Sleep Physiology, Disorders & Treatment – Detailed Study Notes

Sleep Architecture & Stages

  • Two fundamental kinds of sleep

    • Non-REM (NREM)
    • Sub-divided into Stage 1, Stage 2, Stage 3 (sometimes 3 & 4)
    • General physiology vs wakefulness
      • ↓ Blood pressure, heart rate, respiratory rate, cerebral blood flow
      • Skeletal muscles relaxed; no penile erection
      • Thermoregulation (homeothermia) intact
      • Dreaming does occur but is described as lucid, purposeful & story-like
    • REM (Rapid Eye Movement / “Paradoxical” sleep)
    • Brain highly active while body appears asleep
    • ↑ Heart rate, BP, respiratory rate; EEG resembles wakefulness
    • Near-complete skeletal muscle atonia
      • Evolutionary safety mechanism so we do not act out dreams
    • Penile erection / genital engorgement present; vaginal lubrication variable
    • External auditory input suppressed (“physiologic deafness”)
    • Poikilothermia (body temperature drifts with ambient temp → “cold-blooded”)
    • Dreams are abstract, surreal, emotion-laden

  • Typical overnight course (“sleep architecture”)

    • Sleep cycles last ≈ 90\text{ min}
    • Progression: Wake → N1 → N2 → N3 → REM → repeat
    • First half of night: more slow-wave (N3) sleep
    • Second half: longer & more frequent REM periods
    • Brief spontaneous awakenings (≈ 3–30\text{ min}) are normal and usually forgotten
    • Time distribution in healthy adults
    • \approx 75\% NREM (with 25\% of total night in deep N3)
    • \approx 25\% REM
    • \approx 45$–$50\% specifically in light stages (N1 + N2)

Electrophysiology of Each State (Polysomnography)

  • Wake, eyes open (Stage W)
    • EEG: low-voltage (<50\,\mu V), mixed fast + slow frequencies
    • Frequent blinks, high EMG tone
  • Wake, eyes closed (Relaxed wakefulness)
    • Emergence of alpha rhythm 8$–$13\text{ Hz}; still <50\,\mu V
  • NREM Stage 1 (N1) – Drowsiness
    • EEG resembles relaxed wake but shows
    • Theta waves 4$–$7\text{ Hz}
    • Prominent vertex sharp waves (higher voltage spikes)
    • Slow rolling eye movements; mild EMG reduction
  • NREM Stage 2 (N2) – Light sleep
    • Key grapho-elements
    • Sleep spindles: 11$–$16\text{ Hz} bursts
    • K-complexes: sharp negative deflection followed by positive slow wave
    • Eyes still; low EMG tone
  • NREM Stage 3 (N3) – Slow-wave / deep sleep
    • EEG: delta waves
    • Frequency <2\text{ Hz}
    • Amplitude >75\,\mu V
    • Must occupy ≥20\% of epoch
    • No eye movements; minimal EMG
  • REM
    • EEG: low-voltage, mixed frequency (resembles Stage W)
    • “Saw-tooth” waves characteristic
    • Rapid eye movements on EOG
    • EMG atonia (flat line)

Developmental Changes in Sleep

  • Newborns
    • Total sleep ≈ 16\text{ h/day}
    • 50\% of sleep time is REM and they enter REM almost immediately
  • 4 months
    • REM share drops to 40\% as NREM cycles emerge first
  • Adulthood (≈18–60 y)
    • Ideal total sleep 7$–$9\text{ h}
    • REM ~25\%; stable cycle latency (~90\text{ min})
  • Older adults (≥60 y)
    • Shorter total sleep (~6\text{ h})
    • Marked decline in slow-wave sleep and modest drop in REM
    • ↑ Sleep latency and ↑ nocturnal awakenings

Insomnia Disorder (DSM-5)

  • Core feature: dissatisfaction with sleep quantity/quality manifested by ≥1 of:
    • Sleep-onset insomnia (difficulty initiating)
    • Sleep-maintenance insomnia (frequent awakenings)
    • Early-morning awakening (cannot return to sleep)
  • Frequency & chronicity
    • Occurs ≥3 nights/week
    • Minimum duration \ge1\text{ mo} (chronic if >3\text{ mo}; episodic <3\text{ mo}; recurrent = ≥2 episodes / yr)
  • Evaluation essentials
    • Daytime impact: fatigue, cognitive decline, mood lability, social/work impairment
    • Rule-out: other sleep d/o, medical illness, psychiatric disorder, medications, substance use
  • Sub-types
    • Psychophysiologic (learned arousal)
    • Paradoxical insomnia (sleep state misperception)
    • Inadequate sleep hygiene
    • Behavioral insomnia of childhood (sleep-onset & limit-setting types)
    • Comorbid insomnia with medical/psychiatric conditions (e.g., MDD, bipolar)
  • Treatment toolbox
    • Non-pharmacologic first-line
    • Sleep hygiene education; fixed wake time; bed reserved for sleep/sex only
    • Stimulus control & sleep-restriction therapy
    • Relaxation training (breathing, guided imagery, mindfulness)
    • Cognitive Behavioral Therapy-Insomnia (CBT-I)
    • Pharmacologic (short-term or refractory)
    • Low-dose melatonin \approx3\text{ mg} taken \sim1$–$2\text{ h} before habitual bedtime
    • Z-drugs (zolpidem, eszopiclone), short-acting benzodiazepines
    • Sedating antidepressants (trazodone, low-dose doxepin)
    • Ramelteon (melatonin receptor agonist); doxylamine / diphenhydramine PRN

Hypersomnolence Disorders

  • Definition: Excessive sleepiness despite ≥7\text{ h} of main sleep
  • Clinical presentations (one or more)
    • Recurrent sleep episodes or “lapsing into sleep” in same day
    • Prolonged main sleep >9\text{ h} that is non-restorative
    • Sleep inertia (prolonged confusion upon waking)
  • Frequency/duration for DSM-5: ≥3 times/week for ≥3 months
  • Severity index
    • Mild = 1–2 days/wk; Moderate = 3–4; Severe = 5–7
  • Special entities
    • Klein-Levin syndrome: recurrent hypersomnia + hyperphagia, hypersexuality, aggression (episodes 1–10×/yr)
  • Work-up: exclude OSA, medications (sedatives), neuro conditions, circadian rhythm disorders
  • Management
    • Behavioral: regular schedule, strategic naps, circadian entrainment
    • Pharmacologic: wake-promoters (modafinil, amphetamine salts) where available; “drug holidays” to avoid tolerance

Narcolepsy

  • Cardinal dyad: Excessive daytime sleepiness + cataplexy
    • Cataplexy = sudden bilateral loss of muscle tone triggered by emotion (laughter, surprise)
  • Other associative features: hypnagogic/hypnopompic hallucinations, sleep paralysis, fragmented nocturnal sleep
  • Pathophysiology: CSF deficiency of orexin/hypocretin (discovered via narcolepsy research → foundation for dual-orexin receptor antagonists used for insomnia)
  • PSG + Multiple Sleep Latency Test (MSLT)
    • Sleep-onset REM periods (≤8\text{ min} latency) on ≥2 naps
  • Treatment: stimulants (modafinil, methylphenidate), scheduled naps; sodium oxybate for cataplexy

Breathing-Related Sleep Disorders

  • Obstructive Sleep Apnea (OSA)
    • Repetitive collapse of upper airway → apnea/hypopnea events
    • Apnea–Hypopnea Index (AHI)
    • Diagnosis if \text{AHI}>15 events/hr or >5 + symptoms (snoring, witnessed apneas, gasping, HTN, cognitive dysfunction)
    • Daytime consequences: sleepiness, cardiometabolic risk, traffic/work accidents
    • Therapy: CPAP (gold standard), mandibular advancement device, positional therapy, weight loss, surgery (UPPP)
  • Central Sleep Apnea (CSA)
    • Ventilatory drive failure (e.g., CHF, opioids, high altitude)
    • Cheyne-Stokes respiration common
    • Treat underlying cause, adaptive servo-ventilation, acetazolamide in altitude

Circadian Rhythm Sleep-Wake Disorders

  • Intrinsic rhythm deviates from 24 h or misaligned with social schedule
    • Delayed Sleep-Phase Type (sleep >2 h later than desired)
    • Advanced Sleep-Phase Type (sleep >2 h earlier)
    • Non-24-h (“Free-running”) especially in totally blind; tau >24 h
    • Shift-Work Type; Jet-Lag (ICSD but not DSM-5)
    • Irregular sleep–wake rhythm (e.g., dementia, hospitalization)
  • Treatment principles
    • Bright-light therapy (>10{,}000\text{ lux} full-spectrum)
    • To advance phase: expose shortly after habitual wake time
    • To delay phase: expose 1–3 h before usual bedtime
    • Exogenous melatonin timed opposite to light cue
    • Chronotherapy: progressive delay (or advance) of bedtime until alignment achieved

Parasomnias (Disorders of Partial Arousal)

  • Concept: Overlap or intrusion of one sleep stage’s physiology into another → abnormal behaviors or experiences

NREM Parasomnias (first half of night)

  1. Sleep Terrors (Night Terrors)
    • Abrupt scream, autonomic arousal, inconsolable; amnesia afterwards
    • Prevalence: 1–6 % children; ♂>♀; consider frontal lobe pathology if adult onset
  2. Sleepwalking (Somnambulism)
    • Complex motor behaviors with eyes open but unresponsive; peaks age 12
  3. Sleep-related Bruxism (also may occur in REM)
  4. Sleep-related Head-Banging / Body Rocking
  5. Confusional Arousals / Sleep Talking

REM Parasomnias (second half of night)

  1. Nightmare Disorder
    • Elaborate, frightening dreams with full recall; easy awakening
  2. REM Sleep Behavior Disorder (RBD)
    • Loss of REM atonia → acting out dreams (punching, kicking)
    • Strong harbinger of neurodegeneration (α-synucleinopathies—Parkinson’s, DLB, MSA)
  3. Sleep Paralysis
    • Transitional state (wake–REM) where consciousness returns but atonia persists

Management

  • Safety measures (lock windows, remove sharp objects, bed alarms)
  • Treat precipitating factors (sleep deprivation, alcohol)
  • Clonazepam low-dose effective for RBD; melatonin 6–12 mg alt.
  • Night terrors/somnambulism: reassurance; scheduled awakenings in children

Pharmacologic & Other Interventions (Cross-Cutting)

  • Low-dose melatonin (1$–$3\text{ mg}) for circadian misalignment & mild insomnia
  • Dual–Orexin Receptor Antagonists (e.g., suvorexant, lemborexant) target wake-promoting orexin → facilitate sleep onset/maintenance
  • Sedative–hypnotics: use lowest effective dose, shortest duration; educate re: dependence & cognitive side-effects
  • Stimulants / Wake-promoters: modafinil, armodafinil, methylphenidate for narcolepsy & hypersomnolence; monitor BP, tolerance
  • CPAP adherence counseling: mask fit, humidification, desensitization sessions
  • Ethical/Practical note: Always address driving risk, occupational hazards, and comorbid psychiatric illness when treating sleep disorders