Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Mailstop 3063, Boston, MA, 02115, USA.
Division of Pediatric Neurology, University of Saskatchewan, Saskatoon, SK, Canada.
J Neurodev Disord. 2021 Sep 16;13(1):40. doi: 10.1186/s11689-021-09384-z.
CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population.
We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders.
The four most frequently prescribed anti-seizure medications were broad spectrum, prescribed in over 50% of individuals. While the goal was not to ascertain efficacy, we obtained data from 86 individuals regarding response to treatment, with 2-week response achieved in 14-48% and sustained 3-month response in 5-36%, of those with known response. Additional treatments for seizures included cannabis derivatives, tried in over one-third of individuals, and clinical trial medications. In combination with pharmacological treatment, 50% of individuals were treated with ketogenic diet for attempted seizure control. Surgical approaches included vagus nerve stimulators, functional hemispherectomy, and corpus callosotomy, but numbers were too limited to assess response. Nearly one-third of individuals received pharmacologic treatment for sleep disturbances, 13% for behavioral dysregulation and movement disorders, and 43% had gastrostomy tubes.
Treatment for neurologic features of CDD is currently symptom-based and empiric rather than CDD-specific, though clinical trials for CDD are emerging. Epilepsy in this population is highly refractory, and no specific anti-seizure medication was associated with improved seizure control. Ketogenic diet is commonly used in patients with CDD. While behavioral interventions are commonly instituted, information on the use of medications for sleep, behavioral management, and movement disorders is sparse and would benefit from further characterization and optimization of treatment approaches. The heterogeneity in treatment approaches highlights the need for systematic review and guidelines for CDD. Additional disease-specific and disease-modifying treatments are in development.
CDKL5 缺乏症（CDD）与难治性婴儿期起病癫痫、全面发育迟缓以及包括睡眠、行为障碍和运动障碍在内的各种特征有关。目前的治疗主要是基于症状的，并借鉴了对该人群的护理经验。
我们描述了在满足 CDD 标准的 177 名患者队列中，针对癫痫和其他关键神经症状（睡眠障碍、行为问题、运动障碍和吞咽功能障碍）的药物和非药物治疗方法，这些患者在美国的 4 个 CDKL5 卓越中心进行了评估，另外 40 名患者通过 NIH 雷特综合征和相关疾病自然史研究确定。
最常开的四种广谱抗癫痫药物，处方使用于超过 50%的患者。虽然我们的目标不是确定疗效，但我们从 86 名患者那里获得了关于治疗反应的数据，已知有反应的患者中，2 周反应率为 14-48%，3 个月持续反应率为 5-36%。另外，超过三分之一的患者尝试使用大麻衍生药物治疗癫痫发作，并且使用了临床试验药物。为了控制癫痫发作，除了药物治疗外，50%的患者还接受了生酮饮食治疗。手术方法包括迷走神经刺激器、功能性大脑半球切除术和胼胝体切开术，但由于数量有限，无法评估反应。近三分之一的患者接受了睡眠障碍的药物治疗，13%的患者接受了行为失调和运动障碍的药物治疗，43%的患者接受了胃造口术。
目前，CDD 神经症状的治疗是基于症状和经验的，而不是针对 CDD 特异性的，尽管针对 CDD 的临床试验正在出现。该人群的癫痫发作高度难治，没有特定的抗癫痫药物与改善癫痫发作控制相关。生酮饮食在 CDD 患者中常用。虽然行为干预通常被采用，但关于睡眠、行为管理和运动障碍药物治疗的信息很少，需要进一步描述和优化治疗方法。治疗方法的异质性突出表明需要对 CDD 进行系统评价和指南制定。另外，还有针对该疾病的特异性和疾病修饰治疗方法正在开发中。
