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Sleepy Since AdolescenceCase Editor - Victor Kim Reviewed By Respiratory Neurobiology & Sleep Assembly Submitted byJames A. Rowley, MD Associate Professor of Medicine Wayne State University School of Medicine Detroit, MI HistoryA 28-year-old woman presents for evaluation of excessive daytime sleepiness since she was a teenager. Her Epworth Sleepiness Score is 22/24. She complains of falling asleep at traffic lights, and she has had five to six near-miss accidents. She admits to three naps per day, two in the afternoon and one in the evening. Sleep-related symptoms include choking sensation at night, morning headaches, and vivid dreams at sleep onset. Her sleep habits include going to bed around 12 AM with a latency to sleep within 5 minutes, and getting out of bed at 7 AM. She arrives at work by 9 AM and is generally home by 9 PM.
Past medical history is significant only for hyperlipidemia. She is not presently taking any medications. Social history is significant for having three children (ages 6 years, 2 years, and 6 months) and drinking one to two cups of coffee per day. She does not admit to drinking alcohol, and she does not smoke. There is no significant family history. Physical ExamHeight 62 inches; weight 211 pounds; BMI 39 kg/m2. Oral examination demonstrates Mallampati class 3 airway with 3+ tonsils. Remainder of examination is normal.
Lab
PSG Total sleep time: 474 minutes; Time in bed: 479 minutes; Sleep efficiency: 99%
Latency to sleep onset: 1 minute; Latency to REM sleep 58.5 minutes
%Stage 1: 8.3, %Stage 2: 72.3, %Slow wave 3.4, %REM 16.0
AHI 7.5/hr (NREM AHI 10.3/hr; REM AHI 6.9/hr; supine AHI 7.5/hr; non-supine AHI 7.0/hr)
%TST spent with SaO2<90%: 0%
PLMI 0.0/hr
A representative 2 minute fragment from REM sleep is shown.
MSLT 4 naps performed
Mean latency 1.1 minutes with 2 REM-onset naps
Figures
 The recently published American Association of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events (1) provides standardized definitions for the various respiratory events. The fragment illustrates a hypopnea, which has been defined as a ≥30% drop from baseline in the nasal pressure transducer flow signal lasting at least 10 seconds and associated with a ≥4% desaturation. In the fragment, the flow is decreased >30% and is associated with a 8% drop in oxyhemoglobin saturation. The manual provides an alternative definition of hypopnea: ≥50% drop from baseline in the nasal pressure transducer flow signal lasting at least 10 seconds and associated with a ≥3% desaturation or an arousal.
Apneas are defined as a drop in the thermal sensor excursion by ≥90% lasting at least 10 seconds. An apnea is obstructive if there is inspiratory effort, and central if the inspiratory effort is absent. An apnea is mixed generally when there is absent inspiratory effort in the initial portion of the event, followed by a resumption of inspiratory effort in the second portion of the event.
An RERA is defined as a sequence of 10 breaths lasting at least 10 seconds, characterized by increasing respiratory effort or flattening of the nasal pressure waveform leading to an arousal from sleep when the sequence of breaths does not meet the criteria for an apnea or hypopnea. As there is a clear saturation following the respiratory event, the event shown meets the definition of a hypopnea and would not be labeled an RERA.
While the event could be scored as a hypopnea, it is also possible that the desaturation is related to a rapid, shallow breathing pattern rather than upper airway obstruction (flow limitation), which would tend to elevate the patient's dead space ventilation and reduce alveolar ventilation accordingly, resulting in desaturation.
The sleep study is diagnostic of mild OSA, which is consistent with the history of snoring, excessive daytime sleepiness, morning headaches, and findings of obesity and enlarged tonsils. If the MSLT had not been performed, there is no question that the patient’s sleep-disordered breathing (SDB) would have been treated. While tonsillectomy could be performed, the morbid obesity lowers the chance that tonsillectomy alone would be curative. Therefore, many sleep physicians would proceed directly to CPAP therapy, reserving tonsillectomy if there is intolerance of CPAP.
The problem in this case is that the PSG was followed by a MSLT that meets the International Classification of Sleep Disorders (2nd edition) criteria for narcolepsy: mean latency <8 minutes with two rapid eye movements (REM)-onset naps (2). The history of sleepiness since adolescence and vivid dreams (consistent with hypnagogic hallucinations) are also consistent with the diagnosis of narcolepsy. However, the presence of REM-onset naps are not specific for narcolepsy. In one study of 1145 patients with OSA, 4.7% had ≥2 REM-onset naps. Four factors were predictive of REM-onset naps: male gender, short nocturnal REM latency, decreased MSLT latency, and nocturnal desaturation (3). In a community population undergoing MSLT, 6% of men and 1% of women met the Classification of Sleep Disorders (ICSD) criteria for narcolepsy; in men, ≥2 REM-onset naps were more likely with short REM latency on the sleep study, decreased MSLT, and shift work. No significant predictors were found for women. In both men and women, use of antidepressants were associated with REM-onset naps (4). Note that in both studies, the severity of OSA was not a predictor of ≥2 REM-onset naps.
While this patient is a woman, and therefore, less likely to have REM-onset naps not related to narcolepsy (based upon the above studies), most sleep physicians would initiate therapy with CPAP in order to eliminate the OSA as a confounding factor causing her sleepiness. If the patient remains subjectively sleepy, it would be reasonable to repeat the MSLT after 1-2 months of therapy (and after a sleep study wearing the CPAP) to confirm the diagnosis of narcolepsy. However, it should be noted that there are sleep physicians who would diagnose this patient directly with narcolepsy (given that the OSA is mild, no significant desaturations, woman gender, sleepiness since adolescence) and begin treatment immediately with modafinil.
Additional points
1. The patient should be counseled regarding weight loss, as weight loss is the only effective long-term cure for OSA. Given her morbid obesity, she should be referred (by either the sleep physician or her primary care physician) to a weight loss specialist or program.
2. The patient should be counseled regarding adequate sleep hygiene and getting sufficient hours of sleep.
3. If CPAP treatment is initiated, support should be provided to the patient regarding CPAP use. This support may include counseling prior to use on expectations, proper mask fit, and importance of regular use. After initiation, support could include phone calls from either the sleep center or durable medical equipment company and early (within 1 month if possible) follow-up visit with the sleep physican to assess for effectiveness and problems with trouble-shooting as needed.
4. The patient should be counseled not to drive while having her sleepiness evaluated (5). It has been recently shown that near-miss accidents are a good predictor of future accidents (6), making this patient at high-risk for a motor vehicle accident. This is of particular concern, as it is likely that her three young children are frequent passengers in her car. There is controversy in the field as to whether the patient needs to show objective improvement in her sleepiness (by either an MSLT or maintenance of wakefulness test [MWT]) prior to permitting her to drive again (7,8). In most states in the United States, patients with OSA and narcolepsy do not need to be reported to state motor vehicle departments, so most physicians would permit patients to drive if they show compliance with treatment and subjective improvement in their sleepiness. Follow-up should occur within 1 month of treatment, though some sleep physicians would argue for within 1 week, given the severity of the symptoms. For further reading, particularly as it relates to commercial driver license holders in the United States, please see references (9) and (10).
All of the symptoms listed are consistent with the diagnosis of narcolepsy, but only cataplexy is pathognomonic for narcolepsy. Cataplexy occurs when skeletal muscle atonia is triggered by strong emotion such as laughter, anger, surprise, or excitement. The atonia results in muscle weakness in the in limbs, face, and neck (11). Episodes are generally brief (< 2 minutes) and consciousness is generally preserved. Cataplexy is present in 64-80% of patients with narcolepsy; however, the onset of cataplexy may follow the onset of sleepiness by many years. Per the International Classification of Sleep Disorders (2 nd edition), narcolepsy can be diagnosed if there is clear cataplexy on history (2); further testing, including performing a multiple sleep latency test, while confirmatory, is not necessary.
Hypnagogic hallucinations are vivid sensory sensations (generally visual but can be auditory) that occur at sleep onset (if they occur at awakening, they are labeled "hypnopompic"). While present in up to 85% of narcoleptics, they can also occur in normal subjects and patients with OSA and idiopathic hypersomnia. Sleep paralysis is characterized by an inability to move while awake. While approximately two-thirds of narcoleptics complain of sleep paralysis, it can also present as a parasomnia in otherwise normal subjects and also occur in OSA and idiopathic hypersomnia. Finally, automatic behaviors are characterized by performance of routine behaviors such as driving and cooking without conscious knowledge. Automatic behaviors can be observed in narcolepsy, severe sleep deprivation (for example, after an all-night call), and OSA. Given the patient’s history and other testing, the differential diagnosis of continued daytime sleepiness would include narcolepsy (long history of excessive daytime sleepiness (EDS), two REM-onset naps on the MSLT), and behaviorally induced insufficient sleep syndrome (only gets approximately 7 hours of sleep per night). It would be reasonable to repeat the MSLT after a second PSG with the patient wearing the CPAP at the set pressure; if there continues to be a latency <8 minutes with ≥2 REM-onset naps, narcolepsy would be likely (2). In order to properly interpret the MSLT, a 2-week sleep log should be obtained to ensure that the patient is sleeping a sufficient number of hours each night.
However, before either of these studies are performed, it would be important to ascertain whether the patient is using her CPAP on a nightly basis, as noncompliance could be the reason for lack of improvement. Measuring compliance has been recommended by the American Academy of Sleep Medicine (12). Modern CPAP (and bilevel) units are enabled to measure whether the patient is using the machine by determining if a pressure is generated by the machine (which occurs only if the patient is wearing the mask). While each manufacturer’s compliance report may differ, most report the number of days used, the number of hours/minutes the machine generates a pressure when used, and the percentage of nights with use >4 hours. A commonly used definition of adequate compliance is PAP usage for ≥4 hours for >70% of nights. Studies using this definition have found compliance rates ranging from 40 to 80% (13). In addition to measuring compliance, the physician should ask about mask comfort/fit and leak.
A maintenance of wakefulness test (MWT) would not be indicated in this situation. The MWT is generally used to determine if a patient is able to stay awake during soporific conditions. Per AASM practice parameters, the MWT is indicated to assess an individual’s ability to remain awake when his/her inability to remain awake may constitute a public or personal safety issue, e.g., airline pilots and commercial truck drivers (14).Modafinil, an unique wake-promoting agent, has been shown in two studies to be an effective agent for treating patients who remain sleepy despite adequate treatment of OSA with CPAP (15,16). In particular, these studies showed improvements in both subjective (as measured by the Epworth Sleepiness Scale) and objective (as measured by the MSLT or MWT) measures of daytime sleepiness. Modafinil is indicated for the treatment of residual daytime sleepiness in well-treated OSA if the following criteria are met: Epworth sleepiness scale ≥10; adequate CPAP titration (apnea-hypopnea index [AHI] on prescribed pressure <5 - 10/hour), objectively confirmed good CPAP compliance (variably defined, but minimum would be ≥4 hours per night, ≥5 nights per week); adequate sleep hygiene and hours slept; no potential medication side effects (for instance, over-the-counter antihistamine); and no evidence of another sleep disorder. Modafinil is also indicated for narcolepsy and is usually the first pharmacologic agent used in that disorder (17). Modafinil interacts with oral contraceptive agents, resulting in oral contraceptives being less effective; women of child-bearing age should be counseled regarding this interaction. Methyphenidate, dextroamphetamine, and metamphetamine, all indirect sympathomimetics, have been studied as a treatment for residual sleepiness in well-treated OSA, though both are frequently used as treatment for narcolepsy. Sodium oxybate is primarily indicated for the treatment of cataplexy and EDS in patients with narcolepsy; it has not been studied for use in patients with OSA.
References- Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The AASM manual for the scoring of sleep and associated events. American Academy of Sleep Medicine 2007.
- American Academy of Sleep Medicine. The international classification of sleep disorders diagnostic and coding manual. 2nd ed. Westchester, IL 2005.
- Chervin RD, Aldrich MS. Sleep onset REM periods during multiple sleep latency tests in patients evaluated for sleep apnea. Am J Respir Crit Care Med 2000;161(2(1)):426-431.
- Mignot E, Lin L, Finn L, Lopes C, Pluff K, Sundstrom ML et al. Correlates of sleep-onset REM periods during the multiple sleep latency test in community adults. Brain 2006;129(6):1609-1623.
- Sleep apnea, sleepiness, and driving risk. Am J Respir Crit Care Med 1994;150:1463-1473.
- Powell NB, Schechtman KB, Riley RW, Guilleminault C, Chiang RP, Weaver EM. Sleepy driver near-misses may predict accident risks. Sleep 2007;30:331-342.
- Arand DL. The MSLT/MWT should be used for the assessment of workplace safety. J Clin Sleep Med 2006;2:124-127.
- Bonnet MH. The MSLT/MWT should not be used in the assessment of workplace safety. J Clin Sleep Med 2006;2:128-131.
- Hartenbaum N, Collop N, Rosen IM, Phillips B, George CF, Rowley JA et al. Sleep apnea and commercial motor vehicle operators: Statement from the joint task force of the American College of Chest Physicians, the American College of Occupational and Environmental Medicine, and the National Sleep Foundation. Chest 2006;130(3):902-905.
- Miller CM, Khanna A, Strohl KP. Assessment and policy for commercial driver license referrals. J Clin Sleep Med 2007;3(4):417-423.
- Young TJ, Silber MH. Hypersomnias of central origin. Chest 2006;130(3):913-920.
- Kushida CA, Littner MR, Hirshkowitz M, Morgenthaler TI, Alessi CA, Bailey D et al. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep 2006;29(3):375-380.
- Kakkar RK, Berry RB. Positive airway pressure treatment for obstructive sleep apnea. Chest 2007; 132(3):1057-1072.
- Littner MR, Kushida C, Wise M, Davila DG, Morgenthaler T, Lee-Chiong T et al. Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep 2005;28(1):113-121.
- Pack AI, Black JE, Schwartz JR, Matheson JK. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med 2001;164(9):1675-1681.
- Black JE, Hirshkowitz M. Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome. Sleep 2005;28(4):464-471.
- Littner M, Johnson SF, McCall WV, Anderson WM, Davila D, Hartse SK et al. Practice parameters for the treatment of narcolepsy: an update for 2000. Sleep 2001;24(4):451-466.
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