More has been learned about sleep in the last 60 years than in the past 6000 years Mansoor Ahmed. MD, FACCP, FABSM Medical Director, Cleveland Sleep &

OVERVIEW OF SLEEP DISORDERS

SLEEP MEDICINE……60 YEARS OF PROGRESS

More has been learned about sleep in the last 60 years than in the past 6000 years

Mansoor Ahmed. MD, FACCP, FABSMMedical Director, Cleveland Sleep & Research CenterAssistant Professor of MedicineCase Western Reserve UniversityFellow American Academy of Sleep Medicine

History of Sleep Medicine…1953 to PresentFrom Basement To Congress to Wall Street

Until 1975, Sleep Medicine was deemed experimental ,1995 Canada followed

4 Mile Stones : 1: REM Sleep 2: PSG 3 : Circadian Biology 4: OSA

1964: Stanford Narcolepsy Center (C Dement Ad in SF Chronicle for Narcolepsy ..100 responded and 50 were diagnosed to have narcolepsy)1964 Association of Professional Sleep Societies (APSS)

1968: R & K Manual of Sleep Scoring

1970: Stanford Sleep Center

1975: 5 Sleep Centers (Montefiore, OH State, Baylor, U-Pittsburg, and U-Cincinnati

1975-1977: American Sleep Disorders Association, Accreditation

1978: Certification Exam and Journal of SLEEP

1990: US Congress Created National Commission on Sleep Disorders

1991: ICSD-1 , ICSD 2: 2005

1996 – At last…The AMA recognized sleep medicine as a specialty

European Development: First Sleep Text Book, Human EEG, Sleep Apnea.

1963: Paris Symposium: ( Prof Fischgold) Sleep Epilepsy, Sleep Walking, Night Terrors.

1965: Discovery Of Sleep Apnea by Gestualt ,Tassinar and Jung & Khulo

Sleep……. A Vital Sign of Human Health: Bi-Directional relationship

PTSPD

Insomnia and HypersomnolencePTSD, Anxiety Mood Disorders , ADHD

Diabetes, Weight Gain, Hypothyroid

H

OSA and …..Hypertension, A FibMI, Stroke, CHF

Opioids & CSAPain Threshold

Alzheimer's Disease, StrokeParkinson Disease

CFM –Pain & Sleep

Presentation Summary

General Introduction Normal sleep and why we sleep Magnitude of Sleep Disorders , Sleep Deprivation and

Public Health Relationship between sleep and other medical

specialties:

Sleep Disorders : Case Presentation: PTSD

Snoring & Obstructive Sleep Apnea Circadian Rhythm Sleep Problems: Shift Work, Night Owl Syndrome,: ADD-ADHD, Jet Lag Insomnia Narcolepsy

and other Hypersomnolence Disorders Restless Leg Syndrome

Normal Sleep

Put your thoughts to sleep,do not let them cast a shadow

over the moon of your heart. Let go of thinking.

……...Rumi

Sleep is essential for physical, emotional and mental health

Functions of Sleep

We learned more about sleep functions when we don’t sleep Emotional Integration, Memory Consolidation & REM sleep Link between REM sleep and PTSD and other psychiatric

disorders ……………..From Sigmund Freud to current status

Glymphatics Glial channels carrying CSF expand by 60% during sleep Clean-up of any unwanted substances/ by products 2X more

efficient Implications in Alzheimer’s disease, stroke and dementia Shift-workers pre-disposition to neurological disorders

Medication and Sleep

• Hypnotics and sedatives (benzo and non-benzo

• OCD insomnia medications• Stimulants: Caffeine, Ritalin, Modafinil)

• Adverse effects of commonly used medicine on sleep & Breathing :

• Opioids: Center Sleep Apnea, Respiratory arrest

• beta blockers: Melatonin and Insomnia• Alcohol: Most commonly used hypnotic ,

adverse effect on sleep• Caffeine: The most commonly used stimulant, effect on sleep and alertness.

Normal Sleep

1 2 3 5 6 7 84

1

REMAwake

2

3

4

Hours

Rapid eye movement (REM) sleep• 20% to 25% of total sleep time• Active mind and Motor Paralysis• Intellectual Function• Sexual Functionality

Non–rapid eye movement (NREM)

Stage I Transition to sleep5% of total sleep Stage 2 50% of total sleep timeStages 3 and 4 Slow-wave sleep 10% to 20% of total sleep time

• Growth Hormone• Age and delta sleep

Historical Perspective

Greeks: Hypnos &Thanatos

1929: Human EEG Alpha Waves (Hansberger)

1953: REM Sleep (Asrenski, Klietman and Dement)

1968: Sleep Stages Scoring Rules ( R&K)

1965: OSA Clinical Studies (Gastaut)

1970: Stanford First Sleep Clinic ( Dement)

1982: CPAP (John Remmer ,Sullivan)

Magnitude of the Sleep Disorders

Underserved & Under-recognized Discipline

50-60 million American suffer from 80 identified sleep disorders

Sleep and Cardio-Vascular Disorders 51% of CHF patients has underlying sleep-breathing disorder OSA is an independent risk factor for hypertension. 30-40% patients with hypertension has OSA

Mood Disorders and Sleep, PTSD, ADHD 70% of Patients with mood disorders has sleep pathology

Neurological Conditions Sleep disturbance& fatigue are hallmark of MS, Parkinson disease,

Alzheimer's Disease, Narcolepsy, Sleep Waking Disorders

Sleep Deprivation Challenger Tragedy, >100,000 road accidents annually

Circadian Rhythm Shift Work, Delayed Phase Syndrome

Sleep Public Health Challenges : Sleep Deprivation, Shift Work, Under Diagnosis of Sleep Disorders

:

Federal Crash Statistics

100,000 police-report crashes annually 1,550 fatalities (4%) 71,000 injuries $12.5 billion in monetary losses (Knipling 1995) Another 1 million crashes are linked to inattention, which increases

with fatigue (Wang 1996)

The National Highway Traffic Safety Administration estimates

Sleep Disorders

Case Presentation:

A: Snoring & Obstructive Sleep Apnea

B: Circadian Rhythm Sleep Problems: Shift Work, Night Owl Syndrome Jet Lag

C: Insomnia

D: Narcolepsy and other Hypersomnolence Disorders

E: Restless Leg Syndrome

What we are dealing with here, are two gigantic problems for our society – An epidemic of undiagnosed and untreated sleep

disorders; and pervasive sleep deprivation with all its consequences for errors, accidents, disability, damages and death“

SLEEP DISORDERS………ITS NOT ALL ABOUT SLEEP APNEA

47 Year female, history of depression, anxiety, history noted for childhood trauma, subsequent spousal abuse, alcohol abuse; History of Chronic Fibromyalgia referred by pain specialist for snoring and OSA evaluation :

History of Sleep initiation and Sleep Maintenance Insomnia, uncomfortable sensation in legs, night mares, teetth Clenching frequent nocturnal awakening, non-restorative sleep., Wake up tired, severe day-time sleepiness, cataplexy-sleep paralysis

Clinical Evaluations: Sleep Wakefulness history, ENT, PTSD scalesInvestigations: Sleep Diary, PSG-MSLT

Sleep Diagnosis: OSA, Restless Legs Syndrome, Chronic Insomnia

Bruxism, Narcolepsy:

Sleep and Psychiatry are inherently linked together at every level.. From disease mechanism to clinical Symptoms to outcomes

Multiple Psychiatric Pathologies with Multiple Sleep Pathologies

Obstructive Sleep Apnea

ChokingChoking

Stage 2 Sleep with Alpha Intrusions

α intrusions

Rapid Eye Movement SleepIncreased REM frequency

Periodic Limb Movement Syndrome (PLMS)

Limb Movements

Bruxism (Teeth Clenching)

Bruxism

PLMS

Central

Stage 2 Sleep with Alpha Intrusions

α intrusions

Snoring & OSA……A Trojan Horse of Sleep Medicine

Prevalence of Sleep ApneaNo sound epidemiological survey in general population using true random sample and had PSG

Wisconsin: Survey 3513-- 625 Accepted with 25% non snorers participants, age 30-60 underwent overnight PSG;

OSAS definition: AHI>5 with hyper somnolence

Ages 50-60 with RDI >15: 4% Women, 9.1% men

Peak Prevalence: 4.7%, Age: 45-64

Neck Size is more correlated to severity of apnea than BMI

10% increase//Decrease in weight: 32% increase in AHI, 24% decrease

Age: SHHS: 20% Men, 10% women develop SA in 5 years,

48% CHF patients have sleep Apnea,

Sleep Apnea incidence is far higher in patients with resistant hypertension, A -Fib, Diabetes

T Young, NEJM 1993; 328:1230-5

AHI >5 with Hypersomnolence

AHI> 5 alone Snorer and

non snorer

Women 2% 18.9 & 5%

Men 4% 34% & 16.1%

Sleep Disordered BreathingDisease Mechanism

Narrow oropharynx but similar narrowing seen in normal Mechanism different in different patients due to factors related to control of breathingOSA worsens over the time Upper Airway Anatomy Plus Control of Breathing

1. Anatomy: Bony Structure, Soft Tissue, Obesity2. Control of Breathing : Chemo responsiveness, Negative pressure Upper Airway Muscles: Tongue, Palate, Hyoid Bone

•Control Of Breathing : Magdy Younes, John Remmer, Jerry Dempsey, Safwan Badr, Neil Cherniack, • Atul Malhotra, David White , S Javaheri

Obstructive Sleep Apnea

ChokingChoking

Night Symptoms: Loud Snoring, Choking, Frequent awakening, Restless Sleep

Daytime tiredness/Sleepiness, Mood-Memory, Concentration

Consequences: Increased BP, Stroke, Diabetes,

Inhale

Exhale

Airway obstructs Airway opens

Paradoxing

Paradoxing Ends

EKG

Airflow

Thoracic effort

Abd. effort

SAO2

Effort gradually increases

Sleep-Disordered Breathing…. Disease Mechanism

Mechanism of Sleep-Apnea and Sleep Hpoventilation1) Narrow Upper Airway: Obesity, E.N.T problems, Dysmorphism2) Control of Breathing: Hormones, Cardiac Dysfunction

Apnea Hypopnea Hypoventilation

PO2 PCO2 Negative Intra-Thoracic Pressure

Arousal, Sympathetic Activation , Systemic-Pulmonary Vasoconst

Signs & Symptoms: Sleepiness, Hypertension- LV dysfunction ,

Corpulmonale

STOP-BANGA simple screening tool for Sleep Apnea

Snoring

Do you snore loudly (louder than talking or loud enough to be heard through closed doors)?

Tired

Do you often feel tired, fatigued, or sleepy during daytime?

Observed

Has anyone observed you stop breathing during your sleep?

Pressure

Do you have or are you being treated for high blood pressure?

BMI

BMI more than 35 kg/m2

Age

Age over 50 yr old?

Neck circumference

Neck circumference greater than 40 cm , 15.7 inches?

Gender

Gender male?

High Risk

STOP: Yes to 2 or More

STOP BANG: Yes to 3 or more

27

Epworth Sleepiness Scale (ESS)

How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? This refers to your way of life in recent times. Even if you have not done some of these things recently, try to work out how they would have affected you. Use the following scale to choose the most appropriate number for each situation

0 = would never dose; 1 = slight chance of dozing2 = moderate chance of dozing; 3 = high chance of dozing

Situation Chance of Dozing ( 0-3)

Sitting and readingWatching TVSitting, inactive in a public place (eg, a theater or a meeting)As a passenger in a car for an hour without a breakLying down to rest in the afternoon when circumstances permitSitting and talking to someoneSitting quietly after a lunch without alcoholIn a car, while stopped for a few minutes in traffic Mitler and Miller. Behav Med.

1996;21:171.

Consequences of OSALongitudinal Findings- Sleep Health Heart Study

6441 Patients

Direct Cardiovascular Outcomes between 5 and 8.7 years Hyperextension, Stroke, CHF . Increased risk of Hypertension if higher BMI in men With cardiovascular disease larger increases in AHI

Long Term Outcomes Positive association between severity of SDB at PSG 1 and

subsequent increase in BMI Men more likely to have an increase in RDI with increase in weight

than women Both men and women had a greater increase in RDI with weight

gain than a decrease in RDI with weight loss Severe SDB showed increased risk of all-cause mortality in the 8.7

years following PSG

Evaluation & Diagnosis

1. Clinical Questions and Epworth

2. Home Sleep Study

3. PSG

Types of Sleep StudiesHome Sleep Testing ( HST)

Type 1 – Attended in-lab polysomnography

Type 2 – Comprehensive portable polysomnography

– Minimum of 7 channels including EEG, EOG, chin EMG, ECG/HR, airflow, respiratory effort and O2 saturation

HST:

Type 3 – Modified portable sleep apnea testing

– Minimum of 4 channels including ECG/HR, O2 saturation and at least 2 channels of respiratory movement or respiratory movement and airflow

Type 4 – Continuous single or dual bioparameters – For example, airflow and/or O2 saturation

Emergent OSA Therapy

Weight Loss CPAP New PAP Modalities Correction of enlarged tonsils,

Sinuses, UA surgery Oral Advancement Therapy Implantable Neuro-stimulator Provent: PEEP Mechanisms

CPAP is the most effective but compliance is the key issue

Circadian Sleep Disorders

Wake• During the day, SCN activity

promotes arousal• Maintains state of wakefulness

Sleep• At night, SCN arousal is

attenuated• Allows normal sleep to occur

SCN plays a pivotal role in maintaining wakefulness by generating an “alerting signal” that opposes the homeostatic sleep drive.

During the evening, the alerting signal is thought to be attenuated, in part via elevation in melatonin concentration during the night, allowing sleep to occur

Borbély, A., & Achermann, P. (1999). Sleep Homeostasis and Models of Sleep Regulation Journal of Biological Rhythms, 14 (6), 559-570 DOI:

Sleep Homeostasis and Models of Sleep Regulation

Circadian Rhythm Sleep Disorders (CRSD)

“The essential feature of CRSDs is a persistent or recurrent pattern of sleep disturbance due primarily to alterations in the circadian timekeeping system or a misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep.” – ICSD-2.

6 Distinct CRSDs are recognized in the ICSD-2: Delayed Sleep Phase Type (DSPD) Advanced Sleep Phase Type (ASPD) Irregular Sleep-Wake Phase Type (ISWR) Free-Running Type (FRD) Jet Lag Type (JLD) Shift Work Type (SWD)

Treatment- CRSD

Planned napping Timed light exposure Administration of melatonin Enhance Alertness Hypnotic medications

Insomnia

Insomnia is common and can have serious consequences, such as increased risk of depression and hypertension

Acute and chronic insomnia require different management approaches

Chronic insomnia is unlikely to spontaneously remit, and over time will be characterized by cycles of relapse and remission or persistent symptoms

Chronic insomnia is best managed using non-drug strategies and adjunctive use of medications

Insomnia

A symptom of either difficulty in falling asleep maintaining sleep or just sense of having insufficient sleep, causing an uncomfortable subjective experience, in some ways analogous to chronic pain

30% general population experience insomnia

Most of the patients patients with mood disorders has sleep pathology

Psychiatric disorders are the single largest cause of chronic insomnia in sleep-clinic population

Ancoli-Israel1999

Prevalence of Insomnia* in the General Adult Population

10.2

17.716.8

9

11.7

10

0

5

10

15

20P

erce

nt

Ford1989

Ohayon1998

Ohayon2001

Ishigooka1999

Simon1997

*Insomnia = sleep disturbance every night for two weeks or more, or similarly stringent criteria.1. Ford DE, Kamerow DB. JAMA. 1989;262:1479-1484.2. Ohayon MM, et al. Compr Psychiatry. 1998;39:185-197.3. Ohayon MM, Roth T. J Psychosom Res. 2001;51:745-755.4. Ancoli-Israel S, Roth T. Sleep. 1999;22(suppl 2):S347-S353. 5. Ishigooka J, et al. Psychiatry Clin Neurosci. 1999;53:515-522.6. Simon GE, VonKorff M. Am J Psychiatry. 1997;154:1417-1423.

Insomnia in Patients WithChronic Medical Conditions

0

10

20

30

40

50

60

Per

cent

age

of P

atie

nts

With

Ins

omni

a

Diabetes

MI

CHF

Angina

HipImpairment

BPH

ObstructiveAirway

Severe Insomnia†

Insomnia*

*Sleep disturbance “some” or “a good bit” of the time for four weeks.†Sleep disturbance “most” or “all” of the time for four weeks.MI = myocardial infarction; CHF = congestive heart failure; BPH = benign prostatic hypertrophy.Katz DA, McHorney CA. Arch Intern Med. 1998;158:1099-1107.

Insomnia…the most common sleep disorder

Insomnia Treatment

Sleep Hygiene Cognitive Behavior Therapy Pharmacotherapy

Therapeutic Agents

Sedative-hypnotics Sedating antidepressants Selective melatonin agonist and Melatonin Antihistamines Anxiolytics

Alternative and herbal medications- Valerian Root Extract

Hypnotics can be used on long term basis in Primary Insomnia

Exercise, CBT, Sleep Hygiene

Components of Cognitive Behavior Therapy

Stimulus control (daytime and sleeping environments) Sleep restriction Relaxation techniques (progressive relaxation, imagery training, biofeedback,

meditation, hypnosis and autogenic training) to reduce physical and mental arousal

Reduce negative perceptions about battle ground of sleep Write about worries in the evening Stopping thoughts (repeating word “the” every three sec.) Sleep hygiene education

What to do and not to Do

1. Recognize that there is a sleep problem & bring it to the attention

2. What is the nature of Sleep Problem:

Insomnia, Sleep Apnea, Restless Legs, Shift Work

3. Determine Circadian Phase

Diet/light snack , exercise, hot bath, relaxing techniques, Bed timing and sleep timing, prescription medications

What Not to do

Clock watching, thinking about next day issues, worrying about sleep, Coffee/Smoking/Alcohol Catching-up over the week-ends

EXCESSIVE SLEEPINESS DISORDERS

Mechanistic Approach

Sleep-Wake Dysregulation

Circadian Misalignment

Sleep Disruption

•Delayed Phase Syndrome

•Advanced Phase Syndrome

•Shift Work Disorder

•Non-24 hour Rhythm

•Narcolepsy

•Idiopathic Hypersomnia

•Post-Traumatic Hypersomnia

•Mood Disorders

•Sleep Apnea

•PLMS/Leg Movements

•Sleep Walking

Narcolepsy• Characterized by excessive sleepiness + cataplexy and

other REM phenomena1. Sleep paralysis2. Hypnagogic hallucinations

• Etiology unknown

Pathology:

• Genetic predisposition • Hypocretin/orexin deficiency • Autoimmune disease• Neurochemical abnormalities• Environmental triggers• Head trauma

Assessment of Sleepiness

Behavioral• Facial expression, posture, yawning, myosis

Subjective• Epworth Sleepiness Scale (ESS)• Stanford Sleepiness Scale (SSS)

Objective• Multiple Sleep Latency Test (MSLT) • Polysomnography (PSG)• Actigraphy• Maintenance of Wakefulness Test (MWT)

Mitler and Miller. Behav Med. 1996;21:171.

Control N=17Narcolepsy N=57

Adapted from Mitler et al. Psychiatr Clin North Am. 1987;10:593.

Sleepiness and REM Sleep Assessed by Multiple Sleep Latency Test (MSLT)

Sleep Latency

Naps

0

Min

ute

s

4

8

12

16

20

13.4 ± 4

3.0 ± 2.7

1 2 3 4 5

Number of REM PeriodsRecorded in All 5 Naps

RE

M p

eri

od

s/5

na

ps

(mea

n)

0

1

2

3

4

5

0

Narcolepsy

Control

Narcolepsy Control

Narcolepsy: Traditional Management Approaches

Excessive daytime sleepiness• Structured nocturnal sleep• Naps: scheduled and PRN• Stimulants or wake promoting agents

Cataplexy• Antidepressants (TCA or SSRI)

Sleep fragmentation • Sleep hygiene• Hypnotics (limited utility)

General• Personal and family counseling• Support

Parkes. Sleep. 1994;17:S93; Mitler M et al. Sleep. 1994;17:352; Daly and Yoss. Narcolepsy. In: Handbook of clinical Neurology. Vol.15.1994;15:836; Bassetti and Aldrich. Neurol Clin. 1996;14:545; Mamelak et al. Sleep. 1986;9:285.

Restless Legs Syndrome

Key RLS Diagnostic Criteria Urge to move legs-usually accompanied by uncomfortable

sensations Temporary relief with movement Onset or worsening of symptoms at rest or inactivity, such as

lying or sitting Worsening of symptoms in the evening or at night

Other Diagnostic Considerations Positive family history of Restless Legs Syndrome Periodic limb movements during wakefulness or sleep

(PLMW or PLMS) Sleep disturbance

Uncomfortable Leg Sensations

Types of RLS

Primary RLS Genetic or Familial

Secondary RLS Iron deficiency Pregnancy End-stage renal

disease Various

polyneuropathies

Treatment: What to Expect

Treatment of underlying causes of RLS

Several prescription medications very effective

Effectiveness of medication varies for each person

Worsening of symptoms

Key Messages Sleep is critical for physical and mental health, and emotional restoration

Sleep loss / inadequate or disturbed sleep compromises all treatments and therapies

Sleep Function: Emotional Integration, Memory Consolidation, Clean-up of unwanted substances in the brain

50-60 million Americans suffer from chronic sleep disorders, with most common ones being: chronic insomnia; obstructive sleep apnea; restless legs syndrome, and disorders of severe sleepiness including shift work syndrome and narcolepsy

despite the fact that sleep disorders are not difficult to diagnose, a majority of sleep disorder sufferers remain undiagnosed

A greater need for implementing screening tools: STOP-BANG for sleep apnea; Epworth Sleepiness Scale for excessive sleepiness

Sleep and Sleep disturbances play a central role in the mechanism of psychiatric disorders such as PTSD, depression and anxiety. Evaluation of sleep and correction of disturbed sleep should be CRTICAL part of any treatment

Sleep disorders are predictive of Parkinson's and Alzheimer's disease

Sleep disorders can be effectively managed and treated, with significant improvement in quality of life

Importance of Public Health Awareness…….Sleep Education

Cleveland Sleep Centera comprehensive approach

Patient Care• Clinic• Diagnostic Sleep Laboratory• Dental Sleep Medicine• Respiratory Therapy

Education• Public Education• Preceptorship• Physician Education

Research• In-House • Pharmaceutical

Acknowledgments

Fruit Fly Narcoleptic Dog

Rat

Acknowledgments

Parents Mentors: Magdy Younes, J Remmers, Nick Anthonison, M

Kryger Patients Colleagues: Rozina Aamir, Zahra Jishi, Martin Scharf Maryam Ahmed , Abdulrazzak Dardari Staff, Alithea, Sandy, Noel Cyrill, Nancy, Eden

Nazima and Shazeena