A Historical Perspective of Mysthenia Gravis

, who died in 1664, as reported by Virginian chroniclers: “The excessive fatigue he encountered wrecked his constitution; his flesh became macerated; his sinews lost their tone and elasticity; and his eyelids were so heavy that he could not see unless they were lifted up by his attendants . . . he was unable to walk; but his spirit rising above the ruins of his body directed from the litter on which he was carried by his Indians”. In 1672, the English physician Thomas Willis described a patient with the “fatiguable weakness” of limbs and bulbar muscles characteristic of MG . In the late 1800s, the first modern descriptions of patients with myasthenic symptoms were published, and the name myasthenia gravis was coined by fusing the Greek terms for muscle and weakness to yield the noun myasthenia and adding the Latin adjective gravis, which means severe.

Attempts at rational treatments of MG began in the 1930s. A major step forward occurred in 1934 when Mary Walker realized that MG symptoms were similar to those of curare poisoning, which was treated with physostigmine, a cholinesterase inhibitor. She showed that physostigmine promptly improved myasthenic symptoms (5), making anticholinesterase drugs a staple in MG management. Because thymus pathology is common in MG patients, as first noted in the late 1800s (3), in 1937, Blalock removed a mediastinal mass from a young woman who had MG; the patient improved postoperatively. Later, Blalock reported other myasthenic patients who improved after thymus removal, establishing thymectomy as a treatment for MG.

In 1959–1960, Simpson and Nastuck proposed independently that MG has an autoimmune etiology based on several observations: (a) MG patients’ sera compromise contraction in nerve-muscle preparations; (b) the level of serum complement correlates inversely with the severity of MG symptoms; (c) infants of myasthenic mothers may present transient myasthenic symptoms (neonatal MG); (d) inflammatory infiltrates may occur in muscles of MG patients, and pathologic changes are common in their thymi; and (e) MG may be associated with other putative autoimmune disorders.

In 1973, Patrick and Lindstrom demonstrated that rabbits immunized with purified muscle-like AChR developed MG-like symptoms (experimental autoimmune MG [EAMG]) . After that seminal discovery, many studies demonstrated an autoimmune response against muscle AChR in MG and the role of anti-AChR Abs in causing the structural and functional damage of the NMJ. These findings promoted the use of immunosuppressants in MG. In the 1970s, prednisone and azathioprine became established treatments for MG, and plasma exchange was introduced as an effective acute treatment for severe MG, further proving that circulating factors caused MG symptoms.

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