The following cases and commentary, which address sleep disorders, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP14).
Case 1: excessive daytime sleepiness
A 55-year-old man is evaluated for excessive daytime sleepiness and hypertension. His wife reports that he snores loudly, causing her to have to sleep in a separate bedroom. He also had a minor car accident when he fell asleep while driving.
On physical examination, the patient is an obese man (BMI 32) with a thick neck; his blood pressure is 145/90 mm/Hg. Cardiopulmonary examination is otherwise normal.
What is the most appropriate next step in the management of this patient?
A. An attended laboratory polysomnography
B. Nighttime continuous pulse oximetry
C. Automated positive airway pressure (APAP) therapy
D. Modafinil therapy
Case 2: insomnia
A 45-year-old man is evaluated for insomnia. The patient has a history of cardiomyopathy, and his left ventricular ejection fraction is 20%. Nocturnal polysomnography shows Cheyne-Stokes respiratory pattern with crescendo-decrescendo clusters of breaths separated by central apneas lasting 10 to 20 seconds. Oxygen saturation oscillated between 85% and 95% during the breathing cycles.
What is the most likely mechanism for this patient's sleep apnea?
C. Arousal from sleep
D. Fluctuating blood pressure and cardiac output
Case 3: daytime fatigue
A 38-year-old man is evaluated for daytime fatigue and sleepiness. He has had progressive fatigue and somnolence for the past 5 years, and he now takes regular daytime naps during planning periods at the middle school where he teaches. He drinks 10 to 12 cups of coffee daily, eats chocolate-covered espresso beans, and drinks three diet colas in the afternoon to alleviate fatigue. Caffeine makes him more alert but also makes him “fidgety.” His wife reports that he rarely snores and that she has never witnessed apneas while he was asleep.
On physical examination, he appears fatigued and frequently repositions his feet and legs. He is 183 cm (72 in) tall and weighs 77 kg (170 lb). Vital signs are normal, and there are no remarkable physical examination findings.
The patient keeps a sleep diary over the next 2 weeks, which shows a nocturnal sleep interval ranging from 8.5 to 10 hours and frequent brief daytime naps. A formal nocturnal sleep study is performed, and the figure shows a typical segment of the study.
Which one of the following is the most appropriate next step in the management of this patient?
A. Start supplemental oxygen, 2 L/min
B. Advise him to eliminate daytime naps and increase his nocturnal sleep period to 10-12 hours
C. Instruct him to avoid all caffeine-containing foods and beverages
D. Start a trial of codeine, 30 mg three times daily
Case 4: difficulty sleeping with morning headaches
A 58-year-old man with progressive weakness has noted difficulty sleeping, headache on awakening in the morning, and a lack of refreshing sleep. He becomes dyspneic lying supine and has been sleeping in a reclining chair. According to his wife, he used to snore, but no longer does so. He has no swallowing difficulty, but slurs his speech slightly.
On physical examination, he has a respiration rate of 24 breaths per minute; his palate elevates normally, but there are some tongue fasciculations; and he manifests dyspnea and abdominal paradox when lying flat. Nighttime pulse oximetry with the patient breathing room air reveals episodes of oxygen desaturation in the range of 85% to 88%, some episodes lasting longer than five minutes. Forced vital capacity is 46% of predicted when upright, 34% of predicted when supine. Arterial oxygen saturation is normal during the day, and the patient can walk slowly without difficulty.
Which of the following is the most appropriate management at this time?
A. Continuous positive airway pressure (CPAP) by mask at night
B. Tracheostomy and nighttime mechanical ventilation by assist/control mode
C. Noninvasive positive airway pressure ventilation by mask at night
D. Low-flow oxygen supplementation by nasal cannula at night
E. An oral hypnotic
Case 5: difficulty falling asleep
A 47-year-old man is evaluated for difficulty falling asleep and resulting daytime fatigue occurring at least 3 to 4 times per week for the past several months. He denies snoring or sleepwalking, shortness of breath and chest pain. He is employed as an accountant and recently went through a divorce. The divorce has caused some personal and financial stress in his life. He smokes one-half pack per day of cigarettes.
On physical examination, pulse rate is 72/min, and blood pressure is 138/85 mm Hg. The BMI is 26. The remainder of the examination is normal.
Laboratory studies include a hematocrit of 42%, a leukocyte count of 4200/μL, a fasting plasma glucose of 100 mg/dL, and a thyroid-stimulating hormone level of 2.5 μU/mL. Results of a chest radiograph and electrocardiograph are normal.
Which of the following is the most appropriate next diagnostic step?
C. Cardiac stress testing
D. Beck Depression Inventory
Case 6: involuntary leg movements
A 36-year-old woman is evaluated for abnormal, involuntary movements of her legs and a burning sensation of her legs for the past year. The symptoms are most pronounced when she drives long distances and are relieved when she gets out of the car and starts walking.
Which of the following studies is the most appropriate next step in evaluating this patient?
A. Serum copper level
B. Serum thyroid-stimulating hormone level
C. Serum ferritin level
D. Liver function tests
E. Nerve conduction velocities
Case 7: fatigue and morning headaches
A 47-year-old man is evaluated in the emergency department because of fatigue and headaches, which are more frequent in the morning. On physical examination, his body mass index is 42. The heart and lungs are normal, and the neurologic examination is completely normal. Laboratory studies yield normal results except hemoglobin of 16.8 g/dL and serum bicarbonate of 26 meq/L. There is trace edema of the lower extremities. Chest radiograph shows a normal-size heart and clear lung fields.
Which of the following is most likely to show the cause of this patient's fatigue and headaches?
C. Beck Depression Inventory
D. Overnight polysomnography
Answers and commentary
Correct answer: A. An attended laboratory polysomnography.
Polysomnography is indicated for the evaluation of a patient with clinical features suggestive of obstructive sleep apnea. Neither physical examination findings nor continuous nocturnal pulse oximetry is sensitive or specific enough to make the diagnosis. Several methods have been described to determine the optimal continuous positive airway pressure (CPAP) level to manage obstructive sleep apnea, including attended laboratory polysomnography-guided CPAP titration, unattended home titration, or auto-titrating positive airway pressure (APAP) device-directed titration.
The current standard of practice consists of a technician attended laboratory polysomnography with CPAP pressure titration, during which sleep stages and respiratory variables are monitored. An unattended, portable sleep study may be considered only when full polysomnography is unavailable or when the patient's medical condition necessitates a home study. APAP therapy in the absence of a diagnostic study is not recommended.
Modafinil, a wake-promoting agent, is indicated only for patients with residual sleepiness associated with obstructive sleep apnea being treated with CPAP, and not as an alternative to CPAP therapy.
- The standard of practice to determine the optimal continuous positive airway pressure level to manage obstructive sleep apnea is an attended laboratory polysomnography with CPAP pressure titration.
Correct answer: B. Hypocapnia.
Patients with severe heart failure may have Cheyne-Stokes respiration, which is characterized by a crescendo-decrescendo pattern of ventilation with each swing of ventilation ending in apnea. This respiratory pattern may be associated with frequent episodes of central sleep apnea and disordered sleep; it can also worsen heart failure.
Sleep unmasks an apnea threshold for Pco2. Hyperpnea can follow an apnea, and if this lowers the Pco2 below the apnea threshold, apnea will recur. Both arousal from sleep and hypoxia at the end of the apneic episodes can accentuate the hyperpnea and make it more likely that Pco2 will be reduced below the apnea threshold. However, the elimination of hypoxia with supplemental oxygen does not necessarily prevent the apneas. Some studies have shown that hypnotic agents can eliminate Cheyne-Stokes respiratory pattern by attenuating the hyperpnea following the apnea. Fluctuation of blood pressure and cardiac output during Cheyne-Stokes breathing may contribute to the changes in Pco2, but they are not the primary causes of the apneas.
- Hypocapnia is the cause of central sleep apnea in patients with Cheyne-Stokes respiration.
Correct answer: C. Instruct him to avoid all caffeine-containing foods and beverages.
This patient has severe, progressive daytime somnolence but otherwise few signs or symptoms of obstructive sleep apnea. The sleep study shows evidence of periodic limb movement disorder, manifested by recurrent limb movements that typically triggered subsequent arousal. These limb movements are apparent in the anterior tibialis EMG channel (LEMG) and are manifested by 3- to 5-second bursts of activity occurring every 10 to 15 seconds. These bursts of activity usually trigger arousal, demonstrated by brief (< 5 seconds) increases in EEG frequency seen in channels C3A2 and C4A1. This sleep disruption likely accounts for the patient's daytime somnolence.
Periodic limb movement disorder may be associated with various medical conditions, but stimulants such as caffeine and theophylline may trigger or worsen the disorder. Therefore, although medical conditions such as anemia and iron or folate deficiency should be excluded, an important initial step is to avoid caffeine-containing food and beverages. Tricyclic antidepressants and selective serotonin re-uptake inhibitors can also trigger or worsen periodic limb movement disorder.
Nocturnal CPAP or supplemental oxygen is not indicated because there was no evidence from this sleep study of obstructive sleep apnea or nocturnal hypoxemia. However, periodic limb movements may occur in conjunction with obstructive apneas and with upper airway resistance syndrome.
Although the elimination of daytime naps and consolidation of sleep into a single nocturnal interval is generally beneficial, this patient is already achieving more than 8.5 to 10 hours of sleep daily, which should be adequate; therefore increasing his sleep interval would likely be of little benefit. Although codeine has been used with some success in periodic limb movement disorder, narcotics are used only after other medications, such as dopaminergic agents, benzodiazepines, and gabapentin, have failed. No medications should be used in this patient until all potential contributors to this disorder, in this case excessive caffeine consumption, have been eliminated.
- Periodic limb movement disorder may be associated with anemia, iron deficiency, folate deficiency, and other medical disorders, but stimulants (such as caffeine and theophylline), tricyclic antidepressants, and selective serotonin re-uptake inhibitors may trigger or worsen the disorder.
Correct answer: B. Tracheostomy and nighttime mechanical ventilation by assist/control mode.
Early morning headache and a lack of refreshing sleep are symptoms of nocturnal hypercapnia caused by hypoventilation in patients with neuromuscular disease; this patient most likely has amyotrophic lateral sclerosis. Nocturnal hypoxemia is also present in this patient during episodes of hypoventilation. The episodic nature of the hypoxemia raises the possibility of obstructive sleep apnea, which may complicate neuromuscular diseases. The resolution of snoring is a common observation in these patients, may be related to decreasing airflow as weakness progresses and does not mean obstructive sleep apnea is less likely. CPAP alone is therefore a consideration, but this patient's respiratory abnormalities are secondary to neuromuscular weakness and CPAP alone is unlikely to reverse the hypoventilation effectively. The history of orthopnea, abdominal paradox and drop in FVC >25% when the patient goes from the upright to supine position are diagnostic of diaphragm paralysis. Such individuals are excellent candidates for nocturnal noninvasive positive airway pressure to augment their ventilation during sleep. The increased ventilation provided by this modality will likely prevent nocturnal hypercapnia and hypoxemia, something that can be assessed using a follow-up nocturnal oximetry. As the patient's incipient bulbar involvement progresses, tolerance of NPPV may become more difficult, as swallowing and control of secretions become problematic. If hypoxemia persists, it can be corrected with supplementation of inspired oxygen via the noninvasive positive airway pressure apparatus, but this should not be the case if the problem is entirely related to the neuromuscular disease. Use of oxygen or an oral hypnotic alone without ventilatory assistance in such a patient can precipitate severe carbon dioxide retention, and is contraindicated. Tracheostomy and full mechanical ventilation are not required at this point in the patient's course. Although this aggressive therapy will be considered at some point as the disease progresses and the bulbar involvement becomes severe, most patients in the United States (95% in most series) decide against this option because it does nothing to slow the progression of the disease, may lead to a locked-in state, and poses enormous psychological and financial burdens for family members.
- A history of orthopnea, abdominal paradox, and a decrease in forced vital capacity >25% when the patient goes from the upright to supine position are diagnostic of diaphragm paralysis.
- Patients with hypoventilation secondary to diaphragm paralysis should be treated with nocturnal noninvasive positive airway pressure to augment their ventilation during sleep.
Correct answer: D. Beck Depression Inventory.
Depression can be a treatable cause of insomnia, and this patient has some risks for depression, including a recent divorce and other life stressors. Screening for depression is indicated prior to treatment of primary insomnia. The diagnosis of chronic insomnia can be established clinically. It is generally defined as a complaint of insufficient or inadequate sleep when one has the opportunity to sleep. The American Psychiatric Association Diagnostic and Statistical Manual 4th Edition (DSM-IV) defines primary insomnia as difficulty initiating or maintaining sleep or non-restorative sleep for at least one month. The sleep disturbance must cause clinically significant distress or impairment of functioning and not be caused by another diagnosable sleep or mental disorder.
Polysomnography is needed only in patients with insomnia who have symptoms of a sleep-related breathing disorder, narcolepsy, sleepwalking, or are employed as pilots or truck drivers. None of these criteria apply to this case. This patient has risk factors for pulmonary disorders (smoking and being overweight) and cardiac disease (smoking, being overweight, sex, and age); however, he does not have symptoms or findings indicative of chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, or coronary artery disease (CAD). Therefore, further evaluation of COPD with spirometry or stress testing for CAD is not indicated. Sleep hygiene recommendations, including avoidance of strenuous exercise or alcohol within a few hours of bedtime, developing a relaxing evening routine, and avoidance of afternoon caffeine, are an appropriate first step in intervention once a diagnosis of primary insomnia is established.
- Good sleep hygiene includes avoiding strenuous exercise or alcohol close to bedtime, developing a relaxing evening routine, and avoiding afternoon caffeine.
- Depression is a treatable underlying cause for insomnia.
Correct answer: C. Serum ferritin level.
Involuntary movements primarily involving the lower extremities associated with abnormal sensations in the legs and restlessness relieved by movement are consistent with restless legs syndrome. The disorder is treated with dopamine agonists, but it is essential before initiating treatment to check serum iron levels. Oral iron therapy can alleviate symptoms and is recommended if serum ferritin levels are lower than 45 to 50 ng/mL.
The diagnosis of restless legs syndrome is confirmed by polysomnography.
Nerve conduction velocities can be performed and at times can be consistent with peripheral neuropathy but are not essential to make the diagnosis. The clinical presentation of this patient is not consistent with Wilson's disease or thyroid disturbance; therefore, it is not necessary to measure serum copper or thyroid-stimulating hormone levels.
- The restless legs syndrome consists of involuntary movements and abnormal sensation in the legs and restlessness relieved by movement.
- The diagnosis of restless legs syndrome is confirmed by polysomnography.
Correct answer: D. Overnight polysomnography.
This patient likely has the obesity-hypoventilation syndrome, which is characterized by extreme obesity and an elevated Paco2 during wakefulness. The syndrome is often associated with symptoms of sleep-disordered breathing, including morning headaches, hypersomnolence, and sleep arousals. The patient's headaches are due to carbon dioxide retention. Patients with severe disease may also have dyspnea, hypoxemia, and pulmonary hypertension.
The mechanism for development of obesity-hypoventilation syndrome is unknown; however, it is believed to be related primarily to abnormalities in ventilatory drive and response to hypoxia and hypercarbia rather than the mechanical factors related to excessive body weight.
Overnight polysomnography is the appropriate test for this patient, because obstructive sleep apnea almost always accompanies this disorder. Although obesity-hypoventilation syndrome occurs in only a minority of morbidly obese patients, it is important to recognize the syndrome because the consequences of respiratory failure can be severe. Patients with the syndrome cannot adequately increase ventilation in response to mounting hypercapnia. Adequate respiration can be restored in affected patients with noninvasive ventilation.
The diagnosis of obesity-hypoventilation syndrome is made when the Paco2 is elevated (>45 mm Hg) in an obese patient (usually >150% ideal body weight), where other causes of hypoventilation such as hypothyroidism, chronic obstructive pulmonary disease, and neuromuscular disease have been excluded. A body mass index of 42 is diagnostic of morbid obesity. A compensatory metabolic alkalosis (as suggested by this patient's increase in serum bicarbonate level) is often seen in association with the chronic respiratory acidosis.
An echocardiogram might reveal changes suggestive of pulmonary hypertension but would not provide a diagnosis of the patient's problem. The Beck Depression Inventory, a measure of depression symptoms, might be abnormal in this patient but would not diagnose the underlying cause of the symptoms.
- The obesity-hypoventilation syndrome is often associated with symptoms of sleep-disordered breathing, including morning headaches, hypersomnolence and sleep arousals.
- Patients with the obesity-hypoventilation syndrome usually have obstructive sleep apnea, and overnight polysomnography is indicated in patients with the syndrome.
- Noninvasive ventilation can restore adequate respiration in patients with the obesity-hypoventilation syndrome.