Evidence browser

Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin.

Theoharides, Theoharis C, Stewart, Julia M, Hatziagelaki, Erifili et al.·Frontiers in neuroscience·2015

This review discusses 'brain fog'—trouble thinking clearly, concentrating, and remembering—which affects people with ME/CFS and other conditions. Researchers suggest brain fog may be caused by inflammation and immune cells releasing harmful chemicals in the brain. A natural compound called luteolin, which has anti-inflammatory properties, shows promise in early studies for reducing brain fog symptoms.

NeuroinflammationGut MicrobiomeImmune System

The Role of Toll-Like Receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A New Promising Therapeutic Approach?

Gambuzza, Maria Elsa, Salmeri, Francesca Maria, Soraci, Luca et al.·CNS & neurological disorders drug targets·2015

This review examines how certain immune system sensors called Toll-like receptors (TLRs) may contribute to ME/CFS. These receptors sit on cells in the gut and detect bacteria and other microbes, triggering inflammation that may spread to the brain and cause fatigue and other symptoms. The researchers suggest that targeting these TLRs with new medications might help reduce inflammation and improve symptoms.

E3 PreliminaryMechanismPEM unclearCross-Sectional

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study.

Nakatomi, Yasuhito, Mizuno, Kei, Ishii, Akira et al.·Journal of nuclear medicine : official publication, Society of Nuclear Medicine·2014

This study used a special brain imaging technique called PET scans to look for signs of inflammation in the brains of ME/CFS patients. Researchers found that people with ME/CFS had higher levels of brain inflammation markers in several key brain regions compared to healthy controls. The amount of inflammation was linked to how severe patients' cognitive problems, pain, and depression were.

E3 PreliminaryMechanismPEM unclearObservational

Clinical features in patients with long-lasting macrophagic myofasciitis.

Rigolet, Muriel, Aouizerate, Jessie, Couette, Maryline et al.·Frontiers in neurology·2014

This study describes macrophagic myofasciitis (MMF), a condition where aluminum from vaccines persists in muscle tissue and causes long-lasting symptoms similar to ME/CFS, including widespread pain, severe fatigue, and significant problems with thinking and memory. Patients show patterns of brain abnormalities on imaging scans, and their cognitive problems appear to be caused by brain dysfunction rather than just pain or depression. The researchers found that standard treatments don't work well for these patients, making their condition particularly disabling.

Induction of interleukin-1β by activated microglia is a prerequisite for immunologically induced fatigue.

Ifuku, Masataka, Hossain, Shamim M, Noda, Mami et al.·The European journal of neuroscience·2014

This study used rats to understand how an immune trigger (a synthetic viral mimic) causes prolonged fatigue. Researchers found that when this trigger activates immune cells in the brain called microglia, they release a chemical messenger called IL-1β that affects how the brain handles serotonin, leading to reduced activity and fatigue-like behavior.

NeuroinflammationGut MicrobiomeImmune System

The gut microbiome and the brain.

Galland, Leo·Journal of medicinal food·2014

Your gut bacteria can communicate with your brain in several ways: they produce substances that trigger your immune system, create chemicals that affect your mood and sleep, and send signals directly to your brain through a major nerve called the vagus nerve. When the balance of gut bacteria is disrupted, this communication can go wrong and may contribute to problems like chronic fatigue, brain fog, and mood changes.

The glutathione system: a new drug target in neuroimmune disorders.

Morris, Gerwyn, Anderson, George, Dean, Olivia et al.·Molecular neurobiology·2014

This review examines glutathione (GSH), a naturally occurring substance in our cells that protects against damage and helps our immune system work properly. When glutathione levels drop, cells become more stressed and inflamed, which may contribute to ME/CFS and other conditions affecting the brain and immune system. The authors suggest several potential treatments—including supplements like N-acetyl cysteine and natural compounds like curcumin—that might help restore glutathione levels.

A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation.

Yasui, Masaya, Yoshimura, Takashi, Takeuchi, So et al.·Glia·2014

This study used rats exposed to continuous stress to model ME/CFS and fibromyalgia, finding that stress caused pain sensitivity without any actual tissue damage or infection. The researchers discovered that immune cells in the spinal cord called microglia became activated in stressed animals, and blocking this activation with a drug called minocycline reduced their pain. This suggests that abnormal pain in ME/CFS may stem from brain and spinal cord inflammation rather than damage to muscles or skin.

Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).

Morris, Gerwyn, Maes, Michael·Current neuropharmacology·2014

This study proposes that ME/CFS involves a harmful cycle where the body's immune system becomes overactive and produces damaging molecules called oxidative stress. These problems can be triggered by infections, gut bacteria leaking into the bloodstream, or problems with the energy-producing parts of cells called mitochondria. Once started, this cycle feeds on itself, causing brain inflammation, reduced blood flow to the brain, and damage to cells throughout the body.

E3 PreliminaryMechanismPEM unclearMechanistic

Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins.

De Meirleir, Kenny L, Khaiboullina, Svetlana F, Frémont, Marc et al.·In vivo (Athens, Greece)·2013

Researchers found that a specific type of immune cell in the gut (called plasmacytoid dendritic cells) reacts to remnants of ancient viral DNA in 8 out of 12 ME/CFS patients, but not in healthy controls. These cells appear to be displaying signs of viral proteins on their surface, which suggests the gut may be involved in triggering immune problems seen in ME/CFS.

E3 PreliminaryReviewPEM requiredReview-Narrative

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

Morris, Gerwyn, Maes, Michael·Metabolic brain disease·2013

This study proposes a theory about how ME/CFS develops and persists. The researchers suggest that an initial infection triggers the immune system, which then gets stuck in an overactive state even after the infection is cleared. This causes ongoing inflammation, energy problems in cells, and damage to the nervous system, leading to the characteristic symptoms including post-exertional malaise (feeling worse after activity).

NeuroinflammationAutonomic Nervous SystemImmune SystemPost-Exertional Malaise

E3 PreliminaryCommentaryPEM unclearEditorial

New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome.

Pontari, Michel, Giusto, Laura·Current opinion in urology·2013

This article discusses how chronic prostatitis and chronic pelvic pain syndrome in men can present differently—some men have pain localized to the pelvic area, while others experience widespread body symptoms similar to other chronic conditions. The authors review new treatment options including physical therapy, acupuncture, psychological support, and medications, and note that these conditions often occur alongside other chronic pain disorders like fibromyalgia and chronic fatigue syndrome.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor.

Yamamoto, Shigeyuki, Ouchi, Yasuomi, Nakatsuka, Daisaku et al.·PloS one·2012

Some people with ME/CFS have antibodies in their blood that target a chemical receptor in the brain called the muscarinic cholinergic receptor. This study used brain imaging (PET scans) to compare the brains of ME/CFS patients with and without these antibodies. Patients with these antibodies showed lower levels of these receptors in their brains, but this difference did not affect their thinking or memory performance.

E3 PreliminaryMechanismPEM unclearMechanistic

An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Jason, Leonard A, Sorenson, Matthew, Porter, Nicole et al.·Neuroscience and medicine·2011

This study proposes that ME/CFS may develop through a process called 'kindling,' where the brain becomes increasingly sensitive to stress after repeated infections or injuries. Think of it like a fire alarm that has been triggered so many times it stays in an oversensitive state. Once this happens, the brain's stress system stays highly activated even without new triggers, which could explain why ME/CFS patients have such persistent symptoms.

E3 PreliminaryCommentaryPEM unclearEditorial

Chronic fatigue syndrome--a neuroimmunological model.

Arnett, S V, Alleva, L M, Korossy-Horwood, R et al.·Medical hypotheses·2011

This review suggests that ME/CFS may develop when the body has trouble controlling infections early on, leading to long-term inflammation in the brain. The authors propose that this inflammatory process—involving both the immune system and the nervous system—could explain many ME/CFS symptoms and why more women are affected than men. They also suggest that anti-inflammatory treatments targeting a protein called TNF might help patients.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Role of infection and neurologic dysfunction in chronic fatigue syndrome.

Komaroff, Anthony L, Cho, Tracey A·Seminars in neurology·2011

This review examines the connection between infections and ME/CFS, looking at decades of cases where people developed long-lasting fatigue after infections. The authors found evidence that certain viruses and bacteria can cause persistent infections that trigger and maintain ME/CFS symptoms by affecting the nervous system and triggering ongoing immune responses. While no single infection has been proven to cause ME/CFS in all cases, the pattern suggests that chronic infections may be important triggers in some people with the illness.

Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells.

Moriya, Junji, Chen, Rui, Yamakawa, Jun-ichi et al.·Biological & pharmaceutical bulletin·2011

Researchers created mice with chronic fatigue by repeatedly exposing them to a bacterial antigen, which caused them to move less and their brains to shrink in a region called the hippocampus. When they gave these mice resveratrol (a compound found in red grapes), the mice became more active and their hippocampus enlarged. The treatment appeared to work by reducing brain cell death and promoting the growth of new brain cells.

Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways.

Maes, Michael, Kubera, Marta, Obuchowiczwa, Ewa et al.·Neuro endocrinology letters·2011

This review explains why depression often occurs alongside many other diseases, including ME/CFS, autoimmune conditions, heart disease, and neurodegenerative disorders. The common link appears to be activation of inflammatory and oxidative stress pathways in both the brain and body. These pathways may act like a 'warning system' that produces depression symptoms such as fatigue, anxiety, and physical discomfort when the body detects a threat.

Hepatitis C virus enters human peripheral neuroblastoma cells - evidence for extra-hepatic cells sustaining hepatitis C virus penetration.

Bürgel, B, Friesland, M, Koch, A et al.·Journal of viral hepatitis·2011

This study investigated whether hepatitis C virus (HCV) can infect and replicate in nerve cells, since some HCV patients experience fatigue, depression, and memory problems. Researchers tested whether HCV could enter and survive in different types of brain and nerve cells in the laboratory. They found that HCV could enter one type of peripheral nerve cell, but could not replicate in any of the brain or nerve cell types tested.