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Insights into the role of B cells in the cortical pathology of Multiple sclerosis: evidence from animal models and patients.

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS) that affects both white and gray matter. Although it has been traditionally considered as a T cell mediated disease, the role of B cell in MS pathology has become a topic of great research interest. Cortical lesions, key feature of the progressive forms of MS, are involved in cognitive impairment and worsening of the patients' outcome. These lesions present pathognomonic hallmarks, such as: absence of blood-brain barrier (BBB) disruption, limited inflammatory events, reactive microglia, neurodegen…

Myelopathy associated with mixed connective tissue disease: clinical manifestation, diagnosis, treatment, and prognosis.

Mixed connective tissue disease (MCTD) is a chronic autoimmune disease, which has a broad range of clinical manifestations shared by systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis. MCTD is featured with high serum titers of anti-ribonucleoprotein antibodies and multiple system involvement. Its spinal cord involvement mainly manifests as transverse myelopathy (TM) and longitudinal extensive transverse myelopathy (LETM). Myelopathy in MCTD is extremely rare, and is usually characterized by serious neurological complications, such as paral

Cervical spondylotic myelopathy mimicking transverse myelitis.

OBJECTIVE: To describe two cases of cervical spondylotic myelopathy initially misdiagnosed as transverse myelitis. METHODS: Case series. RESULTS: A 44- and 56-year-old man presented with chronic progressive myelopathy. Initial work up revealed cervical spondylosis and an enhancing intramedullary cervical cord lesion. The younger individual was diagnosed with multiple sclerosis, and the other as an unspecified autoimmune demyelinating disorder. They were both treated with immune therapies, but had progression in their symptoms and functional decline, prompting re-evaluation. Due to persistent…

Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review.

The process of finding new therapeutic indications for currently used drugs, defined as 'repurposing', is receiving growing attention. Chlor … mation with pontine perivascular enhancement responsive to corticosteroids, and primary progressive multiple sclerosis. Several ongoing clinical trials have been testing these drugs in non-neoplastic and neoplastic diseases. Moreover, the well-demonstrated good tolerability of chloroquine and hydroxychloroquine make them safe even during pregnancy. Gastrointestinal …

Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases.

UNLABELLED: The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing … ernative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors. LINKED ARTICLES: This article is part of a themed section on Inventing New Therapies Without Reinvent …

External Cervical Resorption: A New Oral Manifestation of Systemic Sclerosis.

Systemic sclerosis (SSc) is a complex, chronic, and progressive autoimmune disease. SSc causes bone resorption of mandible and distal phalanges of fingers through a known mechanism, and it has also been pointed out as a possible cause of apical root resorption of teeth, because tooth resorption is regulated by similar mechanisms to those controlling bone resorption. The objective of this article was to report the first case in the literature of external cervical resorption (ECR) as an oral manifestation of SSc. A 66-year-old female patient with a 35-year history of SSc was diagnosed with multi

Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia.

INTRODUCTION: Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. METHODS: Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matche…

Optic nerve and its arterial-venous vascularization: an ultrasonologic study in multiple sclerosis patients and healthy controls.

BACKGROUND: Recent studies suggest that alterations in the cerebrospinal venous system may play a role in multiple sclerosis (MS) and that chronic cerebrospinal venous insufficiency correlates with clinical features of MS patients. OBJECTIVES: To evaluate the vascularization of optic nerve (ONr) and measure ONe thickness by color Doppler ultrasonography in MS patients with and without previous optic neuritis (ONe). SUBJECTS AND METHODS: We assessed flow variables in the ophthalmic artery, central retinal artery, and central retinal vein and measured the diameter of ONe in 46 relapsing-remitt…

Resolution of dysarthria in multiple sclerosis by treatment with weak electromagnetic fields.

It has been reported that 50% or more of patients diagnosed with multiple sclerosis (MS) exhibit speech impairment (dysarthria) which in some cases can be exceedingly disabling. Currently there is no effective medical treatment for the dysarthria of MS which occurs as a result of lesions to the cerebellum and its outflow tracts. It was reported recently that extracranial application of brief AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity produced in patients with MS sustained improvement in motor functions including cerebellar symptomatology. This communication c…

Chronic progressive myelopathy: investigation with CSF electrophoresis, evoked potentials, and CT scan.

Chronic progressive myelopathy (CPM) is a difficult clinical problem. Many patients who present with CPM turn out to have a spinal form of multiple sclerosis (MS), but until there is clear lesion dissemination, a definite clinical diagnosis cannot be made. We have looked for MS-related abnormalities in 72 patients with CPM. The mean age of onset was 42 years, mean duration was ten years, and mean Kurtzke disability rating was 4.5. Studies performed were cerebrospinal fluid electrophoresis for oligoclonal banding, pattern-reversal visual evoked responses, blink reflex latencies, and computerize…

Effect of β-hydroxybutyrate on behavioral alterations, molecular and morphological changes in CNS of multiple sclerosis mouse model.

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of central nervous system (CNS). Aging is the most significant risk factor for the progression of MS. Dietary modulation (such as ketogenic diet) and caloric restriction, can increase ketone bodies, especially β-hydroxybutyrate (BHB). Increased BHB has been reported to prevent or improve age-related disease. The present studies were performed to understand the therapeutic effect and potential mechanisms of exogenous BHB in cuprizone (CPZ)-induced demyelinating model. In this study, a continuous 35 days CPZ mouse model w…

Specialized pro-resolving mediators and autoimmunity: Recent insights and future perspectives.

Inflammation is a response to injuries involving multiple cellular and molecular mechanisms. Different stimuli, such as trauma or microbial invasion, trigger an acute inflammatory response consisting, at least in principle, of two phases: initiation and resolution. Although the acute phase of inflammatory response represents a protective and usually self-limited mechanism, it can sometimes persist and evolve into chronic inflammation, a key driver in the development of many rheumatic and autoimmune diseases. The biosynthesis of specialized pro-resolving mediators (SPMs) orchestrates the resolu

Experimentally induced puromycine aminonucleoside nephrosis (PAN) in rats: evaluation of angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF) expression in glomeruli.

BACKGROUND: In experimentally induced puromycine aminonucleoside nephrosis (PAN) animal models, nephrotic syndrome with minimal change disease and focal and segmental sclerosis-like nephritis similar to that in human is demonstrated; however, the real mechanism of PAN is not yet elucidated. Platelet derived endothelial cell growth factor (PD-ECGF), an endothelial mitogen protein, is believed to take part in microvessel formation and in stimulation of angiogenesis and its expression has not been totally demonstrated in PAN rats yet. In this study, we aimed to examine PD-ECGF expression in acute

Hair Cortisol as a Biomarker of Chronic Stress in Community-Dwelling Adults With Longstanding Multiple Sclerosis.

BACKGROUND: Chronic stress may play a significant role in disease progression in individuals with multiple sclerosis (MS), but traditional methods of measuring stress through salivary and blood cortisol have limitations. Hair cortisol has emerged as a promising objective measure for chronic stress assessment, but its application in those with MS remains understudied. OBJECTIVE: To explore the feasibility of hair sample collection for cortisol analysis among community-dwelling individuals with longstanding MS (disease duration ≥20 years), including factors associated with participation and rel…

The hypoxia-inflammation cycle as a key mechanism of smoldering inflammation and progression in multiple sclerosis.

Disease progression in multiple sclerosis (MS) remains a major unmet clinical challenge, as it is driven by pathogenic mechanisms that are poorly targeted by currently available disease-modifying treatments. Whereas acute focal inflammation characterizes the relapsing-remitting phase, converging neuropathological, imaging and experimental evidence identifies a chronic low-grade compartmentalized inflammatory process, the so-called "smoldering" inflammation, as a central driver of disease progression in MS. Recent findings suggest that both tissue hypoxia (primarily resulting from vascular dysf…

Обнаружить важную роль гута микробиота и диета в многоразовом склерозе.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся нейродегенерацией, повреждением аксона, обезвоживанием и воспалением. В последнее время кишечный дисбиоз связан с MS и другими аутоиммунными условиями. А именно, кишечная микробиота играет жизненно важную роль в регулировании иммунной функции, оказывая влияние на развитие иммунных клеток, производство цитокина и целостность кишечника. В то время как сбалансированная микробиота способствует иммунной терпимости, дисбиоз нарушает иммунное регулирование, наносит ущерб проницаемо

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by neurodegeneration, axonal damage, demyelination, and inflammation. Recently, gut dysbiosis has been linked to MS and other autoimmune conditions. Namely, gut microbiota has a vital role in regulating immune function by influencing immune cell devel…

Prevention of a chronic progressive form of experimental autoimmune encephalomyelitis by an antibody against mucosal addressin cell adhesion molecule-1, given early in the course of disease progression.

A role for alpha4 and beta7 integrins in mediating leucocyte entry into the central nervous system in the multiple sclerosis (MS)-like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated. However, the individual contributions of their respective ligands mucosal addressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-cadherin expressed on the blood-brain barrier has not been determined. In the present paper, it is shown that an antibody directed against MAdCAM-1, the preferential ligand for alpha4beta7, effectively prevented the …

Relationship of nocturnal melatonin levels to duration and course of multiple sclerosis.

Multiple sclerosis (MS) is the most common of the demyelinating diseases of the CNS. The clinical course and prognosis of the disease are variable. Characteristically, the illness tends to progress in a series of relapses and remissions. Over the years there is a tendency for the patient to enter a phase of slow and steady deterioration of neurologic function. In about 10%-20% of patients, the course of the disease is not punctuated by a fluctuating course, but rather by an inexorable progression from the onset. The pineal gland has been implicated recently in the pathogenesis and clinical cou…

Association of Mediterranean diet adherence with disease progression, quality of life and physical activity, sociodemographic and anthropometric parameters, and serum biomarkers in community-dwelling older adults with multiple sclerosis: a cross-sectional study.

BACKGROUND: Multiple sclerosis (MS) constitutes a chronic inflammatory and degenerative demyelinating disease, which can progressively lead to a broad range of sensorimotor, cognitive, visual, and autonomic function symptoms, independently of patient' age. However, the clinical studies that examine the role of dietary patterns against disease progression and symptomatology remain extremely scarce, especially concerning Mediterranean diet (MD) in the subgroup age of older adults with MS. AIMS: The present study aimed to investigate the potential impact of MD compliance in disease progression a…

Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review.

Multiple sclerosis (MS) is a chronic disease of the central nervous system with an unidentified etiology. We systematically reviewed the literature on the possible risk factors associated with MS disease onset, relapses and progression from 1960 to 2012 by accessing six databases and including relevant systematic reviews, meta-analyses, case-control or cohort studies. The focus was on identifying modifiable risk factors. Fifteen systematic reviews and 169 original articles were quality assessed and integrated into a descriptive review. Best evidence, which included one or more prospective stud…