Evidence-based assessment/Rx4DxTx of Sleep

= Resources for the Assessment and Treatment of Sleep Problems = Sleep problems are relatively common throughout the lifespan, especially during childhood, but can occasionally progress into diagnosable disorder with long-lasting impacts on physical and cognitive functioning. Unfortunately, this disorder is commonly misdiagnosed in children, delaying treatment of it and its co-occurring disorders, which may include endocrinological disorders, anxiety disorder, and mood disorders. Furthermore, there are no ‘gold standard’ treatment options for childhood narcolepsy, and at this time no pharmacological treatments are FDA-approved for treating childhood narcolepsy. This page serves to provide an overview of childhood narcolepsy, its common co-occurring disorders, available treatment options, and additional resources for individuals struggling with narcolepsy.

= Diagnostic Criteria, Prevalence, and Comorbidity =

Current Diagnostic Criteria
Adult and pediatric sleep disorders are commonly diagnosed using either the Diagnostic and Statistical Manual of Mental Disorders or the International Classification of Sleep Disorders. The most recent editions of these publications, the DSM-5 and ICSD-3, were published in 2013 and 2014, respectively, and reflect the most current diagnostic criteria for many disorders. Additionally, the International Statistical Classification of Diseases, or ICD-10, is frequently used to code DSM-5 and ICSD-3 diagnoses for medical record use and insurance/billing practices.

The DSM-5 includes 10 disorder or disorder groups: insomnia disorder, hypersomnolence disorder (hypersomnia), narcolepsy, breathing-related sleep disorders, circadian rhythm sleep-wake disorders, non–rapid eye movement (NREM) sleep arousal disorders, nightmare disorder, rapid eye movement (REM) sleep behavior disorder, restless legs syndrome, and substance/medication-induced sleep disorder.

Narcolepsy
Current DSM-5 criteria require that the individual display excessive daytime sleepiness in conjunction with at least one of the following symptoms: cataplexy, cerebrospinal orexin deficiency, REM sleep latency of ≤ 15 minutes when using nocturnal polysomnography, or REM sleep latency of ≤ 8 minutes with at least 2 sleep-onset REM-sleep periods when using multiple sleep latency testing. Current ICSD-3 criteria requires that the individual display excessive daytime sleepiness in conjunction with DSM-5 REM sleep latency criteria; cataplexy and cerebrospinal orexin deficiency is indicated only for narcolepsy type 1. Clinical information for the ICD-10 includes excessive daytime sleepiness and sleepiness that may be accompanied by cataplexy, sleep paralysis, and hypnagogic, or pre-sleep, hallucinations.

Insomnia
Insomnia is defined as difficulty with sleep initiation, maintenance, consolidation, and or quality of sleep that in some form results in daytime impairment.

A. A predominant complaint of dissatisfaction with sleep quantity or quality, associated with one (or more) of the following symptoms: B. The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning.
 * 1) Difficulty initiating sleep. (In children, this may manifest as difficulty initiating sleep without caregiver intervention.)
 * 2) Difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings. (In children, this may manifest as difficulty returning to sleep without caregiver intervention.)

C. Sleep difficulty occurs at least 3 nights per week.

D. Sleep difficulty is present for at least 3 months.

E. Sleep difficulty occurs despite adequate opportunity for sleep.

F. The insomnia is not better explained by and does not occur exclusively during the course of another sleep-wake disorder (e.g., narcolepsy, a breathing-related sleep disorder, a circadian rhythm sleep-wake disorder, a parasomnia).

G. The insomnia is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication).

H. Coexisting mental disorders and medical conditions do not adequately explain the predominant complaint of insomnia.

Specifiers for comorbid disorders include:
 * With nonsleep disorder mental comorbidity, including substance use disorders
 * With other medical comorbidity
 * With other sleep disorder

Specifiers for symptom duration include:
 * Episodic: Symptoms last at least 1 month but less than 3 months.
 * Persistent: Symptoms last 3 months or longer.
 * Recurrent: Two (or more) episodes within the space of 1 year.
 * Acute and short-term insomnia (i.e., symptoms lasting < 3 months but otherwise meeting all criteria with regard to frequency, intensity, distress, and/or impairment) should be coded as another specified insomnia disorder.

Hypersomnolence disorder
Hypersomnolence disorder refers to either the excessive daytime sleepiness (EDS) or the excessive time spent sleeping and is accompanied by significant distress or impairment.

A. Self-reported excessive sleepiness (hypersomnolence) despite a main sleep period lasting at least 7 hours, with at least one of the following symptoms: B. The hypersomnolence occurs at least three times per week, for at least 3 months.
 * 1) Recurrent periods of sleep or lapses into sleep within the same day.
 * 2) A prolonged main sleep episode of more than 9 hours per day that is nonrestorative (i.e., unrefreshing).
 * 3) Difficulty being fully awake after abrupt awakening.

C. The hypersomnolence is accompanied by significant distress or impairment in cognitive, social, occupational, or other important areas of functioning.

D. The hypersomnolence is not better explained by and does not occur exclusively during the course of another sleep disorder (e.g., narcolepsy, breathing-related sleep disorder, circadian rhythm sleep-wake disorder, or a parasomnia).

E. The hypersomnolence is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication).

F. Coexisting mental and medical disorders do not adequately explain the predominant complaint of hypersomnolence.

Specifiers for comorbid disorders include:
 * With mental disorder, including substance use disorders
 * With medical condition
 * With another sleep disorder

Specifiers for symptom duration include:
 * Acute: Duration of less than 1 month.
 * Subacute: Duration of 1–3 months.
 * Persistent: Duration of more than 3 months.

Specifiers for symptom severity include:
 * Mild: Difficulty maintaining daytime alertness 1–2 days/week.
 * Moderate: Difficulty maintaining daytime alertness 3–4 days/week.
 * Severe: Difficulty maintaining daytime alertness 5–7 days/week.

Limitations of the current criteria
Although these three diagnostic systems are widely used within the United States (DSM-5) and internationally (ICSD-3 and ICD-10), a fair amount of criticisms have been raised for each. Both the ICSD-3 and ICD-10 decline to discriminate between pediatric and adult sleep disorders, despite the fact that symptom presentation in children and adults markedly differ. Furthermore, the DSM-5 does not distinguish between narcolepsy type 1 and type 2, and has been heavily criticized in the past for its lack of attention to disorders of infancy and childhood.

Despite these criticisms, there tends to be a general consensus on the clinical presentation of narcolepsy in children by professionals. Four symptoms are typically seen when considering a patient for the diagnosis of narcolepsy type 1: excessive sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. In contrast, narcolepsy type 2 presents without cataplexy. It has also been well-understood, by both medical and psychiatric practitioners, that childhood sleep disturbances, including narcolepsy, are typically the result of disturbances in the child’s central nervous system and sleep-wake mechanisms, rather than byproducts of medications or secondary medical or mental disorders.

Prevalence
Sleep disorders are relatively common throughout childhood, and affect about 30% to 40% of children at some point in their development. However, less than 1% of children meet the diagnostic criteria for narcolepsy. The exact figure is not known, although narcolepsy prevalence in the adult population is presumed to affect 0.02% to 0.05% of individuals in Western countries. This low prevalence rate may be due to underdiagnosis or misdiagnosis of the disorder.

Several factors may influence the prevalence of childhood narcolepsy. Male children may be more likely to receive a diagnosis than females across all age groups, although this disorder affects both genders at equal rates. Children from low-income families may be more likely to receive a diagnosis of a sleep disorder. Additionally, age at diagnosis and ethnicity may interact: although childhood narcolepsy in African American children presents with earlier symptom onset and higher symptom severity, these children typically remain under-diagnosed until reaching school age.

Common Comorbidities
Both medical and psychiatric co-morbid disorders have been implicated in childhood narcolepsy. Many times, the co-occurrences of these disorders, especially psychiatric disorders, hinder the initial diagnosis of narcolepsy due to similarities in their presentations and symptom overlaps. Two of most common co-morbidities for narcolepsy include endocrinological disorders and anxiety and mood disorders.

Endocrinological Disorders
Precocious puberty and obesity are two well-known endocrinological disorders that co-occur with childhood narcolepsy. Although the exact mechanisms linking these disorders to narcolepsy, and to each other, are unknown, several possible mechanisms have been identified for each. Due to their prevalence and the significant, long-term effects that each disorder may have on the child’s physical and mental health, it is imperative that further research be done to determine these mechanisms and possible avenues for treatment.

Precocious puberty, or puberty that occurs prior to age 8-9 years in female and male children, respectively, is estimated to occur in about 17% of children with narcolepsy; about 41% may display isolated signs of early pubertal development, including breast or pubic hair development. One potential mechanism tying together precocious puberty and childhood narcolepsy is a “more global hypothalamic dysfunction,” as this co-morbidity is more likely to present when narcolepsy is diagnosed prior to puberty.

Obesity is also a common co-occurring endocrinological disorder, affecting anywhere from 25% to 74% of all children diagnosed with narcolepsy type 1. Current research has focused on orexin deficiency as the primary link between obesity and childhood narcolepsy. Orexin deficiency is a hallmark characteristic of narcolepsy type 1, and serves to regulate appetite and satiety alongside the sleep/wake cycle in humans. Because weight gain seems to occur close to when narcolepsy symptoms start, this mechanism seems especially likely; as levels of this neuropeptide begin to decrease, weight and sleep problems begin to appear together.

Anxiety and Mood Disorders
Anxiety and depressed mood are the two most common psychiatric symptoms reported in children with narcolepsy. About one-fourth to one-third of children with narcolepsy report experiencing depressive symptoms, and about one-third of children are able to be diagnosed with an anxiety disorder, typically generalized anxiety disorder or social phobia. Unfortunately, due to the significant overlap between symptoms of depression and symptoms of narcolepsy, it is difficult to assess the precise mechanisms by which depression functions in children with narcolepsy. However, one current hypothesis is that the orexin receptors in the brain affect mood modulation, although results are controversial. Concerning anxiety, it is likely that “altered [orexinergic] transmission” in the brains of children with narcolepsy plays a “direct role”.

Prognosis or Developmental Course
For many children, sleep problems seem to resolve over time, and generally are limited to the pre-grade school ages. However, this is not the case for individuals with narcolepsy, which typically has life-long implications for those afflicted. Unfortunately, narcolepsy is often misdiagnosed or underdiagnosed in childhood, resulting in delayed opportunities for treatment. As a result of this, afflicted children may continue to suffer from problems with executive and/or cognitive functioning for years until the correct diagnosis is made. It is highly likely that individuals diagnosed with childhood narcolepsy will continue to have sleep problems throughout their life, with this diagnosis eventually transitioning into the adult version of narcolepsy.

There is a caveat to this, however. Although narcolepsy has been presumed to have a stable course due to its typical continuance from childhood to adulthood, it is highly likely that the childhood version of this disorder does not follow a stable course. The disorder seems to present with an “abrupt onset” in children, and later symptom improvement may be shown via a decrease in “hypotonic phenomena,” especially when the disorder presents with cataplexy. As such, narcolepsy in children can often be “timed to a particular day” and may not arise out of pre-existing sleeping problems, while adult narcolepsy tends to follow the path started in childhood.

This life-long disorder has several important implications for the individuals it affects. Without treatment, symptoms typically persist and cause problems in multiple domains of daily life. As mentioned previously, children with narcolepsy may have problems in executive and/or cognitive functioning, including problems with memory and attention. These deficits in functioning are likely to continue into adulthood; however, they will do so with more lasting, damaging consequences. Adults with narcolepsy may face problems at work; about 95% of adults with narcolepsy report falling asleep during working hours, and 11% report being forced to take disability leave. On the more fatal side, individuals with narcolepsy also have a high prevalence of falling asleep while driving and/or having “near motor accidents” while driving.

= Evidence Based Assessment =

Screening and Non-Diagnostic Assessment
Prior to referring a child for diagnostic testing for narcolepsy, many providers will provide families with a combination of testing procedures to determine whether or not a sleep disorder is likely present. A physical examination and clinical history are often performed first, and are used to determine whether poor sleep hygiene, medication usage, or underlying physical or psychiatric disorders may be contributing to the child’s abnormal sleep pattern. Following this, other non-diagnostic measures of assessment, such as sleepiness scales, are used to obtain a clearer picture of the child’s presenting sleep problems.

Self-report sleep questionnaires such as the Epworth Sleepiness Scale (ESS), The National Sleep Foundation’s Sleepiness Test, the Insomnia Severity Index™, the STOP BANG Screening Questionnaire, and the Pediatric Daytime Sleepiness Scale (PDSS) are often considered methods of assessment for individuals presenting with symptoms of sleep disorders. At this time, the ESS has not been validated for use in children and adolescents, but a modified version of it has been used to provide clinicians with information about the child’s sleep habits. The PDSS, on the other hand, has been validated for use with children. These subjective tests are inexpensive, quick to administer, and well known by somnologists and other medical professionals. These factors make sleepiness scales an excellent choice for screening and assessing sleep in the pediatric population. In addition, keeping a sleep diary for two to three weeks can provide valuable information about sleep patterns and practices (PDF available).

Finally, with cases in which the cause of inadequate sleep is unclear, sleep studies are used. These studies are done to distinguish between insomnia disorder and differing types of sleep disorders such as sleep apnea, restless leg syndrome, narcolepsy, etc. This test helps to identify sleep issues that may not be able to be identified with a normal office visit. These tests are done overnight and monitor heart rate, breathing rates, snoring, and body movements during sleep.

Diagnostic Assessment


As a requirement for diagnosis, any individual who suspects narcolepsy must have the diagnosis confirmed via the multiple sleep latency test (MSLT) and polysomnography (PSG). These tests are regularly performed in laboratory settings to exclude any other sleep disorder the child presents with, as well as quantify the child’s sleep habits, such as the sleep-wake transition. Although the DSM criteria for a “mean sleep latency of 8 min or less” may be satisfied via the MSLT, PSG is still required in order to rule out any underlying conditions that may be causing the sleep disorder. However, due to their cost and time commitment, these methods are typically reserved for when other methods of assessment, such as the PDSS, indicate that a sleep disorder may be present.

= Evidence-Based Treatment = Although many sleeping difficulties in infants and toddlers seem to disappear as the child grows older, many parents choose to seek treatment for their child’s disorder. A wide range of treatments for childhood narcolepsy are available, including behavioral and pharmacologic interventions. However, it is important to note that no evidence-based treatment guidelines have been developed for treating children with narcolepsy, which may limit the ability of parents to gain access to treatment resources.

Behavioral Interventions
Behavioral interventions are often considered the starting line for treating childhood narcolepsy, due in part to the lack of available treatment options for patients of this age; currently, no pharmacological treatment options have been approved by the FDA for use in children. However, it is important to note that behavioral interventions are only “partially effective” in some cases of childhood narcolepsy, making pharmacologic interventions a necessity for these children. In spite of this, behavioral treatment options are typically implemented in conjunction with drug therapy for these cases.

Generally, improved sleep hygiene and planned daytime naps are recommended for children with narcolepsy in order to manage their daytime sleepiness. Regular exercise and physical activity during the daytime have also been shown to increase daytime alertness in children with narcolepsy. However, these naps, which are typically 15-20 minutes in duration, are considered the most beneficial for children with narcolepsy, and may help decrease episodes of “unscheduled” sleep during the day. These naps may also help with the “memory consolidation process,” which is usually substandard in untreated narcolepsy patients.

Pharmacologic Interventions


Currently, no pharmacologic interventions have been FDA-approved for use in treating narcolepsy in children under the age of 16 years. However, children with narcolepsy are routinely prescribed medication to treat their sleep-related symptoms; these drugs include methylphenidate and SSRIs. Modafinil, a wakefulness-promoting agent, may also be safe for use in children, but is not approved for use in children for any disorder by the FDA.

Methylphenidate is generally considered to be “the second line treatment” for childhood narcolepsy, following modafinil. This drug is considered to be a central nervous system stimulant; as is the case of other stimulant medications, methylphenidate works to inhibit dopamine reuptake. This drug is especially useful when the child presents with co-morbid attention-deficit/hyperactivity disorder (ADHD); stimulants, which are the recommended pharmacological treatment for individuals with ADHD, have “wake-promoting properties” that are useful in treating the daytime sleepiness associated with narcolepsy.

A second pharmacological treatment option are selective serotonin reuptake inhibitors, or SSRIs. Although this class of medication is not labelled for use in treating narcolepsy, it does have an “off-label use” of treating cataplexy, and the SSRI fluoxetine, or Prozac, seems to be highly efficacious in doing so. However, it is important to note that prescription of SSRIs for use in treating narcolepsy-related cataplexy is typically reserved for children who have been referred to a specialized sleep center ; this is not a typical pharmacological treatment option for children with narcolepsy.

= Diet and Narcolepsy =

Diet as a Consequence of Narcolepsy
As mentioned previously, narcolepsy – narcolepsy type 1 in particular – is hallmarked by a deficiency in the neuropeptide orexin, which also functions to regulate the body’s appetite and satiety. Many children diagnosed with narcolepsy are also found to be overweight; obese individuals with narcolepsy have been found to have reduced leptin levels. Leptin, which functions to suppress appetite levels, is impaired in these individuals, resulting in food cravings and increased caloric consumption, which in turn causes weight gain. Interestingly, one study by Schuld et al. hypothesized that reduced orexin levels could contribute to reduced leptin production. Thus, this orexin-leptin link may serve as the mechanism by which obesity and weight gain occur in individuals with narcolepsy.

Orexin is also presumed to influence energy expenditure and metabolic activity in humans; levels of orexin and energy expenditure appear to be linked, as individuals with narcolepsy tend to have lower metabolic rates. Although leptin levels in individuals with narcolepsy may be lowered as a result of decreased orexin levels, lowered basal metabolic rates (BMR) in these individuals may have a larger impact on any potential weight gain. Although many adult individuals with narcolepsy report consuming less calories than controls, their weight gain continues; this suggests that their weight gain may not simply be a result of increased caloric intake resulting from impaired leptin levels.

Diet as a Treatment Approach
Interestingly, diet modification in individuals with narcolepsy, including children, can serve to reduce symptom severity. Although there are “insufficient studies to support any single dietary approach” for combating narcolepsy, many individuals with this disorder report altered levels of alertness following meals. In general, meal consumption, as well as carbohydrate or glucose consumption, tend to increase levels of daytime sleepiness, and many adult narcolepsy patients have found relief from their symptoms when following low-carbohydrate, ketogenic diets.

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