title: A retrospective clinical study of the treatment of slow-channel congenital myasthenic syndrome.
abstract: Slow-channel congenital myasthenic syndrome (CMS) is a rare subtype of CMS caused by dominant "gain of function" mutations in the acetylcholine receptor. Clinically, the cervical and forearm extensor muscles seem to be preferentially weaker; and conventional treatment with anticholinesterases fails to improve symptoms. In contrast, open channel blockers such as fluoxetine and quinidine have been shown to be of benefit. The objectives of our study were to provide further insight into the clinical features of slow-channel CMS and evaluate response to recommended therapy. We carried out a retrospective clinical follow up study of 15 slow-channel CMS patients referred to the Munich CMS Centre. Detailed clinical data were collected by clinicians involved in the care of each patient, with a particular focus on response and tolerability to recommended therapy. Patients varied widely as regard onset of symptoms, severity of disease and mutations involved. Patients received up to four different medications and some had none. Our results strengthen previous reported findings in terms of clinical phenotype variability and the poor response to pyridostigmine. Although treatment with fluoxetine was beneficial in most patients, a number of our patients suffered significant adverse effects that hindered optimum dose titration or led to treatment cessation. Slow-channel CMS is rare and exhibits distinct clinical and genetic characteristics. Our study suggests that fluoxetine, despite being effective in most patients, can be associated with significant side effects, thus reducing treatment effectiveness in clinical practice.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, NE1 3BZ, Newcastle upon Tyne, UK.
authors.forename: Amina
authors.initials: A
authors.lastname: Chaouch
authors.forename: Juliane S
authors.initials: JS
authors.lastname: Müller
authors.forename: Velina
authors.initials: V
authors.lastname: Guergueltcheva
authors.forename: Marina
authors.initials: M
authors.lastname: Dusl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schara
authors.forename: Vidosava
authors.initials: V
authors.lastname: Rakocević-Stojanović
authors.forename: Christopher
authors.initials: C
authors.lastname: Lindberg
authors.forename: Rosana H
authors.initials: RH
authors.lastname: Scola
authors.forename: Lineu C
authors.initials: LC
authors.lastname: Werneck
authors.forename: Jaume
authors.initials: J
authors.lastname: Colomer
authors.forename: Andres
authors.initials: A
authors.lastname: Nascimento
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Vilchez
authors.forename: Nuria
authors.initials: N
authors.lastname: Muelas
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics / Q000628:therapy*; D011729:Pyridostigmine Bromide / Q000627:therapeutic use*; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D005473:Fluoxetine; D011729:Pyridostigmine Bromide; D017367:Selective Serotonin Reuptake Inhibitors