Insomnia, parasomnias, and narcolepsy in children: clinical features, diagnosis, and management

doi:10.1016/S1474-4422(16)30204-6

The Lancet Neurology

Volume 15, Issue 11, October 2016, Pages 1170-1181

https://doi.org/10.1016/S1474-4422(16)30204-6 Get rights and content

Summary

Sleep problems are frequently encountered as presenting complaints in child neurology clinical practice. They can affect the functioning and quality of life of children, particularly those with primary neurological and neurodevelopmental disorders, since coexisting sleep problems can add substantially to neurocognitive and behavioural comorbidities. Additionally, symptoms of some sleep disorders such as parasomnias and narcolepsy can be confused with those of other neurological disorders (eg, epilepsy), posing diagnostic challenges for paediatric neurologists. The understanding of the neurophysiology of sleep disorders such as insomnia, parasomnias, and narcolepsy is still evolving. There is a complex relation between the sleeping brain and its waking function. The interplay among genetic factors, alterations in neurotransmitters, electrophysiological changes, and environmental factors potentially contribute to the genesis of these sleep disorders.

Introduction

Sleep disorders are frequently encountered in paediatric neurological practice and can occur alone or concomitantly with a broad range of neurological diseases. Overall, 25% of children have had at least one sleep problem by adolescence, and this proportion can be as high as 75% in children with autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), epilepsy, or headache.1, 2, 3, 4, 5 Sleep disorders disrupt normal sleep architecture and affect sleep quality or quantity, or both. Sleep medicine is gaining interest among neurology health-care providers as evidence shows that sleep disruptions can impair cognition, emotional regulation, and neurobehavioural functioning;6, 7, 8, 9 increase seizure10, 11 and headache frequencies;12, 13, 14 and prolong recovery from acquired brain injuries such as traumatic brain injury¹⁵ and stroke.¹⁶ Furthermore, neurologists might be expected to diagnose and manage primary sleep disorders, such as narcolepsy and parasomnias. Paediatric neurologists aiming to improve the quality of life of patients and their families should recognise that improving a child's sleep problems can alleviate family stress and caregiver burden.17, 18, 19 Thus, knowledge about sleep disorders is crucial for neurology health-care providers to ensure accurate diagnoses and optimise disease management.

More than 100 sleep disorders are listed in the International Classification of Sleep Disorders,²⁰ but in this Review we focus only on three disorders—insomnia, parasomnia, and narcolepsy—that exemplify the range of pathology in sleep medicine: insufficient sleep, disturbed sleep, and hypersomnia, respectively. These conditions deserve specific attention because they are likely to be encountered by paediatric neurology care providers and, in the cases of narcolepsy and parasomnias, may be misdiagnosed as other neurological conditions. Insomnia is the most common sleep disorder, and the resulting sleep deprivation is associated with daytime neurobehavioural and cognitive dysfunction. Such an association between insomnia and neurobehavioural morbidity is relevant to all paediatric neurology patients, but has been most extensively researched in children with ADHD or autism spectrum disorder. Parasomnias and narcolepsy are commonly misdiagnosed, which can result in delays to suitable management and inappropriate exposure to medications. For example, parasomnias can be difficult to distinguish from hyperkinetic seizure activity; in one study,²¹ 29% of cases eventually diagnosed as nocturnal seizure based on nocturnal polysomnography were initially diagnosed as parasomnias. Likewise, symptoms of cataplexy associated with narcolepsy type 1 are often mistaken for epileptic and non-epileptic seizure activity, contributing to a median diagnostic delay of 10·5 years in patients with narcolepsy.22, 23, 24

In this Review, we aim to provide an overview of the clinical presentation, pathophysiology, diagnostic work-up, and treatment of paediatric insomnia, parasomnia, and narcolepsy. We also highlight the complex relation between sleep and neurobehavioural and cognitive functioning in children. Although other sleep disorders, such as sleep-disordered breathing, circadian disorders, periodic limb movements of sleep, and restless limb syndrome, are also important clinical entities, they are beyond the scope of this Review.

Section snippets

Insomnia

Insomnia is the most common sleep disorder presented to paediatric health-care providers,25, 26 and it is reported in otherwise healthy children as well as children with a range of neurological conditions, including headache,27, 28 epilepsy,²⁹ or neurodevelopmental disorders.3, 30 Insomnia in children is defined by the third edition of the International Classification of Sleep Disorders²⁰ as requiring at least one of the following symptoms to be reported by the patient or caregiver: difficulty

Parasomnias

Arousal parasomnias are commonly experienced by children; in one longitudinal study assessing children between ages 2·5 and 6 years,⁷⁵ the prevalence of any type of parasomnia occurring at least once was as high as 84% (879 of 1041). Parasomnias are not a symptom of any particular neurological conditions but have been more commonly reported in children with epilepsy, ADHD, or developmental coordination disorder than in healthy children.76, 77, 78 Parasomnias are defined as undesirable physical

Narcolepsy

Narcolepsy is a chronic neurological disorder characterised by symptoms of excessive daytime sleepiness with rapid entry into rapid eye movement (REM) sleep, hypnagogic hallucinations, sleep paralysis, and disrupted nocturnal sleep. More than half of patients present with cataplexy, which distinguishes between narcolepsy type 1 (ie, narcolepsy with cataplexy) and narcolepsy type 2 (ie, narcolepsy without cataplexy).²⁰ Narcolepsy is a rare disorder, occurring in 0·025–0·05% of the population,

Conclusions and future directions

Sleep disorders are common in children, particularly those with neurological or neurodevelopmental diseases, and can have a substantial impact on the quality of life of patients and their caregivers. Since sleep problems are associated with daytime behavioural and cognitive functioning deficits that could be mitigated with treatment, screening for sleep complaints in the paediatric neurology clinical setting is crucial to achieve optimal functioning, especially of children with

Search strategy and selection criteria

We searched PubMed for English-language articles published from Jan 1, 1990, to July 1, 2016. We identified studies on the aetiology, pathophysiology, and diagnosis and management of parasomnias, insomnias, and narcolepsy using the following search terms for each condition: “neurobiology”, “neurotransmitters”, “etiology”, “physiology”, “neuroimaging”, “genetic”, “brain”, “neurophysiology”, “power spectral analysis”, “polysomnography”, “sleep study”, “electroencephalography”, “diagnosis”,

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Narcolepsy, a chronic neurologic sleep disorder, has sparked growing interest in the potential role of vitamin B12 in its pathogenic mechanism. However, research on this association has predominantly focused on adults. Our objective was to delineate the phenotypic and genetic connections between serum vitamin B12 levels and paediatric narcolepsy.
To investigate the causal relationship between vitamin B12 and paediatric narcolepsy, we conducted a retrospective analysis involving 60 narcolepsy patients and a matched control group. Univariate and multivariate logistic regression models were employed to identify independent factors influencing paediatric narcolepsy. Furthermore, a bidirectional two-sample Mendelian randomization (MR) analysis was performed to assess the causal connection between serum vitamin B12 levels and narcolepsy.
Paediatric narcolepsy patients showed significantly lower serum levels of vitamin B12 and folate compared to the control group (P < 0.05). Multivariate logistic regression analysis identified serum vitamin B12 as the exclusive independent factor influencing paediatric narcolepsy (P < 0.001; OR = 0.96; 95%CI: 0.94–0.98). Additionally, IVW model results provided compelling evidence supporting a potential causal association between serum vitamin B12 levels and paediatric narcolepsy (OR: 0.958, 95% CI = 0.946–0.969, P = 0.001).
This study establishes connections at both phenotypic and genetic levels, associating vitamin B12 deficiency with an increased risk of paediatric narcolepsy. These findings provide innovative perspectives for clinical strategies in the prevention and treatment of narcolepsy.
Exposure to neighborhood violence and insufficient sleep among adolescents in the United States: Findings from a population-based study
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Although studies have investigated and found an association between victimization and insufficient sleep among adolescents, few studies have examined the association between exposure to neighborhood violence and insufficient sleep among adolescents. The objective of this study was to investigate the cross-sectional association between exposure to neighborhood violence and insufficient sleep among adolescents. Data for this study came from the 2021 Youth Risk Behavior Survey. An analytic sample of 17,033 adolescents aged 14–18 (51.7 % male) was analyzed using binary logistic regression. The outcome variable investigated was insufficient sleep, and the main explanatory variable was exposure to neighborhood violence. Of the 17,033 adolescents, 76.5 % did not obtain the recommended 8 hours of sleep on an average school night, and 18.7 % were exposed to neighborhood violence. Controlling for the effects of other factors, exposure to neighborhood violence was associated with 1.33 times higher odds of having insufficient sleep (AOR = 1.33, 95 % CI = 1.13–1.58). Adolescents were more likely to get insufficient sleep if they were older, non-Hispanic Black, had poor mental health during COVID, felt sad or hopeless, engaged in excessive screen-time behaviors, or used alcohol. Physical activity, school connectedness, and parental monitoring all had protective effects on insufficient sleep. This study found that exposure to neighborhood violence was associated with insufficient sleep among adolescents over and above demographic and other covariates. Future studies that employ longitudinal designs may offer additional insight into the mechanisms underlying the association between exposure to neighborhood violence and insufficient sleep.
Perceived impact of epilepsy on sleep: Views of children with epilepsy, parents and school staff
2023, Epilepsy and Behavior
To gain an understanding of the views of school-aged children with epilepsy, their parents, and school staff regarding the impact of epilepsy on sleep.
As part of the What I Need in School (WINS) study, school-aged children (n = 18) with ‘active epilepsy’ (taking Anti-Seizure Medications, ASMs, for epilepsy), their parents (n = 68) and school staff (n = 56) were interviewed or completed bespoke questionnaires. Questions focussed on the potential impact of epilepsy on the child’s sleep or tiredness in school and the potential impact of sleep/tiredness on learning and behavior.
Fifty-six percent of children believed that epilepsy affects their sleep while 65% of parents believed that their child had more difficulties with sleep than other children of their age. Seventy-eight percent of parents believed that their child’s difficulties were due to epilepsy and 95% believed that their child’s difficulties impacted their learning and behavior. Fifty-four percent of school staff believed that the child with epilepsy they supported was more tired/fatigued than their peers, and 86% of school staff believed that the child’s increased tiredness affected their learning/behavior. Parents of children with intellectual disabilitiy were significantly more likely to indicate that they felt that their child had more sleep difficulties than other children (p = 0.016). Regarding the impact on their sleep, participating children felt that epilepsy contributed to difficulties in falling and staying asleep and daytime tiredness. Their parents reported a range of potential sleep difficulties and potential impacts on the child’s learning and behavior. Parental reported difficulties included daytime tiredness, difficulty falling and staying asleep, and the impact of nocturnal seizures. In terms of impact, parents felt that sleep difficulties impacted negatively cognition and emotional-behavioral functioning. Additionally, parents reported that ASMs and medication for ADHD can contribute to sleep difficulties. School staff felt that many of the children appeared tired/fatigued during the day and this could lead to less engagement with classroom activities, impact attention and processing speed negatively, and contribute to behavioral and emotional difficulties.
The majority of children and parents who responded believed that epilepsy affects the child’s sleep. Most parents and school staff also believed that the child’s sleep difficulties/excess tiredness were due to the child’s epilepsy and that the difficulties significantly impacted the child’s learning and behavior. There is a need to better understand the role epilepsy plays in sleep difficulties and associated learning and behavioral impairments. There is also a need to develop interventions to reduce the subsequent impact on child learning and behavior.
The Japanese version of the children's sleep habits questionnaire (CSHQ-J): A validation study and influencing factors
2022, Brain and Development
Citation Excerpt :
Sleep disorders in children are not rare—at least 25% of children or toddlers experience sleep disorders [1-3].
This study aimed to validate the Japanese version of the Child’s Sleep Habits Questionnaire (CSHQ-J) and identify which factors affect the CHSQ-J total score.
The participants were 3158 children (aged 4–12 years) and their parent/guardian, as community samples from large, medium-sized, and small cities. Each parent/guardian filled in the questionnaire set (CSHQ-J, Pittsburgh Sleep Quality Index, demographic data: family structure, sleep environment, participants’ present illness, and economic information); we also collected 51 clinical samples from our facility to calculate the cutoff score. According to the age of the participants in the original CSHQ (4–10 years), validation was assessed statistically via exploratory and confirmatory factor analyses and internal consistency (verified by Cronbach’s α). Multivariate analysis was conducted to identify factors affecting the CSHQ-J total score.
We received responses from 2687 participants (response rate: 85%) and analyzed 1688 participants who were the age of the original CSHQ participants. The alpha coefficients of each subscale of the CSHQ-J ranged from 0.43 to 0.68. The cutoff score was 48 (sensitivity: 0.69, specificity: 0.79). The confirmatory and exploratory factor analyses did not converge. Multivariate analysis showed that the factors that significantly influenced the CSHQ-J total score were co-sleeping, supplemental sleep, and child’s age. Present illness, especially adenoids, also significantly influenced CSHQ total score.
The CSHQ-J has adequate internal consistency and is useful for screening for pediatric sleep disorders. Supplemental sleep, habit of co-sleeping, and child’s age should be considered when using the CSHQ-J as a screening tool for sleep problems in children.
Melatonin dispensing and polypharmacy rates for New Zealand children with autism or attention deficit hyperactivity disorders: A nationwide pharmacoepidemiological study
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Chronic insomnia is common in children with autism and Attention Deficit Hyperactivity Disorder (ADHD). Melatonin is often used to treat childhood insomnia. However, it may interact with other medications being used to manage other symptoms. This pharmacoepidemiological study examined the rates of general and psychotropic polypharmacy among children with autism and/or ADHD, stratified by melatonin dispensing. The impact of sociodemographic and child characteristics on such dispensing was also examined.
Linked national health and pharmaceutical administrative data for children aged 0–18 years in 2019 was utilized. Overall and melatonin dispensing stratified polypharmacy rates were calculated. Ordinal logistic regression models were employed to compare groups and adjust for confounders.
Data were acquired for 10,209 children with autism (18.5% were dispensed melatonin), 5970 with ADHD (22.3% were dispensed melatonin), 2064 with autism and ADHD (29.9% were dispensed melatonin), and 1156,296 without a diagnosis of autism or ADHD (a control group; 0.5% dispensed melatonin). Relative to controls, rates of melatonin dispensing and polypharmacy were higher in children with autism and ADHD, and highest among those with both conditions. Children dispensed melatonin experienced the greatest rates of polypharmacy, especially if they had both autism and ADHD.
Children with autism and ADHD experience significant medication burden and potentially adverse interactions between psychotropic and sleep-related medication, raising important questions regarding their clinical care.
The Nexus Narcolepsy Registry: methodology, study population characteristics, and patterns and predictors of narcolepsy diagnosis
2021, Sleep Medicine
Citation Excerpt :
A recent French study [28] found a two-fold higher rate of ADHD symptoms in children with narcolepsy compared with non-narcolepsy controls. Cataplexy was misdiagnosed as epilepsy [29] in a small percentage of registry participants, but at a greater frequency in those with pediatric (19.2%) compared with adult onset of symptoms (12.3%). Maski et al. [8] reported that symptoms are more likely to be missed if they develop before 18 years of age, and can be confused with other neurological disorders.
The real-world experience of people with narcolepsy is not well understood.
The Nexus Narcolepsy Registry (NCT02769780) is a longitudinal, web-based patient registry of self-reported data from adults with physician-diagnosed narcolepsy. Surveys were electronically distributed every 6 months; the current analysis reports registry population demographics, narcolepsy diagnosis journey, and predictors of diagnostic delays.
The registry population included in this analysis (N = 1024) was predominantly female (85%) and White (92%), with a mean age of 37.7 years. Most participants had education/training beyond high school (93%). Mean (median) reported ages at narcolepsy symptom onset, first consultation for symptoms, and narcolepsy diagnosis were 18.1 (16), 26.4 (24), and 30.1 (28) years, respectively. A majority (59%) of participants reported ≥1 misdiagnosis, and 29% reported consulting ≥5 physicians before narcolepsy diagnosis. More than half (56%) of participants’ first consultations for narcolepsy symptoms were with a general practitioner, whereas the diagnosing clinician was usually a sleep specialist (64%) or neurologist (27%). Pediatric symptom onset was associated with a longer mean interval to first consultation than adult symptom onset (10.7 and 4.6 years, respectively; P < 0.001) and a longer mean interval between first consultation and diagnosis (4.5 and 2.2 years, respectively; P < 0.001). Overall, mean (95% CI) time from symptom onset to diagnosis was 11.8 (11.1–12.5) years.
The Nexus Narcolepsy Registry data indicate that onset of narcolepsy symptoms frequently occurs in childhood or adolescence. In many individuals, the diagnostic process is long and involves multiple physicians and frequent misdiagnosis.

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ReviewInsomnia, parasomnias, and narcolepsy in children: clinical features, diagnosis, and management

Summary

Introduction

Section snippets

Insomnia

Parasomnias

Narcolepsy

Conclusions and future directions

Search strategy and selection criteria

Prim Care

Sleep Med Rev

Semin Pediatr Neurol

Child Adolesc Psychiatr Clin N Am

Sleep Med Clin

Int J Psychophysiol

Epilepsy Behav

Sleep Med Rev

Res Dev Disabil

Pediatr Neurol

Sleep Med

Sleep Med

Sleep Med Rev

Pediatr Clin North Am

Pediatr Neurol

Psychiatry Res

Res Dev Disabil

Neuroimage

Semin Pediatr Neurol

Lancet Neurol

Sleep Med Rev

Sleep Med

Psychoneuroendocrinology

Biol Psychiatry

Sleep Med

Seizure

Sleep Med

Neurotherapeutics

Sleep Med Rev

Lancet

Epilepsy Res

Actigraphic and parental reports of sleep difficulties in children with attention-deficit/hyperactivity disorder

Arch Pediatr Adolesc Med

Effects of sleep manipulation on cognitive functioning of adolescents: a systematic review

Sleep Med Rev

The role of sleep in cognition and emotion

Ann N Y Acad Sci

Prevalence and associated factors for episodic and chronic daily headache in the Colombian population

Cephalalgia

Psychological, sleep, lifestyle, and comorbid associations with headache

Headache

Associations between sleep disturbance and primary headaches: the third Nord-Trondelag Health Study

J Headache Pain

Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI

Brain Inj

Poststroke fatigue: an emerging, critical issue in stroke medicine

Int J Stroke

Impact of a behavioural sleep intervention on symptoms and sleep in children with attention deficit hyperactivity disorder, and parental mental health: randomised controlled trial

BMJ

Relationships between sleep disruptions, health and care responsibilities among mothers of school-aged children with disabilities

J Paediatr Child Health

International classification of sleep disorders

Nocturnal frontal lobe epilepsy is often misdiagnosed as sleep disorders in children: a case series

Rev Neurol

Hypersomnia in children affected by migraine without aura: a questionnaire-based case-control study

Neuropsychiatr Dis Treat

Insomnia and epilepsy: a questionnaire-based study

J Clin Sleep Med

Sleep behaviors and sleep quality in children with autism spectrum disorders

Sleep

The daily lives of adolescents with an autism spectrum disorder: discretionary time use and activity partners

Autism

Media use and sleep among boys with autism spectrum disorder, ADHD, or typical development

Pediatrics

Associations of child insomnia, sleep movement, and their persistence with mental health symptoms in childhood and adolescence

Sleep

Longitudinal course and outcome of chronic insomnia in Hong Kong Chinese children: a 5-year follow-up study of a community-based cohort

Sleep

Review
Insomnia, parasomnias, and narcolepsy in children: clinical features, diagnosis, and management