Sleep and sleep disorders

Sleep is a physiologically recurring state of rest characterized by relative suspension of consciousness and inaction of voluntary muscles. It is regulated by the circadian rhythm and typically runs through 4–5 cycles of three stages of non-rapid eye movement sleep and one stage of rapid eye movement (REM) sleep. Sleep disorders are a potentially serious and very common concern, affecting up to one third of the US adult population. They may be primary, i.e., due to an intrinsic problem with the sleep-wake cycle, or secondary to an underlying medical condition. Primary sleep disorders are further divided into dyssomnias or parasomnias. Symptoms include difficulty falling asleep, difficulty remaining asleep, or abnormal behavior during sleep. Treatment may include improved sleep hygiene, phototherapy, and sedative pharmacotherapy.

Narcolepsy, restless legs syndrome, and obstructive sleep apnea are discussed in separate learning cards.

Normal sleep cycle

• Sleep stages: A full night's rest typically consists of about 4–5 sleep cycles of approx. 90–120 minutes each. Every cycle consists of 3 non-rapid eye movement (NREM) stages and one rapid eye movement (REM) stage with the percentage of REM sleep gradually increasing as the night progresses.
• Circadian rhythm
  • Definition: A 24-hour cycle of biophysical changes that regulate sleep patterns, feeding patterns, hormone production (e.g., release of melatonin, prolactin, ACTH, and norepinephrine), and body temperature.
  • Regulation of sleep: photosensitive retinal ganglion cells receive light stimulus (dark cues) → retinohypothalamic tract (RHT) → suprachiasmatic nucleus of the hypothalamus releases norepinephrine, which causes the pineal gland to release melatonin, which induces sleep

Phase		Description	EEG findings
Wake		Alert	Beta waves (> 13 Hz) with the lowest amplitude
		Eyes closed	Alpha waves (8–13 Hz)
NREM sleep (Non-rapid eye movement)	Stage N1	Lightest stage of sleep (transitional phase between wakefulness and sleep) 5–10% of total sleep time Sudden myoclonic jerks (sensation of twitching or falling) Disorders: obstructive sleep apnea leads to increased N1 sleep	Theta waves (4–7 Hz)
	Stage N2	Deeper sleep 45–55% of total sleep time Disorders: time during which teeth grinding (bruxism) most commonly occurs.	Theta waves (4–7 Hz) Sleep spindles: Short bursts of EEG waves with a frequency of 12–14 Hz. K-complexes: high amplitude, diphasic, frontocentral slow waves
	Stage N3	Slow-wave sleep (deep sleep) 10–20% of total sleep time High waking threshold The length of N3 stages (deep sleep) decreases over the course of the night Disorders: Reduced delta wave sleep: after consumption of alcohol, barbiturates, TCAs, MAO inhibitors, and benzodiazepines Deep sleep is the time during which NREM-parasomnias (e.g., sleepwalking, night terror disorder, bedwetting) occur	Delta waves (0–4 Hz) with the highest amplitude (> 75 microvolts)
REM sleep (Rapid eye movement)		REM sleep 18–23% of total sleep time REM sleep is paradoxical: high waking threshold despite EEG activity resembling a waking state Maximum muscle relaxation with simultaneous REM Activation of autonomic functions (e.g., ↑ HR, miosis, nocturnal penile tumescence) High dream activity The duration and the proportion of REM sleep in relation to NREM sleep increases over the course of a full night's sleep. Irregular, sharply peaked eye movements Disorders Prolonged REM sleep: e.g., major depressive disorder (MDD) Typical findings in MDD include: Shortened REM latency (i.e., the period between the onset of sleep and the first REM period) Increased REM sleep duration Increased REM density (i.e., frequency of rapid eye movements/REM period) Reduced REM sleep: after consumption of alcohol, barbiturates, TCAs, MAO inhibitors, and benzodiazepines	Mixed EEG pattern (predominantly beta waves)

References:^[1][2][3]

• Prevalence: ∼ 10% (most common sleep-wake disorder)
• Etiology
  • Poor sleep hygiene
  • Subclinical mood or anxiety disorders
• Classification
  • Acute or transient: < 3 months (associated with stress or a disrupted sleep schedule)
  • Chronic: ≥ 3 months (associated with an increased risk of psychiatric illness and functional impairment)
• Clinical features
  • Initial or sleep-onset insomnia: difficulty initiating sleep
  • Middle or sleep-maintenance insomnia: frequently waking from sleep
  • Late or sleep-offset insomnia: awakening early in the morning
  • Nonrestorative sleep: feeling fatigued after waking
• DSM-5 diagnostic criteria (primary insomnia is a diagnosis of exclusion)
  • Problems initiating or maintaining sleep, or awakening in the early morning and being unable to return to sleep
  • Symptoms occur ≥ 3 days/week for ≥ 3 months
  • Symptoms cause functional impairment or distress
  • Symptoms are not caused by an underlying substance or medication use
  • Symptoms occur despite having enough time to sleep
  • No underlying or coexisting psychiatric or medical disorder that explains symptoms
• Treatment
  • Improve sleep hygiene
    • No alcohol 4–6 hours preceding sleep
    • No stimulants (caffeinated drinks and nicotine should be avoided 3–4 hours before bedtime)
    • Quiet, dark, pleasantly cool bedroom and a comfortable bed
    • No large meals before bedtime
    • Regular exercise is beneficial but should be avoided 6 hours before bedtime.
  • Stimulus control therapy: Insomnia disorder may cause the bed and bedroom to become cues for arousal rather than sleep. Stimulus control instructions aim to correct this by re-establishing the association of the bed and bedroom with sleep.
    • Advise waking up at regular times (also during the weekend and holidays).
    • Discourage engaging in other activities in bed such as working or reading.
    • Leave the bedroom when unable to fall asleep within 20 minutes (e.g., to read or listen to music) and return only when sleepy.
    • Advise against afternoon naps; if taken, this should not take place after 3 pm and naps should be no longer than 1 hour.
  • Cognitive-behavioral therapy (CBT): preferred treatment for chronic insomnia
  • Pharmacotherapy (use sparingly and short-term)
    • Benzodiazepines
      • ↓ Sleep latency; ↓ awakenings during sleep
      • Only for short-term use due to high risk of addiction
      • For sleep onset insomnia: short-acting agent, e.g., triazolam
    • Antidepressants: trazodone (most commonly prescribed antidepressant for chronic insomnia and depressive symptoms) or amitriptyline
    • Non-benzodiazepine sedatives
      • Zolpidem, eszopiclone, zaleplon
      • Lower risk of daytime sleepiness, although falls and cognitive impairment are still a concern (especially in the elderly and individuals using zolpidem)

The following are shared features of circadian rhythm sleep-wake disorders:

• Insomnia
• Excessive daytime somnolence
• Irritability
• Frequent waking during abnormal hours
• Headaches and impaired concentration

Delayed sleep phase disorder

• Definition: recurrent delay in sleep onset and waking times
• Risk factors: associated with puberty, stimulant use (e.g., caffeine), and irregular sleep
• Treatment
  • Phototherapy in the morning
  • Melatonin receptor agonist; (e.g., Ramelteon, administered at night)
  • Chronotherapy

Jet lag disorder

• Definition: insomnia or hypersomnia due to travel across time zones
• Risk factor: sleep deprivation prior to travel
• Treatment: resolves spontaneously

Advanced sleep phase disorder

• Definition: earlier than desired sleep onset and awakening times
• Risk factor: associated with older age
• Treatment
  • Reassurance
  • Phototherapy in the evening

Shift-work disorder

• Definition: misaligned circadian rhythm due to nightly working hours and sleep deprivation
• Risk factors: shifts > 16 hours and/or night shifts
• Treatment
  • Modafinil if severe
  • Bright light therapy at night to adapt to work shift

Circadian rhythm sleep-wake disorders may present with excessive daytime sleepiness, decreased daytime performance, interrupted sleep, irritability, insomnia, and difficulty concentrating!

Sleepwalking disorder

• Non-REM sleep arousal disorder (no memory of dream)
• Epidemiology
  • Discrete episodes are common (up to 7% of adults and 30% of children), but the disorder is rare.
  • Associated with sleep deprivation, irregular sleep schedules, some medications
• Etiology: idiopathic or genetic (inherited in 80% of cases)
• Risk factors
  • Stress or fatigue
  • Obstructive sleep apnea
  • Nocturnal seizures
  • Fever
  • Drugs (e.g., lithium)
• Clinical features
  • Recurrent episodes during the first third of the sleep cycle, including sitting up, walking, or eating (rarely, violence)
  • Blank stare and difficulty arousing patient during the episode
  • Followed by amnesia of the event
• Treatment
  • Education and reassurance
  • Ensuring safe sleep environment to reduce the risk of physical harm or wandering outdoors
  • In refractory cases, benzodiazepines

Sleep terror disorder

• Non-REM sleep arousal disorder (no memory of dream)
• Epidemiology: Discrete episodes of sleep terrors are relatively common (up to 2% of adults and 20% of children), but the disorder is rare.
• Etiology: unknown; thought to be genetic (family history)
• Risk factors
  • Stress or fatigue
  • Obstructive sleep apnea
  • Nocturnal seizures
  • Fever
  • Drugs (e.g., lithium)
• Clinical features
  • Screaming or crying suddenly upon awakening
  • Intense fear and agitation
  • Tachypnea, diaphoresis, tachycardia during episodes
  • Difficulty arousing patients during episodes; patients will often return to sleep and not remember the episode the next day
• Treatment
  • Education and reassurance (disorder is usually self-limited)
  • Remove dangerous objects from bedroom to reduce risk of self-injury
  • In refractory cases, benzodiazepines

REM sleep behavior disorder

• REM sleep arousal disorder (patient remembers the dream)
• Epidemiology
  • Prevalence: (∼0.5%)
  • Sex: ♂ > ♀
  • Usually in older patients (> 50 years)
• Risk factors: associated with narcolepsy, psychiatric medications , and neurodegenerative disorders
• Clinical features
  • Physically acting out dreams during sleep (sometimes leading to injury to self or others)
  • Alert and orientated after awakening
• Treatment
  • Remove dangerous objects from the bedroom to reduce risk of self-injury
  • If applicable, discontinue causative medications
  • Benzodiazepines (e.g., clonazepam)
  • Melatonin receptor agonist

Nightmare disorder

• REM sleep arousal disorder (patient remembers the dream)
• Epidemiology
  • Prevalence: up to 2% of adults, most common in early adulthood
  • Sex: ♀ > ♂
• Risk factors: post-traumatic stress disorder (PTSD)
• Clinical features
  • Recurrent frightening dreams during the second half of sleep cycle (middle of the night or early in the morning)
  • Patient remembers the dream after awakening
  • Causes functional impairment or distress
• Treatment
  • Reassurance if the disorder is mild
  • Imagery rehearsal therapy: involves modifying a recurrent nightmare by writing it down and rehearsing new endings that make nightmares less frightening when they occur again
  • Antidepressants if associated with PTSD

Nocturnal enuresis

• See bedwetting

Restless legs syndrome

• See restless legs syndrome.

Normal changes in sleep architecture occur with aging, and include:

• Decrease in total sleep time
  • Decreased time spent in deep sleep and REM sleep
  • Increased sleep latency
  • More frequent nighttime awakenings
    • Likely multifactorial: due to nocturia, pain, and/or less time spent in deeper stages of sleep
• Advanced circadian rhythms resulting in earlier bedtimes and thus morning awakenings

Older patients are at increased risk for certain sleep disorders (e.g., obstructive sleep apnea) and should be screened accordingly!