Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, MA, 02115, USA.
Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
CNS Drugs. 2022 Jun;36(6):591-604. doi: 10.1007/s40263-022-00921-5. Epub 2022 May 28.
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental and epileptic encephalopathy with infantile-onset epilepsy. Most individuals with CDD develop refractory epilepsy with multiple seizure types. Management of seizures in CDD remains challenging for clinicians given the highly refractory nature of seizures and the limited number of disease-specific studies that offer a high level of evidence. Epileptic spasms are the most common seizure type in CDD and are more often refractory to standard first-line treatment than are spasms of other etiologies. In other seizure types, the effectiveness of antiseizure medications is limited and wanes over time. Ketogenic diet and palliative surgical treatments have both had mixed results in observational studies. When treating refractory seizures in CDD, we recommend carefully balancing seizure control and treatment-related side effects to optimize each individual's overall quality of life. Clinical trials of medications targeting epilepsy in CDD have been conducted, and additional investigational small molecules, gene therapy, and other disease-modifying therapies are in development for CDD.
细胞周期蛋白依赖性激酶样 5（CDKL5）缺乏症（CDD）是一种具有婴儿期起病癫痫的发育性和癫痫性脑病。大多数 CDD 患者会出现难治性癫痫，且具有多种癫痫发作类型。由于癫痫发作具有高度难治性，且针对该疾病的研究数量有限，提供的证据水平较低，因此，CDD 患者的癫痫发作管理对临床医生来说仍然具有挑战性。癫痫痉挛是 CDD 中最常见的癫痫发作类型，与其他病因引起的痉挛相比，其对标准一线治疗的反应更差。在其他癫痫发作类型中，抗癫痫药物的疗效有限，且随着时间的推移而减弱。生酮饮食和姑息性手术治疗在观察性研究中均取得了不同的结果。在治疗 CDD 中的难治性癫痫发作时，我们建议仔细平衡控制癫痫发作和治疗相关副作用，以优化每个患者的整体生活质量。已经针对 CDD 中的癫痫开展了药物临床试验，并且正在开发针对 CDD 的其他研究性小分子、基因治疗和其他疾病修饰疗法。
