Electro-clinical Variables Associated with Clobazam Response in Adults Presenting with Refractory Status Epilepticus: A Retrospective Study
Arichena Ramanathan Manmatharayan1, Rene Andrade Machado2, Paul Lee3, Abdalhamid Lagnf4, Hassan Souidan4, Taha Ataya6, Farah Abdelhak4, Rohan Thomas4, Rami Fakhouri5, Younes Motii4, Margerie Durban6, Janaki Patel6, Dennis Parker Jr.6, Cristina Jageka6, Wazim Mohamed3, Mona Elsayed6
1Wayne State University/Detroit Medical Center, 2Children Hospital of Wisocnsin, 3Detroit Medical Center/Wayne State University, 4Wayne State University, 5Neurology, Wayne State University, 6Wayne State University/ Detroit Medical Center
Objective:
To assess the response of clobazam in status epilepticus.
Background:
Status epilepticus is a life-threatening emergency that requires prompt intervention. Seizure resolution is often difficult to attain promptly due to multiple clinical variables. Clobazam is structurally different from typical benzodiazepines with an affinity to the α2 subunit of GABA-A receptors, rendering unique efficacy in seizure termination. 
Design/Methods:

A retrospective review of charts of consecutive patients admitted to the Neurocritical Care Unit diagnosed with status epilepticus was conducted. Adult patients with continuous EEG monitoring with clobazam used as the last anti-epileptic agent were included.

Results:

Sixteen patients were identified out of which eleven patients (68.8%) had convulsive status epilepticus with hemiclonic as the most common semiology. Thirteen (81.2%) of the sixteen patients responded to clobazam within a mean of 23.5 hours since starting clobazam. Of the three non-responders (18.8%), all were diagnosed with generalized SE. On average, 3 other anti-epileptic medications were tried prior to clobazam, with the average time of initiation being 27 hours since status epilepticus onset. Two electrographic patterns were associated with a successful response to clobazam on continuous EEG: the first type as focal onset seizures starting with repetitive spikes that evolved to faster frequencies and the second type as lateralized periodic discharges (LPDs) evolving from 1-1.5 Hz per second to 2-3 Hz per second at the onset of each focal seizure. Rhythmic spikes were seen in eleven patients (68.8%) out of which ten (76.9%) were responders.

Conclusions:

Rapid chemoresistance to standard first-line benzodiazepines and second-line anti-epileptic agents occurs as seizures persist during status epilepticus. Our study provides EEG correlates to the successful use of clobazam in treating status epilepticus based on its unique property of targeting the GABAA subtype receptors involved in phasic inhibition.

 

10.1212/WNL.0000000000205419