Faculty Bibliography

BACKGROUND:Evolution of brain magnetic resonance imaging (MRI) findings in critically ill patients with coronavirus disease 2019 (COVID-19) is unknown. METHODS:We retrospectively reviewed 4530 critically ill patients with COVID-19 admitted to three tertiary care hospitals in New York City from March 1 to June 30, 2020 to identify patients who had more than one brain MRI. We reviewed the initial and final MRI for each patient to (1) measure the percent change in the bicaudate index and third ventricular diameter and (2) evaluate changes in the presence and severity of white matter changes. RESULTS:Twenty-one patients had two MRIs separated by a median of 22 [Interquartile range (IQR) 14-30] days. Ventricle size increased for 15 patients (71%) between scans [median bicaudate index 0.16 (IQR 0.126-0.181) initially and 0.167 (IQR 0.138-0.203) on final imaging (p < 0.001); median third ventricular diameter 6.9 mm (IQR 5.4-10.3) initially and 7.2 mm (IQR 6.4-10.8) on final imaging (p < 0.001)]. Every patient had white matter changes on the initial and final MRI; between images, they worsened for seven patients (33%) and improved for three (14%). CONCLUSIONS:On serial imaging of critically ill patients with COVID-19, ventricle size frequently increased over several weeks. White matter changes were often unchanged, but in some cases they worsened or improved, demonstrating there is likely a spectrum of pathophysiological processes responsible for these changes.

Migraine affects over 40 million Americans and is the world's second most disabling condition. As the majority of medical care for migraine occurs in primary care settings, not in neurology nor headache subspecialty practices, healthcare system interventions should focus on primary care. Though there is grade A evidence for behavioral treatment (e.g., biofeedback, cognitive behavioral therapy (CBT), and relaxation techniques) for migraine, these treatments are underutilized. Behavioral treatments may be a valuable alternative to opioids, which remain widely used for migraine, despite the US opioid epidemic and guidelines that recommend against them. Identifying and removing barriers to the use of headache behavioral therapy could help reduce the disability as well as the personal and social costs of migraine. These techniques will have their greatest impact if offered in primary care settings to the lower socioeconomic status groups at greatest risk for migraine. We review the societal and cultural challenges that impose barriers to optimal use of non-pharmacological treatment services. These barriers include insufficient knowledge of migraine/headache behavioral treatments and insufficient availability of clinicians trained in non-pharmacological treatment delivery; limited access in underserved communities; financial burden; and stigma associated with both headache and mental health diagnoses and treatment. For each barrier, we discuss potential approaches to minimizing its effect and thus enhancing non-pharmacological treatment utilization.Case ExampleA 25-year-old graduate student with a prior history of headaches in college is attending school in the evenings while working a full-time job. Now, his headaches have significant nausea and photophobia. They are twice weekly and are disabling enough that he is unable to complete homework assignments. He does not understand why the headaches occur on Saturdays when he pushes through all week to get through his examinations that take place on Friday evenings. He tried two different migraine preventive medications, but neither led to the 50% reduction in headache days his doctor had hoped for. His doctor had suggested cognitive behavioral therapy (CBT) before initiating the medications, but he had been too busy to attend the appointments, and the challenges in finding an in-network provider proved difficult. Now with the worsening headaches, he opted for the CBT and by the fifth week had already noted improvements in his headache frequency and intensity.

These scientific abstracts are scheduled for presentation at the 2021 Society of Family Planning Annual Meeting. This year, 225 abstracts were submitted for consideration, of which 12 were selected for oral presentation and 84 were selected for poster presentation. The scientific abstract review was completed by the scientific reviewers and selectors.

Objectives Stroke and post-stroke complications are associated with high morbidity, mortality, and cost. Our objective was to examine healthcare utilization and hospice enrollment for stroke patients at the end of life. Materials and methods The 2014 Nationwide Readmissions Database is a national database of > 14 million admissions. We used validated ICD-9 codes to identify fatal ischemic stroke, summarized demographics and hospitalization characteristics, and examined healthcare use within 30 days before fatal stroke admission. We used de-identified 2014 Medicare hospice data to identify stroke and non-stroke patients admitted to hospice. Results Among IS admissions in 2014 (n = 472,969), 22652 (4.8%) had in-hospital death. 28.2% with fatal IS had two or more hospitalizations in 2014. Among those with fatal IS admission, 13.0% were admitted with cerebrovascular disease within 30 days of fatal IS admission. Half of stroke patients discharged to hospice from the Medicare dataset were hospitalized with cerebrovascular disease within the thirty days prior to hospice enrollment. Within the study year, 6.9% of hospice enrollees had one or more emergency room visits, 31.7% had one or more inpatient encounters, and 5.2% had one or more nursing facility encounters (compared to 21.4%, 70.6%, and 27.2% respectively in the 30-day period prior to enrollment). Conclusions High rates of readmission prior to fatal stroke may indicate opportunity for improvement in acute stroke management, secondary prevention, and palliative care involvement as encouraged by AHA/ASA guidelines. For patients who are expected to survive 6 months or less, hospice may offer goal-concordant services for patients and caregivers who desire comfort-focused care.

Background: Ocrelizumab (OCR), a humanized, anti-CD20 antibody therapy for multiple sclerosis (MS), is given at 6-month intervals. Some patients on OCR report worsening of MS-related symptoms in the weeks leading up to their infusion ('wearing-off' phenomena), but there are no published reports quantifying symptom variation in relation to the timing of OCR infusions.
Objective(s): We will measure symptom burden using SymptoMScreen, NeuroQol and WPAI:MS at 3 points in each infusion cycle over 2 infusion cycles and also obtain Ocrelizumab concentration (PK), neurofilament light chain (NfL), B-cell subsets, and routine clinical labs prior to each infusion.
Aim(s): To quantitate change in symptom burden throughout the infusion cycle in OCR-treated MS patients and to determine which clinical and paraclinical variables correlate with symptom worsening.
Method(s): Prospective, observational, two-center study enrolled patients with relapsing and progressive forms of MS that are initiating OCR or who have been on OCR for >= 1 year (ClinicalTrials. gov Identifier: NCT04855617). All patients receive MS care at NYU MS Care Center (NYU) in New York, NY, or the Elliot Lewis MS Center for MS (ELC) in Wellesley, MA. Patients aged 18-80 and with EDSS scores between 0-7 are eligible for enrollment.
Result(s): 110 participants were enrolled and are actively followed in the study (55 from NYU/55 from ELC). At baseline visit, the mean age was 46.0+/-12.7 years; 64.6% were female; 31.8% were non-White; 20.0% were Hispanic/ Latino; disease duration was 12.6+/-9.6 years; OCR treatment duration was 2.8+/-1.0 years; mean EDSS was 3.3+/-2.1 (EDSS<4, n=69 (62.7%), EDSS>=4, n=41 (37.3%)). Breakdown by disease subtypes was: relapsing-remitting, n=68 (61.8%), secondary progressive, n=24 (21.8%), primary progressive, n=18 (16.4%). Among 58 patients who completed at least 2 questionnaires to date, the symptom burden, as assessed with the SymptoMScreen, was unchanged from week 4 post-infusion to week 12 post-infusion (p-values ranged from 0.2-0.9 for each of the 11 individual domains by Wilcoxon nonparametric test).
Conclusion(s): SymBOLS, designed to assess for the wearing-off effect in OCR-treated patients, has successfully enrolled 110 patients across two US sites. Preliminary data suggest there are no changes to symptom burden during the first half of the infusion cycle. Additional data regarding changes during the second half of the cycle as well as NeuroQoL and work productivity (WPAI) data will be presented

Traumatic brain injury (TBI) is one of the main causes of death worldwide. It is a complex injury that influences cellular physiology, causes neuronal cell death, and affects molecular pathways in the brain. This in turn can result in sensory, motor, and behavioral alterations that deeply impact the quality of life. Repetitive mild TBI can progress into chronic traumatic encephalopathy (CTE), a neurodegenerative condition linked to severe behavioral changes. While current animal models of TBI and CTE such as rodents, are useful to explore affected pathways, clinical findings therein have rarely translated into clinical applications, possibly because of the many morphofunctional differences between the model animals and humans. It is therefore important to complement these studies with alternative animal models that may better replicate the individuality of human TBI. Comparative studies in animals with naturally evolved brain protection such as bighorn sheep, woodpeckers, and whales, may provide preventive applications in humans. The advantages of an in-depth study of these unconventional animals are threefold. First, to increase knowledge of the often-understudied species in question; second, to improve common animal models based on the study of their extreme counterparts; and finally, to tap into a source of biological inspiration for comparative studies and translational applications in humans.

BACKGROUND:Asymmetric hemispheric loss of dopaminergic neurons is one of the characteristic features of Parkinson's disease (PD). However, it is still debated if right or left asymmetry differently affects cognitive and motor progression. OBJECTIVES/OBJECTIVE:The objective of this study was to investigate, for the first time, the relevance of dopamine transporter (DAT) asymmetry on cognitive and motor manifestations at onset and at 4-year progression in drug-naïve PD. METHODS:From the Parkinson's Progression Markers Initiative multicenter cohort, we identified 249 right-handed patients with PD with baseline asymmetry greater than 20% in putamen DAT binding at single-photon emission computed tomography. A predominant putamen asymmetry was found on the left in 143 patients (PD-left), and on the right side in 106 patients (PD-right); we compared them with 196 healthy controls. Patients were followed longitudinally (2-year and 4-year visits), examining their clinical, cognitive, and imaging data. RESULTS:At baseline, the PD-left group showed worse performance on the Symbol Digit Modality Test, an attention and processing-speed test, and lower cerebrospinal fluid β-amyloid levels than the PD-right group. These differences were maintained at follow-up, declining over time in both groups. By contrast, the PD-right group showed greater motor impairment at baseline, which increased over 4 years. Striatal DAT binding decreased over time in both groups, but the PD-right group showed a steeper decline, particularly during the first 2-year follow-up. Putaminal asymmetry assessed at baseline was maintained over time. CONCLUSIONS:These findings suggest that hemispheric asymmetric dopaminergic denervation influences PD cognitive and motor performance as well as progression. Predominant right hemisphere nigrostriatal dopaminergic loss is associated with greater motor severity, whereas more pronounced left hemisphere denervation affects cognitive manifestations at onset and their progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Introduction: Patients (pts) with paediatric multiple sclerosis (PedMS) have higher relapse rates and radiological activity, accumulating disability at a younger age vs adult-onset MS. There are challenges in conducting clinical trials for PedMS due to the low number of available pts and competing trials. Moreover, testing a new drug vs placebo or low efficacy control poses ethical concerns due to the high disease activity. Few Phase 3 studies have assessed the efficacy/safety of disease-modifying therapies (DMTs) in PedMS; PARADIGMS demonstrated a significant reduction in annualised relapse rate (ARR) for fingolimod vs interferon (IFN)beta-1a in PedMS. A large unmet need for new studied treatment options for PedMS remains.
Objective(s): To present the innovative Bayesian design of the Phase 3 NEOS study aimed to assess the efficacy and safety of ofatumumab and siponimod in PedMS.
Method(s): NEOS is a 2-year, randomised, 3-arm, double-blind, triple-dummy, parallel-group, multicentre, active-comparator, controlled global study comparing ofatumumab and siponimod vs fingolimod in the core part, followed by 2-5 years of an openlabel extension part. Eligibility criteria include pts aged 10 to <18 years, with Expanded Disability Status Scale score 0-5.5 who had experienced >=1 relapse in the last year or >=2 relapses in last 2 years or evidence of >=1 gadolinium-enhancing lesions on MRI within 12 months before randomisation. The primary objective is to demonstrate the non-inferiority (NI) of ofatumumab and siponimod vs fingolimod, assessed by ARR up to 2 years, and will be analysed using a Bayesian negative binomial regression model. This model incorporates information from historical studies on all 3 treatments to reduce the required sample size. The key secondary objective is to demonstrate superiority of ofatumumab and siponimod vs historical IFNbeta-1a data, assessed by ARR. Other endpoints include number of new/newly enlarging T2 lesions on MRI per year, serum neurofilament light chain and safety/tolerability. Randomisation of ~180 pts (n=60 per arm) will provide >80% power for the demonstration of NI (margin of 2.0) for each test treatment vs fingolimod.
Result(s): Study design will be presented at the congress.
Conclusion(s): The innovative NEOS study design does not include placebo or low efficacy controls and thus offers PedMS pts a DMT already shown to be highly effective in adults. NEOS has the potential to bring 2 new future treatment options-ofatumumab and siponimod for PedMS