Effects of antiepileptic drugs on sleep architecture parameters in adults

Objectives Physiological and restorative sleep is fundamental for physical and mental well-being. Polysomnography parameters are objective methods to access sleep structure. Antiepileptic drugs (AEDs) are a group of drugs whose interference in the sleep structure is still not well known, especially in what concern the new ones. We did a systematic review of the literature to compare the effect of classic and newer AEDs on sleep architecture.

Material and Methods A search was performed in PubMed and Scopus, using keywords “sleep” and “antiepileptics”, and each AED combined with “sleep”. Only studies concerning objective measures were selected.

Results 63 articles were included, only 21 were randomized, controlled and double-blinded. Studies not only in epilepsy, but also in restless leg syndrome, bruxism, insomnia, fibromyalgia and obstructive sleep apnea were found. Among classic AEDs, carbamazepine has a negative effect on sleep while phenobarbitone has a slightly dose-dependent interference and is also the only one to reduce N3 stage. Valproic acid has little to no effect while clobazam and clonazepam have a positive effect. No conclusion can be drawn about phenytoin. All of them reduce REM stage. In the newer AEDs group gabapentine, lamotrigine, perampanel, pregabaline and tiagabine increase N3 sleep in best evidence. Lacosamide and zonisamide appear to be innocent while levetiracetam reduces REM sleep.

Conclusion Studies found used different methodologies not always addressing the analysis on the same parameters. In spite of these, newer AEDs have less effects on sleep structure when compared with classic AEDs but furthermore robust evidence is needed.

Polysomnography - Anticonvulsants - Sleep

Disclosure statement

Financial disclosure: João Chaves has received speaker’s honoraria and/or consultancy fees from Bial and Eisai and was granted with a Tecnifar Bursary.

Non-financial disclosure: authors declared no conflict of interest related to the current work.

Publication History

Received: 20 June 2021

Accepted: 11 October 2021

Article published online:
01 December 2023

• REFERENCES

• 1 Berry RB. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Darien: American Academy of Sleep Medicine (AASM); 2018.
• 2 Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep. 2015 Jun;38(6):843-4.
• 3 Shrivastava D, Jung S, Saadat M, Sirohi R, Crewson K. How to interpret the results of a sleep study. J Community Hosp Intern Med Perspect. 2014 Nov;4(5):24983.
• 4 Bazil CW. Sleep and epilepsy. Semin Neurol. 2017 Aug;37(4):407-12.
• 5 Haas S, Otte A, Weerd A, Van Erp G, Cohen A, Van Gerven J. Exploratory polysomnographic evaluation of pregabalin on sleep disturbance in patients with epilepsy. J Clin Sleep Med. 2007 Aug;3(5):473-8.
• 6 Bazil CW. Effects of antiepileptic drugs on sleep structure: are all drugs equal? CNS Drugs. 2003;17(10):719-28.
• 7 Wolpert EA. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Arch Gen Psychiatry. 1969 Feb;20(2):246-7.
• 8 Iber C, Ancoli-Israel S, Chesson Junior AL, Quan SF. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Wetchester: American Academy of Sleep Medicine (AASM); 2007.
• 9 Moser D, Anderer P, Gruber G, Parapatics S, Loretz E, Boeck M, et al. Sleep classification according to AASM and Rechtschaffen & Kales: effects on sleep scoring parameters. Sleep. 2009 Feb;32(2):139-49.
• 10 Silber MH, Ancoli-Israel S, Bonnet MH, Chokroverty S, Grigg- Damberger MM, Hirshkowitz M, et al. The visual scoring of sleep in adults. J Clin Sleep Med. 2007 Mar;3(2):121-31.
• 11 Parrino L, Ferri R, Bruni O, Terzano MG. Cyclic alternating pattern (CAP): the marker of sleep instability. Sleep Med Rev. 2012 Feb;16(1):27-45.
• 12 Perez-Lloret S, Rojas GM, Menoni MC, Ruiz G, Velasquez C, Rodriguez H, et al. Pregabalin beneficial effects on sleep quality or health-related quality of life are poorly correlated with reduction on pain intensity after an 8-week treatment course. Clin Neuropharmacol. 2012 Jan/ Feb;35(1):21-4.
• 13 Roth T, Bhadra-Brown P, Pitman VW, Resnick EM. Pregabalin improves fibromyalgia - related sleep disturbance. Clin J Pain. 2016 Apr;32(4):308-12.
• 14 Bogan RK, Lee DO, Buchfuhrer MJ, Jaros MJ, Kim R, Shang G. Treatment response to sleep, pain, and mood disturbance and their correlation with sleep disturbance in adult patients with moderate-tosevere primary restless legs syndrome: pooled analyses from 3 trials of gabapentin enacarbil. Ann Med. 2015;47(3):269-77.
• 15 Madani AS, Abdollahian E, Khiavi HA, Radvar M, Foroughipour M, Asadpour H, et al. The efficacy of gabapentin versus stabilization splint in management of sleep bruxism. J Prosthodont. 2013;22(2):126-31.
• 16 Ehrenberg BL, Eisensehr I, Corbett KE, Crowley PF, Walters AS. Valproate for sleep consolidation in periodic limb movement disorder. J Clin Psychopharmacol. 2000 Oct;20(5):574-8.
• 17 Toledo M, Gonzalez-Cuevas M, Miro-Llado J, Molins-Albanell A, Falip M, Martinez AB, et al. Sleep quality and daytime sleepiness in patients treated with adjunctive perampanel for focal seizures. Epilepsy Behav. 2016 Oct;63:57-62.
• 18 Bazil CW, Battista J, Basner RC. Effects of levetiracetam on sleep in normal volunteers. Epilepsy Behav. 2005 Nov;7(3):539-42.
• 19 Silva AM, Mendez M, Bai C, Pandi-Perumal S. Sleep and epilepsy: from interrelationships to influence of antiepileptic drugs. In: Lader M, Cardinali DP, Pandi-Perumal SR, eds. Sleep and sleep disorders. A neuropsychopharmacological approach. Georgetown: Landes- Bioscience; 2006. p. 82-296.
• 20 Placidi F, Marciani MG, Diomedi M, Scalise A, Pauri F, Giacomini P, et al. Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy. Acta Neurol Scand. 2000 Aug;102(2):81-6.
• 21 Placidi F, Scalise A, Marciani MG, Romigi A, Diomedi M, Gigli GL. Effect of antiepileptic drugs on sleep. Clin Neurophysiol. 2000;111(Suppl 2):S115-9.
• 22 Lee SA, No YJ, Jo KD, Kwon JH, Kim JY, Shin DJ. Factors contributing to excessive daytime sleepiness in Korean adults with epilepsy: a sleep questionnaire-based study. Epilepsy Behav. 2019 Jan;90:61-5.
• 23 Romigi A, Izzi F, Marciani MG, Torelli F, Zannino S, Pisani LR, et al. Pregabalin as add-on therapy induces REM sleep enhancement in partial epilepsy: a polysomnographic study. Eur J Neurol. 2009 Jan;16(1):70-5.
• 24 Placidi F, Mattia D, Romigi A, Bassetti MA, Spanedda F, Marciani MG. Gabapentin- induced modulation of interictal epileptiform activity related to different vigilance levels. Clin Neurophysiol. 2000 Sep;111(9):1637-42.
• 25 Sudbrack-Oliveira P, Najar LL, Foldvary-Schaefer N, Gomes MM. Sleep architecture in adults with epilepsy: a systematic review. Sleep Med. 2019 Jan;53:22-7.
• 26 Maestri M, Giorgi FS, Pizzanelli C, Fabbrini M, Di Coscio E, Carnicelli L, et al. Daytime sleepiness in de novo untreated patients with epilepsy. Epilepsy Behav. 2013 Nov;29(2):344-8.
• 27 Zhou JY, Tang XD, Huang LL, Zhong ZQ, Lei F, Zhou D. The acute effects of levetiracetam on nocturnal sleep and daytime sleepiness in patients with partial epilepsy. J Clin Neurosci. 2012 Jul;19(7):956-60.
• 28 Walsh JK, Perlis M, Rosenthal M, Krystal A, Jiang J, Roth T. Tiagabine increases slow- wave sleep in a dose-dependent fashion without affecting traditional efficacy measures in adults with primary insomnia. J Clin Sleep Med. 2006 Jan;2(1):35-41.
• 29 Moher D, Liberati A, Tetzlaff J, Altman DG; The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. PLoS Med. 2009;6(7):e1000097.
• 30 Gronseth GS, Cox J, Getchius TSD. Amendments to the 2011 American Academy of Neurology Clinical Practice Guideline Process Manual. Chicago: American Academy of Neurology; 2019.
• 31 De la Fuente JM, Bobes J, Vizuete C, Mendlewicz J. Effects of carbamazepine on dexamethasone suppression and sleep electroencephalography in borderline personality disorder. Neuropsychobiology. 2002;45(3):113-9.
• 32 Yang JD, Elphick M, Sharpley AL, Cowen PJ. Effects of carbamazepine on sleep in healthy volunteers. Biol Psychiatry. 1989 Jul;26(3):324-8.
• 33 Manni R, Galimberti CA, Zucca C, Parietti L, Tartara A. Sleep patterns in patients with late onset partial epilepsy receiving chronic carbamazepine (CBZ) therapy. Epilepsy Res. 1990 Sep/Oct;7(1):72-6.
• 34 Gigli GL, Placidi F, Diomedi M, Maschio M, Silvestri G, Scalise A, et al. Nocturnal sleep and daytime somnolence in untreated patients with temporal lobe epilepsy: changes after treatment with controlled-release carbamazepine. Epilepsia. 1997 Jun;38(6):696-701.
• 35 Gann H, Riemann D, Hohagen F, Müller WE, Berger M. The influence of carbamazepine on sleep-EEG and the clonidine test in healthy subjects: results of a preliminary study. Biol Psychiatry. 1994 Jun;35(11):893-6.
• 36 Riemann D, Gann H, Hohagen F, Bahro M, Müller WE, Berger M. The effect of carbamazepine on endocrine and sleep EEG variables in a patient with 48-hour rapid cycling, and healthy controls. Neuropsychobiology. 1993;27(3):163-70.
• 37 Cho YW, Kim DH, Motamedi GK. The effect of levetiracetam monotherapy on subjective sleep quality and objective sleep parameters in patients with epilepsy: compared with the effect of carbamazepine- CR monotherapy. Seizure. 2011 May;20(4):336-9.
• 38 Legros B, Bazil CW. Effects of antiepileptic drugs on sleep architecture: a pilot study. Sleep Med. 2003 Jan;4(1):51-5.
• 39 Nayak CS, Sinha S, Nagappa M, Thennarasu K, Taly AB. Effect of carbamazepine on the sleep microstructure of temporal lobe epilepsy patients: a cyclic alternating pattern-based study. Sleep Med. 2016 Nov/ Dec;27-28:80-5.
• 40 Bonanni E, Massetani R, Galli R, Gneri C, Petri M, ludice A, et al. A quantitative study of daytime sleepiness induced by carbamazepine and addon vigabatrin in epileptic patients. Acta Neurol Scand. 1997 Apr;95(4):193-6.
• 41 Nicholson AN, Stone BM, Clarke CH. Effect of the 1,5-benzodiazepines, clobazam and triflubazam, on sleep in man. Br J Clin Pharmacol. 1977 Oct;4(5):567-72.
• 42 Ferri R, Marelli S, Ferini-Strambi L, Oldani A, Colli F, Schenck CH, et al. An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. Sleep Med. 2013;14(1):24-9.
• 43 Sakai T, Kato T, Yoshizawa S, Suganuma T, Takaba M, Ono Y, et al. Effect of clonazepam and clonidine on primary sleep bruxism: a double-blind, crossover, placebo-controlled trial. J Sleep Res. 2017 Feb;26(1):73-83.
• 44 Drake Junior ME, Pakalnis A, Bogner JE, Andrews JM. Outpatient sleep recording during antiepileptic drug monotherapy. Clin Electroencephalogr. 1990 Jul;21(3):170-3.
• 45 Saletu A, Parapatics S, Anderer P, Matejka M, Saletu B. Controlled clinical, polysomnographic and psychometric studies on differences between sleep bruxers and controls and acute effects of clonazepam as compared with placebo. Eur Arch Psychiatry Clin Neurosci. 2010 Mar;260(2):163-74.
• 46 Ferri R, Rundo F, Silvani A, Zucconi M, Bruni O, Ferini-Strambi L, et al. REM Sleep EEG instability in REM sleep behavior disorder and clonazepam effects. Sleep. 2017 Aug;40(8).
• 47 Wolf P, Inoue Y, Roder-Wanner UU, Tsai JJ. Psychiatric complications of absence therapy and their relation to alteration of sleep. Epilepsia. 1984;25(Suppl 1):S56-S9.
• 48 Wang YQ, Zhang MQ, Li R, Qu WM, Huang ZL. The mutual interaction between sleep and epilepsy on the neurobiological basis and therapy. Curr Neuropharmacol. 2018;16(1):5-16.
• 49 Karacan I, Orr W, Roth T, Kramer M, Thornby J, Bingham S, et al. Dose-related effects of phenobarbitone on human sleep-waking patterns. Br J Clin Pharmacol. 1981 Sep;12(3):303-13.
• 50 Prinz PN, Vitiello MV, Roehrs TA, Linnoila M, Weitzman ED. Effect of phenobarbital on sleep and nighttime plasma growth hormone and cortisol levels. Can J Physiol Pharmacol. 1981 Nov;59(11):1139-45.
• 51 Wolf P, Roder-Wanner UU, Brede M. Influence of therapeutic phenobarbital and phenytoin medication on the polygraphic sleep of patients with epilepsy. Epilepsia. 1984 Aug;25(4):467-75.
• 52 Manni R, Ratti MT, Galimberti CA, Morini R, Perucca E, Tartara A. Daytime sleepiness in epileptic patients on long-term monotherapy: MSLT, clinical and psychometric assessment. Neurophysiol Clin. 1993;23(1):71-6.
• 53 Röder-Wanner UU, Noachtar S, Wolf P. Response of polygraphic sleep to phenytoin treatment for epilepsy. A longitudinal study of immediate, short- and long-term effects. Acta Neurol Scand. 1987 Sep;76(3):157-67.
• 54 Eisensehr I, Ehrenberg BL, Solti SR, Noachtar S. Treatment of idiopathic restless legs syndrome (RLS) with slow-release valproic acid compared with slow-release levodopa/benserazid. J Neurol. 2004 May;251(5):579-83.
• 55 Manni R, Ratti MT, Perucca E, Galimberti CA, Tartara A. A multiparametric investigation of daytime sleepiness and psychomotor functions in epileptic patients treated with phenobarbital and sodium valproate: a comparative controlled study. Electroencephalogr Clin Neurophysiol. 1993 May;86(5):322-8.
• 56 Harding GF, Alford CA, Powell TE. The effect of sodium valproate on sleep, reaction times, and visual evoked potential in normal subjects. Epilepsia. 1985 Nov/Dec;26(6):597-601.
• 57 Nayak CS, Sinha S, Nagappa M, Kandavel T, Taly AB. Effect of valproate on the sleep microstructure of juvenile myoclonic epilepsy patients - a cross-sectional CAP based study. Sleep Med. 2016 Jan;17:129-33.
• 58 Marciani MG, Spanedda F, Placidi F, Bassetti MA, Romigi A, Mattia D. Changes of the EEG paroxysmal pattern during felbamate therapy in Lennox-Gastaut syndrome: a case report. Int J Neurosci. 1998 Sep;95(3-4):247-53.
• 59 Foldvary-Schaefer N, Sanchez IL, Karafa M, Mascha E, Dinner D, Morris HH. Gabapentin increases slow-wave sleep in normal adults. Epilepsia. 2002 Dec;43(12):1493-7.
• 60 Rosenberg RP, Hull SG, Lankford DA, Mayleben DW, Seiden DJ, Furey SA, et al. A randomized, double-blind, single-dose, placebocontrolled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med. 2014 Oct;10(10):1093-100.
• 61 Furey SA, Hull SG, Leibowitz MT, Jayawardena S, Roth T. A randomized, double-blind, placebo-controlled, multicenter, 28-day, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med. 2014 Oct;10(10):1101-9.
• 62 Rao ML, Clarenbach P, Vahlensieck M, Kratzschmar S. Gabapentin augments whole blood serotonin in healthy young men. J Neural Transm. 1988;73(2):129-34.
• 63 Piovezan RD, Kase C, Moizinho R, Tufik S, Poyares D. Gabapentin acutely increases the apnea-hypopnea index in older men: data from a randomized, double-blind, placebo-controlled study. J Sleep Res. 2017 Apr;26(2):166-70.
• 64 Lo HS, Yang CM, Lo HG, Lee CY, Ting H, Tzang BS. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol. 2010 Mar/ Apr;33(2):84-90.
• 65 Hamer RM, Simpson PM. Letter regarding “Treatment effects of gabapentin for primary insomnia”. Clin Neuropharmacol. 2011 May/ Jun;34(3):133.
• 66 Foldvary-Schaefer N, Neme-Mercante S, Andrews N, Bruton M, Wang L, Morrison S, et al. Wake up to sleep: the effects of lacosamide on daytime sleepiness in adults with epilepsy. Epilepsy Behav. 2017 Oct;75:176-82.
• 67 Hudson JD, Guptill JT, Byrnes W, Yates SL, Williams P, O’Neill DC. Assessment of the effects of lacosamide on sleep parameters in healthy subjects. Seizure. 2015 Feb;25:155-9.
• 68 Foldvary N, Perry M, Lee J, Dinner D, Morris HH. The effects of lamotrigine on sleep in patients with epilepsy. Epilepsia. 2001 Dec;42(12):1569-73.
• 69 Thelengana A, Shukla G, Srivastava A, Singh MB, Gupta A, Rajan R, et al. Cognitive, behavioural and sleep-related adverse effects on introduction of levetiracetam versus oxcarbazepine for epilepsy. Epilepsy Res. 2019 Feb;150:58-65.
• 70 Bell C, Vanderlinden H, Hiersemenzel R, Otoul C, Nutt D, Wilson S. The effects of levetiracetam on objective and subjective sleep parameters in healthy volunteers and patients with partial epilepsy. J Sleep Res. 2002 Sep;11(3):255-63.
• 71 Cicolin A, Magliola U, Giordano A, Terreni A, Bucca C, Mutani R. Effects of levetiracetam on nocturnal sleep and daytime vigilance in healthy volunteers. Epilepsia. 2006 Jan;47(1):82-5.
• 72 Yilmaz H. Comparison of motor activity and sleep in patients with complex partial seizures on levetiracetam treatment and a group of healthy subjects. Behav Neurol. 2007;18(3):165-70.
• 73 Gonzalez-Cuevas M, Romero O, Toledo M, Quintana M, Cambrodi R, Santamarina E, et al. Effect of adjunctive perampanel on the quality of sleep and daytime somnolence in patients with epilepsy. Epilepsy Behav Case Rep. 2017 Oct;7:13-5.
• 74 Garcia-Borreguero D, Cano I, Granizo JJ. Treatment of restless legs syndrome with the selective AMPA receptor antagonist perampanel. Sleep Med. 2017 Jun;34:105-8.
• 75 Rocamora R, Álvarez I, Chavarria B, Principe A. Perampanel effect on sleep architecture in patients with epilepsy. Seizure. 2020;76:137-42.
• 76 Hindmarch I, Dawson J, Stanley N. A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep. 2005 Feb;28(2):187-93.
• 77 Garcia-Borreguero D, Patrick J, DuBrava S, Becker PM, Lankford A, Chen C, et al. Pregabalin versus pramipexole: effects on sleep disturbance in restless legs syndrome. Sleep. 2014 Apr;37(4):635-43.
• 78 Roth T, Lankford DA, Bhadra P, Whalen E, Resnick EM. Effect of pregabalin on sleep in patients with fibromyalgia and sleep maintenance disturbance: a randomized, placebo- controlled, 2-way crossover polysomnography study. Arthritis Care Res (Hoboken). 2012 Apr;64(4):597-606.
• 79 Garcia-Borreguero D, Larrosa O, Williams AM, Albares J, Pascual M, Palacios JC, et al. Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study. Neurology. 2010 Jun;74(23):1897-904.
• 80 Bazil CW, Dave J, Cole J, Stalvey J, Drake E. Pregabalin increases slowwave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav. 2012 Apr;23(4):422-5.
• 81 Mathias S, Wetter TC, Steiger A, Lancel M. The GABA uptake inhibitor tiagabine promotes slow wave sleep in normal elderly subjects. Neurobiol Aging. 2001 Mar/Apr;22(2):247-53.
• 82 Walsh JK, Randazzo AC, Stone K, Eisenstein R, Feren SD, Kajy S, et al. Tiagabine is associated with sustained attention during sleep restriction: evidence for the value of slow- wave sleep enhancement? Sleep. 2006 Apr;29(4):433.
• 83 Walsh JK, Randazzo AC, Frankowski S, Shannon K, Schweitzer PK, Roth T. Dose-response effects of tiagabine on the sleep of older adults. Sleep. 2005 Jun;28(6):673-6.
• 84 Walsh JK, Zammit G, Schweitzer PK, Ondrasik J, Roth T. Tiagabine enhances slow wave sleep and sleep maintenance in primary insomnia. Sleep Med. 2006 Mar;7(2):155-61.
• 85 Roth T, Wright Junior KP, Walsh J. Effect of tiagabine on sleep in elderly subjects with primary insomnia: a randomized, double-blind, placebo-controlled study. Sleep. 2006 Mar;29(3):335-41.
• 86 Feld GB, Wilhelm I, Ma Y, Groch S, Binkofski F, Molle M, et al. Slow wave sleep induced by GABA agonist tiagabine fails to benefit memory consolidation. Sleep. 2013 Sep;36(9):1317-26.
• 87 Taranto-Montemurro L, Sands SA, Edwards BA, Azarbarzin A, Marques M, Melo C, et al. Effects of tiagabine on slow wave sleep and arousal threshold in patients with obstructive sleep apnea. Sleep. 2017 Feb;40(2):zsw047.
• 88 Bonanni E, Galli R, Maestri M, Pizzanelli C, Fabbrini M, Manca ML, et al. Daytime sleepiness in epilepsy patients receiving topiramate monotherapy. Epilepsia. 2004 Apr;45(4):333-7.
• 89 Eskandari D, Zou D, Karimi M, Stenlof K, Grote L, Hedner J. Zonisamide reduces obstructive sleep apnoea: a randomised placebocontrolled study. Eur Respir J. 2014 Jul;44(1):140-9.
• 90 Romigi A, Izzi F, Placidi F, Zannino S, Evangelista E, Del Bianco C, et al. Effects of zonisamide as add-on therapy on sleep-wake cycle in focal epilepsy: a polysomnographic study. Epilepsy Behav. 2013 Feb;26(2):170-4.
• 91 Assenza G, Mecarelli O, Lanzone J, Assenza F, Tombini M, Di Lazzaro V, et al. The ROME (Retrospective Observational Multicenter study on Eslicarbazepine) study: efficacy and behavioural effects of Eslicarbazepine acetate as adjunctive therapy for adults with partial onset seizures in real life. Seizure. 2018 May;58:35-40.
• 92 Ayala-Guerrero F, Mexicano G, González V, Hernandez M. Effect of oxcarbazepine on sleep architecture. Epilepsy Behav. 2009 Jul;15(3):287-90.
• 93 Fejerman N, Caraballo R, Cersosimo R, Ferraro SM, Galicchio S, Amartino H. Sulthiame add-on therapy in children with focal epilepsies associated with encephalopathy related to electrical status epilepticus during slow sleep (ESES). Epilepsia. 2012 Jul;53(7):1156-61.