Faculty Bibliography

OBJECTIVES/OBJECTIVE:Medical cannabis formulations with cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are widely used to treat epilepsy. We studied the safety and efficacy of two formulations. METHODS:We prospectively observed 29 subjects (12 to 46 years old) with treatment-resistant epilepsies (11 Lennox-Gastaut syndrome; 15 with focal or multifocal epilepsy; three generalized epilepsy) were treated with medical cannabis (1THC:20CBD and/or 1THC:50CBD; maximum of 6 mg THC/day) for ≥24 weeks. The primary outcome was change in convulsive seizure frequency from the pre-treatment baseline to the stable optimal dose phase. RESULTS:There were no significant differences during treatment on stable maximal doses for convulsive seizure frequency, seizure duration, postictal duration, or use of rescue medications compared to baseline. No benefits were seen for behavioral disorders or sleep duration; there was a trend for more frequent bowel movements compared to baseline. Ten adverse events occurred in 6/29 patients, all were transient and most unrelated to study medication. No serious adverse events were related to study medication. INTERPRETATION/CONCLUSIONS:Our prospective observational study of two high-CBD/low-THC formulations found no evidence of efficacy in reducing seizures, seizure duration, postictal duration, or rescue medication use. Behavioral disorders or sleep duration was unchanged. Study medication was generally well tolerated. The doses of CBD used were lower than prior studies. Randomized trials with larger cohorts are needed, but we found no evidence of efficacy for two CBD:THC products in treating epilepsy, sleep, or behavior in our population.

PURPOSE OF REVIEW/OBJECTIVE:Sudden unexpected death in epilepsy (SUDEP) is a major contributor to premature mortality in people with epilepsy. This review provides an update on recent findings on the epidemiology of SUDEP, clinical risk factors and potential mechanisms. RECENT FINDINGS/RESULTS:The overall risk rate of SUDEP is approximately 1 per 1000 patients per year in the general epilepsy population and that children and older adults have a similar incidence. Generalized convulsive seizures (GCS), perhaps through their effects on brainstem cardiopulmonary networks, can cause significant postictal respiratory and autonomic dysfunction though other mechanisms likely exist as well. Work in animal models of SUDEP has identified multiple neurotransmitter systems, which may be future targets for pharmacological intervention. There are also chronic functional and structural changes in autonomic function in patients who subsequently die from SUDEP suggesting that some SUDEP risk is dynamic. Modifiable risks for SUDEP include GCS seizure frequency, medication adherence and nighttime supervision. SUMMARY/CONCLUSIONS:Current knowledge of SUDEP risk factors has identified multiple targets for SUDEP prevention today as we await more specific therapeutic targets that are emerging from translational research studies.

INTRODUCTION/BACKGROUND:We conducted a systematic review and meta-analysis of the cognitive effects of coronavirus disease 2019 (COVID-19) in adults with no prior history of cognitive impairment. METHODS:Searches in Medline/Web of Science/Embase from January 1, 2020, to December 13, 2021, were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.  A meta-analysis of the Montreal Cognitive Assessment (MoCA) total score comparing recovered COVID-19 and healthy controls was performed. RESULTS:Oof 6202 articles, 27 studies with 2049 individuals were included (mean age = 56.05 years, evaluation time ranged from the acute phase to 7 months post-infection). Impairment in executive functions, attention, and memory were found in post-COVID-19 patients.  The meta-analysis was performed with a subgroup of 290 individuals and showed a difference in MoCA score between post-COVID-19 patients versus controls (mean difference = -0.94, 95% confidence interval [CI] -1.59, -0.29; P = .0049). DISCUSSION/CONCLUSIONS:Patients recovered from COVID-19 have lower general cognition compared to healthy controls up to 7 months post-infection.

Parkinson's disease (PD) is a neurological disorder that mainly affects the motor system. Among other symptoms, hypomimia is considered one of the clinical hallmarks of the disease. Despite its great impact on patients' quality of life, it remains still under-investigated. The aim of this work is to provide a quantitative index for hypomimia that can distinguish pathological and healthy subjects and that can be used in the classification of emotions. A face tracking algorithm was implemented based on the Facial Action Coding System. A new easy-to-interpret metric (face mobility index, FMI) was defined considering distances between pairs of geometric features and a classification based on this metric was proposed. Comparison was also provided between healthy controls and PD patients. Results of the study suggest that this index can quantify the degree of impairment in PD and can be used in the classification of emotions. Statistically significant differences were observed for all emotions when distances were taken into account, and for happiness and anger when FMI was considered. The best classification results were obtained with Random Forest and kNN according to the AUC metric.

Understanding how consciousness arises from neural activity remains one of the biggest challenges for neuroscience. Numerous theories have been proposed in recent years, each gaining independent empirical support. Currently, there is no comprehensive, quantitative and theory-neutral overview of the field that enables an evaluation of how theoretical frameworks interact with empirical research. We provide a bird's eye view of studies that interpreted their findings in light of at least one of four leading neuroscientific theories of consciousness (N = 412 experiments), asking how methodological choices of the researchers might affect the final conclusions. We found that supporting a specific theory can be predicted solely from methodological choices, irrespective of findings. Furthermore, most studies interpret their findings post hoc, rather than a priori testing critical predictions of the theories. Our results highlight challenges for the field and provide researchers with an open-access website ( https://ContrastDB.tau.ac.il ) to further analyse trends in the neuroscience of consciousness.

BACKGROUND:The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE:To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS:We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS:The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION/CONCLUSIONS:COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

OBJECTIVE:To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S.. METHODS:We utilized publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021-June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post-vaccination neurological event rates were compared between vaccine types and to age-matched baseline incidence rates in the U.S. and rates of neurological events following COVID. RESULTS:Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0-3) from inoculation. Guillain-Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer-BioNtech (BNT162b2) or Moderna (mRNA-1273; 0.15% versus 0.03% versus 0.03% of doses, respectively,P<0.0001). The observed-to-expected ratios for GBS, CVT and seizure following Janssen vaccination were ≥1.5-fold higher than background rates. However, the rate of neurological events after acute SARS-CoV-2 infection was up to 617-fold higher than after COVID vaccination. INTERPRETATION/CONCLUSIONS:Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS-CoV-2 infection are up to 617-fold higher than after COVID vaccination. This article is protected by copyright. All rights reserved.