Faculty Bibliography

BACKGROUND:Factors driving differences in disease burden between African American and White people with multiple sclerosis (pwMS) remain unclear. Here, we explored whether differences in disability outcomes could be observed after controlling for major sociodemographic factors and comorbidities, and assessed the presence of a possible interaction between MS and race. METHODS:In this cross-sectional study, 120 pwMS within 6 years from disease onset and 82 healthy controls between 18 and 70 years of age, self-identified as either African American or White, were prospectively enrolled. Inclusion criteria for pwMS were: diagnosis of MS according to the revised McDonald criteria, relapsing-remitting phenotype and Expanded Disability Status Scale (EDSS) < 6.5. Study outcomes included: (i) global disability (EDSS); (ii) quantitative mobility and leg function (Timed 25 Foot Walk Test-T25FWT); (iii) quantitative finger dexterity (9-Hole Peg Test-9HPT); (iv) cognitive efficiency and speed performance (Symbol Digit Modalities Test-SDMT). Differences in disability outcomes were assessed employing multivariable linear regression models. Based on their association with MS or disability, covariates included age, gender, race, years of education, total income, body mass index, comorbidities. The interaction between MS and race on disability outcomes was estimated via relative excess risk of interaction and attributable proportion. RESULTS:Accounting for age, gender, total income, education, body mass index and comorbidities, African American pwMS showed significantly worse performances in manual dexterity and cognition than White pwMS (White pwMS coeff. 3.24, 95% CI 1.55, 4.92 vs African American pwMS coeff. 5.52, 95% CI 3.55, 7.48 and White pwMS coeff. -5.87, 95% CI -8.86, -2.87 vs African American pwMS coeff. -7.99, 95% CI -11.58,-4.38). MS and race independently contributed to the observed gradient in disability severity. CONCLUSIONS:Complex social disparities and systemic racism might contribute to clinical heterogeneity in MS.

Background: Although a more aggressive disease course has been reported in African-American (AA) patients with multiple sclerosis (MS) in comparison with Caucasian (CA) patients, differences in disability outcomes might be partly related to socioeconomic factors limiting access to cure or influencing lifestyle choices.
Aim(s): To assess the impact of demographics, socioeconomic status and comorbidities on disability differences between AA and CA MS patients.
Method(s): As part of an ongoing longitudinal study, 120 MS patients (60 AA, 60 CA) and 82 HC (43 AA, 39 CA) were prospectively enrolled. All subjects included in the study self-identified as AA or CA. Data on demographic, socioeconomic and clinical status of all subjects were collected. Differences in disability scales between AA and CA MS patients were assessed via ordinal logistic or multivariable linear regression, as appropriate, entering in the final model demographic features (age, gender), indirect indicators of socioeconomic status (educational level, body mass index) and comorbidities.
Result(s): No difference in disease management (diagnostic delay, number of therapeutic switches, treatment with first or second line disease modifying therapies) was present between the two groups. No differences in strength, sensitivity, balance and verbal fluency were detected between AA and CA MS patients. Differences in Expanded Disability Status Scale, walking endurance and verbal memory disappeared in the models including socioeconomic status and comorbidities. On the contrary, even in complex models accounting for confounders, AA showed higher Multiple Sclerosis Severity Score (3.17 vs 1.96, p=0.017), worse manual dexterity (9-hole peg test 25.34 vs 22.44, p=0.005; grooved pegboard test 12.65 vs 15.02, p=0.001; finger tapping test non dominant hand 48.53 vs 52.94, p=0.009), and worse cognitive performance in the attentional, visuospatial and executive domains (symbol digit modality test 50.82 vs 56.78, p=0.014; multitasking test 3.93 vs 5.13, p=0.002; brief visuospatial memory test 16.43 vs 20.90, p<0.001; Stroop test 37.76 vs 44.29, p=0.020).
Conclusion(s): AA patients with MS present a more severe disability status than CA patients. Observed differences are only partly accounted for by sociodemographic factors

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 determine the patient-perceived effectiveness and tolerability of mirabegron compared to solifenacin in a multiple sclerosis (MS) population with overactive bladder (OAB) symptoms. MATERIALS AND METHODS/METHODS:MS patients with OAB symptoms who were not on medication for their urinary symptoms at enrollment were prospectively recruited. Patients enrolled in years 1-2 were prescribed mirabegron, whereas patients enrolled in years 3-4 were prescribed solifenacin. At enrollment and 6-week followup, patients completed several patient reported outcome measures (PROMs). The primary outcome was change in Overactive Bladder Questionnaire Short Form (OAB-q SF) symptom severity and minimal clinically important difference (MCID) achievement. The Patient Assessment of Constipation Symptoms (PAC-SYM) was used to assess bowel function over the treatment period. RESULTS:61 patients were enrolled. The majority of the mirabegron (70%) and the solifenacin (69%) group achieved the OAB-q SF symptom severity MCID. The solifenacin group had a statistically significant greater decrease in its end of study OAB-q SF score (Δ = -37.87 versus -20.43, p=0.02). Constipation improved in the mirabegron group and worsened in the solifenacin group (ΔPAC-SYM =-0.38 versus +0.22; p=0.02), with 30% of patients prescribed solifenacin experiencing worsening above the MCID threshold. CONCLUSION/CONCLUSIONS:Among MS patients, we demonstrated similar response rates to mirabegron and solifenacin, with approximately 50-70% achieving each PROM's MCID. Though this small study showed some short-term evidence that improvement in urinary symptom severity was greater with solifenacin, this potential benefit must be weighed against the observed risk of worsening constipation. Further studies are needed to confirm these findings.

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.

OBJECTIVE:To determine the underlying etiology in a patient with progressive dementia with extrapyramidal signs and chronic inflammation referred to the National Institutes of Health Undiagnosed Diseases Program. METHODS:Extensive investigations included metabolic profile, autoantibody panel, infectious etiologies, genetic screening, whole exome sequencing and the phage-display assay, VirScan, for viral immune responses. An etiological diagnosis was established post-mortem. RESULTS:Using VirScan, enrichment of dengue viral antibodies were detected in cerebrospinal fluid as compared to serum. No virus was detected in serum or cerebrospinal fluid, but post-mortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction and sequencing. Dengue virus was also detectable by polymerase chain reaction and sequencing from brain biopsy tissue collected 33 months ante-mortem, confirming a chronic infection despite a robust immune response directed against the virus. Immunoprofiling and whole exome sequencing of the patient did not reveal any immunodeficiency and sequencing of the virus demonstrated wild-type dengue virus in the central nervous system. INTERPRETATION/CONCLUSIONS:Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. Infections with dengue virus are usually self-limiting and chronic dengue infections have not been previously reported. Our findings suggest that dengue virus infections may persist in the central nervous system and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Further, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiologies. This article is protected by copyright. All rights reserved.

Introduction: Psychological resilience is a dynamic process of positive adaptation to adversity based on maintenance of positive adjustments under challenging life circumstances. Multiple sclerosis is a chronic and unpredictable illness, accompanied by physical and emotional challenges, yet the role of psychological resilience in MS is understudied. We analyzed the impact of psychological resilience on disability measures in Multiple Sclerosis (MS).
Objective(s): To investigate the effect of psychological resilience on standard measures of disability in MS.
Aim(s): To assess a role of psychological resilience in MS.
Method(s): One hundred and one patients with relapsing-remitting MS: 52 African-American (AA) patients with mean age 38.56 +/- 11.05 yrs and mean disease duration 7.79 +/- 5.38 yrs and 49 Caucasian (CA) patients with mean age 38.92 +/- 10.43 yrs and mean disease duration 6.65 +/- 5.31 yrs were enrolled as part of an ongoing study. Psychological resilience was assessed with the Connor-Davidson Resilience Scale 10 item, a validated measure of psychological resilience. Partial correlations were evaluated between resilience and standard measures of disability in MS (Symbol Digit Modalities Test -SDMT, Nine Hole Peg Test- NHPT, Timed 25 Foot Walk -T25FW), controlling for demographics (age, gender, disease duration), disease burden (brain atrophy and T2 lesion volume), and depression.
Result(s): Psychological resilience was not related to demographics or disease burden however psychological resilience was related to depression (r=-0.65, p< 0.001). Psychological resilience was associated with better performance on SDMT (r=0.39, p=0.001) and NHPT (r=-0.31, p=0.010) with a trend toward significance on T25FW (r=-0.22, p=0.074). After controlling for demographics and disease burden, no difference in resilience or depression was seen between AA and CA patients. Stratified by race, higher psychological resilience was associated with better performance on SDMT (r=0.38, p=0.021) and NHPT (r=-0.43, p=0.008) in AA patients and on SDMT (r=0.46, p=0.019) and T25FW in CA patients (r=-0.42, p=0.035).
Conclusion(s): Our results show a positive impact of psychological resilience on disability in MS, independent from disease severity and mood changes. Identification of patients with lower resilience suggests potential targets for therapeutic intervention. Longitudinal studies are needed to confirm a protective effect of psychological resilience against MS disability