Faculty Bibliography

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described CNS inflammatory disorder that may manifest with optic neuritis, myelitis, seizures, and/or acute disseminated encephalomyelitis. While MOG-specific antibodies in patients with MOGAD are IgG1, a T-cell-dependent antibody isotype, immunologic mechanisms of this disease are not fully understood. Thymic hyperplasia can be associated with certain autoimmune diseases. In this report we describe a case of MOGAD associated with thymic hyperplasia in a young adult.

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: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:The primary objective was to determine the effect of the COVID-19 pandemic on volume, demographics, and mechanisms of injury (MOI) for patients seen at an urban multidisciplinary concussion center. During the first phase of the pandemic in the United States, stay-at-home orders led to decreased group activities and required cancellation of outpatient appointments or initiation of telemedicine visits. METHODS:This study was a retrospective chart review of 3500 patient electronic medical records (EMR). Patients aged 1-99 years were eligible if they had been seen at New York University Langone Health Concussion Center during March 1-December 31, 2019 (control/pre-pandemic period) or during the same period in 2020 (pandemic period). Injury date, appointment date, age, sex, and MOI were captured; statistical analyses were performed using Stata17 (StataCorp, College Station, TX). RESULTS:There were 48% fewer visits during the COVID-19 pandemic period compared to the 2019 control period. There was a decreased proportion of pediatric patients (15% control, 6% pandemic; p = 0.007, chi-square test). Fewer concussions were related to team sports (21% control, 5% pandemic; p < 0.001), and a greater proportion were caused by bicycle accidents (4% control, 8% pandemic; p = 0.037) and assault/domestic violence (3% control, 9% pandemic; p < 0.001). CONCLUSION/CONCLUSIONS:The relative proportions of concussion MOI, age distributions, and visit volumes were significantly associated with pre-pandemic vs. pandemic periods, suggesting that COVID-19 changed concussion epidemiology during the pandemic period. This study demonstrates how epidemiologic data may inform future resource allocation during public health emergencies.

Neurologists have long-recognized the importance of the visual system in the diagnosis and monitoring of neurological disorders. This is particularly true since approximately 50% of the brain's pathways subserve afferent and efferent aspects of vision. During the past 30 years, researchers and clinicians have further refined this concept to include investigation of the visual system for patients with specific neurologic diagnoses, including multiple sclerosis (MS), concussion, Parkinson's disease (PD) and conditions along the spectrum of Alzheimer's disease (AD, mild cognitive impairment [MCI] and subjective cognitive decline [SCD]). This review, highlights the visual "toolbox" that has been developed over the past three decades and beyond to capture both structural and functional aspects of vision in neurologic disease. While the efforts to accelerate the emphasis on structure-function relationships in neurological disorders began with MS during the early 2000's, such investigations have broadened to recognize the need for outcomes of visual pathway structure, function and quality of life for clinical trials of therapies across the spectrum of neurological disorders. This review begins with a patient case study highlighting the importance utilizing the most modern technologies for visual pathway assessment, including optical coherence tomography (OCT). We emphasize that both structural and functional tools for vision testing can be used in parallel to detect what might otherwise be sub-clinical events or markers of visual and, perhaps, more global neurological, decline. Such measures will be critical as clinical trials and therapies become more available across the neurological disease spectrum.

BACKGROUND:Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players. METHODS:One hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests. RESULTS:Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent. CONCLUSIONS:In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.

Approximately half of the brain"™s circuits are involved in vision and control of eye movements. Therefore, visual dysfunction is a common symptom of concussion, the mildest form of traumatic brain injury (TBI). Photosensitivity, vergence dysfunction, saccadic abnormalities, and distortions in visual perception have been reported as vision-related symptoms following concussion. Impaired visual function has also been reported in populations with a lifetime history of TBI. Consequently, vision-based tools have been developed to detect and diagnose concussion in the acute setting, and characterize visual and cognitive function in those with a lifetime history of TBI. Rapid automatized naming (RAN) tasks have provided widely accessible and quantitative measures of visual-cognitive function. Laboratory-based eye tracking approaches demonstrate promise in measuring visual function and validating results from RAN tasks in patients with concussion. Optical coherence tomography (OCT) has detected neurodegeneration in patients with Alzheimer"™s disease and multiple sclerosis and may provide critical insight into chronic conditions related to TBI, such as traumatic encephalopathy syndrome. Here, we review the literature and discuss the future directions of vision-based assessments of concussion and conditions related to TBI.

PURPOSE/OBJECTIVE:Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. METHODS:Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). RESULTS:Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. CONCLUSIONS:Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.

A woman presented at age 18 years with partial myelitis and diplopia and experienced multiple subsequent relapses. Her MRI demonstrated T2 abnormalities characteristic of multiple sclerosis (MS) (white matter ovoid lesions and Dawson fingers), and CSF demonstrated an elevated IgG index and oligoclonal bands restricted to the CSF. Diagnosed with clinically definite relapsing-remitting MS, she was treated with various MS disease-modifying therapies and eventually began experiencing secondary progression. At age 57 years, she developed an acute longitudinally extensive transverse myelitis and was found to have AQP4 antibodies by cell-based assay. Our analysis of the clinical course, radiographic findings, molecular diagnostic methods, and treatment response characteristics support the hypothesis that our patient most likely had 2 CNS inflammatory disorders: MS, which manifested as a teenager, and neuromyelitis optica spectrum disorder, which evolved in her sixth decade of life. This case emphasizes a key principle in neurology practice, which is to reconsider whether the original working diagnosis remains tenable, especially when confronted with evidence (clinical and/or paraclinical) that raises the possibility of a distinctively different disorder.