Course Of Multiple Sclerosis Research Articles

Neuroapraxia of Trigeminal Nerve Controlled by Neuromonitoring During Microvascular Decompression in Multiple Sclerosis Patients Affected by Drug-Resistant Trigeminal Neuralgia Recurrent After Previous Operations

BACKGROUND AND IMPORTANCE: Trigeminal neuralgia (TN) can complicate the clinical course of multiple sclerosis (MS) and can be very difficult to treat. Usually, these patients experience multiple recurrences after surgical procedures with a poor overall outcome. To the best of our knowledge, we report the first 3 cases of drug-resistant MS-related TN recurrent after previous operations in which intraoperative neuromonitoring controlled neuroapraxia of trigeminal nerve was performed. We describe the surgical technique, report the clinical outcomes of patients, and review the pertinent literature. CLINICAL PRESENTATION: Neuroapraxia of trigeminal nerve was conducted using a standard straight Yasargil temporary titanium aneurysm clip on the main trunk of the trigeminal nerve. Trigeminal somatosensory evoked potentials and cortico-bulbar motor evoked potentials registered from trigeminal and facial nerves were recorded during the procedure. The trigeminal nerve clipping was conducted for a maximum of 30 seconds or less in the case of a decrease in neurophysiological responses. The preoperative Barrow Neurological Institute score was V, IV, and IV for the 3 patients, respectively. We obtained acute pain relief in all patients after the procedure. All patients had a Barrow Neurological Institute I at the latest follow-up (10, 10, and 9 months, respectively). No complications were reported postoperatively and at follow-up. CONCLUSION: Intraoperative neuromonitoring controlled neuroapraxia of trigeminal nerve with temporary titanium aneurysm clip application during microvascular decompression is a promising and safe procedure in MS patients with recurrent MS-related TN. Further studies with longer follow-up are needed to confirm our encouraging results.

Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients.

Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS. In this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank. We identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren's syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibodyfinding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis. Our study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.

Paramagnetic rim lesions are associated with inner retinal layer thinning and progression independent of relapse activity in multiple sclerosis.

Paramagnetic rim lesions (PRLs) are chronic active lesions associated with a severe disease course in multiple sclerosis (MS). This study was undertaken to investigate an association between retinal layer thinning (annualized loss of peripapillary retinal nerve fiber layer [aLpRNFL] and ganglion cell-inner plexiform layer [aLGCIPL]) and PRLs in patients with MS (pwMS). In this study, pwMS with brain magnetic resonance imaging and ≥2 optical coherence tomography scans were included. Cox proportional hazard regression models were performed using progression independent of relapse activity (PIRA) as the dependent variable, and aLpRNFL, aLGCIPL, or the number of PRLs as independent variables, adjusted for covariates. We analyzed data from 97 pwMS (mean age = 35.2 years [SD = 9.9], 71.1% female, median disease duration = 2.3 years [interquartile range = 0.9-9.0]). The number of PRLs was associated with aLpRNFL and aLGCIPL. PIRA was observed in 18 (18.6%) pwMS, with aLpRNFL (hazard ratio [HR] = 1.44 per %/year), aLGCIPL (HR = 1.61 per %/year), and the number of PRLs (HR = 1.24 per PRL) being associated with increased risk of PIRA. The number of PRLs is associated with inner retinal layer thinning and increased risk of PIRA. A combination of PRLs and retinal layer thinning could serve as a surrogate for pwMS at highest risk of disability progression.

Observational study of gadolinium-enhancing lesions in MRI in patients with multiple sclerosis from the Spanish Mediterranean coast: seasonal variability and relationship with climatic factors

IntroductionEnvironmental factors appear to play an important role in the development and course of Multiple Sclerosis (MS). Seasonal variability in disease activity has been described and it is postulated that it may vary according to geographical area. The aim of this study is to analyse the monthly distribution of activity observed on Magnetic Resonance Imaging (MRI) and to look for a possible relationship with climate in patients with relapsing remitting MS. Material and methodsRetrospective observational study, carried out in the population of one hospital on the Spanish Mediterranean coast. A total of 238 MRI scans of 51 patients were evaluated. Climatological data were obtained from the Spanish State Meteorological Agency from 2012 to 2016. Activity was defined as contrast-enhancing lesions. ResultsThe distribution of gadolinium-enhancing lesions was found to be non-uniform across months (p=0.008). Visual inspection suggests higher activity in July and August. Regarding weather, tropical nights (defined as days with a minimum temperature above 20°C) were associated with increased risk of MRI activity (OR=1.06, p=0.001). ConclusionThese findings suggest a non-uniform monthly distribution of gadolinium-enhancing lesions and an association between warmer nights and increased MRI activity, pointing to a potential impact of environmental factors on multiple sclerosis activity in neuroimaging.

Effect of Diet and Dietary Patterns on the Progression of Multiple Sclerosis: A Review

The link between diet and the progression of Multiple Sclerosis (MS) is a topic of growing interest and investigation within the medical community. This review explored the mechanisms through which dietary interventions can impact the course of MS and shape the clinical outcomes and quality of life of individuals with the disease. By synthesizing current knowledge from clinical studies and observational research, the review aimed to provide insights into the role of diet in managing MS. A comprehensive literature search was conducted, focusing on the effect of diet and dietary patterns on the progression of MS. Key findings indicated that individuals with higher diet quality exhibit reduced disability levels and lower symptom severity, emphasizing the importance of maintaining a healthy diet and adopting a holistic, healthy lifestyle in managing MS. The review also delved into the potential impact of macronutrients, vitamins, and minerals on the progression of MS, highlighting the importance of adequate nutrient intake for optimal health outcomes. Additionally, the study explored the association between dietary intake variations and the severity of MS, suggesting that further investigation is needed to understand the potential implications of nutrient deficiencies in MS patients. Overall, the review serves as a valuable resource for healthcare professionals and individuals living with MS, providing evidence-based dietary approaches that may help optimize health outcomes and mitigate the burden of the disease. It also calls for future research directions in the critical area of dietary management of MS to enhance our understanding and improve patient care.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study

BackgroundIt remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.MethodsThis large-scale cohort study included persons with MS with CSF data documented...

Selected Interleukins Relevant to Multiple Sclerosis: New Directions, Potential Targets and Therapeutic Perspectives.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that progresses with demyelination and neurodegeneration. To date, many studies have revealed the key role of interleukins in the pathogenesis of MS, but their impact has not been fully explained. The aim of the present study was to collect and review the results obtained so far regarding the influence of interleukins on the development and course of MS and to assess the potential for their further use. Through the platform "PubMed", terms related to interleukins and MS were searched. The following interval was set as the time criterion: 2014-2024. A total of 12,731 articles were found, and 100 papers were subsequently used. Cells that produce IL-10 have a neuroprotective effect, whereas those that synthesize IL-6 most likely exacerbate neuroinflammation. IL-12, IL-23 and IL-18 represent pro-inflammatory cytokines. It was found that treatment with an anti-IL-12p40 monoclonal antibody in a study group of MS patients showed a beneficial effect. IL-4 is a pleiotropic cytokine that plays a significant role in type 2 immune responses and inhibits MS progression. IL-13 is an anti-inflammatory cytokine through which the processes of oligodendrogenesis and remyelination occur more efficiently. The group of interleukins discussed in our paper may represent a promising starting point for further research aimed at finding new therapies and prognostic markers for MS.

Exploring the impact of wearing-off phenomenon in ocrelizumab-treated multiple sclerosis patients: Insights from a comprehensive study

BackgroundOcrelizumab (OCR) effectively modifies the disease course in multiple sclerosis (MS) patients but may cause a preinfusion "wearing-off phenomenon" (WoP). This study explored the prevalence, timing, and severity of this phenomenon in MS patients using the OCR, as well as the associated symptoms and treatment satisfaction. MethodsWe conducted a prospective multicenter study across 11 MS centers involving MS patients aged 18-70 years who had received at least two OCR doses. The study employed a questionnaire addressing demographic, clinical, and radiological data; symptom progression; and treatment satisfaction. ResultsOf the 409 patients included in the study, 406 participated. A significant portion experienced varying degrees of WoP: 39.2% sometimes, 25.9% usually, and 14.3% always, with 55.9% noting symptom onset over four weeks prior to their next dose. Common symptoms included fatigue, walking difficulties, and pain. Subgroup analysis of 334 patients revealed that 78.1% of patients experienced these effects, which correlated with shorter disease durations, a longer delay between the two doses before the last dose, and a greater rate of relapse (P>0.05). ConclusionThe WoP of the OCR is prevalent and significant among MS patients and is influenced by the dosing interval, disease duration, and relapse rate. These insights underscore the need for personalized treatment schedules and more research into factors affecting MS management.

Relapse-Associated and Relapse-Independent Contribution to Overall Expanded Disability Status Scale Progression in Multiple Sclerosis Patients Diagnosed in Different Eras.

The introduction of disease-modifying therapies for multiple sclerosis (MS) has led to a deceleration of disease course over the years. Although decreased relapse rate constitutes a factor, the role of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) in MS course deceleration is still unclear. We retrospectively examined long-term Expanded Disability Status Scale (EDSS) progression in patients referred to the MS Center of Montichiari (Italy) and diagnosed with relapsing-remitting MS from 1980 to 2022. To isolate PIRA, we deducted all EDSS changes associated with relapses from overall EDSS change. We compared the relative contribution of PIRA and RAW to EDSS progression in patients diagnosed in different periods using mixed-effects models. A total of 1,405 patients were included in the study, of whom 231 were diagnosed in 1980-1996 (pre-treatment era), 577 in 1997-2008 (injectable disease-modifying therapy era), and 597 after 2008 (oral drugs, monoclonal antibodies, and anti-CD20 era). Across ages, both PIRA and RAW were reduced in patients diagnosed in more recent periods as compared with earlier periods. The average contribution of PIRA to overall EDSS progression was already predominant in patients diagnosed in 1980-1996 (78%) and in 1997-2008 (76%), but it was significantly increased (p = 0.0009) in patients diagnosed in later years (87%). The deceleration of MS course observed throughout the years is determined not only by fewer RAW events, but also by a reduction in PIRA. However, the shift toward a mostly relapse-independent progression highlights the importance of evaluating new therapies based on their effect on PIRA. ANN NEUROL 2024.

Age-Related Features of Clinical and Neurological Characteristics and Pathogenetic Therapy in Patients with Multiple Sclerosis

INTRODUCTION: Multiple sclerosis (MS) is a neurological demyelinating disease of the central nervous system manifested by pronounced heterogeneous symptoms. Peculiarities of the onset, progression rate, and severity of syndromes are different in different age groups. An increase in the frequency of exacerbations, high degree of disability of patients in different age groups evidence insufficient effectiveness of the conducted pathogenetic therapy. Due to a wide choice of multiple sclerosis disease modifying drugs (MSDMDs), it is important to study the clinical and neurological characteristics of patients with MS in different age groups with the aim of further developing an individual approach to treatment. AIM: To study clinical and neurological features and effectiveness of pathogenetic therapy of MS in patients of different age groups. MATERIALS AND METHODS: A prospective analysis of the data of neurological examination and results of magnetic resonance imaging of 100 patients of different age groups with relapsing-remitting MS, who received outpatient treatment in Kursk Regional Multidisciplinary Clinical Hospital, was conducted in the period of stable remission. RESULTS: The leading syndromes in patients with relapsing-remitting course of MS were cerebellar (78%) and pyramidal (70%) syndromes, besides, dysfunction of the cranial nerves (71%) was also observed. A quantitative parameter of explicitness of pelvic disorder syndrome predominated in middle-aged and elderly patients compared to young ones (p 0.001). Cognitive disorders were more often (14%) recorded in middle-aged and elderly patients (p 0.001). The use of glatiramer acetate permitted to reduce the degree of disability in young subjects (p 0.05); in patients of the middle age group, the most effective was a timely transition from interferon beta to ocrelizumab (p 0.05). The use of first-line MSDMDs (interferon-beta) in elderly patients demonstrated low effectiveness (p 0.05). CONCLUSION: In middle-aged and elderly patients with equal timing of MS onset, the neurological deficit is more expressed than in young ones. First-line pathogenetic therapy, in particular, glatiramer acetate, is more effective in young patients, while patients of middle age are recommended an early transition to second-line MSDMDs.

Olig2+ single-colony-derived cranial bone-marrow mesenchymal stem cells achieve improved regeneration in a cuprizone-induced demyelination mouse model.

Oligodendrocytes are the myelinating cells of the central nervous system. Brain injury and neurodegenerative disease often lead to oligodendrocyte death and subsequent demyelination-related pathological changes, resulting in neurological defects and cognitive impairment (Spaas et al., 2021; Zhang J et al., 2022). Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system. The pathology of MS is characterized by the loss of myelin, oligodendrocytes, and axons in the brain, brain stem, and spinal cord, as well as by white matter lesions (Lassmann et al., 2007). Unfortunately, no definitive cure for MS has been developed. Immunomodulatory and anti-inflammatory drugs are effective in the relapsing-remitting phase of MS because they reduce the frequency of relapses and the formation of inflammatory lesions; however, they do not alter the course of progressive MS and are insufficient to cure chronic neurological dysfunction (Xiao et al., 2015; Zhang et al., 2021). The treatment outcome is even worse for MS patients with primary and secondary progressions. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. MSCs are easy to expand in vitro and exhibit low immunogenicity, no tumorigenic risks, and ethical controversies, making them a promising candidate for regenerative medicine (Zhang L et al., 2022; Xu et al., 2023). Many studies have confirmed the neural differentiation potential of MSCs under certain conditions, making them a prime candidate for treating neurodegenerative diseases (Jang et al., 2010; Yan et al., 2013). The present study investigated the effects of cranial bone-marrow mesenchymal stem cells (cBMMSCs) and oligodendrocyte-specific protein 2-positive (Olig2+) single-colony-derived cBMMSC (sc-cBMMSC), isolated in our previous work (Yang et al., 2022), in a central nervous system demyelination mouse model.

Utility of an Untargeted Metabolomics Approach Using a 2D GC-GC-MS Platform to Distinguish Relapsing and Progressive Multiple Sclerosis.

Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease of the central nervous system (CNS) in young adults and results in progressive neurological defects. The relapsing-remitting phenotype (RRMS) is the most common disease course in MS, which ultimately progresses to secondary progressive MS (SPMS), while primary progressive MS (PPMS) is a type of MS that worsens gradually over time without remissions. There is a gap in knowledge regarding whether the relapsing form can be distinguished from the progressive course, or healthy subjects (HS) based on an altered serum metabolite profile. In this study, we performed global untargeted metabolomics with the 2D GC-GC-MS platform to identify altered metabolites between RRMS, PPMS, and HS. We profiled 235 metabolites in the serum of patients with RRMS (n = 41), PPMS (n = 31), and HS (n = 91). A comparison of RRMS and HS patients revealed 22 significantly altered metabolites at p < 0.05 (false-discovery rate [FDR] = 0.3). The PPMS and HS comparisons revealed 28 altered metabolites at p < 0.05 (FDR = 0.2). Pathway analysis using MetaboAnalyst revealed enrichment of four metabolic pathways in both RRMS and PPMS (hypergeometric test p < 0.05): (1) galactose metabolism; (2) amino sugar and nucleotide sugar metabolism; (3) phenylalanine, tyrosine, and tryptophan biosynthesis; and (4) aminoacyl-tRNA biosynthesis. The Qiagen IPA enrichment test identified the sulfatase 2 (SULF2) (p = 0.0033) and integrin subunit beta 1 binding protein 1 (ITGB1BP1) (p = 0.0067) genes as upstream regulators of altered metabolites in the RRMS vs. HS groups. However, in the PPMS vs. HS comparison, valine was enriched in the neurodegeneration of brain cells (p = 0.05), and heptadecanoic acid, alpha-ketoisocaproic acid, and glycerol participated in inflammation in the CNS (p = 0.03). Overall, our study suggests that RRMS and PPMS may contribute metabolic fingerprints in the form of unique altered metabolites for discriminating MS disease from HS, with the potential for constructing a metabolite panel for progressive autoimmune diseases such as MS.

The Prevalence of Comorbidities and Their Association With Disability Progression in Individuals With Multiple Sclerosis: A Study From Brazil.

Comorbidities negatively impact the course of multiple sclerosis (MS). Identifying them is essential, as they represent potentially modifiable prognostic factors that can adversely influence the disease course. However, comorbidity prevalence remains underexplored in certain populations, including in individuals in Brazil. In this cross-sectional study, we describe the frequency of comorbidities and their correlation with MS disability progression in a Brazilian population by reviewing the medical records of patients from a single MS center in Brazil. Preexisting comorbidities and those present at the time of MS diagnosis were screened. We assessed the prevalence of comorbidities, their prevalence ratios (PR) and the association between them, their number, and the confirmed disability worsening (CDW) that emerged during the follow-up visits. Comorbidities were present in 68.9% of individuals. The most prevalent comorbidities included cardiovascular diseases (19.3%), migraine (13.3%), psychiatric disorders (12.4%), smoking (12.4%), autoimmune diseases (12.0%), respiratory diseases (10.3%), and neoplasms (5.6%). Patients with 1 comorbidity and those with multiple comorbidities (≥ 3) had a significant PR for CDW (2.67, P = .01; 1.25, P = .03, respectively). Cardiovascular and autoimmune diseases presented significant PR for CDW (2.28, P = .03; 4.2, P = .004, respectively). Comorbidities are more prevalent among Brazilian individuals with MS than in the general population and are associated with disease progression. Identifying and managing them may mitigate their adverse effects on disease course.

Brain reserve and timing of clinical onset in multiple sclerosis

Background: A latent period of variable length elapses between multiple sclerosis (MS) biological onset and the occurrence of the first clinical episode reflecting a central nervous system (CNS) demyelinating event. Factors affecting the duration of such interval are unknown. Objective: To explore whether brain reserve, which moderates the impact of structural damage along MS course, could also affect the timing of MS clinical onset. Methods: We conducted a time-to-event analysis in 326 relapsing-onset multiple sclerosis patients to ascertain the effect of brain reserve, that is, larger maximal lifetime brain growth (MLBG) estimated as intracranial volume, on the risk of an earlier disease onset. For this purpose, we carried out a Cox proportional hazards regression model stratified by sex and adjusted by site and pre-morbid MS risk factors. All patients reached the event (i.e. the disease onset) with no censored case; the age (years) at disease onset was set as the main time variable. Results: We identified a protective effect of brain reserve on the time to disease onset (HR = 0.11, 95% CI = 0.02–0.83, p = 0.032), unchanged when accounting for MS risk factors. Conclusion: Brain reserve might counteract the pathological mechanisms ongoing after biological initiation, thus delaying the disease overt clinical manifestation.

Impact of Coping Strategies on Health-Related Quality of Life in Young Adults with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic and progressive neurological disease that affects the central nervous system, resulting in a wide spectrum of cognitive, emotional, and physical deficits. The progressive course of MS poses significant challenges to patients and has a profound impact on health-related quality of life (HRQoL). The style of coping adopted plays a critical role in determining how individuals with MS adapt to and face the challenges of the disease and their overall well-being. This paper aims to examine the impact of coping strategies on HRQoL in young adults un-/minimally impaired (<5 years, EDSS ≤ 2.5) by MS (age 18-35 years). This retrospective cross-sectional cohort study included 98 young adults (33 males and 65 females) with relapsing-remitting MS who underwent neurological assessment using the Expanded Disability Status Scale. Participants completed the Italian version of the Multiple Sclerosis QoL-54 (MSQoL-54), which provides a physical and mental health score, and the Coping Orientation to Problems Experienced Inventory (Brief-COPE). The results showed a significant relationship between COPE scores and physical and mental health. Subjects affected by MS who tend to use more frequent coping strategies such as active planning, personal growth, and acceptance showed a better overall well-being and quality of life. These findings are relevant to clinical practice given the need to understand the coping variable to improve HRQoL. Understanding these relationships is crucial for developing effective interventions to enhance the well-being of MS subjects.

Understanding the Complex Dynamics of Immunosenescence in Multiple Sclerosis: From Pathogenesis to Treatment.

Immunosenescence, the gradual deterioration of immune function with age, holds profound implications for our understanding and management of multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system. Traditionally diagnosed in young adults, advancements in disease-modifying therapies and increased life expectancy have led to a growing number of older individuals with MS. This demographic shift underscores the need for a deeper investigation into how age-related alterations in immune function shape the course of MS, influencing disease progression, treatment effectiveness, and overall patient outcomes. Age-related immunosenescence involves changes such as shifts in cytokine profiles, the accumulation of senescent immune cells, and compromised immune surveillance, collectively contributing to a state known as "inflammaging". In the context of MS, these immunological changes disturb the intricate balance between inflammatory and regulatory responses, thereby impacting mechanisms of central immune tolerance and peripheral regulation. This paper stands out by combining the most recent advancements in immunosenescence with both pathophysiological and treatment perspectives on multiple sclerosis, offering a cohesive and accessible discussion that bridges theory and practice, while also introducing novel insights into underexplored concepts such as therapy discontinuation and the latest senolytic, neuroprotective, and remyelination therapies. Enhancing our understanding of these complexities will guide tailored approaches to MS management, ultimately improving clinical outcomes for affected individuals.

Biomarkers of tau phosphorylation state are associated with the clinical course of multiple sclerosis

BackgroundMechanisms underlying neurodegeneration in multiple sclerosis (MS) remain poorly understood but mostly implicate molecular pathways that are not unique to MS. Recently detected tau seeding activity in MS brain tissues corroborates previous neuropathological reports of hyperphosphorylated tau (p-tau) accumulation in secondary and primary progressive MS (PPMS). We aimed to investigate whether aberrant tau phosphorylation can be detected in the cerebrospinal fluid (CSF) of MS patients by using novel ultrasensitive immunoassays for different p-tau biomarkers. MethodsCSF samples of patients with MS (n = 55) and non-inflammatory neurological disorders (NIND, n = 31) were analysed with in-house Single molecule array (Simoa) assays targeting different tau phosphorylation sites (p-tau181, p-tau212, p-tau217 and p-tau231). Additionally, neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were measured with a multiplexed Simoa assay. Patients were diagnosed with clinically isolated syndrome (CIS, n = 10), relapsing-remitting MS (RRMS, n = 21) and PPMS (n = 24) according to the 2017 McDonald criteria and had MRI, EDSS and basic CSF analysis performed at the time of diagnosis. ResultsPatients with progressive disease course had between 1.4-fold (p-tau217) and 2.2-fold (p-tau212) higher p-tau levels than relapsing MS patients (PPMS compared with CIS + RRMS, p < 0.001 for p-tau181, p-tau212, p-tau231 and p = 0.042 for p-tau217). P-tau biomarkers were associated with disease duration (ρ=0.466–0.622, p < 0.0001), age (ρ=0.318–0.485, p < 0.02, all but p-tau217) and EDSS at diagnosis and follow-up (ρ=0.309–0.440, p < 0.02). In addition, p-tau biomarkers correlated with GFAP (ρ=0.517–0.719, p ≤ 0.0001) but not with the albumin quotient, CSF cell count or NFL. Patients with higher MRI lesion load also had higher p-tau levels p ≤ 0.01 (<10 vs. ≥ 10 lesions, all p ≤ 0.01). ConclusionCSF concentrations of novel p-tau biomarkers point to a higher degree of tau phosphorylation in PPMS than in RRMS. Associations with age, disease duration and EDSS suggest this process increases with disease severity; however, replication of these results in larger cohorts is needed to further clarify the relevance of altered tau phosphorylation throughout the disease course in MS.

Clinical characteristics and disease burden of African, Caribbean, and Black people with multiple sclerosis in Toronto, Canada

BackgroundDifferent racial and ethnic groups have demonstrated heterogeneity in the clinical course of multiple sclerosis(MS). ObjectiveWe aimed to evaluate disease characteristics in African, Caribbean, and Black people with MS(ACB-MS) followed at a single centre in Toronto, Canada. MethodsACB-MS were compared with age- and sex-matched people with MS (pwMS) of European descent(EUR-MS) identified through the clinic registry. Results344 PwMS were included(n = 172 ACB-MS, n = 172 EUR-MS; mean age 43 years, 68 % female). Baseline mean Expanded disability status scale (EDSS) scores (ACB-MS 2.3 ± 2.3 vs. EUR-MS 2.2 ± 2.0, p = 0.38) and subsequent clinical and radiological measures of disease activity were similar between groups, including annualized relapse rate (ARR)(ACB-MS 0.47 ± 0.47 vs. EUR-MS 0.41 ± 0.34, p = 0.2) and most recent EDSS (ACB-MS 2.7 ± 2.2 vs. EUR-MS 2.3 ± 2.1, p = 0.10). However, the proportion of MRI brain demonstrating new disease activity was higher(37% vs. 26 %, p < 0.05) and disability progression greater in ACB-MS vs. EUR-MS(43% vs. 33 %,p < 0.05) but measures of disease severity including MS Severity Score(3.17 vs. 2.58, p = 0.3) and Progression Index(PI) (0.27 vs. 0.30, p = 0.5) were comparable. Conclusion: Disability progression was seen more commonly in ACB-MS, though clinical disease activity and severity were generally comparable between ACB-MS and EUR-MS patients in Toronto, Canada. These findings partially differ from prior studies demonstrating more overtly aggressive MS disease courses in Black and African American PwMS, necessitating further studies to understand how structural determinants of health drive these disparities.

Circulating MAIT cells in multiple sclerosis and amyotrophic lateral sclerosis.

Neurological disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), may be associated with alterations in blood cell composition and phenotype. Here, we focused our attention on circulating mucosal-associated invariant T (MAIT) cells, a CD8+ T cell memory population expressing the invariant Vα7.2 region in the T cell receptor and high surface levels of the CD161 marker. Transcriptomics data relative to peripheral blood mononuclear cells (PBMC) highlighted downregulation of CD161 and other MAIT-associated markers in progressive MS and not relapsing remitting (RR)-MS when gene expressions relative to each disease course were compared to those from healthy controls. Multiparametric flow cytometry of freshly isolated PBMC samples from untreated RR-MS, primary or secondary progressive MS (PP- or SP-MS), ALS and age- and sex-matched healthy controls revealed specific loss of circulating CD8+ MAIT cells in PP-MS and no other MS courses or another neurological disorder such as ALS. Overall, these observations point to the existence of immunological changes in blood specific for the primary progressive course of MS that may support clinical definition of disease.

Safety of fingolimod in patients with relapsing remitting multiple sclerosis: A descriptive analysis of data from the EudraVigilance database

The most prevalent disease course of Multiple Sclerosis (MS) is relapsing remitting multiple sclerosis (RRMS). Fingolimod (Gilenya®) was the first oral disease-modifying therapy to RRMS. Patients affected by MS require long-term treatment, making the ongoing evaluation of the safety profile of fingolimod imperative. The aim of this study was to analyze the post-marketing pharmacovigilance data of fingolimod in Europe.Data of 12-year period (1 January 2011–19 June 2023) were obtained from EudraVigilance, and a descriptive analysis using drug-reaction pairs was performed.A total of 22,957 reports were collected. The most reported adverse events (AEs) were related to nervous system disorders SOC (multiple sclerosis relapse n = 2271; 3.51%, headache n = 921; 1.42%, central nervous system lesion n = 893; 1,38%, dizziness 769; 1,19%, hypoaesthesia 487; 0.75% and multiple sclerosis 449; 0.69%), followed by investigations (lymphocyte count decreased n = 1648; 2.55%, white blood cell count decreased n = 833; 1.29%), blood and lymphatic system disorder (lymphopenia n = 1146; 1.77%), and general disorders and administration site condition (fatigue n = 1106; 1.71%, gait disturbance 564; 0.87%). A percentage of 23.00% of serious adverse events (SAEs), among the most reported were multiple sclerosis relapse (n = 2271; 15.27%), macular oedema (n = 793; 5.33%), bradycardia (n = 678; 4.56%), leukopenia (n = 533; 3.58%), and multiple sclerosis (n = 449; 3.02%).Most of AEs were non-serious, some SAEs related to cardiac, ophthalmic and infectious disorders emerged: their prevalence, along with the alignment of reported AEs with existing literature, supports the overall safety of fingolimod. Considering the rare and long-term ADRs that may arise in patients chronically treated for MS, continuous pharmacovigilance remains essential.