Sleep Medicine Pearls 2nd

Diagnosis: Adjustment sleep disorder. Temporary use of a hypnotic is a reasonable treatment option. Discussion: Adjustment sleep disorder (transient psychophysiologic insomnia) is defined as insomnia related to an acute stress, conflict, or environmental change. Rather than a true disorder, it is a normal reaction to one of life's many stresses. The course usually is brief, lasting only days: an acute state is less than I week; subacute is up to 3 months. However, insomnia can become chronic (duration longer than 3 months) following a precipitating event. It then might be classified as psychophysiologic insomnia if the initial stressor is no longer present or a major concern. An example of the adjustment sleep disorder is the difficulty many people have in sleeping in a novel environment, such as a sleep lab. This is called the first-night effect and usually is rather mild. Benzodiazepines (BZs) are the most widely used hypnotic medications (see table). They are relatively safe and well-tolerated. Generally, it is safer to start with a low dose and increase gradually. The lowest dose should be used in older patients who are susceptible to side effects. Agents with a long halflife tend to cause daytime grogginess (flurazepam, clonazepam), but they can be useful in anxious patients. Benzodiazepines with a short half-life may cause rebound irritability when stopped abruptly (triazolam). All benzodiazepines tend to increase the amount of stage 2 sleep (increased sleep spindles) and cause decreases in slow wave and, to a lesser extent, REM sleep. When ceasing treatment it is wise to slowly decrease the dose, weaning the patient to minimize any rebound effects secondary to withdrawal. The traditional BZs act non-selectively at BZl, BZ2, and BZ3 receptors on the GABA-BZ receptor complex. Binding to BZl is thought to mediate hypnotic effects by increasing the flow of chloride ions produced by action of GABA on the GAB A-A receptor. Action at BZ2 and BZ3 mediates the muscle relaxant, anti-anxiety, and antiseizure actions of BZs. The BZ hypnotics are termed nonselective BZ receptor agonists. The new non-benzodiazepine hypnotic agents zolpidem and zaleplon are termed selective BZ receptor agonists because they selectively bind to BZ I. They do not reduce stages 3, 4, and REM sleep. Sleep latency is decreased and sleep duration is unchanged or increased. These agents do not have muscle relaxant, anti-anxiety, or antiseizure activity. Zolpidem gives little warning of impending sleep and is relatively expensive. Additionally, behavior in some elderly patients is altered by this medication. The usual dose is 10 mg at bedtime (5 mg in older or small patients). Tolerance, rebound insomnia, and psychomotor impairment is usually not seen with Zolpidem. Zaleplon has an ultra-short half-life and is especially useful when a hypnotic must be taken in the middle of the night. It can then be used as a "rescue" medication without causing morning grogginess. Sedating antidepressants are widely used as hypnotics in non-depressed individuals (see table, page 341). Two important facts about this practice must be emphasized. First, sedating antidepressants have not been proved to be effective hypnotics in the non-depressed population. Second, when used as hypnotics these medications often are not given in sufficient doses to be effective as antidepressants. The optimum use of these medications for insomnia is probably in patients with depression. In such patients, the goal should be to reach an effective antidepressant dose (unless the medication is used as a supplement to another antidepressant simply to improve sleep). Again, sedating antidepressants are probably best used in patients with a component of depression as well as insomnia. The sedating antidepressants include certain tricyclic antidepressants, trazodone, nefazodone, and mirtazapine. The tricyclic medications with sedating properties include doxepin (Sinequan) and amitriptyline (Elavil). The tricyclic antidepressants have anticholinergic and cardiovascular side effects (e.g., widened QRS, arrhythmias). Of the tricyclics, doxepin is thought to have a relatively safe cardiovascular profile. Trazodone, a sedating nontricyclic antidepressant, also is used as a hypnotic when depression is present. However, trazodone and all tricyclic antidepressants can cause profound orthostatic hypotension in some patients. Trazodone also can cause intractable priapism, and patients should be cautioned to stop the medication immediately if this occurs. Nefazodone is a blocker of the 5HT2 serotonin receptor and is a mild serotonin reuptake inhibitor. It is sedating without the postural hypotension noted with trazodone. In depressed patients nefazodone actually increases the amount of REM sleep. Rare cases of life-threatening liver failure have been reported with nefazodone. Mirtazapine is an alpha 2 blocker (increases both serotonin and norepinephrine) as well as a 5HT2 and 5HT3 receptor blocker. The drug tends to increase the amount of slow wave sleep and is sedating. It may cause nausea and weight gain. Nefazodone and mirtazapine usually do not cause sexual dysfunction. 339

The following guidelines for hypnotic use are suggested: I. Limit to a course of 4 weeks if possible (unless treating depression with an antidepressant). 2. Use the lowest effective dose. 3. Use a low dose in elderly patients. 4. Monitor for side effects. 5. Avoid abrupt discontinuation of the medication (wean off over several days). In the present patient, the absence of prior sleep problems and the obvious association with the recent death of a family member makes adjustment sleep disorder the likely diagnosis. The need for a sleep study in this case is debatable; it was ordered because of the history of leg kicks. However, the study showed no evidence of significant leg movement. It did document a long sleep latency (> 30 minutes) and a low sleep efficiency consistent with the patient's complaints. The amount of slow wave and REM sleep also was reduced. The patient was treated with zolpidem 10 mg qhs and bereavement counseling. On this therapy his sleep improved, and he was weaned off the zolpidem after 3 weeks. Commonly Prescribed Hypnotics (SIZE AVAILABLE) DOSE* HALF-LIFE COMMENTS Benzodiazepine F1urazepam (Dalmane) Clonazepam (Klonopin)** Temazepam (Restoril) Triazolam (Halcion) Non-Benzodiazepines Zolipdem (Ambien) Zalepelon (Sonata) (15,30 mg) IS-3D mg qhs use lower dose in elderly (0.5, I, 2 mg) 0.5-2 mg qhs (15,30 mg) IS-3D mg qhs 7.5-15 mg qhs in elderly (0.125,0.25 mg) 0.125 -0.25 mg qhs use lower dose in elderly (5, 10 mg) 10 mg qhs 5mg qhs in the elderly 5,10,20 mg 5-10 mg qhs 5 mg qhs in elderly Long Long Intermediate Short Short Very short Daytime drowsiness common; rarely used today Used for PLMD, REM behavior disorder; take I hour before bedtime Can cause morning drowsiness Rebound insomnia may occur if discontinued abruptly Does not decrease slow wave sleep Useful for middle of the night dosing *Use lower dose in elderly ""'Not FDA-approved as a hypnotic PLMD = periodic limb movement disorder 340

Some Sedating Antidepressants Commonly Used As Hypnotics (AVAILABLE SIZE) EFFECT ON NEUROANTIDEPRESSANT DOSE TRANSMITTERS SLEEP EFFECTS* SIDE EFFECTS Doxepin (10,25,50,75,100, Blocks 5HT, NE Increased RL, Anticholinergic (dry (Sinequan) 150) uptake decreased REM mouth, constipa150-300 po qhs sleep tion) Start 25-75 mg po qhs Trazodone (50, I00, 150,300) 5HT2 blocker, NC or increased Priapism, postural 50-100 mg bid to alpha blocker RL, NC or hypotension tid max 400 mg decreased REM 50-100 mg qhs sleep as hypnotic Nefazodone (50, 100,150,200, 5HT blocker, NC or decreased Rare liver toxicity, (Serzone) 250) weak 5HT re- RL, NC or in- drug interactions 100-300 mg po bid uptake inhibitor creased REM Start 100 mg bid sleep Start 50 mg bid in elderly Mirtazapine (15,30,45) Alpha 2 blocker; NC or increased Nausea, weight gain (Remeron) 15--45 mg qhs 5HT2,5HT3 RL, normal or Start 15 mg qhs blocker decreased REM sleep 5HT= serotonin. NC = no change. NE = norepinephrine. RL = REM latency *May vary between studies ofdepressed. normal, orinsomnia patients Clinical Pearls I. The "first-night effect" refers to the insomnia many people experience when sleeping in a novel environment. 2. Adjustment sleep disorder follows an obvious life event and usually is transient. 3. The selection of hypnotics depends on the desired duration of action, the patient's age, and the presence or absence of depression. Use the lowest dose in older patients. 4. When hypnotics are prescribed for treatment of insomnia, the goal should be a limited course with a taper of medication to minimize rebound insomnia. 5. When sedating antidepressants are used in depressed patients with insomnia, the dose should be increased as tolerated to an effective antidepressant dose. 6. Sedating antidepressants have not been proved to be effective as hypnotics in nondepressed patients. 7. The ultra short-acting hypnotic zalepelon may be used in the middle of the night with minimal sedation the following morning. 8. The selective benzodiazepine receptor agonists do not appear to be associated with tolerance, rebound insomnia, or decreased slow wave sleep. REFERENCES I. Agnew H. Webb W. Williams RL: The first-night effect: An EEG study ofsleep. Psychophysiology 1966; 7:263-266. 2. Buysee OJ. Reynolds CF: Insomnia. InThorpy MJ (ed): Handbook ofSleep Disorders. New York, Marcel Dekker, 1990. pp 375-433. 3. Kupfer OJ. Reynolds CF: Management ofinsomnia. NEngl J Med 1997; 336:341-346. 4. Walsh JK. Pollak CPo Scharf MB. et al: Lack ofresidual sedation following middle ofthe night zaleplon administration in sleep maintenance insomnia. Clin Neuopharmacol 2000; 13: 17-21. 341

FUNDAMENTALS OF SLEEP MEDICINE 22 Circadian Sleep Disorders Propensity for sleep and wakefulness, cognitive function, hormonal secretion, and many other physiologic functions cycle regularly across each day. The nadir in body temperature occurs about 1-2 hours after mid-sleep time if awakening is spontaneous (Fig. I; idealized plot of body temperature as a cosine curve). This is usually about 4-5 AM in normal individuals, but may vary considerably-especially in patients with circadian rhythm disorders. Sleep propensity varies during the 24-hour day, with the greatest propensity during periods of low body temperature (usually during the night). Sleep propensity also depends on homeostatic factors such as the amount of time since the previous sleep. Biological rhythms that are periodic are described by period (time between two peaks), amplitude (peak to trough magnitude), mesor (mean value), acrophase (peak), and nadir (minimal value or trough). The term phase is used to describe the temporal position relative to some external event such as the light-dark cycle. Acrophase I 37.2 U 0 37.4 ::J 37.2 Q s 37.0 E 36.8 36.6 co 36.4 V mesor ..... 12 14 16 18 20 22 24 2 4 6 8 10 12 time of day FIGURE I These circadian Cabout a day") rhythms are generated by an internal pacemaker in the suprachiasmic nucleus (SCN) ofthe hypothalamus. The major afferents to the SCN are retinal neurons whose axons leave the optic chiasm and synapse on SCN cells (retinohypothalamic pathway). The afferents transmit nonvisua1light information. The main role of the SCN is to synchronize bodily functions with the environmental light-dark cycle. Light is the most potent stimulus for shifting the phase of the circadian cycle. The amplitude and direction of the phase shifts vary with timing of the stimulus (phase response curve). The point at which light shifts from phase delay to advance occurs close to the time of body temperature nadir in humans. In fact, monitoring body temperature is one method of detecting shifts in phase of the internal cir342

cadian clock. Application of light at times earlier than the nadir in body temperature causes a phase delay, with the magnitude of shift decreasing as one moves to earlier times (Fig. 2, Light C). Application of light after the nadir in body temperature causes a phase advance, with the magnitude of shift decreasing as one moves to later times (Light B compared to Light A). The amount of shift also depends on the intensity of light (measured in lux) and the duration of exposure. Even dim light can cause some phase shift, but outdoor light or indoor bright light of 2500 lux or more is much more potent. Phase response curve to Light Advance light C - large phase delay LightA - large phase advance light B- small phase advance Corresponds to timing of body temperature minimum Light B LightA ( i Light C oI-----==----j----------==-- Delay I I I I I I I 1hr +. I I I I I :t= -& ffi o s: a. '0 +- c 5 - 1hr FIGURE 2 In summary, light exposure in the early-evening-to-bedtime period shifts the internal rhythm to a later time (phase delay) decreasing the propensity to sleep (Fig. 3). Light exposure in the early morning causes a phase advance. While the largest phase shifts are induced by very bright light (outdoor sunlight), regular indoor illumination also can have a small effect. Indoor sources of bright light (> 2500 lux) have been used clinically to effectively shift the circadian clock. Several brands of light boxes are available. Melatonin, a hormone secreted by the pineal gland only during darkness, appears to playa role in synchronizing the SCN to the environment. There are melatonin receptors on the SCN cells. Exogenous melatonin can produce phase-shifting effects, but the required timing of administration for a given direction of shift is opposite to bright light. A few hours before the traditional dark period, ingestion of melatonin induces phase advance, whereas bright light phase delays. Melatonin's phase-shifting effects are not as potent as light and may require several days of medication. Experiments in animals and humans show that there is a limitation to how much the internal cycle can be phase-shifted during anyone day. Measuring the amount ofsalivary melatonin in a dim-light environment is another way of monitoring the internal clock. In the delayed sleep phase syndrome, the circadian rhythms are shifted to a later than normal clock time. Patients are unable to fall asleep until later than normal (2-4 AM). In the advanced sleep phase syndrome, circadian rhythms are shifted to an earlier clock time. These patients fall asleep earlier than normal (7-9 PM) and awaken in the middle of the night. In time zone change (jet lag), the internal circadian rhythms are out of phase with clock time (light-dark phases) because of rapid travel across several time zones. In patients traveling eastward, they are phase-delayed relative to clock time. They have difficulty falling asleep and awakening at the usual wake time in the new time zone. In patients traveling westward, they are phase-advanced relative to clock time. They desire to fall asleep earlier and awaken earlier than appropriate for the new clock time. Because most individuals find it easier to phase delay than advance (easier to stay up than to fall asleep), eastward travel is the most difficult. In the irregular sleep wake pattern, there is temporal disorganization and episodes of sleeping and wake behavior. Diagnostic criteria include complaints of insomnia or excessive daytime sleepiness, and three or more sleep episodes in a 24 hour period. The pattern must have been present for 3 months. Usu343

U 3].6 . • • • 2 . Q 37.0 . s Phaseadvance •• . E • S! •. 36' ...... 12 16 12 • • • • • • • 20 24 12 I. 20 24 4 8 12 hme of day lime of day Pre-Light Post-Light (j 37.0 S! 36 12 16 20 24 12 • • • • • • • 12 16 20 24 4 8 12 time of day time ot day Pre-Light Post-Light FIGURE 3 ally the total amount of sleep for 24 hours is normal. This pattern occurs in patients with brain dysfunction or who are removed from normal environmental clues. The non-24-hour sleep-wake disorder is characterized by a steady pattern consisting of progressive delays in sleep and wake times. Most of these individuals are blind, and the absence of light stimuli to the SeN results in a progressive delay in the circadian rhythms. Sleep Disorders Associated with Alterations in Circadian Rhythm Delayed sleep phase syndrome Advanced sleep phase syndrome Time zone change (jet lag) syndrome Shift work sleep disorder Irregular sleep wake pattern Non-24-hour sleep-wake disorder REFERENCES I. American Sleep Disorders Association: International Classification of Sleep Disorders. Rochester MN, American Sleep Disorders Association, 1997, pp 118-140. 2. Chesson AL, Jr.. Littner M, Davila D, et al: AASM Standards of Practice Committee. Practice parameters for the use of light therapy in the treatment of sleep disorders. Sleep 1999; 22:641-660. 3. Lewy AJ. Bauer VK, Ahmed S, et al: The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light. Chronobiol Int 1998; 15:71-83. 4. Sack RL, Hughes RJ, Edgar DM, Lewy AJ: Sleep-promoting effects of melatonin: At what dose, in whom, under what conditions, and by what mechanisms? Sleep 1997; 20:908-915. 344

PATIENT 104 A 40-year-old woman complaining of difficulty falling asleep A 40-year-old woman had been having trouble falling asleep for more than 10 years. She typically went to bed around II PM, did not fall asleep until 2-3 AM and awakened to the alarm clock at 6 AM. Thus, she obtained only 4 hours of sleep per night during the work week and felt tired throughout the day. On the weekends, she slept until 10-11 AM and awoke feeling refreshed. The patient rarely took naps during the day. There was no history of depression or recent stressful life events. The patient avoided caffeine intake completely. Because she rarely felt sleepy at II PM, she sometimes took either a drink of ethanol or an over-the-counter sleeping medication, both of which were only moderately successful at inducing sleep. Sleeping pills left her feeling groggy in the morning. Physical Examination: Normal Sleep Diary PM Midnight 6 7 8 9 10 11 12 1 2 3 4 AM 5 6 7 8 Noon PM 9 10 11 12 1 2 3 4 5 6 Sun Man Tues Wed Thu Fri Sat Sun Man ,rX T ~>< t .. X t ,.>< I~~ i ,. ~" " , t< ~X ,IX , X , I x=lights out and trying to sleep, +---.+) =asleep, =in bed, t =out of bed Man Tues Wed Thurs Fri Sat Sun Man Tues Question: What is the reason for this patient's difficulty falling asleep? 345

Diagnosis: Delayed sleep-phase syndrome. Discussion: The delayed sleep-phase syndrome (DSPS) is classified as a circadian rhythm sleep disorder. "Circadian" means related to the daily time period (circa, about; dian, day). The physiology of many human processes, including body temperature and sleep onset, is related to the daily 24-hour clock. In DSPS, the timing of sleep onset is delayed relative to clock time. Attempts to start sleep by getting into bed at the usual time are unsuccessful at inducing sleep. Sleep-onset time tends to be regular, but delayed (2-6 AM). There usually is no problem maintaining sleep, and when sleep is undisturbed, the sleep period is of normal length. However, waking at a typical clock time to fulfill social obligations results in a short duration of sleep. The duration of DSPS varies from months to decades. Adolescence is the most common age of onset; onset after age 30 is rare. True DSPS must be differentiated from sleep-onset insomnia in individuals who delay sleep for social reasons and then experience difficulty falling asleep when they sporadically try to go to bed earlier. These individuals have a transient sleep-wake cycle disorder caused by a self-enforced phase shift. When they maintain a regular bedtime and waketime for several days, they quickly adjust to this schedule. Patients with bipolar affective disorder in the mania phase also may have sleep-onset insomnia. The sleep period is short in these patients, but they have no difficulty arising at a conventional time. The non-24-hour sleep-wake syndrome is characterized by a progressive, incremental phase delay in sleep onset and waketimes. Treatment of DSPS often is difficult. While hypnotics may be temporarily successful at inducing sleep at normal clock times, daytime grogginess typically results. Chronotherapy is the traditional therapy for this disorder. This therapy is based on the fact that it is easier to phase delay (delay the time of sleep onset) than phase advance. Bedtime is progressively delayed by several hours on successive days. The sleep period is allowed to run its course, with later and later waketimes. Thus, the sleep period moves around the clock until sleep onset occurs at normal societal times. However, this therapy requires that the patient be free from societal constraints (e.g., job, child care) for the duration of the treatment, and the bedroom must be dark and quiet. Obviously, many patients are unable to commit to chronotherapy. Recently, bright light has been shown to shift the phase of the internal clock if applied at appropriate times. Therapy with bright light in the early morning (end of dark phase) and light restriction af346 ter 4 PM may help phase advance patients with DSPS. Some have used 2500 lux for 3 hours of exposure; others recommend 10,000 lux for a shorter duration. The optimal intensity and duration of light exposure is unknown. Light treatment results in the patient feeling sleepy earlier in the evening (phase advance). The treatment must be continued for several days with hopefully progressively earlier sleep times. Of note, the timing of light can be problematic in some patients who are very phase delayed. For example, suppose a patient naturally falls asleep at 3 AM and would sleep to 10 AM if undisturbed. In such a patient the nadir in body temperature might be around 8 AM. If he or she is forced to wake at 6 AM and apply light, it is possible that this timing is on the phase delay side of the light phase response curve. On the other hand, applying light too late will result in a very small phase shift. It is often difficult to know the exact timing of a patient's nadir in body temperature. One approach would be to start at the habitual wake-up time. If no phase advance occurs, try application 30 minutes to 1 hour earlier. Once phase advancing begins, move the light application time earlier to coincide with an earlier wake-up time. In some patients with DSPS, the bright light can be discontinued after a reasonable sleep-onset time is reached. However, maintaining a fixed bedtime and waketime is essential. Staying up late for any reason tends to reshift the internal clock. Bright light should be avoided near bedtime, as it can induce a phase delay. Commercial bright light units are available for use in the winter months. Another potential treatment of DSPS is the ingestion of melatonin in the evening. This hormone is manufactured in the pineal gland during the dark phase. When given at the end of the day, it can induce a phase advance (opposite timing from bright light). In supraphysiologic doses (> 0.5 mg), it also may have direct, mild, sleep-inducing effects. In one study, 5 mg was given at 2200 hours (5 hours before usual sleep-onset time) for 4 weeks. A mean advance of 72 minutes in sleep-onset time was noted. There are no clinical trials showing longterm efficacy and safety of melatonin. In general, the phase-shifting effects of melatonin are weaker than bright light. In the present patient, the sleep diary shows mainly sleep-onset insomnia. Once asleep, there was little difficulty maintaining sleep. Due to societal constraints, the waketime was set at 6 AM. Thus, a delayed sleep onset resulted in a very reduced total sleep time. The patient underwent a regimen of fixed waketimes (6 AM) on all days and avoided naps. She was treated with bright light

(10,000 lux) at 6 AM for 30 minutes to I hour, but this did not improve her ability to fall asleep. Because her spontaneous waketime on weekends was 9-10 AM, it was decided that the timing of light was possibly on the wrong side of the phase response curve. Bright light timing was delayed to 9:30 AM. After a few days of minimal response, it was moved up to 8:30 AM. The patient then began to note the ability to fall asleep earlier. Over the next few days, the timing of light was moved earlier to correspond to her naturally earlier waketimes. This approach slowly improved her ability to fall asleep. After several weeks of treatment, sleep onset occurred by 12-12:30 on most nights. She maintained this response by sleeping no later than 6:30 AM on any day, including weekends and by continuing early morning outdoor light for 30 minutes to I hour or bright indoor light for at least hour. Clinical Pearls 1. Insomnia primarily of the sleep-onset type suggests the possibility of the delayed sleep-phase syndrome. 2. A sleep log is helpful in documenting a pattern of delayed sleep onset but relatively normal sleep maintenance. 3. Chronotherapy (progressive phase delay) is the traditional treatment for this problem. 4. Bright light therapy in the morning (to induce a phase advance) is an important new treatment for this disorder. 5. The ideal timing of bright light in this syndrome is soon after the nadir in body temperature. The nadir in body temperature is usually about 1-2 hours after spontaneous midsleep time, but may vary in individual patients. If a patient does not respond to light therapy, try adjusting the timing. 6. Melatonin administered 5-7 hours before habitual sleep time (not bed time) may help phase advance sleep. REFERENCES I. Czeisler CA, Richardson GS, Coleman RM, et al: Chronotherapy: Resetting the circadian clocks of patients with delayed sleep phase insomnia. Sleep 1981; 4: 1-21. 2. Weitzman ED, Czeisler CA, Coleman RM, et al: Delayed sleep-phase syndrome: A chronobiological disorder with sleep-onset insomnia. Arch Gen Psych 1981; 38:737-746. 3. Rosenthal NE, Joseph- Vanderpool JR, Levendosky AA, et al: Phase-shifting effects of bright morning light as treatment for delayed sleep-phase syndrome. Sleep 1990; 13:354-361. 4. Dahlitz M, Alvarez B. Vignau J: Delayed sleep-phase syndrome response to melatonin. Lancet 1991; 337: 112-104. 5. Chesson AL Jr. Littner M, Davila D. et al: AASM Standards of Practice Committee. Practice parameters for the use of light therapy in the treatment of sleep disorders. Sleep 1999;22:641-660. 6. Terman M, Terman JS: Light therapy. In Kryger M, Roth T, Dement WC (eds): Principles and Practice of Sleep Medicine, 3rd ed. Philadelphia, WB Saunders, 2000, pp 1258-1274. 347

PATIENT 105 A 70-year-old man with early morning awakening A 70-year-old man was seen for complaints of early morning awakening. This problem had worsened since his retirement 5 years ago. His typical bedtime was 9 PM; he fell asleep within 5 minutes, and staying up later was difficult for him. During the night, the patient awakened twice with nocturia, usually at midnight and 2 AM, but returned quickly to sleep. He then awoke spontaneously between 4 and 5 AM and typically was unable to fall back asleep, but remained in bed until 6:30 AM. The patient's futile efforts to return to sleep caused him considerably distress. During the day, he was able to stay awake without difficulty. He normally took aI-I Y2 hour nap at I PM. He denied feeling sad or depressed. He had many hobbies and a good relationship with his wife. The patient took a diuretic for hypertension and denied taking any hypnotic medication. Physical Examination: Normal. Sleep Diary PM Midnight AM 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 Noon PM 9 10 11 12 1 2 3 4 5 6 Sun Man Tues Wed Thu Fri Sat ....• .. .. iL 1+ .'. r('o ...... ,. ••• " '.' I'T ......... , I " .I .... + I.... '. n .. '" ,. i"" I, .... "" I" 1/ ,. .: + ': .' 1/ .' > ........ I• 11\.. ~X + d. 1 "'.'. 'I ~~(i'" .... ..... + . ~~ 1 ", .' ..': , .... -' .... + ....... "X .... ,. . .I ..... .... ...... ., II.... .... .. .....•.. .... , + •• 1"'" , x=lights out and trying to sleep, +--~) =asleep, t =in bed, t =out of bed Man Tues Wed Thurs Fri Sat Sun Question: What is causing this patient's early awakening time? 348

Diagnosis: Advanced sleep-phase syndrome. Discussion: The advanced sleep-phase syndrome (ASPS) is characterized by an early sleep onset (6-9 PM) and an early waketime (3-4 AM) relative to clock time. There usually is no difficulty initiating sleep or maintaining sleep until early spontaneous awakening. Delaying bedtime past 9 PM is difficult. While some patients complain of an inability to maintain wakefulness for evening social functions, the main presenting complaint is early morning awakening. The early awakening produces anxiety in patients who feel they are not getting a full night of sleep. However, as long as the total amount and quality of sleep is adequate, the early morning awakening causes no physiologic problems. ASPS is exacerbated by naps during the day (they reduce total nocturnal sleep need) and early morning walks in the sunshine- both of which are common habits in the elderly. The exposure to bright light in the early morning hours results in a phase advance. In contrast, exposure to bright light near bedtime results in a phase delay and is a possible treatment for this syndrome. Typical indoor light is not strong enough to reset the circadian phase; therefore, outside daylight or special indoor lighting (> 2500 lux) is required. Avoiding naps and enforcing a delayed bedtime, perhaps by engaging in physical activity in a brightly lit setting, may help. In addition, education can reduce the anxiety and frustration. Severe forms of ASPS (intractable sleepiness before 8 PM) are rare. A tendency for mild phase advancement is common in elderly persons and may be one cause of sleep maintenance problems in these patients. In one study, bright light in the evening induced a phase delay in the nadir of body temperature and improved sleep maintenance. However, this treatment may not be practical on a long-term basis. Depression is the other major cause of early morning awakening. Carefully check for symptoms of depression in older patients (e.g., loss of appetite, weight loss). Evaluation of a patient with suspected ASPS should include a daily sleep log to document the pattern of sleep. A sleep study probably is not useful, unless sleep apnea or periodic leg movement is suspected. If a sleep study is performed, the lights out and on time must be changed from the routine laboratory times. The present patient complained mainly of an early waketime. Daily sleep was reported to be approximately 7 hours at night plus a I-I hour daytime nap. Thus, total sleep time was adequate. Symptoms of depression can be subtle in elderly patients. However, the patient denied any symptoms of depression and reported an active lifestyle. The most likely diagnosis was a mild form of ASPS. The patient was instructed to avoid naps and take his daily walk in the evening (and to avoid early morning light). These changes enabled him to delay his sleep onset to 10 PM and sleep until 5-5:30 AM. Upon awakening, the patient got out of bed and worked on one of his hobbies until breakfast. He seemed satisfied with his new schedule. Clinical Pearls I. A mild form of advanced sleep-phase syndrome (ASPS) is common in elderly patients; severe forms are rare. 2. An early waketime is the main complaint in ASPS. 3. Exposure to bright light (outside sunshine) in the early morning advances the sleep phase and should be avoided in patients with ASPS. 4. The main differential of ASPS (early morning awakening) is depression. REFERENCES I. American Sleep Disorders Association: International Classification of Sleep Disorders: Diagnostic and Coding Manual. Lawrence, Kansas, Allen Press. 1990. pp 133-136. 2. Campbell SS. Dawson D. Anderson MW: Alleviation of sleep-maintenance insomnia with timed exposure to bright light. J Am Geriatr Soc 1993; 41:829-836. 3. Ando K, Kripke DP, Ancoli-Israel S: Estimated prevalence of delayed and advanced sleep-phase syndrome. Sleep Research 1995; 14:509. 349

PATIENT 106 A 44-year-old man with jet lag A 44-year-old business executive was referred for complaints of increasing difficulty adjusting to business trips from the West to the East Coast. He found it extremely difficulty to fall asleep at an East Coast bedtime and wake up for his early morning business appointments. If he did make it to the meetings, he was drowsy and found it hard to stay awake. These problems had seemed to worsen over the last 3 years. His normal bedtime was II PM and normal waketime was 6 AM. At home he awakened refreshed and had no problems with daytime sleepiness. There was no history of snoring. The patient had tried triazolam for the first night on the East Coast- he was able to fall asleep and sleep better, but still had problems maintaining alertness in the morning. Physical Examination: Normal. Question: What treatments would you advise? 350

Answer: Phase advancing with early-morning, bright light exposure. Discussion: Time zone change (jet lag) syndrome describes the condition arising from asynchrony between a patient's internal circadian pacemaker and external clock time secondary to rapid travel across several time zones. Symptoms include problems with sleep onset or maintenance and/or decreased alertness and performance in the new time zone. Traveling eastward is the more difficult direction, as patients find it easier to phase delay than phase advance. For example, West to East Coast travel results in a patient retiring at a clock time of 11 PM but an internal circadian time of 8 PM. Sleep onset is delayed, and sleep is easily disturbed. At 7 AM clock time, the circadian time is 4 AM, and the patient finds it difficult to awaken and achieve normal alertness. It appears that adjusting to jet lag is more difficult with increasing age. A number of maneuvers have been tried to minimize the difficulties of jet lag. Short-acting hypnotics, such as triazolam, improve the continuity of sleep but do not shift the circadian clock. Therefore, awakening and resuming full alertness is still a problem because the internal circadian clock is not truly shifted. Bright light exposure in the morning in the advanced time zone may assist in phase advancing the internal circadian clock, but this is not always practical. Melatonin (0.5-0.3 mg) has been reported to both consolidate sleep and shift the circadian clock. For example, taken in the evening it can help phase advance an eastward traveler. However, the effectiveness and safety of melatonin is not well documented, and the FDA has not approved melatonin for any indication. Traditional stimulants, such as caffeine, are widely used to assist in maintaining alertness. Another approach is to prepare for the eastward trip by going to bed progressively earlier and arising earlier for I week before the trip. This slowly shifts the circadian clock prior to travel. Despite these maneuvers, most individuals still do not feel truly alert in the morning for several days. Scheduling meetings in the afternoon in the East Coast time zone or arriving several days prior to an important meeting are helpful approaches. Of note, the above recommendations for the timing of light exposure change if the patient travels across more than six time zones. For example, if a patient travels eastward for more than six time zones, it is then possible that early morning light falls on the phase-delay side of the individual phase response curve. In this case, early morning light would not assist with adapation to the new time zone. The present patient tried phase advancing himself before his eastward trips by getting bright light exposure in the morning, avoiding light in the evenings, and going to bed earlier for I week prior to his trips. When possible, he attempted to arrive a day or two earlier than his scheduled meetings. While on the East Coast, he tried to get as much early-morning, bright light exposure as possible. These procedures improved but did not eliminate his symptoms. Clinical Pearls I. The jet lag syndrome can be treated with behavioral and scheduling changes, timed daylight exposure, short-acting hypnotics, and, possibly, melatonin. 2. The jet lag syndrome worsens with increasing age. REFERENCES I. Moline ML, Pollack CP, Monk TH. et al: Age-related differences in recovery from simulated jet lag. Sleep 1991; 14:42-48. 2. Sack RL, Lewy AJ, Hughes RJ: Use of melatonin for sleep and circadian rhythm disorders. Ann Med 1998;30: 115-12l. 3. Sack RL. Shift work and jet lag. In Lee-Chiong TL, Sateia MJ, Caraskadon MA (eds): Sleep Medicine. Philadelphia, Hanley and Belfus, 2002, pp 255-263. 351

PATIENT 107 A 40-year-old woman with fibromyalgia A 40-year-old woman was referred for complaints of nonrestorative sleep. She had a history of generalized pain and chronic fatigue of I-year duration. She retired every night at 10 PM and usually took about 1 hour to fall asleep. During the night, she was awakened by discomfort three to four times. She had taken medications, including narcotics, that relieved the pain, but she often felt groggy the next day. There was no history of the restless leg syndrome. The patient's bedpartner had not noted snoring or leg kicks. Physical Examination: Blood pressure 120176, pulse 80, temperature normal. Chest: clear to auscultation and percussion. Extremities: pressure on several points over the shoulders and back caused excruciating pain. Neurologic: normal. Laboratory Findings: Complete blood cell count, thyroid studies: normal. Figure: Below is a tracing obtained during a sleep study. Question: What is your diagnosis? • I I " • , Chin EMG .......I~I-.-'-------------------- 5 Sec 352

Diagnosis: Fibromyalgia manifested as alpha-delta sleep. Discussion: Intrusion of alpha waves into slow wave sleep (alpha-delta sleep) was originally described in psychiatric patients, but the most wellknown association is with fibrositis. Alpha-delta sleep is a nonspecific polysomnographic finding. It has been associated with rheumatoid arthritis, posttraumatic stress syndrome, chronic fatigue syndrome, and chronic pain syndromes. Other medical illnesses that disturb sleep can cause alpha-delta sleep, as well. Patients with alpha-delta sleep typically complain of nonrestorative sleep and fatigue, although frank, excessive daytime sleepiness usually is not prominent. The amount of alpha-delta sleep can vary considerably, and the amount of slow wave sleep often is decreased. Generally, no evidence of respiratory effort-related arousals or changes in the chin EMG is noted. Widespread alpha intrusion has been reported in some patients taking sedative-hypnotics. Therefore, diagnosis of alpha-delta sleep requires that the use of these medications be excluded. Fibromyalgia is a syndrome usually affecting women that is associated with generalized musculoskeletal pain, chronic fatigue (without another explanation), widespread but localized tender points, and complaints of nonrestorative sleep. Despite these complaints, few objective findings are noted except for the tender points. The American College of Rheumatology has published specific criteria for fibrornyalgia, and these include tender points of a specificed number and location (II of 18 locations, with at least nine bilateral). Patients with fibromyalgia commonly show reductions in slow wave and REM sleep. However, in one study only 30% showed alpha-delta sleep. The usual treatment for sleep disturbance associated with fibromyalgia is amitriptyline (Elavil) 25-50 mg qhs. Amitriptyline may improve daytime symptoms as well as patient assessment of sleep quality, although alpha-delta sleep may persist. Complaints related to alpha-delta sleep and associated with other diseases, such as rheumatoid arthritis, also have been treated successfully with this medication. A recent study found that fIuoxetine 20 mg qam or a combination of amitriptyline and f1uoxetine was effective in treating patients with fibromyalgia. In the present patient, monitoring showed alpha intrusion into slow wave sleep (see figure) consistent with alpha-delta sleep. This was not surprising given the history and physical findings. Treatment was begun with amitriptyline 25 mg qhs. The patient reported an improvement in perceived sleep quality and reduced musculoskeletal pain and fatigue. Clinical Pearls I. Alpha-delta sleep is a polysomnographic finding that can be associated with psychiatric disease, fibromyalgia, rheumatoid arthritis, and chronic pain syndromes. 2. Alpha-delta sleep may be associated with complaints of nonrestorative sleep. 3. In fibromyalgia and other conditions associated with chronic pain, low doses of amitriptyline at bedtime or f1uoxetine in the morning may improve sleep and daytime symptoms of pain. REFERENCES I. Hauri P, Hawkins DR: Alpha-delta sleep. Electroencephalogr Clin Neurophysiol 1973; 34:233-237. 2. Whittig RM, Zorick Fl, Blumer 0, et al: Disturbed sleep in patients complaining of chronic pain. 1 Nerv Ment Dis 1982; 170:429-431. 3. Moldosky H, Lue FA, Smythe HA: Alpha EEG sleep and morning symptoms in rheumatoid arthritis. 1 Rheumatol 1983; 10:373-379. 4. Wolfe E, Smythe HA, Yunus MB, et al: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia: Report of multi-center criteria committee. Arthritis Rheum 1990; 33: 160-172. 5. Goldenberg D. Mayskiy M, Mossey C, er al: A randomized, double-blind trial of ftuoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum 1996; 39: 1852-1859. 353

PATIENT 108 A 40-year-old woman with fatigue and disturbed sleep A 40-year-old woman was evaluated for fatigue and disturbed sleep of 6-month duration. The patient went to bed at II PM and fell asleep in from 15-45 minutes. She reported about three awakenings nightly and an earlier-than-normal waketime (5:00 AM). During the day she felt very fatigued. There was no of history of cataplexy or sleep paralysis. The patient's husband reported that she frequently snored, but never kicked or moved her legs during sleep. She denied feeling depressed, but did admit to being under a lot of stress after a recent promotion and worrying that she was not spending enough time with her husband. There was no history of prior treatment for depression or episodes of mania. Physical Examination: Unremarkable. Figure: The 30-second tracing below was noted 40 minutes after sleep onset. Sleep Study (Lights out 11:00 PM, lights on 7:00 AM, final awakening 5: 10 AM) Time in bed Total sleep time Sleep period time (SPT) Sleep efficiency (0/0) Sleep latency REM latency Arousal index Respiratory arousal index 420 min (419-464) 302 min (402-449) 355 min (408-456) 72 (94-98) 15 min (2-14) 40 min (65-99) 10/hr 5/hr Sleep Stages Stage Wake Stage I Stage 2 Stages 3 and 4 Stage REM AHI PLM index O/OSPT 15 (0-11) 13 (3-7) 49(51-64) 2 (5-17) 21 (19-25) 2/hr «5) O/hr Question: What is causing the fatigue and sleep disturbance? , \ I \ , " I 1 1 , I I . " I I C4-Al 02-Al~ r ~--_._"-------~~......... ROC-A1 LOC-A2 . chin EMG 1-1-1,.--.1--+.-+\-+-r-_-+--+- ~..___~,...............-+-...-+--+-_+-"r_....__t__---....._ 354

Diagnosis: Major affective disorder-depression. A high REM density is noted during early REM. Discussion: Approximately 90% of patients with major depression complain of sleep disturbance. If the patient reports feelings of sadness and despair, the diagnosis is obvious. However, a patient may emphasize loss of energy and decreased appetite. Therefore, depression should be considered in anyone complaining of sleep disturbance and fatigue. A medical evaluation is essential to rule out anemia, hypothyroidism, and other causes of fatigue. Fifty percent of sleep studies performed in patients suffering from depression show objective abnormalities (see Table). Common findings include a reduced REM latency, normal or increased amounts of REM sleep, and decreased stages 3 and 4 NREM sleep. The REM latency typically is 40-60 minutes, but occasionally is in the range suggestive of narcolepsy (10-20 min). In addition, the first REM episode is longer (20-25 minutes instead of the usual 10-15 minutes) and has a higher REM density (number ofrapid eye movements per time) than normal. These alterations in REM sleep may persist even after successful treatment ofdepression or between depressive episodes. A short REM latency may be seen with other psychiatric disorders, including schizophrenia and borderline personality. In patients with unipolar depression, insomnia with early-morning awakening usually is the major sleep complaint. Sleep complaints tend to be more pronounced in older patients. Typical sleep study findings are: increased sleep latency, decreased sleep efficiency, increased stage Wake and stage I, decreased stages 3 and 4 sleep, reduced total sleep, and early-morning awakening. The sleep of older patients with depression tends to be more disturbed than that of younger patients. In the depressive phase of bipolar disorder, seasonal affective disorder, and atypical depression, hypersomnia typically is the major complaint, with a prolonged total sleep time and daytime sleepiness. The REM latency is typically normal in depression that is secondary to another disorder. If the diagnosis of depression is obvious, a sleep study is not indicated unless another sleep disorder is suspected. The finding of a short REM latency by itself is not specific for depression, but in the absence of other pathology, it is suggestive. Sometimes it is difficult to determine if the major patient complaint is fatigue or daytime sleepiness. In addition, as stated above. some patients with depression complain of hypersomnia rather than sleep disturbance. Thus, the major utility of a sleep study is to rule out other sleep disorders. Psychological questionnaires also may help uncover suspected depression. In the present case, a sleep study was ordered because of the history of snoring, to rule out obstructive sleep apnea and upper airway resistance syndrome (UARS). The study revealed a modestly shortened nocturnal REM latency, early-morning awakening, and an absence of evidence for sleep apnea and periodic limb movements. UARS remained a possibility, but the arousal index was not very high. Interestingly, the first REM period was quite long (25 minutes) and the REM density (number of eye movements/time) was unusually high during this initial episode of REM. During initial REM sleep, only one or two bursts of eye movements are normally seen per epoch. These findings suggested the presence of depression. Subsequently, symptoms of depression were explored in more detail when the sleep study results were discussed with the patient. At that time, she admitted that she felt torn between her responsibilities to her employer and to her husband and was overwhelmed at times. The patient was referred to a psychiatrist with whom she could explore these issues. Treatment with counseling and fluoxetine 20 mg qd improved her symptoms and early-morning awakening. Findings ill Mood Disorders COMPLAINTS SLEEP STUDY Depression Depressive phase of bipolar disorder Seasonal affective disorder Atypical depression Insomnia Frequent awakening Early morning awakening Fatigue Hypersomnia Increased sleep latency Decreased REM latency Increased REM density/long first REM period Normal or increased amount of REM sleep Decreased slow wave sleep Decreased REM latency Increased total sleep time 355

Clinical Pearls I. A moderately short REM latency and a prolonged initial REM period with an increase in REM density is characteristic of depression. These findings may persist after successful treatment, or may be present between depressive episodes. 2. Depression can present with complaints of disturbed sleep and early-morning awakening (unipolar depression) or hypersomnia (bipolar depression). 3. Depression always should be considered when evaluating insomnia or excessive daytime sleepiness. 4. Consider depression when patients complain of fatigue and disturbed sleep. REFERENCES I. Rush AJ. Erman MK. Giles DE. et al: Polysomnographic findings in recently drug-free and clinically remitted depressed patients. Arch Gen Psychiatry 1986; 43:878-884. 2. Benca RM, Obermeyer WH, Thisted RA, et al: Sleep and psychiatric disorders: A meta-analysis. Arch Gen Psychiatry 1992; 49:651-668. 356

PATIENT 109 A 45-year-old man with persistent insomnia while on treatment for depression A 45-year-old man was referred by his psychiatrist for evaluation and treatment of insomnia. The patient had a long history of major depressive episodes. which generally responded to treatment with tricyclic antidepressants. However, he had difficulty with the side effects of the medication. The current episode was under treatment with fluoxetine 60 mg daily, and although the patient's energy level and feelings ofsadness were much improved, he continued to have difficulty initiating and maintaining sleep. Frequent awakenings during the night were a major problem. The patient felt tired in the morning. There was no history of snoring, and the patient's wife reported an absence of leg kicks and apnea. Physical Examination: Height 6 feet, weight 200 pounds. Vital signs: normal. Neck: l6-inch circumference. Chest: clear. Cardiac: normal. Extremities: no edema. Question: What evaluation and treatment do you recommend? 357

Diagnosis: Treatment of insomnia secondary to antidepressant therapy. Discussion: Insomnia is a common complaint of patients with depression. In patients with known depression, a sleep study adds little to the evaluation unless periodic limb movement in sleep or sleep apnea is suspected. Today, most patients with mildto-moderate depression are started on selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, sertaline, citaloprarn, and tluvoxamine. Venlafaxine, an inhibitor of serotonin and norepinephrine uptake, and bupropion (increases dopamine and serotonin) are also widely used. These agents have fewer side effects than the traditional tricyclic antidepressants (TCAs). Unfortunately, insomnia is a common side effect ofthese medications. All of the previously listed medications (except bupropion) increase the REM latency and decrease the amount of REM sleep. Bupropion can actually increase REM sleep. The MAO inhibitors are sometimes used for refractory depression. They are the most potent inhibitors of REM sleep. Behavior techniques plus improved sleep hygiene should be the first treatment of SSRI-induced insomnia. However, many patients may not respond. In these situations, low doses of trazodone (50-100 mg) at bedtime can be a useful adjunct to SSRI treatment. This medication is sedating, but has fewer anticholinergic side effects than the sedating TCAs. Trazodone has no consistent effect on the amount of REM sleep and either increases or has no effect on the REM latency. Men must be counseled about the side effect of priapism (persistent and painful erections). If a priapism occurs, surgery may be needed, as permanent impotence can result. Trazodone also can cause severe postural hypotension. An alternative is the addition of a benzodiazepine hypnotic or the nonbenzodiazepine hypnotics (zolpidem and zaleplon). A third option in treating severe insomnia in a depressed patient is to switch to a different type of antidepressant. Nefazodone is a mildly sedating antidepressant that is a useful treatment alternative in depressed patients with prominent insomnia. In one study comparing nefazodone and fluoxetine, both were effective antidepressants, but only nefazodone improved objective sleep quality. Interestingly, the fluoxetine group also reported subjective improvements in sleep quality. Thus, the traditional SSRIs may actually improve a patient's perception of sleep by improving mood. Nefazodone is a postsynaptic serotonin type 2 receptor (5HT2) blocker and it also weakly inhibits the reuptake of serotonin. It must be administered twice daily, and the most common side effect is dizziness. Nefazodone inhibits the cytochrome P450 system and has important potential drug interactions (e.g., increases the risk of myopathy with anticholesterol statins). Unlike most other antidepressants, it may increase the amount ofREM sleep and does not increase the REM latency. Bupropion is the only other available antidepressant that increases REM sleep. Mirtazapine is another sedating antidepressant that can be tried if patients have severe insomnia on other agents. This medication increases both serotonin and norepinephrine via alpha 2 receptor blockade rather than reuptake inhibition. Like nefazodone, mirtazapine also blocks 5HT2 receptors, and this may ehance sleep quality. Mirtazapine also blocks 5HT3 receptors and histamine type I receptors. The latter effects may cause sedation and weight gain. Neither nefazodone nor mirtazapine cause sexual dysfunction or postural hypotension. (See Patient 103, dosage table. Also see reference 4 for discussion of pharmacology and use of newer antidepressants.) In the current case, since the patient's depression had responded so well to fluoxetine, trazodone 50 mg at bedtime was added to the fluoxetine regimen. The patient reported slight improvement, and the dose was increased to 100 mg at bedtime. On this combination of medications he reported improved sleep quality and felt rested on awakening in the morning. Clinical Pearls I. Insomnia is a frequent complaint of patients with depression. 2. Insomnia in depressed patients may be exacerbated by treatment with reuptake inhibitors of serotonin. 3. The addition of a low dose of trazodone (50-100 mg) or hypnotics at bedtime may improve sleep in patients having persistent/worsened sleep difficulty on serotonin reuptake inhibitor treatment. 4. Switching from an SSRI to nefazodone or mirtazapine may improve sleep quality in patients with depression and persistent insomnia. 358

REFERENCES I. Nierenberg AA. Adler LA. Peselow E. et al: Trazodone for antidepressant-associated insomnia. Am J Psychiatry 1994; 151:1069. 2. Neylan TC: Treatment of sleep disturbance in depressed patients. J Clin Psychiatry 1995; 56(suppl 2):56-61. 3. Gillin JC. Rapaport M. Erman MK. et al: A comparison of nefazodone and fluoxetine on mood and on objective, subject, and clinician-rated measures of sleep in depressed patients. J Clin Psychiatry 1997; 58: 186-192. 4. Kent JM: SNaRls. NaSSAs. and NaRis: New agents for the treatment of depression. Lancet 2000;355:911-918. 359

PATIENT 110 A 45-year-old man with hyperphagia and hypersomnia A 45-year-old man was evaluated for a 6-month history of daytime sleepiness (Epworth Sleepiness Scale score 16/24). During this time he had developed a tremendous appetite and had gained 20 pounds. He also had increased difficulty dealing with the stresses of his job. His wife reported that he was hypersensitive to criticism and seemed to believe she did not love him anymore. The patient usually retired at 10 PM and slept until the alarm clock awakened him at 6:30 AM. He had tremendous difficulty getting out of bed and was late to work on several occasions. On the weekends he sometimes slept from I I PM until 10-11 AM. The patient was reported to snore, but his wife had not noticed any pauses in breathing. Physical Examination: Height 5 feet II inches, weight 210 pounds. HEENT: slightly edematous uvula; 16-inch neck circumference. Chest: clear. Cardiac: normal. Extremities: no edema. Sleep Study (Lights out 10:30 PM, lights on 6:00 AM) Time in bed Total sleep time Sleep period time (SPT) WASO Sleep efficiency (%) Sleep latency REM latency Respiratory arousal index 450 min (390-468) 391.5 min (343-436) 435 min (378-452) 43.5 min 87 (85-97) 15 min (2-18) 35 min (55-78) 5/hr Sleep Stages Stage Wake Stage I Stage 2 Stages 3 and 4 Stage REM AHI PLM index %SPT 10(1-12) 6 (5-11) 60 (44-66) 4 (2-15) 20 (19-27) l/hr O/hr ( ) = normal values for age. AHI = apnea + hypopnea index, PLM = periodic limb movement Question: What is causing this patient's hypersomnia? 360

Diagnosis: Atypical depression. Discussion: A majority of patients with major depression present with complaints of disturbed sleep. In most cases, insomnia and fatigue are the major complaints, rather than daytime sleepiness. However, hypersomnia is commonly noted in patients experiencing the depressive phase of bipolar disorder, seasonal affective disorder (SAD; winter depression), or atypical depression. Atypical depression is characterized by weight gain (hyperphagia), rejection hypersensitivity, hypersomnia, and leaden paralysis (heavy feeling in the extremities). Treatment of depressed patients with hypersomnia typically involves selective serotonin reuptake inhibitors (fluoxetine, in particular) because these drugs are not sedating. Patients not responding to SSRIs have been treated with MAO inhibitors, but these drugs have the potential for serious drug and food interactions. In bipolar patients, adjunctive treatment with mood stabilizers is indicated to avoid inducing a manic episode. SAD is characterized by a regular temporal relationship between the onset of depression (fall or winter). Remission of depression occurs at a regular time (spring). Patients often complain of sleeping late and feeling tired all the time. SAD often responds to light therapy (usually in the early morning hours). For example, one method of light treatment is to use an intensity of 10,000 lux for a duration of 30 minutes with the daily treatments starting about 3 hours after the midpoint of spontaneous sleep. The differential diagnosis of hypersomnia with depression includes recurrent hypersomnia, sleep apnea, and PLMD. Recurrent hypersomnia (KleineLevin syndrome) is characterized by episodes (at least once or twice yearly) lasting 3-21 days and featuring voracious eating, hypersexuality, and disinhibited behavior (e.g., irritability, aggression). Monosymptomatic forms (hypersomnolence only) also exist. This disorder typically affects males and starts in adolescence. Onset in adulthood and occurrence in women have been described. During intervals between periods of somnolence, individuals appear normal. In the present case, the history of snoring and weight gain prompted a sleep study to rule out obstructive sleep apnea (OSA). The study showed minimal amounts of apnea. The upper airway resistance syndrome also was considered, but the arousal index was low. While personality change can be noted with OSA, the rapidity of onset made this seem less likely. The REM latency was moderately short-a characteristic of a variety of disorders, including sleep apnea, narcolepsy, and depression. However, there was no history consistent with narcolepsy. Onset of recurrent hypersomnia is unlikely at age 45. Given the weight gain, hypersomnia, and recent onset of problems dealing with criticism and rejection, the diagnosis of atypical depression was considered a likely possibility, and the patient was referred to a psychiatrist for evaluation. Treatment with fluoxetine produced considerable improvement within 4 weeks, and the patient lost about 10 pounds. The symptoms of daytime sleepiness resolved. Clinical Pearls I. The depressive phase of bipolar disorder, atypical depression, and seasonal affective disorder (winter depression) can present with symptoms of hypersomnia. 2. Patients with atypical depression may gain weight (hyperphagia), and this may trigger a suspicion of sleep apnea. 3. Seasonal affective disorder (SAD) can be treated effectively with early morning light. 4. Atypical depression is characterized by hypersomnia, hyperphagia/weight gain, and leaden paralysis (heavy feeling in the extremities). REFERENCES I. Billard M. Dolenc L. Aldaz C. et al: Hypersomnia associated with mood disorders: A new perspective. J Psychosom Res 1994; 38(suppll):4I--47. 2. Benca RM: Sleep in psychiatric disorders. Neurol Clin 1996; 14:740-748. 3. Pande AC. Birkett M. Fechner-Bates S. et al: Fluoxetine versus phenelzine in atypical depression. Bioi Psychiatry 1996; 40:1017-1020. 4. Chesson AL, Jr.• Littner M. Davila D. et al: AASM Standards of Practice Committee. Practice parameters for the use of light therapy in the treatment of sleep disorders. Sleep 1999; 22:641---660. 5. Terman JS, Terman M. Lo E. Cooper TB: Circadian time of morning light administration and therapeutic response in winter depression. Arch Gen Psychiatry 2001; 58:69-73. 361

PATIENT 111 A 50-year-old veteran of the Vietnam War with upsetting dreams A 50-year-old man was evaluated for recurrent awakenings with frightening dreams at night. These awakenings had been a frequent problem since his service in the Vietnam War. The dreams often were related to memories of combat, and when they occurred he could not go back to sleep. The patient reported difficulty falling asleep on some nights, and he generally felt unrefreshed in the morning. His wife reported that he frequently thrashed about during the night while asleep. There was no history of snoring. Previous treatment with benzodiazepines had not improved his symptoms. Physical Examination: Unremarkable. Sleep Study Time in bed Total sleep time Sleep period time (SPT) WASO Sleep efficiency (0/0) Sleep latency REM latency Arousal index 470 min (378-468) 365.5 min (340-439) 430 min (361-453) 64.5 min 78 (88-96) 30 min (1-22) 70 min (65-104) 30/hr Sleep Stages Stage Wake Stage I Stage 2 Stages 3 and 4 Stage REM AHI PLM index O/OSPT 15 (2-7) 14 (4-12) 51 (51-72) 0(0-13) 20 (17-25) 4/hr 5/hr ( ) = normal values for age, AHI = apnea + hypopnea index, PLM = periodic limb movement Question: What is causing the patient's sleep disturbance? 362

Diagnosis: Post-traumatic stress disorder. Discussion: The post-traumatic stress disorder (PTSD) occurs in individuals who have experienced a traumatic event in their life, such as combat, physical attack, natural disaster, or traumatic injury. The disorder is characterized by reexperiencing the events in flashbacks, intrusive recollections, or recurrent dreams. While it once was thought that complex dreaming is confined to REM sleep, recent studies suggest dreams may occur in both REM and NREM sleep. Symptoms of PTSD can begin immediately after the event or have a delayed onset (up to years later). Patients with PTSD also report a heightened startle response. Given a common exposure to a traumatic event, PTSD appears to occur more frequently in women than men. Patients with PTSD also may have depression and may abuse ethanol or other substances. The differential of awakening with anxiety includes sleep panic disorder, REM behavior disorder, and night terrors. Unlike patients with panic attacks during sleep, patients with PTSD can recount a dream of a specific traumatic event. In contrast to night terrors, patients become alert quickly after awakening. Sleep studies in patients with PTSD have produced conflicting results. The duration of REM latency and the amount of REM sleep have varied among studies. This may be a reflection of the fact that some patients with PTSD also are suffering from depression. Several studies have found an increase in REM density in patients with PTSD (as in depression), an increase in body movements during sleep, and the presence of periodic limb movements in sleep (PLMS). The treatment of PTSD includes counseling and medication. Although many patients with PTSD have anxiety, benzodiazepines have not been effective, and withdrawal of these medications may produce a flair of symptoms. Any REM-suppressing medication might decrease the incidence of nightmares. However, medications without REM suppression also have been effective (nefazodone). Treatment with tricyclic antidepressants, MAO inhibitors, and selective serotonin reuptake inhibitors has been effective in selected patient groups. Sertaline, an SSRI, was effective in a double-blind placebocontrolled study and is the only antidepressant that has an FDA indication for PTSD treatment. Several open-label studies found that fluoxetine, paroxetine, and nefazodone were also effective. A few studies showed low doses of anticonvulsant medications (e.g., carbmazepine, valproate) to be helpful in some patients. Anticonvulsants do not decrease the amount of REM sleep. Patients with PTSD are a heterogeneous group, and if one medication does not work, others should be tried. For example, fluoxetine is activating and may increase anxiety or sleep disturbance. Nefazodone is mildly sedating, causes less sexual dysfunction, and may be better tolerated in anxious patients. The main side effect of this medication is dizziness, and severe drug interactions can occur as nefazodone inhibits the cytochrome P450 system. The drug should not be used with with the statin cholesterol medications. Rare instances of hepatic failure have been noted. Clonidine and propanolol also have been used for severe anxiety symptoms. Abrupt withdrawal of any of the aforementioned medications can induce a rebound in symptom severity. When starting a new medication, it is wise to start with a low dose and titrate upward slowly. In the present patient, a sleep study was ordered to rule out OSA and PLMS (history of thrashing around in bed). However, no significant amount of PLMS was noted. The sleep study showed a reduced sleep efficiency with increased waketime during the night, and stages 3 and 4 were absent. The patient was started on low-dose amitriptyline (50 mg qhs), resulting in improved sleep and fewer nightmares; however, he felt groggy the next day. This symptom usually resolves after 2 weeks of treatment, but it did not resolve in this patient. Medication was switched to fluoxetine, and nightmares were reduced. However, the patient reported continued frequent awakenings on this medication and increased anxiety during the day. Nefazodone was started at 100 mg po bid, and the patient reported improved sleep and a decrease in nightmares. His wife also noted less thrashing around in bed. 363

Clinical Pearls 1. Sleep disturbance and awakenings with frightening dreams are common manifestations of post-traumatic stress disorder (PTSD). 2. Patients with PTSD have increased REM density but variable amounts of REM sleep. 3. Increased body movements and PLM during sleep also have been reported in PTSD. 4. A wide variety of medications are successful in different patient groups. Treatment must be individualized. 5. While anxiety is a major problem for many patients with PTSD. antidepressants are usually more effective than benzodiazepines REFERENCES I. Ross RJ. Ball WA. Dinges DR. et at: Rapid eye movement sleep disturbance in posttraumatic stress disorder. Bioi Psychiatry 1994; 35: 195-202. 2. Brown TM. Boudewyns PA: Periodic limb movements of sleep in combat veterans with posttraumatic stress disorder. J Trauma Stress 1996; 9: 129-136. 3. Davidson JR: Biological therapies for posttraumatic stress disorder: An overview. J Clin Psychiatry 1997; 58(SuppI9):29-32. 4. Mellman TA, Nolan B, Hedding J, et al: A polysomnographic comparison of veterans with combat-related PTSD. depressed men, and non-ill controls. Sleep 1997; 20:46-51. 5. Davis LL, English BA, Ambrose SM, et al: Pharmacotherapy for post-traumatic stress disorder: A comprehensive review. Expert Opin Pharmacother 200 I; 2: 1583-1595. 6. Davidson JR, Rothbaum BO, van der Kolk BA, et al: Multicenter. double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry 200 I; 58:485-492. 364

PATIENT 112 A 40-year-old woman with terrifying awakenings A 40-year-old woman was evaluated for episodes of awakening from sleep with intense anxiety and fear. These awakenings were first noted at age 38. Similar attacks sometimes occurred during wakefulness, but they did not seem as intense. The patient experienced shortness of breath, palpitations, diaphoresis, and chest pain during these episodes, which usually occurred within 1-2 hours of bedtime. During one of the episodes she had been admitted to a hospital to rule out myocardial infarction. A subsequent evaluation for cardiac disease was negative. The patient denied having frightening dreams preceding the attacks and was able to remember the episodes the following morning. Previously, the patient was under the care of a psychiatrist for phobias related to elevators. Physical Examination: Unremarkable. Question: What is your diagnosis? 365

Diagnosis: Sleep panic attack. Discussion: Panic attacks are repeated occurrences of extreme anxiety accompanied by at least four of the associated symptoms: shortness of breath, choking, palpitations, chest pain, sweating, dizziness, nausea, paresthesia, fear of dying, flushing, and chills. Although panic attacks usually take place while the patient is awake, up to 65% of patients with panic disorder report nocturnal panic attacks as well. The duration of the attacks is usually less than 10 minutes. The symptom of dyspnea appears to be more common in nocturnal panic attacks. The attacks occur from NREM sleep, commonly at the transition from stage 2 to stage 3 sleep. In most patients, sleep architecture is normal (normal REM latency and sleep efficiency). However, some patients may develop sleep phobia, and this can be associated with findings consistent with insomnia. The differential of panic attacks includes night terrors, nightmares, post-traumatic stress disorder, and REM behavior disorder. Night terrors usually begin in childhood, and the affected individual is not well aware of his or her surroundings and does not remember the episodes in the morning. Inpanic attacks, the patient is awake and aware of his or her surroundings. In nightmares, the patient usually is aware of a frightening dream. In contrast, patients with panic attacks remember the episode, but typically do not report a terrifying dream. The treatment of panic attacks includes behavioral psychotherapy or relaxation techniques and pharmacotherapy. Although benzodiazepines (e.g., alprazolam, clonazepam) were the classic treatments for panic disorder, many psychiatrists prefer a trial of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). Both SSRIs (e.g., paroxetine, sertaline) and TCAs (e.g., imipramine) must be started at very low doses, or panic attacks initially may be exacerbated. For example, paroxetine is started at 10 mg daily or imipramine at 10-25 mg daily. The doses are slowly increased to 20-40 mg for paroxetine or 100-200 mg for imipramine, as tolerated. As improvements may take 4-6 weeks or longer, many physicians add benzodiazepines during the early course of therapy. Many of the traditional TCAs are effective (desipramine, nortriptyline, amitryptiline, and doxepin). The antidepressants trazodone, protriptyiine, and bupropion have not been effective in this disorder. In the present case, the patient was referred for psychiatric treatment. She was started on c10- nazepam I mg and imipramine 10 mg at bedtime. Over the next 2 months, the imipramine was slowly increased to 100mg daily, and clonazepam was discontinued. The patient noted almost complete resolution of the nocturnal attacks. Clinical Pearls 1. Patients with sleep panic attacks usually have similar episodes when awake. 2. Nocturnal panic attacks occur most commonly during the transition from stage 2 to stage 3 sleep. 3. Unlike sleep terrors, the patient is awake and alert immediately after the attack begins. 4. Treatment with benzodiazepines, serotonin reuptake inhibitors, or tricyclic antidepressants usually is effective. The usual recommendation is to begin antidepressants at low doses-otherwise the panic attacks may exhibit an initial exacerbation. Concurrent use of a benzodiazepine at the start of treatment may also be needed. REFERENCES I. Mellman TA. Ude TW: Patients with frequent sleep panic: Clinical findings and response to medication treatment. J Clin Psychiatry 1990; 51:513-516. 2. Benca RM: Sleep in psychiatric disorders. Neurol Clin 1996; 14:750-751. 3. Hahn RK. Albers LJ. Reist C: Psychiatry-Current Clinical Strategies. Laguna Hills. CA. Current Clinical Strategies Publishing. 1997. pp 46-48. 4. Moroze G. Rosenbaum JF: Efficacy. safety. and gradual discontinuation of clonazepam in panic disorder: A placebo-controlled. multicenter study using optimized doses. J Clin Psychiatry 1999; 60:604-612. 366

APPENDIX I Sleep Disorders Classification Sleep disorders comprise a diverse set of syndromes. The Diagnostic Classification of Sleep and Arousal Disorders (published in 1979) divided sleep disorders on the basis of the presenting complaint. The major categories included: disorders of initiating and maintaining sleep (DIMS), disorders of excessive sleepiness (DOES), parasornnias, and disorders of the sleep-wake schedule. Some disorders appeared in more than one category. Subsequently. the International Classification of Sleep Disorders (lCSD; published in 1990) used a different approach. Sleep disorders directly affecting sleep (dyssomnias) were classified on the basis of whether they developed from internal, external, or circadian rhythm causes. The 1997 revised classification outline appears below. The reader is referred to the valuable text by the American Academy of Sleep Medicine (formerly the American Sleep Disorders Association) from which it comes.' 1. DYSSOMNIAS A. Intrinsic Sleep Disorders I. Psychophysiologic Insomnia 2. Sleep State Misperception 3. Idiopathic Insomnia 4. Narcolepsy 5. Recurrent Hypersomnia 6. Idiopathic Hypersomnia 7. Post-traumatic Hypersomnia 8. Obstructive Sleep Apnea Syndrome 9. Central Sleep Apnea Syndrome 10. Central Alveolar Hypoventilation Syndrome II. Periodic Limb Movement Disorder 12. Restless Legs Syndrome 13. Intrinsic Sleep Disorder Not Otherwise Specified (NOS) B. Extrinsic Sleep Disorders I. Inadequate Sleep Hygiene 2. Environmental Sleep Disorder 3. Altitude Insomnia 4. Adjustment Sleep Disorder 5. Insufficient Sleep Syndrome 6. Limit-setting Sleep Disorder 7. Sleep-onset Association Disorder 8. Food Allergy Insomnia 9. Nocturnal Eating (Drinking) Syndrome 10. Hypnotic-Dependent Sleep Disorder II. Stimulant-Dependent Sleep Disorder 12. Alcohol-Dependent Sleep Disorder 13. Toxin-Induced Sleep Disorder 14. Extrinsic Sleep Disorder NOS C. Circadian-Rhythm Sleep Disorders I. Time Zone Change (Jet Lag) Syndrome 2. Shift Work Sleep Disorder 3. Irregular Sleep-Wake Pattern 4. Delayed Sleep-Phase Syndrome 5. Advanced Sleep-Phase Syndrome 6. Non-24-Hour Sleep-Wake Disorder 7. Circadian Rhythm Sleep Disorder NOS 2. PARASOMNIAS A. Arousal Disorders 367

I. Confusional Arousals 2. Sleepwalking 3. Sleep Terrors B. Sleep-Wake Transition Disorders I. Rhythmic Movement Disorder 2. Sleep Starts 3. Sleep Talking 4. Nocturnal Leg Cramps C. Parasomnias Usually Associated with REM Sleep l. Nightmares 2. Sleep Paralysis . 3. Impaired Sleep-Related Penile Erections 4. Sleep-Related Painful Erections 5. REM Sleep-Related Sinus Arrest 6. REM Sleep Behavior Disorder D. Other Parasomnias I. Sleep Bruxism 2. Sleep Enuresis 3. Sleep-Related Abnormal Swallowing Syndrome 4. Nocturnal Paroxysmal Dystonia 5. Sudden Unexplained Nocturnal Death Syndrome 6. Primary Snoring 7. Infant Sleep Apnea 8. Congenital Central Hypoventilation Syndrome 9. Sudden Infant Death Syndrome 10. Benign Neonatal Sleep Myoclonus II. Other Parasomnia NOS 3. SLEEP DISORDERS ASSOCIATED WITH MENTAL, NEUROLOGIC, OR OTHER MEDICAL DISORDERS A. Associated with Mental Disorders I. Psychoses 2. Mood Disorders 3. Anxiety Disorders 4. Panic Disorders 5. Alcoholism B. Associated with Neurologic Disorders I. Cerebral Degenerative Disorders 2. Dementia 3. Parkinsonism 4. Fatal Familial Insomnia 5. Sleep-Related Epilepsy 6. Electrical Status Epilepticus of Sleep 7. Sleep-Related Headaches C. Associated with Other Medical Disorders l. Sleeping Sickness 2. Nocturnal Cardiac Ischemia 3. Chronic Obstructive Pulmonary Disease 4. Sleep-Related Asthma 5. Sleep-Related Gastroesophageal Reflux 6. Peptic Ulcer Disease 7. Fibromyalgia 4. PROPOSED SLEEP DISORDERS I. Short Sleeper 2. Long Sleeper 3. Subwakefulness Syndrome 4. Fragmentary Myoclonus 5. Sleep Hyperhidrosis 6. Menstrual-Associated Sleep Disorder 7. Pregnancy-Associated Sleep Disorder 8. Terrifying Hypnagogic Hallucinations 9. Sleep-Related Neurogenic Tachypnea 10. Sleep-Related Laryngospasm II. Sleep Choking Syndrome "Reprinted from American Sleep Disorders Association: International Classification of Sleep Disorders. Rochester, Minnesota, ASDA, 1997; with permission. 368 APPENDIX I

APPENDIX II Sleep Stage Characteristics Stage Characteristics EEG EOG EMG Wake (eyes open) Low voltage, high frequency Eye blinks, Relatively high Attenuated alpha activity REMs Wake (eyes closed) Low voltage, high frequency Slow rolling eye Relatively high > 50% alpha activity movements Slow rolling eye movements Stage I Stage 2 Stage 3 Stage 4 Stage REM Low amplitude, mixed frequency < 50% alpha activity No sleep spindles, no K complexes Sharp waves near transition to stage 2 At least one sleep spindle or K complex < 20% slow wave activity 20-50% slow wave activity > 50% slow wave activity Low voltage, mixed frequency Episodic REMs Saw tooth waves may be present May be lower than in stage Wake May be lower than in stage Wake Usually low Usually low Relatively reduced (equal or lower than the lowest in NREM) Notes: Required characteristics for the determination of each stage are in boldface. Slow wave activity has a frequency < 2 Hz and a peak to peak amplitude> 75 microvolts. Percentages refer to amount of time during each epoch. EEG = electroencephalogram, EOG = electro-oculogram, EMG = electromyogram, REM = rapid eye movements, NREM = nonrapid eye movement sleep. 369

APPENDIX III Disorders Causing Excessive Daytime Sleepiness Sleep apnea syndromes Upper airway resistance syndrome Narcolepsy Depression Periodic limb movement disorder Idiopathic hypersomnia Withdrawal from stimulants Inadequate sleep Sedatives/medications Post-traumatic hypersomnia Common Causes of Insomnia Primary Insomnia Psychophysiological Acute (adjustment sleep disorder) Chronic Idiopathic Sleep state misperception Secondary' Insomnia Other sleep disorders (sleep apnea, PLMD) Psychiatric disorders (depression, panic attacks) Drugs (nicotine, ethanol, caffeine) Medical conditions/medications Fibromyalgia and chronic pain syndromes COPD and other respiratory disorders Medications for illness (theophylline, beta blockers) Circadian disorders Delayed sleep-phase syndrome Advanced sleep-phase syndrome Shift work or jet lag syndrome Inadequate sleep hygiene Environmental sleep disorder 'Secondary means another disorder can be diagnosed. PLMD = periodic limb movement disorder, COPD = chronic obstructive pulmonary disease 371

AASM-American Academy of Sleep Medicine Advanced sleep-phase syndrome (ASPS)-characterized by early sleep onset and final wake time relative to societal (clock) norms in the external world Alpha activity-EEG activity at 8-13 Hz Alpha-delta sleep-prominent alpha activity occurring during slow wave sleep Alpha sleep-prominent alpha activity occurring during sleep Amplitude-the magnitude of deflection in a signal; units depend on calibration. For slow wave activity, refers to peak-to-peak deflection. Apnea - absence of airflow at the nose and mouth for 10seconds or longer Apnea + hypopnea index (AHI)-the number of apneas and hypopneas per hour of sleep, expressed as total number/total sleep time in hours. Also called the respiratory disturbance index (RDI). Arousal-abrupt, possibly brief awakening from sleep. In NREM sleep, an abrupt shift in EEG frequency longer than 3 seconds; in REM sleep, the EMG also must show augmentation to qualify as an arousal (ASDA definition). ASDA-American Sleep Disorders Association, now called the American Academy of Sleep Medicine AutoCPAP-auto-adjusting or auto-titrating CPAP units that deliver the lowest required pressure at any time needed to maintain upper airway patency Automatisms-repetitive movements that may be purposeful, but are not of benefit Beta activity-EEG activity> 13 Hz Bilevel pressure-method of ventilation allowing separate pressure levels in inspiration (inspiratory positive airway pressure, IPAP) and expiration (expiratory positive airway pressure, EPAP). Biocalibration-the initial recording of maneuvers during wakefulness to determine if the corresponding deflections in EEG, EOG, chin EMG, leg EMG, and airflow channels are satisfactory and to adjust amplifier gains, if necessary Bruxism-clinching or grinding of the teeth C4 (C3)-central EEG electrode on the right (left) side of the head Calibration-adjustment of amplifier baseline and gain. In polysomnography, the settings of EEG, GLOSSARY EOG, and EMG amplifiers are adjusted so that a known reference square wave input voltage elicits the desired pen deflections (or tracing deflection on a digital system). The low and high filter settings at the time of calibration are documented, as these affect the amplitude and shape of the deflections for a given calibration voltage. Capnogram- tracing of exhaled CO2, The plateau of the deflection from each exhalation is the endtidal PC02 (an estimate of the arterial PC02). Cataplexy - sudden loss of muscle tone (especially antigravity muscles) at moments of high emotion (e.g., surprise, laughter, fear); characteristic of narcolepsy Central apnea-apnea associated with an absence of respiratory effort Cheyne-Stokes breathing-crescendo-decrescendo pattern of breathing with central apneas or hypopneas at the nadir Chronic obstructive pulmonary disease (COPD)- chronic bronchitis, emphysema, or a mixture Confusional arousals-a parasomnia characterized by confusion following a spontaneous or forced arousal from sleep. Confusional arousals tend to occur out of stages 3 and 4 sleep. In contrast to night terrors, there is no autonomic hyperactivity, signs of fear, or blood-curdling scream. Continuous positive airway pressure (CPAP)- maintenance of positive airway pressure during inspiration and expiration CPAP flow-the flow signal from the positivepressure device utilized in polysomnography Delayed sleep-phase syndrome (DSPS)-characterized by delayed sleep onset and final waketime relative to societal (clock) norms in the external world Delta activity-EEG activity at < 4 Hz. In human sleep staging, the slow wave activity used to determine the sleep stage is < 2 Hz (see Slow wave activity). Derivation - the choice of two electrodes providing input to a differential amplifier (e.g., C4-A I) Desaturation - fall in arterial oxygen saturation ;::: 4% from baseline Diurnal-pertaining to daytime Early-morning awakening- final awakening earlier than expected; characteristic of depression 373

Electroencephalogram (EEG)-recording of brain electrical activity Electromyogram (EMG)-recording of the electrical activity of a muscle. In routine sleep monitoring, surface electrodes monitor EMG activity in the chin area. Electro-oculogram (EOG)- recording of the electrical activity generated during eye movements EPAP-expiratory positive airway pressure Epoch-a period of time usually corresponding to 30 seconds (one page of recording at a paper speed of 10 mm/sec) Epworth Sleepiness Scale (ESS) - a score from 0 to 24 of the propensity to fall asleep in eight normal situations (see Fundamentals of Sleep Medicine II). Normal is:s: 10, and 24 is the maximal ESS score (the most sleepy). FEV,IFVC - ratio of the forced expiratory volume in l second to the forced vital capacity. Reduced in obstructive airway disease. In this text, normal is > 0.70 and 90% of predicted. Forced expiratory volume (FEV)- FEY I is the volume of air in liters exhaled in the first I second of a maximal forced vital capacity maneuver. In this text, normal is assumed to be 80-120% of predicted. Forced vital capacity (FVC)-volume of air in liters exhaled from maximal inhalation (total lung capacity) to residual volume (maximal exhalation) during a forced maneuver. In this text, normal is assumed to be 80-120% of predicted. Hypnagogic-an event occurring on transition from wake to sleep Hypnagogic hallucination-vivid imagery at sleep onset; a feature of narcolepsy in which REM periods occur at sleep onset Hypnic jerk (sleep start)- brief total-body jerk at sleep onset Hypnogram-a graphical overview of the cyclic nature of sleep (see Patient 9) Hypnopompic-an event occurring on transition from sleep to wakefulness Hypocretins-two peptides, Hcrt I and Hcrt 2 (also known as orexins A and B), that are secreted by hypothalamic neurons that project to specific areas of the brainstem and cortex. The peptides are thought to influence the sleep-wake cycle and alertness. A disruption of hypocretin neurotransmission may play a key role in the pathogenesis of canine and human narcolepsy. Hypopnea - reduction in airflow for 10 seconds or longer. Definitions vary (see text). ICSD-International Classification of Sleep Disorders Interictal-refers to transient focal or generalized discharges between seizure events K complex -large-amplitude biphasic deflection ofO.5-second or longer duration; a negative (up) 374 sharp wave followed by a positive (down) slow wave Laser-assisted uvuolopalatoplasty (LAUP)-palatoplasty performed with a laser Left outer canthus (LOC)-electrode placed lateral to the outer corner of the left eye Maintenance of wakefulness test (MWT)-test to determine the ability to stay awake Mean sleep latency-the mean of sleep latencies recorded during naps over the course of a multiple sleep latency test Mixed apnea-apnea composed of an initial central part followed by an obstructive component Montage-the particular arrangement of electrodes by which a number of derivations are displayed simultaneously in a polysomnogram Movement arousal-defined in the R&K scoring manual as an increase in the chin EMG accompanied by a change in pattern on any additional channel. For EEG channels, qualifying changes include a decrease in amplitude, paroxysmal high voltage activity, or an increase in alpha activity. Movement time (MT)-epochs in which the sleep stage is indeterminant due to movement artifact in the EEG Multiple sleep latency test (MSLT) - test to determine the mean sleep latency during daytime naps as an objective measure of daytime sleepiness. The presence/absence of REM sleep during the naps also is determined. Nasal pressure-used to detect airflow; see Fundamentals of Sleep Medicine 10 Non-REM (NREM) sleep-sleep stages I, 2, 3, and 4 02 (Ol)-occipital EEG electrode on the right (left) side of the head Obesity-hypoventilation syndrome (OHS)-daytime hypoventilation (hypercapnia) not secondary to lung disease in an obese patient, usually accompanied by severe obstructive sleep apnea Obstructive apnea-apnea with persistent respiratory effort Obstructive sleep apnea syndrome (OSAS)- syndrome characterized by obstructive and mixed apnea and hypopneas, as well as excessive daytime sleepiness Overlap syndrome-obstructive sleep apnea plus chronic obstructive pulmonary disease (OSA + COPD) Parasomnia - a condition associated with or occurring from sleep. Disorders of arousal or partial arousal. Examples include sleepwalking, night terrors, and REM behavior disorder. Periodic leg (limb) movement(s) (PLM, PLMs)- leg (arm) movements, such as foot flexion, big toe extension, and partial flexion at hip and knee, of about I-second duration that occur every 20- 60 seconds during sleep. To be considered a GLOSSARY

PLM, a leg movement must occur in a group (sequence) of four or more movements separated by > 5 seconds and < 90 seconds. Periodic leg (limb) movements in sleep (PLMS)- the entity describing periodic leg movements during sleep, usually referring to an abnormal number of leg movements or a PLM index> 5/hr Periodic leg (limb) movement disorder (PLMO)- a disorder of excessive daytime sleepiness or insomnia secondary to PLMS Periodic leg (limb) movement index (PLM index)- number of movements per hour of sleep Periodic leg (limb) movement-arousal index (PLM-arousal index)-number of PLMs associated with arousal per hour of sleep Phasic REM sleep - REM sleep in which rapid eye movements are present Phase response curve (PRC)-a curve characterizing the magnitude and direction of the shift of the internal clock (circadian rhythm) induced by light as a function of the timing of light relative to the baseline circadian rhythm (relative to the nadir in body temperature) Polysomnography- the detailed monitoringof sleep Popping artifact-high-voltage artifact caused by temporary disconnection of electrodes from the skin R&K- refers to the sleep staging criteria of Rechtschaffen and Kales, published in their book: A Manual of Standardized Terminology Techniques and Scoring System for Sleep Stages of Human Sleep. Los Angeles, Brain Information Service/ Brain Research Institute, UCLA, 1968. Rapid eye movement (REM)-a sharp (short duration) eye movement Rapid eye movement behavior disorder (RBO)- a parasomnia occurring from REM sleep associated with body movement and violent behavior Rapid eye movement density-number of eye movements per time in REM sleep. Normally highest during the last REM periods of the night. Rapid eye movement sleep-a sleep stage characterized by a low-voltage, mixed-frequency EEG; episodic REMs; and a relatively lowamplitude EMG (:5 the lowest amplitude in NREM sleep) Recording time; time in bed (TIB)-total time of sleep monitoring from lights out to lights on REM latency - time from sleep onset to the start of stage REM Respiratory arousal index (RAI)- arousals secondary to an apnea or hypopnea,and, in many sleep laboratories, respiratory effort-related arousals per hour of sleep Respiratory disturbance index (ROI)-see Apnea + hypopneaindex Respiratory effort-related arousal (RERA)-an event characterized by an arousal following a peGLOSSARY riod of increased respiratory effort that does not qualify as an obstructive apnea or hypopnea. Increased respiratory effort is usually detected by increased esophageal pressure deflections. Respiratory inductance plethysmography (RIP)- a method of detecting chest and abdominal movement secondary to changes in the inductance (a component of impedance) of bands around those regions. See Fundamentals of Sleep Medicine 10. Restless legs syndrome (RLS)-syndrome marked by creeping sensation in the legs that can be temporarily relieved by movement Right outer canthus (ROC)-electrode placed lateral to the outer corner of the right eye Saw tooth waves-form of theta rhythm (jagged up and down) seen in stage REM Sharp wave (vertex sharp wave)-high-voltage, brief, negative (up) wave present in stage I near transition to stage 2. Sharp waves have a duration of 70-200 milliseconds. Sleep architecture-the relative amounts of the different sleep stages composing sleep and timing of sleep cycles. See Fundamentals of Sleep Medicine 7. Sleep efficiency - usually defined as total sleep time * 100/time in bed Sleep hygiene-conditions and practices that promote continuous and effective sleep Sleep latency-time from lights out (start ofmonitoring period) to the first epoch of any stage of sleep Sleep maintenance insomnia-difficulty maintaining sleep; frequent awakenings Sleep onset insomnia-difficulty falling asleep Sleep paralysis-inability to move while still awake at sleep onset (hypnagogic) or at the end of a sleep period (hypnopompic) Sleep period time (SPT)-time from sleep onset until the final awakening; total sleep time (TST) plus wake after sleep onset (WASO) Sleep spindle-EEG activity of 12-14 Hz occurring in bursts of O.5-second or longer duration; characteristic of stage 2 sleep but can be seen in stages 3 and 4 Sleep stages-also see Appendix II • Stage I-sleep characterized by a low-voltage, mixed-frequency EEG; an absence of sleep spindles and K complexes; and alpha activity present in < 50% of the epoch • Stage 2-sleep characterized by an EEG showing at least one sleep spindle or K complex (see Three-minute rule) and slow wave activity present in < 20% of the epoch • Stage 3-sleep with an EEG showing slow wave activity meeting the voltage criteria for 20-50% of the epoch • Stage 4-sleep with an EEG showing slow wave 375

activity meeting the voltage criteria for> 50% of the epoch • Stage REM-see Rapid eye movement sleep Sleep starts (hypnic jerk)- brief whole-body jerk at sleep onset Sleep state misperception - patients do not seem to recognize that they were asleep Sleep terrors-a parasomnia characterized by sudden awakening from NREM sleep (usually stages 3 and 4) with a cry or scream, confusion, and autonomic hyperactivity Sleep walking (somnambulism)-characterized by a partial awakening from NREM sleep (classically from stages 3 and 4) with complex movements including walking Slow rolling eye movement (or slow eye movements)-smooth, undulating eye movements occurring during drowsy wakefulness and stage I sleep Slow wave activity - by convention, oscillations slower than 2 Hz ( > 0.5 seconds in duration) with a minimal peak-to-peak amplitude of 75 microvolts. The amount of slow wave activity determines whether stage 2, 3, or 4 is present. Slow waves (delta waves)-EEG waves with a frequency of 1-4 Hz (see Slow wave activity) Spike-defined as an EEG transient with a pointed peak and a duration of 20-70 milliseconds Sweat artifact-slow undulations in EEG and EOG tracings secondary to sweat 376 Ten-twenty system-an international standard for the placement of EEG electrodes in which spacing of electrodes is 10% or 20% of the distance between landmarks on the head Theta activity - EEG activity at 4-7 Hz Three-minute rule-epochs of sleep between two spindles or K complexes that otherwise would be scored as stage 2 sleep are scored as stage I if the time between the spindles/K complexes is > 3 minutes and as stage 2 if the time is < 3 minutes. Time in bed (TIB); recording time-total monitoring time, from lights out to lights on Tonic REM sleep-REM sleep in which rapid eye movements are absent Total sleep time (TST)-total minutes of stages I, 2, 3, and 4, and REM sleep Upper airway resistance syndrome (UARS)- syndrome characterized by daytime sleepiness secondary to frequent arousals related to increased respiratory effort during periods of high upper airway resistance (narrowing) without an abnormal amount of frank apnea or hypopnea. Some authorities believe it is simply a mild form ofOSA. Uvulopalatopharyngoplasty (UPPP)-an upper airway surgery for sleep apnea and snoring. The uvula, a portion of the soft palate, and excess pharyngeal tissues are removed. Wake after sleep onset (WASO)-wake before the final awakening GLOSSARY

INDEX Abdominal movements, paradoxical, 92 during hypopnea, 84, 98 during obstructive sleep apnea, 91,92,93 Abdominal volume, in respiratory effort measurement,85-86 Acetazolamide, as idiopathic central sleep apnea treatment, 240 Adenoidectomy, 210-212 Adjustment sleep disorder, 333, 338-341, 343, 348-349 Age at onset, in sleep disorders, 100 Airflow monitoring in obstructive sleep apnea, 88-90 techniques in, 84-85 Airway obstruction. See also Upper airway obstruction periodic limb movements of sleep-related, 262- 264 Alcohol use as insomnia cause, 335, 336 sleep architecture effects of, 53 as snoring cause, 113-115,185,186 Alertness, maintenance of wakefulness test documentation of, 180-181 Alpha-delta sleep, 39 Alpha intrusion, 39 Ambient temperature, for prevention of sweat artifacts, 71 Amitriptyline as fibromyalgia treatment, 353 as insomnia treatment, 339 as post-traumatic stress disorder treatment, 363 Amphetamines, as narcolepsy treatment, 283 Anemia, iron-deficiency, as restless legs syndrome cause, 259-261 Anticonvulsants, as restless legs syndrome treatment, 267, 268, 270 Antidepressants, as insomnia treatment, 339 Anxiety panic attacks-related, 365-366 post-traumatic stress disorder-related, 363, 364 Apnea central, 233-252 Cheyne-Stokes breathing associated with, 243-245,246-247 congestive heart failure associated with, 234 definition of, 82, 233 idiopathic, 236-238, 239-240 oxygen therapy for, 239-240 definition of, 82 Apnea (Cont.) differentiated from hypopnea, 84-85 mixed Cheyne-Stokes breathing associated with, 242 definition of, 82 obstructive sleep apnea-associated, 94-95 obstructive. See Obstructive sleep apnea Apnea-hypopnea index in children, 212 effect of continuous positive airway pressure on, 128, 130, 131, 133 definition of, 82 in obstructive sleep apnea, 98, 103, 106, 116, 117,118,122 uvulopalatopharyngoplasty-related reduction of, 167 Apneic threshold, in central sleep apnea, 237 Arousal central sleep apnea-related, 238 Cheyne-Stokes breathing-related, 244 chin EMG evaluation of, 35-36, 38-39 confusional, 300-301,304 electrocortical, 36, 37 nocturnal seizure-related, 324 periodic limb movements of sleep-related, 257 in REM sleep, 43--44 respiratory, 108-118 respiratory effort-related, 108-112 upper respiratory resistance syndrome-related, III somnambulism-related, 307 Arousal index, in excessive daytime sleepiness, 36,37 Arrhythmias, obstructive sleep apnea-related, 194-196 Arterial oxygen desaturation in chronic obstructive pulmonary disease, 216- 218,219-221,222-223,227-229 in congestive heart failure, 242 definition of, 82 during initial continuous positive airway pressure use, 163-165 measurement of, 86 in obstructive sleep apnea, 116-118,205-206 severity of, 106, 107 during REM sleep, 31, 32, 116-118 Artifacts EKG, 62-63, 65 electrode popping, 72-73 377

Artifacts (Cont.) sixty-cycle, 64-66 sweat or respiratory, 70-71 Asthma, nocturnal, 230-232 Auditory monitoring, during polysomnography, 59 Augmentation effect, in levodopa/carbidopa therapy,270 Autoimmune disorders, as narcolepsy risk factor, 275 Automatisms, seizure-related, 321, 324 Automobile accidents, by obstructive sleep apnea patients, 182-183 Awakening. See also Arousal early-morning advanced sleep-phase syndrome-related, 349 depression-related, 354-356 terrifying, 365-366 Bed partners of excessive daytime sleepiness patients, 103 of periodic leg movements in sleep patients, 264,273 of REM sleep behavior disorder patients, 310 of restless leg syndrome patients, 259, 260 of untreated obstructive sleep apnea patients, 134-135 Bed wetting, 30 I Behavior problems, pediatric obstructive sleep apnea-related, 207-209, 210-212 Benzodiazepines as adjustment sleep disorder treatment, 339-340 use in chronic obstructive pulmonary disease patients, 225 obstructive sleep apnea-exacerbating effects of, 273 as panic attack treatment, 366 as restless legs syndrome treatment, 267, 268, 270 sleep architecture effects of, 3-5, 52-53 Beta-agonists, as nocturnal asthma treatment, 231, 232 Bilevel pressure, 157-159 as continuous positive airway pressure alternative, 152 as obesity hypoventilation syndrome treatment, 203,204 use in post-polio syndrome patients, 252 Biocalibrations definition of, 23 EEG during, 23 378 Biocalibrations (Cont.) for eye movement detection, 73 procedures for, 60-61 Bipolar disorder, 361 Birth control medications, interaction with modafinil, 289 "Blue bloater" variant, of chronic obstructive pulmonary disease, 227-229 Body temperature, nadir in, during sleep, 342, 347 Bradytachycardia, 195 Bright light, contraindication in advanced sleepphase syndrome, 349 Bright light therapy, for delayed sleep-phase syndrome, 346-347 Bronchodilator therapy for chronic obstructive pulmonary disease, 220, 225 for nocturnal asthma, 231, 232 Bruxism, 301, 312-314 Caffeine as insomnia cause, 3335, 336, 337 as restless leg syndrome cause, 260 Carbamazepine as cataplexy treatment, 286, 287 as REM sleep behavior disorder treatment, 310, 311 as restless legs syndrome treatment, 268 Carbidopa. See Levodopa/carbidopa Carbon dioxide. See also Partial pressure of carbon dioxide (PC02) exhaled as airflow measure, 85 apnea-related fluctuations in, 88-90 Carbon dioxide retention congenital central hypoventilation syndromerelated, 248-250 unexplained, obesity hypoventilation syndrome-related, 20 I Cardiovascular disease apnea-hypopneaindexin, 83 untreated obstructive sleep apnea-related, 134-135 Cataplexy, 100 drug therapy for, 285-287 narcolepsy-associated,276-278 Chest movements, paradoxical, 92 during hypopnea, 84, 98 during obstructive sleep apnea, 91, 92, 93 during respiratory effort measurement, 85-86 Cheyne-Stokes breathing adaptiveservo ventilation treatment for, 244

Cheyne-Stokes breathing (Cont.) central apnea associated with, 234 congestive heart failure-associated, 241-242, 243-245,247 obstructive sleep apnea-associated, 241-242, 2462-47 "Chicago criteria," for definition of hypopnea, 82-83 Children airflow measurement in, 85 congenital central hypoventilation syndrome in, 248-250 hypoventilation in, 85 night terrors in, 304 obstructive sleep apnea in as behavior problem cause, 207-209, 210-212 tonsillar enlargement-related, 208, 210-212 somnambulism in, 307, 308 Chronic obstructive pulmonary disease, 216- 218 arterial oxygen desaturation associated with, 219-221,222-223,227-229 "blue boater" variant of, 227-229 obstructive sleep apnea (overlap syndrome) associated with, 227-229 pedal edema associated with, 219-220, 222-223,227-229 "pink puffer" variant of, 224-225 Chronotherapy, 346, 347 Circadian rhythm sleep disorders, 342-351 Claustrophobia, in CPAP patients, 140, 145- 147 Clomipramine, as cataplexy treatment, 286 Clonazepam as insomnia treatment, 340 as panic attack treatment, 366 as REM sleep behavior disorder treatment, 310, 311 as restless legs syndrome treatment, 268 side effects of, 267, 268 as somnambulism treatment, 307 Clonidine, as post-traumatic stress disorder treatment,363 Cognitive-behavioral therapy, for insomnia, 336, 337 Congenital central hypoventilation syndrome, 248-250 Congestive heart failure central apnea associated with, 234 Cheyne-Stokes breathing associated with, 241-242,243-245 Continuous positive airway pressure (CPAP), 124-126, 139-201 alternatives to genioglossus advancement, 172-173, 174 hyoid myotomy, 172, 173 maxillary mandibular osteotomy, 173, 174 oral appliances, 175-177, 179 tracheostomy, 171-173 uvulopalatopharyngoplasty, 172-174 in asymptomatic patients, 136-138 auto-adjusted, 151-153 auto-titration, 160-162 chin strap use with, 149 in claustrophobic patients, 140, 145-147 for congestive heart failure-associated CheyneStokes breathing, 244-245, 246-247 decongestant use with, 155 discontinuation following weight loss, 121-123 esophageal pressure in, 128 full face mask (oronasal), 154-156 humidification use with, 149, 150, 155 as idiopathic central sleep apnea treatment, 239-240 initial use of, arterial oxygen desaturation during,163-165 inspiratory positive airway pressure, 157-159 mask interface problems in, 145-147 Medicare reimbursement for, 124, 137, 138 modafinil use with, 143 mouth leaks associated with, 140, 146, 149, 150, 158 nasal and mouth flow and leak recordings in, 125-126,131-133 nasal symptoms associated with, 140, 148-150, 154-156 a night terrors risk factor, 304 nocturnal seizures during, 323-325 as obesity hypoventilation syndrome treatment, 201,202-204 for obstructive sleep apnea diagnosis, 103 oral leaks associated with, 155 overtitration during, 130-133 with oxygen therapy, as overlap syndrome treatment, 228, 229 patients' acceptance/adherence to, 139 inadequate, 142-144 patients' intolerance of, 124, 154-156, 157-159,160-162,175-176 periodic leg movements in sleep associated with, 272-273 persistent daytime sleepiness on, 142-144 post-uvulopalatopharygoplasty use of, 179 379

Continuous positive airway pressure (CPAP) (Cont.) in pregnant patients, 198, 199 pressure intolerance associated with, 151-153 ramp mode of, 152 REM rebound in, 163-165 run time meter documentation of, 13 side effects of, 140 snoring during, 189 as somnambulism treatment, 307, 308 split-night studies with, 128, 129 suboptimal titration in, 160-162 in supine body position, 127-129 time at pressure documentation of, 143 Cor pulmonale chronic obstructive pulmonary disease-related, 227-229 neuromuscular disorders-related, 252 obesity hypoventilation syndrome-related, 20 I obstructive sleep apnea-related, 206 Corticosteroids, inhaled, as nocturnal asthma treatment, 231 Crescendo pattern, of respiratory effort, III Deep sleep, somnambulism during, 28-29 Deflections, K complexes as, 25-26 Delayed sleep-phase syndrome, 329, 343, 345-346 Delta sleep. See Slow wave sleep Depression as early-morning awakening cause, 349 as excessive daytime sleepiness cause, 40-41, 100 hypersomnia associated with, 298, 360-361 insomnia associated with, 329, 330, 339 REM latency in, 354-356 as weight loss cause, 360-361 Dextroamphetamine, as narcolepsy treatment, 283,284 Dopamine agonists, as restless legs syndrome treatment, 265-268 Doxepin, as insomnia treatment, 339, 340 Dreams. See also Nightmares recurrent, post-traumatic stress disorder-related, 362-364 violent, 309-311 Driving risk, posed by obstructive sleep apnea patients, 180-183 Drugs. See also specific drugs sleep architecture effects of, 53, 55-56 Dyspnea nocturnal, chronic obstructive pulmonary disease-related, 225 380 Dyspnea (Cont.) panic attacks-related, 366 Dystonia, nocturnal paroxysmal. 30 I Edema, pedal chronic obstructive pulmonary disease-related, 219-220,222-223,227-229 congestive heart failure-related, 241 EKG artifacts, 62-63, 65 Elderly patients advanced sleep-phase syndrome in, 349 periodic leg movements in sleep in, 262-264 Electrocardiography (EKG) artifacts, 62-63, 65 Electrode impedance, 65, 66 Electrode popping, 72-73 Electrodes, referential, 67-69 Electroencephalography (EEG) alpha activity of background, 39 in insomnia, 6-7 during sleep stage I, 24-25 electrode impedance in, 65, 66 electrode placement in, 315-316 electrode popping artifacts in, 72-73 filter settings in, 74-76 high-amplitude activity of, electro-oculographic detection of, 16-17 lead placement in, 8-11 in nocturnal seizures, 315-318 during continuous positive airway pressure titration, 323-325 spike and wave activity during, 323-325 temporal lobe epilepsy-related, 326-328 patterns of, 1-7 referential leads in, 67-69 saw-tooth patterns of, 31, 32 in REM sleep, 2, 43, 44 for seizure activity evaluation, 321, 322 in stage 2 sleep, 26-27 sweat artifacts in, 70-71 during wakefulness, 6-7 Electromyography (EMG) chin (submental), 18-41 for arousal evaluation, 35-37, 38-39 for bruxism evaluation, 312, 313, 314 for daytime sleepiness evaluation, 25 electrode popping artifacts in, 72-73 for excessive daytime sleepiness evaluation, 30-32,33-34,35-37,40-41,64-66 for insomnia evaluation, 20-21, 22-23, 26-27 muscle artifacts in, 20-21 polysomnographic applications of, 62-63, 64-66,67-69,70-71

Electromyography (EMG) (Cont.) during REM sleep. 18-19, 30-32. 34. 43 for REM sleep behavior disorder evaluation. 310,311 sixty-cycle artifacts in, 64-66 for snoring evaluation, 33-34, 70-71, 186 for somnambulism evaluation, 28-29 hand. for REM behavior disorder evaluation. 300 lead placement in, 12 leg, for periodic leg movements in sleep diagnosis. 256-258 referential leads in, 67-69 sixty-cycle artifacts in, 64-66 sweat artifacts in, 70-71 Electro-oculography (EOG), 12-13 electrode popping artifacts in, 72-73 high-amplitude electroencephalographic activity during, 16-17 lead placement in, 12 referential leads in, 67-69 sweat artifacts in, 70-71 "Elvis legs," 253 End-tidal PCOz monitoring, in pediatric obstructive sleep apnea, 211, 212 Enuresis, 301 Environmental sleep disorder, 333 Epilepsy juvenile myoclonic, 320 temporal lobe, 32\, 326-328 Epochs 70-75, scored as stage REM sleep, 42-43, 45- 49 definition of, 1 of sleep stage 4, in insomnia, 10-11 Epworth Sleepiness Scale, 99-100, 102, 105 Esophageal pressure, apnea-related increase in, 82 Esophageal pressure monitoring of hypopnea, 83 of respiratory effort, 92, 93 of respiratory effort-related arousals, 108 of snoring, 186 of upper respiratory pressure syndrome, 112 Excessive daytime sleepiness, 99-107 arousal index in, 36, 37 Cheyne-Stokes breathing-associated, 241-242 chin EMG evaluation of, 30-32, 33-34, 35-37, 40-41 congestive heart failure-related, 243-245 with CPAP therapy, 142-144 as depression cause, 40-41 EKG artifacts associated with, 62-63 history of, 99-100 Excessive daytome sleepiness (Cont.) idiopathic central sleep apnea associated with, 236-238 idiopathic hypersomnia-related, 297-299 insufficient sleep syndrome-related, 296 maintenance of wakefulness testing for, 78, 180-181 most common causes of, 99 multiple sleep latency testing for, 78, 80-81, 100 narcolepsy-related, 274, 276-278, 279-281, 283-284,293-294 obstructive hypopnea-related, 96-98 periodic leg movements in sleep-related, 273 polysomnographic evaluation of, 100 EEG filter settings in, 74-76 electrode popping artifacts in, 72-73 post-uvulopalapharyngolpasty, 178-179 Prader- Willi syndrome-related, 213-215 REM eye movements in, 16-17 Expiratory reserve volume (ERY), in obstructive sleep apnea, 106, 107 Eye movements. See also Electro-oculography biocalibrations for detection of, 73 patterns during sleep, 14-15 during REM sleep, 31, 32,43-44 effect of selective serotonin reuptake inhibitors on, 40-41 Fatigue alpha-delta sleep-related, 353 depression-related, 354-356 upper airway resistance syndrome-related, 110-112 "Fencing posture," 321 Fibromyalgia, as alpha-delta sleep cause, 330, 352-353 First-night effect, 23, 339, 341 reverse, 333 Flashbacks, 363 F1uoxetine as cataplexy treatment, 286, 287 as fibromyalgia treatment, 353 as hypersomnia treatment, 361 as post-traumatic stress disorder treatment, 363 sleep architecture effects of, 55-56 Flurazepam, as insomnia treatment, 340 Formoterol, as nocturnal asthma treatment, 231 Functional residual capacity, chronic obstructive pulmonary disease-related decrease in, 216-218 Gabapentin, as restless legs syndrome treatment, 268 381

Gamma hydroxybutyrate, as cataplexy treatment, 286 Gasping excessive daytime sleepiness-related, 100 obstructive sleep apnea-related, 103 Genioglossus advancement, 172-173, 174 Glossectomy, laser midline, 173 Grief, as insomnia cause, 338-340 Hallucinations, hypnagogic, 100, 277, 286 Head trauma, as hypersomnia cause, 298, 299 Heart rate variability, in obstructive sleep apnea patients, 195, 196 HLA haplotyping, for narcolepsy evaluation, 294 Homicide, somnambulism-related, 307 Hydrocephalus, progressive, 298 Hypercapnia during initial continuous positive airway pressure therapy, 164 obesity hypoventilation syndrome-related, 200-201 Hyperphagia depression-related, 360-361 Prader-Willi syndrome-related, 214 Hypersomnia depression-related, 355, 360-361 idiopathic, as excessive daytime sleepiness, 297-299 Hypertension, as obstructive sleep apnea risk factor, 103, 104, 191-193 Hypnic jerks (sleep starts), 300 Hypnogram, for somnambulism evaluation, 29 Hypnotics as adjustment sleep disorder treatment, 339-340,341 use in chronic obstructive pulmonary disease patients, 224, 225 as excessive daytime sleepiness cause, 298 as jet lag treatment, 351 Hypocretin, 274-275 Hypopnea central, 83, 233 airflow measurement in, 89 nasal pressure in, 84 in children, as behavior problem cause, 207-209 definition of, 82-82, 97 differentiated from apnea, 84-85 mixed, 83, 84 obstructive, 83-84, 96-98 nasal pressure during, 85 Hypothyroidism, as obstructive sleep apnea risk factor, 188-189 382 Hypotonia, REM sleep-associated skeletal muscle, 31-32 Hypoventilation bilevel pressure treatment for, 158 central sleep apnea-related, 233, 237 in children, 85 chronic obstructive pulmonary diseaserelated, 216-218 congenital central, 248-250 nonapneic, during initial continuous positive airway pressure therapy, 163-165 obstructive, in children, 208, 209 post-polio, 251-252 Prader-Willi syndrome-associated, 213-215 Hypoxemia, during initial continuous positive airway pressure therapy, 164 Hypoxic ventilatory response, in Prader- Willi syndrome, 214 Imipramine, as cataplexy treatment, 285, 286 Insomnia, 329-341 alcohol use-related, 335, 336 delayed sleep-phase syndrome-related, 345-347 depression-related, 355, 356, 357-358 EEG during, 22-23 muscle artifacts in, 20-21 patterns in, 6-7 sleep stage 4-related epochs, 10-11 evaluation of, 329-331 psychophysiologic, 331, 332-333 transient, 339 rebound, 339, 341 selective serotonin reuptake inhibitors-related, 357-358 sleep-onset, sleep latency in, 22-23 treatment of, 335-337 with relaxation therapy, 336, 337 with sleep hygiene therapy, 336, 337 Inspiratory effort, arousal-inducing effect of, 108 Inspiratory positive airway pressure, 157-159 Insufficient sleep syndrome, 295-296, 298 Ipratropium bromide as chronic obstructive pulmonary disease treatment, 224, 225 as nocturnal asthma treatment, 231 Irregular sleep wake patterns, 343-344 Jacksonian march, 321 Jet lag, 343,350-351 K complexes in sleep stage 1, 46 sleep staging between, 42, 46

K complexes (Cant.) in stage I sleep, 42 in stage 2 sleep, 42 Kleine-Levin syndrome, 361 Left ventricular hypertrophy, hypertensionrelated, 192 Leg jerks. See Periodic limb movements in sleep Levodopa/carbidopa, as restless legs syndrome treatment, 266 rebound effect in, 269-271 Light, effect on circadian cycle, 342 Lingualplasty, 173 Lip smacking, during seizures, 320 Locus ceruleus, in narcolepsy, 274 Lung disease. See also Chronic obstructive pulmonary disease arterial oxygen desaturation in, 31, 32 bilevel pressure treatment for, 158 Macroglossia, hypothyroidism-related, 189 Magnetic resonance imaging, for seizure evaluation, 324 Maintenance of wakefulness test (MWT) definition of, 78 use with drivers, 180-181 Major affective disorder, 354-355 Medicare, continuous positive airway pressure coverage by, 124, 137, 138 Medroxyprogesterone, as obesity hypoventilation syndrome treatment, 20 I Melatonin as circadian sleep disorder treatment, 343 as delayed sleep-phase syndrome treatment, 346 as jet lag treatment, 351 Methamphetamine, as narcolepsy treatment, 283, 284 Methylphenidate, as narcolepsy treatment, 283, 284,288-289 Microawakenings, 36 Mirtazapine as insomnia treatment, 339, 341 as selective serotonin reuptake inhibitor-related insomnia treatment, 358 Modafinil as narcolepsy treatment, 283, 284, 288-289 use with continuous positive airway pressure, 143 Mood disorders, 355 Movement time, 50 Multiple sleep latency test (MSLT), 77-81 Multiple sleep latency test (MSLT) (Cant.) comparison with maintenance of wakefulness test, 180-181 definition of, 77 for excessive daytime sleepiness, 78, 80-81 for insufficient sleep syndrome evaluation, 296 mean sleep latency in, 77, 78, 79, 296 for narcolepsy evaluation, 78,80-81,277-278, 279-281,290-291,294 Myoclonus, nocturnal. See Periodic limb movements in sleep Myotomy, hyoid, 172, 173 Nap monitoring, in multiple sleep latency testing, 77,79,80-81 Naps, advanced sleep-phase syndromeexacerbating effect of, 349 Narcolepsy, 274-284, 288-289, 293-294. See also Cataplexy age at onset of, 100 differentiated from idiopathic hypersomnia, 298 drug therapy for, 282-284, 288-289 during pregancy, 198 excessive daytime sleepiness associated with, 274,276-278,279-281,283-284, 293-294 multiple sleep latency test for, 78, 80-81, 277-278,279-281,290-291,294 obstructive sleep apnea associated with, 290-291,293-294 periodic limb movements associated with, 254 REM latency in, 56 secondary, 274 Narcotics, as restless legs syndrome treatment, 267 Nasal cannulas for airflow evaluation, 85, 89, 90 for continuous positive airway pressure administration, 146 Nasal congestion, continuous positive airway pressure-related, 148-150, 154-156 Nasal pressure monitoring, for airflow measurement, 84-85, 89, 90 in obstructive hypopnea, 97, 98 in respiratory effort-related respiratory arousal, 110,111,112 Nasopharyngeal inlet stenosis, postuvulopalatopharyngoplasty, 169-170 Neck circumference, as obstructive sleep apnea risk factor, 103, 104 Nefazodone as insomnia treatment, 339, 341 as post-traumatic stress disorder treatment, 363 383

Nefazodone (Cont.) as selective serotonin reuptake inhibitor-related insomnia treatment, 358 Nightmares definition of, 300 differentiated from night terrors, 303-304 differentiated from panic attacks, 366 Night terrors, 300-30 1,303-304 differential diagnoses of, 304 differentiated from nightmares, 303-304 differentiated from panic attacks, 366 differentiated from REM sleep behavior disorder, 310 REM sleep behavior disorder-associated, 311 somnambulism associated with, 307 Nocturnal spells, 320 Non-24-hour sleep-wake disorder, 344 NREM (nonrapid eye movement) sleep nocturnal seizures during, 324 seizures during, 320, 322 somnambulism during, 28-29, 304, 307 stages of, 1-6 Obese patients, polysomnographic studies in, 70-71 Obesity obstructive sleep apnea associated with, 103, 121-123 in Prader- Willi syndrome patients, 213, 214, 215 respiratory monitoring in, 91-93 Obesity hypoventilation syndrome, 200-201, 202-204 bilevel pressure treatment for, 158 oxygen therapy for, 205-206 Obstructive sleep apnea age at onset of, 100 arterial oxygen desaturation in, 106, 107, 116-118, 205-206 asthma-associated, 231, 232 asymptomatic, 136-138 "blue bloater" variant of, 227-229 Cheyne-Stokes breathing associated with, 246-247 in children as behavior problem cause, 207-209, 210-212 tonsillar enlargement-related, 208, 210-212 chronic obstructi ve pulmonary disease-related (overlap syndrome), 227-229 continuous positive airway pressure treatment for. See Continuous positive airway pressure (CPAP) 384 Obstructive sleep apnea (Cont.) in drivers, 180-183 heart rate variability in, 195, 196 hypertension associated with, 191-193 hypothyroidism associated with, 188-189 insomnia associated with, 330, 333 mild-to-moderate, treatment of, 120 mixed apnea associated with, 94-95 multiple sleep latency testing for, 78 narcolepsy associated with, 290-291 obesity hypoventilation syndrome-related, 201 oxygen therapy for, adverse effects of, 205- 206 paradoxical respiration in, 82 partial-night studies of, 147 periodic leg movements in sleep-related, 261, 262-264 positional, 122, 123 premature ventricular contractions associated with, 194-196 REM latency in, 290-291 REM sleep-specific, 116-118 respiratory effort detection during, 91-93 severity of assessment of, 105-107, 119, 145-147 post-uvulopalatopharyngoplasty, 169-170 snoring associated with, 188-189 split-night studies of, 146, 147 treatment of, 119-123 genioglossus advancement, 172-173, 174 with hyoid myotomy, 172, 173 with maxillary mandibular osteotomy, 173, 174 with tracheostomy, 172-174 with uvulopalatopharyngoplsaty, 166-168 untreated, as cardiovascular events risk factor, 134-135 Opiates, as restless legs syndrome treatment, 270 Oral appliances, as obstructive sleep apnea treatment, 175-177, 189 Overlap syndromes bilevel pressure treatment for, 158 hypercapnic respiratory failure associated with, 202-204 oxygen therapy for arterial oxygen desaturation in, 206 with continuous positive airway pressure, 228, 229 parasomnia, 301 Overtitration, in continuous positive airway pressure, 130-133 Oximetry, nocturnal, 86, 107,220

Oxygen therapy for chronic obstructive pulmonary disease, 220, 223,225 for idiopathic central sleep apnea, 240 for obesity hypoventilation syndrome, 205-206 for overlap syndromes, 206, 228, 229 Painful legs and moving toes syndrome, 260 Palatoplasty, laser-assisted, as snoring treatment, 167,168 Panic attacks, 365-366 Pa02 (partial pressure of oxygen), awake supine, in obstructive sleep apnea, 106 Paradoxical intention, for insomnia, 336 Paralysis, leaden, 361 Parasomnia overlap disorder, 30 I Parasomnias, 300-30 definition of, 300 Parkinson's disease, REM sleep disorder associated with, 310, 311 Partial pressure of carbon dioxide (PCOl ) as airflow measure, 85, 89 in Cheyne-Stokes breathing patients, 244 exhaled, as airflow measure, 85 in idiopathic central sleep apnea, 237 in mixed apnea, 95 Partial pressure of oxygen (Pa02) , awake supine, in obstructive sleep apnea, 106 Pavor nocturnus. See Night terrors Pe02. See Partial pressure of carbon dioxide (PC02) Pemoline, as narcolepsy treatment, 283, 284 use during pregnancy, 198 Pergolide, as restless leg syndrome treatment, 266 Periodic limb movement disorder, 255 Periodic limb movements, definition of, 253-254 Periodic limb movements in sleep, 100 asymptomatic, 264 causes and associations of, 254, 255 definition of, 254 insomnia associated with, 330, 333 obstructive sleep apnea-related, 262-264 pharmacologic treatment for, 265-268 restless leg syndrome associated with, 259 -261 unmasked by continuous positive airway pressure, 272-273 Piezo-electric sensors, for respiratory effort measurement, 85, 92, 98 "Pink puffer" variant, of chronic obstructive pulmonary disease, 224-225 Plethysmography, respiratory impedance, 89 inductance, 85-86 PLM arousal index, 257, 258, 273 PLM index,254,255,257,258 Pneumotachography, 84, 186, 187 Polysomnography, 58-76 for bruxism evaluation, 313, 314 calibration procedures for, 60-61 for central sleep apnea evaluation, 236, 237 definition of, 58 double referencing in, 63 EKG artifacts in, 62-63, 65 for excessive daytime sleepiness evaluation, 62-63 for insomnia evaluation, 330-331, 333 in multiple sleep latency testing, 77-78 for narcolepsy evaluation, 277, 280 for obstructive sleep apnea evaluation, 103, 104 sixty-cycle artifacts in, 64-66 visual and auditory monitoring in, 59 Popping artifacts, 72-73 Position therapy, for obstructive sleep apnea, 122, 123 Positive airway pressure. See Continuous positive airway pressure Positive airway pressure titration, 124-126. See also Bilevel pressure; Continuous positive airway pressure (CPAP) Post-polio syndrome, 251-252 Posttraumatic hypersomnia syndrome, 298, 299 Post-traumatic stress disorder, 301, 362-364 differentiated from night terrors, 304 differentiated from panic attacks, 366 differentiated from REM sleep behavior disorder, 310 Prader-Willi syndrome, 213-215 Prarnipexole, as restless legs syndrome treatment, 266-267,270 Pregnancy, snoring during, 197-199 Premature ventricular contractions, 194-196 Propranolol, as post-traumatic stress disorder treatment, 363 Protriptyline, as cataplexy treatment, 286 Prozac. See Fluoxetine Psychiatric disorders, somnambulism associated with, 306-308 Rapid eye movements. See REM eye movements Rebound effect, in restless legs syndrome treatment, 269-271 Rebound irritability, 339 Referential electrodes, 67-69 Relaxation therapy, for insomnia, 336, 337 REM efficiency, latency of, 50 REM eye movements, 14-15,31,32 385

REM eye movements (Cont.) in excessive daytime sleepiness, 16-17 REM latency benzodiazepines-related increase of, 52 definition of, 81 in depression, 41, 55-56, 354-356 in multiple sleep latency testing, 77 during naps, 80-81 in narcolepsy, 56, 277, 278 in obstructive sleep apnea, 278, 290-291 REM rebound, during continuous positive airway pressure therapy, 163-165 REM rules, 42 REM (rapid eye movement) sleep arterial oxygen desaturation in, 31, 32, 116-118 benzodiazepines-related decrease of, 52 chin EMG during, 30-32, 34 in chronic obstructive pulmonary disease, 225 depression-related decrease of, 41, 55-56 EEG patterns in, 2, 43 eye movements during, 14-15, 16-17,31,32 in post-traumatic stress disorder patients, 363, 364 scoring of, 42-44, 45-49 sleep-onset, 56 REM sleep behavior disorder, 30 I differentiated from night terrors, 304 differentiated from panic attacks, 366 somnambulism associated with, 307 violent dreams associated with, 309-311 Renal failure, restless leg syndrome associated with,254 Respiration monitoring, during sleep, 82-98 airflow or tidal volume measurement techniques in, 84-85 arterial oxygen saturation measurement in, 86 for central apnea evaluation, 91-93 for excessive daytime sleepiness evaluation, 96-98 respiratory effort measurement in, 85-86 for sleep apnea evaluation, 88-90 for snoring evaluation, 94-95 Respiratory arousal index, 108, 109 Respiratory artifacts, 71 Respiratory disturbance index. See Apneahypopneaindex Respiratory effort arousal associated with, 108-112 measurement of, 85-86 paradoxical, in obstructive sleep apnea, 82 Respiratory failure obesity hypoventilation syndrome-related, 202-204 post-polio, 251-252 386 Respiratory muscles, post-polio syndrome-related weakness in, 251,252 Restless leg syndrome, 253-254, 259-261 classification of, 255 definition of, 253 pharmacologic treatment for, 265-268 during pregnancy, 198 rebound effect in, 269-271 Reverse first-night effect, 333 RIPsum signal, 89, 92 Ropinirole, as restless leg syndrome treatment, 266,267,270 Salmeterol as chronic obstructive pulmonary disease treatment, 224, 225 as nocturnal asthma treatment, 231 Seasonal affective disorder, 355, 361 Sedatives, as excessive daytime sleepiness cause, 298 Seizures classification of, 320-321 nocturnal, 319-322 during continuous positive airway pressure titration, 323-325 differentiated from night terrors, 304 differentiated from REM sleep behavior disorder, 310, 311 electroencephalic monitoring of, 315-318 NREM sleep-related, 300 spike and wave activity during, 323-325 Selective serotonin reuptake inhibitors as cataplexy treatment, 285-287 effect on eye movements, 40-41 as hypersomnia treatment, 361 as insomnia cause, 357-358 as panic attack treatment, 366 as post-traumatic stress disorder treatment, 363 as REM sleep behavior cause, 310, 311 Selegiline, as narcolepsy treatment, 283, 284, 289 Sertraline, as post-traumatic stress disorder treatment, 363 Sixty-cycle artifacts, 64-66 Sleep alpha-delta, insomnia associated with, 330, 352-353 amount required for normal function, 296 nonrestorative, alpha-delta sleep as, 353 Sleep architecture, 50-57 definitions of, 50-51 effect of alcohol on, 53 effect of benzodiazepines on, 3-5, 52-53 Sleep attacks, 277

Sleep deprivation, as somnambulism treatment, 306-308 Sleep diary for advanced sleep-phase syndrome evaluation, 348 for delayed sleep phase syndrome evaluation, 345,346 for excessive daytime sleepiness evaluation, 296 for insomnia evaluation, 330, 333, 335 Sleep efficiency, 50 Sleep hygiene, as insomnia treatment, 336, 337 Sleep latency definition of, 81 multiple sleep latency testing of. See Multiple sleep latency testing during naps, 80-81 in narcolepsy, 277, 280, 281 Sleep log. See Sleep diary Sleep misperception, 330-3\ Sleep paralysis, narcolepsy-related, 100, 277 Sleep period time, 50 Sleep restriction therapy, for insomnia, 336, 337 Sleep spindles benzodiazepines-related increase in, 3-5 definition of, I incipient, 44 Sleep stages, 1-7 scoring of, 42-49 stage I definition of, I EEG alpha activity during, 24-25 K complexes of, 12 stage 2 definition of, I K complexes, 26-27, 42, 46 stage 3 benzodiazepine-related decrease of, 52, 53 definition of, I stage 4 benzodiazepine-related decrease of, 52, 53 definition of, I stage REM. See REM sleep Sleep state misperception, 333 Sleep talking, 30I Sleep terrors. See Night terrors Sleepwalking. See Somnambulism Slow frequency artifacts, 70-71 Slow wave sleep in chronic obstructive pulmonary disease, 225 somnambulism during, 28-29 Snoring alcohol use-related, 113-115, 185, 186 in children, 210-212 Snoring (Cant.) chin EMG evaluation of, 33-34 excessi ve daytime sleepiness-related, 33-34 idiopathic central sleep apnea-related, 236, 237, 238 insomnia associated with, 330 mixed apnea-related, 94-95 obesity hypoventilation syndrome-related, 200-201 obstructive sleep apnea-related, 94-95, 102, 104, 127, 188-189 as obstructive sleep apnea risk factor, 103, 104 periodic leg movements in sleep-related, 256, 262-264 polysomnographic evaluation of, 67-69, 70-71 pregnancy-related, 197-199 simple, 185-187 sleep stage scoring in, 45-46 uvulopalatopharyngoplasty treatment for, 166-168, 169-170 Sodium oxybate, as cataplexy treatment, 287 Somnambulism, 300-301 in children, 307, 308 differentiated from REM sleep behavior disorder, 310 night terrors associated with, 304 psychiatric disorders associated with, 306-308 during REM sleep, 28-29 REM sleep behavior disorder-associated, 311 seizure-related, 321 Somniloquy, 30 I "Spousal arousal syndrome," 135 Stanford Sleepiness Scale, 99 Stimulants, as narcolepsy treatment, 283-284 Stimulus control therapy, for insomnia, 336, 337 Stress, as insomnia cause, 339 Sweat artifacts, 70-71 Temazepam as insomnia treatment, 340 as somnambulism treatment, 307 Theophylline as chronic obstructive pulmonary disease treatment, 224, 225 as nocturnal asthma treatment, 231 Thermistors, 84 in obstructive apnea evaluation, 89, 90 in snoring evaluation, 186 Thermocouples in obstructive apnea evaluation, 89, 90 in snoring evaluation, 186, 187 Three-minute rule, 42, 43, 46 Thyroid replacement therapy, 189 387

Tidal volume, measurement of, 85 with respiratory inductance plethysmography, 89 Time in bed (TIB) definition of, 50 in insufficient sleep syndrome patients, 296 Time zone change syndrome. See Jet lag Tonsillar enlargement, as pediatric obstructive sleep apnea cause, 208, 210-212 Tonsillectomy, with adenoidectomy, 210-212 Total sleep time (TST), 50 Tracheostomy as obesity hypoventilation syndrome treatment, 201,206 as obstructive sleep apnea treatment, 171-174 Trazodone as insomnia treatment, 339, 341 as panic attack treatment, 366 as selective serotonin reuptake inhibitorrelated insomnia treatment, 358 Triazolam use in chronic obstructive pulmonary disease patients, 225 as idiopathic central sleep apnea treatment, 240 as jet lag treatment, 351 sleep spindle effects of, 3-5 Tricyclic antidepressants as insomnia treatment, 339, 341 as panic attack treatment, 366 as post-traumatic stress disorder treatment, 363 as REM sleep behavior cause, 310, 311 Upper airway, size of, in obstructive sleep apnea, 122 Upper airway obstruction obstructive hypopnea-related, 83 as obstructive sleep apnea cause, 95 Upper airway resistance, in hypopnea, 83 Upper airway resistance syndrome, excessive daytime sleepiness associated with, 110-112, 298 Urine drug screens, 4, 5 Uvulopalatopharyngoplasty excessive daytime sleepiness following, 178-179 as nasopharyngeal inlet stenosis cause, 169-170 as snoring treatment, 166-168, 169-170 Uvulopalatoplasty, as snoring treatment, 167 388 Ventilation adaptiveservo, as Cheyne-Stokes breathing treatment, 244 positive-pressure. See also Continuous positive airway pressure as obesity hypoventilation syndrome treatment,203 positive-pressure volume-cycled, use in postpolio patients, 252 Ventilation-perfusion mismatch, chronic obstructive pulmonary disease-related, 216-218 Ventilatory drive, during REM sleep, 117 Video recording of parasomnias, 59, 300 of seizure activity, 59, 321,324,325 Vietnam War veterans, post-traumatic stress disorder in, 362-364 Violent behavior seizure-related, 321 somnambulism-related, 307 Violent dreams, 309-311 Visual monitoring, during polysomnography, 59 Vocalization, seizure-related, 321 Wake after sleep onset (WASO), 50 Wakefulness, EEG during eyes-closed, 6-7 eyes-open, 20-21 Wakefulness stimulus, 237 Walks, early-morning, advanced sleep-phase syndrome-exacerbating effect of, 349 Wanderings, episodic nocturnal, 301 Weight control, as Prader-Willi syndrome treatment, 214, 215 Weight gain depression-related, 360-361 in obstructive sleep apnea patients, 103 Weight loss, as obstructive sleep apnea treatment, 121-123, 179, 263 Winter depression. See Seasonal affective disorder Xyrern, as cataplexy treatment, 286 Zaleplon, as insomnia treatment, 339, 340, 341 Zolpidem as adjustment disorder treatment, 339, 340 as insomnia treatment, 339, 340