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Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: A pilot trial of the antioxidant lipoic acid (LA) in secondary progressive multiple sclerosis (MS) demonstrated a reduction in the whole-brain atrophy, suggesting neuroprotection. This study determined whether LA preserved walking speed, reduced brain atrophy, and was safe in progressive MS (PMS). METHODS: This phase 2, 24-month, randomized, double-blind, placebo-controlled clinical trial (2018-2023) recruited a convenience sample from 10 US sites, including 5 Veterans Affairs medical centers and 1 Canadian site. Inclusion criteria were as follows: age ≥18 years, pr…

Effect of siponimod on retinal thickness, a marker of neurodegeneration, in participants with SPMS: Findings from the EXPAND OCT substudy.

BACKGROUND: People with MS show abnormal thinning of the retinal layers, which is associated with clinical disability and brain atrophy, and is a potential surrogate marker of neurodegeneration and treatment effects. OBJECTIVE: To evaluate the utility of retinal thickness as a surrogate marker of neurodegeneration and treatment effect in participants with secondary progressive MS (SPMS) from the optical coherence tomography (OCT) substudy of the EXPAND Phase 3 clinical trial (siponimod versus placebo). METHODS: In the OCT substudy population (n = 159), treatment effects on change in the aver

Associations between physical fitness and structural and functional MRI measures in secondary progressive multiple sclerosis: Cross-sectional findings from the exercise PRO-MS study.

OBJECTIVE: To explore the associations between physical fitness and brain MRI-measures in people with secondary progressive MS (SPMS). METHODS: We assessed associations between physical fitness (i.e., cardiorespiratory fitness, leg muscle strength, and self-reported level of physical activity) and MRI-derived measures (i.e., brain volume, and resting-state functional (rsFC) of the default-mode network with the rest of the brain (DMN-brain) and sensorimotor network with the rest of the brain (SMN-brain)) using multiple linear regression analyses. Physical fitness was compared to published refe

Investigating cortical hypoxia in multiple sclerosis via time-domain near-infrared spectroscopy.

OBJECTIVES: Hypoperfusion and tissue hypoxia have been implicated as contributory mechanisms in the neuropathology of multiple sclerosis (MS). Our objective has been to study cortical oxygenation in vivo in patients with MS and age-matched controls. METHODS: A custom, multiwavelength time-domain near-infrared spectroscopy system was developed for assessing tissue hypoxia from the prefrontal cortex. A cross-sectional case-control study was undertaken assessing patients with secondary progressive MS (SPMS) and age-matched controls. Co-registered magnetic resonance imaging was used to verify the…

How to diagnose difficult white matter disorders.

Genetic and acquired disorders of white matter comprise a diverse group of conditions, with often overlapping clinical and radiological findings. Patients present with a variable combination of cognitive impairment, ataxia, spasticity or movement disorders, among others. There are many genetic causes, and the route to diagnosis involves comprehensive clinical assessment, radiological expertise, metabolic investigations and finally genetic studies. It is essential not to miss the treatable acquired causes. In this review, we present a practical approach to investigating patients with acquired a

Retinal degeneration in primary-progressive multiple sclerosis: A role for cortical lesions?

BACKGROUND: Retinal atrophy in multiple sclerosis (MS) is secondary to optic nerve focal inflammation and to injury of the posterior visual pathway. OBJECTIVES: To investigate the contribution of cortical lesions (CLs) to retinal pathology in primary-progressive multiple sclerosis (PPMS). METHODS: We performed a cross-sectional evaluation of 25 patients and 20 controls, relating magnetic resonance imaging (MRI) metrics of visual pathway integrity with parameters derived from spectral-domain optical coherence tomography (peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell …

Resolution Failure in Multiple Sclerosis: Linking Lipid Mediators to Neuroinflammation and Disease Progression.

Multiple sclerosis (MS) is a chronic immune-mediated and neurodegenerative disorder of the central nervous system characterized by highly heterogeneous clinical courses and progressive accumulation of disability. Traditionally viewed as a relapsing inflammatory disease driven by peripheral autoimmunity, emerging evidence instead supports a continuum in which early immune attacks evolve into compartmentalized, chronic "smoldering" pathology that persists independently of overt relapses. This chapter integrates current knowledge of MS pathogenesis, focusing on the central emerging concept that M…

Physical activity behavior change in persons with neurologic disorders: overview and examples from Parkinson disease and multiple sclerosis.

Persons with chronic progressive neurologic diseases such as Parkinson disease (PD) and multiple sclerosis (MS) face significant declines in mobility and activities of daily living, resulting in a loss of independence and compromised health-related quality of life over the course of the disease. Such undesirable outcomes can be attenuated through participation in exercise and physical activity, yet there is profound and prevalent physical inactivity in persons with PD and MS that may initiate a cycle of deconditioning and worsening of disease consequences, independent of latent disease process…

Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis.

We have investigated the T cell populations in the cerebrospinal fluid (CSF) of chronic progressive multiple sclerosis (MS) patients. Individual T cells from the CSF and blood were cloned before expansion and their clonotypes were defined by analysis of rearranged T cell receptor beta chain and gamma chain genes. 87 T cell clones from blood and CSF of two patients with chronic progressive MS were examined for common TCR gene rearrangement patterns. In one patient, 18 of 28 CSF-derived T cell clones demonstrated common TCR gene rearrangements indicating oligoclonal T cell populations; in the bl…

Традиционная китайская медицина обеспечивает кандидатов на мутил-секлорез: обзор, основанный на прогрессе в области MS и мощной терапии.

Множественный склероз (MS) — хроническое возбудительское и дегенеративное аутоиммунное неврологическое заболевание, характеризующееся инфильтрацией иммунных клеток, демиелинацией, аксонной потерей и дегенерацией нейронов. В настоящее время точный механизм заболевания пока еще не очень ясен. Последние исследования показали, что иммунный дисбаланс, микроглиационная поляризация, окислительный стресс, разрушение кровеносного мозгового барьера (ББД) и кровеносного мозга (БЦБ), а также кишечная флора могут участвовать в патогенезе и способствовать развитию болезни. Традиционная китайская медицина (T

Совпадение в аннотации оригинала
Multiple Sclerosis(MS) is a chronic inflammatory and degenerative autoimmune neurological disease, characterized by immune cells infiltration, demyelination, axonal loss and neuron degeneration. At present, the precise mechanism of the disease is still not very clear. Latest studies clarified that immune imbalance, microglia polarization, oxidative stress, t…

SUMOylation in Neural Health and Disease: From Cellular Homeostasis to Neurodegeneration.

Neurodegenerative diseases (NDDs) represent a growing global health burden, particularly in aging populations. These disorders primarily affect neurons and are characterized by progressive neuronal dysfunction and loss within specific regions of the central nervous system. Major NDDs include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and stroke. Although each disorder exhibits distinct genetic backgrounds and pathological protein aggregates, they share common pathogenic mechanisms, including chronic neuroinflammation, impa…

An Antibody-Dependent Cellular Cytotoxicity Assay for Detecting Ocrelizumab Neutralizing Antibody.

Ocrelizumab (OCREVUS®) is a humanized anti-CD20 monoclonal antibody approved for the treatment of adult patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). Here, we discuss the strategic and technical considerations needed to develop a robust antibody-dependent cellular cytotoxicity (ADCC)-based neutralizing antibody (NAb) assay to detect anti-ocrelizumab NAb in patients enrolled in the ocrelizumab registered clinical trials. The NAb detection assay consisted of a two-tier assay that included a screening assay and a confirmation assay. In the scr…

Neuroendocrine and stress-related aspects of endometriosis.

Endometriosis is a model of a benign gynecologic disease associated with two major symptoms: pain and infertility. When becomes chronic, sev … lgia, chronic fatigue) and even autoimmune diseases (thyroid disease, systemic lupus erythematosus, multiple sclerosis). Neurogenic mechanisms are described in endometriotic lesions and they affect peripheral and central nervous system of these patients increasing pain sensitivity and stress reactivity. In conclusion, endometriosis is a disease which affects reprodu …

Discussions about treatment restrictions in chronic neurologic diseases: a structured review.

OBJECTIVE: Many incurable neurologic diseases have predictable complications during their course or at their end stage. Timely discussions of potential treatment restrictions may improve the quality of treatment decisions toward the end of life. What is known about the actual practice of these discussions? METHODS: We performed a literature search in MEDLINE, EMBASE, and CINAHL for empirical studies about discussions and decisions to restrict treatment in the course of 6 conditions: motor neuron disease (amyotrophic lateral sclerosis [ALS]), primary malignant brain tumors, multiple sclerosis,…

The use of intrathecal phenol for muscle spasms in multiple sclerosis. A description of two cases.

Two cases of multiple sclerosis are described, in both of whom the disease started in yound adult life. This disability gradually progressed to the stage of paraplegia-in-flexion in which the lower limbs were fixed in adduction-and-flexion. Both patients developed painful muscle spasms which made life intolerable. These patients were treated by intrathecal phenol in glycerine in an effort to convert this spastic paralysis into a flaccid paralysis. The three advantages sought were: 1. To relieve the muscle spasms so that the patient could sit in a wheelchair and propel herself. 2. To relieve th…

Поддержание хронической нейроинфламмации в множестве склероза с помощью интерферона сигнала и CD8T с помощью клеток цитотоксичности.

Хроническая нейроинфламмация и нейродегенерация являются важнейшими, но нерешенными факторами накопления инвалидности в прогрессивном множественном склерозе (MS). Хронические активные повреждения белых веществ (CAL), обнаруженные радиологически как повреждения парамагнитных ободов (PRL), указывают на хроническое нейроинфламмирование, имеющее отношение к процессу развития. Используя одноклеточную транскриптомику (scRNAseq) и последовательность рецепторов Т-клеток (scTCR-seq), мы профилировали цереброспинную жидкость (CSF) и кровеносные иммунные клетки 34 человек радиологической характеристики с

Совпадение в аннотации оригинала
Chronic neuroinflammation and neurodegeneration are critical but unresolved drivers of disability accumulation in progressive multiple sclerosis (MS). Chronic active white matter lesions (CAL), identifiable radiologically as paramagnetic rim lesions (PRL), indicate progression-relevant chronic neuroinflammation. Using single-cell transcriptomics (scRNAseq) a…

Pathogenic mechanisms of neurodegeneration based on the phenotypic expression of progressive forms of immune-mediated neurologic disease.

Considering there are no treatments for progressive forms of multiple sclerosis (MS), a comprehensive understanding of the role of neurodegeneration in the pathogenesis of MS should lead to novel therapeutic strategies to treat it. Many studies have implicated viral triggers as a cause of MS, yet no single virus has been exclusively shown to cause MS. Given this, human and animal viral models of MS are used to study its pathogenesis. One example is human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Importantly, HAM/TSP is similar clinically, patholo…

Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese.

BACKGROUND: Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease. OBJECTIVE: The objective of the current study was to clarify immunological differences between the two groups of patients. METHODS: We studied the serum antibody titers against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified their relationships with immunological parameters. RESULTS: Anti-AQP4 an…

Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system.

OBJECTIVES: Validation of cerebrospinal fluid (CSF) indexes as a measure for intrathecal C3 and C4 production. Examination of their role in differential diagnosis of immunological disorders of the central nervous system (CNS). MATERIAL AND METHODS: Correlative study in controls (low back pain without disk herniation) between the CSF/serum ratio (Q) for albumin, and Q C3 and Q C4. Comparative study of C3 and C4 indexes in patients with CNS dysfunction due to relapsing-remitting (RR) multiple sclerosis (MS), secondary progressive (SP) MS, systemic lupus erythematosus (SLE), and human immunodefi…