Faculty Bibliography

Slowed processing on the alerting, orienting and executive control components of attention measured using the Attention Network Test-Interactions (ANT-I) have been widely reported in multiple sclerosis (MS). Despite the assumption that these components correspond to specific neuroanatomical networks in the brain, little is known about gray matter changes that occur in MS and their association with ANT-I performance. We investigated vertex-wise cortical thickness changes and deep gray matter volumetric changes in young MS participants (N = 21, age range: 18-35) with pediatric or young-adult onset and mild disease severity. ANT-I scores and cortical thickness were not significantly different between MS participants and healthy volunteers (N = 19, age range: 18-35), but thalamic volumes were significantly lower in MS. Slowed reaction times on the alerting component in MS correlated significantly with reduced volume of the right pallidum in MS. Slowed reaction times on executive control component correlated significantly with reduced thickness in the frontal, parietal and visual cortical areas and with reduced volume of the left putamen in MS. These findings demonstrate associations between gray matter changes and attentional performance even in the absence of widespread atrophy or slowed attentional processes.

Background/UNASSIGNED:The Symbol Digit Modalities Test (SDMT) is the gold standard for cognitive screening in multiple sclerosis (MS). Objective/UNASSIGNED:Due to the recent COVID-19 pandemic and the increased need for virtual clinical visits, we examined the reliability of remote administration of the SDMT vs. standard in-person administration to individuals with MS. Methods/UNASSIGNED:Pearson's correlation analysis was performed between SDMT scores on the in-person and remote administrations. Results/UNASSIGNED: = .000). Conclusion/UNASSIGNED:Remote administration of the SDMT is a reliable cognitive screening approach in MS.

Background: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating central nervous system (CNS) disorder, characterized by new onset polyfocal neurologic symptoms with encephalopathy and multifocal demyelination, typically occurring in early childhood. The initial diagnosis of ADEM can be challenging as up to 20% of children with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) are initially diagnosed with ADEM.
Objective(s): To describe characteristics of patients with ADEM vs. recurrent demyelinating syndromes (MS or NMOSD) at the time of initial presentation and identify features at disease onset associated with monophasic demyelinating disease.
Method(s): This is a multicenter observational cohort study of children with a demyelinating disease diagnosis of ADEM, multiphasic ADEM, MS, and NMOSD who were followed at 12 regional pediatric MS referral centers in the US Network of Pediatric MS Centers. Descriptive statistics were used to report patient characteristics, clinical/imaging presenting features and clinical followup outcomes. Logistic regression was used to predict features associated with monophasic demyelination and to identify features associated with poor recovery from ADEM in patients with ADEM-like presentation at 2 years from disease onset.
Result(s): As of July 2019, 872 pediatric patients with a final diagnosis of ADEM (n=89), MS (n= 664) and NMOSD (n=119) were identified. The mean follow-up for all patients was 5.7 +/-3.1 years. ADEM patients were the youngest with mean age at first event 5.4 +/-3.7 years and male predominance (62%), p < 0.001. Severe clinical symptoms at onset were more frequent in ADEM (55% vs. 35% NMOSD and 15% MS, p < 0.001). After 2 years of follow-up, 86.2% of patients initially diagnosed with ADEM retained this diagnosis (ADEM to ADEM), while 10.1% were later reclassified as MS and 3.6% with NMOSD. In univariable regression, younger age at first event and having an antecedent infection at onset were associated with ADEM, while presentation with optic neuritis and gadolinium enhancement on brain MRI were associated with ADEM reclassification to MS or NMOSD after 2 years of follow up. In a multivariable analysis, older age at first event (OR 1.29 [95% CI 1.07-1.56], p = 0.007), presenting with optic neuritis (OR 27.56 [95% CI 3.19-238.14], p = 0.003) and presence of gadolinium enhancement on brain MRI at onset (OR 14.36 [95% CI 2.53-81.36], p = 0.003) were associated with reclassification of ADEM to MS or NMOSD within 2 years. Younger age at onset was associated with higher risk of EDSS 2.0 or higher after 2 years of follow-up (p = 0.0422).
Conclusion(s): Those who remain classified as ADEM vs. those who are reclassified as other demyelinating disorders are younger at onset, more likely to be male, have a more severe initial presentation, and are less likely to have optic neuritis or gadolinium enhancing lesions at onset

Background: Cognitive impairment is a common feature of multiple sclerosis (MS). A semi-structured interview, including informant input, can characterize the experience of individuals living with MS and cognitive involvement. Objective: We administered the Cognitive Assessment Interview (CAI), a patient- and informant-based semi-structured interview, to characterize the experience of cognitive impairments in those living with MS. Methods: Trained raters administered the CAI to a sample of MS participants and their informants enrolled for a trial of cognitive remediation. Cognitive impairments on the CAI were characterized and compared to those captured by neuropsychological and self-report measures. Results: A total of n = 109 MS participants (mean age = 50.3 ± 12.2) and their available informants (n = 71) were interviewed. Participants reported experiencing processing speed (90/106, 85%), working memory (87/109, 80%), and learning and memory (79/109, 72%) problems most commonly. CAI-based ratings were moderately correlated with a self-report measure (Multiple Sclerosis Neuropsychological Screening Questionnaire, r_s = 0.52, p < 0.001) and only mildly correlated with objective neuropsychological measures specific to executive functions (r

Pediatric MS occurs in approximately 5% of patients and is defined as MS onset prior to age 18 years Those with pediatric MS tend to have a more inflammatory course but recover from relapses better than adults. Pediatric MS has been associated with cognitive problems in approximately 30% of patients where as 60-70% of adults have impaired cognitive functioning. Cognitive processing speed is the most frequently affected domain. In a recent study, 16% of CIS and 23% of RRMS had impaired cognitive functioning. Of concern is that other work has shown that while those with pediatric onset do well early in their course, over their life-time they may continue to show declines, particularly around 15 years after disease onset. The hope is that, early recognition, more effective symptomatic interventions such as cognitive retraining, and high efficacy disease modifying therapy can forestall the development of cognitive decline in those with pediatric MS onset

Background: Fatigue is among the most frequent and disabling symptoms in RMS patients.
Objective(s): To measure multiple sclerosis (MS) fatigue and its impact on daily life in a real-world population using a survey including the relapsing MS (RMS)-specific Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS).
Method(s): This is an ongoing noninterventional prospective study of RMS patients recruited across the USA via an online survey. Participants completed questionnaires including disease history, disease status, sleep, social and emotional functioning, and the FSIQ-RMS, administered daily for 7 days. The FSIQ-RMS measures self-reported fatigue, and scores range from 0-100 (higher score = greater severity). The impact of fatigue on several aspects of patient's life was rated from 0 (no impact) to 10 (very high impact).
Result(s): A total of 300 RMS participants completed the 7-day assessment: mean age: 43.0 yrs; 88% women; mean diagnosis age: 32 yrs. Fatigue was reported as the symptom with the greatest impact on daily functioning. Participants with lower disability rated fatigue as the most impactful symptom on daily life. Fatigue was rated as severe, with a mean score: 57.3 for the FSIQ-RMS symptom domain; 3 impact sub-domain scores were 42.3, 43.4 and 50.1 (physical, cognitive/emotional, and coping). Fatigue severity did not vary among patients receiving high efficacy disease modifying therapy (DMT) vs other DMTs (44% [n=111] vs 56% [n=143], with score of 57.8?}17.6 vs 55.9?}19.8). Impact of ability to perform daily activities was rated as the highest (6.9/10) in terms of impact on patient's life. Because of MS, 44% of participants did not work. Among those who were working currently (48%), the impact of fatigue on professional life was rated as 4.5/10. Nearly half of the participants (49% of 300) discussed fatigue at each visit with their neurologists and 35% discussed at most visits, with 'impact of fatigue on quality of life' being the most discussed topic (65% of 289). Participants used different approaches to manage their fatigue including avoided heat exposure (77%), took breaks (65%), managed their energy (59%), took non-medicinal products (58%); however, only 6% (of 293) were totally satisfied with these strategies.
Conclusion(s): In this survey including the novel RMS specific FSIQ-RMS, fatigue occurred in most MS participants and adversely influenced patient's daily functioning and life. Fatigue remains a major concern for those with MS

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 evaluate whether multiple sessions of transcranial direct current stimulation (tDCS) applied to the primary motor (M1) cortex paired with aerobic exercise can improve walking functions in multiple sclerosis (MS). METHODS:MS participants were recruited for a double-blind, parallel-arm, randomized, sham-controlled trial and assigned to 10 sessions (5 d/wk for 2 weeks) of either active or sham tDCS paired with unloaded cycling for 20 minutes. Stimulation was administered over the left M1 cortex (2.5 mA; anode over C3/cathode over FP2). Gait spatiotemporal parameters were assessed using a wearable inertial sensor (10-meter and 2-minute walking tests). Measurements were collected at baseline, end of tDCS intervention, and 4-week postintervention to test for duration of any benefits. RESULTS:A total of 15 participants completed the study, nine in the active and six in the sham condition. The active and sham groups were matched according to gender (50% vs. 40% female), neurologic disability (median EDSS 5.5 vs. 5), and age (mean 52.1 ± 12.9 vs. 53.7 ± 9.8 years). The active group had a significantly greater increase in gait speed (0.87 vs. 1.20 m/s, p < 0.001) and distance covered during the 2-minute walking test (118.53 vs. 133.06 m, p < 0.001) at intervention end compared to baseline. At 4-week follow-up, these improvements were maintained (baseline vs. follow-up: gait speed 0.87 vs. 1.18 m/s, p < 0.001; distance traveled 118.53 vs. 143.82 m, p < 0.001). INTERPRETATION/CONCLUSIONS:Multiple sessions of tDCS paired with aerobic exercise lead to cumulative and persisting improvements in walking and endurance in patients with MS.