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  • Review Article
  • Published:

Impact of predictive, preventive and precision medicine strategies in epilepsy

Abstract

Over the last decade, advances in genetics, neuroimaging and EEG have enabled the aetiology of epilepsy to be identified earlier in the disease course than ever before. At the same time, progress in the study of experimental models of epilepsy has provided a better understanding of the mechanisms underlying the condition and has enabled the identification of therapies that target specific aetiologies. We are now witnessing the impact of these advances in our daily clinical practice. Thus, now is the time for a paradigm shift in epilepsy treatment from a reactive attitude, treating patients after the onset of epilepsy and the initiation of seizures, to a proactive attitude that is more broadly integrated into a ‘P4 medicine’ approach. This P4 approach, which is personalized, predictive, preventive and participatory, puts patients at the centre of their own care and, ultimately, aims to prevent the onset of epilepsy. This aim will be achieved by adapting epilepsy treatments not only to a given syndrome but also to a given patient and moving from the usual anti-seizure treatments to personalized treatments designed to target specific aetiologies. In this Review, we present the current state of this ongoing revolution, emphasizing the impact on clinical practice.

Key points

  • Advances in genetics, biochemistry, neurophysiology and imaging have led to the development of diagnostic biomarkers for epilepsy and the redefinition of some epileptic syndromes to incorporate aetiology.

  • Three new types of targeted therapies have been applied to the treatment of epilepsies: substitutive therapy, therapies that block signalling pathways and therapies that normalize ion channel conductance.

  • Targeted therapies and gene therapy are components of personalized medicine, which belongs to ‘P4’ medicine, a new proactive approach that puts the patient at the centre of care.

  • Primary and secondary prevention of epilepsy is becoming a reality in humans, particularly in the case of monogenic epilepsy, where certain therapies seem to have an anti-epileptogenic effect.

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Fig. 1: Use of biomarkers in the management of epilepsy.
Fig. 2: A P4 medicine-type approach applied to the management of epilepsy.

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Acknowledgements

R.N. was supported at Imagine institute by the Bettencourt Schueller Foundation.

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Glossary

Electro-clinical syndromes

Clusters of common clinical and EEG characteristics that enable the grouping of patients with epilepsy into more homogenous patient groups in terms of outcome and response to anti-seizure medicines.

Seizure semiology

Clinical symptoms linked to epileptic seizures.

Ictal

The period of time during an epileptic seizure.

Antisense oligonucleotides

(ASOs). Synthetic oligonucleotides that have a sequence that is complementary to a target messenger RNA resulting in binding of the messenger RNA and inhibition of the synthesis of the target protein.

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Nabbout, R., Kuchenbuch, M. Impact of predictive, preventive and precision medicine strategies in epilepsy. Nat Rev Neurol 16, 674–688 (2020). https://doi.org/10.1038/s41582-020-0409-4

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