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Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study.

BACKGROUND: In recent years, evidence has indicated a metabolic shift towards increased demand for lipids in various lymphoid cell populations from people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We previously screened the mitochondrial function and gene expression of B cell-derived lymphoblastoid cell lines (LCLs) generated from the blood of people with ME/CFS to characterise a model for hypothesis discovery and testing, observing elevated expression of gene products facilitating amino acid and fatty acid degradation for energy. METHOD: In this follow-up study we hav…

Deficient TRPM3-linked mitochondrial Ca2+ influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome.

INTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic illness, commonly associated with dysregulation of the immune system including reduced cytotoxicity of natural killer (NK) cells and post-exertional neuroimmune exhaustion. Previously, transient receptor potential melastatin 3 (TRPM3) ion channel impairment associated with reduced Ca2+ mobilisation in NK cells from ME/CFS patients was reported. To further explore the pathomechanisms involved in ME/CFS, we investigated the downstream impact of TRPM3 ion channel dysfunction on mitochondrial Ca2+ mobilisa…

Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics.

Human endogenous retroviruses (HERVs) are potential driving forces of the pathophysiology of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), linking post-infectious immune dysfunction to chronic inflammation and immune and neurocognitive dysfunction that are hallmark features of ME/CFS. Accumulating evidence from related autoimmune diseases and cancers has shown that reactivated HERVs can contribute to disease pathogenesis by amplifying immune activation through viral protein-mediated innate sensing, long terminal repeat (LTR)-driven transcription, and disrupting epigenetic silenc…

Chronic stress and cognitive dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: HPA axis dysregulation and hippocampal plasticity.

Cognitive dysfunction is a common and disabling clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), often described by patients as "brain fog." These symptoms typically manifest as difficulties in attention, memory, and concentration. Chronic stress has been proposed as an important contributing factor in ME/CFS. The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response, and prolonged adverse stress may contribute to HPA axis dysregulation, including altered cortisol rhythmicity and impaired negative feedback regulation. Such dysregu…

Myelin Oligodendrocyte Glycoprotein (MOG) Antibody-Associated Disease Presenting as Acute Disseminated Encephalomyelitis Following COVID-19 mRNA Vaccination.

Acute disseminated encephalomyelitis (ADEM) is a rapidly progressive autoimmune demyelinating condition that primarily affects the central nervous system. The exact pathogenesis is not well understood, but current literature suggests roles for both environmental triggers and genetic predispositions. Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an increasingly recognized autoimmune demyelinating disorder that can present with an ADEM-like phenotype, particularly in adults. We report the case of a 53-year-old Asian-American female patient of Taiwanese ancestry with …

Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion-Based Neuroinflammation Imaging Study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder with suspected neuroinflammatory pathophysiology. However, previous diffusion tensor imaging (DTI) studies have reported inconsistent white matter abnormalities in ME/CFS, and specific white matter inflammatory changes remain poorly characterised. This study employed an advanced diffusion-based neuroinflammation imaging (NII) model to investigate white matter neuroinflammation in ME/CFS. Diffusion MRI data from 67 ME/CFS patients (median age, 38; and 54 women) and 67 rigorously matched healthy controls (HCs)…

Эпигенетическая ось Лактата-H4K12la-HDAC1 регулирует переход к микроглиальному состоянию во время экспериментального аутоиммунного энцефаломиелита у женских мышей.

Микроглиальная функциональная пластичность формируется метаболическим и эпигенетическим перепрограммированием, но то, как эти процессы регулируют автоиммунитет центральной нервной системы, остается неясным. Мы находим, что уровень цереброспинарной жидкости лактат коррелирует с множественным склерозом. Используя женские модели мыши экспериментального аутоиммунного энцефаломиэлита, аккумуляция спинного лакта приводит к стойкой микроглиальной гистоне лактилации, связывающей с гликолитической активацией. Микроглиавое исключение лактата дегидрогеназы А уменьшает эту лактиляцию и усугубляет остроту

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Microglial functional plasticity is shaped by metabolic and epigenetic reprogramming, but how these processes regulate central nervous system autoimmunity remains unclear. We find that cerebrospinal fluid lactate levels correlate with multiple sclerosis severity. Using female mouse models of experimental autoimmune encephalomyelitis, spinal lactate accumulat…

Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise.

Post-exertional malaise (PEM) is a defining symptom of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its molecular underpinnings remain elusive. This study investigated the temporal-longitudinal DNA methylation changes associated with PEM using a structured two-day maximum repeated effort cardiopulmonary exercise testing (CPET) protocol involving pre- and two post-exercise blood samplings from five ME/CFS patients. Cardiopulmonary measurements revealed complex heterogeneous profiles among the patients compared to typical healthy controls, and VO2 peak indicated all patients …

Under-Served Groups and Myalgic Encephalomyelitis Research Workshop; Multiple Barriers to Effective Healthcare, Research and Public Participation.

Public involvement in research and other initiatives for myalgic encephalomyelitis (ME) (also known as chronic fatigue syndrome) has been crucial in raising awareness of the disease and exposing inadequate healthcare and research funding. An online workshop on ME research and under-served groups took place in July 2024, organised by the first author, a person with ME. The workshop illustrated very low prevalence and thus barriers to healthcare as well as limited research in people from under-served groups, who appear doubly disadvantaged by their illness and their socioeconomic and/or ethnic b…

Steroid refractory immune-related acute disseminated encephalomyelitis (ADEM) successfully treated with 2nd and 3rd line immunosuppressive therapy.

We describe immune-related acute disseminated encephalomyelitis (ADEM) in a woman in her 60s. This was her third immune-related adverse event (IRAE) secondary to immunotherapy treatment for metastatic melanoma. Initially thought to be intracranial metastatic disease, the diagnosis was reconsidered due to atypical radiological findings. With the persistence and open-minded approach of the wider multidisciplinary team (MDT), a definitive diagnosis of ADEM was reached. Refractory to the conventional management of IRAEs with corticosteroids, the patient was successfully treated with intravenous im…

Heat vs. Fatigue: Hyperthermia as a Possible Treatment Option for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

The aetiology and pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have not yet been clarified. Its exact diagnosis is also difficult because it has no biomarkers. This lack of knowledge leads to difficulties in treating the disease. In our work, we are attempting to counteract this problem by analysing the central cellular mechanisms in ME/CFS patients and comparing them with those of healthy individuals. This pilot study provides a small glimpse into the journey of nine people with ME/CFS-more specifically, how their peripheral blood mononuclear cells (PBMCs) re…

Silent triggers and symmetric peduncles - a rare presentation of adult-onset acute disseminated encephalomyelitis: A case report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM), which is rare, primarily affects children. It usually manifests as acute encephalopathy and multifocal neurological impairments after infection or vaccination. Diagnosis is still difficult due to the clinical and radiological similarity to other central nervous system disorders. Adult-onset ADEM calls for thorough reporting in order to improve diagnosis and treatment. CASE SUMMARY: A 55-year-old man with hypertension had a high fever, intense headache and a steady decline in his neurological function after two weeks. Left facial paralys…

A2 astrocyte polarization mediates ketogenic diet protection of blood-central nervous system barriers in experimental autoimmune encephalomyelitis.

Disruption of the blood–brain barrier and blood-spinal cord barrier is a fundamental pathological feature of multiple sclerosis progression. The ketogenic diet has a high therapeutic potential for patients with multiple sclerosis. We previously reported that treating experimental autoimmune encephalomyelitis mice with ketogenic diet results in anti-neuroinflammation and neuroprotection. However, the impact of ketogenic diet administration on the blood–brain barrier/blood–spinal cord barrier in MS remains unclear. Here, we investigated the effects of ketogenic diet on the blood–brain barrier/bl…

Clinical presentation, MR imaging and outcome in children with myelin oligodendrocyte glycoprotein antibody-negative acute disseminated encephalomyelitis.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) without myelin oligodendrocyte glycoprotein (MOG) antibodies (abs) presents a diagnostic challenge. OBJECTIVE: To investigate whether the diagnosis of MOG-negative (neg) ADEM was confirmed over time and to highlight the clinical and neuroradiological characteristics distinguishing monophasic MOG-neg ADEM from alternative diagnoses. MATERIAL AND METHODS: Children diagnosed with a first clinical episode of MOG-neg ADEM and a dataset including clinical presentation, MRI, CSF studies and at least 3-month follow-up were included. RESULTS: 4…

Case report: A case of anti-glycine receptor encephalomyelitis triggered by post-transplant or COVID-19 infection?

Even though long-term immunosuppressant drugs (ISD) are employed to inhibit immune system activity, enhancing graft functionality and patient survival in solid organ transplantation (SOT), these transplants often lead to immune complications, with post-transplant autoimmune diseases of the central nervous system (CNS) being uncommon. Here, we detail the case of a 66-year-old woman who underwent a renal transplantation 8 months prior, who was admitted with subacute onset of encephalomyelitis, accompanied by headaches, paraplegia, weakness, vomiting, and abdominal pain, with a positive COVID-19 …

Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can be triggered by infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the impact of the coronavirus disease 2019 (COVID-19) pandemic on ME/CFS prevalence is not well characterized. METHODS: In this population-based cross-sectional study, we enrolled a stratified random sample of 9,825 adult participants in the Kaiser Permanente Northern California (KPNC) integrated health system from July to October 2022 to assess overall ME/CFS-like illness prevalence and the proportion th…

Крокин как потенциальный терапевтический агент для множественного склероза: наблюдения от экспериментальной аутоиммунной энцефаломиелита в мышах.

ЦЕЛЬ: Множественный склероз (MS) — широко распространенное аутоиммунное расстройство, характеризующееся нейроинфламмацией и обезвоживанием в центральной нервной системе (CNS), приводящее к неврологической дисфункции. Несмотря на успехи в лечении, сохраняется неудовлетворенная потребность в безопасных и эффективных методах лечения. Крокин, биоактивный состав шафрана, продемонстрировал антивоспалительные и иммунорегулирующие свойства в различных моделях болезней. В этом исследовании изучается терапевтический потенциал крокина в модели MS, экспериментальной аутоиммунной энцефаломиелита (EAE). МЕТ

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OBJECTIVE: Multiple sclerosis (MS) is a prevalent autoimmune disorder characterized by neuroinflammation and demyelination in the central ne … y investigates the therapeutic potential of Crocin in a murine model of MS, experimental autoimmune encephalomyelitis (EAE). METHODS AND RESULTS: Female C57BL/6 mice were induced with EAE and treated with different doses of Crocin. Clinical severity, CNS pathology, T cell proliferation, cytokine production, and transcription factor expression were assessed. Crocin …

Профилактическое управление ПЕПИТЕМ в экспериментальном аутоиммунном энцефаломиелите замедляет начало болезни, предотвращает инфильтрацию лейкоцита и смягчает остроту.

Множественный склероз (MS) представляет собой хроническое, иммунопосредованное неврологическое расстройство, при котором иммунная система ошибочно нападает на миелиновую оболочку, что влияет на связь между мозгом и остальной частью тела. ЦЕЛЬ: В этом исследовании изучалось профилактическое использование пептидного ингибитора трансэндетелиальной миграции (PEPITEM), новичка пептида, в целях смягчения экспериментального аутоиммунного энцефаломиелита (EAE), модели мыши для мультислероза (MS). МЕТОДЫ: Женские мыши C57BL/6 были отнесены к контрольной группе, не обработанной EAE или к группе TEPITEM.

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BACKGROUND: Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder in which the immune system mistakenly attacks the my … r of trans-endothelial migration (PEPITEM), a novel peptide, in alleviating experimental autoimmune encephalomyelitis (EAE), a mouse model for Multiple Sclerosis (MS). METHODS: Female C57BL/6 female mice were assigned to the control, untreated EAE, or PEPITEM group. EAE was induced in mice in the untreated EAE and PEPITEM groups through immunization by injecting a …