The clinical limits of myasthenia gravis and differential diagnosis

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The question of the limits of the clinical diagnosis of myasthenia gravis is in part one of definitions superimposed on the evolution in our understanding of normal and abnormal neuromuscular junction anatomy, physiology, and pharmacology, complemented by new knowledge of the immunopathogenic events that take place at the neuromuscular junction in the most common form of myasthenia gravis, acquired autoimmune myasthenia gravis. [1,2] In the past, myasthenia gravis was used to describe a series of disorders, most of them quite uncommon or rare, in which there appeared to be a defect in neuromuscular function based on abnormal neurophysiology and on pharmacologic responses to agents that enhanced or inhibited neuromuscular transmission, acting either presynaptically or postsynaptically. In 1982, we still classified myasthenia gravis as generalized vs. ocular, but in the generalized category we included congenital myasthenia gravis. It was recognized that congenital myasthenia gravis comprised several different disorders that did not appear to be immunologically mediated but that did appear to involve the neuromuscular junction based on the clinical picture, neurophysiology, and/or response to cholinesterase inhibitory drugs. [3] Through the work of several investigators, principally Dr. Andrew Engel and his collaborators (reviewed by Dr. Engel in this supplement and elsewhere [4]), we now understand that congenital myasthenia includes several disorders involving different presynaptic and postsynaptic defects. Some of these have very different neurophysiologic findings from those of classic autoimmune myasthenia gravis, even using traditional clinical neurophysiologic testing. It is of interest that we classified the Lambert-Eaton myasthenic syndrome (LEMS) as a clearly different myasthenic syndrome, although some of the congenital forms of myasthenia are just as clearly presynaptic as LEMS, albeit not immunologically mediated, which we now know is true of LEMS. Should we now reserve the term myasthenia gravis for the acquired, immunologically mediated postsynaptic disorder, be it generalized or …