Результаты поиска

Opposite Interplay between PPAR Gamma and Canonical Wnt/Beta-Catenin Pathway in Amyotrophic Lateral Sclerosis.

The opposite interplay between peroxisome proliferator-activated receptor gamma (PPAR gamma) and Wnt/beta-catenin signaling has led to the categorization of neurodegenerative diseases (NDs) as either NDs in which PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated [amyotrophic lateral sclerosis (ALS), Parkinson's disease, Huntington's disease, multiple sclerosis, Friedreich's ataxia] or NDs in which PPAR gamma is upregulated while the canonical Wnt/beta-catenin signaling is downregulated (bipolar disorder, schizophrenia, Alzheimer's disease). ALS, a common a…

Chronic stress amplifies multidimensional disease activity in multiple sclerosis patients: A year-long within-person analysis.

BACKGROUND: Chronic psychological stress is suspected to intensify disease activity in multiple sclerosis (MS), yet longitudinal real-world evidence remains limited. This study aims to determine whether the first year of the war in Israel during 2023-2024, a period of sustained nationwide stress, was associated with increased composite evidence of disease activity (EDA-3) in people with MS (pwMS). METHODS: We conducted a retrospective case-control study of 930 pwMS followed at Hadassah Medical Center who had ≥1 annual visit across three consecutive years. Within-person comparisons were made b…

Downregulation of dual-specificity phosphatase 1 (DUSP1) in post-mortem brain white matter in progressive multiple sclerosis.

OBJECTIVE: Dual-specificity phosphatase 1 (DUSP1) is a negative regulator of mitogen-activated protein kinase (MAPK) activity, and a player in the control of glial function. Several disease models have identified that the expression of DUSP1 is altered in tissue samples, which may contribute to disease pathogenesis. Using post-mortem brain tissue from a cohort of progressive multiple sclerosis (MS) cases, this study set out to determine if the expression of DUSP1 is altered in the brain in MS. METHODS: We employed the use of a combination of PCR, western immunoblotting and immunohistochemical …

The relationship between cortical lesions and periventricular NAWM abnormalities suggests a shared mechanism of injury in primary-progressive MS.

In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging. To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional…

Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells.

The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressi…

Intermittent theta burst stimulation improves spasticity, pain and cognitive functions in progressive multiple sclerosis: a pilot study.

INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system marked by inflammation and demyelination. Neurofilament light chain (NfL) serves as a biomarker for neurodegeneration. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) may alleviate MS-related symptoms. OBJECTIVE: To assess the effects of intermittent theta burst stimulation (i-TBS), a TMS protocol, on spasticity, disability, quality of life, fatigue, cognition, and serum NfL levels in patients with progressive MS. METHODS: Thirty-six patients with primar…

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

OBJECTIVE: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response - measured by change in magnetisat…

Боязнь прогрессирования заболеваний и рецидива при множественном склерозе: систематический обзор аналитического исследования.

Множественный склероз (MS) является хроническим заболеванием центральной нервной системы, которое чаще всего затрагивает людей в раннем возрасте. Неопределенность в отношении будущих рецидивов и накопления инвалидности может привести к значительным психологическим расстройствам, что будет способствовать снижению качества жизни. ЦЕЛЬ: Цель этого систематического аналитического обзора заключалась в обобщении текущих данных о распространенности, детерминантах и последствиях боязни рецидива и развития болезней у людей, живущих с НР. МЕТОД: Нынешний систематический обзор аналитического исследования

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous system, most commonly affecting individuals in early adulthood. Uncertainty about future relapses and accumulating disability may lead to significant psychological distress, contributing to reduced quality of life. OBJECTIVE: This systematic scoping review aimed to synthesize cu…

Responder rates to fampridine differ between clinical subgroups of MS patients and patient reported outcome influences treatment decision making.

BACKGROUND: Fampridine is an effective treatment to improve ambulation for some multiple sclerosis (MS) patients. Remarkable discrepancies exist between responder rates in clinical trials and the proportion of patients continuing treatment in clinical practice. This may be related to clinical phenotypes of MS patients, and the influence of patient reported outcome (PRO) on treatment decision making. OBJECTIVE: To analyse responder rates to fampridine on ambulation and upper extremity function (UEF) and the influence on treatment decision making in different clinical subgroups in a real-world …

Proteomic pattern analysis discriminates among multiple sclerosis-related disorders.

OBJECTIVE: To use a new, unbiased biomarker discovery strategy to obtain and assess proteomic data from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS)-related disorders. METHODS: CSF protein profiles were analyzed from 107 patients with either MS-related disorders (including relapsing remitting MS [RRMS], primary progressive MS [PPMS], anti-aquaporin4 antibody seropositive-neuromyelitis optica spectrum disorder [SP-NMOSD], and seronegative-NMOSD with long cord lesions on spinal magnetic resonance imaging [SN-NMOSD]), amyotrophic lateral sclerosis (ALS), or other inflammato…

Роль NLRP3 инфламасома в множестве склероза: патогенез и фармакологическое применение.

Множественный склероз (MS) широко признается в качестве хронического провокационного аутоиммунного расстройства, характеризующегося демиэлизацией центральной нервной системы (КНС) и нейродегенерацией. Гиперактивация иммунной и подстрекательской реакции признается в качестве ключевого фактора, способствующего патогенезу и прогрессированию MS. Среди различных иммунных и подстрекательских реакций исследователи все больше концентрируют внимание на воспалении — комплексе белков. Запуск и активация воспламенения неразрывно связаны с началом НР. В частности, NLRP3 воспаляет, наиболее широко изучавший

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is widely acknowledged as a chronic inflammatory autoimmune disorder characterized by central nervous system (CNS) demyelination and neurodegeneration. The hyperactivation of immune and inflammatory responses is recognized as a pivotal factor contributing to the pathogenesis and progression of MS. Among various immune and inflammatory…

Хроническая инфекция транспланта-призрака миелит успешно лечится ритуксимабом.

Хроническая трансплантация стволовых клеток после пересадки аллогенетических стволовых клеток (All-HSCT) представляет собой серьезное осложнение (CGHD) и часто имитирует аутоиммунные заболевания. Симптомы центральной нервной системы (ЦНС) являются редкими проявлениями КГГР и трудно диагностировать. В рамках проекта " Консенсус национальных институтов здравоохранения в области СЖГХД " , разработанного в 2020 году, были обсуждены проявления СНС в виде " нетипичных проявлений СЖГХД " с участием различных органов, помимо классических органов СЖГХ. У нас был случай миелита после

Совпадение в аннотации оригинала
Chronic graft-versus-host disease (cGVHD) is a major serious complication after allogeneic stem-cell transplantation (allo-HSCT), and often … remities. The clinical course and magnetic resonance imaging findings showed some similarities with multiple sclerosis. We decided to use rituximab after the patient became refractory to corticosteroids because rituximab has been reported to be effective in multiple sclerosis by suppressing B cells on both sides of the blood-brain barrier. Rituximab was effective fo …

The role of Epstein-Barr virus in the etiology of multiple sclerosis: a current review.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. While its exact etiology is unknown, it is generally believed that MS is caused by environmental triggers in genetically predisposed individuals. Strong and consistent evidence suggests a key role of Epstein-Barr virus (EBV), a B lymphotropic human gammaherpesvirus, in the etiology of MS. Areas covered: This review summarizes recent developments in the field of EBV and MS with a focus on potential mechanisms underlying the role of EBV in MS. PubMed was searched for the terms 'Ep…

Optic neuritis in chronic relapsing experimental allergic encephalomyelitis in Biozzi ABH mice: demyelination and fast axonal transport changes in disease.

The encephalitogenicity of optic nerve tissue was demonstrated in Biozzi ABH (H-2(dq1)) mice. Acute experimental allergic encephalomyelitis … th physiological deficit in the optic nerve highlights the usefulness of this model in the study of multiple sclerosis in which acute monosymptomatic unilateral optic neuritis is a common manifestation. Furthermore, the novel induction of CREAE with optic nerve homogenate suggests that optic neuritis is a common significant role in the pathophysiology and progressio …

Intrathecal Mesenchymal Stem Cells in Progressive Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial (SMART-MS).

BACKGROUND AND OBJECTIVES: There is an unmet need for neuroregenerative therapies in multiple sclerosis (MS). Mesenchymal stem cells (MSCs) have shown immunomodulatory and regenerative effects in preclinical models and early clinical studies. Intrathecal administration may enhance therapeutic potential by direct delivery to the CNS. However, randomized, placebo-controlled trials are needed to establish safety and efficacy. The objective of this trial was to assess whether a single intrathecal administration of autologous MSCs could provide evidence of a neuroregenerative effect in progressive …

Quantification of central motor conduction deficits in multiple sclerosis patients before and after treatment of acute exacerbation by methylprednisolone.

OBJECTIVE: To compare the effects of intravenous methylprednisolone (IVMP) in patients with relapsing-remitting (RR-MS), secondary progressive (SP-MS), and primary progressive multiple sclerosis (PP-MS). METHODS: Clinical and neurophysiological follow up was undertaken in 24 RR-MS, eight SP-MS, and nine PP-MS patients receiving Solu-Medrol 500 mg/d over five days for exacerbations involving the motor system. Motor evoked potentials (MEPs) were used to measure central motor conduction time (CMCT) and the triple stimulation technique (TST) was applied to assess conduction deficits. The TST allo…

Sleep Disorders in Neurodegenerative Diseases: Pathological Correlations and Underlying Mechanisms.

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), and others, represent an escalating public health burden in aging populations. NDDs are characterized by progressive neuronal loss and misfolded protein aggregation. Despite distinct clinical heterogeneity, these diseases universally present with debilitating non-motor symptoms, among which sleep-wake disorders are highly prevalent. Once considered secondary to neuronal damage, growing evidence now highlights a bidirectional interp

Glutathione and neurodegenerative diseases: immunopharmacological implications.

Neurodegenerative diseases are characterized by progressive neuronal dysfunction, often accompanied by chronic inflammatory states and redox … vity in neurodegenerative diseases, such as Parkinson's Disease (PD), Alzheimer's Disease (AD), and multiple sclerosis (MS). By exploring how redox signaling via GSH influences inflammatory immune phenotypes across different disease states, we will isolate possible therapeutic interventions for treatment of these conditions. By characterizing GSH's function and desi …

Astrocyte Functional Heterogeneity in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by demyelination and axonal degeneration. Astrocytes have emerged as pivotal regulators of MS pathology, playing both pathogenic and regulatory roles. This review explores the mechanisms underlying astrocyte heterogeneity in MS, with a focus on how astrocyte functional states are influenced by extrinsic environmental factors such as inflammatory signals and dynamic interactions with immune cells and other glial populations. We discuss how the astrocyte heterogeneity established during development and further modulated…

A Novel COL7A1 Mutation in a Patient With Dystrophic Epidermolysis Bullosa. Successful Treatment With Upadacitinib.

This report describes a unique case of thoracic vertebral canal stenosis and vertebral instability in a 1 yr old Minuet cat. The cat presented with a history of chronic progressive nonambulatory paraparesis. Myelography with neutral and stress positions revealed dynamic compression at T1-4. Computed tomography and MRI revealed multiple sites of vertebral endplate osteolysis, adjacent bone sclerosis, intervertebral disk space narrowing, and spondylotic bridging within the cervical and cranial thoracic vertebral bodies and pedicles, particularly at C6-T4. The cat underwent a right-sided T1-4 hem