Authors :
Presenting Author: Siyi Wang, MD – Department of Neurology, Xuanwu Hospital, Clinical Center for Epilepsy, Capital Medical University, Beijing 100053, China
Jialin Du, MD – Department of Neurology, Xuanwu Hospital, Clinical Center for Epilepsy, Capital Medical University, Beijing 100053, China
Jinghui Liu, MD – Department of Neurology, Xuanwu Hospital, Clinical Center for Epilepsy, Capital Medical University, Beijing 100053, China
Hongxin Wang, MD – Jinan Hospital of Xuanwu Hospital, Shandong First Medical University, Jinan 250013, China
Lehong Gao, MD – Xuanwu Hospital, Capital Medical University, Beijing, China
Xiaoxiao Man, MD – Jinan Hospital of Xuanwu Hospital, Shandong First Medical University, Jinan 250013, China
Junliang Ge, MD – Department of Neurology, Xuanwu Hospital, Clinical Center for Epilepsy, Capital Medical University, Beijing 100053, China
Shimin Hu, MD – Department of Neurology, Xuanwu Hospital, Clinical Center for Epilepsy, Capital Medical University, Beijing 100053, China
Xianghong Meng, MD – Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, China
Hongyang Zhao, MD – Department of Pediatrics, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
Yuping Wang, MD, PhD – Xuanwu Hospital, Capital Medical University, Beijing, China
Zhiqi Xiong, PhD – Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China.
Guoguang Zhao, MD, PhD – Xuanwu Hospital, Capital Medical University
Liankun Ren, MD, PhD – Xuanwu Hospital, Capital Medical University, Beijing, China
Rationale:
CDKL5 deficiency disorder (CDD) is a rare, severe developmental and epileptic encephalopathy. There is a pressing need to develop effective and sustainable therapeutic strategies. We aimed to clarify the association between fever and seizure frequency for therapeutic implications by investigating the genotype-phenotype correlation in a cohort of CDD patients.
Methods:
The study was a national, cross-sectional survey on CDD patients in China. The detailed phenotypic and genotypic profiles were collected through an online self-administered questionnaire. The primary outcome was seizure frequency changes during and post-fever phase compared to the baseline of 1 month pre-fever phase. This study is registered with ClinicalTrials.gov, NCT06663163.
Results:
Between March 2024 and November 2024, a total of 102 eligible patients from the majority of regions in China were enrolled. Eighteen patients were excluded due to missing data. Ultimately, 84 patients with documented high fever experiences were included. Among these, 47 (55.95%) patients had significant decreased seizure frequency during high fever, and 27 (32.14%) who had daily seizure achieved at least a seizure-free day. Notably, seizure reduction persisted for 1 to 40 days after fever in 20 patients (23.81%). The effect was independent of patients’ clinical characteristics and mutation locations or types.
Conclusions:
Our findings firstly revealed that fever-related seizure frequency reduction is the distinctive and prevalent genotype-phenotype for CDD, thereby providing evidence to support the development of innovative therapeutic strategies and to further fundamental research for patients.
Funding:
This work has been carried out with the support of the Beijing Hospitals Authority Clinical Medicine Development of special funding support (ZLRK202321); National Key R & D Program of China (2024YFA1306903, 2022YFC2503805); National Natural Science Foundation of China (82371457, 82071454).