantadine, modafinil, and methylphenidate as first-line treatments forMS-related fatigue. They also highlight the need for comparative trials to establish evidence-based treatment guidelines for MS symptomatic therapies.
Daily oral doses of 2000 international units (IU) to 4000 IU vitamin D3 are generally sufficient to maintain serum 25-hydroxyvitamin D at optimal levels of 40 mg/mL to 60 mg/mL (specific levels vary by laboratory).
Providers should follow a “start low and go slow” approach to dosing and titration for MS symptom medications. Medications should be selected to tackle multiple symptoms. Dose reductions for older patients are prudent.
Clinicians faced with questions about dietary supplements can refer patients to registered dieticians who can determine the need for any supplementation beyond the preferred dietary sources. It is important for clinicians to include dietary supplements on medication lists and conduct routine blood and urine screenings for safety.
A “top 3” approach helps prioritize the symptoms elicited at clinic visits.
Source:
Continuum 2022
------ CerebrovascularDisease_CERVICAL_ARTERY_DISSECTION.txt ------
ABSTRACT
OBJECTIVE
Cervical artery dissection is a common cause of stroke in young adults. This article reviews the pathophysiology, etiology and risk factors, evaluation, management, and outcomes of spontaneous cervical artery dissection.
LATEST DEVELOPMENTS
Cervical artery dissection is believed to be a multifactorial disease, with environmental factors serving as possible triggers in patients who have a genetic predisposition to dissection formation. Cervical artery dissection can cause local symptoms or ischemic events, such as ischemic stroke or transient ischemic attack. Neuroimaging is used to confirm the diagnosis; classic findings include a long tapered arterial stenosis or occlusion, dissecting aneurysm, intimal flap, double lumen, or intramural hematoma. Patients with cervical artery dissection who present with an acute ischemic stroke should be evaluated for IV thrombolysis, endovascular therapy eligibility, or both. Antithrombotic therapy with either anticoagulation or antiplatelet treatment is used to prevent stroke from cervical artery dissection. The risk of recurrent ischemia appears low and is mostly limited to the first two weeks after symptom onset.
ESSENTIAL POINTS
Cervical artery dissection is a known cause of ischemic strokes. Current data show no difference between the benefits and risks of anticoagulation versus antiplatelet therapy in the acute phase of symptomatic extracranial cervical artery dissection, thereby supporting the recommendation that clinicians can prescribe either treatment. Further research is warranted to better understand the pathophysiology and long-term outcomes of cervical artery dissection.
KEY POINTS
The overall incidence of cervical artery dissection is low at 2.6 to 3.0 per 100,000 people per year.
Dissections result from the separation of the arterial wall layers causing the formation of a false lumen that allows blood to enter the vessel wall.
Dissections can cause subintimal or subadventitial hematomas. Subintimal hematomas may lead to intraluminal stenosis or occlusion. Subadventitial hematomas can cause eccentric hematoma growth and aneurysm formation.
A small portion of cervical artery dissection cases (nearly 2%) have been linked to monogenic connective tissue diseases, such as vascular Ehlers-Danlos syndrome.
Apart from monogenic disorders, which encompass a small group of cervical artery dissection cases, genetic factors may play a role in a more multifactorial process leading to cervical artery dissection.
Minor cervical trauma precedes nearly 41% of identified spontaneous cervical artery dissection cases. These minor traumas can be subtle and involve hyperextension, lateroversion, or rotation of the neck.
Pregnancy and the postpartum period, oral contraceptive use, migraine, recent infection, and vascular risk factors have all been associated with cervical artery dissection.
Common local signs and symptoms of cervical artery dissection include new-onset headache, neck pain, cranial and cervical neuropathies, Horner syndrome, and pulsatile tinnitus.
Ischemic strokes from cervical artery dissection are usually due to artery-to-artery embolism of intraluminal thrombus formed at the site of intraluminal stenosis. Less commonly, ischemia may result from hypoperfusion distal to a high-grade intraluminal stenosis or occlusion.
Subarachnoid hemorrhage may result from intracranial extension of a dissection. Intracranial arteries lack external elastic lamina and have a thinner media, making them more prone to aneurysm formation and subsequent rupture.
The majority of ischemic events from cervical artery dissection occur within the first 1 to 2 weeks after symptom onset.
The diagnosis of cervical artery dissection should be suspected in patients with acute onset of local symptoms of headache, neck pain, Horner syndrome, or any combination of the three, particularly if they are associated with an ipsilateral ischemic stroke.
The most commonly used imaging modalities include CT and CT angiography (CTA), or MRI and magnetic resonance angiography (MRA) of the head and neck.
MRI in cervical artery dissection may show a pathognomonic crescent sign. The crescent sign is formed by an eccentric rim of hyperintensity, corresponding to intramural hematoma, surrounding a hypointense arterial lumen on axial cross-sectional T1-weighted sequences. The combination of MRA with T1-weighted axial cervical MRI imaging with fat suppression allows for better visualization of intramural hematomas.
CTA is an efficient tool with high sensitivity and specificity for diagnosing cervical artery dissection. However, image interpretation may be limited due to inaccurate contrast bolus timing or streak artifacts from implants or beam-hardening artifacts.
Diagnostic cerebral angiography continues to be the gold standard for identifying cervical artery dissection. However, given the high sensitivity and specificity of noninvasive imaging methods, digital subtraction angiography is rarely needed, unless the clinical suspicion for a dissection continues to remain high despite negative noninvasive imaging.
All patients with acute ischemic stroke from cervical artery dissection should be evaluated to determine eligibility for IV thrombolysis and endovascular therapy.
Endovascular therapy should be considered in select patients with cervical artery dissection with acute ischemic stroke from a large vessel occlusion. This includes patients with tandem occlusions, although the optimal treatment method is still being explored.
The most recent American Heart Association (AHA) guidelines recommend either warfarin or aspirin in patients with recent ischemic stroke or transient ischemic attack from extracranial cervical artery dissection.
The AHA recommends at least 3 months of antithrombotic therapy in patients with recent stroke or transient ischemic attack from cervical artery dissection, but the optimal duration of treatment is unclear.
Most cases of vessel recanalization after cervical artery dissection occur within the first few months after the initial event (16% at 1 month, 50% at 3 months, and 60% at 6 and 12 months). Initial occlusion reduces the likelihood of complete recanalization, whereas the presence of only local signs and symptoms increases the odds of complete recanalization.
Repeat neurovascular imaging is typically done 3 to 6 months after symptom onset or diagnosis with the goal of assessing recanalization status of affected arteries and guiding ongoing antithrombotic treatment in cervical artery dissection.
The rate of recurrent ischemic stroke after cervical artery dissection is low at around 2% to 4% at 3 months and 2.5% at 12 months. The greatest risk of recurrent ischemic stroke is within the first 2 weeks of diagnosis. Dissecting aneurysms do not appear to be associated with an increased risk of recurrent stroke.
The rate of cervical artery dissection recurrence is uncertain, ranging from 2% to 9.2% within the first 1 to 3 months. The highest risk of cervical artery dissection recurrence is within the first month of the initial dissection.
Source:
Continuum April 23
------ CerebrovascularDisease_PediatricNeurology_PEDIATRIC_ISCHEMIC_STROKE.txt ------
ABSTRACT
OBJECTIVE
Pediatric cerebrovascular disease is one of the leading causes of death and disability in children. Survivors of childhood stroke and their families are often left to cope with long-lasting sequelae, such as barriers to school reentry and long-term challenges in attaining independence as adults. Because childhood stroke is rare and providers may not be familiar with the disorder, this article reviews the risk factors, acute management, and sequelae of ischemic stroke in children.
LATEST DEVELOPMENTS
High-quality evidence has resulted in an organized approach to emergent treatment of ischemic stroke in adults, but most front-line providers are less prepared for emergent stroke management in children. The level of evidence for reperfusion therapies in children remains low but is growing. Thrombolysis and thrombectomy are sometimes considered for hyperacute treatment of stroke in children. Readiness for pediatric stroke at regional centers should include an organized approach to pediatric stroke triage and management based on extrapolation from adult stroke trials, expert consensus, and emerging pediatric studies.
ESSENTIAL POINTS
This review provides up-to-date information about ischemic stroke risk factors and management in children. Preparation for rapid stroke diagnosis and management in children may improve outcomes.
KEY POINTS
Perinatal arterial ischemic stroke occurs in approximately 1 in 3000 live full-term births, which makes the weeks around birth one of the highest-risk time periods for stroke to occur.
Most children with acute ischemic stroke present with focal neurologic deficits similar to adults with stroke. Unlike adults, children may have a stuttering rather than an abrupt symptom onset and also commonly present with headache or seizure.
Although a myriad of chronic and acute conditions can predispose a child to have a stroke, many children who present with an initial stroke have no significant medical history and were previously considered to be healthy.
As evidence grows, guidelines have cautiously moved from recommending against IV thrombolysis or thrombectomy outside of a research study toward a discussion of selecting children who may benefit from IV thrombolysis and endovascular thrombectomy in certain circumstances.
Although guidelines support consideration of IV thrombolysis or thrombectomy in children in specific circumstances on a case-by-case basis, these treatments are not considered a requirement. Hyperacute treatment decisions should be made in conjunction with neurologists with expertise in the treatment of children with stroke.
MRI and MR angiography or CT and CT angiography are both reasonable options as initial imaging modalities to evaluate for a suspected childhood stroke, taking timing, circumstances, and available resources into account. In either case, obtaining vascular imaging in addition to brain tissue imaging is crucial to identify a large vessel occlusion or an arteriopathy that influences management.
Because of the prevalence of arteriopathies in childhood stroke with subsequent cerebrovascular narrowing or loss of normal hemodynamic compensatory mechanisms, in the setting of acute stroke collateral cerebral flow should be supported by initial fluid resuscitation if needed, keeping the head of bed flat, instituting bedrest, and avoiding hypotension.
Congenital heart disease or acquired heart disease are major risk factors for perinatal or childhood stroke, together accounting for almost one-third of arterial ischemic strokes in children.
Systematic quality measures that preemptively identify children for closer postprocedural neurologic monitoring after higher-risk cardiac procedures are key to reducing time to stroke detection and increasing opportunities for rapid treatment.
Cerebral arteriopathy is present in up to half of all children with ischemic stroke and is a risk factor for initial stroke as well as stroke recurrence.
The acute management of a suspected stroke in children with sickle cell disease differs from other stroke etiologies and should be focused on providing an emergent blood transfusion.
Assessment of function by a rehabilitation specialist and consideration of inpatient rehabilitation are recommended for children following stroke.
Children benefit from early recognition of stroke and should be transferred to a hospital that can provide definitive care as soon as safely possible, but systems of care for children with stroke lag behind those for adults.
Structured and organized health systems that improve the speed of triage, transport, and treatment of children in medical centers with established pediatric stroke guidelines are still lacking in many geographic areas.
Source:
Continuum April 23
------ MuscleNeuromuscularJunction_A_SYMPTOMS_AND_SIGNS_APPROACH_TO_THE_PATIENT_WITH_NEUROMUSCULAR_WEAKNESS.txt ------
ABSTRACT
PURPOSE OF REVIEW
Muscle weakness is a common feature of many neuromuscular disorders. This article outlines a symptoms and signs approach to the patient presenting with neuromuscular weakness, highlighting key aspects of the clinical history and examination.
RECENT FINDINGS
The past several years have seen a dramatic increase in the ability to test for many inherited and autoimmune neuromuscular disorders more reliably and accurately. Similarly, numerous targeted therapies have been recently approved to treat previously untreatable disorders. Therefore, timely and accurate diagnosis is essential so that patients can receive appropriate therapy, ultimately leading to better clinical outcomes.
SUMMARY
Muscle weakness is a common symptom resulting from dysfunction that can occur at any level of the neuraxis and is a cardinal feature of many neuromuscular disorders. An accurate and meticulous history and a thorough neurologic examination are paramount in localizing the lesion in order to generate a differential diagnosis and guide appropriate ancillary testing. The patient’s age at symptom onset, any identified inciting factors, tempo of symptom progression, pattern of weakness, and associated symptoms and signs are all important diagnostic clues in the evaluation of a patient presenting with muscle weakness.
KEY POINTS
It is important to differentiate true muscle weakness from other symptoms such as generalized fatigue or malaise, or physical limitations due to arthralgia, myalgia, or deconditioning.
When evaluating a patient for muscle weakness, it is instructive to ask about the impact of the symptoms on routine activities to differentiate true weakness from other conditions.
Muscle weakness can develop acutely over hours to days, subacutely over weeks, or chronically over months.
Fatigability is often seen in neuromuscular junction disorders and must be differentiated from generalized fatigue or malaise.
The age of the patient at the onset of muscle weakness is also important to accurately determine, as it directly affects the differential diagnosis.
Vaccinations, gastrointestinal symptoms, or upper respiratory tract infections occur 2 to 3 weeks before the development of neurologic symptoms in roughly two-thirds of patients diagnosed with Guillain-Barré syndrome.
With episodic weakness, the associations of symptoms with diet, exercise, rest after exercise, ambient temperature, and underlying illnesses such as infections are important clues to the diagnosis.
Orthopnea is often an early symptom of neuromuscular respiratory failure, as the diaphragm is placed at a mechanical disadvantage in the supine position.
A thorough past medical history is necessary to identify any concomitant diseases that may be associated with muscle weakness, such as organ system dysfunction, malignancy, connective tissue disorders, or autoimmune disorders.
Examining a similarly affected family member with muscle weakness can prove invaluable when eliciting a family history.
The pattern of muscle weakness must be determined using both the history and the neurologic examination.
Most myopathies and disorders of the neuromuscular junction cause proximally predominant weakness.
Distally predominant weakness is often seen initially in motor neuron disorders and neuropathies; it occurs rarely in myopathies and disorders of the neuromuscular junction.
Oculobulbar-predominant weakness leading to ptosis, dysconjugate gaze and diplopia, dysarthria, dysphagia, or dysphonia is typical of myasthenia gravis.
The symmetry or asymmetry of involvement is an important diagnostic clue in the evaluation of muscle weakness.
It is necessary to directly inspect a patient’s muscles to evaluate for the presence of atrophy, hypertrophy, or abnormal movements.
Sensory symptoms can co-occur with muscle weakness and indicate involvement of the spinal cord, nerve roots, or nerves.
Ancillary tests should be ordered using a hypothesis-driven approach based on the differential diagnosis arrived at by the history and examination.
Nerve conduction studies and EMG are invaluable tools to aid in the diagnosis of neuromuscular disorders and are best conceptualized as extensions of the history and neurologic examination.
Source:
Continuum 2022
------ MultipleSclerosisDemyelinating_TREATMENT_OF_MULTIPLE_SCLEROSIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
Given the expansion of options for the treatment of relapsing multiple sclerosis, this review outlines the framework for developing a treatment strategy, with consideration of when to switch or discontinue therapies, and a comprehensive elaboration of the mechanisms of action, efficacy, and safety considerations for each of the therapeutic classes.
RECENT FINDINGS
The armamentarium of immunotherapies has grown rapidly, to encompass 19 US Food and Drug Administration (FDA)-approved immunotherapies available in 2021, which are addressed in the review. The coronavirus pandemic that began in 2020 underscored existing concerns regarding vaccine efficacy in those treated with immune-suppressing immunotherapies, which are also addressed here.
SUMMARY
By choosing a treatment strategy before exploring the individual medications, patients and providers can focus their efforts on a subset of the therapeutic options. Although the mechanisms of action, routes of administration, efficacy, safety, and tolerability of the described agents and classes differ, all are effective in reducing relapse frequency in multiple sclerosis (MS), with most also showing a reduction in the accumulation of neurologic disability. These powerful effects are improving the lives of people with MS. Pharmacovigilance is critical for the safe use of these immune-modulating and-suppressing agents, and vaccine efficacy may be reduced by those with immune-suppressing effects.
Key Points
Shared decision making is associated with better adherence to multiple sclerosis (MS) treatment.
Patients and providers may have different goals when choosing a treatment strategy. Establishing shared goals for treatment is critical to the therapeutic alliance.
A dedicated treatment visit is useful to have an in-depth discussion of the risks, benefits, and treatment options available to the patient to facilitate shared decision making.
Prevailing treatment strategies for relapsing MS include an escalation approach, prioritizing safety with a planned switch to higher-efficacy agents for breakthrough disease activity, and an early high-efficacy approach, where highest-efficacy agents are initiated at the time of diagnosis for expedited control of disease activity.
MRI provides a high-sensitivity assessment of disease-modifying therapy (DMT) efficacy and should be used to set a new baseline. It has been suggested that MRI be done approximately 6 months after treatment initiation and to monitor response to the DMT at least yearly.
Immunosenescence, the decline of immune system function with advancing age, may render an older patient more susceptible to the infectious or neoplastic risks of DMTs.
DMTs for relapsing MS have proliferated and diversified, with improved efficacy, variable routes of administration, and generally an acceptable safety and tolerability profile since the first approval of DMT in 1993. One agent is approved for primary progressive MS, and one for pediatric MS.
The first approved class for relapsing MS in 1993, interferons beta ushered in the treatment era of relapsing MS and have a long-standing safety track record.
A modest-efficacy self-injectable with no monitoring requirements, glatiramer acetate may be particularly appealing to those who are prioritizing safety, are planning a pregnancy, or are risk averse.
Teriflunomide demonstrates a modest reduction in relapse paired with a reduction in confirmed disability progression more commonly seen with higher-efficacy DMTs.
Fumarates require minimal screening for initiation and safety surveillance. Twice daily dosing must be achieved to maintain efficacy.
Sphingosine-1-phosphate modulators offer moderate efficacy with some safety risks including cardiac effects, macular edema, and rebound of relapses but excellent tolerability. Fingolimod is US Food and Drug Administration (FDA) approved for use in pediatric MS.
The short courses of oral cladribine therapy may present a unique opportunity for those with adherence challenges or plans for pregnancy after a full two-cycle course.
Rapid control of relapsingMS can be achieved with natalizumab, but careful pharmacovigilance is needed to surveil for progressive multifocal leukoencephalopathy. Extended interval dosing provides a rational approach to mitigating progressive multifocal leukoencephalopathy risk. Natalizumab is considered safe for patients who are JC virus antibody negative.
Anti-CD20 treatments provide high efficacy with a rapid onset of benefits. Ocrelizumab is the only agent approved for primary progressive MS.
Close therapeutic alliance is critical for prudent use of high-efficacy alemtuzumab, requiring extensive laboratory monitoring for 4 years after a final infusion.
Source:
Continuum 2022
------ MultipleSclerosisDemyelinating_DIAGNOSIS_OF_MULTIPLE_SCLEROSIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
The diagnosis ofmultiple sclerosis (MS) can be made based on clinical symptoms and signs alone or a combination of clinical and paraclinical features. Diagnostic criteria for MS have evolved over time, and the latest version facilitates earlier diagnosis of MS in those presenting with typical clinical syndromes. This article summarizes the current diagnostic criteria forMS, typical and atypical presentations of MS, and when diagnostic criteria should be applied with caution.
RECENT FINDINGS
The most recent version of the MS diagnostic criteria has the benefits of simplicity and greater sensitivity in comparison to previous iterations. However, misdiagnosis remains a significant issue in MS clinical care, even at MS specialty centers. It is, therefore, evident that careful clinical application of the current version of the diagnostic criteria is necessary and that tools improving the diagnostic accuracy of MS would be of substantial clinical utility. Emerging diagnostic biomarkers that may be useful in this regard, including the central vein sign, paramagnetic rim lesions, and fluid biomarkers, are discussed.
SUMMARY
Current MS diagnostic criteria facilitate the early diagnosis of MS in people presenting with typical clinical syndromes but should be used cautiously in those presenting with atypical syndromes and in special populations. Clinical judgment and existing paraclinical tools, including sequential MRIs of the neuraxis and laboratory tests, are useful in minimizing misdiagnosis and facilitating the accurate diagnosis of MS. Diagnostic biomarkers that may facilitate or refute a diagnosis of MS in these settings, and emerging imaging and fluid biomarkers may eventually become available for use in clinical settings.
Key Points
Typical clinical features of a first multiple sclerosis (MS) relapse last for a minimum of 24 hours and present with unilateral visual changes and eye pain, unilateral sensory or motor symptoms with or without accompanying bladder or bowel dysfunction, or infratentorial symptoms.
The 2017 McDonald criteria facilitate the diagnosis of MS in patients presenting with typical clinical syndromes.
The diagnosis of relapsing-remitting MS can bemade based on clinical criteria alone, but MRI of the brain and cervical spinal cord, if possible, is recommended in all patients where the diagnosis is being considered.
Dissemination in time and space can be demonstrated by using clinical and paraclinical criteria.
Misdiagnosis in MS is not uncommon.
MS diagnostic criteria should be applied only to patients presenting with typical clinical syndromes because they were never designed to differentiate between MS and other neurologic conditions.
Even in those presenting with typical clinical syndromes who meet MS diagnostic criteria, the neurologist should use clinical judgment and appropriate tests to ensure no better clinical explanation for the patient’s clinical presentation is present.
It is important to be vigilant for clinical and paraclinical red flags when considering a diagnosis of MS in an individual patient.
The diagnosis of primary progressive MS can be made when clinical and paraclinical criteria are fulfilled as outlined in the 2017 McDonald criteria.
Radiologically isolated syndrome and solitary sclerosis are not yet considered in the diagnostic spectrum of MS, but this may be revisited in future revisions of MS diagnostic criteria. These disorders can be challenging to manage from a clinical standpoint because of a lack of clear guidelines regarding management.
Several emerging imaging and fluid biomarkers are demonstrating utility as diagnostic biomarkers of MS. With further validation, these measures may facilitate diagnosis and prevent misdiagnosis in clinical practice.
Source:
Continuum 2022
------ MultipleSclerosisDemyelinating_EPIDEMIOLOGY_AND_PATHOPHYSIOLOGY_OF_MULTIPLE_SCLEROSIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides an overview of genetic, environmental, and lifestyle risk factors affecting the disease course of multiple sclerosis (MS) and reviews the pathophysiologic characteristics of both relapsing and progressive MS.
RECENT FINDINGS
The prevalence of MS has increased in recent decades, and costs of care for patients with MS have risen dramatically. Black, Asian, and Hispanic individuals may be at risk for more severe MS-related disability.Multiple geneticMS risk factors have been identified. Factors such as low vitamin D levels and a history of Epstein-Barr virus, smoking, and obesity, especially during childhood, also influenceMS risk. Traditionally thought to be a T-cell–mediated disease, recent research has highlighted the additional roles of B cells and microglia in both relapsing and progressive MS.
SUMMARY
Complex interactions between genetic, environmental, and lifestyle factors affect the risk for MS as well as the disease course. People of color have historically been underrepresented in both MS clinical trials and literature, but current research is attempting to better clarify unique considerations in these groups. MS pathology consists of the focal inflammatory lesions that have been well characterized in relapsing MS, as well as a more widespread neurodegenerative component that is posited to drive progressive disease. Recent advances in characterization of both the inflammatory and neurodegenerative aspects of MS pathophysiology have yielded potential targets for future therapeutic options.
KEY POINTS
The prevalence of multiple sclerosis (MS) is increasing, potentially because of changes to diagnostic criteria that allow for earlier diagnosis, more widespread use of MRI, and population aging.
Female predominance inMShas persisted over time, with a female to male ratio of approximately three to one.
Autoreactive T cells are involved in MS pathogenesis and were traditionally felt to be the primary disease-driving immune subset. B cells have been increasingly recognized as important in MS pathophysiology as well, likely through multiple mechanisms.
Microglia are immune cells residing in the central nervous system and are involved in both active and chronic MS lesions. Several therapeutic agents potentially targeting microglia are in development.
Compared with the acute inflammatory lesions that characterize relapsing MS, chronic, inactive, and cortical lesions and more widespread neurodegeneration may predominate in progressive MS.
Low vitamin D levels are associated with an increased risk of MS. Current trials aim to clarify the role of supplementation and vitamin D goal levels in patients with MS.
Human leukocyte antigen (HLA)-DRB1*15:01 genotype increases MS risk, whereas HLA-A*02 may be protective. Other single nucleotide polymorphisms influencing MS risk have also been identified.
Epstein-Barr virus seropositivity and infectious mononucleosis are associated with increased risk of MS. Other viral associations with MS have been less clearly defined.
Smoking, including passive smoke exposure, has been associated with bothMS risk and disease progression. Smoking cessation should be encouraged, and dedicated education by clinicians may increase the likelihood of cessation.
Childhood and adolescent obesity have been associated with increased MS risk, and abdominal obesity has also been associated with a degree of MS-related disability.
Gut microbiome may influence systemic inflammation. A unifying “MS microbiome” has not been demonstrated, and the role of diet in MS outcomes has yet to be clearly defined, but a higher quality diet may assist in improving common symptomatic issues.
Comorbid conditions are common in patients with MS. Comorbidities influence relapse risk, disability scores, health-related quality of life, and treatment adherence.
The incidence of MS is higher than previously recognized in Black people in the United States, and Black, Asian, and Hispanic patients may be at risk for more severe disability related to MS.
Among Hispanic immigrants to the United States, immigration before adolescence has been associated with younger age at MS onset, and later immigration has been associated with worse disability.
Physician awareness regarding patients’ gender identity and sexual orientation is an important opportunity for improved comprehensive care and patient satisfaction.
Socioeconomic factors contribute to MS outcomes, and costs of care related to MS have steadily increased. Many patients with MS experience financial worry, and costs may affect patient adherence and quality of life.
Source:
Continuum 2022
------ CerebrovascularDisease_DIAGNOSIS_AND_TREATMENT_OF_CEREBRAL_VENOUS_THROMBOSIS.txt ------
ABSTRACT
OBJECTIVE
Cerebral venous thrombosis (CVT), thrombosis of the dural sinus, cerebral veins, or both, is a rare cerebrovascular disease. Although mortality rates after CVT have declined over time, this condition can result in devastating neurologic outcomes. This article reviews the latest literature regarding CVT epidemiology, details new factors associated with the development of CVT, and describes advances in CVT treatment. It also contains a discussion of future directions in the field, including novel diagnostic imaging modalities, and potential strategies to reduce the risks associated with CVT.
LATEST DEVELOPMENTS
The incidence of CVT may be as high as 2 per 100,000 adults per year. It remains a difficult condition to diagnose given its variable clinical manifestations and the necessity of neuroimaging for confirmation. The COVID-19 pandemic has revealed a novel CVT trigger, vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as an association between COVID-19 infection and CVT. Although VITT is a very rare event, timely diagnosis and treatment of CVT due to VITT likely improves patient outcomes. Direct oral anticoagulants are currently being used to treat CVT and emerging data suggest that these agents are as safe and effective as vitamin K antagonists. The role of endovascular therapy to treat CVT, despite a recent clinical trial, remains unproven.
ESSENTIAL POINTS
The incidence of CVT has increased, outcomes have improved, and the use of direct oral anticoagulants to treat CVT represents an important advance in the clinical care of these patients. Rates of CVT as a complication of COVID-19 vaccines using adenoviral vectors are very low (<5 per million vaccine doses administered), with the benefits of COVID-19 vaccination far outweighing the risks.
KEY POINTS
Unlike arterial strokes, cerebral venous thrombosis (CVT) has a wide spectrum of clinical presentations, tends to affect younger patients with a female predominance, and is often nonapoplectic in onset.
The latest annual CVT incidence ranges from 1.32 to 2 per 100,000 adults based primarily on data from high-income countries.
Conditions associated with CVT can be classified as either predisposing (eg, genetic prothrombotic diseases, antiphospholipid syndrome, cancer) or precipitating (eg, oral contraceptives, infections).
Data from a 2021 study suggest that a rare but demonstrable association between CVT and COVID-19 infection exists, although the underlying mechanisms of this association are uncertain.
In patients with neurologic symptoms and COVID-19 infection, a high index of suspicion for CVT should be encouraged, and treatment of CVT should be initiated as soon as possible.
The entity implicated in the rare but potentially devastating cases of CVT and thrombocytopenia following adenovirus-based COVID-19 vaccine administration is now called vaccine-induced immune thrombotic thrombocytopenia (VITT), or thrombosis with thrombocytopenia syndrome.
In patients with CVT with symptom onset within 4 to 42 days after having received a COVID-19 vaccine using adenoviral vectors, following an algorithmic approach to evaluate and treat VITT is advised.
Presentations of CVT can be roughly divided into four syndromes: (1) isolated headache or increased intracranial pressure, (2) focal neurologic presentations, (3) subacute encephalopathy, and (4) cavernous sinus syndrome with multiple cranial neuropathies.
A key feature of focal neurologic deficits due to CVT is that they are frequently progressive in nature in contrast to arterial strokes which tend to be maximal at onset.
Contrast-enhanced brain MRI provides detailed information about the brain parenchyma and is probably more accurate for diagnosing CVT than non-contrast-enhanced magnetic resonance venography sequences.
Both the American Heart Association/American Stroke Association (AHA/ASA) and the more recently published European Stroke Organization (ESO) guidelines recommend initiation of parenteral anticoagulation with unfractionated or low-molecular-weight heparin prior to transitioning to oral anticoagulants for CVT treatment.
The ACTION-CVT study and other retrospective treatment studies are prone to confounding by indication; nevertheless, there do not seem to be major safety issues with the use of direct oral anticoagulants as opposed to vitamin K antagonists in clinical practice.
As in heparin-induced thrombocytopenia, therapeutic anticoagulation with non-heparin anticoagulants is the primary treatment for VITT with or without CVT.
Despite the low quality of evidence, the ESO guidelines now strongly recommend using decompressive surgery for patients with acute CVT and parenchymal lesions with impending herniation to prevent death as a randomized controlled trial is unlikely for ethical and feasibility reasons.
In general, CVT has a favorable outcome with an in-hospital mortality rate ranging from 1% to 4% and from 8% to 10% during long-term follow-up.
Source:
Continuum April 23
------ MovementDisorders_SURGICAL_THERAPIES_FOR_PARKINSON_DISEASE.txt ------
ABSTRACT
PURPOSE OF REVIEW
Parkinson disease (PD) is a progressive neurodegenerative disorder that is often difficult to manage with medications alone. This article reviews the current therapeutic surgical interventions for PD, patient selection criteria, timing of patient referral to surgical services, procedure overview, and future directions.
RECENT FINDINGS
Adaptive, or closed-loop, deep brain stimulation is a promising therapy that can detect ongoing circuit changes and deliver appropriate stimulation based on the patient’s dominant symptom and level of dopaminergic medication.
SUMMARY
Patients with PD can benefit from surgical interventions that can be added to their medication regimen. These patients should be referred to comprehensive centers that offer complete multidisciplinary screening evaluation to ensure appropriate patient selection and intervention selection. With the appropriate surgical intervention and continued management from their care team, patients with PD can maximize their quality of life.
KEY POINTS
Surgical interventions do not slow down, stop, or reverse disease progression but are used to manage the symptoms associated with Parkinson disease.
The three indications for deep brain stimulation surgery for the treatment of Parkinson disease include troublesome dyskinesias, frequent dosing because of troublesome off time, and medication-resistant tremor.
Parkinson disease symptoms that are responsive to levodopa can be improved with deep brain stimulation; however, an exception to this is resting tremor, which may not be levodopa responsive but can still improve with deep brain stimulation.
Disadvantages of deep brain stimulation include risks associated with brain surgery, hardware failure, infection risks, and concerns about patients with significant cognitive impairment.
Deep brain stimulation can be performed on both sides of the brain and is adjustable over time.
Commercial deep brain stimulation systems provide continuous stimulation without sensing brain signals for feedback (ie, open loop). There is ongoing research on deep brain stimulation systems that sense brain signals for feedback (ie, closed loop).
MRI-guided focused ultrasound may be considered when there are restrictions to deep brain stimulation or other reasons that prohibit brain surgery.
MRI-guided focused ultrasound uses multiple ultrasound beams that converge on a brain target to create an irreversible lesion.
An advantage of MRI-guided focused ultrasound is that no foreign bodies are present in the patient following surgery. Disadvantages include that the US Food and Drug Administration has only approved this treatment for one side of the brain, and it is not adjustable.
During stereotactic radiosurgery, multiple beams of radiation converge on the brain target to create an irreversible lesion.
An advantage of stereotactic radiosurgery is that no foreign bodies are present in the patient following surgery. Disadvantages include that the US Food and Drug Administration has only approved this treatment for one side of the brain, it is not adjustable, and there is potential radiation risk.
The levodopa/carbidopa intestinal gel infusion system provides levodopa infusion through a percutaneous endoscopic gastrojejunostomy, providing continuous levels throughout the day.
The levodopa/carbidopa intestinal gel infusion system may not be appropriate for patients with poor response to levodopa or who have difficulty handling the infusion pump.
Typically, the levodopa/carbidopa intestinal gel infusion pump is on during the day and is shut off at night.
Advantages of the levodopa/carbidopa intestinal gel infusion system include that the pump can be disconnected when not in use and can be used in patients with significant cognitive impairment. Disadvantages include risks associated with percutaneous endoscopic gastrojejunostomy tube placement and maintenance.
Source:
Continuum 2022
------ Epilepsy_APPROACH_TO_THE_MEDICAL_TREATMENT_OF_EPILEPSY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses the use of antiseizure medications in the treatment of focal and generalized epilepsies using an evidence-based approach.
RECENT FINDINGS
In recent years, several new antiseizure medications with differing mechanisms of action have been introduced in clinical practice, and their efficacy and safety has been evaluated in randomized controlled clinical trials. Currently, all antiseizure medications can prevent seizure occurrence, but they have no proven disease-modifying or antiepileptogenic effects in humans. The choice of therapy should integrate the best available evidence of efficacy, tolerability, and effectiveness derived from clinical trials with other pharmacologic considerations, the clinical expertise of the treating physicians, and patient values and preferences. After the failure of a first antiseizure medication, inadequate evidence is available to inform policy. An alternative monotherapy (especially if the failure is because of adverse effects) or a dual therapy (especially if failure is because of inadequate seizure control) can be used.
SUMMARY
Currently, several antiseizure medications are available for the treatment of focal or generalized epilepsies. They differ in mechanisms of action, frequency of administration, and pharmacologic properties, with a consequent risk of pharmacokinetic interactions. Major unmet needs remain in epilepsy treatment. A substantial proportion of patients with epilepsy continue to experience seizures despite two or more antiseizure medications, with a negative impact on quality of life. Therefore, more antiseizure medications that could provide higher seizure control with good tolerability and that could positively affect the underlying disease are needed.
KEY POINTS
The practice of evidence-based medicine integrates the best available research evidence with clinical expertise and patient values and preferences in making decisions about the care of individuals.
Evaluating and integrating data on efficacy, safety, and effectiveness is essential to obtain the best information upon which to make treatment decisions.
Estimating the risk of seizure recurrence for an individual and the effect of antiseizure medication on that recurrence risk is crucial to inform the decision on whether to start antiseizure medication treatment.
Antiseizure medication treatment following a first unprovoked seizure reduces the risk of a seizure recurrence with no impact on longer-term seizure remission rates.
According to the International League Against Epilepsy classification, every attempt should be made to consider and incorporate etiology when classifying epilepsies, as it often has relevant treatment implications.
The choice of initial antiseizure medication therapy should integrate the best available evidence from clinical trials, other pharmacologic considerations, the clinical expertise of the treating physicians, and patient values and preferences.
Despite the increased availability of antiseizure medications, the prognosis of patients with newly diagnosed epilepsy has not significantly improved.
After monotherapy failure because of inadequate seizure control, the main options are an alternative monotherapy or a dual therapy.
Several antiseizure medications are available for treating focal epilepsy with seizures refractory to a first or alternative monotherapy.
When choosing the add-on treatment, several aspects need to be considered in addition to its efficacy and tolerability, including frequency of administration; pharmacokinetic properties, including the risk of drug interactions; and patient preferences.
The ideal rational polytherapy should have supraadditive or synergistic effects in efficacy (ie, their combined efficacy should be greater than the sum of efficacy of each antiseizure medication alone) with infraadditive toxicity (ie, their combined toxicity should be less than the sum of the toxicity of each antiseizure medication alone).
Source:
Continuum Epilepsy 2022
------ MovementDisorders_PALLIATIVE_CARE_AND_MOVEMENT_DISORDERS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews the role of palliative care in the treatment of patients with life-limiting neurodegenerative movement disorders.
RECENT FINDINGS
Growing evidence indicates that palliative care significantly improves quality of life and symptom burden for people with Parkinson disease and other serious movement disorders, while reducing caregiver burnout. An emphasis on advance care planning guides goal-directed treatment recommendations. Serious illness communication skills are evidence-based methods of relaying bad medical news to patients and mapping out values and goals in a way that provides comfort, emphasizes patient autonomy, and builds coping and resiliency strategies.
SUMMARY
Palliative care, when offered alongside primary medical and neurologic teams, provides an extra layer of support for people with serious illnesses. The goal of palliative care is to intensively treat total pain, which includes all of the physical, emotional, social, and spiritual distress caused by serious illness. Serious illness communication skills are key to providing empathic and goal-concordant care.
KEY POINTS
Palliative care is specialized medical care for people with serious, life-limiting illness.
Total pain is a key concept in palliative care that is defined as all of the physical, emotional, social, and spiritual distress caused by serious illness.
The total symptom burden measured in Parkinson disease has been found to be similar to the total symptom burden reported in metastatic cancer and amyotrophic lateral sclerosis.
Caregivers often experience serious adjustment reactions, burnout, chronic grief, and anticipatory grief.
Growing evidence shows that palliative care significantly improves quality of life and symptom burden for people with Parkinson disease and other serious movement disorders, while reducing caregiver burnout and improving advance care planning.
Palliative care is applicable at all stages of serious illness and in conjunction with other treatments that are focused on prolonging life.
Palliative care serious illness communication skills are evidence-based teachable techniques that enable clinicians to break bad medical news and discuss advance care planning in a way that provides comfort, improves patient and caregiver coping, and guides treatment recommendations.
The SPIKES protocol is a palliative care communication technique used when giving a serious illness diagnosis. SPIKES stands for: setting, perception, invitation, knowledge, emotions, and strategy.
The REMAP protocol is a palliative care communication technique developed by VitalTalk that is used when there is significant worsening of the serious illness. REMAP stands for: reframe, expect emotion, map out, align, and plan.
The high rates of dementia and communication difficulties that occur owing to neurodegenerative movement disorders makes discussing advance care planning early in the course of the illness critical.
A documented advance care plan increases the likelihood of dying at home with hospice in a population of people with Parkinson disease, and movement disorders palliative care clinics have been shown to increase advance care planning.
Requests for medical-aid-in-dying medications are typically a cry for help due to unbearable symptoms from a serious illness and are not usually disclosures of suicidal ideation.
Palliative care considers clinicians to also be caregivers, with a high risk of caregiver burnout. Palliative care makes preventing clinician burnout a top priority by placing importance on developing a balanced lifestyle, building coping and resiliency skills, and developing systems-level improvements.
The stigma surrounding the word “palliative” deters clinicians from recommending the treatment and deters patients/caregivers from accepting the care. Supportive care has been shown to be much better received by both clinicians and patients and caregivers.
Palliative care emphasizes a holistic approach, patient autonomy, aggressive symptom management of total pain, concern for the family, and clinical teamwork to provide goal-concordant care that focuses on optimizing quality of life for people dealing with serious, life-limiting illness.
Source:
Continuum 2022
------ DementiaNeurodegenerativeProcesses_Diagnosis_of_Sleep_Apnoea_Using_a_Mandibular_Monitor_and_Machine_Learning_Analysis__One-Night_Agreement_Compared_to_in-Home_Polysomnography.txt ------
ABSTRACT
PURPOSE OF REVIEW
Alzheimer disease (AD) is the most common cause of dementia in adults (mid to late life), highlighting the importance of understanding the risk factors, clinical manifestations, and recent developments in diagnostic testing and therapeutics.
RECENT FINDINGS
Advances in fluid (CSF and blood-based) and imaging biomarkers are allowing for a more precise and earlier diagnosis of AD (relative to non-AD dementias) across the disease spectrum and in patients with atypical clinical features. Specifically, tau- and amyloid-related AD pathologic changes can now be measured by CSF, plasma, and positron emission tomography (PET) with good precision. Additionally, a better understanding of risk factors for AD has highlighted the need for clinicians to address comorbidities to maximize prevention of cognitive decline in those at risk or to slow decline in patients who are symptomatic. Recent clinical trials of amyloid-lowering drugs have provided not only some optimism that amyloid reduction or prevention may be beneficial but also a recognition that addressing additional targets will be necessary for significant disease modification.
SUMMARY
Recent developments in fluid and imaging biomarkers have led to the improved understanding of AD as a chronic condition with a protracted presymptomatic phase followed by the clinical stage traditionally recognized by neurologists. As clinical trials of potential disease-modifying therapies continue, important developments in the understanding of the disease will improve clinical care now and lead to more effective therapies in the near future.
KEY POINTS
Women have nearly double the lifetime risk of developing Alzheimer disease relative to men.
The older an individual is, the less likely a positive biomarker for Alzheimer disease (AD) is to represent the sole cause of the dementia syndrome, but negative AD biomarkers strongly suggest a non-AD dementia syndrome.
The positive predictive value of positive AD biomarkers in determining AD as the primary cause for dementia increases when used in people in their fifth to seventh decades compared to when used in people their eighth to tenth decades.
The currently available data support the need for screening of sleep-related disorders in the evaluation of patients with cognitive impairment.
The American Academy of Neurology guidelines for the diagnosis of dementia recommend a cognitive screen, structural brain imaging, screening for depression, and assessment of serum thyroid-stimulating hormone and vitamin B12 levels. Although these recommendations capture the minimum that should be performed, a thorough review of medications, potential toxic exposures, and modifiable factors should be included as part of any assessment of a patient with possible dementia.
Although not definitive, the presence of AD-specific biomarkers increases the likelihood of progression to dementia in patients with mild symptoms.
The presence of hippocampal atrophy on brain MRI is insufficient to diagnose AD as the cause of mild cognitive impairment.
The most common core cognitive domain affected in AD is episodic memory.
Mild behavioral impairment is considered a prodromal dementia syndrome of newly developed neuropsychiatric symptoms in cognitively normal older adults.
The presence of noncognitive problems characteristic of the moderate to severe stages of AD in patients with only mild cognitive symptoms should raise concern for an alternative diagnosis.
The presence of atypical motor features (eg, spasticity, ataxia) in a patient with confirmed early-onset AD (with biomarker support) should raise concern for a possible dominantly inherited mutation.
A decrease in CSF Aβ42 and an increase in CSF phosphorylated tau and total tau is the pattern specific for AD.
Current tau positron emission tomography tracers are specific to AD-related tau conformational changes and not to non-AD tauopathies.
Currently three amyloid positron emission tomography (PET) tracers, one tau PET tracer, and a Breakthrough Device Designation for one blood-based biomarker of amyloid pathology have been approved by the US Food and Drug Administration.
No evidence has shown that any of the currently approved symptomatic therapies for AD are beneficial in preventing the progression from mild impairment to more severe stages of AD dementia.
Antipsychotics should be used as a last resort, at the lowest effective doses possible, and with frequent reassessments so that treatment can be discontinued if the targeted symptom has improved or is not responding.
The antipsychotics have been associated with an increased risk of sudden death and stroke and include an FDA boxed warning related to these potential side effects. Therefore, caregivers should be informed of these unlikely but potential risks.
Source:
Continuum 2022
------ MovementDisorders_DIAGNOSIS_AND_TREATMENT_OF_COGNITIVE_AND_NEUROPSYCHIATRIC_SYMPTOMS_IN_PARKINSON_DISEASE_AND_DEMENTIA_WITH_LEWY_BODIES.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article summarizes the underlying biology and current diagnostic and treatment strategies for the cognitive and neuropsychiatric features of Parkinson disease (PD) and dementia with Lewy bodies (DLB).
RECENT FINDINGS
Cognitive impairment and neuropsychiatric symptoms have been increasingly recognized in PD and DLB, leading to improved diagnosis and treatment strategies. While PD is most associated with and diagnosed by the presence of motor symptoms, nonmotor symptoms can often be the most debilitating for patients. Neuropsychiatric symptoms are highly prevalent nonmotor features and include cognitive impairment, depression, anxiety, psychosis, impulse control disorders, and apathy. Neuropsychiatric symptoms can be difficult to recognize and diagnose in patients with PD, in part because of comorbidity and symptom overlap with core PD features. Treatment strategies are a combination of pharmacologic and nonpharmacologic interventions used in the general population and those specific to PD. DLB is a clinical dementia syndrome, often with similar cognitive, behavioral, autonomic, and motor features as PD. Moreover, DLB has shared underlying pathophysiology with PD, as both are associated with postmortem findings of α-synuclein neuropathology at autopsy and have shared genetic risk and prodromal symptoms. DLB is clinically differentiated from PD by the presenting features of cognitive impairment in DLB, compared with the variable onset of cognitive impairment occurring 1 year or more after established motor onset in PD. Thus, diagnosis and treatment of cognitive impairment and neuropsychiatric symptoms in DLB are similar to that of PD and have important implications for maintaining patient independence and providing support for caregivers because motor, cognitive, and neuropsychiatric symptoms have an additive effect on patient functional disability.
SUMMARY
A careful history and physical examination are often needed to accurately diagnose and treat the heterogeneous cognitive and behavioral symptoms of PD and DLB. Accurate diagnosis and treatment of neuropsychiatric symptoms and cognitive impairment in PD and DLB are important, as these are a considerable source of patient disability and caregiver burden.
KEY POINTS
Both Parkinson disease and dementia with Lewy bodies are classified as Lewy body disorders because of the shared underlying α-synuclein neuropathology.
Parkinson disease dementia and dementia with Lewy bodies are differentiated from each other by the timing of the onset of cognitive impairment and dementia; in dementia with Lewy bodies, dementia is an early presenting feature compared with Parkinson disease, where cognitive impairment is variable and dementia occurs at least 1 year after the onset of motor symptoms.
The majority of patients with Parkinson disease, especially those who are older and with long-standing disease, develop significant cognitive impairment.
Patients with Parkinson disease can experience impairments in any of the major cognitive domains, even at the stage of mild cognitive impairment.
Choice of Parkinson disease medication at disease onset does not appear to impact long-term cognitive course, but use of medications with significant anticholinergic properties may be associated with worse long-term cognitive outcomes.
For Parkinson disease dementia, cholinesterase inhibitors are of modest benefit, and there is no clear benefit for memantine. For Parkinson disease–mild cognitive impairment, no medication has been shown to be efficacious.
Management of comorbid medical conditions associated with cognitive impairment in Parkinson disease may lead to improvement in cognitive abilities.
Accurately diagnosing depression in Parkinson disease can be complicated because of symptom overlap between depression symptoms, apathy, and core Parkinson disease symptoms.
A range of antidepressants and Parkinson disease medications have been shown to be efficacious for the treatment of depression in Parkinson disease.
There is increasing evidence for the efficacy of psychotherapy for depression and anxiety in Parkinson disease.
Symptoms occurring as part of nonmotor fluctuations are a common presentation of significant anxiety, even panic attacks, in Parkinson disease.
There have been no efficacy pharmacologic randomized clinical trials for anxiety disorders in Parkinson disease, but in clinical practice, antidepressants and sometimes benzodiazepines are used.
It is now recognized that hallucinations in a range of sensory domains, not just visual hallucinations, can occur in Parkinson disease.
Management of psychosis in Parkinson disease includes a mix of trying to lessen dopamine replacement therapy exposure and judicious use of antipsychotic medication.
Antipsychotic use in patients with Parkinson disease may be associated with an increased risk of mortality and morbidity, as has been reported for Alzheimer disease.
Screening for impulsive-compulsive disorders should include the range of impulse control disorders and related behaviors reported to occur in Parkinson disease, with attention to any comorbid disorders.
Management of impulse control disorders and related behaviors involves a mix of decreasing dopamine replacement therapy, particularly dopamine agonists, psychopharmacology, and psychotherapy.
Although evidence from randomized clinical trials is limited, dopamine agonists, cholinesterase inhibitors, and stimulants can be used in the management of apathy in Parkinson disease.
Overall, deep brain stimulation surgery is associated with an increase in apathy symptoms postoperatively.
Neuropsychiatric symptoms are core features of dementia with Lewy bodies. These include well-formed spontaneous and recurrent visual hallucinations and cognitive fluctuations. Depression, anxiety, and apathy are also common features.
The presence of one or more pathogenic mutations in the glucocerebrosidase A gene, known to cause autosomal recessive Gaucher disease, is an important genetic risk factor for Parkinson disease and dementia with Lewy bodies.
Rapid eye movement (REM) sleep behavior disorder is highly predictive of underlying α-synuclein pathology and eventual clinical conversion to Parkinson disease or dementia with Lewy bodies.
Patients fulfilling criteria for probable dementia with Lewy bodies are highly likely to have underlying α-synuclein pathology, but many patients with clinical Alzheimer disease are found to also have varying amounts of α-synuclein pathology in the brain.
Up to 50% of all Lewy body disorders (ie, Parkinson disease, Parkinson disease mild cognitive impairment, Parkinson disease dementia, and dementia with Lewy bodies) have sufficient plaques and tangles in the brain postmortem for a second neuropathologic diagnosis of Alzheimer disease. These patients with mixed pathology have a worse prognosis and unique clinical features.
There are associations of sex and risk for Lewy body disorders, with greater frequency of men with α-synuclein pathology.
The clinical diagnosis of dementia with Lewy bodies often takes several years to establish in part because of the lack of accurate diagnostic tests specific to cortical α-synuclein and the need to detect progressive cognitive impairment for diagnosis. Efforts to increase accessibility of assessment tools for the unique clinical neuropsychiatric symptoms can help improve diagnosis and treatment of dementia with Lewy bodies.
Core clinical features of dementia in dementia with Lewy bodies are attention, executive, and visuospatial dysfunction, but episodic memory and language difficulties are not uncommon and have been linked to Alzheimer disease co-pathology.
Cognitive fluctuations are core neuropsychiatric symptoms of dementia with Lewy bodies and can range from periodic confusion and disorganized speech to more prolonged episodes of confusion and depressed consciousness as well as excessive daytime fatigue. Detection and treatment of cognitive fluctuations can be aided by standardized caregiver questionnaires.
There is an urgent need for therapeutic trials to guide treatment decisions in dementia with Lewy bodies.
Treatment choices in dementia with Lewy bodies need to be individualized to patient and medical comorbidities. The heterogeneous cognitive, motor, and autonomic symptoms of dementia with Lewy bodies often require careful selection and titration of medications since many symptomatic choices have potentially competing mechanisms of action. Careful titration to the lowest effective dose is often a beneficial strategy.
Data for pharmacologic and nonpharmacologic management of dementia with Lewy bodies are largely restricted to small open-labeled trials and meta-analyses. There are considerable data and general consensus among experts for the use of cholinesterase inhibitors as first-line treatment for cognitive impairment and fluctuations in dementia with Lewy bodies.
Visual hallucinations in patients with dementia with Lewy bodies are often well-formed objects such as people, animals, or objects. Patients initially have good insight but progressively these can cause anxiety or agitation.
It is important to first rule out delirium or other medical etiologies for visual hallucinations and remove or lower potentially exacerbating medications, such as dopaminergic therapies.
The data on effective pharmacotherapy for visual hallucinations in dementia with Lewy bodies are limited. When problematic, careful use of low-dose second-generation neuroleptics may be helpful, but it is important to consider patient age and medical comorbidities. It is also important to first rule out delirium or other medical etiologies and remove or lower potentially exacerbating medications such as dopaminergic therapies.
Source:
Continuum 2022
------ Epilepsy_EVALUATION_OF_FIRST_SEIZURE_AND_NEWLY_DIAGNOSED_EPILEPSY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article focuses on the evaluation of children and adults who present with new-onset seizures, with an emphasis on differential diagnosis, classification, evaluation, and management.
RECENT FINDINGS
New-onset seizures are a common presentation in neurologic practice, affecting approximately 8% to 10% of the population. Accurate diagnosis relies on a careful history to exclude nonepileptic paroxysmal events. A new classification system was accepted in 2017 by the International League Against Epilepsy, which evaluates seizure type(s), epilepsy type, epilepsy syndrome, etiology, and comorbidities. Accurate classification informs the choice of investigations, treatment, and prognosis. Guidelines for neuroimaging and laboratory and genetic testing are summarized.
SUMMARY
Accurate diagnosis and classification of first seizures and new-onset epilepsy are key to choosing optimal therapy to maximize seizure control and minimize comorbidities.
KEY POINTS
Epilepsy is defined as any of the following: (1) at least two unprovoked (or reflex) seizures occurring more than 24 hours apart, (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years, or (3) diagnosis of an epilepsy syndrome.
A careful history taken from both the patient as well as any witnesses to the event(s) is the most critical aspect in distinguishing a seizure from a nonepileptic paroxysmal event.
It is the first convulsive seizure that typically brings the patient to medical attention. Many people presenting with a “first seizure” have a history of prior seizures, which may not have been recognized, and thus have epilepsy.
A diagnosis of an epilepsy syndrome is possible in approximately one-quarter of epilepsy cases beginning in infancy and childhood but is less frequently found in adults. Diagnosis of a specific syndrome provides key information to assist with choosing optimal investigations and treatment and for providing accurate prognosis.
Genetic causes of epilepsy are increasingly recognized. In some cases, such as the idiopathic generalized epilepsies, inheritance is polygenic, and pathogenic variants are typically not found on gene panels. In other cases, particularly in early-onset developmental epileptic encephalopathies, inheritance is monogenic, and pathogenic variants are identified on epilepsy gene panels or whole-exome sequencing.
Increasingly, specific antibodies are being detected in people with autoimmune encephalitis that result in acute symptomatic seizures. These should be distinguished from immune-mediated epilepsies in which an enduring predisposition to seizures is present.
Despite advances in neuroimaging and genetics, approximately 40% of people with new-onset epilepsy have no known etiology found.
Cognitive and psychiatric comorbidities are common in people with epilepsy and often predate seizure onset. The causes are multifactorial, but they are critical to diagnose and treat as they often have an even greater impact than seizures on quality of life.
An EEG is indicated in all patients with new-onset, unprovoked seizures. Care must be taken to avoid misinterpreting normal variants as epileptogenic. The EEG assists with determination of seizure and epilepsy type, choice of further investigations, and prognosis regarding the risk for seizure recurrence.
Neuroimaging is recommended for all patients with new-onset, unprovoked seizures, except those with a well-defined, drug-responsive idiopathic generalized epilepsy or self-limited focal epilepsy of childhood. In patients who have returned to their neurologic baseline and for whom there are no concerns for an acute neurologic process, urgent CT is not needed. Rather, MRI can be obtained on an outpatient basis.
Routine blood and urine studies are commonly obtained but of low yield in patients with new-onset, unprovoked seizures.
A lumbar puncture should be considered if the clinical picture is suggestive of possible meningitis, encephalitis, or subarachnoid hemorrhage but is otherwise is of low yield.
All patients with new-onset, unprovoked seizures must be counseled about lifestyle issues, seizure safety, and what to do if further seizures occur. Water safety is of utmost importance. Showers are safe; however, bathing or swimming alone is not recommended.
Although immediate initiation of antiseizure medication after a first unprovoked seizure does reduce the risk of recurrence, it does not impact long-term epilepsy outcome or quality of life.
Source:
Continuum Epilepsy 2022
------ MultipleSclerosisDemyelinating_PROGRESSIVE_MULTIPLE_SCLEROSIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides an update on progressive forms of multiple sclerosis (MS) commonly referred to as primary progressive MS and secondary progressive MS. It discusses the importance of diagnosing and detecting progression early, the similarities between progressive forms, challenges in detecting progression, factors that could augment progression, and the importance of disease-modifying therapies in patients with evidence of active progressiveMS. It also discusses the overall care of progressive MS.
RECENT FINDINGS
The pathogenesis of primary progressive MS and secondary progressive MS is overlapping, and in both presentations, patients with relapses or focal MRI activity are classified as having active, progressive MS. All currently approved disease-modifying therapies are indicated for active secondary progressive MS. The therapeutic opportunity of anti-inflammatory drugs for the treatment of progressive MS is enhanced in those who are younger and have a shorter disease duration. Vascular comorbidities may contribute to progression in MS.
SUMMARY
Several challenges remain in the diagnosis, follow-up, and treatment of progressive MS. Early identification of active progressiveMS is needed tomaximize treatment benefit. The advantages of optimal comorbidity management (eg, hypertension, hyperlipidemia) in delaying progression are uncertain. Clinical care guidelines for advanced, severe MS are lacking.
Key Points
Disease progression refers to the advancement of disease driven by underlying neurodegenerative processes that can co-occur with inflammatory activity but also develop in its absence.
The term active in the classification of multiple sclerosis (MS) is defined as presence of clinical relapse or MRI activity.
Inflammation that drives tissue injury has become compartmentalized behind an intact blood-brain barrier in progressive MS.
The 2017 McDonald diagnostic criteria for primary progressive MS are the following: (1) 1 year of disease progression independent of clinical relapse and at least two of the following: one or more T2-hyperintense lesions characteristic of MS in one or more of the following regions: periventricular, juxtacortical, cortical, or infratentorial; (2) two ormore T2-hyperintense lesions in the spinal cord; or (3) the presence of CSF-specific oligoclonal bands.
Myelopathy is a common feature of progressive MS.
To be considered progressive MS, progression in disability should be sustained and confirmed at 3 to 6 months.
Better imaging tools are being assessed to help identify progression in MS.
Advanced biomarkers that include measures of brain atrophy and spinal cord damage, including optical coherence tomography and serum neurofilament hold promise to be clinically relevant and feasible in the care of progressive MS.
In a person who has a steady progression of disease since onset for 1 year or more, dissemination in space can be satisfied by the presence of oligoclonal bands in the CSF (2017 McDonald criteria) in addition to two or more T2 spinal cord lesions or one or more MS-typical T2 brain lesions.
Smoking is a modifiable risk factor in the progression of MS and patients should be encouraged to quit smoking.
Vascular comorbidities can increase the risk of progression of MS and likely complicate treatment of progressive MS.
Ocrelizumab is the only US Food and Drug Administration (FDA)-approved disease-modifying therapy (DMT) for the treatment of primary progressive MS.
Stopping DMT use in patients with MS who are 55 and older, are stable, and have no evidence of active disease on DMT is possible.
Before a patient is given a diagnosis of secondary progressive MS, alternative causes for their worsening symptoms should be sought.
Palliative care may be a beneficial option for those who are hospitalized and have accrued significant physical and cognitive disability due to progressive MS.
Source:
Continuum 2022
------ DementiaNeurodegenerativeProcesses_HEALTH_DISPARITIES_IN_DEMENTIA.txt ------
ABSTRACT
PURPOSE OF REVIEW
Causes of health disparities in Alzheimer disease and related dementias (ADRD) in the United States are multifactorial. This article contextualizes health disparities as they relate to the neurodegenerative processes of ADRD.
RECENT FINDINGS
Older adults’ life expectancy has increased such that a 65-year-old is expected to live 19 or more years and an 85-year-old can expect to live, on average, 6 to 7 years longer. Individuals of certain ethnoracial groups (Black, Hispanic/Latino, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander) may be at a higher risk of incident ADRD compared to non-Hispanic/Latino White people. These differences in a higher risk of ADRD across ethnoracial groups persist despite no statistically significant differences in the rate of cognitive decline over time. The intersectionality of social determinants of health, experiences with discrimination and oppression, and access to care are related to the issue of justice and the risk for and expression of ADRD. The theoretical frameworks of various health disparities provide organized approaches to tracking the progression of health disparities for diverse patients.
SUMMARY
ADRD health disparities are complex. Neurologists and their care teams must consider the main reasons for clinical ADRD evaluations of members of ethnoracial groups and the factors that may impact patient adherence and compliance with diagnostic and management recommendations.
KEY POINTS
Physicians and health care providers are increasingly becoming familiar with the terms health disparities, health equity, health inequity, and social determinants of health.
Despite the complexity of health disparities in Alzheimer disease and related dementias, an opportunity exists to address patient quality-of-life concerns using coordinated and patient-centered care.
Appreciating health disparities, health care disparities, and health equity is essential to understand why differences in disease burden and prevalence exist and endure.
Race and ethnicity are distinct socially constructed terms to self-identify that are not based in biology or genetics.
Over the life course, health is created, maintained, and dynamically influenced by biology, behavior, sociocultural values, and the environment.
Health disparities frameworks highlight the intersectionality of health at various systems to understand how disease risk is increased for ethnoracial groups.
Conventional PET and CSF biomarker research is often limited in the sample size of ethnoracial minoritized groups, which can impact the generalizability of the findings.
Blood-based biomarkers can screen a more significant proportion of the population; however, cost, availability, and access remain vital challenges to widespread use.
Health is differentially generated and sustained for ethnoracial groups and profoundly influenced by social (structural racism, institutional discrimination), economic (school quality, insurances), and geographic conditions (proximity to specialty clinics).
Delayed diagnoses for Alzheimer disease and related dementias are prevalent in ethnoracial groups and are compounded by health disparities that are present across the lifespan.
Source:
Continuum 2022
------ Neuroimaging_IMAGING_OF_CENTRAL_NERVOUS_SYSTEM_ISCHEMIA.txt ------
ABSTRACT
OBJECTIVE
This article describes imaging modalities used in the evaluation of patients presenting with symptoms of acute ischemic stroke.
LATEST DEVELOPMENTS
The year 2015 marked the beginning of a new era in acute stroke care with the widespread adoption of mechanical thrombectomy. Subsequent randomized controlled trials in 2017 and 2018 brought the stroke community even further into this new territory with the expansion of the eligibility window for thrombectomy using imaging-based patient selection, which led to an increase in the use of perfusion imaging. Now, after several years of routine use, the debate is ongoing as to when this additional imaging is truly required and when it results in unnecessary delays in time-sensitive stroke care. At this time, more than ever, a robust understanding of neuroimaging techniques, applications, and interpretation is essential for the practicing neurologist.
ESSENTIAL POINTS
CT-based imaging is the first step in most centers for the evaluation of patients presenting with symptoms of acute stroke because of its wide availability, speed, and safety. Noncontrast head CT alone is sufficient for IV thrombolysis decision making. CT angiography is very sensitive for the detection of large-vessel occlusion and can be used reliably to make this determination. Advanced imaging including multiphase CT angiography, CT perfusion, MRI, and MR perfusion can provide additional information useful for therapeutic decision making in specific clinical scenarios. In all cases, it is essential that neuroimaging be performed and interpreted rapidly to allow for timely reperfusion therapy.
KEY POINTS
Early ischemic changes evident on noncontrast CT include obscuration of the lentiform nucleus, loss of the gray-white boundary in the insula (insular ribbon sign), and effacement of the cortical sulci (cortical ribbon sign).
The Alberta Stroke Programme Early CT Score (ASPECTS) is a quantitative assessment of early ischemic changes calculated by visual inspection of 10 specific neuroanatomic regions on noncontrast CT. The maximum score of 10 indicates no evidence of early ischemia.
The American Heart Association/American Stroke Association guidelines recommend proceeding with mechanical thrombectomy for patients with large-vessel occlusion stroke and an Alberta Stroke Programme Early CT Score (ASPECTS) of 6 or greater who present within 6 hours of last known well time, without additional advanced imaging.
The posterior-circulation Alberta Stroke Programme Early CT Score (ASPECTS) is a 10-point scale that assesses eight brain regions supplied by the vertebrobasilar system for evidence of early ischemic changes. It has been shown to improve detection of ischemia and predict functional outcome.
The hyperdense vessel sign can be seen on noncontrast CT and is highly specific for large-vessel occlusion.
It is recommended to proceed with CT angiography before measuring a serum creatinine level in patients eligible for mechanical thrombectomy without known renal impairment to avoid unnecessary delays in reperfusion.
CT angiography is extremely accurate for detecting large-vessel occlusion, with sensitivity and specificity of approximately 98%.
Multiphase CT angiography can be used to obtain a more robust assessment of a patient’s collateral circulation. Quality of collateral flow has been shown to correlate with rate of infarct growth and predict prognosis in some studies.
CT perfusion uses three parameters to assess a given brain region: cerebral blood flow, cerebral blood volume, and mean transit time. Postprocessing software creates maps based on these measures to approximate the size and location of the infarct core and the ischemic penumbra.
MRI is more sensitive and specific than CT for the identification of acute stroke and can detect ischemia as early as a few minutes after stroke onset.
In true restricted diffusion seen in acute ischemic stroke, a region of increased diffusion-weighted imaging signal correlates with a region of low signal intensity on the apparent diffusion coefficient image.
Diffusion-weighted imaging–negative stroke is rare and most frequently seen in patients with small, posterior-circulation, or hyperacute strokes. Repeat diffusion-weighted imaging is recommended if there is a strong clinical suspicion of ischemia.
Diffusion-weighted imaging positivity appears within the first few minutes after stroke onset, whereas fluid-attenuated inversion recovery (FLAIR) signal changes take longer to develop. This mismatch has been used to estimate stroke onset and select patients for thrombolysis.
Acute intraarterial thrombus produces susceptibility artifact and blooming on gradient recalled echo or susceptibility-weighted MRI. This finding is similar to the “hyperdense vessel sign” seen on noncontrast CT and is strongly suggestive of large-vessel occlusion.
The modified Thrombolysis in Cerebral Infarction scale is used to describe the degree of reperfusion achieved after mechanical thrombectomy. A score of 2b, 2c, or 3 is considered successful reperfusion.
Source:
Continuum 2023
------ DementiaNeurodegenerativeProcesses_NEUROPSYCHOLOGICAL_ASSESSMENT_IN_DEMENTIA_DIAGNOSIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses the application of neuropsychological evaluation to the workup of individuals with age-related cognitive impairment and suspected dementia. Referral questions, principles of evaluation, and common instruments to detect abnormalities in cognition and behavior in this population are reviewed. The integration of neuropsychological test findings with other clinical and biomarker information enhances early detection, differential diagnosis, and care planning.
RECENT FINDINGS
Life expectancy is increasing in the United States, and, accordingly, the prevalence and incidence of dementia associated with age-related neurodegenerative brain disease are rising. Age is the greatest risk factor for the dementia associated with Alzheimer disease, the most common neurodegenerative cause of dementia in people over 65 years of age; other etiologies, such as the class of frontotemporal lobar degenerations, are increasingly recognized in individuals both younger and older than 65 years of age. The clinical dementia diagnosis, unfortunately, is imperfectly related to disease etiology; however, probabilistic relationships can aid in diagnosis. Further, mounting evidence from postmortem brain autopsies points to multiple etiologies. The case examples in this article illustrate how the neuropsychological evaluation increases diagnostic accuracy and, most important, identifies salient cognitive and behavioral symptoms to target for nonpharmacologic intervention and caregiver education and support. Sharing the diagnosis with affected individuals is also discussed with reference to prognosis and severity of illness.
SUMMARY
The clinical neuropsychological examination facilitates early detection of dementia, characterizes the level of severity, defines salient clinical features, aids in differential diagnosis, and points to a pathway for care planning and disease education.
KEY POINTS
The most common neurodegenerative disease that causes dementia in people older than 65 years of age is Alzheimer disease, with or without additional neuropathologic and/or vascular lesions.
Cognitive trajectories vary markedly among individuals as they age, ranging from little/no loss to mild cognitive impairment (an intermediate stage of mild cognitive changes that does not affect daily activities) to progressive impairment leading to incapacitating dementia.
Dementia is a progressive cognitive-behavioral syndrome that interferes with the ability to independently perform routine activities of daily living; earlier stages are detectable by neuropsychological testing before they have an impact on daily functioning.
Dementia syndromes that present with unusual symptoms in the early stages (eg, primary progressive aphasia, behavioral variant frontotemporal dementia, posterior cortical atrophy) are easily missed/misdiagnosed in the cursory mental status examination but can be detected with neuropsychological evaluation.
Cognitive impairment often is accompanied by anosognosia, in which case the patient may be unaware of or deny the symptoms obvious to others. It is essential that the clinician seek information from a relative or close friend about any changes they may have noticed in the patient’s cognition or behavior.
Most individuals report a variety of cognitive symptoms as “memory loss.” Deeper probing can determine the neurocognitive domain within which the symptom really falls.
Neuropsychological reports that are brief and easy to interpret, cover all relevant domains, (neurocognitive systems), and provide education and prescriptive guidance for needed additional workup and/or suitable nonpharmacologic interventions for patients and caregivers are a valuable adjunct to clinical care.
Neuropsychological profiles of early dementia (eg, amnestic, aphasic, visuospatial, social-comportmental) can predict the underlying etiology in a probabilistic manner, and test scores can contribute to staging the level of cognitive, behavioral, and functional impairment.
Source:
Continuum 2022
------ CerebrovascularDisease_STROKE_REHABILITATION_AND_MOTOR_RECOVERY.txt ------
ABSTRACT
OBJECTIVE
Up to 50% of the nearly 800,000 patients who experience a new or recurrent stroke each year in the United States fail to achieve full independence afterward. More effective approaches to enhance motor recovery following stroke are needed. This article reviews the rehabilitative principles and strategies that can be used to maximize post-stroke recovery.
LATEST DEVELOPMENTS
Evidence dictates that mobilization should not begin prior to 24 hours following stroke, but detailed guidelines beyond this are lacking. Specific classes of potentially detrimental medications should be avoided in the early days poststroke. Patients with stroke who are unable to return home should be referred for evaluation to an inpatient rehabilitation facility. Research suggests that a substantial increase in both the dose and intensity of upper and lower extremity exercise is beneficial. A clinical trial supports vagus nerve stimulation as an adjunct to occupational therapy for motor recovery in the upper extremity. The data remain somewhat mixed as to whether robotics, transcranial magnetic stimulation, functional electrical stimulation, and transcranial direct current stimulation are better than dose-matched traditional exercise. No current drug therapy has been proven to augment exercise poststroke to enhance motor recovery.
ESSENTIAL POINTS
Neurologists will collaborate with rehabilitation professionals for several months following a patient’s stroke. Many questions still remain about the ideal exercise regimen to maximize motor recovery in patients poststroke. The next several years will likely bring a host of new research studies exploring the latest strategies to enhance motor recovery using poststroke exercise.
KEY POINTS
Motor recovery is the partial or complete improvement of an individual’s motor symptoms such as weakness, coordination, fine control, or ataxia following a stroke.
Functional recovery is a partial or complete improvement in an individual’s performance of activities of daily living, instrumental activities of daily living (eg, housekeeping, cooking, washing clothes, paying bills), mobility (eg, transfers, wheelchair use, walking) or communication.
Although further research is clearly required, the 2018 American Heart Association/American Stroke Association guidelines recommend that specialized acute stroke units “incorporate rehabilitation” into their care and discourage mobilization prior to 24 hours poststroke, but otherwise make only very general recommendations.
Admission to a skilled nursing facility, without inpatient rehabilitation facility consideration, for the sole purpose of decreasing acute care lengths of stay, maintaining historical referral patterns, or preventing “bleed” outside of a constituent health care system should be viewed as incompatible with best practices.
In addition to leading the rehabilitation team, the essential task of the attending physiatrist is to ensure that patients at the inpatient rehabilitation facility are medically stable and free of pain and mood or other issues to the degree that they can participate in therapy, remain on the unit, and benefit from the rehabilitation experience.
Most patients discharged from an inpatient rehabilitation facility to home will continue rehabilitation in an outpatient setting. This could include one to three therapies, two to three times a week from a few weeks to a few months, which likely represents a gross underdosing of therapy.
If the characteristics and content of exercise constitute the “science of stroke rehabilitation,” equally important must be the “art of rehabilitation” as practiced by an outstanding therapist.
Significant questions remain surrounding the ideal exercise protocol following stroke, despite numerous large clinical trials over the past 2 decades.
Given the challenges, expense, and logistics of providing ever greater doses of exercise, identifying strategies to augment the effect of exercise on recovery after stroke is desirable.
To date no pharmacologic agents in well-designed randomized clinical trials have clearly demonstrated enhanced motor recovery after stroke.
Despite an underwhelming track record, upper and lower extremity robotics and exoskeletal devices are commonly offered at larger rehabilitation centers.
Compared to an ankle-foot orthosis, lower extremity functional electrical stimulation may decrease the physiologic cost of gait (based on resting and working heart rate and walking speed) but does not improve gait speed.
The vagus nerve stimulation group in one trial was about twice as likely to achieve a clinically meaningful gain on the Fugl-Meyer Assessment and 3 times as likely to improve on the Wolf Motor Function Test compared with the control group.
Defining the optimal nature, characteristics, intensity, and timing of a patient’s participation in task-specific and repetitious exercise to maximize motor recovery constitutes the fundamental challenge in stroke rehabilitation.
Source:
Continuum April 23
------ MovementDisorders_MULTIPLE_SYSTEM_ATROPHY.txt ------
ABSTRACT
PURPOSE OF REVIEW
Patients with multiple system atrophy (MSA) can present with diverse clinical manifestations, and the clinical care required is complex and requires a thoughtful approach to emerging symptoms and treatment decisions.
RECENT FINDINGS
Even though it is a rare disease, MSA is often encountered in clinical practice. New developments in biofluid biomarkers and diagnostic assessments offer potential for earlier and more accurate diagnosis. This article describes recent findings, such as the use of skin biopsies, neuroimaging, and novel treatment concepts (eg, central noradrenergic augmentation).
SUMMARY
MSA is a complex disease. This article provides a summary of treatment options for diverse symptoms that include autonomic, sleep, mood, and motor manifestations of the disease to help clinicians care for patients with MSA. Providing comprehensive care for patients with MSA requires an understanding of the diverse symptomatology that patients develop over time and should include an interdisciplinary team.
KEY POINTS
Although multiple system atrophy (MSA) has been designated as MSA with predominant parkinsonism or MSA with predominant cerebellar ataxia, it is more common to see an overlap of symptoms that make this distinction difficult.
The most common prodromal symptoms for MSA include rapid eye movement (REM) sleep behavior disorder and autonomic failure.
Patients with pure autonomic failure have a high likelihood of progressing to a central α-synuclein disease; those who progress to MSA tend to be younger and have intact smell and an increase in heart rate after 3 minutes of standing up from a supine position.
A reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 minutes of standing without compensatory heart rate increase is diagnostic of orthostatic hypotension.
Elevating the head of the bed during the night should be encouraged in the management of supine hypertension in patients with MSA.
Early integration of physical therapy and gait safety is key in managing MSA gait symptoms.
Identifying pain symptoms is important in maintaining the quality of life of patients with MSA.
Clinicians can educate local counselors or social workers about the nature of MSA to help establish the framework and goals for interactions.
The use of activity of daily living screening tools for patients, such as the Unified Multiple System Atrophy Rating Scale Part 1, can help direct care of patients with MSA.
Source:
Continuum 2022
------ Epilepsy_UPDATE_ON_ANTISEIZURE_MEDICATIONS_2022.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article is an update from the article on antiepileptic drug therapy (now referred to as antiseizure medication therapy) published in the two previous Continuum issues on epilepsy and is intended to cover the vast majority of agents currently available to the neurologist in the management of patients with epilepsy.
Treatment of epilepsy starts with antiseizure medication monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual antiseizure medications is essential for optimal treatment for epilepsy. This article addresses antiseizure medications individually, focusing on key pharmacokinetic characteristics, indications, and modes of use.
RECENT FINDINGS
Since the most recent version of this article was published, two new antiseizure medications, cenobamate and fenfluramine, have been approved by the US Food and Drug Administration (FDA), and the indications of some approved medications have been expanded.
Older antiseizure medications are effective but have tolerability and pharmacokinetic disadvantages. Several newer antiseizure medications have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older antiseizure medications as first-line therapy for focal epilepsy. The list includes lamotrigine, oxcarbazepine, levetiracetam, topiramate, zonisamide, and lacosamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy for focal epilepsy. Other newer antiseizure medications with a variety of mechanisms of action are suitable for adjunctive therapy. Antiseizure medications marketed since 2016 have benefited from the FDA policy allowing a drug’s efficacy as adjunctive therapy in adults to be extrapolated to efficacy in monotherapy. In addition, efficacy in adults can be extrapolated for efficacy in children 4 years of age and older. Both extrapolations require data demonstrating that an antiseizure medication has equivalent pharmacokinetics between its original approved use and its extrapolated use. Rational antiseizure medication combinations should avoid antiseizure medications with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action.
SUMMARY
Knowledge of antiseizure medication pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate antiseizure medication therapy for patients with epilepsy.
KEY POINTS
Phenobarbital, primidone, phenytoin, and carbamazepine are potent inducers of liver enzymes, reducing the efficacy of drugs metabolized by the cytochrome P450 enzyme system.
Long-term phenobarbital use is associated with decreased bone density, Dupuytren contractures, plantar fibromatosis, and frozen shoulder.
In addition to sedation and other adverse effects of phenobarbital, primidone use may be associated with an acute toxic reaction unrelated to phenobarbital, with potentially debilitating drowsiness, dizziness, ataxia, nausea, and vomiting.
Phenytoin has saturable nonlinear kinetics. Beyond a certain serum concentration, usually within the accepted therapeutic range, phenytoin concentration increases disproportionately with an increase in the dose. Small increments are necessary when increasing the dose at a serum concentration in the therapeutic range.
The traditional sodium channel blockers phenytoin, carbamazepine, and oxcarbazepine may exacerbate generalized absence and myoclonic seizures and should be avoided in idiopathic generalized epilepsy. Other antiseizure medications that have similar potential are gabapentin, pregabalin, tiagabine, and vigabatrin.
Unlike phenytoin, the phenytoin prodrug fosphenytoin may be administered intramuscularly, with reliable absorption, in the absence of IV access.
Carbamazepine induces its own metabolism, so it has to be titrated gradually to the target dose.
The HLA-B1502 allele is predictive of a carbamazepine-induced severe rash in individuals of Asian descent.
Oxcarbazepine is more likely to cause hyponatremia than carbamazepine. Older individuals taking a diuretic are at particularly high risk.
Eslicarbazepine has a long half-life in CSF, justifying once-daily oral dosing.
Valproate has a broad spectrum of efficacy against all focal and generalized seizure types.
Valproate has the highest rate of teratogenicity among antiseizure medications and should be avoided in female patients of childbearing potential.
Ethosuximide is the drug of choice for typical absence seizures as the only seizure type. While valproate is equally effective, it is associated with more cognitive adverse effects.
Tolerance may develop to the therapeutic effect of benzodiazepines; this appears less likely with clobazam than clonazepam.
Felbamate-related aplastic anemia and liver failure are unlikely to start after 1 year of treatment.
Gabapentin bioavailability is low and decreases with increasing doses.
Like gabapentin, pregabalin has a narrow spectrum of efficacy against focal seizures and may exacerbate generalized myoclonic and absence seizures.
Lamotrigine clearance is decreased by valproate and increased by estrogen and pregnancy as well as by enzyme inducers.
Tiagabine may be associated with dose-related episodes of nonconvulsive status epilepticus or encephalopathy, even in subjects who do not have epilepsy.
Levetiracetam is the only antiseizure medication with Class I evidence of efficacy against generalized myoclonic seizures.
Brivaracetam may have fewer behavioral side effects than levetiracetam.
Zonisamide’s long half-life of about 60 hours may be an advantage in reducing the impact of a missed dose.
Lacosamide may produce a dose-dependent prolongation in PR interval, which could be clinically significant in patients with known cardiac conduction problems, or if it is combined with other drugs that have a similar effect.
Long-term vigabatrin use may be associated with irreversible visual field constriction; hence, it should only be continued if it produces a remarkable improvement in seizure control.
Valproate reduces rufinamide clearance; as a result, rufinamide has to be started at a lower dose and titrated more slowly in the presence of valproate.
Perampanel has a very long half-life, justifying once-daily dosing.
Cannabidiol reduces clearance of the active metabolite of clobazam, requiring reduction in the clobazam dose.
Cenobamate requires a very slow titration to avoid allergic skin reactions.
Antiseizure medication combinations with different mechanisms of action may have a greater probability of success.
Source:
Continuum Epilepsy 2022
------ Pregnancy_NEURO-OPHTHALMOLOGY_AND_PREGNANCY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article summarizes the impact of pregnancy on neuro-ophthalmic pathways and presents an approach to the evaluation of pregnant women who have neuro-ophthalmic symptoms or signs.
RECENT FINDINGS
Advances in noninvasive ophthalmic imaging have increased knowledge of the impact of pregnancy on ocular blood flow, which may have relevance for understanding the impact of preeclampsia and eclampsia on the eye.
SUMMARY
The framework for approaching neuro-ophthalmic symptoms and signs in pregnant women is similar to the general approach for people who are not pregnant. Visual symptoms are common in preeclampsia and eclampsia. Some diseases that impact the neuro-ophthalmic pathways are more common in pregnant women. Pregnancy should be considered when recommending the workup and treatment for neuro-ophthalmic symptoms and signs.
KEY POINTS
Ocular surface and cornea changes in pregnancy can cause blur, eye pain, refractive shift, and contact lens discomfort.
Branch retinal vein occlusions, branch retinal artery occlusions, and central serous chorioretinopathy are retinal causes of acute partial vision loss in pregnancy.
Visual symptoms occur in more than one-fourth of patients with preeclampsia and almost half of patients with eclampsia.
The approach to visual symptoms in pregnant patients is similar to the approach to visual symptoms in other patients.
Dilating the pupils with eye drops is regarded to be safe during pregnancy.
Optic neuritis related to multiple sclerosis, neuromyelitis optica, or myelin oligodendrocyte glycoprotein–associated disorder is less common during pregnancy and has increased frequency postpartum.
Bilateral optic disc edema from increased intracranial pressure does not cause visual symptoms in up to half of affected patients.
Regular formal perimetry to monitor visual fields of patients with papilledema from primary or secondary high intracranial pressure is important to detect vision loss so that intracranial pressure–lowering therapy can be advanced to prevent further worsening.
Sixth nerve palsies in pregnancy can result from intracranial hypertension (eg, due to cerebral venous sinus thrombosis) and hypotension (eg, due to dural puncture during anesthesia).
Growth of sellar and suprasellar structures during pregnancy can cause vision loss, diplopia, facial numbness, and Horner syndrome.
Eye movement abnormalities can be caused by thiamine deficiency provoked by hyperemesis gravidarum, which requires urgent treatment.
Facial nerve palsy is the most common cranial nerve palsy in pregnancy.
Artificial tears are the first-line treatment for management of eye pain and blur due to dry eye.
Source:
Continuum 2022
------ Pregnancy_EPILEPSY_AND_PREGNANCY.txt ------
ABSTRACT
PURPOSE OF REVIEW
Seizure disorders are the most frequent major neurologic complication in pregnancy, affecting 0.3% to 0.8% of all gestations. Women of childbearing age with epilepsy require special care related to pregnancy. This article provides up-to-date information to guide practitioners in the management of epilepsy in pregnancy.
RECENT FINDINGS
Ongoing multicenter pregnancy registries and studies continue to provide important information on issues related to pregnancy in women with epilepsy. Valproate poses a special risk for malformations and cognitive/behavioral impairments. A few antiseizure medications pose low risks (eg, lamotrigine, levetiracetam), but the risks for many antiseizure medications remain uncertain. Although pregnancy rates differ, a prospective study found no difference in fertility rates between women with epilepsy who were attempting to get pregnant and healthy controls. During pregnancy, folic acid supplementation is important, and a dose greater than 400 mcg/d during early pregnancy (ie, first 12 weeks) is associated with better neurodevelopmental outcome in children of women with epilepsy. Breastfeeding is not harmful and should be encouraged in women with epilepsy even when they are on antiseizure medication treatment.
SUMMARY
Women with epilepsy should be counseled early and regularly about reproductive health. Practitioners should discuss the risks of various obstetric complications; potential anatomic teratogenicity and neurodevelopmental dysfunction related to fetal antiseizure medication exposure; and a plan of care during pregnancy, delivery, and postpartum. Women with epilepsy should also be reassured that the majority of pregnancies are uneventful.
KEY POINTS
Although pregnancy rates differ, no difference in fertility rate is seen between women with epilepsy who are attempting to get pregnant and healthy controls (60.7% compared to 60.2%).
Certain medications, including valproate and phenobarbital, have been linked to lower fertility, but these findings require further validation in a larger cohort.
Patients treated with CYP3A4 enzyme-inducing antiseizure medications should consider alternative methods of contraception.
Lamotrigine may require substantial titration when it is used in combination with oral hormonal contraceptives.
Knowledge is limited regarding the interaction of oral contraceptives and some of the new antiseizure medications.
Most women with epilepsy will not experience seizure frequency changes during pregnancy.
The diagnosis of epilepsy alone should not be considered as an indication for cesarean delivery.
The risk of gestational hypertension and preeclampsia may be slightly increased in women with epilepsy.
The majority of women with epilepsy have uneventful pregnancies, and 90% of children born to women with epilepsy are healthy.
The risk of major congenital malformations has been associated with first trimester antiseizure medication exposure, the dose and type of antiseizure medication (especially valproate), polytherapy, low folate concentrations, and low maternal level of education.
The teratogenic risks for many antiseizure medications are uncertain. Valproate is the poorest choice of antiseizure medication based on the higher risk profile of both anatomic and behavioral teratogenicity. If used, the dose should be as low as possible.
The impact of neuromodulation therapy on pregnancy outcomes is limited.
Children born to women with epilepsy may have impaired cognitive development; the contributing factors include antenatal antiseizure medication exposure, frequent tonic-clonic seizures in pregnancy, low maternal IQ, and maternal education level.
Women with epilepsy of childbearing potential should be taking folic acid 0.4 mg/d to 4 mg/d.
Monitoring of antiseizure medication levels during pregnancy should be considered.
The most marked decline in serum concentration of antiseizure medications in pregnancy is seen with lamotrigine, levetiracetam, and oxcarbazepine (decrease ranging from 40% to 70%). Carbamazepine and valproate have minimal decreases in serum concentration, usually 10% to 20%.
Breastfeeding while taking antiseizure medication appears to be safe.
Source:
Continuum 2022
------ Epilepsy_EEG_ESSENTIALS.txt ------
ABSTRACT
PURPOSE OF REVIEW
EEG is the best study for evaluating the electrophysiologic function of the brain. The relevance of EEG is based on an accurate interpretation of the recording. Understanding the neuroscientific basis for EEG is essential. The basis for recording and interpreting EEG is both brain site–specific and technique-dependent to detect and represent a complex series of waveforms. Separating normal from abnormal EEG lies at the foundation of essential interpretative skills.
RECENT FINDINGS
Seizures and epilepsy are the primary targets for clinical use of EEG in diagnosis, seizure classification, and management. Interictal epileptiform discharges on EEG support a clinical diagnosis of seizures, but only when an electrographic seizure is recorded is the diagnosis confirmed. New variations of normal waveforms, benign variants, and artifacts can mimic epileptiform patterns and are potential pitfalls for misinterpretation for inexperienced interpreters. A plethora of medical conditions involve nonepileptiform and epileptiform abnormalities on EEG along the continuum of people who appear healthy to those who are critically ill. Emerging trends in long-term EEG monitoring to diagnose, classify, quantify, and characterize patients with seizures have unveiled epilepsy syndromes in patients and expanded medical and surgical options for treatment. Advances in terminology and application of continuous EEG help unify neurologists in the diagnosis of nonconvulsive seizures and status epilepticus in patients with encephalopathy and prognosticate recovery from serious neurologic injury involving the brain.
SUMMARY
After 100 years, EEG has retained a key role in the neurologist’s toolkit as a safe, widely available, versatile, portable test of neurophysiology, and it is likely to remain at the forefront for patients with neurologic diseases. Interpreting EEG is based on qualitative review, and therefore, the accuracy of reporting is based on the interpreter’s training, experience, and exposure to many new and older waveforms.
KEY POINTS
Since the first description in the 1920s, EEG has remained the most relevant testing modality to evaluate people with seizures.
Signals detected and ultimately recorded by EEG are generated by dynamic extracellular currents produced by transmembrane ion flow.
Most standard EEGs are obtained using standard scalp electrodes and acquired in the interictal period when patients are asymptomatic.
A normal EEG is a common result when patients obtain a standard study. However, a normal result does not exclude the possibility that a patient has epilepsy, and EEG should not be used to make an epilepsy diagnosis independent of the clinical context of recording.
Benign variants of uncertain significance, normal waveform variations, and artifacts may be pitfalls to overinterpreting a normal record as abnormal leading to inappropriate treatment with antiseizure medication.
Standard EEG is the diagnostic test of choice to provide electrophysiologic information about the presence of neurophysiologic dysfunction.
An EEG that contains spikes and sharp waves supports a clinical diagnosis of epilepsy.
When EEG records an electrographic seizure in patients with a history of recurrent unprovoked seizures, this is diagnostic of epilepsy.
People who experience a first seizure are at risk for recurrence when EEG demonstrates abnormal interictal epileptiform discharges.
When history and other imaging modalities are considered in addition to an ictal EEG, epilepsy syndromes can usually be defined for the purpose of providing optimal treatment.
Selection of antiseizure medication may be guided by EEG when the historical recount for an observed manifestation is unable to classify the seizures or an epilepsy syndrome.
A significant minority of people are self-unaware of experiencing seizures despite impaired consciousness and overt signs that are visible to other individuals.
Video-EEG classifies focal and diffuse cerebral dysfunction and can support an epilepsy syndromic diagnosis that aids in medical and surgical management.
EEG is the only test in critically ill patients with altered mental status that can result in the diagnosis of nonconvulsive seizures and nonconvulsive status epilepticus.
The goals of therapy for ongoing nonconvulsive seizures and nonconvulsive status epilepticus aim at achieving seizure suppression on continuous EEG and reducing cerebral metabolic rates by achieving a burst-suppression pattern.
Source:
Continuum Epilepsy 2022
------ Pregnancy_MANAGING_CENTRAL_NERVOUS_SYSTEM_TUMORS_DURING_PREGNANCY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses current recommendations and special considerations for the management of central nervous system (CNS) tumors in pregnant women and provides case vignettes to emphasize important clinical concepts.
RECENT FINDINGS
Given that nearly 60% of all intracranial and spinal cord tumors, including both primary and metastatic tumor types, malignant or benign, are diagnosed in women, it is equitable to bring attention to the unique management considerations that pertain to women during specific phases of their lifespan, such as pregnancy. The pregnancy phase is marked by changes in hormonal, immunologic, and other physiologic responses. Although substantial evidence supports a pregnancy influence on tumor oncogenicity, the cumulative effect of the pregnancy state on brain tumor biology remains elusive. Furthermore, as innovative cancer treatments and surveillance technologies expand, providers must consider potential new risks to safe pregnancy maintenance. This article reviews pregnancy considerations in CNS tumor care and offers best practice approaches and considerations.
SUMMARY
Informed neuro-oncology practices on safer surgical, radiation, medical, device, and imaging techniques is of critical importance to pregnancy and fertility maintenance in cancer survivors. Expanding this knowledge relies on advocacy and a commitment to develop equitable and multidisciplinary research within the field. This also requires a focus on patient-reported outcomes and patient-centered conversations to best care for pregnant women with CNS tumors.
KEY POINTS
Nearly 60% of all intracranial and spinal cord tumors, including both primary and metastatic tumor types, malignant or benign, are diagnosed in women.
Brain cancer is among the rarest malignancies found during pregnancy, with a reported incidence comparable to the incidence in nonpregnant age-matched females.
Meningiomas account for almost 55% of all nonmalignant primary brain tumors and make up about 38% of all central nervous system tumors.
In adults, glioblastoma (World Health Organization grade 4) is the deadliest and most common primary brain malignancy (49%), comprising 14.5% of all primary brain tumors.
Overall, schwannomas do not have a known sex predilection; however, vestibular schwannomas are more common in women.
Prolactinomas are the most common hormone-secreting pituitary tumor and are 4.5 times more likely to occur in women.
Breast cancer brain metastases have increased in incidence secondary to improved diagnostic and surveillance technologies as well as to innovative cancer therapies that extend patient survival.
Breast cancer is the most reported cancer concurrent with pregnancy.
Multiple patient case series have reported that although pregnancy does not confer a higher risk for incidence of brain tumor, pregnancy is associated with worsening aggressive tumor behavior.
Vascular endothelial growth factor is highly expressed by specific brain tumors and regulates neoangiogenesis and vascular permeability; it is often targeted to limit brain tumor growth and complications such as vasogenic edema.
Follicle-stimulating hormone and luteinizing hormone are tumor inhibitory hormones, whereas progesterone has been implicated in worsening oncogenicity of several cancer types based on its role in regulating cell apoptosis, proliferation, and tumor metastasis.
The human immune response is more specialized in four vital compartments within the human body: the eyeball, the testis, the brain, and the gravid uterus.
Tolerance of neoantigens is a hallmark characteristic of immune-specialized compartments.
The maternal-fetal interface becomes a site for reeducation of immune cells to the new foreign fetal antigens.
Routine hemodynamic and cardiac monitoring of the mother and fetus over the course of the pregnancy may help prevent adverse pregnancy outcomes.
Noncontrast MRI with a lower than 3T magnet is the best modality for brain tumor imaging in pregnant women.
Head CT for brain tumor imaging during pregnancy is contraindicated as it uses ionizing radiation, a carcinogen, and is reserved for emergent scenarios (eg, hemorrhage or acute stroke) in which the benefit to the mother outweighs the risk to the fetus.
Tumor grade, anatomic location, and tumor rate of growth are important for neuroclinical prognostication.
When considering neurosurgery for pregnant patients with central nervous system tumors, it is important to involve multidisciplinary experts to discuss the patient’s options for pregnancy maintenance or termination as well as any risks for future fertility.
The risk of neurocognitive dysfunction resulting from radiation therapy was higher in fetal exposures between 100 mGy and 500 mGy during the first trimester (6%) as compared to the second trimester (2%).
Targeted therapies and standard chemotherapies cross the placenta and may result in spontaneous abortion or other risks to the developing fetus, especially during the first trimester.
Tumor treating fields therapy has been demonstrated to be effective in extending patient survival when used in combination with standard chemotherapy and has received US Food and Drug Administration clearance for both recurrent and newly diagnosed glioblastoma.
Supportive care issues often arise in patients with brain tumors secondary to tumor treatment or tumor progression.
Steroids may be used during pregnancy for a variety of reasons, ranging from facilitation of fetal lung maturity in high-risk pregnancies to providing a safer alternative to anti-inflammatory or immunosuppressive therapies during pregnancy.
Newly diagnosed and recurrent brain tumors are frequently associated with vasogenic edema causing significant morbidity and require steroids as a temporary supportive care measure.
Although pregnancy is not specifically addressed in the guideline by the Congress of Neurological Surgeons, the recommending body, in general, does not recommend prophylactic use of antiseizure medications in patients with brain tumors.
Source:
Continuum 2022
------ MovementDisorders_CHOREA.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides an overview of the diagnostic and therapeutic approach to a patient with chorea. The phenomenology of chorea is described in addition to other common hyperkinetic movements that may be mistaken for or coexist with chorea. Chorea can be acquired or hereditary. Key historical and clinical features that can aid in determining the etiology are reviewed, and pharmacologic and nonpharmacologic treatment strategies are discussed.
RECENT FINDINGS
Clinical investigations are under way to target transcription and translation of the mutant huntingtin protein as a potential disease-modifying strategy in Huntington disease (HD). Additional heritable factors have been revealed through genome-wide association studies. Symptom-focused treatments for HD are are being studied, including a third vesicular monoamine transporter-2 (VMAT2) inhibitor for chorea attenuation and drugs to target irritability and cognitive impairment. Increased availability of genetic testing has led to increased awareness of HD mimics (eg, C9orf72 and IgLON5).
SUMMARY
Chorea is a relatively common hyperkinetic disorder with a broad differential. The first step in the approach to a patient with chorea is accurately defining the phenomenology. Once it has been determined that the patient has chorea, the investigation into determining an etiology can begin. Factors such as age of onset, time course, family history, unique clinical features, and imaging and laboratory findings can guide the diagnosis. Treatments for most causes of chorea are purely symptomatic, although it is important to recognize causes that are reversible or have disease-modifying interventions.
KEY POINTS
Chorea refers to random, irregular, purposeless movements that flow from one body part to the next.
Chorea is generalized in many patients; however, its localized distribution may act as an important diagnostic factor to determine the underlying etiology. For example, forehead involvement is more common in Huntington disease. Orobuccolingual chorea is more common in tardive syndromes.
Because the differential diagnosis for chorea is broad, it is generally helpful to begin by categorizing chorea as (1) inherited versus acquired and (2) childhood onset versus adult onset.
Clues to differentiate inherited choreas from acquired choreas include the timeline (acute, subacute, or chronic [>1 year]) and course (static, paroxysmal, or progressive).
Huntington disease is the most common cause of adult-onset hereditary chorea. It is imperative that genetic counseling occur before testing.
Huntington disease mimics or phenocopies include several inherited rare degenerative conditions and may be associated with the triad of chorea, dementia, and behavioral disturbances.
Pathogenic variants in ATN1 dentatorubral pallidoluysian atrophy are associated with characteristic MRI changes in the dentate, red nucleus, and pallidum.
Pathogenic variants in C9orf72 can mimic Huntington disease, but variable expression may also include amyotrophic lateral sclerosis and frontotemporal dementia.
Pathogenic variants in VPS13A cause chorea-acanthocytosis, with characteristic orobuccolingual chorea and acanthocytes on blood smear. McLeod syndrome is an X-linked form.
Chorea can result from abnormal mineral accumulation in the basal ganglia. This includes iron (neurodegeneration with brain iron accumulation), calcium (Fahr disease), and copper (Wilson disease), each of which may have corresponding MRI abnormalities.
Mutations in ADCY5 are associated with childhood hypotonia. The chorea that may develop worsens with sleep deprivation.
Paroxysmal disorders of chorea have characteristic triggers. Paroxysmal nonkinesigenic dyskinesia is triggered by stress, extremes of temperature, alcohol, or excitement. Paroxysmal kinesigenic dyskinesia episodes are shorter and more frequent and triggered by movement.
Sydenham chorea is the most common cause of chorea in childhood.
Antiphospholipid antibodies are associated with systemic lupus erythematosus, hypercoagulability, and chorea.
IgLON5 is an antibody that has been discovered recently in association with parasomnias but can be associated with cognitive impairment, gaze palsies, and chorea.
Structural or vascular lesions should be considered in cases of focal or hemibody chorea.
Dopaminergic medications and antidopaminergic medications can cause choreiform movements. Careful medication history and timeline of exposure are important.
Hyperglycemia is a common metabolic cause of acute-onset chorea associated with T1 signal change in the contralateral putamen on MRI.
It is important to determine whether chorea is troublesome or bothersome before initiating a medication. Anosognosia is not uncommon, especially in Huntington disease; therefore, collecting input from the patient and their care partner is essential.
Vesicular monoamine transporter-2 (VMAT2) inhibitors are the only class of medications currently approved by the US Food and Drug Administration for the treatment of tardive dyskinesia and/or chorea associated with Huntington disease.
Source:
Continuum 2022
------ Sleep_Evaluating_the_Sleepy_and_Sleepless_Patient.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article explains the clinical approach to patients presenting with sleepiness or sleeplessness in a neurologic practice setting. Addressing the patient’s sleep symptoms may help improve symptoms of their other underlying primarily neurologic disorder.
RECENT FINDINGS
New diagnostic modalities at home such as home sleep apnea testing have improved access and diagnosis of sleep apnea. Consumer health tracking devices have also helped patients focus on their sleep duration and quality, prompting them to bring their concerns to their neurologist.
SUMMARY
Like many neurologic disorders, a detailed history and physical examination are critical in the evaluation of patients with sleepiness or sleeplessness. Patients who have neurologic disorders are more likely to have poor-quality sleep. Questions about the patient’s sleep schedule or screening patients for common sleep disorders such as sleep apnea and restless legs syndrome (RLS) are useful to add to a typical neurologic evaluation to better recognize sleep disorders in this population. Polysomnography, home sleep apnea testing, multiple sleep latency tests, and actigraphy can be used with the available history and examination to determine the proper diagnosis and management plan for these patients.
KEY POINTS
Patients with neurologic conditions frequently have poor-quality sleep and unrecognized sleep disorders.
Excessive daytime sleepiness can lead to difficulties with school, work, and driving.
Beyond obtaining the history from the patient, it can be equally important to ask a bed partner or other collateral source about the patient’s level of alertness during the day or abnormal behaviors during sleep, as patients are not always fully appreciative of their level of sleepiness or aware of what is occurring while they sleep.
Patients should be getting a sufficient amount of sleep, at least 7 hours for adults, as insufficient sleep is the most common cause of excessive daytime sleepiness in the United States.
Patients reporting excessive daytime sleepiness should be asked about snoring, apneas, morning headaches, and nocturia, which are all common symptoms of obstructive sleep apnea.
Many medications used to treat neurologic conditions and other medical disorders can cause excessive daytime sleepiness.
Obesity, enlarged neck circumference, and high blood pressure are more commonly seen in patients with obstructive sleep apnea.
Abnormal findings on the cardiac, pulmonary, or neurologic examination place a patient at higher risk of sleep disorders such as sleep-disordered breathing (obstructive or central sleep apnea), sleep-related movement disorders, and parasomnias.
Sleep diaries in conjunction with actigraphy are helpful in evaluating duration and timing of sleep and critical for diagnosing circadian rhythm disorders and insufficient sleep syndrome.
Polysomnography can be helpful when evaluating patients for sleep-disordered breathing, hypersomnia, or abnormal movements during sleep. Polysomnography measures sleep time and the apnea-hypopnea index, which is used to make a diagnosis of sleep apnea.
Home sleep apnea tests can be useful in the evaluation of obstructive sleep apnea in adult patients who are considered at risk of moderate or severe obstructive sleep apnea based on history and examination and in those who do not have other neurologic or cardiopulmonary disorders that put them at risk of other sleep-disordered breathing.
The multiple sleep latency test (MSLT) is used to objectively measure hypersomnia and help make a diagnosis of narcolepsy. MSLTs demonstrating a mean sleep latency of 8 minutes or less and at least two sleep-onset rapid eye movement (REM) periods are found in patients with narcolepsy.
Gathering information about a patient’s bedtime, wake time, and sleep routine is critical in determining the cause of a patient’s insomnia or sleeplessness. This information can be obtained during the clinic visit but sometimes requires sleep logs or diaries collected over several days or weeks.
Neurologic and psychiatric disorders commonly cause insomnia. In addition, insomnia can be a side effect of many medications used to treat these disorders, and use and withdrawal of recreational drugs can also cause sleeplessness.
Polysomnography and home sleep apnea testing are not routinely used for the evaluation of insomnia unless the clinician is concerned about another sleep disorder such as obstructive sleep apnea or periodic limb movement disorder contributing to sleep complaints.
Consumer sleep trackers are not currently used in the routine evaluation of patients with sleep problems such as insomnia, although they may help increase awareness of the importance of sleep and may help patients start a conversation with their clinician.
Source:
Continuum Sleep 2020
------ DementiaNeurodegenerativeProcesses_MANAGEMENT_OF_DEMENTIA.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article describes an approach to managing patients following a diagnosis of dementia, including medical management, nonpharmacologic strategies, safety interventions, caregiver support, mobilization of community resources, and advanced care planning.
RECENT FINDINGS
Dementia clinical syndromes are frequently caused by mixed pathologies, leading to varied clinical presentations that include memory loss, behavioral changes, communication challenges, safety concerns, and loss of independent function. Medications for treating dementia currently target cognitive and behavioral symptoms, although disease-modifying therapies for Alzheimer disease may be making their way into widespread clinical practice soon. Identification and treatment of co-occurring medical problems, such as obstructive sleep apnea, adverse medication effects, mood disorders, hearing loss, pain, alcohol misuse, and vascular risk factors, may mitigate the impact of these conditions on cognitive decline. Mobilization of clinical and community-based interprofessional teams will ensure that people with dementia and their care partners have the expertise, support, and access to resources they need. Addressing goals of care early in the disease course will allow people with dementia to contribute to their care plan by expressing their wishes.
SUMMARY
Developing a structured approach to treating common causes of dementia and related comorbid medical conditions, identifying a local network of interprofessional clinical and community-based referrals, and providing readily available educational resources will help clinicians provide quality dementia care management that extends beyond the clinic visit. Encouraging patients and families to engage in clinical research will advance the identification of effective therapies, preventive strategies, and quality care models for the future.
KEY POINTS
Identification of key clinical and community-based interprofessional partners will help neurologists implement a comprehensive quality dementia care plan that extends beyond the clinic.
Recognition and treatment of common co-occurring medical problems, such as sleep and mood disorders, adverse medication effects, hearing loss, pain, and alcohol misuse, can significantly improve cognitive performance.
Obstructive sleep apnea is the most common primary sleep disturbance in older adults, and positive airway pressure treatment improves both sleep parameters and cognitive function in patients with Alzheimer dementia and obstructive sleep apnea.
Treating depression with nonpharmacologic and pharmacologic therapies may improve mood, agitation, and cognition in select patients with dementia.
Vascular risk factors contribute to the onset and progression of Alzheimer and vascular dementia, but it is not clear whether aggressively treating vascular risk factors will beneficially alter the progression of the clinical symptoms of dementia.
Deprescribing is an important therapeutic intervention similar to initiating clinically appropriate therapy and should be done in collaboration with the patient, care partner, and other clinical care providers.
US Food and Drug Administration–approved acetylcholinesterase inhibitors and the N-methyl-d-aspartate (NMDA) antagonist have been the mainstay of treatment for dementia, although disease-modifying therapies may soon be used in widespread clinical practice.
Key safety concerns for people with dementia, including driving, medication management, falls, kitchen safety, wandering, and firearm use, should be assessed on a regular basis, and care partners should develop management plans in conjunction with both the clinical and community-based interprofessional teams.
Engaging patients with dementia early in establishing goals of care while they can contribute to shared decision making and advanced care planning is critical.
Identifying basic educational resources, a point of contact for a local Area Agency on Aging, and local caregiver support groups will facilitate support of the patient and caregiver outside of the clinic setting.
Source:
Continuum 2022
------ Sleep_PediatricNeurology_Sleep-Wake_Disorders_in_Childhood.txt ------
ABSTRACT
PURPOSE OF REVIEW
The presentation of sleep issues in childhood differs from the presentation in adulthood and may be more subtle. Sleep issues may affect children differently than adults, and distinct treatment approaches are often used in children.
RECENT FINDINGS
Sodium oxybate was approved by the US Food and Drug Administration (FDA) in October 2018 for an expanded indication of treatment of sleepiness or cataplexy in patients with narcolepsy type 1 or narcolepsy type 2 aged 7 years or older, with side effect and safety profiles similar to those seen in adults. Restless sleep disorder is a recently proposed entity in which restless sleep, daytime sleepiness, and often iron deficiency are observed, but children do not meet the criteria for restless legs syndrome or periodic limb movement disorder.
SUMMARY
Children’s sleep is discussed in this article, including normal sleep patterns and effects of insufficient sleep. Sleep disorders of childhood are reviewed, including insomnia, obstructive sleep apnea, restless legs syndrome, parasomnias, narcolepsy, and Kleine-Levin syndrome. Children with neurologic issues or neurodevelopmental disorders frequently have sleep disorders arising from an interaction of heterogeneous factors. Further attention to sleep may often be warranted through a polysomnogram or referral to a pediatric sleep specialist. Sleep disorders may cause indelible effects on children’s cognitive functioning, general health, and well-being, and awareness of sleep disorders is imperative for neurologists who treat children.
KEY POINTS
Environmental cues, homeostatic sleep pressure, and individual differences in circadian rhythms help determine sleep timing.
The evolution in sleep schedules may follow brain maturation, with the sleep schedules of younger children providing more frequent opportunities for sleep-related memory consolidation.
The mechanisms by which sleep disorders or sleep restriction may impair development remain unclear.
Sleep disorders such as circadian rhythm disorder (delayed-phase type), restless legs syndrome, or obstructive sleep apnea can exacerbate insomnia, as can medical conditions such as asthma, psychiatric conditions such as depression or anxiety, or medication side effects.
No medications for the treatment of insomnia in children are approved by the US Food and Drug Administration, and the literature on their efficacy is limited.
The threshold for obtaining a polysomnogram should be low because symptoms may be subtle in children.
The American Academy of Sleep Medicine advises against the use of ambulatory sleep studies in children because further research is required to assess whether factors likely to be present in children, such as restless sleep, monitoring intolerance, frequency of arousal-based respiratory events requiring EEG electrodes for detection, and sleep fragmentation, may or may not reduce the validity of ambulatory sleep studies for the pediatric population.
A postoperative polysomnogram is advisable after adenotonsillectomy, especially if presurgical obstructive sleep apnea (OSA) was moderate to severe.
Restless sleep disorder is a newly proposed entity, in which restless sleep and daytime sleepiness are noted but children do not meet the criteria for restless legs syndrome (RLS) or periodic limb movement disorder. Restless sleep disorder is associated with iron deficiency.
Putative mechanisms for RLS include dopaminergic dysfunction and iron deficiency.
Specific populations of children may have a high rate of RLS or increased periodic limb movements, including children taking antidepressants, antipsychotics, or antiepileptic medications or children predisposed to anemia or uremia through chronic kidney disease, former preterm status, or autism.
Vitamin D deficiency may be a particularly important etiologic factor for RLS in children with skin tones with relatively higher concentrations of melanin.
Dopamine agonists should be used sparingly in children, because children appear to be even more likely to experience augmentation than adults.
Parasomnias seem to be relatively common in children with autism.
Conditions that promote arousal or sleep drive can increase the likelihood of parasomnias, such as OSA, periodic limb movement disorder, sleep deprivation, or sedating medications.
The frequency of parasomnias can be lessened by reducing sleep fragmentation, such as by treating OSA or periodic limb movement disorder, and by obtaining adequate sleep.
Safety measures should be discussed for patients with parasomnias, such as locking doors and windows, restricting access to weapons or sharp objects, placing gates on stairs, and possibly installing door alarms to alert others in the household.
In children, it is unclear to what degree narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia are distinct entities.
An autoimmune-induced loss of orexin (hypocretin) neurons in the lateral hypothalamus is thought to be the primary cause of narcolepsy, with resulting instability of sleep-wake states.
The fundamental complaint of patients with narcolepsy is sleepiness that exceeds expectations for a given sleep duration.
Particularly in children, cataplexy can be atypical, with mouth opening, tongue protrusion, and stuttering speech, sometimes with such frequent clustering that episodes present as apparent facial weakness, and sometimes lacking a clear emotional trigger.
Active motor phenomena with a degree of emotional triggering have been described soon after narcolepsy onset in children, including eyebrow-raising, perioral and tongue movements, facial grimacing, body swaying, and stereotyped motor behavior.
Multiple comorbidities have been associated with narcolepsy, including anxiety, depression, thyroid disorders, hypertension, OSA, peripheral neuropathy, headaches, and glucose intolerance.
The first step in establishing a diagnosis of narcolepsy is recognizing a concerning level of hypersomnia and referring patients to a pediatric sleep specialist experienced in treating patients with narcolepsy.
Historical details that identify concerning hypersomnia in children include falling asleep unintentionally, resuming napping, taking multiple daily naps, or struggling to complete homework despite adequate sleep duration.
Diagnosing narcolepsy in children can sometimes be challenging and confounded by testing limitations.
The most common symptomatology of Kleine-Levin syndrome encompasses the tetrad of hypersomnia, confusion, apathy, and derealization.
Menstrual-associated hypersomnia is considered a variant of Kleine-Levin syndrome.
Medical or behavioral issues intrinsic to autism can compound sleep issues, such as epilepsy or gastrointestinal issues, medication side effects, bedtime resistance, or difficulty with self-soothing.
An intrinsic complexity underlies the sleep issues observed in children with neurodevelopmental issues, and multiple molecular mechanisms and sequelae may act in synchrony to affect sleep.
Source:
Continuum Sleep 2020
------ Early_use_of_corticosteroids_BellPalsy.txt ------
Early use of corticosteroids has been widely reported to increase the probability of recovery in patients with new-onset Bell palsy. When administered early, the addition of an antiviral agent to
a steroid may modestly further increase the probability of recovery. Antivirals alone, however, have no value in this setting. Neither physical therapy modalities nor facial nerve decompression has been shown to be of value for the treatment of acute Bell palsy. In the absence of a tick bite, erythema migrans rash, positive Lyme serology, or other clinical suggestion of Lyme disease, it is not appropriate to prescribe doxycycline for Bell palsy.
------ MovementDisorders_DIAGNOSIS_AND_MEDICAL_MANAGEMENT_OF_PARKINSON_DISEASE.txt ------
ABSTRACT
PURPOSE OF REVIEW
Parkinson disease (PD) is a common neurodegenerative movement disorder, the prevalence of which is rising as the world population ages. It may present with motor and nonmotor symptoms, and symptomatic treatment significantly improves quality of life. This article provides an overview of the workup and differential diagnosis for PD and reviews genetic and environmental risk factors and current treatments.
RECENT FINDINGS
Novel treatments for the motor (eg, fluctuations and off times) and nonmotor (eg, hallucinations and orthostatic hypotension) complications of PD have been approved in recent years. In addition, with recent advances in our understanding of the genetics of PD, significant research is focusing on identifying at-risk populations and introducing genetically targeted interventions (precision medicine).
SUMMARY
PD is a heterogeneous neurodegenerative movement disorder. Affected individuals may receive substantial symptomatic relief from nonpharmacologic, pharmacologic, and surgical interventions. Although no intervention to modify the progression of PD is currently available, precision medicine and modulation of the immune system are a major focus of ongoing research.
KEY POINTS
Older age and male sex are the most established risk factors for Parkinson disease (PD). The most established environmental risk factor for PD is pesticide exposure.
The seven genes clearly associated with PD risk are SNCA, LRRK2, and VPS35 (dominant); PRKN, PINK1, and DJ-1 (recessive); and GBA (risk factor).
The definitive diagnosis of PD is based on pathology. The two key required criteria are atrophy of dopaminergic cells in the substantia nigra and accumulation of α-synuclein.
The clinical diagnosis of PD was historically based on motor symptoms. More recently, nonmotor symptoms were added to the criteria to improve accuracy.
Postural instability, which is a feature of parkinsonism, is not a part of the International Parkinson and Movement Disorders Society criteria for PD diagnosis as it usually appears at later stages of PD.
Clinical red flags raise suspicion to an alternative diagnosis, most often multiple system atrophy, progressive supranuclear palsy, or dementia with Lewy bodies.
The Hoehn and Yahr scale is often used to capture the severity and progression of motor symptoms of PD. The Movement Disorders Society Unified Parkinson’s Disease Rating Scale is used to quantify disease severity.
The diagnosis of PD is primarily clinical. Ancillary diagnostic tests can be useful when the clinical diagnosis remains unclear.
MRI or other structural imaging may detect causes of secondary parkinsonism, such as hydrocephalus or stroke.
Dopamine transporter single-photon emission computed tomography may be helpful in detecting dopamine deficiency but is less useful in tracking the progression of intermediate or advanced stages of PD or in distinguishing PD from other neurodegenerative parkinsonian syndromes.
Exercise and physical activity should be recommended for all patients with PD.
No evidence exists that early pharmacologic (eg, levodopa) treatment of Parkinson disease has disease-modifying properties. However, neither does evidence exist for the benefit of delaying pharmacologic treatment.
Comparing levodopa to dopamine agonists and monamine oxidase type B inhibitors has indicated that although all three therapies are efficacious, levodopa treatment is best tolerated and maximizes improvement in mobility scores.
When impulse control disorder occurs, reduction in the dosage of dopamine agonist therapy is warranted; however, this might be complicated by the development of a dopamine agonist withdrawal syndrome.
When motor symptoms advance, a key consideration is to reduce the motor off time and fluctuations. Continuous levodopa administration or deep brain stimulation should be considered.
Careful adjustment of the dopaminergic treatment is a logical first step in the treatment of nonmotor symptoms in PD.
Hallucinations in PD may significantly impair quality of life and limit the use of dopaminergic intervention. Careful management of hallucinations is indicated.
Although the link between rapid eye movement (REM) sleep behavior disorder and PD is well established, evidence on effective management of REM sleep behavior disorder is insufficient.
Source:
Continuum 2022
------ MultipleSclerosisDemyelinating_LEUKODYSTROPHIES.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews the most common leukodystrophies and is focused on diagnosis, clinical features, and emerging therapeutic options.
RECENT FINDINGS
In the past decade, the recognition of leukodystrophies has exponentially increased, and now this class includes more than 30 distinct disorders. Classically recognized as progressive and fatal disorders affecting young children, it is now understood that leukodystrophies are associated with an increasing spectrum of neurologic trajectories and can affect all ages. Next-generation sequencing and newborn screening allowthe opportunity for the recognition of presymptomatic and atypical cases. These new testing opportunities, in combination with growing numbers of natural history studies and clinical consensus guidelines, have helped improve diagnosis and clinical care. Additionally, a more granular understanding of disease outcomes informs clinical trial design and has led to several recent therapeutic advances. This review summarizes the current understanding of the clinical manifestations of disease and treatment options for the most common leukodystrophies.
SUMMARY
As early testing becomes more readily available through next-generation sequencing and newborn screening, neurologists will better understand the true incidence of the leukodystrophies and be able to diagnose children within the therapeutic window. As targeted therapies are developed, it becomes increasingly imperative that this broad spectrum of disorders is recognized and diagnosed. This work summarizes key advances in the leukodystrophy field.
Key Points
Adrenoleukodystrophy is associated with three distinct phenotypes: cerebral adrenoleukodystrophy, adrenomyeloneuropathy, and adrenal insufficiency (Addison only).
As newborn screening becomes more extensively available, the true incidence of each form of adrenoleukodystrophy will be better understood.
Cerebral adrenoleukodystrophy typically presents in school-age boys with attention and behavioral changes.
Themost common formofmetachromatic leukodystrophy presents in early childhood with a decline in gross motor function, but this decline can be preceded by a peripheral neuropathy or eye movement abnormalities, such as strabismus.
The landscape of metachromatic leukodystrophy will be rapidly changing with the development of metachromatic leukodystrophy-targeted therapies and the advent of newborn screening.
Aicardi-Goutières syndrome is an autoinflammatory disorder characterized by neurologic disability and evidence of multiorgan inflammation.
Early-onset Aicardi-Goutières syndrome is a mimic of congenital infection whereas later-onset Aicardi-Goutières syndrome can present similarly to acquired inflammatory conditions, such as acute disseminated encephalomyelitis (ADEM).
Type I Alexander disease is characterized by macrocephaly, developmental delay with prominent feeding issues, and vomiting.
Type II Alexander disease is characterized by autonomic dysfunction, eye movement abnormalities, and prominent bulbar symptoms.
Blood psychosine is a useful diagnostic biomarker in Krabbe disease.
Pelizaeus-Merzbacher disease can present with prominent nystagmus or stridor.
The stochastic decline observed in vanishing white matter disease can be triggered by environmental exposures, such as head trauma or infection.
The imaging findings in vanishing white matter disease often precede neurologic symptoms.
The neurologic features of POLR3-related leukodystrophy are often accompanied by endocrine abnormalities and abnormal dentition.
Cognitive function is less affected compared with motor function in most cases of TUBB4A-related disorders.
The systemic signs and symptoms of cerebrotendinous xanthomatosis often precede the neurologic dysfunction.
Canavan disease and Alexander disease can both be associated with macrocephaly
Source:
Continuum 2022
------ Neuroinfectious_HSV1encephalitistreatment.txt ------
A patient with a 4- to 5-day history of headache, malaise, personality change, anterograde memory deficit, and fever should be presumed to have HSV-1 encephalitis until proven otherwise. The most affected areas of the brain are the medial temporal and orbitofrontal lobes, although the cingulate gyrus is less commonly affected as well. The treatment of choice is acyclovir given IV at 10mg/kg every 8 hours for 3 weeks.
Source:
RITE 2017
------ CerebrovascularDisease_DIAGNOSTIC_EVALUATION_OF_STROKE_ETIOLOGY_1.txt ------
ABSTRACT
OBJECTIVE
Precise therapies require precise diagnoses. This article provides an evidence-based approach to confirming the diagnosis of ischemic stroke, characterizing comorbidities that provide insights into the pathophysiologic mechanisms of stroke, and identifying targets for treatment to optimize the prevention of recurrent stroke.
LATEST DEVELOPMENTS
Identifying the presence of patent foramen ovale, intermittent atrial fibrillation, and unstable plaque is now routinely included in an increasingly nuanced workup in patients with stroke, even as ongoing trials seek to clarify the best approaches for treating these and other comorbidities. Multicenter trials have demonstrated the therapeutic utility of patent foramen ovale closure in select patients younger than age 60 years. Insertable cardiac monitors detect atrial fibrillation lasting more than 30 seconds in about one in ten patients monitored for 12 months following a stroke. MRI of carotid plaque can detect unstable plaque at risk of being a source of cerebral embolism.
ESSENTIAL POINTS
To optimize the prevention of recurrent stroke, it is important to consider pathologies of intracranial and extracranial blood vessels and of cardiac structure and rhythm as well as other inherited or systemic causes of stroke. Some aspects of the stroke workup should be done routinely, while other components will depend on the clinical circumstances and preliminary testing results.
KEY POINTS
The stroke workup is the set of diagnostic tests performed to gain insight into modifiable risk factors and stroke mechanism. The stroke workup has fixed and variable components, the latter being contingent on clinical circumstances, initial testing, and therapeutic objectives.
Recent American Heart Association guidelines on secondary stroke prevention include an algorithm for performing an evidence-based diagnostic evaluation.
Three or more transient ischemic attacks in a 2-week period in the same arterial distribution suggest an unstable atherosclerotic plaque as a mechanism.
A stroke evaluation should include examining the patient for preceding strokes or transient ischemic attacks, atherosclerotic risk factors, head or neck trauma or radiation therapy, migraines, and a family history of stroke or dementia.
Nearly 5% of strokes, most of which are lacunar and infratentorial, have a National Institutes of Health Stroke Scale (NIHSS) score of 0. Although these strokes are usually not treated with thrombolytics, they are nonetheless important to recognize because the stroke recurrence rates for NIHSS 0 and non-0 strokes are very similar.
Nearly 7% of acute ischemic strokes do not have a focal area of restricted diffusion on initial diffusion-weighted imaging. Patients with posterior circulation stroke are 5 times as likely to have diffusion-weighted imaging–negative stroke as patients with anterior circulation stroke.
CT angiography in the oblique and axial planes is the imaging modality of choice for identifying carotid webs.
Long-term cardiac rhythm monitoring detects severalfold more cases of atrial fibrillation than routine inpatient monitoring following a stroke (12.1% versus 1.8%), although the minimum burden of intermittent atrial fibrillation to justify anticoagulation remains uncertain.
Transesophageal echocardiography may be less sensitive in detecting patent foramen ovale than contrasted transthoracic echocardiography.
To diagnose embolic stroke of undetermined source, patients should have a stroke workup that includes, at a minimum, brain imaging, ECG, transthoracic echocardiography, cardiac monitoring for at least 24 hours, and imaging of both intracranial and extracranial arteries.
The yield of testing for genetic stroke syndromes is much higher when patients have a positive family history or a plethora of recurrent strokes and a paucity of conventional risk factors, particularly if the strokes are due to small vessel disease.
Patients with aseptic cerebral venous thrombosis should be screened for thrombophilia.
A C-reactive protein level higher than 10 mg/L should raise suspicion for stroke caused by endocarditis.
Source:
Continuum April 23
------ DementiaNeurodegenerativeProcesses_VASCULAR_COGNITIVE_IMPAIRMENT_AND_DEMENTIA.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article gives a broad overview of vascular cognitive impairment and dementia, including epidemiology, pathophysiology, clinical approach, and management. Emphasis is placed on understanding the common underlying types of cerebrovascular disease (including atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy) and awareness of rare inherited cerebrovascular disorders.
RECENT FINDINGS
The pathophysiology of vascular cognitive impairment and dementia is heterogeneous, and the most recent diagnostic criteria for vascular cognitive impairment and dementia break down the diagnosis of major vascular dementia into four phenotypic categories, including subcortical ischemic vascular dementia, poststroke dementia, multi-infarct dementia, and mixed dementia. Control of cardiovascular risk factors, including management of midlife blood pressure, cholesterol, and blood sugars, remains the mainstay of prevention for vascular cognitive impairment and dementia. Cerebral amyloid angiopathy requires special consideration when it comes to risk factor management given the increased risk of spontaneous intracerebral hemorrhage. Recent trials suggest some improvement in global cognitive function in patients with vascular cognitive impairment and dementia with targeted cognitive rehabilitation.
SUMMARY
Thorough clinical evaluation and neuroimaging form the basis for diagnosis. As vascular cognitive impairment and dementia is the leading nondegenerative cause of dementia, identifying risk factors and optimizing their management is paramount. Once vascular brain injury has occurred, symptomatic management should be offered and secondary prevention pursued.
KEY POINTS
Vascular cognitive impairment and dementia refers to cognitive impairment or dementia that results from vascular brain injury. Vascular brain injury refers to damage to brain parenchyma resulting from ischemia, infarction, and hemorrhage.
The most common risk factors for vascular cognitive impairment and dementia are cardiovascular risk factors, including hypertension, hyperlipidemia, type 2 diabetes mellitus, smoking, and atrial fibrillation.
Vascular dementia is traditionally thought to be the second most common cause of dementia in the United States, comprising approximately 15% to 20% of clinically diagnosed dementia cases in North America and Europe.
The probability of mixed dementia increases with increasing age, and the combination of multiple pathologies has been shown to be significantly correlated with the risk of clinical dementia.
The pathogenesis of vascular cognitive impairment and dementia may be proposed as follows: vascular risk factors lead to cerebrovascular disease that results in vascular brain injury, and disruption of cognitive networks due to vascular brain injury leads to vascular cognitive impairment and dementia.
Parkinsonism due to vascular brain injury may mimic idiopathic Parkinson disease, with bradykinesia, gait disturbance, and rigidity.
The Montreal Cognitive Assessment has been shown to capture deficits due to vascular brain injury with greater sensitivity than the Mini-Mental State Examination given its more robust measures of executive dysfunction.
The most common dementia mixed with vascular cognitive impairment and dementia is Alzheimer disease.
White matter changes associated with cerebral amyloid angiopathy can be virtually indistinguishable from those caused by cardiovascular risk factors.
The distinguishing clinical history with vascular cognitive impairment and dementia caused by cerebral amyloid angiopathy includes slowly progressive cognitive decline (as would be seen in Alzheimer dementia), episodic transient focal neurologic episodes (so-called amyloid spells), and sudden-onset focal neurologic deficits secondary to cortical lobar intracerebral hemorrhages.
A strong family history of vascular cognitive impairment and dementia without significant cardiovascular risk factors may be suggestive of CADASIL/CARASIL, which is important to identify given its implications for future generations.
Of the acquired dementias, vascular dementia is unique in that it has known modifiable risk factors and may, in fact, be nondegenerative if those risk factors are well controlled.
In late life or in people with significant confluent white matter hyperintensities (Fazekas scale grade 3) due to arteriolosclerosis, it seems prudent to maintain systolic blood pressure in the 120 mm Hg to 140 mm Hg range.
No strong evidence suggests that statins should be discontinued or avoided for concern of cognitive impairment, and rather, the known cardiovascular benefit of statin use argues in favor of continued statin use and low-density lipoprotein cholesterol reduction for secondary prevention.
Cerebral superficial siderosis has been found to be one of the greatest predictors of future intracerebral hemorrhage in patients with cerebral amyloid angiopathy.
Donepezil is considered to be of modest cognitive benefit for vascular dementia, and galantamine may be of modest cognitive benefit for patients with mixed Alzheimer/vascular dementia (Class IIa, Level A recommendation).
Source:
Continuum 2022
------ DementiaNeurodegenerativeProcesses_NEUROPATHOLOGY_OF_DEMENTIA_DISORDERS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides an overview of the neuropathology of common age-related dementing disorders, focusing on the pathologies that underlie Alzheimer disease (AD) and related dementias, including Lewy body dementias, frontotemporal dementia, vascular dementia, limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy (LATE), and mixed-etiology dementias. This article also discusses the underlying proteinopathies of neurodegenerative diseases (eg, amyloid-β, paired helical filament tau, α-synuclein, and TDP-43 pathology) and vascular pathologies, including tissue injury (eg, infarcts, hemorrhages) with or without vessel disease.
RECENT FINDINGS
New criteria for AD pathologic diagnosis highlight amyloid-β as the sine qua non of AD; they require molecular markers of amyloid and establish a minimum threshold of Braak neurofibrillary tangle stage 3. Pathologic diagnosis is separated from clinical disease (ie, pathologic diagnosis no longer requires dementia). TDP-43 pathology, a major pathology in a frontotemporal dementia subtype, was found as a central pathology in LATE, a newly named amnestic disorder. Multiple pathologies (often co-occurring with AD) contribute to dementia and add complexity to the clinical picture. Conversely, Lewy body, LATE, and vascular dementias often have accompanying AD pathology. Pathology and biomarker studies highlight subclinical pathologies in older people without cognitive impairment. This resilience to brain pathology is common and is known as cognitive reserve.
SUMMARY
The pathologies of dementia in aging are most commonly amyloid, tangles, Lewy bodies, TDP-43, hippocampal sclerosis, and vascular pathologies. These pathologies often co-occur (mixed pathologies), which may make specific clinical diagnoses difficult. In addition, dementia-related pathologies are often subclinical, suggesting varying levels of resilience in older people.
KEY POINTS
Alzheimer disease (AD) neuropathologic changes are defined by the accumulation of two key abnormal proteins, amyloid-β in the form of extracellular plaques and abnormally phosphorylated microtubule-associated protein tau in the form of neuronal neurofibrillary tangles.
The primary component of plaques is amyloid-β protein.
Adults with trisomy 21, or Down syndrome, commonly have brain accumulation of AD pathology beginning in the fifth decade of life or earlier.
Pathologically, people with the APOE ε4 variant have a greater accumulation of brain amyloid than those with other variants, and people with the less common ε2 variant have less amyloid-β than those with the ε3 variant.
In hemispheric cortical regions, two types of plaques are seen depending on the presence or absence of abnormally distended neurites: diffuse and neuritic. Plaques that have thickened processes that disrupt the brain neuropil are called neuritic plaques. Plaques without these thickened neuritic processes are referred to as diffuse plaques.
Diffuse plaques are commonly seen with neuritic plaques in the cerebral cortex, but they are typically the exclusive plaque type in subcortical and brainstem regions.
Neurofibrillary tangles, composed of abnormally phosphorylated tau protein in the form of paired helical filament neuronal tangles, are an essential pathologic feature of AD.
Current AD pathologic diagnosis also newly incorporates molecular pathology into traditional neuritic plaque and/or neurofibrillary tangle classifications. Specifically, the new National Institute on Aging–Alzheimer’s Association criteria for pathologic diagnosis of AD requires Thal amyloid phase in addition to Braak tangle stage and CERAD neuritic plaque stage.
Two dementia syndromes characteristic of Lewy body pathology are Parkinson disease dementia and dementia with Lewy bodies.
Over the years, the pathologic criteria for confirming the diagnosis of dementia with Lewy bodies have remained relatively stable; dementia with Lewy bodies is classified as nigral type disease, limbic predominant, and neocortical based on presence and/or severity of Lewy bodies in each of these regions.
TDP-43 proteinopathy was first described in frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis, but it was quickly revealed that TDP-43 pathology was also a prominent pathology in aging, often (but not always) accompanied by AD pathology.
The pathologic progression of limbic-predominant age-related TDP-43 encephalopathy (LATE) is divided into three stages. More than 90% of cases of hippocampal sclerosis of aging are associated with LATE.
The term hippocampal sclerosis is not descriptive of one disease but may be associated with one of several different pathologic processes, including temporal lobe epilepsy, hypoxic/ischemic brain injury, and neurodegenerative diseases of aging.
In aging and neurodegeneration, hippocampal sclerosis is most commonly associated with TDP-43 pathology (LATE neuropathologic changes) with or without concomitant AD or Lewy body disease pathology.
The pathologic substrates of vascular dementia include gross (lacunar or cystic) or microscopic infarcts and/or hemorrhages (lobar, deep, and microbleeds).
Small vessel disease is the most common underlying pathologic substrate for vascular cognitive impairment and dementia in aging.
AD is often considered the most common underlying pathology of dementia in aging; however, in the vast majority of older people with dementia, the etiology of the underlying dementia is related to the accumulation of multiple pathologies, including neurodegenerative and vascular pathologies.
Because multiple pathologies in the aging brain often contribute to cognitive impairment, most neuropathologists will report on all of the pathologies that potentially can be contributing to dementia.
FTLD is a distinct pathologic entity that is typically linked to a clinical diagnosis of frontotemporal dementia.
The distribution of the pathology in frontotemporal dementia, as the name implies, is frontal and temporal and often spares the hippocampus early in the disease, consistent with the lack of early memory impairment.
The two main pathologic types of FTLD are FTLD-TDP and FTLD-tau.
Depending on age and other cohort characteristics, about one-third of older individuals have a pathologic diagnosis of intermediate or high AD neuropathologic changes in their seventh decade of life despite having normal cognition proximate to death.
Cognitive resilience varies across individuals and may be related to genetics, pathology, or environment. Many other person-specific factors are important in cognitive resilience, including years of education, physical activity, cognitive activity, social activity, diet, and mood or anxiety disorders. Genetic factors are also likely to play an important role in cognitive resilience.
Neuronal neurofibrillary tangle pathology is not unique to AD and FTLD. It has also been described commonly in aging and is the central proteinopathy in chronic traumatic encephalopathy, progressive supranuclear palsy, and corticobasal degeneration.
Neuronal neurofibrillary tangles are nearly ubiquitous in the aging brain, specifically in the entorhinal and hippocampal cortices. The presence of tangles in the mesial temporal lobe in aging is referred to as primary age-related tauopathy (PART).
Chronic traumatic encephalopathy describes the specific pathology of the brain condition associated with multiple repetitive concussive and/or subconcussive hits to the head.
The neuronal neurofibrillary tangles in chronic traumatic encephalopathy show a specific perivascular pattern, especially in the depths of the cortical sulci of the frontal cortex.
Neuronal neurofibrillary tangles are a central pathology in both progressive supranuclear palsy and corticobasal degeneration, both atypical parkinsonian disorders.
Aging-related tau astrogliopathy is a common astrocytic pathology in older adults and those with AD.
Creutzfeldt-Jakob disease is a very rare rapidly progressive dementia caused by prion proteins. It is a unique disease as it may be infectious, genetic, or sporadic.
Huntington disease is a rare dominantly inherited neurodegenerative disease caused by mutations, specifically CAG (polyglutamine) expansion repeats, within the huntingtin gene (HTT) on chromosome 4.
Wernicke encephalopathy and Korsakoff syndrome, together known as Wernicke-Korsakoff syndrome, are related to thiamine deficiency. Often described in association with alcohol use disorder, Wernicke-Korsakoff syndrome is also observed in other causes of malnutrition and in liver disease.
AD, Lewy body disease, LATE, and vascular pathologies are the most common underlying pathologies in age-related dementias.
Source:
Continuum 2022
------ MovementDisorders_PRODROMAL_α-SYNUCLEINOPATHIES.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article describes prodromal α-synucleinopathies.
RECENT FINDINGS
The pathology underlying α-synucleinopathies, which include Parkinson disease, multiple system atrophy, and dementia with Lewy bodies, begins years before the presence of the full syndrome that is the basis for the clinical diagnosis of each of these disorders. This “prodromal” phase may manifest with various signs or symptoms. In addition to individuals in the prodromal phase, some individuals are asymptomatic but are at risk for α-synucleinopathies owing to genetic predisposition or other risk factors.
SUMMARY
Clinicians are increasingly seeing patients in the clinical setting who are prodromal or at risk for α-synucleinopathies, and this article reviews the approach to these patient populations, which includes identifying clinical features, assessment, and counseling.
KEY POINTS
In determining an individual’s risk for Parkinson disease, behavioral/environmental risk factors, signs and symptoms, and biomarker changes are best considered in combination.
Although several environmental and behavioral factors, including some medications, have been identified as increasing the risk of Parkinson disease, none of these medications should necessarily be prescribed or withheld from patients until further studies link these factors as being causal in Parkinson disease.
Both the clinical history and neurologic examination are an important part of the assessment of individuals who may be at risk or prodromal.
While dysautonomia is necessary for the diagnosis of multiple system atrophy, the presence of mild dysautonomia in someone with other prodromal features does not necessarily imply a multiple system atrophy diagnosis and can occur in people who develop Parkinson disease or dementia with Lewy bodies.
Rapid eye movement (REM) sleep behavior disorder that occurs in the absence of secondary causes (idiopathic or isolated REM sleep behavior disorder) is highly specific of future risk of Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.
Based on current evidence, use of biomarkers to identify individuals with prodromal features would be best confined to the research context and is not yet appropriate in the clinical setting.
Criteria for identifying prodromal Parkinson disease and prodromal dementia with Lewy bodies are useful for research but are not ready to be applied clinically for diagnostic or prognostic purposes.
Longitudinal follow-up of individuals who are prodromal or at risk for an α-synucleinopathy may show an evolution of parkinsonism, cognitive changes, and other signs and symptoms, which may culminate into the clinical syndromes that constitute diagnostic criteria for Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.
In individuals at risk or prodromal for an α-synucleinopathy, currently no treatments are proven to prevent progression to a diagnosed disorder. However, several modifiable risk factors have been identified, and basic risk factor reduction and modification should be instituted where appropriate.
Source:
Continuum
------ Epilepsy_MANAGEMENT_OF_STATUS_EPILEPTICUS_REFRACTORY_STATUS_EPILEPTICUS_AND_SUPER-REFRACTORY_STATUS_EPILEPTICUS.txt ------
ABSTRACT
PURPOSE OF REVIEW
Status epilepticus is a serious condition caused by disorders and diseases that affect the central nervous system. In status epilepticus, hypersynchronous epileptic activity lasts longer than the usual duration of isolated self-limited seizures (time t1), which causes neuronal damage or alteration of neuronal networks at a certain time point (time t2), depending on the type of and duration of status epilepticus. The successful management of status epilepticus includes both the early termination of seizure activity and the earliest possible identification of a causative etiology, which may require independent acute treatment. In nonconvulsive status epilepticus, patients present only with subtle clinical signs or even without any visible clinical manifestations. In these cases, EEG allows for the assessment of cerebral function and identification of patterns in need of urgent treatment.
RECENT FINDINGS
In 2015, the International League Against Epilepsy proposed a new definition and classification of status epilepticus, encompassing four axes: symptomatology, etiology, EEG, and age. Various validation studies determined the practical usefulness of EEG criteria to identify nonconvulsive status epilepticus. The American Clinical Neurophysiology Society has incorporated these criteria into their most recent critical care EEG terminology in 2021. Etiology, age, symptomatology, and the metabolic demand associated with an increasing duration of status epilepticus are the most important determinants of prognosis. The consequences of status epilepticus can be visualized in vivo by MRI studies.
SUMMARY
The current knowledge about status epilepticus allows for a more reliable diagnosis, earlier treatment, and improved cerebral imaging of its consequences. Outcome prediction is a soft tool for estimating the need for intensive care resources.
KEY POINTS
The outcome of status epilepticus depends on etiology, age, symptomatology, and duration of status epilepticus.
At time t1, the diagnosis of status epilepticus is established and therapy is started.
At time t2, treatment should be successful in preventing neuronal damage.
For convulsive (bilateral tonic-clonic) status epilepticus, time t1 is 5 minutes.
For focal status epilepticus with or without impairment of consciousness, time t1 is 10 minutes.
Unsuccessful therapy with a benzodiazepine and one antiseizure medication defines refractory status epilepticus.
The management of status epilepticus should be viewed as a process.
The changing symptomatology within one episode of status epilepticus is called evolution of symptomatology; the status epilepticus symptomatology that comes later determines outcomes.
The epidemiology of status epilepticus is determined by several factors.
The etiology of status epilepticus can be divided into symptomatic (acute, remote, progressive, and electroclinical syndromes) and cryptogenic.
Rare causes of status epilepticus include immunologically mediated disorders, mitochondrial diseases, uncommon infective disorders, genetic disorders, and drugs or toxins.
Status epilepticus and acute stroke share many features (eg, time is brain, the onset is often not witnessed, and both need a structured diagnostic and therapeutic approach).
Acute etiologies of status epilepticus may need a specific emergency treatment (eg, ischemic stroke).
The main reason for unsuccessful treatment of status epilepticus is underdosing.
The electro-paraclinical gap exists if the EEG findings cannot sufficiently be explained by imaging, laboratory, or toxicologic investigations.
The electro-paraclinical gap is a useful tool to diagnose nonconvulsive status epilepticus and to increase specificity.
The Salzburg diagnostic EEG criteria for nonconvulsive status epilepticus are part of the recent American Clinical Neurophysiology Society Standard Criteria for Critical Care EEG Terminology.
The impact of the burden model integrates structural damage and metabolic derangement, the burden of status epilepticus, the success and burden of treatment, and the impact of burden.
The amount of structural and metabolic reserves determines the optimal end point parameters in studies.
MRI is useful to demonstrate ictal hyperperfusion by arterial spin labeling in those with status epilepticus.
New-onset refractory status epilepticus (NORSE) is a form of a clinical presentation of refractory status epilepticus.
Febrile infection–related epilepsy syndrome (FIRES) denotes a condition in which a febrile infection preceded NORSE.
Data from patients with NORSE should be collected in international registries.
A predictive score should have at least a very high positive or negative predictive value.
Source:
Continuum 2022
------ Pregnancy_MATERNAL_STROKE_ASSOCIATED_WITH_PREGNANCY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article summarizes current knowledge of the epidemiology, pathophysiology, prevention, and treatment of cerebrovascular disease in pregnant and postpartum women.
RECENT FINDINGS
Stroke is a leading cause of maternal morbidity and mortality, and most fatal strokes are preventable. Adaptive physiologic changes of pregnancy, including hemodynamic changes, venous stasis, hypercoagulability, and immunomodulation, contribute to increased maternal stroke risk. The highest-risk time period for maternal stroke is the immediate postpartum period. Migraine and hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are major risk factors for maternal stroke. Adverse pregnancy outcomes, including gestational hypertension, preeclampsia, preterm delivery, and fetal growth restriction, are important risk factors for cerebrovascular disease later in life.
SUMMARY
Many catastrophic maternal strokes could be avoided with targeted prevention efforts, early recognition of warning signs, and rapid evaluation of neurologic symptoms. Neurologists play a central role in the care of pregnant patients with cerebrovascular disease, whether acute or chronic, and should be familiar with the unique and complex physiology of pregnancy and its complications, particularly hypertensive disorders of pregnancy.
KEY POINTS
The incidence of stroke in women during pregnancy and the postpartum period is approximately triple the incidence of stroke in nonpregnant women of similar age.
The majority of maternal strokes occur postpartum, often after discharge home following delivery, and up to half are hemorrhagic.
Migraine and hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are important risk factors for maternal stroke.
The adaptive physiologic changes of pregnancy, including hemodynamic changes, venous stasis, hypercoagulability, and immunomodulation, can contribute to increased stroke risk.
Common pregnancy-associated stroke mechanisms include cardioembolism, cervical artery dissection, cerebral venous thrombosis, cerebral vasospasm or subarachnoid hemorrhage due to reversible cerebral vasoconstriction syndrome, and hypertensive intracerebral hemorrhage, often in association with posterior reversible encephalopathy syndrome.
Despite the term reversible in their names, reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome can lead to severe disability or death if complicated by ischemic stroke or intracerebral hemorrhage.
Pregnant or postpartum women who develop cerebral venous thrombosis should be evaluated for underlying hypercoagulable disorders; pregnancy should not be assumed as the sole cause.
Migraine is associated with increased risk of preeclampsia and a 15-fold increase in risk of maternal stroke.
Proteinuria is no longer required for the diagnosis of preeclampsia; new severe headache or neurologic symptoms are considered disease-defining in the presence of new or worsening hypertension.
Hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and chronic hypertension with superimposed preeclampsia, affect up to 1 in 10 pregnancies.
Intracerebral hemorrhage is a leading cause of maternal mortality in patients with preeclampsia, and frequently, no underlying vascular lesion is identified.
No evidence shows that cesarean delivery decreases the risk of rupture of cerebrovascular lesions in pregnancy.
In selected patients with moyamoya, particularly those with recurrent transient ischemic attacks or decreased regional flow on brain imaging, surgical revascularization before pregnancy may decrease the risk of peripartum neurologic complications.
Women with elevated risk for maternal stroke should be counseled on stroke signs and symptoms and warned that the postpartum period is the highest-risk time point for stroke.
A history of stroke or cerebrovascular disease is not, in itself, an indication for cesarean delivery. Delivery planning should be based on obstetric considerations in most cases.
Red flag headache features in a pregnant or postpartum woman, such as lack of headache history, elevated blood pressure, very severe pain, or focal neurologic deficits, should prompt urgent neurologic evaluation.
When a pregnant woman presents with acute disabling neurologic deficits, CT is usually the fastest and most accessible imaging modality and thus is preferred. CT angiography should be performed in pregnant patients with symptoms concerning for large vessel occlusion.
Current guidelines for acute ischemic stroke do not consider pregnancy to be a contraindication to IV thrombolysis if the deficits are disabling and the bleeding risks are acceptable.
Poststroke depression may be exacerbated by the pregnant or postpartum state, particularly if the pregnancy had an adverse outcome, and early involvement of psychiatry is recommended.
Adverse pregnancy outcomes, including hypertensive disorders of pregnancy, preterm delivery, and fetal growth restriction, are associated with higher risk for future cerebrovascular disease, including stroke and vascular cognitive impairment.
Neurologists who treat young women should screen them for a history of pregnancy complications; for women who have experienced pregnancy complications, how to reduce future stroke risk and optimize brain health should be discussed.
Source:
Continuum 2022
------ Neuro_acutedystonicreaction.txt ------
Acute dystonic reactions are often observed after treatment with potent dopamine D2-receptor antagonists, including metoclopramide. Cervical and limb dystonia are most common. Laryngeal dystonia may be a life-threatening form of dystonic reaction in these patients. Anticholinergic medication, including diphenhydramine, is the most appropriate treatment.
Source:
RITE 2017
------ Sleep_Parasomnias_Occurring_in_Non_Rapid_Eye_Movement_Sleep.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses the clinical manifestations, diagnosis and differential diagnosis, pathophysiology, and management of parasomnias occurring in non–rapid eye movement (REM) sleep.
RECENT FINDINGS
Disorders of arousal are characterized by dissociated sleep, with wake and sleep phenomena intermingling, and local sleep, in which different areas of the brain exist simultaneously in different states of wakefulness or sleep. The frequency of arousals from slow-wave sleep with delta or mixed-frequency activity has a high sensitivity but relatively low specificity for the diagnosis of arousal parasomnias.
SUMMARY
Disorders of arousal (sleepwalking, sleep terrors, and confusional arousals) are characterized by incomplete awakenings from slow-wave sleep, limited recall of imagery, and partial or complete amnesia. They occur most frequently in childhood. Management includes correction of precipitating factors, attention to safety, behavioral techniques, and medications. Sleep-related eating disorder is a variant of arousal disorders and may be associated with the use of short-acting hypnotics and restless legs syndrome. Complex nocturnal visual hallucinations can occur with visual loss, dementia with Lewy bodies, use of β-adrenergic receptor antagonists, and anxiety. Exploding head syndrome occurs at wake-sleep transition or on waking during the night, is usually benign, and requires treatment only if significant sleep disruption occurs.
KEY POINTS
Disorders of arousal (sleepwalking, sleep terrors, and confusional arousals) share fundamental characteristics: incomplete awakening from slow-wave sleep usually in the first half of the night, limited recall of imagery, unresponsiveness to attempts to intervene, and partial or complete amnesia for events.
Violent behavior during arousal parasomnias is rare, but occasionally patients may injure themselves or others, usually if the victim attempts to restrain the patient.
Sexsomnias (sexual behaviors during sleep) are a variant of sleepwalking; they are more common in men and potentially associated with medicolegal consequences.
The lifetime prevalence of sleepwalking is about 7%. Approximately 20% of childhood sleepwalkers sleepwalk as adults, whereas the prevalence of de novo sleepwalking in adults is probably less than 1%.
The pathophysiology of disorders of arousal involves dissociated sleep, in which behaviors occur during abnormal states overlapping between wakefulness and slow-wave sleep. During episodes, certain areas of the brain show sleep phenomena (local sleep), whereas other regions appear awake.
Precipitating factors for disorders of arousal include those that deepen slow-wave sleep (eg, sleep deprivation, shift work) and those that fragment sleep (eg, noise, stress, and medical disorders such as sleep apnea).
Sodium oxybate and benzodiazepine receptor agonists such as zolpidem can precipitate disorders of arousal, but evidence for other medications is weak.
Disorders of arousal are usually diagnosed clinically, but video-EEG polysomnography may be needed if uncertainty exists about the diagnosis, an additional sleep disorder such as sleep apnea is suspected, or behaviors are associated with violence.
It is essential to review the video on a polysomnogram whenever an arousal from non–rapid eye movement (REM) sleep occurs, as the EEG findings in disorders of arousal are nonspecific and confusional arousals may be subtle and missed by the recording technologist.
The differential diagnosis of disorders of arousal includes nocturnal seizures, REM sleep behavior disorder, nightmares, and nocturnal panic attacks.
Management of disorders of arousal includes reassurance, correction of precipitating factors, addressing safety, behavioral therapies, and medications such as clonazepam.
Sleep-related eating disorder is a variant of arousal parasomnias in which patients eat often unusual combinations of high-caloric food with complete or partial loss of awareness.
Sleep-related eating disorder is associated with sleepwalking, restless legs syndrome, and the use of zolpidem and similar hypnotics.
Management of sleep-related eating disorder includes controlling restless legs syndrome; discontinuation of short-acting hypnotics; and the use of medications such as clonazepam, selective serotonin reuptake inhibitors, or topiramate.
Complex nocturnal visual hallucinations are vivid images on waking during the night, usually involving immobile people or animals with distorted appearances that vanish if the lights are switched on.
Etiologies of complex nocturnal visual hallucinations include diminished visual acuity (Charles Bonnet syndrome), dementia with Lewy bodies, midbrain or thalamic infarcts (peduncular hallucinations), narcolepsy, the use of β-adrenergic receptor antagonists, and anxiety disorders.
The differential diagnosis of complex nocturnal visual hallucinations includes hypnagogic or hypnopompic hallucinations, nightmares, REM sleep behavior disorder, epileptic seizures, and visual migraine auras.
Exploding head syndrome is characterized by a sudden loud noise or painless explosion in the head occurring at either wake-sleep transition or on waking during sleep.
Exploding head syndrome is a benign parasomnia that should be differentiated from nocturnal headaches by the absence of pain; it generally requires no treatment unless sleep onset or continuity is markedly impacted.
Source:
Continuum Sleep 2020
------ MuscleNeuromuscularJunction_LAMBERT-EATON_MYASTHENIC_SYNDROME_AND_BOTULISM.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and botulism, presynaptic disorders of neuromuscular transmission in which rapid diagnosis improves long-term outcomes.
RECENT FINDINGS
Therapy for LEMS has seen significant advances in recent years due to the approval of amifampridine-based compounds. LEMS is likely still underdiagnosed, particularly when no underlying malignancy is identified. Clinicians must have a strong suspicion for LEMS in any patient presenting with proximal weakness and autonomic dysfunction. Botulism is another rare disorder of presynaptic neuromuscular transmission that is most commonly associated with improper storage or preservation of food products. Over the past 2 decades, wound botulism has been increasingly reported among users of black tar heroin. A high degree of clinical suspicion and electrodiagnostic studies can be beneficial in distinguishing botulism from other acute neurologic disorders, and early involvement of state and federal health authorities may assist in confirming the diagnosis and obtaining treatment. When botulism is suspected, electrodiagnostic studies can provide clinical evidence of disordered neuromuscular transmission in advance of serologic confirmation, and providers should not wait for confirmation of the diagnosis to initiate treatment.
SUMMARY
A targeted clinical history and a thorough neurologic examination with support from serologic and electrodiagnostic studies are key to early diagnosis of LEMS and botulism. Early diagnosis of both conditions creates opportunities for therapy and improves outcomes.
KEY POINTS
Lambert-Eaton myasthenic syndrome is associated with pathogenic P/Q-type voltage-gated calcium channel antibodies that impair the release of acetylcholine vesicles at the presynaptic neuromuscular junction.
Presynaptic defects of neuromuscular transmission can cause weakness and autonomic dysfunction.
Malignancy, particularly small cell lung cancer, is identified in over 50% of patients with Lambert-Eaton myasthenic syndrome.
Lambert-Eaton myasthenic syndrome is a rare disease with worldwide prevalence of approximately 2.8 cases per million individuals.
Misdiagnosis of Lambert-Eaton myasthenic syndrome is frequent because of the lack of awareness and confusion with other more common diseases.
Lambert-Eaton myasthenic syndrome is a treatable condition, and most patients improve with appropriate therapy.
Lambert-Eaton myasthenic syndrome is characterized by a clinical triad of proximal muscle weakness, autonomic dysfunction, and areflexia/hyporeflexia.
Patients may not voluntarily disclose autonomic symptoms, particularly dry mouth, orthostatic hypotension, constipation, and erectile dysfunction.
Symptoms of Lambert-Eaton myasthenic syndrome are often disproportionate to clinical examination abnormalities.
Routine nerve conduction studies and EMG are necessary to narrow the differential diagnosis of Lambert-Eaton myasthenic syndrome.
Electrodiagnostic features of Lambert-Eaton myasthenic syndrome include low-amplitude compound muscle action potentials with incremental increases with repeated stimulation and facilitation following 10 seconds of maximal exercise on 2-Hz to 3-Hz repetitive nerve stimulation.
Malignancy screening should be performed for a minimum of 2 years after diagnosis of Lambert-Eaton myasthenic syndrome.
Symptomatic therapies are first line for Lambert-Eaton myasthenic syndrome and include forms of amifampridine.
Pyridostigmine augments the effects of amifampridine and may improve some autonomic symptoms.
IV immunoglobulin and therapeutic plasma exchange can be used in severe cases of Lambert-Eaton myasthenic syndrome that are unresponsive to symptomatic therapy.
Treatment of underlying malignancy reduces symptoms in cancer-associated Lambert-Eaton myasthenic syndrome.
Immunosuppressive and immunomodulatory therapies such as corticosteroids, azathioprine, and mycophenolate can be used in patients with nontumor Lambert-Eaton myasthenic syndrome who have inadequate control with symptomatic therapies.
Botulism is characterized by a toxidrome of acute, afebrile, descending weakness and autonomic dysfunction.
Botulinum neurotoxin irreversibly binds to presynaptic neurons and cleaves soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins to prevent formation of the synaptic fusion complex and release of acetylcholine vesicles.
Intoxication with botulinum toxin is most commonly due to serotypes A, B, and E.
Sources of botulinum toxin transmission include food, wounds, toxicoinfection, and others (including iatrogenic).
Early botulism may present with limited symptoms, and it is important to look for signs of clinical weakness involving craniobulbar muscles and autonomic dysfunction.
Infant botulism classically presents as “floppy baby.”
An acute, descending paralysis without fever and sensory symptoms should raise suspicion for botulism.
Confirmation of botulism requires identification of the neurotoxin and is performed in collaboration with the Centers for Disease Control and Prevention and state health departments.
Providers should notify state health authorities and the Centers for Disease Control and Prevention immediately when botulism is suspected to assist with source identification, coordination of diagnostic testing, and acquisition of therapeutics.
Moderate, long-lasting postactivation facilitation on 2-Hz to 3-Hz repetitive nerve stimulation and an absence of postactivation exhaustion are key electrodiagnostic features of botulism.
A human immunoglobulin is available for infants and equine heptavalent botulinum antitoxin is available for adults through the Centers for Disease Control and Prevention.
Source:
Continuum 2022
------ Sleep_Neurobiology_and_Neuroprotective_Benefits_of_Sleep.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article outlines the neurocircuitry underlying sleep-wake and circadian physiology with a focus on the fundamental roles that sleep and circadian health play in optimal neurologic function.
RECENT FINDINGS
The foundation of sleep and wake promotion is laid primarily by the “fast-acting” neurotransmitters: γ-aminobutyric acid (GABA) for sleep and glutamate for wake. External to these primary systems are a host of modulatory systems that are characterized by two flip-flop switches of mutually inhibitory neurotransmitter systems that facilitate transitions between wake and sleep as well as non–rapid eye movement (non-REM) and REM sleep. Additional mechanisms are in place to help coordinate the sleep-wake states with environmental, metabolic, and behavioral demands. The complexity of the evolutionarily preserved sleep-wake and circadian systems, the proportion of the day dedicated to the natural sleeping period, as well as the neurocognitive dysfunction and neurodegeneration caused by deficient sleep highlight the importance of defining, assessing, and optimizing the sleep health of our patients and ourselves.
SUMMARY
Exciting discoveries continue to elucidate the underlying mechanisms of sleep and wake state coordination, reinforcing fundamental healthy practices and paving the way for new interventions that preserve and promote optimal neurologic health.
KEY POINTS
All stages of sleep are essential, are actively promoted, and will homeostatically rebound if selectively deprived.
Sleep is dynamic, cycling through stages every 90 to 120 minutes, but also changing from slow-wave predominant to REM predominant over the course of the night.
Sleep health is not just defined by the duration of sleep but also by schedule regularity, alignment with circadian biorhythms, and continuity/stability.
Monoamines (dopamine, norepinephrine, serotonin, and histamine) are modulatory neurotransmitters that promote wakefulness.
The “fast-acting” neurotransmitter, glutamate, is the backbone of the wake-promoting neurocircuitry. The parabrachial/precoeruleus and supramammillary nuclei are the primary wake-promoting glutamatergic centers.
The basal forebrain (using γ-aminobutyric acid [GABA] and acetylcholine) and ventral periaqueductal gray (using dopamine) also strongly promote wake.
A dorsal flow of acetylcholine pathways from the laterodorsal tegmental and pedunculopontine tegmental nuclei to the thalamus promotes cortical processing reflected by a desynchronized EEG.
Orexin (hypocretin) neurons in the lateral hypothalamus are critical to stabilization of the wake state and are virtually absent in individuals with narcolepsy type 1 due to immune-mediated destruction.
GABA is the primary neurotransmitter system involved in active sleep promotion. The main sources of GABA activity are the preoptic area and parafacial zone.
The acetylcholine system becomes active again during REM sleep, allowing for information to transit through the thalamus for cortical processing.
Melanin-concentrating hormone neurons in the lateral hypothalamus facilitate non-REM to REM transitions and promote REM sleep in the context of optimal environmental conditions.
There are two flip-flop switches modulating wake-sleep and non-REM to REM transitions through balances of mutual inhibition: the former is primarily composed of the preoptic area and the monoaminergic system, and the latter is primarily composed of the ventrolateral periaqueductal gray and the sublaterodorsal nucleus.
External to the intrinsic sleep-wake circuitry are processes—homeostatic and circadian—that adapt sleep to the needs of the organism.
A number of state-regulating substances have been identified, the most well-known of which is the sleep-promoting molecule adenosine, which strongly correlates with sleepiness and delta power in the EEG.
An approximately 24-hour (circadian) alerting signal promotes wakefulness during the day but dips in the latter half of the night to maintain sleep.
Light-transducing retinohypothalamic signals are integrated with other time-giving signals in the dorsomedial hypothalamus to align central biorhythms to behavioral and environmental inputs.
Blue light (like that from phone, computer, and television screens) suppresses the sleep-related hormone, melatonin, which begins to elevate 2 hours before habitual bedtime and peaks 2 to 3 hours before habitual wake time.
Allowing for the recommended age-appropriate sleep opportunity every night is essential to ensure optimal daytime neurocognitive function.
Chronic (partial) sleep deprivation of non-REM or REM sleep can result in dysfunction of multiple organ systems, ultimately resulting in death; both non-REM and REM sleep are essential.
Increased production and decreased clearance of toxic proteins—Aβ, tau, and α-synuclein—are a fundamental dimension of the neurodegenerative consequences of sleep/circadian deficiency.
Sufficient sleep is necessary to ensure that the brain and body properly allocate and restore energy stores.
Central neuroinflammation and peripheral immune-compromise are consequences of insufficient sleep.
Cytokines (eg, tumor necrosis factor α and interleukin 1β) are state-regulating substances that promote sleep in the setting of infection/inflammation.
Vigilance and attention are neurocognitive functions most vulnerable to impairment from acute and chronic sleep deprivation, likely as a consequence of microsleeps impinging into wakefulness.
Sleep is essential not only for reinforcing and associating important learning but also for eliminating extraneous and intrusive engrams.
The complex problem solving and emotionally charged content of REM/dream sleep is suggested to be essential for mood regulation.
Source:
Continuum Sleep 2020
------ fibromusculardysplasia_treatment.txt ------
Antiplatelet tx with aspirin is reasonable in patients with fibromuscular dysplasia
Source:
uptodate 2023
------ Epilepsy_PediatricNeurology_aeds_triggerabsenceseizures.txt ------
Rationale: Lamotrigine, phenytoin, and carbamazepine can trigger absence status in a child with absence epilepsy.
Source:
RITE 2021
------ Pregnancy_PREGNANCY_MANAGEMENT_IN_MULTIPLE_SCLEROSIS_AND_OTHER_DEMYELINATING_DISEASES.txt ------
ABSTRACT
PURPOSE OF REVIEW
Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs) are chronic autoimmune demyelinating conditions of the central nervous system often diagnosed in women of childbearing age. Therefore, safe family planning, pregnancy, and postpartum management are important considerations for many patients with MS or NMOSD.
RECENT FINDINGS
Many patients with MS can safely become pregnant and remain well throughout pregnancy and the postpartum period with guidance from specialists on treatment planning. During pregnancy, women with NMOSD may face some increased risk of both neurologic and obstetric complications. Recent attention has focused on evaluating the safety of pharmacologic agents during pregnancy and breastfeeding. Unfortunately, care disparities remain common in both MS and NMOSD, and recovery of function is often not optimally managed in the postpartum period.
SUMMARY
This article reviews the current state of knowledge on peripartum management in these neurologic conditions and offers practical considerations and case studies. When caring for women with MS and NMOSD of childbearing potential, treatment planning is important to optimize outcomes in both patient and newborn.
KEY POINTS
Many patients with multiple sclerosis (MS) can safely go through pregnancy and the postpartum period.
In patients with more serious and active neurologic disease and patients who experience health care disparities with poor access to neurologic or obstetric care, maternal pregnancy and postpartum outcomes are at risk.
In MS, postpartum MRI may reveal elevated inflammatory activity even in women deemed clinically stable and is a useful evaluation tool to decide on treatment selection.
Women with neuromyelitis optica spectrum disorder (NMOSD) face elevated risk of inflammatory activity both during and after pregnancy relative to prepartum and potentially greater pregnancy complications than the general population.
For both MS and NMOSD, there is a trend to use anti-CD20 therapies before pregnancy, which can provide clinical stability before conception, during pregnancy, and, potentially, postpartum.
Intrapartum and postpartum outcomes in patients with MS or NMOSD are linked to disease stability for a year preceding pregnancy.
Asking patients “Would you like to become pregnant in the next year?” allows for a screening assessment of the patient’s family planning needs to help guide the health care provider’s treatment and care plan.
Any form of contraception is safe for patients with MS or NMOSD.
In patients with demyelinating diseases, if pregnancy is not achieved after 3 to 6 months of optimal conception attempts, referral to a fertility clinic should be considered.
Many disease-modifying therapies are used in MS. A thorough understanding of prepregnancy washout and safety in pregnancy exposure recommendations is needed to optimize MS management.
To ensure complete elimination of products before conception, typically waiting at least 5 maximal half-lives is recommended (with the exception of teriflunomide, for which an accelerated washout protocol is recommended).
If natalizumab is continued into the mid to late third trimester, hematologic screening of the newborn is necessary because of an increased risk of transient thrombocytopenia and anemia in some newborns.
MRI without gadolinium can be obtained and compared to the preconception MRI in cases of new neurologic symptoms in pregnancy.
Methylprednisolone, prednisone, and prednisolone are preferred in pregnancy as they are inactivated by placental 11-β-hydroxysteroid dehydrogenase and therefore do not enter the fetal circulation.
Surveillance neuroimaging should be considered within the first few months postpartum to establish a new baseline.
Comprehensive evaluation of women with MS and NMOSD is recommended early postpartum and should include gait, balance, bladder, bowel, mood, fatigue, cognition, strength, pain, social supports, and neuroimaging review.
In MS, exclusive breastfeeding is protective against postpartum inflammatory activity.
Safety data suggest that both first-line self-injectable therapies (glatiramer and interferon beta) and IgG monoclonal antibodies (such as ocrelizumab and rituximab) are reasonable to consider during breastfeeding.
Women with MS and women with NMOSD may face disparities in their obstetric and neurologic care and outcomes. Care coordination between the two specialists is important.
Source:
Continuum Neurology of Pregnancy 2022
------ MovementDisorders_THE_DYSTONIAS.txt ------
THE DYSTONIAS
ABSTRACT
PURPOSE OF REVIEW
This article discusses the most recent findings regarding the diagnosis, classification, and management of genetic and idiopathic dystonia.
RECENT FINDINGS
A new approach to classifying dystonia has been created with the aim to increase the recognition and diagnosis of dystonia. Molecular biology and genetic studies have identified several genes and biological pathways involved in dystonia.
SUMMARY
Dystonia is a common movement disorder involving abnormal, often twisting, postures and is a challenging condition to diagnose. The pathophysiology of dystonia involves abnormalities in brain motor networks in the context of genetic factors. Dystonia has genetic, idiopathic, and acquired forms, with a wide phenotypic spectrum, and is a common feature in complex neurologic disorders. Dystonia can be isolated or combined with another movement disorder and may be focal, segmental, multifocal, or generalized in distribution, with some forms only occurring during the performance of specific tasks (task-specific dystonia). Dystonia is classified by clinical characteristics and presumed etiology. The management of dystonia involves accurate diagnosis, followed by treatment with botulinum toxin injections, oral medications, and surgical therapies (mainly deep brain stimulation), as well as pathogenesis-directed treatments, including the prospect of disease-modifying or gene therapies.
KEY POINTS
The term dystonia can be used as both a clinical descriptor of an abnormal posture, frequently with a twisting, patterned quality and a group of diseases, where dystonia is the main clinical feature.
The dystonias include idiopathic, genetic, acquired, and other causes. No reliable diagnostic test (outside of genetic testing) currently exists, as imaging and laboratory testing are typically normal in patients with dystonia.
Clinical features of dystonia include influence by voluntary action, overflow/mirror dystonia, and a “null point.” Sensory tricks should be specifically inquired about and assessed on examination.
Dystonia is classified based on clinical characteristics (age of onset, body distribution, temporal pattern, and associated clinical features) and etiology (underlying nervous system pathology or whether the condition is inherited, acquired, or idiopathic).
Nomenclature of genetic dystonias involves referring to the movement disorder type (including if combined) and gene name, not DYT locus, using recently updated criteria.
The diagnosis of dystonia is challenging. Common misdiagnoses occur in patients thought to have Parkinson disease, essential tremor, myoclonus, tics, functional (“psychogenic”) dystonia, headaches, and scoliosis.
Despite increasing recognition, limited data exist on dystonia epidemiology. Given the common misdiagnoses, the prevalence of dystonia may be up to 1 in 1000 individuals. There are age, sex, racial, ethnic, and geographic variations.
Adult-onset idiopathic focal/segmental dystonias are the most common dystonic conditions and infrequently generalize, although there may be progression over time. These include cervical, cranial, oromandibular, laryngeal, limb, and truncal dystonia.
Many genetic forms of dystonia exist. Genetic isolated dystonias are mainly autosomal dominant.
Autosomal recessive dystonia is much less common than autosomal dominant cases and should be suspected if there are multiple affected individuals within the same generation, but not in their parents, or parental consanguinity.
Combined dystonias involve dystonia and other movement disorders, frequently parkinsonism or myoclonus. Considerable clinical and genetic heterogeneity exists.
The paroxysmal dystonias/dyskinesias are rare disorders involving episodic hyperkinetic movements, including dyskinesia or dystonic movements. These are typically early-onset disorders arising in childhood or adolescence, occurring very rarely after age 18.
The first step of management requires accurate diagnosis. If an idiopathic (generally late-onset) dystonia is suspected, further diagnostic workup is not typically necessary.
Directed workup includes laboratory testing to rule out Wilson disease and neuroimaging followed by specific targeted testing, including genetic testing with concomitant genetic counseling.
Treatment of dystonia depends on the diagnosis (idiopathic versus genetic) and whether potential pathogenesis-directed treatments are available. Symptomatic medical therapy often involves botulinum toxin injections, oral medications, and rehabilitation, with deep brain stimulation considered for treatment-refractory cases or conditions where good evidence of efficacy exists.
Disorders for which pathogenesis-directed treatments are available include dopa-responsive dystonia, Wilson disease, the paroxysmal dyskinesias, and rare, complex metabolic dystonias. All young-onset cases should have a trial of levodopa to assess for dopa-responsive dystonia.
The goal of symptomatic therapy for dystonia is to provide relief from abnormal movements/postures, associated pain and discomfort, contractures or other orthopedic complications of sustained abnormal postures, and medical comorbidities, including neuropsychiatric symptoms. This should be individualized for each patient.
Treatment of drug-induced/tardive dystonia involves early diagnosis and discontinuation of the offending drug, discontinuation of anticholinergics, and specific antidyskinetic medications, with DBS considered in severe, refractory cases.
Botulinum toxin injections form the cornerstone of focal dystonia treatment. Serotypes A and B are approved for treatment. Patients generally receive injections every 12 weeks, although many patients experience a shorter duration of effect. Patients rarely develop neutralizing antibodies, and this can be assessed with a “frontalis test.”
Oral medications for dystonia treatment are generally considered in cases of generalized dystonia or more severe disease and are much better tolerated in younger patients. These mainly involve dopaminergic therapy, anticholinergics, baclofen, and benzodiazepines.
The paroxysmal dystonias/dyskinesia have specific treatments: Paroxysmal kinesigenic dystonia/dyskinesia is treated with anti-seizure medications, (typically carbamazepine or oxcarbazepine); paroxysmal nonkinesigenic dystonia/dyskinesia is typically treated with low-dose benzodiazepines; and paroxysmal exercise/exertion-induced dystonia/dyskinesia is treated with ketogenic diet, L-carnitine supplementation, and triheptanoin.
Noninvasive brain stimulation is a developing area of potential therapy for dystonia but has mainly been used for research purposes and includes transcranial magnetic stimulation and transcranial direct current stimulation.
Surgical treatments of dystonia include intrathecal baclofen pumps, ablative lesioning, and deep brain stimulation.
Focused ultrasound has evidence for efficacy for dystonia, although symptom recurrence is possible, requiring repeat lesioning. This is only approved for unilateral use.
DBS has potential advantages over focused ultrasound, including a more favorable side effect profile, the potential for reversibility, and the ability to adjust the stimulation direction and field. The main stimulation site is the globus pallidus internus; however, efficacy has also been demonstrated in targeting the subthalamic nucleus and thalamus. Cerebellar stimulation is currently under investigation.
Status dystonicus/dystonic storm is a medical emergency, fatal in 10%. Precipitants include infection, medication changes, or deep brain stimulation hardware failure. Management involves treating triggers and oral dystonia therapies followed by intensive care unit–level care and consideration of rescue deep brain stimulation.
Source:
Continuum 2022
------ status_epilepticus_management.txt ------
In a patient with status epilepticus, hypoglycemia should
be immediately considered as an underlying etiology, particularly in a patient with diabetes. If serum glucose is not immediately available or the value is uncertain, 50 mL of IV 50% dextrose should be administered concurrently with 100 mg of IV thiamine.
------ Epilepsy_SURGICAL_TREATMENTS_FOR_EPILEPSY.txt ------
ABSTRACT
PURPOSE OF REVIEW
More than 20 new antiseizure medications have been approved by the US Food and Drug Administration (FDA) in the past 3 decades; however, outcomes in newly diagnosed epilepsy have not improved, and epilepsy remains drug resistant in up to 40% of patients. Evidence supports improved seizure outcomes and quality of life in those who have undergone epilepsy surgery, but epilepsy surgery remains underutilized. This article outlines indications for epilepsy surgery, describes the presurgical workup, and summarizes current available surgical approaches.
RECENT FINDINGS
Class I evidence has demonstrated the superiority of resective surgery compared to medical therapy for seizure control and quality of life in patients with drug-resistant epilepsy. The use of minimally invasive options, such as laser interstitial thermal therapy and stereotactic radiosurgery, are alternatives to resective surgery in well-selected patients. Neuromodulation techniques, such as responsive neurostimulation, deep brain stimulation, and vagus nerve stimulation, offer a suitable alternative, especially in those where resective surgery is contraindicated or where patients prefer nonresective surgery. Although neuromodulation approaches reduce seizure frequency, they are less likely to be associated with seizure freedom than resective surgery.
SUMMARY
Appropriate patients with drug-resistant epilepsy benefit from epilepsy surgery. If two well-chosen and tolerated medication trials do not achieve seizure control, referral to a comprehensive epilepsy center for a thorough presurgical workup and discussion of surgical options is appropriate. Mounting Class I evidence supports a significantly higher chance of stopping disabling seizures with surgery than with further medication trials.
KEY POINTS
Drug-resistant epilepsy is diagnosed when a person continues to have seizures despite adequate trials of two appropriately chosen and well-tolerated antiseizure medications.
One-third of patients with epilepsy have drug-resistant epilepsy. Drug-resistant epilepsy is associated with higher rates of morbidity (eg, loss of independence, depression, worse quality of life) and mortality.
Epilepsy surgery evaluation is appropriate for anyone with focal disabling seizures that continue to occur despite treatment with two appropriately chosen antiseizure medications.
Evaluation for surgery begins at an established comprehensive epilepsy center, where the diagnosis of epilepsy is confirmed.
A presurgical evaluation is necessary to identify the cortical area that is generating seizures, which, when removed, will result in seizure freedom; this is known as the epileptogenic zone.
Video-EEG monitoring confirms the diagnosis of epilepsy type by recording the patient’s habitual seizures and correlates the patient’s reported symptomatology to aid in localization.
Abnormalities on initial brain MRI may be missed. Careful inspection by an expert neuroradiologist and the use of higher-resolution MRI scanners and positron emission tomography (PET) may identify subtle lesions (eg, dysplasia).
Neuropsychological testing and functional imaging help predict postoperative deficits and localize eloquent cortex.
Resective surgery may be possible without intracranial EEG studies if presurgical findings (eg, ictal and interictal EEG, seizure symptomatology, and MRI) are concordant to the nondominant temporal lobe.
The goals of intracranial EEG are twofold: (1) to further localize the epileptogenic zone and prove/disprove a hypothesis and (2) to determine the location of eloquent cortex with electrical stimulation.
Only 30% to 50% of epilepsy surgeries require intracranial EEG, which includes the use of stereotactic electrodes, subdural grid electrodes, or a combination of the two to aid in delineation of the epileptogenic zone.
Three Class I randomized controlled trials have shown the effectiveness of resective surgery compared to continued medical treatment in adults and children with drug-resistant epilepsy.
Different surgical options are available for drug-resistant epilepsy, including resection, laser ablation, and neurostimulation, which can be tailored to the specific patient.
Verbal memory deficits are the most consistent adverse effect following dominant (typically left) temporal resections when compared to nondominant resection.
Visual field deficits, most commonly a superior quadrantanopia, comprise half of all permanent neurologic deficits after temporal lobe resection and are generally well tolerated.
Surgery for lesional epilepsy, as defined by an unequivocal MRI abnormality responsible for seizures, is associated with better postoperative seizure outcome than nonlesional epilepsy.
The most common lesions associated with seizures include malformations of cortical development, focal cortical dysplasia, cavernous and arteriovenous malformations, and low-grade gliomas.
Laser ablation and stereotactic radiosurgery are minimally invasive options available in some centers for patients who are candidates for resection but do not want a craniotomy.
Three implantable neurostimulation therapies are now available for patients with drug-resistant epilepsy who undergo full surgical evaluation and are deemed poor candidates for resective surgery.
Responsive neurostimulation should be considered as a treatment option in those with seizures that arise from eloquent cortex and/or up to two suspected seizure foci.
Deep brain stimulation and vagus nerve stimulation are reserved as options for poorly localized epilepsy or multifocal epilepsy.
All three available neurostimulation devices are associated with seizure reduction, which improves over time. Rates of adverse events are low and typically perioperative or related to stimulation, which can be modified.
Source:
Continuum Epilepsy 2022
------ Pregnancy_NEUROMUSCULAR_DISORDERS_AND_PREGNANCY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides an overview of neuromuscular disorders in pregnancy, with a focus on diagnosis and management.
RECENT FINDINGS
Neuromuscular disorders with issues that occur in pregnancy include conditions that are acquired (including autoimmune) or genetic; each requires a unique approach to management and treatment prepartum, peripartum, and postpartum. Guidance in the literature regarding management and treatment options is predominantly from case series and retrospective reviews. Treatment can be complex, particularly in autoimmune neuromuscular diseases, because of the risks of side effects of the treatments that may affect the patient and fetus.
SUMMARY
This article summarizes expectations, diagnosis, and management for a wide range of neuromuscular disorders in pregnancy.
KEY POINTS
Treatment of Guillain-Barré syndrome in pregnant women is similar to treatment in nonpregnant patients. Both IV immunoglobulin (IVIg) and plasma exchange are considered to be safe.
Accurate diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy relies on clinical history, examination findings, and electrodiagnostic testing meeting European Federation of Neurological Societies/Peripheral Nerve Society criteria.
IVIg, plasma exchange, or corticosteroids can be used in treatment of chronic inflammatory demyelinating polyradiculoneuropathy during pregnancy, and IVIg is most effective for multifocal motor neuropathy.
If thiamine deficiency is suspected in pregnant women, treatment with vitamin repletion is recommended even while awaiting laboratory results for serum levels of vitamins as no significant harm exists in treatment. Treatment can be stopped if levels are found to be within normal limits.
Pregnancy outcomes in women with Charcot-Marie-Tooth disease have been found to be similar to women without the disease.
Supportive care is often all that is necessary for carpal tunnel syndrome in pregnancy. Resolution has variable timing.
Recovery from idiopathic brachial plexopathy may be partial and can take months to years.
Focal neuropathies associated with pregnancy often improve over time with supportive care.
Recurrence of facial nerve palsy in future pregnancies is rare.
Exacerbations of myasthenia gravis occur more often in the first trimester and postpartum.
Preconception counseling is very important to select the appropriate medications for treatment of myasthenia gravis.
It is typically advised not to initiate or stop steroid-sparing agents during pregnancy, except in unique circumstances, because of the potential risk of myasthenic exacerbations.
It is recommended to use antiseizure medications rather than magnesium in the treatment of eclampsia in women with myasthenia gravis.
It is recommended that women do not breastfeed while taking methotrexate or mycophenolate mofetil.
Women with muscular dystrophies generally have good pregnancy outcomes.
Rhabdomyolysis has not been reported during labor in patients with McArdle disease.
Neonatal outcomes for babies born to women with spinal muscular atrophy are generally good.
Source:
Continuum 2022
------ Headache_mig.txt ------
raine
Source:
------ DementiaNeurodegenerativeProcesses_BEHAVIORAL_VARIANT_FRONTOTEMPORAL_DEMENTIA.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews many of the complex facets of behavioral variant frontotemporal dementia (bvFTD) and frontotemporal lobar degeneration (FTLD). A particular focus is on improving diagnostic accuracy to reduce the arduous diagnostic odyssey that so many patients and families endure. Strategies to promote diagnostic accuracy and approach the management of problematic symptoms are also discussed.
RECENT FINDINGS
Although the International Consensus Criteria for bvFTD were published more than a decade ago and clinicopathologic studies have confirmed their utility, diagnostic confusion continues. This article presents updated data along with illustrative cases to emphasize the clinical pearls that are most useful for clinicians. Although accurate prediction of the underlying proteinopathy remains a challenge, the ability to differentiate bvFTD from atypical Alzheimer disease, psychiatric disorders, and other mimickers has improved. Knowledge about the genetic underpinnings in a significant minority of individuals with familial FTLD is enabling early and accurate diagnosis. Therapeutic optimism has also increased, particularly in familial FTLD, with a few clinical trials in progress and several more planned, some of which are designed to slow progression or delay the onset of symptoms, or both.
SUMMARY
The diagnosis and management of bvFTD is challenging for clinicians and particularly for patients and their families. Although much progress has been gained over recent years, several key research questions persist. Treatments that significantly improve symptoms or alter the course of FTLD remain elusive, but optimism is increasing as pathobiology is better understood and novel therapies are being developed.
KEY POINTS
The altered behavior and cognition during the prediagnosis and postdiagnosis phases of behavioral variant frontotemporal dementia (bvFTD) have many potential consequences, with profound repercussions for patients, their family members, and society.
At least 20% of patients with bvFTD or similar phenotype have a dominantly inherited familial disorder, with mutations being most common in the genes encoding microtubule associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72).
Applying the consensus criteria for bvFTD is useful in clinical practice.
The diagnostic odyssey of frontotemporal dementia (FTD) that many patients and families endure is often convoluted and prolonged.
Any patient with one or more of the following core clinical features should be considered as possibly having bvFTD: behavioral disinhibition; apathy or inertia; loss of sympathy or empathy; perseverative, stereotyped, or compulsive/ritualistic behavior; or hyperorality and dietary changes.
In the setting of suspected bvFTD, interviewing family members separately from the patient may be indicated to more thoroughly query about the core features.
Although no specific findings on laboratory testing of blood, urine, or CSF have yet been identified as characteristic of frontotemporal lobar degeneration (FTLD) pathology, the plasma and CSF biomarkers that are sensitive and specific for Alzheimer disease may aid in differentiating between Alzheimer disease and FTLD.
Neuropsychological test results in patients with suspected bvFTD are usually informative and support the initial clinical impression.
A normal profile or an atypical profile of impairment on neuropsychological testing should not dissuade the clinician from suspecting bvFTD if the history is very compelling.
A “typical bvFTD profile” of impairment on neuropsychological testing should not supersede other clinical features and biomarker findings when making a diagnosis of bvFTD.
Atrophy in the frontal and/or temporal lobes on brain CT or MRI, which can be symmetric or very focal/asymmetric, supports the diagnosis of bvFTD in the appropriate clinical setting. However, the absence of obvious atrophy in the frontal and/or temporal lobes on brain CT or MRI does not rule out bvFTD.
Atrophy in the frontal and/or temporal lobes on brain CT or MRI can be seen in other disorders, including in atypical AD.
Fludeoxyglucose positron emission tomography is reasonable in many patients with suspected bvFTD, particularly if the MRI findings are normal or only questionably consistent with FTD.
The clinical utility of molecular positron emission tomography (PET) imaging with amyloid and tau ligands is not fully defined; amyloid PET imaging may have a role in differentiating underlying Alzheimer disease from non–Alzheimer disease disorders in patients with a bvFTD-like presentation.
Clinical genetic counseling and testing for the known genetic mutations associated with FTLD is reasonable in those with bvFTD and a positive family history of dementia, parkinsonism, or amyotrophic lateral sclerosis, particularly in those with an autosomal dominant pattern of inheritance.
Clinical genetic counseling and testing for the known genetic mutations associated with FTLD may be reasonable in other select circumstances, such as in patients with very-early-onset bvFTD who do not have any known family history of a neurodegenerative disorder.
In the current practice environment with nonspecific biomarkers (except for genetic test results), it is not possible to predict with accuracy the underlying proteinopathy in anyone with bvFTD.
Management of symptoms is challenging in bvFTD, and clinicians should consider several nonpharmacologic and pharmacologic modes of management.
Source:
Continuum 2022
------ NervesandNeuropathy_Bellspalsy.txt ------
Numerous studies and reviews have documented that using steroids early on increases the probability of recovery in patients with new-onset Bell palsy. When used early on, the addition of an antiviral agent to a steroid may modestly further increase the probability of recovery. Antivirals alone have no value in this setting. Neither physical therapy modalities nor facial nerve decompression have been shown to be of value for the treatment of acute Bell palsy. In the absence of a tick bite, erythema migrans rash, positive Lyme serology, or other clinical suggestion of Lyme disease, it is not appropriate to prescribe doxycycline for Bell palsy.
Source:
RITE 2017
------ MultipleSclerosisDemyelinating_fingolimod_SEs.txt ------
Fingolimod interacts with sphingosine-1-phosphate receptor subtypes. Potential side effects include first-dose bradyarrhythmias,macular edema, increased hepatic transaminases, blood pressure elevations and mild decrease in one second forced expiratory volume.
Source:
RITE 2017
------ MovementDisorders_NEURODEGENERATIVE_CEREBELLAR_ATAXIA.txt ------
ABSTRACT
PURPOSE OF REVIEW
Neurodegenerative cerebellar ataxia is a diverse collection of diseases that are unified by gait and balance abnormalities, appendicular incoordination, and abnormalities of eye movement and speech. The differential diagnosis is broad, ranging from paraneoplastic syndromes that progress quite rapidly to unidentified genetic disorders that progress slowly over the course of decades. This article highlights the diagnostic process, including the differential diagnosis, as well as treatment approaches and symptomatic management. The pillars of treatment are physical, occupational, and speech therapy as well as counseling and discussions of disease prognosis, genetics, and reproductive choices. There are many ways to help patients with neurodegenerative cerebellar ataxia and improve their quality of life.
RECENT FINDINGS
Recent years have seen significant improvements in genetic testing, with reductions in cost of both Sanger sequencing and whole exome sequencing and increasing availability of the latter. These improvements increase clinicians’ ability to identify the etiology of neurodegenerative cerebellar ataxia and suggest future treatments. Although no medication has been approved by the US Food and Drug Administration (FDA) for treatment of cerebellar ataxia, research and clinical trials for these diseases are increasing.
SUMMARY
Neurodegenerative cerebellar ataxia is characterized by dysarthria, dysmetria, oculomotor abnormalities, and ataxic gait. It has a broad differential diagnosis, and numerous options exist for managing symptoms. Although no medications have been approved specifically for cerebellar ataxia, treatment options are available to improve patients’ quality of life.
KEY POINTS
Ataxia can be classified into three broad types: (1) sensory ataxia due to neuropathy in the feet; (2) vestibular ataxia due to dysfunction of the semicircular canals, otolith organs, or both; and (3) cerebellar ataxia due to dysfunction of the cerebellum.
The vermis is responsible for axial function, while the paravermis is responsible primarily for limb function.
Patients with cerebellar ataxia describe falls and clumsiness but often describe the initial symptoms as being difficulty maintaining balance on uneven ground, when going up or (primarily) down stairs, or when running.
Examination of individuals with cerebellar ataxia usually reveals a wide-based gait with some titubation observed, specifically on turns.
Speech, swallowing, and eye movement abnormalities are especially important for cerebellar localization, as these findings indicate that the lesion is above the spinal cord.
Eye movement changes, specifically downbeat nystagmus, square-wave jerks, and hypermetric or hypometric saccades, are often the best way to localize the patient’s ataxia to the cerebellum.
Individuals with cerebellar lesions often report difficulty meeting their target with their hands, while individuals with extrapyramidal lesions often report that their fingers will not do what their brain is asking.
Individuals with cerebellar ataxia without extrapyramidal involvement often demonstrate pauses and clumsiness on finger tapping, hand opening and closing, and pronation and supination but do not have a decrementing bradykinesia.
Individuals with what is known as cerebellar cognitive affective syndrome present with challenges in executive function, linguistic processing, and spatial cognition.
Absence of cerebellar atrophy does not change the localization, as an overall normal-sized cerebellum may be observed even among individuals with significant cerebellar dysfunction. The presence of cerebellar atrophy, though, helps to confirm the localization.
Testing for nongenetic and then genetic etiologies is an iterative process, circling back on each possibility to ensure that all reasonable and appropriate testing to identify the etiology has occurred.
When evaluating the results of blood work, it is important to distinguish between those results that are outside of normative values and those results that are actually diagnostic for the cause of the cerebellar ataxia.
For many of the genetically identified spinocerebellar ataxias, as well as other genetic diseases, in vitro fertilization with preimplantation genetic diagnosis allows for eradication of the genetic disease in the next generation.
If genetic testing is not successful in identifying the etiology of cerebellar ataxia, the next step is to evaluate for other diagnostic possibilities.
The most important principle in the treatment of neurodegenerative cerebellar ataxia is that although no disease-modifying therapy or even medications specifically approved to treat cerebellar ataxia are currently known, there is always something that can be done to improve the individual’s quality of life.
Exercise has been shown to improve ataxia motor symptoms and is critical to maintain function for as long as possible.
Swallowing difficulties may be treated by behavioral modifications or dietary changes, both of which have been shown to be effective.
Several therapies for neurodegenerative cerebellar ataxias are in earlier stages of development, increasing the possibilities for new symptomatic or even disease-modifying therapies in the future.
Source:
Continuum 2022
------ CerebrovascularDisease_INTRAVENOUS_THROMBOLYSIS_FOR_ACUTE_ISCHEMIC_STROKE.txt ------
ABSTRACT
OBJECTIVE
This article reviews the history of IV thrombolysis, its current indications and implementation, the duality of the “time is brain” versus “tissue clock” approaches, the impact of endovascular thrombectomy on IV thrombolysis, the emergence of tenecteplase, and future research directions.
LATEST DEVELOPMENTS
The growing use of factor Xa inhibitors has increasingly caused patients with stroke to be excluded from treatment with IV thrombolysis. Important geographic, socioeconomic, sex, race, and ethnic disparities have been identified in the implementation of IV thrombolysis and need to be overcome. IV thrombolysis substantially improves outcomes when provided within the first golden hour after stroke onset in patients treated in mobile stroke units, supporting the “time is brain” concept and encouraging the possible value of more widespread implementation of the mobile stroke unit approach. At the same time, other studies have shown that IV thrombolysis can be successful in patients whose “tissue clock” is still ticking up to 9 hours after stroke onset or in patients who awaken with their stroke, as demonstrated by favorable imaging profiles. These considerations, along with the emergence of endovascular thrombectomy, have fostered examination of our care systems, including the “drip and ship” versus direct to comprehensive or endovascular thrombectomy stroke center approaches, as well as the possibility of skipping IV thrombolysis in certain patients treated with endovascular thrombectomy. Data suggesting that tenecteplase is at least noninferior to alteplase, as well as its more convenient dosing, has led to its increased use. Ongoing studies are evaluating newer thrombolytics and adding antithrombotic therapy to IV thrombolysis.
ESSENTIAL POINTS
IV thrombolysis remains the most common acute stroke treatment. Advances in acting faster to treat stroke have increased its efficacy, and advances in imaging have expanded its use. However, implementing these advances and overcoming disparities in IV thrombolysis use remain major challenges.
KEY POINTS
Extensive clinical trial data and “real world” experience support the efficacy and safety of recombinant tissue plasminogen activator (rtPA) as the primary treatment for acute ischemic stroke.
An improving deficit or low National Institutes of Health Stroke Scale score does not exclude a patient from receiving rtPA if, after a careful neurologic history and examination, the stroke-related deficit would be disabling if it persisted without treatment.
While rtPA is approved by the US Food and Drug Administration (FDA) for only up to 3 hours after symptom onset, data and guidelines support its use for up to 4.5 hours after symptom onset.
The use of factor Xa inhibitors is an increasing cause of exclusion from treatment with IV thrombolysis.
Use of emergency department telestroke, bringing stroke treatment to the patient’s home via mobile stroke units, improved telecommunication, and other devices will help increase the use of IV thrombolysis.
There are many disparities in the availability and use of IV thrombolysis, and overcoming them is an important priority for improving stroke outcomes.
The sooner IV thrombolysis is delivered after symptom onset, the better the outcome; if treatment can be given in the first golden hour via mobile stroke units or by expedited emergency department care, two-thirds of patients will recover with no disability.
Advanced imaging reveals that the temporal progression of stroke is different in each patient; outcomes with treatment out to 9 hours after symptom onset in imaging-selected patients may result in comparable benefit to earlier treatment.
Regional systems of care must balance the need to administer IV thrombolysis as soon as possible to those who qualify while also identifying and expediting triage of patients with large vessel occlusion to the nearest endovascular thrombectomy center.
IV thrombolysis can dissolve 20% to 30% of large vessel occlusion clots and should not be withheld in patients meeting treatment criteria except in rare circumstances.
Compared with rtPA, tenecteplase is more convenient, delivers the full dose faster, and produces comparable outcomes, but is not yet approved by the FDA for IV thrombolysis.
Research is ongoing to study the wider implementation of mobile stroke units in speeding up the delivery of IV thrombolysis to patients with stroke.
Source:
Continuum April 23
------ MultipleSclerosisDemyelinating_NEUROMYELITIS_OPTICA_SPECTRUM_DISORDERS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews the cardinal clinical features, distinct immunopathology, current diagnostic criteria, relapse-related risk factors, emerging biomarkers, and evolving treatment strategies pertaining to neuromyelitis optica spectrum disorders (NMOSD).
RECENT FINDINGS
The discovery of the pathogenic aquaporin-4 (AQP4)-IgG autoantibody and characterization of NMOSD as an autoimmune astrocytopathy have spearheaded the identification of key immunologic therapeutic targets in this disease, including but not limited to the complement system, the interleukin 6 (IL-6) receptor, and B cells. Accordingly, four recent randomized controlled trials have demonstrated the efficacy of three new NMOSD therapies, namely eculizumab, satralizumab, and inebilizumab.
SUMMARY
Currently, NMOSD poses both diagnostic and treatment challenges. It is debated whether individuals who are seropositive for myelin oligodendrocyte glycoprotein (MOG)-IgG belong within the neuromyelitis optica spectrum. This discussion is fueled by disparities in treatment responses between patients who are AQP4-IgG seropositive and seronegative, suggesting different immunopathologic mechanisms may govern these conditions. As our understanding regarding the immune pathophysiology of NMOSD expands, emerging biomarkers, including serum neurofilament light chain and glial fibrillary acidic protein (GFAP), may facilitate earlier relapse detection and inform long-term treatment decisions. Future research focal points should include strategies to optimize relapse management, restorative treatments that augment neurologic recovery, and practical solutions that promote equitable access to approved therapies for all patients with NMOSD.
Key Points
The discovery of the pathogenic aquaporin-4–IgG antibody has helped distinguish neuromyelitis optica spectrum disorders (NMOSD) as an autoimmune astrocytopathy, distinct from multiple sclerosis.
Although optic neuritis and transverse myelitis are common features, the full breadth of neurologic, ophthalmic, and systemic disease manifestations of NMOSD continues to expand.
Red flags for an alternative diagnosis rather than NMOSD include acute symptom onset (less than 4 hours), a chronic progressive course, a comorbidity that could mimic clinical features of NMOSD, cerebralMRI lesions showing persistent enhancement (formore than 3 months), and the presence of oligoclonal bands in the CSF.
Only 25% of long-term disability for patientswith NMOSD is related to the initial presentation, whichmeans a significant amount of neurologic impairment is preventable. The best way to treat an NMOSD relapse is to prevent it.
Vaccination may increase the risk of relapse for 30 days after inoculation, yet studies indicate that vaccination is generally safe for patients with NMOSD who are receiving appropriate immunosuppressant therapy.
High-dose corticosteroid treatment represents themainstay of acute management for NMOSD relapses, but occasionally adjunctive treatmentwith plasma exchange or immunoadsorptionmay be needed for refractory attacks. In this setting, the role of IVIg for NMOSD relapses is less clear.
Serum measures of neurofilament light chain and glial fibrillary acidic protein (GFAP) may complement optical coherence tomography and MRI techniques to improve diagnosis, capture disease activity, and potentially predict outcomes for people living with NMOSD. Although these biomarkers hold promise, their utility in the clinical setting is yet to be determined.
Off-label immunosuppressive therapies including azathioprine, mycophenolate mofetil, and rituximab have traditionally been used in the long-term management of NMOSD.
Many disease-modifying therapies used in the treatment of MS worsen disease course in NMOSD. Instead, patients with NMOSD need targeted immunosuppressive therapies.
A large body of elegant work elucidating the immune pathobiology of NMOSD has led to the discovery of three new approved therapies, namely eculizumab, satralizumab, and inebilizumab, which have all shown robust benefits in preventing relapses.
Immune reconstitution therapy may serve as an induction strategy in patients with NMOSD with severe refractory disease before the initiation of long-term immunomodulation.
Patients with NMOSD can have connective tissue disorders such as systemic lupus erythematosus and Sjögren syndrome. Management approaches should be multidisciplinary to optimize clinical outcomes.
Pregnancy and the postpartum state are vulnerable phases for patients with NMOSD because relapses are more likely to occur and patients may experience miscarriage. Accordingly, pregnant women with NMOSD should be considered high risk, and a multidisciplinary approach to care should be implemented.
Source:
Continuum 2022
------ DementiaNeurodegenerativeProcesses_COGNITIVE_SYNDROMES_ASSOCIATED_WITH_MOVEMENT_DISORDERS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews the recognition and management of cognitive syndromes in movement disorders, including those with parkinsonism, chorea, ataxia, dystonia, and tremor.
RECENT FINDINGS
Cognitive and motor syndromes are often intertwined in neurologic disorders, including neurodegenerative diseases such as Parkinson disease, atypical parkinsonian syndromes, Huntington disease, and other movement disorders. Cognitive symptoms often affect attention, working memory, and executive and visuospatial functions preferentially, rather than language and memory, but heterogeneity can be seen in the various movement disorders. A distinct cognitive syndrome has been recognized in patients with cerebellar syndromes. Appropriate recognition and screening for cognitive changes in movement disorders may play a role in achieving accurate diagnoses and guiding patients and their families regarding progression and management decisions.
SUMMARY
In the comprehensive care of patients with movement disorders, recognition of cognitive syndromes is important. Pharmacologic treatments for the cognitive syndromes, including mild cognitive impairment and dementia, in these movement disorders lag behind the therapeutics available for motor symptoms, and more research is needed. Patient evaluation and management require a comprehensive team approach, often linking neurologists as well as neuropsychologists, psychologists, psychiatrists, social workers, and other professionals.
KEY POINTS
Movement disorders, including dystonia and essential tremor, are increasingly recognized to have cognitive features.
Cognitive impairment is a common feature of Parkinson disease (PD), with a lifetime risk of dementia of up to 90%.
Bradyphrenia, or slowed thinking, is a cognitive analogue of bradykinesia, or slowed movement, in PD and may not necessarily represent cognitive decline.
GBA mutation carriers have a higher risk of cognitive decline in PD.
LRRK2 mutation carriers have a lower risk of cognitive decline in PD.
Executive, attentional, and visuospatial dysfunction are more common in PD compared with the more amnestic deficits seen in Alzheimer disease (AD).
Copathology with AD is very common in dementia with Lewy bodies and can dampen the expression of core clinical features.
Core clinical features of dementia with Lewy bodies include parkinsonism, visual hallucinations, rapid eye movement (REM) sleep behavior disorder, and cognitive fluctuations.
No clinical criteria yet exist for a mild cognitive impairment stage of dementia with Lewy bodies, although nonamnestic mild cognitive impairment with any core clinical features should raise suspicion for prodromal dementia with Lewy bodies.
All core clinical features of dementia with Lewy bodies can also be seen in PD dementia, although at lower frequencies overall.
The main differentiating factor between PD dementia and dementia with Lewy bodies is timing of symptom onset: what came first, motor or cognitive symptoms?
PD dementia and dementia with Lewy bodies may be on a clinical and pathologic spectrum rather than completely separate diagnostic entities.
It is important to delve into examples of the patient’s “memory trouble,” as the affected cognitive domain may not be memory at all.
Cognitive impairment can occur in all atypical parkinsonian conditions, although typically more prominently in progressive supranuclear palsy and corticobasal syndrome than in multiple system atrophy.
With clinical overlap of parkinsonism, behavior/personality changes, and/or primary progressive aphasia, consider testing for frontotemporal dementia genes: C9orf72, GRN, and MAPT.
Lexical fluency impairment can help distinguish progressive supranuclear palsy from other conditions, including PD and AD.
Corticobasal syndrome is the most asymmetric of the parkinsonian disorders.
Side effects of cholinesterase inhibitors include gastrointestinal symptoms, bradycardia, hypotension, and syncope.
Sudden discontinuation of cholinesterase inhibitors can cause abrupt cognitive decline in PD dementia and dementia with Lewy bodies.
Depression, apathy, and irritability are common in Huntington disease and can occur at any stage of disease, including before the onset of motor symptoms.
Cognitive, behavioral, and motor features are highly intertwined in Huntington disease and highlight the involvement of both striatal/subcortical and cortical pathologies.
Psychomotor slowing is one of the earliest and best predictors of Huntington disease progression, which can be demonstrated on timed tasks such as the Stroop Color and Work Test, Symbol Digit Modalities Test, and Trail Making Test.
It is important to screen patients with Huntington disease for behavioral symptoms because they can affect daily function, safety, and performance on cognitive tests.
Genetic counselors play important roles in the diagnosis and management of Huntington disease. In addition, like many of the cognitive-movement syndromes described, a multidisciplinary approach with neurologists, psychiatrists, psychologists, social workers, and other health care specialties is helpful to patients and their families.
In addition to motor features, cerebellar disorders may present with cognitive dysfunction.
Evidence for the cerebellar cognitive affective syndrome comes from studies of patients with cerebellar lesions, including strokes and neurodegenerative conditions.
The cerebellar cognitive affective syndrome includes impairment in processing speed, working memory, executive function, visuospatial function, language, and attention.
The cerebellum may play a role in emotional and affective regulation.
Patients with fragile X-associated tremor/ataxia syndrome may present with action tremor, ataxia, or neuropathy.
Screening for the FMR1 premutation should be considered for patients with atypical parkinsonian syndromes and dementia.
Family history is important in the evaluation of fragile X-associated tremor/ataxia syndrome, including clues of premature ovarian failure and intellectual disabilities.
Cognitive changes are common in spinocerebellar ataxias, with spinocerebellar ataxia type 17 most frequently associated with dementia.
If a patient presents with symptoms similar to those of a behavioral variant frontotemporal dementia with a positive family history of neurologic conditions but genetic testing for frontotemporal dementia genes (C9orf72, MAPT, GRN) is negative, spinocerebellar ataxia type 17 should be considered, especially if cerebellar atrophy is present on neuroimaging.
Although Friedreich ataxia typically presents between the ages of 10 and 15 years, 15% of cases present after the age of 25.
Consider genetic testing for GAA expansion in the Friedreich ataxia gene in any patient with gait and/or limb ataxia, dysarthria, vibratory sensory loss, and/or abnormal eye movements, regardless of the age of onset.
Patients with dystonia or essential tremor with cognitive symptoms should first be evaluated for medication-related effects.
Essential tremor can cause neurologic symptoms beyond an action tremor, which could be termed essential tremor-plus; the distinction etiologically or pathologically between essential tremor and essential tremor-plus is not clear.
Pathologic changes are present in the cerebellum in essential tremor, resulting in reduced inhibitory outflow from the cerebellum to the cortex.
Source:
Continuum 2022
------ Metoclopramide,_a_dopamine_blocker,_is.txt ------
Metoclopramide, a dopamine blocker, is a common cause
of drug-induced parkinsonism. The most effective management of drug-induced parkinsonism is removal of the medication causing the syndrome. The other medication this patient is taking, metronidazole, can cause peripheral neuropathy but is not a known cause of parkinsonism. Copper deficiency causes a myeloneuropathy (and can be seen in patients after gastric bypass) but is not associated with parkinsonism.
------ DementiaNeurodegenerativeProcesses_ATYPICAL_ALZHEIMER_DISEASE_VARIANTS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior cortical atrophy, logopenic variant primary progressive aphasia, dysexecutive variant and behavioral variant AD, and corticobasal syndrome.
RECENT FINDINGS
Significant advances are being made in the recognition and characterization of the syndromically diverse AD variants. These variants are identified by the predominant cognitive and clinical features: early-onset amnestic syndrome, aphasia, visuospatial impairments, dysexecutive and behavioral disturbance, or motor symptoms. Although understanding of regional susceptibility to disease remains in its infancy, visualizing amyloid and tau pathology in vivo and CSF examination of amyloid-β and tau proteins are particularly useful in atypical AD, which can be otherwise prone to misdiagnosis. Large-scale research efforts, such as LEADS (the Longitudinal Early-Onset Alzheimer Disease Study), are currently ongoing and will continue to shed light on our understanding of these diverse presentations.
SUMMARY
Understanding the clinical, neuroimaging, and biomarker profiles of the heterogeneous group of atypical AD syndromes improves diagnostic accuracy in patients who are at increased risk of misdiagnosis. Earlier accurate identification facilitates access to important interventions, social services and disability assistance, and crucial patient and family education.
KEY POINTS
Approximately 3% of the 5.8 million Americans with Alzheimer disease (AD) developed symptoms at age 65 or younger.
Misdiagnosis results in setbacks in access to AD treatments and social and financial support services.
Amnestic variant early-onset AD is the most common atypical AD variant. Compared to late-onset AD, patients with sporadic early-onset AD show more rapid clinical decline and greater impairment in attention, language, visuospatial, and executive functions.
Disease-specific biomarkers are particularly useful when assessing atypical AD presentations, including early-onset AD.
Early-onset AD is associated with greater baseline cortical atrophy and hypometabolism and more severe AD pathology (particularly neurofibrillary tangles and synaptic loss) than late-onset AD.
Patients with posterior cortical atrophy present with striking impairments in visuospatial perception and construction that cut across cognitive domains, including attention, reasoning, and memory.
Ninety-six percent of cases of posterior cortical atrophy are due to AD.
The classic structural imaging finding in posterior cortical atrophy is posterior-predominant atrophy with involvement of the visual associative cortices and, in the caudal variant, also the primary visual cortex.
The functional impairment in posterior cortical atrophy is significant as patients are unable to successfully navigate and interact with their environment.
Of logopenic variant primary progressive aphasia cases, 86% to 90% cases are due to AD, compared to only 11% to 16% of semantic dementia cases and 15% to 20% of primary progressive nonfluent aphasia cases. The primary symptoms of patients with logopenic variant primary progressive aphasia are word-finding difficulties, circumlocution, and mispronouncing words (phonemic paraphasias).
In logopenic variant primary progressive aphasia, MRI, tau positron emission tomography (PET), and fludeoxyglucose PET show left greater than right atrophy, tau deposition, and hypometabolism involving the lateral temporal and temporoparietal cortices.
Early prominent language impairment defines logopenic variant primary progressive aphasia and is the principal cause of impairment in daily living. Anomia, poor word generation, and sentence repetition are the defining features.
Early features of dysexecutive variant AD include difficulty with multitasking, planning, organizing, and project execution.
Many patients with dysexecutive variant AD are initially misdiagnosed as having a primary psychiatric or functional neurologic disorder.
Behavioral variant AD closely resembles behavioral variant frontotemporal dementia.
Patients with behavioral variant AD are commonly diagnosed with behavioral variant frontotemporal dementia because of the early pervasive behavioral and personality changes.
Given that executive functioning and working memory are foundational cognitive skills that support other cognitive abilities, it is common to see a multidomain presentation in dysexecutive variant AD.
Of cases of corticobasal syndrome, 15% to 54% are due to AD.
A detailed neurologic examination is critical in suspected corticobasal syndrome.
Although cognitive impairment is a core criterion for the diagnosis of corticobasal syndrome, the cognitive domains affected can be variable.
Given the substantial overlap of clinical findings between corticobasal syndrome–AD and corticobasal syndrome–corticobasal degeneration (CBD), molecular imaging or CSF biomarkers could prove critical to establishing AD as the causative etiology antemortem.
Within atypical AD, overlapping symptoms can make distinguishing between phenotypes challenging. Differentiation can be assisted by identifying the most prominent symptoms and the timeline of onset.
The pharmacologic management of early-onset or atypical AD is similar to that of late-onset AD.
The atypical AD variants pose even greater safety and day-to-day caregiving challenges than typical AD.
The syndromic diversity in early-onset AD and especially the atypical variants provides a rich platform to improve our understanding of brain region vulnerability and the associated factors driving these atypical presentations.
Source:
Continuum 2022
------ Sleep_Sleep_in_Patients_With_Neurologic_Disease.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides a discussion of the current evidence and contemporary views on the relationship between sleep disorders and neurologic disease.
RECENT FINDINGS
Disrupted or disordered sleep can be associated with increased morbidity and mortality, the risk of cardiovascular events, increased seizure frequency, and altered immune responses. Studies have implicated disrupted sleep and circadian rhythm dysfunction with both amyloid-β (Aβ) deposition and tau deposition. A bidirectional relationship exists between disrupted sleep and the progression of Alzheimer disease pathology. Insomnia has been reported as a prodromal symptom in autoimmune encephalitis. Primary sleep disorders have now been increasingly recognized as a common comorbid condition in multiple sclerosis, making it imperative that neurologists feel comfortable differentiating multiple sclerosis fatigue from excessive daytime sleepiness caused by primary sleep disorders to optimally treat their patients.
SUMMARY
Sleep disorders are common across the population. By recognizing sleep disorders in patients with neurologic conditions, neurologists can provide comprehensive care and, in some cases, reduce neurologic disease burden.
KEY POINTS
Obstructive sleep apnea may lead to inflammation, increasing the risk of stroke.
Atrial fibrillation prevalence is four times higher in patients with sleep apnea, serving as a significant risk factor for cardioembolic stroke.
Sleep period length and circadian rhythm differences can be linked to ischemic stroke risk.
Sleep apnea can be both screened for and diagnosed with various valid tools that include questionnaires that can be completed by the patient or care provider and with in-center or ambulatory sleep diagnostic services.
When deep sleep is attenuated, amyloid-β (Aβ) and tau protein, which are hallmarks for Alzheimer disease, can accumulate.
Patients with Alzheimer disease often have an irregular sleep-wake rhythm. Behavioral interventions, including appropriate timing of natural-light exposure and physical activity, may be helpful in reinforcing an appropriate circadian rhythm.
Rapid eye movement (REM) sleep behavior disorder is commonly a precursor to α-synucleinopathies with reported presentation as much as 10 to 15 years prior to Parkinson disease motor manifestations.
Sleep disruption is common in Parkinson disease, and this often leads to excessive daytime sleepiness in this patient population.
Huntington disease and palatal myoclonus represent the two movement disorders for which movements have been commonly recognized to persist while sleeping, unlike other movement disorders such as Parkinson disease, where sleep allows for a quiescent phase in the stereotyped movements.
Insomnia and other sleep disturbances are often prodromal symptoms in autoimmune encephalitis.
Anti-IgLON5 disease is an autoimmune encephalopathy with sleep disruptions as a prominent part of the presentation. Other common features are bulbar symptoms and gait disturbance.
Fatigue and excessive daytime sleepiness are common symptoms experienced by patients with multiple sclerosis. Optimizing approaches to help distinguish symptoms of fatigue from sleepiness can improve early identification of underlying sleep disorders and, therefore, overall management of these two common and debilitating functional symptoms.
If a patient with multiple sclerosis reports severe daytime sleepiness that does not correlate with the onset of other multiple sclerosis symptoms, an evaluation for a coexisting sleep disorder, such as obstructive sleep apnea (using polysomnography) and particularly narcolepsy (using polysomnography and multiple sleep latency testing), should be considered.
Risk factors for sleep apnea in patients with epilepsy include seizure medications that cause weight gain, benzodiazepine medication use, and obstructive and central sleep apnea events associated with a vagal nerve stimulator.
Further studies are needed to better classify the impact on seizure control incurred by treating sleep apnea.
Central sleep apnea and sudden unexpected death in epilepsy (SUDEP) may be related.
Both migraine headaches and tension headaches are exacerbated by poor sleep.
Patients who concurrently have migraine/tension headaches along with insomnia have reported dual symptom benefit after undergoing cognitive-behavioral therapy for insomnia.
Hypnic headaches are a rare headache type with frequent awakenings due to a dull headache pain. Treatment options include lithium, caffeine, indomethacin, and melatonin.
Source:
Continuum Sleep 2020
------ Neuroimaging_SAFETY_CONSIDERATIONS_IN_MRI_AND_CT.txt ------
ABSTRACT
OBJECTIVE
MRI and CT are indispensable imaging modalities for the evaluation of patients with neurologic disease, and each is particularly well suited to address specific clinical questions. Although both of these imaging modalities have excellent safety profiles in clinical use as a result of concerted and dedicated efforts, each has potential physical and procedural risks that the practitioner should be aware of, which are described in this article.
LATEST DEVELOPMENTS
Recent advancements have been made in understanding and reducing safety risks with MR and CT. The magnetic fields in MRI create risks for dangerous projectile accidents, radiofrequency burns, and deleterious interactions with implanted devices, and serious patient injuries and deaths have occurred. Ionizing radiation in CT may be associated with shorter-term deterministic effects on biological tissues at extremely high doses and longer-term stochastic effects related to mutagenesis and carcinogenesis at low doses. The cancer risk of radiation exposure in diagnostic CT is considered extremely low, and the benefit of an appropriately indicated CT examination far outweighs the potential risk. Continuing major efforts are centered on improving image quality and the diagnostic power of CT while concurrently keeping radiation doses as low as reasonably achievable.
ESSENTIAL POINTS
An understanding of these MRI and CT safety issues that are central to contemporary radiology practice is essential for the safe and effective treatment of patients with neurologic disease.
KEY POINTS
The three different magnetic fields involved in the creation of MRIs are each associated with defined safety risks.
The MRI room is one of the most dangerous environments in the hospital.
The magnet is always “on.” The tremendously powerful magnetic field creates a dangerous projectile risk in the MRI room regardless of whether a patient is being scanned or not.
Only trained MRI personnel should enter the magnet room in a patient emergency (eg, cardiopulmonary arrest).
Accurate information about a patient’s implanted devices should be provided to the MRI team with the MRI order.
Physical spaces related to MRI are defined by a four-zone model. Access to zone III (the technologist control area) and zone IV (the magnet room) is restricted.
Implanted devices are designated as MR-safe, MR-conditional, or MR-unsafe.
Well-designed MRI safety systems and procedures must be in place and rigorously followed to prevent serious safety events and accidents involving dangerous projectiles, burns, and unplanned scanning of implanted devices.
The magnetic fields around the opening of an MRI bore are not uniform; rather, a steep gradient exists in the forces as the magnet is approached.
Older intracranial aneurysm clips contained ferromagnetic metal, resulting in patient deaths during MRI.
Heating and burns related to the radiofrequency field are the most common type of MRI safety events.
Foil-backed medication patches can cause burns during MRI.
Scanning a patient with an MR-unsafe device or with an MR-conditional device without abiding by the conditions for safe scanning can lead to serious patient injury or death.
Intrathecal pumps are the type of device associated with the greatest number of patient deaths during MRI in recent years.
Patients with pacemakers and defibrillators can increasingly be safely scanned if important safety measures are strictly adhered to.
An insulin pump exposed to MRI is likely unreliable and could lead to serious hyperglycemia or hypoglycemia.
Displacement of an intraocular ferromagnetic foreign body during MRI can lead to blindness.
No deleterious clinical effects of gadolinium retention have yet been identified, although continued study of this issue is important.
Radiation dose in CT is commonly quantified in terms of scanner radiation output, patient absorbed dose, and effective dose.
Two types of biological effects from radiation exposure in CT occur. One is the deterministic effect (tissue reaction), and the other is the stochastic effect (cancer induction and hereditary effect).
Deterministic effects rarely occur in diagnostic CT examinations except for some prolonged CT-guided interventional procedures. The risk of radiation exposure in CT refers mostly to stochastic effect.
At low levels of radiation, considerable uncertainty exists regarding the risk of cancer induction. It was stated in a report by the National Academy of Sciences that at doses of 100 mSv or less, “statistical limitations make it difficult to evaluate cancer risk in humans.”
It is generally believed that quantitative estimation of cancer risk for an individual patient receiving a radiation dose of less than 100 mSv during CT does not bring clinical value to the patient.
To maximize the benefit-to-risk ratio, it is still best practice to use the lowest possible radiation dose at each CT examination while generating images with sufficient diagnostic quality. Two basic principles must be followed for managing radiation dose in CT: justification and optimization.
Commonly used radiation dose–reduction techniques include automatic tube current modulation, automatic tube potential selection, iterative reconstruction, and deep learning–based noise reduction.
CT operators are required to receive appropriate training on scanner operation, radiation exposure, and emergency procedures.
The presence of implanted electronic devices should not preclude a clinically justified CT scan. However, to reduce the potential risk of interference between electronic devices and CT radiation, some precautions are needed.
Source:
Continuum 2023
------ DementiaNeurodegenerativeProcesses_RAPIDLY_PROGRESSIVE_DEMENTIA.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article presents a practical approach to the evaluation of patients with rapidly progressive dementia.
RECENT FINDINGS
The approach presented in this article builds upon the standard dementia evaluation, leveraging widely available tests and emergent specific markers of disease to narrow the differential diagnosis and determine the cause(s) of rapid progressive decline. The discovery of treatment-responsive causes of rapidly progressive dementia underscores the need to determine the cause early in the symptomatic course when treatments are most likely to halt or reverse cognitive decline.
SUMMARY
A pragmatic and organized approach to patients with rapidly progressive dementia is essential to mitigate diagnostic and therapeutic challenges and optimize patient outcomes.
KEY POINTS
Although the definition of rapid varies in practice, it is generally accepted that in rapidly progressive dementia (RPD), the interval from first symptom to dementia onset is measured in weeks or months.
Patients who are rapidly declining present a disproportionately great clinical challenge.
The practical approach to RPD builds upon the standard dementia evaluation, with modifications intended to optimize the speed of evaluation and improve early recognition of patients with potentially reversible causes of RPD.
In RPD, as in stroke, time is brain.
As the onset of most neurodegenerative dementias is insidious, patients and caregivers are likely to misinterpret or discount early symptoms.
The breadth of possible causes of RPD mandates a comprehensive yet strategic approach to the evaluation that systematically considers the possible causes of neurologic dysfunction while prioritizing common causes of RPD.
Common causes of RPD differ markedly in populations with limited access to health care and varied exposures.
In RPD, as in all areas of neurology, the past medical history focuses the differential diagnosis.
Medications may directly accelerate cognitive decline in susceptible individuals or indirectly lead to RPD.
Genetic counseling and testing should be considered in patients with a family history of similar conditions, syndromes that affect multiple relatives across multiple generations, or unexplained untimely death in first-degree relatives.
The time course over which symptoms emerge, patterns of decline, and rates of progression may inform the causes of RPD.
A comprehensive and ordered neurologic examination is critical to determine whether cognitive deficits are attributable to a focal, multifocal, or systemic process.
In RPD, the neurologic examination represents a single measure of a dynamic and rapidly evolving process.
It is especially important to differentiate faciobrachial dystonic seizures from the myoclonic movements commonly observed in patients with Creutzfeldt-Jakob disease (CJD), given the similarities in age at symptomatic onset and implications of this finding on treatment.
High-yield core tests include screening serum studies and urinalysis, structural neuroimaging, CSF analyses, and EEG. Specific tests are more varied in accessibility, cost, and application and should be reserved for selected patients when justified by the clinical scenario.
The sensitivity and specificity of MRI for the diagnosis of CJD may exceed 90% in cohorts with suspected CJD, with good interrater reliability when interpreted by experienced neuroradiologists.
Cortical ribboning may be seen in patients with CJD and in patients with other causes of RPD, including subacute sclerosing panencephalitis, autoimmune encephalitis, herpes simplex encephalitis, high-grade glioma (or other malignancies), seizures, and hypoglycemia and other causes of metabolic derangement.
Lumbar puncture can be safely and efficiently performed at the bedside even in patients who are severely impaired and should be completed in all patients with RPD following reasonable exclusion of space-occupying lesions and bleeding diatheses.
Abnormalities on routine measures may point toward a common cause of RPD, focusing further evaluations for etiologies such as CJD; neurodegenerative diseases; or autoimmune, inflammatory, or infectious causes.
Unexpected findings on routine tests may provide an important early clue to an alternative etiology, prompting further evaluation for less common causes of RPD.
The ease of use, wide availability, relatively low cost, and excellent safety profile of EEG justify its inclusion as a core or common test in patients with RPD.
The EEG represents a temporal measure of an evolving process. EEG findings may be subtle early in the symptomatic course, with typical findings associated with specific causes of RPD emerging as the disease progresses.
Good biomarkers provide objective measures of biological or pathogenic processes that may be applied to stratify disease risk or prognosis, inform clinical diagnosis, and monitor response to interventions. A clear need exists to develop and apply disease-specific biomarkers when assessing for and managing patients with RPD.
The development of a real-time quaking induced conversion (RT-QuIC) assay capable of detecting minute amounts of abnormal prion proteins within CSF has transformed the diagnostic approach to CJD. A positive RT-QuIC leaves little doubt as to the underlying cause of RPD.
Although total tau is not a specific biomarker, elevations above approximately 1150 pg/mL are reported in more than 90% of patients with probable or definite CJD.
CSF 14-3-3 protein may add incremental value in the assessment of RPD, although the nonspecific nature of this marker and inferior sensitivity have reduced enthusiasm for its use in the diagnosis of CJD.
Unexpected negative test results in patients with RPD warrant prompt reconsideration of the differential diagnosis and expansion of the clinical evaluation.
Alzheimer disease is the most common cause of dementia, accounting for between 60% and 80% of all cases of typically progressive dementia and for the majority of RPD caused by typical neurodegenerative diseases.
The ability to simultaneously measure multiple analytes presents a substantial advantage for biofluid biomarkers, with the potential to use aggregate data to improve diagnoses and inform the pathologic processes that contribute to rates of progression in patients with RPD.
Although antibodies may be associated with specific clinical syndromes, atypical presentations are the rule, not the exception, in RPD.
Antibody testing should be performed simultaneously in serum and CSF, recognizing the superior sensitivity of antibody measures tested in specific biofluids using commercial platforms.
Rapid evolution in antibody discovery requires the ordering clinician to maintain a reasonable knowledge of clinically relevant autoantibodies, available tests, and their limitations.
Direct tissue evaluation may be necessary when common and specific tests have failed to reveal a definitive etiologic diagnosis in a patient with RPD.
The diagnostic yield of brain biopsy varies but may be as high as 65% in well-evaluated populations with RPD.
The discovery of immune-mediated causes of RPD underscores the need to improve the diagnosis of RPD early in the symptomatic course when treatments are most likely to halt or reverse declines in cognition. Accordingly, treatment-responsive causes of RPD should be considered at each step of the diagnostic evaluation.
Empiric treatment should be promptly considered when infection or acute nutritional deficiencies are suspected.
Thiamine repletion is especially critical in patients with extraocular movement abnormalities (including gaze-evoked nystagmus) and ataxia, who may be at the highest risk of Wernicke-Korsakoff syndrome.
Immunotherapies should be provided to patients with possible autoimmune encephalitis once blood and CSF has been collected for autoantibody testing.
Evaluation for and treatment of potential secondary modifiers of dementia may promote brain health and improve quality of life for patients and caregivers.
Longitudinal studies applying standardized definitions of RPD and systematic protocols are needed to clarify the optimal approach to diagnosis and management of RPD.
Source:
Continuum 2022
------ Pregnancy_HEADACHE_IN_PREGNANCY_AND_LACTATION.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses the many tools available for the treatment of pregnant and postpartum patients with headache. Adequate treatment of headache is an essential part of good prenatal and postnatal care.
RECENT FINDINGS
New therapies such as the calcitonin gene-related peptide monoclonal antibodies, lasmiditan, direct calcitonin gene-related peptide antagonists, and neuromodulation devices are available for the treatment of headache. This article contextualizes these new therapies in practice as they relate to the treatment of migraine in pregnancy and lactation.
SUMMARY
Headache is common in pregnancy, and neurologists should be prepared to care for pregnant patients with headache. Preconception counseling is an important part of providing safe care to patients of childbearing potential with headache. Identifying potentially dangerous secondary headache syndromes during pregnancy and the puerperium is also essential. The repertoire of available acute and preventive headache treatments is expanding. It is important to discuss the effectiveness and safety of these therapies in the context of individual patient circumstances during pregnancy and lactation in coordination with the patient’s obstetric team.
KEY POINTS
In women between the ages of 30 and 39, the prevalence of migraine can be as high as 27%, which is about 3 times higher than the prevalence in men in the same age range.
It is prudent to discuss any potential teratogenicity of medications at the time they are prescribed, regardless of the patient’s current reproductive plan, as plans may unexpectedly change with time.
Patients taking monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) activity should be advised to stop injections approximately 5 to 6 months before conception.
The diagnosis of headache is guided by the International Classification of Headache Disorders, Third Edition.
Women with migraine with aura may be less likely to improve in pregnancy, and aura can present for the first time during pregnancy.
One study showed that the most common secondary headache syndromes in patients who presented to acute care with severe headache were caused by hypertensive disorders of pregnancy. In this study, a lack of headache history was associated with a nearly fivefold risk of secondary headache, and elevated blood pressure was associated with a 17-fold risk of secondary headache.
Warning signs for secondary headache include fever, papilledema or other abnormal neurologic examination findings, thunderclap headache onset, postural provocation, and a history of immunosuppression.
Compared to women without a history of migraine, women with a history of migraine are more likely to have a secondary cause of headache, such as cerebral venous thrombosis, pregnancy-associated stroke, or preeclampsia.
Preeclampsia is quite common, occurring in 3% to 5% of pregnancies.
Pituitary apoplexy characteristically presents with acute or thunderclap headache, and it can lead to bitemporal hemianopia and hypotension.
Intracranial hypotension usually presents with postpartum headache that progressively worsens throughout the day and usually worsens with upright posture.
The US Food and Drug Administration previously categorized medications based on a hierarchical scale from A (safest) to X (contraindicated in pregnancy), but these categories were discontinued in 2015.
To make an accurate assessment of headache burden, it is essential to ask patients about days of complete headache freedom.
Given the natural improvement in headache that many patients experience with pregnancy, it may be reasonable to monitor their headaches without preventive therapy early on to see if preventive therapy is indeed required.
All patients with headache may benefit from a discussion of lifestyle modifications, such as sleep optimization, stress management, adequate hydration, and regular healthy meals.
Given the lower levels of CGRP in patients with preeclampsia compared to normotensive individuals, most headache specialists believe avoidance of CGRP monoclonal antibodies in pregnancy is warranted.
Despite its efficacy, topiramate should be avoided during pregnancy given the known risks of cleft palate and lip, intrauterine growth restriction, and metabolic acidosis.
Feverfew is contraindicated for migraine prevention in pregnancy as it can provoke uterine contractions and spontaneous miscarriage.
Reviewing prescription medications for safety in pregnancy is routine, but clinicians must not forget to specifically ask about over-the-counter medication and supplement use.
The goal of acute therapy for headache is to restore function and resolve pain and other associated symptoms within 2 hours. If a treatment does not reliably help within 2 hours, other options should be explored.
Butalbital-containing medications and opiates are not recommended for the treatment of migraine in the general population; this applies to both pregnant and nonpregnant patients.
The new direct CGRP receptor antagonists ubrogepant and rimegepant and the new serotonin-1F agonist lasmiditan should be avoided in pregnancy given the paucity of available evidence about their safety in pregnancy.
Neuromodulation devices should be theoretically safe to use in pregnant women with migraine or cluster headache, but data are limited.
If headache improved during pregnancy, some women enjoy a continued improvement during lactation and may not require immediate resumption of their prior preventive therapies.
Eletriptan has the lowest milk to plasma ratio of the triptans, and sumatriptan has the most safety data available for breastfeeding.
Ubrogepant, rimegepant, and lasmiditan should be avoided during lactation given the absence of available data.
The CGRP monoclonal antibodies have not been studied in lactation. However, given their large size, it is unlikely that they will pass through into breast milk, and some headache specialists are now considering their use when treating particularly disabling and intractable migraine.
Source:
Continuum 2022
------ DementiaNeurodegenerativeProcesses_FLUID_BIOMARKERS_IN_DEMENTIA_DIAGNOSIS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses how fluid biomarkers can augment the routine dementia evaluation and improve diagnostic accuracy. The tests that are currently available and the indications for their use are described. Further, tests that are under development and likely to be used in the future are identified.
RECENT FINDINGS
Technical improvements in assay sensitivity and precision have led to the rapid development of blood-based biomarkers for Alzheimer disease (AD) over the past several years. Studies have found that the ratio of amyloid-β (Aβ) peptides (Aβ42/Aβ40) and concentrations of phosphorylated tau isoforms in plasma can identify individuals with AD brain pathology. Blood-based tests may enable much broader use of AD biomarkers in the evaluation of patients with cognitive impairment.
SUMMARY
Even after a detailed history, examination, routine laboratory testing, and brain imaging, the cause of dementia sometimes remains unclear. CSF and blood-based biomarkers can evaluate for a range of neurologic disorders that are associated with dementia, including AD. Integrating data from fluid biomarker tests and the routine dementia evaluation may improve the accuracy of dementia diagnosis.
KEY POINTS
The routine dementia evaluation includes a comprehensive history and neurologic examination, laboratory testing, and brain imaging.
The cause or causes of dementia may be unclear despite a thorough evaluation.
Advanced diagnostic testing may improve the accuracy of dementia diagnosis.
Confirmation of Alzheimer disease brain pathology is essential before initiating treatment with amyloid-lowering medications.
One blood-based test for Alzheimer disease is available for clinical use, and more tests are undergoing rapid development.
CSF testing is helpful in evaluating infectious, inflammatory, neoplastic, and neurodegenerative causes of dementia.
Lower CSF levels of Aβ42 may reflect sequestration of Aβ42 in amyloid plaques.
Higher CSF levels of total tau and phosphorylated tau isoforms may reflect neuronal dysfunction in response to amyloid plaques.
Significant amyloid burden is associated with lower Aβ42 and Aβ42/Aβ40 and higher t-tau, p-tau181, t-tau/Aβ42, and p-tau181/Aβ42.
Biomarkers augment but do not replace a thorough diagnostic evaluation.
Clinicians must understand the meaning and limitations of diagnostic tests for dementia.
Source:
Continuum 2022
------ Neuro_casecontrol_vs_crosssectional.txt ------
Rationale: The key feature of a case-control study is that participants are ascertained based on outcome, in this case the presence of MS relapses. All patients in this study have MS and are taking interferon beta: patients in group 1 have had relapses since starting therapy and those in group 2 have not.
The direction of inquiry of the research question is from outcome to exposure. The “exposure” here is the presence of neutralizing antibodies. The investigators inquired about the frequency of neutralizing antibodies among the cases (patients with relapses) and the controls (patients without relapses). In a cross-sectional study, all members of the sample are observed at a single point in time.
Source:
RITE 2021
------ Sleep_Rapid_Eye_Movement_Sleep_Behavior_Disorder_and_Other_Rapid_Eye_Movement_Parasomnias.txt ------
ABSTRACT
PURPOSE OF REVIEW
The discovery of rapid eye movement (REM) sleep and, in particular, REM sleep behavior disorder (RBD) have brought elusive nightmarish experiences to scientific scrutiny. This article summarizes a century of sleep research to examine the maladies of dreaming, their pathophysiologic significance, and management.
RECENT FINDINGS
Under healthy physiologic conditions, REM sleep is characterized by vivid mentation combined with skeletal muscle paralysis. The loss of REM sleep atonia in RBD results in vivid, potentially injurious dream enactment to patients and bed partners. RBD is common, affecting at least 1% of the population and is primarily caused by α-synuclein pathology of REM sleep–related brainstem neurons. The majority of patients with RBD ultimately develop a neurodegenerative syndrome such as Parkinson disease, dementia with Lewy bodies, or multiple system atrophy. Among patients with Parkinson disease, RBD predicts an aggressive disease course with rapid cognitive, motor, and autonomic decline. RBD is diagnosed by the presence of dream enactment episodes (either recorded or clinically recalled) and physiologic evidence of REM sleep without atonia demonstrated on polysomnography. Bedroom safety is of paramount importance in the management of RBD while pharmacokinetic options include melatonin or clonazepam.
SUMMARY
The injurious dream enactment of RBD is common and treatable. It is a syndrome of α-synuclein pathology with most patients ultimately developing Parkinson disease, dementia with Lewy bodies, or a related disorder.
KEY POINTS
Approximately 75 million people worldwide have rapid eye movement (REM) sleep behavior disorder (RBD), 1% of the population and 5% of older adults.
Emotionally salient memories are consolidated during REM sleep.
Nightmares and sleep paralysis peak in incidence prior to adolescence.
In addition to quantifying REM motor activity and characterizing nocturnal behaviors, polysomnography helps rule out mimicking conditions such as obstructive sleep apnea and periodic limb movements, the disorders that primarily compose the differential diagnosis for RBD.
Patients with RBD associated with narcolepsy are more often female, younger, and do not appear to be at higher risk of neurodegeneration.
The most commonly prescribed therapies for RBD are melatonin and clonazepam.
Melatonin treats RBD by normalizing circadian features of REM sleep.
RBD is a prodromal syndrome of α-synuclein neuropathology with the majority of patients converting to a neurodegenerative disorder.
RBD predicts the non–tremor-predominant subtype of Parkinson disease with freezing of gait and a more aggressive clinical course.
Patients who have RBD with comorbid hyposmia and constipation but who are not taking an antidepressant are at high risk of phenoconversion to a neurodegenerative disorder in less than 5 years.
Recent insights suggest that antidepressants do not induce RBD but instead appear to unmask dream enactment in an individual who is already burdened by early α-synuclein pathology.
The North American Prodromal Synucleinopathy Consortium is an important resource for patients with RBD who are interested in enrolling in neuroprotective clinical trials.
Source:
Continuum Sleep 2020
------ CerebrovascularDisease_DiagnosticEvaluation_StrokeEtiology.txt ------
ARTICLE 1: DIAGNOSTIC EVALUATION OF STROKE ETIOLOGY
James F. Meschia, MD, FAAN. Continuum (Minneap Minn). April 2023; 29 (2 Cerebrovascular Disease):412–424.
ABSTRACT
OBJECTIVE
Precise therapies require precise diagnoses. This article provides an evidence-based approach to confirming the diagnosis of ischemic stroke, characterizing comorbidities that provide insights into the pathophysiologic mechanisms of stroke, and identifying targets for treatment to optimize the prevention of recurrent stroke.
LATEST DEVELOPMENTS
Identifying the presence of patent foramen ovale, intermittent atrial fibrillation, and unstable plaque is now routinely included in an increasingly nuanced workup in patients with stroke, even as ongoing trials seek to clarify the best approaches for treating these and other comorbidities. Multicenter trials have demonstrated the therapeutic utility of patent foramen ovale closure in select patients younger than age 60 years. Insertable cardiac monitors detect atrial fibrillation lasting more than 30 seconds in about one in ten patients monitored for 12 months following a stroke. MRI of carotid plaque can detect unstable plaque at risk of being a source of cerebral embolism.
ESSENTIAL POINTS
To optimize the prevention of recurrent stroke, it is important to consider pathologies of intracranial and extracranial blood vessels and of cardiac structure and rhythm as well as other inherited or systemic causes of stroke. Some aspects of the stroke workup should be done routinely, while other components will depend on the clinical circumstances and preliminary testing results.
KEY POINTS
The stroke workup is the set of diagnostic tests performed to gain insight into modifiable risk factors and stroke mechanism. The stroke workup has fixed and variable components, the latter being contingent on clinical circumstances, initial testing, and therapeutic objectives.
Recent American Heart Association guidelines on secondary stroke prevention include an algorithm for performing an evidence-based diagnostic evaluation.
Three or more transient ischemic attacks in a 2-week period in the same arterial distribution suggest an unstable atherosclerotic plaque as a mechanism.
A stroke evaluation should include examining the patient for preceding strokes or transient ischemic attacks, atherosclerotic risk factors, head or neck trauma or radiation therapy, migraines, and a family history of stroke or dementia.
Nearly 5% of strokes, most of which are lacunar and infratentorial, have a National Institutes of Health Stroke Scale (NIHSS) score of 0. Although these strokes are usually not treated with thrombolytics, they are nonetheless important to recognize because the stroke recurrence rates for NIHSS 0 and non-0 strokes are very similar.
Nearly 7% of acute ischemic strokes do not have a focal area of restricted diffusion on initial diffusion-weighted imaging. Patients with posterior circulation stroke are 5 times as likely to have diffusion-weighted imaging–negative stroke as patients with anterior circulation stroke.
CT angiography in the oblique and axial planes is the imaging modality of choice for identifying carotid webs.
Long-term cardiac rhythm monitoring detects severalfold more cases of atrial fibrillation than routine inpatient monitoring following a stroke (12.1% versus 1.8%), although the minimum burden of intermittent atrial fibrillation to justify anticoagulation remains uncertain.
Transesophageal echocardiography may be less sensitive in detecting patent foramen ovale than contrasted transthoracic echocardiography.
To diagnose embolic stroke of undetermined source, patients should have a stroke workup that includes, at a minimum, brain imaging, ECG, transthoracic echocardiography, cardiac monitoring for at least 24 hours, and imaging of both intracranial and extracranial arteries.
The yield of testing for genetic stroke syndromes is much higher when patients have a positive family history or a plethora of recurrent strokes and a paucity of conventional risk factors, particularly if the strokes are due to small vessel disease.
Patients with aseptic cerebral venous thrombosis should be screened for thrombophilia.
A C-reactive protein level higher than 10 mg/L should raise suspicion for stroke caused by endocarditis.
Source:
Continuum Cerebrovascular April 2023
------ MultipleSclerosisDemyelinating_PEDIATRIC_ACQUIRED_DEMYELINATING_DISORDERS.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article reviews the clinical presentation, diagnostic evaluation, treatment, and prognosis of the most common monophasic and relapsing acquired demyelinating disorders presenting in childhood.
RECENT FINDINGS
Our understanding of neuroimmune disorders of the central nervous systemis rapidly expanding. Several clinical and paraclinical factors help to informthe diagnosis and ultimately the suspicion for a monophasic versus relapsing course, including the age of the patient (prepubertal versus postpubertal), presence or absence of clinical encephalopathy, identification of serum autoantibodies (eg, myelin oligodendrocyte glycoprotein [MOG] and aquaporin-4), presence of intrathecally unique oligoclonal bands, and location/extent of radiologic abnormalities. Collaborative international research efforts have facilitated understanding of the safety and efficacy of currently available immunotherapies in children with acquired demyelinating disorders, particularly multiple sclerosis.
SUMMARY
Although many of the demyelinating disorders presented in this article can affect children and adults across the age spectrum, the clinical and radiologic phenotypes, treatment considerations, and long-term prognoses are often distinct in children.
Key Points
Neuroimmune demyelinating disorders manifest across the age spectrum, but the clinical phenotypes, radiologic expression, treatment, and prognostic considerations are often distinct in children compared to adults.
Clinical vigilance is important to ensure that patients with a monophasic disorder are not inappropriately placed on chronic immunotherapy. Close monitoring also ensures that those who exhibit a propensity for ongoing central nervous system demyelination are classified accurately and treated early.
CSF testing should be strongly considered in all children presenting with an initial acquired demyelinating syndrome. This evaluation should include cell counts, protein, glucose, IgG index, and oligoclonal bands (in serum and CSF).
Compared to adult-onset optic neuritis, pediatric optic neuritis ismore often bilateral, particularly in children younger than 10 years of age. Children also have greater rates of optic disc edema (up to 75%) and more severe vision loss, with more than 50% of children exhibiting a visual acuity of 20/200 or worse acutely.
Myelin oligodendrocyte glycoprotein (MOG) antibodies are an important component of the laboratory evaluation of a child presenting with acute or subacute vision loss, with approximately 30% of all pediatric MOG-associated disorder cases manifesting as optic neuritis.
The likelihood of multiple sclerosis (MS) following an isolated optic neuritis is increasingly higher if the patient is older (eg, peripubertal/postpubertal), has at least two oligoclonal bands unique to the intrathecal space, and has concurrent demyelinating lesions within the brain outside of the optic nerve/chiasm.
The risk for a future diagnosis of MS following acute transverse myelitis is approximately 14% to 22% and is highest in those of female sex with concurrent demyelinating lesions in the brain and the presence of CSF oligoclonal bands.
The clinical manifestations of acute disseminated encephalomyelitis (ADEM) include subacute onset of encephalopathy unexplained by fever/illness or postictal symptoms in addition to multifocal neurologic abnormalities that vary based on the central nervous system area(s) impacted.
MOG antibodies are detected in more than half of all pediatric patients with ADEMand should be tested for in any child presenting with an ADEM phenotype.
Less than 10% of children with ADEM will experience a second demyelinating attackmore than 3 months after the sentinel attack, and the majority of these patients who relapse exhibit evidence of MOG antibodies.
The progressive MS phenotype in childhood is very rare and perhaps less common than pediatric neurogenetic disorders that cause progressive neurologic decline (eg, inherited leukodystrophies, metabolic or mitochondrial disorders).
Compared to their adult-onset counterparts, pediatric patientswith MS exhibit a more inflammatory disease course, with a clinical relapse rate that is 2 to 3 times greater and significantly higher inflammatory lesion volumes on brain neuroimaging.
The 2017 McDonald criteria for MS have 71% sensitivity and 95% specificity when applied to the pediatric population, but caution should be used in children younger than 11years of age.
In 2018, fingolimodwas granted US Food and Drug Administration and European Commission approval for the treatment of MS in children aged 10years and older.
The clinical impact and efficacy of MS disease-modifying therapies appear to be highly associated with age, with youth with MS deriving the greatest benefits. The efficacy of these treatments onMS disability declines with advancing age, arguing in favor of treating children with MS early with disease-modifying therapies that effectively eliminate clinical and radiologic progression whilemaintaining or enhancing overall quality of life.
Cognitive impairment affects up to one-third of children with MS and is more common than in those with adult-onset MS, independent of disease duration.
Longitudinally extensive transverse myelitis is not specific to pediatric neuromyelitis optica spectrum disorder (NMOSD) and can be seen in the setting of ADEM, MOG-associated disorders, and MS. In addition, the clinical and radiologic presentation of NMOSD may have features that mimic ADEM, such as the presence of encephalopathy and multifocal demyelination.
Aquaporin-4–positive NMOSD is a highly relapsing disorder that can lead to significant permanent neurologic disability at an early age.
Anti-MOG antibodies are detected in one-third of all children at the time of initial onset of an acquired demyelinating syndrome.
The phenotype of MOG-associated demyelination is somewhat age dependent, with younger children more likely to present with an ADEM phenotype and older children (>11 years of age) more likely to present with optic neuritis.
Children who remain seropositive for MOG antibodies are at higher risk for relapse compared to those who convert to seronegative (38% versus 13%); however, patients who are seronegative for MOG antibodies and patients with a fluctuating serostatus can also experience relapsing disease.
Many children with MOG-associated demyelination experience a monophasic course (particularly if the presenting phenotype is ADEM) and good functional outcomes. Compared with adults, children exhibit better neurologic recovery, with complete recovery occurring in 75% to 96% of all children.
Source:
Continuum 2022
------ CerebrovascularDisease_DIAGNOSIS_AND_MANAGEMENT_OF_CEREBRAL_SMALL_VESSEL_DISEASE.txt ------
ABSTRACT
OBJECTIVE
Cerebral small vessel disease (CSVD) is a common neurologic condition that contributes to considerable mortality and disability because of its impact on ischemic and hemorrhagic stroke risk and dementia. While attributes of the disease have been recognized for over two centuries, gaps in knowledge remain related to its prevention and management. The purpose of this review is to provide an overview of the current state of knowledge for CSVD.
LATEST DEVELOPMENTS
CSVD can be recognized by well-defined radiographic criteria, but the pathogenic mechanism behind the disease is unclear. Hypertension control remains the best-known strategy for stroke prevention in patients with CSVD, and recent guidelines provide a long-term blood pressure target of less than 130/80 mm Hg for patients with ischemic and hemorrhagic stroke, including those with stroke related to CSVD. Cerebral amyloid angiopathy is the second leading cause of intracerebral hemorrhage and may be increasingly recognized because of newer, more sensitive imaging modalities. Transient focal neurologic episodes is a relatively new term used to describe “amyloid spells.” Guidance on distinguishing these events from seizures and transient ischemic attacks has been published.
ESSENTIAL POINTS
CSVD is prevalent and will likely be encountered by all neurologists in clinical practice. It is important for neurologists to be able to recognize CSVD, both radiographically and clinically, and to counsel patients on the prevention of disease progression. Blood pressure control is especially relevant, and strategies are needed to improve blood pressure control for primary and secondary stroke prevention in patients with CSVD.
KEY POINTS
Cerebral small vessel disease (CSVD) contributes to significant morbidity and mortality through its impact on stroke risk, cognitive decline, and dementia.
Several modifiable clinical risk factors are associated with the development of CSVD, including hypertension, obstructive sleep apnea, diabetes mellitus, hyperlipidemia, and tobacco use.
CSVD is increasingly recognized as a dynamic, whole-brain disorder characterized by endothelial dysfunction and alterations in the function of the neurovascular unit. A better understanding of the underlying mechanisms may help to identify therapeutic targets for treatment.
There are six radiographic phenotypes of CSVD: (1) recent small subcortical infarct, (2) white matter hyperintensity, (3) lacune of presumed vascular origin, (4) widened perivascular spaces, (5) cerebral microbleed, and (6) brain atrophy.
Small vessel ischemic (lacunar) stroke is the most commonly encountered acute clinical manifestation of CSVD. It represents 20% to 30% of ischemic stroke cases.
Hypertension, diabetes mellitus, and tobacco use are important risk factors for small vessel ischemic stroke, and hyperlipidemia may also contribute to risk.
The American Heart Association/American Stroke Association (AHA/ASA) Guideline for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack includes a class 1 (level of evidence B-R) recommendation for target blood pressure less than 130/80 mm Hg for patients with ischemic stroke.
Given the relationship between uncontrolled blood pressure and recurrent stroke risk, cognitive decline, and dementia after stroke, interventions to improve blood pressure control in all stroke survivors, including those with small vessel stroke, are urgently needed.
The Boston criteria 2.0 can be used to diagnose cerebral amyloid angiopathy (CAA) based on radiographic features, clinical characteristics, and histopathologic samples when available.
Radiographic findings in CAA include cortical hemorrhage, cerebral microbleeds, superficial siderosis, convexal subarachnoid hemorrhage, silent infarcts, white matter hyperintensities, and MRI-visible perivascular spaces in the centrum semiovale.
Episodes of CAA-related intracerebral hemorrhage (ICH) can recur over weeks, months, or years, with a yearly ICH recurrence risk of 7.4% in CAA compared to 1.1% per year in CAA-unrelated ICH.
Transient focal neurological episodes associated with CAA can present as short (typically less than 30 minutes) disturbances in motor, sensory, language, or visual function which may be difficult to distinguish from transient ischemic attack or seizure.
Patients who have CAA without ICH may have abnormal cognitive profiles in the absence of self-reported cognitive deficits. The cognitive profile appears to be more similar to that seen with vascular cognitive impairment; that is, impairments in executive function and processing with relatively preserved memory.
There are no specific management guidelines for reducing ICH recurrence risk in patients with CAA; however, the most recently published AHA/ASA guideline for the management of patients with ICH recommend reducing blood pressure for patients with spontaneous ICH (class 1 recommendation) and suggest a blood pressure target of less than 130/80 mm Hg (class 2a recommendation).
Migraine is often the first manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) presenting often, but not always, in the third decade of life.
As CADASIL inheritance is autosomal dominant, significant family history also supports the diagnosis, but given the possibility of variable presentation within families and the possibility of sporadic mutation, the absence of family history does not exclude CADASIL as a potential diagnosis.
Clinical management of CADASIL and cerebral autosomal recessive arteriopathy with subcortical strokes and leukoencephalopathy (CARASIL) involves management of known vascular risk factors, including hypertension and tobacco use, which have been shown to contribute to poorer outcomes in patients with CADASIL.
Source:
Continuum April 23
------ Sleep_Central_Disorders_of_Hypersomnolence.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article discusses the central disorders of hypersomnolence, a group of disorders resulting in pathologic daytime sleepiness, particularly narcolepsy type 1 and narcolepsy type 2, idiopathic hypersomnia, and Kleine-Levin syndrome. Disease features, diagnostic testing, epidemiology, pathophysiology, and treatment are reviewed.
RECENT FINDINGS
Increasing evidence implicates autoimmunity in narcolepsy type 1, including a strong association with human leukocyte antigen–DQB1*06:02, association with a polymorphism in the T-cell receptor alpha locus in genome-wide association, and the identification of autoreactive T cells in patients with this type of narcolepsy. In contrast, the cause or causes of narcolepsy type 2 and idiopathic hypersomnia are unknown. Multiple treatment options exist, including two medications approved for the treatment of narcolepsy by the US Food and Drug Administration (FDA) in 2019. These include solriamfetol, a dopamine- and norepinephrine-reuptake inhibitor, and pitolisant, an H3-inverse agonist/antagonist that increases histaminergic neurotransmission.
SUMMARY
The central disorders of hypersomnolence all cause severe sleepiness but can be differentiated based on ancillary symptoms, diagnostic testing, and pathophysiology. It is important that these disorders are identified because multiple treatments are available to improve functioning and quality of life.
KEY POINTS
Diagnosis of hypersomnia due to a medical disorder, hypersomnia due to a medication or substance, or insufficient sleep syndrome requires that the excessive daytime sleepiness is believed to be caused by a diagnosed medical or neurologic disorder, a medication or substance, or short sleep durations.
The diagnosis of hypersomnia associated with a psychiatric disease does not imply that the psychiatric disease is necessarily caused by sleepiness or vice versa, just that the two conditions coexist.
The five core clinical features of narcolepsy type 1 are excessive daytime sleepiness, cataplexy, sleep paralysis, sleep-related hallucinations, and disrupted nocturnal sleep. Many patients will not have all five symptoms.
Cataplexy is very specific to narcolepsy type 1 and is not seen in the other hypersomnia disorders. Clinically, the presence or absence of cataplexy differentiates narcolepsy type 1 and narcolepsy type 2.
The core clinical features of idiopathic hypersomnia are excessive daytime sleepiness, long sleep durations, and prominent sleep inertia, although not all symptoms are present in all patients.
The phenotype of narcolepsy type 2 is intermediate between narcolepsy type 1 and idiopathic hypersomnia and has features of each.
Kleine-Levin syndrome manifests as recurrent, severe hypersomnolence that is associated with cognitive dysfunction, altered perception, altered eating, or disinhibition.
The two main diagnostic outputs of the multiple sleep latency test (MSLT) are the mean sleep latency and the number of sleep-onset rapid eye movement (REM) periods. The REM latency from the preceding night study should be counted toward the total sleep-onset REM period count.
Sleep-onset REM periods can be suppressed by medications, most notably serotonergic antidepressants. Ideally, REM-suppressant medications would be withdrawn prior to testing. A 2-week medication-free period is recommended, although this may be too short for medications with very long half-lives (eg, fluoxetine).
Short habitual sleep times, medications, and illicit drugs may all affect MSLT results and must be considered prior to ordering and interpreting the MSLT.
Excessive daytime sleepiness and CSF orexin (hypocretin) deficiency are sufficient to diagnose narcolepsy type 1, even in the absence of cataplexy.
Patients with hypersomnia who test negative for human leukocyte antigen–DQB1*06:02 are very unlikely to be orexin (hypocretin) deficient, such that the usefulness of lumbar puncture for orexin (hypocretin) is very low in this group.
The MSLT may be normal in a substantial number of patients suspected of having idiopathic hypersomnia. In these patients, idiopathic hypersomnia may alternatively be diagnosed by recording at least 11 hours of sleep per 24 hours, either by polysomnography or estimated by wrist actigraphy over at least 7 days.
The population prevalence of narcolepsy type 1 is approximately 1 per 2000. Narcolepsy type 2 may be 3 to 4 times more common than narcolepsy type 1, based on a large population-based MSLT study and insurance database claims.
Kleine-Levin syndrome is rare, with a prevalence estimated at 1 to 5 cases per 1 million.
Narcolepsy type 1 is strongly suspected to be autoimmune, with multiple alterations within T-cell pathways implicated.
Scheduled naps are likely to be more useful for people with narcolepsy type 1 than with idiopathic hypersomnia.
Modafinil has been shown in randomized controlled trials to improve sleepiness in people with narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia.
Modafinil, armodafinil, and pitolisant may all decrease the efficacy of hormonal birth control pills. Additional or alternative birth control methods should be used while taking these medications and for 21 days after their discontinuation.
Sodium oxybate is dosed at bedtime and in the middle of the night and improves sleep consolidation and deep sleep.
A sodium oxybate prescription requires enrollment in a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy program because of the potential for serious risks.
Solriamfetol is a dopamine- and norepinephrine-reuptake inhibitor approved by the FDA for narcolepsy treatment in 2019. It reduces sleepiness in patients with narcolepsy.
Pitolisant increases histaminergic neurotransmission and was approved by the FDA for narcolepsy treatment in 2019. It reduces sleepiness and cataplexy in people with narcolepsy and may reduce sleepiness in people with idiopathic hypersomnia.
Cataplexy can be treated with sodium oxybate, antidepressants, and pitolisant.
Lithium may aid in the prevention of symptomatic episodes and reduce the severity of episodes in people with Kleine-Levin syndrome.
Source:
Continuum Sleep 2020
------ Sleep_Obstructive_Sleep_Apnea.txt ------
ABSTRACT
PURPOSE OF REVIEW
Obstructive sleep apnea (OSA) is often overlooked by clinicians; however, undiagnosed OSA can lead to negative outcomes for patients, including patients with underlying neurologic conditions. Clinicians should be aware of what questions to ask, what diagnostic tests to use, and what treatments to consider in patients with OSA.
RECENT FINDINGS
OSA influences many neurologic conditions, including stroke, epilepsy, headache, and neuromuscular conditions. Treatment of OSA is effective, especially with patient-tailored options, the correct education, and support.
SUMMARY
OSA is a serious medical condition with impacts on patients’ health, safety, and quality of life. Clinicians should identify patients at high risk for OSA and arrange for appropriate diagnosis and treatment, which, in turn, may lead to the improvement of or reduction in risk for neurologic and other health conditions.
KEY POINTS
Obstructive sleep apnea (OSA) is a common disorder, with nearly 1 billion people worldwide with the condition.
OSA can impact a patient’s quality of life and safety and can complicate comorbid medical conditions, including cardiovascular, psychiatric, and neurologic disorders.
Daytime sleepiness in patients with OSA is one of the most dangerous effects, particularly in patients who are sleepy behind the wheel or who work in jobs requiring alertness for safety.
While weight and neck size are primary physical factors in predicting risk for obstructive sleep apnea, retrognathia is a common finding in patients who have OSA but are of normal weight.
Patients who are at risk for OSA should have a standardized evaluation of their breathing during sleep; two primary methods, which include in-laboratory polysomnography and home sleep apnea testing, define the severity of the sleep-related breathing disorder.
OSA is a treatable condition with a variety of options to improve the patient’s breathing during sleep, which should be applied based on knowledge of the disorder and the patient’s wishes and preferences.
Positive airway pressure therapy is an effective treatment for OSA and, contrary to some opinions, mostly tolerated well by patients when they are well prepared and educated and get appropriate follow-up.
While men have a higher incidence of OSA, women may also have the disease, particularly those in higher-risk groups (eg, postmenopausal, obese, and retrognathic).
OSA is associated with an increased risk for many medical conditions, including hypertension and arrhythmias.
Many screening tools exist to screen for obstructive sleep apnea in different populations, including the STOP-BANG Questionnaire; the American Academy of Neurology also has tools that may be useful in clinical practice.
Source:
Continuum Sleep 2020
------ Epilepsy_NEUROIMAGING_OF_EPILEPSY.txt ------
ABSTRACT
PURPOSE OF REVIEW
This article provides an overview of imaging modalities, important imaging pathologies, and the role each imaging modality can play in the diagnosis, evaluation, and treatment of epilepsy, including epilepsy surgery.
RECENT FINDINGS
The Harmonized Neuroimaging of Epilepsy Structural Sequences (HARNESS-MRI) protocol was proposed to standardize MRI imaging for all patients with seizures. The role of 7-Tesla MRI in finding previously occult epileptogenic lesions is under investigation, and the technique is increasingly used. Developing MRI postprocessing techniques can increase the sensitivity of MRI. Improvements in functional imaging techniques such as EEG–functional MRI (fMRI) and magnetic source imaging provide complementary methods of identifying seizure foci. New epileptogenic pathologies such as multinodular and vacuolating neuronal tumors (MVNT) are being discovered, and the importance of others, such as encephaloceles, is better appreciated.
SUMMARY
Brain imaging is a critical component of the diagnosis and evaluation of patients with epilepsy. Structural imaging modalities such as MRI and CT allow for the identification of a wide variety of potentially epileptogenic lesions. For patients with drug-resistant epilepsy under consideration for resective surgery, both structural and functional neuroimaging may be needed for focus identification and surgical planning for preservation of neurologic function.
KEY POINTS
The finding of an epileptogenic lesion on brain imaging in a patient with a single seizure may lead to the diagnosis of epilepsy if the treating neurologist estimates a risk of seizure recurrence greater than 60%.
In adults with an unprovoked first seizure, significant brain imaging abnormalities are associated with an increased risk of seizure recurrence within 2 years.
Brain imaging assists neurologists in estimating whether a paroxysmal event was likely a seizure, determining whether a patient has epilepsy, classifying the epilepsy type, selecting treatments, predicting the prognosis, and completing a presurgical workup.
A first seizure associated with a cavernous malformation is strongly associated with recurrent seizures, with a 5-year risk of 94%. Only about half of patients achieve seizure freedom with antiseizure medications alone.
In the acute setting, a CT scan of the head is often necessary to ensure that the seizure was not caused by a threatening intracranial pathology.
The International League Against Epilepsy Neuroimaging Task Force recommends that MRI be performed for all patients presenting with a first seizure or newly diagnosed epilepsy where resources allow.
The Harmonized Neuroimaging of Epilepsy Structural Sequences (HARNESS-MRI) protocol is recommended for all patients with seizures. It consists of three mandatory sequences and two optional sequences, optimized for 3-Tesla (T) scanners but compatible with 1.5T scanners.
CT remains useful in the evaluation of potentially epileptogenic calcifications, vascular abnormalities, and encephaloceles.
Malformations of cortical development are a heterogeneous group of mostly congenital and potentially epileptogenic brain lesions arising from disrupted cerebral cortex development that can be caused by genetic, infectious, vascular, or other etiologies.
Focal cortical dysplasia is a common cause of drug-resistant focal epilepsy that may escape detection on routine MRI.
The transmantle sign denotes a long region of T2/fluid-attenuated inversion recovery (FLAIR) hyperintense signal tapering between the affected region of cortex and the ventricular wall, usually associated with focal cortical dysplasia type IIb.
Because focal cortical dysplasia can be masked by the maturation of myelination in childhood, it is essential to obtain high-quality MRI early in the course of epilepsy.
Periventricular nodular heterotopias are solid masses of neurons that line lateral ventricle walls after aborted migration of neurons destined for the cortex. Seizures can emerge from one or more nodules, areas of the overlying cortex, or a complex network.
Periventricular nodular heterotopias are conspicuous on MRI or CT as solid masses isointense/isodense to gray matter; their location in a region where pathologic lesions rarely occur makes them easy to miss.
Cerebral cavernous malformations may have a classic “popcorn” appearance on MRI. T2* sequences such as gradient recalled echo (GRE) or susceptibility-weighted imaging (SWI) show areas of hypointensity and the epileptogenic hemosiderin rim that surrounds the structure.
Low-grade gliomas are infiltrating tumors causing focal seizures. They are treated with surgery, radiation therapy, and chemotherapy. Their continued growth may lead to a more drug-resistant epilepsy.
Dysembryoplastic neuroepithelial tumors (DNETs) are among the most common tumors causing focal epilepsy. MRI displays a classic “bubbly” appearance, with multiple lobulated regions of hyperintensity on T2-weighted sequences.
Multinodular and vacuolating neuronal tumors (MVNTs) are recently described epileptogenic lesions with an MRI appearance of multiple discrete ovoid intra-axial nodules found at the junction of superficial subcortical white matter and a deep cortical ribbon, often surrounding a sulcus.
Mesial temporal sclerosis is a surgically treatable form of drug-resistant epilepsy that can be diagnosed in the clinic.
On MRI, mesial temporal sclerosis is characterized by hippocampal atrophy, T2/FLAIR hyperintensity, and loss of internal architecture. Supportive imaging findings include temporal lobe atrophy or asymmetry of the fornix and mammillary bodies.
An encephalocele is a region of brain herniation through a defect of bone and dura mater. Anterior temporal encephaloceles are a surgically treatable cause of temporal lobe epilepsy, often missed during image interpretation.
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an inflammatory cause of meningoencephalitis with seizures. It has a typical imaging pattern of diffuse perivascular enhancement radiating out from the lateral ventricles on contrast-enhanced MRI.
CT imaging may be necessary as a complement to MRI images for the imaging diagnosis of neurocysticercosis.
In the course of a presurgical evaluation for drug-resistant epilepsy, imaging results are essential for seizure focus identification and surgical planning for the preservation of neurologic function.
In the presurgical evaluation of a patient with focal epilepsy, the presence or absence of an epileptogenic lesion on structural imaging has a major impact on surgical planning and seizure-free outcomes.
MRI postprocessing techniques such as volumetry of mesiotemporal lobe structures, hippocampal T2 relaxometry, and automated texture analysis may be helpful in identifying lesions that were not detectable on simple visual inspection.
Functional imaging evaluates physiologic characteristics of epileptogenic brain regions to identify regions of abnormal function, helping to lateralize or localize the seizure focus.
Fludeoxyglucose positron emission tomography (FDG-PET) imaging identifies regions of interictal glucose hypometabolism. In temporal lobe epilepsy, unilateral temporal hypometabolism is correlated with the side of seizure focus. FDG-PET is less sensitive in extratemporal epilepsy.
Single-photon emission computed tomography (SPECT) uses a radiotracer to detect increased blood flow during the ictal period to identify the seizure focus. The tracer must be injected immediately on seizure onset, creating logistic challenges.
Functional MRI (fMRI) and diffusion tensor imaging (DTI) are imaging modalities that can help identify the location of critical brain tissue and assist with the safe resection of the seizure focus.
Source:
Continuum Epilepsy 2022
------ MovementDisorders_PROGRESSIVE_SUPRANUCLEAR_PALSY_AND_CORTICOBASAL_SYNDROME.txt ------
ABSTRACT
PURPOSE OF REVIEW
The differential diagnosis of parkinsonism (tremor, rigidity, bradykinesia, and gait difficulty/postural instability) is broad and includes two neurodegenerative conditions that exist on a clinicopathologic spectrum: progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Early in their clinical course, PSP and CBS may be difficult to distinguish from Parkinson disease and several other illnesses, but it is crucial to do so because of implications for management and prognosis.
RECENT FINDINGS
Early accurate diagnosis of PSP and CBS remains a challenge because of heterogeneity in presenting symptoms and high frequency of coexisting pathologies (especially Alzheimer disease and vascular disease). It is increasingly recognized that patients with PSP, CBS, and other parkinsonian disorders require multidisciplinary care for optimal outcomes. With the recent proliferation of biomarker studies and therapeutic trials for tauopathies, there is growing hope that better treatments for PSP and CBS are on the horizon.
SUMMARY
Although PSP and CBS currently lack disease-modifying therapies, it is important to diagnose them as early as possible so that the patient can benefit from the many available symptomatic therapies, support groups, and a growing number of clinical trials.
KEY POINTS
The pathologic hallmark of progressive supranuclear palsy is the presence of tau protein isoforms with four microtubule-binding repeats (4-repeat tau), in astrocytic tufts (most specific for progressive supranuclear palsy), oligodendrocytic coils, and neurofibrillary tangles (least specific).
It is important to perform genetic testing in patients with early age at symptom onset or a clear family history of atypical parkinsonism. Among genetic mimics of progressive supranuclear palsy, Niemann-Pick disease type C stands out, as it is a treatable condition.
Progressive supranuclear palsy–Richardson syndrome (classic progressive supranuclear palsy) refers to akinetic-rigid parkinsonism with early falls and vertical eye movement impairment.
Current clinical diagnostic criteria for progressive supranuclear palsy include levels of diagnostic certainty that offer trade-offs between specificity and sensitivity.
Optokinetic nystagmus testing can be helpful in assessing saccades if gross saccade testing is equivocal.
Progressive supranuclear palsy–parkinsonism is the second most common progressive supranuclear palsy variant and can be difficult to distinguish from Parkinson disease for several years from symptom onset.
The parkinsonism in progressive supranuclear palsy–parkinsonism can be tremor-predominant or akinetic-rigid and may have a levodopa response, although typically without motor fluctuations or dyskinesias.
Frontal-executive cognitive impairment is an important feature of both progressive supranuclear palsy and corticobasal syndrome.
Key differential diagnosis considerations for progressive supranuclear palsy include Parkinson disease, other degenerative parkinsonian disorders (such as dementia with Lewy bodies and multiple system atrophy), normal pressure hydrocephalus, and vascular parkinsonism.
The easily measured ratio of midsagittal midbrain to pontine base distances on T1-weighted MRI of less than 0.5 is highly sensitive and specific for progressive supranuclear palsy–Richardson syndrome but not other progressive supranuclear palsy variants.
Corticobasal syndrome refers to the patient’s clinical presentation and typically includes asymmetric presentation of limb rigidity, akinesia, dystonia, myoclonus, and apraxia. Corticobasal degeneration is the term referring to specific 4-repeat tau pathology on brain autopsy.
Corticobasal degeneration is most specifically characterized by astrocytic plaques, whereas progressive supranuclear palsy has tufted astrocytes.
Corticobasal degeneration pathology accounts for only about 50% of corticobasal syndrome cases. The remainder of corticobasal syndrome cases are due to progressive supranuclear palsy, Alzheimer disease, and rarely other pathologies.
Although it is a classic sign, alien limb phenomenon occurs in only about 20% of patients with autopsy-confirmed corticobasal degeneration.
When completing a levodopa trial in progressive supranuclear palsy or corticobasal syndrome, maintain maximum tolerated levodopa dose for at least 1 month before gradual tapering.
Dopaminergic medications other than levodopa are best avoided in progressive supranuclear palsy and corticobasal syndrome because of side effects and lack of efficacy.
Anticholinergic medications should be avoided in progressive supranuclear palsy and corticobasal syndrome whenever possible because of the risk of worsening cognitive impairment.
Pseudobulbar affect is a symptom of both progressive supranuclear palsy and corticobasal syndrome and may improve with selective serotonin reuptake inhibitors or dextromethorphan/quinidine.
Depression and anxiety are common in progressive supranuclear palsy and corticobasal syndrome; selective serotonin reuptake inhibitors can be effective at standard doses.
Modafinil or methylphenidate may be helpful for apathy in progressive supranuclear palsy and corticobasal syndrome.
Botulinum toxin injections can help a range of symptoms in progressive supranuclear palsy and corticobasal syndrome, including sialorrhea, cervical and limb dystonia/spasticity, muscle pain, and eyelid opening apraxia/blepharospasm.
Rehabilitation plays a key role in improving and maintaining function in progressive supranuclear palsy and corticobasal syndrome and should be maintained throughout the entire disease course.
Physical therapy targets gait and balance rehabilitation and fall prevention in progressive supranuclear palsy and corticobasal syndrome.
Occupational therapy targets upper extremity function, range of motion, and adaptive device use in progressive supranuclear palsy and corticobasal syndrome.
Speech/swallow therapy targets dysarthria, aphasia, and dysphagia in progressive supranuclear palsy and corticobasal syndrome.
Periodic swallow evaluations help assess aspiration risk and guide dietary modifications for liquids and solids.
The number of clinical trials for progressive supranuclear palsy and corticobasal syndrome is growing, and it is important to refer patients for trial screening as early as possible.
Source:
Continuum 2022
------ Sleep_Restless_Legs_Syndrome_and_Other_Common_Sleep-Related_Movement_Disorders.txt ------
ABSTRACT
PURPOSE OF REVIEW
In this article, the different sleep-related movement disorders are discussed with special attention given to restless legs syndrome (RLS).
RECENT FINDINGS
The differential diagnosis of sleep-related movement disorders can often be challenging; therefore, it is essential to have accurate information to make a correct diagnosis. This article focuses on RLS, highlighting the change in the paradigm of initial treatment, the role played by iron (pathophysiologic and therapeutic), and how to approach possible complications occurring with long-term treatment.
SUMMARY
RLS is one of the most common neurologic conditions, and it is common in clinical practice to find patients experiencing symptoms suggestive of RLS. Neurologists must be careful and thorough in the diagnosis, excluding RLS mimics. The decisions regarding which specific sleep-related movement disorder is present and how it should be treated are important because in certain cases, especially in RLS, adverse effects and long-term complications are frequently reported with the use of certain drugs.
KEY POINTS
Restless legs syndrome (RLS) is mainly characterized by an uncomfortable urge to move the lower limbs, frequently accompanied by abnormal sensations, and is more common during the evening or night, particularly when the patient is at rest. Most patients with RLS have difficulties initiating or maintaining sleep.
Medical conditions most consistently associated with RLS are iron deficiency, pregnancy, chronic kidney failure, multiple sclerosis, polyneuropathy, Parkinson disease, major depressive disorder, generalized anxiety disorder, and attention deficit hyperactivity disorder.
Periodic limb movements (PLMs) constitute the main motor sign of RLS.
Some studies have found that RLS might be a risk factor for developing cardiovascular disease, including coronary heart disease and stroke.
RLS is a strongly hereditable condition, as suggested by the fact that more than 50% of patients have one first-degree relative who is affected.
Several risk polymorphisms for RLS have been identified.
Because patients with RLS require higher peripheral ferritin levels than controls do to obtain equivalent CSF ferritin levels, it is suggested that impaired transport across the blood-brain barrier constitutes part of the pathophysiology.
Central iron deficiency constitutes the best-documented biological abnormality for RLS.
RLS regional central iron deficiency also involves a failure to provide adequate iron transport across the blood-brain barrier, associated with a regional failure to import adequate iron into critical neuronal cells (eg, neuromelanin cells of the substantia nigra).
Two abnormalities in different neurotransmitter systems are present in RLS, which have, until now, been the main targets of therapeutic action: on the one hand, increased dopaminergic function, leading to sensory symptoms and PLMs, and on the other hand, hyperarousal and sleep loss, and probably PLMs, which are caused by increased glutamatergic function.
Five clinical criteria must be met to establish the diagnosis of RLS.
Laboratory parameters to assess in RLS include a complete blood cell count and systemic iron parameters.
The decision of whether to initiate RLS treatment should strongly depend on a risk-benefit assessment that includes the impact that RLS symptoms have on overall function and quality of life (including sleep disturbance).
Choosing a first-line treatment will depend on iron status. Systemic iron parameters should be assessed with a blood test.
Because of long-term complications, the therapeutic role of dopamine agonists as the first-line treatment of RLS is undergoing reconsideration.
Classic features of initial augmentation are breakthrough episodes during the daytime, an increase in symptom frequency or symptom intensity, shorter duration of treatment effect, symptoms in previously unaffected body parts, worsening of sleep efficacy or sleep quality, increased PLMs during sleep or wakefulness, the need for additional medication, or overall decrease in therapeutic efficacy.
The most effective strategy to prevent augmentation would be to not use dopaminergic treatment at all or to at least keep the dopaminergic load as low as possible by using the minimum effective dose for the shortest required period of time.
Gabapentin, pregabalin, and gabapentin enacarbil have proven various degrees of efficacy for RLS.
Opioids are considered a second-line treatment for RLS when symptoms are refractory to other treatments or when complications derived from them occur.
To define the presence of PLMs as a disorder, polysomnography must show the occurrence of PLMs in a considerable number (≥5 PLMs per hour in children and ≥15 PLMs per hour in adults) in patients who have insomnia or excessive daytime sleepiness.
Painful legs and moving toes is a rare syndrome, characterized by leg pain and repetitive stereotyped toe movements.
Painful legs and moving toes has been associated with alterations in the dopaminergic system.
Sleep-related leg cramps is a frequent disorder. It is considered a disorder when the frequency or intensity of cramps impacts sleep quality.
Sleep-related bruxism is related to the presence of snoring, obstructive sleep apnea, and other sleep disorders. Dental problems, jaw muscle pain, and tension headaches can occur as a consequence.
Sleep-related rhythmic movement disorder is a sleep-related movement disorder, occurring typically in children.
The most common forms of sleep-related rhythmic movement disorder are body rocking, head rolling, or body rolling.
Physiologic hypnic fragmentary myoclonus is commonly a physiologic condition but sometimes can be intense or frequent enough to lead to arousals and, hence, disturbing sleep quality.
Propriospinal myoclonus is an abnormal involuntary movement, occurring in the sleep-wake transition period, consisting of flexion-extension rhythmic-arrhythmic jerks arising in axial muscles and spreading to other body parts.
Source:
Continuum Sleep 2020
------ Neuro_Anatomy_cortical_taste.txt ------
The insula and the lateral aspect of the postcentral gyrus are primarily involved in the initial cortical processing of taste.
Source:
RITE 2017
------ MovementDisorders_globuspallidus.txt ------
The globus pallidum has efferent fibers that synapse on the ventral lateral (VL), ventral anterior (VA), and mediodorsal nucleus. Of those, only the mediodorsal projects to the cingulate gyrus. VA projects to the prefrontal cortex, and VL projects primarily to the premotor cortex. The anterior nuclear group also projects to the cingulate gyrus, but its afferents come from the mammillary bodies via the mammillothalamic tract. The reticular nucleus of the thalamus is responsible for the generation of sleep spindles seen on EEG during sleep. The reticular nucleus has no cortical projections, but instead projects to other thalamic nuclei, including the intralaminar nuclei (IL). The intralaminar nuclei are cell groups within the internal medullary lamina, which separates the medial and lateral subdivisions of the thalamus. Its afferents are from nuclei in the brainstem reticular formation, and has diffuse cortical projections. The pulvinar receives fibers from the superior colliculus and has projections to cortical areas 18 and 19, serving as a component in the extrageniculate visual pathway.
Source:
RITE 2009
------ Neuro_diencephalon.txt ------
diencephalon gives rise to the thalamus, epithalamus, subthalamus and hypothalamus. The telencephalon gives rise to the cerebral hemispheres, the basal ganglia, and the rhinencephalon (hippocampus and piriform lobes)
Source:
RITE 2009
------ CerebrovascularDisease_medialmedullarysyndrome.txt ------
The medial medullary syndrome is most commonly associated with infarction in the anterior spinal artery distribution at the level of the medulla. An occlusion at this level may result in ipsilateral CNXII paralysis (fascicle of CNXII), contralateral hemiparesis (pyramid), and contralateral loss of position and vibratory sensation (medial lemniscus). A bilateral lesion in this vascular territory will result in quadriparesis, bilateral loss of proprioception and vibration, and complete paralysis of the tongue.
Source:
RITE 2009
------ NeuroOphthalmology_abducens.txt ------
The abducens nerve lies immediately adjacent to the internal carotid artery in the cavernous sinus. The oculosympathetic fibers also travel near the abducens nerve while the other cranial nerves lie within the wall.
Source:
RITE 2009
------ Neuropathy_LEnerves.txt ------
The tibial division of the sciatic nerve supplies the tibialis posterior muscle. The tibialis anterior, peroneus longus, peroneus brevis and extensor digitorum brevis are supplied by the common peroneal nerve.
Source:
RITE 2009
------ .DS_Store ------
Bud1spblobbptagbwspblobbplist00
]ShowStatusBar[ShowToolbar[ShowTabView_ContainerShowSidebar\WindowBounds[ShowSidebar _{{275, 380}, {920, 436}} #/;R_klmno
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@ @ @ @
EDSDB ` @ @ @
------ Neuro_MotorCNV.txt ------
The motor portion of the trigeminal nerve innervates the muscles of mastication: masseter, temporalis, and medial and lateral pterygoids. It also supplies the mylohyoid, anterior digrastric, tensor veli palatini, and tensor tympani muscles.
Source:
RITE 2009
------ Neuro_circumventricular.txt ------
The circumventricular organs, which do not have a blood-brain barrier, are the area postrema, subfornical organ, organum vasculosum, neurohypophysis, median eminence, pineal gland, and subcommissural organ. The area postrema has been implicated as a chemoreceptor trigger zone for vomiting.
Source:
RITE 2017
------ Neuro_4thventricleopenings.txt ------
The three openings in the 4th ventricle are the two paired lateral apertures (foramina of Luschka) and the median aperture (foramen of Magendie). CSF flows from the 4th ventricle, via these foramina, to reach the subarachnoid space of the cisterna magna.
Source:
RITE 2017
------ Spinal_Cord_Neurological_disease_1.txt ------
1
Source:
1
------ MovementDisorders_VTA.txt ------
Rationale: The ventral tegmental area (VTA), which lies close to the substantia nigra and red nucleus, contains dopaminergic neurons. Efferents from this region radiate to multiple brain locations. One important system is the mesolimbic system in which axons from the VTA project to nucleus accumbens, the amygdala, hippocampus, and
2021 RITE
| 1
prefrontal cortex. Functions of this pathway include reward, motivation, and emotion.
Reference: Malenka RC, Nestler EJ, Hyman SE et al (eds). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience. 2nd ed. New York: McGraw-Hill Medical; 2009, pp 147–148, 367, 376.
Source:
RITE 2021
------ Neuro_CranialNerves_NervusIntermediusCNVII.txt ------
The nervus intermedius is the portion of the facial nerve carrying all the general visceral efferent, general somatic afferent, and special afferent information. The branchial motor fibers going to the muscles of facial expression travel in a separate bundle. Of the potential answers given, an injury to the nervus intermedius would therefore impair taste from the ipsilateral anterior tongue. Facial muscles would not be affected. The parotid gland is innervated by the glossopharyngeal nerve while the striated muscles of the pharynx are innervated by the vagus nerve.
Source:
RITE 2017
------ Neuro_cerebellumcells.txt ------
Golgi cells are found in the granule cell layer of the cerebellum and provide feedback inhibition of the granule cells. Basket cells, stellate cells, and parallel fibers are found in the molecular layer along with purkinje cell dendrites.
Source:
RITE 2017
------ Neuropathy_ulnar.txt ------
The most common site of compression is the elbow
Source:
colin
------ SpinalCord_highcervicallesion.txt ------
In high cervical cord lesions, ipsilateral diminished pain and temperature sensation in the pre auricular area of the face is due to involvement of cells in the substantia gelatinosa which is the distal continuation of the descending trigeminal nucleus and trac
Source:
RITE 2009
------ Neuro_NeuroOphthalmology_CNIII_efferents.txt ------
Efferent fibers from the subnuclei of cranial nerve III for the medial rectus, inferior rectus, and inferior oblique proceed ipsilaterally. Fibers from the subnucleus for the superior rectus decussate. The central caudal nucleus is a midline cell group of III that gives rise to both crossed and uncrossed fibers that innervate the levator palprebrae muscle.
Source:
RITE 2017
------ Neuro_centraltegmentaltract.txt ------
Climbing fibers originate in the inferior olivary complex and appear to have glutamate as their neurotransmitter. Each climbing fiber possesses an extensive all - or - none excitatory connection with Purkinje cell dendrites in the cerebellar cortex. The red nucleus projects to inferior olivary complex via the central tegmental tract.
Source:
RITE 2009
------ horizantal_gaze.txt ------
Frontal eye fiels -> paramedian pontine reticular formation - > medial longitudinal fasciculus
Source:
nowyouknowneuro
------ NervesandNeuropathy_Anatomy_commonperonealdivisions.txt ------
The common peroneal nerve divides into two branches, the deep and superficial peroneal nerves. The deep peroneal nerve innervates the tibialis anterior and extensor digitorum brevis. The peroneus longus and brevis are supplied by the superficial peroneal nerve. The soleus and tibialis posterior muscles are innervated by the tibial nerve.
Source:
RITE 2017
------ CerebrovascularDisease_PCA.txt ------
The posterior cerebral artery supplies parts of the inferior temporal lobe, occipital lobe, splenium of the corpus callosum and superior parietal lobule.
Source:
RITE 2009
------ NervesandNeuropathy_suprascapularnerve.txt ------
The suprascapular nerve innervates the supraspinatus and infraspinatus muscles. The supraspinatus muscle is responsible for the first 15 degrees of humeral abduction, and the infraspinatus muscle externally rotates the arm.
Source:
RITE 2017
------ SpinalCord_centralcordlesion.txt ------
A central cord lesion which produces pain and temperature dysfunction in a bilateral "shawl" or "cape" distribution is due to involvement of crossing fibers for these modalities in the anterior (aka ventral) white commissure.
Source:
RITE 2009
------ Neuro_mediannervemotor.txt ------
The median nerve has motor branches to lumbricales 1 and 2, the abductor pollicis brevis, the opponens pollicis brevis and the flexor pollicis brevis distal to the carpal tunnel.
Source:
RITE 2009
------ Autonomics_NervesandNeuropathy_SpinalCord_sympathetic_fibers.txt ------
Preganglionic sympathetic fibers leave the spinal cord via the ventral roots of T1 and T2 and then join the paravertebral sympathetic chain and synapse in the superior cervical ganglion. Postganglionic fibers follow the carotid plexus, eventually reaching the pupillodilator muscle.
Source:
RITE 2017
------ Neuro_longitudinalfasiculus.txt ------
With a right unilateral lesion of the medial longitudinal fasciculus, the patient can abduct the left eye on attempted gaze to the left but the right eye cannot be adducted. Nystagmus occurs in the left (abducting) eye.
Source:
RITE 2009
------ CerebrovascularDisease_AICAsyndrome.txt ------
Infarction in the distribution of the anterior inferior cerebellar artery (AICA) involves the cochlea or cochlear nuclei (ipsilateral hearing loss), the vestibular nuclei (vertigo and contralateral beating horizontal/torsional nystagmus), the lateral reticular nucleus (ipsilateral Horner's syndrome), middle cerebellar peduncle (ipsilateral ataxia), the descending tract of V (ipsilateral pain and temperature loss), and lateral spinal thalamic tract (contralateral pain and temperature loss). Infarction of the labyrinthine artery distribution produces acute deafness but not the other findings. Infarction in the posterior inferior cerebellar (PICA) distribution produces a lateral medullary syndrome and does not include hearing loss.
Source:
RITE 2009
------ end_plate_potentials.txt ------
At rest, there is electrical silence in normal muscle except in the region of end plate, where end-plate potentials are recorded. In normal muscle, the mechanical stimulation with a needle produces
a discharge of muscle fibers called insertional activity. Abnormal spontaneous activity includes fibrillation potentials, fasciculation potentials, myotonic discharges, complex repetitive discharges, myokymic discharges, cramps, and neuromyotonic discharges.
------ Neuro_textttest.txt ------
Key variables to consider include sleep stages, sleep-related events, diagnostic and treatment response markers, physiological signals, demographic information, sleep questionnaires, and individualized sleep monitoring5. By integrating these factors and comprehending their interrelationships, we can contribute to the development of comprehensive ground truths. This, in turn, leads to the creation of more accurate and reliable tools that assist in diagnosing and monitoring sleep disorders.
Research Standards for Machine Learning Tools in Sleep Medicine
Establishing research standards that promote transparent machine learning practices in sleep medicine is crucial
Source:
me
------ Neuro_stretchreflex.txt ------
The synapse of the afferent axons for muscle stretch reflexes is located in the anterior (ventral) horn. The muscle stretch reflex is monosynaptic directly from sensory neuron to an alpha motor neuron.
Source:
RITE 2009
------ Neuro_parietal.txt ------
stereoagnosia and statoagnosia (inability to determine body position in space) both localize to the superior parietal lobule (Brodmann area 7) which lies above the intraparietal sulcus.
Source:
RITE 2009
------ Neurological_disease_1.txt ------
1
Source:
1
------ Neuro_CerebrovascularDisease_baroreceptor_nucleustractussolitaris.txt ------
The baroreceptor reflex helps to regulate blood pressure by detecting changes via baroreceptors mostly located in the carotid sinus and aortic arch. Information from the carotid sinus travels via the glossopharyngeal nerve while that from the aortic arch is carried by the vagus. All baroreceptor afferents terminate in the nucleus tractus solitarius, which then projects to the ventrolateral medulla. A decrease in blood pressure results in an increase in sympathetic tone and decrease in parasympathetic tone, with an increase in blood pressure producing the opposite effect.
Source:
RITE 2017
------ Neuro_BandofBallinger.txt ------
Layer IV contains a dense horizontal band of fibers - the external band of Baillarger. This band contains the terminal ramifications of the thalamocortical projections from specific thalamic relay nuclei. It is particularly prominent in the striated or primary visual cortex, and known as the line of Gennari.
Source:
------ Autonomics_sweatglandsM3Muscarinic.txt ------
The sweat glands are innervated by postganglionic sympathetic cholinergic fibers. Cholinergic inputs stimulate sweat production via M3 type muscarinic receptors.
Source:
RITE 2017
------ moya_moya_fun_fact.txt ------
moya moya is likely to involve the ICA
Source:
yacoub
------ Neuropathy_sciaticnervepath.txt ------
The sciatic nerve passes underneath the piriformis muscle and may be entrapped at that location. Amongst the many muscles which the sciatic innervates is the biceps femoris.
Source:
RITE 2009
------ CerebrovascularDisease_acuteaphasia.txt ------
When a patient presents with abrupt onset aphasia and no hemiparesis or facial droop or other lateralizing signs
It is especially important to clarify handedness
Source:
Colin, Isayev
------ Sleep_Neurological_Diseases__Trials_Historical_Relevance_meow.txt ------
roar
Source:
me
------ CerebrovascularDisease_NeuroOphthalmology_CentralRetinalArtery.txt ------
The central retinal artery is a branch of the ophthalmic artery and makes only a minimal contribution to the vascular supply of the optic disc. The short posterior ciliary arteries are branches that also arise from the ophthalmic artery and supply the optic disc and the retro-orbital optic nerve.
Source:
RITE 2017
------ Neuro_CerebrovascularDisease_internalauditoryartery.txt ------
The internal auditory artery (IAA) typically arises from the anterior inferior cerebellar artery (AICA), but may also arise directly from basilar artery. The IAA will then divide into a cochlear and vesitbular branch to supply the labyrinth. AICA ischemia can therefore result in unilateral deafness.
Source:
RITE 2017
------ SpinalCord_gracilis.txt ------
Source:
Proprioceptive and vibratory loss in the lower extremities, due to a spinal cord lesion, involves the fasiculus gracilis which serves these functions below the level of T6.
------ C8_dermatome.txt ------
C8 dermatome includes the 4th and 5th digits
Source:
Colin
------ SpinalCord_proprioception.txt ------
Proprioceptive and vibratory loss in the lower extremities, due to a spinal cord lesion, involves the fasiculus gracilis which serves these functions below the level of T6.
Source:
A central cord lesion which produces pain and temperature dysfunction in a bilateral "shawl" or "cape" distribution is due to involvement of crossing fibers for these modalities in the anterior (aka ventral) white commissure.
------ Neuro_auditoryfibers.txt ------
Secondary auditory fibers from the cochlear nuclei form the dorsal, intermediate, and ventral acoustic striae. The dorsal and intermediate striae cross the midline and enter the lateral lemniscus. The fibers of the ventral stria terminate in the superior olivary nuclei and the nucleus of the trapezoid body. These nuclei give rise to tertiary fibers that enter the lateral leminsci. The lateral lemniscus ascends to the midbrain where most of the fibers terminate in the inferior colliculi.
Source:
RITE 2009
------ CerebrovascularDisease_anteriorchoroidal.txt ------
Occlusion of the anterior choroidal artery can result in hemiparesis and hemisensory loss since the posterior limb of the internal capsule is perfused by this artery. Also, the lateral geniculate nucleus of the thalamus is perfused by the anterior choroidal and dysfunction of this nucleus tends to produce a contralateral homonymous hemianopsia with sparing of the horizontal meridian.
Source:
RITE 2009
------ Neuropathy_CNNervusIntermedius.txt ------
The nervus intermedius is the portion of the facial nerve carrying all the general visceral efferent, general somatic afferent, and special afferent information. The branchial motor fibers going to the muscles of facial expression travel in a separate bundle. Of the potential answers given, an injury to the nervus intermedius would therefore impair taste from the ipsilateral anterior tongue. Facial muscles would not be affected. The parotid gland is innervated by the glossopharyngeal nerve while the striated muscles of the pharynx are innervated by the vagus nerve.
Source:
RITE 2009
------ Neuropathy_MartinGruber.txt ------
The Martin-Gruber anastomosis occurs in 15% to 30% of the population. It consists of a communicating branch from the median nerve, usually from the anterior interosseous nerve, to the ulnar nerve in the forearm. It consists of nerve fibers destined for the first dorsal interosseous, most commonly, followed by the adductor pollicis and abductor digiti minimi.
Source:
RITE 2009
------ NeuroOphthalmology_Frontaleyefields.txt ------
The frontal eye fields project to their subcortical targets via the anterior limb of the internal capsule. Fibers originating in the frontal operculum travel via the corticobulbar tract in the genu of the internal capsule. The output of the primary motor cortex (the corticospinal and corticobulbar tracts) travel in the posterior limb and the genu of the internal capsule.
Source:
RITE 2009
------ Neuro_conductionaphasia.txt ------
A group of long association fibers that interconnects the superior and middle frontal gyri with the posterior superior temporal gyrus is the arcuate fasciculus. In the dominant hemisphere, interuption of the arcuate fasciculus, between Wernicke's and Broca's area results in conduction aphasia.
Source:
RITE 2009
------ CerebrovascularDisease_opthalmic_artery.txt ------
The internal carotid artery (ICA) can be divided into four segments: cervical, intrapetrosal, intracavernous, and supraclinoid. The ophthalmic artery arises from the ICA just as it emerges from the cavernous sinus, in the supraclinoid segment.
Source:
RITE 2009
------ CerebrovascularDisease_percheron.txt ------
djfas;dlf
Source:
edwards