Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy.
Department of Pediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, University Hospital of Lyon, Member of the ERN EpiCARE, Lyon, France.
Eur J Neurol. 2024 Jul;31(7):e16275. doi: 10.1111/ene.16275. Epub 2024 Apr 4.
Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy.
A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement.
A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ-aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted.
These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug-related adverse events in individuals living with PMD-related epilepsy.
原发性线粒体疾病（PMD）是常见的先天性能量代谢错误，估计患病率为每 4300 人中有 1 人。这些疾病通常影响能量需求较高的组织，包括心脏、肌肉和大脑。癫痫可能是 PMD 的首发表现，治疗困难，常代表预后不良的特征。本研究旨在制定关于线粒体性癫痫安全用药和癫痫发作管理的指南和共识建议。
成立了一个由 24 名成人和/或儿童线粒体医学、药理学和癫痫管理专家以及来自七个国家的两名患者代表组成的专家组。专家是五个不同的欧洲参考网络（称为 Mito InterERN 工作组）的成员。采用德尔菲技术，让小组成员考虑有关线粒体性癫痫安全用药和癫痫发作管理的建议草案，两轮投票均设定了预定的共识水平。
对于审查的 25 种药物中的 14 种药物的安全性达成了高度共识，这导致对国家卫生与保健卓越研究所（NICE）癫痫管理指南的认可，同时进行了一些修改。例外情况包括 POLG 疾病中使用丙戊酸、γ-氨基丁酸转氨酶缺乏症中使用氨己烯酸以及有肾小管酸中毒风险的患者中使用托吡酯。
这些共识建议描述了我们的意图，即改善癫痫控制并降低患有 PMD 相关癫痫的个体发生药物相关不良事件的风险。
