MS Cases Research Articles

Algorithmic Identification of Multiple Sclerosis in the SAIL databank

BackgroundMultiple Sclerosis (MS) is a challenging disease to identify within large repositories of healthcare data. Diagnosis can be protracted requiring many modalities that may not form part of the repository data collection. Accurate case finding would have multiple applications for studying epidemiology. AimDevelop a case finding algorithm within the Secure Anonymised Information Linkage (SAIL) Databank that can reliably elicit Multiple Sclerosis. MethodUtilising a cross sectional cohort study we used multiple datasets within SAIL; General Practice, Inpatient, Outpatient and Office of National Statistics to develop our case finding algorithm based on the coding nomenclatures and timing within these datasets. The results of this algorithm were then tested against two patient data sets: The UK MS Register (n=836), consisting of mostly self confirmed disease and a clinical cohort from South West Wales (n=713). ResultsFrom 4,757,428 records, the algorithm identified 6,194 cases of MS within Wales on 31st December 2020 (prevalence 221.65 [95%CI 216.17–227.24] per 100,000). Case finding sensitivity and specificity was 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% from the self-declared registry population. ConclusionWe successfully identified MS cases within Wales and verified this within two independent data sets.

Mirizzi syndrome: Mastering the challenge, characterization and management outcomes in a retrospective study of 60 cases

BackgroundMirizzi Syndrome (MS) is a rare complication of gallstone disease that poses diagnostic and management challenges. MethodsThis retrospective study aimed to review our institutional experience in diagnosing and managing MS over seven years and four months. ResultsAmong 8200 cholecystectomies, 60 cases of MS were identified, with type 1 being the most prevalent (90%). The mean age of the patients was 44 years, with male predominance (75%). Southeast Asians comprised 56.7% of the study population. The most common presenting symptom was right upper quadrant pain, and 58.3% of the patients were diagnosed with acute cholangitis. Liver enzyme and bilirubin levels were significantly higher in the advanced types. Preoperative diagnosis was achieved in 70% of patients, with MRCP and ERCP being the most effective diagnostic tools. Laparoscopic cholecystectomy was the most common surgical approach (76.7%), particularly in type 1 (79.6%), and decreased to 50% in advanced types. Hepaticojejunostomy was more common in the advanced types. ConclusionThis study highlights the importance of early diagnosis and appropriate management of MS considering its rarity and potential complications. The laparoscopic approach is reasonable, especially for type 1 MS and noncomplicated cases. Further research is needed to optimize treatment strategies for this challenging condition.

Disability independent of cerebral white matter demyelination in progressive multiple sclerosis

The pathogenic mechanisms contributing to neurological disability in progressive multiple sclerosis (PMS) are poorly understood. Cortical neuronal loss independent of cerebral white matter (WM) demyelination in myelocortical MS (MCMS) and identification of MS patients with widespread cortical atrophy and disability progression independent of relapse activity (PIRA) support pathogenic mechanisms other than cerebral WM demyelination. The three-dimensional distribution and underlying pathology of myelinated T2 lesions were investigated in postmortem MCMS brains. Postmortem brain slices from previously characterized MCMS (10 cases) and typical MS (TMS) cases (12 cases) were co-registered with in situ postmortem T2 hyperintensities and T1 hypointensities. T1 intensity thresholds were used to establish a classifier that differentiates MCMS from TMS. The classifier was validated in 36 uncharacterized postmortem brains and applied to baseline MRIs from 255 living PMS participants enrolled in SPRINT-MS. Myelinated T2 hyperintensities in postmortem MCMS brains have a contiguous periventricular distribution that expands at the occipital poles of the lateral ventricles where a surface-in gradient of myelinated axonal degeneration was observed. The MRI classifier distinguished pathologically confirmed postmortem MCMS and TMS cases with an accuracy of 94%. For SPRINT-MS patients, the MRI classifier identified 78% as TMS, 10% as MCMS, and 12% with a paucity of cerebral T1 and T2 intensities. In SPRINT-MS, expanded disability status scale and brain atrophy measures were similar in MCMS and TMS cohorts. A paucity of cerebral WM demyelination in 22% of living PMS patients raises questions regarding a primary role for cerebral WM demyelination in disability progression in all MS patients and has implications for clinical management of MS patients and clinical trial outcomes in PMS. Periventricular myelinated fiber degeneration provides additional support for surface-in gradients of neurodegeneration in MS.

Longitudinal epidemiology of multiple sclerosis over 60 years in Newcastle, Australia: 1961 to 2021

IntroductionNewcastle, Australia, has been serially studied for MS epidemiology since 1961, showing consistently increasing prevalence estimates and incidence rates, including to our 2011 study. ObjectivesTo assess the 2011–2021 epidemiology of MS in Newcastle and to compare with previous measures. MethodsDemographic and clinical data were extracted from medical records of MS cases residing in Newcastle, as identified by public and private clinicians. Prevalence (2011 and 2021) and incidence rates (2011-2021, from onset and from diagnosis) and mortality rate (2011–2021) were estimated and age-standardised to the 2021 Australian population. ResultsThe 2021 prevalence was 173.1/100,000 (age-standardised = 178.7/100,000, F/M-sex-ratio = 3.3), a 42.2 % increase from 2011 (F/M-sex-ratio = 3.1), 175.0 % from 1996 (F/M-sex-ratio = 2.6), and 831.0 % from 1961 (F/M-sex-ratio = 1.2). The 2011–21 age-standardised onset incidence rate was 3.5/100,000 person-years (F/M-sex-ratio = 2.8), a 68.7 % increase from 1971 to 81 (F/M-sex-ratio = 1.1) and 44.5 % from 1986 to 96 (F/M-sex-ratio = 2.3). The age-standardised diagnosis incidence rate was 6.1/100,000 (F/M-sex-ratio = 2.2), statistically unchanged from that in 2001–2011 (6.8/100,000, F/M-sex-ratio = 3.2). The 2011–21 mortality rate was 2.1/100,000 person-years (2.2 age-standardised, F/M-sex-ratio = 1.4), with a standardised mortality ratio of 1.6. ConclusionThe Newcastle region continues to be a high frequency zone for MS. The incidence rate from onset is significantly increased from previous estimates, but incidence rate from diagnosis is stable. Prevalence and incidence sex ratios have stabilised at roughly 3.0, similar to other Australian sites.

Use of a novel, mode-switching electroanatomic mapping function and its effect on procedure and fluoroscopy duration in de novo AF procedures

Abstract Background Electroanatomical mapping systems utilize either an impedance-primary (IP) or magnetic-primary (MP) coordinate system for navigation. IP systems allow visualization of metal within the impedance field and can be scaled with supplemental magnetic information. MP systems collect information from catheters with a magnetic sensor, and supplementary impedance information is used to visualize catheters without a sensor. One commercially available mapping system offers both IP and MP navigation modes; however, operators must select a mode at procedure start. A novel software function allowing for near-instant transition between modes was recently introduced; its impact on procedural metrics has not yet been quantified. Objective Assess the impact of a mode-switching software function (MS) on acute procedural metrics in de novo paroxysmal atrial fibrillation (PAF) cases in which both the IP and MP modes were used, compared to procedures in which IP or MP was used alone. Methods Observational data was collected from 309 de novo PAF cases performed at 63 centers in Europe, the US, and Australia. Ablation technology used, procedure duration, fluoroscopy time, and acute outcomes were collected. Results Of 309 cases analyzed, 157 (50.8%) used MS, 97 (31.4%) used MP alone, and 55 (17.8%) used IP alone. Radiofrequency ablation (RFA) was used in 291 (94.2%) cases, while the remaining 18 (5.8%) used cryoablation. Irrigated, contact force sensing RFA catheters were used in 153 (97.4%) MS, 89 (91.8%) MP, and 29 (52.7%) IP cases. Mean procedure durations for MS and MP cases were similar: 106.2±51.6 min and 106.8±53.0 min, respectively (p=0.93). However, IP cases were significantly longer than both MS and MP cases, 134.2±53.8 min (p=0.002). Fluoroscopy time was significantly less in the MS group compared to MP and IP groups: 3.9±5.5, 6.1±5.2, and 7.8±6.4 min, respectively (p<0.001). No fluoroscopy was used in significantly more MS compared to MP or IP cases: 72 (45.9%) MS, 10 (10.3%) MP, and 8 (14.5%) IP cases (p<0.001). When these 90 cases were excluded, mean fluoroscopy times were similar between MS, MP, and IP cases (7.1±5.6, 6.8±5.0, and 9.2±5.9 min, respectively (p=0.05)). Acute success rates were not significantly different between modes: 98.6% MS, 100% MP, and 100% IP (p=0.49). Conclusions In this analysis of international usage of a novel software function, cases utilizing MS had significantly shorter fluoroscopy durations with similar acute success rates and procedure durations than those using MP or IP. When zero fluoroscopy cases were excluded, there was no significant difference in fluoroscopy times; however, there were significantly more zero fluoroscopy cases in the MS group, indicating that, while MS supports and may encourage low-fluoroscopy workflows, differences in procedural metrics seen may be biased by operator preference. Future analyses are warranted to provide insight into operator-specific metrics when using MS.Fluoroscopy Duration Comparison

Current and Emerging Treatment Options in Pediatric Onset Multiple Sclerosis

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, this review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Syntaxin 1A gene polymorphism in multiple sclerosis: a case–control study

BackgroundSyntaxin 1A is a member of a membrane-integrated nervous system-specific protein superfamily involved in the neuromediator release from synaptic vesicles and one of the proteins included in axonal integrity. Studies that discussed the role of Syntaxin 1A in multiple sclerosis are few and limited. Gene studying sometimes shows unexpected results in different populations. The aim of this work was to investigate Syntaxin 1A genetic polymorphism (rs1569061) in a sample of Egyptian patients with MS and the relation between Syntaxin 1A gene polymorphism and disease course and disability. A case–control study included 150 subjects; 75 Egyptian MS patients of different clinical courses and 75 age and sex matched healthy controls. Patients were subjected to clinical evaluation, assessment of disability, and cognition. Both patient and control groups were subjected to Syntaxin 1A genotyping.ResultsThere was no significant difference between different genotypes distribution for Syntaxin 1A (rs 1569061) between MS patients and controls.No significant difference was found between genotypes and allele distribution for Syntaxin 1A (rs 1569061) among cases of MS regarding EDSS or results of BICAMS). There was no statistically significant difference between syntaxin genotypes among cases of MS regarding demographic or clinical characteristics of the disease.ConclusionHere we show no statistically significant difference between MS patients and control regarding Syntaxin 1A genotypes and different alleles. Syntaxin 1A genotypes have no impact on clinical characteristics of the disease, disability, or cognition. These negative findings open the floor for the study of other MS related genes in Egypt.

Algorithm for predicting valvular heart disease from heart sounds in an unselected cohort.

This study aims to assess the ability of state-of-the-art machine learning algorithms to detect valvular heart disease (VHD) from digital heart sound recordings in a general population that includes asymptomatic cases and intermediate stages of disease progression. We trained a recurrent neural network to predict murmurs from heart sound audio using annotated recordings collected with digital stethoscopes from four auscultation positions in 2,124 participants from the Tromsø7 study. The predicted murmurs were used to predict VHD as determined by echocardiography. The presence of aortic stenosis (AS) was detected with a sensitivity of 90.9%, a specificity of 94.5%, and an area under the curve (AUC) of 0.979 (CI: 0.963-0.995). At least moderate AS was detected with an AUC of 0.993 (CI: 0.989-0.997). Moderate or greater aortic and mitral regurgitation (AR and MR) were predicted with AUC values of 0.634 (CI: 0.565-703) and 0.549 (CI: 0.506-0.593), respectively, which increased to 0.766 and 0.677 when clinical variables were added as predictors. The AUC for predicting symptomatic cases was higher for AR and MR, 0.756 and 0.711, respectively. Screening jointly for symptomatic regurgitation or presence of stenosis resulted in an AUC of 0.86, with 97.7% of AS cases (n = 44) and all 12 MS cases detected. The algorithm demonstrated excellent performance in detecting AS in a general cohort, surpassing observations from similar studies on selected cohorts. The detection of AR and MR based on HS audio was poor, but accuracy was considerably higher for symptomatic cases, and the inclusion of clinical variables improved the performance of the model significantly.

CNS erythroblastic sarcoma: a potential emerging pediatric tumor type characterized by NFIA::RUNX1T1/3 fusions

Erythroblastic sarcoma (ES) (previously called chloroma or granulocytic sarcoma) are rare hematological neoplams characterized by the proliferation of myeloid blasts at extramedullary sites, and primarily involve the skin and soft tissue of middle-aged adults. ES may be concomitant with or secondary to myeloid neoplasms (mostly acute myeloid leukemia (AML)) or in isolated cases (de novo) without infiltration of the bone marrow by blasts. ES share cytogenetic and molecular abnormalities with AML, including RUNX1T1 fusions. Some of these alterations seem to be correlated with particular sites of involvement. Herein, we report an isolated erythroblastic sarcoma with NFIA::RUNX1T1 located in the central nervous system (CNS) of a 3-year-old boy. Recently, two pediatric cases of CNS MS with complete molecular characterization have been documented. Like the current case, they concerned infants (2 and 3 years-old) presenting a brain tumor (pineal involvement) with leptomeningeal dissemination. Both cases also harbored a NFIA::RUNX1T3 fusion. ES constitutes a diagnostic challenge for neuropathologists because it does not express differentiation markers such as CD45, and may express CD99 which could be confused with CNS Ewing sarcoma. CD43 is the earliest pan-hematopoietic marker and CD45 is not expressed by erythroid lineage cells. E-cadherin (also a marker of erythroid precursors) and CD117 (expressed on the surface of erythroid lineage cells) constitute other immunhistochemical hallmarks of ES. The prognosis of patients with ES is similar to that of other patients with AML but de novo forms seem to have a poorer prognosis, like the current case. To conclude, pediatric ES with NFIA::RUNX1T1/3 fusions seem to have a tropism for the CNS and thus constitute a potential pitfall for neuropathologists. Due to the absence of circulating blasts and a DNA-methylation signature, the diagnosis must currently be made by highlighting the translocation and expression of erythroid markers.

Not all hematological malignancies in the gastrointestinal tract are lymphoma

Abstract Introduction/Objective Myeloid sarcoma (MS) is a rare entity that may develop in patients with acute myeloid leukemia (AML). Presentation of MS in the gastrointestinal (GI) tract is uncommon. We describe two cases of MS involving unusual sites: the stomach and appendix. Methods/Case Report A 64-year-old female consulted for fatigue and abdominal pain. A CT scan of abdomen/pelvis revealed appendicitis and CBC showed 76% blasts. An appendectomy was performed. Histologic examination demonstrated the appendiceal wall infiltrated by malignant cells, ultimately demonstrated to be positive for MPO and weak/variable CD117. In the second case, a 50-year-old male presented to the emergency department for nausea, vomiting, and elevated amylase. Esophagogastroduodenoscopy with endoscopic ultrasound demonstrated pancreatic inflammatory changes and a subepithelial nodule in the gastric fundus. Biopsy of the nodule revealed gastric epithelium infiltrated by sheets of malignant cells, ultimately demonstrated to be positive for CD34, myeloperoxidase and CD43. Results (if a Case Study enter NA) NA Conclusion MS is defined as a tumor of myeloid blasts forming outside the bone marrow. Overall, it is an uncommon entity that can occur in patients with known AML, and rarely, as the first sign of AML. Presentation of MS in the GI tract is infrequent (10%), involving primarily the small intestine (63%). The differential diagnosis includes lymphoma, poorly differentiated carcinomas, and melanomas. A review of the clinical history for AML or other myeloproliferative neoplasms should raise suspicion of MS. Expression of lymphoid markers and scant tissue for IHC studies can be diagnostic challenges, rendering B cell lymphoma as the most common misdiagnosis of MS in up to 40-47% of cases. Our two MS cases presented exclusively with GI symptoms without previously known AML and involved unusual GI sites. IHC for myeloid lineage, monocytic or myelomonocytic differentiation should be considered in specific cases. In patients without prior AML diagnosis, especially without hematologic findings, MS is a diagnostic challenge.

Accuracy of Noncontrast T2 SPACE in Active MS Cord Lesion Detection.

The diagnosis of active MS lesions is often based on postgadolinium T1-weighted MR imaging. Recent studies suggest a risk of IV gadolinium to patients, predominantly based on gadolinium deposition in tissue. Noncontrast sequences have shown promise in MS diagnosis, but none differentiate acute from chronic MS lesions. We hypothesized that 3D T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) MR imaging can help detect and differentiate active-versus-chronic MS lesions without the need for IV contrast. In this single-center retrospective study, 340 spinal MR imaging cases of MS were collected in a 24-month period. Two senior neuroradiologists blindly and independently reviewed postcontrast T1-weighted sagittal and T2-SPACE sagittal images for the presence of MS lesions, associated cord expansion/atrophy on T2-SPACE, and enhancement on postcontrast T1WI. Discrepancies were resolved by consensus between the readers. Sensitivity, specificity, and accuracy of T2-SPACE compared with postcontrast T1WI were computed, and interobserver agreement was calculated. The sensitivity of lesion detection on T2-SPACE was 85.71%, 95% CI, 63.66%-96.95%; with a specificity of 93.52%, 95% CI, 90.06%-96.05%; and an accuracy of 92.99%, 95% CI, 89.58%-95.56. Additionally, 16/21 (84.2%) acute enhancing cord lesions showed cord expansion on T2-SPACE. The interobserver agreement was 92%. Our study shows that T2-SPACE facilitates noncontrast detection of acute MS lesions with high accuracy compared with postcontrast T1WI and with high interobserver agreement. The lack of gadolinium use provides an advantage, bypassing any potential adverse effects of repetitive contrast administration.

Occupational risk factors for multiple sclerosis: a systematic review with meta-analysis.

We decided to conduct the first systematic review with meta-analysis to provide the highest level of up-to-date evidence on the occupational risk factors for Multiple Sclerosis. A systematic, comprehensive literature search was performed in four electronic academic databases. We included any case-control study that enrolled working-age subjects and compared the proportion of MS cases with controls who were not exposed to an occupational risk factor. The primary outcome was the occurrence of MS. The quality assessment was performed with the Critical Appraisal Checklist for Case Control Studies, developed, and validated by the Joanna Briggs Institute. All the selection process was also carried out by two independent and previously trained researchers. Overall, the total sample included 19,004 people with MS and 4,164,162 controls. Agricultural workers (OR = 1.44, 95% CI 1.13-1.83), offshore workers (OR = 3.56, 95% CI 2.74-4.61), and hairdressers (OR = 8.25, 95% CI 1.02-66.52) were associated with a higher probability of being diagnosed with MS. In parallel, workers exposed to toxic fumes from oil wells (OR = 16.80, 95% CI 8.33-33.90), low-frequency magnetic fields (OR = 1.71, 95% CI 1.03-2.72), and pesticides (OR = 3.17, 95% CI = 2.53-3.99) also had an increased likelihood of having MS. Our study has the potential to influence more assertive public policies. Nevertheless, future studies on how the occupational setting may contribute to the incidence of MS are highly recommended. The protocol was registered in the international prospective register of systematic reviews (PROSPERO- CRD42023443257).

B-134 Artificial Intelligence (AI)-Driven Clinical Decision Support: Potential to Predict the Risk for Multiple Sclerosis

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, gliosis, and neuronal loss. Globally, over 2.8 million people have MS, and 300 people receive a diagnosis of MS every day. It is 3 times more common in females than males. Autoimmunity, environmental factors, Epstein-Barr virus, and genetics are implicated in the etiology of MS. The pathophysiology of MS is limited to the central nervous system, resulting in focal inflammation of the blood-brain barrier and neurodegeneration of the axons, neurons, and synapse. Diagnosis is made based on clinical history, physical examination, imaging, and cerebrospinal fluid (CSF) studies. Early diagnosis is key to controlling the progression of the disease using disease-modifying therapies. Methods We trained machine learning models with over 3000 sets of patient data with and without MS. The data was sourced from MIMIC-IV, a hospital-wide electronic health record (EHR) from Beth Israel Deaconess Medical Center, Boston, MA. A random forest model with 300 trees with a maximal depth of 30 layers and gain ratio was used as the criterion for selecting the attributes for splitting. The model was tested with 10-fold cross-validation. This model produced optimal performance. The input parameters consisted of age, gender, and the results of routine blood markers, such as complete blood counts, differential counts, comprehensive metabolic panels, and lipid panels recorded up to 3 years before the diagnosis of MS was identified. An evaluation of the performance was conducted using the area under the receiver operating characteristic curve (AUC). Results We were able to show that the model could predict the risk for MS, with an AUC of 0.98 and accuracy of 0.92. This gave the model 0.91 sensitivity, 0.92 specificity, 0.92 positive predictive value, and 0.91 negative predictive value. Neutrophils, lymphocytes, monocytes, eosinophils, red blood cell counts, hemoglobin, and hematocrit seemed predominantly to contribute to the identification of risk for MS. Prediction accuracy was consistent up to 3 years prior to diagnosis. Conclusion Studies have shown that five types of immune cells (plasma cells, monocytes, macrophage M2, neutrophils, and eosinophils) in cerebrospinal fluid (CSF) were significantly altered in MS cases compared to the control group. Brain shrinkage in patients with MS may be linked to hemoglobin protein in the blood leaked through the blood-brain barrier. Albumin, the most abundant protein in plasma, gains access to CNS tissue, where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Our model identified the pattern of the combined values of these markers, contributing to the prediction. Thus AI/ML-based prediction models may be able to help identify the risk for MS years before neurological symptoms appear. This may help to prompt close monitoring of these patients for periodic neurological and cognitive exams as soon as the first symptoms appear. Early confirmation of the diagnosis with imaging and CSF studies may ensure prompt consideration for disease-modifying therapies.

Psychiatric Comorbidity During the Prodromal Period in Patients With Multiple Sclerosis.

Psychiatric morbidity is common after a multiple sclerosis (MS) diagnosis. However, little is known about psychiatric comorbidity during the prodromal phase (before MS onset). To compare the prevalence and relative burden of psychiatric morbidity in individuals with MS with matched controls before MS onset. Using linked administrative and clinical data from British Columbia, Canada, we identified cases with MS through a validated algorithm or from neurologist-diagnosed MS clinic attendees. Cases were matched by age, sex, and geographical location with up to 5 general population controls. We identified psychiatric morbidity through a validated definition and determined its prevalence in cases/controls in the 5 years before the first demyelinating claim of cases with MS ("administrative cohort") or symptom onset ("clinical cohort") and estimated case/control prevalence ratios with 95% CIs. We also compared the yearly number of physician visits for psychiatric morbidity, visits to psychiatrists, psychiatric-related admissions, and psychotropic dispensations pre-MS onset in cases/controls regardless of whether psychiatric morbidity algorithm was fulfilled using negative binomial regression fitted through generalized estimating equations; results were reported as adjusted rate ratios with 95% CIs. We assessed yearly trends through interaction terms between cases/controls and each year pre-MS onset. The administrative cohort comprised 6,863/31,865 cases/controls; the clinical cohort comprised 966/4,534 cases/controls. Over the entire 5-year period pre-MS onset, 28.0% (1,920/6,863) of cases and 14.9% (4,738/31,865) of controls (administrative cohort) had psychiatric morbidity, as did 22.0% (213/966) of clinical cases and 14.1% (638/4,534) controls. Psychiatric morbidity prevalence ratios ranged from 1.58; 95% CI 1.38-1.81 (clinical cohort) to 1.91; 95% CI 1.83-2.00 (administrative cohort). In the administrative cohort, health care use was higher for cases in each year pre-MS onset (all 95% CIs >1); physician visits were 78% higher in year 5 pre-MS onset and 124% 1 year before; visits to psychiatrists were 132% higher in year 5 and 146% in year 1; hospitalizations were 129% higher in year 5 and 197% in year 1; and prescription dispensations were 72% higher in year 5 and 100% in year 1. Results were not significant in the clinical cohort. Psychiatric morbidity represents a significant burden before MS onset and may be a feature of the MS prodrome.

MULTIPLE SCLEROSIS IN A CHILD. CLINICAL CASE

Introduction. Pediatric-onset multiple sclerosis (POMS) is defined as MS with onset before 18 years of age, using the 2017 McDonald Criteria. 3-5% of all MS cases have pediatric onset. Mean age of onset in POMS is 11 years, however, most patients are older than 15. There is a known female predilection for MS, although not in the younger than 11 years age group. Materials and methods. Our article presents a clinical case of MS in children. We think that this information will be interesting for neurologists and pediatricians. Results. Our patient is a boy 13 years, born from the 3 pregnancy, 3 birth. His development was appropriate for his age. There is no patient with multiple sclerosis in the offspring. Symptoms started with blurred vision in one eye when he was 11 years old. He was under the supervision of a neurologist and received treatment. His condition has stabilized. Symptoms repeated after 6 months. In addition to the weakness of vision, there is also a difficulty in performing precise movements. In neurological status: Pupils reaction to light was preserved. Left-sided oculomotor deficiency is noted. Swallowing and hearing N. In the motor sphere: peripheral muscle tone D=S, hypotonia, reflexes D=S, hyperreflexia, muscle strength D=S, normal. Reflexogenic zones in the lower limbs have expanded. Sensory system without any changes. He is unstable in the Romberg state. In finger- nose test intentional tremor is seen. Brain MRI: active demyelinating lesions (largest 14x8) in supratentorial and infratentorial region. Spine MRI: contrast enhancing demyelinating lesions in C1 and C5. 3 months later, an increase of demyelinating lesions was noted in the MRI examination of the brain and spinal cord. Ophthalmologist's examination: retrobulbar neuritis. LP: Oligoclonal band was positive. General and biochemical analysis of blood was normal. Conclusion. There is quite a lot of information about multiple sclerosis in adults in the literature. However, it has not been adequately studied in children. Thus, we believe that studying the characteristics of the course of multiple sclerosis in the pediatric population is important and of social importance.

Quantifying the Association between Objectively Measured Physical Activity and Multiple Sclerosis in the UK Biobank.

Objectively measured physical activity (PA) data were collected in the accelerometry substudy of the UK Biobank. UK Biobank also contains information about multiple sclerosis (MS) diagnosis at the time of and after PA collection. This study aimed to 1) quantify the difference in PA between prevalent MS cases and matched healthy controls, and 2) evaluate the predictive performance of objective PA measures for incident MS cases. The first analysis compared eight accelerometer-derived PA summaries between MS patients ( N = 316) and matched controls (30 controls for each MS case). The second analysis focused on predicting time to MS diagnosis among participants who were not diagnosed with MS. A total of 19 predictors including eight measures of objective PA were compared using Cox proportional hazards models (number of events = 47; 585,900 person-years of follow-up). In the prevalent MS study, the difference between MS cases and matched controls was statistically significant for all PA summaries ( P < 0.001). In the incident MS study, the most predictive variable of progression to MS in univariate Cox regression models was lower age ( C = 0.604), and the most predictive PA variable was lower relative amplitude (RA, C = 0.594). A two-stage forward selection using Cox regression resulted in a model with concordance C = 0.693 and four predictors: age ( P = 0.015), stroke ( P = 0.009), Townsend deprivation index ( P = 0.874), and RA ( P = 0.004). A model including age, stroke, and RA had a concordance of C = 0.691. Objective PA summaries were significantly different and consistent with lower activity among study participants who had MS at the time of the accelerometry study. Among individuals who did not have MS, younger age, stroke history, and lower RA were significantly associated with a higher risk of a future MS diagnosis.

Mechanisms of metabolic stress induced cell death of human oligodendrocytes: relevance for progressive multiple sclerosis

Oligodendrocyte (OL) injury and loss are central features of evolving lesions in multiple sclerosis. Potential causative mechanisms of OL loss include metabolic stress within the lesion microenvironment. Here we use the injury response of primary human OLs (hOLs) to metabolic stress (reduced glucose/nutrients) in vitro to help define the basis for the in situ features of OLs in cases of MS. Under metabolic stress in vitro, we detected reduction in ATP levels per cell that precede changes in survival. Autophagy was initially activated, although ATP levels were not altered by inhibitors (chloroquine) or activators (Torin-1). Prolonged stress resulted in autophagy failure, documented by non-fusion of autophagosomes and lysosomes. Consistent with our in vitro results, we detected higher expression of LC3, a marker of autophagosomes in OLs, in MS lesions compared to controls. Both in vitro and in situ, we observe a reduction in nuclear size of remaining OLs. Prolonged stress resulted in increased ROS and cleavage of spectrin, a target of Ca2+-dependent proteases. Cell death was however not prevented by inhibitors of ferroptosis or MPT-driven necrosis, the regulated cell death (RCD) pathways most likely to be activated by metabolic stress. hOLs have decreased expression of VDAC1, VDAC2, and of genes regulating iron accumulation and cyclophilin. RNA sequencing analyses did not identify activation of these RCD pathways in vitro or in MS cases. We conclude that this distinct response of hOLs, including resistance to RCD, reflects the combined impact of autophagy failure, increased ROS, and calcium influx, resulting in metabolic collapse and degeneration of cellular structural integrity. Defining the basis of OL injury and death provides guidance for development of neuro-protective strategies.

Assessment of Fatigue and Quality of Life in Multiple Sclerosis Patients: A Cross-Sectional Study

IntroductionMultiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system that is associated with a range of devastating symptoms including fatigue. In addition, the accumulation of disability that occurs in most MS patients can have a detrimental effect on their quality of life.ObjectivesTo assess fatigue and quality of life in patients with MS.MethodsDescriptive cross-sectional study that interested MS patients referred to the occupational pathology consultation of Charles Nicolle Hospital, during the period from 1 July 2020 to 30 September 2022. The data collected concerned socio-demographic and occupational characteristics. The impact of MS on quality of life was studied using the SF-12 quality of life scale. Fatigue was assessed by the Fatigue Severity Scale (FSS).ResultsTwenty-six cases of MS were identified. The mean age was 38 ± 9 years with a sex ratio (M/F) of 0.3. The average occupational seniority was 11 ± 8 years. The health sector was the most represented (23%, n= 6) followed by the transport sector (19%, n= 5). The main occupations were manual workers (31%), drivers, and administrative agents (19% each). The occupational constraints were physical in 44% of cases and psychological in 24% of cases. Fourteen patients (87% of the cases) lost their jobs because of the disease. The decision on occupational fitness was definitive incapacity in 44% of cases. The mean FSS score was 4±1.74. Sixteen patients (62%) had moderate fatigue (FSS 36-52), eight patients (31%) had mild fatigue (FSS &lt;36) and two patients (8%) had severe fatigue (FSS &gt;52). In addition, the mean scores for the physical and mental components of perceived health were estimated to be 37.04±7.67 and 44.93±7.23, respectively. The mean global score (SG) of SF12 was 40.98±7.23. The majority of patients (92%, n=24) had an average quality of life (SG- SF12 between 30 and 60) and two patients (8%) had a poor quality of life (SG &lt;30).ConclusionsThe impact of MS on the socio-professional quality of life of patients was noted in the majority of cases. It is therefore imperative to improve the care of our patients on both the physical and psychological levels.Disclosure of InterestNone Declared

Analysis of determinants of treatment change in adult paediatric-onset MS patients.

Paediatric-onset multiple sclerosis (POMS) is increasing worldwide and represents approximately 5% of all MS cases. Although this patient group has similar characteristics to the adult group, it is important for this patient group to receive effective treatment due to the early onset of cognitive involvement, higher lesion burden, and secondary progression at an earlier age than adults. In this study, we aimed to evaluate the factors that cause treatment change in POMS patients. Adult patients with a first MS attack at age 18 years or younger who were followed up with the diagnosis of MS at the Clinical Neuroimmunology and Demyelinating Diseases outpatient clinic of Cerrahpaşa Medical School between 1987 and 2020 were included in our study. Patient files were reviewed retrospectively, and demographic and clinical characteristics, imaging, first attack characteristics, and treatment change were noted. We included 269 patients with a definite diagnosis of MS in the study, and these patients were evaluated in two groups: negative for treatment change and positive for treatment change. Multifocal involvement was detected more frequently in the group with treatment change (p=0,049). Cerebellar involvement as a first attack symptom was more common in male patients (p=0,023) The age at first MS attack was found to be younger (p=0,006), and the disease duration was longer in the positive for treatment change group (p=0,003). Spinal cord involvement was more common in the positive for treatment change group (p=0,016). Abnormal VEP findings were observed more frequently in the group without treatment change (p=0.018). In multivariant analysis, spinal cord involvement, younger age at first attack, and abnormal VEP findings in the group without treatment change were found to be significant. Among the reasons for treatment change, the most common reason was radiological and clinical progression. The higher inflammatory load in POMS patients compared with adults necessitates early initiation of treatment in this group and timely treatment change to prevent disability. Furthermore, this patient group should be followed closely and receive effective treatment.

Changes in diffusion tensor imaging indices in basal ganglia and thalamus of patients with Relapsing-Remitting Multiple Sclerosis and relation with clinical conditions: A case-control study

BackgroundMultiple sclerosis (MS) is recognized as the most prevalent autoimmune abnormality of the CNS. T1WI, T2WI, and FLAIR are limited in the quantification of tissue damage and detection of tissue alterations in white and grey matter in MS. This study aimed to the evaluation of changes in DTI indices in these patients at the thalamus and basal ganglia. Methods30 relapsing-remitting MS (RRMS) cases and 30 normal individuals were included. Conventional MRI (T2, FLAIR) was acquired to confirm NAGM in MS patients. A T1 MPRAGE protocol was used to normalize DTI images. FSL, SPM, and Explore DTI software were employed to reach Mean Diffusivities (MD), Axial Diffusivities (AD), Fractional anisotropy (FA), and Radial Diffusivity (RD) at the thalamus and the basal ganglia. ResultsThe FA and RD of the thalamus were decreased in healthy controls compared to MS cases (0.319 vs. 0.296 and 0.0009 vs. 0.0006, respectively) (P < 0.05). The AD value in the thalamus and the FA value in the caudate nucleus were significantly lower in MS cases than in controls (0.0009 vs. 0.0011 and 0.16 vs. 0.18, respectively) (P < 0.05). MD values in the thalamus or basal ganglia were not significantly different between groups. ConclusionsDTI measures including FA, RD, and AD have a good diagnostic performance in detecting microstructural changes in the normal-appearing thalamus in cases with RRMS while they had no significant relationship with clinical signs in terms of EDSS. Availability of data and materialNot applicable