Does myasthenia gravis affect the brain?

Associations between myasthenia gravis (MG) and CNS functions have been mad e for over 80 years. An increased incidence of psychiatric disorders, epile psy and multiple sclerosis as well as electroencephalographic (EEG) abnorma lities and abnormal evoked responses have been noted in patients with MG. D escriptions of sleep and memory disturbances in MG patients appeared as kno wledge accumulated about the role of brain cholinergic systems in sleep and memory. The inference of many of these studies has been that the alleged c entral cholinergic effects in MG were caused either by the anticholinestera ses used to treat MG or by antibodies to muscle nicotinic acetylcholine rec eptor (nAchR) present in the serum and cerebrospinal fluid (CSF) of MG pati ents. The antigenic differences between muscle nAchR and neuronal nAchRs, t ogether with the very low concentrations of muscle nAchR antibodies in the CSF, make highly unlikely the claims that CNS cholinergic systems are affec ted by these muscle antibodies in MG patients. Evoked response abnormalitie s, if indeed present, are more likely caused by peripheral than central mec hanisms, and sleep abnormalities in MG also probably originate in the perip hery rather than in the CNS, the result of hypoxia caused by oropharyngeal, intercostal and diaphragmatic muscle weakness which may worsen during slee p, especially during REM sleep. Such hypoxia may account for some of the EE G abnormalities noted in MG patients, but the association of MG with epilep sy appears to be either coincidental or the result of uncontrolled MG. Sign ificant excessive daytime sleepiness resulting from sleep disturbances can also impair memory and the performance of MG patients on neuropsychological tests, as can the presence of mental depression. The psychological aspects of MG can be attributed to the expected consequences of a chronic but unpr edictable neuromuscular disease involving weakness of breathing, swallowing , talking, limb and eye movement. Considering the number and variety of cla ims for direct CNS involvement in MG, the evidence for this is remarkably u nconvincing. The quality of MG treatment, both physical and psychological, is a presently undefined variable which might help explain the diametricall y opposed results which have been obtained in some of the studies reviewed. Adequate respiratory muscle strength during sleep is an often overlooked p eripheral influence upon mental functioning and general well-being of MG pa tients. (C) 1999 Elsevier Science B.V. All rights reserved.