The Impact of Interictal Discharges on Performance
- 14 Downloads
Purpose of Review
Our purpose is to review evidence relating to the concept that interictal epileptiform discharges (IEDs) impair brain performance.
Sophisticated measures of motor and cognitive performance have clarified older observations, confirming that in both animals and humans, IEDs affect aspects of performance, IED morphology, frequency, anatomical distribution, and duration matter. However, we now know that it is difficult to draw a line between IEDs and seizures, not only by electrical criteria but even by metabolic and molecular measures.
IEDs impair performance acutely and probably chronically. Thus, there are good theoretical reasons for suppressing them, but no consensus has been reached on how much effort this deserves. Many antiepileptic medications effective for control of clinical seizures have little effect on IEDs. Better methods of measuring outcomes may allow selection of individual patients for whom treatment aimed at IEDs is worthwhile.
KeywordsEpilepsy Interictal discharges Performance Antiepileptic drugs EEG
Compliance with Ethical Standards
Conflict of Interest
Edward Faught reports grants and personal fees from UCB Pharma, personal fees from Eisai, grants from Brain Sentinel, personal fees from Biogen, grants from NINDS/University of Alabama at Birmingham, outside the submitted work. Ioannis Karakis declares no potential conflict of interest. Daniel L. Drane reports grants from Medtronic, Inc., personal fees from Neuropace, grants from NIH/NINDS, outside the submitted work.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.• Rubinos C, Reynolds AS, Claasen J. The ictal-interictal continuum: to treat or not to treat (and how)? Neurocrit Care. 2018;29:3–8 This paper outlines the difficulty of distinguishing between interictal and ictal phenomena by EEG criteria and suggests practical approaches to treatment. CrossRefGoogle Scholar
- 8.Schwab RS. A method of measuring consciousness in petit-mal epilepsy. J Nerv Ment Dis. 1939;89:690–1.Google Scholar
- 13.• Ebus SC, Ijff DM, den Boer JT, van Hall MJ, Klinkenberg S, van der Does A, et al. Changes in the frequency of benign focal spikes accompany changes in central information processing speed: a prospective 2-year follow-up study. Epilepsy Behav. 2015;43:8–15 One of the few longitudinal studies correlating spike frequency with well-defined neuropsychological concepts. CrossRefGoogle Scholar
- 14.Baglietto MG, Battaglia FM, Nobili L, Tortorelli S, De Negri E, Calevo MG, et al. Neuropsychological disorders related to interictal epileptic discharges during sleep in benign epilepsy of childhood with centrotemporal or Rolandic spikes. Dev Med Child Neurol. 2001;43(6):407–12.CrossRefGoogle Scholar
- 19.• De Curtis M, Jefferys JG, Avoli M. Interictal epileptiform discharges in partial epilepsy: complex neurobiological mechanisms based on clinical and experimental evidence. In: Noebels JL, Avoli M, Rogawski M, editors. Jasper’s Basic Mechanisms of the Epilepsies. 4th ed. Rockville: Bethesda; 2012. Although a little dated, a thorough review of the neurobiology of IEDs. Google Scholar
- 26.• Hernan AE, Alexander A, Jenks KR, Barry J, Lenck-Santini PP, Isaeva E, et al. Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits. Neurobiol Dis. 2014;63:25–34. https://doi.org/10.1016/j.nbd.2013.11.012 One of the only studies bearing on personality (though in rats) rather than specific performance measures. CrossRefPubMedGoogle Scholar
- 34.• Glennon JM, Weiss-Croft L, Harrison S, Cross JH, Boyd SG, Baldeweg T. Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy. Epilepsia. 2016;57:1436–42 Embodies one of the more cogent arguments for caring about IEDs, especially in the developing brain. CrossRefGoogle Scholar
- 39.• Dinkelacker V, Xin X, Baulac M, Samson S, Dupont S. Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy. Epilepsy Behav. 2016;62:197–203 An example of the modern trend in IED research which focuses on very specific operationally-defined performance measures. CrossRefGoogle Scholar
- 44.• Ung H, Cazares C, Nanivadekar A, Kini L, Wagenaar J, Becker D, et al. Interictal epileptiform activity outside the seizure onset zone impacts cognition. Brain. 2017;140:2157–68 This paper suggests that the potential harm of IEDs extend beyond those that occur in the seizure focus itself, a troubling finding. CrossRefGoogle Scholar
- 45.• Nirkko AC, Bernasconi C, von Allmen A, Liechti C, Mathis J, Krestel H. Virtual car accidents of epilepsy patients, interictal epileptic activity, and medication. Epilepsia. 2016;57(5):832–40. https://doi.org/10.1111/epi.13361 Measuring the effect of IEDs on a critical real-world task with computer simulation. CrossRefPubMedGoogle Scholar
- 48.• Ibrahim GM, Cassel D, Morgan BR, Smith ML, Otsubo H, Ochi A, et al. Resilience of developing brain networks to interictal epileptiform discharges is associated with cognitive outcome. Brain. 2014;137:2690–702 Why are some individuals more affected by IEDs than others? A possible path to treatment decisions for individual patients. CrossRefGoogle Scholar
- 50.• Young MG, Vadera S, Lin JJ, Mnatsakanyan L. Using electrocorticogram baseline seizure frequency to assess the efficacy of responsive neurostimulation. Epilepsy Behav. 2018;85:7–9. https://doi.org/10.1016/j.yebeh.2018.05.008 The first of a series of studies using long-term implanted electrodes to quantify seizures and IEDs more accurately. CrossRefPubMedGoogle Scholar
- 51.• Giannina R, Iannotti F, Grouiller F, Centeno M, Carmichael DW, Abela E, et al. Epileptic networks are strongly connected with and without the effects of interictal discharges. Epilepsia. 2016;57(7):1086–96 This paper emphasizes the importance of network connectivity and demonstrates that epilepsy is more than the electrical discharge; it also involves other measurable physiological effects. CrossRefGoogle Scholar
- 52.Kasteleijn-Nolst Trenité DG, Riemersma JB, Binnie CD, Smit AM, Meinardi H. The influence of subclinical epileptiform EEG discharges on driving behaviour. Electroencephalogr Clin Neurophysiol. 1987;67(2):167–70.Google Scholar