Clinical manifestations

Presentation and course

Idiopathic insomnia is a chronic and serious inability to initiate and maintain sleep that can often be observed as early as the first few weeks of life. Sleep latency is long. Sleep is riddled with many awakenings and may show sleep-stage abnormalities, such as REM sleep with few eye movements or ill-formed sleep spindles during stage II sleep. Paradoxically, idiopathic insomniacs may show fewer body movements per unit of sleep than normal sleepers do. As the presumed underlying neurologic abnormality may vary from mild to severe, the range of insomnia encountered in this condition may also vary from mild (essentially a light sleeper) to severe and incapacitating. Daytime features typically include decreased attention and vigilance, low levels of energy and concentration, and a deterioration of mood commonly described as grim and subdued, rather than obviously depressed or anxious. In mild or moderate idiopathic insomnia, psychological functioning is remarkably intact. In severe cases, daytime functioning may be severely disrupted, and affected patients may be unable to hold a job. During childhood and adolescence, idiopathic insomnia is often associated with soft neurologic signs (eg, as dyslexia or hyperactivity). Many cases show diffuse nonspecific abnormalities on the EEG (03).

The broad diagnostic criteria according to the third edition of the International Classification of Sleep Disorders are as follows:

Criteria A through F should be met:

(A) The patient experiences repeated problems with one or more of the following:
	• sleep initiation
	• maintenance
	• waking up earlier
(B) The patient experiences one or more of the following due to nighttime sleep difficulty:
	• fatigue/malaise
	• attention, concentration, or memory impairment
	• impaired social, family, occupational, or academic performance
	• mood disturbance/irritability
	• daytime sleepiness
	• behavioral problems
	• reduced motivation/energy/initiative
	• proneness for errors/accidents
	• dissatisfaction with sleep
(C) The sleep complaint cannot be explained by inadequate opportunity/circumstances for sleep
(D) The sleep disturbance and associated daytime symptoms occur at least 3x/week
(E) The course is chronic with symptoms longer than 3 months (typically onset in infancy or childhood, the lack of an identifiable etiology, and a persistent course without prolonged episodes of remission)
(F) The sleep difficulty is not explained by another sleep disorder
(02)

Prognosis and complications

The suspected underlying neurologic abnormality in idiopathic insomnia is presumably life-long. Complications often involve attempts to treat the condition either by self-medication (such as in alcohol) or by prescriptions (high doses of benzodiazepines or barbiturates). Other complications involve excessive use of stimulants to promote wakefulness (03).

Clinical vignette

A 36-year-old, right-handed man presented to the sleep center clinic for a first-time evaluation concerning his longstanding inability to fall asleep or stay asleep. He stated that as far back as he could remember, even as a child in grade school, he had trouble falling asleep. His mother had told him that as a newborn he slept much less than his siblings. He went to bed around 10 PM and tossed and turned for an hour or so before he fell asleep. The patient stated that his sleep was very light, and he tended to wake up once or twice in the middle of the night and stay awake for an undetermined amount of time. Whenever he was unable to fall asleep, he became restless, constantly watching the digital clock on his bedside table or, rarely, getting out of bed to watch television. He went to bed every night anticipating not falling asleep. The patient routinely received only 4 to 5 hours of sleep a night and did not feel refreshed in the morning. Rarely, after a few bad nights with little sleep, he could sleep for one night up to 7 hours, after which he would awaken refreshed. He denied feeling subjectively sleepy during the day and never fell asleep in inappropriate situations. The patient reported the inability to nap and stated that no matter where he attempted to sleep (at home or away), he had difficulty falling and staying asleep. He denied symptoms suggestive of restless legs syndrome, obstructive sleep apnea, or narcolepsy. In the past, treatments with over-the-counter sleeping aids and zaleplon were not effective. Although trazodone helped him sleep, it produced an intolerable hangover effect. He did not drink excessive caffeinated or alcoholic beverages, but he did chew tobacco throughout the day into the late evening. He had no other complaints.

Family history was significant for a similar type of insomnia in his grandmother and mother, but not in his father or siblings.

Physical examination was normal.

All night polysomnogram revealed increased sleep latency and poor sleep efficiency at 48% due to prolonged unexplained awakenings. An actigraph, worn for a week, confirmed his subjective reports of 4 to 5 hours of fragmented sleep at night.

With strict compliance with sleep hygiene regulations and 1 mg of estazolam at bedtime, he was able to improve his sleep efficiency to a considerable degree but not to resolve his insomnia entirely.

Biological basis

Etiology and pathogenesis

Idiopathic insomnia may be due to some dysfunction in the sleep-wake center in the brain. It may represent either hyperactivity in the wake center or hypoactivity in the sleep center (24). Due to early onset, lifelong, and stable course over time, it is presumed to be genetically determined or congenital due to anomaly in central nervous system sleep inducing or arousal system or both. No specific genetic loci or neuropathology have been identified.

Central sleep-wake mechanisms include the basic sleep onset systems (which involve nuclei in the preoptic area of the hypothalamus, the brainstem raphe nuclei, and the medial forebrain area) and the basic wake-promoting systems of the ascending reticular activating system (which include the perifornical lateral and tuberomammillary nuclei of the hypothalamus and the locus coeruleus and pedunculopontine/lateral dorsal tegmental nuclear complex of the brainstem) (03; 24; 13). Whether a person is awake or asleep depends on the neurophysiological balance between the reticular activating system and the sleep-inducing maintenance systems (16). Idiopathic insomnia presumably is due to a shift of this balance toward arousal. Patients coming to clinical attention may simply represent the wakeful end of the normal spectrum of sleep. Other patients may have a neurochemical, neuroanatomical, or neurophysiological dysfunction or lesions interfering with normal sleep (16). Either hyperactivity in the arousal system or hypoactivity in the sleep system may cause idiopathic insomnia (24). Empirically, idiopathic insomniacs are hyperaroused during wakefulness on questionnaires, auditory evoked potentials, and EEG. Physiologic hyperarousal in many systems (cardiac, core temperature, corticosteroids, etc.) is also frequently found in other types of insomnia, including idiopathic insomnia (08). High-density EEG of insomnia patients (based on DSM-V criteria) shows broad beta band activity during wakefulness that, combined with prior reports of this activity during sleep, suggests a state of persistent hyperarousal in patients with insomnia (11). Daytime symptom patterns characterized by mood disturbance and low sleepiness also support an internal etiologic component to idiopathic insomnia, in contrast to learned forms of insomnia (23). Although insomniac animals have been created with lesions (eg, in the medial forebrain), no direct human evidence for structural neuropathology exists for such a lesion in idiopathic insomnia. A study investigating the phase angle between self-selected bedtime and the dim light melatonin onset among patients with insomnia (60 patients with primary insomnia) without obvious circadian phase disorders demonstrated that a substantial proportion of patients (10% to 22%) initiate sleep at too early a circadian phase, leading to the complaints of long sleep latency and, hence, implicating circadian contribution (15).

Another resting state functional magnetic resonance imaging study aimed to assess whether the brain activity of primary insomnia patients varied according to age and gender and whether these factors could affect the distribution of hyper-arousal brain regions (31). The results suggested that the gender-related difference of brain activity mainly existed in superior temporal gyrus, cerebellum posterior lobe, and middle frontal gyrus; the age-related difference mainly existed in cerebellum anterior lobe, superior temporal gyrus, brainstem, para hippocampal gyrus, anterior cingulate, and cingulate gyrus. Furthermore, the gender factor did not influence the distribution of the altered regions, whereas the age factor could affect the distribution. The age-related and gender-related difference of brain activity in primary insomnia patients were found to be associated with emotional and cognitive function, which was suggested to be the possible cause of different insomnia incidence, sleep experience, and efficacy of intervention in primary insomnia patients with different gender and age.

Epidemiology

A predisposition toward poor sleep exists in many insomniacs. However, in its pure form as a serious insomnia beginning in early childhood in the absence of any medical or psychiatric disorder, idiopathic insomnia is rare (less than 5% of all insomniacs) (10), with an estimated prevalence of approximately 0.7% for adolescents and 1.0% for very young adults (01). Evidence shows that insomnia is often familial, but is not specific to idiopathic insomnia (01). A study showed prevalence of idiopathic insomnia in women of 0.6% and in men of 0.5%, respectively (21).

Prevention

Difficult birth and prematurity are likely risk factors (03).

Differential diagnosis

Not all insomnia in childhood is idiopathic or childhood-onset insomnia. In children, insomnia is most frequently caused by environmental, behavioral, and psychological factors (07). Unlike the fairly common behavioral insomnia of childhood, idiopathic insomnia has no identifiable precipitating or perpetuating factors.

Although the complaints of insomnia are seen in up to 41% of children (05), idiopathic insomnia in its pure form is rarely seen. This is due to the fact that a lifetime of serious, chronic insomnia typically results in complications such as poor sleep hygiene, alcohol or drug abuse, or maladaptive associations aggravating the insomnia. Idiopathic insomnia is diagnosed when insomnia predates the development of these complications and when the imbalance of the sleep-wake system plays a paramount role (03).

Childhood-onset restless legs syndrome is differentiated from idiopathic insomnia by the dysesthesias associated with restless legs syndrome. This irresistible urge to move the limbs tends to occur primarily in the evening or at night, typically getting better in the early morning hours. The associated insomnia, therefore, is mainly sleep onset insomnia (17).

Idiopathic insomnia is differentiated from short sleeping by the accompanying fatigue and daytime performance impairment. Short sleepers feel and function well during waking hours and do not routinely have difficulties falling asleep, nor suffer from repeated awakenings and poor-quality sleep.

Idiopathic insomnia can be difficult to distinguish from psychophysiological insomnia, which is also accompanied by an innate predisposition toward poor sleep. In idiopathic insomnia, the presumed sleep-wake imbalance is enough to cause the insomnia by itself; in psychophysiological insomnia, the inherent sleep-wake disturbance is weaker, needing the addition of the stress of maladaptive conditioning to trigger the insomnia, and it typically begins during adulthood (01).

Psychologically, most patients with idiopathic insomnia are remarkably healthy, given their chronic lack of sleep. Also, the insomnia is relentless and almost unvaried through both poor and good periods of emotional adaptation (03).

Diagnostic workup

Idiopathic insomnia is diagnosed after exclusion, where a thorough psychiatric interview reveals no psychological reason severe enough to explain the insomnia. Specifically, no psychological distress explains the early onset. A general medical evaluation reveals no causative medical factors such as allergies, pain, or thyroid abnormalities that might have been operative since early childhood. A polysomnogram, if performed, reveals severely impaired sleep, and sleep stages may be difficult to score according to accepted criteria. However, because idiopathic insomniacs often show a "reverse first night effect," more than one night in the sleep laboratory may be necessary. Another way of bypassing the "reverse first night effect" is to use actigraphy. Actigraphy is an invaluable tool in evaluating insomnia, especially in patients with unusual complaints (such as "I don't sleep at all"). It supplements subjective sleep logs. An actigraph is a small wrist mounted device that records the activity plotted against time, usually 1 or 2 weeks at a time. A close correlation exists between the rest activity recorded by the actigraph and the wake sleep pattern as determined by the polysomnogram (20). Nonspecific EEG abnormalities may be seen but are highly idiosyncratic and not diagnostic of idiopathic insomnia. Overall, polysomnograms offer little diagnostic value in idiopathic insomnia.

Management

Behavioral intervention. Impeccable sleep hygiene is essential, including regular, somewhat curtailed sleep hours, excellent relaxation skills, and active waking lifestyles (16). Cognitive behavioral therapy for insomnia, an approach often cited by patients as preferable to pharmacotherapy and more effective in relapse prevention, can be helpful in addressing dysfunctional beliefs about sleep and, alternatively or adjunctively, acceptance-based psychotherapeutic approaches may be more beneficial to patients with idiopathic insomnia (14).

Pharmacological intervention. Benzodiazepines and zolpidem are effective as hypnotics (24). Long-term use of drugs has raised the question of tolerance and dependence (24). Some studies, however, have shown that the risk for tolerance, dependence, and addiction is minimal in patients using long-term benzodiazepines for insomnia or for other sleep disorders (20; 22; 12). Melatonin has been shown to be helpful in treating chronic insomnia in school-aged children (26; 29) and in improving health status and advancing the sleep-wake rhythm in children with chronic insomnia (27; 28; 09). It is recommended to use melatonin in doses of 0.05 mg/kg 1 to 2 hours before dim light melatonin onset and before bedtime (29). A metaanalysis of 13 studies showed that short-term use of ramelteon (melatonin receptor 1 and 2 agonist) was associated with some improvement in sleep parameters such as subjective sleep latency and sleep quality, but overall clinical impact was modest (18).

Another review of four randomized trials demonstrated that suvorexant, which is a dual orexin receptor antagonist, was associated with significant improvements in subjective time to sleep onset, subjective total sleep time, and subjective quality of sleep (19).

Alternative medical strategies. A patient-assessor-blinded, randomized, sham-controlled acupuncture trial suggests that acupuncture can improve clinical symptoms (30). Also, the combination of multi-acupoints may enhance clinical efficacy further. The study showed improvement in the clinical outcomes of PSQI (Pittsburg sleep quality index) and TST (total sleep time) on polysomnogram.

Other strategies such as transcranial magnetic stimulation have also been explored by scientists to demonstrate some effect but have not been established as standard treatment option yet (04).