TY - JOUR
T1 - Identification of clinically relevant biomarkers of epileptogenesis — a strategic roadmap
AU - Simonato, Michele
AU - Agoston, Denes V.
AU - Brooks-Kayal, Amy
AU - Dulla, Chris
AU - Fureman, Brandy
AU - Henshall, David C.
AU - Pitkänen, Asla
AU - Theodore, William H.
AU - Twyman, Roy E.
AU - Kobeissy, Firas H.
AU - Wang, Kevin K.
AU - Whittemore, Vicky
AU - Wilcox, Karen S.
N1 - Publisher Copyright:
© 2021, Springer Nature Limited.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85100910470&partnerID=8YFLogxK
U2 - 10.1038/s41582-021-00461-4
DO - 10.1038/s41582-021-00461-4
M3 - Review article
C2 - 33594276
AN - SCOPUS:85100910470
SN - 1759-4758
VL - 17
SP - 231
EP - 242
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
IS - 4
ER -