Inflammation at the neuromuscular junction in myasthenia gravis.
To better define the pathogenic mechanisms in the antibody-mediated autoimmune disease myasthenia gravis (MG), we analyzed the morphology and electrophysiology of the neuromuscular junction in anconeus muscle biopsy specimens from eight patients with MG and seven control subjects. There were inflammatory cells at the neuromuscular junction in seven of the eight biopsies from MG patients. The endplate index (length of the postsynaptic membrane divided by the length of the apposed presynaptic membrane) was abnormally reduced in all the MG patients, and fiber type grouping, suggestive of reinnervation, was present in six of the eight MG patients. Intracellular recording revealed diminished amplitude of miniature endplate potentials and miniature endplate currents in the MG patients compared with the controls. The time constant of decay of miniature endplate currents did not differ from that of controls, suggesting no change in mean channel open time of the acetylcholine receptor. The endplate receptor sensitivity to iontophoretically applied acetylcholine was also decreased in MG patients compared with controls. The quantal content of neurally evoked endplate potentials was reduced in six of the eight MG patients, demonstrating abnormal presynaptic function as well. The presence of inflammatory cells at the neuromuscular junctions of limb muscles in MG reconciles an apparent disparity between the animal model of MG, experimental autoimmune myasthenia gravis, and the human disease. This study also demonstrates a frequent presynaptic component to the abnormal neuromuscular transmission in MG.
Maselli
R A
RA
Department of Neurology, University of Chicago, IL 60637.
Richman
D P
DP
Wollmann
R L
RL
D000200:Action Potentials; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005542:Forearm; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000473:pathology / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000473:pathology