Faculty Bibliography

Since the onset of the COVID-19 pandemic, a substantial proportion of COVID-19 patients had documented thrombotic complications and ischemic stroke. Several mechanisms related to immune mediated thrombosis, the renin angiotensin system, and the effect of SARS-CoV-2 in cardiac and brain tissue may contribute to the pathogenesis of ischemic stroke in patients with COVID-19. Simultaneously, significant strains on global healthcare delivery, including ischemic stroke management, have made treatment of stroke in the setting of COVID-19 particularly challenging. In this review we summarize the current knowledge on epidemiology, clinical manifestation and pathophysiology of ischemic stroke in patients with COVID-19 to bridge the gap from bench to bedside and clinical practice during the most challenging global health crisis of the last decades.

Background/Purpose: Sudden unexpected death in epilepsy (SUDEP) is a sudden death in epilepsy patients not explained by status epilepticus, trauma, or any another known cause. In Dravet syndrome (DS) the incidence of SUDEP is about 6- fold higher than in other forms of epilepsy. The objective of this study was to compare the incidence of SUDEP in FFA-treated DS patients with literature reports of SUDEP incidence in patients with DS receiving anticonvulsive treatment without FFA.
Method(s): For the study group without FFA, publications were identified in PubMed searching 'Dravet [title] AND (mortality OR death OR SUDEP).' The FFA-treated population comprised patients from 3 sources: international phase 3 clinical trials, US and European Early Access Programs (EAPs), and a long-term, open-label study spanning 32 years. The incidence of SUDEP was expressed as deaths per 1,000 person-years of observation.
Result(s): Nine studies describing the incidence of SUDEP in DS were identified. Cooper (Cooper MS, Epilepsy Res 2016;128:43-47) was considered the most rigorous, reporting a SUDEP rate of 9.32 per 1000 person-years (98% CI, 4.46- 19.45). 732 patients treated with fenfluramine provided 1185.3 person-years. The FFA-SUDEP rate was below the lower limit of 98% CI reported by Cooper, whereas the SUDEP rate before starting FFA was similar to the literature numbers.
Conclusion(s): Results show a lower incidence of SUDEP and all-cause mortality in the FFA-treated population compared to patients without FFA of the literature. Further research is warranted to clarify influencing factors on SUDEP to reduce its risks. The data were first presented at AES 2020 (Virtual 74th American Epilepsy Society Annual Meeting)

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T_FH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T_H1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T_FH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.

BACKGROUND:As medical education shifted to a virtual environment during the early coronavirus disease 2019 (COVID-19) pandemic, we evaluated how neurology podcasting may have been utilized during this period, and which features of podcasts have been more highly sought by a medical audience. METHODS:We conducted a retrospective analysis of neurology-themed blogs and/or podcasts between April 2019 and May 2020. Programs were eligible if they reported mean monthly downloads > 2000, were affiliated with an academic society, or offered continuing medical education credit. Thirty-day download counts were compared between study months, with adjustment for multiple testing. Exploratory analyses were performed to determine which podcast features were associated with higher downloads. RESULTS: = 0.80). The non-significant increase in overall downloads during April 2020 corresponded to an increase in unique episodes during that month (r = 0.48, p = 0.003). There was no difference in 30-day downloads among episodes including COVID-19 content versus not (median 1979 [IQR 791-2873] vs. 1171 [IQR 405-2665], p = 0.28). CONCLUSIONS:In this unique, exploratory study of academic neurology-themed podcasts, there was no significant increase in episode downloads during the early COVID-19 pandemic. A more comprehensive analysis of general and subspecialty medical podcasts is underway.

OBJECTIVES/OBJECTIVE:We contrasted the relative risks (RR) of short [<7 h] and long [>8 h] sleep experienced by middle-aged (45-64 years) and older (≥65 years) adults, compared with young adults (20-44 years). METHODS:We utilized NHANES data (2005-2016), capturing sociodemographic, socioeconomic, and health-related data among US adults. RESULTS:The Relative Risk (RR) of short sleep between young and middle-aged adults did not differ [RR = 1.02, NS]. However, the RR of short sleep was significantly reduced among older participants [RR = 0.81, p < 0.01]. Middle-aged adults had significantly lower RR of long sleep [RR = 0.80, p < 0.01], whereas older adults had significantly greater RR of long sleep [RR = 1.41, p < 0.01]. Compared with young adults, older adults with or without increased disease burden had significantly lower RR of short sleep [RR = 0.81, p < 0.01 and RR = 0.80, p < 0.01], respectively. However, for middle-aged adults, the RR of short sleep did not differ whether they reported a greater disease burden. Relative to young adults, older adults with or without disease burden had higher RRs of long sleep [RR = 1.39, p < 0.01] and [RR = 1.45, p < 0.01], respectively. For middle-aged adults without disease burden, the RR of long sleep was lower than among young adults [RR = 0.72, p < 0.01]. CONCLUSIONS:Compared with young adults, older adults were not at increased risk for short sleep. Rather, they reported longer sleep time regardless of the presence of disease burden. Future studies should investigate longitudinal effects of aging on objective sleep time, with or without common diseases.