Faculty Bibliography

OBJECTIVE:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

OBJECTIVE:To report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness. METHODS:From March 16 to April 30, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records. RESULTS:We identified 76 patients (55 with relapsing MS, of which 9 had pediatric onset; 17 with progressive MS; and 4 with related disorders). Thirty-seven underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n = 34, 44.7%) and sphingosine-1-phosphate receptor modulators (n = 10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a nonambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome. CONCLUSIONS:Most patients with MS with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at-risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.

The COVID-19 pandemic dramatically affected the operations of New York City hospitals during March and April of 2020. This article describes the transformation of a neurology division at a 450-bed tertiary care hospital in a multi-ethnic community in Brooklyn during this initial wave of COVID-19. In lieu of a mass redeployment of staff to internal medicine teams, we report a novel method for a neurology division to participate in a hospital's expansion of care for patients with COVID-19 while maintaining existing team structures and their inherent supervisory and interpersonal support mechanisms.

OBJECTIVE:To outline changes made to a neurology residency program in response to coronavirus disease 2019 (COVID-19). METHODS:In early March 2020, the first cases of COVID-19 were announced in the United States. New York City quickly became the epicenter of a global pandemic, and our training program needed to rapidly adapt to the increasing number of inpatient cases while being mindful of protecting providers and continuing education. Many of these changes unfolded over days, including removing residents from outpatient services, minimizing the number of residents on inpatient services, deploying residents to medicine services and medical intensive care units, converting continuity clinic patient visits to virtual options, transforming didactics to online platforms only, and maintaining connectedness in an era of social distancing. We have been able to accomplish this through daily virtual meetings among leadership, faculty, and residents. RESULTS:Over time, our program has successfully rolled out initiatives to service the growing number of COVID-related inpatients while maintaining neurologic care for those in need and continuing our neurologic education curriculum. CONCLUSION/CONCLUSIONS:It has been necessary and feasible for our residency training program to undergo rapid structural changes to adapt to a medical crisis. The key ingredients in doing this successfully have been flexibility and teamwork. We suspect that many of the implemented changes will persist long after the COVID-19 crisis has passed and will change the approach to neurologic and medical training.

INTRODUCTION: Neurological deficits that occur during treatment with tumor necrosis factor (TNF)-alpha antagonists are rare, and their clinical features have not been fully elucidated. METHODS: Retrospective review of medical records of 9 patients who were given TNF-alpha antagonists, subsequently developed neurological deficits and were cared for at the Medical University of South Carolina between January 2002 and May 2010. Adverse drug reaction probability scale was used for the assessment of their causal connection. RESULTS: The underlying diseases for which TNF-alpha antagonists were administered included rheumatologic disorders (4), sarcoidosis (3), psoriasis (1) and Crohn's disease (1). Etanercept, infliximab or adalimumab was administered to these patients. Neurological complications included central or peripheral demyelination (5), antiphospholipid syndrome/central nervous system lupus (1), Epstein-Barr virus encephalitis (1), axonal sensory polyneuropathy (1) and small fiber polyneuropathy (1). TNF-alpha antagonists were discontinued in 8 patients and clinical improvement was seen in 3 of them. Additional therapies were given in 4 patients. An adverse drug reaction probability score suggested probable (3/9) and possible (6/9) causal relationships. CONCLUSIONS: Neurological deficits that develop during treatment with TNF-alpha antagonists are relatively rare but important potential complications of these drugs. Determining if the relationship between the neurological deficits and TNF-alpha antagonist therapy is causal can be challenging and can impact patient care.

Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin-specific T cells into the central nervous system (CNS). During active disease, pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells. Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs) activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO gene expression in MS PBMCs, which was markedly decreased in calpain expressing cells. Functional assay showed that incubation of MS patient PBMCs with calpain inhibitor or recombinant IDO attenuates T cell proliferation. These results suggest that calpain inhibition may attenuate MS pathology and augment the efficacy of standard immunomodulatory agents used to treat this disease.

Marburg variant multiple sclerosis (MS) is an acute, fulminant and monophasic variant of MS that usually leads to death within weeks to months. No consistently successful treatment is known. We describe a 26-year-old woman who developed acute and progressive motor and sensory deficits. Demyelinating disease was suspected based on brain and spinal MRI and cerebrospinal fluid results. Multiple treatments including corticosteroids, plasma exchange and intravenous immunoglobulin could not halt her clinical and radiological deterioration. She became near quadriplegic and developed motor aphasia. A diagnosis of Marburg variant MS was considered and she was given high dose cyclophosphamide (HiCy) at 50mg/kg/day for four consecutive days, followed by granulocyte colony-stimulating factor six days after the completion of the cyclophosphamide treatment. HiCy successfully induced neutropenia. She started to show a steady neurological improvement from day 17 of HiCy treatment. MR studies two months after HiCy treatment showed significant decrease in the size and enhancement of the lesions. Five months later she had minimal residual right-sided weakness and was able to ambulate without assistance. The great outcome seen in our case suggests that HiCy should be considered as a potential treatment for patients with Marburg variant MS who fail to respond to standard therapy.