Neurology of ME/CFS

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex neurological disease, that is often considered to be neuroimmune, or more recently, neurovascular. Myriad neurological abnormalities have been found, such as changes in brain structure and metabolism, and autonomic nervous system dysfunction. Neuroinflammation, indicated by elevated brain lactate and choline, is suggested as a key mechanism, though evidence is mixed.

Brain imaging

Main article: Brain

Main article: Neuroinflammation

Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study (2018) Source: Finkelmeyer et al. NeuroImage: Clinical 17 pp.24-30. https://doi.org/10.1016/j.nicl.2017.09.024

Reduced Activation in Basal Ganglia Structures in CFS compared to Controls for the Win-Lose Contrast.
Source: Miller et al. (2014). PLoS ONE 9(5): e98156. doi:10.1371/journal.pone.0098156

Spine

Main article: Spine

Neural strain

Main article: Neural strain

In a study of neuromuscular strain in ME/CFS, 60 people with ME/CFS and 20 healthy controls randomly were assigned to undergo a neuromuscular strain maneuver or sham maneuver. Those with ME/CFS in the strain condition group had significantly increased symptoms for up to 24 hours.

Causes of neurological symptoms

Key neurological pathomechanisms in ME/CFS are intracranial hypertension, impaired cerebral blood flow, hyperventilation/hypocapnia, and adrenergic hyperactivity.

Source:
Wirth, K.J., Scheibenbogen, C. & Paul, F. An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Transl Med 19, 471 (2021). https://doi.org/10.1186/s12967-021-03143-3

Causes of neurological symptoms in ME/CFS include:

• hyperventilation/hypnocapnia (reduced carbon dioxide levels in the blood)
• intracranial hypertension (increased pressure within the skull and around brain)
• reduced blood flow to the brain
• brain inflammation may also be a factor

These can explain cognitive impairment, brain fog, headache, psychomotor slowing, ataxia and loss of coordination of movements, hypersensitivity, sleep disturbances and dysautonomia.

Neurovascular symptoms

Research by Wirth, Scheibenbogen, and colleagues has found evidence of neurovascular abnormalities which are potentially the key cause of most neurological symptoms in ME/CFS, in particular ß2 adrenergic receptor antibodies. Evidence of abnormal neurovascular coupling (NVC) has also been found in ME/CFS patients.

Notable studies

• 2021, An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - (Full text)
• 2022, Neurovascular dysregulation and acute exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome: a randomized, placebo-controlled trial of pyridostigmine - (Full text)

Talks and interviews

• 2016, 77. ME & the brain, part 1 / ME & de hersenen, deel 1 - Dr. Neil Harrison
• 2016, 78. ME & the brain, part 2 / ME & de hersenen, deel 2 - Dr. Neil Harrison

• 2016, 79. ME & inflammation, part 1 / ME & inflammatie, deel 1 - Dr Harrison
• 2018, ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study, sponsored by Solve ME/CFS Initiative

See also

• Brain
• Basal ganglia
• Microglia
• QEEG
• Neuroinflammation
• List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis

Researchers

• Neil Harrison
• Jose Montoya
• Jarred Younger

Learn more

• 2014, Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder

• 2016, Laggard: Is an Under-Active Brain the Problem in Chronic Fatigue Syndrome (ME/CFS)
• 2017, Reference List of Neurology studies ME CFS 2017.pdf
• 2018, Brain on Fire: Widespread Neuroinflammation Found in Chronic Fatigue Syndrome (ME/CFS)
• 2019, Brain Imaging and Behavior publication from Dr. Jarred Younger’s SMCI Ramsay pilot study supports involvement of neuroinflammation in ME/CFS

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

muscle strain An injury involving a stretched or torn muscle or tendon (tendons are fibrous cords of tissue that connect muscle to bone).

cerebral blood flow (CBF) - the amount of blood that goes through the arterial tree in the brain in a given amount of time

cognition Thought processes, including attention, reasoning, and memory.

dysautonomia disorders of the autonomic nervous system that cause disturbances in all or some autonomic functions, may cause problems regulating autonomic functions, including heart rate, blood pressure, body temperature, and digestion. Can cause symptoms including lightheadedness, fainting, unstable blood pressure, and orthostatic intolerance.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

International Classification of Diseases (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)