Cognitive-motor Interference in Individuals With a Neurologic Disorder: A Systematic Review of Neural Correlates.

BACKGROUND: Performing a cognitive task and a motor task simultaneously is an everyday act that can lead to decreased performance on both tasks. OBJECTIVE: To provide insight into the neural correlates associated with cognitive-motor dual tasking in individuals with a neurologic disorder. METHOD: We searched the PubMed and Web of Science databases for studies that had been published up to January 16th, 2019. Studies investigating the neural correlates of cognitive-motor dual task performance in individuals with a variety of neurologic disorders were included, independently from whether the study included healthy controls. Clinical and imaging data were abstracted for the comparison between single tasks and a dual task in the individuals with a neurologic disorder and for the comparison between the healthy controls and the individuals with a neurologic disorder. RESULTS: Eighteen studies met the inclusion criteria. Study populations included individuals with Parkinson disease, multiple sclerosis, mild cognitive impairment, Alzheimer disease, traumatic brain injury, and stroke. Neuroimaging types used to study the neural correlates of cognitive-motor dual tasking during upper limb or gait tasks included fMRI, functional near-infrared spectroscopy, EEG, and PET. CONCLUSION: Despite large heterogeneity in study methodologies, some recurrent patterns were noted. Particularly, in neurologic patients, an already higher brain activation during single tasks was seen compared with healthy controls, perhaps compromising the patients' ability to further adapt brain activation with increasing load during dual tasking and resulting in reduced behavioral dual task performance.

Can we define a rehabilitation strategy for cognitive impairment in progressive multiple sclerosis? A critical appraisal.

Cognitive impairment (CI) has been shown to be severe in patients with progressive forms of multiple sclerosis (MS), and the most frequently impaired domains are sustained attention, information processing speed, memory, and executive functions. In contrast to relapsing forms of MS, where studies have shown favorable results from cognitive rehabilitation, there is a lack of data on cognitive rehabilitation in progressive forms of MS. A specific approach in assessing CI and in designing and administering rehabilitation training for patients with progressive forms of MS is needed.

Offspring Number Does Not Influence Reaching the Disability's Milestones in Multiple Sclerosis: A Seven-Year Follow-Up Study.

OBJECTIVES: Data on pregnancy long-term effects on multiple sclerosis (MS) course are still controversial; whether experiencing more than one pregnancy exposes one to risk of the disability's accrual is still unknown. We investigated differences existing in terms of disability progression among women with MS (wwMS) who had one or more children after their MS onset. METHODS: Monoparous and multiparous wwMS were enrolled from the Catania MS Center, Italy, in a monocenter retrospective study. A Cox proportional hazards model was used to examine the effect of the number of parities on time from MS disease onset to EDSS 4.0 and 6.0. The study protocol was approved by the local Ethical Committee. RESULTS: During the seven years of observation, 32.1% and 23.2% of the monoparous group reached expanded disability disease status (EDSS) 4.0 and 6.0 respectively, compared to 13.3% and 3.3% of the multiparous group (p = 0.057 and p = 0.017; respectively). The Kaplan-Meier curve analysis showed no statistically-significant differences between the two groups in reaching the two milestones. The multiparous group showed a longer time to reach the EDSS 4.0 (3.5 vs. 2.6 years, log-rank 0.57, p = 0.45). The Cox regression analysis showed that the EDSS at the time of first pregnancy (Exp(B) 9.4, CI 4.5-19.7, p< 0.001) and the time from MS onset to first pregnancy (Exp(B) 0.96, CI = 0.93-0.98, p < 0.05) were significant predictors of reaching the EDSS 4.0, whereas a model including only the EDSS one year after the first pregnancy significantly predicted (Exp(B) value of 6.4, CI 2.6-15.4, p < 0.001) the reaching of EDSS 6.0. CONCLUSIONS: Our results suggest that experiencing more than one pregnancy could not convey a different clinical outcome in wwMS. Further research is needed to confirm our results.

Measuring the cost of cognitive-motor dual tasking during walking in multiple sclerosis.

Purposeful, safe locomotion requires higher-level cortical processes, to meet the real-life demands of walking while performing concurrent cognitive tasks (e.g. recalling a shopping list or attending to a conversation). The assessment of walking and a secondary cognitive task under these 'dual tasking' conditions may represent a more valid outcome measure in multiple sclerosis (MS), by examining the occurrence and magnitude of the cognitive-motor interference of walking. This topical review provides a state-of-the-art overview of research into dual-tasking during walking in persons with MS, based on 14 recent papers. Studies consistently demonstrate a slowing of ambulation under dual tasking, regardless of the cognitive task demand, the stage of the disease and the disability level. The reciprocal effect of walking on the cognitive tasks was rarely assessed. We present our main findings, highlight the different factors contributing to dual-task deficits, identify methodological shortcomings and offer recommendations for constructing dual-tasking paradigms useful in clinical practice and research.

Clinical and radiologic rebound after discontinuation of natalizumab therapy in a highly active multiple sclerosis patient was not halted by dimethyl-fumarate: a case report.

BACKGROUND: The evidence on the use of the oral dimethyl-fumarate after the discontinuation of treatment with natalizumab in people with Multiple Sclerosis is still little. Natalizumab discontinuation may induce the recurrence or rebound of the clinical and neuroradiological disease activity. Currently no therapeutic approach has been established to abolish disease reactivation and rebound after natalizumab interruption. CASE PRESENTATION: We describe a case of a 21-year-old woman affected from a highly active relapsing-remitting Multiple Sclerosis who developed a clinical and radiological rebound 5 months after the last infusion of natalizumab, while she was being treated with dimethyl-fumarate 240 mg twice daily. She had received a bridge "therapy" with Cyclophosphamide before staring dimethyl-fumarate. CONCLUSION: We report on this case to stimulate further research to establish whether new current and future drugs available for multiple sclerosis are able to halt the disease rebound after the natalizumab interruption.

Understanding the role of agency in the navigation of regional dementia care and support service pathways.

INTRODUCTION: Reliable dementia care and support service pathways are essential for timely diagnoses and for reducing the delay in time from diagnosis to care and support. However, carers commonly experience difficulties in finding information about where to go and what to do before and following a dementia diagnosis. In rural and regional areas, accessing dementia care and support services can be especially challenging. This qualitative, narrative inquiry study explores the agency of carers, and people living with dementia, in their navigation of regional dementia care and support service pathways. METHODS: Semi-structured interviews were conducted with ten carers of people living with dementia from a regional location in Victoria, Australia. Data analysis was guided by the tripartite framework of Giddens' Theory of Structuration which considered the carers' intentionality, capacity and power to act in the navigation of their dementia care and support service pathways. FINDINGS: Carers had intentionality; however, they did not always have the capacity and power to act. Information played a critical role in facilitating agency. Health literacy was important - as knowledge about where to look for/find information, and knowledge gained through experience, education or learning from others. Where carers encountered barriers, they lacked capacity and power. This occurred where there was an absence of information or knowledge, incorrect information (e.g. misdiagnoses), and where government bodies impeded carers' efforts. CONCLUSIONS: Information and knowledge are critical to the progression of dementia care and support service pathways. Health literacy is a significant resource, and carers would benefit from dementia education/training. The agency of carers in navigating their dementia care and support service pathways relies on carers themselves finding information and seeking out knowledge and education. However, GPs, local health providers, and dementia organisations have an important role to play in helping carers to find information towards accessing dementia care and support services.

Cognitive impairment and "invisible symptoms" are not associated with CCSVI in MS.

BACKGROUND: We investigated the association between chronic cerebrospinal venous insufficiency (CCSVI) and cognitive impairment (CI) in multiple sclerosis (MS). Moreover, we evaluated the association between CCSVI and other frequent self-reported MS symptoms. METHODS: We looked at the presence of CI in incident MS patients with CCVSI in a population-based cohort of Catania, Italy. All subjects were group-matched by age, sex, disease duration and EDSS score with MS patients without CCSVI, serving as controls. CI was assessed with the Brief Repeatable Battery (BRB) and the Stroop Test (ST) and it was defined by the presence of at least three impaired tests. Fatigue and depressive symptoms were assessed with Fatigue Severity Scale (FSS) and Hamilton Depressive Rating Scale (HDRS), respectively. Bladder and sexual symptoms were assessed with the respective items of the Italian version of Guy's Neurological Disability Scale (GNDS). Quality of life was evaluated with Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54). RESULTS: Out of 61 MS patients enrolled in the study, 27 were CCSVI positive and 34 were CCSVI negative. Of them, 43 were women (70.5%); the mean age was 43.9 ± 11.8 years; the mean disease duration was 159.7 ± 113.7 months; mean EDSS was 3.0 ± 2.6. Of them, 36 (59.0%) were classified relapsing-remitting (RR), 12 (19.7%) secondary progressive (SP), seven (11.5%) primary progressive (PP) and six (9.3%) Clinically Isolated Syndrome (CIS). Overall, CI was detected in 29/61 (47.5%) MS patients; particularly 13/27 (48.1%) in the CCSVI positive group and 16/34 (47.0%) in the CCSVI negative group. Presence of CCSVI was not significantly associated with the presence of CI (OR 1.04; 95% CI 0.37-2.87; p-value = 0.9). Not significant differences were found between the two groups regarding the other MS symptoms investigated. CONCLUSIONS: Our findings suggest a lack of association between CCSVI and CI in MS patients. Fatigue, depressive, bladder/sexual symptoms and self-reported quality of life are not associated with CCSVI.

Media discourses on the socio-spatial rights of older people living with dementia and their carers.

INTRODUCTION: Media discourses about people living with dementia and carers contribute to the ways in which public, social spaces are designed, planned, and used. Negative media discourses play an important role in the socio-spatial exclusion of people living with dementia and stigmatising and dehumanising language prevents the achievement of genuine, rights-based dementia-friendly environments. Because the media plays a powerful role in shaping public attitudes, there is a need to understand media constructions of people living with dementia and carers in relation to their socio-spatial rights, which is the aim of this paper. METHOD: A Foucauldian-inspired discourse analysis (FDA) was conducted on the public news media texts of one regional Australian city, to identify discourses relating to the socio-spatial rights of people living with dementia and carers. Lefebvre's (1996) 'right to the city' concept was used as a conceptual framework, to define socio-spatial rights. RESULTS: Analysis revealed discourses relating to the right to urban citizenship, the right to difference and socio-spatial justice. Representations of participatory democracy, important to urban citizenship, are absent, as are the voices of people living with dementia. Through advocacy from others and a lens of citizenship, socio-spatial rights for people living with dementia, and in one instance carers, are recognised, in the context of dementia-awareness and dementia-friendly initiatives. While a lens of personhood constructs people living with dementia as historical and relational beings, a citizenship lens adds a spatial dimension. CONCLUSIONS: Advocacy and the lenses of personhood and citizenship are important in creating positive constructions of people living with dementia, however, their participation in decision-making processes would confer an active citizenship status, and the inclusion of their authentic voices in media discourse would contribute to raising awareness towards rights-based dementia-friendly communities.

Asynchronous combined central and peripheral demyelination (CCPD) in a girl with anti-MOG positivity: A case report and review of the literature.

The occurrence of combined central and peripheral demyelination (CCPD) is rare, data are limited to small case and cohort studies, mainly concerning adults. In few patients positivity to anti MOG antibody is reported, thus widening the spectrum of anti-MOG associated disorders (MOGAD). We describe a 7-year-old girl with optic neuritis followed 8 years later by peripheral demyelination, with fluctuating anti-MOG antibody positivity at cell-based assay. From the review of the literature, MOGAD-CCPD appear very rare in childhood, especially with asynchronous course. Clinicians should keep this possibility in mind to better define diagnosis in atypical demyelination syndromes, with therapeutical implications.

Treatment options of cognitive impairment in multiple sclerosis.

Multiple sclerosis (MS) is a progressive disease of the CNS, characterized by the production of widespread lesions in the brain and spinal cord. Inflammatory demyelination has traditionally been seen as the main disease process in MS; however, axonal damage or loss is increasingly being documented to occur early in the disease. Cognitive deficits can occur independently of physical disability, which complicates their identification and recognition. More recently, cortical demyelination has been identified among possible causes of cognitive impairment in MS. Neuropsychological studies have consistently demonstrated that 40-65% of patients with MS experience cognitive dysfunction, particularly in recent memory, information processing speed, and sustained attention. Early detection of cognitive impairment is essential to enable therapeutic intervention to alleviate symptoms or prevent further cognitive decline, although how best to manage MS-related cognitive impairment is currently unclear. Treatment strategies for cognitive impairment in MS are still in their infancy. This article will summarize several pharmacological attempts to enhance cognitive performances in people with MS.

Comparing 16 Different Dual-Tasking Paradigms in Individuals With Multiple Sclerosis and Healthy Controls: Working Memory Tasks Indicate Cognitive-Motor Interference.

Background: Cognitive-motor interference (CMI) is measured by dual-tasking (DT), which involves motor and cognitive tasks. There is no consensus as to whether CMI is present in multiple sclerosis (MS). Objectives: We investigated the effects of 16 DT conditions by measuring motor complexity, cognitive domain, and task difficulty. Method: In total, 40 persons with MS (pwMSs) with Expanded Disease Status Scale (EDSS) 3.2 ± 1.7 and 31 age- and sex-matched healthy controls (HCs) completed 2 single walking, 8 single cognitive, and 2 complex walking tasks and 16 cognitive-motor DT. The main outcomes were mean values of gait velocity and the percentage change from single to DT (motor DT costs, mDTCs) and mean values of cognitive task accuracy and the percentage changes (cognitive DTC, cDTC). Results: Two-way analyses of variance showed the main effect of cognitive task yielded an F ratio of F (4, 268) = 72.35, p < 0.01, for mean gait velocity, and an F ratio of F (4, 304) = 17.12, p < 0.001, for mDTC, indicating that the mean velocity was significantly lower and the mDTC significantly higher for DS_B (mean = 1.27, SD = 0.03, and mean = 13.52, SD = 1.28, respectively). The main effect of cognitive task yielded an F ratio of F (4, 116) = 84.32, p < 0.001, with the lowest average accuracy for DS_B (mean = 43.95, SD = 3.33); no effect was found for cDTC. In pwMSs, the EDSS accounted for 28% (F = 13.65, p = 0.001) of variance in a model predicting the highest mDTC. Conclusions: Overall, among different cognitive tasks added, the Digit Span backward was the most interfering cognitive task over gait velocity and accuracy. The effect was similar independently from the motor complexity and the group. PwMSs and HCs behaved in a similar manner at all motor complexity levels and during all cognitive task.

Test-Retest Reliability of Cognitive-Motor Interference Assessments in Walking With Various Task Complexities in Persons With Multiple Sclerosis.

Background. Simultaneous execution of motor and cognitive tasks can result in worsened performance on one or both tasks, indicating cognitive-motor interference (CMI). A growing amount of research on CMI in persons with multiple sclerosis (pwMS) is observed. However, psychometric properties of dual-task outcomes have been scarcely reported. Objective. To investigate the between-day test-retest reliability of the motor and cognitive dual-task costs (DTCs) during multiple CMI test conditions with various task complexities in pwMS and matched healthy controls (HCs). Methods. A total of 34 pwMS (Expanded Disability Status Scale score 3.0 ± 0.8) and 31 HCs were tested and retested on 3 single cognitive, 4 single motor, and 12 cognitive-motor dual tasks. Cognitive tasks included serial subtraction by 7, titrated digit span backward, and auditory vigilance. Motor tasks were walking at self-selected speed, over obstacles, crisscross, and while carrying a water-filled cup. Outcome measures were cognitive and motor DTC, calculated as percentage change of dual-task performance compared with single-task performance. Intraclass correlations (ICCs) and Spearman correlation coefficients were calculated as appropriate. Results. For DTCmotor of gait speed, ICCs ranged from 0.45 to 0.81 and Spearman correlations from 0.74 to 0.82. For DTCcognitive, ICCs ranged from -0.18 to 0.49 and Spearman correlations from -0.28 to 0.26. Reliability depended on the type of motor and cognitive task. Conclusion. Reliability of the DTCmotor was, overall, good, whereas that of the DTCcognitive was poor. The "walking" and "cup" dual-task conditions were the most reliable regardless of the integrated cognitive task.

Effects of Rehabilitation on Gait Pattern at Usual and Fast Speeds Depend on Walking Impairment Level in Multiple Sclerosis.

BACKGROUND: Physical rehabilitation can improve walking capacity in persons with multiple sclerosis (MS). However, changes in spatiotemporal gait parameters after rehabilitation are not frequently evaluated, and it is unknown to what extent potential effects depend on baseline disability level. The objective was to investigate the effectiveness of rehabilitation programs on gait parameters at usual and fastest speeds in persons with MS categorized according to walking speed. METHODS: This nonrandomized multinational study in "real-world" settings evaluated participants before and after conventional rehabilitation. Outcome measurements included spatiotemporal gait parameters assessed by an electronic walkway (at usual and fastest speeds), walking capacity tests (Timed 25-Foot Walk test, 2-Minute Walk Test, 6-Minute Walk Test), and the patient-reported 12-item Multiple Sclerosis Walking Scale. Patients were allocated into three subgroups based on walking speed (<0.82 m/s and >1.14 m/s) and MS center. Results were calculated for the total group and subgroups. RESULTS: Forty-two persons with MS (26 women; mean ± SD age, 44.6 ± 11.0 years; mean ± SD Expanded Disability Status Scale score, 3.5 ± 1.5) receiving rehabilitation treatment were enrolled. After rehabilitation treatment, the group demonstrated a significant decrease in double support time and an increase in stride length and step length (left leg) at usual and fastest speeds. Velocity and step length (right leg) increased only at usual speed. Subgroup analysis revealed greatest and clinically meaningful improvements in more disabled persons with MS. CONCLUSIONS: Physical rehabilitation induced changes in spatiotemporal gait parameters in persons with MS. The magnitude of improvement was greater in participants with more walking impairment.

Effectiveness of music-based interventions on motricity or cognitive functioning in neurological populations: a systematic review.

BACKGROUND: Motor and cognitive symptoms are frequent in persons with neurological disorders and often require extensive long-term rehabilitation. Recently, a variety of music-based interventions have been introduced into neurological rehabilitation as training tools. EVIDENCE ACQUISITION: This review aims to 1) describe and define music-based intervention modalities and content which are applied in experimental studies; and 2) describe the effects of these interventions on motor and/or cognitive symptoms in the neurological population. The databases PubMed and Web of Science were searched. Cited references of included articles where screened for potential inclusion. A systematic literature search up to 20th of June 2016 was conducted to include controlled trials and cohort studies that have used music-based interventions for ≥3 weeks in the neurological population (in- and outpatients) targeting motor and/or cognitive symptoms. No limitations to publication date was set. EVIDENCE SYNTHESISː Nineteen articles comprising thirteen randomized controlled trials (total participants Nexp=241, Nctrl=269), four controlled trials (Nexp=59, Nctrl=53) and two cohort studies (N.=27) were included. Fourteen studies were conducted in stroke, three in Parkinson's disease, and two in multiple sclerosis population. Modalities of music-based interventions were clustered into four groups: instrument-based, listening-based, rhythm-based, and multicomponent-based music interventions. Overall, studies consistently showed that music-based interventions had similar or larger effects than conventional rehabilitation on upper limb function (N.=16; fine motricity, hand and arm capacity, finger and hand tapping velocity/variability), mobility (N.=7; gait parameters), and cognition (N.=4; verbal memory and focused attention). CONCLUSIONSː Variety of modalities using music-based interventions has been identified and grouped into four clusters. Effects of interventions demonstrate an improvement in the domains assessed. Evidence is most available for improving motricity in stroke. More studies are warranted to investigate cognition as well as motor and cognition dysfunctions in combination. Instrument-based music interventions can improve fine motor dexterity and gross motor functions in stroke. Rhythm-based music interventions can improve gait parameters of velocity and cadence in stroke, Parkinson's disease and multiple sclerosis. Cognition in the domains of verbal memory and focused attention can improve after listening-based music interventions in stroke.

Cognitive-motor dual-task interference: A systematic review of neural correlates.

Cognitive-motor interference refers to dual-tasking (DT) interference (DTi) occurring when the simultaneous performance of a cognitive and a motor task leads to a percentage change in one or both tasks. Several theories exist to explain DTi in humans: the capacity-sharing, the bottleneck and the cross-talk theories. Numerous studies investigating whether a specific brain locus is associated with cognitive-motor DTi have been conducted, but not systematically reviewed. We aimed to review the evidences on brain activity associated with the cognitive-motor DT, in order to better understand the neurological basis of the CMi. Results were reported according to the technique used to assess brain activity. Twenty-three articles met the inclusion criteria. Out of them, nine studies used functional magnetic resonance imaging to show an additive, under-additive, over- additive, or a mixed activation pattern of the brain. Seven studies used near-infrared spectroscopy, and seven neurophysiological instruments. Yet a specific DT locus in the brain cannot be concluded from the overall current literature. Future studies are warranted to overcome the shortcomings identified.

Disability may influence patient willingness to participate in decision making on first-line therapy in multiple sclerosis.

Patient autonomy is a concept that implies variable degrees of patient participation in different aspects of health and healthcare, including the choice of therapy. This study, conducted in patients with multiple sclerosis (MS), examined several factors in relation to the patient's role in the therapeutic decision-making process. One hundred newly diagnosed patients with MS attending their first ever specialist consultation at the MS center of Catania, Italy, were consecutively enrolled in a single-center, open, observational study. Clinical and demographic data were collected as part of this routine first consultation. Through administration of the Control Preferences Scale, we ascertained the patients' willingness to participate in the decision-making process on their first-line treatment, classifying them, on the basis of their attitude, as passive, collaborative or active. Of 100 patients with MS, 40 had a passive attitude, while 35 were willing to collaborate and 25 wanted to play an active role in the decision-making process. The patients showing an active attitude had a significantly higher Expanded Disability Status Scale score and a significantly higher number of relapses (p<0.5 for both) than those who showed other attitudes. Persons with MS prefer to know the benefits and risks related to the first-line treatment. Those with higher disability prefer to be active in the decision-making process.

Lateral and escalation therapy in relapsing-remitting multiple sclerosis: a comparative study.

Performing a therapeutic switch in MS is still a matter of debate. Objective of our study is to compare switching to another first-line therapy with switching to a second-line therapy in persons with relapsing-remitting multiple sclerosis (pwRRMS). A retrospective analysis of data prospectively collected was performed. PwRRMS experiencing on-treatment disease activity were included. No clinical relapse, no sustained disability progression by the Expanded Disability Status Scale (EDSS), and no radiological activity (new T2 and/or gadolinium-enhanced brain lesions) were used as indicators of no disease activity (NEDA 3). Time to reach the first relapse after switch and time to reach an EDSS of 4.0 were also evaluated. Ninety-one pwRRMS were enrolled. Forty-eight (52.7 %) were on lateral switch, and 43 (47.3 %) on escalation switch. At baseline, the two groups differed for T2 and T1 brain lesions number (higher in the escalation group, p < 0.005). The proportion of pwRRMS who were NEDA 3 after 24 months from the switch was similar in the two groups (20.8 % in lateral group and 18.6 % in escalation group). No difference in timing to reach the first relapse after switch and an EDSS of 4.0 were found. Therefore, in selected pwRRMS, lateral and escalation strategies showed similar efficacy in delaying MS progression.

Treatment-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: A Comprehensive Review of Current Evidence and Future Needs.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV) that has been associated with therapeutic immunosuppression in patients with multiple sclerosis (MS). So far, more than 600 cases of PML have been reported in association with natalizumab administration. There have also been confirmed cases of PML in individuals who received fingolimod and dimethyl fumarate without previous natalizumab treatment. The new licensed disease-modifying therapies for MS carry the risk of immunosuppressant and so of JCV reactivation. Various factors have been identified with increased risk of developing PML, including a positive JCV serology, natalizumab administration for >2 years, and prior use of immunosuppressive agents. Clinicians can employ such tools for patients' risk stratification, but the incidence of PML among patients receiving natalizumab therapy has not changed. In this review we outline the current state of understanding of PML pathogenesis and patients' risk stratification. The landscape of MS is dramatically changing and knowledge of the side effects of the licensed therapies is imperative to enable optimal decision making.

Prevalence of Walking-Related Motor Fatigue in Persons With Multiple Sclerosis: Decline in Walking Distance Induced by the 6-Minute Walk Test.

OBJECTIVE: To investigate the individual occurrence of walking-related motor fatigue in persons with multiple sclerosis (PwMS), according to disability level and disease phenotype.Study design This was a cross-sectional, multinational study.Participants They were 208 PwMS from 11 centers with Expanded Disability Status Scale (EDSS) scores up to 6.5. METHODS: The percentage change in distance walked (distance walked index, DWI) was calculated between minute 6 and 1 (DWI(6-1)) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify participants into 4 subgroups: (1) DWI(6-1)[≥5%], (2) DWI(6-1)[5%; -5%], (3) DWI(6-1)[-5%; > -15%], and (4) DWI(6-1)[≤-15%]. The latter group was labeled as having walking-related motor fatigue. PwMS were stratified into 5 subgroups based on the EDSS (0-2.5, 3-4, 4.5-5.5, 6, 6.5) and 3 subgroups based on MS phenotype (relapsing remitting [RR], primary progressive [PP], and secondary progressive [SP]). RESULTS: The DWI6-1was ≥5% in 16 PwMS (7.7%), between 5% and -5% in 70 PwMS (33.6%), between -5% and -15% in 58 PwMS (24%), and ≤-15% in 64 PwMS (30.8%). The prevalence of walking-related motor fatigue (DWI(6-1)[≤-15%]) was significantly higher among the progressive phenotype (PP = 50% and SP = 39%; RR = 15.6%) and PwMS with higher disability level (EDSS 4.5-5.5 = 48.3%, 6 = 46.3% and 6.5 = 51.5%, compared with EDSS 0-2.5 = 7.8% and 3-4 = 16.7%;P< .05). Stepwise multiple regression analysis indicated that EDSS, but not MS phenotype, explained a significant part of the variance in DWI(6-1)(R(2)= 0.086;P< .001). CONCLUSION: More than one-third of PwMS showed walking-related motor fatigue during the 6MWT, with its prevalence greatest in more disabled persons (up to 51%) and in those with progressive MS phenotype (up to 50%). Identification of walking-related motor fatigue may lead to better-tailored interventions.