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A glial oxidative signature predicts disability in primary progressive multiple sclerosis and is associated with long-term cognitive decline.

BACKGROUND: Progressive multiple sclerosis (MS) involves heterogeneous mechanisms, and primary progressive MS without inflammatory activity (PPMS-NA) is poorly understood. OBJECTIVE: To characterize the immune-oxidative profile of PPMS-NA and assess plasma IL-6, IL-8, IFNα2, and cerebrospinal fluid (CSF) reactive oxygen species (ROS) as predictors of disability and cognitive decline. METHODS: We conducted a multicenter longitudinal study with two cohorts. Cohort 1 included participants across MS phenotypes (n = 146 baseline; n = 36 follow-up) and other neurological disorders, measuring plasm…

Критическое демиелионирование повреждений в прогрессивном множественном склерозе: перспективное исследование наблюдений.

Критические повреждения от демиелина представляют собой отдельные повреждения, анатомически связанные с прогрессивным повреждением двигателя, первоначально описываемые в высоко отобранных группах с демиелинизирующим заболеванием. Мы стремимся определить, как часто отдельные критические повреждения от демиелина были обнаружены в неотобранной последовательной группе людей с прогрессивным множественным склерозом (MS) в третичной клинике MS в течение одного года. МЕТОДЫ: Перспективное последовательное когортное исследование вновь обследованных и установившихся лиц с прогрессивным MS в клинике Майо

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVE: Critical demyelinating lesions are individual lesions anatomically associated with progressive motor impairment in … cal demyelinating lesions were found in an unselected consecutive cohort of people with progressive multiple sclerosis (MS) at a tertiary MS clinic over a one-year duration. METHODS: Prospective consecutively enrolled observational cohort study of newly evaluated and established people with progressive MS at Mayo Clinic from July 1, 2021 to June 30, 2022. Demograph …

Multiple Sclerosis Presenting with Facial Twitching (Myokymia and Hemifacial Spasms).

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The etiology is insufficiently understood. Autoimmune, genetic, viral, and environmental factors have been hypothesized. MS is twice as common in women as in men between the ages of 20 and 50 years. There is no known cure for MS. Current medical treatment helps to prevent new attacks and improve function after an attack. MS is diagnosed by physical examination, diagnostic imaging, and examination of cerebral spinal fluid. The most common physical signs and symptoms of MS include constitutiona…

WITHDRAWN: Interventions for fatigue and weight loss in adults with advanced progressive illness.

BACKGROUND: Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. … s and 748 participants); the interventions were progressive resistive exercise and aerobic exercise.Multiple sclerosis (MS) - we identified five systematic reviews (23 studies and 1502 participants); the pharmacological interventions were amantadine and carnitine. The non pharmacological interventions were diet, exercise and occupational therapy.Mixed conditions in …

Interventions for fatigue and weight loss in adults with advanced progressive illness.

BACKGROUND: Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. … s and 748 participants); the interventions were progressive resistive exercise and aerobic exercise.Multiple sclerosis (MS) - we identified five systematic reviews (23 studies and 1502 participants); the pharmacological interventions were amantadine and carnitine. The non pharmacological interventions were diet, exercise and occupational therapy.Mixed conditions in …

Case Report: CD20/BCMA bispecific CAR-T therapy for progressive multiple sclerosis.

Refractory secondary progressive multiple sclerosis (SPMS) remains an area of unmet need, particularly once disability continues to accumulate despite multiple disease-modifying therapies. Two SPMS patients are reported with C-CAR168 treatment, a bispecific CD20/BCMA CAR-T product, achieving 12- and 6-month drug-free remission. Patient 001 (EDSS 4.0→3.0) showed improvement of oculomotor dysfunction, ataxia, and cognitive impairment. Patient 002 (EDSS 6.5→6.0) demonstrated halted lower-limb progression and relieved bowel/bladder dysfunction. C-CAR168 infiltrated into the cerebrospinal fluid (CS…

Оказывается помощь АИ в выявлении моделей инвалидности в рамках идентичных классов ЕДСС.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: В ходе испытаний на множественные склерозы (МС) наиболее часто используется шкала, расширяемая по статусу неевростатусной инвалидности (EDSS). Тем не менее, оценки EDS ⩾4.5 , основываются главным образом на амбулировании и могут не отражать соответствующие модели инвалидности в других функциональных областях. ЦЕЛЬ: Цель заключалась в том, чтобы определить, каким образом оценки, отнесенные к одной и той же категории, могут отражать различные формы инвалидности. Методы: Мы проанализировали 13,103 ОЦЕНКИ 1636 Люди со вторичным прогрессивным MS, с суда EXPAND. Комплект данны

Совпадение в аннотации оригинала
BACKGROUND: The Neurostatus-Expanded Disability Status Scale (EDSS) is the most frequently used measure of disability in multiple sclerosis (MS) trials. However, EDSS scores ⩾4.5 are mainly based on ambulation and may fail to capture relevant disability patterns in other functional domains. OBJECTIVE: The objective was to determine how assessments categoriz…

A novel tool for characterising upper limb function in progressive multiple sclerosis through kinematic assessment.

INTRODUCTION: Current upper limb assessment methods in MS rely on measuring duration in tasks like the nine-hole peg test (9HPT). Kinematic techniques may provide a more useful measure of functional change in clinical and research practice. The aim of this study was to assess upper limb function prospectively in people with progressive MS using a kinematic 3D motion capture system and compare with current measures. METHODS: 42 people with progressive MS (PwPMS) and 15 healthy controls reached-and-grasped different objects whilst recorded by a kinematic assessment system. 9HPT, Expanded Disabi

Episodic gaze deviation in multiple sclerosis - Versive seizures or oculogyric crises?

Ictal gaze deviation and oculogyric crisis (OGC) can show identical clinical manifestations. We report a case of repeated drug induced OGCs in a 38 year old patient with secondary progressive multiple sclerosis. He was referred to our center for treatment of "intractable" epilepsy manifesting as episodic eye and head deviations with apparent unresponsiveness. In the epilepsy monitoring unit, ten typical spells were captured without epileptiform electroencephalographic correlates, but we discovered chronic exposure to metoclopramide. A diagnosis of OGC was suspected and Metoclopramide was stopp…

Нейродегенеративные биомаркеры при множественном склерозе: на стыке между исследованиями и клинической практикой.

Множественный склероз (MS) — хроническое аутоиммунное расстройство, характеризующееся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе (CNS). Хотя подстрекательские компоненты MS были тщательно изучены, прогрессивный нейродегенеративный аспект по-прежнему является одним из важнейших факторов, способствующих долгосрочной инвалидности. Поэтому выявление и проверка биомаркеров, связанных с нейродегенеративными процессами, имеют важнейшее значение для улучшения диагностики, прогнозирования и мониторинга лечения. В рамках этого обзора изучаются цереброспинные жидкости (

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration within the central nervous system (CNS). While the inflammatory components of MS have been extensively studied, the progressive neurodegenerative aspect remains a critical factor contributing to long-term disability. Therefore, the ide…

Increased PET 11C-PBR28 binding in multiple sclerosis normal-appearing white matter correlates with MRI measures of myelin loss.

INTRODUCTION: The Positron Emission Tomography (PET) tracer 11C-PBR28 binds to the Translocator Protein (TSPO), a marker of activated microglia. Advanced Magnetic Resonance (MR) techniques are sensitive to different tissue properties such as myelin (myelin water fraction, MWF; magnetisation transfer ratio, MTR; radial diffusivity, RD; choline, tCho), axons (axial diffusivity, AD; n-acetylaspartate, tNAA) and gliosis (myo-inositol, mI). OBJECTIVE: To compare 11C-PBR28 binding across MS subtypes and investigate the correlation between 11C-PBR28 binding and advanced MR measures in normal-appeari

Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Spectroscopic examination of multiple sclerosis (MS) patients has revealed abnormally low N-acetyl-aspartate (NAA) signal intensity, even in brain tissue that appears normal on high-resolution structural MR images but has yielded inconclusive evidence to distinguish the well-documented clinical differences between MS subtypes. This study used proton MR spectroscopic imaging (MRSI) and high-resolution MR imaging to characterize metabolite profiles in normal-appearing brain tissue of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive (SP) MS. METHODS…

A type 2 biomarker separates relapsing-remitting from secondary progressive multiple sclerosis.

OBJECTIVE: We tested whether it is possible to differentiate relapsing-remitting (RR) from secondary progressive (SP) disease stages in patients with multiple sclerosis (MS) using a combination of nuclear magnetic resonance (NMR) metabolomics and partial least squares discriminant analysis (PLS-DA) of biofluids, which makes no assumptions on the underlying mechanisms of disease. METHODS: Serum samples were obtained from patients with primary progressive MS (PPMS), SPMS, and RRMS; patients with other neurodegenerative conditions; and age-matched controls. Samples were analyzed by NMR and PLS-D…

Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone.

Low-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met5]-enkephalin) facilitating interaction…

Safety and acceptability of clozapine and risperidone in progressive multiple sclerosis: a phase I, randomised, blinded, placebo-controlled trial.

OBJECTIVE: Because clozapine and risperidone have been shown to reduce neuroinflammation in humans and mice, the Clozapine and Risperidone in Progressive Multiple Sclerosis (CRISP) trial was conducted to determine whether clozapine and risperidone are suitable for progressive multiple sclerosis (pMS). METHODS: The CRISP trial (ACTRN12616000178448) was a blinded, randomised, placebo-controlled trial with three parallel arms (n=12/arm). Participants with pMS were randomised to clozapine (100-150 mg/day), risperidone (2.0-3.5 mg/day) or placebo for 6 months. The primary outcome measures were saf…

Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo.

Multiple sclerosis involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system. Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells are stem cells in the central nervous system and the principal source of myelinating oligodendrocytes. These cells are abundant in demyelinated regions of patients with multiple sclerosis, yet fail to differentiate, thereby representing a cell…

Exploring Progressive Multiple Sclerosis and the Therapeutic Potential of BTK Inhibitors Based on EBV-driven B Cell-microglia Interactions.

Progressive Multiple Sclerosis (PMS) remains a major cause of irreversible disability in Multiple Sclerosis (MS), yet current disease-modifying therapies incompletely address the compartmentalized Central Nervous System (CNS) inflammation, sustained microglial activation, chronic demyelination, and axonal degeneration that characterize progression. This topic is timely because the evidence linking Epstein-Barr Virus (EBV) to MS susceptibility, the recognition of B cell-myeloid interactions within the CNS, and the clinical development of CNS-penetrant Bruton's Tyrosine Kinase inhibitors (BTKi) …

Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis.

Serum vitamin B12 levels and unsaturated vitamin B12 binding capacities were measured in 24 patients with multiple sclerosis (MS), 73 patients with other neurological disorders and 21 healthy subjects. There was no decrease in the vitamin B12 levels, however, a significant decrease in the unsaturated vitamin B12 binding capacities was observed in patients with MS when compared with other groups. A massive dose of methyl vitamin B12 (60 mg every day for 6 months) was administered to 6 patients with chronic progressive MS, a disease which usually had a morbid prognosis and widespread demyelinati…

[Cladribine in the treatment of relapsing multiple sclerosis].

Multiple sclerosis is a chronic neurological disease of the central nervous system where inflammation and neurodegeneration converge, inducing a disorder with both a progressive course and a high degree of disability. Multiple sclerosis usually begins between the ages of 20 and 40 and affects two to three times as many women as men. The main objective of pharmacological management is to reduce the inflammation and to delay the disability onset. Many of the currently available drugs have shown different degrees of efficacy associated to a specific adverse events profile. In routine clinical pra…

The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system manifested morphologically by inflammation, demyelination, axonal loss and gliosis. The inflammatory lesions are characterized by massive infiltration by a heterogeneous population of cellular and soluble mediators of the immune system, including T cells, B cells, macrophages and mi croglia, as well as a broad range of cytokines, chemokines, antibodies, complement and other toxic substances. The appearance of such lesions is associated with clinical relapses. Recent detailed immunopathological stud…