Abstracts

RATIONALE: Childhood epilepsy syndromes have poor clinical outcome if EEG abnormalities remain intractable and clinical seizures persist. Prior studies have described the use of diazepam for treatment of CSWS. We detail our experience with a modified diazepam protocol for treating continuous spike wave activity in sleep (CSWS). In the current study, we performed the intervention on an outpatient basis in conjunction with simultaneous EEG recording in children with Lennox-Gastaut Syndrome (LGS) or Landau-Kleffner Syndrome (LKS). We hypothesized that improvements in both EEG and control of epileptic seizures would be apparent if the diazepam protocol was successful.
METHODS: In order to be included in the study, all children had failed at least two seizure medications including valproic acid and steroids. All children had pulse-oximetry and vitals checked during the diazepam ingestion on Day 1. Nine children (7 LGS, 2 LKS, (9F/3M, age range 2-10 years) were administered rectal or oral diazepam (1-1.5 mg/kg doses given during Day 1 of protocol), followed by a 0.5-0.75 mg/kg daily diazepam dosing for 2-3 additional weeks. EEG studies were performed on day 1, 2, and 21 or 28 of the protocol.
RESULTS: When sustained EEG improvement occurred, it was readily observable on the Digitrace within 30-90 minutes after high-dose diazepam ingestion. These improvements were notable in 4/7 LGS and 2/2 LKS patients. Follow-up on Day 21 or 28 revealed EEG in 3 /4 initial responders with LGS and 2/2 with LKS showed significant changes. Clinical correlation for these 6 patients revealed continued improvement of overt seizures. No complications occurred other than irritability or intoxication during the first 24 hours in 6/7 patients, and prolonged irritability in 3/7 patients. The symptoms of mood change resolved with tapering diazepam over several weeks.
CONCLUSIONS: Severe childhood seizure syndromes such as LGS or LKS typically have limited pharmacologic responses. Steroids, high-dose valproic acid or poly-AED therapy are often implemented without benefit. High dose diazepam short-term protocols may offer an alternative to these more prolonged therapies with only transient side-effects. Future studies should evaluate the long-term efficacy of this short-term intervention.