Course Of Multiple Sclerosis Research Articles

Cerebellar and/or Brainstem Lesions Indicate Poor Prognosis in Multiple Sclerosis: A Systematic Review

Multiple sclerosis is a serious neurological disease that affects millions of people worldwide. Cerebellar and brainstem symptoms are common in the course of multiple sclerosis, but their prognostic value is unclear. This systematic review aimed to determine the relationship between the location of lesions in the cerebellum and/or brainstem and the prognosis in multiple sclerosis. In this systematic review, we searched and comprehensively read articles related to this research topic in Chinese and English electronic databases (PubMed, Embase, Cochrane Library, CNKI, and CBM) using search terms “multiple sclerosis,” “cerebellum,” “brainstem,” “prognosis,” and others. Cerebellar and brainstem clinically isolated syndromes and clinically definite multiple sclerosis were important predictors of transformation (hazard ratio, 2.58; 95% confidence interval, 1.58–4.22). Cerebellar and/or brainstem lesions indicate a poor overall prognosis in multiple sclerosis, but because of inconsistency, more clinical data are needed.

Fatigue in Multiple Sclerosis: A Review of the Exploratory and Therapeutic Potential of Non-Invasive Brain Stimulation.

Fatigue is the most commonly reported symptom in patients with multiple sclerosis (MS). It is a worrisome, frequent, and debilitating manifestation that could occur at any time during the course of MS and in all its subtypes. It could engender professional, familial, and socioeconomic consequences and could severely compromise the patients' quality of life. Clinically, the symptom exhibits motor, cognitive, and psychosocial facets. It is also important to differentiate between perceived or subjective self-reported fatigue and fatigability which is an objective measure of decrement in the performance of cognitive or motor tasks. The pathophysiology of MS fatigue is complex, and its management remains a challenge, despite the existing body of literature on this matter. Hence, unraveling its neural mechanisms and developing treatment options that target the latter might constitute a promising field to explore. A PubMed/Medline/Scopus search was conducted to perform this review which aims (a) to reappraise the available electrophysiological studies that explored fatigue in patients with MS with a particular focus on corticospinal excitability measures obtained using transcranial magnetic stimulation and (b) to assess the potential utility of employing neuromodulation (i.e., non-invasive brain stimulation techniques) in this context. A special focus will be put on the role of transcranial direct current stimulation and transcranial magnetic stimulation. We have provided some suggestions that will help overcome the current limitations in upcoming research.

Synaptic pathology in multiple sclerosis: a role for Nogo-A signaling in astrocytes?

Synaptic pathology in multiple sclerosis: a role for Nogo-A signaling in astrocytes?

Adhesion Molecule Profile and the Effect of Anti-VLA-4 mAb Treatment in Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis.

In the course of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the infiltration of lymphocytes and other inflammatory cells across the blood–brain barrier is associated with interactions between adhesion molecules expressed by infiltrating cells and vascular endothelium. Monoclonal antibodies (mAb) against the α4 subunit of α4-β1 integrin (VLA-4) show beneficial effects in both MS and EAE. (1) Background: The aim of this study was to examine the expression of selected adhesion molecules: VLA-4, VCAM-1, LFA-1, ICAM-1 and PECAM-1 in the successive phases of EAE and the effect of anti-VLA-4 mAb treatment on that expression. (2) Methods: EAE was induced in C57BL/6 mice by immunization with MOG35–55 peptide. The animals were killed in three successive phases of the disease: onset (day 13), peak (day 18) and chronic (day 28). Frozen sections of the lumbar spinal cord were examined by quantitative immunofluorescence microscopy. The expression of the studied molecules was quantified as the percentage of the cross-sectioned spinal cord lesion area occupied by immunopositive structures. (3) Results: The expression of the studied molecules showed two temporal patterns: (1) an increase in the onset phase, a maximum in the peak phase and a decrease in the chronic phase, which corresponded to the temporal pattern of the clinical score, the number of lesions and the inflammation level (ICAM-1, LFA-1 and PECAM-1), and (2) an increase in the peak phase and no significant change or further increase in the chronic phase (VCAM-1, VLA-4). Among the molecules studied, ICAM-1 and LFA-1 exhibited the highest expression levels in the peak phase of EAE. Anti-VLA-4 mAb inhibited the expression of not only VLA-4 but also other adhesion molecules. (4) Conclusions: The interactions of adhesion molecules governing the migration of leukocytes across the blood–brain barrier change in the successive phases of EAE. The therapeutic mechanism of anti-VLA-4 mAb treatment seems to include a complex influence on a variety of adhesion molecules expressed by infiltrating cells and vascular endothelium.

Treatment Challenges in Multiple Sclerosis - A Continued Role for Glatiramer Acetate?

Earlier diagnosis, access to disease-modifying therapies (DMTs), and improved supportive care have favorably altered the disease course of multiple sclerosis (MS), leading to an improvement in long-term outcomes for people with MS (PwMS). This success has changed the medical characteristics of the population seen in MS clinics. Comorbidities and the accompanying polypharmacy, immune senescence, and the growing number of approved DMTs make selecting the optimal agent for an individual patient more challenging. Glatiramer acetate (GA), a moderately effective DMT, interacts only minimally with comorbidities, other medications, or immune senescence. We describe here several populations in which GA may represent a useful treatment option to overcome challenges due to advanced age or comorbidities (e.g., hepatic or renal disease, cancer). Further, we weigh GA's potential merits in other settings where PwMS and their neurologists must base treatment decisions on factors other than selecting the most effective DMT, e.g., family planning, conception and pregnancy, or the need for vaccination.

Prominent D‐dimer elevation and pretibial edema related to alemtuzumab treatment: A case report and literature review

Alemtuzumab is one of the most effective agents in the treatment of multiple sclerosis (MS). On the other hand, the spectrum of possible side effects is wide and carries the potential to cause a variety of inflammatory and thrombotic complications. In this report firstly, a case who developed a systemic thrombotic and inflammatory response after alemtuzumab administration and then presented with pretibial edema in a period of 1 month is discussed. Then, based on the findings detected via this case, the possible side effects of alemtuzumab, both during drug infusion and in the early and late periods after administration, were classified. This classification was created by compiling the reported adverse effects in the literature related to the use of alemtuzumab for the treatment of multiple sclerosis. This presented case shows that prothrombotic predisposition after alemtuzumab administration may result in peripheral microvascular circulatory disorders even in the long term and one of them is pretibial edema. According to the current literature data, side effects of alemtuzumab treatment which is used for multiple sclerosis are categorized as follows: (i) infusion-related reactions, (ii) acute/subacute inflammatory and pro-thrombotic effects, (iii) immunosuppression-related opportunistic infections, (iv) immune reconstitution-related secondary autoimmune disorders. Increasing awareness of the possible side effects of alemtuzumab treatment used in the course of multiple sclerosis will enable both the development of possible prophylactic treatment options and the early control of emerging complications.

Hidden Markov Model and multifractal method-based predictive quantization complexity models vis-á-vis the differential prognosis and differentiation of Multiple Sclerosis’ subgroups

Hidden Markov Model (HMM) is a stochastic process where implicit or latent stochastic processes can be inferred indirectly through a sequence of observed states. HMM as a mathematical model for uncertain phenomena is applicable for the description and computation of complex dynamical behaviours enabling the mathematical formulation of neural dynamics across spatial and temporal scales. The human brain with its fractal structure demonstrates complex dynamics and fractals in the brain are characterized by irregularity, singularity and self-similarity in terms of form at different observation levels, making detection difficult as observations in real-time occurrences can be time variant, discrete, continuous or noisy. Multiple Sclerosis (MS) is an autoimmune degenerative disease with time and space related dissemination, leading to neuronal apoptosis, coupled with some subtle features that could be overlooked by physicians. This study, through the proposed integrated approach with multi-source complex spatial data, aims to attain accurate prediction, diagnosis and prognosis of MS subgroups by HMM with Viterbi algorithm and Forward–Backward algorithm as the dynamic and efficient products of knowledge-based and Artificial Intelligence (AI)-based systems within the framework of precision medicine. Multifractal Bayesian method (MFM) accordingly applied to identify and eliminate “insignificant” irregularities while maintaining “significant” singularities. An efficient modelling of HMM is proposed to diagnose and predict the course of MS while using MFM method. Unlike the methods employed in previous studies, our proposed integrated novel method encompasses the subsequent approaches based on reliable MS dataset (X) collected: (i) MFM method was applied (X) to MS dataset to characterize the irregular, self-similar and significant attributes, thus, attributes with “insignificant” irregularities were eliminated and “significant” singularities were maintained. MFM-MS dataset (Xˆ) was generated. (ii) The continuous values in the MS dataset (X) and MFM-MS dataset (Xˆ) were converted into discrete values through vector quantization method of the HMM (iii) Through transitional matrices, different observation matrices were computed from the both datasets. (v) Computational complexity has been computed for both datasets. (vi) The results of the HMM models based on observation matrices obtained from both datasets were compared. In terms of the integrated HMM model proposed and the MS dataset handled, no earlier work exists in the literature. The experimental results demonstrate the applicability and accuracy of our novel proposed integrated method, HMM and Multifractal (HMM-MFM) method, for the application to the MS dataset (X). Compared with conventional methods, our novel method has achieved more superiority regarding extracting subtle and hidden details, which are significant for distinguishing different dynamic and complex systems including engineering and other related applied sciences. Thus, we have aimed at pointing a new frontier by providing a novel alternative mathematical model to facilitate the critical decision-making, management and prediction processes among the related areas in chaotic, dynamic complex systems with intricate and transient states.

Вторично-прогрессирующий рассеянный склероз в России: проблемы и потребности пациентов, оценка качества оказания медицинской помощи глазами пациентов и специалистов

The article discusses the most unfavorable course of multiple sclerosis — the secondary progressive form. In the course of the study, conducted by a questionnaire survey of patients with secondary progressive multiple sclerosis and specialists from multiple sclerosis centers from 15 regions of Russia, medical, labor and other characteristics of patients, their problems and needs, subjective attitude to the effectiveness of therapy and rehabilitation were clarified. The main, according to doctors, defects in the organization of medical care for patients with secondary progressive multiple sclerosis have been identified. In conclusion, it was concluded that there is a significant variability in the social status and living conditions of patients with secondary progressive multiple sclerosis. The authors consider the registration in the Russian Federation of highly effective drugs for the treatment of patients with secondary progressive multiple sclerosis to be one of the most important measures.

S100B inhibition protects from chronic experimental autoimmune encephalomyelitis.

Studies have correlated excessive S100B, a small inflammatory molecule, with demyelination and associated inflammatory processes occurring in multiple sclerosis. The relevance of S100B in multiple sclerosis pathology brought an emerging curiosity highlighting its use as a potential therapeutic target to reduce damage during the multiple sclerosis course, namely during inflammatory relapses. We examined the relevance of S100B and further investigated the potential of S100B-neutralizing small-molecule pentamidine in chronic experimental autoimmune encephalomyelitis. S100B depletion had beneficial pathological outcomes and based on promising results of a variety of S100B blockade strategies in an ex vivo demyelinating model, we choose pentamidine to assay its role in the in vivo experimental autoimmune encephalomyelitis. We report that pentamidine prevents more aggressive clinical symptoms and improves recovery of chronic experimental autoimmune encephalomyelitis. Blockade of S100B by pentamidine protects against oligodendrogenesis impairment and neuroinflammation by reducing astrocyte reactivity and microglia pro-inflammatory phenotype. Pentamidine also increased regulatory T cell density in the spinal cord suggesting an additional immunomodulatory action. These results showed the relevance of S100B as a main driver of neuroinflammation in experimental autoimmune encephalomyelitis and identified an uncharacterized mode of action of pentamidine, strengthening the possibility to use this drug as an anti-inflammatory and remyelinating therapy for progressive multiple sclerosis.

Association of pregnancies with risk of multiple sclerosis

Background: Pregnancies have an impact on the disease course of multiple sclerosis (MS), but their relationship with MS risk is yet unclear. Objective: To determine the relationships of pregnancies and gynecological diagnoses with MS risk. Methods: In this retrospective case–control study, we assessed differences in gynecological International Classification of Diseases, 10th Revision (ICD-10) code recording rates between women with MS (n = 5720), Crohn’s disease (n = 6280), or psoriasis (n = 40,555) and women without these autoimmune diseases (n = 26,729) in the 5 years before diagnosis. Results: Twenty-eight ICD-10 codes were recorded less frequently for women with MS as compared to women without autoimmune disease, 18 of which are pregnancy-related. After adjustment for pregnancies, all codes unrelated to pregnancies were still negatively associated with MS. In a sensitivity analysis excluding women with evidence for possible demyelinating events before diagnosis, all associations were more pronounced. In comparison to women with psoriasis, most associations could be confirmed; that was not true in comparison to women with Crohn’s disease. Conclusion: Our findings provide evidence for a possible protective effect of pregnancies on MS risk likely independent of or in addition to a previously suggested reversed causality. The negative associations of gynecological disorders with disease risk need further investigation. The associations might be shared by different autoimmune diseases.

Investigating the potential disease-modifying and neuroprotective efficacy of exercise therapy early in the disease course of multiple sclerosis: The Early Multiple Sclerosis Exercise Study (EMSES)

Background: Potential supplemental disease-modifying and neuroprotective treatment strategies are warranted in multiple sclerosis (MS). Exercise is a promising non-pharmacological approach, and an uninvestigated ‘window of opportunity’ exists early in the disease course. Objective: To investigate the effect of early exercise on relapse rate, global brain atrophy and secondary magnetic resonance imaging (MRI) outcomes. Methods: This randomized controlled trial (n = 84, disease duration <2 years) included 48 weeks of supervised aerobic exercise or control condition. Population-based control data (Danish MS Registry) was included (n = 850, disease duration <2 years). Relapse rates were obtained from medical records, and patients underwent structural and diffusion-kurtosis MRI at baseline, 24 and 48 weeks. Results: No between-group differences were observed for primary outcomes, relapse rate (incidence-rate-ratio exercise relative to control: (0.49 (0.15; 1.66), p = 0.25) and global brain atrophy rate (−0.04 (−0.48; 0.40)%, p = 0.87), or secondary measures of lesion load. Aerobic fitness increased in favour of the exercise group. Microstructural integrity was higher in four of eight a priori defined motor-related tracts and nuclei in the exercise group compared with the control (thalamus, corticospinal tract, globus pallidus, cingulate gyrus) at 48 weeks. Conclusion: Early supervised aerobic exercise did not reduce relapse rate or global brain atrophy, but does positively affect the microstructural integrity of important motor-related tracts and nuclei.

The Role of Diet and Interventions on Multiple Sclerosis: A Review.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. The most prominent clinical features include visual loss and sensorimotor symptoms and mainly affects those of young age. Some of the factors affecting its pathogenesis are genetic and/or environmental including viruses, smoking, obesity, and nutrition. Current research provides evidence that diet may influence MS onset, course, and quality of life of the patients. In this review, we address the role of nutrition on MS pathogenesis as well as dietary interventions that show promising beneficial results with respect to MS activity and progression. Investigation with large prospective clinical studies is required in order to thoroughly evaluate the role of diet in MS.

High Levels of Cerebrospinal Fluid Kappa Free Light Chains Relate to IgM Intrathecal Synthesis and Might Have Prognostic Implications in Relapsing Multiple Sclerosis.

Cerebrospinal kappa free light chain (KFLC)-index is a marker of intrathecal immunoglobulin synthesis that aids in the diagnosis of multiple sclerosis (MS). However, little evidence exists on its prognostic role. Our aim is to analyze the relationship between KFLC-index and other MS biomarkers and to explore its prognostic role. This is a monocentric observational study in a cohort of 52 people with relapsing MS (pwRMS) performed on prospectively acquired clinical data and with retrospective evaluation of biomarkers. We measured KFLC-index, immunoglobulin intrathecal synthesis, cerebrospinal fluid (CSF) chitinase 3-like 1 (CHI3L1), and neurofilament light protein (NFL) and reviewed MRI to detect leptomeningeal contrast enhancement (LMCE). We compared time to Expanded Disability Status Scale (EDSS) 3 and to initiation of high-efficacy disease-modifying therapies (heDMTs) by multivariate Cox regression analysis. Median KFLC-index correlated with IgG/IgM indexes (p < 0.0001/p < 0.05) and IgG-oligoclonal bands (OCGBs) (p < 0.001). Patients with IgM-oligoclonal bands (OCMBs) had a higher KFLC-index (p = 0.049). KFLC-index was higher in patients with LMCE (p = 0.008) and correlated with CHI3L1 (p = 0.007), but disease activity had no effect on its value. Bivariate and multivariate analyses confirmed KFLC-index > 58 as an independent risk factor for reaching an EDSS of 3 (hazard ratio (HR) = 12.4; 95% CI = 1.1–147; p = 0.047) and for the need of treatment with heDMTs (HR = 3.0; 95% CI = 1.2–7.1; p = 0.0013). To conclude, our data suggest a potential prognostic role of the KFLC-index during the MS course.

Psychotic Symptoms Revealing Multiple Sclerosis: Case Report

Background: Multiple sclerosis (MS) is a demyelinating disease that shows variable clinical presentation.The presence of psychotic disorders in MS patients is rare and occurs in 2-3% of cases. Some studies reported that 95% of adult patients with MS experience psychiatric symptoms and up to 1% of MS has psychiatric onset. Little data has been reported on psychotic symptoms occurring during the MS course or preceding the onset of MS population.

A one year follow of patients with multiple sclerosis during COVID-19 pandemic: A cross-sectional study in Qom province, Iran

BackgroundIn the current COVID-19 pandemic, Multiple Sclerosis (MS) patients represent a population of particular interest as they might be at higher risk of COVID-19 infection and it's complications. The present study aimed to investigate a one year follow up of patients with MS during the COVID-19 pandemic, in Qom province, Iran. MethodsThis study was performed at the MS Clinic of Beheshti Hospital from June 1, 2020 to November 1, 2021. 202 patients with a diagnosis of MS and negative self-reported history of COVID-19 at the beginning of the pandemic, were enrolled. First, the demographic characteristics of patients were collected. Second, the patients underwent serological testing for anti-SARS-CoV-2 IgG antibodies. Then, a year later, they were revalauted and asked about the occurrence of clinical relapse leading to hospitalization, disease progression, DMT profile, COVID-19 vaccination, and history of COVID-19 infection. We considered six weeks after COVID-19 regarding relapse occurrence. Eventually, statistical analysis was carried out by using SPSS 26.0 ResultsOf 202 patients, 26 patients (12.87%) had initially a positive index antibody result. During the follow-up periods, 25 patients (12.37%) were infected with COVID-19 which was mainly mild (74.8%), and significantly lower than general population. 118 patients (58.41%) were vaccinated for COVID-19 which reduced the risk of COVID-19 development (P<001). Except a case of myelitis associated with vaccination, no serious adverse event was reported. Additionally, only one patient developed MS relapse following COVID-19 infection. Except clinical relapse (P = 0.001), other demographic and MS characteristics, and DMT type were not associated with COVID-19. In terms of MS course, 12 patients (5.94%) discontinued their DMTs regardless of the DMT adverse events or treatment failure. 41 patients (20.3%) experienced a clinical relapse, of whom 12 were escalated to a second line DMT. Further, 27 patients (13.4%) noted a history of worsening disability which mainly occurred after COIVD-19 infection. ConclusionThe present study showed a significant lower incidence of COVID-19 infection in MS patients. Except for clinical relapse, other demographic and MS characteristics, and DMT type were not associated with COVID-19 infection. In addition, COVID-19 vaccination reduced the risk of COVID-19 development, and the prognosis was favorable in the majority of MS patients.

Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study

BackgroundSome current evidence is pointing towards an association between COVID-19 and worsening of multiple sclerosis (MS), stressing the importance of preventing COVID-19 among people with MS (pwMS). However, population-based evidence regarding the long-term post-COVID-19 course of relapsing-remitting multiple sclerosis (RRMS) was limited when this study was initiated.ObjectiveTo detect possible changes in MS clinical disease activity after COVID-19.MethodsWe conducted an observational study from July 2020 until July 2021 in the Isfahan MS clinic, comparing the trends of probable disability progression (PDP) – defined as a three-month sustained increase in expanded disability status scale (EDSS) score – and relapses before and after probable/definitive COVID-19 diagnosis in a cohort of people with RRMS (pwRRMS).ResultsNinety pwRRMS were identified with definitive COVID-19, 53 of which were included in the final analysis. The PDP rate was significantly (0.06 vs 0.19, P = 0.04), and the relapse rate was insignificantly (0.21 vs 0.30, P = 0.30) lower post-COVID-19, compared to the pre-COVID-19 period. The results were maintained after offsetting by follow-up period in the matched binary logistic model. Survival analysis did not indicate significant difference in PDP-free (Hazard Ratio [HR] [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse-free (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36) survivals between the pre- and post-COVID-19 periods. Sensitivity analysis resulted similar measurements, although statistical significance was not achieved.ConclusionWhile subject to replication in future research settings, our results did not confirm any increase in the long-term clinical disease activity measures after COVID-19 contraction among pwRRMS.

The prognostic value of neurofilament light chain in serum

Interest in the use of fluid biomarkers for monitoring disease course in multiple sclerosis is growing. Neurofilaments are structural proteins, and neurofilament light chain (NfL) is released after neuroaxonal injury. 1 Gafson AR Barthélemy NR Bomont P et al. Neurofilaments: neurobiological foundations for biomarker applications. Brain. 2020; 143: 1975-1998 Google Scholar NfL can be measured in blood by ultrasensitive assays, with good correlation between blood and CSF levels. 1 Gafson AR Barthélemy NR Bomont P et al. Neurofilaments: neurobiological foundations for biomarker applications. Brain. 2020; 143: 1975-1998 Google Scholar , 2 Kuhle J Barro C Andreasson U et al. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. ClinChemLab Med. 2016; 54: 1655-1661 Google Scholar Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation studyThe use of sNfL percentiles and Z scores allows for identification of individual people with multiple sclerosis at risk for a detrimental disease course and suboptimal therapy response beyond clinical and MRI measures, specifically in people with disease activity-free status. Additionally, sNfL might be used as an endpoint for comparing effectiveness across drug classes in pragmatic trials. Full-Text PDF

Effectiveness of Anti-Cluster of Differentiation 20 as a Disease-Modifying Therapy in Multiple Sclerosis Across Its Different Phenotypes at the University Hospital of Caen.

BackgroundMultiple sclerosis is a chronic, demyelinating disorder occurring primarily as two main forms of relapsing-remitting multiple sclerosis (RRMS) found predominantly in women, and primary progressive multiple sclerosis (PPMS) occurring predominantly in men. In this retrospective single-center study, we aimed to explore the effects of anti-cluster of differentiation (CD)20 treatment for both relapsing-remitting and primary progressive forms of multiple sclerosis (MS) in a population-based cohort treated at the university hospital. MethodologyThe diagnostic factors being assessed were forms of multiple sclerosis (MS), age at first relapse, whereas therapeutic factors were age at first disease-modifying therapy (DMT), age at starting anti-CD20, reason to switch to anti-CD20 and the duration of anti-CD20 treatment. Primary outcomes measured were number of relapses and progression in disability as measured by the Expanded Disability Status Scale, while secondary outcomes measures being assessed number of cerebral lesions on MRI and level of IgG at the beginning and end of the 12-month treatment.ResultsTreatment with anti-CD20 demonstrated a reduction in number of relapses 12 months after treatment, no change in the progression of disability in RRMS type, but an increase in PPMS type. No change was observed in cerebral MRI lesions at the end of treatment after 12 months. A statistically significant reduction in serum IgG value was observed after 12 months from the start of treatment, where only one out of 26 (3.8%) patients developed hypogammaglobulinemia with IgG less than 6 g/L but none developed hypogammaglobulinemia of less than 5 g/L.ConclusionAnti-CD20 antibodies as disease-modifying therapy can profoundly impact the course and progression of MS in both its forms if utilized at an earlier stage in patients and therefore greatly improve the quality of life in patients living with multiple sclerosis.

The BDNF Val66Met Polymorphism (rs6265) Modulates Inflammation and Neurodegeneration in the Early Phases of Multiple Sclerosis

The clinical course of multiple sclerosis (MS) is critically influenced by the interplay between inflammatory and neurodegenerative processes. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265), one of the most studied single-nucleotide polymorphisms (SNPs), influences brain functioning and neurodegenerative processes in healthy individuals and in several neuropsychiatric diseases. However, the role of this polymorphism in MS is still controversial. In 218 relapsing–remitting (RR)-MS patients, we explored, at the time of diagnosis, the associations between the Val66Met polymorphism, clinical characteristics, and the cerebrospinal fluid (CSF) levels of a large set of pro-inflammatory and anti-inflammatory molecules. In addition, associations between Val66Met and structural MRI measures were assessed. We identified an association between the presence of Met and a combination of cytokines, identified by principal component analysis (PCA), including the pro-inflammatory molecules MCP-1, IL-8, TNF, Eotaxin, and MIP-1b. No significant associations emerged with clinical characteristics. Analysis of MRI measures evidenced reduced cortical thickness at the time of diagnosis in patients with Val66Met. We report for the first time an association between the Val66Met polymorphism and central inflammation in MS patients at the time of diagnosis. The role of this polymorphism in both inflammatory and neurodegenerative processes may explain its complex influence on the MS course.

Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.