Sleep Disorders

1.  Sleep Disorders Dr. Jeff Edmondson June 2007

2. Objectives Upon completion of this presentation, the audience should be able to: Diagnose the more common sleep disorders Discuss therapeutic options for individuals with obstructive sleep apnea Effectively counsel patients on circadian rhythm disorders and the components of good sleep hygiene Listed here are the main objectives from today�s lecture. Listed here are the main objectives from today�s lecture.

3. Question? Sleep apnea is known to be associated with Hypertension Respiratory muscle dysfunction Carpel tunnel syndrome Hypercalcemia Previous tonsillectomy (ISTE 2004 Question 47) I reviewed the Family Medicine In service Training Exams for the past three years and found an average of 2 to 3 questions per exam on the topic of sleep disorders. I have included the most relevant questions in this talk. I also included one case study from the ISTE. The answer to this question will be covered during the topic on Obstructive Sleep Apnea. I reviewed the Family Medicine In service Training Exams for the past three years and found an average of 2 to 3 questions per exam on the topic of sleep disorders. I have included the most relevant questions in this talk. I also included one case study from the ISTE. The answer to this question will be covered during the topic on Obstructive Sleep Apnea.

4.  Prevalence Americans sleep 25% less than we did a generation ago 2/3 of Americans get less than the recommended 8 hours of sleep per night 50% of older Americans (>60) have SDB and 45% have periodic limb movement disorders compared to < 5% in younger adults* *Anacoli-Israel S, Cooke JR J Am Geriatr Soc 2005;53(suppl): S265-S271 From the Sleep in American Polls, we know that American sleep 25% less and feel interrupted more per night than we did even a generation ago. At least 2/3 of American�s polled say that they get less than the recommend 8 hours of sleep each night. As expected, older Americans have more sleep related compalints compared to younger adults. All of us have probably at one time said we wish we could sleep like we did when we were younger. From the Sleep in American Polls, we know that American sleep 25% less and feel interrupted more per night than we did even a generation ago. At least 2/3 of American�s polled say that they get less than the recommend 8 hours of sleep each night. As expected, older Americans have more sleep related compalints compared to younger adults. All of us have probably at one time said we wish we could sleep like we did when we were younger.

5. Impacts 30% of adults have complaints of sleep disruption (NSF and NIH) 28% of American missed work due to sleep problems (2005 Sleep in American Poll) 25% of married couples reported losing sleep due to their partner�s sleep problems (2005 Sleep in American Poll) 25% of crashes or near crashes attributed to moderate to severe drowsiness (2004 NHSC, VA Tech Trans) The National Science Foundation and the NIH estimate that 30% of adults complain of disrupted sleep at least several nights a week. The results of the 2005 Sleep in America Poll showed that 28% of Americans missed work at least one time a year due to problems related to sleep disruption and 25% of married couples complain about their partner having sleep issues. And lastly and most importantly, the National Highway Safety Commission in 2004 estimated that about 25% of vehicle crashes or near crashes were due to moderate or severe drowsiness that occurred while driving. The National Science Foundation and the NIH estimate that 30% of adults complain of disrupted sleep at least several nights a week. The results of the 2005 Sleep in America Poll showed that 28% of Americans missed work at least one time a year due to problems related to sleep disruption and 25% of married couples complain about their partner having sleep issues. And lastly and most importantly, the National Highway Safety Commission in 2004 estimated that about 25% of vehicle crashes or near crashes were due to moderate or severe drowsiness that occurred while driving.

6. Insomnia Complaints regarding the quantity, quality or timing of sleep at least 3 X per week for 1 month or more. These disruptions must result in a perceived impairment of daytime function (DSM IV) Per DSM IV, insomnia is defined as complaints about the quantity, quality or timing of sleep for at least 3 times a week for at least one month. These disruptions in sleep must be perceived by the patient to result in an impairment in daytime function. Per DSM IV, insomnia is defined as complaints about the quantity, quality or timing of sleep for at least 3 times a week for at least one month. These disruptions in sleep must be perceived by the patient to result in an impairment in daytime function.

7. Of the medical conditions associated with insomnia, Major depression tops the list of mental disorders. Hip impairments tops the list of physical co-morbid conditions. Of the medical conditions associated with insomnia, Major depression tops the list of mental disorders. Hip impairments tops the list of physical co-morbid conditions.

8. The Sleep Cycle Sleep cycle length is ~ 90-110 minutes Each cycle is repeated 3 to 6 times per night Two stages of sleep Non-REM sleep REM sleep Hypnogram � a recording of the sleep cycle Before discussing specific sleep disorders, I would like to take just a minute to talk about the components of the sleep cycle and sleep architecture. There are two main stages of sleep. Non-REM sleep and REM sleep. Together they make up a sleep cycle. Each cycle lasts about 1 and a half to two hours and the cycle is repeated about 3-6 times each night. Before discussing specific sleep disorders, I would like to take just a minute to talk about the components of the sleep cycle and sleep architecture. There are two main stages of sleep. Non-REM sleep and REM sleep. Together they make up a sleep cycle. Each cycle lasts about 1 and a half to two hours and the cycle is repeated about 3-6 times each night.

9. Sleep Tracing This may be why physicians call it sleep architecture because it looks like the New York City Skyline. This is a hypnogram from a man in his early twenties. It shows the four stages of non-REM sleep followed by lengthening periods of REM sleep in a 1,2,3,4,3,2 REM pattern. Note that several arousal spikes or awakenings can be seen throughout the night. Despite how erratic it looks, this could be called a good normal nights sleep. This may be why physicians call it sleep architecture because it looks like the New York City Skyline. This is a hypnogram from a man in his early twenties. It shows the four stages of non-REM sleep followed by lengthening periods of REM sleep in a 1,2,3,4,3,2 REM pattern. Note that several arousal spikes or awakenings can be seen throughout the night. Despite how erratic it looks, this could be called a good normal nights sleep.

10. Evaluation H&P Sleep Diary for at least 2-3 wks Diet Medications - to include herbals Alcohol and caffeine intake Smoking Physical activity Approximate time falls asleep and time of awakening Periods of excessive daytime sleepiness (EDS) Naps Epworth Sleepiness Scale (ESS) Every sleep evaluation should start with a thorough history and physical. The physical examination should include routine vital signs, Body Mass Index, an examination of the oral airway looking for a narrowing in the hypopharyngeal area, enlarged tonsils, size of the tongue looking for macroglossia, chin and mandible looking for micrognathia and retrognathia and neck shape and size. A sleep diary is always recommended and should include time to bed, time of awakening, estimated time to fall asleep, estimated number of awakenings, any disturbances, how refreshed the patient felt on awakening, naps during the day, alcohol and caffeine consumed, exercise, daily stressors, medications, overall impression of how they felt during the day and what they did one hour before going to sleep? This should be monitored for at least 2 to 3 weeks. Sample sleep diaries are available on the internet. Every sleep evaluation should start with a thorough history and physical. The physical examination should include routine vital signs, Body Mass Index, an examination of the oral airway looking for a narrowing in the hypopharyngeal area, enlarged tonsils, size of the tongue looking for macroglossia, chin and mandible looking for micrognathia and retrognathia and neck shape and size. A sleep diary is always recommended and should include time to bed, time of awakening, estimated time to fall asleep, estimated number of awakenings, any disturbances, how refreshed the patient felt on awakening, naps during the day, alcohol and caffeine consumed, exercise, daily stressors, medications, overall impression of how they felt during the day and what they did one hour before going to sleep? This should be monitored for at least 2 to 3 weeks. Sample sleep diaries are available on the internet.

11. Question? T/F As part of the patient�s evaluation you administer an Epworth Sleepiness Scale questionnaire. The patient scores a �10�. This indicates that he has mild sleepiness. Answer: True 8-10 = mild 11-15 moderate 16-20 severe 21-24 excessive

12. An Epworth Sleepiness Scale should always be administered. The ESS is a very well validated, self-administered screening questionnaire that asks the patient to assess their chances of dozing off or falling asleep while doing routine daily activities. 8 to 10 is mild sleepiness 11 to 15 is moderate sleepiness Note that excessive from 21 to 24 is higher than severe at 16 to 20 An Epworth Sleepiness Scale should always be administered. The ESS is a very well validated, self-administered screening questionnaire that asks the patient to assess their chances of dozing off or falling asleep while doing routine daily activities. 8 to 10 is mild sleepiness 11 to 15 is moderate sleepiness Note that excessive from 21 to 24 is higher than severe at 16 to 20

13. Question? A 5-year-old overweight African-American male presents with behavior problems noted in the first 3 months of kindergarten. The mother explains that the child does not pay attention and often naps in class. He average 10 hours of sleep nightly and is heard snoring frequently. The mother has a history of attention-deficit disorders and take atomoxetine (Strattera). The boy�s examination is within normal limits for his being in the > 95th percentile for weight and having 3+ tonsilar enlargement.

14. Question? The most reasonable plan at this point would include which one of the following: An electroencephalogram Polysomography Atomoxetine Methylphenidate (Ritalin) The answer is B � a polysomnogram. The answer is B � a polysomnogram.

15. OSA/HAS A syndrome characterized by recurrent episodes of partial or complete upper airway obstruction during sleep that usually are terminated by an arousal. Triad of: Loud snoring Oxygen de-saturations Frequent arousals Incidence/prevalence 4% men 2% women (Wisconsin sleep cohort study) Obstructive sleep apnea, or more correctly termed, obstructive sleep apnea / hypoapnea syndrome is a syndrome characterized by recurrent episodes of partial or complete upper airway obstruction during sleep that usually are terminated by an arousal Obstructive sleep apnea, or more correctly termed, obstructive sleep apnea / hypoapnea syndrome is a syndrome characterized by recurrent episodes of partial or complete upper airway obstruction during sleep that usually are terminated by an arousal

16. Risks Associated With Untreated OSA/HAS Hypertension Angina/CAD/MI Strokes/CVA Pulmonary HTN Erectile Dysfunction Nocturnal cardiac arrhythmias MVA and other injuries (3-7X) Chronic headaches and decreased cognitive functioning Premature mortality This is the answer to the first question � Hypertension. The risks of untreated obstructive sleep apnea are listed here and are well documented in hundreds of studies. Not surprisingly, the primary impacts are cardiovascular and pulmonary. This is the answer to the first question � Hypertension. The risks of untreated obstructive sleep apnea are listed here and are well documented in hundreds of studies. Not surprisingly, the primary impacts are cardiovascular and pulmonary.

17. Physical Features Of OSA/HAS Small upper lip with associated overbite Large tongue Narrow hypopharyngeal airway Enlarged tonsils Large, curling and protruding lower lip Small chin, maxilla and mandible Short thick neck Males > 17 inches in have increased risk Females > 16 inches in have increased risk Central obesity with an increased BMI Caution: 25% of patients with OSA are NOT obese 1 kg/m2 increase in BMI ? 30% increased RR of developing sleep disorder over the next 4 years Other risks: M>F (2:1) Weaker associations: Menopause Smoking Family history HS nasal congestion Most, but not all, patients with obstructive sleep apnea have an increased body mass index. The risk of OSA is increased in women with a neck circumference greater than 16 inches, and in men with a circumference greater than 17 inches. Note that a 1kg/m2 increase in BMI results in a 30% increased RR of developing a sleep disorder over the next 4 yearsMost, but not all, patients with obstructive sleep apnea have an increased body mass index. The risk of OSA is increased in women with a neck circumference greater than 16 inches, and in men with a circumference greater than 17 inches. Note that a 1kg/m2 increase in BMI results in a 30% increased RR of developing a sleep disorder over the next 4 years

18. Diagnosis Of  OSA/HAS Overnight PSG Labs : none routinely recommended In office pulse oximetry of ? benefit Severe OSA RDI > 35 plus EDS (ESS > 10) or MSLT < 5 min The gold standard is a PSG plus MSLT. Labs are not routinely recommended but should include a TSH to rule out a thyroid disorder in obese patients and labs routinely required in patients with hypertension. In office pulse oximetry has not found to be of any added benefit. The gold standard is a PSG plus MSLT. Labs are not routinely recommended but should include a TSH to rule out a thyroid disorder in obese patients and labs routinely required in patients with hypertension. In office pulse oximetry has not found to be of any added benefit.

19. Case Study PSG on obese 20 y/o female with EDS Total study time 7.9 hr Total sleep time 7.2 hr Sleep efficiency of 92% Sleep onset (stage 1) at 8 min REM at 108 min RDI in REM � 77 per hr PLMS � 2 per hr Minimum oxygen saturation � 85%

20. This is the overnight polysomnogram for the previous case. The area highlighted in the lower right hand corner demonstrates decreased oxygen saturations resulting from increased airflow obstruction. Note the increased wave patterns in the nasal, thoracic and abdominal areas right above the oxygen saturation monitor. This is the overnight polysomnogram for the previous case. The area highlighted in the lower right hand corner demonstrates decreased oxygen saturations resulting from increased airflow obstruction. Note the increased wave patterns in the nasal, thoracic and abdominal areas right above the oxygen saturation monitor.

21. Treatments For OSA/HAS Surgical and non-surgical Non-surgical : CPAP/Bi-PAP titrated during PSG Treat RDI > 20 regardless of symptoms In the absence of symptoms, some authorities recommend treating only those with RDI > 30 Medicare covers CPAP for the following: RDI > 15 or RDI > 5 with HTN, CAD, CVA, EDS, impaired cognition, mood disorders or insomnia Oral appliances � intolerant of or failed CPAP Weight loss Medications � stimulants (limited beneficial effects) Treatments are either surgical or non-surgical The primary Non-surgical treatment is: CPAP or Bi-PAP titrated during PSG There is general agreement to treat patients with RDI > 20 regardless of symptoms In the absence of symptoms, some authorities recommend treating only those with RDI > 30 Oral appliances are another non-surgical option recommended for patients who are non-compliant or intolerant of CPAP. Weight loss is recommended for overweight patients Stimulants have been studied and shown to have a very limited beneficial Treatments are either surgical or non-surgical The primary Non-surgical treatment is: CPAP or Bi-PAP titrated during PSG There is general agreement to treat patients with RDI > 20 regardless of symptoms In the absence of symptoms, some authorities recommend treating only those with RDI > 30 Oral appliances are another non-surgical option recommended for patients who are non-compliant or intolerant of CPAP. Weight loss is recommended for overweight patients Stimulants have been studied and shown to have a very limited beneficial

22. CPAP Advantages Disadvantages Non-Compliance Up to 40% still have EDS despite therapy The main advantage of CPAP is an increased rate of survival compared with no treatment. The main disadvantage of CPAP is non-compliance. Patients complain that they feel like they are drowning. Bi-PAP with pressures adjusted to settings such as 11 and 8 allowing the patient to exhale helps some patients. Other compliance problems include sneezing, drying of mucous membranes, rhinorrhea, facial irritation, claustrophobia and panic attack symptoms. The main advantage of CPAP is an increased rate of survival compared with no treatment. The main disadvantage of CPAP is non-compliance. Patients complain that they feel like they are drowning. Bi-PAP with pressures adjusted to settings such as 11 and 8 allowing the patient to exhale helps some patients. Other compliance problems include sneezing, drying of mucous membranes, rhinorrhea, facial irritation, claustrophobia and panic attack symptoms.

23. Questions? T/F Oral appliances are considered first line treatment for OSA/HAS? Answer: False. Cochraine Review http://cochraine.org T/F Laser-assisted uvulopalatopharyngoplasty is effective for alleviating the complete syndrome of OSA/HAS? Answer: False. Effective for snoring

24. Surgery is very patient dependent. Per Dr. Ian McLeod, ENT at DeWitt, UPPP is only 50% successful in either reducing the RDI or eliminating symptoms. Non-obese patients with large tonsils will have much better success. Surgery is very patient dependent. Per Dr. Ian McLeod, ENT at DeWitt, UPPP is only 50% successful in either reducing the RDI or eliminating symptoms. Non-obese patients with large tonsils will have much better success.

25. Narcolepsy Oldest described sleep disorder first described in 1880 Incidence/prevalence - 1 in 2000 Age of onset � teenage years but reported in children as young as 2 yr of age Classic tetrad of: EDS Sleep paralysis Hypnagogic hallucinations Cataplexy* Narcolepsy is the oldest recognized disorder of excessive sleepiness and has an incidence of about 1 in 2000. It usually presents during the teenage years but has been reported in children as young as 2 years of age. Narcolepsy is characterized by excessive daytime sleepiness with an increased propensity to fall asleep during the day. The other features of the classic tetrad include hypnagogic hallucinations and cataplexy.Narcolepsy is the oldest recognized disorder of excessive sleepiness and has an incidence of about 1 in 2000. It usually presents during the teenage years but has been reported in children as young as 2 years of age. Narcolepsy is characterized by excessive daytime sleepiness with an increased propensity to fall asleep during the day. The other features of the classic tetrad include hypnagogic hallucinations and cataplexy.

26. Genetics Only 25-30% concordance in twins Strongly associated with the DQB1*0602 allele 85-95% of patients with cataplexy test homozygous for this allele DDx: OSA, RLS, Psycogenic, APSD, SWSD A number of variant alleles located in the HLA region of chromosome 6 have proved to be strongly, although not invariably, associated with narcolepsy. Cataplexy is strongly associated with the DQB1*0602 allele and 85-95% of patients with cataplexy test homozygous for this allele. A number of variant alleles located in the HLA region of chromosome 6 have proved to be strongly, although not invariably, associated with narcolepsy. Cataplexy is strongly associated with the DQB1*0602 allele and 85-95% of patients with cataplexy test homozygous for this allele.

27. Cataplexy Most specific finding for narcolepsy Considered pathognomonic � diagnosis of narcolepsy in the absence of cataplexy is controversial Total loss of body muscle tone Patients cannot move muscles voluntarily No loss of consciousness Common triggers include fatigue, emotional outbursts such as laughter, crying, anger Cataplexy is the most specific finding for narcolepsy and any diagnosis in the absence of cataplexy is controversial. Cataplexy is a sudden loss of muscle tone that leads to feelings of weakness and a loss of voluntary muscle control. Attacks can occur at any time during the waking period, with patients usually experiencing their first episodes several weeks or months after the onset of EDS. But in about 10 percent of all cases, cataplexy is the first symptom to appear and can be misdiagnosed as a manifestation of a seizure disorder. Cataplectic attacks vary in duration and severity. The loss of muscle tone can be barely perceptible, involving no more than a momentary sense of slight weakness in a limited number of muscles, such as mild drooping of the eyelids. The most severe attacks result in a complete loss of tone in all voluntary muscles, leading to total physical collapse in which patients are unable to move, speak, or keep their eyes open. But even during the most severe episodes, people remain fully conscious, a characteristic that distinguishes cataplexy from seizure disorders. Although cataplexy can occur spontaneously, it is more often triggered by sudden, strong emotions such as fear, anger, stress, excitement, or humor. Laughter is reportedly the most frequent trigger. Cataplexy is the most specific finding for narcolepsy and any diagnosis in the absence of cataplexy is controversial. Cataplexy is a sudden loss of muscle tone that leads to feelings of weakness and a loss of voluntary muscle control. Attacks can occur at any time during the waking period, with patients usually experiencing their first episodes several weeks or months after the onset of EDS. But in about 10 percent of all cases, cataplexy is the first symptom to appear and can be misdiagnosed as a manifestation of a seizure disorder. Cataplectic attacks vary in duration and severity. The loss of muscle tone can be barely perceptible, involving no more than a momentary sense of slight weakness in a limited number of muscles, such as mild drooping of the eyelids. The most severe attacks result in a complete loss of tone in all voluntary muscles, leading to total physical collapse in which patients are unable to move, speak, or keep their eyes open. But even during the most severe episodes, people remain fully conscious, a characteristic that distinguishes cataplexy from seizure disorders. Although cataplexy can occur spontaneously, it is more often triggered by sudden, strong emotions such as fear, anger, stress, excitement, or humor. Laughter is reportedly the most frequent trigger.

28. Evaluation and Diagnosis PSG plus MSLT Time required to fall asleep during 4 or 5 scheduled naps Sleep latency > 10 minutes is normal Sleep latency < 5 minutes is pathologic Presence of REM sleep within 15 minutes during at least 2 or more nap episodes is diagnostic (except in infants/children) As the name suggests, the sleep latency test measures the amount of time it takes for a person to fall asleep. Because sleep latency periods are normally 10 minutes or longer, a latency period of 5 minutes or less is considered suggestive of narcolepsy. If a person enters REM sleep either at the beginning or within a few minutes of sleep onset during at least two of the scheduled naps, this is also considered a positive indication of narcolepsy. As the name suggests, the sleep latency test measures the amount of time it takes for a person to fall asleep. Because sleep latency periods are normally 10 minutes or longer, a latency period of 5 minutes or less is considered suggestive of narcolepsy. If a person enters REM sleep either at the beginning or within a few minutes of sleep onset during at least two of the scheduled naps, this is also considered a positive indication of narcolepsy.

29. Treatments Behavioral � sleep hygiene Scheduled sleep and wake periods 7-8 hours of sleep per night plus scheduled naps Scheduled physical activity Avoidance of daytime environments conducive to sleep (lectures) Medications Amphetamines � schedule II Methylphenidate � schedule II Modafinil (Provigil) � schedule IV FDA approved in narcolepy and shift work sleep disorder. Residual sleepiness in OSA Gamma hydroxybutryrate (Xyrem) to treat cataplexy (�date rape drug�)? TCAs, SSRIs for cataplexy, hallucinations and sleep paralysis For decades, doctors have used central nervous system stimulants-amphetamines such as methylphenidate, dextroamphetamine, methamphetamine, and pemoline-to alleviate EDS and reduce the incidence of sleep attacks. For most patients these medications are generally quite effective at reducing daytime drowsiness and improving levels of alertness. However, they are associated with a wide array of undesirable side effects so their use must be carefully monitored. Common side effects include irritability and nervousness, shakiness, disturbances in heart rhythm, stomach upset, nighttime sleep disruption, and anorexia. Patients may also develop tolerance with long-term use, leading to the need for increased dosages to maintain effectiveness. In addition, doctors should be careful when prescribing these drugs and patients should be careful using them because the potential for abuse is high with any amphetamine. In 1999, the FDA approved a new non-amphetamine wake-promoting drug called modafinil for the treatment of EDS. In clinical trials, modafinil proved to be effective in alleviating EDS while producing fewer, less serious side effects that do ampehtmines. Headache is the most commonly reported adverse effect. Long-term use of modafinil does not appear to lead to tolerance. Two classes of antidepressant drugs have proved effective in controlling cataplexy in many patients: tricyclics (including imipramine, desipramine, clomipramine, and protriptyline) and selective serotonin reuptake inhibitors (including fluoxetine and sertraline). In general, antidepressants produce fewer adverse effects than do amphetamines. But troublesome side effects still occur in some patients, including impotence, high blood pressure, and heart rhythm irregularities. On July 17, 2002, the FDA approved Xyrem (sodium oxybate or gamma hydroxybutyrate, also known as GHB) for treating people with narcolepsy who experience episodes of cataplexy.� Due to safety concerns associated with the use of this drug, the distribution of Xyrem is tightly restricted. For decades, doctors have used central nervous system stimulants-amphetamines such as methylphenidate, dextroamphetamine, methamphetamine, and pemoline-to alleviate EDS and reduce the incidence of sleep attacks. For most patients these medications are generally quite effective at reducing daytime drowsiness and improving levels of alertness. However, they are associated with a wide array of undesirable side effects so their use must be carefully monitored. Common side effects include irritability and nervousness, shakiness, disturbances in heart rhythm, stomach upset, nighttime sleep disruption, and anorexia. Patients may also develop tolerance with long-term use, leading to the need for increased dosages to maintain effectiveness. In addition, doctors should be careful when prescribing these drugs and patients should be careful using them because the potential for abuse is high with any amphetamine. In 1999, the FDA approved a new non-amphetamine wake-promoting drug called modafinil for the treatment of EDS. In clinical trials, modafinil proved to be effective in alleviating EDS while producing fewer, less serious side effects that do ampehtmines. Headache is the most commonly reported adverse effect. Long-term use of modafinil does not appear to lead to tolerance. Two classes of antidepressant drugs have proved effective in controlling cataplexy in many patients: tricyclics (including imipramine, desipramine, clomipramine, and protriptyline) and selective serotonin reuptake inhibitors (including fluoxetine and sertraline). In general, antidepressants produce fewer adverse effects than do amphetamines. But troublesome side effects still occur in some patients, including impotence, high blood pressure, and heart rhythm irregularities. On July 17, 2002, the FDA approved Xyrem (sodium oxybate or gamma hydroxybutyrate, also known as GHB) for treating people with narcolepsy who experience episodes of cataplexy.� Due to safety concerns associated with the use of this drug, the distribution of Xyrem is tightly restricted.

30. Case Study PSG on 49 y/o female referred for c/o insomnia Total study time: 424 min Awake 12% Stage 1 � 12% Stage 2 � 60% Stage 3 & 4 � 8% REM � 9% Total sleep time: 377 min Sleep efficiency: 89% REM latency: 156 minutes Total arousal index - 5 per hr of sleep RDI � 2 per hr PLMS - 18 per hr

31. RLS and PLMD RLS is a syndrome characterized by sensory and motor disturbances of the lower extremities occurring primarily at rest Episodes are often painful and result in severe insomnia A desire to move the limbs, usually associated with parasthesias and dysesthesias Motor restlessness causing voluntary limb movements Nocturnal worsening of symptoms Restless legs syndrome (RLS) is a neurological disorder first described by Karl Ekbom in 1945 and characterized by unpleasant sensations in the legs and an uncontrollable urge to move them for relief. Individuals affected with the disorder describe the sensations as burning, creeping, tugging, or like insects crawling inside the legs. The sensations range in severity from uncomfortable to irritating to painful. It wasn�t until May 2005 that the FDA approved the first drug specifically for RLS. Reduced activity of the dopamine in the CNS and abnormalities in the use and storage of iron have been strongly associated with the syndrome. It is seen primarily in elderly patients and worsens with age. The later the onset the more progressive the symptoms. RLS is characterized as either primary or secondary. In Primary RLS over half of patients have a family history. There is a strong genetic association with genes located on chromosome 9, 12 and 14 Secondary � Associated with medical conditions to include iron deficiency, pregnancy, ESRD, peripheral neuropathy and medications Restless legs syndrome (RLS) is a neurological disorder first described by Karl Ekbom in 1945 and characterized by unpleasant sensations in the legs and an uncontrollable urge to move them for relief. Individuals affected with the disorder describe the sensations as burning, creeping, tugging, or like insects crawling inside the legs. The sensations range in severity from uncomfortable to irritating to painful. It wasn�t until May 2005 that the FDA approved the first drug specifically for RLS. Reduced activity of the dopamine in the CNS and abnormalities in the use and storage of iron have been strongly associated with the syndrome. It is seen primarily in elderly patients and worsens with age. The later the onset the more progressive the symptoms. RLS is characterized as either primary or secondary. In Primary RLS over half of patients have a family history. There is a strong genetic association with genes located on chromosome 9, 12 and 14 Secondary � Associated with medical conditions to include iron deficiency, pregnancy, ESRD, peripheral neuropathy and medications

32. Evaluation  And Diagnosis RLS - diagnosed from the H&P PLMD requires a PSG Labs : CBC, BUN, Cr, fasting glucose, Fe, Ferritin, folate and TSH Consider EMG/NCV as indicated for neuropathy symptoms RLS is diagnosed primarily from the history and physical exam. PLMD requires a PSG for diagnosis. PLMD is estimated to occur in about 85 % of patients with RLS. Labs to evaluate for anemia, kidney and thyroid and other metabolic diseases should always be done. A serum ferritin of < 50 ug/L has been associated with increased severity of RLS and may be associated with an increased risk of RLS. Iron supplementation should be always be considered for symptomatic patients with low ferritin levels but has been found to be less efficacious in patients with normal ferritin levels. RLS is diagnosed primarily from the history and physical exam. PLMD requires a PSG for diagnosis. PLMD is estimated to occur in about 85 % of patients with RLS. Labs to evaluate for anemia, kidney and thyroid and other metabolic diseases should always be done. A serum ferritin of < 50 ug/L has been associated with increased severity of RLS and may be associated with an increased risk of RLS. Iron supplementation should be always be considered for symptomatic patients with low ferritin levels but has been found to be less efficacious in patients with normal ferritin levels.

33. Question? Which of the following is the best treatment for restless legs syndrome? Ropinirole (Requip) Continuous positive airway pressure Tricyclic anitdepressants (TCAs) SSRIs Cyclobenzaprine (Flexeril) (ISTE 2006 Question 31)

34. Treatment For RLS And PLMD The answer is A. Ropinirole or Requip Nearly all patients with RLS show at least an initial positive therapeutic response to a dopamine-receptor agonist and these medications are recommended for all patients with daily symptoms. Benzodiazepines and opiates are usually reserved for patients with episodic symptoms. The answer is A. Ropinirole or Requip Nearly all patients with RLS show at least an initial positive therapeutic response to a dopamine-receptor agonist and these medications are recommended for all patients with daily symptoms. Benzodiazepines and opiates are usually reserved for patients with episodic symptoms.

35. Question? Which one of the following sleep disorders is in the general class of circadian sleep disorders and may respond to bright light therapy? Shift-work insomnia Alcohol dependent sleep disorder Inadequate sleep hygiene Sleep-related myoclonus

36. Circadian Rhythm Disorders Advanced Sleep-Phase Syndrome Delayed Sleep-Phase Syndrome Jet Lag Shift Work Sleep Disorder (SWSD) The answer is A Shift-work insomnia Listed here are four major circadian rhythm disorders which we have probably all experienced at some point in our lifetime, especially during training and military duties. The answer is A Shift-work insomnia Listed here are four major circadian rhythm disorders which we have probably all experienced at some point in our lifetime, especially during training and military duties.

37. Circadian Rhythm Disorders This slide shows the normal sleep range and illustrates the characteristics of Advanced Sleep-Phase Syndrome versus Delayed Sleep Phase Syndrome. Advanced Sleep-Phase Syndrome is more common in older adults. They complain that they get sleepier early and wake up earlier in the morning. This slide shows the normal sleep range and illustrates the characteristics of Advanced Sleep-Phase Syndrome versus Delayed Sleep Phase Syndrome. Advanced Sleep-Phase Syndrome is more common in older adults. They complain that they get sleepier early and wake up earlier in the morning.

38. Treatments Sleep hygiene Light therapy � limited studies using 2 hour exposure to 2500 lux light from 7 am to 9 am advanced circadian pattern by 1.4 hours Medications Benzodiazepines Non-Benzo hypnotics Melatonin - at least 3 mg HS for jet lag Modafinil � SWSD (also for Narcolepsy) Treatments for all of these disorders includes good sleep hygiene, light therapy and medications as required. Treatments for all of these disorders includes good sleep hygiene, light therapy and medications as required.

39. Question? Promoting good sleep hygiene is basic in the treatment of insomnia. Which one of the following measures will aid in promoting healthy sleep habits? Vigorous evening exercise Taking an enjoyable book or magazine to bed to read Drinking a glass of wine as a sedative close to bedtime Eating the heaviest meal of the day close to bedtime Maintaining a regular sleep/wake schedule

40. Sleep Hygiene Avoid excessive time in bed and naps Exercise regularly in the morning or afternoon Maintain regular sleep and wake up times Increase exposure to bright light Avoid eating a heavy meal or drinking 3 hours before bedtime Keep the room dark Maintain a comfortable room temperature Avoid caffeine in the afternoon and evening Do not drink alcohol or smoke to help with sleep Avoid unfamiliar sleep environments The answer to the previous question is E � maintaing a regular sleep / wake schedule. This slide lists the major components of good sleep hygiene and should be reviewed with any and all patients with insomnia complaints. The answer to the previous question is E � maintaing a regular sleep / wake schedule. This slide lists the major components of good sleep hygiene and should be reviewed with any and all patients with insomnia complaints.

41. Question? Which one of the following benzodiazepines has the shortest half-life? Flurazepam (Dalmane) Alprazolam (Xanax) Cloazepate (Tranxene) Diazepam (Valium) Clonazepam (Klonipin) (ISTE 2004 Question 129)

42. BENZODIAZEPINE  Hypnotics Drug Half-life (hr) Flurazepam (Dalmane) 50 hours Alprazolam (Xanax) 12 hours Cloazepate (Tranxene) 50 hours Diazepam (Valium) 50 hours Clonazepam (Klonipin) 25 hours The answer is B. Xanax. Five main hypnotics are approved by the FDA. They have all been well studied for 4-6 week periods. The main concerns deal with the development of tolerance with long-term use. As a general rule, the longer acting agents contribute to next day impairment and the shortest acting agent has the lowest next day impairment but highest retrograde amnesia. The answer is B. Xanax. Five main hypnotics are approved by the FDA. They have all been well studied for 4-6 week periods. The main concerns deal with the development of tolerance with long-term use. As a general rule, the longer acting agents contribute to next day impairment and the shortest acting agent has the lowest next day impairment but highest retrograde amnesia.

43. Non-BENZODIAZEPINE Hypnotics Drug Dose (mg) Half-life (hr) Zolpidem 5-10 2-3 Zolpidem CR 6.25-12.5 2.8 Zaleplon 5-10 1-2 Eszopiclone* 1-3 6 Indiplon** (IR and CR) *FDA approved without a specified time limit ** Not yet FDA approved The non-benzodiazepine hypnotics have shorter half-lives, faster sleep onset, decreased next day impairment and less potential for habituation and addiction than the benzodiazepine hypnotics. Ambien �The main concern is side effects to include amnesia and hallucinations Sonata � The primary effect is on sleep onset and less on sleep maintenance. Lunesta has the longest half-life and has better effects on sleep maintenance. It is the only one approved without a specified time limit. The non-benzodiazepine hypnotics have shorter half-lives, faster sleep onset, decreased next day impairment and less potential for habituation and addiction than the benzodiazepine hypnotics. Ambien �The main concern is side effects to include amnesia and hallucinations Sonata � The primary effect is on sleep onset and less on sleep maintenance. Lunesta has the longest half-life and has better effects on sleep maintenance. It is the only one approved without a specified time limit.

44. Melatonin Receptor Agonist Drug Dose (mg) Half-life (hr) Ramelteon* 8 1.0-2.6 * FDA approved without a specified time limit The melatonin receptor agonist Ramelteon or Rozerem is the only non-scheduled prescription medication for insomnia. It is a potent MT1/MT2 receptor agonist with negligible affinity for MT3, GABA, dopamine, serotonin, Ach, glutamate and opiate receptors. It has not been compared directly with other hypnotics or melatonin. Clinical studies show it promotes rapid sleep onset, has no abuse potential and no development of tolerance. In studies lasting 35 days, it did not cause rebound insomnia and did not produce residual hangover effects. Caution: It has been associated with decreased testosterone levels and increased prolactin levels. It is a pregnancy Category C drug and should not be used in nursing mothers. It should also not be used in patients taking Luvox or in patients with severe hepatic impairment. Ketoconazole or fluconazole increase blood levels. The melatonin receptor agonist Ramelteon or Rozerem is the only non-scheduled prescription medication for insomnia. It is a potent MT1/MT2 receptor agonist with negligible affinity for MT3, GABA, dopamine, serotonin, Ach, glutamate and opiate receptors. It has not been compared directly with other hypnotics or melatonin. Clinical studies show it promotes rapid sleep onset, has no abuse potential and no development of tolerance. In studies lasting 35 days, it did not cause rebound insomnia and did not produce residual hangover effects. Caution: It has been associated with decreased testosterone levels and increased prolactin levels. It is a pregnancy Category C drug and should not be used in nursing mothers. It should also not be used in patients taking Luvox or in patients with severe hepatic impairment. Ketoconazole or fluconazole increase blood levels.

45. Case Study At a routine office visit, a 55 year old female tells you about a long history of intermittent �crawling� sensation in her legs at night, which has become more frequent in the past year. She says that the sensation is difficult to describe, but when pressed says it feels like �worms crawling under my skin.� After taking additional history, you suspect the diagnosis of restless leg syndrome (RLS).

46. Case Study Which of the following would be consistent with this syndrome? Stereotyped, repetitive flexion of the limbs A compelling urge to move the limbs, usually associated with parasthesias /dyesthesias Symptoms that are worse at rest, or present only at rest Involvement of only one leg at a time during most episodes, but not necessarily the same leg each time A normal neurologic examination

47. Case Study Which of the following would be consistent with this syndrome? T or F Stereotyped, repetitive flexion of the limbs (F) A compelling urge to move the limbs, usually associated with parasthesias /dyesthesias (T) Symptoms that are worse at rest, or present only at rest (T) Involvement of only one leg at a time during most episodes, but not necessarily the same leg each time (F) A normal neurologic examination (T) The correct answers are B, C and E.The correct answers are B, C and E.

48. References And Resources National Sleep Foundation http://www.sleepfoundation.org American Academy of Sleep Medicine http://www.aasmnet.org Kryger MH, Roth T, Dement WC Principles and practice of sleep medicine AAFP Monograph 286 March 2003 Sleep This concludes my lecture. Are there any questions?This concludes my lecture. Are there any questions?