Does myasthenia gravis affect the brain?

Abstract

Associations between myasthenia gravis (MG) and CNS functions have been made for over 80 years. An increased incidence of psychiatric disorders, epilepsy and multiple sclerosis as well as electroencephalographic (EEG) abnormalities and abnormal evoked responses have been noted in patients with MG. Descriptions of sleep and memory disturbances in MG patients appeared as knowledge accumulated about the role of brain cholinergic systems in sleep and memory. The inference of many of these studies has been that the alleged central cholinergic effects in MG were caused either by the anticholinesterases used to treat MG or by antibodies to muscle nicotinic acetylcholine receptor (nAchR) present in the serum and cerebrospinal fluid (CSF) of MG patients. The antigenic differences between muscle nAchR and neuronal nAchRs, together with the very low concentrations of muscle nAchR antibodies in the CSF, make highly unlikely the claims that CNS cholinergic systems are affected by these muscle antibodies in MG patients. Evoked response abnormalities, if indeed present, are more likely caused by peripheral than central mechanisms, and sleep abnormalities in MG also probably originate in the periphery rather than in the CNS, the result of hypoxia caused by oropharyngeal, intercostal and diaphragmatic muscle weakness which may worsen during sleep, especially during REM sleep. Such hypoxia may account for some of the EEG abnormalities noted in MG patients, but the association of MG with epilepsy appears to be either coincidental or the result of uncontrolled MG. Significant 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 unpredictable neuromuscular disease involving weakness of breathing, swallowing, talking, limb and eye movement. Considering the number and variety of claims for direct CNS involvement in MG, the evidence for this is remarkably unconvincing. The quality of MG treatment, both physical and psychological, is a presently undefined variable which might help explain the diametrically opposed results which have been obtained in some of the studies reviewed. Adequate respiratory muscle strength during sleep is an often overlooked peripheral influence upon mental functioning and general well-being of MG patients.