Multiple Sclerosis Cases Research Articles

Obesity and Multiple Sclerosis Severity: A Mendelian Randomization Study.

Obesity is implicated in the development of multiple sclerosis (MS), but its effect on disability is less well-established. This study examined the effects of various obesity measures on MS severity in 12,584 MS cases, using Mendelian randomization to mitigate confounding. Results showed a significant association between higher genetically-determined body mass index (N = 806,834) and increased MS severity (P = 0.02). This finding was supported by additional measures of general obesity but not adiposity distribution. The convergence of this genetic evidence with prior observational studies strengthens the association between obesity and adverse long-term disability in MS, suggesting weight management as a potential therapeutic strategy. ANN NEUROL 2024.

Multiple Sclerosis: Appearance after Covid Vaccination

Background: Multiple sclerosis (MS) is a chronic autoimmune disease that primarily affects the central nervous system, often emerging in young adults. In the context of the global COVID-19 vaccination campaign, concerns have been raised about the potential link between vaccination and autoimmune conditions, including MS. This study aims to assess the incidence of MS post-COVID-19 vaccination across different age groups and vaccine types, with a specific focus on identifying at-risk populations. Methods: A retrospective cohort study was conducted using publicly available registries, case reports, and clinical data. The study included 450 individuals who developed MS after receiving a COVID-19 vaccine, with an analysis performed on incidence rates, relative risk (RR), and demographic factors such as age, sex, and vaccine type. The data was compared with a control group of 3,000 vaccinated individuals without MS onset. Results: The overall incidence of MS among vaccinated individuals was 15 per 100,000. Adults aged 18-40 years had the highest incidence (18 per 100,000), while children under 12 had the lowest (3 per 100,000). Females were disproportionately affected, accounting for 63.3% of MS cases, with an incidence of 18 per 100,000 compared to 12 per 100,000 in males. A higher proportion of cases were linked to mRNA vaccines, particularly Pfizer-BioNTech (54.4% of total cases), though no statistically significant difference was observed among vaccine types. The relative risk of MS in vaccinated adults was 1.35 (95% CI: 1.12-1.60) compared to the general population. Conclusion: While there is a slight increase in the incidence of MS among adults following COVID-19 vaccination, particularly with mRNA vaccines, the overall risk remains low. No significant increase in MS risk was observed in younger populations. The benefits of vaccination against severe COVID-19 far outweigh the potential risks of MS onset. Ongoing surveillance and further research are essential to better understand vaccine-related autoimmune responses.

RNA Binding Protein Dysfunction Links Smoldering/Slowly Expanding Lesions to Neurodegeneration in Multiple Sclerosis.

Despite the advances in treatments for multiple sclerosis (MS), unremitting neurodegeneration continues to drive disability and disease progression. Smoldering/slowly expanding lesions (SELs) and dysfunction of the RNA binding protein (RBP) heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) are pathologic hallmarks of MS cortex and intricately tied to disability and neurodegeneration, respectively. We hypothesized that neuronal hnRNP A1 dysfunction contributes to neurodegeneration and is exacerbated by smoldering/SELs in progressive MS. Neuronal hnRNP A1 pathology (nucleocytoplasmic mislocalization of hnRNP A1) was examined in healthy control and MS brains using immunohistochemistry. MS cases were stratified by severity of hnRNP A1 pathology to examine the link between RBP dysfunction, demyelination, and neurodegeneration. We found that smoldering/SELs were only present within a subset of MS tissues characterized by elevated neuronal hnRNP A1 pathology (MS-A1high) in adjacent cortical gray matter. In contrast to healthy controls and MS with low hnRNP A1 pathology (MS-A1low), MS-A1high showed elevated markers of neurodegeneration, including neuronal loss and injury, brain atrophy, axonal loss, and axon degeneration. Additionally, we discovered a subpopulation of morphologically intact neurons lacking expression of NeuN, a neuron-specific RBP, in cortical projection neurons in MS-A1high cases. hnRNP A1 dysfunction contributes to neurodegeneration and may be exacerbated by smoldering/SELs in progressive MS. The discovery of NeuN-negative neurons suggests that some cortical neurons may only be injured and not lost. By characterizing RBP pathology in MS cortex, this study has important implications for understanding the pathogenic mechanisms driving neurodegeneration, the substrate of disability and disease progression. ANN NEUROL 2024.

Role of Medicinal Plants in the Management of Multiple Sclerosis.

There is a rapid spread of Multiple Sclerosis disorder across the globe, around 2.8 million cases of Multiple Sclerosis in the world. Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by demyelination, neuroinflammation, and a wide spectrum of clinical manifestations. Many drugs have been tested on MS patients but there is no effective treatment for MS till now. So to inhibit the symptoms caused by MS we performed a study in which we identified various naturally occurring materials with neuroprotective effects on the body that can treat Multiple Sclerosis. The therapeutic strategies portion of the paper reviews the array of disease-modifying therapies currently available for MS management. This paper evaluated their mechanisms of action, efficacy, and safety profiles. It also addressed emerging treatment paradigms by using different naturally occurring materials, including personalized medicine approaches and novel therapies in development. This paper provides a comprehensive overview of the current state of knowledge regarding MS, focusing on its pathogenesis, diagnostic approaches, and therapeutic strategies.

A Morphological Study of HLA-DR-Immunopositive Cells in Multiple Sclerosis Lesions and Their Implications for Pathogenesis

Background: Multiple sclerosis (MS) is characterized by white matter demyelinating plaques, which can be classified as active, chronic active, or chronic inactive based on the extent of demyelination, cellularity, and inflammation. Microglia and macrophages play a central role in these processes. This study aimed to investigate the morphological characteristics of HLA-DR-immunopositive cells in these plaques to improve our understanding of the roles of these cells in MS plaques. Methods: This study is a retrospective post-mortem histopathological study. We analyzed 90 plaques from 6 MS cases. Of the plaques studied, 77 were grouped into three categories: 28 active, 34 chronic active, and 15 chronic inactive. Additionally, five vacuolated white matter lesions, two axonal degeneration lesions, and six lesions with mixed histological features were included. Six control cases were also examined to assess HLA-DR-immunopositive cell expression across various age groups. The cells were classified based on their morphology into two types: round cells without processes (macrophages) and cells with varying processes and shapes (ramified microglia). Results: Both macrophages and ramified microglia were present in all lesion types, with a focus on identifying the predominant cell type. Of the 28 active plaques, macrophages were the primary cell type in 25 plaques, while ramified microglia predominated in 3. In the center of 49 chronic plaques, scattered ramified microglia were observed in 46, with three plaques showing a predominance of macrophages. Among the 34 chronic active lesions, ramified microglia were the main cell type in the periphery of 32 plaques, with the remaining two predominantly exhibiting macrophages. Conclusions: The predominance of macrophages in active lesions and the presence of scattered ramified microglia in the center of chronic plaques are consistent with the phagocytic role of macrophages. Meanwhile, the prevalence of ramified microglia at the periphery of chronic active lesions suggests a potential protective function in maintaining lesion stability.

Complex case of multiple sclerosis with multiple demyelinating locations

Multiple sclerosis (MS) is a chronic inflammatory disorder with an unpredictable progression that affects the central nervous system and has significant emotional, social, and professional implications. The therapeutic approach is multifactorial and requires complex management coordinated by a specialized, multidisciplinary team over the long term. Current non-pharmacological treatment strategies under study, which may improve the course of the disease, focus on the gut microbiome and include the administration of probiotics and fecal transplantation. This study presents a case of secondary progressive multiple sclerosis in a young patient, with rapidly progressive evolution despite ongoing background therapy. The study analyzed literature data regarding both medical rehabilitation programs used in secondary progressive multiple sclerosis and other therapeutic strategies that can improve the quality of life. Medical rehabilitation has no proven impact on disease progression but can enhance the quality of life for patients with multiple sclerosis through spasticity management, improved mental health, increased mobility, and muscle strength. These therapeutic strategies can improve involvement in professional activities and participation in social and family life for patients with multiple sclerosis.

Distinct plasma lipids predict axonal injury and multiple sclerosis activity

BackgroundLipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this...

Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity. This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage. MS cases (64% female, mean age 15.4 years, SD 2.8) were demographically similar to controls (60% female, mean age 14.9 years, SD 3.9). Cases were less likely to have a mother with a bachelor's degree or higher (OR 0.42, 95% CI 0.22-0.80, p = 0.009) and were more likely to experience childhood neighborhood disadvantage (OR 1.04 for each additional point on the neighborhood socioeconomic disadvantage score, 95% CI 1.00-1.07; p = 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS. Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.

Building and validating trend-based multiple sclerosis case definitions: a population-based cohort study for Manitoba, Canada

ObjectiveThis study aims to (1) build and validate model-based case definitions for multiple sclerosis (MS) that use trends (ie, trend-based case definitions) and (2) to apply dynamic classification to identify...

Link Between Autoimmunity and Epilepsy: Neuronal Autoantibodies

Introduction: Autoimmune epilepsy remains under-recognized, and its true incidence remains uncertain. Objective: This study aimed to determine the prevalence of neuronal autoantibodies in patients with epilepsy of unknown etiology. Materials and Methods: An observational, longitudinal, prospective, and analytical study was conducted to assess the presence of autoantibodies associated with autoimmune encephalitis, glutamic acid decarboxylase-65 (GAD65), and onconeural antibodies in the serum and cerebrospinal fluid of consecutive patients with epilepsy of unknown etiology. Results: Sixty patients and 80 controls (30 healthy individuals, 30 with multiple sclerosis, 10 with systemic lupus erythematosus, and 10 with Sjögren's syndrome) were included to detect neuronal antibodies. Among epilepsy patients, 28 out of 60 (47%) tested positive for antibodies against N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2), leucine-rich glioma-inactivated 1 (LGI1), and glutamic acid decarboxylase (GAD), which was significantly higher (p < 0.001) than in the combined control cohort. No onconeural antibodies were detected in epilepsy patients except for 6 cases of epilepsy, 1 case of multiple sclerosis, and 3 cases of lupus with positive GAD by immunofluorescence assay and immunoblotting. There was no significant difference in antibody incidence between male and female epilepsy patients. The incidence of positive autoantibodies was significantly higher in patients with focal epilepsy compared to those with generalized epilepsy (p < 0.01). Conclusions: The findings indicate the presence of antibodies against NMDAR, VGKC-associated proteins (LGI1, CASPR2), and intracellular antigens (GAD65) in the serum and cerebrospinal fluid of patients with epilepsy, suggesting an autoimmune etiology. These results underscore the need for further research to elucidate the role of autoantibodies in epilepsy pathogenesis and to explore immunotherapeutic interventions.

Mediterranean diet and associations with the gut microbiota and pediatric-onset multiple sclerosis using trivariate analysis

BackgroundThe interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS.MethodsWe conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample.ResultsHere we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%–53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet.ConclusionsOur findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.

Changes of Target Essential Trace Elements in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

(1) Background: Multiple sclerosis (MS) is a chronic, complex, and demyelinating disease closely associated with altered levels of trace elements. Although the first studies into the role of trace elements in MS were published in the 1970s, for five decades it has remained unknown whether trace elements can be part of this heterogeneous neurological disease. (2) Materials and methods: To drive toward at a potential solution, we conducted a systematic review and meta-analysis to elucidate whether there were differences in circulating levels of neurologically important essential trace elements (Zn, Fe, Co, Cu, Mn, and Se) between MS cases and controls. (3) Results: This study revealed significantly lower serum/plasma Zn and Fe levels and higher Cu levels in MS-affected individuals compared to controls. At the same time, no significant differences were found between the MS cases and controls regarding their serum/plasma levels of Co, Mn, or Se. Thus, the loss of Fe and Zn should be considered in supplementation/nutrition strategies for MS patients. On the other hand, since high serum Cu levels indicate a burden on the bloodstreams of MS patients, Cu should be excluded from mineral supplement strategies. Furthermore, all three trace elements (Fe, Zn, and Cu) should be considered from an etiological point of view, and, most importantly, their levels in the bloodstreams of MS patients should be monitored. (4) Conclusions: This study highlights the way for personalized and targeted strategies in the management of MS.

Transplantation of human umbilical cord mesenchymal stem cells optimized with IFN-γ is a potential procedure for modification of motor impairment in multiple sclerosis cases: a preclinical systematic review and meta-analysis study.

Stem cells transplantation (SCT) is known as a newfound strategy for multiple sclerosis (MS) treatment. Human umbilical cord mesenchymal stem cells (hUCMSCs) contain various regenerative features. Experimental autoimmune encephalomyelitis (EAE) is a laboratory model of MS. This meta-analysis study was conducted to assess the overall therapeutic effects of hUCMSCs on reduction of clinical score (CS) and restoration of active movement in EAE-induced animals. For comprehensive searching (in various English and Persian databases until May 1, 2024), the main keywords of "Experimental Autoimmune Encephalomyelitis", "Multiple Sclerosis", "Human", "Umbilical Cord", "Mesenchymal", and "Stem Cell" were hired. Collected data were transferred to the citation manager software (EndNote x8) and duplicate papers were merged. Primary and secondary screenings were applied (according to the inclusion and exclusion criteria) and eligible studies were prepared for data collection. CS of two phases of peak and recovery of EAE were extracted as the difference in means and various analyses including heterogeneity, publication bias, funnel plot, and sensitivity index were reported. Meta-analysis was applied by CMA software (v.2), P<0.05 was considered a significant level, and the confidence interval (CI) was determined 95% (95% CI). Six eligible high-quality (approved by ARRIVE checklist) papers were gathered. The difference in means of peak and recovery phases were -0.775 (-1.325 to -0.225; P=0.006; I2=90.417%) and -1.230 (-1.759 to -0.700; P<0.001; I2=93.402%), respectively. The overall therapeutic effects of SCT of hUCMSCs on the EAE cases was -1.011 (95% CI=-1.392 to -0.629; P=0.001). hUCMSCs transplantation through the intravenous route to the animal MS model (EAE) seems a considerably effective procedure for the alleviation of motor defects in both phases of peak and recovery.

Spinal Cord Involvement in Children with Acquired Demyelinating Syndromes: A Single Centre Study

Abstract Background Myelitis may be the first presentation of relapsing acquired demyelinating syndromes (ADS) such as neuromyelitis optica (NMO) or multiple sclerosis (MS) and in association with connective tissue diseases. It may also occur in the context of acute disseminated encephalomyelitis (ADEM). Early recognition of myelitis in these disorders will allow better management plan including theprognosis. Objective To evaluate the frequency of myelitis among children with acquired demyelinating neurological diseases, and the variability of clinical features, neuroimaging findings and treatments given. Methods A pilot observational study with both retrospective and prospective components was conducted on children and adolescents fulfilling the diagnostic criteria for any of the acquired demyelination syndromes admitted inChildren’s Hospital, Ain Shams University whose ages were below 18 years during the period from July 2020 to February 2022. Results Forty-three children were included in our study with mean (SD)age of onset 7.63 (4.28) years. The most common diagnosis was ADEM (n (%) =20 (46.5%), followed by transverse myelitis (TM) (n (%) =11 (25.6%) and NMO (n (%) =7(16.3%). Progression to develop encephalopathy was recorded in 55.8%of cases (100% of ADEM and autoimmune encephalitis (AE) cases). Seizures developed in 23.3% of cases (35% of ADEM, 50% of AE and 14.29% of NMO cases). MRI brain abnormalities were observed in 76.7% of cases (100% of ADEM, NMO, AE and MS cases), and abnormalities of MRI spine were seen in 59% of cases (100% of TM and MS cases, 85.7% of NMO, 33.3% of AE and 23.5% of ADEM cases). Spinal cord affection was most commonly cervical(86.9%) and mostly short segment. All cases received pulsed methylprednisolone therapy, while intravenous immunoglobulins (IVIG) were used in 32.5% of cases and plasmapheresis in 13.9% of cases as a stepwise approach. Nearly half of the cases (53.5%) had monophasic illnesses without the need for long term therapy. Conclusion Spinal cord involvement is frequently observed in childhood acute demyelinating syndromes, and is most commonly cervical and short-segment. MRI spine should be regarded as a sensitive tool for diagnosis of myelitis in the context of ADEM and MS. MRI Brain is a sensitive tool accounting forfindings in 100% of ADEM, NMO, AE and MS cases. Patients with ADEM and AE has higher risk to develop encephalopathy and seizures unlike TM, NMO and MS patients.

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.

The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes. In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes. The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL. The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.

Non-Modifiable Factors Associated with Progression to Irreversible Disability in Multiple Sclerosis Patients

Introduction: Multiple sclerosis (MS) is the leading cause of acquired motor disability in young adults. The increase in disability follows the progression of the disease and imposes on those affected a permanent multidimensional handicap. The identification of the factors associated with the evolution towards an irreversible handicap is important for an adequate therapeutic management. Objective: Identify the non-modifiable factors associated with progression to irreversible disability in patients with MS. Material and Methods: This is a prospective collection study that was carried out in the physical medicine and rehabilitation departments of the University Hospital of Oran and the HMRU of Oran, between January 2017 and December 2019. For the main analysis, we retained an EDSS score (Expanded Disability Status Scale) for the patient if he had the same functional status during the last six months. Results/Discussion: This study included 103 MS cases, including 72 women and 31 men, with a mean age at onset of symptoms of 31.83 years and a mean EDSS of 5.12 ± 1.97. The progression of the disability assessed by the EDSS scale is related to: male gender, age at advanced onset and progressive form of MS. we did not find a correlation between the severity of the handicap and the place of birth and/or residence. Our results are unanimous in the literature for certain parameters, and the same is not true for others. Conclusion: Non-modifiable factors in MS, such as age, gender and place of birth and/or residence, are important predictors of disability and should alert the clinician to appropriate and specific management even at an early stage of the disease.

The effect of COVID-19 vaccination on multiple sclerosis activity as reflected by MRI.

Examining the safety oftheBNT162b2 mRNA vaccine in multiple sclerosis (MS) patientsremains inconclusive, particularly regarding the potential for disease exacerbations. Thisstudyaims to assess the effects ofBNT162b2 COVID-19vaccination on disease activityin MS patientsthroughsequential MRI imaging. A retrospective study of 84 MS patients from five Israeli hospitals was conducted. MS lesion load was determined from three brain MRI scans, one postvaccination and two prevaccination scans. Apost hocanalysis comparedsubgroupsfeaturingvaccinated and unvaccinated patientsrespectively,with early onset MS. The cohort included 70 women with early onset (mean age 16.4±0.8years) and adult onset (mean age 34.9±1.1years)MS. Among the early onset group, vaccinated patients showed an increased risk of new lesions (p=.00026), while there was no increased risk among adult-onset patients. Additionally, a comparison between early onset vaccinated and nonvaccinated groups revealed a higher risk of increased lesions in the vaccinated group (p=.024). Overall, the study suggests that the BNT162b2 vaccine is generally safe in MS patients, with no association found between vaccination and new lesions in most patients. However, close MRI follow-up is recommended for early-onset MS cases to monitor lesion development.

Disentangling Multiple Sclerosis heterogeneity in the French territory among genetic and environmental factors via Bayesian heritability analysis

BackgroundThis study aimed to investigate the factors contributing to the variability of Multiple Sclerosis (MS) among individuals born and residing in France. Geographical variation in MS prevalence was observed in France, but the role of genetic and environmental factors in explaining this heterogeneity has not been yet elucidated. MethodsWe employed a heritability analysis on a cohort of 403 trios with an MS-affected proband in the French population. This sample was retrieved from REFGENSEP register of MS cases collected in 23 French hospital centers from 1992 to 2017. Our objective was to quantify the proportion of MS liability variability explained by genetic variability, sex, shared environment effects, region of birth and year of birth. We further considered gene x environment (GxE) interaction effects between genetic variability and region of birth. We have implemented a Bayesian liability threshold model to obtain posterior distributions for the parameters of interest adjusting for ascertainment bias. ResultsOur analysis revealed that GxE interaction effects between genetic variability and region of birth represent the primary significant explanatory factor for MS liability variability in French individuals (29 % [95 %CI: 5 %; 53 %]), suggesting that additive genetic effects are modified by environmental factors associated to the region of birth. The individual contributions of genetic variability and region of birth explained, respectively, ≈15 % and ≈16 % of MS variability, highlighting a significantly higher MS liability in individuals born in the Northern regions compared to the Southern region. Overall, the joint contribution of genetic variability, region of birth, and their interaction was then estimated to explain 65 % [95 %CI: 35 %; 92 %] of MS liability variability. The remaining proportion of MS variability is attributed to environmental exposures associated with the year of birth, shared within the same household, and specific to individuals. ConclusionOverall, our analysis highlighted the interaction between genetic variability and environmental exposures linked to the region of birth as the main factor explaining MS variability within individuals born and residing in France. Among the environmental exposures prevalent in the Northern regions, and potentially interacting with genetic variability, lower vitamin D levels due to reduced sun exposure, higher obesity prevalence and higher pollution levels represent the main risk factors in influencing MS risk. These findings emphasize the importance of accounting for environmental factors linked to geographical location in the investigation of MS risk factors, as well as to further explore the influence of GxE interactions in modifying genetic risk.

Long-term outcomes of ADEM-like and tumefactive presentations of CNS demyelination: a case-comparison analysis

A minority of initial multiple sclerosis (MS) presentations clinically or radiologically resemble other central nervous system (CNS) pathologies, acute disseminated encephalomyelitis (ADEM) or tumefactive demyelination (atypical demyelination presentations). With the aim of better defining the long-term outcomes of this group we have performed a retrospective cohort comparison of atypical demyelination versus ‘typical’ MS presentations. Twenty-seven cases with atypical presentations (both first and subsequent demyelinating events) were identified and compared with typical MS cases. Disease features analysed included relapse rates, disability severity, whole brain and lesion volumes, lesion number and distribution. Atypical cases represented 3.9% of all MS cases. There was considerable overlap in the magnetic resonance imaging (MRI) features of ADEM-like and tumefactive demyelination cases. ADEM-like cases tended to be younger but not significantly so. Atypical cases showed a trend towards higher peak expanded disability severity score (EDSS) score at the time of their atypical presentation. Motor, cranial nerve, cerebellar, cerebral and multifocal presentations were all more common in atypical cases, and less likely to present with optic neuritis. Cerebrospinal fluid (CSF) white cell counts were higher in atypical cases (p = 0.002). One atypical case was associated with peripheral blood myelin oligodendrocyte glycoprotein (MOG) antibodies, but subsequent clinical and radiological course was in keeping with MS. There was no difference in long-term clinical outcomes including annualised relapse rates (ARR), brain volume, lesion numbers or lesion distributions. Atypical demyelination cases were more likely to receive high potency disease modifying therapy early in the course of their illness. Despite the severity of initial illness, our cohort analysis suggests that atypical demyelination presentations do not confer a higher risk of long-term adverse outcomes.

CSF sphingolipids are correlated with neuroinflammatory cytokines and differentiate neuromyelitis optica spectrum disorder from multiple sclerosis

BackgroundThere is a need for biomarkers of disease progression and therapeutic response in multiple sclerosis (MS). This study aimed to identify cerebrospinal fluid (CSF) lipids that differentiate MS from other...