When Seizures Strike Sleep

Additionally, AEDs may affect sleep architecture and induce somnolence. Gabapentin increases slow wave sleep in normal adults.¹³ Lamotrigine increases REM sleep, and reduces stage shifts and arousals in patients with focal epilepsy.^14,15 Barbiturates and benzodiazepines decrease sleep latency and arousals; however, they decrease REM sleep in patients with epilepsy.13 Most AEDs may increase daytime somnolence.^4,12,15 Lamotrigine, zonisamide, phenytoin, ethosuximide, and felbatol have been associated with insomnia.^4,12

In addition to direct effects on sleep, some AEDs may have secondary effects on sleep. Many AEDs are associated with weight gain.^4,6,16 Obesity is a known risk factor for OSA. Additionally, carbamazepine has been associated with exacerbation of periodic limb movements during sleep.^4,12 Several antiepileptic drugs, including gabapentin, are commonly used off-label for treatment of restless legs syndrome and/or periodic limb movement disorder.^4,17

Screening for comorbid sleep disorder symptoms can be assessed quickly during an outpatient visit. Focused sleep history should inquire about the presence of daytime sleepiness, bedtimes and arising times, difficulty initiating and maintaining sleep, snoring, observed apneas during sleep, unrefreshed awakenings, restless legs symptoms, and nocturnal behaviors or seizures. The ESS is an eight-question tool used to measure the propensity of falling asleep in several daytime settings. ESS scores range from 0 to 24 points with scores of greater than 10 associated with increased sleepiness.¹⁸ In a population of patients with epilepsy, abnormal ESS (>10) correlated with loud habitual snoring, witnessed apneas, and recurrence of seizures within the last 12 months.⁷ If sleep history is positive, further investigation (eg, laboratory studies, PSG) and treatment may be warranted.

There are several studies noting the common occurrence of OSA in patients with epilepsy.^3,6-8,16,19 Treatment of OSA in these patients resulted in improved seizure control^8,20-22 and quality of life.^9,16 Our patient developed recurrent seizures after many years of seizure freedom. He also had daytime sleepiness, significant weight gain, and signs and symptoms of OSA. Polysomnographic evaluation diagnosed significant OSA and respiratory event-associated generalized tonic-clonic seizures. Nocturnal seizures and OSA can disrupt sleep architecture and lead to sleep deprivation and daytime sleepiness. CPAP titration PSG demonstrated a 75% reduction in frequency of respiratory event-associated electrographic epileptiform activity and total resolution of clinical seizures. Continued CPAP therapy controlled OSA symptoms and clinical seizures.

This case study demonstrates the importance of evaluating for comorbid sleep disorders in patients with epilepsy who develop breakthrough seizures. Sleep evaluation may lead to the diagnosis of a comorbid sleep disorder, thus revealing a contributing factor for the development of breakthrough seizures. Treatment of comorbid sleep disorders may improve seizure control, sleep, and quality of life.

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Jennifer L. DeWolfe, DO, is an assistant professor of neurology at the University of Alabama at Birmingham. She is the director of UAB Neurology Sleep Services and of the Birmingham Veterans Affairs Sleep Center. She is board certified by the American Board of Psychiatry and Neurology and specializes in epilepsy and sleep medicine. Contact her at [email protected].

REFERENCES

1. Chadwick D, Taylor J, Johnson T. Outcomes after seizure recurrence in people with well-controlled epilepsy and the factors that influence it. The MRC Antiepileptic Drug Withdrawal Group. Epilepsia. 1996;37(11):1043-50.
2. Badawy RA, Curatolo JM, Newton M, Berkovic SF, Macdonell RA. Sleep deprivation increases cortical excitability in epilepsy: syndrome-specific effects. Neurology. 2006;67(6):1018-22.
3. Bazil CW. Sleep, sleep apnea, and epilepsy. Curr Treat Options Neurol. 2004;6(4):339-345.
4. Bazil C. AEDs, sleep, and epilepsy. October 1, 2007. http://www.epilepsy.com/articles/ar_1191272878:[. Accessed August 15, 2008.
5. Dinner DS. Effect of sleep on epilepsy. J Clin Neurophysiol. 2002;19(6):504-13.
6. Malow BA, Bowes RJ, Lin X. Predictors of sleepiness in epilepsy patients. Sleep. 1997;20(12):1105-10.
7. Manni R, Politini L, Sartori I, Ratti MT, Galimberti CA, Tartara A. Daytime sleepiness in epilepsy patients: evaluation by means of the Epworth sleepiness scale. J Neurol. 2000;247(9):716-7.
8. Vaughn BV, Miller MT, D’Cruz OF, Messenheimer J. Prevalence of sleep complaints in patients with epilepsy: application of the Epworth sleepiness scale. J Sleep Res. 1996;25:453.
9. Piperidou C, Karlovasitou A, Triantafyllou N, et al. Influence of sleep disturbance on quality of life of patients with epilepsy. Seizure. 2008;17(7):588-94.
10. Bazil CW, Castro LH, Walczak TS. Reduction of rapid eye movement sleep by diurnal and nocturnal seizures in temporal lobe epilepsy. Arch Neurol. 2000;57(3):363-8.
11. Kotagal P, Yardi N. The relationship between sleep and epilepsy. Semin Pediatr Neurol. 2008;15(2):42-9.
12. Adverse reactions to antiepileptic drugs: a multicenter survey of clinical practice. Collaborative Group for Epidemiology of Epilepsy. Epilepsia. 1986;27(4):323-30.
13. Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, Mascha E, Dinner D, Morris HH. Gabapentin increases slow-wave sleep in normal adults. Epilepsia. 2002;43(12):1493-7.
14. Foldvary N, Perry M, Lee J, Dinner D, Morris HH. The effects of lamotrigine on sleep in patients with epilepsy. Epilepsia. 2001;42(12):1569-73.
15. Placidi F, Marciani MG, Diomedi M, et al. Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy. Acta Neurol Scand. 2000;102(2):81-6.
16. Bazil CW. Sleep and epilepsy. Curr Opin Neurol. 2000;13(2):171-5.
17. Satija P, Ondo WG. Restless legs syndrome: pathophysiology, diagnosis and treatment. CNS Drugs. 2008;22(6):497-518.
18. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-5.
19. Chihorek AM, Abou-Khalil B, Malow BA. Obstructive sleep apnea is associated with seizure occurrence in older adults with epilepsy. Neurology. 2007;69(19):1823-7.
20. Devinsky O, Ehrenberg B, Barthlen GM, Abramson HS, Luciano D. Epilepsy and sleep apnea syndrome. Neurology. 1994;44(11):2060-4.
21. Hollinger P, Khatami R, Gugger M, Hess CW, Bassetti CL. Epilepsy and obstructive sleep apnea. Eur Neurol. 2006;55(2):74-9.
22. Wyler AR, Weymuller EA Jr. Epilepsy complicated by sleep apnea. Ann Neurol. 1981;9(4):403-4.