Management of Status Epilepticus in Lennox Gastaut Syndrome
AUTHORS
Tobias Loddenkemper, MD; Robert Tasker, MBBS, MD; Alejandra Vasquez, MD; Marta Gual, MD; Cristina Aguilar, MD; Justice Clark, MD; Theodore Sheehan, MD; Bo Zhang, PhD; Jennifer Gettings, MD FRCPC; Katrina Peariso, MD; Ravindra Arya, MD, DM; Mohamad Mikati, MD; Joshua Goldstein, MD; Nicholas Brenton, MD; Howard Goodkin, MD, PhD; James Riviello, MD; Tristan Sands, MD, PhD; Lindsey Morgan, MD; Edward Novotny, MD; Adam Ostendorf, MD; Sarah Kelley, MD; Christa Habela, MD, PhD; Tracy Glauser, MD; Mark Wainwright, MD, PhD; Eric Payne, MD; Robert Kahoud, MD; Juan Piantino, MD; Angus Wilfong, MD; Korwyn Williams, MD; Brian Appavu, MD
ABSTRACT
Rationale: Lennox Gastaut Syndrome (LGS) affects approximately 1 in 2000 individuals. This refractory epilepsy syndrome is associated with significant morbidity and mortality with frequent bouts of status epilepticus and increased healthcare utilization in comparison to other children with epilepsy. There is a paucity of research evaluating the management of status epilepticus in this patient population.
Methods: We performed a retrospective cross-sectional study based on prospective data collected by the pediatric Status Epilepticus Research Group (pSERG), a consortium of 21 tertiary pediatric hospitals in the United States and Canada. The base study population of pSERG is comprised of pediatric patients with status epilepticus (SE), or refractory status epilepticus (RSE). Patients with a diagnosis of LGS, or with a history of developmental delays and tonic seizures were extracted from this population. SE was defined as five minutes of continuous seizure activity with convulsive seizures at onset. RSE was defined as a failure to achieve seizure control after administration of 2 or more anti-seizure medications (ASMs) or initiation of a continuous infusion.
Results: Among the 845 patients in the pSERG database, 51 children (6%; including 24 females) had a diagnosis of LGS or a history of developmental delays with tonic seizures. The duration of SE ranged from 1 hour to up to 8 days. The most common etiology of SE was a systemic infection (33%; n=17), change in medication regimen (13%; n=7), and unknown (19%; n=10). While 12/51 patients had continuous seizure activity, 39/51 (76%) had intermittent seizures without returning to baseline in between seizures on presentation. 50/51 (98%) patients received a benzodiazepine as a first line abortive agent. 32/50 (64%) received a second dose, 18/32 (56%) a 3rd dose, 10/18 received a 4th dose, 5/10 received a 5th dose, and 2/5 received a 6th dose of a benzodiazepine. The timing of administration of a benzodiazepine from seizure onset ranged from 0-1260 minutes with a median of 9 minutes. Twenty-two patients were placed on a continuous infusion, including 18/22 (81%) on midazolam. Six patients required a second continuous infusion, including treatment with pentobarbital in 66% (n= 4), ketamine in 17% (n=1), and propofol in 17% (n=1). One patient required a third infusion and received pentobarbital after trialing midazolam and ketamine.
Conclusions: Patients with LGS represent a sizable fraction of SE patients, and present frequently with intermittent seizures and delayed treatment, in the setting of seizure triggers. Duration of SE in these patients may be reduced with a targeted, preventative, and individualized approach, including possible medication adjustment around seizure clusters and triggers. A clear understanding of patients’ triggers and seizure susceptibility patterns may help reduce emergency room visits, duration and level of hospital stays, morbidity, mortality, and healthcare costs.