Figura. a) Ondas motoras peroneas que estimulan debajo de la cabeza del peroné y registran el músculo tibial anterior: un solo estímulo supramaximal provoca un segundo potencial de acción muscular compuesto más pequeño 7,5 ms después del pico de la onda M principal (asterisco); b) La estimulación nerviosa repetitiva a 3 Hz en el mismo nervio produce una disminución de la amplitud de potencial de acción muscular compuesto del 23,9% en reposo: obsérvese que la respuesta decreciente está presente tanto en la onda M como en el segundo potencial de acción muscular compuesto (asterisco).
Clinical and neurophysiological response to ephedrine in a patient affected with slow-channel congenital myasthenic syndrome
Introduction. Slow-channel congenital myasthenic syndrome is an autosomal dominant inherited progressive neuromuscular disorder caused by abnormal gating of mutant acetylcholine receptors in the neuromuscular junction. Its pathological hallmark is selective degeneration of the endplate and postsynaptic membrane due to calcium overload. Pyridostigmine should be avoided in this syndrome, being quinidine or fluoxetine the current recommended therapies.
Case report. An 11-year-old girl with a limb-girdle phenotype of slow-channel congenital myasthenic syndrome presenting with a slowly progressive fatigable weakness at the age of 8 years. After a clinical worsening with pyridostigmine, empirically started before the exome sequencing results were available, a dramatic and sustained response to ephedrine monotherapy was observed. Whole exome sequencing revealed a de novo heterozygous mutation in CHRNB1 gene: c.865G>A; p.Val289Met (NM_000747.2). An abnormal decrement in amplitude (23.9%) from the first to fifth intravollley waveform was revealed after repetitive peroneal nerve stimulation at low frequencies. In addition, a second smaller compound muscle action potential after the peak of the main M-wave in median, ulnar and peroneal motor nerves was observed.
Conclusion. Favorable responses to adrenergic agonists added to fluoxetine had been reported. However, to the best of our knowledge this is the first report on effective monotherapy with ephedrine in a slow-channel congenital myasthenic syndrome patient. Adrenergic agonists may be considered as a therapeutic option in patients with this syndrome.
Key words. Adrenergic agonists. CHRNB1 gene. Congenital myasthenic syndrome. Ephedrine. Repetitive nerve stimulation. Slow-channel.