Authors :
Presenting Author: Katharina Schiller, PhD – Montreal Neurological Hospital and Institute, McGill University
John Thomas, PhD – Montreal Neurological Hospital and Institute; Tamir Avigdor, MSc – Montreal Neurological Hospital and Institute; Daniel Mansilla, MD – Montreal Neurological Hospital and Institute; Aline Kortas, MD – Children's Hospital Kaufbeuren; Gabriele Unterholzner, MD – Children's Hospital Kaufbeuren; Markus Rauchenzauner, Prof., MD – Children's Hospital Kaufbeuren; Birgit Frauscher, Prof., MD – Montreal Neurological Hospital and Institute
Rationale:
Corticosteroids and adrenocorticotrophic hormones (ACTH) are the therapy of choice to treat infantile spasms (1). However, systematic studies about the use in other types of childhood epilepsies remain rare (2), ACTH can have severe side effects, and studies using oral steroids vary widely in dosage and dosing interval (3). This study compares the epileptic burden in children with genetic drug-resistant epilepsy before and after a standardized treatment with pulsatile corticoid therapy (PCT) using an objective (automated) and subjective (paediatric neurologist and parents) approach.Methods:
Twenty-four consecutive children with genetic drug-resistant epilepsy underwent a standardized protocol for PCT with cycles of three days hospitalization and high-dose dexamethasone (20mg/m2 body surface) intravenously. Recordings of electroencephalogram (EEG) during sleep and wake were obtained at baseline before initiation of treatment and at the end of PCT. We computed the epileptic burden (% of EEG burdened with spikes) before and after treatment. Secondary objectives were the sleep spindle rate as physiological marker, the seizure frequency, and subjective evaluation by the parents in a standardized interview between both time points.Results:
In the final study cohort of 24 children (10 female, 6.2±3.4 years), the spike burden was significantly lower in the EEG after PCT versus the baseline (baseline vs. after PCT: 5.4% [0.7-97.3] vs. 1.5% [0-96.9], p=0.001, d=-0.41, Figure 1 & 2). Sleep physiology improved with significantly higher fast spindle rates in the EEG after PCT compared to the baseline EEG (0.8/min [0-2.2] vs. 1.5/min [0.2-3.4], p=0.015, d=0.36). Seventeen patients (70.8%) showed an improvement in seizure frequency and one patient became seizure-free. The highest improvement in everyday functioning was reported for quality of life (79.2%), cognition (70.8%), alertness (54.2%) and sleep (54.2%). No severe adverse effects were registered.Conclusions:
This study systematically assessed the effect of pulsatile corticoid in children with different types of genetic drug-resistant epilepsy. Using objective and subjective markers, PCT was found to not only reduce the epileptic burden but also to improve physiological measurements important for cognitive functioning.Funding:
This study was supported by a project grant of the Canadian Institutes of Health Research (PJT-175056) to BF. KS & JT were funded by a postdoctoral fellowship (Savoy Epilepsy Foundation to KS, Jeanne Timmins Costello to JT). B.F. was supported by the Fonds de Recherche du Québec–Santé 2021-2025 Salary Award “Chercheur-boursier clinicien Senior”.
References:
1. Lombroso CT. A prospective study of infantile spasms: clinical and therapeutic correlations. Epilepsia. 1983;24(2):135-58.
2. Mehta V et al. Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms. Cochrane Database Syst Rev. 2015(6).
3. Haberlandt E et al. Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes. Pediatr Neurol. 2010;42(1):21-7.