Non-rapid eye movement (NREM) parasomnias are fascinating and bizarre physical and behavioral phenomena that occur out of sleep. As NREM parasomnias are most common among children, they can be upsetting to parents and caregivers witnessing events, thus prompting medical evaluation. Additionally, this generally benign sleep disorder can overlap in semiology with nocturnal frontal lobe seizures and result in misdiagnoses and/or treatment delays. Thus, it is important for pediatric health care providers to understand the clinical features, pathophysiology, triggers, management, and prognosis of NREM parasomnias.
The patient was a 15-year-old girl with a medical history of seasonal allergies who presented to a clinic for sleepwalking episodes. Her mother reported that these sleepwalking episodes had occurred infrequently in childhood. The sleepwalking began again about 1 month prior to the clinic visit, and the episodes were occurring 2 to 3 times per week. A patient history revealed that the sleepwalking began after the patient started taking a montelukast inhibitor for allergies. The patient had moved to boarding school approximately 1 year prior to the clinic visit and reported no current stressors. These sleepwalking episodes had been witnessed by her roommate. The roommate described the patient engaging in bizarre activities at night such as cuddling with the night light, mumbling, and walking over to her roommate's bed at least once per night. Usually, these events occurred in the first couple of hours of sleep. On one occasion, the patient was observed to wake from sleep, put her jacket on over her pajamas, and leave the dorm room. Her roommate found the patient wandering outside and directed her back to the room without incident. The patient did not remember the events reported. Her bed time was typically around 11 pm and wake up time around 6:30 am. The episodes of sleepwalking and talking generally occur between 12 am and 1 am.
The patient denied symptoms of sleep apnea, narcolepsy, and restless legs and denied drug or alcohol use. She had no personal or family history of seizures. However, the patient's mother and father had episodes of sleepwalking during their childhood. Her younger brother had night terrors. The patient's physical examination was normal. Based on the semiology and timing of events, she was diagnosed with a NREM arousal parasomnia and, specifically, sleepwalking.
NREM parasomnias are common, affecting 13% of children and 1% to 4% of young adults.1 Parasomnias are not specific to any particular neurological conditions but have been more commonly reported among children with epilepsy, attention-deficit/hyperactivity disorder (ADHD), and developmental coordination disorders compared to controls.2,3
Disorders of arousal from NREM sleep are recurrent, incomplete arousals from sleep and encompass sleep terrors, sleepwalking, and confusional arousals.4
These disorders of arousal typically last for a few minutes (5–15 minutes) but can continue for more than an hour. Events are typically described as bizarre, and patients are typically amnestic for the event. Notably, disorders of arousal can overlap in semiology and typically occur in the first few hours of sleep when slow wave sleep (SWS) predominates.5
Confusional arousals are characterized by confusion, disorientation, grogginess, and agitation upon awakening from NREM sleep. Clinical characteristics of confusional arousals include agitation, crying or moaning, disorientation, and particularly slow mentation on arousal from sleep. During these episodes, children may even resist soothing and become more agitated with caregivers' attempts to comfort them. The duration of episodes is typically brief, lasting only a few minutes, and they occur most commonly in infants, toddlers, and children younger than age 5 years.5,6
In contrast, sleep terrors usually occur in children younger than age 5 years and have a more dramatic appearance. The child with sleep terrors suddenly appears extremely agitated, frightened, and confused, often with crying and/or screaming, and has evidence of heightened autonomic activity (eg, hyperventilation, tachycardia, diaphoresis, mydriasis). Sleep terrors are common among pre-school children and reported in up to 34% of children younger than age 7 years.5,6 Furthermore, children with a history of sleep terrors are almost twice as likely to develop sleepwalking episodes after age 5 years when compared with children without any history of sleep terrors.6
Sleepwalking is characterized by ambulation and/or other complex behaviors out of bed. During sleepwalking episodes, the child appears confused or dazed and the eyes are usually open. The patient may mumble, give inappropriate answers to questions, and/or occasionally appear agitated. Most of these events are complex, coordinated, and programmed movements such as opening a drawer, unlocking a door, or getting dressed. Children mostly walk calmly from one room to another room with their eyes open. Sometimes the actions can be bizarre, such as urinating in a closet. Judgment is impaired during sleepwalking and likely accounts for reports of associated accidents, injuries, and harm, as well as wandering out of the home. Sleepwalking is most common among school-aged children, with a peak prevalence around age 10 years.6
Arousal parasomnias are believed to represent a dissociated state that occurs between deep NREM sleep and wakefulness.7 More specifically, arousal parasomnias often emerge from NREM stage 3 SWS, the sleep stage in which the arousal threshold is at its highest compared to other sleep stages. Children are more vulnerable to arousal parasomnias because they have an increased amount of SWS, which subsequently decreases after puberty. Conditions that increase the depth of NREM sleep (such as somnogenic medications, sleep deprivation) and/or increase cortical arousals from sleep (such as environmental sounds and other sleep disorders) may produce parasomnia behavior. A biomarker of this destabilized state, cyclic alternating pattern (CAP), has been described, and CAP represents the intrinsic oscillation of subcortical/cortical arousal with sleep.8 Certain conditions such as neuropsychiatric disease, sleep-disordered breathing, innate genetic factors, and externalizing circumstances (such as a noisy environment), may predispose patients to an increase in CAP and parasomnia behavior.7 Another theory is that inactivation of the frontal lobe during NREM sleep results in disinhibition of the basal ganglia and activation of central pattern generators (functional groups of motor neurons) during parasomnia behavior.9 However, single photon emission computed tomography studies have not supported this theory.10,11 One study showed higher cerebral perfusion to the areas of the brain associated with the wake state (anterior cerebellum, posterior cingulate cortex), highlighting a unique dissociated state during somnambulism.10 Genetic etiologies have also been explored. Mutation of chromosome 20q12-q13 has been identified in a single four-generation family of adult sleepwalkers, with the adenosine deaminase gene representing the most likely candidate gene.12 It is unknown if this gene anomaly is unique to adult sleepwalkers or may be involved in the more common presentation described in children.
Children with ADHD, autism spectrum disorder, and other developmental disorders seem to have an increased prevalence of arousal parasomnias compared to typically developing children.3,13,14 Although the relationship remains unclear, children with neurodevelopmental disorders frequently also have other sleep problems, including bedtime resistance, sleep onset delays, nocturnal waking, sleep-disordered breathing, and periodic limb movements,14–16 that may produce more nocturnal arousals and opportunities for arousal disorders to present.
Diagnosis is typically based on the clinical history, but supplementary video recording of events by caregivers can be helpful. Family history is informative because patients with sleepwalking are twice as likely to have a first-degree family member with a similar history.6 Triggers include sleep deprivation (due to a compensatory increase in deep sleep), alcohol, withdrawal of SWS-suppressing medications (eg, benzodiazepines), and environmental stimuli that induce arousals from sleep (eg, environmental noise). Montelukast inhibitors have been reported to increase arousal parasomnias, as occurred in the Illustrative Case in this article.17 Additionally, the patient reported nocturnal sleep duration of 7.5 hours (less than the 8–10 hours of sleep recommended for her age), and this may have caused increased homeostatic sleep drive that increases early SWS. Overnight polysomnography is not necessary for the diagnosis of NREM arousal parasomnias unless the patient history is notable for atypical clinical features, the presence of another sleep disorder (such as obstructive sleep apnea), and/or potentially injurious behaviors.18 If the differential diagnosis includes nocturnal seizures, polysomnography with full 20-lead electroencephalogram and video recording may be requested.
Distinguishing Arousal Parasomnias from Nocturnal Frontal Lobe Seizures
The symptoms of NREM arousal parasomnias can overlap with nocturnal frontal lobe epilepsy (NFLE), resulting in the potential for misdiagnosis. NFLE is often characterized by thrashing limb movements or tonic-dystonic posturing out of NREM sleep. Children with NFLE may exhibit pelvic thrusting, repetitive gestures, nocturnal wandering, the appearance of fear, and yelling and screaming. Video polysomnography analysis yields some discriminating factors between NFLE and NREM parasomnias: (1) NREM parasomnias typically start with arousal-like behavior (eg, eye opening, head elevation, staring, face rubbing, yawning, stretching); (2) NREM parasomnias typically occur within the first 3 hours of sleep (a time when SWS has the longest duration), whereas NFLE can occur at any time of night; (3) NFLE events tend to be less than 2 minutes long and are stereotyped motor patterns with abrupt onset and offset, whereas NREM parasomnias have more variable patterns and more gradual offset; and (4) a triggering stimulus (eg, noise, obstructive event) is present in about 50% of NREM parasomnias but less commonly so in NFLE.19,20 An electroencephalogram in NFLE can be normal in up to 80% of cases.19Table 1 summarizes the key factors differentiating NFLE from arousal parasomnias.19
Factors Differentiating NFLE from NREM Arousal Parasomnias
Management of NREM arousal parasomnias should first include reassurance and education to the family regarding the benign and self-limited nature of the disorder. Interim management should include institution of appropriate safety measures (use of gates, locking of outside doors and windows, installation of parent notification measures such as alarm systems, keeping sharp objects/weapons in the bedroom inaccessible) and avoidance of triggers and exacerbating factors. Scheduled awakening is a behavioral technique that has been reported to be successful in situations in which episodes occur on a nightly basis.21 It involves having the parent wake the child fully approximately 15 to 30 minutes prior to the time of night that the first NREM arousal parasomnia typically occurs for approximately 2 to 4 weeks. In our experience, scheduled wakings have limited utility because they simply push the parasomnia event later into the night. Hypnosis has been reported to be effective in a case series of children and adults with arousal parasomnias who underwent 1 to 2 hypnotherapy sessions, with 45% improvement at the 1-month follow-up visit and 40% improvement at the 5-year follow-up visit.22 However, this study was limited by small sample size and lack of placebo or sham hypnosis. Pharmacologic treatment may be indicated in cases of frequent or severe episodes, high risk of injury, violent behavior, or serious disruption to the family. The pharmacologic agents most often used are potent SWS suppressants, primarily benzodiazepines (most commonly clonazepam) and tricyclic antidepressants.23
To manage the sleepwalking of the patient in the Illustrative Case, she was advised to discontinue her montelukast inhibitor because of evidence suggesting it may exacerbate sleepwalking,17 and she was advised to get 8 to 10 hours of sleep at consistent times 7 days a week. Additionally, she was advised to implement various safety measures such as setting an alarm bell at the dorm room door, removing sharp objects in the room, and placing locks on the dorm windows. Her sleepwalking had resolved at her 3-month follow-up visit to the clinic.
NREM arousal parasomnias are benign, self-limiting, and common pediatric sleep disorders. Most children outgrow this condition by adolescence. Arousal parasomnias can evolve at different ages, with confusional arousals most common in children younger than age 5 years, sleep terrors most commonly presenting before age 7 years, and sleepwalking developing between school age and adolescence. NREM arousal parasomnias typically decrease after adolescence because the amount of SWS reduces to adult values during the teenage years. The pathophysiology of this dissociative state between wake and sleep is unknown and a potential area of future research. History and video of events are necessary to distinguish parasomnia from NFLE, as electroencephalograms of NFLE patients are often normal. Importantly, sleep hygiene and safety counseling are paramount for management, but in severe cases medication management can be considered for a prespecified treatment period.
- Laberge L, Tremblay RE, Vitaro F, Montplaisir J. Development of parasomnias from childhood to early adolescence. Pediatrics. 2000;106(1 Pt 1):67–74. doi:10.1542/peds.106.1.67 [CrossRef]
- Rodopman-Arman A, Perdahli-Fis N, Ekinci O, Berkem M. Sleep habits, parasomnias and associated behaviors in school children with attention deficit hyperactivity disorder (ADHD). Turk J Pediatr. 2011;53(4):397–403.
- Barnett AL, Wiggs L. Sleep behaviour in children with developmental co-ordination disorder. Child Care Health Dev. 2012;38(3):403–411. doi: . doi:10.1111/j.1365-2214.2011.01260.x [CrossRef]
- American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.
- Petit D, Touchette E, Tremblay RE, Boivin M, Montplaisir J. Dyssomnias and parasomnias in early childhood. Pediatrics. 2007;119(5):e1016–1025. doi: . doi:10.1542/peds.2006-2132 [CrossRef]
- Petit DP, Pennestri MH, Paquet J, et al. Childhood sleepwalking and sleep terrors: a longitudinal study of prevalence and familial aggregation. JAMA Pediatr. 2015;169(7):653–658. doi: . doi:10.1001/jamapediatrics.2015.127 [CrossRef]
- Howell MJ. Parasomnias: an updated review. Neurotherapeutics. 2012;9(4):753–775. doi: . doi:10.1007/s13311-012-0143-8 [CrossRef]
- Terzano MG, Parrino L. Origin and significance of the cyclic alternating pattern (CAP). Sleep Med Rev. 2000;4(1):101–123. doi:10.1053/smrv.1999.0083 [CrossRef]
- Venkatraman V, Huettel SA, Chuah LY, Payne JW, Chee MW. Sleep deprivation biases the neural mechanisms underlying economic preferences. J Neurosci. 2011;31(10):3712–3718. doi: . doi:10.1523/JNEUROSCI.4407-10.2011 [CrossRef]
- Bassetti C, Vella S, Donati F, Wielepp P, Weder B. SPECT during sleepwalking. Lancet. 2000;356(9228):484–485. doi:10.1016/S0140-6736(00)02561-7 [CrossRef]
- Dang-Vu TT, Zadra A, Labelle MA, Petit D, Soucy JP, Montplaisir J. Sleep deprivation reveals altered brain perfusion patterns in somnambulism. PloS One. 2015;10(8):e0133474. doi: . doi:10.1371/journal.pone.0133474 [CrossRef]
- Licis AK, Desruisseau DM, Yamada KA, Duntley SP, Gurnett CA. Novel genetic findings in an extended family pedigree with sleepwalking. Neurology. 2011;76(1):49–52. doi: . doi:10.1212/WNL.0b013e318203e964 [CrossRef]
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- Alkhuja S, Gazizov N, Alexander ME. Sleeptalking! Sleepwalking! Side effects of montelukast. Case Rep Pulmonol. 2013;2013:813786. doi:10.1155/2013/813786 [CrossRef].
- Aurora RN, Lamm CI, Zak RS, et al. Practice parameters for the non-respiratory indications for polysomnography and multiple sleep latency testing for children. Sleep. 2012;35(11):1467–1473. doi: . doi:10.5665/sleep.2190 [CrossRef]
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Factors Differentiating NFLE from NREM Arousal Parasomnias
|Factor||NFLE||NREM Arousal Parasomnias|
|Age at onset||Variable, usually childhood or adolescence||Usually <10 years|
|Attacks per nights||3 or more||1–2|
|Attacks per month||20–40||<1–4|
|Course over years||Stable with increasing age||Disappear by adolescence|
|Disease duration (mean)||About 20 years||About 7 years|
|Episode duration||Seconds to 3 minutes||Seconds to 30 minutes|
|Semiology||Vigorous movements, highly stereotyped||Variable complexity, not stereotyped|
|Trigger factors||Often none identified||Sleep deprivation, febrile illness, alcohol, stress|
|Associated conditions||Often none identified||Obstructive sleep apnea|
|Ictal EEG||Often normal, obscured by artifact, clearly epileptiform in <10%||Slow waves, no epileptiform activity|
|Time of episodes during sleep||Anytime, but may occur in first 60–90 minutes||First third of night, after 90 minutes of sleep|
|PSG sleep stage||NREM stage 2, rarely 3||NREM stage 3|