STAGES OF SLEEP AND SLEEP DISORDERS

INTRODUCTION

PART I: STAGES OF SLEEP

Classification

1. NREM sleep (Non-Rapid Eye Movement) — Stages N1, N2, N3
2. REM sleep (Rapid Eye Movement) — Stage R

EEG Patterns at Each Stage

Stage N1 (Light NREM Sleep)

• Transition from wakefulness to sleep
• EEG: Alpha waves disappear; replaced by low-voltage, mixed-frequency theta (4–7 Hz); vertex sharp waves (V waves) may appear over central regions
• EOG: Slow, rolling eye movements
• EMG: Muscle tone mildly reduced
• Patient may not subjectively recognize this as sleep; decreased awareness of sensory stimuli, especially visual; mental activity becomes dreamlike
• Comprises ~3–5% of total sleep time (TST)

Stage N2 (Light-to-Intermediate NREM Sleep)

• Heralded by two cardinal EEG features:
  • Sleep spindles: 11–16 Hz sinusoidal bursts lasting ≥0.5 seconds; generated by thalamo-cortical circuits
  • K-complexes: High-amplitude negative sharp wave followed by positive slow wave, lasting ≥0.5 seconds; thought to reflect cortical response to environmental stimuli
• EOG: No eye movements
• EMG: Further decreased muscle tone
• Comprises ~50% of TST in healthy young adults

Stage N3 (Slow-Wave Sleep / Deep Sleep)

• Also called delta sleep or slow-wave sleep (SWS)
• EEG: High-amplitude (≥75 μV) slow delta waves at 0.5–2 Hz occupying ≥20% of epoch; most prominent over frontal regions
• Previously subdivided into Stage 3 (20–50% slow waves) and Stage 4 (>50% slow waves) — now combined into N3
• Arousal threshold is highest; person is most difficult to wake
• Comprises ~10–20% of TST; decreases markedly with age (virtually absent in persons >70 years)
• Functions: physical restoration, growth hormone secretion, memory consolidation

Stage R (REM Sleep)

• Tonic features (persistent throughout REM):
  • Desynchronized (activated) low-voltage mixed-frequency EEG
  • Generalized skeletal muscle atonia (except extraocular muscles and diaphragm) — mediated by glycinergic/GABAergic inhibition of spinal motor neurons from the pons
  • Sawtooth waves (triangular, 2–6 Hz trains)
• Phasic features (episodic):
  • Rapid conjugate eye movements (horizontal > vertical)
  • Muscle twitches in face, hands, feet
  • Fluctuations in heart rate, blood pressure, respiration (sympathetic activation)
  • Penile/clitoral tumescence
• Dreaming: Most vivid, narrative dreams occur in REM; patients awoken from REM recall dreams most consistently
• Comprises ~20–25% of TST

Sleep Architecture and Cycling

• A young adult enters sleep through N1 → N2 → N3 → back to N2 → then R (REM)
• First REM period occurs after ~70–100 minutes, is brief (5–10 min)
• NREM-REM cycle repeats 4–6 times per night, approximately every 90–100 minutes
• Early night: dominated by N3 (slow-wave) sleep
• Late night: cycles consist mainly of N2 and progressively longer REM periods

• N1: 3–5%
• N2: 50–60%
• N3: 10–20%
• REM: 20–25%

• Neonates: ~50% REM; 60-min cycles
• REM remains relatively constant across adult life
• N3 (slow-wave sleep) progressively decreases with age and is virtually absent after age 70

Neurobiological Control of Sleep

• VLPO (ventrolateral preoptic nucleus): GABAergic/galaninergic sleep-promoting neurons; inhibit arousal centers during sleep
• Arousal centers: Locus coeruleus (NE), dorsal raphe (5-HT), tuberomammillary nucleus (histamine) — all inhibit VLPO during wakefulness
• Orexin (hypocretin) neurons (lateral hypothalamus): stabilize the flip-flop switch; loss of these neurons → narcolepsy

PART II: SLEEP DISORDERS

Classification (ICSD-3, AASM 2014)

1. Insomnia disorders
2. Sleep-related breathing disorders
3. Central disorders of hypersomnolence (narcolepsy, hypersomnia)
4. Circadian rhythm sleep-wake disorders
5. Parasomnias
6. Sleep-related movement disorders

1. INSOMNIA

• Short-term insomnia disorder (<3 months): Precipitated by identifiable stressor; resolves when stressor is removed
• Chronic insomnia disorder (≥3 months, ≥3 nights/week): Usually comorbid with psychiatric (depression, anxiety), medical, neurological disorders, or substance abuse

• First-line: Cognitive behavioral therapy for insomnia (CBT-I) — sleep restriction, stimulus control, relaxation techniques
• Pharmacological: benzodiazepines (temazepam), non-BZD hypnotics (zolpidem, eszopiclone), melatonin receptor agonists (ramelteon), dual orexin receptor antagonists (suvorexant)

2. OBSTRUCTIVE SLEEP APNEA (OSA)

• Mild: 5–14 events/hour
• Moderate: 15–30 events/hour
• Severe: >30 events/hour

• CPAP (continuous positive airway pressure) — first-line for moderate-severe OSA
• Weight loss (strongly recommended)
• Oral appliances (mandibular advancement device) — for mild-moderate OSA
• Positional therapy
• Surgical options: uvulopalatopharyngoplasty (UPPP), maxillomandibular advancement, hypoglossal nerve stimulation

3. NARCOLEPSY

1. Excessive daytime sleepiness (EDS) — irresistible sleep attacks; most prominent feature
2. Cataplexy — sudden bilateral loss of muscle tone triggered by strong emotion (laughter, surprise), without loss of consciousness; pathognomonic
3. Sleep paralysis — temporary inability to move at sleep onset or awakening
4. Hypnagogic/hypnopompic hallucinations — vivid hallucinations at sleep onset (hypnagogic) or on awakening (hypnopompic)

• Narcolepsy type 1: With cataplexy; low/absent CSF orexin-A (<110 pg/mL)
• Narcolepsy type 2: Without cataplexy; CSF orexin usually normal

• EDS: Modafinil (first-line), amphetamines, methylphenidate, sodium oxybate (GHB)
• Cataplexy: Sodium oxybate, TCAs (clomipramine), SSRIs, venlafaxine, selegiline
• Behavioral: Regular sleep schedules, scheduled daytime naps

4. PARASOMNIAS

• Sleepwalking (somnambulism): Complex motor behaviors; amnesia for event; may be triggered by alcohol, sleep deprivation
• Sleep terrors: Sudden arousal from N3; intense autonomic arousal; screaming, tachycardia, sweating; no recall
• Confusional arousals: Disorientation on awakening from N3
• All share: occur in first third of night, from N3 sleep; no dream recall; HLA associations

• REM Sleep Behavior Disorder (RBD): Loss of normal REM atonia → acting out of vivid/violent dreams; potential self/bed-partner injury; strong association with synucleinopathies (Parkinson's disease, Lewy body dementia, MSA — may precede neurodegeneration by decades); diagnosed by PSG showing REM without atonia; treatment: clonazepam, melatonin
• Nightmare disorder: Recurrent distressing dreams recalled on awakening; differ from sleep terrors (occur from REM; full recall; minimal autonomic features)
• Sleep paralysis (isolated): Transient inability to move at sleep-wake transition; fully conscious

5. RESTLESS LEGS SYNDROME (RLS) / PERIODIC LIMB MOVEMENT DISORDER (PLMD)

• Uncomfortable sensory urge to move legs, worse at rest, worse in evening/night, relieved by movement
• May be primary (idiopathic) or secondary to iron deficiency, uremia, pregnancy, medications (dopamine antagonists, SSRIs, antihistamines)
• Treatment (AASM first-line): Dopamine agonists (ropinirole, pramipexole) in the evening; gabapentin/pregabalin

6. CIRCADIAN RHYTHM SLEEP-WAKE DISORDERS

• Delayed sleep phase disorder: Unable to sleep until late; cannot wake early; common in adolescents
• Advanced sleep phase disorder: Sleepy in early evening; wake in early morning; common in elderly
• Shift-work disorder / Jet lag
• Treatment: Light therapy, melatonin, chronotherapy

SUMMARY TABLE