sleep disorders diagnosis ,patho physiology and management

sleep disorders diagnosis, pathophysiology and management

1. SLEEP DISORDERS Prepared by: Dr Prabidhi Adhikari Moderator: Assoc. Prof. Dr Tanveer Ahmed Khan

2. Contents

3. Introduction Sleep was defined by (>2000 years ago ) the Roman poet and philosopher Lucretius as the “ absence of wakefulness ” ( Chokroverty , 2009 ). Sleep as a state characterized by a suspension of voluntary functions - 19th century. Modern definition: Sleep is not as a simple absence of wakefulness and perception or a suspension of sensorial processes but the result of a combination of a passive withdrawal of afferent stimuli to the brain and functional activation of certain neurons in specific brain areas. Sleep is considered an active rather than a passive process.

4. Normal sleep A universal behavior in all animal species Occupies ~1/3 of the human life Important for maintaining normal homeostasis and body functioning Prolonged sleep deprivation can eventually lead to death

5. Physiology of Sleep Sleep is comprised of 2 states: REM (rapid eye movement) sleep NREM (non-rapid eye movement) sleep NREM: 75% of total sleep time Stages 1-4 Physiological state of hypoarousal Slow HR (5-10 beats slower), low BP, reduced muscle tone, low RR Increases after exercise and starvation

6. Physiology of Sleep NREM Stages: Stage 1 (5%): Theta waves ( initiation ) Stage 2 (45%): K-complexes and Sleep spindles ( light sleep ) Stage 3 and 4 (25%): Delta waves “ deep sleep ” Most stage 4 sleep occurs in the first 1/3 of the night stages 3 &4: nocturnal enuresis, sleepwalking & night terrors Arousal from stage 3 or 4 sleep can result in unusual characteristics such as disorientation . Brief arousals are associated with amnesia for events that occur during the arousal

7. Physiology of Sleep

8. Physiology of Sleep REM 25% of total sleep time Called “ Paradoxical Sleep ” REM occurs every 90-100 minutes First REM period is shortest, lasting less than 10 minutes Later REM periods can last 15-40 minutes Most REM sleep occurs in the last 1/3 of the night EEG looks the same as awake state

9. Physiology of Sleep HR, RR, BP are all higher than during wakefulness Brain oxygen use increases Poikilothermic condition Penile erection Almost total paralysis of skeletal muscles Dreams – abstract and surreal Increases after strong psychological stimuli, such as difficult learning situations and stress Extraocular movement is due to activity of PPRF (paramedian pontine reticular formation/ conjugate gaze center)

10. Physiological changes in Sleep

11. Neuroendocrine changes GH – Released in early part of SWS Prolactin – midnight and increases REM TSH peaks evening, stimulated by sleep deprivation; inhibited by sleep. Sleep onset inhibits cortisol release, ACTH and cortisol rise at the end of sleep – likely to contribute in arousal

12. Electrophysiology of Sleep

13. Sleep Architecture Progression of sleep across the night is called sleep architecture displayed on a sleep histogram . NREM sleep Stage 3 and 4 generally observed during the first half of the sleep period REM sleep Occurs most frequently during the last 1/3 of the sleep period

14. Normal Changes with Aging

15. Changes of Sleep With Age

16. Changes in REM sleep with age

17. Sleep regulation Human sleep is regulated by two processes, a homeostatic factor and a circadian factor. Alertness level is determined by the interaction between two processes. Homeostatic drive (Process S) : promotes sleep and builds up during wake, reaching a maximum in the late evening (near the usual sleep time). depends on the amount of prior sleep and wakefulness

18. Sleep regulation Circadian rhythm Is driven by an endogenous circadian pacemaker, generating nearly 24-hour cycles of behavior . “Master circadian clock” Suprachiasmatic nuclei (SCN) of the hypothalamus. SCN are bilaterally paired nuclei located slightly above the optic chiasma in the anterior hypothalamus SCN regulates the timing of body rhythms . Also controls sleep-wake cycle.

19. Sleep regulation The circadian clock is “set” primarily by visual cues of light and darkness that are communicated along a pathway from the eyes to the SCN. Circadian clocks normally are synchronized to environmental cues ( zeitgebers )- Entrainment . The process of entrainment of SCN cells is mediated through glutamate stimulating the N-methyl-D-aspartate receptor Circadian rhythms and their sensitivity to time cues may change as a person ages.

20. Sleep regulation Light hitting the retina activates the release of glutamate through the retino -hypothalamic tract projecting to the SCN .

21. Physiology of Sleep The circadian rhythm system (Process C) promotes wakefulness during the day. It is biphasic and tends to dip in the midafternoon. Process C also reaches its peak in the evening to counterbalance the accumulation of homeostatic drive that has built up throughout the day and it begins to fall just before the usual bedtime. This system promotes wakefulness during the day and consolidates sleep at night

22. Physiology of Sleep The APA Textbook of Psychiatry, Fifth Edition.

23. Neuroanatomy Wake promoting areas: Basal forebrain (BF) Posterior/ lateral hypothalamus Latero-dorsal tegmental nucleus (LDT) Pedunculopontine nucleus (PPT) Thalamus Sleep promoting areas: GABA- ergic neurons of Basal forebrain Caudal cholinergic nuclei – LDT & PPT (REMS-on) Aminergic nuclei – Locus Ceruleus and Dorsal raphe (REMS-off) VLPO –Anterior hypothalamus

24. Neurotransmitters in Sleep-Wake Regulation

25. Neurobiology of wakefullness Controlled by ARAS – Ascending arousal system Ascending arousal system – Cluster of nerve cells extending from upper pons to hypothalmus & basal forebrain Arousal system activates cerebral cortex, thalamus and other forebrain regions using neurotransmitters

26. Acetylcholine originate in the latero-dorsal and pedunculopontine tegmental nuclei (LDT/PPT) of the midbrain reticular formation reach the cortex by ascending through the thalamus and hypothalamus. midbrain LDT and PPT areas contain two interspersed subsets of cholinergic neurons

27. Acetylcholine 1 st subset is responsible for the fast-frequency and low-voltage EEG pattern of ‘‘ cortical activation ,’’ which appears in REM sleep and restful wakefulness. 2 nd subset is responsible for generations of REM sleep . These cholinergic neurons are called REM-on cells. The REM-on cholinergic neurons promote REM sleep by sending excitatory input to the pontine reticular formation (PRF) -> causes the rapid firing of the PRF, which produces the three cardinal physiologic components of REM sleep. PRF is shut off during NREM sleep

28. Orexin system Orexin system reinforces activity in other arousal cell groups. Reduced activity of hypocretin systems may be partly responsible for inducing sleepiness . Orexin system also suppress REM sleep through activation of aminergic REM off neurons.

29. Orexin system Hypocretin concentration - highest during the waking period Hypocretin levels - increase during a period of forced sleep deprivation. Hypocretin input to the brainstem REM-on cells controls the switch into REM by reducing the firing rate of the REM-on cells during the wake period . Specific loss of the orexin neurons causes narcolepsy

30. Serotonin and Norepinephrine Serotonin and norepinephrine neurons promote cortical activation during wakefulness by rapid firing. During the NREM sleep period, at the beginning of the first sleep cycle, the serotoninergic and noradrenergic neurons significantly reduce their firing rate- removes the inhibition from the REM leading to the first REM sleep period approximately 90 minutes later .

31. Histamine Histaminergic neurons originate from the TMN of the posterior hypothalamus and project diffusely throughout the brain. facilitates cortical arousal fire most rapidly during cortical activation in the wake state and turn off during REM sleep

32. Sleep disorders A group of conditions that disturb normal sleep patterns . Inadequate or non-restorative sleep can interfere with normal physical, mental, social, and emotional functioning. A ffect overall health, safety, and quality of life. I mpairment in the quality of life in patients with insomnia

33. Categories Primary sleep disorders : Not caused by other mental disorders, medications, substance use or medical conditions Dyssomnias Difficulty getting enough sleep Problems in the timing of sleep Complaints about the quality of sleep Parasomnias Abnormal behavioral & physiological events during sleep e.g. nightmares, sleep walking, sleep talking

34. International Classification of Sleep Disorders (ICSD)-3 Insomnia Sleep-disordered breathing  Central disorders of hypersomnolence Circadian rhythm sleep-wake disorders Parasomnias Sleep-related movement disorders

35. Classification Sleep-wake disorders DSM-5 ICD 11 Insomnia Disorder Hypersomnolence Disorder Narcolepsy Obstructive Sleep Apnea Central Sleep Apnea Sleep-Related Hypoventilation Circadian Rhythm Sleep Wake Disorders Non-REM Sleep Arousal Disorders Nightmare Disorder REM Sleep Behavior Disorder Restless Legs Syndrome Substance/Medication – Induced Sleep Disorder Insomnia disorders  (7A00-7A0Z) Hypersomnolence disorders  (7A20-7A2Z) Sleep-related breathing disorders  (7A40-7A4Z) Circadian rhythm sleep-wake disorders  (7A60-7A6Z) Sleep-related movement disorders  (7A80-7A8Z) Parasomnia disorders  (7B00-7B0Z) Other specified sleep-wake disorders  (7B2Y) Sleep-wake disorders, unspecified  (7B2Z)

36. Primary Insomnia/Insomnia disorder Difficulty initiating sleep, maintaining sleep, &/or nonrestorative Primary: insomnia is not related to other medical or psychiatric problems 1/3 of general population report Symptoms prevalence : 10%

37. Primary Insomnia/Insomnia disorder F:M= 1.44:1 First episode : young adulthood New onset insomnia in female during menopause and persists even after other symptoms resolve. Chronic course : 45 to 75 % cases

38. Diagnostic criteria DSM-5 “Insomnia Disorder” Dissatisfaction with sleep quantity/quality(one or more) Initiation, maintenance or early morning waking Clinically significant distress Minimum 3 nights/week Minimum 3 months Adequate sleep opportunity Not better explained or exclusively during the course of another sleep-wake disorder Not caused by substance Coexisting conditions don’t adequately explain Specify: with non-sleep mental comorbidity; with other medical comorbidity; with other sleep disorder Can be episodic, persistent or recurrent ICSD-3 “Chronic Insomnia Disorder” One or more difficulty Initiating sleep Maintaining sleep Waking too early Resistance to appropriate bedtime Difficulty sleeping without parent or caregiver intervention Related to sleep difficulty, one or more Fatigue Attention/concentration/memory impairment Social/family/occupational/academic impairment Mood disturbance Daytime sleepiness Behavioral problems Reduced motivation Error proneness Dissatisfaction with/concerns about sleep Not explained by inadequate sleep opportunity 3 times per week 3 months Not better explained by another sleep disorder

39. Management(Diagnosis) Clinical interview: sleep history and rule out of other sleep disorders Data collection: sleep diary Standardized measures: Insomnia Severity Index Dysfunctional Attitudes and Beliefs about Sleep

40. Management(Diagnosis) Actigraph: A ctigraphy are used to assess total sleep time, sleep onset latency, and number of awakenings Actigraphy is a procedure where the patient continuously wears a relatively unobtrusive device on the wrist or ankle for days to weeks. The device measures the occurrence and degree of limb movements over time to provide information on sleep phases, sleep duration, daily patterns, and efficiency of sleep

41. Management(Diagnosis)

42. Management(Treatment) CBT-I: first-line therapy in adults with insomnia preferred to hypnotic medications because it has better long-term effectiveness , more improvement in daytime symptoms, and fewer adverse effects. delivered in weekly sessions for six to eight weeks . primary care physician can effectively provide CBT for insomnia. Individual or group therapy. Web-based CBT for insomnia is equally effective

43. Management(Treatment) Even in cases of short-term insomnia, CBT-I is about as effective as sleeping pills. At a 3-year follow-up, both the CBT-I and CBT for depression groups continued to experience similar reductions in depression severity, but the insomnia treatment continued to have superior effects on sleep. (AJP, Vol. 159, 2002).

44. Management(Treatment)

45. Management(Treatment) Sleep hygiene education: Alone provides minimal improvements; Effective when combined other therapies Measures : Avoid alcohol for 4 to 6 hours before bed Avoid caffeine or nicotine after 4 p.m. Avoid exercise close to bedtime Go to bed and wake up at the same time every day Keep bedroom cool and conducive to sleep No clock watching No napping during the day No watching television or other electronic devices in bed

46. Management(pharmacotherapy ) Pharmacotherapy Initiated when CBT for insomnia is ineffective or when there is incomplete symptom resolution. Medication choice should include the patient’s predominant sleep problem and the risk of potential adverse effects. American Academy of Sleep Medicine does not reccomend use of : Anti- histaminics : D/t side effects Melatonin : there are no consistent benefits, and multiple formulations are found in over-the-counter preparations Trazodone : harms outweigh the benefits

47. Management ( Pharmaco therapy) US FDA approved medication for treatment of insomnia

48. Hypersomnolence Disorder Self-reported excessive sleepiness despite a main sleep period lasting at least 7 hours and at least one of the following: Recurrent sleep periods within the same day More than 9 hours of sleep that is nonrestorative Difficulty being fully awake after abrupt awakening At least 3 nights per week; for at least 3 months Functional impairment The somnolence does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or a parasomnia. Specify : with other condition, severity and course

49. Hypersomnolence Disorder 5% to 10% of patients who seek treatment for excessive daytime sleepiness suffer from hypersomnolence disorder. Estimated to affect 1% of U.S. and European populations. Males and females are equally affected . onset : 15 and 25 years Progressive nature Risk factors Psychological stress Alcohol use Viral infections: 10 % cases ; HIV, pneumonia, IM,GBS(within 1 month of infection); Genetic: May be familial with AD inheritance

50. Diagnostic markers : Nocturnal PSG : Prolong sleep duration Short sleep latency: <10 minutes and in some patients < 8 minutes Sleep efficacy : >90 % Sleep onset REM periods : onset of REM within 20 mins of sleep onset

51. Klein –levin syndrome rare disease characterized by recurrent episodes of hypersomnia and to various degrees, behavioral or cognitive disturbances, compulsive eating behavior, and hypersexuality. First case of KLS was reported by Brierre de Boismont in 1862 Age of onset : 15 years (range, 4–80 years);mostly Affects teenagers M:F = 2:1 Prevalence: one in a million.

52. Klein –levin syndrome Diffuse brain hypoperfusion, mostly focused on the thalamic and frontotemporal areas, has been reported. abnormalities in serotonin and dopamine metabolism have been reported Viral and autoimmune causative factors have been suggested, on the basis of the frequent report of flu-like symptoms at onset, and the most frequent precipitating factor (70%). Occurred most often in autumn (31.1%) or winter (31.1%)

53. Clinical features Hypersomnia: a major clinical symptom of KLS, is mandatory for diagnosis. Sudden overwhelming tiredness, i.e. “ feeling drawn toward bed ,” or “ reluctant to get up in the morning .” sleep duration : 12 to 24 h/day patients remain arousable Cognitive disturbances such as confusion, concentration, attention, and memory defects. Treatment : Amphetamines , lithium and carbamazepine

54. Management (Treatment) Lifestyle modifications Sleep hygiene Caffeine : 600 mg of caffeine produced similar effects on psychomotor vigilance in sleep-deprived subjects taking 400 mg of modafinil. modafinil : 100 and 400 mg, given once or twice daily Amphetamines Sodium Oxybet Methylphenidate, Atomoxetine Clarithromycin: Typical starting dose reported was 500 mg taken orally with breakfast and lunch for a 2-week trial period.

55. Narcolepsy In 1880, Jean Bapiste Gelineau first described Narcolepsy as: “ a rare neurosis characterized by an urgent necessity to sleep, sudden and of short duration which recurred at intervals more or less long ”. " sleep attacks " that the patient cannot fight . The sleep attacks are about 10-20 minutes long. The patient feels refreshed by the sleep, but typically feels sleepy again several hours later.

56. Epidemiology Male: Female= 1:1 Onset : 7 to 25 years Prevalence: Narcolepsy type 1 (narcolepsy with cataplexy): 25 to 50 per 100,000 people . Narcolepsy type 2 (narcolepsy without cataplexy) : 20 to 34 per 100,00 About 40% of patients with narcolepsy have or have had another mental disorder

57. Etiology Autoimmune disorders loss of the neuropeptides, orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2). They are products of the prepro -orexin gene and are made by neurons in the lateral hypothalamus. Orexin-A and -B have excitatory effects when they bind the OX1 and OX2 receptors on postsynaptic neurons.

58. Etiology Genetic HLA-DQB1*06:02 and other HLA gene variations may increase susceptibility to an immune attack on hypocretin neurons 98% of patients with NT1 carry the HLA class II allele DQB1*06:02; this allele is present in 50% of patients with NT2 and only 12–30% of the general population  Family history : Most cases of narcolepsy are sporadic up to 10 percent of individuals diagnosed with narcolepsy with cataplexy report having a close relative with similar symptoms

59. Pathophysiology Narcoleptics often have REM sleep within 5 minutes of sleep onset, in contrast to normal individuals who rarely show such ‘‘ sleep- onset REM sleep .’ Cell populations in the pons and medulla that are tonically active only during REM sleep in normal, become active during cataplexy in narcoleptics. Cells in the locus coeruleus, which cease discharge only in REM sleep in normal animals, invariably cease discharge in cataplexy. In 2001, it was discovered that most human narcolepsy was caused by a loss of hypothalamic cells containing the peptide hypocretin . On average 90% of these cells are lost in narcolepsy.

60. Tetrad of narcolepsy Excessive daytime sleepiness (EDS) Cataplexy Sleep paralysis Hallucinations

61. Tetrad of narcolepsy Excessive daytime sleepiness (EDS): C haracterized by persistent sleepiness, regardless of how much sleep an individual gets at night. more like a “ sleep attack ,” where an overwhelming sense of sleepiness comes on quickly. In between sleep attacks, individuals have normal levels of alertness , particularly if doing activities that keep their attention.

62. Tetrad of narcolepsy Cataplexy sudden loss of muscle tone while a person is awake leads to weakness and a loss of voluntary muscle control. triggered by sudden, strong emotions such as laughter, fear, anger, stress, or excitement. symptoms may appear weeks or even years after the onset of EDS. Variation in frequency of attacks . In about 10 percent of cases of narcolepsy, cataplexy is the first symptom to appear ( can be misdiagnosed as a seizure disorder). Attacks may be mild and involve only a momentary sense of minor weakness in a limited number of muscles, such as a slight drooping of the eyelids.

63. Tetrad of narcolepsy Cataplexy The most severe attacks result in a total body collapse during which individuals are unable to move, speak, or keep their eyes open. even during the most severe episodes, people remain fully conscious, a characteristic that distinguishes cataplexy from fainting or seizure disorders. The loss of muscle tone during cataplexy resembles paralysis of muscle activity that naturally occurs during REM sleep. Episodes last a few minutes at most and resolve almost instantly on their own. While scary, the episodes are not dangerous as long as the individual finds a safe place in which to collapse.

64. Tetrad of narcolepsy Sleep paralysis The temporary inability to move or speak while falling asleep or waking up usually lasts only a few seconds or minutes and is similar to REM-induced inhibitions of voluntary muscle activity. Sleep paralysis resembles cataplexy except it occurs at the edges of sleep. people remain fully conscious. cataplexy and sleep paralysis do not result in permanent dysfunction—after episodes end, people rapidly recover their full capacity to move and speak.

65. Tetrad of narcolepsy Hallucinations: Hypnagogic and hypnopompic Most often the content is primarily visual, but any of the other senses can be involved.

66. Narcolepsy Prevalence of classic narcolepsy with emotion-triggered cataplexy is approximately .02% to .05%. Equal incidence in men and women Approximately 30% of narcoleptics suffer from excessive daytime sleepiness and sleep-onset REM but have no history of cataplexy Approximately 20% report sleep paralysis upon falling asleep or awakening Associated with insomnia.

67. Diagnostic criteria Recurrent periods of irrepressible need to sleep, lapsing into sleep, or napping occurring within the same day, occurring at least three times per week over the past 3 months The presence of one of the following:- Episodes of cataplexy, defined as either: In individuals with long-standing disease, episodes of sudden bilateral loss of muscle tone with maintained consciousness that are precipitated by laughter or joking. In children or in individuals within 6 months of onset, spontaneous grimaces or jaw-opening episodes with tongue thrusting or a global hypotonia, without any obvious emotional triggers- Hypocretin deficiency, as measured using cerebrospinal fluid (CSF) Nocturnal sleep polysomnography showing REM sleep latency less than or equal to 15 minutes, or a MSLT showing a mean sleep latency less than or equal to 8 minutes and two or more sleep-onset REM periods Specify : with cataplexy, with hypocretin deficiency,Autosominal dominant ,secondary to another medical condition Specify: severity

68. Diagnosis Sleep diary Polysomnogram (PSG or sleep study) The PSG is an overnight recording of brain and muscle activity, breathing, and eye movements. A PSG can help reveal whether REM sleep occurs early in the sleep cycle and if an individual's symptoms result from another condition such as sleep apnea. Level of Hypocretin in CSF: hypocretin-1 level less than 110 pg /mL is diagnostic of narcolepsy with cataplexy, but levels are normal in 85 %–90 % of narcolepsy without cataplexy and in idiopathic hypersomnia.

69. Diagnosis Multiple sleep latency test (MSLT): A person is given 4-5 opportunities to sleep every two hours during normal wake times. M easures the extent of daytime sleepiness (sleep latency), and how quickly REM sleep begins. A positive MSLT (diagnostic for narcolepsy) is obtained when the patient fall asleep with a mean sleep latency below 8 minutes in the naps and had at least 2 naps where REM sleep was reached.

70. Treatment Non-pharmacological: Sleep hygiene E xcessive daytime sleepiness (EDS) Modafinil : Approved by the FDA and EMA. Dosage: in tablets of 100–400 mg orally. Initially, treatment is started with 100 mg, which can be divided into two intakes of 50 mg at least 2 hours apart. Methylphenidate: 10 and 60 mg orally and should not exceed 72 mg

71. Treatment E xcessive daytime sleepiness (EDS) Amphetamines or dextroamphetamine: doses between 5 and 30 mg orally, twice a day, or 20 mg in a sustained release formulation twice a day are usually used. Pitolisant: histamine H3-receptor antagonist recently approved by FDA as the only non-scheduled product

72. Treatment cataplexy and symptoms resulting from dysregulation of REM sleep Sodium oxybate :( also known as gamma hydroxybutyrate) approved by the U.S. (FDA).  Dosage: it is an oral solution (500 mg/ml). The recommended initial dose is 4.5 g/night (divided into 2 doses, each of 2.25 grams) spaced at least 2.5–4 hours apart before the new dose, so that most of the drug has been eliminated when the patient wakes up. Up to a maximum of 9 g/day (7 g/day in children <12 years).

73. Treatment C ataplexy and symptoms resulting from dysregulation of REM sleep Pitolisant: single morning dose (9–36 mg/day) orally. 4.5 mg and 18 mg tablets Tricyclic antidepressants: clomipramine - most commonly used Dose : lower than antidepressant selective serotonin reuptake inhibitors (SSRIs)

74. Treatment C ataplexy and symptoms resulting from dysregulation of REM sleep MAO: Phenelzine has been used successfully in seven patients with resistant narcolepsy, with persistent efficacy after 1 year of treatment. Selegeline MAO-A inhibitors such as brofaromine Venlafaxine, Duloxetene : Started at 37.5 mg Reboxetine. Solriamfetol a selective dopamine and noradrenaline reuptake inhibitor the FDA approved it for narcolepsy-associated drowsiness  Dose: range 75–150 mg/day of oral administration

75. Breathing related sleep disorders

76. Obstructive sleep apnea Affects : 1-2 % children; 2-15 % adults and > 20% older individuals M>F Follows J saped pattern: peak 3-8 years, again increase in adults Insidious onset, gradual progression Risk factors: Obesity Family history Jaw /facial abnormalities; Acromegaly Syndromes: down, teacher collin’s syndrome Menopause Adenoid hypertrophy

77. Diagnostic criteria Either 1 0r 2 Evidence by polysomnography of at least  5  obstructive apneas or hypopneas per  1  hour of sleep and either of the following sleep symptoms: (A)  Nocturnal breathing disturbances: snoring, snorting/gasping, or breathing pauses during sleep.  (B)  Daytime sleepiness, fatigue, or unrefreshing sleep despite sufficient opportunities to sleep that is not better explained by another mental disorder (including a sleep disorder) and is not attributable to another medical condition. Evidence by polysomnography of  15  or more obstructive apneas and/or hypopneas per hour of sleep  regardless  of accompanying symptoms

78. Pathophysiology

79. Treatment Lifestyle modification: A 10% reduction in weight can lead to a 26% decrease in the AHI. Cont inuous positive airway pressure (CPAP) therapy : first line of treatment for moderate to severe sleep apnea. Surgical interventions include uvulopalatopharyngoplasty, soft palate implants (Pillar Procedure), and hyoid advancement Positional Sleep Trainer Dental device

80. Central sleep apnea CSA is a sleep disorder characterized by episodes of apnea (cessation of breathing) during sleep because the brain does not cue the body to continue breathing. Cheyne-Stokes breathing is a subtype of CSA, seen in patients with severe cardiac, neurologic, or renal impairment. In CSA, breathing stops because there is no  drive  to breathe. On the other hand, in OSA, there is  always  a drive to breath , but that drive is impeded by airway collapse CSA occurs in approximately 20% of individuals with acute stroke. 30% of individuals taking chronic opioids ; individuals receiving methadone maintenance therapy.

81. Epidemiology prevalence idiopathic central sleep apnea unknown (rare) central sleep apnea is high in individuals with depressed cardiac ventricular ejection fraction(ejection fraction of less than 45%, the prevalence has been reported to be 20% or higher.) M>F Prevalence increases with age, and most patients are older than 60 years

82. Diagnostic criteria Criterion A Evidence by polysomnography of  5  or more central apneas for each  1  hour of sleep. Criterion B The disorder is not better explained by another current sleep disorder .. Specify : Idiopathic CSA Chyne stroke breathing CSA with co-morbid opoid use

83. Management Physical examination: Findings consistent with heart failure, such as jugular venous distension, S3 heart sound, lung crackles, and lower extremity edema, may be present. Investigations : PSG Treatment: Positive airway pressure therapy may be considered for the treatment of primary central sleep apnea syndromes. Zolpidem and triazolam (if no risk of RD) Bilevel positive airway pressure (apnea related to CHF.) Adaptive servo-ventilation(apnea related to CHF.) Nocturnal o2 therapy (apnea related to CHF.) Acetazolamide and theophylline (apnea related to CHF.)

84. Sleep related hypoventilation sleep disorder related to progressive respiratory impairment. When this disorder occurs comorbidly with other disorders (e.g., COPD, neuromuscular disorders, obesity), disease severity reflects the severity of the underlying condition, and the disorder progresses as the condition worsens. Idiopathic sleep-related hypoventilation in adults is very uncommon. The prevalence of congenital central alveolar hypoventilation is unknown, but the disorder is rare. Comorbid sleep-related hypoventilation (COPD, neuromuscular disorders, or obesity) is the most common.

85. Diagnostic criteria Criterion A Polysomnography demonstrates episodes of decreased respiration associated with elevated CO2 levels. Note: In the absence of objective measurement of CO2 , persistent low levels of hemoglobin oxygen saturation unassociated with apneic/ hypopneic events may indicate hypoventilation . The disturbance is not better explained by another current sleep disorder. Specify if: Idiopathic hypoventilation : This subtype is not attributable to any readily identified condition. Congenital central alveolar hypoventilation:  This subtype isa rare congenital disorder in which the individual typically presents in the perinatal period with shallow breathing, or cyanosis and apnea during sleep. Comorbid sleep-related hypoventilation: (medical condition) Severity: is graded according to the degree of hypoxemia and hypercarbia present during sleep and evidence of end organ impairment due to these abnormalities (e.g., right sided heart failure). The presence of blood gas abnormalities during wakefulness is an indicator of greater severity.

86. Pathophysiology Children Congenital central alveolar hypoventilation usually manifests at birth with shallow, erratic, or absent breathing. This disorder can also manifest during infancy, childhood, and adulthood because of variable penetrance of the PHOX2B mutation. Adults Pulmonary hypertension, cor pulmonale, cardiac dysrhythmias, polycythemia, neurocognitive dysfunction, and worsening respiratory failure can be the cause of sleep-related hypoventilation. The disorder severity corresponds with increasing severity of blood gas abnormalities

87. Management PSG: D iagnosed using polysomnography showing sleep-related hypoxemia and hypercapnia that is not better explained by another breathing-related sleep disorder. Arterial CO2 : The documentation of increased arterial pC02 levels to greater than 55 mmHg during sleep or a 10 mmHg or greater increase in pC02 levels (to a level that also exceeds 50 mmHg) during sleep in comparison to awake supine values, for 10 minutes or longer, is the gold standard for diagnosis.  O2 saturation: Prolonged and sustained decreases in oxygen saturation (oxygen saturation of less than 90% for more than 5 minutes with a nadir of at least 85%, or oxygen saturation of less than 90% for at least 30% of sleep time) in the absence of evidence of upper airway obstruction

88. Treatment Treatment will be determined on the underlying cause of the sleep-related hypoventilation, as well as the levels of carbon dioxide present in the blood. Positive Airway Pressure (PAP) therapy (often in the form of Bilevel Positive Airway Pressure (BPAP)

89. Circadin rhythm sleep-wake disorder A re sleep disorders that involve a change in the timing of when an individual sleeps and is awake. The human body has a master circadian clock in a control centre of the brain known as the suprachiasmatic nucleus (SCN). Subtypes:   Advanced Sleep Phase Type   Delayed Sleep Phase Type   Irregular Sleep-Wake Type   Non-24-Hour Sleep-Wake Type   Shift Work Type

90. Diagnostic criteria Criterion A A persistent or recurrent pattern of sleep disruption that is primarily due to an alteration of the circadian system or to a misalignment between the endogenous circadian rhythm and the sleep-wake schedule required by an individual’s physical environment or social or professional schedule. Criterion B The sleep disruption leads to excessive sleepiness or insomnia, or both. Criterion C The sleep disturbance causes clinically significant distress or impairment in social, occupational, and other important areas of functioning Specifier: subtype and course: episodic, persistent , recurrent

91. Delayed sleep phase disorder (DSP) characterized by a delay in the timing of the major sleep period (usually more than 2 hours) in relation to the desired sleep and wake-up time, resulting in symptoms of insomnia and excessive sleepiness. “ evening types ” who typically stay awake until 1 a.m. or later and wake-up in the late morning or afternoon. If able to go to bed at the preferred late time on a regular basis, a person with DSP will have a very stable sleep pattern. prevalence : 7-16%; common in teens and young adults Familial type: A positive family history may be present in approximately 40% of individuals with DPS.

92. Advanced sleep phase type C haracterized by sleep-wake times that are several hours earlier than desired or conventional times. “ morning types ” who typically wake up between 2 a.m. and 5 a.m. and go to sleep between 6 p.m. and 9 p.m. If able to go to bed at the preferred early time on a regular basis, a person with ASP will have a very stable sleep pattern. prevalence : 1% ; common in middle aged and old Familial: A family history of advanced sleep phase is present.

93. Irregular sleep awake type characterized by symptoms of insomnia at night (during the usual sleep period) and excessive sleepiness (napping) during the day . T here is no discernable sleep-wake circadian rhythm, no major sleep period, and sleep is fragmented into at least three periods during a 24-hour day. nursing home residents( who have light deprivation ) more common in patients with neurodegenerative disorders and children with neurodevelopmental disorder

94. Non-24-Hour Sleep-Wake Type characterized by symptoms of insomnia or excessive sleepiness due to abnormal synchronization between the 24-hour light-dark cycle and the individual's endogenous circadian rhythm. Non-24-hour sleep-wake type is most common among individuals who are blind, are visually impaired, or have decreased light perception. rare in sighted individuals The prevalence in blind individuals is estimated to be as high as 50%

95. Shift Work Type  characterized by a history of an individual working outside of the normal hours (i. e. 8:00 A.M. to 6:00 P.M) on a regular schedule. Individuals will have symptoms of excessive sleepiness at work, and sleep impairment at home. 5 to 10% of night shift workers

96. Jet-Lag disorder occurs when long travel by airplane quickly puts a person in another time zone. temporary condition with symptoms that begin approximately one to two days after air travel across at least two time zones . severity of the problem increases with the number of time zones that are crossed. The body tends to have more trouble adjusting to eastward travel than to westward travel Elderly- symptoms may be more pronounced

97. Circadin rhythm sleep-wake disorder (management) Lifestyle changes: adjusting their exposure to daylight, making changes in the timing of their daily routines, and strategically scheduling naps Sleep hygiene Bright light therapy : This therapy synchronizes the body clock by exposing the eyes to safe levels of intense, bright light for brief durations at strategic times of day. Medications: hypnotic -to promote sleep or a stimulant -to promote wakefulness Melatonin

98. Non-REM Sleep Arousal Disorders 10% to 30% of children have at least one sleepwalking episode and 2% sleepwalk often. Prevalence is lower in adults (1–7%)Sleep terrors more common in children. 20% young children, with 4% to 5% experiencing one or more episodes per week 75% of patients with sleep terrors will report sleepwalking

99. Diagnostic criteria Recurrent episodes of incomplete arousals from non-REM sleep; usually occurring during the first third of the nighttime sleep episode; typically brief (10 minutes – 1 hour), accompanied by one of the following: Sleepwalking: Repeated episodes of rising from bed during sleep and walking about; while sleepwalking, the person has a blank, staring face, is relatively unresponsive to the communication efforts of others to communicate, and can be awakened only with great difficulty Sleep terrors: Recurrent episodes of abrupt terror arousals from sleep, usually beginning with a panicky scream; intense fear and autonomic arousal is present (tachycardia, rapid breathing, sweating); relatively unresponsive to efforts of others to comfort.

100. Diagnostic criteria Little or no dream image is recalled. Amnesia for the episode is present. Episodes cause significant impairment in functioning Not attributed to physiological effect of substance Not explained by other conditions Specify Types: Sleepwalking type: With sleep related eating With sleep related sexual behavior

101. Treatment nonpharmacological strategies of ensuring safety, providing reassurance and education, and advising patients to avoid triggers (priming and precipitating factors) such as sleep deprivation. Benzodiazepines: P articularly clonazepam—are the typical next step B ehavioral interventions : scheduled awakenings hypnosis mindfulness-based stress reduction,  cognitive behavioral therapy for insomnia (CBT-I),CBT for stress and anxiety

102. Nightmare Disorder C ommon in childhood About 6% of adults have one nightmare per week Only 1% to 2% have more frequent nightmares Peak ages are 10 to 29 for women; 30 to 49 for men Highly associated with PTSD May produce clinically significant insomnia.

103. Nightmare Disorder(Diagnostic criteria) Repeated occurrences of extended, extremely dysphoric, and well-remembered dreams that usually involve efforts to avoid threats to survival, security, or physical integrity. Occurs almost exclusively during REM sleep and thus more likely to occur during the second half of the sleep period. On awakening, individual rapidly becomes oriented and alert. Episodes cause significant impairment in functioning Not attributed to physiological effect of substance Not explained by other conditions Specify : Types: during sleep onset ; with non sleep disorder,othermedical condition or other sleep disorder Course and severity

104. Nightmares (Treatment ) Imagery rehearsal therapy (IRT) is one of the most used and well-supported interventions for nightmares in people with PTSD. IRT had large effects on the frequency of nightmares, sleep quality, and PTSD symptoms. combination of IRT and CBT-I resulted in even greater improvements in sleep quality ( Clinical Psychology Review, 2012 ).

105. Nightmares (Treatment ) Prazosin Benzodiazepines Associated with PTSD Atypical anti psycotics TCA Fluvoxamine Topiramate Clonidine Cyproheptadine Gabapentin Trazadone

106. REM Sleep Behavior Disorder parasomnia involving dream enactment behavior associated with loss of atonia during rapid eye movement (REM) sleep. These symptoms may bring serious harm to the individual themselves and their sleeping partners. Usually appears in adulthood Men over age 50 most likely to be affected 1:1 gender prevalence : 0.5% in general population

107. REM Sleep Behavior Disorder Often able to recall dream content Usually noticed when it causes danger to the patient Comorbid narcolepsy occurs in approximately 30% of cases comorbid neurodegenerative alpha- synucleinopathies (i.e., Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy). Symptoms may precede neurodegenerative disorders by decades

108. REM Sleep Behavior Disorder Types Idiopathic RBD: 60% of cases are idiopathic Drug-induced RBD: 5-fold and 10-fold more likely to develop in patients receiving antidepressants  SSRI(fluoxetine), TCA(mirtazapine, amitriptyline, nortriptyline, desipramine, imipramine), and MAO (phenelzine and selegiline) Ethanol use Secondary RBD due to medical condition

109. Pathophysiology   Intermittent loss of atonia during REM sleep, which leads to dreaming-related motor behaviors. Muscle atonia during normal REM sleep is controlled within the pontine tegmentum and medial medulla. Excitatory glutamatergic neurons within the dorsal pre-coeruleus nucleus activate the spinal cord inhibitory interneurons, thereby initiating REM sleep atonia. Animal models and diagnostic imaging of case reports suggesting interruption or disinhibition of these brainstem areas is the pathophysiology of RBD.

110. REM SBD (Diagnostic criteria) Repeated episodes of arousal during sleep associated with vocalization and/or complex motor behaviors. Behaviors arise during REM sleep and therefore usually occur more than 90 minutes after sleep onset; more frequent during the later portions of the sleep period; uncommon during daytime naps. Upon awakening from the episode, the individual is completely awake, alert, and not confused or disoriented Either of the following: REM sleep without atonia on PSG recording History suggestive of REM sleep behavior disorder and an established synucleinopathy diagnosis (e.g., Parkinson’s disease)

111. REM SBD (Management) Screening: PSG, Mayo Sleep Questionnaire  Safety measures and Bed alarm Discontinue medications known to exacerbate RBD. Bupropion is DOC for comorbid depression Prognostic counseling: early marker of neurodegenerative disease.

112. REM SBD (Management) First-line treatment: long-acting benzodiazepine low-dose clonazepam at doses from 0.5-1 mg/day. Effective in 90% Avoid in OSA and elderly Melatonin at high-doses: alternative first line 3-15 mg at bedtime I mmediate-release melatonin(preferred in old age ) Second-line drugs: considered in treatment refractory patients Pramipexole and rivastigmine Others: temazepam, lorazepam, zolpidem, zopiclone, cannabinoids, and sodium oxybate .

113. Restless leg syndrome(Willis Ekbom Disease) I s a motor-sensory neurological sleep disorder characterized by uncomfortable sensations in the lower extremities that are accompanied by an almost irresistible urge to move the legs or arms. described as creeping, crawling, tingling, burning, or itching sensations. Symptoms typically occur at night and are relieved by movement. Prevalence: 5 to 10% ; higher in Caucasians (up to 15%), and may be lower in Asian and African populations. 2 to 3 times during pregnancy RLS also increases with age F:M = 2:1

114. Restless leg syndrome onset : second or third decade of life. Comorbidity: Depressive disorders, anxiety disorders, ADHD CVD , HTN, narcolepsy, migraine, Parkinson's disease, multiple sclerosis, peripheral neuropathy, OSA,DM, fibromyalgia, osteoporosis, obesity,  thyroid disease and cancer. Iron deficiency, and CRF Risk Factors SSRIs  and  mirtazapine  ( up to 30%)

115. Restless leg syndrome(Willis Ekbom Disease) Diagnostic criteria : “URGE” Unpleasant sensation U – rge to move legs R – est – symptoms worsened at rest G – ets better with movement E – vening – symptoms worse in evening ≥ 3x/week, ≥ 3months Significant distress Not due to medical condition, substance

116. RLS(Management) Non-ergotamine dopamine agonists : pramipexole(0.125 mg titrate every 5 days to) effective dosage 0.125-0.75 mg , maximum 1.5 mg and ropinirole : ED - 1.5-2.5 mg Ergotamine agonists: Cabergoline: 0.5-2 mg 6 ; Bromocriptine:5-15 mg antiepileptic drugs (e.g., carbamazepine: 100-400 mg , levetiracetam) Clonazepam: . 0.5-2 mg is usual dose Gabapentin : 600-1200 mg, maximum 2700 mg Others : clonidine, levodopa, opioids Iron replacement therapy: Serum ferritin concentration lower than 45 to 50 mcg/L (ng/mL) has been associated with an increased severity of restless legs syndrome.

117. Substance/medicine induced sleep disorder Criterion A A prominent and severe disturbance in sleep. Criterion B There is evidence from time history, physical examination, or laboratory findings of both (1) and (2): The symptoms in  Criterion A  developed during or soon after substance intoxication or after withdrawal from or exposure to a medication. The involved substance/medication is capable of producing the symptoms in  Criterion A . Criterion C The disturbance is not better explained by a sleep disorder that is not substance/medication-induced. Such evidence of an independent sleep disorder Criterion D The disturbance does not occur exclusively during the course of a  delirium . Criterion E The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning

118. Substance/medicine induced sleep disorder occur most commonly with intoxication or withdrawal from substance. certain medications (agonists/antagonists): dopamine, cholinergic, serotonergic, antihistamines, and corticosteroids can also cause sleep disturbances. opioids sedatives/hypnotics stimulants (including amphetamines) cocaine anxiolytics tobacco alcohol caffeine cannabis other substances

119. Substance/medicine induced sleep disorder Objective and subjective sleep disturbances at each stage of AUD

120. Substance/medicine induced sleep disorder ICSD 3 Central Sleep Apnea Due to Medication or Substance: opioids- ataxic Breathing Sleep related Hypoventilation: opioids, BZ Hypersomnia: barbiturates, BZ, GHB, opioids, Marijuana Parasomnia: Marijuana Sleep related Movement Disorders: opioids withdrawal, BZ withdrawal, stimulants, alcohol withdrawal

121. Sleep in psychiatric disorders

122. References Comprehensive textbook of psychiatry 10 th edition Diagnostic and statistical manual – 5 , APA International classification of sleep disorder –3 rd edition American academy of sleep medicine guidelines European medical association sleep disorder guidelines International classification of mental and behavioral disoreder-11 th edition Behavior psychology-4 th edition Indian Journal of Psychiatry , February 2018

123. THANK YOU