Circadian Rhythm Sleep–Wake Disorder

Overview

Definition

Circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake disorders describe an imbalance between the internal circadian system and awakening times. These disorders affect sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep timing rather than sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep generation. The etiology of circadian sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake rhythm disorders can be divided into:

• Intrinsic:
  • Abnormality in the circadian system itself, which can be due to age, genetic factors, or medical conditions.
  • Seen in delayed/advance sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake phase disorder
• Extrinsic:
  • Abnormality in the environment, which requires the patient to be awake at unusual times 
  • Seen in jet lag, shift work

Intrinsic circadian system

• Endogenous biologically active 24-hour cyclic system that controls sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep 
• Regulated by the suprachiasmatic nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles of the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus 
• Functions:
  • Influences depth, quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement, and waking time of sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep episodes
  • Maintains wakefulness during the day
  • Modulates other systems such as:
    • Core body temperature Body Temperature The measure of the level of heat of a human or animal. Heatstroke
    • Cortisol Cortisol Glucocorticoids
    • Appetite

Clinical Presentation

Types of circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disorders

Delayed sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake phase disorder:

• Description:
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep onset: delayed
  • Awakening times: delayed
  • Preserved sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement and duration
• Risk factors:
  • Puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty (associated with changes in melatonin secretion Secretion Coagulation Studies)
  • Caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants and nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants use
  • Irregular sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep schedule
  • Depression
  • ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder in children
• Presentation:
  • Difficulty with jobs that start in the morning
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep is normal when patient is able to arrange his/her schedule. 
  • Example: Patient cannot fall asleep until 3 AM and wakes up at 11 AM feeling well.
  • Night owl

Advanced sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake phase disorder:

• Description:
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep onset: earlier than desired
  • Awakening: earlier than desired
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement and duration: preserved
• Risk factors:
  • Old age 
  • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance familial variant (missense mutations shorten the circadian period)
• Presentation:
  • Patient cannot stay awake during the evening. 
  • Example: Patient goes to bed at 8:00 PM to arise early in the morning.
  • Early bird

Irregular sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake rhythm disorder:

• Description:
  • Periods of wakefulness and sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep are not consolidated, leading to fragmented sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep episodes in 24 hours.
  • Dysfunction of the suprachiasmatic nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles likely has a major impact.
• Risk factors: neurodegenerative disorders (e.g., dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders)
• Presentation: Patient reports ≥ 3 bouts of sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep, with each lasting 1–4 hours.

Non-24-hour sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake rhythm disorder:

• Description:
  • Circadian sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake cycle > 24 hours or < 24 hours without reset in the morning
  • Free-running disorder
• Risk factors:
  • Blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity (loss of light–dark cycle)
  • Traumatic brain injury Traumatic brain injury A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. Le Fort Fractures
  • Developmental delay, such as autism (impaired perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment of environmental time cues)
• Presentation:
  • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia at night
  • Difficulty in morning arousal
  • Increased daytime sleepiness Daytime sleepiness Narcolepsy
  • At times, patient’s sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake timing is aligned with the environment.

Shift-work disorder:

• Description: impaired sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep cycle secondary to work shifts that are opposite to the light–dark cycle
• Risk factors:
  • Inverted schedule of night-shift workers
  • Shift > 16 hours
• Presentation:
  • Sleepiness while awake
  • Decreased cognition and psychomotor function
  • Errors and accidents (e.g., while driving)

Jet-lag disorder:

• Description:
  • Difficulty in initiating and/or maintaining sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep after travel across ≥ 2 time zones
  • Also affected by travel conditions (e.g., mobility, alcohol intake) and direction of travel (e.g., more difficult to adapt when going east)
  • Transient
• Presentation:
  • Excessive daytime sleepiness Daytime sleepiness Narcolepsy until there is alignment with light–dark cycle
  • Somatic symptoms Somatic symptoms Major Depressive Disorder: decreased appetite, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation

Clinical features of disorders

Symptoms:

• Daytime sleepiness Daytime sleepiness Narcolepsy
• Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia (difficulty sleeping)
• Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep inertia (cognitive and sensory-motor impairment after awakening)
• Headaches
• Irritability
• Diminished concentration and increased performance errors
• Awakening at inappropriate times
• Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia

Symptoms can be:

• Episodic: occur for ≥ 1 month but < 3 months
• Persistent: symptoms present for ≥ 3 months
• Recurrent: ≥ 2 within a year

Diagnosis

Approach

• Diagnosis is made clinically on the basis of the criteria outlined above.
• Polysomnography Polysomnography Simultaneous and continuous monitoring of several parameters during sleep to study normal and abnormal sleep. The study includes monitoring of brain waves, to assess sleep stages, and other physiological variables such as breathing, eye movements, and blood oxygen levels which exhibit a disrupted pattern with sleep disturbances. Physiology of Sleep:
  • Usually not indicated
  • Perform if other sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep pathology (e.g., obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea) is suspected

Tests

• Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep diary:
  • Useful self-report tool to aid diagnosis
  • Patient is asked to record:
    • Bedtime and wake-up time
    • Estimated time to fall asleep
    • Frequency of awakenings
    • Total sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep time
• Actigraphy:
  • Patient wears movement sensor on nondominant wrist to determine total sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep time and sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep efficiency.
  • Useful when sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep diary is not feasible (e.g., in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with neurodegenerative disorders) 
• Melatonin sampling:
  • Can provide objective evaluation of impairment of circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies 
  • Melatonin:
    • Released by the pineal gland Pineal gland A light-sensitive neuroendocrine organ attached to the roof of the third ventricle of the brain. The pineal gland secretes melatonin, other biogenic amines and neuropeptides. Hormones: Overview and Types about 90–120 minutes before usual bedtime
    • Suppressed by bright light
  • Dim light melatonin onset (DLMO) protocol:
    • Commonly uses saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy sample (other option is blood)
    • Sample is obtained every 30–60 minutes for 6 hours before and 1 hour after usual sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep time.
    • The timing of melatonin increasing above the threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction is a marker for the circadian phase.

Management

Treatment approach

The goal of management is to achieve realignment of sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake timing.

Nonpharmacologic options:

• Behavioral intervention:
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep hygiene:
    • Avoid stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants such as caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants and alcohol before bedtime.
    • Use bed for sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep or sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria only. 
    • Avoid stimulating activities for 2 hours before bedtime.
    • Avoid daytime naps.
    • Regular Regular Insulin exercise
  • Chronotherapy:
    • Technique used to reset biologic clock
    • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake cycle adjusted gradually (e.g., delaying bedtime and waking time) until desired schedule is achieved.
• Light or phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn (at a specific and regular Regular Insulin length of time):
  • Bright-light therapy (e.g., using light boxes with 10,000 lux) 
  • Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn with blue-enriched light during the morning hours (to stimulate wakefulness)

Pharmacologic:

• Melatonin:
  • Functions as the signal of night; levels rise in the evening
  • Options: exogenous melatonin or melatonin agonists 
• Modafinil Modafinil Stimulants: indicated for treating drowsiness during nighttime shift work

Treatment of specific disorders

Differential Diagnosis

• Parasomnias Parasomnias Parasomnias are a pattern of sleep disorders marked by unusual actions, activities, or physiological events that occur during sleep or sleep-wake transitions. Parasomnias are divided into which sleep phase the symptoms occur, either rapid eye movement (REM) or non-REM (NREM). Parasomnias: sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disorders marked by unusual actions, activities, or physiologic events that occur during sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep or sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake transitions. Symptoms may include abnormal movements, emotions, dreams, and autonomic activity. Unlike parasomnias Parasomnias Parasomnias are a pattern of sleep disorders marked by unusual actions, activities, or physiological events that occur during sleep or sleep-wake transitions. Parasomnias are divided into which sleep phase the symptoms occur, either rapid eye movement (REM) or non-REM (NREM). Parasomnias, circadian sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake disorder does not require polysomnography Polysomnography Simultaneous and continuous monitoring of several parameters during sleep to study normal and abnormal sleep. The study includes monitoring of brain waves, to assess sleep stages, and other physiological variables such as breathing, eye movements, and blood oxygen levels which exhibit a disrupted pattern with sleep disturbances. Physiology of Sleep for diagnosis and patient is fully aware of problems with sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep. 
• Narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy: sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disorder characterized by excessive daytime sleepiness Daytime sleepiness Narcolepsy and falling asleep at inappropriate times. Narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy is associated with hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia (hypnagogic and hypnopompic, which occur upon falling asleep and waking from sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep, respectively), cataplexy Cataplexy A condition characterized by transient weakness or paralysis of somatic musculature triggered by an emotional stimulus or physical exertion. Cataplexy is frequently associated with narcolepsy. During a cataplectic attack, there is a marked reduction in muscle tone similar to the normal physiologic hypotonia that accompanies rapid eye movement sleep (sleep, rem). Narcolepsy (emotionally triggered loss of muscle tone Muscle tone The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. Skeletal Muscle Contraction). Unlike narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy, circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disorders are marked by impairment in sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep initiation. 
• Obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea: episodic apnea, or cessation of breathing during sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep, in which the period of apnea lasts > 10 seconds. Obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea is usually due to a partial or complete collapse of the upper airway Airway ABCDE Assessment and is associated with snoring, restlessness, daytime headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, and somnolence.