The symptoms of CFS/ME patients display some similarities to those found in neurological channelopathies. One of the symptoms CFS/ME has in common with ion channel disorders is its fluctuating nature. All known channelopathies of the excitable tissues result in episodic episodes of fatigue. As in CFS/ME some cause symptoms that indicate both peripheral and central disruption. Neurological channelopathies (hypoakalemic periodic paralysis, episodic ataxia) are often characterized by sudden attacks of fatigue, weakness, cramping or even paralysis. As in CFS/ME many channelopathies can be induced by physical activity and/or stress.

While there has been much discussion regarding the need for longitudinal studies to capture the fluctuations present in CFS/ME Many question how episodic CFS/ME is. Their experience is that it is no more episodic than would probably be expected in a chronic disorder; that is, there are better or worse days but few days with truly dramatic shifts in well-being.

CFS/ME patients share with epileptics a predisposition to several autonomic related symptoms such as frequent near syncope (fainting) and low blood pressure, particularly during TILT table testing. A great deal of evidence since 1999 indicates many CFS/ME patients display abnormalities during TILT table testing or during standing.

CFS/ME patients share with migraine sufferers such symptoms as headache, confusion, increased sensitivity to lights, sounds and smells as well as exacerbated responses to serotonin. Symptom exacerbation during menstruation and muscle pain, disequilibrium and unusual sweating are often seen in both diseases. White brain matter abnormalities and reduced cerebral blood flows are also seen in both diseases and stress, alcohol and caffeine can exacerbate symptoms in both diseases. Transient or chronic fatigue is also common in migraine.

Finally, there is evidence of a channelopathy in CFS/ME. Some indirect evidence of ion channel disruption is provided by Chaudhuri et al's finding of increased resting energy expenditure (REE) in CFS/ME patients. Since about 25% of the energy expended during resting goes to maintaining ion gradients in the cell, the authors speculate the increased REE seen in CFS/ME could be due to compensation for faulty ion channel functioning. CFS/ME patients also appear to be particularly susceptible to some substances (alcohol, anesthesia, some cholesterol lowering drugs) known to effect either membrane integrity (alcohol) and/or ion function (anesthethetics). Indeed fatigue is a common symptom of a new anti-epileptic drug, dezinamide, targeting sodium channels. Results from a thallium scan of the cardiac muscle in CFS/ME patients suggest a potassium ion channel dysfunction that may be responsible for the cardiomyopathy reported by Lerner and now advocated by Cheney. Chaudhuri and Behan believe a potassium channelopathy is mostly likely to occur in CFS/ME.

Potential causes of channel dysfunction - The natural history of CFS/ME suggests that an early pathogenic or toxic insult often occurs. Several viruses, including HIV and the picornaviruses are able to alter ion channel flow. Herpes viruses have also been linked, interestingly enough given their history in CFS/ME, to altered ion channel functioning. Ciguatoxin, a neuronal sodium channel disrupter, produces many symptoms, including fatigue, similar to those that occur in CFS/ME. Studies indicate a substantial number of CFS/ME patients have extremely high levels of the ciguatera epitope. Toxic insults from organophosphate's, lead, insecticides, pesticides can also alter ion channel activity.