MS Disease Research Articles

What an adult multiple sclerosis registry can tell us about pediatric onset multiple sclerosis?

BackgroundMultiple Sclerosis (MS) is an immune-mediated, chronic disease of the central nervous system that affects mainly adults. However, it is increasingly recognized that MS may start in childhood resulting in a relentlessly progressive disability and cognitive impairment. Registries across the globe are reporting inconstant data about their Pediatric-Onset Multiple Sclerosis (POMS) patients. Moreover, newer lines of treatments are emerging and showing efficacy in controlling the MS disease regardless of the onset. Therefore, there is a requirement for more research into the clinical profile of POMS in different populations and ethnicities. MethodsThis study was a cross-sectional study that included MS patients who visited the MS unit at Alexandria University from January 2019 to January 2021. We analyzed their epidemiological, clinical, radiological data, and cerebrospinal fluid (CSF) results from their updated records as well as follow-up interviews. ResultsAnnual Relapse Rate (ARR) was marginally less in POMS than AOMS (0.72 ± 0.57 vs 1.04 ± 0.78 relapse/year, P =.008). POMS patients had a bigger gap to their first relapse (40.0 ± 47.35 vs 22.71 ± 34.33 months, p= .066). The difference in relapse rate between the two groups was abolished after the exclusion of patients who had a gap of more than 5 years to their first relapse. AOMS patients were significantly more likely to start with a second-line disease-modifying treatment (DMT) than POMS patients (11.5% vs 31%, p= .04), whereas POMS patients were more likely to be escalated to the second line (34.6% vs 19.3%, p= .07). ARR had a positive and significant correlation with expanded disability status scale (EDSS) progression per year (rs(24)= .57 p=.003). A Mann-Whitney test indicated that POMS patients who had infratentorial involvement in the initial MRI brain had higher EDSS (3.08 ± 1.99) than POMS who did not (1.07 ± 0.79) U=24 P =.013. IgG index had a significant and positive correlation with annual EDSS progression rate rs (8) = 0.8 p=.001. ConclusionEarly disease onset does not mean a higher relapse rate when including the full spectrum of POMS and longer follow-up duration. POMS patients relapsed more on the first-line DMT and escalation should be considered early. Infratentorial involvement in the initial magnetic resonance imaging (MRI) brain and high IgG index are potential predictors for aggressive disease course in POMS.

Restless leg syndrome in multiple sclerosis: a case-control study.

This study assessed the prevalence of restless leg syndrome (RLS) among patients with multiple sclerosis (pwMS) and the association between RLS and MS disease duration, sleep disturbance, and daytime fatigue. In this cross-sectional study, we interviewed 123 patients via phone calls using preset questionnaires containing the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria, Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) diagnostic criteria validated in both Arabic and English. The prevalence of RLS in MS was compared to a group of healthy controls. The prevalence of RLS in pwMS, defined by meeting all four requirements included in the IRLSSG diagnostic criteria, was 30.3% compared to 8.3% in the control group. About 27.3% had mild RLS, 36.4% presented with moderate, and the remaining had severe or very severe symptoms. Patients with MS who experience RLS had a 2.8 times higher risk of fatigue compared to pwMS without RLS. pwMS with RLS had worse sleep quality, with a mean difference of 0.64 in the global PSQI score. Sleep disturbance and latency had the most significant impact on sleep quality. The prevalence of RLS among MS patients was significantly higher compared to the control group. We recommend educating neurologists and general physicians to increase their awareness of the increasing prevalence of RLS and its association with fatigue and sleep disturbance in patients with MS.

Early miR-320b and miR-25-3p miRNA levels correlate with multiple sclerosis severity at 10 years: a cohort study

BackgroundMultiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up.Main bodyWe included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA.ConclusionsOur results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions.

Vascular disease risk factors in multiple sclerosis: Effect on metabolism and brain volumes.

Vascular disease risk factors (VDRF) such as hypertension, hyperlipidemia, obesity, diabetes and heart disease likely play a role in disease progression in people with multiple sclerosis (PwMS) (Marrie, Rudick etal. 2010). Studies exploring the mechanistic connection between vascular disease and MS disease progression are scant. We hypothesized that phosphate energy metabolism impairment in PwMS with VDRFs (VDRF+) will be greater compared to PwMS without VDRFs (VDRF-) and is related to increased brain atrophy in VDRF+. To test this hypothesis, we planned to study the differences in the high energy phosphate (HEP) metabolites in cerebral gray matter as assessed by 31P magnetic resonance spectroscopic imaging (MRSI) and MRI brain volumetric in the VDRF+ and VDRF- PwMS at four different timepoints over a 3 yearlong period using a 7T MR system. We present here the results from the cross-sectional evaluation of HEP metabolites and brain volumes. We also evaluated the differences in clinical impairment, blood metabolic biomarkers and quality of life in VDRF+ and VDRF- PwMS in this cohort. Group differences in high energy phosphate metabolites were assessed from a volume of interest in the occipital region using linear mixed models. Brain parenchymal and white matter lesion volumes were determined from MR anatomic images. We present here the cross-sectional analysis of the baseline data collected as part of a longitudinal 3 yearlong study where we obtained baseline and subsequent 6-monthly clinical and laboratory data and annual 7T MRI volumetric and 31P MR spectroscopic imaging (MRSI) data on 52 PwMS with and without VDRF. Key clinical and laboratory outcomes included: body mass index (BMI), waist and thigh circumferences and disability [Expanded Disability Status Scale (EDSS)], safety (complete blood count with differential, complete metabolic), lipid panel including total cholesterol and HbA1C. We analyzed clinical and laboratory data for the group differences using student's t or χ2 test. We investigated relationship between phosphate metabolites and VDRF using mixed effect linear regression. Complete MRI data were available for 29 VDRF+, age 56.3 (6.8) years [mean (SD)] (83% female), and 23 VDRF-, age 52.5 (7.5) years (57% female) individuals with MS. The mean value of normalized adenosine triphosphate (ATP) (calculated as the ratio of ATP to total phosphate signal in a voxel) was decreased by 4.5% (p < .05) in VDRF+ compared to VDRF- MS group. White matter lesion (WML) volume fraction in VDRF+ individuals {0.007 (0.007)} was more than doubled compared to VDRF- participants {0.003 (0.006), p= .02}. We found significantly lower brain ATP and higher inorganic phosphate (Pi) in those PwMS with VDRFs compared to those without. ATP depletion may reflect mitochondrial dysfunction. Ongoing longitudinal data analysis from this study, not presented here, will evaluate the relationship of phosphate metabolites, brain atrophy and disease progression in PwMS with and without vascular disease.

Obesity Modulated Gut Microbiota Exacerbate Disease Severity in HLA-Class II Transgenic Mouse Model of Multiple Sclerosis

Abstract Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS where interaction among multiple environmental and genetic factors influence disease outcome. HLA class II alleles such as HLA-DR2 and –DR3 are considered strongest genetic factors linked with MS, whereas recently gut microbiota have emerged as an important environmental factor linked to MS. Additionally, obesity has been shown to promote MS disease severity. However, the mechanistic link between gut microbiota and obesity in pathobiology of MS is unknown. HLA-DR3 transgenic mice on a high-fat diet (HFD) to induce obesity, resulted in severe EAE compared to normal chow diet (NCD). Antibiotic-mediated gut microbiota depletion and fecal transplant studies established that the microbiota is necessary and sufficient for obesity to potentiate EAE severity. Obesity-associated microbiota alterations included increases in bacterial genes linked with hydrogen sulfide (H 2S)-metabolism, with concordant increases in fecal H 2S. Further, mice on HFD showed increased gut permeability and systemic inflammation compared with NCD group. Altogether, this study provides evidence for involvement of the gut microbiome and associated H 2S-metabolism microbial genes in obesity induced modulation of EAE severity. Dissection of these pathways will help to identify novel therapeutic targets to reduce disease severity in obese patients. The Author acknowledge funding from the National Multiple Sclerosis Society grant (RG 5138A1/1T), National Institutes of Health/NIAID (1R01AI137075), the University of Iowa Environmental Health Sciences Research Center, NIEHS/NIH (P30 ES005605), and a gift from P. Heppelmann and M. Wacek to AM.

BAFF and APRIL signaling through B cell maturation antigen affects regulatory transitional B cells in multiple sclerosis.

Abstract Multiple sclerosis (MS) is a debilitating neuro-autoimmune disease that can be stratified into relapsing remitting (RR) MS, secondary progressive (SP) MS, and primary progressive (PP) MS. B cells can have both inflammatory and regulatory functions in MS. Transitional B cells are considered to have regulatory functions in MS. BAFF and APRIL, two cytokines, signals through the receptors BAFFR, TACI and BCMA and are thought to drive the regulatory function of transitional B cells. Here, we assessed the frequencies and expression of BAFFR, TACI and BCMA on the surface of regulatory transitional B cells in the blood of RRMS, PPMS and healthy individuals along with soluble versions of these receptors in the plasma. We found that transitional B cells were decreased in both RRMS and PPMS patients. The surface expression of BCMA was significantly lower on transitional B cells from RRMS patients but not PPMS patients compared to healthy individuals with no change in the expression of TACI and BAFFR. In addition, we found elevated levels of soluble BCMA in blood of PPMS patients but not RRMS patients compared to healthy and no difference in soluble BAFFR and TACI. Our data suggests that reduced BCMA signaling is associated with reduced numbers of transitional B cells in RRMS and PPMS. In RRMS, expression of BCMA is reduced on regulatory transitional B cells. In PPMS patients, there are higher levels of soluble BCMA which could act as a blocker of APRIL signaling through BCMA on the surface of transitional B cells. Altogether, our data suggests that reduced BCMA signaling in transitional B cells is contributing to the MS disease and the dysregulation of the BCMA signaling in RRMS and PPMS may be through a different mechanism. This study was supported by grants from the NMSS (RG-1602-07722), the NIH (R01AI137047 and R01EY027346) awarded to R.C. Axtell.

Predicting MRI Changes in Patients with MS in the Absence of Acute Inflammation (P11-3.010)

Predicting MRI Changes in Patients with MS in the Absence of Acute Inflammation (P11-3.010)

Impact of Assisted Reproductive Technologies (ART) on Relapse Risk in Women with Multiple Sclerosis (S31.005)

Impact of Assisted Reproductive Technologies (ART) on Relapse Risk in Women with Multiple Sclerosis (S31.005)

African-Americans With Multiple Sclerosis Have a Higher Proportion of B-Cell Lineage Cells in Their Cerebrospinal Fluid (CSF) Than White Patients (P9-3.010)

<h3>Objective:</h3> To compare proportions of B-cell lineage CD19+ and CD20+ cells in CSF of African-Americans (AA) and White (W) patients with MS. <h3>Background:</h3> Compared to W patients, AA patients with MS are more likely to have oligoclonal bands in CSF; have higher IgG index in CSF; and have higher circulating plasmablasts in blood. It is unknown whether the proportion of B-cells in CSF differs between AA and white patients in MS. <h3>Design/Methods:</h3> Demographics, disease-related information, and treatment history were retrospectively collected on patients with neurologist-diagnosed MS who self-identified as AA or W, received care at NYU MS Care Center, and underwent flow cytometry of CSF during diagnostic work-up. Lymphocyte subsets (B-lymphocytes, T-lymphocytes, NK cells), monocytes and plasma cells were analyzed with flow cytometry (BD FACSCanto™ and FACSCanto™ II Cell Analyzers). <h3>Results:</h3> 20 AA and 57 W MS patients fulfilled inclusion criteria. The groups had similar age at lumbar puncture, sex ratio, CSF cell counts, protein and glucose CSF concentrations, and oligoclonal band number. IgG index was higher in AA compared to W (<i>1.08 v 0.87, p=0.044</i>). With respect to mononuclear cell counts in CSF, AA had higher proportions of CD19+ (<i>5.45% AA v. 2.27% W, p=0.0061</i>) and CD20+ (<i>5.00% AA v. 1.95% W, p=0.0046</i>) cells, but did not significantly differ in proportion of CD4+, CD8+, CD38+ bright B-cells, NK cells and monocytes. Sensitivity analyses that excluded all patients on disease-modifying therapy at the time of lumbar puncture (n=8) yielded similar conclusions. <h3>Conclusions:</h3> B-cells are overrepresented in the CSF of African American patients with MS relative to Whites. Whether this finding bears on the increased severity of MS disease course in AA patients warrants investigation. <b>Disclosure:</b> Mr. Xue has nothing to disclose. Dr. Arbini has nothing to disclose. Mr. Melton has received personal compensation for serving as an employee of Janssen Pharmaceuticals. Dr. Kister has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech-Roche. The institution of Dr. Kister has received research support from Genentech. Dr. Kister has received publishing royalties from a publication relating to health care.

In a Digital Version of the 9-Hole Peg Test, Intra-Task Speed, Accounting for Variance in Distance Traveled, May be a Better Measure of MS-Related Upper-Limb Disability Than Completion Time. (P3-3.006)

In a Digital Version of the 9-Hole Peg Test, Intra-Task Speed, Accounting for Variance in Distance Traveled, May be a Better Measure of MS-Related Upper-Limb Disability Than Completion Time. (P3-3.006)

Depression status of elderly patients with metabolic syndrome in three provinces of China

Objective: To understand the depression status and its influencing factors in elderly patients with MS in China and to explore the correlation between various components of elderly MS and depression. Methods: This study is based on the "Prevention and Intervention of Key Diseases in Elderly" project. We used a multi-stage stratified cluster random sampling method to complete 16 199 elderly aged 60 years and above in 16 counties (districts) in Liaoning, Henan, and Guangdong Provinces in 2019, excluding 1 001 missing variables. Finally, 15 198 valid samples were included for analysis. The respondents' MS disease was obtained through questionnaires and physical examinations, and the respondents' depression status within the past half month was assessed using the PHQ-9 Depression Screening Scale. The correlation between elderly MS and its components and depression and its influencing factors were analyzed by logistic regression. Results: A total of 15 198 elderly aged 60 years and above were included in this study, with the prevalence of MS at 10.84% and the detection rate of depressive symptoms in MS patients at 25.49%. The detection rates of depressive symptoms in patients with 0, 1, 2, 3, and 4 MS abnormal group scores were 14.56%, 15.17%, 18.01%, 25.21%, and 26.65%, respectively. The number of abnormal components of MS was positively correlated with the detection rate of depressive symptoms, and the difference between groups was statistically significant (P<0.05). The risk of depression symptoms in patients with MS, overweight/obesity, hypertension, diabetes, and dyslipidemia was 1.73 times (OR=1.73, 95%CI:1.51-1.97), 1.13 times (OR=1.13, 95%CI:1.03-1.24), 1.25 times (OR=1.25, 95%CI:1.14-1.38), 1.41 times (OR=1.41, 95%CI:1.24-1.60), 1.81 times (OR=1.81,95%CI:1.61-2.04), respectively, more than those without the disease. Multivariate logistic regression analysis showed that the detection rate of depressive symptoms in patients with sleep disorders was higher than that with normal sleep (OR=4.89, 95%CI: 3.79-6.32). The detection rate of depressive symptoms in patients with cognitive dysfunction was 2.12 times higher than that in the average population (OR=2.12, 95%CI: 1.56-2.89). The detection rate of depressive symptoms in patients with impaired instrumental activities of daily living (IADL) was 2.31 times (OR=2.31, 95%CI: 1.64-3.26) higher than that in the average population. Tea drinking (OR=0.73, 95%CI: 0.54-0.98) and physical exercise (OR=0.67, 95%CI: 0.49-0.90) seemed to be protective factors for depression in elderly MS patients (P<0.05). Conclusions: Older patients with MS and its component abnormalities have a higher risk of depression than the average population. Sleep disorders, cognitive impairment, and IADL impairment are important influencing factors for depression in elderly MS patients, while tea drinking and physical exercise may help to reduce the risk of the disease.

Inducible nitric oxide synthase deficiency promotes murine-β-coronavirus induced demyelination

BackgroundMultiple sclerosis (MS) is characterized by neuroinflammation and demyelination orchestrated by activated neuroglial cells, CNS infiltrating leukocytes, and their reciprocal interactions through inflammatory signals. An inflammatory stimulus triggers inducible nitric oxide synthase (NOS2), a pro-inflammatory marker of microglia/macrophages (MG/Mφ) to catalyze sustained nitric oxide production. NOS2 during neuroinflammation, has been associated with MS disease pathology; however, studies dissecting its role in demyelination are limited. We studied the role of NOS2 in a recombinant β-coronavirus-MHV-RSA59 induced neuroinflammation, an experimental animal model mimicking the pathological hallmarks of MS: neuroinflammatory demyelination and axonal degeneration.ObjectiveUnderstanding the role of NOS2 in murine-β-coronavirus-MHV-RSA59 demyelination.MethodsBrain and spinal cords from mock and RSA59 infected 4–5-week-old MHV-free C57BL/6 mice (WT) and NOS2-/- mice were harvested at different disease phases post infection (p.i.) (day 5/6-acute, day 9/10-acute-adaptive and day 30-chronic phase) and compared for pathological outcomes.ResultsNOS2 was upregulated at the acute phase of RSA59-induced disease in WT mice and its deficiency resulted in severe disease and reduced survival at the acute-adaptive transition phase. Low survival in NOS2-/- mice was attributed to (i) high neuroinflammation resulting from increased accumulation of macrophages and neutrophils and (ii) Iba1 + phagocytic MG/Mφ mediated-early demyelination as observed at this phase. The phagocytic phenotype of CNS MG/Mφ was confirmed by significantly higher mRNA transcripts of phagocyte markers-CD206, TREM2, and Arg1 and double immunolabelling of Iba1 with MBP and PLP. Further, NOS2 deficiency led to exacerbated demyelination at the chronic phase as well.ConclusionTaken together the results imply that the immune system failed to control the disease progression in the absence of NOS2. Thus, our observations highlight a protective role of NOS2 in murine-β-coronavirus induced demyelination.

Deciphering crucial genes in multiple sclerosis pathogenesis and drug repurposing: A systems biology approach

This study employed systems biology and high-throughput technologies to analyze complex molecular components of MS pathophysiology, combining data from multiple omics sources to identify potential biomarkers and propose therapeutic targets and repurposed drugs for MS treatment.This study analyzed GEO microarray datasets and MS proteomics data using geWorkbench, CTD, and COREMINE to identify differentially expressed genes associated with MS disease. Protein-protein interaction networks were constructed using Cytoscape and its plugins, and functional enrichment analysis was performed to identify crucial molecules. A drug-gene interaction network was also created using DGIdb to propose medications.This study identified 592 differentially expressed genes (DEGs) associated with MS disease using GEO, proteomics, and text-mining datasets. 37 DEGs were found to be important by topographical network studies, and 6 were identified as the most significant for MS pathophysiology. Additionally, we proposed six drugs that target these key genes.Crucial molecules identified in this study were dysregulated in MS and likely play a key role in the disease mechanism, warranting further research. Additionally, we proposed repurposing certain FDA-approved drugs for MS treatment. Our in silico results were supported by previous experimental research on some of the target genes and drugs. SignificanceAs the long-lasting investigations continue to discover new pathological territories in neurodegeneration, here we apply a systems biology approach to determine multiple sclerosis's molecular and pathophysiological origin and identify multiple sclerosis crucial genes that contribute to candidating new biomarkers and proposing new medications.

Assessment of cognitive performance in multiple sclerosis using smartphone-based training games: a feasibility study

BackgroundCognitive impairment occurs in up to 70% of people with MS (pwMS) and has a large impact on quality of life and working capacity. As part of the development of a smartphone-app (dreaMS) for monitoring MS disease activity and progression, we assessed the feasibility and acceptance of using cognitive games as assessment tools for cognitive domains.MethodsWe integrated ten cognitive games in the dreaMS app. Participants were asked to play these games twice a week for 5 weeks. All subjects underwent a battery of established neuropsychological tests. User feedback on acceptance was obtained via a five-point Likert-scale questionnaire. We correlated game performance measures with predetermined reference tests (Spearman’s rho) and analyzed differences between pwMS and Healthy Controls (rank biserial correlation).ResultsWe included 31 pwMS (mean age 43.4 ± 12.0 years; 68% females; median Expanded Disability Status Scale score 3.0, range 1.0–6.0) and 31 age- and sex-matched HC. All but one game showed moderate–strong correlations with their reference tests, (|rs|= 0.34–0.77). Performance improved in both groups over the 5 weeks. Average ratings for overall impression and meaningfulness were 4.6 (range 4.2–4.9) and 4.7 (range 4.5–4.8), respectively.ConclusionModerate–strong correlations with reference tests suggest that adaptive cognitive games may be used as measures of cognitive domains. The practice effects observed suggest that game-derived measures may capture change over time. All games were perceived as enjoyable and meaningful, features crucial for long-term adherence. Our results encourage further validation of adaptive cognitive games as monitoring tools for cognition in larger studies of longer duration.Study RegisterClinicalTrials.gov: NCT04413032.

Gene network reveals LASP1, TUBA1C, and S100A6 are likely playing regulatory roles in multiple sclerosis.

Multiple sclerosis (MS), a non-contagious and chronic disease of the central nervous system, is an unpredictable and indirectly inherited disease affecting different people in different ways. Using Omics platforms genomics, transcriptomics, proteomics, epigenomics, interactomics, and metabolomics database, it is now possible to construct sound systems biology models to extract full knowledge of the MS and recognize the pathway to uncover the personalized therapeutic tools. In this study, we used several Bayesian Networks in order to find the transcriptional gene regulation networks that drive MS disease. We used a set of BN algorithms using the R add-on package bnlearn. The BN results underwent further downstream analysis and were validated using a wide range of Cytoscape algorithms, web based computational tools and qPCR amplification of blood samples from 56 MS patients and 44 healthy controls. The results were semantically integrated to improve understanding of the complex molecular architecture underlying MS, distinguishing distinct metabolic pathways and providing a valuable foundation for the discovery of involved genes and possibly new treatments. Results show that the LASP1, TUBA1C, and S100A6 genes were most likely playing a biological role in MS development. Results from qPCR showed a significant increase (P < 0.05) in LASP1 and S100A6 gene expression levels in MS patients compared to that in controls. However, a significant down regulation of TUBA1C gene was observed in the same comparison. This study provides potential diagnostic and therapeutic biomarkers for enhanced understanding of gene regulation underlying MS.

A CASE OF MULTIPLE SCLEROSİS PRESENTING AS DEPRESSION IN A YOUNG PERSON

IntroductionMultiple sclerosis(MS)is a chronic immune-mediated, inflammatory disease of the central nervous system. Depression is one of the most common psychiatric conditions associated with MS. Lifetime prevalence of major depression has been estimated to be around 50%.ObjectivesAlthough the prevalence of depression in MS patients has been shown by many studies, there has not been a case in the literature demonstrating the onset of MS disease with depressive symptoms. In this article, a case of multiple sclerosis (undiagnosed before) presenting as depression in a young woman is presented and discussed.MethodsAn eighteen years-old female patient visited the emergency room of Erenkoy Mental and Neurological Diseases Hospital with complaints of unhappiness,malaise,anhedonia,introversion,sleepiness,lack of appetite and nausea. She was admitted to another hospital one and a half years ago with similar complaints and duloxetine 30 mg/day treatment was started. The patient, who did not benefit from this treatment, stopped using the drug by herself and did not consult a doctor again. Her complaints regressed over time without treatment.Her current symptoms started four days prior to her visit. She had no other medically diagnosed condition. No pathology was detected in the emergency blood test parameters of the patient.Her brain tomography was normal. The patient, who had periventricular ovoid hyperintense lesions on cranial MRI, was diagnosed with multiple sclerosis and was admitted to the neurology unit of our hospital. The lumbar puncture was performed during the hospitalization, oligoclonal band positivity was detected. The IgG index was found to be increased at CSF (cerebrospinal fluid). She underwent pulse steroid therapy for seven days. The patient was discharged since her symptoms regressed after treatment.ResultsHere we present a case of MS presenting as depression in a young woman. Depression is a very common, and very important comorbidity in multiple sclerosis. The etiology of depression in MS is likely to be multifactorial, and to include biological, psychological, and social determinants. Although the relationship between depression and MS has been clearly demonstrated in all of these studies, there is no case of MS presenting as depression in the literature.ConclusionsWe know that depression may occur as a prodromal symptom in some organic diseases that affect brain such as dementia and Parkinson. In this case, we wanted to emphasize that organic etiological research is necessary for patients who present with psychiatric complaints for the first time, and that psychiatric complaints may be a symptom of organic diseases that may affect the brain.Disclosure of InterestNone Declared

The Rate and Pattern of Changes in MS Disease Modifying Drugs in Tehran, Iran; a Cross-Sectional Study from Tehran MS Registry

The Rate and Pattern of Changes in MS Disease Modifying Drugs in Tehran, Iran; a Cross-Sectional Study from Tehran MS Registry

Electronic health record data for assessing risk of hospitalization for COVID-19: Methodological considerations applied to multiple sclerosis.

During the COVID-19 pandemic, electronic health record (EHR) data has been used to investigate disease severity and risk factors for severe COVID-19 in people with multiple sclerosis (pwMS). Methodological challenges including sampling bias, and residual confounding should be considered when conducting EHR-based studies. We aimed to address these limitations related to the use of EHR data in order to identify risk factors, including the use of disease modifying therapies (DMTs), associated with hospitalization for COVID-19 amongst pwMS. We performed a retrospective cohort study including a sample of 47,051 pwMS using a large US-based EHR and claims linked database. Follow-up started at the beginning of the pandemic, February 20th 2020, and continued until September 30th 2020. COVID-19 diagnosis was determined by the presence of ICD-10 diagnostic code for COVID-19, or a positive diagnostic laboratory test, or an ICD-10 diagnostic code for coronaviruses. We used Cox regression modeling to assess the impact of baseline demographics, MS disease history and pre-existing comorbidities on the risk of hospitalization for COVID-19. Then, we identified 5,169 pwMS using ocrelizumab (OCR) and 3,351 pwMS using dimethyl fumarate (DMF) at baseline, and evaluated the distribution of the identified COVID-19 risk factors between the two groups. Finally, we used Cox regression models, adjusted for the identified confounders, to estimate the risk of hospitalization for COVID-19 in pwMS treated with OCR compared to DMF. Among the pwMS cohort, we identified 799 COVID-19 cases (1.7%) which resulted in 182 hospitalizations for COVID-19 (0.4%). Population differences between the pwMS and COVID-19 cohorts were observed. Statistical modeling identified older age, male gender, African-American race, walking with assistance, non-ambulatory status, severe relapse requiring hospitalization in year prior to baseline, and specific comorbidities to be associated with a higher risk of COVID-19 related-hospitalization. Comparing the COVID-19 risk factors between OCR users and DMF users, MS characteristics including ambulatory status and MS subtype were highly imbalanced, likely arising from key differences in the labelled indications for these therapies. Compared to DMF use, in unadjusted (HR 1.58, 95% CI 0.73 - 3.44), adjusted (HR 1.28, 95% CI 0.58 - 2.83), propensity score weighted (HR 1.25, 95% CI 0.56 - 2.80), and doubly robust models (HR 1.29, 95% CI 0.57 - 2.89), no significantly increased risk of hospitalization for COVID-19 was associated with OCR use. We observed significant population differences when comparing all pwMS to COVID-19 cases, as well as significant differences in key confounders between OCR and DMF treated patients. In unadjusted analyses we did not observe a statistically significant higher risk of COVID-19 hospitalization in pwMS treated with OCR compared to DMF, with further attenuation of risk when adjusting for the key confounders. This study re-emphasises the importance to appropriately consider both sampling and confounding bias in EHR-based MS research.

Skeletal muscle metastases in neuroblastoma share common progenitors with primary tumor and biologically resemble stage MS disease.

While subcutaneous metastases are often observed with stage MS neuroblastoma, an entity that usually resolves spontaneously, skeletal muscle metastases (SMM) have been rarely described. The purpose of this retrospective study was to investigate the significance of SMM in neuroblastoma. Seventeen patients with neuroblastoma SMM were diagnosed at a median age of 4.3 (0.1-15.6) months. All had SMM at diagnosis and metastases at other sites. Fifteen (88%) had ≥ 2 SMM in disparate muscle groups. One, 14, and 2 patients had low, intermediate, and high-risk disease respectively. Fifteen tumors had favorable histology without MYCN amplification, and 2 were MYCN-amplified. Most SMM (80%; n=12/15 evaluated) were MIBG-avid. Only 1 patient (with MYCN-non-amplified neuroblastoma) had disease progression. All survive at median follow-up of 47.9 (16.9-318.9) months post-diagnosis. Biological markers (histology, chromosomal and genetic aberrations) were not prognostic. Whole genome sequencing of 3 matched primary and SMM lesions suggested that both primary and metastatic tumors arose from the same progenitor. SMM completely resolved in 10 patients by 12 months post-diagnosis. Of 4 patients managed with watchful observation alone without any cytotoxic therapy, 3 maintain complete remission with SMM resolving by 5, 13, and 21 months post-diagnosis respectively. Children with neuroblastoma SMM have an excellent prognosis, with a clinical course suggestive of stage MS disease. Based on these results, the initial management of infants with non-MYCN-amplified NB with SMM could be watchful observation, which could eliminate or reduce exposure to genotoxic therapy.

Role of MR in Evaluating Multiple Sclerosis

Introduction: Multiple sclerosis is an inflammatory disease that attacks the central nervous system CNS (brain and spinal cord). Specifically, it attacks the myeline sheath of the neuron cells (1-3). Up to now there is no known pathophysiological cause of the MS disease but it is believed to be autoimmune. Autoimmune means the immunity system attacks normal tissues without obvious cause. It results in progressive neurological deficits leading to accumulating disabilities. The wide distribution of plaques (name of MS lesion) produces a variety of clinical symptoms. Key words: Multiple sclerosis, evaluation, MRI