Anatomy of the Upper Airway

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SLEEP DISORDERS
Esra Tasali, MD
March 4th, 2003
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The National Sleep Foundations 1999 Omnibus
Sleep in America Poll

• 62 of adult Americans report having sleep
  problems
• Only 4 of these adults with sleep problems are
  seeing a doctor or other health care provider for
  advice or treatment

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International Classification of Sleep Disorders

• Dyssomnias
• Excessive sleepiness or difficulty in
  initiating or maintaining sleep
• - Intrinsic sleep disorders OSA,
  narcolepsy, insomnia, RLS/PLMD
• - Extrinsic sleep disorders
• - Circadian rhythm sleep disorders
  DSPS, ASPS

• Parasomnias
• Undesirable physical phenomena predominantly
  during sleep
• - Arousal disorders sleep walking,
  sleep terrors
• - Sleep-wake transition disorders
  sleep talking
• - Parasomnias usually associated with
  REM sleep nightmares, RBD
• - Other parasomnias sleep bruxism

• Sleep Disorders Associated with Mental,
  Neurologic, and Other Medical Disorders

• Proposed Sleep Disorders

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Prevalence of Sleep Disorders
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Sleep Disordered Breathing /Sleep Apnea
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Sleep Disordered Breathing (SDB)
Definition Increasingly common chronic condition
characterized by recurrent episodes of partial or
complete upper airway obstruction during sleep
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SDB a public health concern

• Associated with increased cardiovascular
  morbidity
• - systemic hypertension, left
  ventricular hypertrophy
• - myocardial ischemia, cardiac
  arrhythmias
• - pulmonary hypertension
• - stroke

• Many have features of metabolic syndrome
• central obesity, hypertension, insulin
  resistance,
• dyslipidemia (syndrome Z )

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SDB syndrome definitions

• Obstructive sleep apnea hypopnea syndrome
• Central sleep apnea-hypopnea syndrome
• Cheyne-Stokes breathing syndrome
• Sleep hypoventilation syndrome
• Upper airway resistance syndrome
• Simple snoring

AASM Task Force, Sleep 1999
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SDB risk factors

• Obesity (particularly central), increased
  visceral fat
• Male gender, African American race
• Craniofacial abnormalities ( mandibular/maxillary
  hypoplasia )
• Increased pharyngeal soft or lymphoid tissue
  including tonsillary hypertrophy
• Increased neck circumference ( gt 40cm )
• Nasal obstruction
• Familial history
• Endocrine abnormalities hypothyroidism,
  acromegaly
• Aggravated by alcohol, sedatives, sleep
  deprivation, supine position, respiratory
  allergies, nasal congestion

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SDB symptoms
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Normal
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Obstructive Apnea

Airway obstructs
Airway opens
Exhale
Effort gradually increases
Inhale
Paradoxing
Paradoxing ends
Desaturations
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Mixed Apnea

ECG
Airway opens
No airflow
Exhale
Airflow
Respiratory effort
Inhale
no effort
Thor. Effort
Paradoxing
Abd. Effort
Paradoxing ends
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SDB Diagnostic criteria (AASM Task Force, Sleep
1999)

• Apnea-hypopnea index (AHI) number of apneas and
  hyponeas per hour of sleep
• Respiratory events should last at least 10 sec
  in duration

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Hypoxic stress / Sympathetic overactivity
Somers et al, J Clin Invest 1995
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State of sleep debt
Sleep Disordered Breathing
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SDB Treatment of choice CPAP
General measures - Weight reduction -
Sleep hygiene - Positional therapy -
Avoiding alcohol, smoking
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SDB Alternative treatments
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Narcolepsy
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The narcolepsy tetrad

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

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Excessive daytime sleepiness (EDS)

• Continuous subjective feeling of sleepiness
  or irresistible sleep attacks

• Duration of sleep attacks is usually lt 20 min, a
  refractory period of 1 to several hours before
  the next episode occurs

• Usually they wake up feeling refreshed

• Not only during passive activities but also in
  situations when the subject is fully involved in
  a task

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Differential diagnosis of EDS

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

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Cataplexy

• Sudden bilateral loss of muscle tone, provoked by
  strong emotions, most typically by laughter

• Jaw sags, head falls forward, arms drop to the
  side, knees unlock or buckle

• Consciousness is preserved, eye movements and
  respiration are not compromised

• Few seconds to a couple of minutes

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Hypnagogic hallucinations

• Vivid dream like experiences that occur during
  sleep onset

• Usually content is bizarre and frightening

• Visual imagery is predominant
• Auditory and tactile components are present

• Lasts less than 10 minutes
• May occur with sleep paralysis

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Sleep Paralysis

• Inability to move the limbs, to open the eyes, to
  speak or even to breath deeply

• Occurs either on falling asleep or awakening and
  the patient is fully aware of the condition

• People are usually terrified during an attack,
  particularly the first time

• Up to 10 min and ends spontaneously or after mild
  sensory stimulation ( shake out of it)

• Can occur in 15 of otherwise normal persons,
  with familial clustering and association with
  sleep loss

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Other associated features

• Automatic behavior

• Memory disturbances

• Tiredness or fatigue

• REM behavior disorder (RBD)

• Depression

• Obesity

• Hypothyroidism

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Evaluation of sleepiness

• Subjective scales
• - Stanford Sleepiness Scale
• - Epworth Sleepiness Scale
• Objective testing
• - Multiple Sleep Latency Test (MSLT)
• - Maintenance of Wakefulness Test (MWT)

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Multiple Sleep Latency Test (MSLT)
Roth T Roehrs T, 2000
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PSG and MSLT findings in narcolepsy

• PSG Sleep latency lt10 min
• PSG REM latency lt 20 min
• MSLT mean sleep latency lt 5min
• MSLT ? 2 sleep onset REM periods

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Narcolepsy diagnostic criteria (ICSD)

• Recurrent daytime naps or lapses into sleep
  occurs almost daily for at least 3 months
• cataplexy

Excessive sleepiness or sudden muscle
weakness Associated features sleep paralysis,
hypogogic hallucinations, automatic behaviors,
disrupted major sleep episode ? 1 PSG or
MSLT findings
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Narcolepsy pathophysiology

• REM dysregulation inappropriate intrusions of
  REM sleep into wakefulness

• HLA-DQB10602 (gt 90 with narcolepsy-cataplexy )
  is the best HLA marker

• Recent studies have shown that narcolepsy with
  cataplexy is usually caused (gt90) by the lack of
  two related brain chemicals called "hypocretin-1"
  and "hypocretin-2"

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What are hypocretin (orexin) molecules?

• Were found on hypotalamus and some resemblance to
  gut secretin
• Also found to stimulate food intake orexin A,
  orexin B

• Small neuronal group with dense projections to
  cortex and to brain stem

• Excitatory stimulus to locus coeruleus

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The discovery of the hypocretin/orexin peptides
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Hypocretin/orexin in human narcoleptics

• Undetectable levels of hypocretin in CSF
• ( Lancet, 2000)
• Absence of hypocretin neurons in the hypotalamus
  by histopathologic examination of brains of
  narcoleptic patients
• ( Nature Med, 2000 Neuron, 2000)

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Narcolepsy Treatment

• Nonpharmacologic
• - Regular timing of nocturnal sleep, avoiding
  shifts
• - Avoid heavy meals and alcohol intake
• - Scheduled naps 15 min at lunch time and at
  530pm

• Pharmacologic
• For sleepiness Stimulants ( Modafinil,
  Methylphenidate )
• For cataplexy TCA, SSRI , sodium oxybate
  (Xyrem)

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Restless Leg Syndrome / Periodic Limb Movement
Disorder
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Restless Leg Syndrome Disagreeable leg
sensations that usually occur prior to sleep
onset and cause almost an irresistible urge to
move the legs
Periodic Limb Movement Disorder Periodic
episodes of repetitive and highly stereotyped
limb movements that occur during sleep
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Pathogenesis of RLS

• Primary or idiopathic
• - no identifiable predisposing factor
• - tends to occur in families ( genetic?)

• Secondary
• - Iron deficiency anemia
• - Uremia ( 15-40 of dialysis patients)
• - Pregnancy
• - Neuropathies
• - Drug induced (TCA, SSRI, lithium,
  neuroleptics)
• - Diabetes, Parkinson disease, Rheumatoid
  Arthritis

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RLS essential features (IRLSSG criteria)

• Desire to move the limbs usually associated with
  paresthesias or dysesthesias

• Motor restlessness

• Symptoms worse at rest partially relieved by
  activity

• Symptoms worse in the evening or at night

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Uncomfortable Sensations

• Creepy, crawly, tingly
• Like worms or bugs crawling under the skin
• Painful, burning, achy, itchy
• Like water running over the skin
• Sometimes indescribable

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RLS additional common features

• Sleep disturbance and its consequences (EDS)

• Involuntary movements while awake and at rest,
  disappearing when patient gets up to walk

• Usually chronic course but spontaneous remissions
  relapses may occur

• Circadian variability symptoms typically peak
  between midnight and 4 am

• Periodic limb movement disorder (PLMD)

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Management of RLS
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Insomnia
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Insomnia
The perception of insufficient, disturbed or
non restorative sleep

• Medical
• Psychiatric
• Pharmacologic
• Primary sleep disorder
• Genetic (Fatal Familial Insomnia)
• Tobacco/ Alcohol

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Transient Insomnia (Short term )

• Environment related ( noise,temperature,sleep
  surface, sleep position, altitude )
• Stress-related
• Sleep schedule related ( jet lag, shift work)
• Drug discontinuation or initiation

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• Primary Insomnia

• Psychophysiological insomnia
• Sleep-state misperception
• Idiopathic insomnia

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Insomnia Management

• Behavioral therapy
• - Relaxation techniques
• - Sleep restriction
• - Stimulus control
• Sleep Hygiene
• Medications

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Circadian Disorders of Sleep-Wake Cycle
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Sleep wake cycle in circadian sleep phase
disorders
CLOCK TIME
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Advanced sleep phase syndrome
Typical sleep phase
Delayed sleep phase syndrome
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• Delayed Sleep Phase Syndrome (DSPS)
• - onset is often during adolescence
• - poor school or job performance
• - may report a history of prolonged
  sedative-hypnotic use, bedtime use of alcohol,
  behavioral interventions, psychotherapy,
  depression, personality disorders

• Advanced Sleep Phase Syndrome (ASPS)
• - mostly older than 50 years
• - genetic studies

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Management

• Chronotherapy
• Successive advancement or delay of sleep times
  by 3h daily over a 5-6 day period until the
  desired sleep time is achieved

• Light therapy

• Melatonin

• Physical exercise

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Light Therapy

• Light at sunset (dusk)/ light at the end of the
  day
• - clock slows down
• - phase delay

• Light at sunrise (dawn)/ light at the beginning
  of the day
• - clock speeds up
• - phase advance

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Behavioral Parasomnias
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• Wake-to-sleep transition disorders
• - Intensified Sleep Starts (Hypnic Jerks)
• - Rhythmic Movement Disorder (Jactatio Capitis
  Nocturna)

NREM sleep disorders (SWS arousal disorders) -
Sleep Walking (Somnambulism) - Sleep Terrors
REM sleep disorders - Nightmares (Terrifying
Dreams ) - REM sleep behavior disorder (RBD)
Light sleep stage (stage 1,2) disorders - Sleep
Talking - Bruxism
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Intensified Sleep Starts (Hypnic Jerks)

• Otherwise normal physiological event, often
  self-limiting

• Principally involve legs

• Usually are brief muscle jerks at sleep onset

• The intensity of the contraction may cause an
  abrupt expiratory cry

• Sometimes related to intake of stimulants
  (caffeine, nicotine, intense evening exercise,
  stress)

• Tx avoidance of precipitating factors or
  irregular sleep schedule

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Rhythmic Movement Disorder (Jactatio Capitis
Nocturna)

• Repetitive stereotyped movements involving large
  body areas (head banging, body rocking)
• Typically just before sleep onset
• Common in infants and young children who are
  otherwise normal
• Male predominance
• Self limiting, disappears before late childhood
• Parents need to be reassured restraining is
  generally ineffective, padding in bed area or
  protective helmet may be useful

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Sleep Walking (Somnambulism)

• Without awakening, exhibit complex automatic
  behaviors
• Child crawling into parents bed, adult trying to
  prepare meals,mumbling even comprehensible
  speech,rarely, eating or aggression
• Communication with them is difficult or
  impossible
• Typically 1-5 min duration
• Commonly in children aged 4-6 years, in adults
  with strong family history
• Parents need to be reassured, frequently
  disappears during adolescence, avoidance of
  precipitating factors, minimize injury,
  clonazepam, TCA

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REM Sleep Behavior Disorder (RBD)

• Explosive, violent movements that appear to be
  dream enactment with markedly increased muscle
  tone during REM sleep
• May reappear in cyclic fashion (every 90 min)
• Injury to self or bed partner is common
• Violent nocturnal behavior is typically
  discordant with dreamers daytime personality
• Elderly with history of dementia, SAH, Parkinson
  disease, MS, chronic alcoholism, idiopathic (60
  )
• Treatment is with medication clonazepam

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Stage REM
EOG 1
EOG 2
EEG
EEG
EMG
ECG

• EEG Low voltage, mixed frequency, Sawtooth
  waves, theta (3-7cps)
  activity
• EOG Phasic rapid eye movements
• Submental EMG lowest tonic activity, phasic
  twiches

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REM behavior sleep disorder in a 64-year old
man