Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.
Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.
复制标题
DOI：
10.1136/jnnp-2020-325932
复制
发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Sisodiya SM
中科院分区：
文献类型：
--
作者：
Balestrini S;Chiarello D;Gogou M;Silvennoinen K;Puvirajasinghe C;Jones WD;Reif P;Klein KM;Rosenow F;Weber YG;Lerche H;Schubert-Bast S;Borggraefe I;Coppola A;Troisi S;Møller RS;Riva A;Striano P;Zara F;Hemingway C;Marini C;Rosati A;Mei D;Montomoli M;Guerrini R;Cross JH;Sisodiya SM
“精准医学”一词描述了一种针对一个人的合理治疗策略，可以逆转或改变疾病的病理生理学。在癫痫中，单个病例和小队列报告记录了特定遗传性癫痫的新生精准医学策略。这项多中心观察性研究的目的是研究癫痫精准医学的更深层次的复杂性。在包括儿童和成人在内的六个三级癫痫中心对癫痫患者进行了分子遗传学诊断的系统调查。使用标准化问卷进行数据收集，包括遗传学发现以及对临床和治疗管理的影响。我们纳入了293例遗传性癫痫患者，137名儿童和156名成人，162名女性和131名男性。由于94例患者（32%）的遗传学发现而进行了治疗变更，包括合理的精确药物治疗和/或遗传学诊断提示的治疗变更，但与已知的病理生理学机制无直接关系。56例患者（19%）接受了合理的精确药物治疗，33/56例（59%）尝试了这种治疗，10/33例（30%）患者成功（即癫痫发作减少>50%）。在73/293（25%）的患者中，基因诊断促使治疗发生变化，但与已知的病理生理机制没有直接关系，其中24/73（33%）的治疗取得了成功。我们对专门癫痫中心临床实践的调查显示，在确定癫痫的遗传原因后，临床结果具有很高的变异性。对许多癫痫患者来说，基因检测后治疗模式的有意义的改变尚不可能。这项系统性调查概述了目前精准医学在癫痫中的应用，并建议采用更深思熟虑的方法。
The term ‘precision medicine’ describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy. A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management. We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%). Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
登录
查看更多内容
影响因子：
3.5
作者：
Balestrini S;Sisodiya SM
通讯作者：
Sisodiya SM
影响因子：
2.3
作者：
Balestrini, Simona;Arzimanoglou, Alexis;Walker, Matthew C.
通讯作者：
Walker, Matthew C.
影响因子：
2.5
作者：
Balestrini S;Sisodiya SM
通讯作者：
Sisodiya SM
影响因子：
14.5
作者：
Harkin, Louise A.;McMahon, Jacinta M.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
影响因子：
9.9
作者：
Larsen, Jan;Carvill, Gemma L.;Moller, Rikke S.
通讯作者：
Moller, Rikke S.