Narcolepsy, Parasomnias & Circadian Rhythm Disorders

Narcolepsy: Clinical Picture and Mechanism

The mandatory symptom. Narcolepsy is defined by excessive daytime sleepiness: an irrepressible need to sleep, or unplanned lapses into sleep, at least 3 times a week for 3 months or more. Onset is usually in adolescence or early adulthood. A short nap leaves the patient refreshed for a while, unlike idiopathic hypersomnia, where naps are long and unrefreshing and waking brings "sleep drunkenness."

REM intrusion phenomena. The other features are fragments of REM sleep appearing during wakefulness:

• Cataplexy: sudden bilateral loss of tone triggered by strong emotion (laughter above all, also surprise or anger), ranging from jaw sag or head drop to collapse; lasts seconds to 2 minutes with preserved awareness and briefly absent reflexes. It is essentially pathognomonic of narcolepsy type 1.
• Hypnagogic (sleep-onset) and hypnopompic (on-waking) hallucinations.
• Sleep paralysis: brief inability to move while falling asleep or waking, with full awareness.
• Fragmented night sleep despite the daytime sleepiness.

Mechanism. Type 1 results from immune-mediated loss of hypocretin (orexin) neurons in the lateral hypothalamus, which normally stabilize wakefulness and keep REM from spilling into waking. More than 90% of type 1 patients carry HLA-DQB1*06:02, and cases rose after the 2009 H1N1 pandemic and the Pandemrix vaccine campaign in Europe.

Diagnosis

Exclude common causes first. Insufficient sleep is the most frequent cause of daytime sleepiness, followed by obstructive sleep apnea, sedating drugs, depression, and circadian misalignment.

A sleep-onset REM period on the preceding night's polysomnogram can count as one of the two SOREMPs required on the MSLT.

Treating Narcolepsy

Behavioral foundation. A fixed sleep–wake schedule, one or two planned 15–20-minute naps, avoidance of alcohol and sedatives, and counseling about drowsy driving. Drugs are chosen by the dominant symptom.

Sodium oxybate is taken at bedtime and again 2.5–4 hours later and carries a boxed warning for respiratory depression and misuse: never combine it with alcohol, benzodiazepines, or opioids. A lower-sodium mixed-salt form suits patients with hypertension or heart failure.

Parasomnias

Timing reveals the stage. Slow-wave (N3) sleep is concentrated in the first third of the night, while REM periods lengthen toward morning. Early-night events with amnesia suggest an NREM arousal disorder; early-morning events with vivid recall suggest REM.

NREM arousal disorders. Sleepwalking, sleep terrors, and confusional arousals are partial awakenings from N3: the patient is hard to rouse, confused, and amnestic. A sleep terror is a scream with tachycardia, sweating, and dilated pupils in an inconsolable child. These are common in school-age children, often familial, and usually outgrown by adolescence. Triggers include sleep deprivation, fever, stress, OSA, and zolpidem. Management is reassurance and a safe home (locked or alarmed doors and windows, no top bunk, hazards removed), regular sufficient sleep, and guiding the child back to bed rather than forcing awakening. Scheduled awakenings 15–30 minutes before a predictable episode can break the cycle; clonazepam is reserved for dangerous or refractory cases. Video polysomnography is needed only for atypical events (stereotyped, several per night, adult onset, injury) to exclude nocturnal seizures.

REM sleep behavior disorder (RBD). Loss of normal REM atonia lets patients, typically men older than 50, act out vivid, often violent dreams in the second half of the night; they wake quickly and recount a dream that matches the movements. Diagnosis requires video polysomnography showing REM sleep without atonia. Idiopathic RBD is a prodrome of α-synucleinopathy: most patients develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy within 10–15 years. SSRIs, SNRIs, TCAs, mirtazapine, and narcolepsy cause secondary RBD. Treat with bedroom safety plus melatonin (preferred in older adults) or clonazepam (sedation, falls, worsened sleep apnea).

Nightmare disorder. Repeated, well-remembered, dysphoric REM dreams late in the night; the dreamer wakes rapidly, fully oriented and consolable. It is common in PTSD. First-line is imagery rehearsal therapy (rewriting the dream and rehearsing the new version while awake); prazosin, an α1 blocker, may be used for PTSD-associated nightmares (evidence is mixed) but can cause first-dose orthostatic hypotension.

Circadian Rhythm Sleep–Wake Disorders

The clock. The suprachiasmatic nucleus of the hypothalamus is entrained mainly by light via the retinohypothalamic tract; the pineal gland secretes melatonin in darkness. Morning light advances the clock, evening light delays it, and evening melatonin advances it. Sleep is normal when these patients follow their own schedule, so treatment is timed light, melatonin, and a fixed wake time rather than hypnotics.

• Delayed phase: adolescents who cannot fall asleep until about 2–3 am or wake for school but sleep well on weekends. Give low-dose melatonin in the early evening and bright light on waking.
• Advanced phase: older adults sleepy by 7–8 pm and awake at 3–4 am. Give bright light in the evening; a rare familial form involves PER2 mutations.
• Shift work disorder: bright light during the night shift, dark glasses on the commute home, blackout curtains, melatonin before daytime sleep, and a pre-shift nap; modafinil or armodafinil is approved for the sleepiness.
• Jet lag: eastward travel requires a phase advance and is harder; melatonin at the destination bedtime helps, and adaptation otherwise takes about 1 day per time zone.
• Non-24-hour rhythm: totally blind people lack light entrainment and drift later each day; tasimelteon, a melatonin receptor agonist, re-entrains them.