Thymic Pathology and Myasthenia Gravis

Abstract

From a historical perspective, myasthenia gravis (MG) was first described in 1672 by an Oxford clinician, Sir Thomas Willis, who noted a patient with temporary loss of speech [1]. It wasn’t until two and a half centuries later in 1911 that the first thymectomy was performed by Ferdinard Sauerbruch in Zurich on a 21-year-old woman with hyperthyroidism and MG. Thymectomy was performed in an attempt to treat her hyperthyroidism, and following surgery both conditions showed improvement temporarily. In 1934, Mary Walker recognized clinical similarities between MG and curaré poisoning and hence introduced the anticholinesterase treatment, physostigmine, producing significant improvement in muscle strength for a MG patient. This was an important discovery implicating the pathogenesis of MG at the neuromuscular junction. Later in 1944, Alfred Blalock at Johns Hopkins reported improvement in MG patients following resection of normal thymus and also introduced this as a surgical therapy for this condition. Clinical use of edrophonium was introduced around 1950 and later taken over by the more popular pyridostigmine. John Simpson first proposed in 1960 that MG might be an autoimmune disease, which was later confirmed in 1973 by Patrick and Lindstrom through animal studies by immunizing rabbits with purified acetylcholine receptors. It is now common knowledge that MG is an autoimmune disorder of the postsynaptic nicotinic acetylcholine receptor, characterized by weakness and fatiguability of voluntary muscles. The ocular muscles are frequently involved, rendering ptosis and diplopia the most common modes of presentation. Despite the discovery of the condition centuries ago, considerable controversies still remain over its diagnosis, natural history, and therapy both medical and surgical. Nevertheless, thymectomy is now an established therapy in the management of generalized MG in conjunction with medical treatment. A meta-analysis of 28 controlled studies has previously shown that MG patients undergoing thymectomy were twice as likely to attain medication-free remission, 1.6 times as likely to become asymptomatic, and 1.7 times as likely to improve. Different demographics and baseline characteristics however existed between groups [2]. A recent randomized prospective trial investigating the role of thymectomy for myasthenia gravis has shown improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis [3]. Uncertainties remain over the role of thymectomy for patients with purely ocular symptom and those with late onset of disease.