Pulsatile corticoid therapy reduces interictal epileptic activity burden in children with genetic drug-resistant
Katharina Schiller1,2,3, John Thomas1, Tamir Avigdor1
1Analytical Neurophysiology Lab, Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, Montreal, Quebec, Canada.
Insights
Pulsatile corticoid therapy (PCT) significantly reduced interictal epileptic activity burden in children with drug-resistant epilepsy. This treatment also improved sleep spindle rates and quality of life, offering a potential new therapeutic avenue.
Area of Science:
- Pediatric Neurology
- Epileptology
- Pharmacology
Background:
- Corticosteroids and adrenocorticotropic hormone (ACTH) are standard for infantile spasms but less studied in other childhood epilepsies.
- ACTH carries risks of serious side effects.
- Limited data exists on the efficacy of corticosteroids in genetic, drug-resistant childhood epilepsies.
Purpose of the Study:
- To evaluate the impact of a standardized pulsatile corticoid therapy (PCT) protocol on interictal epileptic activity (IEA) burden in children with genetic drug-resistant epilepsy.
- To assess secondary outcomes including sleep spindle rates, seizure frequency, and quality of life.
Main Methods:
- A cohort of 24 children with drug-resistant epilepsy received standardized PCT using high-dose intravenous dexamethasone.
- Electroencephalography (EEG) recordings were obtained at baseline and during treatment cycles.
- IEA burden, sleep spindle rates, and seizure frequency were compared before and after PCT.
Main Results:
- PCT significantly reduced IEA burden (baseline: 5.4% vs. post-PCT: 1.5%, p=0.001).
- Sleep spindle rates increased significantly (p=0.045), indicating improved sleep physiology.
- Seventy-one percent of patients experienced decreased seizure frequency, with most reporting improved quality of life and sleep. No serious adverse effects were noted.
Conclusions:
- PCT is effective in reducing IEA burden in children with genetic drug-resistant epilepsy.
- PCT improves sleep physiology, evidenced by increased sleep spindle rates.
- These findings support the potential expansion of corticosteroid use in managing pediatric drug-resistant epilepsy.
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.
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