Clinical Course Of Multiple Sclerosis Research Articles

Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis

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

Real-world effectiveness of disease-modifying therapies in older adults with multiple sclerosis

BackgroundDisease-modifying therapies (DMTs) can alter multiple sclerosis (MS) disease course.Peak prevalence age for people with MS (pwMS) has increased, but little is known about MS clinical course or DMT response in older pwMS.The objective of this retrospective analysis of a US administrative claims database to was to evaluate MS disease course, DMT use, healthcare utilisation, and time to relapse during follow-up, in pwMS ≥50 years with active disease. MethodsInclusion criteria were ≥3 years’ continuous enrolment, ≥1 MS relapse (index event), and age ≥50 years. Baseline period was 1 year prior to index event. Follow-up was 2 years.Two patient categories were considered: (i) not under DMT treatment at index date (untreated group) and (ii) under DMT treatment at index date (treated group). ResultsFollowing propensity score matching there were 3,869 patients in the treated and 3,869 patients in the untreated groups.The untreated group numerically spent more days in hospital than the treated group (9.4 vs 7.8 days) and had more emergency room (ER)/urgent care visits (1.3 vs 1.0 visits).There were no observed differences in time to relapse between groups.At index relapse, pwMS were treated with glatiramer acetate (29%), interferons (27%), oral DMTs (29%), or intravenous DMTs (15%). During follow-up, 32% of the untreated group were treated with a DMT, mostly intravenous and oral DMTs. DMT treatment remained largely unchanged in the treated group. ConclusionDMTs may provide shorter hospital stays and less frequent ER visits in older pwMS with active MS. Treatment inertia after relapse was high.

Olfactory threshold as a biomarker of long-term relapse activity in multiple sclerosis

BackgroundOlfactory threshold (OT) is a marker of short-term inflammatory activity in multiple sclerosis (MS). ObjectiveTo investigate whether OT predicts long-term MS clinical disease course. MethodsThis was a 6-year prospective longitudinal study on MS patients at the MS clinic Innsbruck. Clinical visits assessing the occurrence of relapses, Expanded Disability Status Scale (EDSS) scores, and disease-modifying treatment (DMT), were conducted biannually. OT testing was performed at baseline (BL), year 1 (Y1), year 2 (Y2) and year 6 (Y6), using the threshold subscore of the “Sniffin’ Sticks” test. Cognitive function was assessed by the Symbol Digit Modalities Test. ResultsOf 139 MS patients, 92 were eligible for Y6 follow-up. 68% experienced relapses, 53% EDSS worsening, 29% progression independent of relapse activity (PIRA) and 41% cognitive deterioration. OT scores were lower at BL, Y1 and Y2 in patients requiring DMT escalation. In multivariable analysis, higher OT scores at BL, Y1, Y2 and Y6 were associated with lower risk of relapse (hazard ratio, HR: 0.65–0.92) and EDSS worsening (HR: 0.86–0.89), while no associations were found for PIRA and cognitive deterioration. ConclusionsOT is a potential surrogate marker for long-term inflammatory disease activity and DMT failure in MS.

Co-occurrence of Myasthenia Gravis and Multiple Sclerosis: A Case Report

Myasthenia gravis (MG) and multiple sclerosis (MS) are thought to have a common autoimmune mechanism as the number of reported co-occurrences of both diseases is increasing. The involvement of both T cells and B cells in the pathogenesis of these two diseases is suspected. As the symptoms and clinical course of MS and MG can be similar in some cases, this makes it difficult to consider the possibility of the coexistence of these disorders. However, laboratory and imagining findings are helpful in distinguishing both diseases and differentiating them from other neurological conditions. Additionally, there can be obstacles in effective treatment selection for patients with MS and MG coexistence. This article presents a clinical case of a woman with previously diagnosed MG who was admitted to hospital 12 years later with new-onset symptoms and was additionally diagnosed with relapsing-remitting multiple sclerosis (RRMS). Remission of MG was achieved with medications and thymectomy, but treatment of MS had its challenges, as first-line immunomodulating drugs interferon beta-1a and dimethyl fumarate were not effective, and second line treatment with monoclonal antibody medication rituximab and ocrelizumab showed efficacy for both diseases, MG and MS. The presented case highlights the importance of considering a manifestation of another disease when treating an already diagnosed disorder. It also emphasizes the importance of further research into the relationship between MG and MS.

Relationship between pattern reversal visual evoked potential P100 wave latency and dysfunctional HDL in patients with multiple sclerosis subjected to an optic neuritis attack: A case-control study.

Optic neuritis frequently occurs during the clinical course of multiple sclerosis (MS). In this condition, demyelination of the optic nerve occurs, which electrophysiologically causes a delay in P100 wave latency. Sensitive cholesterol homeostasis is critical for the formation of the myelin sheath and for myelin to become functionally mature. High-density lipoprotein (HDL) becomes dysfunctional under oxidative stress and plays an important role in the pathogenesis of MS. In this study, HDL levels of MS patients suffering from optic neuritis were compared with those of healthy individuals, and the relationship between pattern reversal visual evoked potential (PRVEP) P100 wave latency and HDL levels in patients with optic neuritis attacks was analyzed. PRVEP studies were performed in patients with MS who had an episode of optic neuritis, and P100 wave latencies were measured. Peripheral blood samples were collected from healthy participants and patients. Lipid levels and myeloperoxidase (MPO) and paraoxonase (PON) activities were measured, and the MPO/PON ratio was then calculated. The lipid profiles and dysfunctional HDL levels in the healthy and patient groups were compared. Finally, the relationship between these parameters and the PRVEP-P100 wave latency was examined. Total cholesterol and low-density lipoprotein (LDL) levels were significantly higher in the patient group (P = .044; P = .038, respectively). There was no statistically significant difference in HDL levels between groups (P = .659). The distribution of MPO values was similar between groups (P = .452). PON values were significantly lower, whereas the MPO/PON ratios were significantly higher in the patient group than in the control group (P = .025; P = .028, respectively). A statistically significant positive correlation was found between the elevated MPO/PON ratio, representing dysfunctional HDL, and both the mean and maximum PRVEP-P100 wave latencies (P < .001, R = 0.690; P < .001, R = 0.815, respectively). A dysfunctional form of HDL may lead to poor deactivation of remyelination-limiting factors and may ultimately be associated with poor outcomes in optic neuritis.

Association between active and passive smoking and the clinical course of multiple sclerosis and neuromyelitis optica spectrum disorder

&lt;i&gt;Objective&lt;/i&gt;: Active and passive smoking are common environmental risk factors, but there is no definite conclusion about their effects on relapse and disability progression in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). &lt;i&gt;Methods&lt;/i&gt;: This was a retrospective cohort study. Patients were included from four centers. Demographic and clinical data were extracted from the clinical database, while data involving environmental exposures during daily life, relapse, and disability progression were obtained through telephone follow-up interviews. Determinants of relapse were assessed by Cox proportional models, and disability progression was assessed by linear regression. Kaplan‒Meier survival was used to estimate relapse within five years after the first attack. &lt;i&gt;Results&lt;/i&gt;: A total of 130 MS patients and 318 NMOSD patients were included in this study, and females accounted for 60% and 79.6%, respectively. MS patients with an active smoking history had a higher risk of relapse, for which the association became borderline significant after accounting for covariates (aHR=1.52, 95% CI=1.00, 2.31; &lt;i&gt;p&lt;/i&gt;=0.052). The relapse risk between ever-smokers who smoked more than 10 cigarettes per day and smokers who smoked less than 10 cigarettes per day was not significantly different (aHR=0.96, 95% CI=0.63, 1.47; &lt;i&gt;p&lt;/i&gt;=0.859). However, exposure to passive smoking was associated with a reduced risk of MS relapse (aHR=0.75, 95% CI=0.56, 1.00; &lt;i&gt;p&lt;/i&gt;=0.044) compared with never-exposed patients. No associations were observed between active smoking/passive smoking and the risk of NMOSD relapse, but patients with a history of smoking were associated with a lower annual progression rate by Expanded Disability Status Scale (EDSS) (aβ=−0.20, 95% CI=−0.38, −0.01; &lt;i&gt;p&lt;/i&gt;=0.036) and Multiple Sclerosis Severity Score (MSSS) (aβ=−0.23, 95% CI=−0.44, −0.03; &lt;i&gt;p&lt;/i&gt;=0.028). &lt;i&gt;Conclusion&lt;/i&gt;: Our research shows that active smoking increases the relapse risk of MS and has a negative impact on disability progression; thus, smoking cessation should be encouraged.

The Effects of Selective Serotonin Reuptake Inhibitors on Neurological and Depressive Symptoms in Multiple Sclerosis: A Systematic Review and Meta‐analysis of Randomized Controlled Trials: SSRIs in Multiple Sclerosis: Meta-analysis

Background: Multiple sclerosis (MS) affects the central nervous system and creates plaques by demyelination of neurons. Several studies have investigated the effect of selective serotonin reuptake inhibitors (SSRIs) on MS clinical courses. The current meta-analysis was conducted to determine the effect of SSRIs on neurological and depressive symptoms of MS disease based on a systematic review and meta-analysis of randomized controlled trials. Materials and Methods: We searched the PubMed/Medline, Scopus, EMBASE, Google scholar, Web of Science, and Cochrane Library until June 2023. The effects of SSRI were assessed through indictors such as symbol digit modalities test (SDMT), expanded disability status scale (EDSS), modified fatigue impact scale (MFIS), and Beck's depression inventory/psychiatric (BDI). Results: Considering the inclusion criteria, seven articles (including eight trials) were included in this review. The meta-analysis results demonstrated that SSRIs treatments did not have significant effects on indicators of neurological and depressive symptoms, such as SDMT (Weighted Mean Difference (WMD)=-0.87; 95% CI, -7.74, 5.99, P=0.35; I2=0.0%), EDSS (WMD=-0.05; 95% CI, -0.24, 0.14, P=0.62; I2=0.0%), MFIS (WMD=5.29; 95% CI, -18.10, 28.68, P=0.21; I2=0.0%), and BDI (WMD=-0.47; 95% CI, -2.61, 1.67, P=0.67; I2=32.05%) in patients with MS compared with controls. Conclusion: This study shows that the consumption of SSRIs in MS patients compared to the control group does not bring about a significant change in the indices related to neurological and depressive symptoms. Further meta-analyses are required in order to provide stronger evidence in the future.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study

BackgroundEndometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. ObjectiveTo characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. MethodsWe retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). ResultsUsing a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. ConclusionWhen controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

Prospective analyses of alertness, sleep, and fitness to drive one year after de novo multiple sclerosis diagnosis.

The prevalence and functional burden of the chronic demyelinating disease multiple sclerosis (MS) are well documented; however, little is known about the initial clinical course of alertness, sleep, cognitive, and psychological symptoms. This exploratory, prospective, longitudinal study multidimensionally investigated the development and progression of alertness, sleep, fitness to drive, and psychological symptoms in the first year after de novo MS diagnosis. Twenty-five people with MS (pwMS) were assessed cognitively, psychologically, and using polysomnography soon after diagnosis and one year later, with outcomes compared to matched healthy controls. In the early stage of the disease, psychological symptoms of pwMS were comparable with those of controls, and patient conditions did not deteriorate within the first disease year. A small percentage of pwMS experienced increased levels of anxiety and depression after diagnosis. Alertness, sustained attention, and fitness to drive were comparable between both groups, and fatigue levels remained low over the course of the year. This study highlights patient experiences within the initial clinical course of MS in a small group of patients. Further research is needed to understand the progression of symptoms and impairments in MS over a longer period and in different stages of the disease.

Association of intestinal dysbiosis with susceptibility to multiple sclerosis: Evidence from different population studies (Review).

Understanding the relationship between microorganisms that live in our intestines and neuroinflammatory and neurodegenerative pathologies of the central nervous system (CNS) is essential, since they have been shown to have an immunomodulatory effect in neurological disorders, such as multiple sclerosis (MS). The gut microbiota can be affected by several environmental factors, including infections, physical and emotional stress and diet, the latter known as the main modulator of intestinal bacteria. An abrupt shift in the gut microbiota composition and function is known as dysbiosis, a state of local and systemic inflammation produced by pathogenic bacteria and its metabolites responsible for numerous neurological symptoms. It may also trigger neuronal damage in patients diagnosed with MS. Intestinal dysbiosis affects the permeability of the intestine, allowing chronic low-grade bacterial translocation from the intestine to the circulation, which may overstimulate immune cells and cells resident in the CNS, break immune tolerance and, in addition, alter the permeability of the blood-brain barrier (BBB). This way, toxins, inflammatory molecules and oxidative stress molecules can pass freely into the CNS and cause extensive damage to the brain. However, commensal bacteria, such as the Lactobacillus genus and Bacteroides fragilis, and their metabolites (with anti-inflammatory potential), produce neurotransmitters such as γ-aminobutyric acid, histamine, dopamine, norepinephrine, acetylcholine and serotonin, which are important for neurological regulation. In addition, reprogramming the gut microbiota of patients with MS with a healthy gut microbiota may help improve the integrity of the gut and BBB, by providing clinically protective anti-inflammatory effects and reducing the disease's degenerative progression. The present review provides valuable information about the relationship between gut microbiota and neuroinflammatory processes of the CNS. Most importantly, it highlights the importance of intestinal bacteria as an environmental factor that may mediate the clinical course of MS, or even predispose to the outbreak of this disease.

Optical coherence tomography with voxel-based morphometry: a new tool to unveil focal retinal neurodegeneration in multiple sclerosis.

Neurodegeneration is the main contributor to disability accumulation in multiple sclerosis. Previous studies in neuro-ophthalmology have revealed that neurodegeneration in multiple sclerosis also affects the neuro-retina. Optical coherence tomography has been used to measure thinning of retinal layers, which correlates with several other markers for axonal/neuronal loss in multiple sclerosis. However, the existing analytical tools have limitations in terms of sensitivity and do not provide topographical information. In this study, we aim to evaluate whether voxel-based morphometry can increase sensitivity in detecting neuroaxonal degeneration in the retina and offer topographical information. A total of 131 people with multiple sclerosis (41 clinically isolated syndrome, 53 relapsing-remitting and 37 progressive multiple sclerosis) and 50 healthy subjects were included. Only eyes with normal global peripapillary retinal nerve fibre layer thickness and no history of optic neuritis were considered. Voxel-based morphometry and voxel-wise statistical comparisons were performed on the following: (i) patients at different disease stages and 2) patients who experienced the first demyelination attack without subclinical optic neuritis, assessed by visual evoked potentials. Standard parameters failed to discern any differences; however, voxel-based morphometry-optical coherence tomography successfully detected focal macular atrophy of retinal nerve fibre layer and ganglion cell/inner plexiform layer, along with thickening of inner nuclear layer in patients who experienced the first demyelination attack (disease duration = 4.2 months). Notably, the atrophy pattern of the ganglion cell/inner plexiform layer was comparable across disease phenotypes. In contrast, the retinal nerve fibre layer atrophy spread from the optic nerve head to the fovea as the disease evolved towards the progressive phase. Furthermore, for patients who experienced the first neurological episode, the severity of retinal nerve fibre layer atrophy at entry could predict a second attack. Our results demonstrate that voxel-based morphometry-optical coherence tomography exhibits greater sensitivity than standard parameters in detecting focal retinal atrophy, even at clinical presentation, in eyes with no history of optic neuritis and with normal latency of visual evoked potentials. Thinning of the ganglion cell/inner plexiform layer primarily concentrated in nasal perifovea in all disease phenotypes, indicating selective vulnerability of retinal ganglion cells and their perifoveal axons. Conversely, the degree of retinal nerve fibre layer thinning seems to be related to the clinical course of multiple sclerosis. The findings suggest bidirectional neurodegeneration in the visual pathway. Voxel-based morphometry-optical coherence tomography shows potential as a valuable tool for monitoring neurodegeneration on a patient level and evaluating the efficacy of novel neuroprotective treatments.

Do the current MS clinical course descriptors need to change and if so how? A survey of the MS community

Background and Objectives: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS. Methods: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics. Results: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS. Conclusion: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles.

CHARACTERISTICS OF PATIENTS WITH MULTIPLE SCLEROSIS BY SEX

Introduction. Multiple sclerosis (MS) is a chronic inflammatory demyelinating, neurodegenerative disease of the central nervous system, with an unknown etiology and complete treatment. Many studies have shown that the incidence of MS among women is 2-3.5 times higher in comparison with men. The aim of the study was providing the sex characteristics of patients diagnosed with MS in Azerbaijan. Materials and methods of research. During the study period (01.01.2013–31.12.2022), 1796 patients with MS were examined. Patients were divided into two comparison groups (Group I – men, 616 patients; Group II – women, 1180 patients). Share of patients by sex, age (at diagnosis, probable disease onset, and the end of the study), clinical course of MS, and deathes were investigated in the comparison groups. Statistical analysis was performed with χ2-Pearson and t-Student-Bonferroni tests, and the acquired statistical results were rechecked with the U-Mann-Whitney test. Results and discussion. 65.7% of the patients were women, and 34.3% were men. Male-to-female ratio was 1:1.92. 66.4% of patients were urban residents, while rural residents were 33.6%. Among women, urban residents (68.1±1.4%) prevailed men (63.0±1.9%), and this difference was statistically significant (P&lt;0.05). The average age at diagnosis was 34.9±0.2 years (35.2±0.4 years in men; 34.7±0.3 years in women). At the time of presumed first attacks, the average age was 29.7±0.2 years (29.9±0.3 years in men and 29.6±0.2 years in women). During the study years, 43 patients died. The average age of death was 56.8±1.2 years (in men, 55.2±1.6; in women, 58.0±1.6) (P&gt;0.05). After diagnosis of MS, the average life expectancy was 15.7±1.0 years (minimum life expectancy was 4 years, maximum was 40 years). The period between disease onset and the diagnosis of MS was on average 5.3±0.2 years in men and 5.2±0.1 years in women. The distribution of patients by 5-year age groups on the age of diagnosis showed that more incidence rate among men was in the 35-39 age group (20.1±1.6% of male patients) and among women in the 30-34 age group (20.8±1.2% of female patients). However, these indicators did not differ statistically (P&gt;0.05). The most frequent clinical course was Relapsing Remitting MS in both sexes – 78.6±1.7% in men, 77.4±1.2% in women. Although CIS is more common in women (4.2±0.6%), the difference was not statistically significant (P&gt;0.05). Other types of MS were found almost equally in both sexes. Conclusion. Extensive research on sex differences in MS can improve our understanding of the disease's pathophysiology and treatment. The findings lay the groundwork for future research into the sexdepending approach to the clinical course and treatment of MS.

Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis.

Growing evidence from cerebrospinal fluid samples and post-mortem brain tissue from individuals with multiple sclerosis (MS) and rodent models indicates that the meninges have a key role in the inflammatory and neurodegenerative mechanisms underlying progressive MS pathology. The subarachnoid space and associated perivascular spaces between the membranes of the meninges are the access points for entry of lymphocytes, monocytes and macrophages into the brain parenchyma, and the main route for diffusion of inflammatory and cytotoxic molecules from the cerebrospinal fluid into the brain tissue. In addition, the meningeal spaces act as an exit route for CNS-derived antigens, immune cells and metabolites. A number of studies have demonstrated an association between chronic meningeal inflammation and a more severe clinical course of MS, suggesting that the build-up of immune cell aggregates in the meninges represents a rational target for therapeutic intervention. Therefore, understanding the precise cell and molecular mechanisms, timing and anatomical features involved in the compartmentalization of inflammation within the meningeal spaces in MS is vital. Here, we present a detailed review and discussion of the cellular, molecular and radiological evidence for a role of meningeal inflammation in MS, alongside the clinical and therapeutic implications.

Association Between Anti-CD20 Therapies and COVID-19 Severity Among Patients With Relapsing-Remitting and Progressive Multiple Sclerosis

In patients with multiple sclerosis (MS), factors associated with severe COVID-19 include anti-CD20 therapies and neurologic disability, but it is still unclear whether these 2 variables are independently associated with severe COVID-19 or whether the association depends on MS clinical course. To assess the association between anti-CD20 therapies and COVID-19 severity in patients with relapsing-remitting MS (RRMS) and progressive MS (PMS). This multicenter, retrospective cohort study used data from the COVISEP study, which included patients with MS and COVID-19 from February 1, 2020, to June 30, 2022, at 46 French MS expert centers, general hospitals, and private neurology practices. Eligible patients with RRMS were those treated with high-efficacy MS therapy (ie, anti-CD20, fingolimod, or natalizumab), and eligible patients with PMS were those younger than 70 years with an Expanded Disability Status Scale (EDSS) score of 8 or lower. Patients were monitored from COVID-19 symptom onset until recovery or death. Current anti-CD20 therapy (ocrelizumab or rituximab). The main outcome was severe COVID-19 (ie, hospitalization with any mode of oxygenation or death). All analyses were conducted separately in patients with RRMS and PMS using propensity score-weighted logistic regression. Subgroup analyses were performed according to COVID-19 vaccine status, sex, EDSS score, and age. A total of 1400 patients, 971 with RRMS (median age, 39.14 years [IQR, 31.38-46.80 years]; 737 [76.1%] female) and 429 with PMS (median age, 54.21 years [IQR, 48.42-60.14 years]; 250 [58.3%] female) were included in the study. A total of 418 patients with RRMS (43.0%) and 226 with PMS (52.7%) were treated with anti-CD20 therapies. In weighted analysis, 13.4% and 2.9% of patients with RRMS treated and not treated with anti-CD20 had severe COVID-19, respectively, and anti-CD20 treatment was associated with increased risk of severe COVID-19 (odds ratio [OR], 5.20; 95% CI, 2.78-9.71); this association persisted among vaccinated patients (7.0% vs 0.9%; OR, 8.85; 95% CI, 1.26-62.12). Among patients with PMS, 19.0% and 15.5% of patients treated and not treated with anti-CD20 had severe COVID-19, respectively, and there was no association between anti-CD20 treatment and severe COVID-19 (OR, 1.28; 95% CI, 0.76-2.16). In PMS subgroup analysis, anti-CD20 exposure interacted negatively with EDSS score (P = .009 for interaction) and age (P = .03 for interaction); anti-CD20 therapies were associated with risk of severe COVID-19 only in patients with less neurologic disability and younger patients with PMS. In this cohort study, risk of severe COVID-19 was higher in patients with PMS than in those with RRMS. Use of anti-CD20 therapies was associated with an increased risk of severe COVID-19 among patients with RRMS. In patients with PMS, there was no association between anti-CD20 therapies and risk of severe COVID-19.

Clinical course of multiple sclerosis and patient experiences during breast cancer treatment

Background: Over one-third of multiple sclerosis (MS) patients are post-menopausal women, the primary demographic affected by breast cancer. After breast cancer diagnosis, there is little information about patients’ clinical experiences with both diseases. Objective: Utilize a case series of MS patients diagnosed with breast cancer to characterize oncologic and MS trajectories, and generate novel insights about clinical considerations using qualitative analysis. Methods: A single-center retrospective review was performed on medical record data of patients with MS and breast cancer. Thematic analysis was used to characterize experiences with the concurrent diagnoses. Results: For the 43 patients identified, mean age was 56.7 years at cancer diagnosis and MS duration was 16.5 years. Approximately half were treated with MS disease modifying therapy at cancer diagnosis, and half of these subsequently discontinued or changed therapy. Altogether 14% experienced MS relapse(s) during follow-up (with 2 relapses in the first 2 years), with mean annualized relapse rate of 0.03. Cohort Expanded Disability Status Scale (EDSS) scores remained stable during follow-up. Qualitative insights unique to this population were identified regarding immunosuppression use and neurologic symptoms. Conclusions: MS relapses were infrequent, and there was modest progression during breast cancer treatment. Oncologic outcomes were comparable to non-MS patients with similarly staged cancer.

Effect of Metabolic and Bariatric Surgery on the Clinical Course of Multiple Sclerosis in Patients with Severe Obesity: a Systematic Review.

Multiple sclerosis (MS) is an autoimmune inflammatory condition affecting the central nervous system (CNS). A systematic review following the PRISMA guidelines was performed to explore the effect of metabolic and bariatric surgery (MBS) on the clinical course and outcomes in patients with multiple sclerosis. Eleven articles examining 394 patients were included in the final analysis. The mean MS duration at the time of surgery was 7.6 ± 4.6 years, and the mean postoperative follow-up was 35.5 ± 5.3 months. MBS leads to the same weight loss with the same complication rate as in patients without MS. Most of patients experienced improvement in clinical course of MS after MBS, compared to non-surgical group. However, there is a risk for MS exacerbation in a number of patients after MBS; they should not be disadvantaged from having MBS, since surgery leads to the same weight loss outcomes with the same complication rate as in patients without MS.

Diagnosis of Coexistent Neurodegenerative Dementias in Multiple Sclerosis (P12-3.018)

<h3>Objective:</h3> Use biomarkers such as PET and CSF proteins to distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease. <h3>Background:</h3> Among people with multiple sclerosis, cognitive impairment occurs commonly and is a potent predictor of disability. Some multiple sclerosis patients present with severe cognitive impairment, and distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease poses a diagnostic challenge. <h3>Design/Methods:</h3> The study was a retrospective, descriptive study on convenience samples of separate cohorts, one of cognitively impaired multiple sclerosis patients evaluated on autopsy to demonstrate coincidence of both multiple sclerosis and neurodegenerative cognitive diseases. The second cohort were cognitively impaired multiple sclerosis patients evaluated by biomarker to investigate possible additional neurodegenerative cognitive disorders contributing to the cognitive impairment. <h3>Results:</h3> We investigated selected biomarkers among 31 severely impaired patients (biomarker cohort) and 12 severely impaired patients assessed at autopsy and selected 24 (23 biomarker cohort, 1 autopsy cohort) had comprehensive neurocognitive testing. Biomarker cohort investigations included 18F-Fluorodeoxyglucose PET and/or CSF amyloid Aβ1–42, phospho-tau and total tau levels. The autopsy cohort was evaluated with comprehensive neuropathological assessment for aetiology of cognitive impairment. The cohorts shared similar sex, age at multiple sclerosis onset and multiple sclerosis clinical course. The autopsy-cohort patients were older at diagnosis (69.5 versus 57 years, P=0.006), had longer disease duration [median (range) 20 years (3–59) versus 9 (1–32), P=0.001] and had more impaired bedside mental status scores at last follow-up [Kokmen median (range) 23 (1–38) versus 31 (9–34) P=0.01]. Autopsy-cohort patients confirmed, or excluded, coexistent neurogenerative disease by neuropathology gold standard. Most bio marker-cohort patients had informative results evaluating coexistent neurogenerative disease. <h3>Conclusions:</h3> Biomarkers may be useful in indicating a coexistent neurodegenerative disease earlier, and in life, in patients with multiple sclerosis and significant cognitive impairment. <b>Disclosure:</b> Dr. Londono has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Arumaithurai has nothing to disclose. Eleni Constantopoulos has nothing to disclose. Dr. Basso has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Ross Reichard has received research support from NIH. An immediate family member of Ross Reichard has received publishing royalties from a publication relating to health care. The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received research support from Viela Bio. Dr. Flanagan has received research support from UCB. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Keegan has received publishing royalties from a publication relating to health care.

BACE1 influences clinical manifestations and central inflammation in relapsing remitting multiple sclerosis.

Neurodegenerative and inflammatory processes influence the clinical course of multiple sclerosis (MS). The β-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been associated with cognitive dysfunction, amyloid deposition and neuroinflammation in Alzheimer's disease. We explored in a group of 50 patients with relapsing-remitting MS the association between the cerebrospinal fluid (CSF) levels of BACE1, clinical characteristics at the time of diagnosis and prospective disability after three-years follow-up. In addition, we assessed the correlations between the CSF levels of BACE 1, amyloid β (Aβ) 1-40 and 1-42, phosphorylated tau (pTau), lactate, and a set of inflammatory and anti-inflammatory molecules. BACE1 CSF levels were correlated positively with depression as measured with Beck Depression Inventory-Second Edition scale, and negatively with visuospatial memory performance evaluated by the Brief Visuospatial Memory Test-Revised. In addition, BACE CSF levels were positively correlated with Bayesian Risk Estimate for MS at onset, and with Expanded Disability Status Scale score assessed three years after diagnosis. Furthermore, a positive correlation was found between BACE1, amyloid β 42/40 ratio (Spearman's r=0.334, p=0.018, n=50), pTau (Spearman's r=0.304, p=0.032, n=50) and lactate concentrations (Spearman's r=0.361, p=0.01, n=50). Finally, an association emerged between BACE1 CSF levels and a group of pro and anti-inflammatory molecules, including interleukin (IL)-4, IL-17, IL-13, IL-9 and interferon-γ. BACE1 may have a role in different key mechanisms such as neurodegeneration, oxidative stress and inflammation, influencing mood, cognitive disorders and disability progression in MS.

A coffee enriched with guarana, selenium, and l-carnitine (GSC) has nutrigenomic effects on oxi-inflammatory markers of relapsing-remitting multiple sclerosis patients: A pilot study.

Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical course of multiple sclerosis (MS), characterized by a chronic inflammatory state and elevated levels of oxidative markers. Food supplements with potential anti-inflammatory, antioxidant and neuroprotective effects have been tested as possible adjuvants in the treatment of MS. In this sense, this pilot study was carried out with the aim of verifying whether a minimum daily dose of a guarana, selenium and l-carnitine (GSC) based multi supplement, mixed in cappuccino-type coffee, administered for 12 weeks to 28 patients with RRMS could differentially modulate oxidative blood markers (lipoperoxidation, protein carbonylation and DNA oxidation) and inflammatory blood markers (protein levels of cytokines IL-1β, IL-6, TNF-α, IFN-γ, IL-10, gene expression of these cytokines, and NLRP3 and CASP-1 molecules, and C-reactive protein levels). The results indicate that a low concentration of GSC is capable of decreasing the plasma levels of oxidized DNA and pro-inflammatory cytokines of RRMS patients. The results support further research into the action of GSC on clinical symptoms, not only in patients with MS, but also with other neurological conditions.