Neuromuscular junction disorders

Ten seminal papers on disorders of the neuromuscular junction are described, covering historical aspects, recent advances in immunological, biological, and genetic researches, and future perspectives. Early descriptions of myasthenia gravis (MG) date back to the seventeenth century, and MG acquired its name in the nineteenth century. The first symptomatic treatment with cholinesterase inhibitors was reported in 1934, leading to the development of modern immunological therapies. Following the discovery of anti-MuSK (muscle-specific tyrosine kinase) antibody in 2001, MG is currently classified into three categories: AChR-positive, MuSK-positive, and dual-seronegative. Lambert-Eaton myasthenic syndrome was recognized in 1956, followed by the discovery of antibodies to voltage-gated calcium channels in the pre-synaptic membrane, facilitating diagnosis and improving the understanding of the pathophysiological mechanisms. Since the late twentieth century, many types of congenital myasthenic syndromes with pre-synaptic, synaptic, and post-synaptic defects have been identified, and a classification based on molecular genetics is in evolution.