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Sleep Disorder


Sleep Disorder

Article Author:
Bibek Karna
Article Editor:
Vikas Gupta
Updated:
10/5/2020 10:04:35 AM
For CME on this topic:
Sleep Disorder CME
PubMed Link:
Sleep Disorder

Introduction

Sleep is a complex biological process. It is a reversible state of unconsciousness in which there are reduced metabolism and motor activity. There are two different kinds of sleep: rapid eye movement (REM) sleep and non-REM (NREM) sleep. Most young adults first enter NREM sleep from the drowsy state. NREM sleep (dreamless sleep) is further divided into four stages (1-4). The first stage N1, is the lightest stage, characterized by a transition from wakefulness to sleep. Then, the second stage N2 follows, which comprises the largest percentage of total sleep. Benzodiazepines work by increasing stage N2 sleep. Then, the adult enters into deep stages of sleep N3 and N4. After about 70 to 80 minutes of a deep sleep, sleep lightens, and a REM period follows, which is usually associated with active dreaming and bodily movements. This cycle is repeated at intervals of about 90 minutes. Towards morning, there is less stage 3 & 4 sleep and more REM sleep.

Sleep disorders are a group of conditions that disturb the normal sleep patterns of a person. Sleep disorders are one of the most common clinical problems encountered. Inadequate or non-restorative sleep can interfere with normal physical, mental, social, and emotional functioning. Sleep disorders can affect overall health, safety, and quality of life. There is a study showing significant impairment in quality of life in patients with insomnia.[1] 

There are many different types of sleep disorders. They can be broadly categorized into primary and secondary. Primary sleep disorders result from endogenous disturbances, whereas secondary sleep disorders are the result of various medical and psychiatric conditions such as depression, thyroid problems, and stroke. 

Primary sleep disorders can be further divided into parasomnias and dyssomnias:

  • Parasomnias are unusual experiences or behaviors during sleep. Sleep terror disorder, sleepwalking (occurring during stage 4 sleep), and nightmare disorder (occurring during REM sleep) are some of the parasomnias.
  • Dyssomnias are the abnormalities in the amount, quality, or timing of sleep. Primary insomnia and hypersomnia, narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder are some of the dyssomnias. When a person suffers from difficulty falling asleep and/or staying asleep, it is referred to as primary insomnia.

Sleep disorders are common in both adults and children. However, children with sleep disorders may present with different symptoms than adults. Children with sleep problems may exhibit motor overactivity, inattentiveness, irritability, or oppositional behavior rather than overt sleepiness.[2]

Etiology

There are different causes for different sleep disorders. Sometimes the cause is unknown. The major causes may be broadly divided into medical conditions, psychological conditions, and other factors. 

Medical conditions:

  • Cardiac: heart failure (patient may awaken during the night feeling short of breath)
  • Neurologic: stroke, central sleep apnea, hypnic jerk, restless leg syndrome, headache, cerebral degenerative disorders[3]
  • Endocrine: hyperthyroidism, pregnancy, menopause, diabetes mellitus, vitamin D deficiency[4]
  • Pulmonary: obstructive sleep apnea, asthma, chronic obstructive pulmonary disease
  • Gastrointestinal: GERD
  • Musculoskeletal: pain from arthritis, fibromyalgia, or any chronic pain[5]

Psychiatric conditions:

  • Depression: Insomnia is very common among depressed patients. These patients have difficulty falling asleep, nocturnal awakenings, decreased slow-wave sleep, reduced REM latency, and increased REM intensity. Some patients with atypical depression may exhibit hypersomnia.
  • Anxiety: Anxiety disorders predispose to insomnia. Patients with anxiety have trouble falling asleep, staying asleep, and not feeling rested after sleep.
  • Phobias and panic attacks: Sleep-related panic attacks do not occur during dreaming, but rather in stage N2 (light sleep) and stage N3 (deep sleep). Post-traumatic stress disorder (PTSD) can produce vivid and terrifying nightmares.
  • Psychotropic medications: Anti-depressants may interfere with normal REM sleep patterns. Benzodiazepines may produce rebound insomnia, especially in the elderly.

Other factors causing sleep problems:

  • Environmental problems: Shift work may disturb the sleep cycle, as may jet lag. Likewise, loud environmental noise, high temperature, or frequent environmental intrusions may cause sleep deprivation.
  • Medications: Various medications cause sleep problems. Corticosteroids cause daytime jitters, insomnia, decreased REM sleep. Diuretics cause increased urination during sleep and painful calf cramps during sleep. Similarly, the use of substances such as caffeine, opioids, alcohol, or their withdrawal may result in insomnia.
  • Aging: Almost half of the elderly population have sleeping problems. The sleep changes in the elderly include difficulty in falling asleep i.e., increased sleep latency, multiple awakenings during the night, and early morning awakening. The elderly people spend very little time in deep, dreamless sleep.
  • Childhood trauma: Some traumatic childhood experiences (family conflicts or sexual assault) increases the risk of sleep disorders in adulthood like narcolepsy, insomnia, and sleep apnea. 

Epidemiology

Parasomnias such as sleepwalking, confusional arousals, sleep terrors, sleep talking, and nightmares are very common during childhood. Obstructive sleep apnea occurs in about 1% to 5% of children.[6] As people age, the incidence of sleep problems also rise. Approximately 50% of older adults have sleep problems.[7] 

Other comorbid conditions of old age, such as diabetes, hypertension, dementia, and anxiety, are all associated with sleep disturbances. Restless leg syndrome and periodic limb movement disorder are also more prevalent in the elderly.[8] Primary insomnia is more common in women over age 50 than their male counterparts.[7]

History and Physical

History

The symptoms of sleep disorders depend on the specific disorder.

Insomnia may present as difficulty falling asleep and/or staying asleep. Patients report taking thirty minutes or more to fall asleep (for those with sleep initiation difficulties) or spending thirty minutes or more awake during the night (for those with sleep maintenance difficulties). The diagnosis of insomnia also requires the presence of compromised daytime function, which includes one or more symptoms like fatigue, daytime sleepiness, poor attention, increased accidents, aggression, reduced motivation, or energy. Insomnia can often be a persistent or recurrent condition with exacerbations connected to medical, psychiatric, and psychosocial stressors.

Hypersomnia is generally seen in adolescents or young adults. The patients with hypersomnia complain of disabling excessive day time sleepiness. They find it difficult to maintain alertness during the major waking hours of the day with sleep occurring unintentionally or at inappropriate times that interferes with the daily routine.

Narcolepsy is a chronic neurological disorder caused due to the brain's inability to control sleep and wakefulness. It is associated with a low cerebrospinal fluid level of orexin-A/hypocretin-1. Patients with narcolepsy complain of excessive chronic daytime sleepiness with varying amount of cataplexy (transient loss of muscle tone in response to intense emotion such as laughter), hallucinations while falling asleep (hypnagogic hallucinations) or hallucinations while waking (hypnopompic hallucinations), and sleep paralysis (inability to move immediately after awakening).

Obstructive sleep apnea (OSA) is a disorder characterized by obstructive apneas/hypopneas caused due to the laxity of pharyngeal musculature leading to the repetitive collapse of the upper airway during sleep. The patients with OSA complain of excessive daytime sleepiness, morning headaches, poor judgment, impotence, and depression. Loud snoring, gasping, choking, snorting, or interruptions in breathing while sleeping is often reported by their bed partners. OSA is a very common comorbidity in a patient with bipolar disorder. Higher BMI and residual depressive symptoms are the two best independent predictors of OSA in a patient with bipolar disorder.[9]

Advanced sleep phase syndrome is a circadian rhythm disorder characterized by an inability to stay awake in the evening (usually after 7 pm). These patients complain of early morning insomnia due to their early bedtime.

Delayed sleep phase syndrome is also a circadian rhythm disorder in which the affected individuals generally go to bed and usually arise two or more hours late than the desired time. These patients often complain of sleep-onset insomnia and excessive morning sleepiness.

REM sleep behavior disorder is a parasomnia characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. The patients with REM sleep behavior disorder show movements such as kicking, punching, arm-flailing, or jumping from bed in response to violent dreams. Patients are generally brought to medical attention due to potentially injurious actions to themselves or their bed partners. The patient can recall the dream if he awakens during the episode. This disorder may be associated with other medical conditions such as Parkinson's disease, Lewy body dementia, or multiple system atrophy.

Night terrors are most common in children aged 2 to 12 years of age, which usually resolve spontaneously as child ages. It occurs in non-REM sleep. Parents usually complain of their child exhibiting features like screaming, intense fear, and flailing while still asleep during an episode of the night terror. There is no memory of the event.

Nightmare is a parasomnia that occurs during REM sleep, usually in the middle of the night and early morning. During a nightmare, the person may scream and yell out things. The difference of nightmare with a night terror is that the person can become fully alert when awakened during a nightmare. Also, there is a memory of the event in a nightmare i.e., and a person can recall a nightmare.

Restless leg syndrome is a sleep movement disorder in which the patients have an uncomfortable sensation and an urge to move the legs while trying to fall asleep. The symptoms are relieved by walking or moving the legs. 

Physical Examination

Signs of sleep disorders are as follows:

  • Poor concentration
  • Drowsiness
  • Slowed reaction time
  • Hypertension (which can be caused by sleep apnea)
  • Poor growth, enlarged tonsils, and narrowed airway (findings of OSA)

Evaluation

A variety of information is required to evaluate sleep problems. After a detailed medical history, medication history, and physical examination; some of the investigations appropriate to diagnose sleep disorders are as follows:

Sleep diary: The sleep diary, or sleep log, is a subjective paper record of sleep and wakefulness over a period of weeks to a month. Patients should record the detailed description of sleep, such as bedtime, duration until sleep onset, the number of awakenings, duration of awakenings, and nap times. 

Sleep studies: Objective measures of sleep may be obtained by sleep studies such as electroencephalography (EEG) or polysomnography (PSG). PSG is largely regarded as the gold standard for the diagnosis of OSA and other sleep disorders. During PSG, numerous monitoring devices are connected to the patient, and the patient is allowed to sleep. Various physiologic parameters such as respiratory effort, sleep stages, electrocardiography, airflow, body position, and limb movements are assessed. The information obtained from these parameters helps to diagnose various REM & NREM sleep disorders as well as determine the causes of sleep disturbance.

Laboratory studies: Some of the lab studies appropriate for those with sleep disorders include:

  • Hemoglobin and hematocrit
  • Arterial blood gases (ABG) 
  • Thyroid function tests
  • Drug and alcohol toxicity screening 
  • Iron studies
  • CRP (increased in patients with OSA).[10]

Overnight oximetry: This involves the use of a probe that is worn on the finger or earlobe, which continuously measures oxygen levels and heart rate. It identifies the individuals who are at risk for nocturnal breathing disorders such as sleep apnea.

Actigraphy: In this test, a device called the actigraph is worn on the wrist like a watch. The signals are detected when there is movement. Very few to no signals are recorded during sleep/inactivity. This device can be used to assess sleep-wake cycles or circadian rhythm over an extended period of time and thus can be used to diagnose advanced or delayed sleep phase syndrome.

Multiple sleep latency testing (MSLT): This is an objective test which determines the degree of sleepiness. This test is often called a nap study. On the day following an overnight PSG study, the patient is asked to take four or five naps over a period of 8-10 hours. Each nap lasts about 20 minutes. These tests are useful in identifying excessive daytime sleepiness, which can be present in various disorders such as sleep apnea, hypersomnia, and narcolepsy.

Indices and scoring systems: If there is a suspicion of depression causing insomnia, Beck Depression Inventory can be used. Similarly, tools like a structured clinical interview for sleep disorders (SCISD) is a brief, reliable interview assessment tool for sleep disorders.[11]

Treatment / Management

Treatments for sleep disorders depend on the type of sleep disorder. Treatment of insomnia can be broadly categorized into non-pharmacological and pharmacological treatments.

Non-pharmacological treatments:

  • Cognitive-behavioral therapy (CBT): these are psychological and behavioral techniques that can be helpful for treating insomnia. Depending on the specific symptoms, some of the techniques employed in CBT are:
  • Sleep restriction therapy (SRT): SRT limits the total time allowed in bed so that the drive to sleep increases.
  • Stimulus control therapy: it helps in changing sleep habits so that the patients don't have difficulty falling asleep. Patients should not go to bed until they are sleepy. Also, the bed should be used only for sleeping and not for watching television or reading books.
  • Relaxation training: Relaxation techniques may be implemented before sleep. Meditation and breathing exercises are some of the relaxation techniques. It begins with being in a comfortable position and closing eyes. The mind and thoughts should be redirected towards a peaceful image, and relaxation should be allowed to spread throughout the body.
  • Hypnosis: the hypnotherapist uses different therapeutic techniques like verbal repetition and mental images, which makes the patient feel calm and relaxed, promoting restful sleep.
  • Sleep hygiene : (see: patient education section)

Pharmacologic therapy:

  • Histamine type 1 receptor blockers: due to their sedative effects, these drugs can be helpful in patients with sleep disorders. However, due to their anticholinergic effect, these drugs should be avoided in the elderly. Examples include chlorpheniramine and diphenhydramine.
  • Benzodiazepines (BZD): these drugs are the mainstay in the treatment of insomnia. The drugs bind to a special benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex, enhancing the activity of neurotransmitters. These drugs suppress the REM sleep, reduces stages 3 & 4 sleep while increasing stage 2 sleep. Examples include flurazepam and temazepam.
  • Non-benzodiazepine hypnotics: these agents are used for the treatment of acute and short term insomnia. These drugs have non-BZD like chemical structures but interact with the GABA-BZD receptor, causing sedation. Examples include zolpidem and zaleplon.
  • Melatonin receptor agonists: the melatonin receptors MT1 and MT2 are implicated in regulating sleepiness and the sleep-wake cycle. Melatonin receptor agonists act on these receptors and hence improve sleep through the endogenous regulating system. These drugs are used in circadian rhythm sleep disorders, jet lag, delayed sleep-wake phase disorder (insomnia with difficulty in sleep onset).[12] [13][14]Example includes ramelteon. 
  • Orexin receptor antagonists: orexin promotes wakefulness. Thus, antagonism of this receptor helps in sleep. An example includes suvorexant.

Other interventions:

  • Sleep apnea can be alleviated by losing weight, the use of continuous positive airway pressure (CPAP), and, sometimes, surgical treatment. The drug solriamfetol, selective dopamine, and norepinephrine reuptake inhibitor can be used to increase wakefulness in patients with OSA who have excessive sleepiness.[15]
  • A number of medications can be used for the treatment of narcolepsy. Modafinil, a non-amphetamine stimulant that promotes wakefulness, is considered as first-line therapy for narcolepsy as it reduces daytime sleepiness, is well tolerated, and has less abuse potential compared to traditional stimulants (amphetamines, methylphenidate). These traditional drugs are second-line drugs. Patients with significant cataplexy may benefit from REM suppressing drugs such as anti-depressants and sodium oxybate.
  • Light-phase shift therapy is useful for sleep disturbances associated with circadian rhythm abnormalities.[16] Patients may be exposed to bright light to help normalize the sleep schedule.
  • Gabapentin enacarbil significantly improves restless leg syndrome and hence alleviates sleep disturbance.[17]

Differential Diagnosis

The differential diagnosis of sleep disorder are as follows:

  • Post-traumatic stress disorder (PTSD)
  • Depression
  • Anxiety disorder
  • Bipolar disorder
  • Opioid abuse
  • Alcoholism
  • Stimulants abuse (amphetamine)
  • Chronic obstructive pulmonary disease (COPD)
  • Hyperthyroidism

Prognosis

Insufficient sleep can result in industrial or motor vehicle accidents, decreased work performance, and cognitive dysfunction. The prognosis of sleep disorders depends widely on the cause of the sleep disorder. Insomnia due to OSA generally resolves with the treatment, whereas the patients with chronic insomnia have increased risk of depression, anxiety, and reduced quality of life.

Complications

Untreated sleep disorders may lead to the development of various serious complications. Mood and anxiety disorders may develop. Sleep deprivation can lead to the formation of false memory and a decline in cognitive functioning.[18]

The patients with periodic limb movement disorder of sleep have a higher risk of cerebrovascular accidents.[19]

Obstructive sleep apnea, apart from the loss of sleep, can damage the brain, and affect the cardiovascular system. Obstructive sleep apnea can also reduce the thickness of the retinal nerve fiber layer.[20]

Deterrence and Patient Education

All patients should be educated well and encouraged to practice good sleep hygiene. "Sleep hygiene" is a term used to describe good sleep habits.

The following advice should be given to the patients to practice good sleep hygiene:

  • maintain a regular schedule i.e, go to bed and wake up at the same time every day
  • use the bed for sleep and sex only. Avoid watching television, looking at phones or reading in the bed
  • exercise almost every day, but not right before bedtime
  • avoid caffeine or smoking mostly during the evening
  • maintain a dark, cool, and quiet environment in the bedroom
  • avoid struggling to fall asleep in bed. If you can't sleep, get up and try again later or change the bed

Also, if the patient is taking sedative-hypnotic medications, it should be clearly documented in the medical record. Patients should be counseled to avoid driving and operating machines when under these medications.

Enhancing Healthcare Team Outcomes

The proper management of sleep disorders requires the efforts of an interpersonal healthcare team. Consultation can help evaluate patients for medical and psychiatric causes of insomnia. The management team includes a psychiatrist, neurologist, pulmonologist, sleep medicine specialist, and dietitian. Surgical consultations are required for some of the underlying causes of insomnia, such as in cases of OSA, which may require palate surgery. Interdisciplinary collaboration is important for good patient outcomes in sleep disorders.


References

[1] Zammit GK,Weiner J,Damato N,Sillup GP,McMillan CA, Quality of life in people with insomnia. Sleep. 1999 May 1;     [PubMed PMID: 10394611]
[2] Huyett P,Siegel N,Bhattacharyya N, Prevalence of Sleep Disorders and Association With Mortality: Results From the NHANES 2009-2010. The Laryngoscope. 2020 Jul 18     [PubMed PMID: 32681735]
[3] Malhotra RK, Neurodegenerative Disorders and Sleep. Sleep medicine clinics. 2018 Mar;     [PubMed PMID: 29412984]
[4] Gao Q,Kou T,Zhuang B,Ren Y,Dong X,Wang Q, The Association between Vitamin D Deficiency and Sleep Disorders: A Systematic Review and Meta-Analysis. Nutrients. 2018 Oct 1;     [PubMed PMID: 30275418]
[5] Mathias JL,Cant ML,Burke ALJ, Sleep disturbances and sleep disorders in adults living with chronic pain: a meta-analysis. Sleep medicine. 2018 Dec;     [PubMed PMID: 30314881]
[6] Carter KA,Hathaway NE,Lettieri CF, Common sleep disorders in children. American family physician. 2014 Mar 1;     [PubMed PMID: 24695508]
[7] Rodriguez JC,Dzierzewski JM,Alessi CA, Sleep problems in the elderly. The Medical clinics of North America. 2015 Mar;     [PubMed PMID: 25700593]
[8] Gulia KK,Kumar VM, Sleep disorders in the elderly: a growing challenge. Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society. 2018 May;     [PubMed PMID: 29878472]
[9] Geoffroy PA,Micoulaud Franchi JA,Maruani J,Philip P,Boudebesse C,Benizri C,Yeim S,Benard V,Brochard H,Leboyer M,Bellivier F,Etain B, Clinical characteristics of obstructive sleep apnea in bipolar disorders. Journal of affective disorders. 2019 Feb 15;     [PubMed PMID: 30359809]
[10] Van der Touw T,Andronicos NM,Smart N, Is C-reactive protein elevated in obstructive sleep apnea? a systematic review and meta-analysis. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 2019 Jul;     [PubMed PMID: 30908094]
[11] Taylor DJ,Wilkerson AK,Pruiksma KE,Williams JM,Ruggero CJ,Hale W,Mintz J,Organek KM,Nicholson KL,Litz BT,Young-McCaughan S,Dondanville KA,Borah EV,Brundige A,Peterson AL, Reliability of the Structured Clinical Interview for DSM-5 Sleep Disorders Module. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2018 Mar 15;     [PubMed PMID: 29458705]
[12] Xie Z,Chen F,Li WA,Geng X,Li C,Meng X,Feng Y,Liu W,Yu F, A review of sleep disorders and melatonin. Neurological research. 2017 Jun;     [PubMed PMID: 28460563]
[13] Sletten TL,Magee M,Murray JM,Gordon CJ,Lovato N,Kennaway DJ,Gwini SM,Bartlett DJ,Lockley SW,Lack LC,Grunstein RR,Rajaratnam SMW, Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLoS medicine. 2018 Jun;     [PubMed PMID: 29912983]
[14] Auld F,Maschauer EL,Morrison I,Skene DJ,Riha RL, Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep medicine reviews. 2017 Aug;     [PubMed PMID: 28648359]
[15] Schweitzer PK,Rosenberg R,Zammit GK,Gotfried M,Chen D,Carter LP,Wang H,Lu Y,Black J,Malhotra A,Strohl KP, Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial. American journal of respiratory and critical care medicine. 2019 Jun 1;     [PubMed PMID: 30521757]
[16] Faulkner SM,Bee PE,Meyer N,Dijk DJ,Drake RJ, Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis. Sleep medicine reviews. 2019 Aug;     [PubMed PMID: 31108433]
[17] Ahmed M,Hays R,Steven Poceta J,Jaros MJ,Kim R,Shang G, Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials. Clinical therapeutics. 2016 Jul;     [PubMed PMID: 27288210]
[18] Lo JC,Chong PL,Ganesan S,Leong RL,Chee MW, Sleep deprivation increases formation of false memory. Journal of sleep research. 2016 Dec;     [PubMed PMID: 27381857]
[19] Lin TC,Zeng BY,Chen YW,Wu MN,Chen TY,Lin PY,Wu CK,Tseng PT,Hsu CY, Cerebrovascular Accident Risk in a Population with Periodic Limb Movements of Sleep: A Preliminary Meta-Analysis. Cerebrovascular diseases (Basel, Switzerland). 2018;     [PubMed PMID: 29982243]
[20] Wang W,He M,Huang W, Changes of Retinal Nerve Fiber Layer Thickness in Obstructive Sleep Apnea Syndrome: A Systematic Review and Meta-analysis. Current eye research. 2017 May;     [PubMed PMID: 27854132]