NeurologyPEM-relevant

Neuroinflammation

174 studies in the atlas

Neuroinflammation has emerged as a significant area of ME/CFS research, supported by PET imaging studies showing elevated microglial activation in patients relative to healthy controls. Brain imaging, including MRI and functional connectivity studies, has documented structural and functional abnormalities in multiple brain regions. Central nervous system involvement may help explain cognitive impairment, sensory sensitivity, and the characteristic post-exertional symptom worsening seen in ME/CFS. Research in this area explores the relationship between peripheral immune dysfunction, central nervous system inflammation, and the neurological symptom profile of the illness.

What we know

PET imaging studies have detected microglial activation in some ME/CFS patients, particularly in regions associated with cognition and autonomic function
Reduced cerebral blood flow during upright posture has been replicated across multiple studies
Cognitive dysfunction (brain fog) is one of the most commonly reported symptoms and correlates with functional impairment
Neurological symptoms including sensory sensitivity, headache, and poor concentration are reported by a majority of patients

What remains uncertain

Whether microglial activation is a primary driver or a downstream consequence of systemic inflammation
Peripheral immune signals may cross the blood-brain barrier and trigger central neuroinflammation
Small fiber neuropathy, found in a subset of patients, may contribute to both neurological and autonomic symptoms
Whether neuroimaging findings correlate with symptom severity remains unclear — sample sizes have been small

What is emerging

The precise mechanisms linking systemic immune activation to CNS inflammation
Whether anti-neuroinflammatory treatments could benefit ME/CFS patients
The relationship between neuroinflammation and cognitive impairment at the cellular level
Whether neuroinflammation patterns differ between post-infectious and gradual-onset ME/CFS

Start here

E0 ConsensusPEM required

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.

Kim, Do-Young, Youn, Jaeyoung, Kang, Naeun et al.·Journal of translational medicine·2026

This study looked at how treating the connection between the brain and gut might help people with ME/CFS and Long COVID. Researchers reviewed eight previous studies testing different treatments—including special nerve stimulation and probiotics—and also followed one patient who improved with a type of needle stimulation. Many of these treatments showed promise in reducing fatigue and post-exertional malaise, possibly by helping restore healthy gut bacteria and reduce brain inflammation.

Research Momentum

171 publications over 28 years. Recent trend: steady (15/year over the last 3 years).

Top Studies

60 of 174, sorted by evidence level and year

Neuroinflammation

What we know

What remains uncertain

What is emerging

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.

Research Momentum

Top Studies

Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Aetiology and Potential Treatments.

Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

The microbiota-gut-brain axis in myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review of an emerging field.

Brain-regional characteristics and neuroinflammation in ME/CFS patients from neuroimaging: A systematic review and meta-analysis.

Microglia and Sleep Disorders.

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?

Animal Models for Neuroinflammation and Potential Treatment Methods.

Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings.

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease.

Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data.

Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation.

The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.

Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.

A systematic scoping review and conceptual analysis of new-onset fibromyalgia manifestations after non-hospitalized COVID-19: empirics, definitions, methodologies, pathophysiology, mapping of literature, and knowledge gaps.

Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management.

Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.

Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID.

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.

[Long COVID - neurological or somatoform disease?].

Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions.

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.

Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities.

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome.

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

Autoantibodies associated with psychiatric disorders.

The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial.

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

Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling.

Free-water-corrected diffusion and adrenergic/muscarinic antibodies in myalgic encephalomyelitis/chronic fatigue syndrome.

Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage.

Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy.

Hyperintense sensorimotor T1 spin echo MRI is associated with brainstem abnormality in chronic fatigue syndrome.

The neuroinflammatory hypothesis of chronic fatigue syndrome/myalgic encephalomyelitis: an update

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

Spinal fluid abnormalities in patients with chronic fatigue syndrome.

Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.

Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to long COVID.

Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection.

Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways.

Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.

Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.

In Schizophrenia, Chronic Fatigue Syndrome- and Fibromyalgia-Like Symptoms are Driven by Breakdown of the Paracellular Pathway with Increased Zonulin and Immune Activation-Associated Neurotoxicity.

Exercise modifies glutamate and other metabolic biomarkers in cerebrospinal fluid from Gulf War Illness and Myalgic encephalomyelitis / Chronic Fatigue Syndrome.

Kynurenine metabolites and ratios differ between Chronic Fatigue Syndrome, Fibromyalgia, and healthy controls.

Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls.

Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome.

In transfusion-dependent thalassemia, neuronal damage biomarkers are associated with affective and chronic fatigue symptoms.

Affective and chronic fatigue symptoms are associated with serum neuronal damage markers in Parkinson's disease.

[Association of inflammation and chronic fatigue syndrome in patients with Parkinson's disease].

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium.

In Schizophrenia, Depression, Anxiety, and Physiosomatic Symptoms Are Strongly Related to Psychotic Symptoms and Excitation, Impairments in Episodic Memory, and Increased Production of Neurotoxic Tryptophan Catabolites: a Multivariate and Machine Learning Study.

Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME/CFS.

Immunosenescence-Driven Hemodynamic Dysregulation and Cognitive Impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Integrative Perspective.

Chronic fatigue syndrome induced by environmental toxic exposure: Effects of polyhexamethyleneguanidine phosphate exposure on mitochondrial function and neural health.

Immunomodulatory and locomotor regulations via Diosgenin treatment in lipopolysaccharide-induced chronic fatigue syndrome (CFS)/ depressive despair symptom: an in vivo assessment.

PKM2 accelerated the progression of chronic fatigue syndrome via promoting the H4K12la/ NF-κB induced neuroinflammation and mitochondrial damage.