Sleep Disorders

Sleep Physiology

Non-REM sleep is delineated into stages N1-3 or N1-4; N3 stage is sometimes delineated into N3 and N4 depending on the classification system. N1 is the lightest stage of sleep, while N3-4 is the deepest, most relaxed part of sleep.

More time is spent in N2 sleep (45%) than any other stage.

Bruxism (teeth-grinding) occurs in stage N2 sleep.

Sleepwalking and enuresis occur in N3-4 sleep.

REM

REM sleep is characterized by dreaming, penile/clitoral erections, increased pulse and blood pressure, and loss of motor tone.

REM typically lasts for 10-40 minutes and occur every 90 minutes.

The eye movements are driven by the PPRF (paramedian pontine reticular formation).

For more information on REM sleep actions and other sleep behaviors, see the parasomnias topic.

Stage N1 sleep is characterized by theta waves.

Stage N2 sleep is characterized by K-complexes and sleep spindles.

Stage N3 sleep is characterized by delta waves (slow waves).

REM sleep is characterized by "sawtooth" waves.

Alpha waves occur during awake, relaxed (not concentrating) states.

Beta waves are most strongly associated with active thinking and concentration.

Insomnia

Primary insomnia includes several symptoms that interfere with sleep quality, such as:

• Sleep-onset insomnia: Difficulty initiating sleep

• Middle insomnia: Difficulty staying asleep

• Sleep-offset insomnia: Early morning awakening

CBT and measures to improve sleep hygiene are two non-pharmacological solutions to primary insomnia. Sleep hygiene measures include:

• Minimizing caffeine and smoking before bedtime

• Not sleeping in on weekends

• Minimizing excessively long naps, particularly those late at night

Pharmacotherapy includes the following medication options:

• Benzodiazepines

• Non-benzodiazepine GABA agonists (zolpidem, eszopiclone, zaleplon)

• Sedating non-GABAergic agents(trazodone, doxepin)

Circadian rhythm sleep disorders

The suprachiasmatic nucleus in the hypothalamus dictates 24-hour sleep rhythmicity.

Circadian rhythm sleep disorders are a group of disorders that share a common theme of misalignment of one's circadian rhythm with one's sleep patterns. Subtypes include:

• Delayed sleep phase type

• Advanced sleep phase type

• Irregular sleep-wake type

• Non-24-hour sleep-wake type

• Shift work type

Delayed sleep phase type is characterized by a circadian rhythm that is displaced later in the night (e.g. 3 am to 11 am). It is commonly observed in puberty. Patients may be thought of as "night owls".

Advanced sleep phase type is characterized by a circadian rhythm that is displaced earlier in the night (e.g. 8 pm to 4 am). It is more common in elderly patients. Patients may be thought of as "early birds".

Irregular sleep-wake type is characterized by an irregular or inconsistent sleep pattern. Patients may not have any single period of significant sleep, such that their sleep is fragmented erratically into naps. Alternatively, their primary sleep period may vary erratically into various extremes of time.

Non-24-hour sleep-wake type exhibits a circadian rhythm that is malformed into a non-diurnal pattern (e.g. the circadian rhythm is 30 hours). This disorder is most common in blind patients. As their sleep pattern synchronizes in and out of a diurnal period, their daytime fatigue waxes and wanes.

Shift work type is a sleep disorder caused by work shifts that occur while the patient's circadian rhythm would otherwise dictate sleep. For example, a patient with shift work type may experience insomnia and wake-time fatigue after beginning a "graveyard" shift.

An important concept in circadian rhythm disorders is differentiating shift work type from either advanced or delayed sleep phase disorders. The key is to note the onset of insomnia and wake-time fatigue.

• Example: A patient working a night shift has no sleep problems until she switches to a traditional 9-5 schedule. She has a history of difficulty waking up for early-morning classes when she was in college. Diagnosis: Delayed sleep phase disorder.

• Example: A patient experiences insomnia and wake-time fatigue after beginning a new job on night shift. Diagnosis: Shift work disorder.

Narcolepsy

Narcolepsy is characterized by excessive daytime sleepiness leading to "sleep attacks" where patients suddenly fall asleep at inappropriate times. Cataplexy is a unique finding of narcolepsy, where sudden loss of muscle tone is precipitated by emotion or surprise. Sleep paralysis is also indicative of narcolepsy, and is a phenomenon in which patients temporarily feel "frozen" upon waking.

Patients with narcolepsy may experience hypnagogic (just before sleeping) and hypnopompic (occur during awakening) hallucinations.

Narcolepsy is caused by a deficiency in hypocretin (orexin). Hypocretin levels can be immunoassayed with a CSF sample. The pathophysiology of hypocretin neuronal loss is thought to be autoimmune, as 99% of affected individuals have a particular HLA-DQB1 allele.

Hypocretin-secreting neurons are located in the hypothalamus.

Treatments for narcolepsy center around CNS stimulants. The current 1st line therapy is modafinil, a wakefulness-promoting agent with an unknown mechanism of action. Other CNS stimulants to consider include methylphenidate and amphetamines.

The treatment of choice for cataplexy in the setting of narcolepsy is REM sleep-suppressing agents, such as venlafaxine, fluoxetine, atomoxetine. If cataplexy is not controlled with one of these medications, sodium oxybate is the next line of treatment.

Sleep Apnea

Sleep apnea is characterized by periods of breathing cessation that occur during sleep. There are two types:

• Obstructive sleep apnea is the obstruction of respiration due to the weight of tissue compressing the airway. Rule out obstructive sleep apneain an obese patient with daytime fatigue.

• Central sleep apnea is characterized by a lack of central respiratory drive.

In obstructive sleep apnea, chronic hypoxemia due to nocturnal apnea has a multitude of cardiovascular complications:

• Pulmonary hypertension (as well as potential for cor pulmonale)

• Systemic hypertension

• Arrhythmia

• Polycythemia

Central sleep apnea can be caused by:

• Neurological conditions (e.g. stroke, Parkinson's, etc.)

• High-altitude climbing

• Nocturnal Cheyne-Stokes breathing (secondary to conditions such as heart failure, toxic encephalopathy, and renal failure)

Both types of sleep apnea are diagnosed with polysomnography during sleep.

The mainstay of treatment of both types of sleep apnea is CPAP (continuous positive airway pressure). Additional measures include treatment of the underlying cause (weight loss for obstructive sleep apnea, and resolution of underlying pathology in central).

Restless leg syndrome

Restless leg syndrome is a subjective feeling of restlessness and an uncomfortable sensation in the legs that is relieved by moving them. Iron deficiency is an important correctable cause to rule out; also look for symptoms or associated characteristics of iron deficiency, such as pica, a history of chronic menorrhagia, etc.

The most effective pharmacological treatment for restless leg syndrome is a dopamine agonist such as ropinirole or pramipexole. Alternatively, anticonvulsants (especially gabapentin), opioids, benzodiazepines can be used.

Kleine- Levin

Rare disorder in which patients experience hypersomnia, hyperphagia, hypersexuality, and aggression. The diagnosis is clinical. Patients sleep a median of 18 hours/day during hypersomnic episodes.,

Parasomnia

Parasomnias are abnormal behaviors or experiences that occur during sleep, often disturbing the patient and affecting sleep quality. They include:

• REM sleep behavior disorder

• Sleepwalking

• Sleep terrors

• Nightmare disorder

Parasomnias, particularly REM sleep behavior disorder, are caused by an incomplete inhibition of skeletal muscle during REM sleep.

Nightmare and terror

A key difference in distinguishing nightmare disorder from sleep terrors is that patients with nightmare disorder recall their dreams. This is because of the difference in sleep stage during which the nightmares/terrors occur.

Sleep terrors are episodes of sudden arousal with screaming. Patients do not recall their dream and may be disoriented upon waking. Sleep terrors occur during sleep stages N3-4 (delta wave sleep).

Nightmares in nightmare disorder occur during REM sleep.

Nightmare kids are consolable. Night terror kids are inconsolable.

Nightmare disorder is marked by recurrent frightening dreams, which are particularly vivid. This disorder has a strong association with PTSD.

Imagery rehearsal therapy (IRT) involves using mental imagery to modify the outcome of a recurrent nightmare. It is very successful in treating recurrent nightmares in PTSD.

REM Sleep Disorder

Characterized by dream-enacting behaviors, where patients may jerk limbs, walk, yell, and perform various actions. The first line treatment is melatonin, and second line is clonazepam.,

Rapid eye movement (REM) sleep behavior disorder is characterized by complex motor behaviors that occur during REM sleep. Dream enactment can occur if the muscle atonia that usually accompanies REM sleep is absent or incomplete. These behaviors are more likely to occur during the latter part of the night, when the percentage of REM sleep is higher. Patients can be awakened quickly, and after very transient confusion can become fully alert. They may not recall their movements during sleep but can recall their dreams.

REM sleep behavior disorder is more likely to occur in older adult men. If frequent and recurrent, it may be a prodromal sign of neurodegeneration in patients with Parkinson disease or dementia with Lewy bodies. It occurs with other prodromal symptoms such as subtle motor deficits (eg, changes in gait), anosmia, and constipation.

Sleep walking

Sleepwalking is characterized by walking during sleep, with or without the presence of other complex behaviors. Patients' eyes are open with a "glassy" look, and they have amnesia for the episode. Sleepwalking is associated with:

• Sleep deprivation

• Stress

• Hyperthyroidism

• Sleep apnea

• Magnesium deficiency