Abstracts

Rationale: CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy caused by pathogenic variants in the CDKL5 gene. Ganaxolone is a neurosteroid recently approved specifically for the treatment of CDD. There is no published data on the early initiation of ganaxolone in individuals with CDD.


Methods: We identified CDD patients initiated on ganaxolone before the age of 2 years in the CDKL5 Registry at the Cleveland Clinic CDKL5 Center of Excellence. We included only patients who had received ganaxolone for more than 6 months. We extracted cross-sectional demographic and genetic information, as well as longitudinal data on patients' seizure frequencies, antiseizure medications (AMS) doses, and EEG evaluations. We provide a descriptive summary of the included cases.


Results: We included four CDD patients started on ganaxolone before 2 years of age. One additional patient who recently started on ganaxolone at age 17 months was not included. Clinical details on the patients can be found in the Table. All patients received genetic diagnoses within one month from seizure onset. The timelines of each patient's seizure frequencies, developmental milestones, and ASMs until the last follow-up are displayed in the Figure. Patients 1, 2 and 4 received ketogenic diet (KD) at ratio 3:1 starting at age 5, 6 and 4 months respectively. Patient 4 discontinued KD at 20 months due to loss of efficacy. Patient 2 was initiated on ganaxolone at the earliest (at 5 months), and patient 4 – at the latest (at 17 months). All patients responded to ganaxolone with decrease in seizure burden from daily to at least weekly. One individual with mild phenotype (Patient 3) attained seizure freedom on monotherapy and had a relapse upon attempt to decrease the dose. Restitution of the dose lead to regaining seizure freedom. None of the patients had side effects related to ganaxolone.


Conclusions: Ganaxolone was well tolerated, safe and provided seizure reduction in our case series of children with CDD under the age of 2 years. Some of the patients entered honeymoon after initiating treatment with ganaxolone, nevertheless the reason for honeymoon in patients with CDD is not well understood. Early genetic diagnosis allows for early initiation of the medication. Further controlled studies are needed to investigate seizure- and development-related benefits of early ganaxolone initiation, and continued advocacy efforts are required to enable early ganaxolone access through insurance.


Funding: none