Faculty Bibliography

New-onset psychosis in the pediatric population poses many diagnostic challenges. Given the diversity of underlying causes, which fall under the purview of multiple medical specialties, a timely, targeted, yet thorough workup requires a systematic and coordinated approach. A committee of expert pediatric physicians from the divisions of emergency medicine, psychiatry, neurology, hospitalist medicine, and radiology convened to create and implement a novel clinical pathway and approach to the pediatric patient presenting with new-onset psychosis. Here we provide background and review the evidence supporting the investigations recommended in our pathway to screen for a comprehensive range of etiologies of pediatric psychosis.

BACKGROUND:Neurology faculty care for complex patients, teach, and work within multidisciplinary teams. It is imperative for faculty to have strong communication skills. METHODS:We surveyed NYU neurology teaching faculty to determine levels of comfort and experience over the past year with providing negative feedback to a trainee; debriefing after an adverse clinical outcome; and assisting a struggling colleague. We examined the relationship between levels of comfort and experience with 1) faculty self-identified sex and 2) number of years since completion of medical training. RESULTS:The survey was completed by 36/83 teaching neurology faculty (43 %); 17 (47 %) respondents were female and 21 (58 %) were ≤10 years post-training. The proportions of faculty who reported feeling uncomfortable were 44 % (16/36) for assisting a struggling colleague, 28 % (10/36) for providing negative feedback, and 19 % (7/36) for debriefing an adverse outcome. Proportions of faculty who reported they had no experience were 75 % (27/36) for assisting a struggling colleague, 39 % (14/36) for debriefing an adverse clinical event, and 17 % (6/36) for providing negative feedback. Female respondents and faculty who were ≤10 years post-training were more likely to report feeling uncomfortable with assisting a struggling colleague and to have had no experience doing so in the past year. On multivariate analyses accounting for sex and experience, sex remained independently associated with feeling uncomfortable with assisting a struggling colleague (OR = 12.2, 95 % CI: 2.1-69.6, p = 0.005). CONCLUSION/CONCLUSIONS:Faculty development may be needed to improve comfort and experience with challenging communication-based interactions. Female faculty and faculty early in their careers may benefit most.

OBJECTIVE:and to assess the ability of the IC-CoDE to produce definable and stable cognitive phenotypes in a large, multi-center temporal lobe epilepsy (TLE) patient sample. METHOD/METHODS:were derived across samples using the IC-CoDE and compared to distributions of phenotypes reported in existing studies. RESULTS:Impairment rates were highest on tests of language, followed by memory, executive functioning, attention/processing speed, and visuospatial ability. Application of the IC-CoDE using varying operational definitions of impairment (≤ 1.0 and ≤ 1.5 SD) produced cognitive phenotypes with the following distribution: cognitively intact (30%-50%), single-domain (26%-29%), bi-domain (14%-19%), and generalized (10%-22%) impairment. Application of the ≤ 1.5 cutoff produced a distribution of phenotypes that was consistent across cohorts and approximated the distribution produced using data-driven approaches in prior studies. CONCLUSIONS:The IC-CoDE is the first iteration of a classification system for harmonizing cognitive diagnostics in epilepsy research that can be applied across neuropsychological tests and TLE cohorts. This proof-of-principle study in TLE offers a promising path for enhancing research collaborations globally and accelerating scientific discoveries in epilepsy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

OBJECTIVE:Cannabidiol (CBD) expanded access program, initiated in 2014, provided add-on CBD to patients with treatment-resistant epilepsies (TREs) at 35 US epilepsy centers. Prior publications reported results through December 2016; herein, we present efficacy and safety results through January 2019. METHODS:Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/ml oral solution), increasing from 2 to 10 mg/kg/day to tolerance or maximum 25-50 mg/kg/day dose, depending on the study site. Efficacy endpoints included percentage change from baseline in median monthly convulsive and total seizure frequency and ≥50%, ≥75%, and 100% responder rates across 12-week visit windows for up to 192 weeks. Adverse events (AEs) were documented at each visit. RESULTS:Of 892 patients in the safety analysis set, 322 (36%) withdrew; lack of efficacy (19%) and AEs (7%) were the most commonly reported primary reasons for withdrawal. Median (range) age was 11.8 years (range = 0-74.5), and patients were taking a median of three (range = 0-10) antiseizure medications (ASMs) at baseline; the most common ASMs were clobazam (47%), levetiracetam (34%), and valproate (28%). Median top CBD dose was 25 mg/kg/day; median exposure duration was 694 days. Median percentage reduction from baseline ranged 50%-67% for convulsive seizures and 46%-66% for total seizures. Convulsive seizure responder rates (≥50%, ≥75%, and 100% reduction) ranged 51%-59%, 33%-42%, and 11%-17% of patients across visit windows, respectively. AEs were reported in 88% of patients and serious AEs in 41%; 8% withdrew because of an AE. There were 20 deaths during the study deemed unrelated to treatment by the investigator. The most common AEs (≥20% of patients) were diarrhea (33%), seizure (24%), and somnolence (23%). SIGNIFICANCE/CONCLUSIONS:Add-on CBD was associated with sustained seizure reduction up to 192 weeks with an acceptable safety profile and can be used for long-term treatment of TREs.

BACKGROUND:STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE:Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs). METHODS:Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE. The Symbol Digit Modalities Test (SDMT) was used as a measure of cognitive processing speed. PROs were assessed using the Multiple Sclerosis Impact Score (MSIS-29) and the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS:At all four annual assessments, the proportion of patients in the intent-to-treat (ITT) population (N = 222) who exhibited clinically meaningful improvement in their SDMT score from baseline (i.e., change ≥ 4 points) ranged from 41.9 to 54.0%. The cumulative probability of CDI at 4 years in patients in the ITT population with a baseline Expanded Disability Status Scale score ≥ 2 (N = 133) was 43.9%. Statistically significant reductions in the mean change from screening in the MSIS-29 physical and psychological scores, indicating improved quality of life, were observed over all 4 years (P ≤ 0.0012 for all). A statistically significant decrease from screening in the impact of MS on regular activities, signifying an improvement in this WPAI measure, was also observed over all 4 years of the study. CONCLUSION/CONCLUSIONS:These results further extend our knowledge of the effectiveness, specifically regarding improvements in cognitive processing speed, disability and PROs, of long-term natalizumab treatment in early RRMS patients. CLINICALTRIALS/RESULTS:GOV: NCT01485003 (5 December 2011).

BACKGROUND:Depression is a common neuropsychiatric consequence of stroke, but there is little empiric evidence regarding clinical diagnosis and management of poststroke depression. METHODS:Retrospective cohort study among 831 471 privately insured patients with first stroke in the USA from 2003 to 2020. We identified diagnoses of poststroke depression using codes from the International Classification of Diseases. We identified treatment based on prescriptions for antidepressants. We used Cox proportional hazards regression analysis to examine rates of poststroke depression diagnosis by gender, age and race/ethnicity. Among individuals who received a diagnosis of poststroke depression, we estimated treatment rates by gender, race/ethnicity and age using negative binomial regression analysis. RESULTS:Annual diagnosis and treatment rates for poststroke depression increased from 2003 to 2020 (both p for trend<0.001). Diagnosis rates were higher in women than men (HR 1.53, 95% CI 1.51 to 1.55), lower among members of racial/ethnic minorities (vs white patients: Asian HR 0.63, 95% CI 0.60 to 0.66; Black HR 0.76, 95% CI 0.74 to 0.78; Hispanic HR 0.88, 95% CI 0.86 to 0.90) and varied by age. Among individuals diagnosed with poststroke depression, 69.8% were prescribed an antidepressant. Rates of treatment were higher in women vs men (rate ratio, RR=1.19, 95% CI: 1.17 to 1.21), lower among members of racial/ethnic minorities (vs white patients: Asian RR 0.85, 95% CI 0.80 to 0.90; Black RR 0.92, 95% CI 0.89 to 0.94; Hispanic RR 0.96, 95% CI 0.93 to 0.99) and higher among older patients. CONCLUSIONS:In this insured population, we identify potential inequities in clinical management of poststroke depression by gender, race/ethnicity and age that may reflect barriers other than access to healthcare.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3% to 5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD. METHODS:This retrospective cohort study evaluated children with NMOSD cases followed at 12 clinics in the US Network of Pediatric MS Centers. Cases were classified as Aquaporin-4 antibody positive (AQP4+) and double-seronegative (DS) when negative for AQP4+ and for myelin oligodendrocyte glycoprotein (MOG) antibody. Effect of initial DMTs including rituximab, mycophenolate, azathioprine, and intravenous immunoglobulin (IVIg) on annualized relapse rate (ARR) was assessed by negative binomial regression. Time to disability progression (EDSS increase ≥1.0 point) was modeled with a Cox proportional-hazards model. RESULTS:91 children with NMOSD were identified: 77 AQP4+ and 14 DS (85.7% females; 43.2% Caucasian, 46.6% African American). 81 patients were started on a DMT and 10 were treatment naïve at the time of the analysis. The ARR calculated in all serogroups was 0.25 (95% CI 0.13-0.49) for rituximab, 0.33 (95% CI 0.19-0.58) for mycophenolate, 0.40 (95% CI 0.13-1.24) for azathioprine and 0.54 (95% CI 0.28-1.04) for IVIg. The ARR in the AQP4+ subgroup was 0.28 (95% CI 0.14-0.55) for rituximab, 0.39 (95% CI 0.21-0.70) for mycophenolate, 0.41 (95% CI 0.13-1.29) for azathioprine and 0.54 (95% CI 0.23-1.26) for IVIg. The ARR in the treatment naïve group was 0.97 (95% CI 0.58-1.60) in all serogroups and 0.91 (95% CI 0.53-1.56) in the AQP4+ subgroup. None of the initial DMT had a statistically significant effect on EDSS progression. DISCUSSION/CONCLUSIONS:The use of DMTs, in particular rituximab, is associated with a lowered annualized relapse rate in children with NMOSD AQP4+. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class IV evidence that use of disease-modifying treatments is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.

There are multiple treatment alternatives for cavernous dAVFs, with transvenous routes being most common. Among these routes, occluded inferior petrosal sinus is well-described, and, apart from being imaginative and elegant, it is also safe and effective. Herein we describe the application of this method to reach the fistulous pouch of a cavernous dAVF via an occluded superior petrosal sinus.

BACKGROUND:Clinical and real-world effectiveness data for the COVID-19 vaccines have shown that they are the best defense in preventing severe illness and death throughout the pandemic. However, in the US, some groups remain more hesitant than others about receiving COVID-19 vaccines. One important group is long-term care workers (LTCWs), especially because they risk infecting the vulnerable and clinically complex populations they serve. There is a lack of research about how best to increase vaccine confidence, especially in frontline LTCWs and healthcare staff. Our aims are to: (1) compare the impact of two interventions delivered online to enhanced usual practice on LTCW COVID-19 vaccine confidence and other pre-specified secondary outcomes, (2) determine if LTCWs' characteristics and other factors mediate and moderate the interventions' effect on study outcomes, and (3) explore the implementation characteristics, contexts, and processes needed to sustain a wider use of the interventions. METHODS:We will conduct a three-arm randomized controlled effectiveness-implementation hybrid (type 2) trial, with randomization at the participant level. Arm 1 is a dialogue-based webinar intervention facilitated by a LTCW and a medical expert and guided by an evidence-based COVID-19 vaccine decision tool. Arm 2 is a curated social media web application intervention featuring interactive, dynamic content about COVID-19 and relevant vaccines. Arm 3 is enhanced usual practice, which directs participants to online public health information about COVID-19 vaccines. Participants will be recruited via online posts and advertisements, email invitations, and in-person visits to care settings. Trial data will be collected at four time points using online surveys. The primary outcome is COVID-19 vaccine confidence. Secondary outcomes include vaccine uptake, vaccine and booster intent for those unvaccinated, likelihood of recommending vaccination (both initial series and booster), feeling informed about the vaccines, identification of vaccine information and misinformation, and trust in COVID-19 vaccine information provided by different people and organizations. Exploration of intervention implementation will involve interviews with study participants and other stakeholders, an in-depth process evaluation, and testing during a subsequent sustainability phase. DISCUSSION:Study findings will contribute new knowledge about how to increase COVID-19 vaccine confidence and effective informational modalities for LTCWs. TRIAL REGISTRATION:NCT05168800 at ClinicalTrials.gov, registered December 23, 2021.