Authors :
Presenting Author: Kette Valente, MD,PhD – Clinics Hospital, Faculty of Medicine, University of Sao Paulo (USP)
Rachel Marin, MD – Clinics Hospital, Faculty of Medicine, University of Sao Paulo (USP); Fernanda Melo, Med Student – Faculty of Medicine, University of Sao Paulo (USP); Gustavo Vega, MD – Clinics Hospital, Faculty of Medicine, University of Sao Paulo (USP); Silvia Vincentiis, MD, PhD – Clinics Hospital, Faculty of Medicine, University of Sao Paulo (USP); Ana Neves-Borg, Representative – Association of CDKL5 Brasil; Bianca Spagnol, Representative – Association of CDKL5 Brasil
Rationale: To better understand the needs of physicians and patients in Brazil, a Task Force representing a liaison between researchers of the University of São Paulo and the Association of CDKL5 collaborated to evaluate current diagnostic and treatment practices for CDKL5 among the Brazilian population.
Methods: A 54-question online survey was conducted to gather information from families in the CDKL5 Association. Survey domains included demographics, epilepsy-related factors, and treatment. Non-seizure symptoms were not evaluated.
Results: This sample comprised 43 patients (86% female; mean age of 8 yrs [IQR: 1.3- 25]). Early seizure onset, within the first two months of life (mean 2.4 mo), occurred in 32 (74.4%) children, with thirteen during the neonatal period.
The mean age of diagnosis was three years, ranging from 38 days to 16 years, with a mean gap of 4.9 years between the first symptom and the genetic diagnosis. Patients were seen by 4.42 (1-15) physicians before referral. The primary indicators that led to the genetic exam were epilepsy [35 (81.4%)], hypotonia [15 (34.9%)], and developmental delay [27 (62.8%)]. Most patients were referred to an epilepsy panel ( 34.9%) or an exome (39.5%). Genetic exams were considered the last resort for 15 children (34.88%). The primary obstacles to genetic testing were the cost, which affected 24 patients (55.81%), and non-referral, which impacted 12 patients (27.9%).
During follow-up, the most frequent seizures were epileptic spasms (65.8%), TCG (57.9%), tonic (39.5%), atypical absence (34.2%), and myoclonic (31.6%). Twenty-five (65.8%) children had daily and 13 (34.2%) had weekly seizures. Thirty-six (83.7%) patients experienced clusters, and 22 (52.4%) had prolonged seizures. Four families had adequate rescue medication.
Patients received a mean of 3.58 ASMs/day (ranging from 1-5) and a mean of 6.3 (1-15) throughout life. Current or previous non-pharmacological treatment was reported by 16 respondents (14 with a therapeutic diet and four with VNS). 86% of respondents knew about ongoing or newly approved CDKL5 studies; only two would refuse inclusion in clinical trials for their children.
Conclusions: Individuals diagnosed with DEE-CDKL5 experience severe epilepsy, often accompanied by hypotonia and developmental delays. Lack of knowledge and costs determined late diagnosis. It led to empirical treatment showing the need for a paradigm shift in diagnosis and treatment. Caregivers of these individuals know the potential benefits of clinical trials and are willing to participate to help their children.
Funding: No funding.