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Sleep 20102


									Sleep Physiology and Disorders

         Michael Guido III
        Assistant Professor
      Department of Neurology
       SUNY – Stony Brook
• Anatomy of sleep
  – Brief description of sleep stages
• Physiology of sleep
  – Neurotransmitters
  – Circadian rhythm
• Role of sleep
• Sleep disorders
        Neural Generators of
• Ascending reticular activating system
  – Loose collection of neurons in rostral pons and
  – Destruction results in coma
  – Receives input from somatic, visceral, special
• Posterior hypothalamus
                 Sleep Stages
• Non REM sleep              • REM sleep
  – Early in sleep cycle       –   Later in sleep cycle
  – 4 stages of increasing     –   Brain activity increases
    depth                      –   Muscle tone reduced
  – Brain activity             –   Rapid eye movements
    decreases with each        –   Dreams
     Neural Generators of NREM
•   Raphe nuclei
•   Nucleus of solitary tract
•   Reticular nuclei of thalamus
•   Anterior hypothalamus
•   Basal forebrain
Neural Generators of REM Sleep
• Nucleus reticularis pontalis oralis
  – Dorsal pons, lateral to locus cereulus
  – Responsible for atonia
     • Sends inhibitory signals to corticospinal tract
• Nucleus reticularis magnocellularis
  – Medial medulla
NREM sleep
REM sleep
• Wake
  – Catecholamines
     • Dopamine
     • Norepinephrine
  – Acetylcholine
• Slow wave sleep
  – Serotonin
• REM sleep
  – Acetylcholine
              Circadian Rhythm
• Body rhythm generated by our internal clock
   –   Suprachiasmatic nucleus of hypothalamus
   –   Sleep-wake cycle
   –   Temperature/immune system
   –   Corticosteroid and prolactin levels
   –   Feeding behavior
• Natural sleep-wake cycle lasts 25 hrs
• There are mechanisms by which we can control
  and synchronize the sleep-wake cycle to the sun
Regulation of Circadian Rhythm
• Retina
    – Melanopsin containing cells (not rods/cones)
•   Retino-hypothalamic tract
•   Suprachiasmatic nucleus
•   Paraventricular nucleus of the thalamus
•   Pineal gland
    – Via intermediolateral column of thoracic cord
    – Synapse in superior cervical ganglion
Regulation of Circadian Rhythm
• Darkness perceived by retina causes
  stimulation of suprachiasmatic nucleus
• This, in turn, stimulates pineal gland to
  release melatonin
• Melatonin then is distributed to numerous
  sites in brain, including sleep/wake
  generators, to pass along the message that it
  is dark out
          Physiologic Effects
• NREM                      • REM
  – Parasympathetic           – Sympathetic
  – Drop in pulse & BP by     – Increase in pulse, BP,
    10%                         and respirations
                              – Psychic activity
  – Respirations slow &         common
                              – 70% remember dreams
  – Minimal psychic           – Minimal muscle tone
                              – Visible muscle
  – 7% remember dreams          twitches
             Role of Sleep
• Unknown
• Both NREM and REM are needed
• Selective deprivation of either causes
  rebound for several days
• Complete sleep deprivation leads to several
  days of NREM rebound, followed by
  several days of REM rebound
            Role of Sleep
• NREM – conservation of metabolic energy
  and temperature regulation
• REM – regulates sensitivity of
  norepinephrine and 5-HT receptors; also
  involved in memory consolidation
             Sleep Disorders
• Insomnia
  – Too little sleep
• Disorders of circadian rhythm
  – Sleep at abnormal times
• Excessive daytime sleepiness
  – Too much sleep
• Parasomnia
  – Abnormal sleep
• Psychogenic
   – Sleep difficulties which interfere with daytime
   – Conditioned component
   – Anxiety associated with bedtime
   – Improved with change in routine
   – Treat with sleep hygiene and short term sedatives
• Insomnia associated with psychiatric disorders
   – Treat underlying condition
• Idiopathic
  – Lifelong inability to sleep with daytime fatigue
  – No identifiable disorder
  – Treat with long-term sedatives
• Sleep State Misperception
  – Patient overestimates sleep latency and
    underestimates sleep time
  – Treat with reassurance
   Circadian Rhythm Disorders
• Disorders of the timing of the sleep-wake
• Incongruity between the patient’s intrinsic
  cycle and the demands of society
• Patients generally do not complain of
  daytime sleepiness if allowed to follow their
  intrinsic sleep patterns
Advanced Sleep-phase Syndrome
• People who would choose to sleep early
  relative to sunset and awake early relative to
• Incidence increases with increasing age
• Sleep cycle is normal
 Delayed Sleep-phase Syndrome
• People who would choose to go to sleep late
  relative to sunset and awake late relative to
• Occurs primarily in adolescence
• Sleep cycle is normal
• Treatment is needed only if the disorder
  interferes with the quality of the patient’s
  work/school, social, or family life
• Options
  – Chronotherapy
  – Light therapy
    Hypernycthermal Syndrome
• Inability to reconcile the intrinsic 25 hour sleep-
  wake cycle to the sun’s 24 hour cycle
• Bedtime is delayed ~1 hr every day
• Have severe insomnia when trying to keep to a
  fixed schedule when native cycle is out of phase
• Seen in some blind people and patients with
  hypothalamic lesions
• No successful treatment
 Disorders of Excessive Daytime
• 30% of population report daytime sleepiness
• 5% of those have a true sleep disorder
• The others are due to self-imposed restriction of
• Diseases
   – Narcolepsy
   – Obstructive Sleep Apnea Syndrome
   – Central Sleep Apnea Syndrome
• Dissociation between wakefulness and sleep
   – Inappropriate REM sleep
• REM sleep interrupts waking rhythms resulting in
  sleep attacks
   – sudden bursts of dream-laden naps at inappropriate
• Cataplexy
   – Attacks of weakness associated with strong emotions
      • Generalized but predominant in legs
• Hypnogogic/Hypnopompic hallucinations
  – Frightening visual, auditory, or movement
    perceptions at sleep onset or just after
    awakening, which represent dreaming while
• Sleep paralysis
  – Brief paralysis during the transition from sleep
    to wake
•   Onset during puberty or young adulthood
•   Decreased REM latency
•   Short sleep latency
•   Reduced sleep efficiency
•   Associated with
    – HLA DQB1*0602
    – Decreased CSF orexin
    – Abnormalities in the hypocretin receptor 2 gene
• Treatment
  – Sleep Attacks
     • CNS stimulants
     • Naps at lunch and dinner
     • Strict and sufficient sleep schedule
  – Cataplexy, hallucinations, and sleep paralysis
     • Antidepressants
• Unexplained activity or movements during
• Three disorders
  – Sleep Terrors/Sleepwalking
  – REM Sleep Behavior Disorder
  – Restless Leg Syndrome/Periodic Limb
    Movements of Sleep
    Sleep Terrors/Sleepwalking
• Occur in childhood, males > females
• Both are caused by a sudden arousal during stage
  3/4 of NREM sleep
• Sleepwalking
   –   Do not respond to environment
   –   Exhibit automatic actions
   –   Appear confused and disoriented
   –   May injure themselves
• Sleep Terrors
   – Patient is glassy eyed and frightened with inconsolable
   – Tachycardia, tachypnea, hypertension, diaphoresis
    Sleep Terrors/Sleepwalking
• After either spell, the patient returns to
  stage 3/4 NREM sleep
• Since there is little psychic activity during
  NREM sleep, patients do not remember the
    Sleep Terrors/Sleepwalking
• Treatment
   – Protect from injury
      • Pad side of bed
      • Block stairwells
      • Remove obstacles
   – Sedatives
   – Antidepressants
• Usually benign and self-limited in all children and
  in 70% of adults
  REM Sleep Behavior Disorder
• Pathological loss of atonia normally
  accompanying REM sleep
• Due to dysfunction of the dorsal pontine
  atonia generators
• Patients act out their (usually unpleasant)
• May injure bed partner
  REM Sleep Behavior Disorder
• Must also perform full EEG to rule out nocturnal
• Usually idiopathic but may be due to:
   – Brainstem stroke
   – Neurodegenerative disorders
      • Parkinson disease
      • Lewy body disease
      • Multiple system atrophy
• Treatment
   – Protection
   – Clonazepam
• Restless leg syndrome
  – Creeping, crawling, unpleasant sensations in legs
    usually while lying awake in bed
       • Irresistible urge to move
  – Relieved by stretching, rubbing legs, walking
• Periodic Limb Movements of Sleep
  –   Stereotyped, repetitive, rhythmic leg movements
  –   Duration 0.5-5 sec at intervals 20-40 sec
  –   Occur in first half of sleep
  –   Prevalence 44%
• Usually occur together, but may be separate
• Isolated RLS may be familial
• Usually idiopathic but may de due to
   –   Anemia
   –   B12 deficiency
   –   Neuropathy
   –   Myelopathy
   –   Rheumatoid arthritis
   –   Thyroid disease
   –   Uremia (Kidney Failure)
   –   Parkinson’s disease
• Treatment
  – Dopamine agonists
    • Same as treatment for Parkinson’s Disease
  – Gabapentin
  – Clonazepam
  – Opioids

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