Features Of Multiple Sclerosis Research Articles

Explaining cognitive function in multiple sclerosis through networks of grey and white matter features: a joint independent component analysis

Cognitive impairment (CI) in multiple sclerosis (MS) is only partially explained by whole-brain volume measures, but independent component analysis (ICA) can extract regional patterns of damage in grey matter (GM) or white matter (WM) that have proven more closely associated with CI. Pathology in GM and WM occurs in parallel, and so patterns can span both. This study assessed whether joint-ICA of GM and WM features better explained cognitive function compared to single-tissue ICA. 89 people with MS underwent cognitive testing and magnetic resonance imaging. Structural T1 and diffusion-weighted images were used to measure GM volumes and WM connectomes (based on fractional anisotropy weighted by the number of streamlines). ICA was performed for each tissue type separately and as joint-ICA. For each tissue type and joint-ICA, 20 components were extracted. In stepwise linear regression models, joint-ICA components were significantly associated with all cognitive domains. Joint-ICA showed the highest variance explained for executive function (Adjusted R2 = 0.35) and visual memory (Adjusted R2 = 0.30), while WM-ICA explained the highest variance for working memory (Adjusted R2 = 0.23). No significant differences were found between joint-ICA and single-tissue ICA in information processing speed or verbal memory. This is the first MS study to explore GM and WM features in a joint-ICA approach and shows that joint-ICA outperforms single-tissue analysis in some, but not all cognitive domains. This highlights that cognitive domains are differentially affected by tissue-specific features in MS and that processes spanning GM and WM should be considered when explaining cognition.

Dorsoventral photobiomodulation therapy safely reduces inflammation and sensorimotor deficits in a mouse model of multiple sclerosis

BackgroundNon-invasive photobiomodulation therapy (PBMT), employing specific infrared light wavelengths to stimulate biological tissues, has recently gained attention for its application to treat neurological disorders. Here, we aimed to uncover the cellular targets of PBMT and assess its potential as a therapeutic intervention for multiple sclerosis (MS).MethodsWe applied daily dorsoventral PBMT in an experimental autoimmune encephalomyelitis (EAE) mouse model, which recapitulates key features of MS, and revealed a strong positive impact of PBMT on the sensorimotor deficits. To understand the cellular mechanisms underlying these striking effects, we used state-of-the-art tools and methods ranging from two-photon longitudinal imaging of triple fluorescent reporter mice to histological investigations and patch-clamp electrophysiological recordings.ResultsWe found that PBMT induced anti-inflammatory and neuroprotective effects in the dorsal spinal cord. PBMT prevented peripheral immune cell infiltration, glial reactivity, as well as the EAE-induced hyperexcitability of spinal interneurons, both in dorsal and ventral areas, which likely underlies the behavioral effects of the treatment. Thus, aside from confirming the safety of PBMT in healthy mice, our preclinical investigation suggests that PBMT exerts a systemic and beneficial effect on the physiopathology of EAE, primarily resulting in the modulation of the inflammatory processes.ConclusionPBMT may therefore represent a new valuable therapeutic option to treat MS symptoms.

Symptoms Prior to Diagnosis of Multiple Sclerosis in Individuals Younger Than 18 Years

A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS). To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease-related diagnostic code in pediatric patients compared with controls without MS and controls with another immune-mediated disorder, juvenile idiopathic arthritis (JIA). This population-based, matched case-control study included children and adolescents (aged <18 years) in Germany with statutory health insurance from January 2010 to December 2020. The study population consisted of 3 groups: case individuals with MS, control individuals without MS, and control individuals with JIA. Data were analyzed from November 2023 to April 2024. Diagnoses coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM). The main outcome was incident cases of MS, defined as the first confirmed diagnosis of MS (ICD-10-GM code G35) in 1 quarter between 2013 and 2020 and at least 1 additional diagnosis in the following quarters. In total, 163 ICD-10-GM codes before a first MS diagnosis were assessed using univariable and multivariable logistic regression analyses. The study population consisted of 1091 children and adolescents with MS, 10 910 without MS, and 1068 with JIA. Of the children and adolescents with MS, 788 (72.2%) were female. Mean (SD) age at disease diagnosis was 15.7 (1.7) years. Nine ICD-10-GM codes were present more frequently among children and adolescents with MS in the 5 years before their first MS diagnosis than among controls without MS: obesity (adjusted odds ratio [AOR], 1.70; 95% CI, 1.42-2.02), disorders of eye refraction and accommodation (AOR, 1.26; 95% CI, 1.09-1.47), visual disturbances (AOR, 1.31; 95% CI, 1.10-1.55), gastritis and duodenitis (AOR, 1.35; 95% CI, 1.08-1.70), patella disorders (AOR, 1.47; 95% CI, 1.13-1.90), heartbeat abnormalities (AOR, 1.94; 95% CI, 1.27-2.96), flatulence (AOR, 1.43; 95% CI, 1.01-2.01), skin sensation disturbances (AOR, 12.93; 95% CI, 8.98-18.62), as well as dizziness and giddiness (AOR, 1.52; 95% CI, 1.22-1.89). Four of these ICD-10-GM codes were significantly more prevalent in children and adolescents with MS than in controls with JIA: obesity (AOR, 3.19; 95% CI, 2.03-5.02), refraction and accommodation disorders (AOR, 3.08; 95% CI, 2.33-4.08), visual disturbances (AOR, 1.62; 95% CI, 1.13-2.33), and skin sensation disturbances (AOR, 27.70; 95% CI, 6.52-117.64). In this population-based, matched case-control study, children and adolescents with MS had diverse metabolic, ocular, musculoskeletal, gastrointestinal, and cardiovascular symptoms, signs, or diagnoses within 5 years before their first MS diagnosis. Better characterization of early symptoms and/or risk factors, comorbid disorders, and possible prodromal features of MS may have considerable implications for early recognition and subsequent progression of the disease.

Prevalence of, and Disability Due to, Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder in Japan by the Fifth Nationwide Survey.

All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey. The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire. The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth. The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

The relationship between ethnicity and multiple sclerosis characteristics in the United Kingdom: A UK MS Register study.

Previous studies have suggested differences in multiple sclerosis (MS) severity according to ethnicity. Data were obtained from the UK MS Register, a prospective longitudinal cohort study of persons with MS. We examined the association between self-reported ethnic background and age at onset, symptom of onset and a variety of participant-reported severity measures. We used adjusted multivariable linear regression models to explore the association between ethnicity and impact of MS, and Cox proportional hazards models to assess disability progression. We analysed data from 17,314 people with MS, including participants from self-reported Black (n = 157) or South Asian (n = 230) ethnic backgrounds. Age at MS onset and diagnosis was lower in those of South Asian (median 30.0) and Black (median 33.0) ethnicity compared with White ethnicity (median 35.0). In participants with online MS severity measures available, we found no statistically significant evidence for an association between ethnic background and physical disability in MS in both cross-sectional and longitudinal analyses. We found no association between ethnic background and MS severity in a large, diverse UK cohort. These findings suggest that other factors, such as socioeconomic status and structural inequalities, may explain previous findings.

The influence of MOGAD on diagnosis of multiple sclerosis using MRI.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders.

Characteristics of Patients with Newly Diagnosed Multiple Sclerosis – A 5-year Study at Benghazi Medical Center, Benghazi, Libya

Abstract Background: Epidemiology of multiple sclerosis (MS) in Libya had been studied at different intervals, but not focused on newly diagnosed patients with MS (pwMS). Objective: The objective of this study was to study the demographic, clinical, and paraclinical characteristics of pwMS and to find out whether the Libyan population had similar features of MS compared to other Arab countries and the rest of the world. Materials and Methods: This was a retrospective study conducted at MS clinic in Benghazi Medical Centre, Libya, from November 1, 2016 to December 31, 2021. The patients who were fulfilling the 2017 McDonald’s diagnostic criteria and registered at the MS clinic were included in the study. Data were collected and statistically analyzed with appropriate statistical tools. Results: The study included 102 patients, 69 (68%) were females. The mean age of participants was 28 ± 10 and 30 ± 9 years, at symptom and diagnosis onset, respectively. The most common symptoms were motor (n = 63, 62%). Relapsing-remitting course was reported in 96 (94%). Eighty-four patients (82%) had a low disability score (1.5 ± 1.6). Magnetic resonance imaging (MRI) images showed hyperintense white matter lesions, supratentorial (n = 102, 100%), infratentorial (n = 20, 20%), and spinal cord (n = 47, 46%). Half of the patients (50%) underwent MRI with gadolinium, and only four patients showed an enhancing lesion. Visual evoked potential was performed in 61/102 (60%), of whom 37/61 (60%) had optic neuritis. All patients (n = 102, 100%) received treatment with interferon b. The mean value for Vitamin D was 17.25 ± 12.37 ng/ml. Conclusion: Newly diagnosed pwMS in the eastern part of Libya is characterized by a mild disability as manifested by a low disability score. Other features are comparable to results from neighboring Arab countries and the rest of the world. Research on regional MS should be improved and facilitated through the establishment of a Libyan MS registry, which will explore data about disease severity and/or progression and the response to treatment.

Typical and Emerging Diagnostic MRI Features in Multiple Sclerosis.

Magnetic resonance imaging (MRI) stands as the most sensitive paraclinical technique for detecting the demyelinating lesions characteristic of multiple sclerosis (MS). Consequently, MRI plays a pivotal role in establishing an accurate and timely diagnosis of the disease, ultimately based on the application of the McDonald criteria. Early diagnosis is particularly important as it facilitates the prompt initiation of disease-modifying treatments, deemed most effective during the initial phases of MS. This review article examines the recommended standardized MRI protocol, as well as the classic imaging features of MS in the brain, optic nerve, and spinal cord, capable of discriminating, in most cases, MS from other disorders that can mimic this disease. Additionally, novel MR imaging findings, such as the central vein sign and paramagnetic rim lesion, which have been proposed as new imaging biomarkers to enhance diagnostic specificity for MS, are also discussed. These emerging features are likely to be incorporated in the future iterations of the McDonald criteria, and therefore, radiologists should be familiar with their appearance and with the optimal MRI protocols required for their detection.

Paramagnetic rim lesions as a biomarker to discriminate between multiple sclerosis and cerebral small vessel disease.

Multiple sclerosis (MS) and Cerebral Small Vessel Disease (CSVD) exhibit some similarities in Magnetic resonance imaging (MRI), potentially leading to misdiagnosis and delaying effective treatment windows. It is unclear whether CSVD can be detected with Paramagnetic Rim Lesions (PRL), which is special in MS. We aimed to investigate whether PRL can serve as a neuroimaging marker for discriminating between MS and CSVD. In this retrospective study, 49 MS and 104 CSVD patients underwent 3.0 T Magnetic resonance imaging (MRI). Visual assessment of 37 MS patients and 89 CSVD patients with or without lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH), central vein sign (CVS), and PRL. The distribution and number of PRL were then counted. Our study found that PRL was detected in over half of the MS patients but was entirely absent in CSVD patients (78.38 vs. 0%, p < 0.0001), and PRL showed high specificity with good sensitivity in discriminating between MS and CSVD (sensitivity: 78.38%, specificity: 100%, AUC: 0.96). Paramagnetic Rim Lesions is a special imaging feature in MS, absent in CSVD. Detection of PRL can be very helpful in the clinical management of MS and CSVD.

COMBAT-MS: A Population-Based Observational Cohort Study Addressing the Benefit-Risk Balance of Multiple Sclerosis Therapies Compared with Rituximab.

To assess comparative effectiveness, safety, and tolerability of off-label rituximab, compared with frequently used therapies approved for multiple sclerosis (MS). A Swedish cohort study of persons with relapsing-remitting MS, age 18 to 75 years at inclusion and with a first therapy start or a first therapy switch between 2011 and 2018. Low-dose rituximab was compared with MS-approved therapies. Primary outcomes were proportions with 12 months confirmed disability worsening and change in MS Impact Scale-29 (MSIS-29) scores, respectively. Secondary endpoints included relapses, therapy discontinuation, and serious adverse events. Analyses used an intention-to-treat approach and were adjusted for demographics, MS features, and health characteristics. We included 2,449 participants as first therapy start and 2,463 as first therapy switch. Proportions with disability worsening at 3 years were 9.1% for rituximab as first therapy and 5.1% after therapy switch, with no differences to MS-approved comparators. Worsening on rituximab was mostly independent of relapses. MSIS-29 with rituximab at 3 years improved by 1.3/8.4 points (physical/psychological) for first disease-modifying therapy (DMT) and 0.4/3.6 for DMT switch, and was mostly similar across therapies. Rituximab had lower relapse rates and higher therapy persistence in both groups. The rate of hospital-treated infections was higher with rituximab after a therapy switch, but not as a first therapy. This population-based real-world cohort study found low rates of disability progression, mostly independent of relapses, and without significant differences between rituximab and MS-approved comparators. Rituximab led to lower rates of inflammatory activity and higher treatment persistence, but was associated with an increased rate of serious infections. ANN NEUROL 2024;96:678-693.

Tango classes in people with Multiple Sclerosis (PwMS): Impact on motor and non-motor functions

BackgroundWhile music-based therapy (MBT) has been shown to improve motor and non-motor features in multiple sclerosis (MS), benefits of tango have never been assessed. ObjectiveTo evaluate the benefits of tango classes on quality of life (QoL), mood, fatigue, gait, balance, perception of cognitive disorder and sexuality in people with MS. Methods7 participants (age 41.14 ± 14.27 years, disease duration 14.14 ± 7.6 years) and respective partners undertook one-hour weekly classes for 20 weeks. Participants had early-stage MS (EDSS<3.5). They were assessed for mood (ZUNG rating scale; Beck Depression Inventory -II); balance (Berg Balance Test; Tinetti scale), cognition (MS Neuropsychological Screening Questionnaire), SD (Multiple Sclerosis Intimacy and Sexuality Questionnaire), fatigue (Fatigue Severity Scale) and QoL (36-Item Short Form Survey). ResultsGroup comparison of pre-post change scores showed a general improvement in all the outcome measures, which was significant in mood, SD, cognition and QoL. Discussions and conclusionTango classes provides benefits to pwMS, especially on non-motor symptoms. Follow-up assessment is required to confirm the durability of these effects.

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 &lt; 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 &lt; 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