1.Classification of Sleep disorders 1

2. Sleep Medicine Sleep Medicine is a young field and its nosology is far from fixed. The first attempt to classify sleep disorders had its origin in a workshop at the 1972 annual meeting of the Association for the Psychophysiological Study of Sleep (APSS), resulting in the establishment of a Nosology Committee in 1976. 2 3. Sleep Medicine In 1979, a 137 page classification of sleep disorders (THE DIAGNOSTIC CLASSIFICATION OF SLEEP AND AROUSAL DISORDERS) sponsored by the Association of Professional Sleep Disorders Centers and the APSS was published in the newly formed journal Sleep. Classification of Sleep and Arousal Disorders: 1979 A. DIMS: Disorders of initiating and maintaining sleep (insomnias) B. DOES: Disorders of excessive somnolence C. Disorders of the sleep-wake schedule D. Dysfunctions associated with sleep, sleep stages or partial arousals (parasomnias) 3 4. Sleep Medicine THE INTERNATIONAL CLASSIFICATION OF SLEEP DISORDERS (ICSD) : By 1985 it had become apparent that knowledge had progressed to the point that a new classification was needed. The American Sleep Disorders Association (ASDA), in collaboration with European Sleep Research Society, the Japanese Society of Sleep Research and the Latin American Sleep Society, commissioned a new nosology that was published in 1990 . ICSD: The classification comprised 84 disorders and utilize a somewhat different grouping of topics based on pathophysiological concepts . 4 5. Sleep Medicine : ICSD DYSSOMNIAS Intrinsic sleep disorders Extrinsic sleep disorders Circadian rhythm PARASOMNIAS Arousal disorders Sleep-wake transition disorders Parasomnias usually associated with REM sleep Other parasomnias Sleep disorders associated with other medical or psychiatric disorders Associated with mental disorders Associated with neurological disorders Associated with other medical disorders Proposed sleep disorders 5 6. Sleep Medicine In 2002 the American Academy of Sleep Medicine, set up a committee to revise once again the classification of sleep disorders. Under the direction of Dr Peter Hauri, the committee has proposed a more pragmatic classification, based on current clinical concepts of the grouping of sleep disorders. The goals of ICSD-2 are: 1. To describe all currently recognized sleep and arousal disorders, and to base the description on scientific and clinical evidence. 2. To present the sleep and arousal disorders in an overall structure that is rational and scientifically valid 3. To render the sleep and arousal disorders as compatible with ICD-9 and ICD-10 as possible. Based on the thought express above, ICSD-2 sorts the sleep disorders into the following eight categories: 6 7. ICSD-2 ( 2005) I. Insomnias 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 of Disturbed Nocturnal Sleep. IV. Circadian Rhythm Sleep Disorders V. Parasomnias VI. Sleep Related Movement Disorders VII. Isolated Symptoms, Apparently Normal Variants, and Unresolved Issues. VIII. Other Sleep Diorders.7 8. OVERVIEW OF SLEEP DISORDERS : ICSD-28 9. 9 10. Insomnias 10 11. 11 12. 5-9 12 13. Insomnias Insomnia is a symptom of perceived reduction in the quantity or quality of sleep and is not a single clinical entity. However, certain causes of chronic insomnia are believed to be due to intrinsic disturbances of brain function.13 14. Insomnia () : DSM-IV ( nonrestorative), 14 15. General Criteria for Insomnia : ICSD-2 ( 2005) A. A complaint for difficulty initiating sleep, difficulty maintaining sleep, or waking up too early or sleep that is chronically nonrestorative or poor in quality. In children, the sleep difficulty is often reported by the caretaker and may consist of observed bedtime resistance or inability to sleep independently. B. The above sleep difficulty occurs despite adequate opportunity and circumstances for sleep. C. At least one of the following forms of daytime impairment related to the nighttime sleep difficulty is reported by the patient: i.Fatigue or malaise ii.Attention, concentration, or memory impairment iii.Social or vocational dysfunction or poor school performance iv. Mood disturbance or irritability v.Daytime sleepiness vi. Motivation, energy, or initiative reduction vii.Proneness for errors or accidents at work or while driving viii. Tension, headaches, or gastrointestinal symptoms in response to sleep loss 15 ix. Concerns or worries about sleep 16. Insomnia : ICSD-2 1. Adjustment Insomnia (Acute Insomnia) 2. Psychophysiological Insomnia 3. Paradoxical Insomnia 4. Idiopathic Insomnia 5. Insomnia Due to Mental Disorder 6. Inadequate Sleep Hygiene 7. Behavioral Insomnia of Childhood 8. Insomnia Due to Drug or Substance 9. Insomnia Due to Medical Condition 10. Insomnia Not Due to Substance or Known Physiological Condition, Unspecified (Nonorganic Insomnia, NOS) 11. Physiological (Organic) Insomnia, Unspecified 16 17. Adjustment Insomnia (Acute Insomnia) Alternate Names :Acute insomnia, transient insomnia, short-term insomnia, stress related insomnia, transient psychophysiological insomnia, adjustment disorder. Diagnostic Criteria: A. The patients symptoms meet the criteria for insomnia. B. The sleep disturbance is temporally associated with an identifiable stressor that is psychological, psychosocial, interpersonal, environmental, or physical nature. C.The sleep disturbance is expected to resolve when the acute stressor resolves or when the individual adapts to the stressor. D. The sleep disturbance lasts for less than three months. E. The sleep disturbance is not better explained by another current sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder.17 18. Psychophysiological Insomnia Alternate Names : Learned insomnia, conditioned insomnia, functionally autonomous insomnia, chronic insomnia, primary insomnia, chronic somatized tension, internal arousal without psychopathology. Diagnostic Criteria : A. The patients symptoms meet the criteria for insomnia B. The insomnia is present for at least one month. C. The patient has evidence of conditioned sleep difficulty and/or heightened arousal in bed as indicated by one or more of the following: i.Excessive focus on and heightened anxiety about sleep ii. Difficulty falling asleep in bed at the desired bedtime or during planned naps, but no difficulty falling asleep during other monotonous activities when not intending to sleep iii. Ability to sleep better away from home than at home iv.Mental arousal in bed characterized either by intrusive thoughts or a perceived inability to volitionally cease sleep-preventing mental activity v.Heightened somatic tension in bed reflected by a perceived inability to relax the body sufficiently to allow the onset of sleep D. The sleep disturbance is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder. 18 19. Paradoxical Insomnia Alternate Names: Sleep state misperception, subjective insomnia, pseudo-insomnia, subjective complaint of sleep initiation and maintenance difficulty without objective findings, insomnia without objective findings, sleep hypochondriasis, subjective sleep complaint. Diagnostic Criteria : A. The patients symptoms meet the criteria for insomnia. B. The insomnia is present for at least one month. C. One or more of the following criteria apply: i. The patient reports a chronic pattern of little or no sleep most nights with rare nights during which relatively normal amounts of sleep are obtained. ii.Sleep-log data during one or more weeks of monitoring show an average sleep time well below published age-adjusted normative values, often with no sleep at all indicated for several nights per week; typically there is an absence of daytime naps following such nights iii.The patients show a consistent marked mismatch between objective findings from polysomnography or actigraphy and subjective sleep estimates derived either from self-report or a sleep diary D. At least one of the following is observed: i. The patients reports constant or near constant awareness of environmental stimuli throughout most nights ii. The patient reports a pattern of conscious thoughts or rumination throughout most nights while maintaining a recumbent posture E. The daytime impairment reported is consistent with that reported by other insomnia subtypes, but it is much less severe than expected given the extreme level of sleep deprivation reported; there is no report of intrusive daytime sleep episodes, disorientation, or serious mishaps due to marked loss of alertness or vigilance, even following reportedly sleepless nights. F. The reported sleep disturbance is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder.19 20. Idiopathic Insomnia Alternate Names :Childhood-onset insomnia, life-long insomnia, insomnia first evident during infancy or childhood. Diagnostic Criteria : A. The patients symptoms meet the criteria for insomnia. B. The course of the disorder is chronic, as indicated by each of the following: i. Onset during infancy or childhood ii. No identifiable precipitant or cause iii.Persistent course with no periods of sustained remission C. The sleep disturbance is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder. 20 21. Insomnia Due to Mental Disorder Alternate Names : Insomnia related to psychopathology, psychiatric insomnia; insomnia due to depression, insomnia due to anxiety disorder. Diagnostic Criteria A. The patients symptoms meet the criteria for insomnia. B. The insomnia is present at least one month. C.A mental disorder has been diagnosed according to standard criteria (i.e., formal criteria as provided in the Diagnostic and Statistical Manual of Mental Disorders- see Appendix B). D. The insomnia is temporally associated with the mental disorder, however, in some cases, insomnia may appear a few days or weeks before the emergence of the underlying mental disorder. E.The insomnia is more prominent than that typically associated with the mental disorders, as indicated by causing marked distress or constituting an independent focus of treatment. F.The sleep disturbance is not better explained by another sleep disorder, medical or neurological disorder, medication use, or substance use disorder. 21 22. Inadequate Sleep Hygiene Alternate Names : Poor sleep hygiene, sleep hygiene abuse, bad sleep habits, irregular sleep habits, excessive napping, sleep incompatible behaviors. Diagnostic Criteria : A. The patients symptoms meet the criteria for insomnia. B. The insomnia is present for at least one month C.Inadequate sleep hygiene practices are evident as indicated by the presence of at least one of the following: i.Improper sleep scheduling consisting of frequent daytime napping, selecting highly variable bedtimes or rising times, or spending excessive amounts of time in bed ii.Routine use of products containing alcohol, nicotine, or caffeine especially in the period preceding bedtime iii.Engagement in mentally stimulating physically activating, or emotionally upsetting activities to close to bedtime iv.Frequent use of the bed for activities other than sleep (e.g., television watching, reading studying, snacking, thinking, planning) v. Failure to maintain a comfortable sleeping environment The sleep disturbance is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder.22 23. Behavioral Insomnia Of Childhood Alternate Names: Childhood insomnia, limit-setting sleep disorder, sleep-onset association disorder. Diagnostic Criteria : A.A childs symptoms meet the criteria for insomnia based upon reports of parents or other adult caregivers. B. The child shows a pattern consistent with either the sleep-onset association or limit-setting type of insomnia described below. i.Sleep-onset association type includes each of the following: 1. Falling asleep in an extended process that requires special conditions. 2. Sleep-onset associations are highly problematic or demanding. 3.In the absence of the associated conditions, sleep onset is significantly delayed or sleep is otherwise disrupted. 4.Nighttime awakenings require caregiver intervention for the child to return to sleep. ii. Limit-setting type includes each of the following: 1. The individual has difficulty initiating or maintaining sleep. 2. The individual stalls or refuses to go to bed at an appropriate time or refuses to return t o bed following a nighttime awakening. 3. The caregiver demonstrates insufficient or inappropriate limit setting to establish appropriate sleeping behavior in the child. The sleep disturbance is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, or medication use.23 24. Insomnia Due To Drug Or Substance Alternate Names : Substance-induced sleep disorder, alcohol-dependent sleep disorder,alcohol-dependency insomnia, stimulant-dependent sleep disorder, drug-induced sleepdisorder, substance abuse, insomnia related to drug abuse, rebound insomnia,medication side effect, medication reaction, food reaction insomnia, toxin-induced sleepdisorder. Diagnostic Criteria : A. The patients symptoms meet the criteria for insomnia. B. The insomnia is present for at least one month. C.One of the following applies: i. There is current ongoing dependence on or abuse of a drug or substance known to havesleep disruptive properties either during periods of use or intoxication or during periodsof withdrawal ii. The patient has current ongoing use of or exposure to a medication, food, or toxin knownto have sleep-disruptive properties in susceptible individuals D.The insomnia is temporally associated with the substance exposure, use or abuse, or acutewithdrawal. E.The sleep disturbance is not better explained by another sleep disorder, medical orneurological disorder, or mental disorder. 24 25. Insomnia Due to Medical Condition Alternate Names : Sleep disorder due to a general medical condition, medically based insomnia, organic insomnia, insomnia due to a known organic condition. Diagnostic Criteria : A. The patients symptoms meet the criteria for insomnia. B. The insomnia is present for at least one month. C. The patient has a coexisting medical or physiologic condition known to disrupt sleep. D. Insomnia is clearly associated with the medical or physiologic condition. The insomnia began near the time of onset or with significant progression of the medical or physiologic condition and waxes and wanes with fluctuations in the severity of this condition. The sleep disturbance is not better explained by another sleep disorder, mental disorder, medication use, or substance use disorder. 25 26. Insomnia Not Due to Substance or Known Physiologic Condition, Unspecified (NonOrganicInsomnia, NOS) This diagnosis is used for forms of insomnia that cannot be classified elsewhere but are suspected to be related to an underlying mental disorder, psychological factors, or sleep-disruptive practices. In some cases, this diagnosis may be assigned on a temporary basis when an insomnia diagnosis seems appropriate but further evaluation is required to determine the specific mental condition or psychological and behavioral factors responsible for the reported sleep difficulty. In other cases, this diagnosis may be assigned when psychological or behavioral factors appear to contribute to the insomnia but the patients symptoms fail to meet criteria for one of the other insomnia diagnoses.26 27. Physiologic (Organic) Insomnia,Unspecified This diagnosis is used for forms of insomnia that cannot be classified elsewhere but are suspected to be related to an underlying medical disorder, physiological state, or substance used or exposure. In some cases, this diagnosis may be assigned on a temporary basis when an insomnia diagnosis seems appropriate but further evaluation is required to determine the specific medical condition or toxin exposure responsible for the reported sleep difficulty. This diagnosis can also be assigned when substance abuse or dependence-related insomnia is suspected but is yet to be confirmed. In other cases, this diagnosis may be assigned when an endogenous physiologic disorder or condition appears to contribute to the insomnia but the patients symptoms fail to meet the criteria for one of the other insomnia diagnoses. 27 28. Insomnia () 5 % ( ) 3.4 % ( ) 9.3 % ( ):( ): (): () 28 29. 30-35% 15-25% 10-15% 5-10% 15-20% 29 30. 30 31. Physiological Changes in Insomnia PatientsBody temperature Daytime sleep latencyEMG , EEG , EEG Heart rateCorticosteroid Sympathetic activityAdrenaline Parasympathetic activityV O2 Skin resistance Phasic vasoconstriction 31 32. Muscle relaxation () Stimulus control () Cognitive therapy () 32 33. Lab study Sleep Lab ( PSG) for insomnia ? 33 34. 34 35. Sleep-related breathing disorders This category includes disorder of sleepiness caused by dysfunction of the upper airway or respiratory control mechanisms. Obstructive sleep apnea, obstructive sleep hypopnea and upper airway resistance syndromes are a spectrum of disorders characterized by hypotonia of upper airway muscles during sleep, resulting in varying degrees of reduce airflow with resultant hypoxemia and recurrent arousals. These disorders are highly prevalent increasing in incidence with age and body mass index. 35 36. Sleep-related breathing disorders Central sleep apnea syndrome is a rarer form of sleep-disorderedbreathing in which dysfunction of respiratory control results inrecurrent apneas with open airway. Causes include left ventricularfailure (in which central apneas are a poor prognostic sign) andsleeping at high altitudes. Central alveolar hypoventilation syndrome includesconditions of reduced respiratory drive during sleep related toneuromuscular diseases or brainstem dysfunction, and results innocturnal hypoxemia and hypercapnia. Other respiratory disorders with sleep-related symptoms includeasthma, in which attacks of bronchopasm may occur in the early hoursof the morning, and chronic obstructive pulmonary disease withnocturnal hypoxemia.36 37. 37 38. Hypersomnias not related to respiratory issues Certain disorders of excessive daytime somnolence are believed to be caused by intrinsic brain dysfunction. Narcolepsy, recognized for over a century, consist of excessive daytime sleepiness usually associated with weakness of muscles with emotion (known as cataplexy) and the premature occurrence of rapid eye movement (REM) sleep. In most instances this appears to be due to dysfunction of the hypocretin (orexin) neurotransmitter system. 38 39. Hypersomnias not related to respiratory issues Idiophatic hypersomnia is a similar but less well defined disorder, with hypersomnolence but no cataplexy and no disturbance in the timing of REM sleep. Recurrent hypersomnia is a very rare disorder with periods of sleep lasting days to weeks, often associated with behavioral disturbances ( KLS). 39 40. Hypersomnias not related to respiratory issues Insufficient sleep syndrome is a major societal problem in which voluntary sleep deprivation can result in impairment of alertness and cognitive abilities. Medications and illicit drug use can cause excessive daytime sleepiness. Hypersomnia may also be due to medical conditions, such as Parkinsons disease and dementias.40 41. NarcolepsyPsychiatrist: Yu-Shu Huang Department of Child Psychiatry 41 42. 42 43. Daytime sleepiness with and without cataplexy in Chinese-Taiwanese. Yu-shu Huang MD1, Mehdi Tafti PhD2, Christian Guilleminault MD BiolD31-Sleep Disorders Clinic, Chang-Gung University Hospital, Taipei, Taiwan 2-Center for Integrative Genomics University of Lausanne, Switzerland 3-Stanford University Sleep Medicine Program, Stanford, CA, USAAbstractWe evaluated 35 Chinese- Taiwaneses successively referred between 2002 and 2004 for excessive daytime sleepiness with presence or absence of cataplexy and no association with other sleep disorders. Subjects had in depth investigation including polysomnography, repeat multiple sleep latency test (MSLT), and HLA typing. Three patients without cataplexy also had CSF hypocretin measurements. As in other ethnies, DQB1-0602 was associated with cataplexy in over 90% of Chinese-Taiwanese cases. Absence of cataplexy and < 2 sleep onset REM periods (SOREMP) was seen in only 2 subjects, but presence of 2 SOREMP did not dissociate DQB1-0602 positive and negative or cataplexy positive and negative subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs and the mean sleep latency was much shorter in narcoleptics with cataplexy than in the non cataplectic patients independently of number of SOREMPs. Our study indicates that Chinese Taiwanese with cataplexy presents with similar HLA findings as Black and Caucasian, but presence of two or more SOREMPs in Chinese Taiwanese patients is not a good diagnostic tool to identify Narcolepsy. When cataplexy is not present description of polysomnographic and HLA findings may be a better approach than using a label with little scientific43 significance: It would allows collecting better patients phenotype. 44. Canine narcolepsy was first reported in the early 1970s The term narcolepsy was first coined by Glinean in 1880 to designate a pathologic condition characterized by irresistible episodes of sleep of short duration recurring at close intervals. ( Gelinean, 1880 Gaz Hop Paris). See video: canine narcolepsy 44 45. Narcolepsy Narcolepsy is a disorder of unknown etiology, which is characterized by excessive sleepiness that typically is associated with cataplexy and other REM sleep phenomena such as sleep paralysis and hypnagogic hallucinations. ( original definition)45 46. Narcolepsy Symptoms Excessive sleepiness and sleep attacks Cataplexy Muscle weakness precipitated by emotion Hypnagogic hallucinations Dreamlike perceptions at sleep onset Sleep paralysis Inability to move at sleep onset or upon awakening Disturbed nocturnal sleep ( Guilleminault , 1975 in narcolepsy simposium and 1994; Mitler et al, 1990)(International Classification of Sleep Disorders, 1990)46 47. The definition is being revised : In most cases with cataplexy and in fewer cases without cataplexy, a deficiency in the neuropeptide hypocretin (Hcrt) system is involved. A tight association with the HLA DQB1* O602 is also found only in cases with cataplexy.(International: 2005); (S. Nishino et al. , 2000); (E. Mignot et al., 2002; Am JHum Gnet 2001; Neurology 1998; Sleep 1997); (T. Kanbayashi et al., 2002) 47 48. 48 49. Prevalence: (0.02% to 0.18%in US) (narcolepsy with cataplexy) In Finland:0.026%. ( Hublin et al.,1996) Great Britain, France , Czech Republic and US: 0.013% to 0.067 % .( Dauvilliers et al., 2003 ; Mignot, 1998) African Americans: 0.02% .( Solomon, 1945) Japan:0.16% and 0.18%(did not use PSG to confirm the diagnosis). ( Honda et al., 1979) Israel: as low as 0.002%. ( Lavie and Peled, 1987) Southern Chinese (Hong Kong): 0.034% .( Yun-Kwok Wing et al., 2002)49 50. The prevalence of narcolepsy without cataplexy: Unknown cases of narcolepsy without cataplexy represent 10% to 50% of the narcoleptic population. (45.5% in Chang Gung hospital) . ( Rosen et al., 2003) Adult population: 1% to 3% may have unexplained sleepiness and SoREM during MSLT. Higher Prevalence in adolescents or young adults : Because of voluntary chronic sleep deprivation. ( ICSD-2)50 51. 51 52. Assessing Sleepiness Observation Facial expression, posture, yawning Subjective Stanford Sleepiness Scale (SSS) Epworth Sleepiness Scale (ESS) Objective Multiple Sleep Latency Test (MSLT) Maintenance of Wakefulness Test (MWT) Pupillography PSG 24-hour monitoring( video) Carskadon et al, 1986 52 53. : ESS (Epworth sleepiness scale ) (12) 53 54. PSG Criteria and Findings Short sleep latency Sleep-onset REM period occurs in about 50% of narcoleptics Increased frequency of arousals Increased amounts of Stage 1 sleep If cataplexy is absent, narcolepsy is difficult to diagnose in the presence of sleep fragmentation from other sleep disorders 54 55. MSLT Criteria for Narcolepsy Mean sleep latency of less than 8 minutes 2 or more sleep-onset REM periods (SOREMPs) No other sleep disorder that accounts for the findings MSLT should be performed following sufficiend nocturnal sleep (minimum 6 hours).(ICSD-II) 55 56. 56 57. Clinical Features: (see video)Excessive daytime sleepiness Is usually the first symptom to manifest. (100%) Narcoleptic pts characteristically wake up feeling refreshed, and there is a refractory period of 1 to several hours before the next episode occurs. 57 58. Clinical Features: Cataplexy (seevideo) Most often occurs with in a year of onset Recurrent, brief episodes of muscle weakness triggered by laughter or at least two of the following: anger, surprise, elation, amusement One or more of the following symptoms: knees buckling, weakness in legs, jaw, head and neck, complete fall with no injury At least 5 episodes over lifetime58 59. Clinical Features: Cataplexy Most episodes are bilateral Consciousness is maintained, at least at the beginning of the episodes Most episodes last less than 2 minutes( a few seconds to several minutes). Twitches and jerks may occur, particularly in face (as pt is trying to fight the episode). Cataplexy may vary in pattern, frequency and severity. 59 60. Associated Features: Hypnagogic hallucinations:Are vival perceptual experience typicallyoccurring at sleep onsetInclude visual, tactile, kinetic, and auditoryphenomena.Recurrent hypnagogic hallucinations areexperience by 40% to 80% of patients withnarcolepsy with cataplexy. 60 61. Associated Features: Sleep paralysisA transient, generalized inability to move orto speak during the transition between sleepand wakefulness.Sleep paralysis is experienced by 40% to80% of narcoleptic patients.61 62. Associated Features: Nocturnal sleep disruption:Occurs in approximately 50% ofnarcoleptics.Most typically sleep-maintenance ratherthan sleep-onset insomnia. 62 63. Associated Features: Memory lapses:Especially during automatic behaviorwithout awareness of sleepiness.It may show inappropriate activity and pooradjustment to abrupt environmentaldemands.63 64. Associated Features: REM sleep behavior disorder (RBD):It can be either an isolatedpolysomnographic finding (REM sleepwithout atonia) or a clinically significantcomplaint.64 65. Associated Features: Narcolepsy with cataplexy is often associated with increased BMI, obesity (especially when untreated), and predispose the individual to developing OSA. 65 66. Narcolepsy Symptoms Many of the symptoms of narcolepsy can occur in any person who is severe sleep deprived, only cataplexy is unique to narcolepsy. 66 67. Pathophysiology Electrophysiology Sleep-onset REM periods, fragmented sleep, polyphasic 24-hour sleep-wake cycles Neurochemistry Cholinergic and aminergic dysfunction Neuroanatomy Postulated pontine and limbic abnormalities Genetic HLA association in humans Genetic transmission in canines 67 68. Genetic and familial aspectsof narcolepsy 68 69. 69 70. DNA sequence innarcoleptic patients.THE SUSCEPTIBILITY GENE FOR NARCOLEPSY IS : HLA DQB1-0602 RATHER THAN DR2. In all narcolepsy the active DQA1*0102/ DQB1*0602 heterodimer is necessary for disease predisposition . (E. Mignet: Tissue Antigens 1997) 70 71. CANINE NARCOLEPSY IS ANAUTOSOMAL RECESSIVEDISORDER Autosomal recessive forms of canine narcolepsy are due to mutations in the hypocretin receptor type 2 gene. (Hungs et al.,2001; Lin et al., 1999) 71 72. Hypocretin deficiency in humanNarcolepsyHUMAN NARCOLEPTICS HAVE REDUCED LEVELS OF Hcert-1 IN THEIR CEREBRO- SPINAL FLUID. Nishino et al., 2000 72 73. Functions potentially interested by Hypocretin containing neurons: FEEDING BLOOD PRESSURE REGULATION NEURO-ENDOCRINE REGULATION THERMOREGULATION SLEEP-WAKING CYCLE (effect on arousal)Peyron et al., 1998 73 74. Human Narcolepsy is:HETEROGENEOUSMULTIGENICENVORONMENTALLY INFLUENCED 74 75. Multi-dimensional Treatment 1.goal : ( 2.Behavioral : ( slep hygiene)8 ;13~410 20. 3. Supportive therapy: ; workenviroment; ( narcolepsy association).4. 75 76. 76 77. 77 78. Circadian rhythm sleep disorders This group of conditions includes both intrinsic and environmental disorders in which the timing of sleep within the 24-h circadian cycle becomes disturbed.78 79. Circadian rhythm sleep disorders Delayed sleep phase syndrome is a pathological exaggeration of the normal tendency of teenagers to go to bed later and wake later than first-decade children or adults. This may result in school or college failure or inability to succeed in the workplace.Advanced sleep phase syndrome is a rarer condition with initiation of sleep early in evening and thus waking earlier than desired. It is usually seen sporadically in the elderly, but a familial form of the disorder has been described. 79 80. Circadian rhythm sleep disorders Non-24-h sleep-wake disorder occurs when the biological clock fails to entrain to the 24-h geosynchronous cycle, resulting in the sleep period slowly rotating around the clock. This may be seen in blind patients with inadequate light stimulation of the hypothalamic suprachiasmatic nuclei. Shift work sleep disorder occurs specially in shift workers who rotate shifts, with frequent changes in work times between day, evening and night. Insomnia and other physical and psychological disturbances are common. Jet leg syndrome occurs with air travel across time zones from east to west or the reverse. Several days are needed for the biological clock to adopt to such alterations and travelers develop insomnia, excessive sleepiness and mood and somatic symptoms. 80 81. 81 82. Parasomnias Parasomnias are undesirable physical phenomena that occur predominantly during sleep. Arousal disorders, comprising sleep-walking, sleep terrors and confusional arousals, are a spectrum of conditions in which a sudden arousal from slow-wave sleep is associated with abnormal behavior due to the patients inability to make a rapid transition to complete wakefulness. They are common in childhood but can persist or even develop in adulthood, and may be associated with potentially injurious behavior. 82 83. Parasomnias Parasomnias usually associated with REM sleep include nightmares, which are frightening dreams during REM sleep resulting in wakening. Sleep paralysis,occurign at sleep onset or on wakening, is an inability to move from seconds to minutes. It is believed to be due to the muscle atonia of REM sleep developing inappropriately, and may occur both as a normal phenomenon and in patients with narcolepsy. REM sleep behavior disorder occurs when the normal muscle atonia of REM sleep is lost, allowing the enactment of dreams. Patients flail their arms, kick and vocalize, frequently resulting in injuries to themselves or their bed partners. The conditions occurs predominantly in older men, and is often associated with neurodegenerative diseases, especially Parkinsonian syndromes.83 84. Parasomnias Other parasomnias (not state-related) include sleep enuresis, the continued occurrence of bedwetting in children beyond the age when it normally ceases. Parasomnias related to a known psychiatric disorder include nocturnal panic attacks and nightmares in post- traumatic stress disorder. Parasomnias related to medical conditions include confusional behavior at night in patients with dementia.84 85. 85 86. Sleep-related movementdisorders Restless legs syndrome, is characterized by an overwhelming urge to move the legs while sitting or lying and relief by movement. It is a very common cause of insomnia, It is often familial and appears to be due to central dopaminergic dysfunction. Periodic limb movements disorder is usually associated with rhythmic kicking of the legs during sleep. But PLM may also accompany other sleep disorders and may occasionally alone be a cause of insomnia or hypersomnina.86 87. Sleep-related movement disorders Rhythmic movement disorder can occur during any stage of sleep, but is commonest during drowsiness. It consist of large rhythmic movements, usually of the axial musculature, and includes the conditions previously known as body rocking and head banging. Bruxism (tooth grinding) may occur during any stage of sleep and can result in jaw pain and damage to teeth.87 88. 88 89. Isolated symptoms, apparently normalvariants and unresolved issues The category of isolated symptoms, apparently normal variants, and unresolved issues lists concerns that may appropriately come to the attention of a sleep clinician, without necessarily indicating sleep pathology. This category includes a number of miscellaneous entities whose clinical significance is uncertain. Other entries in this category span the borderline between normal and pathological.89 90. Isolated symptoms, apparently normalvariants and unresolved issues such as excessively long sleep without daytime hypersomnolence. Sleep starts, also known as hypnic jerks, are sudden muscle contractions at sleep onset that are noted at times by most people, but can occasionally cause initial insomnia. Primary snoring is also included in this section. 90 91. 91 92. Other sleep disorders If a sleep disorder is not specifically listed in ICSD-2, use the appropriate other diagnoses. This category includes sleep-related epilepsy, headaches, gastroesophageal reflux disease and laryngospasm. These conditions can occur predominantly or exclusively during sleep. 92 93. Other sleep disorders Similarly, a sleep disorder may clearly belong to one of the eight disorders categories (e.g., parasomnia), but cannot be diagnosed as any specific disorder within the category because it does not satisfy all the listed diagnostic criteria. Use the appropriate other diagnoses. However if it cannot be classified because not enough information has been collected to know if all the diagnostic criteria have been met, the unspecified or NOS (not otherwise specified) would be the appropriate diagnosis. 93 94. 94 95. ICSD-2 ICSD-2 classifies sleep disorders in both adult and pediatric patients. In three sleep disorders, however, the pediatric presentation or diagnostic criteria are so unique as to warrant a specific pediatric designation: behavioral insomnia of childhood; obstructive sleep apnea, pediatric; and primary sleep apnea of infancy.95 96. ICSD-2 Many sleep disorders are multifactorial. For example, a case of insomnia maybe related to a delayed sleep phase syndrome, inadequate sleep hygiene, and depression. There is no code for multifactorial, but the identified elements are coded separately. Thus the sample above would carry three diagnoses. 96 97. 97 98. 98 99. Thank you for your attention. 99