Faculty Bibliography

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 investigate sensory-motor disability in African Americans (AA) with MS.
Background(s): A more severe disease course has been reported in AA in comparison with Caucasians (CA) MS patients. Sociodemographic differences, such as longer disease duration related to younger age at onset or disparity in income wich may lead to delayed diagnosis and limited access to treatment have been often used to explain the different disability profile in the two groups. To date, an objective assessment of sensorymotor disability in AA and potential differences with CA patients is still lacking.
Method(s): Fifty-two AA patients (41F, mean age 38.56 +/- 11.05 yrs, mean disease duration 7.79 +/- 5.38 yrs), 38 AA healthy controls (HC) (26F, mean age 36.13 +/- 12.31 yrs), 49 CA patients (33F, mean age 38.92 +/- 10.43 yrs, mean disease duration 6.65 +/- 5.31 yrs) and 26 CA HC (16F, mean age 31.69 +/- 10.82 yrs) were prospectively enrolled as part of an ongoing longitudinal study. In all subjects, an extensive sensory-motor evaluation was performed, including 9-hole peg test (9-HPT), grooved pegboard test (GPT), finger tapping test (FTT), 25-foot walk test (25-FWT), 2-minutes walk test (2-MWT), evaluation of segmental strength, grip strength, vibration sensitivity and balance. Each patient's group was compared with a race-matched HC group via ANCOVA analysis, accounting for age, gender and socioeconomic status expressed as yearly income.
Result(s): AA and CA patients did not differ in age, gender, disease duration, while they did differ in yearly income (p=0.008). AA patients and AA HC did not differ in gender, age or socioeconomic status. CA patients and CA HC did not differ in gender, while they did differ in age (p=0.002) and socioeconomic status (p=0.031). Significant differences in 9-HPT (p=0.001), GPT (p=0.015), FTT (p=0.034), grip strength (p=0.033), 2-MWT (p=0.010), balance (p=0.001) and foot vibration sensitivity (p=0.046) were identified between AA patients and AA HC. Significant differences in 9-HPT (p=0.011), GPT (p< 0.001), 25-FWT (p=0.049) and 2-MWT (p< 0.001) were identified between CA patients and CA HC.
Conclusion(s): AA and CA patients showed similar deficits in ambulation and manual dexterity but AA patients showed additional involvement of motor speed and coordination, balance, strenght and sensitivity. These results suggest that, even accounting for sociodemographic features, AA patients with MS indeed show more severe and widespread disability than CAs patients with MS

Objective: To investigate cognitive deficits in African Americans (AA) with MS.
Background(s): Cognitive impairment is one of the most frequent and burdensome symptoms of MS. Although a more severe disease course has been descibed in AA in comparison with Caucasians (CA) patients, an objective assessment of the cognitive profile of AA and potential differences with CA patients has not been investigated yet.
Method(s): Fifty-one AA patients (40F, mean age 38.45 +/- 11.13 yrs, mean disease duration 7.88 +/- 5.39 yrs), 37 AA healthy controls (HC) (25F, mean age 35.97 +/- 12.44 yrs), 43 CA patients (32F, mean age 39.00 +/- 10.56 yrs, mean disease duration 6.67 +/- 7.00 yrs) and 18 CA HC (12F, mean age 30.72 +/- 6.94 yrs) were prospectively enrolled as part of an ongoing longitudinal study. In all subjects, an extensive neuropsychological evaluation was performed, including: Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT), Brief Visuospatial Memory Test-Revised (BVMT), Stroop Color and Word Test (SCVT), Controlled Oral Word Association Test (COWAT), Pattern Comparison Processing Speed Test (PCPST) and a multitasking attention-memory test (MAMT). Each patient's group was compared with a race-matched HC group via ANCOVA analysis, accounting for age, gender, years of education, premorbid intelligence estimated with the Wechsler Test of Adult Reading (WTAR) and socioeconomic status expressed as yearly income.
Result(s): AA patients and HC did not differ in gender, age, years of education, WTAR score or socioeconomic status. CA patients and HC did not differ in gender, years of education and socioeconomic status, while significantly differ in age and WTAR scores (p=0.001 for both). Significant differences in SDMT (p=0.002), BVMT (p=0.012), COWAT (p=0.006), PCPST (p=0.008) and MAMT (p=0.018) scores were identified between AA patients and AA HC. Significant differences in SDMT (p=0.003), CVLT (p=0.009), BVMT (p=0.021), COWAT (p=0.003) and PCPST (p< 0.0001) scores were identified between CA patients and CA HC.
Conclusion(s): AA and CA patients showed similar deficits in information processing speed, attention, visuospatial memory and verbal fluency. CA patients showed additional impairment in the verbal memory domain, while AA patients showed deficits in multitasking capability. These results suggest that the cognitive profile of MS patients mostly overlaps across different races, although it seem to show group-specific deficits in specific domains

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

The prevalence of nocturia in patients with multiple sclerosis (MS) is high, ranging from 20.9% to 48.8% in this population. Its underlying pathophysiology is complex and different from the non-neurogenic population. In the MS population, the pathophysiology may involve neurogenic lower urinary tract dysfunction (NLUTD) such as detrusor overactivity (NDO), detrusor-sphincter dyssynergia, or detrusor underactivity resulting in reduced bladder capacity. Nocturnal polyuria is also a significant contributor to the pathogenesis of nocturia in MS patients and may be the result of specific mechanisms such as nocturnal hypertension through autonomic cardiovascular dysfunction or lack of diurnal variation of antidiuretic hormone production (ADH) due to demyelinating lesions of the spinal cord. Nocturia might be particularly burdensome in MS patients by contributing to fatigue, a common and highly debilitating symptom in this population. There is likely a complex and multidirectional relationship between nocturia, other sleep disorders, and fatigue in the MS population that has yet to be explored. The assessment of nocturia in MS should rely upon a thorough history and physical examination. Urinalysis should be done to rule out urinary tract infection, a frequency-volume chart might help elucidating the underlying mechanisms, and post-void residual volume may be of interest to screen for urinary retention that could be asymptomatic in MS patients. Other tests such as urodynamics or polysomnography are indicated in selected patients. The treatment should be tailored to the underlying cause. The first steps involve behavioral interventions and treatment of cofactors. When possible, the predominant mechanism should be addressed first. In case of predominant NDO, antimuscarinics and beta-3 agonists should be offered as a first-line treatment and intradetrusor injections of botulinum toxin as a second-line treatment. In cases of incomplete bladder emptying, clean-intermittent self-catheterization is often used as part of multiple other interventions. In cases of nocturnal polyuria, desmopressin may be offered, inclusive of use of newer formulations (desmopressin acetate nasal spray, desmopressin orally disintegrated tablet) in countries where they are approved.

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.