title: Neurophysiological characteristics of MuSK antibody positive myasthenia gravis mice: focal denervation and hypersensitivity to acetylcholinesterase inhibitors.
abstract: Myasthenia Gravis (MG) patients with antibodies against the muscle specific tyrosine kinase (MuSK+) typically present with focal fatigue and atrophy of the facial and bulbar muscles, along with unbeneficial reactions upon administration of acetylcholinesterase inhibitors (AChEIs). This study addresses the neurophysiological characteristics in facial versus limb muscles, before and after intraperitoneal injection of AChEIs, in mice immunized with MuSK. We performed in-vivo neurophysiological examinations in the masseter and gastrocnemius muscles of mice with MuSK+experimental autoimmune MG (EAMG) and in healthy control mice before and after administration of AChEIs. Abnormal spontaneous activity (fibrillations) was observed in the masseter muscle of MuSK+mice. Furthermore, 94% of MuSK-immunized mice displayed so called extra discharges (EDs) upon administration of a therapeutic AChEI dose, in contrast to 22% of the control mice, indicating neuromuscular hyperactivity. These findings support functional denervation in the masseter muscle and neuromuscular hypersensitivity already at a standard dose of AChEIs in MuSK+EAMG.
authors.affiliation: Department of Neurology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Chroni
authors.forename: Anna Rostedt
authors.initials: AR
authors.lastname: Punga
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003714:Denervation / Q000379:methods; D005260:Female; D008406:Masseter Muscle / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000294:innervation; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000276:immunology; D011897:Random Allocation; D020794:Receptor Protein-Tyrosine Kinases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D002800:Cholinesterase Inhibitors; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases