SLEEP DISORDERS 2007 Fidaa Shaib, MD, DABSM,CBSM

Assistant Professor of MedicineDirector, the Center for Sleep and Wake Disorders

Division of Pulmonary, Critical Care, and Sleep MedicineUniversity of Louisville

“Sleep is the intermediate state between wakefulness and death; wakefulness being regarded as the active state of all the animal and intellectual function , and death as that of their total suspension”

MacNish. The philosophy of sleep

European Philosophy

An active and prescient perception of sleepwith the concept of human life being spent

inthree states: (1) Wakefulness (2) Dreaming sleep(3) Dreamless sleep

Hindu Philosophy

“Sleep is a dynamic behavior. Not simply the absence of waking, sleep is a special activity of the brain, controlled by elaborate and precise mechanisms”

Hobson, Sleep.

Non Rapid Eye Movement Sleep (NREM):

a relatively inactive yet actively regulating brain in a movable body

Rapid Eye Movement Sleep (REM): a highly activated brain in a paralyzed

body

The Duality of Sleep

Fragmented mental activity Relative autonomic stability and functional

coordination between respiration, pumping action of the heart, and maintenance of arterial blood pressure

Non Rapid Eye Movement Sleep (NREM) Stages 1,2,3,4

Stage I (5-10%) : a transition between wake and sleep. It occurs upon falling asleep and during brief arousal periods within sleep.

Stage II (40-50% ): occurs throughout the sleep period

Stages III and IV “delta sleep” (40-50%) mostly in the first third of the night.

Non Rapid Eye Movement Sleep (NREM) Stages 1,2,3,4

20-25%

2 Stages: phasic and tonic

Cerebral activation with active motor inhibition

↠Dreaming and very organized complex brain activity

Rapid Eye Movement Sleep (REM)

The 2 Process Model of Sleep:Process C and Process S

Circadian pacemaker

Sleep debt

Sleepiness and alertnessProcess C: Circadian

A mechanism defining the alternation of periods with high and low sleep propensity

Absolutely independent from the duration of precedent wake or sleep

◦ The Suprachiasmatic nuclei◦ Light and Melatonin

Sleepiness and alertnessProcess S: Sleep homeostasis

Describing the sleep-pressure's course during wake-time and its lowering during sleep;

  Accumulates during wakefulness and eliminated during slow wave

sleep◦ Adenosine / antagonist Caffeine

Max alertness

Max sleepiness

Normal sleep Adult: 8-8.4 hours is considered fully

restorative Insufficient sleep : most common cause

of excessive daytime sleepiness Alternating NREM/REM sleep

Whitehall II Cohort:

◦ Decrease in Sleep Duration: affects all cause mortality via increase in cardiovascular deaths

◦ Increase in Sleep Duration: affects overall mortality via increase in non-cardiovascular deaths

Sleep Duration and Mortality

A Prospective Study of Change in Sleep Duration: Associations with Mortality in the Whitehall II Cohort

et al. Sleep Dec 2007

First National Health and Nutrition Examination Survey (NAHNES I) ◦ 8992 subjects, 32-86 yr◦ 8-10 period follow up

< 5 Hrs : OR = 1.47(1.03-2.09) > 9 hrs : OR = 1.52(1.02-2.18)

More likely to have incident Diabetes

Sleep Duration and Diabetes

Sleep Disorders Charles Dickens Pickwick Papers

1836 Joe, the fat boy

◦ Excessively sleepy, loud snorer

◦ ? Right heart failure

(young dropsy)

Dyssomnias: primary disorders of initiating or maintaining sleep or of excessive sleepiness and are characterized by a disturbance in the amount, quality, or timing of sleep

Parasominas: disorders that intrude into the sleep process and create disruptive sleep-related events (NREM and REM)

Sleep disorders associated with neurologic, mental, or medical disorders

Proposed sleep disorders

Sleep Disorders

Difficulties at sleep onset

Problems during sleep that cause disruption or awakening

Inability to awaken from sleep at desired time

Daytime sleepiness

Patient presentation

Focused History: BEARS

◦ Bed time, sleep time, wake up time

◦ Excessive daytime sleepiness

◦ Awakenings, restless sleep

◦ Regularity

◦ Snoring, choking, witnessed apneas, morning headaches

Plus abnormal behavior

Medical History

Behavioral/Psychiatric History

Alcohol and Drugs

Evaluation

Sleep Quality Profile (SQP) Berlin Questionnaire: snoring behavior, daytime

sleepiness, obesity, and hypertension

Screening Tools

Prevalence of Symptoms and Risk of Sleep Apnea in the US Population Results From the National Sleep Foundation Sleep in America 2005 PollChest - Volume 130, Issue 3 (September 2006)  - 

Initial Clinic Evaluation ◦ Epworth Sleepiness Scale (ESS) (>10 suggest and >12 confirms chronic

sleepiness )

◦ Beck depression inventory (BDI)

◦ RLS severity score

Evaluation Tools

Nocturnal PolySomnoGram (NPSG) “ Sleep Study”

Multiple Sleep Latency Test (MSLT)

Maintenance of Wakefulness Test (MWT)

Actigraphy

Sleep Diary

Evaluation Tools

51 yo woman with episodic disorientation and memory loss◦ Neurology workup with normal MRI / Angiogram◦ PMH: HTN, migraine headaches, 100 lb weight

gain and possible fibromyalgia◦ Meds: acetazolamide, lorazepam, atenolol and

paroxetine

Case#1

Sleep history reveals EDS, restless sleep, snoring, urinary incontinence, naps are non-refreshing

BMI 36.5 Large tongue, Mallampati 3 ESS= 16

Case#1

Common:◦ Snoring*

Excessive daytime sleepiness*Sudden arousals with choking*Non-refreshing sleepFatigueLethargyDepressionMorning dry throatMorning headachesImpotenceEnuresisNocturnal sweating

Nocturia

Women:◦ Insomnia◦ Palpitation◦ LE edema

Sleep Disordered Breathing ( SDB)

Physical exam◦ BMI ( >25

overwieght and > 30 obese)

◦ Neck circumference (>16 cm)

◦ Anatomy of the oropharynx

◦ Alignment of the Jaw

Evaluation

Snoring

Upper Airway Resistance Syndrome (UARS) SDB characterized by Obstructive hypopneas

Obstructive Sleep Apnea

Sleep Disordered Breathing ( SDB)

Upper Airway Resistance Syndrome

SDB characterized by Obstructive hypopneas

Obstructive Sleep Apnea

Prevalence in the United States estimated to be between 5% and 10%

1993 Wisconsin Sleep Cohort: 2% of women and 4% of men (EDS and AHI>5)

NSFSleep in America 2005 Poll: ◦ 9% of women and 24% of men had an AHI of ≥ 5

events per hour, ◦ 44% of men and 28% of women were habitual

snorers. Only 10% of the population has been adequately

screened for appropriate diagnosis. Maximum prevalence of OSA occurs between

the fifth and seventh decades

Obstructive Sleep Apnea

Prevalence of chronic illnesses among individuals with high-risk Berlin questionnaire score :

Prevalence of Symptoms and Risk of Sleep Apnea in the US Population Results From the National Sleep Foundation Sleep in America 2005 PollChest - Volume 130, Issue 3 (September 2006

Consequences

Daytime somnolence resulting in significant impairment of functional capacity and reduced quality of life

Decreased cognitive function Increased risk for depression Loss in work productivity Increased risk of automobile crashes

OSA: Consequences

MS Hypertension0

10

20

30

40

50

60

70

80

90

Prevalence of Metabolic Syndrome ( MS) and Hypertension in Patients

with or without OSA

OSANo OSA

Relationship of metabolic syndrome and obstructive sleep apnea.J Clin Sleep Med. 2007 Aug 15;3(5):467

Pathophysiologic pathways in the development of cardiovascular disease in obstructive sleep apnea

Pathophysiologic Mechanisms of Cardiovascular Disease in Obstructive Sleep ApneaSleep Medicine Clinics - Volume 2, Issue 4 (December 2007

SDB: Treatment

Primary Therapy Alternative Therapy

Positive Airway Pressure

Weight loss

Behavioral therapies

Avoidance of CNS Depressants

Sleep hygiene practices

Mandibular repositioning devices

Uvulopharyngopalatoplasty (UPPP): 40-50% success rate

Tonsillectomy/adenoidectomy

Tracheotomy: 100 % cure rate

Jaw advancement techniques:97%

Pickwickian Syndrome Obesity Hypoventilation Syndrome

BMI>30 Awake PCO2>45 A. Obstructive sleep apnea-

hypopnea syndrome B. Sleep hypoventilation

syndrome: 1. An increase in PaCO2 >10 mm Hg from awake supine values

2. Oxygen desaturation not explained by apneic or hypopneic events

C. A combination of obstructive sleep apnea-hypopnea events and sleep hypoventilation

CPAP/ tracheotomy: if associated with SDB BiPAP: if Hypoventilation alone Progesterone: improve ventilation but does

not improve apnea frequency or symptoms of sleepiness.

Treatment:

65 yo man with history of insomnia, non-refreshing sleep, and irregular breathing with witnessed apneas per wife

PMH: HTN, CHF with EF 30% Meds: Lasix, digoxin, Lisinopril NPSG

Case#2

Hypercapnic central apnea •Central congenital hypoventilation

• Arnold-Chiarri malformation• Muscular dystrophy• Amyotrophic lateral sclerosis• Postpolio syndrome• Kyphoscoliosis

Central Sleep Apnea

Nonhypercapnic central apnea • Central apnea of sleep onset

• Periodic breathing at high altitude

• Congestive heart failure• Acromegaly• Hypothyroidism• Chronic renal failure• Idiopathic CSA

Central Sleep Apnea

Javaheri et al :◦ 51% of male CHF patients had sleep-

disordered breathing 40% had CSA 11% had obstructive apnea

Risk factors for CSA:◦ Male gender◦ Atrial fibrillation◦ Age greater than 60 years◦ Hypocapnia (PCO2<38 mm Hg) during

wakefulness

Central sleep apnea and CHF

Survival of patients with heart failure, with or without central sleep apnea, after accounting for all confounders

Central sleep apnea, right ventricular dysfunction, and low diastolic blood pressure are predictors of mortality in systolic heart failure. J Am Coll Cardiol 2007;49:2028

Nasal continuous positive airway pressure (CPAP):◦ Combined OSA/CSA◦ CSA in supine position ◦ CSA in CHF: Canadian Positive Airway

Pressure (CANPAP) trial: transplant-free survival curve favored the control group

NIPPV: hypercapnic central apnea/hypopnea and nocturnal ventilatory failure

CSA Treatment

Pharmacologic:◦ Acetazolamide◦ Theophylline ameliorates Cheyne-Stokes

respiration (CSR) in patients who have CHF Supplemental O2: idiopathic CSA and

CHF with Cheyne-Stokes respiration Supplemental CO2: effective in

eliminating central apnea by virtue of elevating PaCO2 above the apneic threshold

CSA Treatment

35 yo male nurse with excessive daytime sleepiness since age of 15

Denies snoring, witnessed apneas reports irresistible sleep attacks, short naps

are refreshing Jaw drop and knee buckling when laughing

or angry

Case#3

NPSG : ◦ no sleep disorder/ treated sleep disorder◦ Short latency to REM sleep◦ Fragmented sleep

MSLT:◦ 5 naps:

mean sleep latency is less than 5 or 6 minutes Sleep Onset REM Period (SOREMP) on 2 or more

naps

Narcolepsy

Morrish et al (Factors associated with a delay in the diagnosis of narcolepsy.

Sleep Med. 2004 Jan;5(1):37-41)

◦ Survey of members of the Narcolepsy Association UK: The interval between symptom onset

and diagnosis ranged from within 1 to 61 years with a median of 10.5 years

Narcolepsy

0.05% in the United States Narcolepsy pentad:

◦ Excessive daytime sleepiness◦ Cataplexy◦ Sleep paralysis◦ Hypnagogic / hypnopompic hallucinations◦ Fragmented sleep

Narcolepsy

HLA DQB1∗0602 in >90% of patients with cataplexy

Narcolepsy in dogs has been linked to an AR mutation of the gene coding for the hypocretin (orexin) receptor 2

In humans, no detectable hypocretin (orexin) can be found in the cerebrospinal fluid (CSF) of up to 90% of narcoleptics who have cataplexy

Narcolepsy

Narcolepsy:◦ Sleep hygiene◦ Scheduled Naps and regular nocturnal sleep

times◦ Medications: Amphetamines, modafenil and

armodafenil, Sodium oxybate Cataplexy:

◦ TCA and Fluoxetin, Sodium oxybate Future Directions

◦ Fetal cell transplant ◦ Orexin/ Hypocretin agonists

Treatment

36 yo woman CC of difficulty initiating sleep Regular bed time unpleasant crawling sensation in legs,

relieved by moving legs or walking Tired during the day, bed partner reports

frequent kicking No snoring or witnessed apneas

Case#4

PE: unremarkable, normal neurologic exam Laboratory: within normal including iron

studies NPSG: prolonged latency to sleep onset,

increased leg movement prior to sleep onset

Case#4

PLM’s : “periodic episodes of repetitive and highly stereotyped limb movements that occur during sleep.”◦ Clinically: insomnia and excessive daytime sleepiness

◦ no significant association with objective or symptomatic reports of insomnia or daytime sleepiness

◦ PLMD: in association with medications, narcolepsy and obstructive sleep apnea

Periodic Limb Movement Disorder

PRO : ◦ Marker of sleep

fragmentation◦ Potential

cardiovascular risk factor

◦ Predictor of mortality in end-stage renal disease.

CON◦ 49% of the EEG arousals

occurred before the leg movement,31% simul-

taneous ,23% after.◦ NO valid studies

documenting that treating isolated PLMs improves either nighttime sleep or daytime functioning in any condition.

PLM’s: Do they have any clinical relevance?

RLS: 2% and 6% of the population (1) an urge to move the limbs with or without sensations (2) worsening at rest (3) improving with activity (4) worsening in the evening or night

Restless Leg Syndrome

Pathophysiology : ◦ central nervous system (CNS) iron homeostatic

dysregulation◦ Iron seems to play a role in normal

dopaminergic function in the central nervous system, related to dopamine transport and dopamine synthesis

Work up: ◦ Ferritin level < 50 μg/L ◦ Elctrolytes, renal function◦ B12, Folate, and cobalamine

Restless leg syndrome

Familial: positive family history Primary : if no other explanation Secondary :

◦ renal failure◦ iron deficiency◦ Neuropathy/ myelinopathy◦ pregnancy◦ Parkinson's disease (PD)/essential

tremor◦ genetic ataxias ◦ fibromyalgia /other rheumatologic

diseases

Restless leg syndrome

Caffeine Antidepressant medications:

fluoxetine, paroxetine (Paxil), sertraline (Zoloft), mirtazapine (Remeron), and mianserin

Neuroleptics, such as olanzapine (Zyprexa) and risperidone (Risperdal)

Others: β-blockers, phenytoin (Dilantin), zonisamide (Zonegran), methosuximide, and lithium

??? smoking

Medicaction Induced RLS/PLMD

Dopamine agonists: ropinirole, pramipexole, pergolide, bromocriptine, apomorphine, cabergoline

Opiates Gabapentin Iron supplement if Ferritin < 50 Bupropion (Wellbutrin)

Treatment

35 yo woman◦ Cc: difficulty initiating and maintaining sleep

for years◦ Daytime fatigue, no excessive

daytimesleepiness◦ Now newly engaged and experiencing

worsening of insomnia◦ PMH – anxiety, phobia of flying in recent

years◦ Meds – OCP

Case # 5

Medical History Alcohol/ caffeine/ medications Bedtime routine Bedroom environment Bedtime / time to sleep onset / continuity of

sleep / awakenings Daytime function

Insomnia Interview

Model for evolution of Insomnia

Model for evolution of Insomnia

Sleep medications:◦ may provide rapid relief of the symptoms of

insomnia◦ many of these medications have side effects ◦ Have not been shown to be effective for long-term

treatment of insomnia.

Insomnia Treatment Pharmacologic therapy

Hypnotic medications: FDA approved for short term use (Eszopiclone for long term)

Antidepressants (amitriptyline and trazodone): have a calming or sedative effect can be used to aid sleep.

Antihistamines: may be effective for short-term relief of sleeplessness.

Non prescription sleep medications: habit-forming and cause rebound insomnia. Should not be used for more than 7 to 10 days.

Rozerem: Melatonin Agonist. Future direction: Orexin/ Hypocretin

Antagonists

Insomnia Treatment Pharmacologic therapy

The most successful long term treatment

Relaxation therapy : progressive muscle relaxation, in which different muscle groups are tensed and relaxed, as well as attention-focusing techniques such as meditation, which can help stop sleep-disturbing habits.

Cognitive behavioral therapy: recognize certain beliefs a patient holds about self and sleep, to change those beliefs that may contribute to unhealthy patterns, and to introduce positive behaviors that will help create an inviting environment for sleep.

Sleep hygiene measures: simple actions that address sleep habits and factors that may keep people from good sleep.

Stimulus control therapy: reestablishes the bed as a place for sleeping and sex only-not for sleeplessness. ( can't fall asleep in 15 minutes, get out of bed and do something quiet and relaxing until sleepy again).

Sleep restriction therapy: limits the time spent in bed to time spent sleeping.

Non-Pharmacologic Insomnia Treatment

Sleep Medicine Specialists Behavioral Sleep Medicine Specialists Dental Sleep Medicine Specialist

Louisville Sleep

www.louisville.edu/medschool/pulmonary

Thank You

QUESTIONS?????