Neuromuscular excitability changes produced by sustained voluntary contraction and response to mexiletine in myotonia congenita.
OBJECTIVE
To investigate the cause of transient weakness in myotonia congenita (MC) and the mechanism of action of mexiletine in reducing weakness.


METHODS
The changes in neuromuscular excitability produced by 1min of maximal voluntary contractions (MVC) were measured on the amplitude of compound muscle action potentials (CMAP) in two patients with either recessive or dominant MC, compared to control values obtained in 20 healthy subjects. Measurements were performed again in MC patients after mexiletine therapy.


RESULTS
Transient reduction in maximal CMAP amplitude lasting several minutes after MVC was evident in MC patients, whereas no change was observed in controls. Mexiletine efficiently reduced this transient CMAP depression in both patients.


CONCLUSIONS
Transient CMAP depression following sustained MVC may represent the electrophysiological correlate of the weakness clinically experienced by the patients. In MC, the low chloride conductance could induce self-sustaining action potentials after MVC, determining progressive membrane depolarization and a loss of excitability of muscle fibers, thus resulting in transient paresis. Mexiletine may prevent conduction block due to excessive membrane depolarization, thus reducing the transient CMAP depression following sustained MVC.
Department of Medical, Surgical and Neurological Sciences, Neurology-Neurophysiology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy. Electronic address: ginanneschi@unisi.it.
Federica
F
Ginanneschi
Department of Medical, Surgical and Neurological Sciences, Neurology-Neurophysiology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy.
Andrea
A
Mignarri
Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Sabrina
S
Lucchiari
Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Gianna
G
Ulzi
Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Giacomo P
GP
Comi
Department of Medical, Surgical and Neurological Sciences, Neurology-Neurophysiology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy.
Alessandro
A
Rossi
Department of Medical, Surgical and Neurological Sciences, Neurology-Neurophysiology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy.
Maria Teresa
MT
Dotti
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000627:therapeutic use*; D009119:Muscle Contraction; D018908:Muscle Weakness / Q000188:drug therapy / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology*; D009224:Myotonia Congenita / Q000188:drug therapy* / Q000503:physiopathology*; D004561:Transcutaneous Electric Nerve Stimulation; D016896:Treatment Outcome
D008801:Mexiletine
Activité naturelle; Canal sodique; Chloride conductance; Conductance chlore; Faiblesse; Myotonia; Myotonie; Natural activity; Sodium channel; Weakness