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Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition

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A special issue of Sclerosis (ISSN 2813-3064).

Deadline for manuscript submissions: 10 November 2026 | Viewed by 13070

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Prof. Dr. Pasquale Calabrese

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Neuropsychology and Behavioral Neurology Unit, Division of Molecular and Cognitive Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland
Interests: memory; neurodegenerative diseases; neurological diseases; cognitive neuroscience; behavioral neuroscience; learning
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Dear Colleagues,

Multiple sclerosis (MS) remains one of the most prevalent chronic neurological disorders affecting young adults worldwide. Beyond the well-known sensorimotor challenges, MS often presents with a range of neuropsychiatric symptoms, including cognitive impairments, mood disturbances, and fatigue. These symptoms, which can sometimes appear as the initial manifestation of the disease, significantly affect both daily functioning and overall well-being. The impact of MS on quality of life (QoL) is profound, as these neuropsychiatric issues often become intertwined with the physical aspects of the disease.

Following the success of the first edition of this Special Issue, which featured 10 papers, we continue to explore the intricate relationship between cognitive and neuropsychiatric conditions in MS. This second edition invites original research articles, reviews, and case studies that advance our understanding of the impact of these conditions on mental health, QoL, and patient care. The aim is to further contribute to the growing body of knowledge and encourage interdisciplinary approaches that can lead to more effective management strategies for patients with MS facing these complex challenges.

Prof. Dr. Pasquale Calabrese
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Sclerosis is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

multiple sclerosis
neuropsychiatric symptoms
quality of life
mental health

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Related Special Issue

Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis in Sclerosis (10 articles)

Published Papers (7 papers)

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11 pages, 245 KB

Open AccessArticle

Modifiable Lifestyle Factors as Effect Modifiers of Diet-Induced Changes in the Physical and Psychological Impacts of Multiple Sclerosis: A Secondary Analysis of the WAVES Trial

by Lauren R. Berry, Tyler J. Titcomb, Farnoosh Shemirani, Patrick Ten Eyck, Lucas J. Carr, Warren G. Darling, Karin F. Hoth, Linda G. Snetselaar and Terry L. Wahls

Sclerosis 2026, 4(1), 7; https://doi.org/10.3390/sclerosis4010007 - 23 Mar 2026

Viewed by 484

Abstract

Background/Objectives: Evidence suggests that modifiable lifestyle interventions improve disability in relapsing multiple sclerosis (MS); however, interactions between different factors may impact outcomes. Thus, the objective of this secondary analysis was to investigate diet-induced effects on the impact of MS and effect modification by other modifiable lifestyle factors. Methods: The physical and psychological impact of MS was assessed with the MS Impact Scale-29 (MSIS) at run-in, baseline, 12 weeks, and 24 weeks. Participants were randomized at baseline to the Swank low-saturated fat or Wahls modified Paleolithic elimination diets and instructed to maintain usual physical activity, objectively measured with an accelerometer, throughout the trial. Baseline information on sleep, physical activity, alcohol, and smoking was explored as effect modifiers. Results: Among the Swank group, MSIS-Physical scores improved from 33.8 ± 3.8 at baseline to 28.7 ± 3.6 at 12 weeks (p = 0.04) and 25.3 ± 3.5 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 35.7 ± 3.3 at baseline to 25.6 ± 2.6 at 12 weeks (p = 0.001) and 22.8 ± 2.4 at 24 weeks (p < 0.001). Among the Wahls group, MSIS-Physical scores improved from 33.8 ± 3.1 at baseline to 21.7 ± 3.0 at 12 weeks (p < 0.001) and 19.0 ± 3.1 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 38.4 ± 3.8 at baseline to 25.5 ± 3.8 at 12 weeks (p < 0.001) and 20.6 ± 3.6 at 24 weeks (p < 0.001). Improvements in MSIS-Physical were greater among participants who were physically inactive or drank little alcohol at baseline. Conclusions: Both diets led to favorable within-group improvements in the perceived impact of MS. People with MS who are physically inactive or drink little alcohol may benefit the most from dietary interventions. Full article

(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition)

12 pages, 877 KB

Open AccessArticle

Cognitive Impairment Screening in Multiple Sclerosis Using CoGeval: Clinical and Functional Predictors in a Mexican Cohort

by Luis F. Hernández Salomón, José A. Mejía Chávez, Diana M. S. Sánchez Galván and Luis E. Zapata Mercado

Sclerosis 2025, 3(4), 39; https://doi.org/10.3390/sclerosis3040039 - 29 Nov 2025

Viewed by 1075

Abstract

Background/Objectives: Cognitive impairment is frequent in multiple sclerosis, yet routine screening is inconsistently implemented. We aimed to characterize cognitive impairment using CogEval in a Mexican cohort and to identify clinical and functional correlates. Methods: We conducted a cross-sectional study at UMAE No. 71 (Torreón, Mexico). Adults with MS (n = 81) underwent CogEval screening (classified as normal, mild, or severe). Disability, upper-limb dexterity (9-Hole Peg Test, mean of both hands), and gait speed (Timed 25-Foot Walk) were assessed. Bivariate tests and multivariable logistic regression examined associations with cognitive impairment. Results: Participants were 61.7% women; mean age was 35.7 ± 9.9 years. Median EDSS was 2.0 (IQR 1.0–4.0); 28.4% had EDSS ≥ 4. CogEval identified impairment in 49.4% (40/81), with 62.5% severe and 37.5% mild. In bivariate analyses, impairment was associated with higher EDSS (p < 0.001), slower 9-HPT (p < 0.001), and slower T25FW (p = 0.0058), but not with age, sex, or disease duration. In adjusted models, EDSS (OR 1.86, 95% CI 1.14–3.03; p = 0.012) and 9-HPT per second (OR 1.31, 95% CI 1.09–1.58; p = 0.005) independently predicted impairment, whereas T25FW and age were not significant. Discrimination was good (AUC = 0.863). Conclusions: About half of this Mexican MS cohort screened positive for cognitive impairment, particularly those with greater disability and reduced manual dexterity. CogEval appears feasible for routine screening and may help prioritize comprehensive neuropsychological assessment and rehabilitation. Full article

(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition)

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12 pages, 833 KB

Open AccessArticle

Acute Effects of Intermittent Walking on Gait Parameters and Fatigability in People with Mild Multiple Sclerosis

by Cintia Ramari, Ana R. Diniz, Felipe von Glehn and Ana C. de David

Sclerosis 2025, 3(3), 21; https://doi.org/10.3390/sclerosis3030021 - 20 Jun 2025

Cited by 1 | Viewed by 1576

Abstract

Introduction: Walking is perceived as the most important bodily function for persons with multiple sclerosis (pwMS) and is impaired in more than 70% of pwMS. In addition, the effect of multiple sclerosis (MS) on gait pattern increases in fast walking and during fatiguing exercises, altering the spatiotemporal gait parameters and walking reserve. Objectives: The objective of this study is to investigate the impact of a 12 min intermittent-walking protocol on spatiotemporal gait parameters and on the fatigability of pwMS, as well as the association with perceived exertion and reported symptoms of fatigue. Methods: Twenty-six persons with relapse-remitting MS and twenty-eight healthy controls (HCs) were included in this cross-sectional study. The Modified Fatigue Impact Scale and the Symbol Digit Modality Test were used to evaluate fatigue symptoms and cognitive function, respectively. Participants walked six times during an uninterrupted 2-min period. Before, during the rest periods and after the last 2 min walk, the rate of perceived exertion (RPE) was measured using the Borg Scale, and the spatiotemporal gait parameters were assessed with GaitRite. The cut-off value of 10% deceleration of the distance walked index classified pwMS into two groups: MS Fatigable (MS-F) and MS Non-Fatigable (MS-NF). One-way and two-way Analyses of variance (ANOVAs) were used to verify the effect of time and groups, respectively. Results: PwMS walked slower, travelled shorter distances, and presented shorter step lengths compared to HCs. No effects of the intermittent-walking protocol were found for all pwMS, but the MS-F group had deteriorated walking speed, step length, and cadence. Walking dysfunction was associated with perceived fatigability, reported symptoms of fatigue, cognitive function, and disability. Reported symptoms of fatigue was associated with perceived exertion but not with performance fatigability. Conclusions: Changes in gait parameters were weak to moderately associated with performance fatigability and the perception of effort and disability but not with reported fatigue symptoms, highlighting distinct constructs. The walking speed reserve and step length reserve also emerged as potential early markers of performance decline. Full article

(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition)

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13 pages, 1651 KB

Open AccessArticle

A Healthcare Providers’ Survey for the Cognitive Rehabilitation of Multiple Sclerosis in France: From Research to Real Life

by Hélène Brissart, Héloïse Joly, Clémentine Castro and Bruno Lenne

Sclerosis 2025, 3(2), 14; https://doi.org/10.3390/sclerosis3020014 - 17 Apr 2025

Viewed by 1915

Abstract

Introduction: Cognitive impairment (CI) is recognized as a very frequent feature of persons with multiple sclerosis (pwMSs). Multiple studies have demonstrated the effectiveness of cognitive rehabilitation (CR) in improving CI linked to cerebral functional connectivity facilitation and increased strategies to cope with daily living activities. Nevertheless, there is considerable heterogeneity in the methodologies and protocols proposed to pwMSs. Aim: This study aimed to establish a current state of CR for pwMSs, among different types of healthcare providers (HCPs) in France. Methods: A Web-based survey was conducted between March and September 2024 among HCPs involved in the care of pwMSs. Results: One hundred and one HCPs involved in the care of pwMSs participated in this survey. CR was considered efficient by 97% of HCPs, especially when multimodal. Based on the responses, CR is proposed mainly following cognitive complaints, for moderate or severe cognitive disorders, and at the onset of the disease (45%). HCPs mentioned several obstacles to the implementation of CR, notably the cost of remediation (37%), and the lack of availability of both professionals (58%) and patients (51%). Conclusions: This rehabilitation requires specific tools combined with psychoeducative advice provided by multidisciplinary HCPs. Full article

(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition)

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15 pages, 1007 KB

Open AccessFeature PaperArticle

Health Locus of Control and Its Relationship with Quality of Life and Functioning in Multiple Sclerosis: Exploring the Mediating Role of Self-Efficacy

by Isaac Rothman, Alan Tennant, Roger Mills and Carolyn Young

Sclerosis 2025, 3(2), 10; https://doi.org/10.3390/sclerosis3020010 - 29 Mar 2025

Viewed by 2503

Abstract

Background/Objectives: Health locus of control (LOC) refers to one’s perceptions of who or what controls one’s health. Recent evidence has found that chance LOC (CLOC) is associated with improved quality of life (QoL) in multiple sclerosis (MS). The purpose of the current study was to identify mediators and moderators of the LOC-QoL relationship in MS. Methods: For this study, 5266 participants with MS completed a questionnaire pack that included the Multidimensional Health Locus of Control Scale, the Unidimensional Self-Efficacy Scale for MS (USE-MS), and the World Health Organization Quality of Life Scale—BREF (WHOQoL-BREF). The relationship between LOC and QoL was examined within a structural equation model (SEM). Results: In the total sample, self-efficacy was found to fully mediate the relationship between LOC and QoL for both internal (ILOC) and CLOC orientations. Powerful others LOC (PLOC) had no association with QoL. The same results were found for the relationship of LOC to functioning. In the secondary progressive MS subgroup, the relationship between CLOC and QoL was only partially mediated by self-efficacy. Conclusions: LOC influences QoL through its impact on self-efficacy, one of several potentially mediating factors between LOC and QoL in MS. Disability did not moderate the associations of LOC, but moderation of the CLOC-QoL relationship by disease subtype was found. Psychological training to improve self-efficacy in MS may be particularly useful in those subgroups where LOC-QoL is largely mediated by self-efficacy. Full article

(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition)

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15 pages, 1176 KB

Open AccessArticle

The Use of Augmented Reality on a Self-Paced Treadmill to Quantify Attention and Footfall Placement Variability in Middle-Aged to Older-Aged Adults with Multiple Sclerosis

by Manuel E. Hernandez, Roee Holtzer, Meltem Izzetoglu and Robert W. Motl

Sclerosis 2025, 3(1), 3; https://doi.org/10.3390/sclerosis3010003 - 17 Jan 2025

Cited by 2 | Viewed by 2492

Abstract

Background/Objectives: Footfall placement variability is associated with falls in older adults and neurological diseases. Thus, the study of dual-task gait impairment in middle-aged to older-aged adults with multiple sclerosis (MS) is clinically relevant, particularly in environments that mimic the obstacles experienced in daily ambulation. Methods: A total of 10 middle-aged to older-aged adults with MS (eight female, mean ± SD age = 56 ± 5 years), 12 healthy older adults (HOAs, nine female, age = 63 ± 4 years), and 10 healthy young adults (HYAs, five female, age = 22 ± 3) were asked to perform cued walking (CW) or obstacle walking (OW) tasks without or with a concurrent backward alphabet recitation task (CWT, OWT), or dual tasks. Gait performance and attentional demands were measured using hit rate, stride velocity, footfall placement bias and variance, and prefrontal cortex (PFC) oxygenated hemoglobin HbO levels. Results: A significant dual-task condition-by-cohort interaction was seen in footfall placement bias and variance as indicated by a higher footfall placement bias and variance in dual-task vs. single-task conditions seen in HOAs, in comparison to HYAs and adults with MS. Further, a significant walking condition-by-cohort interaction was seen in the HbO levels as indicated by the higher PFC HbO levels seen in OW vs. CW in adults with MS, compared to adults without MS. Conclusions: The decreased accuracy and increased attention in footfall placement to visual cues on the ground observed in adults with MS and HOAs, relative to HYAs, may provide a marker for gait impairment and fall risk in older adults with MS. Full article

(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition)

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9 pages, 753 KB

Open AccessOpinion

Behavioral Activation Therapy for Multiple Sclerosis: Potential Effects on Cognition, Neuropsychiatric Symptoms, and Quality of Life

by Daniela Taranu, Hayrettin Tumani, Visal Tumani and Patrick Fissler

Sclerosis 2025, 3(2), 12; https://doi.org/10.3390/sclerosis3020012 - 31 Mar 2025

Viewed by 1747

Abstract

Behavioral activation therapy (BAT) was initially developed to treat depression and was subsequently extended as a transdiagnostic therapy for other psychiatric and neurocognitive disorders. However, research on its impact in people with multiple sclerosis (MS) is lacking. We suggest that MS-adapted BAT reduces neuropsychiatric symptoms, neurocognitive impairment, social isolation, and impairment of activities of daily living—key components of MS-related quality of life. Our proposed adaptation of the traditional therapy includes a focus on increasing engagement in cognitive, physical, or social activities (activity demand characteristics) to improve cognition and daily life function. In addition, these activities should be individually perceived as energizing, relaxing, or meaningful (subjective activity characteristics) to benefit neuropsychiatric symptoms and social connectedness. Finally, we propose that BAT in MS should specifically focus on reducing stressful activities (i.e., unenjoyable, high-arousal activities) and increasing relaxing activities (i.e., enjoyable, low-arousal activities), as this dimension might tackle the neuroinflammatory etiology of MS. Full article

(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis, 2nd Edition)

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