Ephedrine therapy in eight patients with congenital myasthenic syndrome due to DOK7 mutations

Dept. of Pediatric Neurology, University of Essen, Germany.
Neuromuscular Disorders (Impact Factor: 3.13). 10/2009; 19(12):828-32. DOI: 10.1016/j.nmd.2009.09.008
Source: PubMed

ABSTRACT In congenital myasthenic syndrome with DOK7 mutations ephedrine was reported to be beneficial in single patients. We carried out a small, open and prospective cohort study in eight European patients manifesting from birth to 12 years. Five patients showed limb-girdle and facial weakness, three a floppy infant syndrome with bulbar symptoms and/or respiratory distress. Ephedrine was started with 25 mg/day and slowly increased to 75-100 mg/day. Within weeks after starting therapy an improvement was observed in all patients and clinical follow-up disclosed positive effects more pronounced on proximal muscle weakness and strength using MRC scale. Effects on facial weakness were less pronounced. Vital capacity measurements and repetitive stimulation tests did not improve in the same way as clinical symptoms did. These investigations are appropriate to confirm the diagnosis in case of pathological results, but they might not be appropriate means to monitor patients under ephedrine therapy.

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    • "Ephedrine has been shown to be helpful, with patients reporting an improvement over a 1–24 month period [5] [6]. However, ephedrine has both a and b-adrenergic effects and concern remains regarding central and cardiac adverse effects, particularly with long term use in children. "
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    ABSTRACT: Congenital myasthenic syndromes due to DOK7 mutations cause fatigable limb girdle weakness. Treatment with ephedrine improves muscle strength. Salbutamol, a β(2)-adrenergic receptor agonist with fewer side effects and more readily available, has been effective in adult and anecdotal childhood cases. This study reports the effects of salbutamol on motor function in childhood DOK7 congenital myasthenic syndrome. Nine children (age range 5.9-15.1years) were treated with oral salbutamol, 2-4mg TDS. The effect on timed tests of motor function, pre- and up to 28months post-treatment, was audited retrospectively. All 9 reported functional benefit within 1month, with progressive improvement to a plateau at 12-18months. Within the first month, all 3 non-ambulant children resumed walking with assistance. Although improvements were seen in some timed tests (timed 10m, arm raise time, 6min walk time) this did not fully reflect the observed functional benefits in daily living activities. No major side effects were reported. We conclude that oral salbutamol treatment significantly improves strength in children with DOK7 congenital myasthenic syndrome and is well tolerated. Outcome measures need to be refined further, both to accurately reflect functional abilities in children and to document progress and treatment response.
    Neuromuscular Disorders 12/2012; 23(2). DOI:10.1016/j.nmd.2012.11.004 · 3.13 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Neurology 05/2010; 74(19):1517-23. DOI:10.1212/WNL.0b013e3181dd43bf · 8.30 Impact Factor
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