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PBMC-Humanized Mouse Model for Multical Sclerosis: Изучение неуменные изменения и участие CNS.

Гуманизированная иммунная система (HIS) мыши являются мощными инструментами для изучения функций и дисфункций иммунной системы человека и разработки иммунотерапевтической системы человека. Наличие изощренных штаммов супериммунодефицитной мыши позволило гуманизировать иммунную систему, используя трансплантацию человеческих периферийных моноядерных клеток крови (PBMC) или гематополиетических стволовых клеток. Его мыши широко используются в иммунной онкологии, в то время как проводится меньше исследований в области автономного иммунитета, особенно в области множественного склероза (MS). Используя

Совпадение в аннотации оригинала
Humanized immune system (HIS) mice are powerful tools for studying human immune system function and dysfunction and developing human-specifi … are used extensively in immune-oncology, while there are fewer studies in autoimmunity, especially multiple sclerosis (MS). Using the protocol described here, we generated HIS mice that show key features of MS not represented in other widely used MS models [1]. Severely immunodeficient NOD.Cg-B2mem1Tac Prkdcscid Il2rgtm1Sug /JicTac (B2m-NOG) mice, which lack murine …

TSPO PET в множестве склерозов: новые знания в патофизиологии, прогнозе и мониторинге лечения.

Множественный склероз (MS) — хроническое аутоиммунное заболевание центральной нервной системы (CNS), характеризующееся воспалением, обезвоживанием и нейродегенерацией. Белок транслокатора 18 кДа (TSPO) перевыражается на активированном микроглии, ключевом посреднике острой и хронической воспаления в MS. Позитронная томография выбросов (PET), ориентированная на TSPO, позволяет вживо обнаруживать микроглиальную активацию в MS, выявляя высокую долю повреждений активных белых веществ (WM). Она также обнаруживает значительную врожденную иммунную активацию в обычно встречающемся белом веществе (NAWM)

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and neurodegeneration. The 18 kDa translocator protein (TSPO) is overexpressed on activated microglia, a key mediator of acute and chronic inflammation in MS. Positron emission tomography (PET) targeting TSPO enables in viv…

Activation of Kir4.1 Channels by 2-D08 Promotes Myelin Repair in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease that leads to myelin loss and neurological dysfunction. Clinical studies show increased anti-Kir4.1 antibody levels in MS patients' serum, indicating its diagnostic potential. However, the specific mechanism has remained elusive. In a mouse model of experimental autoimmune encephalomyelitis (EAE), it is found that impaired Kir4.1 channels in oligodendrocyte precursor cells (OPCs) hindered myelin repair in the spinal cord. Using a thermal shift assay (TSA), the small molecule 2-D08 is identified, which effectively activated Kir4.1 channe…

Агрессивная внутричерепная менингиома, связанная с множественным склерозом.

Менингиомы являются наиболее распространенными первичными опухолями центральной нервной системы (КНС) и часто требуют радиационной терапии (RT), которая может привести к возникновению таких осложнений, как вызванное радиацией обезвоживание. В настоящем исследовании описывается случай с 40-летним пациентом мужского пола, у которого появились демиелионирующие повреждения после РТ в случае менингиомы первого класса ВОЗ, в конечном счете диагностированной с помощью MS. Это состояние имеет клинические и радиологические особенности с множественным склерозом, в том числе повреждения олигодендроцитов,

Совпадение в аннотации оригинала
Meningiomas are the most common primary tumors of the central nervous system (CNS) and often require radiation therapy (RT), which can lead … ngioma, ultimately diagnosed with MS. This condition shares clinical and radiological features with multiple sclerosis, including damage to oligodendrocytes, which are the cells responsible for myelination in the CNS, cognitive impairment, motor dysfunction, and white matter abnormalities on magnetic resonance imaging (MRI). Distinguishing between radiation-induced …

Роль знака центральной вены в управлении множественным склерозом: систематический обзор литературы.

ВВЕДЕНИЕ: Множественный склероз (MS) известен как воспалительное заболевание центральной нервной системы (CNS), при этом его типичными нейропатологическими характеристиками являются демиелингирующие повреждения белых веществ, относительное сохранение аксонов и астроглиоз. Хотя критерии диагностирования MS регулярно обновляются, два основных элемента остаются неизменными: обязательное доказательство распространения патологических повреждений как во времени, так и в пространстве. Однако не все презентации ясны, и иногда возникают сомнения относительно диагноза. Знак центральной вены (CVS) предст

Совпадение в аннотации оригинала
INTRODUCTION: Multiple sclerosis (MS) is known to be an inflammatory disease of the central nervous system (CNS), with its typical neuropathological characteristics being demyelinating white matter lesions, relative preservation of axons, and astrogliosis. Although the criteria for MS diagnosis have been regularly updated, two main elements have remained unc…

Teriflunomide in pediatric patients with relapsing multiple sclerosis: Open-label extension of TERIKIDS.

BACKGROUND: The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension. METHODS: In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg adult-equivalent dose) for ⩽ 96 weeks. Participants received teriflunomide for ⩽ 192 weeks post-randomization in the open-label extension. RESULTS: The mean age at screening was 14.6 years. For teriflunomide/teriflunomide versus placebo/teriflun

Diagnosis of multiple sclerosis using optical coherence tomography supported by explainable artificial intelligence.

BACKGROUND/OBJECTIVES: Study of retinal structure based on optical coherence tomography (OCT) data can facilitate early diagnosis of relapsing-remitting multiple sclerosis (RRMS). Although artificial intelligence can provide highly reliable diagnoses, the results obtained must be explainable. SUBJECTS/METHODS: The study included 79 recently diagnosed RRMS patients and 69 age matched healthy control subjects. Thickness (Avg) and inter-eye difference (Diff) features are obtained in 4 retinal layers using the posterior pole protocol. Each layer is divided into six analysis zones. The Support Vec…

Two Cases of Acute Diverticulitis Following Ocrelizumab Infusion in Patients With Multiple Sclerosis.

Ocrelizumab is an anti-CD20 monoclonal antibody used to treat primary progressive and relapsing-remitting multiple sclerosis. Several prior case reports have demonstrated colitis in association with ocrelizumab infusion, and one case report has shown ocrelizumab-associated diverticulitis. We report on two cases in which ocrelizumab treatment of multiple sclerosis was complicated by acute diverticulitis. A 50-year-old woman and a 41-year-old man, both with relapsing-remitting multiple sclerosis, presented with acute abdominal pain. One patient had no known gastrointestinal history while the oth…

Causal relationship between thyroid function and multiple sclerosis: A bidirectional Mendelian randomization study.

An association between thyroid function and multiple sclerosis (MS) has been reported in several observational studies, but the causal relationship between them is still unclear. Thus, this study used a bidirectional Mendelian randomization (MR) to investigate the associations between thyroid function and MS. Bidirectional MR was used to explore the causal relationship between thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [FT4], hyperthyroidism, and hypothyroidism) and MS. Genome-wide association study (GWAS) data of thyroid function and MS were obtained from the ThyroidO…

Cognitive function influences cognitive-motor interference during dual task walking in multiple sclerosis.

BACKGROUND: Both physical and cognitive impairments are common in people with multiple sclerosis (PwMS). Performing a cognitive task while walking (i.e., dual-task walking) can introduce cognitive-motor interference (CMI), resulting in changes in walking performance. The association between the levels of cognitive impairment and of CMI in MS remains unclear. OBJECTIVES: To examine the association between cognitive functioning and differences in walking performance arise between single- and dual-task walking. METHODS: Ninety-five PwMS performed self-preferred pace walking and dual-task walkin…

Predictive factors and treatment challenges in malignant progression of relapsing-remitting multiple sclerosis.

OBJECTIVE: Our objective was to uncover the predictive factors that can help anticipate the malignant progression of individuals with Relapsing-Remitting Multiple Sclerosis (RRMS). Additionally, we sought to analyze and compare the response to treatment between patients with benign and malignant forms of RRMS. METHODS: This cohort study included RRMS patients categorized as benign (≥10 years since disease onset, Expanded Disability Status Scale (EDSS) ≤ 1) or malignant (≤5 years since disease onset, EDSS ≥6). Patients' data, including demographics, medical history, treatment, and MRI (Magneti…

Cost avoidance from health system specialty pharmacist interventions in patients with multiple sclerosis.

BACKGROUND: Specialty pharmacists monitor patients taking multiple sclerosis (MS) disease-modifying therapies (DMTs) to evaluate response to therapy and intervene on adverse effects. These interventions have the potential to avoid health care costs by discontinuing inappropriate therapies and avoiding downstream health care utilization. OBJECTIVE: To calculate the costs avoided by specialty pharmacist interventions in MS. METHODS: A retrospective observational cohort study including patients at the Vanderbilt MS Clinic who received a specialty pharmacist intervention between February 1, 2022…

Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis.

Among the intrathecal inflammatory niches where compartmentalized inflammation persists and plays a pivotal role in progressive multiple sclerosis (MS), choroid plexus (CP) has recently received renewed attention. To better characterize the neuropathological/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post-mortem pathologically confirmed MS and 10 healthy do…

An AQP-4-IgG-Positive Patient with Neuroimaging Findings Suggestive of Multiple Sclerosis.

BACKGROUND Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs) are 2 similar but distinct diseases. These diseases were difficult to distinguish from each other until aquaporin-4-IgG (AQP-4-IgG) was discovered. The accurate identification of these 2 diseases is crucial for appropriate drug treatment in clinical practice. Herein, we report a case of AQP-4-IgG seroconversion with magnetic resonance imaging (MRI) findings suggestive of MS. CASE REPORT A 54-year-old woman developed weakness in her right lower extremity that gradually returned to normal 4 years ago. Recentl…

AI-assisted assessment of fall risk in multiple sclerosis: A systematic literature review.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease that can increase the risk of falls in patients due to various factors. Traditional clinical assessments may not effectively identify those at risk of falling. OBJECTIVE: This study aimed to use artificial intelligence and machine learning techniques to predict the likelihood of falls in patients with MS based on a review of previous research. METHODS: A systematic review was conducted following PRISMA guidelines, searching electronic databases from 1990 to 2024. Data extraction and quality assessment were carried out. RESULTS: Se…

Gut microbial factors predict disease severity in a mouse model of multiple sclerosis.

Gut bacteria are linked to neurodegenerative diseases but the risk factors beyond microbiota composition are limited. Here we used a pre-clinical model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), to identify microbial risk factors. Mice with different genotypes and complex microbiotas or six combinations of a synthetic human microbiota were analysed, resulting in varying probabilities of severe neuroinflammation. However, the presence or relative abundances of suspected microbial risk factors failed to predict disease severity. Akkermansia muciniphila, often as…

Optic nerve topography in multiple sclerosis diagnostic criteria: Existing knowledge and future directions.

Current diagnostic criteria for multiple sclerosis (MS) do not consider the optic nerve as a typical topography for establishing the diagnosis. Recent studies have proved the utility of optic nerve magnetic resonance imaging, optical coherence tomography and visual evoked potentials in detecting optic nerve lesions during the early stages of MS. In addition, emerging evidence supports the inclusion of optic nerve topography as a fifth region to fulfil the dissemination in space criteria. Anticipating a modification in the McDonald criteria, it is crucial for neurologists to familiarize with th…

Genetic susceptibility and causal pathway analysis of eye disorders coexisting in multiple sclerosis.

INTRODUCTION: The comorbidity of optic neuritis with multiple sclerosis has been well recognized. However, the causal association between multiple sclerosis and optic neuritis, as well as other eye disorders, remains incompletely understood. To address these gaps, we investigated the genetically relationship between multiple sclerosis and eye disorders, and explored potential drugs. METHODS: In order to elucidate the genetic susceptibility and causal links between multiple sclerosis and eye disorders, we performed two-sample Mendelian randomization analyses to examine the causality between mu…

Roflumilast: Modulating neuroinflammation and improving motor function and depressive symptoms in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease causing central nervous system demyelination, often associated with depression. Current treatments for MS do not effectively address both physical disability and depression. Roflumilast, a phosphodiesterase-4 inhibitor with anti-inflammatory properties, has shown promise for autoimmune diseases. METHODS: We used an experimental autoimmune encephalomyelitis (EAE) rat model to study roflumilast's effects. Motor dysfunction and depression symptoms were assessed, and histopathological analysis evaluated its anti-inflammatory properties.…