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Early neuropsychological markers of cognitive involvement in multiple sclerosis

Eilam-Stock, Tehila; Shaw, Michael T; Krupp, Lauren B; Charvet, Leigh E
BACKGROUND:Cognitive impairment due to multiple sclerosis (MS) is common and often limits occupational functioning, contributes to disability, and reduces quality of life. Early detection of cognitive involvement in MS is critical for treatment planning and intervention, and frequent, regular cognitive monitoring may provide insight into subtle changes in disease progression. OBJECTIVE:To compare the sensitivity and specificity of clinical, computer-based and experimental measures to early cognitive involvement in MS. METHODS:Cognitive functioning was compared in MS participants early in the disease course to matched healthy controls using conventional, computer-based and functional assessments: the Brief International Cognitive Assessment in MS (BICAMS); the computer-based Cogstate Brief Battery (CBB); the Attention Network Test-Interaction (ANT-I), including intra-individual variability; and the Test of Everyday Cognitive Ability (TECA), a functional measure of instrumental activities of daily living. RESULTS:MS participants (n = 25, mean disease duration= 5.82 ± 3.65 years) and demographically matched healthy controls (n = 29) completed the cognitive assessments. The Cogstate measure of choice reaction time (AUC = 0.73, p = .004), intra-individual variability on the ANT-I (AUC = 0.79, p = .001), and TECA (AUC = 0.78, p = .001) scores were the most sensitive and specific markers of cognitive involvement in MS. CONCLUSIONS:Brief, repeatable, computer-based measures of reaction time and variability detect early MS associated cognitive involvement.
PMID: 33639421
ISSN: 1878-5883
CID: 4800932

Gray Matter Morphometry Correlates with Attentional Efficiency in Young-Adult Multiple Sclerosis

Govindarajan, Sindhuja T; Pan, Ruiqi; Krupp, Lauren; Charvet, Leigh; Duong, Tim Q
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.
PMCID:7826940
PMID: 33435314
ISSN: 2076-3425
CID: 4771442

Remote administration of the symbol digit modalities test to individuals with multiple sclerosis is reliable: A short report

Eilam-Stock, Tehila; Shaw, Michael T; Sherman, Kathleen; Krupp, Lauren B; Charvet, Leigh E
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.
PMCID:7890734
PMID: 33643663
ISSN: 2055-2173
CID: 4801092

An Interview-Based Assessment of the Experience of Cognitive Impairment in Multiple Sclerosis: The Cognitive Assessment Interview (CAI)

Eilam-Stock, Tehila; Best, Pamela; Sherman, Kathleen; Shaw, Michael T; Ventura, Joseph; Krupp, Lauren B; Charvet, Leigh E
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, rs = 0.52, p < 0.001) and only mildly correlated with objective neuropsychological measures specific to executive functions (r
PMCID:7905222
PMID: 33643211
ISSN: 1664-2295
CID: 4801072

A Systematic Review and Meta-Analysis on the Efficacy of Repeated Transcranial Direct Current Stimulation for Migraine

Cai, Guoshuai; Xia, Zhu; Charvet, Leigh; Xiao, Feifei; Datta, Abhishek; Androulakis, X Michelle
Purpose/UNASSIGNED:Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine. Methods/UNASSIGNED:In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities. Results/UNASSIGNED:Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of migraine pain intensity (MD: -1.44; CI: [-2.13, -0.76]) in active vs sham tDCS treated patients. Within active treatment groups, pain intensity and duration were significantly improved from baseline after tDCS treatment (intensity MD: -1.86; CI: [-3.30, -0.43]; duration MD: -4.42; CI: [-8.11, -0.74]) and during a follow-up period (intensity MD: -1.52; CI: [-1.84, -1.20]; duration MD: -1.94; CI: [-3.10, -0.77]). There was a significant reduction of pain intensity by both anodal (MD: -1.74; CI: [-2.80, -0.68]) and cathodal (MD: -1.49; CI: [-1.89, -1.09]) stimulation conditions. Conclusion/UNASSIGNED:tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode. The benefit of tDCS can persist for at least 4 weeks after the completion of last tDCS session. Both anodal and cathodal stimulation are effective for reducing migraine pain intensity.
PMCID:8090858
PMID: 33953607
ISSN: 1178-7090
CID: 4898002

Mobile Attention Bias Modification Training Is a Digital Health Solution for Managing Distress in Multiple Sclerosis: A Pilot Study in Pediatric Onset

Charvet, Leigh; George, Allan; Cho, Hyein; Krupp, Lauren B; Dennis-Tiwary, Tracy A
PMCID:8355356
PMID: 34393986
ISSN: 1664-2295
CID: 5006312

Walking in multiple sclerosis improves with tDCS: a randomized, double-blind, sham-controlled study

Pilloni, Giuseppina; Choi, Claire; Shaw, Michael T; Coghe, Giancarlo; Krupp, Lauren; Moffat, Marilyn; Cocco, Eleonora; Pau, Massimiliano; Charvet, Leigh
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.
PMID: 33080122
ISSN: 2328-9503
CID: 4651992

COVID-19 outcomes in MS: Observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center

Parrotta, Erica; Kister, Ilya; Charvet, Leigh; Sammarco, Carrie; Saha, Valerie; Charlson, Robert Erik; Howard, Jonathan; Gutman, Josef Maxwell; Gottesman, Malcolm; Abou-Fayssal, Nada; Wolintz, Robyn; Keilson, Marshall; Fernandez-Carbonell, Cristina; Krupp, Lauren B; Zhovtis Ryerson, Lana
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.
PMID: 32646885
ISSN: 2332-7812
CID: 4518282

Functional Connectivity and Structural Disruption in the Default-Mode Network Predicts Cognitive Rehabilitation Outcomes in Multiple Sclerosis

Fuchs, Tom A; Ziccardi, Stefano; Benedict, Ralph H B; Bartnik, Alexander; Kuceyeski, Amy; Charvet, Leigh E; Oship, Devon; Weinstock-Guttman, Bianca; Wojcik, Curtis; Hojnacki, David; Kolb, Channa; Escobar, Jose; Campbell, Rebecca; Tran, Hoan Duc; Bergsland, Niels; Jakimovski, Dejan; Zivadinov, Robert; Dwyer, Michael G
BACKGROUND AND PURPOSE/OBJECTIVE:Efficacy of restorative cognitive rehabilitation can be predicted from baseline patient factors. In addition, patient profiles of functional connectivity are associated with cognitive reserve and moderate the structure-cognition relationship in people with multiple sclerosis (PwMS). Such interactions may help predict which PwMS will benefit most from cognitive rehabilitation. Our objective was to determine whether patient response to restorative cognitive rehabilitation is predictable from baseline structural network disruption and whether this relationship is moderated by functional connectivity. METHODS:For this single-arm repeated measures study, we recruited 25 PwMS for a 12-week program. Following magnetic resonance imaging, participants were tested using the Symbol Digit Modalities Test (SDMT) pre- and postrehabilitation. Baseline patterns of structural and functional connectivity were characterized relative to healthy controls. RESULTS:= .385, P = .017, Interaction β = -.415). CONCLUSION/CONCLUSIONS:Patient response to restorative cognitive rehabilitation is predictable from the interaction between structural network disruption and functional connectivity in the default-mode network. This effect may be related to cognitive reserve.
PMID: 32391981
ISSN: 1552-6569
CID: 4430992

Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic

Bikson, Marom; Hanlon, Colleen A; Woods, Adam J; Gillick, Bernadette T; Charvet, Leigh; Lamm, Claus; Madeo, Graziella; Holczer, Adrienn; Almeida, Jorge; Antal, Andrea; Ay, Mohammad Reza; Baeken, Chris; Blumberger, Daniel M; Campanella, Salvatore; Camprodon, Joan A; Christiansen, Lasse; Loo, Colleen; Crinion, Jennifer T; Fitzgerald, Paul; Gallimberti, Luigi; Ghobadi-Azbari, Peyman; Ghodratitoostani, Iman; Grabner, Roland H; Hartwigsen, Gesa; Hirata, Akimasa; Kirton, Adam; Knotkova, Helena; Krupitsky, Evgeny; Marangolo, Paola; Nakamura-Palacios, Ester M; Potok, Weronika; Praharaj, Samir K; Ruff, Christian C; Schlaug, Gottfried; Siebner, Hartwig R; Stagg, Charlotte J; Thielscher, Axel; Wenderoth, Nicole; Yuan, Ti-Fei; Zhang, Xiaochu; Ekhtiari, Hamed
BACKGROUND:The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE:To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS:The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS:A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION/CONCLUSIONS:There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.
PMCID:7217075
PMID: 32413554
ISSN: 1876-4754
CID: 4464542