Antimyoclonic Effect of Levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A>G Mutation

Chin Med J (Engl). 2018 Oct 20;131(20):2433-2438. doi: 10.4103/0366-6999.243568.


Background: Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers (MERRFs) has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects of monotherapies, including levetiracetam (LEV), clonazepam (CZP), valproic acid (VPA), and topiramate (TPM) compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures.

Methods: Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months of follow-up (mean: 82.9 ± 28.1 days), 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The follow-up period was 4-144 months (mean: 66.3 ± 45.3 months), the effective rates of monotherapy group (17 patients) and combination therapy group (12 patients) were analyzed by Chi-square test.

Results: The m.8344 A>G mutation was detected in all patients. There were four patients with partial response (4/17, two in the CZP group and two in the LEV group), ten patients with stable disease (10/17, six in the CZP group, three in the LEV group, and one in the TPM group), and three patients with progressive disease (3/18, two in the VPA group and one in the TPM group). Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance (12/12), eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy group in the efficacy of antimyoclonic seizures (χ2 = 13.7, P < 0.001).

Conclusions: LEV in combination with CZP is an efficient and safe treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A>G mutation.

左乙拉西坦联合氯硝西泮治疗携带m.8344A>G突变的MERRF患者肌阵挛癫痫发作的疗效研究 摘要 背景:目前,对MERRF患者肌阵挛癫痫发作的治疗主要靠医生的临床经验,疗效较差,尚无统一的标准和指南。需要更多的临床实验来总结经验探索更适宜的治疗方法。本研究通过观察丙戊酸、氯硝西泮、托吡酯和左乙拉西坦单药治疗组与左乙拉西坦和氯硝西泮联合治疗组的疗效,探索控制MERRF患者肌阵挛癫痫发作的更好的方法。 方法:齐鲁医院神经内科从2003年到2016年共收集17例MERRF患者,这些患者均依靠临床资料和基因检测结果进行确诊。首先根据临床初诊情况以丙戊酸钠、氯硝西泮、托吡酯、左乙拉西坦作为单药治疗,观察疗效。经过1-4月的随访,12例疗效差的患者再联合应用左乙拉西坦和氯硝西泮治疗,单药治疗组(17例患者)和联合用药组(12例患者)的疗效最后以卡方检验进行分析。 结果:17例患者均携带m.8344 A>G突变,单药治疗组中共4例患者部分缓解(4/17,氯硝西泮组2例,左乙拉西坦组2例),10例患者无明显变化(10/17,氯硝西泮组6例,左乙拉西坦组3例,托吡酯组1例),3例患者癫痫发作加重(3/17,丙戊酸钠组2例,托吡酯组1例)。12例疗效差并接受左乙拉西坦和氯硝西泮联合治疗的患者,均出现较好疗效和耐受性(12/12),而且有8例患者在智能和共济运动方面也有不同程度改善。单药治疗组(17例患者)和联合用药组(12例患者)在抗肌阵挛癫痫发作方面的疗效有显著差异性 (χ2=13.7, P < 0.001)。 结论左乙拉西坦联合氯硝西泮在治疗MERRF患者肌阵挛癫痫发作方面具有良好疗效及安全性。.

Keywords: Clonazepam; Levetiracetam; Myoclonic Epilepsy with Ragged-Red Fibers; Myoclonic Seizures.

MeSH terms

  • Adolescent
  • Adult
  • Chi-Square Distribution
  • Clonazepam / therapeutic use*
  • Epilepsies, Myoclonic / diagnostic imaging*
  • Epilepsies, Myoclonic / drug therapy*
  • Epilepsies, Myoclonic / genetics
  • Female
  • Humans
  • Levetiracetam / therapeutic use*
  • MERRF Syndrome / diagnostic imaging*
  • MERRF Syndrome / drug therapy*
  • MERRF Syndrome / genetics
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics
  • Young Adult


  • Levetiracetam
  • Clonazepam