Sleep Awake DisordersSleep Awake Disorders

• Hypersomnolence disorder ( DSM-V)

• Hypersomnia (DSM-IV)

Definition

• In the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders, published in May 2013, hypersomnia appears under sleep-wake disorders as hypersomnolence, of which there are several subtypes

What is hypersomnia?

- Excessive daytime sleepiness coupled with sleep of excessive duration.

• Self-reported excessive sleepiness despite a main sleep period lasting at least 7 hours

• 1. Recurrent periods of sleep within same time• 2. Prolonged sleep episode more 9 h nonrestorative • 3. Difficulty being fully awake after abrupt awakening• B. At least 3 times per weeks at least 3 months• C. Significant distress or impairment social occupational • D. Is not better explained another sleep disorder or a

parasomnia • E. Not attributable to physiological effects of a substance • F. Coexisting mental and medical disorders do not

adequately explain complaint of hypersomnia

Specify

•  

• Mental disorder including substance use disorder

• With medical condition

• With another sleep disorder

 

• Acute : Duration of less than 1 month

• Sub acute : 1-3 months

• Persistent : more than 3 months

• Mild : Difficulty maintaining daytime alertness 1-2 days/week

• Moderate : 3-4 days/week

• Severe : 5-7 days/week

•  

Diagnostic Features

broad diagnostic term

symptoms of excessive quantity of sleep (e.g., extended nocturnal sleep or involuntary daytime sleep)

Deteriorated quality of wakefulness (i.e., sleep propensity during wakefulness as shown by difficulty awakening

inability to remain awake when required)

sleep inertia (i.e., a period of impaired

performance reduced vigilance following awakening from the regular sleep episode or from a nap)

Symptoms

• The main symptom of hypersomnia is excessive daytime sleepiness (EDS), or prolonged nighttime sleep, which has occurred for at least 3 months prior to diagnosis

• fall asleep quickly • good sleep efficiency (>90%)• difficulty waking up in the morning• sometimes confused, combative, or ataxic• This prolonged impairment of alertness at the

sleep-wake transition is often referred to as sleep inertia (i.e., sleep drunkenness).

• behavior may be very inappropriate,• memory deficits, disorientation in time and space• automatic behavior

Associated Features Supporting Diagnosis

• Nonrestorative sleep

•A subset of individuals with hypersomnolence disorder have a family history of hypersomnolence

• autonomic nervous system dysfunction, including recurrent vascular-type headaches, reactivity of the peripheral vascular system (Raynaud's phenomenon)

• fainting

Prevalence

• 5%-10% of individuals who consult in sleep disorders clinics with complaints of daytime sleepiness are diagnosed as having hypersomnolence disorder

• 1% of the European and U.S. general population has episodes of sleep Inertia

• equal in males and females.

Pathology

• Subcortical circuits mediating sleep-wake functions disrupted

• (narcolepsy and Kleine-Levin Syndrome)

•  MRI shows instability of cortical networks in individuals with Cognitive flactuations

Retinohypothalamic pathway

Suprachiasmatic Nucleus

– Part of hypothalamus– Damage disrupts rhythm.

Diagnosis

• "The severity of daytime sleepiness needs to be quantified by subjective scales (at least the Epworth Sleepiness Scale) and objective tests such as the multiple sleep latency test (MSLT)." The Stanford sleepiness scale (SSS) is another frequently-used subjective measurement of sleepines

Development and Course

• persistent course• sleep episodes can last up to 20 hours • average nighttime sleep duration is around 9 hours

Awakenings are very difficult and accompanied by sleep inertia episodes in nearly 40% of cases

• Pediatric cases are rare

For most individuals, the course is then persistent and stable, unless treatment is initiated

• The development of other sleep disorders (e.g., breathing-related sleep disorder) may worsen the degree of sleepiness.

• hyperactivity may be one of the presenting signs of daytime sleepiness in• children

Risk and Prognostic Factors

• Environmental• increased temporarily by psychological stress• and alcohol use• infectious• about 10% of cases• Viral infections, such as HIV pneumonia, • mononucleosis, and Guillain-Barre syndrome• 6-18 months following a head trauma• Genetic and physiological• Hypersomnolence may be familial, with an

autosomal dominant

Kleine-Levine syndrome

• Recurrent hypersomnia • Male• Early adolescence • Voracious eating• Hypersexuality• Disinhibition and aggression• Extreme sleepiness ( 18-20 hour sleep

period)

Menstrual-related hypersomnia

 •Symptoms last 1 week and resolve with menstruation

•Treatment with OCP is effective•Secondary to hormone imbalance

• •Menstrual-related hypersomnia

•Symptoms last 1 week and resolve with menstruation•Treatment with OCP is effective•Secondary to hormone imbalance

Comorbidity

• Associated with depressive disorders, bipolar disorders (during a depressive episode), and major depressive disorder, with seasonal pattern

• at risk for substance-related disorders, particularly related to self-medication with stimulants

• Neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and multiple system atrophy

Brain activity is measured as electric waves

Different types of brain waves exist during our sleep cycle

• All mammals and birds sleep. Fish, reptiles & amphibians have periods of inactivity too• - Large species differences in sleep: Not related to body size/ temperature• Little/no Effect of exercise on sleep duration in humans (Youngstedt & Kline, 2006• Sloths hardly move, yet need 20 hrs/day • Lions can do little else but sleep• For 2 days after a kill

• Mammal• Hrs of sleep/day• Giant Sloth 20• Tree Shrew 15• Cat, Hamster 14• Mouse, rat, squirrel 13• Hedgehog 10• Humans, rabbit, pig 8• Cow, Goat, Elephant 3• Horse, Roe deer 2

Long sleeper syndrome• 2% of the population•  people suffering from this kind of syndrome are in need of more sleep compared to

the conventional sleeping patterns of normal individuals.• M>F• ten to twelve hours• no other symptoms• Sleep pattern and PSG are Normal

Narcolepsy

Narcolepsy – what is it?

- A sleep disorder where people experience sudden uncontrollable sleep attacks during the day where a person may go from being awake straight into REM sleep.

-This can occur without any warning and may be accompanied by cataplexy, a total loss of muscle tone (causing collapse).

-At least 3 times/week in 3 past months

Narcolepsy – what is it?

- A sleep disorder where people experience sudden uncontrollable sleep attacks during the day where a person may go from being awake straight into REM sleep.

- This can occur without any warning and may be accompanied by cataplexy, a total loss of muscle tone (causing collapse).

Nocturnal sleep polysomnography showing rapid eye movement (REM) sleep latencyless than or equal to 15 minutes, or a multiple sleep latency test showing amean sleep latency less than or equal to 8 minutes and two or more sleep-onsetREM periods.

Narcolepsy

Narcolepsy without cataplexy but with hypocretine deficiency

Low CSF hypocretine levels positive polysomnography

Classic form

•Narcolepsy with cataplexy but without hypocretine deficiency

• •Rare subtype

•MSLT

•Hypocretine csf Normal

•Autosomal dominant cerebellar ataxia , deafness , narcolepsy

• •Exone 21 DNA (Cystine -5) Mutation

•Late onset : 30-40 years

Narcolepsy secondary to another medical condition:

• This subtype is for narcolepsy that develops secondary to medical conditions that cause infectious

• (e.g., Whipple’s disease, sarcoidosis), traumatic, or tumoral destruction of

• hypocretin neurons.

Narcolepsy: MSLT, SOREMs

Postprandial somnolence•  cloud food•  foodland•  food coma • carb coma is a normal state of drowsiness or 

lassitude following a meal• Postprandial somnolence has two components: a

general state of low energy related to activation of the parasympathetic nervous system in response to mass in thegastrointestinal tract, and a specific state of sleepiness by hormonal and neurochemical changes related to the rate at which glucose enters the bloodstream and its downstream effects on

amino acid transport in the central nervous system.

Hypocretin/orexin hypothesis

• small rise in blood glucose that occurs after a meal is sensed by glucose-inhibited neurons in the lateral hypothalamus.

•  These orexin-expressing neurons appear to be hyperpolarised (inhibited) by a glucose-activated potassium channel. This inhibition is hypothesized to then reduce output from orexigenic neurons to amineregic,cholinergic, and glutamatergic arousal pathways of the brain, thus decreasing the activity of those pathways, and therefore brain arousal.

Sleeping sickness (disambiguation)

• African trypanosomiasis

•  Disruption of the sleep cycle is a leading symptom of this stage

• Infected individuals experience a disorganized and fragmented 24-hour rhythm of the sleep-wake cycle, resulting in daytime sleep episodes and nighttime periods of wakefulness

Primary hypersomnia mimics

genetic disorders

•  Prader-Willi syndrome; Norrie disease; Niemann–Pick disease, and myotonic dystrophy).

• myotonic dystrophy is often associated with SOREMPs (sleep onset REM periods, such as occur in narcolepsy)

Primary hypersomnia mimicsNeurological disorder

•Brain tumors; stroke-provoking lesions; and dysfunction in the thalamus, hypothalamus, or brainstem. Also, neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, or multiple system atrophy are frequently associated with hypersomnia

Behaviorally-induced Insufficient Sleep Syndrome

Unintentional chronic restriction of sleep (e.g., by working two jobs) that leads to Excessive Daytime Sleepiness (EDS) and a decreased level of alertness .

The most prevalent cause of EDS and daytime fatigue

Diagnostic feature

• Narcolepsy-cataplexy nearly always results from the loss of hypothalamic hypocretin

• (orexin)-producing cells, causing hypocretin deficiency (less than or equal to one-third of

• control values, or 110 pg/mL in most laboratories). Cell loss is likely autoimmune, and approximately 99% of affected individuals carry HLA-DQBl*06:02

Associated Features Supporting Diagnosis

• When sleepiness is severe, automatic behaviors may occur• Approximately 20%-60% of individuals experience vivid hypnagogic hallucinations• hypnopompic hallucinations just after awakening• Nightmares and vivid dreaming are also frequent in narcolepsy, as is REM sleep behavior

disorder• However, many normal sleepers also report sleep paralysis, especially with stress or

sleep deprivation• Nocturnal eating may occur• Obesity is common• Nocturnal sleep disruption with frequent long or short awakenings is common and• can be disabling.• Individuals may appear sleepy or fall asleep in the waiting area or during clinical

examination.• During cataplexy, individuals may slump in a chair and have slurred speech or• drooping eyelids

Prevalence

• Narcolepsy-cataplexy affects 0.02%-0.04% of the general population in most countries

• Narcolepsy affects both genders, with possibly a slight male preponderance

Cataplexy is an abrupt temporary loss of voluntary muscular function and tone, evoked by an emotional stimulus such as laughter, pleasure, anger, or excitement.Cataplexy occurs when a person experiences an emotional stimulation - hearing a good joke (laughter), taking a trip (excitement), having an argument (anger), being in a crowded store (stress)stimulation leads to a very rapid loss of voluntary muscle control - often the person will immediately collapse as a result. The collapse occurs because the person can no longer control their leg muscles to remain standing

Development and Course• Onset is typically in children and adolescents/young adults but rarely in older adults• Two peaks of onset are suggested, at ages 15-25 years and ages 30-35 years• Abrupt onset in young, prepubescent children can be associated• with obesity and premature puberty

• In 90% of cases, the first symptom to manifest is sleepiness or increased sleep, followed• by cataplexy • Sleepiness, hypnagogic hallucinations, vivid dreaming, and REM sleep behavior

disorder (excessive movements during REM sleep) are early symptoms• In the first months, cataplexy may be atypical, especially in• Children• Young children and adolescents with narcolepsy often develop aggression or behavioral• problems secondary to sleepiness and/or nighttime sleep disruption. Workload and• social pressure increase through high school and college, reducing available sleep time at• Night• Pregnancy does not seem to modify symptoms consistently

Risk and Prognostic Factors

• Temperamental• Parasomnias, such as sleepwalking, bruxism, REM sleep behavior

disorder, and enuresis, may be more common in individuals who develop narcolepsy

• Environmental• Group A streptococcal throat infection, influenza (notably pandemic• HlNl 2009), or other winter infections are likely triggers of the

autoimmune process, producing• narcolepsy a few months later. Head trauma and abrupt changes in

sleep-wake patterns (e.g., job changes, stress) may be additional triggers.

• Genetic and physiological• Monozygotic twins are 25%-32% concordant for narcolepsy

SCNclock

DA (+)

Histam. (+)

NA (+)

5HT (+)

Orexin /

Hypocretin

Monoamine Monoamine Control by Control by HypocretinHypocretin

+/-

Worm in lateral

hypothalamus causing

narcolepsy.

(neurocysticercosis)

J. Clin. Sleep Med. 1(1) 2005, p. 41.

Culture-Related Diagnostic issues

• In all ethnic groups and in many cultures

• African Americans

Functional Consequences of Narcolepsy

• Driving and working are impaired

• that place themselves (e.g., working with machinery) or others (e.g., bus driver, pilot) in danger

• Once the narcolepsy is controlled with therapy, patients can usually drive, although rarely long distances alone

• Untreated individuals are also at risk for social isolation and accidental injury to themselves or others

Differential Diagnosis

• Sleep apnea syndromes• obesity

• Major depressive disorder• Cataplexy is not present in depression. The

MSLT results are most often normal, and there is dissociation between subjective and objective sleepiness, as measured by the mean sleep latency during the MSLT

.

Conversion disorder (functional neurological symptom disorder).

• such as long-lasting cataplexy or unusual triggers, may be present in conversion disorder

• may report sleeping and dreaming,• MSLT does not show the characteristic sleep-

onset REM period• Full-blown, long-lasting pseudocataplexy may

occur during consultation, allowing the examining• physician enough time to verify reflexes, which

remain intact

DDx

• Seizures• In young children, cataplexy can be

misdiagnosed as seizures• Seizures are not triggered by emotions, the

trigger is not usually laughing or Joking• During a seizure, individuals are more likely

to hurt themselves when falling Seizures• characterized by isolated atonia are rarely

seen in isolation of other seizures, and they also have signatures on electroencephalogram

Schizophrenia

• In the presence of vivid hypnagogic hallucinations, individuals may think these experiences are real a feature that suggests schizophrenia

with stimulant treatment, persecutory delusions may develop

• If cataplexy is present, the clinician should first assume that these symptoms are secondary to narcolepsy before considering a co-occurring diagnosis of schizophrenia.

Comorbidity

• Narcolepsy can co-occur with bipolar, depressive, and anxiety disorders, and in rare cases with schizophrenia

• Increased body mass index or obesity

• sleep apnea should be considered

Causes Hereditary in Labrador retrievers, poodles, dachshunds, and Doberman pinschersPossible immune system involvementNerve disorderIdiopathic (unknown)

Narcolepsy and Cataplexy are common in Dogs

What are the causes of narcolepsy?

- narcolepsy is a rare disorder occurring in less than 1% of people- actual cause is unknown, may be a biochemical imbalance- possibly a genetic predisposition

What is the best treatment for narcolepsy?- no cure- stimulants help prevent daytime sleepiness- drugs to prevent the onset of REM sleep- leading a lifestyle which allows for a regular sleep-wake cycle including daytime naps

Treating hypersomnia  

• Avoidancy of Alcohol and Caffeine

• First line treatment : Modafinil

• Traditional psychostimulants : Amphetamines

•  

• In Narcolepsy : REM sleep suppressing drugs ( Antidepressants )

• Used for cataplexy

• Imipramine Protryptiline

• SSRIs

• Sodium Oxorbate reducing cataplexy

• Psychological counseling , Sheduled naps lifestyle adjustment ,  

Modafinil ( Provigil)

a putative central alpha 1 adrenergic agonist, in idiopathic hypersomnia and narcolepsy.

• Sleep attacks and drowsiness were significantly decreased

• Modafinil has an excellent benefit/risk ratio in idiopathic hypersomnia

• When cataplectic episodes were not totally suppressed the association of a low dose of Clomipramine was successful in improving them.

• Tablet 200 mg

pregnancy category C

Children less than 30 kg: 200-340 mg once dailyChildren more than 30 kg: 300-425 mg

 Armodafinil

•  Armodafinil is a FDA approved drug that is a purer version of the active ingredient in Modafinil.

Alcover

• Sodium oxybate is the sodium salt ofγ-hydroxybutyric acid (GHB)

• alcohol withdrawal and dependence

• Clarithromicine• Concerta• Dextroamphetamine• Flumazinel• Gluten Free Diet• Levothyroxine• Melatonin