Disrupted hemodynamic response within dorsolateral prefrontal cortex during cognitive tasks among people with multiple sclerosis-related fatigue.

INTRODUCTION: Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls. METHODS: We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score). RESULTS: In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks. CONCLUSIONS: Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.

[Optical coherence tomography angiography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike rasseyannogo skleroza.

PURPOSE: This study analyzes the main changes in retinal microcirculation in patients with multiple sclerosis (MS) and their relationship with the type of disease course. MATERIAL AND METHODS: 159 patients (318 eyes) were examined. The groups were formed according to the type of course and duration of MS: group 1 - 37 patients (74 eyes; 23.27%) with relapsing-remitting MS (RRMS) less than 1 year; group 2 - 47 patients (94 eyes; 29.56%) with RRMS from 1 year to 10 years; group 3 - 44 patients (86 eyes; 27.05%) with RRMS >10 years; group 4 - 32 patients (64 eyes; 20.12%) with secondary progressive MS (SPMS). Subgroups A and B were allocated within each group depending on the absence or presence of optic neuritis (ON). Patients underwent standard ophthalmological examination, including optical coherence tomography angiography (OCTA). RESULTS: A decrease in the vessel density (wiVD) and perfusion density (wiPD) in the macular and peripapillary regions was revealed, progressing with the duration of the disease and with its transition to the progressive type. The minimum values were observed in patients with SPMS (group 4), with the most pronounced in the subgroup with ON (wiVD = 16.06±3.65 mm/mm2, wiPD = 39.38±9.46%, ppwiPD = 44.06±3.09%, ppwiF = 0.41±0.05). CONCLUSION: OCTA provides the ability to detect subclinical vascular changes and can be considered a comprehensive, reliable method for early diagnosis and monitoring of MS progression.

Effects of multidisciplinary inpatient rehabilitation on everyday life physical activity and gait in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a progressive neurological disease that affects the central nervous system, resulting in various symptoms. Among these, impaired mobility and fatigue stand out as the most prevalent. The progressive worsening of symptoms adversely alters quality of life, social interactions and participation in activities of daily living. The main objective of this study is to bring new insights into the impact of a multidisciplinary inpatient rehabilitation on supervised walking tests, physical activity (PA) behavior and everyday gait patterns. METHODS: A total of 52 patients, diagnosed with multiple sclerosis, were evaluated before and after 3 weeks of inpatient rehabilitation. Each measurement period consisted of clinical assessments and 7 days home monitoring using foot-mounted sensors. In addition, we considered two subgroups based on the Expanded Disability Status Scale (EDSS) scores: 'mild' (EDSS < 5) and 'severe' (EDSS ≥ 5) disability levels. RESULTS: Significant improvements in fatigue, quality of life and perceived mobility were reported. In addition, walking capacity, as assessed by the 10-m walking test, two-minute walk test and timed-up-and-go test, improved significantly after rehabilitation. Regarding the home assessment, mildly disabled patients significantly increased their locomotion per day and complexity of daily PA pattern after rehabilitation, while severely disabled patients did not significantly change. There were distinct and significant differences in gait metrics (i.e., gait speed, stride length, cadence) between mildly and severely disabled patients, but the statistical models did not show a significant overall rehabilitation effect on these gait metrics. CONCLUSION: Inpatient rehabilitation showed beneficial effects on self-reported mobility, self-rated health questionnaires, and walking capacity in both mildly and severely disabled patients. However, these improvements do not necessarily translate to home performance in severely disabled patients, or only marginally in mildly disabled patients. Motivational and behavioral factors should also be considered and incorporated into treatment strategies.

The relationship between trunk control, spinal posture, and spinal mobility in patients with multiple sclerosis: a cross-sectional study.

Background/aim: Trunk control, which plays a key role in balance and mobility, decreases in patients with multiple sclerosis (PwMS) and many parameters such as sensory, motor, and musculoskeletal systems affect trunk control. The aim of this study was to compare trunk control, spinal mobility, and spinal posture in PwMS with healthy controls and investigate the relationship between trunk control with spinal posture and spinal mobility in PwMS. Materials and methods: The study was completed with 38 PwMS and 38 healthy controls with matched age and sex. Trunk control was evaluated with the Trunk Impairment Scale (TIS). Spinal posture and mobility were evaluated in sagittal and frontal planes using an IDIAG M360 Spinal Mouse. Spinal posture was evaluated in upright, maximum flexion, extension, left and right lateral flexion positions, and spinal mobility was evaluated from upright to flexion, extension, right and left flexion positions in sagittal and frontal planes. Results: TIS scores, thoracic mobility angles (from upright to flexion and left lateral flexion), lumbar mobility angles (from upright to extension and right lateral flexion) and lumbar posture angle (maximum right lateral flexion) were lower, and thoracic posture angles (upright and maximum extension) were higher in PwMS than healthy controls (p < 0.05). No significant difference was found between other spinal postures and mobility values. In addition, there was only a negative relationship between thoracic spinal mobility from upright to extension and trunk control in PwMS (r = -0.349; p = 0.032). Conclusion: These findings indicate the importance of early detection of trunk disturbances in PwMS. Thus, even in the early stages of multiple sclerosis, detailed trunk assessment will guide the implementation of comprehensive exercise programs.

Rehabilitation therapy versus drug-only therapy in patients with multiple sclerosis.

Background/aim: The treatment for multiple sclerosis (MS) does not cure the disease, but it is intended to reduce the intensity, duration, and frequency of symptoms. Rehabilitation therapy (RT), including an individualized physical therapy program (PTP) and adapted occupational therapy (OT), has benefits in terms of aerobic capacity, muscle strength, coordination, and ability to perform activities of daily living (ADL). The primary objective of this study was to examine the efficacy of RT comprising PTP, OT, and drug treatment (DT) versus DT alone in patients with MS. Another objective was to highlight the importance of continuing the PT and OT at home, in the long term, practically for their entire life. Materials and methods: Between 2020 and 2022, a follow-up observational study was conducted that included 77 patients diagnosed with MS, independent in terms of ability to perform ADL, divided into two groups: group A (39 patients who complied with the RT) and group B (38 patients who did not comply). At the beginning and end of the study, the following parameters were assessed: timed walk for 25 feet [Timed 25-Foot Walk test (T25FW test)], dexterity of the upper limbs [9-Hole Peg Test (9HPT)], and cognitive function [Paced Auditory Serial Addition Test (PASAT)]. Results: Significant improvement in the experimental group was observed regarding the mobility and the performance of leg function (T25FW, p < 0.05) and finger dexterity (9HPT, p < 0.05) for the dominant hand. Conclusion: The current study proves the importance of combining DT with RT in MS therapy with clear benefits in regaining muscle strength in the lower limbs, thus improving coordination and balance while walking and improving dexterity in the dominant hand.

Improving explanation of motor disability with diffusion-based graph metrics at onset of the first demyelinating event.

BACKGROUND: Conventional magnetic resonance imaging (MRI) does not account for all disability in multiple sclerosis. OBJECTIVE: The objective was to assess the ability of graph metrics from diffusion-based structural connectomes to explain motor function beyond conventional MRI in early demyelinating clinically isolated syndrome (CIS). METHODS: A total of 73 people with CIS underwent conventional MRI, diffusion-weighted imaging and clinical assessment within 3 months from onset. A total of 28 healthy controls underwent MRI. Structural connectomes were produced. Differences between patients and controls were explored; clinical associations were assessed in patients. Linear regression models were compared to establish relevance of graph metrics over conventional MRI. RESULTS: Local efficiency (p = 0.045), clustering (p = 0.034) and transitivity (p = 0.036) were reduced in patients. Higher assortativity was associated with higher Expanded Disability Status Scale (EDSS) (ß = 74.9, p = 0.026) scores. Faster timed 25-foot walk (T25FW) was associated with higher assortativity (ß = 5.39, p = 0.026), local efficiency (ß = 27.1, p = 0.041) and clustering (ß = 36.1, p = 0.032) and lower small-worldness (ß = -3.27, p = 0.015). Adding graph metrics to conventional MRI improved EDSS (p = 0.045, ΔR2 = 4) and T25FW (p < 0.001, ΔR2 = 13.6) prediction. CONCLUSION: Graph metrics are relevant early in demyelination. They show differences between patients and controls and have relationships with clinical outcomes. Segregation (local efficiency, clustering, transitivity) was particularly relevant. Combining graph metrics with conventional MRI better explained disability.

Renal disease associated with multiple sclerosis: A narrative review.

Multiple sclerosis (MS) is a chronic autoimmune neurological disorder characterized by central nervous system demyelination, leading to various neurological impairments. While the primary focus of research and clinical management has centered on the neurological aspects of MS, emerging evidence suggests a complex interplay between MS and renal disease. This narrative review endeavors to elucidate the intriguing association between MS and renal disease, providing a comprehensive overview of the current knowledge on this topic. Our review begins by outlining the pathophysiology of MS and the diverse mechanisms contributing to its progression. We then delve into renal disease, categorizing the various types and their clinical presentations. This review focuses on exploring the intricate relationship between these seemingly distinct conditions. We analyze existing literature to uncover shared risk factors, potential pathophysiological links, and the impact of MS on renal function. Furthermore, we discuss the clinical presentation and diagnostic challenges in identifying renal disease in MS patients. Importantly, we examine available treatment options and their efficacy in managing renal complications in this unique patient population. The consequences of renal disease on the overall quality of life (QOL) for individuals living with MS are also examined, shedding light on the multifaceted burden of these coexisting conditions.

Meaningful cognitive change for the Minimal Assessment of Cognitive Function in Multiple Sclerosis.

BACKGROUND: There is limited information on interpretation of cognitive changes over time in multiple sclerosis (MS). OBJECTIVE: This study aimed to provide normative data for the assessment of statistically meaningful change in all tests of the Minimal Assessment of Cognitive Function in MS (MACFIMS). METHODS: We applied the reliable change methodology to a healthy Italian cohort, assessed with two alternate versions of the MACFIMS 1 year apart. We calculated confidence intervals of retest score variance using the reliable change index (RCI). Moreover, multivariable linear regression models adjusted for age, sex, education, and baseline score were built to calculate the regression-based change index (RB-CI). RESULTS: Overall, 200 healthy individuals were enrolled. Thresholds for interpreting change in each test were calculated. In the multivariable models, baseline score was associated with retest score in all tests (B from 0.439 to 0.760; p < 0.001). RB-CI can be calculated with data of the multivariable models. CONCLUSION: We provide normative data for reliable cognitive change evaluation for all the tests of the MACFIMS, which includes the Symbol Digit Modalities Test and Brief International Cognitive Assessment in MS, two widely used tools for screening and monitoring cognition in MS. Our findings can significantly improve the interpretation of cognitive changes in MS.

Functional gradients reveal cortical hierarchy changes in multiple sclerosis.

Functional gradient (FG) analysis represents an increasingly popular methodological perspective for investigating brain hierarchical organization but whether and how network hierarchy changes concomitant with functional connectivity alterations in multiple sclerosis (MS) has remained elusive. Here, we analyzed FG components to uncover possible alterations in cortical hierarchy using resting-state functional MRI (rs-fMRI) data acquired in 122 MS patients and 97 healthy control (HC) subjects. Cortical hierarchy was assessed by deriving regional FG scores from rs-fMRI connectivity matrices using a functional parcellation of the cerebral cortex. The FG analysis identified a primary (visual-to-sensorimotor) and a secondary (sensory-to-transmodal) component. Results showed a significant alteration in cortical hierarchy as indexed by regional changes in FG scores in MS patients within the sensorimotor network and a compression (i.e., a reduced standard deviation across all cortical parcels) of the sensory-transmodal gradient axis, suggesting disrupted segregation between sensory and cognitive processing. Moreover, FG scores within limbic and default mode networks were significantly correlated ( ρ = 0.30 $$ \rho =0.30 $$ , p < .005 after Bonferroni correction for both) with the symbol digit modality test (SDMT) score, a measure of information processing speed commonly used in MS neuropsychological assessments. Finally, leveraging supervised machine learning, we tested the predictive value of network-level FG features, highlighting the prominent role of the FG scores within the default mode network in the accurate prediction of SDMT scores in MS patients (average mean absolute error of 1.22 ± 0.07 points on a hold-out set of 24 patients). Our work provides a comprehensive evaluation of FG alterations in MS, shedding light on the hierarchical organization of the MS brain and suggesting that FG connectivity analysis can be regarded as a valuable approach in rs-fMRI studies across different MS populations.

Right Brain: The Unraveling.

"The Unraveling" is a personal reflection from my perspective as a new fellow in Multiple Sclerosis/Neuroimmunology on the impact of multiple sclerosis on patients and their loved ones. I compare my more recent patient encounters with past experiences working with a different, also mostly female, patient population that included those affected by intimate partner violence. Female vulnerability and the spectrum of human suffering serve as common themes throughout. However, my ultimate goal is to empower readers, from trainees to faculty to patients, to overcome their unique challenges in life and help others do the same.

Objectively assessed sleep quality parameters in Multiple Sclerosis at home: Association to disease, disease severity and physical activity.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory autoimmune, neurodegenerative disease that affects regular mobility and leads predominantly to physical disability. Poor sleep quality, commonly reported in MS patients, impacts their physical activity (PA). Accelerometers monitor 24-h activity patterns, offering insights into disease progression in daily life. OBJECTIVE: To test if the sleep quality variables of MS patients, as assessed with wrist-worn accelerometers, differ from those of controls and are associated with PA and disease severity variables. METHODS: Seven-day raw accelerometer data collected from 40 MS patients and 24 controls was processed using an open-source GGIR package, from which variables of sleep quality (sleep efficiency, wake after sleep onset (WASO), sleep regularity index (SRI), intradaily variability (IV)) and PA (of different intensities: inactivity, light (LPA), moderate (MPA), vigorous (VPA)) were analyzed. The variables were compared between the two study groups and in MS patients, correlation tested associations among the variables of sleep quality, PA, and disease severity (assessed with the Expanded Disability Status Scale, EDSS). RESULTS: Sleep efficiency was the only variable that differed significantly between MS patients and controls (lower in MS, p = 0.01). Both SRI (positively) and IV (negatively) correlated with the time spent in LPA and MPA. WASO correlated negatively with inactivity. CONCLUSION: This is one of the few studies with a wrist-worn accelerometer that shows a difference in sleep efficiency between MS patients and controls and, in MS, an association of sleep quality variables with PA variables.

Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18 F-PBR06 Study.

PURPOSE OF THE REPORT: 18 F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using 18 F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients. PATIENTS AND METHODS: Thirty 18 F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs). Logarithmically transformed "glial activity load on PET" scores (calculated as the sum of voxel-by-voxel z -scores ≥4), "lnGALP," were compared between MS and HC and between MS subjects on high-efficacy DMTs (H-DMT, n = 13) and those on no or lower-efficacy treatment, and correlated with clinical measures, serum biomarkers, and cortical thickness. RESULTS: Cortical gray matter (CoGM) and white matter (WM) lnGALP scores were higher in MS versus HC (+33% and +48%, P < 0.001). In H-DMT group, CoGM and WM lnGALP scores were significantly lower than lower-efficacy treatment ( P < 0.01) but remained abnormally higher than in HC group ( P = 0.006). Within H-DMT patients, CoGM lnGALP scores correlated positively with physical disability, fatigue and serum glial fibrillary acid protein levels ( r = 0.65-0.79, all P 's < 0.05), and inversely with cortical thickness ( r = -0.66, P < 0.05). CONCLUSIONS: High-efficacy DMTs decrease, but do not normalize, CoGM and WM MA in MS patients. Such "residual" MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration. Individualized mapping of translocator protein PET using 18 F-PBR06 is clinically feasible and can potentially serve as an imaging biomarker for evaluating "smoldering" inflammation in MS patients.

Structural and functional correlates of disability, motor and cognitive performances in multiple sclerosis: Focus on the globus pallidus.

OBJECTIVES: To explore structural and functional alterations of external (GPe) and internal (GPi) globus pallidus in people with multiple sclerosis (pwMS) compared to healthy controls (HC) and analyze their relationship with measures of clinical disability, motor and cognitive impairment. METHODS: Sixty pwMS and 30 HC comparable for age and sex underwent 3.0T MRI, including conventional, diffusion tensor MRI and resting state (RS) functional MRI. Expanded Disability Status Scale (EDSS) scores were rated and timed 25-foot walk (T25FW) test, nine-hole peg test (9HPT), and paced auditory serial addition test (PASAT) were administered. Two operators segmented the GP into GPe and GPi. Volumes, T1/T2 ratio, diffusivity indices and seed-based RS functional connectivity (FC) of the GP and its components were assessed. RESULTS: PwMS had no atrophy or altered diffusivity measures of the GP. Compared to HC, pwMS had higher T1/T2 ratio in both GP regions, which correlated with EDSS score (r = 0.26-0.39, p = 0.01-0.05). RS FC analysis highlighted component-specific functional alterations in pwMS: the GPe had decreased RS FC with fronto-parietal cortices, whereas the GPi had decreased intra-GP RS FC and increased RS FC with the thalamus. Worse EDSS, 9HPT, T25FW and PASAT scores were associated with GP RS FC modifications (r=-0.51‒0.51, p < 0.001). CONCLUSIONS: Structural GP involvement in MS was homogeneous across its portions. Increased T1/T2 ratio values, possibly representing iron accumulation, were related to more severe disability. RS FC alterations of the GPe and GPi were consistent with their roles within the basal ganglia network and correlated with worse functional status, suggesting less efficient communication between structures.

Passive assessment of tapping speed through smartphone is useful for monitoring multiple sclerosis.

INTRODUCTION: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in patients with MS. METHODS: Single-center prospective study in patients with MS. We passively assessed TS during first week, measured by an "in house" smartphone application. Reliability was assessed by intraclass correlation coefficient (ICC). Correlations between median and maximum keys/s of first week of assessment and baseline disability measures were explored. RESULTS: One-hundred three patients were included: 62.1 % women, with a median (IQR) age of 47 (40.4-54.8) years-old and an EDSS score of 3.0 (2.0-4.0). Distribution by MS subtypes was: 77.7 % relapsing-remitting MS (RRMS), 17.5 % secondary-progressive MS (SPMS) and 4.9 % primary-progressive MS (PPMS). ICC during first week was 0.714 (p < 0.00001). Both median and maximum keys/s showed a negative correlation with Expanded Disability Status Score, 9-hole peg test and timed 25-foot walk and a positive correlation with Processing Speed Test CogEval® raw and Z-score. Median and maximum keys/s were lower in patients diagnosed with SPMS than in RRMS. Both measures of tapping speed were associated with MS phenotype independently of age. CONCLUSION: TS measured through our application is reliable and correlates with baseline disability scales.

Event-related desynchronization and synchronization in multiple sclerosis.

BACKGROUND: Motor preparation and execution can be impaired in patients with multiple sclerosis (pwMS). These neural processes can be assessed using electroencephalography (EEG). During a self-paced movement, EEG signal amplitude decreases before movement (event-related desynchronization, ERD) and increases after movement (event-related synchronization, ERS). OBJECTIVE: To reappraise ERD/ERS changes in pwMS compared to healthy controls (HC). METHODS: This single-center study included 13 pwMS and 10 sex/age-matched HC. 60-channel EEG was recorded during two self-paced movements of the right hand: a simple index finger extension task and a more complex finger tapping task. Clinical variables included MS type, sex, age, disease duration, disability, grip strength, fatigue and attentional performance. EEG variables included ERD and ERS onset latency, duration, and amplitude determined using two methods of signal analyses (based on visual or automated determination) in the alpha and beta frequency bands in five cortical regions: right and left frontocentral and centroparietal regions and a midline region. Neuroimaging variables included the volumes of four deep brain structures (thalamus, putamen, pallidum and caudate nucleus) and the relative lesion load. RESULTS: ERD/ERS changes in pwMS compared to HC were observed only in the beta band. In pwMS, beta-ERD had a delayed onset in the midline and right parietocentral regions and a shortened duration or increased amplitude in the parietocentral region; beta-ERS had a shorter duration, delayed onset, or reduced amplitude in the left parieto/frontocentral region. In addition, pwMS with a more delayed beta-ERD in the midline region had less impaired executive functions but increased caudate nuclei volume, while pwMS with a more delayed beta-ERS in the parietocentral region contralateral to the movement had less fatigue but increased thalami volume. CONCLUSION: This study confirms an alteration of movement preparation and execution in pwMS, mainly characterized by a delayed cortical activation (ERD) and a delayed and reduced post-movement inhibition (ERS) in the beta band. Compensatory mechanisms could be involved in these changes, associating more preserved clinical performance and overactivation of deep brain structures.

Effects of photobiomodulation therapy on muscle function in individuals with multiple sclerosis.

BACKGROUND: In people with multiple sclerosis (pwMS), muscle fatigue and weakness are common issues that can interfere with daily activities. Photobiomodulation therapy (PBMT), comprising light in a 600-1100 nm bandwidth, is a low-level laser therapy thought to improve muscle performance in non-disease populations, in part, by improving mitochondrial function and thus, might be beneficial in pwMS. Given this potential, we aimed to investigate the effects of PBMT on muscle performance in pwMS, both in the short-term and over an extended period. METHODS: This study consisted of two parts with a randomized double-blind crossover design. In study I, muscle function was assessed in four sessions before and after PBMT in ambulatory pwMS (N = 17, F = 14) as follows: maximal voluntary contraction (MVC) and muscle fatigue of the right tibialis anterior (TA) muscle was compared at baseline and following a two-min submaximal fatiguing contraction. Then, PBMT was administered to the belly of TA muscle at different doses of energy of an active device (40 J, 80 J, 120 J) or placebo. The muscle function assessment was then repeated. OUTCOME VARIABLES: muscle force recovery (%), muscle fatigue (%). Statistical tests included McNemar's exact test, Wilcoxon signed-rank test, and the Friedman test. In study II, a subgroup from study I (N = 12, F = 11) received individualized doses (i.e., best dose-effect observed in study I) of active, or placebo PBMT, which was administered on the TA muscle for two weeks. Muscle function assessments were performed pre- and post-PBMT in four sessions similar to study I. OUTCOME VARIABLES: Baseline strength (N), endurance time (s), and muscle fatigue (%). The Wilcoxon signed-rank test was used for statistical analysis. Values are reported as mean (SD). RESULTS: In study I, participants who received a high dose of PBMT showed significant improvement in force recovery (101.89 % (13.55 %)) compared to the placebo group (96.3 % (18.48 %); p = 0.03). Muscle fatigue did not significantly improve with either active PBMT or placebo. In study II, active PBMT resulted in a significant improvement in muscle strength compared to both the baseline (pre-PBMT = 162.70 N (37.52 N); post-PBMT = 185.56 N (33.95 N); p = 0.01) and the placebo group (active PBMT: mean-change = 22.87 N (23.67 N); placebo: mean-change = -4.12 N (31.95 N); p = 0.02). Endurance time and muscle fatigue did not show significant improvement with either active PBMT or placebo. CONCLUSION: Our findings suggest that an individualized dose of PBMT might improve muscle performance, including force recovery and strength in individuals with mild-moderate MS. Therefore, PBMT might be a novel therapeutic modality, either as a standalone treatment or in combination with other interventions, to improve muscle performance in pwMS.

Leukocyte telomere length in multiple sclerosis: relationship between disability severity and pregnancy history.

BACKGROUND: Aging-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of biological aging such as leukocyte telomere length (LTL) could help personalise prognosis. Pregnancy has been shown to be protective against disability accumulation in women with MS, though it is unclear if this effect relates to aging mechanisms or LTL. OBJECTIVES: This study aimed to cross-sectionally characterise LTL in a cohort of individuals with MS, and to correlate LTL with disability severity and pregnancy history. METHODS: We extracted DNA from the whole blood of 501 people with MS in Melbourne, Australia. Expanded Disability Status Scale (EDSS) score and demographic data, as well as pregnancy history for 197 females, were obtained at sample collection. Additional data were extracted from the MSBase Registry. LTL was determined in base pairs (bp) using real-time quantitative polymerase chain reaction. RESULTS: A relationship between EDSS score and shorter LTL was robust to multivariable adjustment for demographic and clinical factors including chronological age, with an adjusted LTL reduction per 1.0 increase in EDSS of 97.1 bp (95 % CI = 9.7-184.5 bp, p = 0.030). Adjusted mediation analysis found chronological age accounted for 33.6 % of the relationship between LTL and EDSS score (p = 0.018). In females with pregnancy data, history of pregnancy was associated with older age (median 49.7 vs 33.0 years, p < 0.001). There were no significant relationships between adjusted LTL and any history of pregnancy (LTL increase of 65.3 bp, 95 % CI = -471.0-601.5 bp, p = 0.81) or number of completed pregnancies (LTL increase of 14.6 bp per pregnancy, 95 % CI = -170.3-199.6 bp, p = 0.87). CONCLUSIONS: The correlation between LTL and disability independent of chronological age and other factors points to a link between neurological reserve in MS and biological aging, and a potential research target for pathophysiological and therapeutic mechanisms. Although LTL did not significantly differ by pregnancy history, longitudinal analyses could help identify interactions with prospectively captured pregnancy effects.

Diet and omega-3 and vitamin D supplement use predict five-year fatigue and disability trajectories in people with multiple sclerosis.

BACKGROUND: Fatigue and disability are indicators of disease progression experienced by many people with multiple sclerosis (pwMS). Understanding trajectories of these outcomes, and their predictors, may provide insight to potential interventions for MS management. METHODS: Survey data from 839 pwMS from the Health Outcomes and Lifestyle in pwMS study were analysed. Fatigue was defined as mean Fatigue Severity Scale >5, and severe disability as Patient Determined Disease Steps >5. Group-based trajectory modelling was used to identify fatigue and disability trajectories over five-years. Dietary predictors associated with outcome trajectory group membership were assessed using log-binomial regression. Demographic and clinical characteristics were considered in multivariable models. RESULTS: Distinct trajectories for fatigue and disability were identified. For fatigue, 58 % of pwMS were assigned to low-, and 42 % to high-, fatigue trajectory groups. For disability, 85 % of pwMS were assigned to low-, and 15 % to high-, disability groups. Baseline high-quality diet, and omega-3 and vitamin D supplement use, were associated with reduced risk of being in high-fatigue and high-disability trajectories, while meat and dairy consumption were associated with increased risk. CONCLUSIONS: A high-quality diet, avoiding meat and dairy, and omega-3 and vitamin D supplement use, individually predict better fatigue and disability trajectories. Dietary modifications should be considered in MS management.

Health-related quality of life and utilities among Lebanese patients with Multiple Sclerosis: A cross-sectional study.

OBJECTIVE: This study assessed the Health-Related Quality of Life (HRQoL) and utilities of Multiple Sclerosis (MS) patients in Lebanon using generic and MS-specific QoL instruments, categorized by disease severity, and explored factors associated with HRQoL. METHODS: This was a cross-sectional, retrospective HRQoL study collecting data through face-to-face interviews using the EQ-5D-5 L and the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaires. We enrolled Lebanese patients aged ≥18 years, diagnosed with MS for >6 months. Patients were categorized by disease severity using the expanded disability status scale (EDSS) scores: 0-3 (mild MS), 4-6.5 (moderate MS), and 7-9 (severe MS). Bivariate and linear regression analyses were performed to study factors associated with HRQoL. RESULTS: A total of 210 patients (mean age: 43.3 years; 65.7 % females) were included. The mean EQ-5D-5 L utility score was 0.74. This score decreased significantly with disease severity (p < 0.001 for the trend): 0.93, 0.60, and 0.32 for mild, moderate, and severe MS, respectively. The mean MusiQoL global index score was 71.33 and was significantly lower for severe MS (58.68), than for moderate (65.23) and mild (77.80), (p < 0.001 for the trend). Higher educational level, lower EDSS scores, and longer disease duration were associated significantly with a higher EQ-5D-5 L utility (R2 = 0.67), while employment, lower EDSS scores, and decrease in cognitive difficulties were associated with better MusiQoL utility (R2 = 0.46). CONCLUSIONS: This study reveals a significant and gradual deterioration in HRQoL as MS progresses, resulting in low utility scores for patients with severe MS.

The contribution of EEG to assess and treat motor disorders in multiple sclerosis.

OBJECTIVE: Electroencephalography (EEG) can highlight significant changes in spontaneous electrical activity of the brain produced by altered brain network connectivity linked to inflammatory demyelinating lesions and neuronal loss occurring in multiple sclerosis (MS). In this review, we describe the main EEG findings reported in the literature to characterize motor network alteration in term of local activity or functional connectivity changes in patients with MS (pwMS). METHODS: A comprehensive literature search was conducted to include articles with quantitative analyses of resting-state EEG recordings (spectrograms or advanced methods for assessing spatial and temporal dynamics, such as coherence, theory of graphs, recurrent quantification, microstates) or dynamic EEG recordings during a motor task, with or without connectivity analyses. RESULTS: In this systematic review, we identified 26 original articles using EEG in the evaluation of MS-related motor disorders. Various resting or dynamic EEG parameters could serve as diagnostic biomarkers of motor control impairment to differentiate pwMS from healthy subjects or be related to a specific clinical condition (fatigue) or neuroradiological aspects (lesion load). CONCLUSIONS: We highlight some key EEG patterns in pwMS at rest and during movement, both suggesting an alteration or disruption of brain connectivity, more specifically involving sensorimotor networks. SIGNIFICANCE: Some of these EEG biomarkers of motor disturbance could be used to design future therapeutic strategies in MS based on neuromodulation approaches, or to predict the effects of motor training and rehabilitation in pwMS.