BACKGROUND: Mutations in the postsynaptic adaptor protein Dok-7 underlie congenital myasthenic syndrome (CMS) with a characteristic limb girdle pattern of muscle weakness. Patients usually do not respond to or worsen with the standard CMS treatments: cholinesterase inhibitors and 3,4-diaminopyridine. However, anecdotal reports suggest they may improve with ephedrine. METHODS: This was an open prospective follow-up study to determine muscle strength in response to ephedrine in Dok-7 CMS. Patients were first evaluated as inpatients for suitability for a trial of treatment with ephedrine. The response was assessed at 2 and 6 to 8 months follow-up clinic visits using a quantitative myasthenia gravis (severity) score (QMG) and mobility measures. RESULTS: Ten out of 12 of the cohort with DOK7 mutations tolerated ephedrine. We noted a progressive response to treatment over the 6 to 8 months assessment period with a significant improvement at the final QMG score (p = 0.009). Mobility scores also improved (p = 0.0006). Improvements in the subcomponents of the QMG score that measured proximal muscle function (those muscle groups most severely affected) were most marked, and in some cases were dramatic. All patients reported enhanced activities of daily living at 6-8 months. CONCLUSION: Ephedrine appears to be an effective treatment for Dok-7 CMS. It is well-tolerated by most patients and improvement in strength can be profound. Determining the long-term response and the most effective dosing regimen will require further research. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ephedrine given at doses between 15 and 90 mg/day improves muscle strength in patients with documented mutations in DOK7.
BACKGROUND: Mutations in the postsynaptic adaptor protein Dok-7 underlie congenital myasthenic syndrome (CMS) with a characteristic limb girdle pattern of muscle weakness. Patients usually do not respond to or worsen with the standard CMS treatments: cholinesterase inhibitors and 3,4-diaminopyridine. However, anecdotal reports suggest they may improve with ephedrine. METHODS: This was an open prospective follow-up study to determine muscle strength in response to ephedrine in Dok-7 CMS. Patients were first evaluated as inpatients for suitability for a trial of treatment with ephedrine. The response was assessed at 2 and 6 to 8 months follow-up clinic visits using a quantitative myasthenia gravis (severity) score (QMG) and mobility measures. RESULTS: Ten out of 12 of the cohort with DOK7 mutations tolerated ephedrine. We noted a progressive response to treatment over the 6 to 8 months assessment period with a significant improvement at the final QMG score (p = 0.009). Mobility scores also improved (p = 0.0006). Improvements in the subcomponents of the QMG score that measured proximal muscle function (those muscle groups most severely affected) were most marked, and in some cases were dramatic. All patients reported enhanced activities of daily living at 6-8 months. CONCLUSION:Ephedrine appears to be an effective treatment for Dok-7 CMS. It is well-tolerated by most patients and improvement in strength can be profound. Determining the long-term response and the most effective dosing regimen will require further research. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ephedrine given at doses between 15 and 90 mg/day improves muscle strength in patients with documented mutations in DOK7.
Authors: U Schara; N Barisic; M Deschauer; C Lindberg; V Straub; N Strigl-Pill; M Wendt; A Abicht; J S Müller; H Lochmüller Journal: Neuromuscul Disord Date: 2009-10-17 Impact factor: 4.296
Authors: Violeta Mihaylova; Juliane S Müller; Juan J Vilchez; Mustafa A Salih; Mohammad M Kabiraj; Adele D'Amico; Enrico Bertini; Joachim Wölfle; Felix Schreiner; Gerhard Kurlemann; Vedrana Milic Rasic; Dana Siskova; Jaume Colomer; Agnes Herczegfalvi; Katarina Fabriciova; Bernhard Weschke; Rosana Scola; Friederike Hoellen; Ulrike Schara; Angela Abicht; Hanns Lochmüller Journal: Brain Date: 2008-01-07 Impact factor: 13.501
Authors: C R Slater; P R W Fawcett; T J Walls; P R Lyons; S J Bailey; D Beeson; C Young; D Gardner-Medwin Journal: Brain Date: 2006-08 Impact factor: 13.501
Authors: Samantha J Bryen; Himanshu Joshi; Frances J Evesson; Cyrille Girard; Roula Ghaoui; Leigh B Waddell; Alison C Testa; Beryl Cummings; Susan Arbuckle; Nicole Graf; Richard Webster; Daniel G MacArthur; Nigel G Laing; Mark R Davis; Reinhard Lührmann; Sandra T Cooper Journal: Am J Hum Genet Date: 2019-08-22 Impact factor: 11.025
Authors: Charlotte Vrinten; Angeli M van der Zwaag; Stephanie S Weinreich; Rob J P M Scholten; Jan J G M Verschuuren Journal: Cochrane Database Syst Rev Date: 2014-12-17