The neurobiological substrate of hypersomnia

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The neurobiological substrate of hypersomnia

• Waldemar Szelenberger
• Medical University of Warsaw

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• 
  (Guilleminault 2001)
• Syndromes of sleepiness
• Insufficient sleep
• Fragmented sleep
• Sleep-related breathing disorders
• Periodic limb movements
• Other (i.e. pain, asthma, urinary
  dysfunction)
• Primary disorders of alertness
• Narcolepsy
• Idiopathic hypersomnia
• Kleine-Levin syndrome
• Circadian disorders
• Delayed sleep phase syndrome
• Advanced sleep phase syndrome
• Nervous system disorders
• Psychiatric disorders
• Atypical depression, bipolar depression
• Drugs

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(Zeman et al 2004) Brain areas
subserving sleep and waking
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F51.1 Nonorganic hypersomnia

• A complaint of excessive daytime sleepiness or
  sleep attacks or prolonged transition to the
  fully aroused state
• This sleep disturbance occurs nearly every day
  for at least one month or recurrently for shorter
  periods of time and causes marked distress
• Absence of auxiliary symptoms of narcolepsy or
  of clinical evidence for sleep apnoea
• Absence of any known causative organic factor

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Diagnostic criteria of nonorganic hypersomnia
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Billiard (2001) Prevalence of idiopathic
hypersomnia as of diagnoses of narcolepsy

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Patients admitted to Medical University Sleep
Disorders Clinic in Warsaw (2003 2004)
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Patients with hypersomnia admitted to Medical
University Sleep Disorders Clinic in Warsaw (2003
2004)
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(Guilleminault 2000)Clinical differences between
idiopathic hypersomnia and atypical depression

• Idiopathic hypersomnia
• Long nonrefreshing naps
• Normal activity between naps
• Moderately elevated depression scores
• Sleep latency
• in MSLT lt 5 min

• Atypical depression
• Feeling sleepiness without napping
• Long time in bed (clinophilia)
• Elevated depression scores
• Sleep latency
• in MSLT 8-12 min

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• 
  
  (Vgontzas et al 2000)Sleep PSG differences
  between primary hypersomnia and hypersomnia due
  to mental disorder (DSM-IV)
• Longer sleep latency
• Shorter sleep time
• Longer total waking time
• Less REM periods
• Shorter sleep latency during day naps

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(Sforza et al
2000) Delta power density in controls and
patients with idiopathic hypersomnia
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Case of dysthymia and nonorganic
hypersomnia Daytime sleepiness from high school.
Naps became longer and nonrefreshing. Stimulants
were without effect. Referred to our clinic
because of danger of loosing job, when she fell
asleep at the stage during spectacle. Considerabl
e subjective improvement during treatment with
reboxetine. Diminished sleepiness evenings
allowed her for successful work.
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Case of dysthymia and nonorganic
hypersomnia Sleep recordings
August 2004 January 2005 SL
11.3 5.7
TST 412.7
359.0 WASO 11.6
69.7 SWS 18.1 12.9 MSLT
1 7.0 5.0 MSLT 2 5.7 2.3 MSLT
3 5.7 5.3 MSLT 4 5.0 7.0 MSLT 5 7.0
--
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Recurrent hypersomnia or Kleine-Levin syndrome
(ICSD) Recurrent episodes of hypersomnia lasting
several days to several weeks, which appear twice
or more a year. When it is accompanied by binge
eating and hypersexuality, typical Kleine-Levin
syndrome is diagnosed.
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Reported cases of Kleine-Levin syndrome till 2005
Total number- 236
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• Case of recurrent hypersomnia
• Complaints of periodic sleep attack lasting up to
  6 days and repeating with 6 weeks intervals
• Beginning of the illness at the age of 17 years
• No other mental/medical disorders
• Normal MRI, EEG, blood tests
• IQ124, normal neuropsychological tests
• MMPI passive-aggressive traits, hopelessness in
  projective tests
• Several trials of treatment with stimulants and
  antidepressives without effect
• From 13 years disability pension

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Patient with recurrent hypersomnia 7-day of
subjective activity monitoring - and actigraphy
-
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Patient with recurrent hypersomnia 13 hours of
sleep recording
Sleep Latency - 37 min Total Sleep Time 366
min REM Latency 101 min
Slow Wave Sleep 14.3 Waking After Sleep Onset
216 min Waking After Final Awakening 186 min
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Delta power spectrum in patient with recurrent
hypersomnia
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EEG during last 150 min of sleep recording
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(Roth et al 1972) Incidences
of hypersomnia with sleep drunkeness in three
families
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HLA antigens in idiopathic hypersomnia

• High frequency
• Poirier et al (1986)
• Mignot et al (2002)

• Low frequency
• Honda et al (1986)
• Kanbayashi et al (2002)
• Bassetti et al (2003)
• Dauvilliers et al (2003)
• Ebrahim et al (2003)

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CSF hypocretin-1 in idiopathic hypersomnia

• Low
• Ebrahim et al (2003)

• Normal
• Kanbayashi et al (2002)
• Bassetti et al (2003)
• Dauvilliers et al (2003)

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Conclusions

• Idiopathic hypersomnia is a syndrome arising from
  many causes, with no specific biological findings
• Ratio of idiopathic hypersomnia/narcolepsy
  systematically decreases due to improved
  diagnoses
• It can be expected that in some cases specific
  organic pathology will be found and other will be
  included to the affective spectrum disorders