Topic

Neuroinflammation

Domain: Neurology

PEM-relevant research

11 studies in the atlas

Brain inflammation and glial activation detected by PET imaging in ME/CFS patients.

What We Know

PET imaging studies from Stanford and Japanese groups found evidence of widespread neuroinflammation in ME/CFS brains, particularly in areas associated with fatigue and cognition. The degree of inflammation correlates with symptom severity.

What We Think

Next-generation PET tracers and MR spectroscopy may provide more specific and accessible neuroinflammation markers. CSF studies are ongoing.

What We Don't Know

PET neuroinflammation findings have not been replicated at scale. The tracer used (PK11195) has limited specificity. It is unknown whether neuroinflammation is causal or downstream of peripheral immune activation.

Studies in this Topic

E0 ConsensusPEM ?Moderate confidenceReviewed

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

Komaroff, Anthony L, Dantzer, Robert·Cell reports. Medicine·2025

This review examines why long COVID and ME/CFS cause such severe, lasting symptoms. Researchers found that both conditions share similar biological problems, including immune system misbehavior, problems with blood vessel function, and issues with how cells produce energy. The study suggests that symptoms may come from both these biological problems and from ancient survival responses in the brain that were meant to protect us during serious illness.

NeuroinflammationGut Microbiome

E0 ConsensusPEM ?Moderate confidenceReviewed

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

Fan, Jin, Jiao, Jiao, Chang, Hai-Qing et al.·Journal of translational medicine·2025

This comprehensive review examines how ME/CFS is diagnosed and treated based on current medical knowledge. The authors found that ME/CFS is caused by problems with the immune system, energy production in cells, and brain inflammation, but there are currently no definitive blood tests to confirm the disease. Treatment options include both medication approaches (targeting immune dysfunction and cell energy) and non-medication strategies like activity pacing and cognitive behavioral therapy, though doctors now recognize that exercise programs can actually harm some patients.

BiomarkersNeuroinflammationImmune Dysregulation

E0 ConsensusPEM ?Moderate confidenceReviewed

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

Bansal, Amolak Singh, Seton, Katharine A, Brooks, Jonathan C W et al.·International journal of molecular sciences·2025

Many ME/CFS patients experience brain fog and difficulty concentrating, which can be as disabling as physical symptoms. This review examined how ongoing low-level inflammation and viral activity in the body may damage thinking and memory by affecting blood flow and nerve function in the brain. The researchers suggest that treating inflammation, controlling viral reactivation, and improving how cells produce energy could potentially help restore cognitive function.

NeuroinflammationImmune Dysregulation

E0 ConsensusPEM ?PreliminaryMachine draft

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

Kavyani, Bahar, Lidbury, Brett A, Schloeffel, Richard et al.·Cellular and molecular life sciences : CMLS·2022

This review explores whether problems with how your body processes an amino acid called tryptophan might explain ME/CFS symptoms. The kynurenine pathway is a biochemical process that helps your cells make energy and affects immune function and brain inflammation. The authors suggest that abnormalities in this pathway could be a missing piece in understanding why ME/CFS develops.

BiomarkersNeuroinflammation

E0 ConsensusPEM ✓Moderate confidenceMachine draft

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

Paul, Bindu D, Lemle, Marian D, Komaroff, Anthony L et al.·Proceedings of the National Academy of Sciences of the United States of America·2021

This review examines how COVID-19 and ME/CFS may share similar biological problems, particularly an imbalance in how the body handles harmful molecules called free radicals. Both conditions appear to involve problems with inflammation, energy production in cells, and a slowed metabolism. While this research shows these biological abnormalities exist in both illnesses, more studies are needed to understand exactly how they work together and how to treat them.

NeuroinflammationPost-Exertional Malaise

E0 ConsensusPEM ✓Moderate confidenceMachine draft

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

Dudova, Dobrina, Bozhkova, Martina, Petrov, Steliyan et al.·International journal of molecular sciences·2025

This review brings together research showing that ME/CFS involves multiple body systems going wrong at the same time—including problems with the immune system, energy production in cells, hormone balance, and gut health. These problems appear to feed into each other, creating a cycle that keeps the illness going. The findings suggest ME/CFS is not just one thing breaking down, but rather many interconnected systems all struggling together.

Metabolic DysfunctionNeuroinflammationPost-Exertional MalaiseImmune Dysregulation

E2 ModeratePEM ?PreliminaryReviewed

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

Jarred W. Younger, Linda Yan, Sean Mackey·Journal of Neuroinflammation·2014·n=18

Using thermography and brain temperature imaging at Stanford, this study found evidence consistent with neuroinflammation — specifically elevated brain temperature — in ME/CFS patients compared to healthy controls. Brain regions associated with pain and fatigue showed the strongest signal.

Neuroinflammation

E2 ModeratePEM ?PreliminaryReviewed

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Yasuhito Nakatomi, Kei Mizuno, Akira Ishii et al.·Brain, Behavior, and Immunity·2014·n=9

Japanese researchers used PET imaging with a neuroinflammation tracer (PK11195) in 9 ME/CFS patients and healthy controls. They found significantly elevated neuroinflammation signals across multiple brain regions in ME/CFS patients, particularly in the cingulate cortex, thalamus, and brainstem — areas regulating fatigue and cognition.

Neuroinflammation

E2 ModeratePEM ✓Moderate confidenceMachine draft

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.

Hunter, Ewan, Alshaker, Heba, Bundock, Oliver et al.·Journal of translational medicine·2025

Researchers developed a new blood test called EpiSwitch®CFS that may help diagnose ME/CFS by detecting specific patterns in how DNA is organized in blood cells. When tested on stored blood samples from 47 ME/CFS patients and 61 healthy people, the test correctly identified 92% of ME/CFS patients and correctly ruled out 98% of healthy controls. This could potentially help doctors diagnose ME/CFS more reliably, since there is currently no standard blood test for the condition.

BiomarkersNeuroinflammationImmune Dysregulation

E3 PreliminaryPEM ?PreliminaryMachine draft

[Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)].

Yamamura, Takashi, Ono, Hirohiko, Sato, Wakiro·Brain and nerve = Shinkei kenkyu no shinpo·2018

This study found that people with ME/CFS have unusual patterns of immune system chemicals (cytokines) in their blood and spinal fluid, and some patients have antibodies that attack their own bodies. When researchers treated some ME/CFS patients with a medication that removes certain immune cells called B cells, patients improved. This suggests that ME/CFS may be caused by the immune system mistakenly attacking the body.

NeuroinflammationImmune Dysregulation

E3 PreliminaryPEM ?PreliminaryMachine draft

The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Glassford, Julian A G·Frontiers in physiology·2017

This article reviews research suggesting that ME/CFS may result from problems in how the nervous system and immune system interact. The author discusses how physical strain on the spine and nerves, combined with prolonged infections and immune activation, may trigger a chain reaction of inflammation in the brain and throughout the body. This inflammation can affect energy production, hormone balance, and how the body processes pain.

Neuroinflammation