Pulsatile corticoid therapy reduces interictal epileptic activity burden in children with genetic drug-resistant epilepsy.

ABSTRACT

OBJECTIVE: Corticosteroids and adrenocorticotropic hormone (ACTH) are the therapy of choice to treat infantile spasms. However, systematic studies about their use in other types of childhood epilepsies remain rare and ACTH can have serious side effects. This study compares the interictal epileptic activity (IEA) burden (% of electroencephalography (EEG) time with IEDs) in children with genetic drug-resistant epilepsy before and after a standardized treatment with pulsatile corticoid therapy (PCT). METHODS: Children with drug-resistant epilepsy underwent a standardized protocol for PCT with cycles of high-dose dexamethasone (20 mg/m2 body surface) intravenously. Patients were hospitalized for 3 days per PCT cycle and EEGs were obtained before initiation of treatment (baseline) and during the hospitalization around the time of every second cycle. EEG recordings during sleep and wakefulness were obtained. IEA burden was compared before and after PCT. Secondary outcome measures included the sleep spindle rate, the seizure frequency and subjective evaluation in a standardized interview. RESULTS: In the cohort of 24 children (10 female, 6.2 ± 3.4 years), IEA burden was lower in the EEG after PCT compared to the baseline (baseline 5.4% [0.7-97.3] vs. after PCT 1.5% [0-96.9], p = 0.001, d = -0.41). Sleep physiology expressed by sleep spindles improved after PCT with enhanced fast spindle rates (0.8/min [0-2.2] vs. 1.5/min [0.2-3.4], p = 0.045, d = 0.36). Seizure frequency was decreased in 17 of the 24 patients (70.8%) with one patient achieving seizure freedom. The majority of patients improved in quality of life (79.2%), and sleep (81.3%). No serious adverse effects were documented. SIGNIFICANCE: This study systematically assessed the effect of PCT in children with genetic / suspected genetic drug-resistant epilepsy. PCT was found to not only reduce the IEA burden but also increase sleep spindle rates, which are important for cognitive functioning. PLAIN LANGUAGE SUMMARY: In this study, children with a form of epilepsy, which is resistant against antiseizure medication, received a systematic treatment with corticosteroids over multiple cycles in the hospital. It was found that not only the epileptic activity was reduced but also the sleep of the patients was improved after the treatment. These findings could provide the basis for extending the use of corticosteroids in children with epilepsy.