Sleep and Epilepsy

Sleep and epilepsy affect each other in complicated ways. Understanding the ways that each influences the other can be important for patient care. Research is making the relationship clearer:

  • Effects of sleep on interictal epileptiform activity: Sleep—particularly deep non-REM sleep— increases interictal epileptiform activity.
  • Effects of sleep and sleep deprivation on the occurrence of seizures: Sleep increases certain seizure types and the rate of generalization of partial seizures. REM sleep, however, seems to suppress seizures.
  • Specific syndromes of sleep and epilepsy: Many varied epilepsy syndromes are related to sleep. Some of them present problems of diagnosis.
  • Effects of seizures and antiepileptic drugs on sleep structure: Seizures can disrupt sleep structure, particularly REM sleep.
  • Sleep disorders in patients with epilepsy: Sleep disorders such as sleep apnea exacerbate seizures. Doctors have often overlooked sleep disturbances in patients with epilepsy, but it is now clear that they may contribute to decreased daytime functioning and increased seizure activity.
  • Sleep disorders in patients with epilepsy: Sleep disorders such as sleep apnea exacerbate seizures. Doctors have often overlooked sleep disturbances in patients with epilepsy, but it is now clear that they may contribute to decreased daytime functioning and increased seizure activity.
  • References

Other reviews of these interactions between sleep and epilepsy have been published for adults1 and children.2 Shouse et al.3 reviewed the circadian distribution of ictal and interictal events.

Effects of sleep on interictal epileptiform activity

It has been known for decades that EEGs performed during sleep or with sleep deprivation are more likely than routine EEGs to show interictal epileptiform discharges (IEDs). Recent studies have confirmed and refined this knowledge. In a study of 24 patients with refractory temporal lobe epilepsy, Malow and colleagues4 compared routine daytime EEGs with overnight EEG recordings. All 24 patients showed IEDs in the overnight studies, versus only 11 in the daytime studies. There was high concordance with the site of seizure onset. This study shows the value of overnight EEGs, especially if daytime EEGs are normal.

A retrospective report by Fountain and coworkers5 looked at the effect of sleep deprivation on the EEGs of 29 epilepsy patients whose routine EEGs had not shown any IEDs, even if that EEG included a period of sleep. When EEGs were performed after a period of sleep deprivation, 15 (52%) included IEDs, independent of the duration or depth of sleep during the test, showing that sleep deprivation has its own effect on IEDs.

The importance of the clinical context in EEG interpretation was highlighted by a study6 of EEGs recorded during sleep in people who did not have epilepsy. During two consecutive nights of continuous EEG recording, these researchers found frontal sharp waves in 68% of these normal people, and temporal sharp waves in 37%. True epileptiform spike-wave activity was seen in 13%.

The number of interictal spikes and sharp waves is affected by the stage of sleep. More occur during slow wave sleep and fewer during REM.7 Another study8 showed an increase in spike frequency with increasing sleep depth. The IEDs that occur during REM sleep have been found to be more accurate for focus localization, however.7,9

Effects of sleep and sleep deprivation on the occurrence of seizures

Sleep influences the onset of seizures (especially those of partial onset) in both animals and humans. One study10 compared the time when seizures occurred in people with various types of localized seizures to the time when they occurred in rats with a model of epilepsy similar to mesial temporal lobe epilepsy. (The rats were kept on a 12-hour light-dark schedule, with the lights on during the day.) The peak incidence of seizures for both the rats and the humans with mesial temporal lobe epilepsy occurred during the afternoon. (This is an interesting finding considering that rats are predominantly nocturnal.) The authors concluded that a circadian pattern exists for mesial temporal lobe epilepsy, but the influence of sleep is unknown. The humans in the study who had extratemporal seizures or lesional temporal lobe epilepsy did not show this pattern.

A similar pattern appeared in a study11 that used 5 days of continuous video-EEG monitoring to examine the occurrence of frontal and temporal lobe seizures in 15 patients with each type. Most (61%) of the frontal lobe seizures occurred during sleep, versus only 11% of temporal lobe seizures. This difference persisted after medication withdrawal and sleep deprivation.

A large study of refractory epilepsy patients12 added more information about seizures occurring during sleep. The researchers retrospectively examined over 1100 seizures in 188 consecutive patients undergoing video-EEG monitoring. Overall, 20% of the seizures occurred during sleep. Frontal lobe seizures began during sleep more often (37%) than temporal lobe seizures (26%). Most (54%) of sleep seizures occurred during stage 2, with only 13% during slow wave sleep and few (3%) during REM. Complex partial seizures lasted longer when they arose during slow-wave sleep than when they started during wakefulness or stage 2 sleep. Temporal lobe seizures were more likely to secondarily generalize when they arose during sleep, but frontal lobe seizures were not.

Another retrospective study13 of sleep-related seizures in 14 patients with temporal lobe epilepsy found that most seizures occurred during non-REM sleep and preceded arousals This study and the previous one suggest that the hypersynchrony present during non-REM sleep may facilitate the onset or spread of certain partial seizures.

Studies of patients with seizures occurring only during sleep14,15 have shown an excellent prognosis in most cases. One study14 showed that partial seizures were more difficult to control. These patients (many of whom had a history of head trauma or other CNS lesion) frequently developed daytime seizures.

Whether sleep deprivation increases seizures, as generally thought, was not supported by one controlled study of patients with refractory epilepsy.16 Seventeen patients were sleep deprived on alternate nights, and 13 received eight hours of sleep per night. There was no difference in the number of seizures or time to first seizure.

Specific syndromes of sleep and epilepsy

Many and varied epilepsy syndromes are related to sleep. They include childhood epilepsy with occipital paroxysms, childhood epilepsy with centrotemporal spikes, juvenile myoclonic epilepsy, and awakening grand-mal epilepsy. Two syndromes that have been studied recently are nocturnal frontal lobe epilepsy and Landau-Kleffner syndrome.

Nocturnal frontal lobe epilepsies

Frontal lobe epilepsies that occur at night represent a diagnostic dilemma. The seizures are frequently unwitnessed and the symptoms are often bizarre. Prominent choking and abnormal motor activity can lead to a misdiagnosis of sleep apnea17 or other sleep disturbance.18 A review of 100 consecutive cases19 described various types of episodes involving sudden awakening with bizarre posture or ambulation. Many of the patients were unaware of the episodes, which lasted from seconds to almost 2 minutes. Nearly all occurred in stage 2 or stage 3-4 sleep; only 3% occurred during REM sleep. Over half of patients had normal interictal EEG findings (both asleep and awake), and many ictal EEGs also were normal. Mean seizure frequency was 20 /- 11 per month, with only 34% reporting rare seizures during daytime wakefulness. Twenty-five percent showed a familial occurrence. The short duration, high frequency, and stereotypic features of the episodes suggest a diagnosis of nocturnal frontal lobe epilepsy. About two-thirds of the patients responded to antiepileptic drugs, a rate similar to the rate for many other types of partial epilepsy.

Another group20 reported on 40 patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The clinical picture included enuresis, sudden awakenings with dystonic or dyskinetic movements (42%), complex behavior (13%) and violent behavior in sleep (5%). Most patients showed ictal or rhythmic activity over the frontal region. Pedigree analysis was consistent with autosomal dominant inheritance with reduced penetrance in 81%. Locus heterogeneity was seen with DNA analysis. Another study showed heterogeneity in families with ADNFLE from Norway and Australia. Ictal recordings showed epileptiform activity in only 3 of 10 patients.

All of these studies suggest that nocturnal frontal lobe epilepsies are frequently misdiagnosed but easily controlled with medication.

Landau-Kleffner syndrome

Landau-Kleffner syndrome (LKS) is a condition of acquired aphasia, frequently (but not always) with epileptic seizures and a markedly epileptiform EEG, particularly during sleep. O’Regan and colleagues22 studied 25 children who had an acquired disorder of communication and seizures but did not strictly meet criteria for LKS. EEGs were uniformly epileptiform, and most of them (16/25) worsened with sleep. MRI was typically normal, but 22 of the 25 children showed hypometabolism on SPECT. This suggests persistent epileptic discharges that may be responsible for their language deficits, usually a receptive aphasia.

A study23 of 32 patients with continuous spike-and-wave activity during slow-wave sleep (CSWS) showed a variety of clinical syndromes, including 4 cases of LKS. Nearly half had symptomatic epilepsy and showed the CSWS pattern for variable periods.

Sleep disorders to rule out

Another important consideration in differential diagnosis is that some paroxysmal disorders of sleep can be confused with seizure disorders:

Disorders of REM sleep Non-REM disorders
cataplexy sleep terrors
hypnagogic hallucinations sleep enuresis
sleep paralysis periodic limb movements
REM behavior disorder confusional arousals

Roberts24 presents a complete discussion of this area of differential diagnosis.

Effects of seizures and antiepileptic drugs on sleep structure

Seizures during sleep obviously will disrupt sleep structure. Most seizures cause at least a brief awakening, and normal sleep is unlikely during a postictal state. Polysomnography has been used to study the effects of various kinds of partial seizures, particularly frontal11,18 and temporal11,25. Tachibana and colleagues18 specifically reported on two patients with supplementary motor area seizures who were misdiagnosed with sleep disorders. Treatment of the seizures improved sleep efficiency, increased slow-wave sleep and (in one case) increased REM sleep. In a more extensive study, twelve patients with temporal lobe epilepsy and ten with frontal lobe epilepsy were studied with polysomnography in the absence of seizures11 (Crespel et al 1998). There were no differences in percentage in each sleep stage between the two groups or between either group and controls. Temporal lobe patients showed increased wakefulness after sleep onset compared with frontal lobe patients, and therefore decreased sleep efficiency.

To examine the specific effects of temporal lobe seizures on sleep structure, patients in an epilepsy monitoring unit were studied with polysomnography under baseline conditions (seizure-free) and following complex partial or secondarily generalized seizures.25 Following daytime seizures, REM was significantly decreased the following night (from 18% for baseline to 12%) without significant changes in other sleep stages or in sleep efficiency. When seizures occurred at night, the decrease in REM was more pronounced (from 16% to 7%); stage 1 sleep increased and sleep efficiency decreased. Both day and night seizures resulted in a delay in the first REM period. This study suggests that daytime seizures and particularly nighttime seizures disrupt sleep structure and these changes may be partly responsible for decreased performance the following day.

The distinct population of patients with severe mental retardation and seizures (usually of several types) was studied by Espie and coworkers.26 These patients had frequent seizures and most were taking multiple antiseizure medications. The studies were somewhat limited in that they were performed in an outpatient setting. In 2 of 28 subjects it was not possible to distinguish between sleep and wakefulness. Only 43% had REM sleep recorded, and in these cases mean time in REM was limited to an average of 30 minutes. Decreased REM was thought due to mental retardation and antiepileptic drugs, although seizure activity was not mentioned in this study.

All of these studies show sleep disruption with uncontrolled seizures, with REM especially affected. Clinically, this may explain some of the dullness many patients feel even a day or two following seizures. The effects of certain antiepileptic medications, particularly phenytoin and carbamazepine, may independently reduce REM.27

Sleep disorders in patients with epilepsy

Although certain populations with epilepsy almost universally report sleepiness, sleep disorders are grossly underdiagnosed. Many practitioners attribute consistent tiredness to the effects of antiepileptic medication, but in fact, current research confirms that sleep disorders commonly coexist with epilepsy. This has important implications for treatment.

One study28 used the Epworth Sleepiness Scale to compare patients with epilepsy to a control group of neurology patients without epilepsy. Those with epilepsy scored higher on the sleepiness scale, but the difference was no longer significant if scores on a sleep apnea scale and symptoms of restless legs were considered. Medications and the number, type, or timing of seizures did not significantly predict a high score for daytime sleepiness in the epilepsy patients. Both the epilepsy patients and the controls were more likely to have excessive daytime sleepiness if they had symptoms of the treatable sleep disorders.

A similar investigation was performed prospectively in children, using a nonstandardized sleep questionnaire and the Conners Revised Parent Rating Scale.29 Children with epilepsy showed higher scores for poor quality sleep, anxiety about sleep, and disordered breathing. Only anxiety was affected by seizure number. Similar findings were seen in a survey given to parents of 89 children with idiopathic epilepsy.30 Children with epilepsy showed more sleep problems than did controls, and these were associated with seizure frequency, age, paroxysmal activity on EEG, duration of illness, and behavioral problems.

In a retrospective study of 63 epilepsy patients who underwent polysomnography,31 the vast majority of patients (49, or 78%) were referred for obstructive sleep apnea, with many others (46%) referred for excessive sleepiness, and 12 (19%) for characterization of nocturnal spells. Studies diagnosed obstructive sleep apnea in 71% of referrals, 96% of whom were referred for that reason. Nocturnal seizures were diagnosed in 4. One patient had narcolepsy and one had insufficient sleep syndrome. Six patients had frequent periodic limb movements, but these were not clinically significant. Most of those who were subsequently treated for sleep disorders reported an improvement in sleepiness or seizure control.

In a similar investigation,32 researchers reported on 50 patients with epilepsy who were referred to a sleep laboratory for all-night polysomnography. Fifty-four percent had sleep apnea, and 32% had periodic limb movements of sleep (6 requiring medication). Of the 36 patients who were prescribed therapy based on the evaluation, 6 had significant improvement in seizures.

Both of these studies stress the prevalence of sleep disorders (particularly obstructive sleep apnea) in the epilepsy population, and the underutilization of polysomnography in these patients. The authors rightly point out the importance of diagnosing sleep apnea, as previous studies33,34 also have shown that treatment of this condition improves seizure control.

Conclusions

Attention to sleep in patients with epilepsy has important implications for diagnosis, seizure control, and quality of life. Recent advances have helped clarify the value of recording sleep EEG in diagnosing and localizing partial epilepsy. Syndromes of sleep and epilepsy, particularly nocturnal frontal lobe epilepsy, are better understood. Finally, it is becoming clearer that seizures themselves cause sleep disturbance and that independent sleep disorders frequently coexist with epilepsy.

The common complaint of drowsiness can no longer be dismissed in patients with refractory epilepsy. Sleep studies with polysomnography or video-EEG polysomnography can improve diagnosis and suggest treatments that can clearly improve both seizure control and sleep.

References

1. Malow BA. Sleep and Epilepsy. Neurol Clin 1996; 14(4):765-89.

2. Bourgeois B The relationship between sleep and epilepsy in children. Seminars Ped Neurol 1996; 3(1):29-35.

3. Shouse MN, Martins da Silva A, Sammaritano M. Circadian rhythm, sleep, and epilepsy. J Clin Neurophysiol 1996; 13(1):32-50.

4. Malow BA, Selwa LM, Ross D, Aldrich MS. Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy. Epilepsia 1999; 40(11):1587-92.

This paper demonstrates the value of obtaining overnight studies, particularly when daytime routine EEGs are normal.

5. Fountain NB, Kim JS, Lee SI. Sleep deprivation activates epileptiform discharges independent of the activating effects of sleep. J Clin Neurophysiol 1998; 15(1):69-75.

This paper convincingly demonstrates increased IEDs following sleep deprivation compared with the same patients with sleep EEGs and no sleep deprivation, supporting an independent effect of sleep deprivation.

6. Beun AM, van Emde Boas W, Dekker E. Sharp transients in the sleep EEG of healthy adults: a possible pitfall in the diagnostic assessment of seizure disorders. Electroencephalogr Clin Neurophysiol 1998; 106:44-51.

7. Sammaritano M, Gigli GL, Gotman J. Interictal spiking during wakefulness and sleep and localization of foci in temporal lobe epilepsy. Neurology 1991; 41:290-7.

8. Malow BA, Lin X, Kushwaha R, Aldrich MS. Interictal spiking increases with sleep depth in temporal lobe epilepsy. Epilepsia 1998; 39(12):1309-16.

This study uses the relatively novel concept of delta power to show that IEDs increase with sleep depth, as previously shown with conventional sleep staging.

9. Malow BA, Aldrich MS. Localizing value of rapid eye movement sleep in temporal lobe epilepsy. Sleep Med 2000 1(1):57-60. PMID 10733621.

10. Quigg M, Straume M, Menaker M, Bertram EH. Temporal distribution of partial seizures: Comparison of an animal model with human partial epilepsy. Ann Neurol 1998; 43:748-55.

This paper includes both animal and human data showing a circadian distribution of temporal lobe seizures for both.

11. Crespel A, Baldy-Moulinier M, Coubes P. The relationship between sleep and epilepsy in frontal and temporal lobe epilepsies: Practical and physiopathologic considerations. Epilepsia 1998; 39(2):150-7.

This investigation of 30 epilepsy patients with video EEG and polysomnography shows a relative increase in frontal lobe onset seizures with sleep and sleep disruption by temporal (but not frontal) onset seizures.

12. Bazil CW, Walczak TS. Effects of sleep and sleep stage on epileptic and nonepileptic seizures. Epilepsia 1997; 38(1):56-62.

13. Malow BA, Bowes RJ, Ross D. Relationship of temporal lobe seizures to sleep and arousal: a combined scalp-intracranial electrode study. Sleep 2000 23(2):231-4. PMID 10737340.

14. Park SA, Lee BI, Lee SJ, Kim WJ, Lee JH, Kim JY. Clinical courses of pure sleep epilepsies. Seizure 1998; 7:369-77.

This retrospective study of nocturnal seizures shows excellent prognosis for generalized seizures with more variable outcome for partial seizures.

15. Yaqub BA, Waheed G, Kabiraj MM. Nocturnal epilepsies in adults. Seizure 1997; 6:145-9.

This prospective study of 64 patients with nocturnal seizures shows the range of nocturnal seizure types and demonstrates an overall excellent prognosis.

16. Malow BA, Passaro EA, Hall JH, Abdulrazzak M, Anderson W, Khan I et al. Sleep deprivation does not increase seizure frequency during long term monitoring. Epilepsia 1999; 40(Suppl 7):99-100 (abstract)

17. Oldani A, Zucconi M, Smirne S, Ferini-Strambi L. The neurophysiological evaluation of nocturnal frontal lobe epilepsy. Seizure 1998; 7:317-20

18. Tachibana N, Shinde A, Ikeda A, Akiguchi I, Kimura J, Shibasaki H. Supplementary motor area seizure resembling sleep disorder. Sleep 1996; 19(10):811-6.

19. Provini F, Plazzi G, Tinuper P, Vandi S, Lugaresi E, Montagna P. Nocturnal frontal lobe epilepsy. A clinical and polygraphic overview of 100 consecutive cases. Brain 1999; 122:1017-31.

This large, comprehensive study of nocturnal frontal lobe epilepsy clearly describes typical clinical characteristics, EEG findings, and response to therapy.

20. Oldani A, Zucconi M, Asselta R, Modugno M, Bonati T, Dalpra L et al. Autosomal dominant nocturnal frontal lobe epilepsy. A video-polysomnographic and genetic appraisal of 40 patients and delineation of the epileptic syndrome. Brain 1998; 121:205-23.

A study of 40 patients with familial nocturnal frontal lobe epilepsy, demonstrating that most families show autosomal dominant pattern with reduced penetrance.

21. Nakken KO, Magnusson A, Steinlein OK. Autosomal dominant nocturnal frontal lobe epilepsy: An electroclinical study of a Norwegian family with ten affected members. Epilepsia 1999; 40(1):88-92.

22. O’Regan ME, Brown JK, Goodwin GM, Clarke M. Epileptic aphasia: a consequence of regional hypometabolic encephalopathy? Dev Med Child Neurol 1998; 40:508-16.

23. Veggiotti P, Beccaria F, Guerrini R, Capvilla G, Lanzi G. Continuous spike-and-wave activity during slow-wave sleep: syndrome or EEG pattern? Epilepsia 1999; 40(11):1593-1601.

24. Roberts R. Differential diagnosis of sleep disorders, non-epileptic attacks and epileptic seizures. Curr Opin Neurol 1998; 11:135-9.

Concise, clear review of the differential diagnosis of sleep disorders and epilepsy.

25. Bazil CW, Castro LHM, Walczak TS. Reduction of rapid eye movement sleep by diurnal and nocturnal seizures in temporal lobe epilepsy. Arch Neurol 2000 57(3):363-8. PMID 10714662.

This video-EEG polysomnography study of 21 patients with temporal lobe epilepsy clearly shows decreased REM with both nocturnal and diurnal seizures, and decreased sleep efficiency and increased stage 1 sleep with nocturnal seizures.

26. Espie CA, Paul A, McFie J, Amos P, Hamilton D, McColl JH, Tarassenko L, Pardey J. Sleep studies of adults with severe or profound mental retardation and epilepsy. Am J Mental Retardation 1998; 103(1):47-59.

This is a study of 28 patients with severe mental retardation and epilepsy. Overnight polysomnography showed overall decreases in REM sleep.

27. Bazil CW and Walczak TS (1998) Anticonvulsants and seizures independently reduce REM sleep in patients with temporal lobe epilepsy. Epilepsia 39(Supp 6):69. (Abstract)

28. Malow BA, Bowes RJ, Lin X. Predictors of sleepiness in epilepsy patients. Sleep 1997; 20(12):1105-10.

28. Malow BA, Bowes RJ, Lin X. Predictors of sleepiness in epilepsy patients. Sleep 1997; 20(12):1105-10.

This study of sleepiness in children shows that, like adults, children with epilepsy are more likely to have sleep disturbances than normal control subjects.

30. Cortesi F, Giannotti F, Ottaviano S. Sleep problems and daytime behavior in childhood idiopathic epilepsy. 1999; Epilepsia 40(11):1557-65.

This study used surveys administered to parents of children with idiopathic epilepsy, showing increased sleepiness compared to control children.

31. Malow BA, Fromes GA, Aldrich MS. Usefulness of polysomnography in epilepsy patients. Neurology 1997; 48:1389-94.

32. Beran RG, Plunkett MJ, Holland GJ. Interface of epilepsy and sleep disorders. 1999; Seizure 8:97-102.

This is a large study of epilepsy patients referred for polysomnography, showing a high prevalence of sleep apnea and other sleep disorders.

33. Devinsky O. Ehrenberg B, Barthlen GM, Abramson HS, Luciano D. Epilepsy and sleep apnea syndrome. Neurology 1994;44:2060-4

34. Vaughn BV, D’Cruz OF, Beach R, Messenheimer JA. Improvement of epileptic seizure control with treatment of obstructive sleep apnoea. Seizure 1996; 5:73-8.

This article is based on--
Bazil CW. Sleep and epilepsy. Curr Opin Neurol 2000 13(2):171-5, PMID: 10987575.

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