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An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography.

Axonal loss is thought to be the predominant cause of disability in progressive multiple sclerosis (MS). The retinal nerve fibre layer (RNFL) is composed largely of unmyelinated axons of retinal ganglion cells, and is accessible to study with optical coherence tomography (OCT), giving a measure of axonal loss. OCT measures of the RNFL thickness (RNFLT) and macular volume were studied in 23 patients with primary progressive multiple sclerosis (primary progressive MS) (13 male; 10 female; mean age 52 years; median EDSS 6.0; mean disease duration 11 years), and 27 patients with secondary progress…

Plasma proteome analysis in HTLV-1-associated myelopathy/tropical spastic paraparesis.

BACKGROUND: Human T lymphotropic virus Type 1 (HTLV-1) causes a chronic inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) which resembles chronic spinal forms of multiple sclerosis (MS). The pathogenesis of HAM remains uncertain. To aid in the differential diagnosis of HAM and to identify pathogenetic mechanisms, we analysed the plasma proteome in asymptomatic HTLV-1 carriers (ACs), patients with HAM, uninfected controls, and patients with MS. We used surface-enhanced laser desorption-ionization (SELDI) mass spectrometry…

Monoclonal remyelination-promoting natural autoantibody SCH 94.03: pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis.

Chronic inflammatory demyelination of the central nervous system is usually incompletely repaired. However, we previously reported that in vivo treatment with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14: 6230-6238). A major issue regarding site and mechanism of action of this antibody is whether SCH 94.03 enters demyelinated CNS lesions and reacts with oligodendrocytes and myelin. To address this question, we…

The Palliative Use of Intrathecal Baclofen in Niemann-Pick Disease Type C.

Niemann-Pick disease type C is a rare progressive genetic disorder that leads to the abnormal accumulation of lipids within various tissues … cord injury with relatively long life expectancies. In adults, they have been used in patients with multiple sclerosis; however, use in pediatric neurodegenerative diseases has scarcely been reported. The use of intrathecal baclofen in palliative settings might provide an additional resource to provide comfort and quality of life for children with neurodegenerative …

Patterns of blood-brain barrier breakdown in inflammatory demyelination.

The evolution of the changes in the blood-brain barrier (BBB) in chronic relapsing experimental allergic encephalomyelitis (CREAE), a model … g and progressive disease. The broad similarities in the pattern of BBB breakdown seen in CREAE and multiple sclerosis support the hypothesis that the initial vascular changes in the human disease are due to inflammation which could be mediated immunologically.

Chlamydophila pneumoniae Infection and Its Role in Neurological Disorders.

Chlamydophila pneumoniae is an intracellular pathogen responsible for a number of different acute and chronic infections. The recent deepeni … of this pathogen in chronic neurological disorders and particularly in Alzheimer's disease (AD) and Multiple Sclerosis (MS). Monocytes may traffic C. pneumoniae across the blood-brain-barrier, shed the organism in the CNS and induce neuroinflammation. The demonstration of C. pneumoniae by histopathological, molecular and culture techniques in the late-onset AD demen …

Correlates of Processing Speed Change With Combined Cognitive Rehabilitation and Exercise in Progressive MS: Secondary Analysis of the CogEx Trial.

BackgroundCognitive rehabilitation and exercise training are promising approaches for improving cognition in persons with progressive multiple sclerosis (MS). Identifying heterogeneity of change and factors that influence the effects of cognitive rehabilitation and/or exercise training on cognitive outcomes at the individual level have direct relevance for developing tailored and optimized rehabilitation interventions for improving cognition in progressive MS.ObjectiveThis study involved a secondary data analysis from the CogEx trial in progressive MS. This study first described heterogeneity …

Intrathecal, polyspecific antiviral immune response in oligoclonal band negative multiple sclerosis.

BACKGROUND: Oligoclonal bands (OCB) are detected in the cerebrospinal fluid (CSF) in more than 95% of patients with multiple sclerosis (MS) in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients. METHODOLOGY/PRINCIPAL FINDINGS: We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation serve…

Fluid biomarkers in multiple sclerosis: Indicators of disease activity, progression, and treatment response.

Multiple sclerosis (MS) is a chronic immune-mediated CNS disorder marked by inflammation, demyelination, and neurodegeneration. Standard clinical evaluation, neurological exams, disability scoring, and MRI often miss subclinical activity and poorly predict progression. Fluid biomarkers in cerebrospinal fluid (CSF) and blood provide objective, quantifiable indicators of disease activity, progression, and therapeutic response. Essential fluid biomarkers for monitoring MS include neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Chitinase-3-like protein 1 (CHI3L1), C-X-C Mo…

Somatic variation in multiple sclerosis: from blood to brain.

Multiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system (CNS) that affects nearly 3 million people worldwide. Pathologically, MS is characterised by inflammation, demyelination and neurodegeneration, leading to declining neurological function and increasing disability. To date, investigations of somatic variation in MS have focused primarily on peripheral immune cells and, more recently, neurons. Deep targeted and exome sequencing of blood‑derived T cells have not demonstrated enrichment of somatic driver mutations in individuals with MS compared with controls…

Carabrone alleviates neuroinflammation by covalently targeting ubiquitin conjugating enzyme UBE2D3 in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an incurable and progressive inflammatory disease of the central nervous system (CNS) characterized by inflammatory demyelination, chronic axonal damage, and neurodegeneration. Carabrone (CA), a sesquiterpene lactone from the traditional Chinese herb Carpesium abrotanoides L., demonstrates diverse pharmacological properties. However, its therapeutic effects on MS and the underlying mechanisms remain unexplored. In the present study, we reported the beneficial effects of CA on experimental autoimmune encephalomyelitis (EAE), a well-established mouse model of MS, for t…

Immune-mediated excitotoxicity in brain disorders.

Balanced activity of neuronal and immune networks is essential for maintaining central nervous system (CNS) function and mental health, wher … in which misfolded protein aggregates act as immune stressors that amplify local inflammation; and multiple sclerosis, characterized by persistent, compartmentalized inflammation that drives chronic excitotoxic cycles. Across these examples, we define three hallmarks - feedback, stressor and chronicity - as organizing principles of this paradigm and describe the dy …

Повторение множественных склерозов с помощью клеточной терапии CAR-T.

Множественный склероз (MS) — хроническое аутоиммунное расстройство центральной нервной системы, характеризующееся аберрантной иммунной реакцией на миелин и нейрональные антигены, приводящее к обезвоживанию, аксоновой травме и прогрессивному неврологическому расстройству. Несмотря на то, что нынешняя иммунодуляторная терапия может уменьшить частоту рецидивов и медленные темпы развития заболеваний, она редко вызывает долговременную ремиссию или обратно установившуюся патологию. В качестве перспективной стратегии лечения аутоиммунных заболеваний недавно была разработана клеточная терапия химерног

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by aberrant immune responses against myelin and neuronal antigens, resulting in demyelination, axonal injury, and progressive neurological impairment. Although current immunomodulatory therapies can reduce relapse frequency and slow disease progression, they …

Адипокины в множестве склерозов: иммунная диагностика, нейроинфламмация и терапевтические возможности.

Множественный склероз (MS) — хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризующееся обезвоживанием, нейроинфламмацией и постепенным накоплением неврологических дефицитов. Адиповидные ткани скрывают преимущественно биоактивные молекулы, известные как адипокины, которые привлекли значительное внимание к их роли в модуляции иммунных и метаболических путей у людей с MS (PwMS). Дисрегулированные адипокины, такие, как резистентность, лептин и химик, провоцируют воспламенительную поляризацию Т-клеток при одновременном ухудшении целостности барьера между кровью и мо

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS), characterized by demyelination, neuroinflammation, and the progressive accumulation of neurologic deficits. Adipose tissue secretes predominantly the bioactive molecules, known as adipokines, which have drawn considerable attention for their roles in modulating immu…

Disease-modifying therapies for Parkinson disease: lessons from multiple sclerosis.

The development of disease-modifying therapies (DMTs) for neurological disorders is an important goal in modern neurology, and the associated challenges are similar in many chronic neurological conditions. Major advances have been made in the multiple sclerosis (MS) field, with a range of DMTs being approved for relapsing MS and the introduction of the first DMTs for progressive MS. By contrast, people with Parkinson disease (PD) still lack such treatment options, relying instead on decades-old therapeutic approaches that provide only symptomatic relief. To address this unmet need, an in-perso…

Palliative Care Aspects in Multiple Sclerosis.

CONTEXT: Multiple sclerosis (MS) is an inflammatory, chronic, demyelinating, and neurodegenerative disorder of central nervous system, determined by an auto-immune dysfunction. Severe disability generally occurs in patients with progressive forms of MS that typically develop either after an earlier relapsing phase or less commonly from disease onset. Despite advances in research to slow the progression of MS, this condition remains a life-limiting disease with symptoms impacting negatively the lives of patients and caregivers. OBJECTIVES: To analyze the difefrent aspects of palliative cae in …

Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis.

Growing evidence from cerebrospinal fluid samples and post-mortem brain tissue from individuals with multiple sclerosis (MS) and rodent models indicates that the meninges have a key role in the inflammatory and neurodegenerative mechanisms underlying progressive MS pathology. The subarachnoid space and associated perivascular spaces between the membranes of the meninges are the access points for entry of lymphocytes, monocytes and macrophages into the brain parenchyma, and the main route for diffusion of inflammatory and cytotoxic molecules from the cerebrospinal fluid into the brain tissue. I…

Current Perspectives: Evidence to Date on BTK Inhibitors in the Management of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system leading to demyelination and neurodegeneration. Basic and translational studies have shown that B cells and myeloid cells are critical players for the development and course of the disease. Bruton's tyrosine kinase (BTK) is essential for B cell receptor-mediated B cell activation and for normal B cell development and maturation. In addition to its role in B cells, BTK is also involved in several functions of myeloid cells. Although significant number of disease-modifying treatments (DMTs) have been approved…

Bone-marrow mononuclear cell therapy in a mouse model of amyotrophic lateral sclerosis: Functional outcomes from different administration routes.

Amyotrophic lateral sclerosis (ALS) is a chronic degenerative disease that mainly affects motor neurons, leading to progressive paralysis and death. Recently, cell therapy has emerged as a therapeutic alternative for several neurological diseases, including ALS, and bone-marrow cells are one of the major cell sources. Considering the importance of pre-clinical trials to determine the best therapeutic protocol and the hope of translating this protocol to the clinical setting, we tested bone-marrow mononuclear cell (BMMC) therapy administered by different routes in the SOD1G93A model of ALS. BMM

Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE).

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to dise…