Multiple Sclerosis Research Articles

Multimodal Feedback Methods for Advancing the Accessibility of Immersive Virtual Reality for People With Balance Impairments Due to Multiple Sclerosis.

Maintaining balance in immersive virtual reality (VR) environments poses a significant challenge for users, particularly affecting those with pre-existing balance disorders. This study investigates the efficacy of multimodal feedback-comprising auditory, vibrotactile, and visual stimuli-in mitigating balance issues within VR. A sample of 68 participants, divided equally between individuals with balance deficits related to multiple sclerosis and those without, was evaluated. The research explored the impact of various feedback conditions on balance performance. The results demonstrated that the multimodal feedback condition significantly enhanced balance control compared to other conditions, with statistical analysis confirming this improvement (p<.001). These findings underscore the potential of integrated sensory feedback in addressing balance-related difficulties in VR, thereby improving the overall accessibility and user experience for individuals affected by balance impairments. This research contributes valuable insights into optimizing VR environments for enhanced stability and user comfort.

Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli

Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli

Cancer and mortality risks among people with multiple sclerosis: A population-based study in Isfahan, Iran.

Multiple sclerosis (MS) and cancer present substantial global health challenges. Understanding cancer patterns among people with MS (PwMS) is crucial due to potential variations across demographics and geographic regions. Isfahan province in Iran, known for its high MS incidence ratio, offers a significant population for comprehensive studies on MS. In this study, we aim to investigate the association between risk of cancer and MS. Data on PwMS were collected utilizing the National Multiple Sclerosis Registry System of Iran (NMSRI), with diagnoses confirmed using McDonald criteria by neurologists specialized in MS. Cancer incidence was investigated using the Iranian National Population-Based Cancer Registry (INPCR) data, collected following international protocols. Descriptive statistics and regression analyses were employed to assess factors associated with cancer and mortality risks among PwMS. Survival analysis was conducted using Kaplan-Meier curves. Out of 10,049 PwMS, 123 were diagnosed with cancer, with an mean age at the time of cancer diagnosis being 40.41 years and a mean MS duration of 6.76 years. The majority had relapsing-remitting MS (81.2%), and Interferon-β was the most common disease-modifying therapy (DMT) (42.4%). Cancer incidence was 125.6 per 100,000 person-years, peaking at ages 60-64 (677.9 per 100,000 person-years). Receiving monoclonal antibody medications and older age were significantly associated with higher cancer risk (OR:1.542 (1.009-2.357), OR:1.033 (1.015-1.051), respectively). Female breast cancer had the highest incidence ratio among PwMS (40.17 per 100,000 person-years), followed by thyroid (18.38 per 100,000 person-years) and digestive system cancers (17.36 per 100,000 person-years). Breast cancer was the predominant cancer in women, while digestive system cancers were most common among men. Being male and having longer MS duration were linked to higher cancer mortality risk (HR: 2.683, 1.087, respectively). Cancer incidence among 10,049 people with multiple sclerosis was significant, especially in older individuals, with breast cancer being the most common. Male gender and longer MS duration were linked to higher cancer mortality risk.

Sodelovanje in vztrajanje bolnikov z multiplo sklerozo pri zdravljenju z zdravili

Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system that presents the second highest cause of disability among young adults in their thirties. Medication treatments are based on parenteral and novel oral disease-modifying therapies (DMTs) for their simple dosage form, increased efficacy, and safety. Medication adherence (MA) assesses the extent to which patients’ medication administration corresponds with the agreed-upon treatment recommendations from health-care providers. Medication persistence (MP) is part of the MA continuum and defined as the interval between the initiation and last dose of the applied medication immediately preceding discontinuation. Adherence measures are based on medication availability and gaps over the period it is dispensed. Medication adherence in persons with MS is complex due to disease chronicity and more demanding routes of administration. Adherence is higher in patients on oral compared to older injectable parenteral treatment. Younger age, female gender, and longer disease course are key risk factors leading to lower adherence, which declines substantially after six months of treatment. The association of disability with adherence remains unknown. The major adherence barriers in the course of treatment are adverse effects, injectophobia, and dosage frequency. Common non-adherence reasons among patients are forgetfulness, depression, and fatigue. Medication non-adherence is associated with lower health and economic outcomes. Interventions for increasing MA in persons with MS are complex and individualized. Overcoming adherence barriers in MS should be aimed at injectophobia, coping with adverse effects, and increasing beliefs towards treatment necessity.

Improvement of fatigue, depression, and processing speed two weeks post Natalizumab infusion in Multiple Sclerosis: No difference between standard and extended interval dosing schedules

BackgroundFatigue, depression and slow processing speed are debilitating symptoms in people with Relapsing-Remitting Multiple Sclerosis (RRMS) that significantly impacts on the quality of life. Natalizumab, a disease-modifying treatment, improves clinical symptoms but questions remain about the comparative efficacy between its standard interval dosing (SID) and extended interval dosing (EID) schedules. ObjectiveTo examine the impact of short term natalizumab dosing schedules—SID versus EID—on the so called “invisible symptoms”, specifically focusing on symptom exacerbation during the 'wearing-off' phase before infusion and the subsequent relief post-infusion. MethodsForty-two RRMS patients were assessed one week before (T0) and two weeks after pre-and post-natalizumab infusion (T1) for fatigue symptoms using the Fatigue Scale for Motor and Cognitive Functions (FSMC), the Modified Fatigue Impact Scale (MFIS), and the Fatigue Symptoms and Impacts Questionnaire–Relapsing Multiple Sclerosis (FSIQ-RMS). Processing speed and depression were measured by the symbol digit modality test (SDMT), and the Beck Depression Inventory-II (BDI-II). Participants were categorized into either the SID or EID dosing schedules of natalizumab, and their outcomes were compared. ResultsForty-two patients (21 SID; 21 EID) completed the study. Fatigue severity scales, SDMT, and BDI-II scores improved from T0 to T1. No significant differences in fatigue symptoms were found between the SID and EID groups, whether during the "wearing-off" period (T0) or post-infusion (T1). ConclusionsBoth SID and EID dosing regimens of natalizumab are similarly effective in reducing fatigue symptoms, depression and improving processing speed in individuals with RRMS, with no observed differences during the "wearing-off" periods or after re-infusion.

Recurrent late-onset neutropenia following treatment with different B cell-depleting strategies in multiple sclerosis.

As B cell-depleting therapies in multiple sclerosis (MS) have gained significant importance in the last several years, their long-term safety profile is of considerable clinical interest. Late-onset neutropenia (LON) is a rare, but potentially severe, adverse event that was first described in patients with rheumatic disorders under therapy with rituximab. Ofatumumab was approved in 2021 for the treatment of relapsing-remitting multiple sclerosis (RRMS). Neutropenia occurred in 0.2% of patients in clinical phase 3 trials, and to date, no cases of LON have been reported under ofatumumab treatment. Here, we report a case of repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment. Additionally, we review the literature on rare occurrences of LON in patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) undergoing B cell-depleting therapies, including rituximab, ocrelizumab, ofatumumab, inebilizumab, and ublituximab. In our case, the patient presented with repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment leading to febrile infections, subsequent use of antibiotics, and application of granulocyte-colony-stimulating factor. After repetitive episodes of LON under both B cell-depleting strategies, cladribine was subsequently initiated. A nine-month follow-up showed a normal neutrophil count and no evidence of disease activity. This case highlights the significance of symptomatic late-onset blood count changes under both ocrelizumab and ofatumumab and emphasizes the importance of continuous monitoring of the differential blood count under B cell-depleting treatment. This study was supported by the Deutsche Forschungsgemeinschaft (DFG; SFB CRC-TR-128 to F.Z., V.F., and S.B..; SFB 1080 and SFB CRC-1292 to F.Z..; and SFB/TRR 355 to S.B.) and the Hermann and Lilly Schilling Foundation (to S.B.).

Effectiveness of Non-Pharmacological Interventions for Spasticity Management in Multiple Sclerosis: A Systematic Review.

This systematic review aims to determine the effectiveness of non-pharmacological interventions for the management of spasticity in people with multiple sclerosis (pwMS). A comprehensive literature search in health science databases (MEDLINE, Embase, CENTRAL, CINHAL) was performed to identify randomized controlled trials (RCTs) (up to April 2024). Manual searching in journals and screening of the reference lists of identified studies were conducted. Two authors independently selected the studies, assessed the methodological quality, and summarized the evidence. A meta-analysis was not feasible due to the methodological, clinical, and statistical diversity of the included studies. Overall, 32 RCTs (n=1,481 participants) investigated various types of non-pharmacological interventions including: physical activity, transcranial magnetic stimulation (intermittent theta burst stimulation [iTBS], repetitive transcranial magnetic stimulation [rTMS]), electromagnetic therapy, transcutaneous electrical nerve stimulation, vibration therapy, shock wave therapy, self-management educational programs, and acupuncture. All studies scored 'low' on the methodological quality assessment, implying a high risk of bias. The findings suggest 'moderate to low certainty' evidence for physical activity programs used in isolation or combination with other interventions (pharmacological or non-pharmacological), and for iTBS/rTMS with or without adjuvant exercise therapy in improving spasticity in adults with MS. There is 'very low certainty' evidence supporting the use of other modalities for treating spasticity in this population. Despite a wide range of non-pharmacological interventions used for the management of spasticity in pwMS, there is a lack of conclusive evidence for many. More robust trials with larger sample sizes and longer-term follow-ups are needed to build evidence for these interventions.

Quantitative proteomics and multi-omics analysis identifies potential biomarkers and the underlying pathological molecular networks in Chinese patients with multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS.

Optic Neuritis and its Prevalence in Immunocompromised Patients: A Review Article

Optic neuritis is an inflammation that affects the optic nerve, causing vision loss, eye pain, and changes in color perception. The condition can be associated with autoimmune diseases such as multiple sclerosis (MS) or infections, especially in immunocompromised individuals such as HIV/AIDS patients or those undergoing chemotherapy. In these individuals, optic neuritis usually results from opportunistic infections like toxoplasmosis and syphilis, complicating diagnosis and treatment. In immunocompetent patients, optic neuritis may indicate autoimmune diseases like MS or neuromyelitis optica (NMO), with better prognoses when treated early with corticosteroids. However, in immunocompromised individuals, the prognosis tends to be worse due to underlying infections and a limited response to immunosuppressive treatment. The management of optic neuritis involves anti-inflammatory therapies and, in cases of infections, specific antimicrobials. Continuous clinical and visual follow-up is also crucial. Studies suggest that clinical outcomes vary depending on the etiology and the patient's immune status, highlighting the need for personalized therapeutic strategies. Early diagnosis is critical to improving vision and quality of life for patients.

Prolonged Visual Evoked Potential Latencies in Dogs Naturally Infected with Canine Distemper Virus

Canine distemper (CD) is a deadly, multi-system infection caused by a Morbillivirus. The canine distemper virus (CDV) frequently affects the nervous system with demyelinating leukoencephalitis, the most common neurological lesion. The disease has been linked to multiple sclerosis (MS) in humans due to similar clinical presentation and pathophysiological mechanisms. In MS, visual evoked potentials (VEPs) have been identified as a reliable marker for disease progression, enabling the early detection of clinically suspected lesions. The aim of this study was to determine if there are any abnormalities in VEP responses in dogs with neurological CD. Visual evoked potentials and electroretinogram (ERG) were recorded at both the cranial and spinal levels in dogs naturally infected with CDV and in healthy dogs. The results in the CDV-infected group revealed a bilateral increase in the latency of N1, P1, N2, P2, and N3 waves of the VEPs, without any alterations in their amplitudes. No significant differences were observed in the ERG between the groups. These results suggest that altered VEP responses could serve as an early diagnostic indicator of neurological damage caused by distemper. Therefore, conducting these studies could potentially aid in the detection of central nervous conduction disorders during the subclinical phases of the disease.

An insect cell-derived extracellular vesicle-based gB vaccine elicits robust adaptive immune responses against Epstein-Barr virus.

Epstein-Barr virus (EBV), the first identified human tumor virus, is implicated in various human malignancies, infectious mononucleosis, and more recently, multiple sclerosis. Prophylactic vaccines have the potential to effectively prevent EBV infection. Glycoprotein B (gB) serves as the fusogen and plays a pivotal role in the virus entry process, making it a critical target for EBV vaccine development. Surface membrane proteins of enveloped viruses serve as native conformational antigens, making them susceptible to immune recognition. Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context. In this study, we employed a truncated design for gB proteins, observing that these truncated gB proteins prompted a substantial release of extracellular vesicles (EVs) in insect cells. We verified that EVs exhibited abundant gB proteins, displaying the typical virus particle morphology and extracellular vesicle characteristics. gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice. Moreover, the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity. Consequently, gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.

Two-Sample Mendelian Randomization Study Identifies Tissue-Dependent Risk Genes in Autoimmune Diseases

Autoimmune diseases are among the most prevalent diseases across the world with genetic and environmental factors that contribute to their etiology. Because the exact causes of autoimmune diseases are largely unknown, a Mendelian randomization (MR) approach is used here to examine the potential causal association between gene expression levels and disease risk across various tissues. Specifically, this study focuses on six autoimmune diseases including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus. Several of these diseases are currently treatable with immunosuppressants that target specific genes, such as TNF-alpha, IL-23, CD20, and more. In this study, a two-sample MR analysis is performed with multitissue expression quantitative trait loci (eQTLs) and large-scale genome-wide association studies to investigate how gene expression can influence the risk of developing these diseases. Our results show that genes HLA-DQA1/2, HLA-DRB1/6, HLA-DQB2, C4A, CYP21A2, and HLA-DQB1-AS1 have a high causal effect across several diseases and tissues, and almost all of these findings originate from the major histocompatibility complex (MHC) region on Chromosome 6. Our findings support the current knowledge of genes associated with these diseases while also revealing novel genes that can be used for drug therapies in the future. Although several drug therapies currently exist to treat this selection of autoimmune diseases, we provide further insights into the main, common pathways responsible for autoimmune disease pathogenesis and discuss novel genes that lack research focus.

More than microglia: myeloid cells and biomarkers in neurodegeneration.

The role of myeloid cells (granulocytes and monocytes) in neurodegeneration and neurodegenerative disorders (NDD) is indisputable. Here we discuss the roles of myeloid cells in neurodegenerative diseases, and the recent advances in biofluid and imaging myeloid biomarker research with a focus on methods that can be used in the clinic. For this review, evidence from three neurodegenerative diseases will be included, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). We discuss the potential for these biomarkers to be used in humans with suspected NDD as prognostic, diagnostic, or monitoring tools, identify knowledge gaps in literature, and propose potential approaches to further elucidate the role of myeloid cells in neurodegeneration and better utilize myeloid biomarkers in the understanding and treatment of NDD.

Up-regulation of miR-485-3p in Iranian patients with relapsing-remitting multiple sclerosis by targeting HLADRB1

Up-regulation of miR-485-3p in Iranian patients with relapsing-remitting multiple sclerosis by targeting HLADRB1

Molecular Motors in Myelination and Their Misregulation in Disease.

Molecular motors are cellular components involved in the intracellular transport of organelles and materials to ensure cell homeostasis. This is particularly relevant in neurons, where the synaptic components synthesized in the soma need to travel overlong distances to their destination. They can walk on microtubules (kinesins and dyneins) or actin filaments (myosins), themajor components of cell cytoskeleton. While kinesins mostly perform the anterograde transport of intracellular components toward the plus ends of microtubules located distally in cell processes, cytoplasmic dyneins allow the retrograde flux of intracellular cargo toward the minus ends of microtubules located at the cell soma. Axon myelination represents a major aspect of neuronal maturation and is essential for neuronal function, as it speeds up the transmission of electrical signals. Increasing evidence supports a role for molecular motors in the homeostatic control of myelination. This role includes the trafficking of myelin components along the processes of myelinating cells and local regulation of pathways that ensure axon wrapping. Dysfunctional control of the intracellular transport machinery has thereforebeen linked to several brain pathologies, including demyelinating diseases. These disordersinclude a broad spectrum of conditions characterized by pathological demyelination of axons within the nervous system, ultimately leading to axonal degeneration and neuronal death, withmultiple sclerosis representing the most prevalent and studied condition. This review highlights the involvement of molecular motors in the homeostatic control of myelination. It also discusses studies that have yielded insights into the dysfunctional activity of molecular motors in the pathophysiology of multiple sclerosis.

Resilience, Mental Health, Sleep, and Smoking Mediate Pathways Between Lifetime Stressors and Multiple Sclerosis Severity

Introduction: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to features of multiple sclerosis (MS); yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim: To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods: Adults with MS (N = 924) participated in an online survey through the National MS Society listserv. Structural equation modeling was used to examine the direct and indirect effects of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity, and interference) via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results: The final analytic model had an excellent fit (GFI = 0.998). Lifetime stressors had a direct relationship with MS severity (β = 0.27, p &lt; 0.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of the mediation was significant (β = 0.45). Conclusions: This work provides foundational evidence to inform the conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate the effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve the disease course.

Compensatory mechanisms amidst demyelinating disorders: insights into cognitive preservation.

Demyelination disrupts the transmission of electrical signals in the brain and affects neurodevelopment in children with disorders such as multiple sclerosis and myelin oligodendrocyte glycoprotein-associated disorders. Although cognitive impairments are prevalent in these conditions, some children maintain cognitive function despite substantial structural injury. These findings raise an important question: in addition to the degenerative process, do compensatory neural mechanisms exist to mitigate the effects of myelin loss? We propose that a multi-dimensional approach integrating multiple neuroimaging modalities, including diffusion tensor imaging, magnetoencephalography and eye-tracking, is key to investigating this question. We examine the structural and functional connectivity of the default mode and executive control networks due to their significant roles in supporting higher-order cognitive processes. As cognitive proxies, we examine saccade reaction times and direction errors during an interleaved pro- (eye movement towards a target) and anti-saccade (eye movement away from a target) task. 28 typically developing children, 18 children with multiple sclerosis and 14 children with myelin oligodendrocyte glycoprotein-associated disorders between 5 and 18.9 years old were scanned at the Hospital for Sick Children. Tractography of diffusion MRI data examined structural connectivity. Intracellular and extracellular microstructural parameters were extracted using a white matter tract integrity model to provide specific inferences on myelin and axon structure. Magnetoencephalography scanning was conducted to examine functional connectivity. Within groups, participants had longer saccade reaction times and greater direction errors on the anti- versus pro-saccade task; there were no group differences on either task. Despite similar behavioural performance, children with demyelinating disorders had significant structural compromise and lower bilateral high gamma, higher left-hemisphere theta and higher right-hemisphere alpha synchrony relative to typically developing children. Children diagnosed with multiple sclerosis had greater structural compromise relative to children with myelin oligodendrocyte glycoprotein-associated disorders; there were no group differences in neural synchrony. For both patient groups, increased disease disability predicted greater structural compromise, which predicted longer saccade reaction times and greater direction errors on both tasks. Structural compromise also predicted increased functional connectivity, highlighting potential adaptive functional reorganisation in response to structural compromise. In turn, increased functional connectivity predicted faster saccade reaction times and fewer direction errors. These findings suggest that increased functional connectivity, indicated by increased alpha and theta synchrony, may be necessary to compensate for structural compromise and preserve cognitive abilities. Further understanding these compensatory neural mechanisms could pave the way for the development of targeted therapeutic interventions aimed at enhancing these mechanisms, ultimately improving cognitive outcomes for affected individuals.

Aldehyde dehydrogenase-2 deficiency aggravates neuroinflammation, nociception, and motor impairment in a mouse model of multiple sclerosis

Aldehyde dehydrogenase-2 deficiency (ALDH2∗2) found in 36 % of Han Chinese, affects approximately 8 % of the world population. ALDH2 is a mitochondrial key enzyme in detoxifying reactive aldehydes to less reactive forms. Studies demonstrate a potential link between ALDH2∗2 mutation and neurodegenerative diseases. Multiple sclerosis (MS) is an incurable and disabling neurodegenerative autoimmune disease that induces motor, and cognitive impairment, and hypersensitivity, including chronic pain. Accumulating evidence suggests that reactive aldehydes, such as 4-hydroxynonenal (4-HNE), contribute to MS pathogenesis. Here, using knock-in mice carrying the inactivating point mutation in ALDH2, identical to the mutation found in Han Chinese, we showed that the impairment in ALDH2 activity heightens motor disabilities, and hypernociception induced by experimental autoimmune encephalomyelitis (EAE). The deleterious clinical signs are followed by glial cell activation in the spinal cord and increased 4-HNE levels in the spinal cord and serum. Importantly, the pharmacological ALDH2 activation by Alda-1 ameliorates EAE-induced hypernociception and motor impairment in both wild-type and ALDH2∗2KI mice. Reduced hypernociception was associated with less early growth response protein 1 (EGR1), neuronal and glial activation, and reactive aldehyde accumulation in the spinal cord and serum. Taken together, our data suggest that the mitochondrial enzyme ALDH2 plays a role in regulating clinical, cellular, and molecular responses associated with EAE. This indicates that ALDH2 could serve as a molecular target for MS control, with ALDH2 activators, like Alda-1 as potential neuroprotective candidates. Furthermore, ALDH2∗2 carriers may be at increased risk of developing more accentuated MS symptoms.

Human β-Defensin 2 as a Link between EBV Infection and Multiple Sclerosis

Multiple sclerosis (MS) is the result of a complex interaction between environmental factors and genetic predisposition. Epstein-Barr virus (EBV) is a significant environmental risk factor associated with MS. Human- beta defensin 2 (HβD-2) is a crucial innate immune response proteint that as an inflammatory marker protects humans from pathogens invading the body like viruses. Therefore, a case-control study was conducted on 90 subjected (48 patients with MS and 42 healthy controls) to examine the role of HβD-2 in EBV viral load infection and MS patients. An enzyme-linked immunosorbentassay kit was used to measure HβD-2 levels in serum. The viral load of EBV was determined using a real-time PCR. The findings revealed that median HβD-2 levels in patients were significantly lower than in controls. (96.62 vs.124.8 ng/mL; p &lt; 0.01). According to the receiver operating characteristic curve analysis, HβD-2 is good predictor for MS disease (area under the curve=0.739; p &lt; 0.001). EBV frequency was lower in MS patients compared to the controls, although difference was not statistically significant (25 vs. 38.1%; p = 0.181).On other hand, the median (EBV) load was substantially greater in patients than in healthy controls ( 8.55 vs. 1.4 DNA copy/100 cells). This study concluded that HβD-2 levels showed no significant differences in each age group, sex, Expanded Disability Status Scale (EDSS) of multiple sclerosis patients, rather showed an inverse significant correlation (correlation coefficient = - 0.432) with EBV load, which protect against human viral infections.

Clinical trajectories of patients with multiple sclerosis from onset and their relationship with serum neurofilament light chain levels.

Serum neurofilament light chain (sNfL) is a biomarker of neuroaxonal destruction that correlates with acute inflammation (AI) in multiple sclerosis (MS). However, in the treatment era, progression without AI is the main driver of long-term disability. sNfL may provide added value in detecting ongoing axonal damage and neurological worsening in patients without AI. We conducted a prospective three-year study on patients with a first MS relapse to evaluate the basal cut-off value predicting early increased disability unrelated to relapses. sNfL levels and AI presence were measured every 6 months during the first year and the Expanded Disability Status Scale (EDSS) was monitored until the third year. Baseline cohorts were stratified by sNfL levels, using a cut-off derived from patients without AI (absence of clinical relapses, new/enlarging T2 lesions, or gadolinium enhancement in magnetic resonance imaging) at year one. Fifty-one patients were included. A sNfL cut-off of 11 pg/mL predicted sustained neurological worsening independent of AI. Patients exceeding this threshold exhibited features of highly active MS (higher proportion of AI, oligoclonal M bands and higher EDSS). Despite AI ablation, sNfL levels persisted elevated and were significantly associated with increased EDSS at baseline and year 3. Patients with low sNfL and concurrent AI (n = 8) experienced relapses in the optic nerve, brainstem, and spinal cord topographies. sNfL elevation may detect patients with increased disability even when AI is controlled. This may reveal mechanisms associated with early axonal degeneration and help identify patients at higher risk of progression.