Abstracts

Early Clinical and Electroencephalographic Features in Patients with CDKL5 Deficiency Disorder: A Case Series Study

Abstract number : 1.177
Submission category : 18. Case Studies
Year : 2024
Submission ID : 962
Source : www.aesnet.org
Presentation date : 12/7/2024 12:00:00 AM
Published date :

Authors :
Presenting Author: guojun zhang, MD – National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University

Laura Davids, MMS – children's Healthcare of Atlanta
Jenny Lin, MD – Children's Healthcare of Atlanta
Sonam Bhalla, MD – Emory University School of Medicine, Children's Healthcare of Atlanta
david wolf, MD. PhD – Children's Healthcare of Atlanta

Rationale: CDKL5 deficiency disorder (CDD) is associated with severe early-onset epileptic encephalopathy. Most affected individuals are female, with surviving males typically exhibiting a more severe clinical course. Clinical and electroencephalographic (EEG) studies have identified various features of epileptic encephalopathy commonly encountered in individuals with CDD, including focal seizures, tonic seizures, myoclonic seizures, hypermotor seizures, and infantile spasms. However, no study has specifically addressed the early clinical and electrophysiological features following seizure onset. Early detection of initial seizure semiology and specific EEG patterns is crucial for more targeted molecular genetic testing, differential diagnosis, and clinical management.

Methods:
We evaluated the medical records of 10 females and 6 males with CDD, focusing our analysis on the first seizure semiology and initial EEG findings within the first two weeks after seizure onset. Specifically, we analyzed the initial interictal EEG findings of 12 patients and the ictal EEG findings of 11 patients.




Results:
The median age of seizure onset was 8.1 weeks (range: 2-12 weeks). None of the patients had developmental delays except for hypotonia or hypertonia observed during neurological examinations, which were more common in male patients (5/6) compared to female patients (3/10). The initial seizure types included hypermotor (13/16), tonic (8/16), and focal (5/16) seizures. Thirteen out of sixteen patients exhibited at least two types of seizures. The EEG background was normal in all patients. Initial interictal EEG did not show epileptiform discharges in 3 out of 12 patients. Four out of 12 patients showed focal sharp waves in the central/parasagittal regions, 2 out of 12 patients showed focal sharp waves in the bilateral temporal/posterior regions, and 3 out of 12 patients demonstrated epileptiform discharges in both regions. The associated ictal EEG in 11 patients showed central/parasagittal generalized fast activities (6/11) or rhythmic sharp waves (5/11) in the temporal or posterior head regions.




Conclusions:
This case series study is the first to analyze seizure semiology and initial EEG findings within the first two weeks after seizure onset in 16 patients with CDD. Unlike previous reports, this cohort includes a large proportion of male patients (6 out of 16, 37.5%), significantly higher than previously reported in literature. The most common EEG finding was focal and multifocal sharp waves without hypsarrhythmia or burst suppression patterns. This suggests that in developmentally normal neonates or young infants, especially females with focal, tonic, or hypermotor seizures and the aforementioned EEG findings, genetic testing should be conducted to confirm or rule out a diagnosis of CDD. These unique features were not seen in other neonatal onset developmental epileptic encephalopathies (DEE), such as those associated with KCNQ2, SCN2A, SCN8A, and STXBP1 mutations, all of which are often accompanied by more severe EEG abnormalities.




Funding: None

Case Studies