Faculty Collaboration Database

Pharmacotherapy for Pediatric Convulsive Status Epilepticus. CNS Drugs 2020 Jan;34(1):47-63

Date

12/28/2019

Pubmed ID

31879852

Pubmed Central ID

PMC6982635

DOI

10.1007/s40263-019-00690-8

Scopus ID

2-s2.0-85077384955 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABA_A receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.

Author List

Singh A, Stredny CM, Loddenkemper T

Author

Avantika Singh MBBS Assistant Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anticonvulsants
Child
Humans
Seizures
Status Epilepticus