Nonresponsiveness to anticholinesterase agents in patients with MuSK-antibody-positive MG

Abstract

Patients with seronegative myasthenia gravis (MG) often harbor antibodies for muscle-specific tyrosine kinase (MuSK).1 Nonresponsiveness or poor tolerability of anticholinesterase therapy has been mentioned in reports of this population2,3 but not comprehensively studied. We report anticholinesterase nonresponsiveness in 14 MuSK-antibody (Ab) positive patients seen at the University of Alabama at Birmingham (UAB) and University of Texas Southwestern Medical Center (UTSW), comparing them to MuSK-Ab-negative and acetylcholine receptor (AChR)-Ab seropositive patients from the UAB. Anticholinesterase hypersensitivity was defined when myasthenic symptoms worsened with medication; anticholinesterase intolerance when the patient developed severe cholinergic side effects with small doses of pyridostigmine or edrophonium, even with the administration of atropine or glycopyrrolate; and no improvement when there was no clinical benefit following administration of pyridostigmine. Hypersensitivity, intolerance, and no improvement were grouped together as anticholinesterase nonresponsiveness. At UAB, the AChR-Ab test was positive in 73 (72%) of 102 patients with generalized MG; the MuSK antibody test was positive in 7 (24%) of the …