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Choroid plexus enlargement in secondary progressive MS: phenotype comparison.

BACKGROUND: The choroid plexus (CP) is increasingly recognised as a contributor to chronic inflammation in multiple sclerosis (MS). While CP enlargement is reported in early MS, its role in secondary progressive MS (SPMS) is poorly understood. We aimed to quantify CP volume in SPMS and compare it to relapsing-remitting MS (RRMS) and clinically isolated syndrome (CIS), and to assess associations with disease severity and progression. METHODS: CP volumes were manually segmented and normalised to intracranial volume in 121 MS patients (32 CIS, 49 RRMS, 39 SPMS). Age correction was applied using …

Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial.

BACKGROUND: Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource. METHODS: We did a phase 2b, multiarm, parallel group, double-blind, randomised placebo-controlled trial at 13 clinical neuroscience centres in the UK. We recruited patients (aged 25-65 years) with secondary progressi…

Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA.

OBJECTIVE: 1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML). METHODS: The prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JC…

Lesion-specific circular RNA and mRNA signatures in secondary progressive multiple sclerosis.

Circular RNAs (circRNAs) are single-stranded RNAs with a covalently closed loop structure which have been increasingly recognised as stable and functionally relevant regulators of gene expression via sponging miRNAs. Recently, studies have revealed their roles in human diseases, subsequently emerging as potential biomarkers. Multiple sclerosis (MS) is an inflammatory, neurodegenerative, and immune-related disease of the central nervous system characterised by distinct lesion types that reflect different stages of brain tissue injury and repair. Our study conducted a comprehensive transcriptomi…

Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Studies to Assess the Safety and Efficacy of Elezanumab when Added to Standard of Care in Relapsing and Progressive Forms of Multiple Sclerosis.

OBJECTIVE: Elezanumab is a monoclonal antibody that binds repulsive guidance molecule a (RGMa), an inhibitor of central nervous system regeneration after inflammation or injury. The aim was to assess the safety and efficacy of elezanumab in relapsing and progressive forms of multiple sclerosis (MS). METHODS: RADIUS-R and RADIUS-P were phase 2 trials in relapsing (RADIUS-R) or progressive (RADIUS-P) MS. Participants were randomized to intravenous elezanumab 400mg, 1800mg, or placebo every 4 weeks through week 48. The primary endpoint was the mean Overall Response Score (ORS). RESULTS: In RADI…

Effectiveness of rituximab in the treatment of multiple sclerosis: A multicenter, retrospective, observational study in morocco.

INTRODUCTION: The demonstration of the strong efficacy of selective B-cell-depleting therapies, such as anti-CD20 monoclonal antibodies in multiple sclerosis (MS), point out the key role of B cells in triggering MS disease activity. OBJECTIVE: To investigate the effectiveness and safety of rituximab (RTX) in MS. MATERIALS AND METHODS: We report a retrospective observational study to describe the effectiveness of off-label Rituximab (RTX) in the treatment of a population of 93 Moroccan MS patients including 66 (71 %) relapsing-remitting multiple sclerosis (RRMS) and 27 (29 %) progressive form…

Circulatory Indicators of Lipid Peroxidation, the Driver of Ferroptosis, Reflect Differences between Relapsing-Remitting and Progressive Multiple Sclerosis.

Ferroptosis, a lipid peroxidation- and iron-mediated type of regulated cell death, relates to both neuroinflammation, which is common in relapsing-remitting multiple sclerosis (RRMS), and neurodegeneration, which is prevalent in progressive (P)MS. Currently, findings related to the molecular markers proposed in this paper in patients are scarce. We analyzed circulatory molecular indicators of the main ferroptosis-related processes, comprising lipid peroxidation (malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and hexanoyl-lysine adduct (HEL)), glutathione-related antioxidant defense (total gl…

Alopecia Universalis в пациенте с множественным склерозом после перехода от Rituximab на Ocrelizumab: A Case Report.

Ocrelizumab является гуманизированным моноколональным антителом, который действует как анти-CD20. Он используется как для лечения релапсирующих многократных склерозов (RRMS), так и для лечения прогрессивных типов. Цель этого исследования состоит в том, чтобы сообщить о первом пациенте с алопесией Универсальности после перехода с ritoximab на ocrelizumab. 37-летняя женщина с историей СМПС, диагноз которой был 8 лет назад, лечилась ритюксимабом. Её лекарство было переключено на окрилизумаб 6 месяцев назад. Через день после получения второй дозы оррелизумаба она подарила ей щекотливые волосы. Пот

Совпадение в аннотации оригинала
Ocrelizumab is a humanized monoclonal antibody, which acts as an anti-CD20 antibody. It is used as a treatment of both relapsing-remitting multiple sclerosis (RRMS) and Progressive types. The aim of this study is to report the first patient with alopecia universalis after switching from rituximab to ocrelizumab. A 37-year-old woman with a history of SPMS, di…

The neutrophil-to-lymphocyte ratio as disease actvity marker in multiple sclerosis and optic neuritis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). The neutrophil-to-lymphocyte ratio (NLR) has been identified as a disease activity marker in several diseases. We aim to evaluate the significance of the NLR in the different subtypes of MS, optic neuritis (ON) and in relation to disease activity and Expanded Disability Status Scale (EDSS). METHODS: We included 378 patients and 813 healthy controls (HC) from The Nordic Reference Interval Project 2000 (NORIP). Complete blood count, demographic and clinical data from patients were evaluate…

Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis.

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-at…

Dynamic alterations of dural and bone marrow B cells in an animal model of progressive multiple sclerosis.

In multiple sclerosis (MS), the leptomeninges (LM) are populated with immune cell aggregates that correlate with disease progression. The impact of LM inflammation on the adjacent dura is largely unknown. Using a mouse model of MS that induces brain LM inflammation and age-dependent disease progression, we found that encephalitogenic T cells and B220high B cells accumulate substantially in the brain LM and parenchyma of both young and aged mice, while the adjacent dura remains relatively inert. We also observed a population of anti-CD20-resistant B220low B cells in the dura and bone marrow tha…

Optic neuritis: a review.

Acute demyelinating optic neuritis (ON) is the initial presentation in approximately 20% of cases of multiple sclerosis (MS) and is characterized by unilateral, subacute, painful visual loss without systemic or neurological symptoms. The Optic Neuritis Treatment Trial (ONTT) has provided valuable insights into both the natural history and clinical course of demyelinating ON with respect to treatment. Visual function improves spontaneously over weeks and within 12 months 93% have recovered to a visual acuity of at least 20/40. Treatment with high-dose corticosteroids may accelerate visual recov…

Twelve-week intermittent hypoxia intervention in multiple sclerosis - A safety and feasibility trial.

Intermittent hypoxia intervention may provide an alternative therapeutic approach to enhance neuroprotection in people with multiple sclerosis (pwMS). However, clinical data on its safety and feasibility in pwMS are lacking. In this prospective single-arm safety and feasibility trial, individuals with primarily progressive MS (18-60 years; Expanded Disability Status Scale ≤6.5) were recruited from the MS outpatient clinic of the University Medical Center Hamburg-Eppendorf and underwent a 12-week repetitive continuous hypoxia (RCH). Participants completed two to three standardized 2-hour sessio…

Discontinuation of disease-modifying therapy in MS patients over 60 years old and its impact on relapse rate and disease progression.

BACKGROUND / AIMS: The benefit of disease-modifying therapy (DMT) is unclear for older patients with multiple sclerosis (MS), namely those who have not experienced clinical disease activity for a prolonged time. We aimed to compare baseline differences and clinical outcomes between DMT discontinuers and continuers in a cohort of MS patients older than 60 years. METHODS: Retrospective, observational study identifying MS patients aged over 60 years, stable on DMT> 24 months. Additional inclusion criteria were a previous diagnosis of relapsing MS and a minimum follow-up period of 24 months. Diff…

Neuroanatomic Correlates of Female Sexual Dysfunction in Multiple Sclerosis.

OBJECTIVE: This study intended to determine associations between alterations of female sexual arousal as well as vaginal lubrication and the site of cerebral multiple sclerosis (MS) lesions. METHODS: In 44 women with MS (mean age: 36.5 ± 9.9 years), we assessed their medical history and evaluated sexual function using the Female Sexual Function Index scores for arousal and vaginal lubrication. We determined potential confounding factors of sexual dysfunction: age; disease duration; physical disability; depression; bladder or urinary dysfunction; and total volume of cerebral lesions. Arousal a…

Immunonephelometric quantitation of central nervous system IgG daily synthesis in multiple sclerosis. Clinical evaluation using predictive value theory.

With a laser nephelometric immunoassay and an empirical formula for the quantitation of central nervous system (CNS) daily IgG synthesis, we studied prospectively a population of 101 individuals divided into four groups: 31 normals, 25 patients with definite multiple sclerosis (DMS), 18 patients with probable or possible multiple sclerosis (PMS), and 27 patients with neurologic disease other than multiple sclerosis (NMS). By the Kruskal-Wallis, test the results of the DMS and PMS patients were significantly different from the normals and NMS patients (P less than 0.0003). Considering normals, …

The proteasome is a major autoantigen in multiple sclerosis.

Multiple sclerosis seems to be an autoimmune disease of unknown aetiology affecting the white matter of the CNS. It is generally accepted that the autoimmune response is directed against specific components of myelin. We show here that proteasome, a ubiquitous protease complex composed of 14 different subunits, is a target for autoantibodies (IgG and IgM classes) present in the serum (66%, 73 out of 110) and in the CSF (61%, 16 out of 26) of patients with multiple sclerosis. Using recombinant proteasomal subunits we demonstrate the presence of specific autoantibodies against subunits C2, C8, C…

Cortical grey matter sodium accumulation is associated with disability and secondary progressive disease course in relapse-onset multiple sclerosis.

OBJECTIVE: Sodium (23Na)-MRI is an emerging imaging technique to investigate in vivo changes in tissue viability, reflecting neuroaxonal integrity and metabolism. Using an optimised 23Na-MRI protocol with smaller voxel sizes and improved tissue contrast, we wanted to investigate whether brain total sodium concentration (TSC) is a biomarker for long-term disease outcomes in a cohort of patients with relapse-onset multiple sclerosis (MS), followed from disease onset. METHODS: We performed a cross-sectional study in 96 patients followed up ~ 15 years after a clinically isolated syndrome (CIS) an…

MicroRNAs in blood and cerebrospinal fluid as diagnostic biomarkers of multiple sclerosis and to monitor disease progression.

Multiple sclerosis is a chronic autoimmune disease of the central nervous system. It is the main cause of non-traumatic neurological disability in young adults. Multiple sclerosis mostly affects people aged 20-50 years; however, it can occur in young children and much older adults. Factors identified in the distribution of MS include age, gender, genetics, environment, and ethnic background. Multiple sclerosis is usually associated with progressive degrees of disability. The disease involves demyelination of axons of the central nervous system and causes brain and spinal cord neuronal loss and…