Evidence browser

Postulated vasoactive neuropeptide immunopathology affecting the blood-brain/blood-spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment?

Staines, Donald R, Brenu, Ekua W, Marshall-Gradisnik, Sonya·Neuropsychiatric disease and treatment·2009

This paper proposes that ME/CFS, along with MS, Parkinson's disease, and ALS, may involve immune system problems affecting the protective barriers around the brain and spinal cord. Specifically, the authors suggest that certain signaling molecules called PACAP and VIP, which normally help maintain these barriers, may become targets of autoimmune attack. They propose that a class of drugs called phosphodiesterase inhibitors might help restore normal function by boosting protective immune responses.

Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Jason, L A, Porter, N, Herrington, J et al.·Journal of behavioral and neuroscience research·2009

ME/CFS is a complex illness that often starts suddenly, sometimes after a viral infection, and affects multiple body systems including the immune system, nervous system, and heart. This study proposes that two processes—'kindling' (where repeated small stresses build up over time) and oxidative stress (cellular damage from harmful molecules)—may help explain why different ME/CFS patients have such different symptoms and test results.

E3 PreliminaryMechanismPEM not requiredMechanistic

Lymphatic drainage of the neuraxis in chronic fatigue syndrome: a hypothetical model for the cranial rhythmic impulse.

Perrin, Raymond N·The Journal of the American Osteopathic Association·2007

This study proposes that ME/CFS may be connected to problems with how fluid drains from the brain and spinal cord. The author suggests that the cranial rhythmic impulse—a subtle body rhythm that practitioners can feel—reflects cerebrospinal fluid drainage and lymphatic system activity controlled by the nervous system. When this drainage process becomes disrupted, the author argues it could cause the fatigue and other symptoms of ME/CFS.

NeuroinflammationPost-Exertional Malaise

[Possible mechanisms of chronic fatigue syndrome in multiple sclerosis].

Kasatkin, D S, Spirin, N N·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2006

This review describes how fatigue in multiple sclerosis (MS) can happen in different ways: tiredness even at rest, exhaustion during activity, and fatigue linked to MS flare-ups. The authors explain that fatigue likely involves both brain-based and body-based mechanisms, and often occurs alongside depression and sleep problems, suggesting these conditions may share common biological causes related to brain chemicals like serotonin.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Neuropathology in rhinosinusitis.

Baraniuk, James N, Petrie, Kristina Naranch, Le, Uyenphuong et al.·American journal of respiratory and critical care medicine·2005

Researchers tested how the nasal passages of people with ME/CFS, sinusitis, allergies, and healthy controls responded to salt water spray. They found that people with ME/CFS experienced unusual nerve sensitivity (feeling more pain) but their mucus-producing glands didn't respond normally to the stimulus. This suggests that ME/CFS involves a different pattern of how nerves and mucus glands work in the nose compared to other nasal conditions.

E3 PreliminaryCommentaryPEM not requiredEditorial

Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation?

Nijs, Jo, Van de Velde, Bart, De Meirleir, Kenny·Medical hypotheses·2005

This study proposes a theory about why ME/CFS patients experience widespread pain. The researchers suggest that a molecule called nitric oxide may cause the central nervous system (the brain and spinal cord) to become overly sensitive, amplifying pain signals throughout the body. They propose that viral infections or other pathogens associated with ME/CFS may trigger this chain reaction, and that behaviors like catastrophizing or avoiding activity may either contribute to or result from this heightened sensitivity.

E3 PreliminaryCohortPEM unclearCase-Control

A Chronic Fatigue Syndrome - related proteome in human cerebrospinal fluid.

Baraniuk, James N, Casado, Begona, Maibach, Hilda et al.·BMC neurology·2005

Researchers examined fluid from around the spine (cerebrospinal fluid) in people with ME/CFS and found specific proteins that were present in patients but absent in healthy people. Using advanced laboratory techniques, they identified a set of 5 key proteins that could correctly identify ME/CFS in 80% of cases. These findings suggest ME/CFS may involve immune system and brain inflammation, offering hope for an objective test in the future.

NeuroinflammationBiomarkers

E3 PreliminaryReviewPEM not requiredReview-Narrative

The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

Anyanwu, Ebere, Campbell, Andrew W, Jones, Joseph et al.·TheScientificWorldJournal·2003

This review examines how toxic molds found in homes and buildings can damage the immune system, specifically affecting natural killer cells—white blood cells that help fight infections. When people are exposed to these molds over time, their natural killer cells may stop working normally, which could contribute to symptoms like fatigue, memory problems, sleep trouble, depression, headaches, and fevers that resemble ME/CFS.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Connecting cytokines and brain: a review of current issues.

Quan, N, Herkenham, M·Histology and histopathology·2002

This review examines how immune molecules called cytokines communicate with the brain and affect how it works. Scientists have found that cytokines can trigger fatigue, changes in mood and behavior, and problems with the nervous system. The authors suggest that cytokines may play a role in several brain-related conditions, including chronic fatigue syndrome.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: neurological findings may be related to blood--brain barrier permeability.

Bested, A C, Saunders, P R, Logan, A C·Medical hypotheses·2001

This study proposes that ME/CFS symptoms may be caused by a breakdown in the blood-brain barrier (BBB), a protective layer that normally keeps harmful substances out of the brain. The researchers reviewed scientific literature to identify factors that could damage this barrier in ME/CFS patients, including viral infections, stress, and certain chemical imbalances. They suggest that if this protective barrier becomes leaky, it could allow harmful substances into the brain and disrupt normal nerve function, potentially explaining many ME/CFS symptoms.

E3 PreliminaryMechanismPEM unclearObservational

Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome.

Evengard, B, Nilsson, C G, Lindh, G et al.·Pain·1998

Researchers measured a pain-signaling chemical called substance P in the spinal fluid of 15 people with ME/CFS. They found that all the ME/CFS patients had normal levels of this chemical. This is important because fibromyalgia—a condition with similar symptoms—typically shows elevated substance P levels. This finding suggests that ME/CFS and fibromyalgia may be caused by different biological problems, even though patients experience some overlapping symptoms.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Are cytokines associated with neuropsychiatric syndromes in humans?

Hickie, I, Lloyd, A·International journal of immunopharmacology·1995

This paper suggests that immune molecules called cytokines—which your body produces during infections or inflammation—may affect your brain and behavior in ways that look like psychiatric symptoms such as depression, fatigue, loss of appetite, and difficulty thinking clearly. The authors review evidence from various illnesses where these immune-related behavioral changes happen together, including ME/CFS, and propose that cytokines may be the biological link between immune activation and these symptoms.

Stealth viruses as neuropathogens.

Martin, W J·CAP today·1994

This article suggests that certain stealth viruses may damage the nervous system and contribute to various brain-related conditions, including ME/CFS. The authors note that diseases like ME/CFS, fibromyalgia, depression, and autism share overlapping symptoms—such as pain, mood changes, and cognitive problems—which may reflect a common underlying problem in how the brain responds to different triggers.

E3 PreliminaryCommentaryPEM unclearEditorial

Raphe nucleus encephalopathy (myalgic encephalomyelitis, epidemic neuromyasthenia).

Maurizi, C P·Medical hypotheses·1985

This 1985 paper proposes that ME/CFS may be caused by damage to a specific brain region called the dorsal raphe nucleus, potentially triggered by Coxsackie B viruses. The symptoms of ME/CFS match what doctors would expect to see if serotonin levels were too low in this area of the brain. The authors suggest that stress and nutritional deficiencies in tryptophan (a building block for serotonin) may make the condition more likely to develop.