In this blog series, IFCR’s Science Director, Heidi Grabenstatter, breaks down CDKL5 publications in easy-to-understand language.

Publication: Olson HE, Demarest S, Pestana- Knight E, Moosa AN, Zhang X, Pérez- Pérez JR, et al. Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first- line therapies. Epilepsia. 2023;00:1–12. https://doi.org/10.1111/epi.17630

What was the researcher looking to learn in this research? Using a retrospective study approach, Olson and colleagues aimed to investigate how patients with CDKL5 deficiency disorder (CDD) responded to common infantile-onset epileptic spasms (ES) treatments relative to other disorders found in the National Infantile Spasms Consortium (NISC).

What did they learn? Time to treatment of ES is often prolonged in CDD, and CDD patients have a poorer response to first-line therapies (i.e., ACTH, prednisolone, or vigabatrin) relative to other disorders. In the CDD cohort, the response rates to treatment appeared to be similar between those with shorter vs longer time to treatment.

The majority of CDD patients with ES have other seizure types that preceded their spasms. The most common types were focal motor, generalized tonic, generalized tonic-clonic, and myoclonic. The minority (34% in this report) of CDD patients with ES have hypsarrhythmia on EEG (i.e., abnormal high amplitude waves and a background of irregular spikes) at spasms onset.  Lower rates of hypsarrhythmia at ES diagnosis may have contributed to the delay in treatment or lower rates of use of first-line treatment in the CDD cohort.

What does this mean for the landscape of CDKL5 research? This study is the first to evaluate ES treatment response in CDKL5 deficiency disorder (CDD).

In the CDD cohort, clinical remission of ES by 14 days was slightly higher with vigabatrin as the first treatment than ACTH or prednisolone, but the number of CDD patients who were initially treated with vigabatrin was small and not significant.

The rare remission of ES to first-line treatments in CDD raises the questions of whether benefit outweighs risks of side effects for the treatments, and whether new treatment approaches are needed.

Anecdotal reports from CDKL5 Centers of Excellence suggest that the ketogenic diet treatment may prevent or delay ES onset in infants with CDD. Firm conclusions regarding the efficacy of the ketogenic diet could not be made as the diet was initiated early after ES onset in only a few patients. Thus, future studies may be considered to assess the efficacy of the ketogenic diet in early infancy for the treatment of ES in the CDD population.

How was IFCR connected to this research? Retrospective data collected in this study used a standardized form from the IFCR-funded CDKL5 Centers of Excellence.

We know this is complex information and we encourage you to always have discussions with your medical provider to make decisions that work best for your family.