Title:Treatment of Epileptic Encephalopathies
Volume: 23
Issue: 37
Author(s): Simona Balestrini*Sanjay M. Sisodiya
Affiliation:
- Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, and Epilepsy Society, Chalfont-St- Peter, Bucks,United Kingdom
Keywords:
Seizures, antiepileptic treatment, precision medicine, genomics, Epileptic encephalopathies, phenotypes.
Abstract: Background: Epileptic encephalopathies represent the most severe epilepsies, with onset in infancy
and childhood and seizures continuing in adulthood in most cases. New genetic causes are being identified at a
rapid rate. Treatment is challenging and the overall outcome remains poor. Available targeted treatments, based
on the precision medicine approach, are currently few.
Objective: To provide an overview of the treatment of epileptic encephalopathies with known genetic determinants,
including established treatment, anecdotal reports of specific treatment, and potential tailored precision
medicine strategies.
Method: Genes known to be associated to epileptic encephalopathy were selected. Genes where the association
was uncertain or with no reports of details on treatment, were not included. Although some of the genes included
are associated with multiple epilepsy phenotypes or other organ involvement, we have mainly focused on the
epileptic encephalopathies and their antiepileptic treatments.
Results: Most epileptic encephalopathies show genotypic and phenotypic heterogeneity. The treatment of seizures
is difficult in most cases. The available evidence may provide some guidance for treatment: for example,
ACTH seems to be effective in controlling infantile spams in a number of genetic epileptic encephalopathies.
There are potentially effective tailored precision medicine strategies available for some of the encephalopathies,
and therapies with currently unexplained effectiveness in others.
Conclusions: Understanding the effect of the mutation is crucial for targeted treatment. There is a broad range of
disease mechanisms underlying epileptic encephalopathies, and this makes the application of targeted treatments
challenging. However, there is evidence that tailored treatment could significantly improve epilepsy treatment
and prognosis.
