Curriculum Innovation: Design and Implementation of Synchronous and Asynchronous Curricula to Enhance Residents' EEG Knowledge and Experience.

Introduction and Problem Statement: There is a need for structured EEG education opportunities to enhance neurology resident education. To address this need, the American Epilepsy Society (AES) supported the development and implementation of both synchronous and asynchronous EEG courses. Objectives: To produce EEG curricula that enhance resident EEG learning, increase interest in EEG and improve participants' knowledge, and to ensure that courses were highly used and available to the broadest range of learners. Methods and Curriculum Description: A multi-institutional group of EEG educators developed both courses. The synchronous curriculum consisted of a mixture of brief "mini-lectures" and interactive small group activities with self-assessment quizzes at the start and end of the course. The online asynchronous EEG curriculum consisted of self-directed slide sets, multiple-choice self-assessment quizzes and a structured EEG self-assessment tool. Courses were evaluated using postcourse surveys, analysis of pretest and posttest data, and analysis of user data from the asynchronous curriculum. Results and Assessment Data: Between 2019 and 2021, 56 residents participated in the synchronous EEG courses. On the resident survey, mean Likert scores for course design, planning, and learning outcomes ranged from 4.6 to 5.0 for the in-person courses and from 3.9 to 4.5 for the virtual course. On the 24-item pretests and posttests, overall median scores increased from 60% (14.5/24) to 75% (18/24; p < 0.001). More than 2,300 learners completed the first submodule of the asynchronous curriculum, but only 164 completed all sections. Most of those who completed the asynchronous curriculum reported that it was effective and appropriate for resident-level learning. Discussion and Lessons Learned: The AES EEG courses provide EEG learning opportunities for neurology residents beyond what is available at their home institutions. There is evidence for the effectiveness of the synchronous course, but the scope is limited to a small number of attendees. The asynchronous curriculum is more broadly available, but very few learners completed all elements. Future steps will include expansion of the in-person synchronous course and providing guidance to learners about the core and optional components of the asynchronous curriculum to increase the impact of both educational offerings.

Time to onset of cannabidiol treatment effects in Dravet syndrome: Analysis from two randomized controlled trials.

OBJECTIVE: We conducted a post hoc analysis of two randomized controlled trials, GWPCARE1 (NCT02091375) and GWPCARE2 (NCT02224703), to estimate the time to onset of cannabidiol (CBD) treatment effects (seizure reduction and adverse events [AEs]) in patients with Dravet syndrome (DS). METHODS: Patients received either plant-derived highly purified CBD (Epidiolex in the United States; 100 mg/ml oral solution) 10 mg/kg/day (CBD10; GWPCARE2) or 20 mg/kg/day (CBD20; GWPCARE1&2), or matching placebo for 14 weeks. Treatment started at 2.5 mg/kg/day, reached 10 mg/kg/day on Day 7, and went up to 20 mg/kg/day on Day 11 during the 14-day titration period. Percentage change from baseline in convulsive seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were also evaluated. RESULTS: Overall, 124 patients received placebo and 194 received CBD (CBD10, n = 64; CBD20, n = 130). Mean age was 9.5 years (range = 2.2-18.9). Patients had discontinued a median of four antiepileptic drugs (range = 0-26) and were currently taking a median of three (range = 1-5). Differences in convulsive seizure reduction between placebo and CBD emerged during titration and became nominally significant by Day 12 for CBD20 (p = .02) and Day 13 for CBD10 (p = .03). Additionally, differences in the 50% responder rate between placebo and CBD became apparent during titration. Onset of the first reported AE occurred during the titration period in 48.4% of placebo patients and 54.1% of CBD patients. The three most common AEs of somnolence, decreased appetite, and diarrhea resolved within 4 weeks of onset in the majority of CBD-treated patients (56.3%-72.9%). SIGNIFICANCE: The therapeutic effect of CBD in DS may start within 2 weeks of treatment in some patients. Although AEs lasted longer for CBD than placebo, most resolved within the 14-week study period.

Exploratory proteomic analysis implicates the alternative complement cascade in primary CNS vasculitis.

OBJECTIVE: To identify molecular correlates of primary angiitis of the CNS (PACNS) through proteomic analysis of CSF from a biopsy-proven patient cohort. METHODS: Using mass spectrometry, we quantitatively compared the CSF proteome of patients with biopsy-proven PACNS (n = 8) to CSF from individuals with noninflammatory conditions (n = 11). Significantly enriched molecular pathways were identified with a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.5 and concordant Benjamini-Hochberg-adjusted p < 0.05 on DeSeq and t test) were identified as differentially regulated proteins. RESULTS: Compared to noninflammatory controls, 283 proteins were differentially expressed in the CSF of patients with PACNS, with significant enrichment of the complement cascade pathway (C4-binding protein, CD55, CD59, properdin, complement C5, complement C8, and complement C9) and neural cell adhesion molecules. A subset of clinically relevant findings were validated by Western blot and commercial ELISA. CONCLUSIONS: In this exploratory study, we found evidence of deregulation of the alternative complement cascade in CSF from biopsy-proven PACNS compared to noninflammatory controls. More specifically, several regulators of the C3 and C5 convertases and components of the terminal cascade were significantly altered. These preliminary findings shed light on a previously unappreciated similarity between PACNS and systemic vasculitides, especially anti-neutrophil cytoplasmic antibody-associated vasculitis. The therapeutic implications of this common biology and the diagnostic and therapeutic utility of individual proteomic findings warrant validation in larger cohorts.

The effect of constipation on valproic acid dosage in a 17-year-old.

Although valproic acid absorption measurements have been reported for animal models, there have been no reports that correlate this to clinical experience with a patient. Reported here is the case of a patient who required twice the dose of valproic acid after colostomy for chronic constipation. The increased dosage required may have been due to rapid intestinal transit time or to bypass of the left colon. This case highlights the importance of gastrointestinal function in patients on valproic acid therapy.