Narcolepsy: Why the Advanced Practice Nurse Should Care

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Narcolepsy Why the Advanced Practice Nurse
Should Care
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History of Narcolepsy

• 1870s first descriptions of narcolepsy/cataplexy
• 1920 description of post-encephalitic narcolepsy
• 1950s treatment with methylphenidate
  Description of the tetrad Description of
  idiopathic hypersomnia
• 1960s use of TCAs for cataplexy Discovery of
  SOREMs First reports of OSA
• 1970s consensus definition of narcolepsy First
  sleep nosology
• 1990 international classification of sleep
  disorders (ICSD)

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Classification of Sleep Disorders

• Dyssomnias
• Parasomnias
• Medical-psychiatric sleep disorders
• Proposed sleep disorders

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The Narcolepsy Tetrad

• Excessive daytime sleepiness (EDS)
• Cataplexy
• Hypnogogic hallucinations
• Sleep paralysis
• (Disrupted nocturnal sleep)

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Excessive Daytime Sleepiness

• Sleep attacks are neither sensitive nor
  specific markers of narcolepsy
• EDS is the sine qua non of narcolepsy
• monosymptomatic narcolepsy
• Sleepiness of narcolepsy is no different from
  other kinds of sleepiness

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Measuring Sleepiness

• Subjective scales
• Stanford sleepiness scale
• Epworth sleepiness scale
• Objective testing
• Multiple sleep latency testing (MSLT)
• Maintenance of wakefulness test (MWT)

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Cataplexy

• Episodic weakness without altered consciousness
  lasting seconds to minutes and precipitated by
  excitement or emotion
• May occur several times/day or a few times/year
• Sagging of face, eyelid, or jaw dysarthria Head
  drop Blurred vision Knee buckling Drop
  attack
• Laughter is most common precipitator
• Usually develops within a few months of EDS
  symptoms, but may develop 10-30 years later
• Do you ever feel your muscles give out, your jaw
  sag, or your vision blur when you get tickled?

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Hondas Definition of Cataplexy

• Sudden bilateral weakness involving skeletal
  muscles
• Provocation by a sudden strong wave of emotion
• Lack of impairment of consciousness and memory
• Short duration(lt a few minutes)
• Responsiveness to rx with TCAs

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Sleep Paralysis

• The inability to move for a few seconds or
  minutes during sleep onset or offset
• Probably occurs in the majority of narcoleptics
• Paralysis ends spontaneously or after mild
  sensory stimulation (shake out of it)
• How often do you feel that you are awake, but
  you just cant move?

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Hypnogogic Hallucinations

• Vivid, waking dreams that occur during
  transitions between sleep and wakefulness
• Hypnogogic _at_ sleep onset
• hypnopompic _at_ awakening
• May accompany sleep paralysis or occur
  independently
• May be tactile or auditory
• Some awareness of surroundings is preserved
• How often do you feel that you are awake, but
  dreaming when you first wake up?

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Caution!

• Sleep paralysis and hypnogogic hallucinations are
  not specific for narcolepsy!
• These symptoms can occur in 15 of otherwise
  normal persons
• often precipitated by sleep loss, schedule
  change, or alcohol
• These symptoms can occur in idiopathic hypersomnia

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Epidemiology of Narcolepsy

• MF
• 0.03-0.07 prevalence in U.S.
• Prevalence varies with ethnicity
• 1/600 in Japan
• 1/4000 in north America and Europe
• 1/500,000 in Israel
• Symptoms usually appear in teens or 20s (but
  diagnosis is generally made in mid-life)

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Pathophysiology

• Sleep-onset REM accounts for associated symptoms
  (intrusion of REM atonia)
• Impaired sleep/wake regulation is the primary
  problem

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Whats Wrong With Sleep Regulation in Narcolepsy?

• Defective monominergic regulation of cholinergic
  REM sleep mechanisms?
• Stimulants increase synaptic availability of NE
  and DA
• TCAs inhibit NE uptake
• Dopamine D1 and D2 receptor binding is increased
  in the striatum of human narcoleptic brain tissue
• Autoimmune-mediated neuronal damage?

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Genetic and Family Studies

• Older historic accounts did not control for OSA
  (which is much more common)
• Class II HLA testing shows a strong genetic link
• gt90 European/Caucasians narcoleptics with
  cataplexy have HLA-DR2 (subtype DR15) and HLA-DQ1
  (subtype DQB1-0602) antigens
• worldwide, DQB1-0602 is most strongly associated
  with narcolepsy
• Children of narcoleptics have a 1 risk (40 X
  that of general population)

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Making the Diagnosis

• History
• Physical examination
• Specific testing

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Differential Diagnosis of EDS

• Sleep deprivation
• Another sleep disorder (OSA, RLS)
• Poor sleep quality due to illness (CHF)
• Medications, drugs, toxins
• Depression
• Delayed sleep-phase syndrome
• Idiopathic hypersomnia

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Narcolepsy Vs Idiopathic Hypersomnia

• IH has considerable overlap with narcolepsy (all
  symptoms except cataplexy exist)
• Presence of DQ1 antigen is increased in IH
• IH may include misdiagnosed UARS, depression, and
  narcolepsy

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Comparison of Narcolepsy and IH

• Narcolepsy
• sleepiness
• naps are frequent
• naps are restorative
• cataplexy
• disrupted nocturnal sleep
• other associated symptoms
• never remits

• IH
• prolonged or deep sleep
• naps are not restorative
• no cataplexy
• reports of remission
• may follow viral infection, head trauma

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IN-Lab Testing for Narcolepsy

• Polysomnography (PSG)
• Multiple Sleep Latency Testing (MSLT)

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MSLT Protocol

• Consider drug testing
• Should follow an overnight PSG
• 4 or 5 naps, 2 hours apart
• naps last 20 minutes, or 15 minutes after onset
  of sleep (longest can be 35 mins)
• unit of measure
• minutes to sleep onset (stage 1)
• minutes to REM sleep onset (beginning with stage
  1)

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MSLT Findings

• Mean sleep latency
• Normal is gt 10 minutes
• 5-10 minutes is gray zone
• lt5 minutes is pathological sleepiness
• REM-onset sleep periods
• Normal is lt 2
• If there is only one, it is most likely to be in
  first nap
• One SOREM obligates you to 5th nap or second SOREM

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Diagnostic Criteria for Narcolepsy and IH

• Narcolepsy
• PSG short sleep latency
• PSG short REM sleep latency
• MSLT sleep latencylt5 minutes
• MSLT gt 2 SOREMs

• IH
• PSG short sleep latency
• PSG normal REM latency
• PSG prolonged sleep period
• MSLT sleep latencylt 10 minutes
• MSLT lt 2 SOREMs

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HLA Testing in Narcolepsy?

• Dr2-negative and DQI-negative narcolepsy patients
  exist
• Dr2-positive monozygotic twins discordant for
  narcolepsy exist
• DR2 has a 20-35 prevalence in the general
  population (gt99 of those with this antigen do
  not have narcolepsy)
• Environmental factors must play a role
• HLA-D gene neither necessary nor sufficient to
  make the diagnosis

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Management of Narcolepsy

• Patient and family education
• Sleep hygiene
• Napping
• Safety issues
• Medications

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Drug Treatment for Narcolepsy

• EDS-stimulants
• REM-associated phenomena-TCAs

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Stimulants-Schedule IV

• Pemoline / Cylert Ò
• 18.75 and 37.5 mg tablets
• up to 112.5 mg/day
• once or twice a day
• liver disease
• Modafinil / Provigil Ò
• 100 and 200 mg tablets
• up to 400 mg
• once or twice a day
• headache, nausea, insomnia

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Stimulants-Schedule II

• Methylphenidate / Ritalin Ò
• 5, 10, and 20 mg tabs/ 20 mg SR tablets
• up to 60 mg/day
• bid or tid
• nervousness, rash, insomnia, CV effects
• Dextroamphetamine/ Dexedrine Ò
• 5 mg tablets/5, 10, and 15 mg spansules
• up to 60 mg/day
• bid or tid
• CV effects, insomnia, psychosis

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Tricyclics

• Protriptyline, 5-30 mg/day
• Imipramine, 50-250 mg/day
• Nortriptyline, 50-200 mg/day
• (Fluoxetine, 20-60 mg/day)

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Drug Therapy Issues

• Abuse (not!)
• Compliance
• Drug holidays

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Social and Economic Costs

• Poor school performance
• Avoidance of social interaction
• Workplace injury
• Automobile accidents
• Interpersonal difficulty (divorce)
• Depression

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The Future of Narcolepsy

• Dysfunction of the hpocretin (AKA orexin) peptide
  system is associated with narcolepsy in dogs and
  in mice
• hypocretins affect gamma amino butyric acid
  (GABA) and glutamate secretion
• hypocretins also have a role in appetite
  stimulation
• Can we treat narcolepsy by hypocretin
  administration?

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Take Home Points

• We can do better than diagnosing narcolepsy 2
  decades after Sx appear!
• EDS, cataplexy, hallucinations, paralysis
  constitute the tetrad
• Specific in-lab diagnostic criteria are normal
  PSG, MSLT with SLlt 5 minutes, gt 2 SOREMs
• Treat with stimulants, follow with symptoms and
  Epworth
• APNs are integral to the diagnosis and treatment
  of narcolepsy!