Fatigue gets a bad press. The word can be confused with ordinary, everyday tiredness (particularly in the media), or used non-specifically, such as in the umbrella term Chronic Fatigue Syndrome. As many patients belonging to ME/ CFS support groups point out, fatigue is not their primary problem. Musculoskeletal weakness and post-exertional myalgia, along with other physical signs and symptoms, are far more prominent, and correspond more closely to the original definition of myalgic encephalomyelitis. Nevertheless, ‘fatigue’ as scientists use the term, should not be disparaged, as the symptom is actually a core feature of several chronic neurological diseases, as a review in Physical Medicine and Rehabilitation (2010) makes clear.

Fatigue can be caused by a primary disease process, but other factors (depression, sleep disturbance, medication, etc.) can contribute to the overall burden of an individual patient. Multiple sclerosis (MS) is an example of ‘central fatigue’. More than 40% of MS patients complain of fatigue, and the symptom is believed to be caused by a primary disease process, although depression and sleep disturbance are often co-existing problems. The actual cause of the fatigue remains unknown, but MRI and PET studies suggest that it is related to disease in the grey matter of the brain, particularly in the cerebral cortex, although destruction of nerves is also likely to be a factor.

Myasthenia gravis, in contrast, is an example of a disease where ‘peripheral fatigue’ is prominent. In this case, we know far more about the mechanism of weakness and fatigue. There is good evidence that changes in neurotransmitters at the junctions between muscle and nerve are involved, causing the force of muscle contractions to be reduced, and fatigue and weakness to be felt by the patient.

So, MS and myasthenia gravis are examples of two very different types of neurologically based fatigue — one central and one peripheral. ME/CFS, with its range of neurological symptoms and signs, muscle pain, and intense physical or mental exhaustion, will ultimately be found to resemble one more than the other. But which remains a mystery at present.

Reference: Central and peripheral fatigue: exemplified by multiple sclerosis and myasthenia gravis. Cantor F. PMR 2010 May; 2(5): 399-405.