Clinical Vignette

A 37-year-old man was seen at the request of his wife, for loud snoring. She noticed occasional snoring when they were first married 10 years earlier. Since then, however, he gained 15 pounds, and his shirt collar size had increased from 16 to 17. If he has two or more alcoholic beverages and sleeps on his back, the snoring can be heard in a room down the hall. The patient’s wife was not certain whether he stops breathing in his sleep. He initially denied daytime sleepiness, but his wife reminded him that he tended to fall asleep with visitors present, and he confessed that he was having trouble staying awake during his 30-minute drive to work. He had hypertension and a family history of stroke in both parents.

On examination, he appeared fatigued and modestly overweight. He was 5 feet 11 inches tall, and weighed 220 pounds (body mass index of 30.7). His blood pressure was 154/95.

An all-night sleep test demonstrated 245 apneas, with an apnea index (number of apneas/hour) of 33. His oxygen saturation during the apneas decreased to 88 from a baseline of 92, although occasionally it was as low as 81. Subsequently, he had a second night in the sleep laboratory for continuous positive airway pressure (CPAP) titration. A repeat all-night sleep test demonstrated that a CPAP of 9 cm H₂O eliminated.

After using CPAP, he and his wife noted a distinct change in his alertness. He commented that he had not realized how sleepy he was until he saw how well he could feel under treatment.

Disorders causing excessive daytime sleepiness are a result of either sleep disruption at night, such as sleep apnea syndrome or periodic limb movements in sleep, or a disorder of the brain’s sleep–wake system, such as narcolepsy or idiopathic hypersomnolence. The patient in the preceding vignette had severe obstructive sleep apnea. Many similar patients deny or minimize their symptoms. Often they come at the bed partner’s insistence, or the patient may present with nonspecific fatigue and weakness.

During an episode of obstructive sleep apnea, the soft palate and tongue relax excessively, producing upper airway obstruction, which results in snoring, apneas, and hypopneas (partial apneas). Predisposing factors include male gender; excessive weight; abnormal structure of the palate, uvula, tongue, and jaw; increasing age; use of alcohol; use of testosterone or reduction in female hormones; and positive family history.

Clinical Presentation

Loud snoring, caused by upper airway tissue vibration, is a warning sign of sleep apnea syndrome. When the obstruction becomes complete, an apneic event occurs. Concomitantly, blood oxygen saturation decreases and carbon dioxide increases. When this develops, a sleep arousal occurs. Although the patient is usually unaware of the event, often the partner is aroused and frightened by the individual’s having ceased to breathe. Loud snoring, in combination with daytime sleepiness, raises the suspicion of clinically significant obstructive sleep apnea (Fig. 15-2A). Paradoxically, the majority of patients with obstructive sleep apnea do not report choking or gasping for breath, are unaware of their apneas, and often believe that they have had an adequate night’s sleep.

Figure 15-2 Sleep Disorders with Hypersomnia.

The cumulative effect of hundreds of such nighttime arousals is excessive daytime sleepiness. Patients with severe (≥30 episodes per hour), and possibly, those with moderate (15–29 episodes per hour) sleep apnea are at increased risk for cardiovascular complications of hypertension, myocardial infarction, arrhythmias, and stroke.

Sleep fragmentation may lead to arousal in which there are higher levels of catecholamines present on average through the night; in turn this may lead to hypertension. The amount of respiratory effort is increased in compensation as oxygen desaturation is detected. Increase in central negative intrathoracic pressure may lead to increased secretion of aldosterone or catecholamines. Ultimately this promotes increased intravascular fluid volume and central venous pressure.

The associated elevated mean intrathoracic negative pressure may also lead to abnormal transmural forces affecting the heart, leading to remodeling of central cardiovascular structures and in turn leading to release of additional humoral factors contributing to various cardiac arrhythmias. A metabolic syndrome develops with resultant insulin resistance and further weight gain; its pathogenesis has yet to be defined. In turn this leads to progressive worsening of hypertension. Fortunately, many patients treated with continuous positive airway pressure (CPAP) subsequently are now able to control both their hypertension and its associated cardiovascular risks. CPAP allows the airway to be maintained by pneumatic pressure, eliminating airway collapse; oxygen desaturation no longer occurs, and the above-defined pathophysiologic cascade is aborted and treated.

Diagnosis and Treatment

An all-night sleep study is the best means to detect and quantitate apneic events. Treatment with CPAP is used to reduce daytime sleepiness and reduce cardiovascular risk. Healthy people may experience up to 4 apneas per hour of sleep at night. Patients with severe and even moderate sleep apnea will significantly benefit from CPAP use by improving daytime alertness and reducing cardiovascular risk. Reduction of risk factors, such as obesity and use of alcohol in the evening, may help.

Although surgical efforts to restructure the oropharynx are often helpful for relieving snoring, they are not as useful for obstructive sleep apnea and, therefore, are considered secondary treatment measures for the patient with sleep apnea. Respiratory stimulant medications but generally have minimal clinical usefulness.

Clinical Vignette

A 22-year-old man began having difficulty staying awake during college. Even with 8–9 hours of sleep at night, he fell asleep during class or when he was trying to study at home. Sometimes, he had a “second wind” and would be alert later in the evening. He found that a 5–10-minute nap was moderately refreshing, at least for an hour or two.

The patient had noticed that he would lean against a wall or sit when he was laughing, as he otherwise might precipitously drop to the floor as his legs unexpectedly collapsed. On another occasion, he had a very frightening episode, when he woke from a nap but was unable to move. At that time, he had the sense of an evil stranger peering over him and tried to scream, but could not. After 45 seconds, he was able to move and talk.

Results of an all-night sleep test were normal, aside from a borderline early REM latency of 51 minutes. A multiple sleep latency test (MSLT), containing five daytime naps, showed an average latency to sleep onset of 3.2 minutes, and three of the naps contained REM sleep. He was treated with modafinil, with some improvement in his sleepiness. However, he continued to have episodes of cataplexy and sleep paralysis. The addition of fluoxetine, 10–20 mg daily, helped to ameliorate those symptoms.

Narcolepsy is a primary sleep disorder wherein the central nervous system regulation of sleep, and particularly REM sleep, is impaired. Patients with narcolepsy tend to be much sleepier than the average person, although even in narcolepsy it is unusual to fall asleep under extreme circumstances, such as when crossing a street or answering a question. Depending on the severity of the illness, the external circumstances, and the patient’s willpower, he or she may or may not succumb to a severe urge to sleep.

Treatment includes CNS stimulants, such as modafinil or amphetamines, for sleepiness. Ancillary symptoms are treated with SSRI drugs, such as fluoxetine or sodium oxybate.

Clinical Presentation

The symptoms of the narcolepsy tetrad include excessive daytime sleepiness, which is present in almost all patients, and the ancillary symptoms of cataplexy, sleep paralysis, and hypnagogic hallucinations (Fig. 15-2B). One or more of these ancillary symptoms are present in about 50–60% of narcoleptics, and they are due to the inappropriate occurrence of partial episodes of REM sleep. During REM sleep, healthy individuals are often dreaming, and except for the extraocular and respiratory musculature, most muscles are paralyzed. This paralysis is subclinical in healthy individuals because it occurs while they are asleep.

In contrast, patients with narcolepsy may enter partial REM sleep at inappropriate times. Typically these events occur in two specific settings: cataplexy, which is sudden paralysis occurring in response to strong emotions including laughter or anger, and sleep paralysis, which includes waking with paralysis and often hallucinations. Hypnagogic hallucinations are realistic—often frightening—dreams that occur at sleep onset while the patient retains some degree of consciousness. The etiology of narcolepsy is multifactorial. There is an association with reduced hypocretin levels in the hypothalamus, and genetic and environmental factors may also play a role.

Diagnosis

Narcolepsy is diagnosed clinically by the combination of a classic history of excessive daytime sleepiness relieved by brief naps, associated in about half of cases with other portions of the narcolepsy tetrad: cataplexy, sleep paralysis, and hypnagogic hallucinations. By measuring the average latency to sleep onset and the appearance of REM sleep on MSLT during the naps in a sleep lab, a diagnosis of narcolepsy can be supported. An all-night sleep test needs to be done on the night preceding a MSLT, because the MSLT cannot be properly interpreted unless the quality and quantity of the preceding night’s sleep is assessed.

Idiopathic hypersomnolence is a disorder seen in a small percentage of patients who have excessive daytime sleepiness but do not have narcolepsy or a nocturnal sleep disturbance. In contrast to narcolepsy, these individuals have prolonged periods of sleep at night as well as prolonged daytime naps. This is documented by a combination of all-night sleep study showing adequate sleep and no significant sleep disruption and a MSLT demonstrating excessive daytime sleepiness but no daytime REM sleep. Similar to narcolepsy, it is treated with stimulants.

Clinical Vignette

A 45-year-old woman saw her physician for excessive daytime sleepiness. She was tired much of the day but, if necessary, could stay awake. Soft snoring was noted if she slept on her back. Her husband noted that she had trouble sitting still in the evening. She remarked that if she was trying to sit and read or watch television, she needed to move her legs or get up and walk around. This provided momentary relief, but after she sat or lay down, the symptoms recurred. Her sister has similar evening symptoms.

Physical examination and neurologic examination were unremarkable. Blood tests demonstrated a low ferritin level, but no anemia. Depression or hypothyroidism were ruled out by her primary care physician.

An all-night sleep test showed frequent periodic limb movements of sleep associated with arousals. The Periodic Limb Movement (PLM) index was 59 episodes per hour, 46/hour of which were associated with arousals. A diagnosis of restless leg syndrome (RLS) and periodic limb movement syndrome (PLMS) was made. Treatment with iron resulted in 50% symptomatic improvement. Treatment with 0.25 mg pramipexole at 6:00 PM and again at 9:00 PM led to additional significant improvement.

Periodic limb movements are another important consideration in the differential diagnosis of excessive daytime sleepiness. They consist of repeated brief episodes of movements of the lower extremities. These movements range from simple dorsiflexion of the great toe to violent movements of the whole lower extremity. Many patients and their bed partners are unaware that they have PLMs during sleep. Individuals with PLMS present with excessive daytime sleepiness because each episode disrupts their sleep.

Many of these patients also have RLS (an irresistible urge to move the legs while sitting or lying down), especially those with iron deficiency, and treatment with iron may help. Symptoms are also treated with dopamine agonists, benzodiazepines, or narcotics. Antidepressants and stimulants may exacerbate RLS and PLMS.

Clinical Vignette

An 82-year-old man was brought to the neurologist by his wife for violent activity in his sleep that concerned her for both of their safety. She recently noted him waving his fists, kicking, and occasionally banging his head against the headboard, all in his sleep. On one occasion, he fell out of bed, but, fortunately, did not hurt himself. Once, she had to wake him because he was punching her, completely contrary to his character and past behavior. When she woke him after this episode, he told her that he had dreamt that someone was trying to attack him. During the day, he was becoming more clumsy, took a long time to dress, and occasionally had a tremor of his right hand at rest.

On exam, he had findings of subtle right hemiparkinsonism. An all-night sleep test demonstrated abundant tonic muscle activity during REM sleep. The diagnosis of REM behavior disorder was made on the basis of the wife’s history and the abnormal all-night sleep study. He was treated with clonazepam 0.5 mg nightly, and the spells resolved by approximately 90%. A diagnosis of possible Parkinson disease was also entertained, with a plan to follow him for any additional Parkinson symptoms.

Parasomnias, characterized by certain unusual or unwanted symptoms occurring during nighttime sleep, are another major category of sleep disorders.

REM Behavior Disorder

The vignette above has a typical history for REM sleep behavior disorder (RBD). The patient is unaware of the episodes during sleep. Treatment with clonazepam is usually successful. Some of these patients have RBD as a first manifestation of degenerative neurologic disease, and in this case, the patient may have early Parkinson’s disease.

Most healthy individuals are paralyzed and dreaming during REM sleep. The characteristic paralysis, sparing both eye movements and respiratory muscles, is from activation of inhibitory reticulospinal pathways, which results in an inhibition of anterior horn cells within the spinal cord, preventing patients from acting out dreams. In sleep paralysis, this otherwise normal phenomenon occurs while the patient is awake. In RBD, this activation fails to occur, resulting in the patient acting out a dream (Fig. 15-3).

Figure 15-3 REM Sleep Behavior Disorder.

After age 70 years, some people lose this ability to be paralyzed during REM sleep. Subsequently, they begin to act out their dreams by talking, yelling, kicking, or in extreme cases, attacking their bed partner. If awakened, they relate that they are in the middle of a violent dream. A third or more of patients with RBD have, or will develop, a neurodegenerative disease, such as Parkinson disease or Lewy body disease. Most of the patients are male and respond positively to treatment with 0.5 mg clonazepam at bedtime.

Night Terrors

Night terrors are common in children and occasionally persist into adult life. The patient suddenly sits up in bed, has dilated pupils, a frightened expression, and a rapid pulse. Occasionally affected individuals dash from the bed, sustaining injury. Children often return to sleep without memory of the event. If awakened, they describe a frightened feeling or image but not a complex dream, because these episodes arise during stage 3 or 4 sleep, in which dreams do not usually occur. Somnambulism tends to occur in the same patients, also during stage 3 or 4 sleep. Often an explanation of the problem is sufficient, but tricyclic antidepressants or benzodiazepines may be helpful.

Delayed Sleep Phase Syndrome

Delayed sleep phase syndrome is a circadian rhythm disorder. Individuals are not able to adjust their circadian clock to the time used by the rest of the world.

Most people can delay their sleep–wake cycle 1 hour or more daily and can advance it to an earlier time by approximately a half-hour daily. Therefore, it is commonly easier to sleep and awaken later, than to sleep and awaken earlier.

Some people have particular difficulty advancing to an earlier time. For example, a student with delayed sleep phase syndrome who spends 2 weeks staying up late may find it impossible to learn to go to bed early and wake up early for a summer job. She will report insomnia because she cannot fall asleep at night, or daytime sleepiness because she cannot awaken before 11:00 AM. Treatments include medication, light therapy, or a program to delay sleep by 3 hours every day until sleep time returns to the new desired bedtime.