Criteria For Multiple Sclerosis Research Articles

Uncovering alternative diagnoses in patients with clinical syndromes suggestive of multiple sclerosis: A transversal study from the prospective Barcelona CIS cohort.

It is essential to exclude alternative diagnoses to diagnose multiple sclerosis (MS). However, detailed descriptions of alternative diagnoses in patients with suspected MS presenting with clinically isolated syndrome (CIS) are limited. To describe alternative diagnoses in patients presenting with CIS suggestive of MS. We conducted a descriptive analysis of patients from the Barcelona CIS cohort including subjects under 50 years of age with a CIS suggestive of MS but later diagnosed with conditions other than MS. We collected clinical, biological, and radiological data, and described the alternative etiologies identified. Among 1468 patients in the Barcelona CIS cohort, 100 (6.8%) were diagnosed with an alternative condition. The most common neurological syndrome was optic neuritis (43.0%). Four patients (4.0%) had inflammatory-demyelinating lesions in at least two typical MS topographies on baseline magnetic resonance imaging (MRI), and 2 (2.0%) met the 2017 McDonald MS criteria. The most common etiologies were immune-mediated diseases (42.0%), especially MOGAD, followed by functional neurological disorders (15.0%) and vascular disease (10.0%). The range of alternative diagnoses encountered during the MS diagnostic process highlights the need to rule out better explanations than MS. However, current MS diagnostic criteria effectively identify patients without MS in this context.

Exploring proteomic immunoprofiles: common neurological and immunological pathways in multiple sclerosis and type 1 diabetes mellitus

BackgroundInterest in the study of type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) has increased because of their significant negative impact on the patient quality of life and the profound implications for the health care system. Although the clinical symptoms of T1DM differ from those of MS, such as pancreatic β-cell failure in T1DM and demyelination in the central nervous system (CNS) in MS, both pathologies are considered as autoimmune-related diseases with shared pathogenic pathways, which include autophagy, inflammation and degeneration, among others. Considering the challenges in obtaining pancreatic β-cells and CNS tissue from patients with T1DM and MS, respectively, it is fundamental to explore alternative methods for evaluating disease status. Proteomic analysis of peripheral blood mononuclear cells (PBMCs) is an ideal approach for identifying novel and potential biomarkers for both autoimmune diseases.MethodsWe conducted a proteomic analysis of PBMCs from patients with T1DM and relapsing remitting Multiple Sclerosis (herein forth MS) patients (n = 9 per condition), using a label-free quantitative proteomics approach. The patients were diagnosed following the American Diabetes Association (ADA) criteria for T1DM and McDonald criteria for MS respectively, and were aged over 18 years and more than 2 years from the onset respectively.ResultsA total of 2476 proteins were differentially expressed in PBMCs from patients with T1DM and MS patients compared with those form healthy controls (H). Predictive analysis highlighted 15 common proteins, up- or downregulated in PBMCs from patients with T1DM and MS patients vs. healthy controls, involved in the immune system activity (BTF3, TTR, CD59, CSTB), diseases of the neuronal system (TTR), signal transduction (STMN1, LAMTOR5), metabolism of nucleotides (RPS21), proteins (TTR, ENAM, CD59, RPS21, SRP9) and RNA (SRSF10, RPS21). In addition, this study revealed both shared and distinct molecular patterns between the two conditions.ConclusionsCompared with H, patients with T1DM and MS presented a specific expression pattern of common proteins has been identified. This pattern underscores the shared mechanisms involved in their immune responses and neurological complications, alongside dysregulation of the autophagy pathway. Notably, CSTB has emerged as a differential biomarker, distinguishing between these two autoimmune diseases.

The value of magnetic resonance imaging of the optic nerve for the diagnosis of multiple sclerosis in patients with optic neuritis

BackgroundAlthough optic neuritis (ON) is common in multiple sclerosis (MS), lesions of the optic nerve are not included as an anatomical substrate for dissemination in space and time (DIS and DIT).ObjectiveTo assess the increase in sensitivity of including MRI lesions of the optic nerve for the diagnosis of MS in patients with ON.MethodsWe included patients consecutively referred with first time, monosymptomatic ON, with no known cause of the ON, who underwent orbital MRI including fat suppressed T2 and T1-sequences with and without gadolinium contrast.ResultsOne hundred and twenty patients were included. Optic nerve T2 lesions and/or T1-contrast enhancement was shown in 104 patients. Sixty-three patients were diagnosed with MS at baseline. Nine patients developed MS during follow-up. The inclusion of optic nerve MRI lesions led to the diagnosis of 8 additional patients and increased sensitivity to 0.99 (95% CI 0.96–1.00) compared to 0.88 (95% CI 0.79–0.95) for 2017 criteria, while decreasing the specificity to 0.81 (95% CI 0.70–0.92) compared to 1.00.ConclusionAmending the diagnostic criteria for MS to include MRI lesions of the optic nerve as a substrate for DIS and DIT may increase sensitivity and lead to more rapid diagnosis of MS.

NCMP-22. CO-OCCURRENCE OF MULTIPLE SCLEROSIS AND HODGKIN LYMPHOMA. IS THERE A COMMON PATHOPHYSIOLOGY?

Abstract BACKGROUND Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. However, occurrence of these two distinct clinical conditions is rare. We present a case of a woman with transverse myelitis fulfilling criteria for MS with synchronous HL. CASE REPORT A 37-year-old woman presented to the emergency room with bilateral leg weakness, numbness and urinary retention. A contrasted MRI of the brain and thoracic spine showed non-specific, non-enhancing white-matter lesions in the brain, and patchy areas of peripheral contrast-enhancement with T2-hyperintensity in the thoracic cord. Treatment with steroid infusion resulted in mild improvements of leg weakness and numbness. Cerebrospinal fluid (CSF) demonstrated oligoclonal bands (OCB) and increased IgG index. Serum was positive for JCV antibody. Due to the atypical MRI findings, namely the peripheral nature of thoracic contrast-enhancement, we were concerned for other inflammatory or autoimmune etiologies. A computed tomography of the chest, abdomen and pelvis revealed a large mediastinal mass and enlarged lymph nodes. A biopsy revealed classic HL. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. A repeat CSF study revealed normal OCBs and IgG index. CSF was negative for malignant cells and JC virus DNA. To rule out a rare possibility of central nervous system HL, a biopsy of an enhancing brain lesion was obtained, which showed focal gliosis and focal perivascular lymphocytic infiltrates. No malignant cells were observed. She was diagnosed with multiple sclerosis and started systemic chemotherapy (doxorubicin, bleomycin, dacarbazine and vinblastine) for HL. CONCLUSIONS We report a case of an atypical transverse myelitis with HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity.

Evaluation of Brain and Spinal Cord Lesions and Cerebrospinal Fluid Analysis in Detecting Demyelinating Diseases in Patients with Optic Neuritis

ABSTRACT Optic neuritis can be an early sign of demyelinating diseases like multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). We investigated the presence or absence of head and spinal cord lesions on magnetic resonance imaging (MRI) and assessed whether cerebrospinal fluid (CSF) tests are useful in detecting demyelinating disease in patients with first diagnosed optic neuritis. We conducted a retrospective study of 111 patients (47 idiopathic, 19 NMOSD, 16 MOGAD, 16 MS, 6 optic neuritis with cerebral lesions but that does not meet the McDonald’s criteria for MS (ON+)), and 7 chronic relapsing inflammatory optic neuropathy) diagnosed with optic neuritis without cerebral or spinal symptoms. Patients underwent evaluations including orbital, head, and spine MRI, along with CSF analysis. Among the 111 patients, 20 (35.1%: 4 NMOSD, 4 MOGAD, 7 MS, and 6 ON+) exhibited intracerebral or spinal cord lesions. Twelve patients showed findings on both orbital and head MRI, while six had no orbital MRI findings except for optic neuritis but exhibited lesions on head MRI. Five patients had spinal lesions without intracerebral lesions. CSF analysis revealed positive oligoclonal bands and elevated myelin basic protein levels indicate the high likelihood with systemic inflammatory demyelinating diseases. Even in the absence of concomitant encephalitis or myelitis symptoms or a history of these conditions, MRI images of patients with optic neuritis sometimes reveal lesions in the brain or spinal cord. CSF abnormalities were indicative of systemic demyelinating disease presence, extending beyond MS to NMOSD and MOGAD.

Picturing the Multiple Sclerosis Patient Journey: A Symptomatic Overview.

Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease's natural history. This study aimed to assess the clinical symptoms of MS patients in a modern population at various stages: before diagnosis, at diagnosis, during the disease course, and at the time of the survey. Methods: This was an observational study with retrospective and cross-sectional components; patients that fulfilled the 2017 revised McDonald criteria for MS completed a survey evaluating demographic and clinical data. Results: We included 163 patients, 69.9% female, with a mean age of 48.21 years; 87.1% had relapsing-remitting MS (RRMS), with a median EDSS of 2.0. Before diagnosis, 74.2% of patients experienced symptoms, mainly sensory issues (39.3%), fatigue (29.4%), and imbalance (27%). Motor and coordination symptoms were more common in progressive forms. At diagnosis, sensory (46.6%) and motor complaints (36.8%) were most prevalent. In RRMS and secondary progressive MS (SPMS), sensory and motor complaints predominated alongside imbalance, while primary progressive MS (PPMS) was characterized by motor, imbalance, and genitourinary symptoms. Throughout the disease, sensory symptoms were most common (76.1%), with fatigue (73%) and motor issues (62.6%) more prevalent in progressive forms. At the time of the survey, 50.7% of RRMS patients were asymptomatic, while progressive patients continued to experience motor symptoms, imbalance, and fatigue. Conclusions: The study reflects the modern spectrum of MS symptoms, consistent with previous research.

Early Disease-Modifying Treatments for Presymptomatic Multiple Sclerosis.

Radiologically isolated syndrome (RIS) is the earliest stage in the disease continuum of multiple sclerosis (MS). RIS is discovered incidentally in individuals who are asymptomatic but have typical lesions in the brain and/or spinal cord suggestive of demyelination. The2009 and revised 2023 RIS criteria weredeveloped for diagnosis.Presymptomatic individuals who fulfill the 2009 RIS criteria by having 3-4 of 4 dissemination in spaceMcDonald 2005 MS criteria are still diagnosed with RIS using therevised 2023 RIS criteria.Inpresymptomatic individuals who do not fulfill the 2009 RIS criteria, the revised 2023 RIS criteria target to secure an accurate and timely diagnosis: In addition to (a) having one lesion in two of four locations (periventricular, juxtacortical/cortical, infratentorial, spinal cord), (b) two of three features (spinal cord lesion, cerebrospinal fluid (CSF)-restricted oligoclonal bands, and new T2 or gadolinium-enhancing lesion) should be fulfilled. Among laboratory biomarkers,CSF kappa-free light chain can also increase diagnostic accuracy. Once the diagnosis is confirmed, the established risk factors, including demographics, imaging, and laboratory biomarkers, should be evaluated for symptomatic MS transition and prognosis. Younger age, male sex, increased neurofilament-light chain, CSF abnormality, and the presence of infratentorial, spinal cord, or gadolinium-enhancing lesions on imaging are the main risk factors for transition to symptomatic MS. Two randomized clinical trials showed significant efficacy of disease-modifying treatments in delaying or preventing the development of the first clinical event in RIS. However, because some individuals remain as RIS, it is crucial to identify the individuals with a higher number of risk factors to optimize disease outcomes by early intervention while minimizing adverse events. Discussing each RIS case with an expert MS team is recommended because there is still a lack of clinical guidelines to improve care, counseling, and surveillance.

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.

Терапия рассеянного склероза препаратами первой линии: уровень цитокинов и влияние герпетической инфекции

The effects of the disease modifying drugs (DMDs) for multiple sclerosis (MS), interferon beta (IFNβ) and glatiramer acetate (GA), on the cytokine levels of individuals with MS are poorly understood. The effects of persistent herpesvirus infection (PHVI) on the cytokine production during treatment with DMDs for MS have not been identified. The role of cytokines and PHVI in the development of the treatment-related adverse events (AEs) has not been determined. The study was aimed to assess serum cytokine levels in patients with MS treated or not treated with DMDs for MS, and to determine the relationships between the cytokine levels, herpesvirus infection, and AEs. A total of 36 patients (12 males and 24 females, median age 38.50 (28.00; 48.50) years) with relapsing-remitting MS (criteria by McDonald, 2010) were examined. PHVI reactivation was observed in 18 individuals; in 10 of them it was associated with the history of the virus-associated exacerbation (VAE) of MS or VAE detected during assessment. A total of 30 patients were treated with DMDs for MS: 16 individuals with IFNβ, 14 individuals with GA. Systemic AEs were reported in 9 individuals. Serum levels of 15 cytokines were determined using the xMAP multiplex technique. Patients with MS showed a significant increase in the levels of IL10 (p < 0.01) and IL33 (p < 0.001) relative to donors when treated or not treated with DMDs for MS; the increase in IL31 levels was reported only in naïve patients (p < 0.05). At the same time, individuals with MS had low levels of IL1β, IL17F, IL22, IL25, IL23, and TNFα (p < 0.01). We revealed no differences in cytokine levels in the context of taking IFNβ or GA. Elevated IL10 levels were associated with PHVI reactivation (p < 0.01). We revealed significant correlations between high levels of IL31 and VAE (p < 0.01), IL33 and PHVI (p < 0.01). The IL1β levels were significantly higher in individuals with PHVI reactivation treated with DMDs for MS. There were no differences in cytokine levels associated with the presence or absence of systemic AEs. The latter predominated in individuals with PHVI reactivation and VAE. The cytokine levels of individuals with MS are affected by treatment with DMDs for MS and herpesvirus infections.

Exploring Factors Associated with Falls in Multiple Sclerosis: Insights from a Scoping Review.

Multiple sclerosis (MS) is a chronic inflammatory condition that causes demyelination of the central nervous system accompanied by a wide range of symptoms. The high prevalence of falls among patients diagnosed with MS within the initial six months highlights the importance of this issue. The objective of this study is to identify factors associated with falls in MS patients in order to increase awareness and reduce the risk of falls. This scoping review used specific Mesh terms to formulate the literature search around falls and MS using Medline, Google Scholar, Scopus, and Embase search engines. English papers published between 2012 and 2022, studies with a clear definition of falls, McDonald's diagnostic criteria for MS, and those with Expanded Disability Status Scale (EDSS) or Patient Determined Disease Steps (PDDS) scores were included. Critical data from the selected articles were extracted and classified according to the different factors associated with falls in MS patients. Eighteen articles were included in this review. The most important factors associated with falls in MS patients identified were the severity and progression of the disease, mobility and balance problems, bladder dysfunction, fear of falling, fatigue, and cognitive dysfunction. In conclusion, this scoping review yielded the most common factors associated with falls in patients with MS. Study findings can be used to develop future interventions focusing on improving mobility, proprioception, and balance to decrease fall risk and injury amongst MS patients.

Clinical and paraclinical characteristics of optic neuritis in the context of the McDonald criteria 2017

Optic neuritis is often an initial symptom in multiple sclerosis (MS) or clinically isolated syndrome (CIS), yet comprehensive studies using the 2017 McDonald criteria for MS are scarce. Patient records from our academic centre (2010–2018) were reviewed. Using the 2017 McDonald criteria, three groups were formed: MS optic neuritis (optic neuritis with confirmed MS), CIS optic neuritis (optic neuritis without confirmed MS) and suspected optic neuritis (sON). We compared clinical and paraclinical findings among the groups to identify predictors for CIS- or MS-optic neuritis. The study included 129 MS, 108 CIS, and 44 sON cases. The combination of visual impairment, dyschromatopsia, and retrobulbar pain was observed in 47% of MS patients, 42% of CIS patients, and 30% of sON patients. Dyschromatopsia was the strongest indicator of MS or CIS diagnosis in the backward regression model. 56% of MS patients had relative afferent pupillary defect, 61% optic nerve anomalies within magnetic resonance imaging, and 81% abnormal visual evoked potentials. Our results emphasize the challenges in diagnosing optic neuritis, as not all patients with objectively diagnosed MS exhibit the triad of typical symptoms. To address potentially missing clinical features, incorporating additional paraclinical findings is proposed.

Senescence marker p16INK4a expression in patients with multiple sclerosis

ObjectivesTelomere attrition is associated with disability accumulation and brain atrophy in multiple sclerosis (MS). Downstream of telomere attrition is cellular senescence. We sought to determine differences in the cellular senescence marker p16INK4a expression between MS and healthy control participants and the association of p16INK4a expression with MS disability and treatment exposure. MethodsPatients meeting diagnostic criteria for MS and healthy controls were recruited for a cross-sectional pilot study. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and p16INK4a expression levels were measured using qRT PCR. Spearman correlation coefficients and regression models were applied to compare expression levels to chronological age, assess case control differences, and determine associations with clinical outcome measures. ResultsFifty-two participants with MS (67 % female, ages 25–70) and 38 healthy controls (66 % female, ages 23–65) were included. p16INK4a levels were not linearly correlated with chronological age in MS (rhos = −0.01, p = 0.94) or control participants (rhos = 0.02, p = 0.92). Higher median p16INK4a levels were observed in the >50-year age group for MS (0.25, IQR 0.14–0.35) vs. controls (0.12, IQR 0.05–0.15) and in this age group B cell depletion therapy was associated with lower expression levels. p16INK4a expression was not associated with any of the measured MS disability outcomes. DiscussionCaution is needed with using p16INK4a expression level from PBMCs as an aging biomarker in MS participants, given lack of correlation with chronological age or large associations with clinical outcomes.

Prevalence, Incidence, and Mortality of Multiple Sclerosis in Coimbra, Portugal

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system in young adults, representing the leading cause of nontraumatic disability in this population. The rising prevalence of MS worldwide makes it critical to recognize the absolute number of patients with MS, demanding the execution of a sustainable healthcare policy. In Portugal, only six studies evaluating MS rates were published, disclosing a prevalence of 64 cases per 100,000 persons and an incidence of 3.1 cases per 100,000 persons/year, but the mortality rates have not been reported. Thus, this observational, cross-sectional study aimed to assess MS prevalence, incidence, and mortality in the city of Coimbra, a region in the center of Portugal. Patients who fulfilled McDonald’s Diagnosis Criteria (2017) for MS were recruited. Inclusion criteria were defined according to prevalence, incidence, and mortality studies. The baseline demographic and clinical characterization of the prevalence study population was performed. The MS prevalence rate in Coimbra was 143.45 cases per 100,000 inhabitants. Between 2018 and 2021, the cumulative incidence was 8.52 new cases per 100,000 persons/year. The mortality rate between 2018 and 2021 was 2.84 deaths per 100,000 inhabitants. MS prevalence and incidence in Coimbra are higher than reported in previous similar studies and comparable to Europe’s mean prevalence and incidence.

Metabolomics of Cerebrospinal Fluid Amino and Fatty Acids in Early Stages of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative autoimmune disease of the central nervous system (CNS) damaging myelin and axons. Diagnosis is based on the combination of clinical findings, magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid (CSF). Metabolomics is a systematic study that allows us to track amounts of different metabolites in a chosen medium. The aim of this study was to establish metabolomic differences between the cerebrospinal fluid of patients in the early stages of multiple sclerosis and healthy controls, which could potentially serve as markers for predicting disease activity. We collected CSF from 40 patients after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS, and the CSF of 33 controls. Analyses of CSF samples were performed by using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector. Significant changes in concentrations of arginine, histidine, spermidine, glutamate, choline, tyrosine, serine, oleic acid, stearic acid and linoleic acid were observed. More prominently, Expanded Disability Status Scale values significantly correlated with lower concentrations of histidine. We conclude that these metabolites could potentially play a role as a biomarker of disease activity and predict presumable inflammatory changes.

A Rare Occurrence of Demyelinating Lesions of Bilateral Trigeminal Nerves: An Atypical Presentation of Pediatric Multiple Sclerosis

AbstractPontine trigeminal root entry zone is a typical, although uncommon, location for multiple sclerosis (MS) lesions to occur. Here, we present a 17-year-old girl with nausea, vomiting, and vertigo. Neurological examination was consistent with central nystagmus, positive Romberg's test, and left-sided hyperreflexia. Baseline magnetic resonance imaging fulfilled McDonald 2017 criteria for MS and showed T2-hyperintense and T1-hypointense bilateral demyelinating lesions at the intramedullary portion of the trigeminal root of the fifth nerve, with no contrast enhancement or restricted diffusion. Bilateral intrapontine trigeminal involvement is a rare finding in MS, as well as the combined central and peripheral demyelination. Furthermore, very limited information and cases have been described in pediatric patients.

The NHANES Biological Age Index demonstrates accelerated aging in MS patients.

Chronological age is associated with disability accumulation in multiple sclerosis (MS). Biological age may give more precise estimates of aging pathways associations with MS severity. Both normal aging and accelerated aging from MS may negatively impact disease course. Multi-marker indices of aging, such as the NHANES biological age index (BAI), may be more robust than single biomarkers in capturing biological age and are strongly associated with mortality risk and aging-related diseases. We sought to investigate whether the NHANES BAI, utilizing readily available measures in the clinic, captures accelerating aging and correlates with disability in MS participants. We conducted a prospective, cross-sectional case-control pilot study. Consecutive patients who met the 2017 McDonald's Criteria for MS were recruited from May 2020 to May 2022 along with age-similar healthy controls. BAI components included blood pressure, FEV1, serum creatinine, C-reactive protein, blood-urea nitrogen, albumin, alkaline phosphatase, cholesterol, CMV IgG, and hemoglobin A1c. The index was calculated using the Klemara and Doubal method. Spearman correlation and multivariable linear regression models were used to assess the association between BAI and MS clinical outcomes. A total of 51 MS (68.6% female) and 38 control (68.4% female) participants were recruited. BAI correlated with chronological age (CA) in MS (r2=0.90,p<0.0001) and control participants (r2 =0.87,p<0.0001). The mean BAI was 1.4 years older than CA in MS participants (range +15 to -10.5 years) and 2.2 years younger in control participants (range +11.2 to -14.1 years). In unadjusted Spearman analyses, BAI correlated with the timed 25-foot walk (T25FW, rhos=0.31, p=0.045) and symbol digit modalities test (SDMT rhos=0.35, p=0.018). In a multivariable regression model, a 5-year older BAI was associated with a 1.2-point lower score on SDMT (95%CI -2.2 to -0.25, p=0.014). MS participants were biologically older than their own chronological age and age-similar controls. In this modest-sized pilot sample, there was strongest correlation for MS outcome measures between BAI and the SDMT. These results support further study of the BAI as a marker of biological age variability in MS.

The prevalence and incidence of multiple sclerosis over the past 20 years in northern Japan

The prevalence of multiple sclerosis (MS) in East Asia is thought to be lower than in Western countries. Globally, there is a trend of increasing MS prevalence. We investigated the changes in the prevalence and clinical phenotype of MS in the Tokachi province of Hokkaido in northern Japan, from 2001 to 2021. Data processing sheets were sent to all related institutions inside and outside the Tokachi area of Hokkaido island in Japan and were collected from April to May 2021. The prevalence according to the Poser's diagnostic criteria for MS was determined on March 31, 2021. In 2021, the crude MS prevalence in northern Japan was 22.4/100,000 (95% confidence interval, 17.6-28.0). The prevalences of MS standardized by the Japanese national population in 2001, 2006, 2011, 2016, and 2021 were 6.9, 11.5, 15.3, 18.5, and 23.3, respectively. The female/male ratio was 4.0 in 2021, increased from 2.6 in 2001. We checked the prevalence using the 2017 revised McDonald criteria, and found only additional male patient who had not fulfilled Poser's criteria. The age- and sex-adjusted incidence of MS per 100,000 individuals increased from 0.09 in 1980-1984 to 0.99 in 2005-2009; since then, it has remained stable. The proportions of primary-progressive, relapsing-remitting, and secondary-progressive MS types in 2021 were 3%, 82%, and 15%, respectively. Our results demonstrated a consistent increase in the prevalence of MS among the northern Japanese over 20 years, particularly in females, and consistently lower rates of progressive MS in northern Japan than elsewhere in the world.

Most Opticospinal Demyelination is NMOSD, not MS-A 17-year UK Longitudinal Cohort Study (P5-3.003)

<h3>Objective:</h3> To evaluate clinical outcomes in a cohort of patients with Opticospinal Demyelination (OSD). <h3>Background:</h3> Classification of central nervous system inflammation has progressed with the identification of aquaporin-4 (AQP4) antibodies in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibodies in MOG antibody disease (MOGAD) in addition to multiple sclerosis (MS). However, as defined in 2003, patients with opticospinal demyelination (optic neuritis (ON), short-segment transverse myelitis (TM), and brain imaging not supportive of MS) do not fulfil internationally approved criteria for MS, NMOSD, or MOGAD. <h3>Design/Methods:</h3> Between 2003–2005, 128 cases of OSD were reported via the British Neurological Surveillance Unit. In 2011, 2015 and 2022 patients and physicians were contacted for clinical, radiological, and serological (e.g., AQP4-IgG and MOG-IgG) data as part of a prospective longitudinal cohort study. <h3>Results:</h3> Of 128 cases, 67 (52%) patients fulfilled OSD diagnostic criteria. At 17 years 39/60 patients (65%) now met NMOSD diagnostic criteria, 14 (23%) had MS and 7 (12%) had OSD. The median time to diagnosis of NMOSD was 107 months (85–261) and to MS was 189 months (79–346). The median age of OSD patients at onset was 37 (25–48) years and 5/7 were male. A relapsing course was observed in 6/7 patients with a median annualised relapse rate of 0.22 (0.13–0.49). At last follow-up the median EDSS was 2.5 (range; 1–6.5) and only 2/7 patients had an EDSS&gt;3.5. <h3>Conclusions:</h3> OSD is diagnostically distinct from MS, NMOSD, and MOGAD. However, after 2 decades most OSD patients reached a diagnosis of NMOSD or MS, so OSD may lie on a spectrum with these conditions. Of the 12% of cases that retained OSD classification, all but 1 had a relapsing course but rates of significant disability were low. Future studies should focus on characterising diagnostic and prognostic biomarkers in this unique subtype of non-MS CNS inflammation. <b>Disclosure:</b> Dr. Forcadela has nothing to disclose. Dr. Rocchi has nothing to disclose. Dr. Panicker has nothing to disclose. Kerry Mutch has nothing to disclose. Dr. Huda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint. Dr. Jacob has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ALEXION. Dr. Hamid has nothing to disclose.

Early beginning of alemtuzumab: Changing the multiple sclerosis treatment paradigm. Interim analysis of the LEMVIDA study

IntroductionLEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain. MethodsThis is an interim analysis evaluating the baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria. Results161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed). ConclusionsUnlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.

Sjögren syndrome in childhood mimicking pediatric multiple sclerosis

Abstract The differential diagnosis of pediatric multiple sclerosis (MS) presents a wide spectrum of diseases. Sjögren syndrome (SS) is also a rare cause of this disease. Neurological involvement in SS ranges from peripheral neuropathies to the central nervous system (CNS). We report the case of a 5-year-old boy with a possible diagnosis with SS based on positive minor salivary gland biopsy findings and positive anti-smooth muscle antibodies, also fulfilling the 2017 McDonald criteria. If a patient is younger and meets the MS criteria clinically and radiologically, it is suggested to carefully examine the CNS demyelination in a patient for autoimmune diseases, particularly SS.