Sleep and Epilepsy

Sejal V. Jain, MD,* and Sanjeev V. Kothare, MD†

Sleep and epilepsy are common bedfellows. Sleep can affect frequency and occurrence of
interictal spikes and occurrence, timing, and threshold of seizure. Epilepsy can worsen
sleep architecture and severity of sleep disorders. Thus, a vicious cycle is set. Certain
epilepsy syndromes are so intertwined with sleep that they are considered sleep-related
epilepsies. Poor sleep in epilepsy is multifactorial and is worsened by poorly controlled
seizures. On the contrary, poor sleep is associated with worsened quality of life,
psychological function, and memory. Improving sleep has been noted to improve seizure
frequency and an overall well-being in patients with epilepsy. Hence, an emphasis should
be given to address sleep in patients with epilepsy. These interactions are discussed in
detail in this review.
Semin Pediatr Neurol ]:]]]-]]] C 2015 Elsevier Inc. All rights reserved.

Introduction described that seizures affected sleep.3-5 The effects of sleep

Epilepsy affects 1% of the population in the USA.1
Occurrence of 2 or more unprovoked seizures, more than
24 hours apart, or a single unprovoked seizure (reflex
seizure) with at least 60% chances of recurrence or diagnosis
of an epileptic syndrome defines epilepsy.2 The tendency
toward seizures or epilepsy is measured by an electro-
encephalogram (EEG). EEG abnormalities in between seiz-
ures are called spikes or sharp waves or interictal
epileptiform discharges (IEDs). Electrographically, seizures
can be identified by distinct, rhythmic, epileptiform patterns
that disrupt the normal EEG background, evolve in ampli-
tude and frequency, often spread to involve other brain
regions, and end abruptly. Despite advances in localizing
seizures, new devices, and several new medications, epilepsy
remains incurable in a fraction of patients. Significant
comorbidities have also been reported, one of which is
coexisting sleep disorders.
Sleep and epilepsy are interrelated. The importance of
sleep in epilepsy is well known since the ancient times.
Aristotle wrote that sleep is similar to epilepsy and in some
way epilepsy is to sleep. In 1885, Gower described that 21%
of children had nocturnal seizures. He also reported that
nocturnal seizures occurred at specific times in sleep. Fere
From the *Division of Neurology, Cincinnati Children’s Hospital Medical
Center, Cincinnati, OH.
†Department of Neurology, NYU Langone Medical Center, New York, NY.
Address reprint requests to: Sanjeev V. Kothare, MD, Department of
Neurology, NYU Langone Medical Center. New York, NY 10016.
E-mail: sanjeev.kothare@nyumc.org
and epileptiform discharges were first described by Gibbs
and Gibbs in 1947.3-5 Here we review how sleep affects
epilepsy and vice versa.
Effect of Sleep on EEG, Seizures,
and Epilepsy
Sleep is well known to activate IEDs. IEDs are activated by
non-rapid eye movement (NREM) sleep in adults with focal
epilepsy. The spike frequency increases with increasing
depth of sleep and is significantly reduced in REM sleep.6,7
The field of discharges also expands in sleep with more
diffuse discharges during N3 and restricted field during
REM.8 Owing to both of these phenomena, IEDs occurring
in REM often help to lateralize seizures.9,10 Studies in
children showed that some children may have spikes only
during sleep.11 In children, the IEDs in focal epilepsies are
more common during N1 and N2.12 The NREM sleep
represents hypersynchrony of neuronal networks and hence,
believed to perpetuate the IEDs. Additionally, a cyclic
alternating pattern during NREM sleep is described based
on sleep microarchitecture such as sleep spindles, K-com-
plexes, and delta activity, which is divided into A (A1, A2,
and A3) and B phases. IEDs are more commonly seen
during phase A1 which reflects the synchronized NREM
sleep elements. Based on this observation, it is suggested
that IEDs represent the epileptic variant of thalamo-cortical
system, which is normally responsible for NREM sleep
architecture.13 Moreover, adenosine which is shown to have

1071-9091/14/$-see front matter & 2015 Elsevier Inc. All rights reserved. 1
http://dx.doi.org/10.1016/j.spen.2015.03.005
2 S. V. Jain
antiepileptic properties is reduced during sleep. This may
also be a mechanism of activation of IEDS in sleep.14,15
Seizures are also known to occur during specific sleep
stages. It is well documented that seizures are rare in REM
sleep. In a recent study that reviewed 42 studies, REM sleep
was protective of seizure occurrence. On an average
7.8 times fewer focal and 3.3 times fewer generalized
seizures were seen in REM as compared with wakefulness.
Most seizures occur during N1 and N2 sleep. In the
aforementioned study, seizures in N1, N2, and N3 were
87, 68, and 51 times more common than in REM sleep,
respectively.16 Additionally, the seizure type and site of
onset also influence the seizure occurrence patterns. In a
study, 78% of frontal lobe seizures were sleep related,
whereas only 20% of temporal lobe seizures were sleep
related.17 The temporal lobe seizures were more likely to
generalize in sleep.18 Additionally, psychogenic nonepileptic
seizures do not occur in sleep, so occurrence of events
during sleep can also differentiate seizures from psychogenic
non-epileptic seizures.19
In studies, seizures are shown to follow circadian
rhythms. Tonic and tonic-clonic seizures occurred more
frequently in sleep whereas clonic, absence, atonic, and
myoclonic seizures occurred in wakefulness. Epileptic
spasms had 2 peaks at 6-9 AM and 3-6 PM in wakeful-
ness.20 Seizures of temporal lobe origin occurred mainly
between 1100 and 1700 and frontal seizures were seen
mostly between 2300 and 0500.21 Among seizures localized
on intracranial EEG, occipital seizures peaked at 1600-1900,
parietal and frontal at 0400-0700, and temporal seizures
peaked bimodally at 0700- and 1600-1900.22 When corre-
lated with dim light melatonin onset (DLMO), temporal
seizures occurred most frequently during times 6 hours
before DLMO and frontal seizures mainly in 6-12 hour after
the DLMO, suggesting that temporal and frontal seizures
occur synchronized to circadian rhythm.23 These studies
were performed in hospitals, which may show differences
compared with home environment. Hence, a recent study
evaluated the circadian pattern to seizures on ambulatory
EEG where patients are in the home environment. The
results showed that frontal lobe seizures occurred more
frequently between 12 AM and 12 PM and temporal lobe
seizures occurred more frequently between 12 PM and 12
AM. Moreover, frontal lobe seizures clustered between 5:15
and 7:30 AM whereas temporal lobe seizures clustered
between 6:45 and 11:56 PM.24 Furthermore, in a study,
complex partial seizures were less likely to occur on bright
sunny days than dull days after controlling for seasonal
patterns.25
Information on circadian nature of seizures can guide
therapies in future including possibility of light therapy. A
recent study reported treatment of nocturnal or early-
morning seizures in 17 children who were switched to a
proportionally higher dose of antiepileptic medications in
the evening. This differential dosing led to seizure freedom
in 64.7% of patients, whereas 88.2% experienced more than
50% reductions in seizures.26 The study also demonstrated
modeling for peak levels of antiepileptic drugs (AEDs). The
results indicate that there is mild increase in nocturnal peak
levels as compared with daytime levels with the differential
dosing. This approach may also be helpful in reducing side
effects of medications, that is, daytime sleepiness.
Sleep deprivation is one of the most commonly reported
seizure precipitating factor in children with intractable
epilepsy.27 Sleep deprivation increases IEDs. This activation
is seen even if no sleep is recorded on the EEG. Hence, most
EEG laboratories have established protocols for sleep-
deprived EEGs. Sleep deprivation is also known to induce
seizures in certain epilepsies and in patients with no history
of seizures.28-30
Sleep-Related Epilepsies
A distinct, syndrome-specific pattern of seizure frequency or
EEG pattern is seen in certain epilepsy syndromes. Patients
with generalized tonic-clonic seizures on awakening have
generalized seizures that occur in the morning. Juvenile
myoclonic epilepsy is characterized by myoclonic, absence,
and generalized tonic-clonic seizures. Myoclonus occurs
soon after awakening, which may progress to a generalized
seizure. Other syndromes are described in the following
sections.
West Syndrome
This is a catastrophic epilepsy syndrome characterized by a
triad of epileptic flexor-extensor spasms of the body,
variable intellectual disability, and chaotic hypsarrhythmic
EEG, with onset between ages 3-18 months. These spasms
or tonic seizures tend to cluster on awakening in the
morning.31 Additionally, at the onset of the disorder,
hypsarrhythmia first occurs in NREM sleep.
Benign Occipital Lobe Epilepsy
It is a benign epilepsy syndrome seen in children ages 2-6
years, characterized by prolonged periods of eye deviation
and autonomic instability (temperature, heart rate, respira-
tion, and blood pressure) and hemiconvulsive and general-
ized tonic-clonic seizures in sleep, with vomiting on
awakening. Interictal EEGs show occipital spikes, whereas
ictal EEGs show electrographic seizures emanating from the
occipital region during sleep.32 Remission occurs within
2 years of onset.
Electrical Status Epilepticus in Slow-Wave
Sleep
Epilepticus in slow-wave sleep is characterized by spike-
wave complexes occurring in 85% or more of the NREM
sleep with persistence on 3 or more recordings over a period
of 1 month.33 The epileptiform activity becomes virtually
continuous during NREM sleep, such that it may be
impossible to distinguish sleep stages. The onset is typically
at approximately 4-5 years of age with behavioral and
language regression. Cognitive decline and mental
Sleep and epilepsy
retardation are also common. The associated seizures can be
partial or generalized. Aggressive treatment with cortico-
steroids, intravenous gamma globulins, and high-dose anti-
epileptic medications is used to correct the EEG
abnormalities.
Landau-Kleffner Syndrome
Landau-Kleffner syndrome, also called acquired epileptic
aphasia, is a rare childhood neurologic disorder in which
children present with language regression or verbal auditory
agnosia. Onset is usually between 3 and 8 years of age.
Epileptiform activity during sleep, behavioral disturbances,
and sometimes overt seizures are seen.33 In Landau-Kleffner
syndrome, spike-wave activity is mainly in the temporal
channels.
Benign Epilepsy With Centrotemporal
Spikes
Benign epilepsy with centrotemporal spikes, or benign
rolandic epilepsy, is the most common partial epilepsy
syndrome in children, with an onset between 3 and 13
years of age and remission in adolescence.34 The typical
presentation is a partial seizure with paraesthesias and tonic
or clonic activity of the lower face, associated with drooling
and dysarthria. The seizures are mostly nocturnal, with
55%-59% of patients having seizures exclusively during
sleep.35 On EEG, central and temporal spikes are seen,
which may be independent and bilateral with a horizontal
dipole. Sleep activates these discharges significantly. Just like
most idiopathic epilepsies, despite the increased frequency
of seizures and spikes IEDs during sleep, the sleep archi-
tecture is unaffected. The response to medications is
excellent, and the prognosis is universally good from an
epilepsy perspective. The syndrome is no longer considered
benign as cognitive deficits have been described in children
with it. Additionally, increased sleep problems are
reported.36
Autosomal Dominant Nocturnal Frontal
Lobe Epilepsy
Autosomal dominant nocturnal frontal lobe epilepsy
(NFLE) is an inheritable epilepsy, resulting from a muta-
tion in the genes coding for the alpha4 and beta2 subunits
of the nicotinic acetylcholine receptor (CHRNA4 or
CHRNB2), with onset in adolescence or young adult-
hood.28 The clinical manifestations can vary between
individuals in the family, but for the same individual, the
seizures are stereotypic. These can include sudden awak-
enings with dystonic or dyskinetic movements (42.1%),
complex behaviors (13.2%), and sleep-related violent
behavior (5.3%).37 The corresponding EEG findings
include ictal epileptiform abnormalities predominantly
over frontal areas in 31.6% of patients or rhythmic ictal
slow-wave activity over larger anterior cortical areas in
another 47.4%. A third of patients also have associated
NREM parasomnias.38
3
Effect of Seizures and Epilepsy
on Sleep
A seizure occurring in sleep causes significant reduction of
REM sleep, sleep efficiency, and increases N1. If the seizure
occurs before the first REM cycle, the REM sleep and sleep
efficiency are further reduced. Decrease in total sleep time
owing to reduced REM sleep and increased wake times have
also been reported.39
Effect of AEDs on Sleep
A recent study reviewed 45 studies describing the effects of
AEDs on sleep architecture.40 Phenobarbital, phenytoin, and
gabapentin reduced sleep-onset latency. Phenobarbital and
gabapentin also reduced arousals from sleep. Pregabalin,
carbamazepine and gabapentin increased slow-wave sleep
(N3) whereas levetiracetam and ethosuximide reduced it.
Phenobarbital and phenytoin reduced REM sleep whereas
ethosuximide and gabapentin increased it. On objective
sleep measures like multiple sleep latency test, topiramate,
lamotrigine, zonisamide, and vigabatrin did not cause day-
time sleepiness. Phenobarbital, possibly valproic acid and
levetiracetam, at higher doses might cause sleepiness.
Ketogenic diet, successful epilepsy surgery and vagus nerve
stimulator improved nocturnal sleep. The latter also
improved daytime sleepiness. However, it is important to
mention the limitations of the studies. Because most of these
studies were performed in patients with active epilepsy, the
effect on sleep architecture may also be due to the improve-
ment in seizure frequency, which as described previously
could produce a large effect on sleep architecture.
Additionally, vagus nerve stimulator use has been asso-
ciated with sleep-related breathing disorders such as
obstructive sleep apnea (OSA) and central apneic
patterns.41,42
Sleep Disorders in Epilepsy and
Effect of Treatment of Sleep
Disorders on Epilepsy
Sleep disorders are common in epilepsy, and many of the
disorders have a higher prevalence in patients with epilepsy
than in the general population.
Obstructive Sleep Apnea
A study in adults with refractory epilepsy showed that 33%
had OSA. The predictors for OSA were increasing age, male
sex, and seizures during sleep. No correlation was identified
with seizure frequency or type, AED number or type, seizure
localization, and sleepiness.43 Similar results are reported in
other studies.29,44 In a retrospective review in children with
epilepsy, uncontrolled epilepsy was a risk factor for OSA as
compared with primary snoring. Obstructive index
increased with increasing number of AEDs.45 In another
4 S. V. Jain
study, children with epilepsy had higher number of
arousals, prolonged sleep latency, and higher O2 desatura-
tions as compared with controls with higher severity of
OSA.46
Central Sleep Apnea
In a study, 3.7% of patients with epilepsy had central sleep
apnea (CSA) and 7.9% had complex sleep apnea. CSA was
more common among men. Focal seizures were more
prevalent in patients with CSA.47 CSAs are also associated
with seizures.28
Restless Leg Syndrome or Periodic Limb
Movement Disorder
In children with epilepsy, referred to sleep laboratory,
periodic limb movements or periodic limb movement
disorder was found in 5%-10%.46,48 In studies in adults
with epilepsy, 15% had periodic limb movement disorder
and 17% had periodic limb movements in sleep.49,50 In
adult patients with epilepsy, restless leg syndrome was
identified in 18%-35%.49,51
Insomnia
In children with epilepsy referred for sleep evaluation,
insomnia was identified in 11%.48 In adult with epilepsy,
40%-55% subjects had insomnia.52,53 Insomnia correlated
with number of AEDs, and higher scores on depression
scales. Insomnia and poor sleep quality were predictors for
poor quality of life.54 In 100 consecutive adult patients with
epilepsy, sleep-onset insomnia was reported in 34% and
maintenance insomnia in 52%.51
Sleepiness or Hypersomnia
Overall, 28%-48% of patients with epilepsy report daytime
sleepiness. In a questionnaire-based study, 70% of the
neurologists attributed sleepiness to AEDs.48 However,
prospective studies in adults with epilepsy evaluating
sleepiness with subjective and objective tools identified that
sleepiness correlated with sleep apnea and restless leg
syndrome symptoms, habitual snoring, observed apneas,
recurrence of seizures, neck circumference, and anxiety. No
correlation was found for type of AED, number of AEDs,
type of seizures, and seizure frequency.49,55,56 Similarly, in
children with epilepsy, 46.2% of children with epilepsy had
sleepiness that was associated with symptoms of sleep
disordered breathing and parasomnia. No correlation was
found with epilepsy syndrome, AEDs, and presence or
absence of seizure freedom.57
Parasomnia
Parasomnias are also common in children with epilepsy.
Nocturnal seizures may be difficult to differentiate from
parasomnia. In patients with NFLE, 30% have arousal
parasomnia and 12% have REM behavioral disorder.58
Hence, differentiating parasomnia and nocturnal seizures is
not only very important but also challenging. The onset of
parasomnia is typically seen in children younger than 10
years of age whereas seizures of NFLE start at a later age.
The parasomnia events are longer, have different behavior
patterns, occur during earlier part of the night, and are out
of N3. On the contrary, NFLE seizures are brief, highly
stereotypic, may occur multiple times in night, and are
usually out of N1 or N2.59
Effect of Treatment of Sleep Disorders on
Epilepsy
Treatment of sleep disorders improves the seizure control.
This is well established for OSA. A retrospective review in
adult patients with OSA and epilepsy, treated with contin-
uous positive airway pressure (CPAP) at least for 6 months,
showed decreased seizure frequency. Of 28 CPAP-compliant
subjects, 16 became seizure free. In the noncompliant
group, no significant differences were seen.60 CPAP also
improved IEDs in wakefulness and sleep except for REM
sleep.61 In a randomized study, 50% or more seizure
reduction was seen in 28% of subjects on CPAP as
compared with 15% of controls.62 A recent study showed
that the odds of more than 50% reduction or seizure
freedom in PAP-treated subjects were 9.9 and 3.91 times
compared with untreated OSA and no OSA, respectively.
PAP-treated subjects had 32.3 times the odds of having 50%
or more seizure reduction compared with the untreated
OSA and 6.13 times compared with no OSA.44 Additionally,
treatment of underlying OSA with adenotonsillectomy
resulted in improvement in seizure frequency.63 Moreover,
in a randomized study, in patients with insomnia and
epilepsy, melatonin improved seizure frequency; however,
no significant improvement in sleep was noted.64 In a recent
randomized placebo-controlled study, melatonin improved
sleep with nonsignificant improvement in IEDs and seizure
frequency.65
Sudden Unexpected Death in
Epilepsy, Sleep, and
Cardiorespiratory Abnormalities
Sudden unexpected death in epilepsy is defined as a
“sudden, unexpected, witnessed or unwitnessed, non-
traumatic and non-drowning death in patients with epilepsy
with or without evidence for a seizure and excluding
documented status epilepticus in which postmortem exami-
nation does not reveal a toxicologic or anatomic cause for
death.”66 The incidence is as high as 6.0-9.3 per 1000
patient-years among patients evaluated for or treated with
epilepsy surgery or vagus nerve stimulation for epilepsy.67
The risk factors in children are major neurologic impair-
ment, refractory seizures, and generalized tonic-clonic
seizures. The death typically occurs in bed. One of the
mechanisms thought to be responsible for sudden unex-
pected death in epilepsy is respiratory and cardiac changes
Sleep and epilepsy
during seizures. The respiratory abnormalities include
central and obstructive apneas, hypoventilation, hypercap-
nia, and desaturation with acidosis, bradypnea, and tachyp-
nea. The cardiac abnormalities include postictal changes in
heart rate variability caused by sympathetic activation, ictal
bradycardia, asystole, repolarization, anomalies (prolonged
or shortened QTc interval), and atrial fibrillation. Moreover,
cerebral seen as postictal EEG suppression may be another
mechanism.68
Other Associations With Sleep
and Epilepsy
Anxiety and depression in adults and behavioral problems
in children with epilepsy are common. Studies suggest that
these problems are even higher when sleep disturbances or
disorders are associated.29 In a recent study, suicidal
ideation was also linked to poor sleep quality in patients
with epilepsy.69 Additionally, patients with epilepsy and
sleep problems have poorer quality of life as compared with
patients without sleep problems.70-72 Several studies have
shown that children with sleep problems and epilepsy have
more behavioral problems and poorer psychological func-
tioning than without sleep problems.29,73 Even in children
with new-onset seizures, sleep disturbances are associated
with higher behavioral problems as well as poorer neuro-
psychological function.52 Moreover, poor quality of life in
the domains of physical cognitive and social functional, and
behavior have been reported.74 In a recent study, children
with idiopathic focal epilepsies had poorer sleep-related
memory consolidation. This also correlated with IEDs in
NREM sleep.75
Conclusion
Despite this compelling evidence for improving quality and
quantity of sleep, a recent study showed that more than a
third of the patients with epilepsy slept 6 hours or less.76
Moreover, a study evaluated sleep screening practices of
neurology providers who had referred patients for sleep
evaluation. The results showed that 94% of the providers
used routine sleep screening, but only 30% using detailed
questions about sleep.48 Similarly, pediatricians used 1-4
questions, which pertain to sleep-wake times and routine
sleep problems. One of the barriers for asking more
questions was the assumption that the parents or patients
will bring up sleep problems.77 However, it was found that
most patients did not discuss sleep-related issues with the
providers.78 These suggest that direct questions by providers
are necessary to identify sleep problems.
Sleep and epilepsy are related, and poor sleep induces
worsened seizure control, which in turn deteriorates sleep.
Hence a vicious cycle is established. Behavior, quality of life,
and memory are affected by poor sleep. Moreover, sleep
disorders are also very common, and treatment of them may
improve seizure control. Hence, education on improving
5
sleep quality and screening, evaluation, and treatment for
sleep problems should be a part of routine care in patients
with epilepsy.
References
1. Kwan P, Brodie MJ: Early identification of refractory epilepsy. N Engl J
Med 342:314-319, 2000
2. Fisher RS, Acevedo C, Arzimanoglou A, et al: ILAE official report:
A practical clinical definition of epilepsy. Epilepsia 55:475-482, 2014
3. Bazil CW, Malow BA, Sammaritano MR: Sleep and Epilepsy: The
Clinical Spectrum, (ed 1) Amsterdam, New York, Elsevier, 2002
4. Lüders H, Dinner DS: Epilepsy and Sleep: Physiological and Clinical
Relationships. San Diego, Academic Press, 2001
5. Kotagal P: The relationship between sleep and epilepsy. Semin Pediatr
Neurol 8:241-250, 2001
6. Malow BA, Lin X, Kushwaha R, et al: Interictal spiking increases with
sleep depth in temporal lobe epilepsy. Epilepsia 39:1309-1316, 1998
7. Sammaritano M, Gigli GL, Gotman J: Interictal spiking during
wakefulness and sleep and the localization of foci in temporal lobe
epilepsy. Neurology 41:290-297, 1991
8. Foldvary-Schaefer N, Grigg-Damberger M: Sleep and epilepsy. Semin
Neurol 29:419-428, 2009
9. Malow BA, Aldrich MS: Localizing value of rapid eye movement sleep
in temporal lobe epilepsy. Sleep Med 1:57-60, 2000
10. Rocamora R, Andrzejak RG, Jimenez-Conde J, et al: Sleep modulation
of epileptic activity in mesial and neocortical temporal lobe epilepsy:
A study with depth and subdural electrodes. Epilepsy Behav
28:185-190, 2013
11. Shinnar S, Kang H, Berg AT, et al: EEG abnormalities in children with a
first unprovoked seizure. Epilepsia 35:471-476, 1994
12. Kothare SV, Kaleyias J. Sleep and epilepsy in children and adolescents.
Sleep Med11:674-685.
13. Halasz P, Terzano MG, Parrino L: Spike-wave discharge and the
microstructure of sleep-wake continuum in idiopathic generalised
epilepsy. Neurophysiol Clin 32:38-53, 2002
14. Huang ZL, Zhang Z, Qu WM: Roles of adenosine and its receptors in
sleep-wake regulation. Int Rev Neurobiol 119:349-371, 2014
15. Swiader MJ, Kotowski J, Luszczki JJ: Modulation of adenosinergic
system and its application for the treatment of epilepsy. Pharmacol Rep
66:335-342, 2014
16. Ng M, Pavlova M: Why are seizures rare in rapid eye movement sleep?
Review of the frequency of seizures in different sleep stages. Epilepsy
Res Treat 2013:932790, 2013
17. Crespel A, Coubes P, Baldy-Moulinier M: Sleep influence on seizures
and epilepsy effects on sleep in partial frontal and temporal lobe
epilepsies. Clin Neurophysiol 111:S54-S59, 2000. (suppl 2)
18. Herman ST, Walczak TS, Bazil CW: Distribution of partial seizures
during the sleep—wake cycle: Differences by seizure onset site.
Neurology 56:1453-1459, 2001
19. Bazil CW, Walczak TS: Effects of sleep and sleep stage on epileptic and
nonepileptic seizures. Epilepsia 38:56-62, 1997
20. Zarowski M, Loddenkemper T, Vendrame M, et al: Circadian distri-
bution and sleep/wake patterns of generalized seizures in children.
Epilepsia 52:1076-1083, 2011
21. Hofstra WA, Spetgens WP, Leijten FS, et al: Diurnal rhythms in
seizures detected by intracranial electrocorticographic monitoring:
An observational study. Epilepsy Behav 14:617-621, 2009
22. Durazzo TS, Spencer SS, Duckrow RB, et al: Temporal distributions of
seizure occurrence from various epileptogenic regions. Neurology
70:1265-1271, 2008
23. Hofstra WA, Gordijn MC, van der Palen J, et al: Timing of temporal
and frontal seizures in relation to the circadian phase: A prospective
pilot study. Epilepsy Res 94:158-162, 2011
24. Pavlova MK, Woo Lee J, Yilmaz F, et al: Diurnal pattern of seizures
outside the hospital: Is there a time of circadian vulnerability?
Neurology 78:1488-1492, 2012
25. Baxendale S: Seeing the light? Seizures and sunlight. Epilepsy Res
84:72-76, 2009
6 S. V. Jain
26. Guilhoto LM, Loddenkemper T, Vendrame M, et al: Higher evening
antiepileptic drug dose for nocturnal and early-morning seizures.
Epilepsy Behav 20:334-337, 2011
27. Fang PC, Chen YJ, Lee IC: Seizure precipitants in children with
intractable epilepsy. Brain Dev 30:527-532, 2008
28. Kothare SV, Kaleyias J: Sleep and epilepsy in children and adolescents.
Sleep Med 11:674-685, 2010
29. van Golde EG, Gutter T, de Weerd AW: Sleep disturbances in people
with epilepsy; prevalence, impact and treatment. Sleep MedRev
15:357-368, 2011
30. Malow BA: Sleep deprivation and epilepsy. Epilepsy Curr 4:193-195,
2004
31. Ramgopal S, Shah A, Zarowski M, et al: Diurnal and sleep/wake patterns
of epileptic spasms in different age groups. Epilepsia 53:1170-1177, 2012
32. Capovilla G, Striano P, Beccaria F: Changes in Panayiotopoulos
syndrome over time. Epilepsia 50:45-48, 2009. (suppl 5)
33. Sanchez Fernandez I, Loddenkemper T, Peters JM, et al: Electrical
status epilepticus in sleep: Clinical presentation and pathophysiology.
Pediatr Neurol 47:390-410, 2012
34. Wirrell EC: Benign epilepsy of childhood with centrotemporal spikes.
Epilepsia 39:S32-S41, 1998. (suppl 4)
35. Mendez M, Radtke RA: Interactions between sleep and epilepsy. J Clin
Neurophysiol 18:106-127, 2001
36. Tang SS, Clarke T, Owens J, et al: Sleep behavior disturbances in
rolandic epilepsy. J Child Neurol 26:239-243, 2011
37. Oldani A, Zucconi M, Asselta R, et al: Autosomal dominant nocturnal
frontal lobe epilepsy. A video-polysomnographic and genetic appraisal
of 40 patients and delineation of the epileptic syndrome. Brain
121:205-223, 1998, (Pt 2)
38. Provini F, Plazzi G, Tinuper P, et al: Nocturnal frontal lobe epilepsy.
A clinical and polygraphic overview of 100 consecutive cases. Brain
122:1017-1031, 1999, (Pt 6)
39. Touchon J, Baldy-Moulinier M, Billiard M, et al: Sleep organization and
epilepsy. Epilepsy Res Suppl 2:73-81, 1991
40. Jain SV, Glauser TA: Effects of epilepsy treatments on sleep architecture
and daytime sleepiness: An evidence-based review of objective sleep
metrics. Epilepsia 55:26-37, 2014
41. Parhizgar F, Nugent K, Raj R: Obstructive sleep apnea and respiratory
complications associated with vagus nerve stimulators. J Clin Sleep
Med 7:401-407, 2011
42. Khurana DS, Reumann M, Hobdell EF, et al: Vagus nerve stimulation
in children with refractory epilepsy: Unusual complications and
relationship to sleep-disordered breathing. Childs Nerv Syst 23:
1309-1312, 2007
43. Malow BA, Levy K, Maturen K, et al: Obstructive sleep apnea is
common in medically refractory epilepsy patients. Neurology
55:1002-1007, 2000
44. Pornsriniyom D, Kim H, Bena J, et al: Effect of positive airway pressure
therapy on seizure control in patients with epilepsy and obstructive
sleep apnea. Epilepsy Behav 37:270-275, 2014
45. Jain SV, Horn PS, Simakajornboon N, et al: Obstructive Sleep Apnea
and Primary Snoring in Children With Epilepsy. J Child Neurol
28:77-82, 2012
46. Kaleyias J, Cruz M, Goraya JS, et al: Spectrum of polysomnographic
abnormalities in children with epilepsy. Pediatr Neurol 39:170-176, 2008
47. Vendrame M, Jackson S, Syed S, et al: Central sleep apnea and com-
plex sleep apnea in patients with epilepsy. Sleep Breath 18:119-124,
2014
48. Jain SV, Simakajornboon N, Glauser TA: Provider practices impact
adequate diagnosis of sleep disorders in children with epilepsy. J Child
Neurol 28:589-595, 2012
49. Malow BA, Bowes RJ, Lin X: Predictors of sleepiness in epilepsy
patients. Sleep 20:1105-1110, 1997
50. Malow BA, Fromes GA, Aldrich MS: Usefulness of polysomnography in
epilepsy patients. Neurology 48:1389-1394, 1997
51. Khatami R, Zutter D, Siegel A, et al: Sleep-wake habits and disorders in
a series of 100 adult epilepsy patients—a prospective study. Seizure
15:299-306, 2006
52. Byars AW, Byars KC, Johnson CS, et al: The relationship between sleep
problems and neuropsychological functioning in children with first
recognized seizures. Epilepsy Behav 13:607-613, 2008
53. Lopez MR, Cheng JY, Kanner AM, et al: Insomnia symptoms in South
Florida military veterans with epilepsy. Epilepsy Behav 27:159-164,
2013
54. Vendrame M, Yang B, Jackson S, et al: Insomnia and epilepsy:
A questionnaire-based study. J Clin Sleep Med 9:141-146, 2013
55. Manni R, Politini L, Sartori I, et al: Daytime sleepiness in epilepsy
patients: Evaluation by means of the Epworth sleepiness scale. J Neurol
247:716-717, 2000
56. Giorelli AS, Neves GS, Venturi M, et al: Excessive daytime sleepiness
in patients with epilepsy: A subjective evaluation. Epilepsy Behav
21:449-452, 2011
57. Maganti R, Hausman N, Koehn M, et al: Excessive daytime sleepiness
and sleep complaints among children with epilepsy. Epilepsy Behav
8:272-277, 2006
58. Bisulli F, Vignatelli L, Naldi I, et al: Increased frequency of arousal
parasomnias in families with nocturnal frontal lobe epilepsy:
A common mechanism? Epilepsia 51:1852-1860, 2010
59. Derry CP, Duncan JS, Berkovic SF: Paroxysmal motor disorders of
sleep: The clinical spectrum and differentiation from epilepsy. Epilepsia
47:1775-1791, 2006
60. Vendrame M, Auerbach S, Loddenkemper T, et al: Effect of continuous
positive airway pressure treatment on seizure control in patients with
obstructive sleep apnea and epilepsy. Epilepsia 52:e168-e171, 2011
61. Pornsriniyom D, Shinlapawittayatorn K, Fong J, et al: Continuous
positive airway pressure therapy for obstructive sleep apnea reduces
interictal epileptiform discharges in adults with epilepsy. Epilepsy
Behav 37:171-174, 2014
62. Malow BA, Foldvary-Schaefer N, Vaughn BV, et al: Treating obstructive
sleep apnea in adults with epilepsy: A randomized pilot trial.
Neurology 71:572-577, 2008
63. Segal E, Vendrame M, Gregas M, et al: Effect of treatment of obstructive
sleep apnea on seizure outcomes in children with epilepsy. Pediatr
Neurol 46:359-362, 2012
64. Goldberg-Stern H, Oren H, Peled N, et al: Effect of melatonin on
seizure frequency in intractable epilepsy: A pilot study. J Child Neurol
27:1524-1528, 2012
65. Jain SV, Horn PS, Simakajornboon N, et al: Melatonin improves sleep
in children with epilepsy: Randomized, double-blind cross-over study.
Sleep Med 2015. pii: S1389-9457(15)00047-7, http://dx.doi.org/
10.1016/j.sleep.2015.01.005 [Epub ahead of print]
66. Nashef L: Sudden unexpected death in epilepsy: Terminology and
definitions. Epilepsia 38:S6-S8, 1997
67. Devinsky O: Sudden, unexpected death in epilepsy. N Engl J Med
365:1801-1811, 2011
68. Kothare SV, Singh K: Cardiorespiratory abnormalities during epileptic
seizures. Sleep Med 15:1433-1439, 2014
69. Wigg CM, Filgueiras A, Gomes Mda M: The relationship between sleep
quality, depression, and anxiety in patients with epilepsy and suicidal
ideation. Arq Neuropsiquiatr 72:344-348, 2014
70. de Weerd A, de Haas S, Otte A, et al: Subjective sleep disturbance in
patients with partial epilepsy: A questionnaire-based study on
prevalence and impact on quality of life. Epilepsia 45:1397-1404,
2004
71. Xu X, Brandenburg NA, McDermott AM, et al: Sleep disturbances
reported by refractory partial-onset epilepsy patients receiving poly-
therapy. Epilepsia 47:1176-1183, 2006
72. Piperidou C, Karlovasitou A, Triantafyllou N, et al: Influence of sleep
disturbance on quality of life of patients with epilepsy. Seizure
17:588-594, 2008
73. Stores G, Wiggs L, Campling G: Sleep disorders and their relationship
to psychological disturbance in children with epilepsy. Child Care
Health Dev 24:5-19, 1998
74. Wirrell E, Blackman M, Barlow K, et al: Sleep disturbances in children
with epilepsy compared with their nearest-aged siblings. Dev Med
Child Neurol 47:754-759, 2005
Sleep and epilepsy
75. Galer S, Urbain C, De Tiege X, et al: Impaired sleep-related
consolidation of declarative memories in idiopathic focal epilepsies of
childhood. Epilepsy Behav 43C:16-23, 2014
76. Cui W, Zack MM, Kobau R, et al: Health behaviors among people with
epilepsy-Results from the 2010 National Health Interview Survey.
Epilepsy Behav 44C:121-126, 2015
7
77. Faruqui F, Khubchandani J, Price JH, et al: Sleep disorders in children:
A national assessment of primary care pediatrician practices and
perceptions. Pediatrics 128:539-546, 2011
78. Bailes S, Baltzan M, Rizzo D, et al: Sleep disorder symptoms are
common and unspoken in Canadian general practice. Fam Pract
26:294-300, 2009