Результаты поиска

HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity.

Research of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance and etiology. Despite prior detection of human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value of HERV expression profiles for their diagnosis, and the relationship of HERV expression profiles with patient immune systems and symptoms had remained unexplored. By using HERV-V3 high-density microarrays (including over 350k HERV elements and more than 1500…

Clinical Features and Outcomes of Glutamic Acid Decarboxylase-65 Antibody-Associated Pure Cerebellar Ataxia and Stiff Person Syndrome Spectrum Disorders: A Single-Center Cohort Study.

BACKGROUND: Cerebellar ataxia is associated with greater disability in glutamic acid decarboxylase-65 (GAD65) antibody-associated neurologic … ded into two groups based on cerebellar dysfunction in the presence (SPSD; SPS-plus and progressive encephalomyelitis with rigidity and myoclonus [PERM]) or absence (pure cerebellar ataxia [pCA]) of classic SPS features. Clinical and paraclinical findings were analyzed descriptively. RESULTS: Seventy-two patients were selected among 356 (62 SPSD, 10 pCA). Mean age …

Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies.

OBJECTIVE: We sought to characterize the sixth most common finding in our neuroimmunological laboratory practice (tissue assay-observed uncl … ed assay (5/5 performed). Clinical accompaniments were: encephalitis, 6; brainstem encephalitis, 2; encephalomyelitis, 2; cerebellar ataxia, 2; longitudinally extensive transverse myelitis (LETM), 2; sensory neuronopathy, 1; peripheral neuropathy, 4, and movement disorders, 2. Inflammatory MRI abnormalities were identified in 5/16 patients (31%) with CNS disorders: …

Картирование CD4+T разнообразия клеток в CSF для выявления эндофенотипов множественного склероза.

Множественный склероз (MS) является хроническим подстрекательским заболеванием CNS с разнородными проявлениями. В настоящее время изучается вопрос о перспективных маркерах для ранней классификации НР. Более высокое диагностическое разрешение цереброспинной жидкости (CSF) может в значительной степени способствовать стратификации пациента, что должно иметь особенно важное значение для подгруппы пациентов с высоким риском перехода на курс прогрессивных заболеваний. Цель этого исследования состояла в том, чтобы определить, может ли спектральная цитометрия клеток CSF идентифицировать патогенный под

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory CNS disease with heterogeneous manifestation. Prognostic markers for early classification … MS and our own single-cell RNA sequencing (scRNA-seq) in acute and chronic experimental autoimmune encephalomyelitis (EAE), a murine MS model. Notably, chronic ('phase') markers such as Il7r and Ramp3 (associated with memory T cells), Itgb1 (integrin beta-1) and anti-apoptotic genes like Dnaja1, Hsph1 and Jun/AP-1 were enriched in EAE. These markers reflect pro-su …

Comparative Analysis of Genetic Risk for Viral-Induced Axonal Loss in Genetically Diverse Mice.

Among mouse models of neurological disease, Theiler's murine encephalomyelitis virus (TMEV) provides a unique platform by using a naturally occurring viral trigger, paralleling the role of infections like Epstein-Barr virus in multiple sclerosis (MS). Just as not all individuals with predisposing viral infections develop the same neurological disease, not all mouse strains develop the same diseases following TMEV infection, so susceptibility is dictated by genetic background. For example, certain sets of alleles, called haplotypes, of the major histocompatibility complex (MHC) region have been…

Unlocking dexmedetomidine's therapeutic potential in multiple sclerosis: Dual modulation of PI3K/Akt/BDNF and TLR4/NF-κB pathways in EAE rats.

Multiple sclerosis (MS) is an enduring autoimmune and neurodegenerative disease affecting the central nervous system with inflammation, demyelination, and axonal degeneration that progresses to neurological impairment. Despite available treatments, their limited efficacy, inability to promote remyelination, and associated adverse reactions highlight the need for unconventional therapies. This study investigated the therapeutic potential of dexmedetomidine (DEX), a selective α2-adrenergic receptor (α2AR) agonist, in a rat model of MS triggered by experimental autoimmune encephalomyelitis (EAE).…

Изменение баланса иммунитета: формирующаяся роль селективных модуляторов рецепторов эстрогена в иммунитете и автоматическом иммунитете.

Селективные модуляторы рецепторов эстрогенов (SERM) представляют собой специфические для тканей и контекста регуляторы сигнала эстрогенных рецепторов (ER), первоначально разработанные для лечения рака груди и остеопороза. Растущее признание роли ERα и ERβ в модуляции развития иммунных клеток, терпимости, воспаления и противовирусной защиты привело к росту интереса к ERM как к потенциальной терапии аутоиммунных заболеваний. В настоящем обзоре резюмируются текущие механистические, предклинические и клинические данные о СЕРМ и связанных с ними ОВП агентах в аутоиммунных и иммунных условиях. Докли

Совпадение в аннотации оригинала
Selective estrogen receptor modulators (SERMs) are tissue- and context-specific regulators of estrogen receptor (ER) signaling, originally d … lerosis, ERα-dependent mechanisms mediate estradiol's protective effects in experimental autoimmune encephalomyelitis (EAE), illustrating the broader immunologic relevance of estrogen pathways. Given the high burden of glucocorticoid exposure, premature ovarian insufficiency, and osteoporosis among individuals with autoimmune diseases, SERMs may offer dual benefit …

Evodiamine inhibits NLRP3 inflammasome-mediated microglial pyroptosis and promotes remyelination via SLC2A4-regulated autophagy.

BACKGROUND: Activation of the NLRP3 inflammasome triggers pyroptosis, a pro-inflammatory type of cell death, in multiple sclerosis (MS). Evodiamine (EVO) possesses anti-inflammatory and neuroprotective properties; however, its potential molecular and signaling pathways in MS remain to be elucidated. This study aimed to explore the therapeutic potential of EVO for remyelination in MS and elucidated its underlying mechanisms. METHODS: We utilized cuprizon (CPZ)/experimental autoimmune encephalomyelitis (EAE)-induced demyelinated mice and lipopolysaccharide+adenosine triphosphate (LPS+ATP)-induc…

A Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets.

OBJECTIVE: X-linked adrenoleukodystrophy (ALD) is caused by mutations in ABCD1, a peroxisomal gene. More than half of males with an ABCD1 mu … ype in Abcd1-knockout mice using a 2-hit method that combines cuprizone and experimental autoimmune encephalomyelitis models. We then used magnetic resonance imaging (MRI) and immunohistochemistry to assess the fidelity of cALD molecular markers in the mice. RESULTS: Human and mouse cALD lesions shared histologic features of myelin phagocytosis, myelin loss, abund …

Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.

BACKGROUND: Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients. METHODS: 15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; B…

Longitudinal Progression of Patients with Long COVID Treated in a Post-COVID Clinic: A Cross-Sectional Survey.

BACKGROUND: In addition to the morbidity and mortality associated with acute infection, COVID-19 has been associated with persistent symptoms (>30 days), often referred to as Long COVID (LC). LC symptoms often cluster into phenotypes, resembling conditions such as fibromyalgia, postural orthostatic tachycardiac syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). LC clinics have been established to best address the needs of LC patients and continuity of care. We developed a cross-sectional survey to assess treatment response through our LC Clinic (LCC). METHODS: A…

TNFR2 signaling in oligodendrocyte precursor cells suppresses their immune-inflammatory function and detrimental microglia activation in CNS demyelinating disease.

Multiple Sclerosis (MS) is a chronic degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, … ve TNFR2 ablation in OPCs, we observed an earlier onset and disease peak in experimental autoimmune encephalomyelitis (EAE). This was associated with accelerated immune cell infiltration and increased microglia activation in the spinal cord. Similarly, PdgfrαCreERT:Tnfrsf1bfl/fl:Eyfp mice showed rapid and increased microglia reactivity compared to control mice in t …

Does E-learning Facilitate Medical Education in Pediatric Neurology?

BACKGROUND: E-learning has become commonplace in medical education. Incorporation of multimedia, clinical cases, and interactive elements ha … positive change for Duchenne muscular dystrophy, childhood absence epilepsy, and acute disseminated encephalomyelitis. Learning topics showed statistical relationship to post-test scores (p = 0.04). Depending on topic, 57-92% (N = 59-66) of respondents favored e-learning over review article learning. CONCLUSIONS: Ebrain users scored higher on post-tests than revie …

Severe and rare neurological manifestations following COVID-19 infection in children: A Malaysian tertiary centre experience.

INTRODUCTION: Since the emergence of COVID-19, we have experienced potent variants and sub-variants of the virus with non-specific neurologi … l findings, two of them had febrile infection-related epilepsy syndrome, two had acute disseminated encephalomyelitis, two had acute necrotising encephalopathy of childhood, one each had hemiconvulsion-hemiplegia-epilepsy syndrome, acute encephalopathy with bilateral striatal necrosis, hemi-acute encephalopathy with biphasic seizures and reduced diffusion, infectio …

Co-modulation of TNFR1 and TNFR2 in an animal model of multiple sclerosis.

BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine and master regulator of the immune system. It acts through two receptors … 1 whilst simultaneously stimulating TNFR2 in a mouse model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced with myelin oligodendrocyte glycoprotein (MOG35-55) in humanized TNFR1 knock-in mice. These were treated with a human-specific TNFR1-selective antagonistic antibody (H398) and a mouse-specific TNFR2 agonist (EHD2-sc-mTNFR2), both i …

Amyloid processing in COVID-19-associated neurological syndromes.

SARS-CoV-2 infection can damage the nervous system with multiple neurological manifestations described. However, there is limited understanding of the mechanisms underlying COVID-19 neurological injury. This is a cross-sectional exploratory prospective biomarker cohort study of 21 patients with COVID-19 neurological syndromes (Guillain-Barre Syndrome [GBS], encephalitis, encephalopathy, acute disseminated encephalomyelitis [ADEM], intracranial hypertension, and central pain syndrome) and 23 healthy COVID-19 negative controls. We measured cerebrospinal fluid (CSF) and serum biomarkers of amyloi…

Can SARS-CoV-2 trigger new onset of autoimmune disease in adults? A case-based review.

INTRODUCTION: Although it has been proposed that SARS-CoV-2 can cause autoimmunity by inducing a transient immunodeficiency of both innate a … , autoimmune haemolytic anemia, latent autoimmune diabetes in adults, myositis, acute demyelinating encephalomyelitis, autoimmune encephalitis, central nervous system vasculitis, and autoimmune thyroid diseases. CONCLUSION: SARS-CoV-2 can trigger new onset of a variety of autoimmune diseases. Doctors who take care patients infected by COVID-19 must be aware of the …

Neurological and Neuroradiological Patterns with COVID-19 Infection in Children: A Single Institutional Study.

Background  Varied neurological manifestations in pediatric patients with coronavirus disease 2019 (COVID-19) have been increasingly reporte … nfection. Postinfectious immune-mediated cauda equina nerve root enhancement or acute demyelinating encephalomyelitis-like brain imaging, followed by small acute infarcts and hippocampal/thalamic signal changes were most common imaging patterns. We found overlapping neurological and MRI patterns in many children, suggesting that various pathophysiological mechanism …

Nanoparticle-mediated targeting of autoantigen peptide to cross-presenting liver sinusoidal endothelial cells protects from CD8 T-cell-driven autoimmune cholangitis.

Autoimmune diseases are caused by adaptive immune responses to self-antigens. The development of antigen-specific therapies that suppress disease-related, but not unrelated immune responses in general, is an important goal of biomedical research. We have previously shown that delivery of myelin peptides to liver sinusoidal endothelial cells (LSECs) using LSEC-targeting nanoparticles provides effective protection from CD4 T-cell-driven autoimmune encephalomyelitis. Here, we investigated whether this methodology might also serve antigen-specific treatment of a CD8 T-cell-driven autoimmune diseas…

Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome.

CONTEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. OBJECTIVE: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. METHODS: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukud…