LEEP DISORDERS

Sleep Architecture and Sleep Stages

• divided into two independent states: NREM and REM sleep

• NREM - further divided into three stages ie N1, N2, N3

• After sleep onset, progresses through NREM stages N1–N3 sleep within 45–60 min

• NREM and REM sleep alternate, with each cycle lasting for approximately 90 to 100 minutes

• Four to six such cycles are noted during a normal sleep period

• N3 predominates in the first third of the night and comprises 15–25% of total nocturnal sleep

• REM sleep dominates the last third• Overall, REM sleep constitutes 20–25% of total

sleep, and NREM stages N1 and N2 are 50–60%

Sleep Requirements and Quantity of Sleep

• Sleep requirement is defined as the optimal amount of sleep required to remain alert and fully awake and to function adequately throughout the day

• for an average adult is approximately 7.5 to 8 hours

Classification of Sleep Disorders

• International Classification of Sleep Disorders• latest edition of the International

Classification of Sleep Disorders (ICSD-2) (AASM, 2005)

• eight broad categories of disordered sleep, along with several subcategories

• I. Insomnia• II. Sleep-related breathing disorders• III. Hypersomnias of central origin not due to a

circadian rhythm sleep disorder, sleep-related breathing disorder, or other cause

• IV. Circadian rhythm sleep disorders

• V. Parasomnias• VI. Sleep-related movement disorders• VII. Isolated symptoms, apparently normal

variants, and unresolved issues• VIII. Other sleep disorders

Approach to the Patient: Sleep Disorders

• an acute or chronic inability to initiate or maintain sleep adequately at night (insomnia)

• chronic fatigue, sleepiness, or tiredness during the day (EDS)

• Inability to sleep at the right time• Abnormal movements and behavioural

manifestation associated with sleep itself

SUBJECTIVE MEASURES OF SLEEPINESS

Narcolepsy

• characterized by recurrent "sleep attacks" that the patient cannot fight

• Irresistible desire to fall asleep in inappropriate circumstances and at inappropriate places

• e.g., while talking, driving, eating, playing, walking, running, working, sitting, listening to lectures, watching television or movies

• The sleep attacks are about 20-30 minutes long.

• The patient feels refreshed by the sleep, but typically feels sleepy again several hours later

Narcolepsy • Symptoms of narcolepsy typically begin in the

second decade• Once established, the disease is chronic

without remissions• Men and women are equally affected• affects about 1 in 4000 people in the United

States

ICSD-2 (AASM,2005)

• narcolepsy withcataplexy• narcolepsy without cataplexy• secondary narcolepsy

Narcolepsy TetradEDS plus 3 specific symptoms: 1. Cataplexy sudden weakness or loss of

muscle tone without loss of consciousness, often elicited by emotion

2. Hallucinations at sleep onset (hypnagogic hallucinations) or upon awakening(hypnopompic hallucinations)- visual

3. Sleep paralysis occurs during the transition from being asleep to waking up.

GENETICS

• Most are sporadic, some are AD• 10 to 40 times greater prevalence in families• hypothalamic neuropeptide hypocretin

(orexin) is involved in the pathogenesis• narcoleptics with cataplexy are positive for

HLA DQB1*0602, suggesting that an autoimmune process

CURRENT THEORY

• Results from a depletion ( degeneration or autoimmune) of hypocretin neurons in lateral and perifornical regions of hypothalamus

Symptomatic or secondary narcolepsy-cataplexy

• diencephalic and midbrain tumors, MS, strokes, cysts,

• vascular malformations, encephalitis, cerebral trauma, and

• paraneoplastic syndrome with anti-Ma2 antibodies

Treatment of Narcolepsy-CataplexySyndrome

Nonpharmacological measures include• scheduled short daytime naps,• sleep hygiene measures • attendance at narcolepsy support groups

Breathing-related Sleep Disorders

syndromes in which the patient's sleep is interrupted by problems with his or her

breathing

types of breathing-related sleep disorders:Obstructive sleep apnea syndrome. most common form, marked by episodes of blockage in the upper airway during sleep. It is found primarily in obese people. Central sleep apnea syndrome. primarily found in elderly patients with heart or neurological conditions that affect their ability to breathe properly.Problem lies in the ventilator control mechanisms in CNS.

Sleep-Disordered Breathing Terminology

Apnea - three types: obstructive, central, and mixed• central apnea - Cessation of airflow with no

respiratory effort, both diaphragmatic and intercostal muscle activities as well as gas exchange through the nose or mouth are absent

• obstructive apnea - airflow stops while the effort continues

• mixed apnea - there is an initial cessation of airflow with no respiratory effort (central apnea) followed by a period of upper airway obstructive sleep apnea

• Apneas are defined in adults as breathing pauses lasting >10 s

• hypopneas as events >10 s in which there is continued breathing but ventilation is reduced by at least 50% from the previous baseline during sleep

OBSTRUCTIVE SLEEP APNEA

• defined as the coexistence of unexplained EDS with at least five obstructed breathing events (apnea or hypopnea) per hour of sleep

• Factors contributing to the pathogenesis include local anatomical, neurological, and vascular factors, as well as familial predisposition

Pathogenesis

• Collapse of the pharyngeal airway is the fundamental factor

• During sleep, muscle tone decreases - causes these muscles to relax - increasing upper airway resistance and narrowing the upper airway space

Epidemiology

• prevalence is 4% in men and 2% in women between the ages of 30 and 60

• also occurs in childhood—usually associated with tonsil or adenoid enlargement

Factors predisposing to OSAS

• obesity—in Western populations around 50% of OSAHS patients have a body mass index (BMI) >30 kg/m2

• Hypothyroidism and acromegaly - narrowing the upper airway with tissue infiltration

• male sex, middle age (40–65 years)

Symptoms and Signs

• sleep attacks lasting 0.5 to 2 hours and occurring mostly when the patient is relaxing.

• The prolonged duration and the nonrefreshing nature of these sleep attacks in OSAS differentiate these from narcoleptic sleep attacks

Consequences

• increased morbidity and mortality• short-term consequences (impairment of

quality of life and increasing traffic- and work-related accidents)

• long-term consequences from associated and comorbid conditions such as hypertension, heart failure, MI, cardiac arrhythmias, stroke, transient ischemic attacks, cognitive dysfunction, depression, and insomnia

Mallampati classification

General Measures

• Avoid alcohol and sedative-hypnotics, especially in the evening

• Reduce body weight if overweight• Avoid sleep deprivation• Participate in regular exercise program• Avoid supine sleeping position

Mechanical Devices

• Continuous positive airway pressure (CPAP) titration - treatment of choice

• Bilevel positive airway pressure (BiPAP) titration

• Auto-CPAP• Oral appliances, including mandibular

advancement device• Tongue-retaining device

Surgical Techniques

• Uvulopalatopharyngoplasty (UPP)• Laser-assisted UPP (LAUP)• Radiofrequency UPP (somnoplasty)• Palatal implants• Nasal surgery• Maxillomandibular advancement• Anterior hyoid advancement• Tonsillectomy and adenoidectomy

Insomnia

• most common sleep disorder• Inability to initiate or maintain sleep, early

awakening, inadequate sleep time, or poor sleep quality associated with a lack of feeling restored and refreshed in the morning, leading to poor daytime functioning - AASM (2005)

Primary Insomnia

• onset occurs in early childhood

• lifelong difficulty with initiating or maintaining sleep

• exclusion of concomitant comorbid medical, neurological, psychiatric, or psychological disturbances.

Medical Disorders Comorbidwith Insomnia

• Ischemic heart disease• Congestive cardiac failure• Chronic obstructive pulmonary disease• Bronchial asthma• Peptic ulcer disease• Gastroesophageal reflux disease• Rheumatic disorders

Treatment of Insomnia

• most commonly used hypnotics are the benzodiazepine receptor agonists – zolpidem, zaleplon, and eszopiclone

• Melatonin receptor agonists(ramelteon) - sleep-onset insomnia

PARASOMNIAS

• abnormal movements or behaviours that occur in sleep or during arousals from sleep

• may be intermittent or episodic, and sleep architecture may not be disturbed

ICSD-2 (AASM, 2005)

• Disorders of arousal (from NREM sleep), which include confusional arousals, sleepwalking, and sleep terror

• Parasomnias associated with REM sleep, which include RBD, recurrent isolated sleep paralysis, and nightmare disorder

• other parasomnias including sleep-related dissociative disorders, sleep enuresis, sleep-related groaning (catathrenia)

Sleepwalking• Somnambulism• Onset: common between ages 5

and 12 yr• High incidence of positive family

history• Abrupt onset of motor activity

arising out of slow-wave sleep(NREM stage N3 sleep), during first one-third of the night

• Duration: less than 10 min• Injuries and violent activity occasionally

reported• Precipitating factors: sleep deprivation,

fatigue, concurrent illness, sedatives• Treatment: precaution, benzodiazepines,

imipramine

Sleep Terror

• pavor nocturnus• Onset: peak is between ages

5 and 7 yr• High incidence of familial

occurrences• Abrupt arousal from slow-

wave sleep during first one-third of the night, with a loud piercing scream

• Intense autonomic and motor components

• Precipitating factors: stress, sleep deprivation, fever

• Treatment: psychotherapy, benzodiazepines, tricyclic antidepressants

Rapid Eye Movement SleepBehavior Disorder (RBD)

• Onset: middle-aged or elderly men• Presents with violent dream-enacting

behavior during sleep, causing injury to self or bed partner

• Often misdiagnosed as a psychiatric disorder or nocturnal seizure (partial complex seizure)

• Etiology: 40% idiopathic, 60% causal association with structural central nervous system lesion or related to alcohol or drugs (sedative-hypnotics, tricyclic antidepressants, anticholinergics)

• Polysomnography: rapid eye movement sleep without muscle atonia

• Treatment: 90% response to clonazepam, melatonin

Nightmare Disorder • Dream anxiety attacks

• fearful, vivid, often frightening dreams, mostly visual but sometimes auditory, and seen during REM sleep

• most commonly occur during the middle to late part of sleep at night

• mostly a normal phenomenon, up to 50% of children have nightmares beginning at age 3 to 5 years

• side effects of certain medications such as antiparkinsonian drugs (pergolide, levodopa), anticholinergics, and antihypertensive drugs, particularly beta-blockers

• generally do not require any treatment except reassurance

Sleep-Related Movement Disorders

Restless Legs Syndrome (RLS)

• most common movement disorder but is uncommonly recognized and treated

• irresistible urge to move their legs while at rest.

• experience a vague, uncomfortable feeling while at rest that is only relieved by moving the legs.

• mostly diagnosed in the middle or later years

Clinical Diagnostic Criteria

Essential Criteria• An urge to move the legs, usually

accompanied by or caused by uncomfortable sensations in the legs

• begins or worsens during periods of rest or inactivity, such as lying or sitting

• partially or totally relieved by movement such as walking or stretching

• worse in the evening or night

Supportive Features• Dopaminergic responsiveness• Presence of periodic limb movements in sleep

or wakefulness – 80%• Positive family history

Associated Features• Usually progressive clinical course• Normal neurological examination in the

idiopathic form• Sleep disturbance

Secondary - Medical Disorders

• Anemia: iron and folate deficiency• Diabetes mellitus• Amyloidosis• Uremia• Chronic obstructive pulmonary disease• Peripheral vascular (arterial or venous)

disorder• Rheumatoid arthritis• Hypothyroidism

Pathophysiology

• iron-dopamine dysfunction• abnormalities in the body’s use and storage of

iron• dopamine dysfunction - changes in dopamine

receptors or dopamine uptake

Drug Treatment of RestlessLegs Syndrome

Dopaminergic agents:• Pramipexole• RopiniroleBenzodiazepines:• Clonazepam• TemazepamAntiepileptic agents:• Gabapentin• Pregabalin

Circadian Rhythm Sleep Disorders

• Mismatch between the body’s internal clock and geophysical environment

• either as a result of malfunction of the biological clock or a shift in the environment causing this to be out of phase

• Most common are jet lag and shift-work sleep disorder

Types of Circadian Rhythm Sleep Disorders

Jet lag

sleepiness and alertness that occur at an inappropriate

time of day relative to local time, occurring after

repeated travel across more than one time zone

Shift work

insomnia during the major sleep period or excessive sleepiness during the major awake

period associated with night shift work or frequently changing shift work

• Modafinil (200 mg, taken 30–60 min before the start of each night shift) is approved by the U.S. Food and Drug Administration as a treatment for the excessive sleepiness during night work in patients with SWD

Laboratory Assessment ofSleep Disorders

• The two most important laboratory tests for diagnosis of sleep disturbance are PSG and the MSLT

• overnight PSG study is the single most important laboratory test for the diagnosis and treatment of patients with sleep disorders

Multiple Sleep Latency Test

• important test to effectively document EDS• Narcolepsy is the single most important

indication• presence of two sleep-onset REMs on four or

five nap studies and sleep-onset latency of less than 8 minutes strongly suggest a diagnosis of narcolepsy

• circadian rhythm sleep disturbance - REM sleep abnormalities

Sleep Education"Sleep hygiene" or sleep education for sleep disorders often

includes instructing the patient in methods to enhance sleep. Patients are advised to:

• wait until he or she is sleepy before going to bed• avoid using the bedroom for work, reading, or watching

television• get up at the same time every morning no matter how much

or how little he or she slept• avoid smoking and avoid drinking liquids with caffeine• get some physical exercise early in the day every day• limit fluid intake after dinner; in particular, avoid alcohol

because it frequently causes interrupted sleep• learn to meditate or practice relaxation techniques• avoid tossing and turning in bed; instead, he or she should get

up and listen to relaxing music or read