1 What are the considerations in the differential diagnosis?

Depression, sleep apnea, sleep disorders (dyssomnias), adjustment disorder, hypothyroidism, chronic renal failure, anemia, dementia, substance abuse or withdrawal, and anxiety should be considered.

He has had relationship troubles with his wife and is recently divorced. He reports that her primary reason for leaving him was that he no longer seemed to care about her, as he never wanted to go out or do the things they used to do. She even went so far as to accuse him of having an affair. They stopped sleeping in the same room 2 years ago because his excessive snoring, with intermittent bursts of awakening short of breath, kept her up at night. He says he just doesn’t have energy to do things anymore. He also relates having been recently reprimanded at work for falling asleep. On examination, he is a moderately obese, otherwise healthy-appearing middle-aged man. His mental status examination is unremarkable. He denies any thoughts of suicide, appetite disturbances, or feelings of guilt or hopelessness. He does feel like he has had depressed mood since his wife has left.

2 In addition to a diagnosis of adjustment disorder with depressed mood, what sleep-related disorder likely explains most of this patient’s problem?

This patient is suffering from sleep apnea and would appropriately be diagnosed with a breathing-related sleep disorder. These patients are often obese, and a collar size greater than 17 inches should be a red flag; presumably, the weight of the fat around the neck collapses the airway. Sleep is often interrupted at night because of the occluded airway, leading to excessive daytime sleepiness and fatigue. Chronic poor sleep can lead to irritability, poor concentration, and the need to “nap” during the day.

3 What treatment can be employed to allow this man to sleep at night?

The therapy used to allow these patients to sleep involves pressurizing the airway to keep it patent. The patient wears a mask that provides positive airway pressure to keep the airway from being obstructed. Positive airway pressure is only one treatment option for those patients who suffer from obstructive sleep apnea, as does this man. As always, lifestyle modifications are important as well. This patient should be encouraged to lose weight, which should reduce the compressive forces on the airway and thereby decrease the airway obstruction. Uvuloplasty or nasal surgery may also be indicated.

Note: Sleep studies will show apneic episodes with increasing breathing effort against an obstructed airway, frequent arousals, and decreased rapid eye movement (REM) sleep.

1 What are the considerations in the differential diagnosis?

Sleep deprivation, primary hypersomnia, narcolepsy, sleep apnea, substance abuse or withdrawal, hypothyroidism, and anemia are considerations.

In addition, she states that sometimes she awakens but is utterly “unable to move a muscle.” She states she has always been able to fall asleep quickly. She denies any use of drugs or medications. You excuse yourself to answer a page and find her asleep when you return to your office. On awakening she is startled at first but then seems to regain her orientation and asks, “What is wrong with me?”

2 What is the likely diagnosis and what would be the expected electroencephalographic findings?

This patient has narcolepsy. The electroencephalogram (EEG) in a sleep study would likely show a decreased REM latency, meaning she rapidly progresses into REM sleep. This accounts for the restfulness these patients feel upon falling asleep.

Note: Patients with primary hypersomnia have a completely normal sleep architecture.

3 Which treatment is available for patients with narcolepsy?

A regimen of a regular schedule of forced naps during the day can be a successful treatment for some patients. In severe cases of narcolepsy, amphetamines such as methylphenidate (Ritalin) are also used in the treatment of narcolepsy. These agents cause the release of norepinephrine, dopamine, and serotonin, but all have some abuse potential. A newer agent, modafinil, has been added that has lower abuse liability. Modafinil appears to selectively decrease somnolence in narcoleptic patients; however, the mechanism of action is unknown.

4 What are the stages of sleep and what happens physiologically in these stages?

Sleep is divided into non-REM (NREM) and REM sleep. NREM sleep is divided into four stages, each being a deeper sleep. The stages are further described as fast wave or slow wave sleep. The earliest two stages are fast wave sleep and stages 3 and 4 are termed slow wave sleep based on the EEG appearance of brain waves. REM refers to rapid conjugate eye movement. As a person falls asleep, he passes through stages 1 to 4 and then enters REM sleep the first time, normally after approximately 90 minutes. The first REM episode lasts typically less than 10 minutes, and then the person cycles through the stages again, with further REM episodes of about 15 to 40 minutes each.

Physiologically, during NREM sleep, a person’s pulse, respiration rate, and blood pressure are decreased and show less minute-to-minute variation. Resting muscle tone is relaxed somewhat, and there are episodic body movements during NREM sleep. Males do not experience erection, and blood flow, including cerebral circulation, is somewhat lower. By contrast, REM sleep is characterized by higher pulse rate, respiratory rate, and blood pressure; EEG patterns are similar to those of one who is awake. REM sleep is also termed paradoxical sleep because of its similarities on EEG to a person who is awake. Men will experience partial or full erection. Additionally, a person in REM sleep experiences near total skeletal muscle paralysis, and movement is quite rare. Abstract and surreal dreams occur during this phase of sleep. Most REM sleep occurs in the last one third of the night.

5 In Table 24-1, cover the columns to the right, and for each stage of sleep listed in the left column, name the EEG appearance and describe the frequency and voltage of the waves seen:

6 How do nightmares differ from night terrors?

Nightmares occur almost exclusively in REM sleep. Patients who experience nightmares are able to recall the events of these frightening events, which usually involve threat to life, security, or self-esteem. Upon awakening, the person rapidly becomes oriented. Night terrors occur in deep NREM sleep (stages 3 and 4). Often, the person wakes with a panicky scream. These patients are often unresponsive upon awakening, have amnesia for the episode, and show signs of autonomic arousal, such as tachycardia, tachypnea, and diaphoresis. Night terrors can be treated with benzodiazepines.

7 An 82-year-old woman complains that her sleep patterns have changed as she has aged. What changes in sleep are typical as people age?

Though this is somewhat controversial, for the purpose of boards you should assume that as people age, they experience a decrease in the amount of time in slow wave sleep (stages 3 and 4) and REM sleep. This typically results in a reduced need for time spent sleeping. Insomnia is common in the elderly population.

8 This woman had been given a benzodiazepine to assist her sleep, which improved for a while, but now she complains of poor sleep once more. Why have her sleep problems returned?

She is experiencing tolerance to the effects of her medication. Benzodiazepines may be used for short-term management of insomnia, especially when there is an identifiable precipitant, but not for long-term management, because tolerance and dependence may result. Reevaluation should follow a 7- to 10-day trial of a benzodiazepine, and other agents should be considered.

9 How do benzodiazepines manifest their pharmacologic effect?

Benzodiazepines are agonists of γ-aminobutyric acid (GABA) receptors, which are bound to chloride channels. GABA is the primary inhibitory neurotransmitter in the central nervous system (CNS). This CNS inhibition leads to decreased alertness, drowsiness, and less agitation.

10 Why would this be another reason benzodiazepines should be avoided in the elderly population?

The aged population has a markedly increased (about 25%) incidence of falls when given these types of medications, due to drowsiness and impaired balance. This effect would be especially concerning in this elderly postmenopausal woman, who may have underlying osteopenia or frank osteoporosis. Additionally, the geriatric population is more sensitive to this effect and should be started on a lower dose initially.

11 There are now a number of drugs other than benzodiazopines that also act on the γ-aminobutyric acid benzodiazepine receptor and that reach hypnotic effects with less tolerance and less daytime sedation. What are some examples of these?

Zaleplon, zolpidem, and eszopiclone are examples of these drugs.

Note: Sedating antidepressants such as trazodone and nefazodone (remember the zzzzzzzz group) may also be used.

12 When evaluating a person for sleep problems, perhaps the first and most important step is to make sure that the patient has good sleep hygiene. What does good sleep hygiene entail?

Summary Box: Sleep Disturbance

Narcolepsy: daytime sleepiness, sleep attacks, decreased rapid eye movement (REM) latency, rested after sleep

Primary hypersomnia: excessive somnolence (>1 month), normal sleep architecture

Treatment for narcolepsy and primary hypersomnia: methylphenidate or modafinil

Insomnia: difficulty initiating or maintaining sleep

Nonbenzodiazopines acting at the benzodiazepine γ-aminobutyric acid (GABA) receptor may be the best treatment for insomnia because they allow for hypnotic effects with less tolerance and less daytime sedation.

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