Status Epilepticus, Refractory Status Epilepticus, and Super-refractory Status Epilepticus

Sarah E. Nelson, MD; Panayiotis N. Varelas, MD, PhD, FNCS, FAAN p. 1683-1707 December 2018, Vol.24, No.6 doi: 10.1212/CON.0000000000000668
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PURPOSE OF REVIEW: Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus can be life-threatening conditions. This article presents an overview of the three conditions and discusses their management and outcomes.

RECENT FINDINGS: Status epilepticus was previously defined as lasting for 30 minutes or longer but now is more often defined as lasting 5 minutes or longer. A variety of potential causes exist for status epilepticus, refractory status epilepticus, and super-refractory status epilepticus, but all three ultimately involve changes at the cellular and molecular level. Management of patients with status epilepticus generally requires several studies, with EEG of utmost importance given the pathophysiologic changes that can occur during the course of status epilepticus. Status epilepticus is treated with benzodiazepines as first-line antiepileptic drugs, followed by phenytoin, valproic acid, or levetiracetam. If status epilepticus does not resolve, these are followed by an IV anesthetic and then alternative therapies based on limited data/evidence, such as repetitive transcranial magnetic stimulation, therapeutic hypothermia, immunomodulatory agents, and the ketogenic diet. Scores have been developed to help predict the outcome of status epilepticus. Neurologic injury and outcome seem to worsen as the duration of status epilepticus increases, with outcomes generally worse in super-refractory status epilepticus compared to status epilepticus and sometimes also to refractory status epilepticus.

SUMMARY: Status epilepticus can be a life-threatening condition associated with multiple complications, including death, and can progress to refractory status epilepticus and super-refractory status epilepticus. More studies are needed to delineate the best management of these three entities.

Address correspondence to Dr Sarah E. Nelson, Johns Hopkins University, 600 N Wolfe St, Phipps 455, Baltimore, MD 21287,

RELATIONSHIP DISCLOSURE: Dr Nelson receives grant support from the Johns Hopkins Anesthesiology and Critical Care Medicine (ACCM) Stimulating and Advancing ACCM Research (StAAR) program. Dr Varelas serves on the board of directors of the Neurocritical Care Society, on the editorial board of Neurocritical Care, and on an advisory board of Portola Pharmaceuticals, Inc. Dr Varelas has received personal compensation for speaking engagements for Portola Pharmaceuticals, Inc and UCB SA and receives publishing royalties from Springer. Dr Varelas receives research/grant support from Bard Pharmaceuticals Limited; Edge Therapeutics, Inc; Marinus Pharmaceuticals, Inc; the National Institutes of Health; the Patient-Centered Outcomes Research Institute; and Portola Pharmaceuticals, Inc.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Nelson and Varelas discuss the unlabeled/investigational use of allopregnanolone, deep brain stimulation, desflurane, diazepam, electroconvulsive therapy, fosphenytoin, gabapentin, isoflurane, IV immunoglobulin, ketamine, ketogenic diet, lacosamide, levetiracetam, lidocaine, lorazepam, methylprednisolone, midazolam, pentobarbital, phenobarbital, phenytoin, plasma exchange, propofol, pyridoxine, thiopental, topiramate, vagal nerve stimulation, and valproic acid for the treatment of refractory status epilepticus.


© 2018 American Academy of Neurology.