Sexual dysfunction is prevalent in people with multiple sclerosis (PwMS) and considerably affects their quality of life. Although sexual function (SF) is crucial in PwMS, its relationship with other characteristics remains insufficiently understood.

This review aimed to consolidate the evidence comparing SF between PwMS and healthy controls (HCs) and to explore its correlation with various demographic, clinical, and psychological factors.

The PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were systematically searched up to July 28, 2024, to identify studies comparing SF between PwMS and HCs or assess its correlation with various demographic, clinical, and psychological characteristics. Random effects models were used in R software version 4.4.0 to estimate the pooled standardized mean difference (SMD) and pooled correlations, with their 95% CIs as the effect size metrics.

In this review, 61 studies comprising 16 266 PwMS were included. The meta-analysis indicated that SF was significantly reduced in PwMS compared to HCs, with females with MS (FwMS) showing lower Female Sexual Function Index scores (SMD: -0.41, 95% CI, -0.61 to -0.20, P < .0001) and males with MS (MwMS) demonstrating reduced International Index of Erectile Function scores (SMD: -0.77, 95% CI, -1.32 to -0.22, P < .01). Correlation analyses highlighted associations between reduced SF and higher Expanded Disability Status Scale (EDSS), longer disease duration, and depression in gender-aggregated analyses. Reduced SF was also found to correlate with older age, higher EDSS scores, depression, and fatigue in FwMS.

The findings of the included studies indicated that SF is lower in PwMS compared to HCs and is influenced by age, disease duration, depression, and the EDSS. Further studies on the effects of comorbidities, medications, and MS classification on the SF of PwMS are warranted.

Objective: Although numerous studies have investigated personality traits in people with multiple sclerosis (PwMS), a thorough systematic review and meta-analysis of this evidence has not been conducted. This review aimed to elucidate the personality profile of PwMS relative to healthy controls (HCs) and to assess the overall correlations between personality traits and mood, cognitive performances, fatigue, and physical function in PwMS. Methods: PubMed/MEDLINE, Scopus, Embase, and Web of Sciences were systematically searched up to 18 August 2024, to identify studies (1) comparing personality traits, including Agreeableness, Conscientiousness, Extraversion, Neuroticism, and Openness, between PwMS and HCs or (2) assessing the correlation between personality traits, anxiety, depression, cognition, fatigue, and physical function in PwMS. The pooled standardized mean differences (SMDs) or correlations were estimated. Results: Sixty-three studies on 8068 PwMS and 1588 HCs were included. PwMS exhibited different personality traits, notably higher Neuroticism, compared to HCs. Furthermore, Neuroticism showed the most significant pooled correlations with mood and fatigue, while Conscientiousness demonstrated the greatest pooled correlations with disability and cognitive performance in PwMS. The meta-analysis confirmed these findings, revealing that PwMS have higher Neuroticism (SMD = 0.35) than HCs. Additionally, higher Neuroticism was significantly linked to increased anxiety (r = 0.78), depression (r = 0.53), and fatigue (r = 0.35), and Conscientiousness was significantly correlated with decreased Expanded Disability Status Scale (EDSS) (r = -0.21) and Symbol Digit Modalities Test (SDMT) (r = 0.13). Conclusions: PwMS exhibited distinct personality traits compared to healthy individuals. Additionally, personality traits, particularly Neuroticism and Conscientiousness, had relationships with mood, cognitive performance, fatigue, and physical function of PwMS.

Background: Multiple sclerosis (MS) is a chronic and heterogeneous disease characterized by demyelination and axonal loss and damage. Magnetic resonance imaging (MRI) has been employed to distinguish these changes in various types of MS lesions. Objectives: We aimed to evaluate intravoxel incoherent motion (IVIM) diffusion and perfusion MRI metrics across different brain regions in healthy individuals and various types of MS lesions, including enhanced, non-enhanced, and black hole lesions. Methods: A prospective study included 237 patients with MS (65 males and 172 females) and 29 healthy control participants (25 males and 4 females). The field strength was 1.5 Tesla. The imaging sequences included three-dimensional (3D) T1, 3D fluid-attenuated inversion recovery, two-dimensional (2D) T1, T2-weighted imaging, and 2D diffusion-weighted imaging (DWI) sequences. IVIM-derived parameters-apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion (D*), and perfusion fraction (f)-were quantified for commonly observed lesion types (2506 lesions from 224 patients with MS, excluding 13 patients due to MRI artifacts or not meeting the diagnostic criteria for RR-MS) and for corresponding brain regions in 29 healthy control participants. A one-way analysis of variance, followed by post-hoc analysis (Tukey's test), was performed to compare mean values between the healthy and MS groups. Receiver operating characteristic curve analyses, including area under the curve, sensitivity, and specificity, were conducted to determine the cutoff values of IVIM parameters for distinguishing between the groups. A p-value of ≤0.05 and 95% confidence intervals were used to report statistical significance and precision, respectively. Results: All IVIM parametric maps in this study discriminated among most MS lesion types. ADC, D, and D* values for MS black hole lesions were significantly higher (p < 0.0001) than those for other MS lesions and healthy controls. ADC, D, and D* maps demonstrated high sensitivity and specificity, whereas f maps exhibited low sensitivity but high specificity. Conclusions: IVIM parameters provide valuable diagnostic and clinical insights by demonstrating high sensitivity and specificity in evaluating different categories of MS lesions.

This systematic literature review (SLR) was conducted to explore the role of serum neurofilament light chain (sNfL) as a biomarker in multiple sclerosis (MS) disease management.

The review was conducted in accordance with the recommendation laid by the Cochrane Handbook for Systematic Reviews. A comprehensive literature search was performed in key biomedical databases (EMBASE®, MEDLINE®, MEDLINE®-In-Process, and all Evidence-Based Medicine [EBM] Reviews databases) to retrieve studies reporting the association between sNfL and disease activity in patients with MS. Additional evidence was also identified through hand searching of key conference proceedings and gray literature.

Following review of 1831 records, 75 studies from 180 publications were included in the review. The studies included in the SLR consistently demonstrated an association between higher sNfL levels and an increased risk of future relapses within 2 years and MS disease progression. Higher levels of sNfL were also linked to an increased likelihood of experiencing gadolinium-enhancing T1 and T2 lesions. Patients with lower sNfL levels had a higher likelihood of achieving no evidence of disease activity status. Furthermore, an inverse correlation was observed between sNfL levels and cognitive impairment as assessed via the Symbol Digit Modalities Test performance and Timed 25-Foot Walk scores.

This SLR demonstrates the significance of sNfL as a sensitive biomarker for monitoring MS progression. Convenient and reliable sNfL measurement could benefit routine clinical practice, providing clinicians with a simple and effective tool to monitor disease and treatment response.

The interleukin-2 receptor alpha chain (IL2RA) gene has been implicated in multiple sclerosis (MS) susceptibility, particularly through the rs2104286 and rs12722489 SNPs. However, previous studies have yielded inconsistent results across different populations, likely due to small sample sizes and ethnic variations. This study aimed to investigate the association of IL2RA SNPs with MS risk in eastern Iranian population and through a comprehensive meta-analysis. Our case-control study included 400 Iranian individuals from North Khorasan and Sistan & Baluchistan provinces, comprising 200 MS patients across all subtypes and genders and 200 controls. The meta-analysis incorporated pooled odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the strength of these associations. Our case-control findings demonstrated a significant association between rs2104286 and MS risk, which was further supported by the meta-analysis in Iranian populations. Specifically, the association was observed at both the genotype (P = 0.001) and allelic (P = 0.003) levels in North Khorasan and at the genotype level in Sistan & Baluchistan (P = 0.001). A global meta-analysis of rs2104286, encompassing 24,931 MS patients and 36,036 controls, revealed a significant association between the A allele and all genotype models with increased MS risk (P < 0.05). Similarly, a meta-analysis of rs12722489, including 19,797 MS patients and 32,085 controls, identified the CC + CT genotype as a risk factor for MS (P = 0.04). In conclusion, our findings suggest that the rs2104286 A allele and rs12722489 CC + CT genotype are associated with an increased risk of MS in both Caucasian and Asian populations, including Iranians.

Disability accumulation in multiple sclerosis (MS) is driven by relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Early PIRA (EP), occurring within five years of disease onset, has been proposed as a critical marker of poor prognosis. However, risk factors for EP remain poorly defined.

To identify clinical and demographic factors associated with EP and assess its impact on long-term disability accumulation.

This retrospective cohort study included 143 relapsing-remitting MS patients with disability progression (EDSS 4, 6, or 8) primarily due to PIRA. Patients were categorized as EP (PIRA within five years of onset) or late PIRA (LP, after five years). Cox regression and Kaplan-Meier survival analyses assessed risk factors and disability progression.

EP was identified in 39/77 (51 %) of PIRA patients. EP patients were older at diagnosis (38.6 vs. 34 years, p = 0.01), predominantly female (p = 0.02), and more likely to have spinal cord onset symptoms (p < 0.01). EP patients reached EDSS 4, 6, and 8 significantly faster than LP patients (p < 0.01). In multivariate analysis, spinal cord onset was the strongest predictor of EP (HR=2.1, 95 %CI=1.05-4.44, p = 0.03).

EP occurs in half of PIRA patients and is associated with spinal cord onset and older age at diagnosis. These findings highlight the need for early identification and aggressive treatment to mitigate long-term disability. Further research is required to refine predictive models and optimize therapeutic strategies for high-risk patients.

Multiple sclerosis (MS) is a chronic neurologic disorder with significant implications for public health as being the first cause of nontraumatic neurologic disability in young adults. Although the global prevalence of MS has been increasing, recent temporal trends in incidence remain unclear. We aimed to evaluate current MS incidence trends in France over 11 years using the Système National des Données de Santé, a nationwide administrative database covering 99% of the French population.

We used a published algorithm that incorporates multiple data sources, including benefits from long-term diseases, specific disease-modifying treatment prescriptions, and hospital discharge, to identify incident MS cases from January 1, 2011, to December 31, 2021. Sex-standardized and age-standardized incidence and prevalence were estimated using a "specific" and a "sensitive" definition providing bounds on the evolution of recent incidence. We used multivariable Poisson regression models to estimate temporal trends in incidence rates, calculating incidence rate ratios (IRRs) along with corresponding 95% CIs. In a sensitivity analysis, the time lag between past visits to neurologists and the database recording of MS was analyzed to ensure that the diagnosis extraction date was reliable.

A total of 67,311 individuals with suspected MS were identified between 2011 and 2021, with 50,320 individuals classified as incident MS using the specific definition. The sensitive definition identified 56,918 individuals with incident cases. The median age at diagnosis was 40.6 years for the specific definition and 41.5 years for the sensitive definition. The study found stable incidence of MS over the 11-year period (adjusted IRR: 0.998 [95% CI 0.996-1.001] for the specific cohort). The female-to-male ratio of incident MS cases remained stable while sex-standardized and age-standardized prevalence of MS continued to rise. The median time lag between probable diagnosis and database recording was estimated to be less than 18 months, with variations depending on age and method of patient identification.

This study provides a comprehensive analysis of MS epidemiology in France, demonstrating stable incidence and sex ratio. The increase in prevalence suggests improved management and survival and highlights the ongoing need for health care systems to support the growing population of individuals with MS.

We conducted a meta-analysis to assess the frequency of incomplete recovery from multiple sclerosis (MS) relapses and a systematic review to evaluate the influence of six factors on incomplete recovery: relapse severity, age, sex, disease duration, disease-modifying treatment use, and the presence of contrast-enhancing lesions at relapse.

We searched Scientific databases to identify suitable publications. Our outcome was MS relapse incomplete recovery, defined as a post-relapse EDSS measured at least 6 months after the event higher than the pre-relapse EDSS. We synthesized the rate of incomplete recovery using meta-analysis (random effect model). and summarized the effect estimates (or HR) for demographic and clinical factors.

We included 13 studies (with a total of 19,920 patients and 27672 relapses having at least six month of follow up) . The pooled rate of incomplete recovery was 0.42 (95 % confidence interval 0.31 to 0.54). The subgroup systematic review identified that relapse severity was the most consistent and strongest predictor of incomplete recovery, with odds ratios ranging from 2.4 to 17.2. Other factors were less consistently associated with relapse recovery.

This systematic review indicates that relapse recovery is often incomplete, with relapse severity being the strongest and most consistent predictor of incomplete recovery.

The existence and definition of benign multiple sclerosis (MS) remain controversial, particularly given the discrepancy between clinical presentation and underlying imaging changes. In this study, we aimed to investigate the brain atrophy patterns related to benign relapsing-remitting MS (BRRMS), particularly regarding location and extent.

We analyzed global and regional gray matter (GM) and white matter (WM) volumes, WM lesion load, corpus callosum index (CCI) and corpus callosum area (CCA) in well-defined benign relapsing-remitting MS patients (BRRMS, n = 35) compared to healthy controls (HC, n = 35). Imaging data were analyzed using an AI-based volumetric analysis MRI (cNeuro®) and confirmed visually by an experienced neuroradiologist, ensuring robust validation.

Total brain tissue volume was significantly smaller in patients with BRRMS compared to HC (p < 0.001), but the cortical (p = 0.011) and cerebral (p = 0.002) GM volumes, as well as cingulate gyrus (p=0.032) and entorhinal area volumes (p < 0.001), were larger in BRRMS. GM volumes in the postcentral gyrus (p = 0.001), precentral gyrus (p < 0.001), the medial segment of the precentral gyrus (p < 0.001), supplementary motor cortex (p < 0.001) and thalamus (p < 0.001) were reduced in BRRMS compared to HC. Furthermore, both CCI and CCA were significantly smaller in BRRMS (p < 0.001 and p = 0.001, respectively).

Despite the overall reduced brain volume compared to HC, distinct cortical regions, especially within the limbic system (i.e., cingulate gyrus and entorhinal area) GM may be relatively well preserved, indicating a possible compensatory volume increase. Based on this study, the corpus callosum is a crucial structure in monitoring disease progression in BRRMS.

The perception of Biological Motion (BM) is critical for understanding social cues. A limited number of moving light dots resembling a moving individual, can suggest social intention information, providing an attentional orienting. This ability to predict other's intentions from BM cues refers to social cognition, an ability impaired in several neurological diseases. As in patients with Multiple Sclerosis (MS) an impairment in visuo-spatial attention and social cognition has been observed, we aim to investigate the possible differences in the visuo-spatial attention between MS patients and healthy individuals by using BM stimuli as cues. We tested 37 MS patients and 40 healthy controls (HC), who performed a modified central cue Posner task, using BM stimuli as cues that are not always predictive of the target location. They were represented by Point Light Walker (PLW) configuration, a series of dots arranged at the human joints and walking through the left or right of the screen, shown in the global (whole body) or local (two dots, indicating the feet of the PLW) configuration. MS patients exhibited overall slower responses compared to HC. In MS patients, a weaker advantage of valid trial over invalid ones was evident when cue had a local than global BM configuration. Also, MS patients showed a slower performance than HC in valid trials with local BM cues. The difference between groups was attenuated when the cue had a global BM configuration. These findings suggest possible impairment of local BM cue processing in MS patients, possibly due to delays or deficits in interpreting feet motion as biological information, reducing the cue's predictive power.

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) sequence sensitive to substances that alter the local magnetic field, such as calcium and iron, allowing phase information to distinguish between them. SWI is a 3D gradient-echo sequence with high spatial resolution that leverages both phase and magnitude effects. The interaction of paramagnetic (such as hemosiderin and deoxyhemoglobin), diamagnetic (including calcifications and minerals), and ferromagnetic substances with the local magnetic field distorts it, leading to signal changes. Neurodegenerative diseases are typically characterized by the progressive loss of neurons and their supporting cells within the neurovascular unit. This cellular decline is associated with a corresponding deterioration of both cognitive and motor abilities. Many neurodegenerative disorders are associated with increased iron accumulation or microhemorrhages in various brain regions, making SWI a valuable diagnostic tool in clinical practice. Suggestive SWI findings are known in Parkinson's disease, Lewy body dementia, atypical parkinsonian syndromes, multiple sclerosis, cerebral amyloid angiopathy, amyotrophic lateral sclerosis, hereditary ataxias, Huntington's disease, neurodegeneration with brain iron accumulation, and chronic traumatic encephalopathy. This review will assist radiologists in understanding the technical framework of SWI sequences for a correct interpretation of currently established MRI findings and for its potential future clinical applications.

Macrophages are integral components of the innate immune system, present in nearly all tissues and organs throughout the body. They exhibit a high degree of plasticity and heterogeneity, participating in immune responses to maintain immune homeostasis. When the immune system loses tolerance, macrophages rapidly proliferate and polarize in response to various signaling pathways within a disrupted microenvironment. The direction of macrophage polarization can be regulated by a variety of factors, including transcription factors, non-coding RNAs, and metabolic reprogramming. Autoimmune diseases arise from the immune system's activation against host cells, with macrophage polarization playing a critical role in the pathogenesis of numerous chronic inflammatory and autoimmune conditions, such as rheumatoid arthritis, systemic lupus erythematosus, immune thrombocytopenic purpura, and type 1 diabetes. Consequently, elucidating the molecular mechanisms underlying macrophage development and function presents opportunities for the development of novel therapeutic targets. This review outlines the functions of macrophage polarization in prevalent autoimmune diseases and the underlying mechanisms involved. Furthermore, we discuss the immunotherapeutic potential of targeting macrophage polarization and highlight the characteristics and recent advancements of promising therapeutic targets. Our aim is to inspire further strategies to restore macrophage balance in preventing and treating autoimmune diseases.

'Brain age' is a numerical estimate of the biological age of the brain and an overall effort to measure neurodegeneration, regardless of disease type. In multiple sclerosis, accelerated brain ageing has been linked to disability accrual. Artificial intelligence has emerged as a promising tool for the assessment and quantification of the impact of neurodegenerative diseases. Despite the existence of numerous AI models, there is a noticeable lack of comparative imaging data for traditional machine learning versus deep learning in conditions such as multiple sclerosis. A retrospective observational study was initiated to analyse clinical and MRI data (4584 MRIs) from various scanners in a large longitudinal cohort (n = 1516) of people with multiple sclerosis collected from two institutions (Karolinska Institute and Oslo University Hospital) using a uniform data post-processing pipeline. We conducted a comparative assessment of brain age using a deep learning simple fully convolutional network and a well-established traditional machine learning model. This study was primarily aimed to validate the deep learning brain age model in multiple sclerosis. The correlation between estimated brain age and chronological age was stronger for the deep learning estimates (r = 0.90, P < 0.001) than the traditional machine learning estimates (r = 0.75, P < 0.001). An increase in brain age was significantly associated with higher expanded disability status scale scores (traditional machine learning: t = 5.3, P < 0.001; deep learning: t = 3.7, P < 0.001) and longer disease duration (traditional machine learning: t = 6.5, P < 0.001; deep learning: t = 5.8, P < 0.001). No significant inter-model difference in clinical correlation or effect measure was found, but significant differences for traditional machine learning-derived brain age estimates were found between several scanners. Our study suggests that the deep learning-derived brain age is significantly associated with clinical disability, performed equally well to the traditional machine learning-derived brain age measures, and may counteract scanner variability.

Patients With Multiple Sclerosis (MS) Have Higher Mortality Than Matched Background Populations. We Compare Relative and Excess Mortality in MS Over the Matched Background Populations Between Primary Progressive MS (PPMS), relapsing Onset MS (ROMS), and Secondary Progressive MS (SPMS).

We included all patients from the nationwide and complete Danish MS Registry with onset 1994-2022 and compared the extra mortality of the MS phenotypes in terms of relative and excess mortality, with adjustment for sex, age at onset, disease-modifying treatment, and number of recorded relapses. We calculated the adjusted ratios of relative and excess mortalities between PPMS and ROMS and between PPMS and SPMS.

The initial course was unknown in 221, leaving 1412 cases with PPMS (which includes progressive relapsing MS) and 12,449 cases with ROMS. 627 had died during follow-up by the end of 2022. After adjustment, both ratios between PPMS and ROMS came close to unity, indicating that the excess mortality is equal for PPMS and ROMS in the long run. The adjusted relative and additive mortalities were factors 6.05 (95% CI 4.42-8.27) and 1.90 (95% CI 1.65-2.18) higher in SPMS than in PPMS.

Compared with the matched population, the adjusted relative and excess mortalities are the same for PPMS and ROMS. However, SPMS had a higher relative and excess mortality than PPMS, probably in part owing to the burden of disease carried over from the pre-progressive phase. This underlines the need for effective treatment in this later stage of the disease and more attention to comorbidity.

This study aims to evaluate the reliability and validity of the Community Balance and Mobility Scale (CB&M) in people with multiple sclerosis (PwMS).

A total of 65 PwMS (Expanded Disability Status Scale (EDSS) ≤ 5.5) were included in the study. Test-retest, internal consistency (item-total score correlation, Cronbach's alpha coefficient) intra-rater, and inter-rater reliability were investigated for the reliability of the CB&M. For intra-rater and inter-rater reliability, CB&M measurements of 34 PwMS were videotaped. The validity of the CB&M was assessed through criterion (predictive and concurrent validity) and construct validity. Construct validity was evaluated using hypothesis testing which included examining correlations with EDSS, Timed Up and Go Test (TUG), and Dynamic Gait Index (DGI).

Test-retest reliability demonstrated a good to excellent correlation (ICC = 0.995, p < 0.001). Cronbach's alpha was 0.971 (p < 0.001). Intra-rater (ICC = 0.993, p < 0.001) and inter-rater reliability (ICC = 0.986, p < 0.001) of the CB&M were also good to excellent. Cohen's kappa range values ​​of the scale vary between 0.958 - 0.665, and the percentage agreement varies between 97% and 75%. For the convergent validity of CB&M, strong correlations were observed with EDSS (r=-0.831, p < 0.001), TUG (r=-0.854, p < 0.001), and DGI (r = 0.865, p < 0.001). Additionally, the CB&M demonstrated an excellent correlation with the BBS (r = 0.907, p < 0.001). The scale exhibited no floor-ceiling effect.

CB&M is a reliable and valid tool for assessing balance and mobility in PwMS and offers significant advantages for evaluating balance in PwMS, as it provides comprehensive information about the balance and mobility requirements essential for community living.

This study assessed the effect of cladribine tablets (CladT) on the pharmacokinetics (PK) of a combined oral contraceptive (COC) in pre-menopausal women with relapsing multiple sclerosis. It was a randomized, double-blind, two-period, two-sequence crossover study to assess steady-state plasma PK (area under the concentration-time curve and peak concentration) of COC (ethinylestradiol [EE] 30 μg and levonorgestrel [LNG] 150 μg) when co-administered with CladT or placebo. Participants received 2 weeks of active CladT treatment per course (Weeks 1 and 5 per year) to have a cumulative dose of 3.5 mg/kg over 2 years as per label. Of the 24 randomized participants, 23 completed the study. The results showed that the concentration-time profiles as well as PK parameters of EE and LNG in the plasma were similar when co-administered with CladT or placebo. Analysis of variance confirmed the bioequivalence of EE and LNG in COC when co-administered with either CladT or placebo. All participants were adequately exposed to cladribine. Repeat-dose administration of CladT had no apparent effect on serum luteinizing hormone, follicle-stimulating hormone, progesterone, or sex hormone-binding globulin concentrations during concomitant treatment with COC. Co-administration with COC did not change the known safety and tolerability profile of CladT and did not alter the PK of EE or LNG in a COC during the study. Therefore, the concomitant use of CladT is not expected to decrease the efficacy of COCs containing EE and LNG. Trial Registration: EudraCT Number: 2018-001015-70.

Reduced quality of life (QoL) is an early feature of multiple sclerosis (MS). The effect of progression independent of relapse activity (PIRA) on QoL is poorly investigated.

To assess the impact of PIRA on QoL using patient-reported outcome measures (PROMs).

In a prospective observational study, 125 newly diagnosed persons with relapsing-remitting MS (PwRRMS) were assessed over 5 years with: EuroQoL-5-Dimension-3-level (EQ-5D-3L), EQ-visual-analogous-scale (EQ-VAS) and 29-item-MS-Impact-Scale (MSIS-29). PwRRMS were dichotomized: PIRA (worsening of expanded disability status scale (EDSS), timed-25-foot-walk or 9-hole-peg-test, independent of relapses) versus non-PIRA. PwRRMS were compared at baseline, year 5 (y5) and delta values (baseline scores subtracted from y5 scores) and annually using linear-mixed-effects-models.

At y5, 19.2% had PIRA. PIRA versus non-PIRA PwRRMS were older (p < 0.001). At y5 PIRA PwRRMS had lower EQ-5D-3L (p = 0.001), higher MSIS-29-PHYS (p < 0.001), delta values showed lower EQ-5D-3L (p < 0.001) and EQ-VAS (p = 0.010), higher MSIS-29-PHYS (p = 0.004) and MSIS-29-PSYCH (p = 0.036). Linear-mixed-effects-models showed that, compared to PIRA, non-PIRA PwRRMS had an improvement in QoL: EQ-5D-3L: β = 0.039, p < 0.001; EQ-VAS: β = 2.401, p < 0.001; MSIS-29-PHYS: β = -0.107, p < 0.001; MSIS-29-PSYCH, β = -0.115, p < 0.001, during the 5-year study period.

Deteriorating QoL in the early course of relapsing-remitting multiple sclerosis (RRMS) is strongly associated with PIRA. Our results suggest that QoL PROMs should be monitored and recognized as an important aspect of progression.

Predicting treatment response and disease progression in multiple sclerosis (MS) is challenging. Treatment Response Scoring Systems (TRSS) are potentially useful, but their utility in patients receiving high-efficacy therapies and very high-efficacy therapies (HET/vHET) remains unclear.

This study aimed to evaluate the performance of TRSS in patients treated with HET/vHET.

We retrospectively studied MS patients treated with HET/vHET in an MS specialized centre. TRSS, including the Rio Score, modified Rio Score and MAGNIMS score, were applied to assess response to treatment. We evaluated the predictive value of the TRSS on disease activity and disability progression.

TRSS effectively predicted disease activity and progression of disability in patients treated with HET/vHET. Patients with high TRSS scores at 12 months post-HET/vHET initiation had a significantly increased risk of relapses, new lesions on magnetic resonance imaging (MRI) scans and progression of disability at 4 years.

Our findings highlight the importance of personalized treatment strategies in MS. TRSS are valuable tools for monitoring treatment response, guiding clinical decision-making and optimizing patient care.

Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, leading to motor and cognitive impairment. These impairments become especially evident during dual-tasks, such as walking while performing a cognitive activity. Previous research has highlighted changes in gait-specific parameters during dual-tasks, but the cognitive component remains underexamined in MS. This study aims to expand on prior findings by using wearable inertial sensors and the Paced Auditory Serial Addition Test (PASAT) to evaluate the effects of dual-tasks on gait and cognitive performance in persons with MS (PwMS) compared to healthy controls.

Eighty-six adults (54 PwMS and 32 healthy controls) participated. PwMS were further divided into groups with lower (MS_LCP) and higher (MS_HCP) cognitive performance based on performance on the Symbol-Digit-Modalities Test (SDMT). Gait parameters were assessed using wearable inertial sensors during single- and dual-task 3-min-walking. Statistical analyses compared gait and cognitive performance across conditions and groups.

Under dual-task conditions, PwMS showed significant changes in all gait parameters, including reduced walking speed, stride length, percentage of swing phase and toe clearance, and increased stride time and percentage of stance phase compared to single-task condition. However, under dual-task condition in PwMS only walking speed, stride length and stride time differed from healthy controls. MS_LCP exhibited greater changes in both gait and PASAT performance than MS_HCP and healthy controls. While MS_HCP showed gait parameters comparable to healthy controls during single-tasks, deficits became apparent during dual-tasks. Correlations revealed strong associations between SDMT and PASAT scores but weak links between cognitive and self-reported measures.

The findings confirm that dual-task conditions exacerbate gait impairments in PwMS, particularly in those with lower cognitive performance. The use of PASAT as a dual-task cognitive challenge was feasible and had a considerable influence on gait. Results support the capacity sharing theory, suggesting that limited cognitive resources are redistributed between tasks under dual-task conditions.

Several studies show that optical coherence tomography (OCT) metrics e with cognition, disability, and brain structure in people with multiple sclerosis (PwMS). This review the correlation between OCT parameters and magnetic resonance imaging (MRI) measurements in PwMS.

A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was performed, including studies published in English up to November 29, 2024 to identify studies reporting quantitative data on the correlation between baseline OCT parameters and MRI measurements in PwMS. The meta-analysis was performed using R software version 4.4.0.

From 4931 studies, 68 studies on 6168 PwMS (67.4 % female) were included. The most significant correlations were found between peripapillary retinal nerve fiber layer (pRNFL) thickness and lower T1 lesion volume r = -0.42 (95 % CI: -0.52 to -0.31, p-value <0.001, I2 = 24 %), greater thalamic volume r = 0.39 (95 % CI: 0.17 to 0.61, p-value <0.001, I2 = 81 %), and lower T2 lesion volume r = -0.37 (95 % CI: -0.54 to -0.21, p-value <0.001, I2 = 85 %), respectively. Additionally, lower macular ganglion cell-inner plexiform layer (mGCIPL) thickness showed the most significant correlations with positive and lower thalamic volume r = 0.37 (95 % CI: 0.1 to 0.64, p-value = 0.008, I2 = 88 %), and positive and lower grey matter volume (GMV) 0.33 (95 % CI: 0.15 to 0.52, p-value <0.001, I2 = 81 %), respectively.

pRNFL and mGCIPL thickness are correlated with MRI measurements, suggesting that OCT can serve as a non-invasive, cost-effective, and complementary tool to MRI for enhancing the exploring of brain structural changes in PwMS.

Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. This updates the 2021 version of the review.

To assess the benefits and harms of rituximab as 'first choice' and 'switching' treatment for adults with any form of MS.

We searched CENTRAL, MEDLINE, Embase, CINAHL, and three trials registers on 31 December 2023, together with reference checking and contacting study authors to identify unpublished studies.

We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with any form of MS.

We followed standard Cochrane methods. We used RoB 1 to assess risk of bias in RCTs and ROBINS-I in NRSIs. We assessed the certainty of evidence for critical and important prioritised outcomes using GRADE: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching' treatment, relapsing or progressive MS, comparison with placebo or another DMT, and RCTs or NRSIs.

In this update, the number of study participants increased from 16,429 (15 studies) to 37,443 (28 studies; 13 new studies: 1 RCT and 12 NRSIs). The studies were conducted worldwide; most originated from high-income countries (25 studies). Public institutions funded 22 (79%) of the studies. Most studies investigated the effects of rituximab on people with relapsing MS (19 studies; 27,500 (73%) participants). We identified 12 ongoing studies. Rituximab as 'first choice' for active relapsing MS None of the included studies compared rituximab to placebo. One RCT compared rituximab to dimethyl fumarate, with 24 months' follow-up. Rituximab may reduce the recurrence of relapse (odds ratio (OR) 0.16, 95% confidence interval (CI) 0.04 to 0.57; 195 participants; low-certainty evidence). The evidence is very uncertain on disability worsening and SAEs. Rituximab may result in little to no difference in upper respiratory tract infections (rate ratio (RR) 1.03, 95% CI 0.79 to 1.34; low-certainty evidence). The evidence is very uncertain for urinary tract, skin, and viral infections. HRQoL, cancer, and mortality were not reported. One NRSI compared rituximab to other DMTs, with 24 months' follow-up. Disability worsening was not reported. Compared with interferon beta or glatiramer acetate, rituximab likely delays relapse (hazard ratio (HR) 0.14, 95% CI 0.05 to 0.39; 1 study, 335 participants; moderate-certainty evidence). Compared with dimethyl fumarate and natalizumab, rituximab may delay relapse (dimethyl fumarate: HR 0.29, 95% CI 0.08 to 1.00; 1 study, 206 participants; low-certainty evidence; natalizumab: HR 0.24, 95% CI 0.06 to 1.00; 1 study, 170 participants; low-certainty evidence). The evidence for relapse is very uncertain when comparing rituximab to fingolimod. The effect on SAEs is uncertain due to very few events in all the comparison groups. No deaths were reported. HRQoL, common infections, and cancer were not reported. Rituximab as 'first choice' for primary progressive MS One RCT compared rituximab to placebo, with 24 months' follow-up. Rituximab likely results in little or no difference in disability worsening (OR 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). The evidence is very uncertain on relapse, SAEs, common infections, cancer, and mortality. HRQoL was not reported. None of the included studies compared rituximab as 'first choice' treatment to other DMTs for primary or secondary progressive MS. Rituximab as 'switching' treatment for relapsing MS One small RCT compared rituximab to placebo, with 12 months' follow-up. Disability worsening was not reported. Rituximab may reduce recurrence of relapses (OR 0.38, 95% CI 0.16 to 0.93; 1 study, 104 participants; low-certainty evidence). The evidence is very uncertain regarding SAEs, common infections, cancer, and mortality. HRQoL was not reported. Twelve NRSIs compared rituximab to other DMTs, with 24 months' follow-up. The evidence on disability worsening is very uncertain in comparison with interferons or glatiramer acetate, natalizumab, alemtuzumab, and ocrelizumab. Rituximab likely delays time to relapse in comparison with interferons or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 study, 1383 participants; moderate-certainty evidence), fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 study, 256 participants; moderate-certainty evidence), and may result in little or no difference compared with natalizumab (HR 0.96, 95% CI 0.83 to 1.10; 3 studies, 1922 participants; low-certainty evidence). The evidence is very uncertain on relapse in comparison with alemtuzumab. There is uncertainty regarding SAEs when comparing rituximab to natalizumab and fingolimod. Rituximab likely increases serious common infections when compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 study, 5477 participants; moderate-certainty evidence) and natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 studies, 5001 participants; moderate-certainty evidence). The evidence for common infections is very uncertain when comparing rituximab to fingolimod and ocrelizumab. Rituximab may slightly reduce the risk of cancer compared with natalizumab (HR 0.79, 95% CI 0.62 to 0.99; 2 studies, 6202 participants; low-certainty evidence), whereas the evidence is very uncertain in comparison with fingolimod. The effect of rituximab on mortality is very uncertain due to very few events in all the comparison groups. HRQoL was not reported.

For preventing relapses in relapsing MS, rituximab as 'first choice' and 'switching' treatment compares favourably with a wide range of approved DMTs. The protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab on primary progressive MS. There is limited evidence for long-term adverse events of rituximab in people with MS. Evidence for serious adverse events, cancer, and mortality was of very low certainty due to few events. There is an increased risk of serious (hospital-treated) infections with rituximab compared with other DMTs, although the absolute risk is low. High-quality (prospectively registered) NRSIs should be conducted to draw more reliable conclusions about the potential benefits and harms of rituximab in people with MS.

Previous genetic and epidemiological studies have examined subpopulations from the Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) patient cohort, but an encompassing analysis of the study population has not yet been carried out.

This retrospective study examines patterns of multiple sclerosis (MS) prevalence in 13,663 cohort members, including 4,821 persons with MS or suspected MS and 8,842 family members.

We grouped participants into epidemiologic subgroups based on age of MS onset, clinical stage at diagnosis, symptom type at disease onset, sex, proband status, disability as measured by the EDSS, and ancestry based on reported ethnicity.

We observed a 2.7:1 MS prevalence ratio of women to men, though disease severity was greater for male patients. Variation in the age of disease onset between patients was only slightly associated with sex and strongly associated with disease type. Specific types of clinical symptoms at disease onset were associated with the prognosis. Regional residence did not correlate with disease onset, type, or severity.

Population trends, as presented here, are not explained by environmental factors alone, highlighting the need for a comprehensive genetic analysis to understand disease variance across families.

Multiple Sclerosis (MS) is a common chronic disease among young adults. It affects various aspects of Quality of Life (QOL). Dysphagia is a problem associated with neurological damage in MS patients. This study aimed to compare MS patients' QOL with and without dysphagia. This is a cross-sectional study performed on 40 patients with MS (20 with and 20 without dysphagia) selected from the MS Society members of Ahvaz, Iran. Research tools included the Persian version of Dysphagia in Multiple Sclerosis (DYMUS), Mini-Mental State Examination (MMSE), and Multiple Sclerosis Quality of Life-54 (MSQOL-54). The data were analyzed by SPSS software version 22 and the Mann-Whitney test. The results showed a significant difference in QOL score amongst patients with and without dysphagia. The QOL score of patients with dysphagia was significantly lower than patients without dysphagia. The main differences in the subscale of the QOL Index were mental component and physical activity. MS patients with dysphagia had lower QOL than patients without it. The results show that the quality of life of MS patients with dysphagia is lower than the quality of life of MS patients without dysphagia, and this issue includes different physical and mental aspects of the quality of life of these patients. According to the findings of this study, it seems that early referral of patients with MS to speech and language pathologists for the management of swallowing disorders in the early stages of the disease can be very important and help improve the wellbeing of these patients and their families.

Multiple sclerosis (MS) is a heterogeneous disease, and each MS patient exhibits different clinical symptoms that are reflected in their magnetic resonance imaging (MRI) results. Each MS lesion should be interpreted carefully and evaluated in conjunction with a clinical examination. MRI plays a major role in evaluating how MS lesions are aggregated in the central nervous system and how they change over time. There are several conventional MRI biomarkers of MS that could be utilized to evaluate each MS phenotype. MRI is useful for clinical decisions, aiding in the determination of disease-modifying treatment or disease prognosis. Despite its higher sensitivity, MRI provides low specificity due to the heterogeneity of MS lesions. However, advanced MRI biomarkers show promise in terms of defining MS lesions, as each imaging biomarker correlates differently with the clinical scenario of each MS phenotype. The aim of this review is to summarise the current state of MRI biomarkers for MS in the brain and how they relate to neurological disabilities.

Invasive procedures may delay the diagnostic process in multiple sclerosis (MS). We investigated the added value of serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), chitinase-3-like 1 (sCHI3L1), and the immune responses to the Epstein-Barr virus-encoded nuclear antigen 1 to current MS diagnostic criteria.

In this multicentric study, we selected patients from 2 prospective cohorts presenting a clinically isolated syndrome (CIS). Patients were classified as (1) not presenting dissemination in space (DIS) nor dissemination in time (DIT) (noDIS and noDIT); (2) presenting DIS without DIT (DIS and noDIT); and (3) presenting both (DIS and DIT), which were used as a reference. sNfL, sGFAP, and sCHI3L1 levels were measured with single-molecule array immunoassays and EBNA1-specific IgG levels with ELISA. Biomarker levels were compared between groups using linear regression models. Receiver operating characteristic curve analyses and Youden Index were used to determine cutoff values associated with MS diagnosis during follow-up.

We included 181 patients (66.3% females, mean [SD] age of 35.0 [9.7] years). At baseline, 25 (13.8%) were classified as noDIS and noDIT, 62 (34.3%) as DIS and noDIT, and 94 (51.9%) as DIS and DIT. Only sNfL Z-scores discriminated between groups (DIS and DIT vs DIS and noDIT [p = 0.002], DIS and DIT vs noDIS and noDIT [p < 0.001], and DIS and noDIT vs noDIS and noDIT [p = 0.026]). In noDIS and noDIT patients (median interquartile range [IQR] follow-up of 8.1 [5.0-11.7] years), high sNfL Z-scores best predicted MS diagnosis (specificity [SP] and 95% CI of 93.3% [68.1-99.8] and positive predictive value [PPV] of 87.5% [47.3-99.7]). Among DIS and noDIT patients (median [IQR] follow-up of 6.8 [4.0-9.1] years), high sNfL Z-scores best predicted MS diagnosis (SP of 80% [28.4-99.5] and PPV of 97.3% [85.8-99.9]) without considering oligoclonal band (OB) status. In the subset of patients of this group with negative OBs, a combination of high sNfL Z-scores and sGFAP levels predicted MS diagnosis (SP of 100% [39.8-100] and PPV of 100% [54.1-100]).

These results suggest that sNfL and sGFAP may be incorporated in particular scenarios to diagnose MS in patients with CIS not fulfilling current diagnostic criteria.

To evaluated the predictive value of several cerebrospinal fluid (CSF) cytokines in the conversion of clinically isolated syndrome (CIS) patients to neuromyelitis optica spectrum disorder (NMOSD) or multiple sclerosis (MS).

We enrolled 33 CIS patients whose CSF samples were collected during the acute phase of the first onset before immunotherapy. The CSF levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13, IL-17A, IL-21, IL-23, interferon-γ (IFN-γ) and transforming growth factor beta 1 (TGF-β1) were measured using the human cytokine multiplex assay or ELISA. Patients were seen every 3 to 6 months. Unscheduled visits occur in case of exacerbations. Clinical measures of disease progression were recorded.

The mean follow-up of CIS patients was 23.2 ± 7.9 months. Six patients converted to NMOSD, six patients converted to MS. The CSF IL-21 and IL-6 levels were significantly elevated in CIS patients converted to NMOSD than those who did not. High CSF IL-6 levels are a predictor of conversion to NMOSD in patients with CIS and are associated with a shorter time to conversion. Increased CSF IL-6 levels correlated with CSF WBC count, protein level and IgG index, segment of myelitis, EDSS scores. There was no significant difference in cytokine levels between patients who converted to MS and those who did not.

These findings validate CSF IL-6 as an independent predictive factor for the risk of clinical conversion to NMOSD in CIS. The above CSF cytokines levels in CIS patients can't predict conversion to MS.

The 2017 McDonald criteria continued the separation of diagnostic criteria for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS) for historical, rather than biological, reasons. We aimed to explore the feasibility of a single, unified set of diagnostic criteria when applied to patients with suspected PPMS.

We retrospectively identified patients evaluated for suspected PPMS at 5 European centers. The 2017 McDonald PPMS criteria was the gold standard against which the 2017 McDonald RRMS dissemination in space (DIS) and dissemination in time criteria were evaluated. We also investigated modified RRMS DIS criteria, including: (i) optic nerve lesions; (ii) ≥2 spinal cord lesions; and (iii) higher fulfilment of DIS criteria alone (lesions in ≥3 regions) without dissemination in time/positive cerebrospinal fluid, for a diagnosis of PPMS.

A total of 282 patients were diagnosed with PPMS using the 2017 McDonald criteria, and 40 with alternate disorders. The 2017 McDonald RRMS DIS criteria and the modified DIS criteria including the optic nerve or ≥2 spinal cord lesions performed well in PPMS diagnosis when combined with dissemination in time/positive cerebrospinal fluid (sensitivity 92.9-95.4%, specificity 95%, accuracy 93.2-95.3%). A diagnosis of PPMS based on high fulfillment of modified RRMS DIS criteria had high specificity, but low sensitivity. A diagnostic algorithm applicable to patients evaluated for suspected MS is proposed.

The 2017 McDonald RRMS criteria and modifications to DIS criteria, currently under consideration, performed well in PPMS diagnosis. Forthcoming revisions to the McDonald criteria should consider a single, unified set of diagnostic criteria for MS. ANN NEUROL 2025;97:571-582.

Objective: Cognitive impairments are one of the most common and disabling symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here, we address the possibility of a specific cognitive profile inherent to ME/CFS. Due to the occurrence of cognitive deficits, fatigue, and pain in both pathologies, multiple sclerosis (MS) is a relevant comparison model. For this purpose, we carried out a comparative study between cognitive profiles of patients with ME/CFS and patients suffering from MS. Methods: In total, 40 ME/CFS and 40 MS patients were included. A complete screening of all cognitive functions was carried out through an extensive battery of tests routinely used in clinical practice. Results: ME/CFS and MS patients showed deficits in episodic memory retrieval, visual selective attention and reading speed. ME/CFS patients also elicited a lower level of performance than MS patients regarding consolidation. For both groups, levels of performance on these cognitive tests did not correlate with levels of fatigue, pain, and depression. Conclusions: This study highlighted both similarities and differences in the cognitive profiles of ME/CFS and MS patients. While both groups exhibited deficits in episodic memory retrieval, visual selective attention, and reading speed, ME/CFS patients showed distinct impairment in consolidation processes. These cognitive deficits were not correlated with fatigue, pain, or depression, reinforcing the hypothesis of intrinsic cognitive dysfunction in ME/CFS. These findings define a specific cognitive phenotype for ME/CFS, which could improve diagnostic accuracy and therapeutic strategies. Future research, particularly in functional imaging, may elucidate the neurobiological mechanisms underlying these impairments.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) are a hallmark of MS and reflect intrathecal IgG synthesis and inflammation. This study aims to analyze the temporal distribution of IgG OCBs in the CSF of patients with a definitive diagnosis of MS. Methods: This retrospective study included 500 patients with diagnosed MS. Patients were divided into four groups according to diagnostic epochs: Group 1 (Pre-2001 or Pre-McDonald), Group 2 (2001-2010 or McDonald 2001-Polman 2010), Group 3 (2010-2018 or Polman 2010), and Group 4 (Post-2018 or Thompson 2017). Statistical analyses examined temporal and sex differences in OCB positivity rates. Results: OCB positivity was lower in Group 4 (69.2%) compared to Group 1 (85.4%) in the overall population (p = 0.0022). A decrease in OCB positivity was observed in Groups 3 (62.5%) and 4 (71.8%) compared to Group 1 (92.5%) among males (p = 0.0117 and p = 0.0198, respectively) and in Group 4 (68.1%) compared to Group 1 (82.5%) among females (p = 0.0274). Conclusions: The present study provides valuable insights into temporal trends in CSF positivity among patients diagnosed with MS. There was an overall decrease in OCB positivity rates over the years, particularly in the post-2018 period.

Multiple sclerosis (MS) is a chronic autoimmune disorder that significantly impacts individuals' quality of life and imposes a substantial social burden on patients and society. Despite its global socioeconomic implications, limited research has focused on the social burden of MS. This study aimed to assess the social burden of MS in Georgia by evaluating the health-related quality of life of MS patients and exploring the correlation between disease burden and quality of life.

This cross-sectional study was performed to assess the social burden of the disease by evaluating the impact of the disease on the quality of life of 384 patients with MS. The Multiple Sclerosis Quality of Life-54 questionnaire was administered to assess quality of life.

The Expanded Disability Status Scale score was significantly negatively correlated with the physical health composite score (r = -0.249, P < .001) and the general quality of life score (r = -0.220, P < .001). The quality of life was highly associated with gender, employment status, living/residence place, and moderately with age.

This study revealed the intricate interplay between disability, quality of life, and sociodemographic factors among Georgian MS patients. The results of the study highlight the need for specialized therapies, networks of support, and public health initiatives to lessen the societal cost of MS.

(Poly)phenols are a wide and heterogeneous class of substances with several potential health benefits. Their role in neuroprotection and cognition is still questionable. This study's scope is to examine the possible association between total and individual (poly)phenol intake, major dietary sources, and the severity of multiple sclerosis (MS) in a cohort of MS patients. Participants' demographics, physical activity, smoking, and dietary information were collected, alongside clinical parameters including the Expanded Disability Status Score (EDSS), Multiple Sclerosis Severity Score (MSSS), MS phenotype, and current therapy. A validated 110-item food frequency questionnaire (FFQ) was used to assess participants' habits. The (poly)phenol content of foods was estimated using the Phenol-Explorer database. Data from 106 participants were analyzed. A high intake of vegetables was associated with a 4.6-fold higher probability of mild MS (95% CI: 1.49, 14.28), whereas no association was found for other food and beverage sources. Hydroxycinnamic acids were significantly related to MSSS (OR: 6.55, 95% CI: 2.15, 19.92). Although coffee intake differed significantly between patients with mild and severe MS (90.5 ± 53.9 vs. 59.4 ± 40.8 mL/d, respectively), linear regression analysis did not confirm an association with MSSS. A higher intake of hydroxycinnamic acids and vegetables may impact MS severity. Coffee's role remains unclear and needs to be further investigated.

Neuromyelitis optica spectrum disorder (NMOSD) with positivity for aquaporin-4 antibody (AQP4-IgG) represents one of the mains etiologies of longitudinally extensive transverse myelitis (LETM). Advancements in early diagnosis and treatment have led to a decline in NMOSD-related mortality. However, long-term prognostic data for patients experiencing their first episode of LETM remain scarce, especially in Brazil. This study aims to evaluate the final diagnosis and long-term prognosis of patients with first episode of LETM and investigate factors associated with worse prognosis.

This is an observational retrospective study involving all consecutive patients diagnosed with longitudinally extensive myelopathy who were sequentially referred to the clinical neurology department of a brazilian tertiary hospital between January 2005 and December 2011. Only patients meeting the criteria for the first episode of idiopathic LETM were included. Data were retrieved from electronic medical records from October 2023 to January 2024.

39 patients met the inclusion criteria. After a median follow-up of 12 years, 51% patients remained with isolated monophasic seronegative LETM, 28% were diagnosed with NMOSD AQP4-IgG positive, 7.7% with NMOSD AQP4-IgG negative, 5% with MOGAD, 5% experienced recurrent seronegative LETM, and only 1 (2.6%) developed multiple sclerosis. The mortality rate was 10% at last follow-up, with a median time to death of 3 years. Deceased patients had a higher age at onset of LETM (OR 1.09, 95% CI 1.01-1.21). Among survivors, 17% had an Expanded Disability Status Scale (EDSS) ≥7 at last follow-up. Predictors of severe sequelae included higher EDSS at nadir (OR 5.29; 95% CI 1.38-39), pain as an initial myelitis symptom (OR 11.1; 95% CI 1.51-230) and spinal shock during the first myelitis (p < 0.001).

In this cohort, after a median 12-year follow-up, half of the patients remained as isolated monophasic seronegative LETM, mortality reached 10% and 83% of survivors were ambulatory. Predictors of poor prognosis included older age, presence of pain as an initial symptom and higher initial severity.

Alterations in structural connectivity of brain networks have been linked to complex cognitive functions in people with multiple sclerosis (PwMS). However, a definitive consensus on the optimal diffusion tensor imaging (DTI) markers as indicators of cognitive performance remains incomplete and inconclusive. This systematic review and meta-analysis aimed to explore the evidence on the correlation between DTI metrics and cognitive functions in PwMS.

A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, and the Web of Science up to March 2024 to identify studies reporting the correlation between DTI metrics and cognitive functions. Cognitive function was assessed using the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT), and Brief Visuospatial Memory Test-Revised (BVMT-R). The pooled correlation coefficients were estimated using R software version 4.4.0 with the random effect model.

Out of 1952 studies, 38 studies on 2055 PwMS fulfilled the inclusion criteria. The meta-analysis indicated that the SDMT exhibited the greatest correlation with corpus callosum fractional anisotropy (FA) (r = 0.54, 95 % CI: 0.4 to 0.66, p-value < 0.001, I2 = 34.1 %, p-heterogeneity = 0.19) and mean diffusivity (MD) (r = -0.48, 95 % CI: 0.61 to -0.33, p-value < 0.001, I2 = 0 %, p-heterogeneity = 0.77), white matter FA (r = 0.39, 95 % CI: 0.24 to 0.52, p-value < 0.001, I2 = 0 %, p-heterogeneity = 0.1), and fornix FA (r = 0.35, 95 % CI: 0.12 to 0.54, p-value = 0.003, I2 = 50.7 %, p-heterogeneity = 0.18) and MD (r = -0.35, 95 % CI: 0.49 to -0.19, p-value < 0.001, I2 = 0 %, p-heterogeneity = 0.5).

DTI measurements, including corpus callosum FA and MD, white matter FA, and fornix FA and MD, represent the indicators of cognitive performance in PwMS. Nonetheless, these findings warrant cautious interpretation due to the restricted kinds of cognitive tests and methodological variability across studies.

Multiple sclerosis (MS) is a chronic autoimmune condition characterized by central nervous system demyelination. Its coexistence with primary biliary cholangitis (PBC), another autoimmune disease, is rarely described in the literature. This is the case of a 35-year-old Emirati female patient with a history of PBC who presented with unsteady gait and neurological symptoms. Neurological examination revealed dysmetria, wide-based gait, and brisk reflexes. MRI findings confirmed MS, and she was treated with methylprednisolone and disease-modifying therapies. MS and PBC share immune dysregulation, involving genetic loci like CD28 and T-cell-mediated mechanisms. Their coexistence complicates diagnosis due to overlapping symptoms such as fatigue and neurological impairment. While rare, concurrent autoimmune diseases in MS patients may influence disease progression and disability outcomes. This case emphasizes the need for multidisciplinary care in managing coexisting autoimmune diseases and for further research regarding the shared mechanisms of these coexisting autoimmune diseases.

McDonald criteria (MC) are a globally accepted standard for the diagnosis of multiple sclerosis (MS). Misdiagnosis of MS is a common problem that has significant clinical consequences for patients. Misapplication of MC is a potential source of MS misdiagnosis. Recent research has identified elements of the criteria that are frequently misunderstood by neurologists in the US.

To assess application of MC by German neurologists.

A previously developed survey instrument was modified and distributed to neurology residents and specialists (general neurology, not MS-subspecialists).

68 neurologists (42 neurology residents (NR) and 26 neurology specialists (NS) completed the survey. We found frequent misapplication of MC. Symptoms atypical for MS were mistaken as typical by 31 % of participants. Understanding of MRI dissemination in space criteria was poor. Periventricular and juxtacortical lesions were incorrectly identified by 46 % and 55 %, respectively. Most participants accepted purely anamnestic reports of previous neurological symptoms without objective clinical evidence as sufficient to prove dissemination in time.

Training and continuing education on MS diagnostic criteria needs to be improved, especially concurrent with dissemination of future iterations of MC.