Identification of clinically relevant biomarkers of epileptogenesis — a strategic roadmap

• Published in: Nature reviews. Neurology Vol. 17; no. 4; pp. 231 - 242
• Main Authors: Simonato, Michele, Agoston, Denes V., Brooks-Kayal, Amy, Dulla, Chris, Fureman, Brandy, Henshall, David C., Pitkänen, Asla, Theodore, William H., Twyman, Roy E., Kobeissy, Firas H., Wang, Kevin K., Whittemore, Vicky, Wilcox, Karen S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2021; Nature Publishing Group
• Subjects: 692/617/375/178; Animals; Biological markers; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Development and progression; Diagnosis; Electroencephalography; Epilepsy; Epilepsy - blood; Epilepsy - cerebrospinal fluid; Epilepsy - diagnosis; Epilepsy - physiopathology; Humans; Medicine; Medicine & Public Health; MicroRNAs - blood; MicroRNAs - cerebrospinal fluid; Neuroimaging; Neurological research; Neurology; Practice Guidelines as Topic; Review Article; Italy
• ISSN: 1759-4758; 1759-4766; 1759-4766
• DOI: 10.1038/s41582-021-00461-4

Onset of many forms of epilepsy occurs after an initial epileptogenic insult or as a result of an identified genetic defect. Given that the precipitating insult is known, these epilepsies are, in principle, amenable to secondary prevention. However, development of preventive treatments is difficult because only a subset of individuals will develop epilepsy and we cannot currently predict which individuals are at the highest risk. Biomarkers that enable identification of these individuals would facilitate clinical trials of potential anti-epileptogenic treatments, but no such prognostic biomarkers currently exist. Several putative molecular, imaging, electroencephalographic and behavioural biomarkers of epileptogenesis have been identified, but clinical translation has been hampered by fragmented and poorly coordinated efforts, issues with inter-model reproducibility, study design and statistical approaches, and difficulties with validation in patients. These challenges demand a strategic roadmap to facilitate the identification, characterization and clinical validation of biomarkers for epileptogenesis. In this Review, we summarize the state of the art with respect to biomarker research in epileptogenesis and propose a five-phase roadmap, adapted from those developed for cancer and Alzheimer disease, that provides a conceptual structure for biomarker research. Biomarkers of epileptogenesis would enable identification of individuals who are risk of developing epilepsy after an insult or as a result of a genetic defect. In this article, Simonato et al. review progress towards such biomarkers and set out a five-phase roadmap to facilitate their development. Key points Many forms of epilepsy manifest and/or are diagnosed months or even years after an epileptogenic insult or identification of a genetic defect. Epilepsies that result from an insult or genetic defect could be amenable to secondary prevention but preventive treatments are not available. Development of preventive therapies is complicated by the fact that only a subset of at-risk individuals develop clinical epilepsy. Biomarkers are needed to clearly identify individuals who have the highest risk of developing epilepsy after an epileptogenic insult. We propose a strategic roadmap designed to facilitate the identification, characterization and clinical validation of biomarkers for epileptogenesis.