Long-term response to high-dose diazepam treatment in continuous spikes and waves during sleep

Abstract

Background: This study evaluated whether the reduction in epileptiform activity after treatment with high-dose diazepam in continuous spikes and waves during sleep persists over time.

Patients: Patients aged 1 to 21 years with continuous spikes and waves during sleep who received high-dose nocturnal diazepam and who had electroencephalogram follow-up were included. Twenty-nine patients met the inclusion criteria and underwent a total of 48 high-dose diazepam treatment cycles.

Results: An overnight reduction of the spike wave percentage of at least 25% (i.e., 75-50%) occurred in 29 cycles (20 patients), and persisted within 6 months in 16 of 29 cycles (12 patients), but returned to baseline in three of 29 cycles (three patients). An overnight reduction of at least 50% (i.e., 75-25%) occurred in 15 cycles (13 patients), and persisted within 6 months in eight of 15 cycles (eight patients), but returned to baseline in three cycles (three patients). Twenty of 29 cycles that responded in the short term had persistent response on follow-up. Thirteen cycles of treatment were associated with mild side effects that did not recur with repeated treatment cycles.

Conclusions: Treatment with high-dose diazepam reduced epileptiform activity in continuous spikes and waves during sleep in the short term, and improvement persisted for several months in most cycles. Short-term response predicted persistence of this effect on subsequent follow-up.

Conflict of interest statement

The rest of the authors do not have potential conflict of interests to disclose.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Figure 1.. Flowchart of included and excluded patients in our study.

This figure demonstrates steps for inclusion and exclusion of patients. Patients were excluded due to insufficient clinical information, lack of EEG features meeting diagnostic criteria of electrical status epilepticus in sleep or lack of regression and developmental stagnation. Legend: EEG: Electroencephalogram. ESES: Electrical status epilepticus in sleep.

Figure 2.. Graphical representation of the clinical and EEG evolution in two representative patients in our population.

We provide information on patients 1 and 3 in this figure. The information in our whole patient population can be found in Supplementary Figure 1. The y-axis displays spike wave percentage on EEG and the x-axis displays the timing of clinical events, including different stages of the condition (as marked by abbrevations for epilepsy onset (EO), electrical status epilepticus in sleep (ESES), regression(R), and seizure freedom (SF) on the bottom of each figure), spike wave percentage as demonstrated by red flags, and antiepileptic treatment choices and respective duration displayed as horizontal bars on top of each figure. The different clinical events are displayed as triangles in the orange timeline. The vertical dotted line represents the time of last follow-up. Treatment with high-dose diazepam reduces epileptiform activity even when it is very elevated and this reduction persists for a period of several months in most cases. Legend: B: Birth. EO: Epilepsy onset. HDDZP: High-dose diazepam. LEV: Levetiracetam. R: Regression/stagnation. SF: Seizure freedom. T HDDZP: Taper high-dose diazepam. VPA: Valproate. ZNS: Zonisamide.