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Antiepileptogenesis in humans: disappointing clinical evidence and ways to move forward

Eugen Trinka1, Francesco Brigo

  • 1aDepartment of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University bCentre for Cognitive Neuroscience, Salzburg, Austria cDepartment of Neurological and Movement Sciences, Section of Clinical Neurology, University of Verona, Verona dDepartment of Neurology, Franz Tappeiner Hospital, Merano, Italy.

Current Opinion in Neurology
|February 22, 2014
PubMed
Abstract

Insights

Developing drugs to prevent epilepsy (antiepileptogenesis) has shown promise in preclinical studies but failed in human trials. Further research is needed to create effective antiepileptogenic drugs and clinical trial designs for epilepsy prevention.

Area of Science:

  • Epileptology
  • Neuroscience
  • Pharmacology

Background:

  • Preclinical research has successfully developed antiseizure drugs (ASDs).
  • Proof-of-concept studies show potential for antiepileptogenic drugs to prevent epilepsy development.
  • Human trials for antiepileptogenesis have consistently failed to prevent epilepsy after brain insults.

Purpose of the Study:

  • To review the current state of antiepileptogenesis research.
  • To identify reasons for the failure of human antiepileptogenesis trials.
  • To outline future directions for developing effective epilepsy prevention strategies.

Main Methods:

  • Review of preclinical and clinical studies in epileptology.
  • Analysis of outcomes from antiepileptogenesis trials.
  • Examination of retrospective data and post-hoc analyses of clinical trials.

Main Results:

  • Current antiseizure drugs (ASDs) do not prevent epilepsy post-stroke, TBI, or in brain tumors.
  • Valproate may improve survival in glioblastoma patients, suggesting a role in managing epilepsy comorbidity.
  • Investigational drugs like rapamycin and everolimus are being studied for epilepsy prevention in tuberous sclerosis.

Conclusions:

  • A coordinated effort between basic and clinical scientists is crucial.
  • Development of effective antiepileptogenic drugs requires further research.
  • Robust biomarkers and valid clinical trial designs are essential for successful epilepsy prevention therapies.

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