Immediate Treatment of Seizure Clusters: A Conceptual Roadmap to Expedited Seizure Management

Abstract

James W Wheless,1 Danielle A Becker,2 Selim R Benbadis,3 Vinay Puri,4 Proleta Datta,5 Dave Clarke,6 Deepa Panjeti-Moore,7 Enrique Carrazana,8,9 Adrian L Rabinowicz8,10 1Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, TN, USA; 2Department of Neurology, Ohio State University Wexner Medical Center, Columbus, OH, USA; 3Comprehensive Epilepsy Program, University of South Florida & Tampa General Hospital, Tampa, FL, USA; 4Norton Children’s Neuroscience Institute, Affiliated with University of Louisville, Louisville, KY, USA; 5Department of Neurology, School of Medicine, Oregon Health & Science University, Portland, OR, USA; 6Dell Children’s Comprehensive Pediatric Epilepsy Center, University of Texas at Austin, Austin, TX, USA; 7Epilepsy Program; Neurology Consultants of Dallas, Dallas, TX, USA; 8Clinical Development and Medical Affairs, Neurelis, Inc., San Diego, CA, USA; 9Department of Family Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; 10Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL, USACorrespondence: James W Wheless, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, 777 Washington Avenue, Suite 335, Memphis, TN, 38105, USA, Tel [phone], Fax [phone], Email [email protected]: Some patients with epilepsy continue to have seizures despite daily treatment with antiseizure medications. This includes seizure clusters (also known as acute repetitive seizures), which are an increase in seizure frequency that is different from the usual seizure pattern for that patient. In the literature, the term “rescue” is used for pharmacologic treatment for seizure clusters, but clarity regarding timing or whether a caregiver or patient should wait until a moment of life-threatening urgency before administering the medication is lacking. Additionally, the concept of waiting 5 minutes to identify and initiate treatment of status epilepticus has been carried over to the treatment of seizure clusters, as well as the idea of waiting owing to safety concerns, without reevaluation in the context of the reported safety profiles for currently available as-needed therapies when administered as prescribed. Delaying treatment of seizure clusters may have negative outcomes, including injury, emergency room use, hospitalization, and progression to status epilepticus. Additionally, increased time for administration of benzodiazepines, the cornerstone therapies for seizure clusters, may lower the potency and effectiveness once administration takes place, because of physiologic changes. Thus, clarifying the importance of timing in the treatment terminology may be of benefit in the acute context. The term “immediate-use seizure medication” (ISM), meaning treatment that is administered as quickly as possible once a seizure cluster is recognized, may help to clarify the timing of as-needed treatment. This review examines the recognition and definitions of seizure clusters, the physiologic rationale for ISM for seizure clusters, and the effectiveness and safety of early treatment. Remaining knowledge gaps are also discussed. The findings of this review suggest that it may be time to revisit the terminology of “rescue”, which implies waiting to administer treatment for seizure clusters, as doing so is not supported by pathophysiologic, effectiveness, or safety data.Plain Language Summary: Some people with epilepsy have seizures even if they take daily medication for their seizures. If they have more seizures than usual in a day, this may be called a seizure cluster. Drugs used to treat clusters are often said to be “rescue” medicines. But the word “rescue” may imply that the medication should only be administered when serious danger is present. Additionally, possibly because of previous instructions, people may think they have to wait to see if the seizure lasts more than 5 minutes to give the medicine, or they may be concerned about how safe the medicine will be if they give it. This older approach needs to be revisited and replaced. Waiting to give medicine could make it more likely that a person could get hurt or require a hospital or emergency room visit or their seizure condition could worsen. Waiting also may allow for changes in the body that may make a medicine less effective once it is given. Because of this, it may be better to say these medicines are for “immediate use” rather than for “rescue”. That way, the people giving the medicine know that they should give it as soon as they see the patient needs it. This paper discusses how seizure clusters are described and what can happen if someone waits to give medicine versus giving it right away. The paper shows that waiting may not be needed.Keywords: benzodiazepine, early intervention, epilepsy, rescue therapy

Keywords

• benzodiazepine
• early intervention
• epilepsy
• rescue therapy