2024-03-28T19:52:21Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:02000298
2022-12-15T04:16:28Z
453:455
471:561:562
Clinical manifestations and epilepsy treatment in Japanese patients with pathogenic CDKL5 variants
CDKL5遺伝子病的バリアントを持つ日本人患者の臨床的特徴とてんかん治療について
Kobayashi, Yu
小林, 悠
open access
【○!C】 2020 Published by Elsevier B.V.
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
CDKL5
Pathogenic variants
Developmental and epileptic encephalopathy
Involuntary movements
Antiepileptic drugs
Adrenocorticotrophic hormone
Ketogenic diet
Rational polytherapy
Objective: Patients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments. Methods: We recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis. We retrospectively reviewed clinical, electroencephalogram, neuroimaging, and genetic information. Results: We identified 29 patients (21 females, eight males). All patients showed severe developmental delay, especially in males. Involuntary movements were observed in 15 patients. No antiepileptic drugs (AEDs) achieved seizure freedom by monotherapy. AEDs achieving ≥ 50% reduction in seizure frequency were sodium valproate in two patients, vigabatrin in one, and lamotrigine in one. Seizure aggravation was observed during the use of lamotrigine, potassium bromide, and levetiracetam. Adrenocorticotrophic hormone (ACTH) was the most effective treatment. The ketogenic diet (KD), corpus callosotomy and vagus nerve stimulation did not improve seizure frequency in most patients, but KD was remarkably effective in one. The degree of brain atrophy on magnetic resonance imaging (MRI) reflected disease severity. Compared with females, males had lower levels of attained motor development and more severe cerebral atrophy on MRI. Conclusion: Our patients showed more severe global developmental delay than those in previous studies and had intractable epilepsy, likely because previous studies had lower numbers of males. Further studies are needed to investigate appropriate therapy for CDD, such as AED polytherapy or combination treatment involving ACTH, KD, and AEDs.
Brain and Development. 2021, 43(4), 505-514.
新大院博(医)第993号
eng
doctoral thesis
http://hdl.handle.net/10191/0002000298
https://niigata-u.repo.nii.ac.jp/records/2000298
https://doi.org/10.1016/j.braindev.2020.12.006
甲第4839号
博士(医学)
2021-03-23
13101
新潟大学
Niigata University
https://niigata-u.repo.nii.ac.jp/record/2000298/files/r2nmk993.pdf
application/pdf
386KB
2022-04-04
https://niigata-u.repo.nii.ac.jp/record/2000298/files/r2nmk993_a.pdf
application/pdf
546KB
2022-04-04