The management of epilepsy in children and adults

Perucca, Piero; Scheffer, Ingrid E; Kiley, Michelle

doi:10.5694/mja17.00951

ARTICLE
AUTHORS
REFERENCES

Topics

Nervous system diseases

Pharmaceutical preparations

Summary

The International League Against Epilepsy has recently published a new classification of epileptic seizures and epilepsies to reflect the major scientific advances in our understanding of the epilepsies since the last formal classification 28 years ago. The classification emphasises the importance of aetiology, which allows the optimisation of management.
Antiepileptic drugs (AEDs) are the main approach to epilepsy treatment and achieve seizure freedom in about two-thirds of patients.
More than 15 second generation AEDs have been introduced since the 1990s, expanding opportunities to tailor treatment for each patient. However, they have not substantially altered the overall seizure-free outcomes.
Epilepsy surgery is the most effective treatment for drug-resistant focal epilepsy and should be considered as soon as appropriate trials of two AEDs have failed. The success of epilepsy surgery is influenced by different factors, including epilepsy syndrome, presence and type of epileptogenic lesion, and duration of post-operative follow-up.
For patients who are not eligible for epilepsy surgery or for whom surgery has failed, trials of alternative AEDs or other non-pharmacological therapies, such as the ketogenic diet and neurostimulation, may improve seizure control.
Ongoing research into novel antiepileptic agents, improved techniques to optimise epilepsy surgery, and other non-pharmacological therapies fuel hope to reduce the proportion of individuals with uncontrolled seizures. With the plethora of gene discoveries in the epilepsies, “precision therapies” specifically targeting the molecular underpinnings are beginning to emerge and hold great promise for future therapeutic approaches.

1 Royal Melbourne Hospital, Melbourne, VIC
2 Monash University, Melbourne, VIC
3 Epilepsy Research Centre, Austin Health, University of Melbourne, Melbourne, VIC
4 Florey Institute of Neuroscience and Mental Health, Melbourne, VIC
5 Royal Adelaide Hospital, Adelaide, SA

Correspondence: piero.perucca@mh.org.au

Acknowledgements:

This work was supported by the Melbourne International Research Scholarship and the Melbourne International Fee Remission Scholarship from the University of Melbourne and the Warren Haynes Neuroscience Research Fellowship from the Royal Melbourne Hospital Neuroscience Foundation (P Perucca); and by a National Health and Medical Research Council (NHMRC) Program Grant (1091593, 2016–2020) and an NHMRC Senior Practitioner Fellowship (1104831, 2016–2020) (IE Scheffer).

Competing interests:

P Perucca has received honoraria from Eisai. IE Scheffer serves on the editorial boards of and ; may accrue future revenue on a pending patent on a therapeutic compound; has received speaker honoraria from Athena Diagnostics, UCB, GlaxoSmithKline, Eisai, and Transgenomic; has received scientific advisory board honoraria from Nutricia, UCB and GlaxoSmithKline; has received funding for travel from Athena Diagnostics, UCB and GlaxoSmithKline; and receives research support from the NHMRC, the Australian Research Council, the National Institutes of Health, the Health Research Council of New Zealand, March of Dimes, the Weizmann Institute of Science, Citizens United for Research in Epilepsy (CURE), the United States Department of Defense and the Perpetual Charitable Trustees.

1. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46: 470-472.
2. Beghi E, Hesdorffer D. Prevalence of epilepsy — an unknown quantity. Epilepsia 2014; 55: 963-967.
3. Salomon JA, Vos T, Hogan DR, et al. Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2129-2143.
4. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55: 475-482.
5. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58: 522-530.
6. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58: 512-521.
7. Raspall-Chaure M, Neville BG, Scott RC. The medical management of the epilepsies in children: conceptual and practical considerations. Lancet Neurol 2008; 7: 57-69.
8. Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol 2011; 10: 446-456.
9. Perucca E. Introduction to the choice of antiepileptic drugs. In: Shorvon SD, Perucca E, Engel J, editors. The treatment of epilepsy, 4th ed. Oxford: Wiley-Blackwell, 2015; pp 365-375.
10. Perucca P, Jacoby A, Marson AG, et al. Adverse antiepileptic drug effects in new-onset seizures: a case-control study. Neurology 2011; 76: 273-279.
11. Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology 2012; 78: 1548-1554.
12. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369: 1000-1015.
13. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369: 1016-1026.
14. Brodie MJ, Perucca E, Ryvlin P, et al; Levetiracetam Monotherapy Study Group. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007; 68: 402-408.
15. Baulac M, Brodie MJ, Patten A, et al. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol 2012; 11: 579-588.
16. Baulac M, Rosenow F, Toledo M, et al. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol 2017; 16: 43-54.
17. Tomson T, Marson A, Boon P, et al. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia 2015; 56: 1006-1019.
18. Patel SI, Pennell PB. Management of epilepsy during pregnancy: an update. Ther Adv Neurol Disord 2016; 9: 118-129.
19. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51: 1069-1077.
20. Ryvlin P, Cross JH, Rheims S. Epilepsy surgery in children and adults. Lancet Neurol 2014; 13: 1114-1126.
21. Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. N Engl J Med 2015; 373: 1048-1058.
22. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017; 376: 2011-2020.
23. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia 2015; 56: 1246-1251.
24. French J, Thiele E, Mazurkiewicz-Beldzinska M, et al. Cannabidiol (CBD) significantly reduces drop seizure frequency in Lennox-Gastaut syndrome (LGS): results of a multi-center, randomized, double-blind, placebo controlled trial (GWPCARE4)(S21.001). Neurology 2017; 88: S21.001.
25. Wirrell E, Devinsky O, Patel A, et al. Cannabidiol (CBD) significantly reduces drop and total seizure frequency in Lennox-Gastaut syndrome (LGS): results of a dose ranging, multicenter, randomized, double blind, placebo controlled trial (GWPCARE3). Ann Neurol 2017; 82: S279.
26. Therapeutic Goods Administration. Access to medicinal cannabis products [website]. Canberra: TGA; 2017. https://www.tga.gov.au/access-medicinal-cannabis-products (viewed Aug 2017).
27. Wiebe S, Blume WT, Girvin JP, Eliasziw M; Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 2001; 345: 311-318.
28. Choi H, Sell RL, Lenert L, et al. Epilepsy surgery for pharmacoresistant temporal lobe epilepsy: a decision analysis. JAMA 2008; 300: 2497-2505.
29. Engel J, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 2003; 60: 538-547.
30. Englot DJ, Ouyang D, Garcia PA, et al. Epilepsy surgery trends in the United States, 1990–2008. Neurology 2012; 78: 1200-1206.
31. Engel J, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA 2012; 307: 922-930.
32. Englot DJ, Chang EF, Auguste KI. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg 2011; 115: 1248-1255.
33. DeGiorgio CM, Krahl SE. Neurostimulation for drug-resistant epilepsy. Continuum (Minneap Minn) 2013; 19: 743-755.
34. Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010; 51: 899-908.
35. Morrell MJ; RNS System in Epilepsy Study Group. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 2011; 77: 1295-1304.
36. Winesett SP, Bessone SK, Kossoff EH. The ketogenic diet in pharmacoresistant childhood epilepsy. Expert Rev Neurother 2015; 15: 621-628.
37. Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 2008; 7: 500-506.
38. Klein P, Tyrlikova I, Mathews GC. Dietary treatment in adults with refractory epilepsy: a review. Neurology 2014; 83: 1978-1985.
39. Franco V, Perucca E. The pharmacogenomics of epilepsy. Expert Rev Neurother 2015; 15: 1161-1170.
40. Chung WH, Hung SI, Hong HS, et al. Medical genetics: a marker for Stevens–Johnson syndrome. Nature 2004; 428: 486.
41. Amstutz U, Shear NH, Rieder MJ, et al. Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia 2014; 55: 496-506.
42. McCormack M, Alfirevic A, Bourgeois S, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 2011; 364: 1134-1143.
43. Chung WH, Chang WC, Lee YS, et al. Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA 2014; 312: 525-534.
44. Speed D, Hoggart C, Petrovski S, et al. A genome-wide association study and biological pathway analysis of epilepsy prognosis in a prospective cohort of newly treated epilepsy. Hum Mol Genet 2014; 23: 247-258.
45. EpiPM Consortium. A roadmap for precision medicine in the epilepsies. Lancet Neurol 2015; 14: 1219-1228.
46. Perucca P, Scheffer IE, Harvey AS, et al. Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy. Epilepsy Res 2017; 131: 1-8.
47. Engelsen BA, Tzoulis C, Karlsen B, et al. POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection. Brain 2008; 131: 818-828.
48. Devinsky O, Hesdorffer DC, Thurman DJ, et al. Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Lancet Neurol 2016; 15: 1075-1088.
49. Nashef L. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997; 38: S6-S8.
50. Harden C, Tomson T, Gloss D, et al. Practice guideline summary: sudden unexpected death in epilepsy incidence rates and risk factors: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2017; 88: 1674-1680.

Online responses are no longer available. Please refer to our instructions for authors page for more information.

The management of epilepsy in children and adults

Topics

Summary

Author

Comment

Do you have any competing interests to declare? *