Sleep

Sleep Stages

Stage	EEG Pattern	Key Features	% of Sleep
Wake	Alpha (8-13 Hz) relaxed; Beta alert	Alpha = posterior, eyes closed	—
N1	Theta (4-7 Hz); vertex sharp waves	Light sleep; easily aroused; slow eye movements	5%
N2	Sleep spindles (12-14 Hz) + K-complexes	Majority of sleep; memory consolidation	45-55%
N3 (Slow Wave)	Delta (<4 Hz); >20% of epoch	Deep sleep; restorative; GH release; hardest to arouse	15-20%
REM	Low voltage, mixed frequency; sawtooth waves	Rapid eye movements; muscle atonia; dreaming	20-25%

Sleep Cycle Organization

• Cycle duration: 90-120 minutes
• Cycles per night: 4-6
• First half of night: More N3 (slow wave sleep)
• Second half of night: More REM sleep
• REM latency: ~90 minutes (shortened in narcolepsy, depression)

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Wake-Promoting Systems

Structure	Neurotransmitter	Notes
Locus coeruleus	Norepinephrine	Off during REM
Raphe nuclei	Serotonin	Off during REM
Tuberomammillary nucleus	Histamine	Antihistamines cause sedation
Basal forebrain	Acetylcholine	Also active in REM
Lateral hypothalamus	Orexin/Hypocretin	Stabilizes wake; lost in narcolepsy type 1

Sleep-Promoting Systems

Structure	Neurotransmitter	Function
VLPO	GABA, Galanin	Inhibits wake centers; “sleep switch”
Adenosine	—	Builds during wake; caffeine blocks receptors

REM Sleep Regulation

REM-on: PPT/LDT (ACh), sublaterodorsal nucleus

REM-off: Locus coeruleus (NE), raphe (5-HT)

REM atonia: Sublaterodorsal nucleus inhibits spinal motor neurons. Loss → REM sleep behavior disorder.

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Suprachiasmatic Nucleus (SCN)

• Location: Anterior hypothalamus, above optic chiasm
• Function: Master circadian pacemaker
• Input: Light via retinohypothalamic tract (melanopsin RGCs)
• Output: Pineal gland (melatonin), temperature, cortisol
• Intrinsic cycle: ~24.2 hours (needs daily light entrainment)

Melatonin

• Source: Pineal gland
• Regulation: Suppressed by light; peaks at night
• Function: Signals darkness; promotes sleep onset
• Clinical use: Circadian rhythm disorders, jet lag

Circadian Rhythm Disorders

Disorder	Features	Treatment
Delayed Sleep Phase	Sleep onset 2+ hrs late; common in adolescents; “night owls”	Morning bright light; evening melatonin
Advanced Sleep Phase	Sleep onset/wake too early; common in elderly	Evening bright light; morning melatonin
Non-24-Hour	Free-running rhythm; common in blind	Melatonin agonists (tasimelteon)
Shift Work	Misalignment with work schedule	Strategic light exposure; melatonin

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Narcolepsy

Feature	Type 1 (with Cataplexy)	Type 2 (without Cataplexy)
Orexin/CSF	Low (<110 pg/mL, usually <90)	Normal
Cataplexy	Present (emotion-triggered atonia)	Absent
HLA association	DQB1*06:02 (>90%)	Less strong
MSLT criteria	Mean sleep latency ≤8 min + ≥2 SOREMPs

Narcolepsy tetrad:

1. Excessive daytime sleepiness (100%)
2. Cataplexy (emotion-triggered weakness; type 1 only)
3. Sleep paralysis (can’t move at sleep-wake transitions)
4. Hypnagogic/hypnopompic hallucinations

Treatment:

• EDS: Modafinil, armodafinil, solriamfetol, pitolisant; stimulants
• Cataplexy: Sodium oxybate, antidepressants (SNRIs, TCAs)

Parasomnias

Feature	NREM Parasomnias	REM Parasomnias
Timing	First third of night (N3 predominant)	Last third of night (REM predominant)
Recall	No memory of event	Vivid dream recall
Eyes	Open, glassy	Closed
Examples	Sleepwalking, sleep terrors, confusional arousals	REM sleep behavior disorder, nightmare disorder
Age	Children (usually outgrow)	RBD: older adults (>50)

REM Sleep Behavior Disorder (RBD)

• Pathophysiology: Loss of REM atonia → dream enactment
• Clinical: Violent movements during dreams; may injure self/bed partner
• PSG: REM without atonia (increased chin EMG tone during REM)
• Association: Strongly linked to α-synucleinopathies (Parkinson’s, DLB, MSA)
• Conversion: >80% develop parkinsonism within 10-15 years
• Treatment: Melatonin (first line), clonazepam; bedroom safety

Restless Legs Syndrome (RLS)

• Criteria: Urge to move legs + worse at rest + better with movement + worse at night
• Associations: Iron deficiency (check ferritin), uremia, pregnancy, neuropathy
• Pathophysiology: Dopaminergic dysfunction; low brain iron
• Treatment:
  • Iron supplementation if ferritin <75 ng/mL
  • Dopamine agonists (pramipexole, ropinirole) – watch for augmentation
  • Alpha-2-delta ligands (gabapentin, pregabalin) – now often first line
• Augmentation: Symptoms occur earlier, spread to arms, worsen with dopamine agonists

Sleep Apnea

Feature	Obstructive (OSA)	Central (CSA)
Mechanism	Upper airway collapse	Loss of respiratory drive
Respiratory effort	Present (paradoxical breathing)	Absent
Associations	Obesity, large neck, retrognathia	Heart failure, opioids, brainstem lesions
Treatment	CPAP, weight loss, oral appliance	Treat underlying cause; ASV (not in HFrEF)

AHI (Apnea-Hypopnea Index):

• 5-15: Mild
• 15-30: Moderate
• >30: Severe

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Sleep Stage Quick Reference

EEG Finding	Stage
Alpha waves (posterior)	Relaxed wake
Theta + vertex sharp waves	N1
Sleep spindles + K-complexes	N2
Delta waves (>20%)	N3
Low voltage + sawtooth waves	REM

Sleep Disorder Quick Recognition

Clinical Clue	Diagnosis
EDS + cataplexy + low CSF orexin	Narcolepsy type 1
Elderly + dream enactment + later develops PD	REM sleep behavior disorder
Child + first third of night + no recall + eyes open	NREM parasomnia (sleepwalking/terror)
Urge to move legs + worse at rest + better with movement	Restless legs syndrome
Snoring + witnessed apneas + EDS + obesity	Obstructive sleep apnea
Adolescent can’t fall asleep until 2 AM	Delayed sleep phase disorder
Blind patient with free-running rhythm	Non-24-hour sleep-wake disorder

Key Clinical Pearls

Red Flags

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