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Epilepsy

Abstract

Epilepsy affects all age groups and is one of the most common and most disabling neurological disorders. The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences. Although many patients have seizure control using a single medication, others require multiple medications, resective surgery, neuromodulation devices or dietary therapies. In addition, one-third of patients will continue to have uncontrolled seizures. Epilepsy can substantially impair quality of life owing to seizures, comorbid mood and psychiatric disorders, cognitive deficits and adverse effects of medications. In addition, seizures can be fatal owing to direct effects on autonomic and arousal functions or owing to indirect effects such as drowning and other accidents. Deciphering the pathophysiology of epilepsy has advanced the understanding of the cellular and molecular events initiated by pathogenetic insults that transform normal circuits into epileptic circuits (epileptogenesis) and the mechanisms that generate seizures (ictogenesis). The discovery of >500 genes associated with epilepsy has led to new animal models, more precise diagnoses and, in some cases, targeted therapies.

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Figure 1: Seizure classification.
Figure 2: Framework for the classification of the epilepsies.
Figure 3: Mechanisms of epileptogenesis.
Figure 4: | Ictogenesis of focal seizures.
Figure 5: Interictal abnormalities detected using EEG.
Figure 6: Epileptogenic lesions.

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Authors and Affiliations

Authors

Contributions

Introduction (O.D. and I.E.S.); Epidemiology (N.J.); Mechanisms/pathophysiology (A.V., M.d.C. and I.E.S.); Diagnosis, screening and prevention (P.P. and I.E.S.); Management (T.J.O.B.); Quality of life (O.D.); Outlook (I.E.S. and O.D.); and Overview of Primer (O.D.).

Corresponding author

Correspondence to Orrin Devinsky.

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Competing interests

O.D. has received research funding from the US NIH, GW Pharmaceuticals, Novartis and PTC Pharmaceuticals. He has equity in Egg Rock Holdings, Empatica, Engage Therapeutics, Pairnomix, Rettco and Tilray. He is the Principal Investigator for the North American SUDEP Registry and the SUDC Registry and Research Collaborative. He currently receives research funding from NIH and the US Centers for Disease Control and Prevention. He consults for the Center for Discovery. A.V. has received consultancy fees from UCB Pharma and research grants from Ovid, Pfizer and Takeda. T.J.O.B. has received research funding from Eisai, the National Health and Medical Research Council of Australia, the NIH, the Royal Melbourne Hospital Neuroscience Foundation and UCB Pharma. N.J. currently receives research funding from Alberta Health, the Canadian Institute of Health Research and the NIH, and is an associate editor of Epilepsia and serves on the editorial board of Neurology. I.E.S. has served on scientific advisory boards for BioMarin, Eisai, GlaxoSmithKline, Nutricia and UCB Pharma, sits on the editorial boards of Epileptic Disorders and Neurology and might accrue future revenue on a pending patent. I.E.S. has also received speaker honoraria from Athena Diagnostics, Eisai, GlaxoSmithKline, Transgenomics and UCB Pharma, has received funding for travel from Athena Diagnostics, Biocodex, BioMarin, Eisai, GlaxoSmithKline and UCB Pharma, and has received research support from the American Epilepsy Society, the Australian Research Council, CURE, the Health Research Council of New Zealand, the March of Dimes, the National Health and Medical Research Council of Australia, the NIH, the US Department of Defense Autism Spectrum Disorder Research Program, and Perpetual Charitable Trustees. P.P. has received honoraria from Eisai. All other authors declare no competing interests.

Supplementary information

Supplementary box 1

Epilepsy syndromes by age of seizure onset. (PDF 88 kb)

Supplementary Table 1

Precision therapies. (PDF 124 kb)

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Devinsky, O., Vezzani, A., O'Brien, T. et al. Epilepsy. Nat Rev Dis Primers 4, 18024 (2018). https://doi.org/10.1038/nrdp.2018.24

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