Use of B-Cell–Depleting Therapy in Women of Childbearing Potential With Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Purposeof Review: There is considerable heterogeneity in the use of B cell depletion in women of childbearing age, likely driven at least in part by the discrepancy between the product labels and what is known about the physiology of IgG1, including breastmilk and placental transfer.Recent Findings:We provide practical considerations on the use of this medication class in women of childbearing potential. We discuss pre-pregnancy planning including vaccinations, safety of B cell depletion during pregnancy as well as postpartum considerations including breastfeeding.Summary:B cell depleting monoclonal antibodies have shown to be effective for pre-pregnancy and postpartum prevention of inflammatory activity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). B cell depleting therapies are large IgG1 monoclonal antibodies which have minimal transfer across the placenta and into breastmilk. Consideration of risks and benefits of these therapies should be considered in counseling women planning pregnancy and postpartum.

Confirming a Historical Diagnosis of Multiple Sclerosis: Challenges and Recommendations

Patients with a historical diagnosis of multiple sclerosis (MS) — a patient presenting with a diagnosis of MS made previously and by a different clinician — present specific diagnostic and therapeutic challenges in clinical practice. Application of the McDonald criteria is most straightforward when applied contemporaneously with a syndrome typical of an MS attack or relapse; however, retrospective application of the criteria in some patients with a historical diagnosis of MS can be problematic. Limited patient recollection of symptoms and evolution of neurological examination and MRI findings complicate confirmation of an earlier MS diagnosis and assessment of subsequent disease activity or clinical progression. Adequate records for review of prior clinical examinations, laboratory results, and/or MRI scans obtained at the time of diagnosis or during ensuing care may be inadequate or unavailable. This paper provides recommendations for a clinical approach to the evaluation of patients with a historical diagnosis of MS to aid diagnostic confirmation, avoid misdiagnosis, and inform therapeutic decision-making.

Case Series of Guillain-Barré Syndrome After the ChAdOx1 nCoV-19 (Oxford–AstraZeneca) Vaccine

Purposeof Review: Vaccination has been associated with Guillain-Barre Syndrome (GBS). Amidst a global vaccination campaign to stop the spread of COVID-19, fears of GBS can contribute to vaccine-hesitancy. We describe three cases of GBS in Calgary, Canada presenting within 2 weeks of receiving the ChAdOx1 nCoV-19 (COVISHIELD) Oxford-AstraZeneca vaccination and review the available literature.Recent Findings:All three patients presented to hospital in Calgary, Alberta, Canada within a one-month time frame with GBS. Their clinical courses ranged from mild to severe impairment, all requiring immunomodulatory treatment.Summary:There is currently little evidence to support a causal relationship between vaccination and GBS. Furthermore, there is limited evidence to support recurrent GBS in patients with GBS temporally associated with vaccination. Neurologists should approach discussions with patients regarding GBS after vaccination carefully, so as not to misrepresent this relationship, and to educate patients that the risk of COVID-19 infection outweighs the small individual risk of a vaccine-associated adverse event.

Essential Tremor: Five New Things

ABSTRACTPurpose of the review:To highlight five new things in the research and clinical aspects of essential tremor (ET).Recent findings:The introduction of a new definition of ET and a new category “ET plus” were the major themes of the recent consensus statement. This new change demands a change in the approach to the clinical diagnosis of ET and related diseases. From the pathogenesis standpoint, the cerebellar neurodegenerative model seems to have numerous evidence in its favor compared to the olivary model which has largely fallen out of favor. From the standpoint of therapeutics, magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has enriched the therapeutic armamentarium.Summary:There has been considerable progress in the field of ET. We discuss five new things in this article which include- (i) new definition (ii) ET plus (iii) approach to the diagnosis of ET, (iv) cerebellar degeneration, and (v) MRgFUS thalamotomy.

Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ABSTRACTPurposeof Review: To investigate the efficacy and safety of CVT-301 for motor fluctuation in Parkinson’s disease (PD).Recent Findings:This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (OR=2.68; 95% CI: 1.86-3.86; p<0.00001). Moreover, CVT-301 had also shown to improve motor function by UPDRS-III score (SMD=3.83; 95% CI: 2.44-5.23; p<0.00001) and promote an overall improvement of PD by PGIC self-rating (OR=2.95; 95% CI: 1.78-4.9; p<0.00001). The most common adverse events encountered were respiratory symptoms (OR=12.18; 95% CI: 5.01-29.62; p<0.00001) and nausea (OR=3.95; 95% CI: 1.01-15.41; p=0.05).Summary:CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in PD patients.

Practical Considerations in the Administration of Aducanumab for the Neurologist

Aducanumab (Aduhelm®), developed by the biotechnology firm Biogen in Cambridge, Massachusetts, was approved using the less common accelerated approval pathway by the Federal Drug Administration (FDA) reserved for treatments that fill a significant unmet need.1 Its approval on June 7, 2021 has been met with an outpouring of opinions from prescribers, insurers, advocacy groups and hospital systems regarding its risk benefit profile.2-4 Originally approved for all forms of Alzheimer’s disease (AD), the FDA updated aducanumab’s labeling on July 8th, 2021 for “treatment in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.5 With six million people nationally in the United States who suffer from AD and an anticipated one third of those who may now fulfill the criteria under the revised labeling, the implications of aducanumab’s approval continue to generate national interest.6

Neurofilament Light Chain Is Related to Longitudinal Decline in Frontotemporal Lobar Degeneration

In the Research article “Neurofilament Light Chain Is Related to Longitudinal Decline in Frontotemporal Lobar Degeneration” by Zhang et al.1, the data in the third column of Table 4 labeled “F letter fluency” were incorrect. A corrected Table 4 is below. The authors regret the error.

Primitive Reflexes and Dementia in Adults With Down Syndrome

ABSTRACTObjective:To determine whether primitive reflexes serve as an indicator of dementia in adults with Down syndrome (DS), we collected neurologic examination data, cognitive and behavioral assessments, and clinical consensus diagnoses of dementia from 92 adults with DS.Methods:In a cross-sectional, observational study of a regional cohort, chi-square and Fisher’s exact tests examined individual reflexes across diagnostic group (No, Possible, or Probable Dementia). In 64 participants with all 8 reflexes assessed, the number of primitive reflexes was assessed as a predictor of diagnosis using age-controlled multinomial logistic regression and of performance on clinical assessments (Brief Praxis Test [BPT], Severe Impairment Battery [SIB], and the Dementia Questionnaire for People with Learning Disabilities [DLD] using age-adjusted linear regression.Results:Primitive palmomental, grasp, snout, and suck reflexes were more frequent in individuals with probable dementia, but all participants showed at least one primitive reflex. Multiple primitive reflexes in combination served as a better indicator of dementia, with each additional abnormal reflex tripling probability of Probable Dementia group membership controlling for age. Abnormal reflex count was not associated with direct assessment of cognition and praxis (SIB and BPT) but associated with informant ratings of cognitive and behavioral functioning (DLD).Conclusions:The presence of multiple reflexes serves as an indicator of dementia status in DS as a supplement to direct assessment of cognition and praxis. The reflex examination may serve as a tool in the multimethod evaluation for dementia in DS, as it appears unaffected by intellectual disability and language mastery.

EEG Abnormalities and Their Radiographic Correlates in a COVID-19 Inpatient Cohort

ABSTRACT:Objective:To identify the prevalence of EEG abnormalities in patients with COVID-19 with neurologic changes, their associated neuroimaging abnormalities and rates of mortality.Methods:A retrospective case series of 192 adult COVID-19 positive inpatients with EEG performed between March and June 2020 at 4 hospitals: 161 undergoing continuous, 24 routine, and 7 reduced- montage EEG. Study indication, epilepsy history, intubation status, administration of sedatives or antiseizure medications, metabolic abnormalities, neuroimaging pathology associated with epileptiform abnormalities, and in-hospital mortality were analyzed.Results:EEG indications included encephalopathy (54.7%), seizure (18.2%), coma (17.2%), focal deficit (5.2%), and abnormal movements (4.6%). Epileptiform abnormalities occurred in 39.6% of patients: focal intermittent epileptiform discharges in 25.0%, lateralized periodic discharges in 6.3%, and generalized periodic discharges in 19.3%. Seizures were recorded in 8 patients, 3 with status epilepticus. Antiseizure medication administration, epilepsy history, and older age were associated with epileptiform abnormalities. Only 26.3% of patients with any epileptiform abnormality, 37.5% with electrographic seizures, and 25.7% patients with clinical seizures had known epilepsy. Background findings included generalized slowing (88.5%), focal slowing (15.6%), burst suppression (3.6%), attenuation (3.1%), and normal EEG (3.1%). Neuroimaging pathology was identified in 67.1% of patients with epileptiform abnormalities, over two-thirds acute. In-hospital mortality was 39.5% for patients with epileptiform abnormalities, 36.2% for those without. Risk factors for mortality were coma and ventilator support at time of EEG.Significance:This article highlights the range of EEG abnormalities frequently associated with acute neuroimaging abnormalities in COVID-19. Mortality rates were high, particularly for patients in coma requiring mechanical ventilation. These findings may guide the prognosis and management of patients with COVID-19 and neurologic changes.

Cerebral Venous Sinus Thrombosis With Severe Thrombocytopenia: A Fatal Adverse Event Following Johnson & Johnson COVID-19 Vaccination

Approximately 7.98 million doses of the Johnson and Johnson adenovirus vector SARS-CoV-2 vaccine (J&J vaccine) have been administered since EUA authorization by the FDA on February 27, 20211, 2. On April 13th, the CDC/FDA recommended a pause in administration after 6 cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia were identified through the vaccine adverse event reporting system in women aged 18-48. To date, 15 cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with J&J, with three reported fatalities2. Here we report one of those fatalities in a 35-year-old woman who developed CVST with thrombocytopenia following vaccination with the J&J vaccine.