Features Of Multiple Sclerosis Research Articles

A novel in vitro model for investigating oligodendroglial maturation and myelin deposition under demyelinating and remyelinating conditions: Impact of microglial depletion and repopulation

Experimental models of multiple sclerosis (MS) have significantly contributed to our understanding of pathophysiology and the development of therapeutic interventions. Various in vivo animal models have successfully replicated key features of MS and associated pathophysiological processes, shedding light on the sequence of events leading to disease initiation, progression, and resolution. Nevertheless, these models often entail substantial costs and prolonged treatment periods. In contrast, in vitro models offer distinct advantages, including cost-effectiveness and precise control over experimental conditions, thereby facilitating more reproducible results. We have developed a novel in vitro model tailored to the study of oligodendroglial maturation and myelin deposition under demyelinating and remyelinating conditions, which encompasses all the cell types present in the central nervous system (CNS). Of note, our model enables the evaluation of microglial cell commitment through a protocol involving their depletion and subsequent repopulation. Given that the development and survival of microglia are critically reliant on colony-stimulating factor-1 receptor (CSF-1R) signaling, we have employed CSF-1R inhibition to effectively deplete microglia. This versatile model holds promise for the assessment of potential therapies aimed at promoting oligodendroglial differentiation to safeguard and repair myelin, hence mitigate neurodegenerative processes.

Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis

BackgroundCriteria for multiple sclerosis (MS) diagnosis rely upon clinical and paraclinical data that are supportive of MS in the absence of a better explanation. Patients referred for consideration of a MS diagnosis often undergo an extensive serologic workup including antinuclear antibody (ANA) testing, even when an individual already meets diagnostic criteria for MS. It is unclear whether ANA serostatus is associated with clinical outcomes in MS. The present study aims to determine if ANA seropositivity in those referred with concern for MS differs in those who meet 2017 revised McDonald criteria compared to those who did not receive a diagnosis of MS. Associations between ANA seropositivity and clinical or radiological phenotype of MS patients are also explored. MethodsThe cohort included people at least 18 years old, referred to our tertiary care MS center with concern for MS (regardless of prior diagnosis) who had an ANA test with known titer completed within one year of first evaluation. Electronic health record (EHR) charts were manually reviewed, and MRIs underwent blinded review by a radiologist with training in neuroradiology. Diagnosis of MS was determined by a neuroimmunologist and was based on 2017 revised McDonald Criteria. Results are reported as odds ratios from multivariable logistic regression analyses adjusted for age, sex at birth, race, smoking history, personal history of comorbid autoimmune conditions, and family history of autoimmunity. Within the MS cohort, similar analytical models were performed to assess association between ANA and clinical and radiological characteristics. ResultsA final cohort of 258 patients was analyzed (out of 542 referrals): 106 nonMS and 152 with MS. There was no association between MS (vs. nonMS) diagnosis and ANA status (ANA positive n = 74) in the multivariable models (OR 1.5, 95 % CI 0.82, 2.72, p = 0.20). Among those with MS, there was no association of ANA seropositivity with the odds of atypical brain MRI features, number of cardinal MRI areas involved, location of MRI lesions, or of having an atypical presentation of first demyelinating event. Black race (OR 2.8, 95 % CI 1.27, 6.26, p = 0.01) and family history of autoimmunity (OR 2.1, 95 % CI 1.09, 3.98, p = 0.03) were independently associated with increased odds of ANA positivity. Within the MS cohort analysis, progressive MS (PMS; vs relapsing-remitting MS), a covariate in the model, appeared to be at higher odds of being ANA positive (OR 3.6, 95 % CI 1.03, 13.05, p = 0.046) but only when assessing mean area of cardinal MS locations. ConclusionsWhile ANA testing does not appear to be useful in distinguishing MS from non-MS, it remains less clear as to whether it may be associated with differences in the clinical course of MS (relapsing-remitting vs progressive). Future studies should aim to systematically evaluate whether those who are ANA positive are more likely, in well-designed and representative prospective cohorts, to be diagnosed with or develop progressive MS. Whether a positive ANA early in MS is associated with increased risk over time of developing or diagnosing another systemic autoimmune disease would also be of interest.

Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus

Cognitive dysfunction is a feature in multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. A notable aspect of MS brains is hippocampal demyelination, which is closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear. Chitinase-3-like (CHI3L1), secreted by activated astrocytes, has been identified as a biomarker for MS progression. Our study investigates CHI3L1's function within the demyelinating hippocampus and demonstrates a correlation between CHI3L1 expression and cognitive impairment in patients with MS. Activated astrocytes release CHI3L1 in reaction to induced demyelination, which adversely affects the proliferation and differentiation of neural stem cells and impairs dendritic growth, complexity, and spine formation in neurons. Our findings indicate that the astrocytic deletion of CHI3L1 can mitigate neurogenic deficits and cognitive dysfunction. We showed that CHI3L1 interacts with CRTH2/receptor for advanced glycation end (RAGE) by attenuating β-catenin signaling. The reactivation of β-catenin signaling can revitalize neurogenesis, which holds promise for therapy of inflammatory demyelination.

Twin study dissects CXCR3+ memory B cells as non-heritable feature in multiple sclerosis

In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk factors. Studies on monozygotic twins discordant for MS offer a unique way to reduce this complexity and reveal discrepant subsets. In this study, we analyzed B cell subsets in blood samples of monozygotic twins with and without MS using publicly available data. We verified functional characteristics by exploring the role of therapy and performed separate analyses in unrelated individuals. The frequencies of CXCR3+ memory B cells were reduced in the blood of genetically identical twins with MS compared to their unaffected twin siblings. Natalizumab (anti-VLA-4 antibody) was the only treatment regimen under which these frequencies were reversed. The CNS-homing features of CXCR3+ memory B cells were supported by elevated CXCL10 levels in MS cerebrospinal fluid and their invitro propensity to develop into antibody-secreting cells. Circulating CXCR3+ memory B cells are affected by non-heritable cues in people who develop MS. This underlines the requirement of environmental risk factors such as Epstein-Barr virus in triggering these B cells. We propose that after CXCL10-mediated entry into the CNS, CXCR3+ memory B cells mature into antibody-secreting cells to drive MS. This work was supported by Nationaal MS Fonds (OZ2021-016), Stichting MS Research (19-1057 MS, 20-490f MS, and 21-1142 MS), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program grant agreement no.882424, and the Swiss National Science Foundation (733 310030_170320, 310030_188450, and CRSII5_183478).

Multiple Sclerosis in Comparison to Sporadic Multiple Sclerosis in Iraqi Patients

Multiple Sclerosis (MS) is a complex autoimmune disease affecting the central nervous system, characterized by diverse symptoms based on lesion locations. Familial MS (FMS) indicates a genetic predisposition, potentially leading to a more severe disease course than sporadic MS, which lacks familial clustering. This distinction is critical for diagnosing and treating MS, particularly in the Iraqi patient population. The study aims to evaluate and compare the clinical and radiological features of FMS and sporadic MS among patients at the Baghdad Teaching Hospital's MS outpatient clinic. In this observational retrospective cross-sectional study, conducted from July 1, 2023, to December 31, 2023, at the Baghdad M.S outpatient clinic within the Medical City complex in Baghdad, Iraq, 100 MS patients were enrolled, with an equal division between FMS (n=50) and sporadic MS (n=50) cases. Participants were selected based on a definitive MS diagnosis, with FMS patients having a first or second-degree relative with MS. Data were collected via a questionnaire focusing on demographics, clinical presentations, MRI findings, and EDSS scores. Analysis was performed using SPSS version 26, employing Pearson Chi-square tests and Fisher's Exact test, with significance set at P ≤ 0.05. The demographic analysis revealed a predominant female representation (89%), with a significant age range between 20-30 years (48%). Time to diagnosis was notably longer for FMS cases, averaging 25.235 months, compared to 10.295 months for sporadic cases (P=0.002). Clinical presentations did not significantly differ between groups, but FMS cases exhibited greater disability severity, with higher EDSS scores indicating moderate to severe disability in 31% of FMS cases compared to only 19% in sporadic cases (P=0.035). MRI findings showed a higher prevalence of spinal cord and corpus callosum lesions in FMS (P=0.001 and P=0.027, respectively), with no significant differences in juxtacortical, cortical, or infratentorial lesions. This study illuminates that MS mainly affects females in their twenties and thirties, with familial MS cases taking longer to diagnose than sporadic ones. Familial cases exhibited more severe disabilities and more lesions in the spinal cord and corpus callosum. This indicates a complex interplay between genetics and MS, underscoring the importance of further research to enhance our understanding of the disease.

Clinical significance and prognostic value of serum autoantibody tests in multiple sclerosis.

It is known that multiple sclerosis (MS) often coexists with other autoimmune diseases. Hence, autoantibody (auto-Ab) tests may prove useful in the differential diagnosis of MS. The objectives of this study were to: (a) investigate the prevalence of auto-Ab positivity at the beginning of the MS diagnostic process; (b) assess whether Auto-Ab+ and Auto-Ab- patients differ in baseline clinical, laboratory, and radiological parameters; and (c) investigate the prognostic value during a two-year follow-up period. This retrospective study consisted of 450 patients aged between 18 and 55 years. All patients underwent a wide range of auto-Ab tests, anti-nuclear antibody (ANA) tests in particular. The expanded disability status scale (EDSS) scores of the patients were recorded at the time of diagnosis and at the end of a two-year follow-up period. The mean age of the 212 patients, 148 (69.8%) female and 64 (30.2%) male, included in the study sample was 37 ± 10.83 years. The rate of relapsing cases was 84% (178). Oligoclonal band (OCB) was positive in 142 (86.6%) of the 164 tested cases. At least one of the auto-Ab tests was positive in 51 (24.1%) of the cases. ANA test was positive in 21 (9.9%) cases. There was no significant difference between patients with at least one positive auto-Ab test and without any positive auto-Ab test and between ANA-positive and ANA-negative patients in terms of age, gender, clinical features of MS, presence of brain stem lesion, presence of spinal lesion, OCB positivity, level of clinical improvement after the first pulse steroid treatment, family history, presence of comorbidity, presence of autoimmune disease, or EDSS scores recorded at the end of the two-year follow-up period (p > 0.05). Our study findings revealed that Auto-Ab positivity was more common in MS patients than in the general population. However, given their limited contribution to the diagnosis and differential diagnosis of MS with no effect on the prognostic process, auto-Ab tests should be requested only in the event of accompanying autoimmune disease symptoms, and in cases where the diagnosis of MS may be suspected.

Vocabulary knowledge as a reliable proxy of cognitive reserve in multiple sclerosis: a validation study

IntroductionThe present study aimed to explore the suitability of the vocabulary knowledge (VOC) test as an accurate and reliable proxy of cognitive reserve (CR) by evaluating its psychometric properties and discrimination accuracy compared with other CR measures in multiple sclerosis (MS).MethodsSixty-eight consecutive people with multiple sclerosis (pwMS), followed at our MS outpatient clinic, completed a clinical evaluation and neuropsychological assessment including: VOC, Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), Beck Depression Inventory-II, and State-Trait Anxiety Inventory. Reliability, convergent and divergent validity, and discrimination accuracy of the VOC were assessed using educational level as reference standard. The possible effects of sociodemographic and clinical factors on VOC and their role in predicting global cognitive status were also explored.ResultsVOC demonstrated good internal consistency (Cronbach’s α = 0.894) and adequate construct validity. It showed an acceptable level of discrimination between pwMS with high and low CR, comparable to the CRIq score. Education strongly affected VOC scores, which in turn were independent of MS features. VOC emerged as an independent predictor of global cognitive status together with MS-related disability.ConclusionWe demonstrated the validity of VOC as a reliable CR measure in pwMS. Thus, CR may also be estimated using fixed objective measures, independent of brain pathology and clinical features. Early CR estimation may help clinicians identify pwMS at a higher risk of cognitive decline and plan strict neuropsychological monitoring and cognitive interventions.

COVID-19 and multiple sclerosis: is there a connection?

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, which is based on inflammatory demyelination and neurodegeneration. Over the course of the COVID-19 pandemic, there has been a perception that the virus has an effect on the course of immune processes. The questions of whether the frequency of autoimmune diseases, including the nervous system, and their course has changed have been discussed. Aim of the study was to assess the clinical and epidemiological characteristics of MS during the COVID-19 pandemic from 01.01.2020 to 01.01.2023 in Novosibirsk. In the course of our work, we studied the incidence of MS and the features of the clinical picture of the debut of MS associated with COVID-19 infection. Material and methods. The study included 628 patients with MS living in Novosibirsk with the onset of the disease in the period before the pandemic from 01.01.2017 to 12/31/2019 (341 patients) and during the pandemic from 01.01.2020 to 01.1.2023 (287 patients). Results. The incidence rates of MS in Novosibirsk were calculated, it was 7.1 7.6 6.4 7.38 6.92 and 3.2 per 100 thousand population in 2017, 2018, 2019, 2020, 2021 and 2020, respectively. The average incidence of MS in the study period before the pandemic was 7.03 per 100 thousand population, during the pandemic – 5.83 per 100 thousand population (critical value of the Student’s t-test = 1.972, with a significance level of a = 0.05). When analyzing the association of clinical manifestations of the onset of MS with COVID-19, it was found that coordination disorders were observed in patients with moderate infection more often than in patients with mild infection (p < 0.05; odds ratio 0.410, 95% confidence interval 0.162–1.035). No statistically significant correlation of clinical manifestations with the severity of infection was shown for patients with primary progressive MS, however, the predominance of the multi-focal nature of disease after a more severe course of COVID-19 was noted (40 %). After the first clinical demyelinating episode in the group of patients with relapsing-remitting MS, the chances of complete recovery in patients with mild infection are 2.8 times higher than in patients with moderate infection (p < 0.05). Conclusions. Thus, as a result of the conducted study, the effect of COVID-19 on the change in the incidence of MS was not revealed. In the process of analyzing the clinical features of MS during the pandemic, it was found that COVID-19 infection can contribute to an unfavorable course of MS with worse recovery of neurological deficits after episodes of exacerbations, which leads to the accumulation of disability of patients.

Definition and Characteristics of Multiple Sclerosis with Predominant Cognitive Presentation

Definition and Characteristics of Multiple Sclerosis with Predominant Cognitive Presentation

Qualification and predictors of the development of affective disorders in multiple sclerosi

Affective disorders occupy one of the leading places in the structure of comorbidity in multiple sclerosis, but the questions concerning etiopathogenesis, qualification, diagnosis, and prediction of these disorders remain controversial. The most important consequences of affective disorders in MS include a decrease in the patient's quality of life, adherence to treatment, and their daily activities, and an increased risk of suicide and death from cardiovascular diseases. In this regard, the need for early detection and prediction of the development of depression in patients with MS is obvious. The following factors are considered among the predictors of the development of emotional distress and affective disorders: social, psychological, demographic, neurocognitive, and treatment-related factors, neuroimaging data, lifestyle features, comorbidities, characteristics of multiple sclerosis and its social implications. Specifically, younger age at the time of diagnosis, the presence of dyssomnia, fatigue, consumption of dairy products, atrophy of cortical areas in the frontal lobes, and decreased white matter volume of the uncinate fasciculus predict the development of depression. This article reviews the features of depressive and bipolar spectrum disorders in patients with MS.

Fatigue, pain interference, and psychiatric morbidity in multiple sclerosis: The role of childhood stress.

Multiple sclerosis (MS) is a progressive, autoimmune disease of the central nervous system that affects nearly one million Americans. Despite the existence of immunomodulatory therapies to slow physical and cognitive disability progression, interventions to ameliorate common symptoms of MS, including fatigue and pain, remain limited. Poor understanding of risk factors for these symptoms may contribute to treatment challenges. In recent years, childhood stress has been investigated as a risk factor for chronic autoimmune conditions including MS; yet remarkably few studies have investigated the relationship between childhood stressors and chronic MS symptoms. Our aim was to examine clusters of stressors and three key features of MS: fatigue, pain interference, and psychiatric morbidity. Cross-sectional data were collected from a sample of People with MS (PwMS) via a national web-based survey that assessed the presence and type of childhood stressors and MS clinical features. Hierarchical block regression was used to assess associations among emotional, physical, and environmental childhood stressors and three clinical features commonly experienced by PwMS. N = 719 adults with MS (aged 21-85) completed the survey. Childhood emotional and physical stressors were significantly associated with overall presence of fatigue (p = 0.02; p<0.03) and pain interference (p<0.001; p<0.001) in adulthood, as well as the magnitude of both outcomes. Environmental stressors (p<0.001), in addition to emotional (p<0.001) and physical (p<0.001) stressors were significantly associated with psychiatric morbidity in PwMS. Childhood stress may predict fatigue, psychiatric morbidity, and pain in adults with MS. Further research is needed to show cause and effect; however, if an association exists, strategies to mitigate the impact of childhood stress could offer new pathways to reduce the severity of these symptoms. Broadly, this work adds to the body of evidence supporting upstream preventive measures to help address the stress on children and families.

The fluctuations of expression profiles of critical genes in the miRNA maturation process and pro-and anti-inflammatory cytokines in the pathogenesis and progression of multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system disease known for immune-mediated demyelination, inflammatory, and neurodegeneration symptoms. Discovering molecular biomarkers to classify RRMS and SPMS patients, monitor the disease activity, and response to particular treatments is one area that has received notable attraction. MicroRNA (miRNA), a single-stranded non-coding RNA molecule, is a significant regulator of gene expression recruited in pathogenic mechanisms in diverse diseases, especially cancer and MS. Also, the relapsing-remitting features of MS exhibit that both inflammatory and anti-inflammatory cytokines are effective in the progression of the disease over time. It was assessed the expression patterns of the genes (Drosha, Pasha(DGCR8), and Dicer) encoding the critical enzymes in the processing steps of miRNA maturation and major pro-inflammatory and anti-inflammatory cytokines (IFN-α, IFN-β, and IL-6) in blood cells of 40 MS patients (two groups of 10 men and women in both clinical courses of RR and SPMS patients) in comparison with 20 healthy control group (10 males and 10 females). The highest transcription activity of Drosha was observed for RRMS patients (4.2 and 3.6-fold, respectively), and the expression ratio was down regulated in male and female patients with SPMS (3.9- and 3.1-fold, respectively). Considering the studied cytokines, the increase in expression ratio of IL-6 in SPMS patients and the decrease in transcript abundance of INF-α, and INF-β cytokines are consistent with the progression of the disease. Our findings showed that the high and low transcriptional levels of the considered genes seem to be effective in the pathogenesis and progression of MS.

Social Cognition Impairments in Association to Clinical, Cognitive, Mood, and Fatigue Features in Multiple Sclerosis: A Study Protocol.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS), characterized by the diffuse grey and white matter damage. Cognitive impairment (CI) is a frequent clinical feature in patients with MS (PwMS) that can be prevalent even in early disease stages, affecting the physical activity and active social participation of PwMS. Limited information is available regarding the influence of MS in social cognition (SC), which may occur independently from the overall neurocognitive dysfunction. In addition, the available information regarding the factors that influence SC in PwMS is limited, e.g., factors such as a patient's physical disability, different cognitive phenotypes, mood status, fatigue. Considering that SC is an important domain of CI in MS and may contribute to subjects' social participation and quality of life, we herein conceptualize and present the methodological design of a cross-sectional study in 100 PwMS of different disease subtypes. The study aims (a) to characterize SC impairment in PwMS in the Greek population and (b) to unveil the relationship between clinical symptoms, phenotypes of CI, mood status and fatigue in PwMS and the potential underlying impairment on tasks of SC.

Features of multiple sclerosis in childhood in the Republic of Tatarstan

Multiple sclerosis (MS) in children and adolescents is a genuine concern of pediatric neurology that specialists in all countries are dealing with. To date, neither the causes of onset nor the individual components of the pathogenesis of the disease have been reliably clarified, and the modern, changing picture of the clinical manifestation of the disease sometimes complicates timely diagnosis even in adult patients. There are more such questions in pediatric MS.Objective: to study the prevalence and clinical features of MS in children in the Republic of Tatarstan.Material and methods. We conducted a survey and data analysis of 128 children and adolescents aged 0 to 18 years inclusive. The examination of patients included neurological examination according to the classical scheme, neuroimaging examination, neurophysiological examination and cerebrospinal fluid examination. The diagnosis was based on the current (as of the time of diagnosis) criteria of McDonald and the International Pediatrics MS Study Group criteria. The severity of the patients' clinical condition was assessed using the Expanded Disability Status Scale (EDSS).Results. MS was diagnosed in 99 cases (77.3%), clinically isolated syndrome – in 10 (7.8%), acute disseminated encephalomyelitis – in 5 (3.9%), bilateral optic neuritis – in two patients (1.6%), disseminated encephalomyelitis – in one case (0.8%); other central nervous system diseases were diagnosed in 11 (8.6%) patients. After a detailed examination, the group “other diseases of the central nervous system” included such conditions as cerebral angiopathy, neurofibromatosis, brain mass, structural focal epilepsy, sequelae of viral encephalitis, and hereditary leukodystrophy. Among the patients, girls aged 15–17 years predominated. Monofocal manifestations were more frequently observed at debut. Moreover, the absolute predominance of the remitting type of course was also noted.Conclusion. The data obtained suggest a predominance of the predominantly remitting course type of MS with a monofocal onset, which is consistent with data from other studies of MS in pediatric practice.

Characteristics of multiple sclerosis and demyelinating disease in an Asian American population

Background: Race and ancestry influence the course of multiple sclerosis (MS). Objectives: Explore clinical characteristics of MS and neuromyelitis optica spectrum disorder (NMOSD) in Asian American patients. Methods: Chart review was performed for 282 adults with demyelinating disease who self-identified as Asian at a single North American MS center. Demographics and clinical characteristics were compared to non-Asian MS patients and by region of Asian ancestry. Results: Region of ancestry was known for 181 patients. Most (94.7%) preferred English, but fewer East Asian patients did (80%, p = 0.0001). South Asian patients had higher neighborhood household income (p = 0.002). Diagnoses included MS (76.2%) and NMOSD (13.8%). More patients with NMOSD than MS were East and Southeast Asian (p = 0.004). For MS patients, optic nerve and spinal cord involvement were similar across regions of ancestry. Asian MS patients were younger at symptom onset and diagnosis than non-Asian MS patients. MS Severity Scale scores were similar to non-Asian MS patients but worse among Southeast Asians (p = 0.006). Conclusions: MS severity was similar between Asian American patients and non-Asian patients. Region of ancestry was associated with differences in sociodemographics and MS severity. Further research is needed to uncover genetic, socioeconomic, or environmental factors causing these differences.

Shaping membrane interfaces in lipid vesicles mimicking the cytoplasmic leaflet of myelin through variation of cholesterol and myelin basic protein contents

Myelin basic protein (MBP) is an intrinsically disordered protein and in the central nervous system (CNS) mainly responsible for connecting the cytoplasmic surfaces of the multilamellar, compact myelin. Increased posttranslational modification of MBP is linked to both, the natural development (from adolescent to adult brains) of myelin, and features of multiple sclerosis. Here, we study how a combination of this intrinsically disordered myelin protein with varying the natural cholesterol content may alter the characteristics of myelin-like membranes and interactions between these membranes. Large unilamellar vesicles (LUVs) with a composition mimicking the cytoplasmic leaflet of myelin were chosen as the model system, in which different parameters contributing to the interactions between the lipid membrane and MBP were investigated. While we use cryo-transmission electron microscopy (TEM) for imaging, dynamic light scattering (DLS) and electrophoretic measurements through continuously-monitored phase-analysis light scattering (cmPALS) were used for a more global overview of particle size and charge, and electron paramagnetic resonance (EPR) spectroscopy was utilized for local behavior of lipids in the vesicles' membranes in aqueous solution. The cholesterol content was varied from 060 % in these LUVs and measurements were performed in the presence and absence of MBP. We find that the composition of the lipid layers is relevant to the interaction with MBP. Not only the size, the shape and the aggregation behavior of the vesicles depend on the cholesterol content, but also within each membrane, cholesterol's freedom of movement, its environmental polarity and its distribution were found to depend on the content using the EPR-active spin-labeled cholesterol (CSOSL). In addition, DLS and EPR measurements probing the transition temperatures of the lipid phases allow a correlation of specific behavior with the human body temperature of 37 °C. Overall, our results aid in understanding the importance of the native cholesterol content in the healthy myelin membrane, which serves as the basis for stable and optimum protein-bilayer interactions. Although studied in this specific myelin-like system, from a more general and materials science-oriented point of view, we could establish how membrane and vesicle properties depend on cholesterol and/or MBP content, which might be useful generally when specific membrane and vesicle characteristics are sought for.

FREQUENCY AND PREDICTORS OF LHERMITTE PHENOMENON IN MULTIPLE SCLEROSIS (2-YEAR PROSPECTIVE STUDY)

Neuropathic pain in multiple sclerosis can manifest itself in the form of the Lhermitte phenomenon, short-term unpleasant sensations along the spine that occur when the head is bent. The purpose of this study is to investigate the factors that act as predictors of the Lhermitte phenomenon and their frequency in multiple sclerosis. 308 patients with multiple sclerosis were involved in the study, 258 of them agreed to follow-up, of them there were 67 men (26.0%) and 191 women (74.0%), aged 21 to 60 years. Out of the total cases, 187 (72.5%) patient had the relapsing-remitting type of multiple sclerosis, 2 (0.8%) had primary progressive type, and 69 (26.7%) showed secondary progressive type. Among the 258 patients who initially agreed to participate in the study at the Centre, 18 (7.0%) individuals discontinued their involvement during the first year, and 13 (5.0%) individuals prematurely withdrew from the study during the second year due to various reasons.&#x0D; Among the characteristics of multiple sclerosis, the age of the patient when diagnosed, the duration and the type of course, and the overall assessment of neurological deficit were determined. Psychopathological and cognitive states, socio-demographic factors, and comorbid pathology were assessed using appropriate scales. Statistical research methods were employed to analyze the collected data.&#x0D; The results indicate that the risk of developing the Lhermitte phenomenon remains relatively consistent over a two-year period: 2.5% in the first year and 2.3% in the second year. Pain associated with the Lhermitte phenomenon is most commonly experienced in the neck (63.6%), followed by the upper back (54.6%), lower back (72.7%), and least frequently in the upper limbs (18.2%) and lower limbs (36.4%). The Lhermitte phenomenon typically spreads to two or three affected areas of the body in 33.3% and 48.2% of cases, respectively. The most commonly used descriptors for the Lhermitte phenomenon are "shooting" (72.7%), "tingling" (18.2%), and "crawling ants" (9.1%).&#x0D; No significant differences in social, demographic, neuropsychological, and neurocognitive characteristics were observed between patients with and without Lhermitte phenomenon. According to the results of univariate Cox regression analysis, we has found that during the 2-year period, an increase in the duration of the disease for each subsequent year is associated with a decrease in the relative risk of Lhermitte phenomenon by 1.15 times (1.02-1.29, p=0.02). In patients with multiple sclerosis, the average risk of experiencing the Lhermitte phenomenon remains consistent at approximately 2.3-2.5% per year throughout the course of the disease.&#x0D; Patients who have a short history of multiple sclerosis are a risk group for the occurrence of the Lhermitte phenomenon. It is quite difficult to explain the regularity we have identified, for its clarification a detailed study of a special additional study is necessary. But, in any case, from a practical point of view, patients in the early stages of multiple sclerosis can be considered as a group of increased risk for the occurrence of the Lhermitte phenomenon.

Familial Mediterranean Fever and multiple sclerosis treated with ocrelizumab: Case report

BackgroundFamilial Mediterranean Fever (FMF) is associated with increased risk of multiple sclerosis (MS). Optimal treatment of patients with comorbid FMF and MS remains uncertain. CaseA 28-year-old woman with FMF, treated with colchicine, had symptomatic onset of relapsing remitting MS following four simultaneous vaccines. MRI brain with a 7-Tesla magnet demonstrated several areas of leptomeningeal enhancement with predominant linear, spread/fill and rare nodular patterns. Central vein signs were present in supratentorial white matter lesions. She received four cycles of ocrelizumab and achieved no evidence of disease activity (NEDA-3) at 20 months' follow up. DiscussionFMF with incident CNS demyelinating disease demonstrated neuroimaging features typical for classic RRMS including the central vein sign and leptomeningeal enhancement. Treatment with B-cell depleting therapy for FMF-MS led to clinical stability and symptomatic improvement at 20 months' follow up. We add to the sparse literature characterizing the course of FMF as a genetic risk factor for CNS demyelinating disease, demonstrating pathognomonic imaging features of MS on 7 T imaging and treatment efficacy with B-cell depletion.

Characteristics of Multiple Sclerosis and Demyelinating Disease in an Asian American Population (P9-3.009)

<h3>Objective:</h3> To explore the clinical presentation of MS and neuromyelitis optica spectrum disorder (NMOSD) in patients of Asian ancestry in the United States. <h3>Background:</h3> Race and ancestry influence the course of demyelinating conditions like Multiple Sclerosis (MS). Asian patients are underrepresented in clinical research in the United States. <h3>Design/Methods:</h3> Demographic, clinical and radiologic data were extracted from the medical record for adults with Asian self-identified race and diagnosis of demyelinating disease cared for at a single North American MS center between 2006/02/06 and 2022/06/09. Descriptive statistics were used to describe the cohort, then demographic and clinical factors were compared according to region of ancestry. <h3>Results:</h3> The cohort included 282 patients from 11 different countries; 73.1% were born in Asia. Most patients (94.7%) preferred English for medical communication, but fewer of East Asian ancestry did (p=0.0001). South Asian ancestry was associated with higher neighborhood household income (p=0.002) and Southeast Asian ancestry with smoking (p=0.08). Diagnoses included MS (76.2%) and NMOSD (13.8%). More patients with NMOSD than MS were of East Asian and Southeast Asian ancestry (p=0.004). For MS patients, levels of optic nerve and spinal cord involvement were similar across regions of ancestry. Most (83.7%) patients were currently on MS treatment (42.3% on antiCD20 therapies). MS Severity Scale (MSSS), while similar to the clinic average. was worse with Southeast Asian ancestry (p=0.006) and also worse with smoking, and lower neighborhood median household income or educational attainment. <h3>Conclusions:</h3> Patients of Asian ancestry are underrepresented in research in the United States. In this cohort, Asian patients with MS were actively treated and disease severity reflected the overall clinic. Both region of origin and neighborhood socioeconomic factors were associated with disease characteristics. Further research is needed to uncover genetic, socioeconomic, or environmental factors accounting for worse MSSS in Southeast Asian patients. <b>Disclosure:</b> Dr. Fan has nothing to disclose. Ms. Alexander has nothing to disclose. Mr. Poole has nothing to disclose. Ms. Wijangco has received research support from National Institutes of Health. Dr. Henson has received personal compensation for serving as an employee of Piedmont Healthcare. An immediate family member of Dr. Henson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Tempus. Dr. Henson has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for various law firms. Ruth Dobson has nothing to disclose. Dr. Guo has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis.

Gray Matter Microstructure Alterations in People with Multiple Sclerosis Based on Cell Body and Neurite Density Imaging (P10-3.007)

<h3>Objective:</h3> To evaluate a novel compartment-based model for apparent cell body and neurite density imaging (SANDI) in gray matter (GM) in people with multiple sclerosis (MS) compared to healthy controls (HC) and its correlation with brain atrophy. <h3>Background:</h3> MS features focal cortical lesions and microstructural changes in normal-appearing GM, which can impact clinical function and disability. High gradient diffusion MRI has potential to optimize GM tissue microstructure characterization by overcoming challenges due to the complexity of underlying components. <h3>Design/Methods:</h3> 41 people with MS and 37 age- and sex-matched HC were scanned on a 3T Connectom MRI scanner equipped with 300mT/m gradients using a multi-shell acquisition protocol consisting of eight b-values at 19msec diffusion time. Microstructural metrics of SANDI, including a measure of soma density (f_soma) in the cortex and deep GM, were compared between MS and HC and correlated with cortical and thalamic atrophy, correcting for multiple comparisons. <h3>Results:</h3> Cortical cell body signal fraction (f_soma) was decreased in MS compared to HC (0.56 vs. 0.58, <i>p</i>=0.027, not surviving FDR-correction). In deep GM, f_soma and extra-cellular signal fraction were significantly decreased in MS compared to HC (<i>FDR-p</i>=0.045 in both), which was most pronounced in progressive MS. Based on spatial analysis, f_soma of caudate nucleus and thalamus were significantly decreased in MS compared to HC (<i>FDR-p</i>=0.003 and <i>FDR-p</i>=0.027, respectively). Whereas cortical atrophy in MS was poorly correlated with cortical f_soma, thalamic atrophy in MS demonstrated moderate correlation with decreased thalamic f_soma (r=0.311, <i>p</i>=0.054) and decreased cortical f_soma (r=0.474, <i>p</i>=0.008). <h3>Conclusions:</h3> SANDI metrics, in particular f_soma, provide detailed GM characterization beyond cortical and thalamic volumes and are able to characterize MS-related microstructural pathology. Decreased cortical cell density correlates with declining thalamic volume and may precede volumetric measures of cortical atrophy in people with MS. <b>Disclosure:</b> Ms. Krijnen has nothing to disclose. Andrew Russo has nothing to disclose. Dr. Salim Karam has nothing to disclose. The institution of Menno M Schoonheim has received research support from Dutch MS Research Foundation. The institution of Menno M Schoonheim has received research support from Eurostars-EUREKA. The institution of Menno M Schoonheim has received research support from ARSEP. The institution of Menno M Schoonheim has received research support from Amsterdam Neuroscience. The institution of Menno M Schoonheim has received research support from MAGNIMS. The institution of Menno M Schoonheim has received research support from ZonMW. The institution of Menno M Schoonheim has received research support from Atara Biotherapeutics. The institution of Menno M Schoonheim has received research support from Biogen. The institution of Menno M Schoonheim has received research support from Celgene/Bristol Meyers Squibb. The institution of Menno M Schoonheim has received research support from Genzyme. The institution of Menno M Schoonheim has received research support from MedDay. The institution of Menno M Schoonheim has received research support from Merck. Dr. Huang has received personal compensation in the range of $0-$499 for serving as a Consultant for Siemens Healthineers. The institution of Dr. Huang has received research support from Siemens Healthineers. The institution of Dr. Huang has received research support from Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Galen/Atlantica. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Banner Life Sciences. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Klawiter has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for OM1. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Klawiter has received research support from Biogen. The institution of Dr. Klawiter has received research support from Abbvie. The institution of Dr. Klawiter has received research support from Genentech.