by Elena Moro
For October 2017, we have selected: Andersen G, Hedermann G, Witting N, Duno M, Andersen H, Vissing J. The antimyotonic effect of lamotrigine in non-dystrophic myotonias: a double-blind randomized study. Brain 2017;140:2295-2305.
Patients with myotonia congenita and paramyotonia congenita can be disabled by the myotonic phenomenon in the activities of daily living, with a huge impact on their quality of life. In these two channelopaties, impaired chloride (myotonia congenita) or sodium (paramyotonia congenita) conductance provokes sarcolemmal hyperexcitability, which has justified the treatment of myotonia with several anticonvulsant and anti-arrhythmic drugs. Mexiletine, a voltage-gated sodium channel blocker, has been to date the only drug with proven efficacy in myotonia. Mexiletine is not always well tolerated, and has limited availability.
In this phase II randomized, double-blind, placebo-controlled crossover Danish trial, the authors investigated the effects of lamotrigine, a voltage-gated sodium channel blocker, in patients with non-dystrophic myotonia. Adult patients with genetically confirmed myotonia congenita or paramyotonia congenita, disabled by myotonia phenomena and with normal kidney and liver function were included in the study. Participants were randomized in two groups, one with 8-week treatment with lamotrigine first and then placebo for another 8 weeks (Group 1), and the other with placebo first and lamotrigine afterward (Group 2). Between the two 8-week periods a washout time of 1-3 weeks was established. Lamotrigine dose was increased every second week from 25 mg to 300 mg (one single intake in the morning). Primary outcome was the change in the Myotonic Behavior Scale (MBS) at 0, 6, and 8 weeks of each treatment. Secondary outcomes were changes in four functional timed tests, the short form (SF-36) questionnaire, and the use of escape medications. Twenty-six patients were included within almost a two-year period. Twenty-two patients completed the study, which was stopped after the interim analysis because the treatment effect was highly significant. Lamotrigine significantly improved the MBS (from 3.2 ± 1.1 to 1.3 ± 0.2, P<0.001) compared to placebo. He standardized effect of lamotrigine was 1.5 (CI: 1.2-1.8). Lamotrigine also improved significantly the four timed tests and the overall health status, whereas there was no beneficial effect of placebo. Common side effects were observed in both groups.
“This study shows that lamotrigine is effective in improving non-dystrophic myotonias”, says Prof. B. Schoser, Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Germany. “Although a direct comparison with mexiletine was not possible in this trial, lamotrigine significantly improved all patient-related outcomes and objective measures of clinical myotonia over 16 weeks.”
“Compared to mexiletine, lamotrigine has a distinct safety profile, and is much more available,” says Prof. A. Toscano, Department of Neurology, University of Messina, Italy. “All these characteristics are important to patients and neurologists and encourage the use of lamotrigine in both myotonia congenita and paramyotonia congenita. However, further studies need to confirm the long-term effects of lamotrigine in myotonias.”
The other nominees for the October 2017 paper of the month are:
- Athauda D, Maclagan K, Skene SS, et al.Exenatide once weekly versus placebo in Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. Lancet 2017 Aug 3. doi: 10.1016/S0140-6736(17)31585-4. In this single center trial, the effects of exenatide, a glucagon-like peptide-1 receptor agonist, were studied in 62 parkinsonian patients versus placebo. At 60 weeks, the exenatide group (31 patients) showed an improvement of 1.0 point in the motor score whereas the placebo group worsened by 2.1 points. Exenatide seems to be have positive effects in Parkinsonian patients but its mechanism of action needs to be determined.
- Mistry EA, Mistry AM, Nakawah MO, et al. Mechanical thrombectomy outcomes with and without intravenous thrombolysis in stroke patients. A meta-analysis. Stroke 2017;48:2450-2456. Thirteen studies were included in this meta-analysis to investigate the functional outcome at 3-month, the successful recanalization rate, and the symptomatic intracerebral hemorrhage rate in patients who underwent mechanical thrombectomy with or without intravenous thrombolysis. Patients who had thrombectomy plus thrombolysis had overall better outcomes.
- Pahwa R, Tanner CM, Hauser RA, et al. ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study): A Randomized Clinical Trial. JAMA 2017;74:941-949. The authors investigated the efficacy of a single-dose of extended-release amantadine on levodopa-induce dyskinesia in 126 parkinsonian patients. At 3 months, the Unified Dyskinesia Rating Scale was significantly improved in the active drug group compared to placebo group. Amantadine was also effective in reducing the off time.
