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Lymphotoxin-alpha expression in the meninges causes lymphoid tissue formation and neurodegeneration.

Organized meningeal immune cell infiltrates are suggested to play an important role in cortical grey matter pathology in the multiple sclerosis brain, but the mechanisms involved are as yet unresolved. Lymphotoxin-alpha plays a key role in lymphoid organ development and cellular cytotoxicity in the immune system and its expression is increased in the CSF of naïve and progressive multiple sclerosis patients and post-mortem meningeal tissue. Here we show that persistently increased levels of lymphotoxin-alpha in the cerebral meninges can give rise to lymphoid-like structures and underlying multi…

Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis.

BACKGROUND: Throughout the course of multiple sclerosis, gradually progressive neurologic impairment can occur, which has been called disability accrual. Current disease-modifying therapies for multiple sclerosis have limited effects on disability accrual unrelated to relapses, which is thought to be partially caused by chronic, nonresolving neuroinflammation within the central nervous system. Tolebrutinib is an oral, brain-penetrant Bruton's tyrosine kinase inhibitor that targets myeloid cells (including microglia) and B cells in both the periphery and central nervous system. There are no app…

Дифференцированные метакогнитивные характеристики при повторном излучении и прогрессивном многоразовом склерозе: ассоциации с утомлением, когнитивированием и нетрудоспособностью.

ЦЕЛЬ: В рамках этого исследования были изучены метакогнитивные профили веры у лиц с множественным склерозом (MS) и их связи с когнитивными, эмоциональными и функциональными результатами. В частности, мы сравнили повторные выбросы MS (RRMS), вторичные прогрессивные MS (SPMS) и первичные прогрессивные MS (PPMS) для определения того, характеризуют ли различные фенотипы болезней различные метакогнитивные модели. МЕТОД: Из неврологической клиники было нанято в общей сложности 504 участника (75,6 процента RMS, 9,9 процента SPMS, 14,5 процента PPMS). Участники заполнили вопросник по метакогнитивам-30

Совпадение в аннотации оригинала
OBJECTIVE: This study examined metacognitive belief profiles in individuals with multiple sclerosis (MS) and their associations with cognitive, emotional, and functional outcomes. Specifically, we compared relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) to determine whether distinct metacognitive patterns cha…

Comparison of practice-related changes in dual task walking performance and neural efficiency between older adults with progressive and relapsing-remitting multiple sclerosis.

BACKGROUND: There is limited research comparing both performance and brain control of walking between older adults with progressive and relapsing-remitting MS. OBJECTIVE: This study compared older adults with progressive and relapsing-remitting MS for differences in prefrontal cortex (PFC) activation in single- and dual-task-walking and practice-related effects on neural efficiency, walking, and cognitive performances. METHODS: Older adults with progressive (n = 32, age=65±6ys) and relapsing-remitting (n = 63, age=65±4ys) MS completed three conditions (single-task walk, single-task-alpha, i.

Serum glial fibrillary acidic protein and disability progression in progressive multiple sclerosis.

OBJECTIVE: Progression prediction is a significant unmet need in people with progressive multiple sclerosis (pwPMS). Studies on glial fibrillary acidic protein (GFAP) have either been limited to single center with relapsing MS or were based solely on Expanded Disability Status Scale (EDSS), which limits its generalizability to state-of-the-art clinical settings and trials applying combined outcome parameters. METHODS: Serum GFAP and NfL (neurofilament light chain) were investigated in EmBioProMS participants with primary (PP) or secondary progressive MS. Six months confirmed disability progre…

The Role of T Cells in Multiple Sclerosis: Molecular Mechanisms, Drivers, and Therapeutic Targets.

Multiple sclerosis is a chronic immune-mediated disease of the central nervous system, marked by demyelination, axonal damage, and progressive neurological decline. T lymphocytes-particularly CD4+, T helper (Th)1 and Th17 cells, as well as cytotoxic CD8+ cells-play a pivotal role in initiating and sustaining central nervous system inflammation. Acute inflammation is driven by peripheral immune activation, while progressive disease reflects compartmentalized, smouldering inflammation within the central nervous system, dominated by CD8+ T cells and microglia. A relative deficiency or dysfunction…

Белая материя в кризисе: Олигодендроциты и патофизиология множественного склероза.

Множественный склероз — это хроническое нервно-дегенеративное расстройство центральной нервной системы с иммунной подоплекой, характеризующееся широко распространенным обезвоживанием, аксонной травмой и прогрессивным неврологическим расстройством. Патофизиология множественного склероза включает сложные взаимодействия между иммунными клетками и постоянными клетками центральной нервной системы, при этом олигодендроциты (милиновые глиальные клетки) играют центральную роль как в наступлении, так и в развитии болезни. Дисфункция олигодендроцитов, включая снижение регенеративной способности, повышен

Совпадение в аннотации оригинала
Multiple sclerosis is a chronic, immune-mediated neurodegenerative disorder of the central nervous system, characterized by widespread demyelination, axonal injury, and progressive neurological impairment. The pathophysiology of multiple sclerosis involves complex interactions between immune cells and central nervous system resident cells, with oligodendrocy…

Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis.

Clinically isolated syndromes (CIS), such as optic neuritis, brainstem or spinal cord syndromes are frequently the first clinical presentations of multiple sclerosis. However, not all CIS patients develop multiple sclerosis and in those who do, disability is highly variable. In previous follow-up studies, brain lesions on T2-weighted MRI are associated with increased risk of multiple sclerosis and to an extent disability. We evaluated the longitudinal relationships between the MRI lesions and clinical course over a period of 20 years. CIS patients were recruited between 1984 and 1987 and previ…

Ongoing phase 2 agents for multiple sclerosis: could we break the phase 3 trial deadlock?

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system. While disease-modifying therapies have significantly improved the management of relapsing MS, progressive MS remains a major clinical challenge. AREAS COVERED: This review provides a general overview of recent and ongoing phase 2 clinical trials investigating treatments for MS, summarizing emerging results when available. The trials are categorized based on the desired therapeutic effect: immunomodulatory treatments, neuroprotection, and remyelination. A comprehensive l…

Choroid plexus enlargement is associated with future periventricular neurodegeneration in multiple sclerosis.

BACKGROUND: The choroid plexus (CP), located within the ventricles of the brain and the primary producer of cerebrospinal fluid, has been shown to be enlarged in patients with multiple sclerosis (MS) and linked to periventricular remyelination failure. Atrophied T2-lesion volume (aT2-LV), a promising neurodegenerative imaging marker in progressive MS (PMS), reflects the volume of periventricular lesions subsumed into cerebrospinal fluid over the follow-up. METHODS: In a cohort of 143 people with relapsing-remitting MS (RRMS) and 53 with PMS, we used 3T magnetic resonance imaging (MRI) to quan…

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter.

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-monthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotrop…

Real-world evidence of ocrelizumab in Chilean patients with multiple sclerosis.

BACKGROUND: Real-world studies are needed to expand our knowledge concerning populations underrepresented in clinical trials. OBJECTIVE: This study aimed to evaluate the safety and effectiveness of ocrelizumab in Hispanic/Latino people with multiple sclerosis (pwMS). METHODS: Prospective longitudinal observational study including pwMS who received at least one dose of ocrelizumab between June 2018 and October 2023. RESULTS: A total of 305 pwMS (223 relapsing-remitting MS (RRMS), 29 secondary progressive MS (SPMS), and 53 primary progressive MS (PPMS)), 67% female, mean age 38.7, mean diseas…

Central nervous system-specific antinuclear antibodies in patients with multiple sclerosis.

BACKGROUND: Nuclear antigen released from central nervous system (CNS) cells undergoing destruction may induce production of antinuclear antibodies (ANA). We characterized the CNS-specific production of ANA in multiple sclerosis (MS). METHODS: We assessed CNS-ANA binding to mouse cerebellar cell nuclei by immunofluorescence assay (IFA) with sera from 104 MS patients (91 relapsing-remitting; 13 secondary progressive), 30 patients with neuromyelitis optica spectrum disorders (NMOSD), and 30 healthy controls (HCs). Conventional ANA (cANA) was detected by IFA using human epithelial type-2 cells. …

The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review.

Multiple sclerosis (MS), is a chronic disease of the central nervous system (CNS) characterized by loss of motor and sensory function, that results from immune-mediated inflammation, demyelination and subsequent axonal damage. MS is one of the most common causes of neurological disability in young adults. Several variants of MS (and CNS demyelinating syndromes in general) have been nowadays defined in an effort to increase the diagnostic accuracy, to identify the unique immunopathogenic profile and to tailor treatment in each individual patient. These include the initial events of demyelinatio…

[A little known cause of chronic renal insufficiency in the adult: systemic tuberous sclerosis].

BACKGROUND: Angiomyolipomas and renal cysts are commonly observed in patients with systemic tuberous sclerosis. Hemorrhagic complications related to the angiomyolipomas are well known. CASE REPORT: A 63-year old woman was hospitalized for severe chronic renal failure. Physical examination revealed skin manifestations of systemic tuberous sclerosis, which the patient had hidden to date. The radiographic work-up demonstrated complete disorganization of the renal parenchyma in both kidneys due to multiple cysts and angiomyolipomas. DISCUSSION: Chronic renal failure can be the inaugural manifest

Изучение перспективной роли нейрофильтров и SEMA3A в многоразовом склерозном прогрессе.

Переход от многократного склероза (RRMS) с повторным излучением к вторичному прогрессивному множественному склерозу (SPMS) характеризуется увеличением нейродегенеративного компонента. Определение биомаркеров, которые отличают эти стадии заболевания, имеет решающее значение для ранней диагностики и оптимизации лечения. Цель этого исследования заключалась в сопоставлении уровней сыворотки програнулина, интерлейкина-6 (IL-6), семафорина 3А (SEMA3A) и нейрофильмов между пациентами RCMS и SPMS, а также в изучении их корреляции с клиническими характеристиками, включая инвалидность, измеряемую по рас

Совпадение в аннотации оригинала
The transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is characterized by an increasing neurodegenerative component. Identifying biomarkers that distinguish these disease stages is crucial for early diagnosis and treatment optimization. This study aimed to compare serum levels of progranulin, int…

Extracellular miR-145, miR-223 and miR-326 expression signature allow for differential diagnosis of immune-mediated neuroinflammatory diseases.

BACKGROUND: Although misdiagnosis of neuromyelitis optica spectrum disorder (NMOSD) with neuropsychiatric systemic lupus erythematosus (NPSLE) or multiple sclerosis (MS) is not infrequent, reliable biomarkers remains an unmet need. Extracellular microRNAs (miRNAs) represent a worthy avenue to identify biomarkers for differential diagnosis. We aimed to explore the potential role of some selected circulating miRNAs as biomarkers for the differential diagnosis in immune-mediated neuroinflammatory diseases. METHODS: A total of 80 subjects were enrolled in the present study, including 37 patients …

The Role of Lifestyle Factors in Multiple Sclerosis: An Integrative Perspective.

Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder characterized by inflammation, demyelination, and progressive neurodegeneration. While genetic susceptibility contributes to disease risk, a growing body of evidence highlights the crucial role of modifiable lifestyle factors in influencing MS onset, disease activity, progression, and overall quality of life. In this narrative review, we explored the relevant literature from commonly used datasets (PubMed, Scopus, Google Scholar), using search terms such as "Lifestyle and Multiple Sclerosis", "Diet and Multiple Scleros…

Hemodynamic patterns of chronic cerebrospinal venous insufficiency in multiple sclerosis. Correlation with symptoms at onset and clinical course.

AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS). CCSVI is detected by transcranial and extracranial color-Doppler high-resolution examination (TCCS-ECD) and venography that permit to identify five types of venous malformations and four major (A-D) hemodynamic patterns of anomalous extracranial-extravertebral venous outflow. We investigated possible correlation between such hemodynamic patterns and both the symptoms at onset and clinical course in patients with MS and CCSVI. METHODS: TCCS-ECD, selective venography and clinical records of 65 pa…

Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades: A Nationwide Population-Based Cohort Study in Sweden.

IMPORTANCE: Clinicians' experience and findings from recent natural history studies suggest that multiple sclerosis (MS) may now be running a more slowly progressing course than before. OBJECTIVE: To investigate whether the risk of reaching MS disability milestones has changed over the last decade in Sweden. DESIGN, SETTING, AND PARTICIPANTS: A nationwide population-based retrospective cohort study. By April 2017, 12 512 patients with available information on demographics, MS phenotype, and date of MS onset and diagnosis were registered in the Swedish MS Registry of which 7331 patients with …