Stiripentol for Status Epilepticus

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Wednesday, March 25, 2015

What is the problem?

Epilepsy is characterized by recurring and unprovoked abnormal synchronous brain activity leading to the disruption of normal brain function. While the majority of these seizures stop on their own, a fraction may persist. These types of continuous seizures are called status epilepticus (SE). SE is a neurologic emergency and is defined as a single seizure lasting longer than 5 minutes, or when two seizures occur without complete recovery between them.

Benzodiazepines (BZDs), a class of anti-seizure medications, are considered the first line of treatment for SE, but BZDs may lose effectiveness during the progression of SE. Thus as the length of SE increases, the ability of BZDs to safely and effectively stop the seizure decreases. This phenomenon, referred to as refractory-SE, occurs in as many as 45% of patients, putting them at an increased risk for death.

The goal of the current study was to examine the effectiveness of stiripentol (STP, Diacomit) in stopping BZD-refractory status epilepticus. STP is currently approved in Europe for treatment of Dravet syndrome, a severe form of epilepsy occurring in infants.

How was the question approached?

In this study, the authors assessed the effectiveness of STP in experimental rats by asking three questions:

  1. Can STP stop a brief seizure when given alone?
  2. Is STP effective in stopping prolonged SE at a time when resistance to BZDs has developed?
  3. How does STP work?

Rats received either STP or a BZD at the onset of seizures (brief SE) or 45 minutes after the first seizure (prolonged SE). Additionally, the effect of these compounds on neurotransmission was examined in prolonged-SE experienced rats to understand a potential mechanism of action.

What did the study conclude?

Using an established animal model of SE, it was determined that STP is able to stop a brief seizure. Most importantly, STP remains effective in terminating SE at a time when resistance to BZDs has developed. Additionally, it was concluded that the ability of STP to stop prolonged-SE is partly due to its ability to positively regulate neurotransmission which, unlike the BZD, is not impaired during the course of SE.

What do these findings mean?

These findings suggest that STP may be effective in stopping BZD-refractory SE. While these results should be confirmed with more experiments, they open the door for further exploration of Stiripentol and other novel compounds with similar pharmacological profiles for the treatment of SE, as currently available therapeutics are limited.

Authored by: Denise Grosenbaugh PhD on 3/2015
Reviewed by: Sloka Iyengar PhD | Basic Science Editor on 3/2015

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The mission of the Epilepsy Foundation is to lead the fight to overcome the challenges of living with epilepsy and to accelerate therapies to stop seizures, find cures, and save lives.

 
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