Myasthenia, thymoma, presynaptic antibodies, and a continuum of neuromuscular hyperexcitability

Background: Autoantibodies specific for the nicotinic acetylcholine recepto r (AChR) of skeletal muscle impair neuromuscular transmission in myasthenia gravis (MG), Autoantibodies specific for alpha 3 neuronal AChRs or voltage -gated potassium channels have been reported in patients with Isaacs syndro me, an acquired disorder of continuous muscle fiber activity characterized by neuromyotonia. Objective: To report the neuromuscular autoantibody profi les of three patients with a syndrome of MG and neuromuscular hyperexcitabi lity. Results: All three patients reported here had clinical and electrophy siologic evidence of MG and neuromuscular hyperexcitability, None had neuro myotonia. Thymoma was proven in two patients and suspected in the third. On e had MG and thymoma and subsequently developed cramp-fasciculation syndrom e; MG and rippling muscle syndrome appeared simultaneously in the other two . All patients had muscle and neuronal AChR binding antibodies and striatio nal antibodies. Only one had antibodies reactive with oc-dendrotoxin-comple xed potassium channels. Conclusions: The coexistence of cramp-fasciculation syndrome and acquired rippling muscle syndrome with MG, thymoma, and neuro nal AChR autoantibodies suggests that there is a continuum of autoimmune ne uromuscular hyperexcitability disorders related pathogenically to Isaacs sy ndrome. Manifestations of neuromuscular hyperexcitability may be altered an d less apparent in the context of MG because of the coexisting defect of ne uromuscular transmission.