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.

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Objective: Report outcomes on patients with Multiple Sclerosis (MS) and related disorders with COVID-19 illness.Methods: From March 16 to April 30 th , 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center (MSCC) 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). 37 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 non-ambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome. Conclusions: Most MS patients 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.

ObjectiveTo report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness.MethodsFrom 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.ResultsWe 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.ConclusionsMost 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.

Objectives:To investigate the immune response to vaccinations in patients with relapsing forms of MS treated with delayed-release dimethyl fumarate (DMF) vs nonpegylated interferon (IFN).Methods:In this open-label, multicenter study, patients received 3 vaccinations: (1) tetanus-diphtheria toxoid (Td) to test T-cell–dependent recall response, (2) pneumococcal vaccine polyvalent to test T-cell–independent humoral response, and (3) meningococcal (groups A, C, W-135, and Y) oligosaccharide CRM197 conjugate to test T-cell–dependent neoantigen response. Eligible patients were aged 18–55 years, diagnosed with relapsing-remitting MS (RRMS), and either treated for ≥6 months with an approved dose of DMF or for ≥3 months with an approved dose of nonpegylated IFN. Primary end point was the proportion of patients with ≥2-fold rise in antitetanus serum IgG levels from prevaccination to 4 weeks after vaccination.Results:Seventy-one patients (DMF treated, 38; IFN treated, 33) were enrolled. The mean age was 45.3 years (range 27–55); 86% were women. Responder rates (≥2-fold rise) to Td vaccination were comparable between DMF- and IFN-treated groups (68% vs 73%). Responder rates (≥2-fold rise) were also similar between DMF- and IFN-treated groups for diphtheria antitoxoid (58% vs 61%), pneumococcal serotype 3 (66% vs 79%), pneumococcal serotype 8 (95% vs 88%), and meningococcal serogroup C (53% vs 53%), all p > 0.05. In a post hoc analysis, no meaningful differences were observed between groups in the proportion of responders when stratified by age category or lymphocyte count.Conclusions:DMF-treated patients mount an immune response to recall, neoantigens, and T-cell–independent antigens, which was comparable with that of IFN-treated patients and provided adequate seroprotection.ClinicalTrials.gov identifier:NCT02097849.Classification of evidence:This study provides Class II evidence that patients with RRMS treated with DMF respond to vaccinations comparably with IFN-treated patients.

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Highlights A patient developed encephalopathy two months after a mild case of COVID-19. MRI Brain demonstrated extensive white matter lesions juxtacortically and subcortically. Workup for infectious, paraneoplastic, toxic process was negative. MBP was elevated, prompting diagnosis of post-infectious ADEM following COVID-19. COVID-19 patients without hypoxia may have post-infectious leukoencephalopathy.

IMPORTANCEThe investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS. OBJECTIVE To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking MAIN OUTCOMES AND MEASURES Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability). RESULTS The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm 3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm 3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm 3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm 3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm 3 [P < .001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm 3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm 3 ; cortical lesion number , 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm 3 ; r = −0.52; P < .01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm 3 ; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = −0.60; P < .01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage.CONCLUSIONS AND RELEVANCE In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype. Royal Infirmary, Leicester, England, helped with the spinal cord post processing. None of the contributors received compensation for their roles. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis.