Faculty Bibliography

OBJECTIVE:Distinctive differences in multiple sclerosis (MS) disease severity, progression, and mortality have been observed among different races. Social determinants of health (SDH) can contribute to such racial disparities. This study aims to: 1) compare Non-Hispanic White (NHW) and Black (Bl) persons with MS in terms of MS and SDH; 2) explore the impact of SDH-adjustment in the association between race and Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25-FW), 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT). METHODS:120 patients, self-identified as Bl (n = 60) or NHW (n = 60) persons, were included in this cross-sectional analysis from a prospectively enrolled cohort. We used parametric and non-parametric tests; logistic models were performed to select the most relevant SDH. Univariable linear regression models were used to explore differences in EDSS, T25-FW, 9-HPT, SDMT and models were adjusted for relevant SDH using propensity scores (PS). RESULTS:Significant racial disparities in adverse SDH were identified in Black persons with MS (BpwMS). BpwMS patients had a higher EDSS (β=0.66, p = 0.022), log-transformed T25-FW (β=0.16, p = 0.001), 9-HPT (β=2.89, p = 0.001) and lower SDMT (β=-5.97, p = 0.003); after PS-adjustment, associations were no longer significant except for T25-FW (β=0.13, p = 0.030) and the magnitude of all coefficients was reduced (EDSS: -27 %, T25-FW: -19 %, 9-HPT: -36 %, SDMT: -45 %). INTERPRETATION/CONCLUSIONS:More efforts are necessary to adequately address the SDH that distinguish Bl from NHW persons with MS; additional unknown or unmeasured variables, including biologic differences as well as other SDH, should be explored to elucidate the mechanisms behind worse MS outcomes in BpwMS.

BACKGROUND/UNASSIGNED:There is a greater risk of complications from severe COVID-19 in immunocompromised patients with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs), as well as a diminished vaccine response. METHODS/UNASSIGNED:In this exploratory, observational study, we recruited 28 patients with Relapsing Remitting MS (RRMS, n=24) or Secondary Progressive MS (SPMS, n=4), that were receiving treatment with either natalizumab or fumarates (diroximel or dimethyl) prior to baseline sample collection. Blood samples were collected before vaccination (baseline), between 4 weeks and 6 months post vaccination, and post booster administration. A multiplex bead immunoassay (MBI) was used to measure anti-Spike IgG, while IFNγ and IL-2 ELISpot assays were used to determine T cell activation. A 35-color spectral flow cytometry panel was used to phenotype bulk B and T cells and SARS-CoV-2-specific T cells, while dimensionality reduction was performed for further phenotypic analysis. RESULTS/UNASSIGNED:We observed a significantly increased absolute lymphocyte count (ALC) (p=0.0003) in natalizumab-treated pwMS when compared to fumarate-treated pwMS primarily due to increased circulating CD19+ B cells. Fumarate-treated pwMS exhibited a diminished Th1/Th2 ratio when compared to natalizumab-treated pwMS (p=0.0004) or healthy controls (p=0.0745), while natalizumab treatment marginally increased the Th1/Th2 ratio compared to healthy controls (p=0.1311). The observed increase in B cells in natalizumab-treated pwMS were predominantly memory B cells, and double negative (DN) B cells. However, no significant differences between the treatment groups were seen in terms of Spike IgG titers following the initial vaccination course or booster dose, nor in SARS-CoV-2-specific CD4+ responses, all of which remained robust for at least 6 months post-vaccination. The magnitude of humoral and cellular immune responses in both treatment groups were comparable to vaccinated healthy controls. Additionally, SARS-CoV-2 spike-specific CD4+ T cell phenotyping revealed a Th2 dominant response to booster dose in natalizumab-treated pwMS (p=0.0485) but not fumarate-treated pwMS. CONCLUSION/UNASSIGNED:pwMS treated with natalizumab or fumarates exhibit similarly robust and durable SARS-CoV-2 specific T cell and humoral responses following vaccination and booster dose. DMT-treated pwMS showing comparable responses to healthy individuals following initial vaccination supports the notion that treatment with these specific DMTs does not diminish strong, long-lasting immunity conferred by COVID-19 vaccination, despite the phenotypic differences modulated by each therapy.

Public health systems reported low mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in East Asia, in low-income countries, and for children during the first year of the SARS-CoV-2 pandemic. These reports led commentators to suggest that cross-reactive immunity from prior exposure to other pathogens reduced fatality risk. Resolution of initial infection waves also contributed to speculation that herd immunity prevented further waves prior to vaccination. Serology instead implied that immunity was too limited to achieve herd immunity and that there was little impact from cross-reactive protection. Paediatric deaths exceeded those from influenza, with higher age-specific fatality risk in lower-income nations and similar fatality risk in East Asia compared with demographically similar regions. Neither pre-outbreak exposure to related pathogens nor immunity induced by initial infection waves are necessarily a reliable response to future pathogen outbreaks. Preparedness for future pathogen outbreaks should instead focus on strategies such as voluntary behavioural changes, nonpharmaceutical interventions, and vaccination.

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.