| 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% |
Process S (Homeostatic): Sleep pressure builds during waking hours. Mediated by adenosine accumulation. Caffeine blocks adenosine receptors. Determines NREM sleep intensity (delta power).
Process C (Circadian): SCN-driven ~24h rhythm independent of sleep debt. Controls timing of sleep propensity. Peaks of alertness in late morning and early evening (“forbidden zone for sleep”).
The interaction: Process S builds during wake, Process C gates when sleep can occur. Mismatch between the two processes leads to jet lag and shift work problems.
Sleep spindles + K-complexes = N2. Sleep spindles generated by thalamic reticular nucleus. K-complexes are cortical responses to stimuli. N2 is the most abundant stage (~50%).
| 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 |
| Structure | Neurotransmitter | Function |
|---|---|---|
| VLPO | GABA, Galanin | Inhibits wake centers; “sleep switch” |
| Adenosine | — | Builds during wake; caffeine blocks receptors |
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.
Orexin/hypocretin from lateral hypothalamus stabilizes wakefulness. Loss = narcolepsy type 1. CSF orexin <90 pg/mL is diagnostic. Orexin receptor antagonists (suvorexant) treat insomnia.
| 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 |
Delayed = give melatonin in evening + morning light. Advanced = opposite. Non-24-hour rhythm is common in totally blind patients due to loss of light entrainment.
| 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:
Treatment:
Cataplexy is pathognomonic for narcolepsy type 1. Triggered by strong emotions (laughter, surprise). Consciousness preserved. CSF orexin <90 pg/mL is diagnostic even without MSLT.
| 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) |
RBD is a prodrome of α-synucleinopathies. New RBD in elderly = high risk for PD, DLB, MSA. Can precede motor symptoms by years. Also seen with antidepressants (especially SSRIs, SNRIs).
| 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):
| Drug Class | Mechanism | Examples | Clinical Notes |
|---|---|---|---|
| Benzodiazepines | GABA-A positive allosteric modulator | Clonazepam, temazepam | ↑ N2, ↓ N3 and REM; tolerance and dependence risk |
| Z-drugs | Selective GABA-A (α1 subunit) | Zolpidem, zaleplon, eszopiclone | Less effect on sleep architecture than benzos; complex sleep behaviors |
| Melatonin agonists | MT1/MT2 receptor agonists | Ramelteon, tasimelteon | Circadian rhythm disorders; Non-24-hr (tasimelteon) |
| Orexin antagonists (DORAs) | Block orexin receptors | Suvorexant, lemborexant | Promotes sleep without GABA; lower abuse potential |
| Antihistamines | H1 receptor blockade | Diphenhydramine, doxepin (low dose) | Sedation; low-dose doxepin FDA-approved for insomnia maintenance |
| Gabapentinoids | α2δ calcium channel | Gabapentin, pregabalin | ↑ Slow wave sleep; useful in RLS, comorbid pain |
| Sodium oxybate | GABA-B agonist | Xyrem, Xywav | Narcolepsy (consolidates sleep, ↑ N3, improves cataplexy); controlled substance |
Z-drugs (zolpidem) target α1 subunit of GABA-A → sedation with less anxiolytic/muscle relaxant effect than benzos. Both suppress N3 (deep sleep). Sodium oxybate is unique in INCREASING N3.
| Condition | Sleep Disturbance | Key Points |
|---|---|---|
| Parkinson’s disease | RBD, insomnia, EDS, sleep fragmentation | RBD may precede motor symptoms by >10 years; nocturnal OFF symptoms; restless legs common |
| Alzheimer’s/Dementia | Sundowning, circadian disruption, ↓ slow wave sleep | Loss of cholinergic neurons affects sleep-wake cycling; ↓ melatonin production |
| Epilepsy | Sleep deprivation triggers seizures; seizures disrupt sleep; NREM activates IEDs | Some epilepsies are sleep-related (Rolandic, ESES, frontal lobe epilepsy); AEDs affect sleep architecture |
| Multiple Sclerosis | Fatigue, RLS, OSA, insomnia | Central fatigue from demyelination; hypothalamic lesions can cause narcolepsy-like symptoms |
| Stroke | Central sleep apnea, insomnia, circadian disruption | Brainstem strokes can cause central apnea; sleep disorders impair recovery |
| Fatal Familial Insomnia | Progressive insomnia → autonomic dysfunction → death | Prion disease affecting thalamus; no treatment; very rare but board-favorite |
Fatal familial insomnia = prion disease of the thalamus (mediodorsal and anterior nuclei). Progressive total insomnia, dysautonomia, and death. Autosomal dominant mutation in PRNP gene.
| 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 |
| 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 |
