Sleep Disorders

1. Sleep Disorders Audrea Elliott

3. Sleep Cycle There are five stages of sleep; four stages are considered non-REM sleep and one stage of REM sleep Allan & Bacon 2004 Alpha activity: A smooth electrical activity of 8 � 12 Hz recorded from the brain; generally associated with a state of relaxation or meditation (transition from wakefulness to sleep); 5% of sleep Beta activity: Irregular electrical activity of 13 � 30 Hz recorded from the brain; generally associated with a state of arousal; 50% of sleep Theta activity: EEG activity of 3.5 � 7.5 Hz that occurs intermittently during early stages of slow wave sleep and REM sleep. Delta activity: Regular, synchronous electrical activity of less than 4 Hz recorded from the brain; occurs during the deepest stages of slow-wave sleep. Alpha activity: A smooth electrical activity of 8 � 12 Hz recorded from the brain; generally associated with a state of relaxation or meditation (transition from wakefulness to sleep); 5% of sleep Beta activity: Irregular electrical activity of 13 � 30 Hz recorded from the brain; generally associated with a state of arousal; 50% of sleep Theta activity: EEG activity of 3.5 � 7.5 Hz that occurs intermittently during early stages of slow wave sleep and REM sleep. Delta activity: Regular, synchronous electrical activity of less than 4 Hz recorded from the brain; occurs during the deepest stages of slow-wave sleep.

4. REM Sleep Accounts for about 25% of sleep. In humans, occurs once every 90 minutes. Brain activity is high during REM.

5. Sleep Deprivation Studies with humans have found that sleep deprivation takes it�s greatest toll on cognitive abilities. When allowed to sleep again, all stages of sleep are not made up evenly. Studies with lab animals have shown that with enough sleep deprivation the animals will become sick and eventually die. Make up much more of stage 4(68%) and REM sleep (53%) then one and two (7%). Make up much more of stage 4(68%) and REM sleep (53%) then one and two (7%).

6. Neural Control of Arousal and Sleep Different neural systems promote sleep and arousal. wake-promoting area in the posterior hypothalamus and a sleep-promoting region in the preoptic area PGO wave (Pontine, Geniculate, Occipital): Bursts of phasic electrical activity originating in the pons (parabracial area), followed by activity in the lateral geniculate nucleus (LGN) and visual cortex, a characteristic of REM sleep. Locus ceoruleus: A group of norepinephrine cell bodies located in the pons near the rostral end of the floor of the fourth ventricle; involved in arousal and vigilance. Peribrachial area: The region around the brachium conjunctivum, located in the dorsolateral pons; contains acetylcholinergic neurons involved in the initiation of REM sleep; Carbachol drug Ach agonist; induce REM sleep when put into the pons Tuberomammillary nucleus: A nucleus in the ventral posterior hypothalamus, just rostral to the mammillary bodies; contains histaminergic neurons involved in cortical activation and behavioral arousal. Medial pontine reticular formation (MPRF): A region that contains neurons involved in the initiation of REM sleep; activated by acetylcholinergic neurons of the peribrachial area. Magnocellular nucleus: A nucleus in the medulla; involved in the atonia (muscular paralysis) that accompanies REM sleep. Ventrolateral preoptic area (VLPA): A group of GABAergic neurons in the preoptic area whose activity suppresses alertness and behavioral arousal and promotes sleep. Destruction of this area has been reporter to result in total insomnia, coma, and eventual death in rats. Hypocretin is involved in regulating the sleep on/off cells in this area. Raphe nucleus: A group of nuclei located in the reticular formation of the medulla, pons, and midbrain, situated along the midline; contain serotonergic neurons. Were most serotonin neurons are found The function of sleep is altered by Norepinephrine (arousal) Serotonin (promotes sleep) Dopamine (arousal) Acetylcholine (two groups of neurons located in the pons and basal forebrain affect arousal) Histamine (arousal) GABA (promotes sleep) Opioid/opiates (promotes sleep) Hypocretin/ orexin (arousal) Hypocretin/ orexin Also promotes eating. http://www.modafinil.com/orexins.html Different neural systems promote sleep and arousal. wake-promoting area in the posterior hypothalamus and a sleep-promoting region in the preoptic area PGO wave (Pontine, Geniculate, Occipital): Bursts of phasic electrical activity originating in the pons (parabracial area), followed by activity in the lateral geniculate nucleus (LGN) and visual cortex, a characteristic of REM sleep. Locus ceoruleus: A group of norepinephrine cell bodies located in the pons near the rostral end of the floor of the fourth ventricle; involved in arousal and vigilance. Peribrachial area: The region around the brachium conjunctivum, located in the dorsolateral pons; contains acetylcholinergic neurons involved in the initiation of REM sleep; Carbachol drug Ach agonist; induce REM sleep when put into the pons Tuberomammillary nucleus: A nucleus in the ventral posterior hypothalamus, just rostral to the mammillary bodies; contains histaminergic neurons involved in cortical activation and behavioral arousal. Medial pontine reticular formation (MPRF): A region that contains neurons involved in the initiation of REM sleep; activated by acetylcholinergic neurons of the peribrachial area. Magnocellular nucleus: A nucleus in the medulla; involved in the atonia (muscular paralysis) that accompanies REM sleep. Ventrolateral preoptic area (VLPA): A group of GABAergic neurons in the preoptic area whose activity suppresses alertness and behavioral arousal and promotes sleep. Destruction of this area has been reporter to result in total insomnia, coma, and eventual death in rats. Hypocretin is involved in regulating the sleep on/off cells in this area. Raphe nucleus: A group of nuclei located in the reticular formation of the medulla, pons, and midbrain, situated along the midline; contain serotonergic neurons. Were most serotonin neurons are found The function of sleep is altered by Norepinephrine (arousal) Serotonin (promotes sleep) Dopamine (arousal) Acetylcholine (two groups of neurons located in the pons and basal forebrain affect arousal) Histamine (arousal) GABA (promotes sleep) Opioid/opiates (promotes sleep) Hypocretin/ orexin (arousal) Hypocretin/ orexin Also promotes eating. http://www.modafinil.com/orexins.html

7. Sleep Disorders DSM-IV-TR Primary Sleep Disorders- -Dyssomnias - Insomnia - Hypersomnia - Narcolepsy - Breathing-Related Sleeping Disorders - Circadian Rhythm Sleep Disorders - NOS - Parasomnias - Nightmare Disorder - Sleep Terror Disorder - Sleepwalking Disorder - POS Secondary Sleep Disorders- - Sleep Disorder Related to Another Mental Disorder - Sleep Disorder Due to a General Medical Condition - Substance- Induced Sleep Disorder -Dyssomnias; abnormalities in the amount, quality, or timing of sleep - Parasomnias: abnormal behavior or psyiological events occuring in association with sleep, specific stages, or sleep-wake regulations. Secondary Sleep Disorders- result of other health problems, such as depression, heartburn, asthma, arthritis, cancer, pain, medications, etc. 40% of population -Dyssomnias; abnormalities in the amount, quality, or timing of sleep - Parasomnias: abnormal behavior or psyiological events occuring in association with sleep, specific stages, or sleep-wake regulations. Secondary Sleep Disorders- result of other health problems, such as depression, heartburn, asthma, arthritis, cancer, pain, medications, etc. 40% of population

8. Insomnia Difficulty initiating and maintaining sleep; non restorative sleep. Clinically significant distress/impairment in social, occupational, or other important areas. Disturbance of sleep is not due to another sleep disorder. Disturbance of sleep is not due to another mental disorder Not due to direct effects of substance use or general medical condition. Affects about 60 million Americans have chronic insomnia. About two percent have excessive sleepiness. Most common sleep complaint. Affects 40% of women and 30 % of men. # 1 cause is thought to be sleep medication Acute or Chronic Treatment: medication or behavior modification. Acute is last from 1 day to a few weeks and is often caused by emotional or physical discomfort. (significant life stress, illness, anything thing tat can interfere with sleep, & normal sleep schedule interruptions. Chronic: long-term) insomnia is when a person has insomnia at least 3 nights a week for 1 month or longer. It can be caused by many things and often occurs along with other health problems. Common causes of chronic insomnia are depression, chronic stress, and pain or discomfort at night Sleep Hygiene: Sleep only when sleepy. If can�t fall asleep in 20 min, get up and do something boring, no naps, get up & go to bed at same time every night, no exercise 4 hr before bed, sleep rituals, bed for sleeping only, no alcohol, nicotine, or caffeine 4-6 hr before bed. Have a light snack, take a hot bath 90 min before bed, quite & comfy bedroom, use sunlight to set biological clock. Since ancient times alcohol and opium used to promote sleep. 1800�s morphine, potassium bromide and chloral hydrate. Early 20th century barbiturates. All effective, but addictive. Then nonbenzodiazepine receptor agonist (1960). Also used antidepressents, atypical antipsychotics, and anticonvulsants (none FDA approved) Medication: (benzodiazepine temazepam, trizolam), (nonBenzodiazepine 7-10 days: zaleplon, zolpidem), trazodone, and tricyclic antidepressants (antihistimane effects) and SSRI�s (usually given if depression could be core issue and many think promote sleep) main issue of antidep is side effetcs New drugs: ramelteon (Rozerem) first medication not a controled substance- melatonin receptor agonist causing sleep promoting activities at the melatonin MT1 and MT2 receptors (Long term 8 mg 30 minutes before bedtime, helps with sleep onset) no hang over effect, Eszopiclone (Lunesta)- non benzodiazepine benzodiazepine agonist; treats difficulty in falling asleep (2mg just before sleep) and sleep mainience (3 mg daily):, and zolpidem extended release (Ambien CR): 6.25mg (elderly) and 12.5 doses immediately before bed. For sleep onset or sleep duration difficulties; relases 5 or 10 mg initially then remainder over next 3 hrs. Indiplon shorter half life then zaleplon set to come out this year, allows for treatment custiminization; immediate relaesate or modified releaseAcute is last from 1 day to a few weeks and is often caused by emotional or physical discomfort. (significant life stress, illness, anything thing tat can interfere with sleep, & normal sleep schedule interruptions. Chronic: long-term) insomnia is when a person has insomnia at least 3 nights a week for 1 month or longer. It can be caused by many things and often occurs along with other health problems. Common causes of chronic insomnia are depression, chronic stress, and pain or discomfort at night Sleep Hygiene: Sleep only when sleepy. If can�t fall asleep in 20 min, get up and do something boring, no naps, get up & go to bed at same time every night, no exercise 4 hr before bed, sleep rituals, bed for sleeping only, no alcohol, nicotine, or caffeine 4-6 hr before bed. Have a light snack, take a hot bath 90 min before bed, quite & comfy bedroom, use sunlight to set biological clock. Since ancient times alcohol and opium used to promote sleep. 1800�s morphine, potassium bromide and chloral hydrate. Early 20th century barbiturates. All effective, but addictive. Then nonbenzodiazepine receptor agonist (1960). Also used antidepressents, atypical antipsychotics, and anticonvulsants (none FDA approved) Medication: (benzodiazepine temazepam, trizolam), (nonBenzodiazepine 7-10 days: zaleplon, zolpidem), trazodone, and tricyclic antidepressants (antihistimane effects) and SSRI�s (usually given if depression could be core issue and many think promote sleep) main issue of antidep is side effetcs New drugs: ramelteon (Rozerem) first medication not a controled substance- melatonin receptor agonist causing sleep promoting activities at the melatonin MT1 and MT2 receptors (Long term 8 mg 30 minutes before bedtime, helps with sleep onset) no hang over effect, Eszopiclone (Lunesta)- non benzodiazepine benzodiazepine agonist; treats difficulty in falling asleep (2mg just before sleep) and sleep mainience (3 mg daily):, and zolpidem extended release (Ambien CR): 6.25mg (elderly) and 12.5 doses immediately before bed. For sleep onset or sleep duration difficulties; relases 5 or 10 mg initially then remainder over next 3 hrs. Indiplon shorter half life then zaleplon set to come out this year, allows for treatment custiminization; immediate relaesate or modified release

9. Hypersomnia Excessive sleepiness with one month as evidence by either sleep episodes or day time sleep episodes that occur almost daily. Excessive sleepiness caused clinically significant distress/impairment in social, occupational, or other important areas Excessive sleepiness not better accounted for by insomnia, other sleep disorder, or inadequate sleep. Not a result of other mental disorder, physical condition, substance use, or medical condition. Recurrent: 3 days concurrent several times a year for at least two years. 5-10% of sleep clinic patients Lifetime prevalence of at least 16%. Adult population prevalence is 0.5- 5%. Four year prevalence about 8%.

10. Narcolepsy Sleep attack must occur daily over period of one year over a period of at least three months. Must experience either cataplexy or recurrent intrusions of elements of REM sleep. Disturbance not due to physical condition, substance use, or medical condition. A disorder characterized by sudden and uncontrollable, though often brief, attacks of deep sleep. Sometimes is accompanied by paralysis and hallucinations Chronic disease due to brains inability to regulate sleep-wake cycles. Hypocretin system implicated in development. Treatment: keep a regular schedule, take short daytime naps, drug therapy Many people go years before seeking treatment. Symptoms: excessive daytime sleepiness. cataplexy, sleep paralysis, vivid hallucinations during sleep onset or upon awakening Drugs: GHB is Gamma hydroxybutyrate (date rape drug), Ritalin�, modafinil, dextroamphetamine, and pemoline Affects about 100, 000 thousand people in America Hypocretin-1 significantly reduced in those with cataplexy. Treatment: treat symptoms: stimulants for day time sleepiness. Antidepressents and sodium oxybate for cataplexy New medicines such as histamine antagonist, hypocretin agonist, slow wave sleep enahancers, intravenous y-globulin, tramadol, and corticosteroids. Either sleep paralysis or halluciations or sleep paralysis at the begaining or end of sleep. Prevelance: 0.02-0.16% Other Cataplexy 70% Halluciantions 20-40% Sleep paralysis 30-50% May be genetic component 5-15% 1st degree biological relatives. 25-50% relatives have another sleep disorder Dog studies: increased cholinergic and decreased monoaminergic No gender difference; age onse 13-24 years. 6% start before 10 Dog Symptoms: excessive daytime sleepiness. cataplexy, sleep paralysis, vivid hallucinations during sleep onset or upon awakening Drugs: GHB is Gamma hydroxybutyrate (date rape drug), Ritalin�, modafinil, dextroamphetamine, and pemoline Affects about 100, 000 thousand people in America Hypocretin-1 significantly reduced in those with cataplexy. Treatment: treat symptoms: stimulants for day time sleepiness. Antidepressents and sodium oxybate for cataplexy New medicines such as histamine antagonist, hypocretin agonist, slow wave sleep enahancers, intravenous y-globulin, tramadol, and corticosteroids. Either sleep paralysis or halluciations or sleep paralysis at the begaining or end of sleep. Prevelance: 0.02-0.16% Other Cataplexy 70% Halluciantions 20-40% Sleep paralysis 30-50% May be genetic component 5-15% 1st degree biological relatives. 25-50% relatives have another sleep disorder Dog studies: increased cholinergic and decreased monoaminergic No gender difference; age onse 13-24 years. 6% start before 10 Dog

11. Cataplexy Neurological condition in which the person experiences sudden bilateral loss of muscle tone and falls, usually experienced right after a strong emotion (anger, fear, or excitement). Can last from seconds to minutes. Can be a symptom of Narcolepsy (60-100%) Treated with antidepressants; imipramine or desipramine Can be confused with epilepsy Laughter caused more effects then negative emotions. SSRI�sCan be confused with epilepsy Laughter caused more effects then negative emotions. SSRI�s

12. Sleep Paralysis A condition either at on set of sleep or at awaking when a person is aware of their surroundings, but not able to move. Often associated with Narcolepsy. Treated with antidepressants and SSRI�s

13. Sleep Apnea Sleep disruption leading to excessive sleepiness or less commonly insomnia due to abnormalities of ventilation during sleep. Sleep disruption not accounted for by another sleep disorder, mental disorder, physical condition, substance use, or medical condition. Physiological disorder in which reduced muscle tone results in blocked air passages. Apnea is the cessation of breath for ten or more seconds. This leads to frequent brief arousals from sleep. May be caused by decreased levels of Serotonin in the hypoglossal nucleus. Treatment: Continual Positive Airway Pressure (CPAP), Lifestyle Changes, and Surgery. A new medicine modafinil (Provigil) is some times given to prevent day time sleepiness along with CPAP Behan, M. and M. S. Brownfield. 1999 Age-related changes in serotonin in the hypoglossal nucleus of rat: Implications for sleep-disordered breathing. Neurosci. Lett. 267:133-136. Fuller, D.D., Baker, T.L., Behan, M. and G.S. Mitchell, 2001.Expression of hypoglossal long term facilitation differs between sub-strains of Sprague-Dawley rat. Physiol. Genomics 4;175-181 http://www.vetmed.wisc.edu/cbs/behan/miscfiles/behan3.htm Lifestyle changes - including stopping smoking, cutting back on the use of alcohol and weight loss. Prevalence 1-10% adults; maybe higher in elderly; usually appears 40-60 daysBehan, M. and M. S. Brownfield. 1999 Age-related changes in serotonin in the hypoglossal nucleus of rat: Implications for sleep-disordered breathing. Neurosci. Lett. 267:133-136. Fuller, D.D., Baker, T.L., Behan, M. and G.S. Mitchell, 2001.Expression of hypoglossal long term facilitation differs between sub-strains of Sprague-Dawley rat. Physiol. Genomics 4;175-181 http://www.vetmed.wisc.edu/cbs/behan/miscfiles/behan3.htm Lifestyle changes - including stopping smoking, cutting back on the use of alcohol and weight loss. Prevalence 1-10% adults; maybe higher in elderly; usually appears 40-60 days

14. Circadian Rhythm Sleep Disorder Persistent or recurrent pattern of sleep disruption leading to excessive sleepiness or insomnia due to mismatch between sleep-wake schedule. Clinically significant distress/impairment in social, occupational, or other important areas. Disturbance of sleep is not due to another sleep disorder. Disturbance of sleep is not due to another mental disorder Not due to direct effects of substance use or general medical condition. Delayed Sleep Phase Type - A persistent pattern of late sleep onset and late awakening times with an inability to fall asleep and awaken at a desired earlier time. Shift Work Type - Night shift or shift changes - Can start in adolescence and last for years or decades without intervention. - shift work: sleep back to normal within 2 weeks after shift change. - Jet Lag: one day per time zone Not just a night owl, It bothers those effected. Prevalence 0.1-4% adults, 7% adolescents; family 40%Not just a night owl, It bothers those effected. Prevalence 0.1-4% adults, 7% adolescents; family 40%

15. Nightmares Repeated awakening from the major sleep period or naps with detailed recall of extended and extremely frightening dreams, usually involving threats of survival, security, or self-esteem. On awakening from frightening dreams, person rapidly becomes oriented and alert. Dream experience or sleep disturbance resulting from the awakening results in clinically significant distress/impairment in social, occupational, or other important areas. Nightmares not due to another sleep disorder, mental disorder, physical condition, substance use, or medical condition. Dreams that occur in REM sleep, less intense then sleep terrors. Awakening usually occurs in second half of sleep period. Prevalence 10-50% kids 3-5 years old; 3% young adults; 50% adults suffer occasional nightmares. Likely to reoccur in children that are exposed to severe psychosocial stressors

16. Sleep Terrors Recurrent episodes of abrupt awaking from sleep. Intense fear and signs of autonomic arousal such as tachycardia, rapid breathing, & sweating. Relative unresponsiveness to efforts of others to comfort the person during the episode. No detailed dreams are recalled and there is amnesia for the episode. The episode causes clinically significant distress/impairment in social, occupational, or other important areas. Not due to another sleep disorder, mental disorder, physical condition, substance use, or medical condition. Abrupt autonomic arousal in Stage 3-4 sleep that is interpreted as fear. Often occurs between 4-12 years or 20-30 years. Often resolves in adolescence. Chronic sleep terrors waxes and wanes. Psychopathology is likely to be associated with PTSD and general anxiety. Prevalence 1-6% children; less then 1% adults. No treatment in children, usually go away. Can give sleep medication. Also may be related to personality disorders Adults even gender Children more males 10 increase among family membersAlso may be related to personality disorders Adults even gender Children more males 10 increase among family members

17. Sleep Walking (somnambulism) Repeated episodes of rising from bed during sleep and walking about. While sleep walking person has a blank staring face; is relatively unresponsive of others to communicate with him/her, and can be awakened only with great difficulty. On waking the person has amnesia. Within several minutes after awakening from sleep walking episode. There is no impairment, mental activity, or behavior. (May be a period of confusion disorientation.) Sleep walking causes clinically significant distress. Not due to another sleep disorder, mental disorder, physical condition, substance use, or medical condition. Stage 3 and 4 sleep Prevalence 10-30% of children at least once; 2-3% often. Occurs 1-7% of adults and 0.5%-0.7% have weekly or monthly attacks Gender differences occurs more often in females during childhood. Occurs mostly in males in adulthood. ; usually occurs in first 1/3 of sleep ; usually occurs in first 1/3 of sleep

18. REM Behavior Disorder A neurological disorder in which a person does not become paralyzed during REM sleep, and acts out dreams his/her dreams. Degenerative neurological illness in 50% of affected persons. Often give Clonazepam

19. Restless Leg Syndrome Neurological disorder that is characterized by unpleasant sensations of legs and an urge to move them when at the rest. Sleep movements can be so severe that causes chronic sleep disturbances and sleep deprivation Effects about 12 million Americans. Causes: Mostly unknown (idiopathic) Treatment: underlying cause, some meds, and exercise. Prevalence- 5-10%. Increases with age 15% of geriatric About 50% unknown People with low iron levels or anemia may be prone to developing RLS. Once iron levels or anemia is corrected, patients may see a reduction in symptoms. Chronic diseases such as kidney failure, diabetes, Parkinson's disease, and peripheral neuropathy are associated with RLS. Treating the underlying condition often provides relief from RLS symptoms. Some pregnant women experience RLS, especially in their last trimester. For most of these women, symptoms usually disappear within 4 weeks after delivery. Certain medications-such as antinausea drugs (prochlorperazine or metoclopramide), antiseizure drugs (phenytoin or droperidol), antipsychotic drugs (haloperidol or phenothiazine derivatives), and some cold and allergy medications-may aggravate symptoms. Patients can talk with their physicians about the possibility of changing medications. May be exacerbated by alcohol, caffeine, and nicotine dopaminergics, benzodiazepines, opioids, and anticonvulsants. Dopaminergic agents, largely used to treat Parkinson's disease Prevalence- 5-10%. Increases with age 15% of geriatric About 50% unknown People with low iron levels or anemia may be prone to developing RLS. Once iron levels or anemia is corrected, patients may see a reduction in symptoms. Chronic diseases such as kidney failure, diabetes, Parkinson's disease, and peripheral neuropathy are associated with RLS. Treating the underlying condition often provides relief from RLS symptoms. Some pregnant women experience RLS, especially in their last trimester. For most of these women, symptoms usually disappear within 4 weeks after delivery. Certain medications-such as antinausea drugs (prochlorperazine or metoclopramide), antiseizure drugs (phenytoin or droperidol), antipsychotic drugs (haloperidol or phenothiazine derivatives), and some cold and allergy medications-may aggravate symptoms. Patients can talk with their physicians about the possibility of changing medications. May be exacerbated by alcohol, caffeine, and nicotine dopaminergics, benzodiazepines, opioids, and anticonvulsants. Dopaminergic agents, largely used to treat Parkinson's disease

20. Reference Abad, V.C. & Guilleminault, C.(2004). Emerging drugs for narcolepsy. Expert Opinion Emerging Drugs, 9(2), 281-291. Erman, M.K. (2005). Therapeutic options in the treatment of insomnia. The journal of clinical psychiatry, 66(9), 18-23. Lemon, M.D. (2006). New medication choices for the treatment of insomnia. South Dakota journal of medicine, 59(2), 66-67. Roth, T. (2005). Prevalence, associated risks, and treatment patterns of insomnia. The journal of clinical psychiatry, 66(9), 10-13.