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From inflammation to neurodegeneration: an exploratory pilot study of a diagnostic framework for progression in MS.

BACKGROUND: The pathogenesis of Multiple Sclerosis (MS) involves a dynamic interplay between (auto-)inflammation and neurodegeneration, driving its relapsing and progressive course. While both processes have been shown to be involved throughout disease with different emphasis, relapsing MS (RMS) is characterized by acute inflammatory activity, and secondary progressive MS (SPMS) involves chronic, diffuse neurodegeneration. Identifying biomarkers to predict progression independent of relapse activity (PIRA) is critical for improving diagnostic accuracy and treatment strategies. This study aimed…

Появляющаяся роль BTK Inhibitors в многоразовом склерозе: от иммунобиологии к клиническому переводу.

Множественный склероз (MS), аутоиммунное заболевание, предполагает периферическую иммунную активацию, за которой следует воспаление CNS в разрозненной форме. Несмотря на то, что высокоэффективные методы коррекции заболеваний (HO-DMT) оказались эффективными в борьбе с рецидивами у пациентов с синдромом MS, они не позволяют эффективно ориентироваться на хроническую микрогильевую активацию и удушающие повреждения у пациентов с синдромом MS. Тейросиновые ингибиторы киназы Брютона (BTKis), которые являются перорально активными и способными пересечь мозговой барьер, были признаны эффективными для мо

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS), an autoimmune disease, involves peripheral immune activation followed by CNS inflammation in a compartmentalized manner. Although high-efficacy disease-modifying therapies (HE-DMTs) have been effective in suppressing relapses in MS patients, they fail to effectively target chronic microglial activation and smoldering lesi…

Siponimod treatment response shows partial BDNF dependency in multiple sclerosis models.

So far, only a small number of medications are effective in progressive multiple sclerosis (MS). The sphingosine-1-phosphate-receptor (S1PR)-1,5 modulator siponimod, licensed for progressive MS, is acting both on peripheral immune cells and in the central nervous system (CNS). So far it remains elusive, whether those effects are related to the neurotrophin brain derived neurotrophic factor (BDNF). We hypothesized that BDNF in immune cells might be a prerequisite to reduce disease activity in experimental autoimmune encephalomyelitis (EAE) and prevent neurotoxicity. MOG35-55 immunized wild type…

Essential trace element levels in multiple sclerosis: Bridging demographic and clinical gaps, assessing the need for supplementation.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disorder intricately linked to perturbations in trace element levels. While previous studies have explored circulating trace elements in a limited sample, understanding the impact of demographic and clinical variables on the elemental profile within a larger cohort remains elusive. METHODS: This study aimed to evaluate essential trace elements (Cr, Mn, Co, Cu, Zn, and Se) in the sera of 215 MS patients compared to a meticulously matched control group of 100 individuals with similar gender and age. Our main objective was to identif…

The Assessment of the Prevalence and Disability Severity of Musculoskeletal Pain in Patients With Multiple Sclerosis in Saudi Arabia.

Background Multiple sclerosis (MS) is an autoimmune disease of the nervous system that causes chronic demyelination over time and may lead to physical disability. MS-related pain may be musculoskeletal, paroxysmal, or persistently neurogenic in nature. The most common type of pain is musculoskeletal discomfort, which is typically brought on by muscle weakening, stiffness, and generalized imbalance as the condition progresses. Pain often manifests after prolonged immobilization of muscles, tendons, and ligaments. Aim We aimed to evaluate the prevalence and severity of musculoskeletal pain (MSP)…

Rationale and design of a single-blind, randomised controlled trial of exercise training for managing learning and memory impairment in persons with multiple sclerosis.

INTRODUCTION: This randomised controlled trial (RCT) examines treadmill walking exercise training effects on learning and memory performance, hippocampal volume, and hippocampal resting-state functional connectivity in persons with multiple sclerosis (MS) who have objective impairments in learning new information. METHODS AND ANALYSIS: Forty fully ambulatory persons with MS who demonstrate objective learning and memory impairments will be randomly assigned into either the intervention or active control study conditions. The intervention condition involves supervised, progressive treadmill wal…

Rethinking MS Therapeutics: From Disease Pathogenesis Mechanisms to AI-Driven Drug Discovery.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the CNS, characterized by inflammation, demyelination, and progressive neurodegeneration. Disease progression involves four key interconnected stages: the activation of immune cells in peripheral lymph regions, the migration of autoreactive cells across the blood-brain barrier, demyelination, and an often incomplete remyelination response. Despite such significant therapeutic advances, major challenges remain in early diagnosis, patient stratification, and personalized intervention. Artificial intelligence has emerged as a powerful to…

Seronegative Chronic Relapsing Inflammatory Optic Neuropathy.

Chronic relapsing inflammatory optic neuropathy (CRION) is a rare cause of recurrent optic neuritis characterized by steroid responsiveness … c resonance imaging and responded promptly to intravenous corticosteroids. Extensive evaluation for multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody disease was consistently negative. A diagnosis of seronegative CRION was established based on the recurrent steroid-responsive clinical patt …

В Silico Research of BTK как потенциальная цель иммуномодулирования: изучение новых терапевтических подходов к множественному склерозу.

Множественный склероз (MS) — хроническое аутоиммунное демиелинирующее заболевание, характеризующееся прогрессивным неврологическим расстройством. Тирозиновая киназа Брютона (BTK) стала важнейшей терапевтической целью в силу ее роли в активации клеток B и врожденном иммунном сигнале. В то время как ингибиторы BTK (BTKi) показали, что они способны лечить MS и подстрекательские расстройства, их высокая токсичность и ингибиция нецелевой киназы создают проблемы, особенно с учетом того, что многие пациенты испытывают мягкие симптомы. В этом исследовании представлен L2-a, структурно оптимизированный,

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease characterized by progressive neurological impairment. Bruton's tyrosine kinase (BTK) has emerged as a crucial therapeutic target due to its role in B-cell activation and innate immune signaling. While BTK inhibitors (BTKi) have shown promise for treating MS and inflammatory disorders, thei…

Эффективность корректирующих заболеваний веществ в деле улучшения множественных склерозов - перекрестное исследование наблюдений.

Множественный склероз (MS) - хроническое провокационное демиелионирующее расстройство центральной нервной системы известно как вызывающее прогрессивное неврологическое ухудшение. Это сказывается на качестве жизни этих пациентов и их производительности. Для лечения MS имеются различные пероральные и инъекционные лекарственные средства для лечения болезней (DMD). Несмотря на наличие многих лекарств, качество жизни этих пациентов продолжает беспокоить. Настоящее исследование было проведено для оценки эффективности обычной терапии в РС. МЕТОДЫ: В одном центре было проведено перекрестное исследован

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) - A chronic inflammatory demyelinating disorder of the central nervous system is notorious for causing progressive neurological deterioration. This affects the quality of life of these patients and their productivity. Various oral and injectable disease-modifying drugs (DMDs) are available for the treatment of MS. In spite…

Twenty Years of Subcutaneous Interferon-Beta-1a for Multiple Sclerosis: Contemporary Perspectives.

Multiple sclerosis (MS) is a chronic, progressive, inflammatory disorder of the central nervous system. Relapsing-remitting MS (RRMS), the most common form of the disease, is characterized by transient neurological dysfunction with concurrent accumulation of disability. Over the past three decades, disease-modifying therapies (DMTs) capable of reducing the frequency of relapses and slowing disability worsening have been studied and approved for use in patients with RRMS. The first DMTs were interferon-betas (IFN-βs), which were approved in the 1990s. Among them was IFN-β-1a for subcutaneous (s…

MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System.

Quantifying O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation plays an essential role in assessing the potential efficacy o … ed MGMT promoter methylation in individual cases of inflammatory demyelinating CNS diseases such as multiple sclerosis and progressive multifocal leucencephalopathy (PML), as well as in other demyelinating diseases such as central pontine and exptrapontine myelinolysis, and diseases with myelin damage such as Wallerian degeneration. In this context, we identified a …

The Role of Plasma Exchange in the Treatment of Refractory Autoimmune Neurological Diseases: a Narrative Review.

Autoimmune neurological disorders are commonly treated with immunosuppressive therapy. In patients with refractory conditions, standard immu … idlands Neurological Society meeting on PLEX in refractory neurology: Autoimmune Encephalitis (AE), Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum disorders (NMOSD), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Myasthenia Gravis (MG). The diagnosis of inflammatory neuropathies is often challenging, and while PLEX can be very effective …

The role of Nrf2 in neural stem/progenitors cells: From maintaining stemness and self-renewal to promoting differentiation capability and facilitating therapeutic application in neurodegenerative disease.

Neurodegenerative diseases (NDs) cause progressive loss of neurons in nervous system. NDs are categorized as acute NDs such as stroke and head injury, besides chronic NDs including Alzheimer's, Parkinson's, Huntington's diseases, Friedreich's Ataxia, Multiple Sclerosis. The exact etiology of NDs is not understood but oxidative stress, inflammation and synaptic dysfunction are main hallmarks. Oxidative stress leads to free radical attack on neural cells which contributes to protein misfolding, glia cell activation, mitochondrial dysfunction, impairment of DNA repair system and subsequently cell…

Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease.

Progressive multifocal leukoencephalopathy (PML) is a devastating CNS infection caused by JC virus (JCV), a polyomavirus that commonly estab … immunosuppression that can be difficult to reverse. These treatments - most notably natalizumab for multiple sclerosis - have led to a surge of iatrogenic PML. The spectrum of presentations of JCV-related disease has evolved over time and may challenge current diagnostic criteria. Immunotherapeutic interventions, such as use of checkpoint inhibitors and adoptive T c …

Matrix metalloproteinase-12 deficiency ameliorates the clinical course and demyelination in Theiler's murine encephalomyelitis.

Matrix metalloproteinases (MMPs) are a family of extracellular proteases involved in the pathogenesis of demyelinating diseases like multiple sclerosis (MS). The aim of the present study was to investigate whether MMPs induce direct myelin degradation, leukocyte infiltration, disruption of the blood-brain barrier (BBB), and/or extracellular matrix remodeling in the pathogenesis of Theiler's murine encephalomyelitis (TME), a virus-induced model of MS. During the demyelinating phase of TME, the highest transcriptional upregulation was detected for Mmp12, followed by Mmp3. Mmp12 (-/-) mice showed…

Characterization of brain lesions in a mouse model of progressive multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by damage to the neuronal myelin sheath, which results in different levels of muscle paralysis that can lead to neuronal death. In most MS mouse models, the neurologic damage mostly affects the spinal cord with limited damage to the brain, which cannot be monitored by magnetic resonance imaging (MRI) as used for humans. We show that immunization of non-obese diabetic (NOD) mice with myelin oligodendrocyte glycoprotein peptide 35-55 leads to the development of relapsing-remitting stages, evident from da…

Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis.

BACKGROUND AND OBJECTIVES: Pirfenidone is an orally available antifibrotic agent that has shown benefit in animal models of pulmonary and renal fibrosis and in clinical trials of pulmonary fibrosis, multiple sclerosis, and hepatic cirrhosis. Our objective was to determine whether pirfenidone slows the loss of renal function in focal segmental glomerulosclerosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: An open-label trial was performed to evaluate the safety and efficacy of pirfenidone in patients with idiopathic and postadaptive focal segmental glomerulosclerosis. The monthly change in…

[Disseminated sclerosis and sexuality].

Since the onset of multiple sclerosis (MS) mainly occurs in younger persons between the age of 20 and 40, sexual dysfunctions have great impact on their quality of life. About 50% of all female and about 75% of all male patients complain of sexual dysfunctions. The primary symptoms among males are erective and ejaculative dysfunctions and reduced libido, while female patients mainly complain of reduced libido, problems achieving orgasm, decreased vaginal lubrication and changes in vaginal sensitivity. Secondary organic symptoms include fatigue, spasticity, muscular weakness, bladder problems, …

Reversal of an acute parkinsonian syndrome associated with multiple sclerosis by application of weak electromagnetic fields.

The occurrence of movement disorders and particularly Parkinsonian symptoms is uncommon in patients with multiple sclerosis (MS) despite the rather frequent presence of demyelinating plaques in the basal ganglia. This disparity between the occurrence of clinical symptoms in MS and the distribution of demyelinating plaques suggests that impairment of neurotransmitter functions rather than demyelination may be critical to the clinical manifestations of the disease. A 48 year old woman with remitting-progressive MS developed a bilateral Parkinsonian syndrome in association with acute emotional st…