Rare Diseases Report 2022

Staying alert for patients with narcolepsy


Almost half of Americans report feeling daytime sleepiness on at least 3 days per week. For most patients, this sleepiness results from insufficient nighttime sleep. But a minority of these patients have narcolepsy, a chronic neurologic disorder that impairs the brain’s control of sleep-wake cycles. This disorder often goes undiagnosed, but neurologists can make a significant difference by learning how to recognize and treat it.

Dr. Michael Thorpy

What is narcolepsy?

Narcolepsy is characterized by excessive daytime sleepiness (EDS) and sudden attacks of sleep. Patients have difficulty staying awake for long periods of time, and the disorder can make performing daily tasks difficult. Problems with concentration and alertness are common.

Narcolepsy is considered to have two subtypes. Patients with narcolepsy type 1 also have cataplexy, a sudden loss of muscle tone. Attacks of cataplexy are triggered by strong, usually positive, emotions. These attacks have manifestations ranging from slurred speech to complete weakness of most muscles. Patients with narcolepsy type 2, however, do not have cataplexy.

Dysregulation of rapid eye movement (REM) sleep, which is when most dreaming occurs, is another symptom of narcolepsy. The transition to REM sleep is quicker in patients with narcolepsy and usually occurs within 15 minutes of sleep onset. A related symptom is sleep paralysis, an inability to move while falling asleep or waking up. This symptom resembles a state that normally occurs during REM sleep.

Thomas E. Scammell, MD, professor of neurology at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston.

Dr. Thomas E. Scammell

Hallucinations also are common in patients with narcolepsy and can be especially vivid. Hypnagogic hallucinations occur during the transition to sleep, and hypnopompic hallucinations arise while the patient is waking up. Patients may think they see a stranger in their bedroom, and children sometimes report seeing animals.

Although it is easy for patients with narcolepsy to fall asleep at night, they often have disrupted sleep. Patients have frequent, brief arousals throughout the night that may become disturbing. Dream content often is affected in narcolepsy, too. Patients have described lucid dreams of flying or out-of-body experiences. After such intense dreams, patients often feel that their sleep has not been restful.

Criteria and diagnosis

To receive a diagnosis of narcolepsy type 1, a patient must have EDS that persists for at least 3 months and at least one of the following two features: cataplexy and objective evidence of quick sleep onset and early start of REM sleep or low cerebrospinal fluid (CSF) levels (that is, less than 110 pg/mL) of hypocretin. Hypocretin, also known as orexin, is a neuropeptide that regulates wakefulness and arousal.

Kiran Maski, MD, MPH, assistant professor of neurology at Harvard Medical School and neurologist and sleep physician at Boston Children’s Hospital.

Dr. Kiran Maski

Patients must meet five criteria to receive a diagnosis of narcolepsy type 2. They must have EDS that persists for at least 3 months. They must have test results that show quick sleep onset and early start of REM sleep. They must have no cataplexy. Their CSF levels of hypocretin must be normal or unknown. Finally, they must have no other conditions that provide a better explanation for their symptoms and test results.

“The diagnosis of narcolepsy is made primarily by history on the clinical features of the disorder,” said Michael J. Thorpy, MB, ChB, professor of neurology at Albert Einstein College of Medicine and director of the Sleep–Wake Disorders Center at Montefiore Medical Center in New York. When narcolepsy is suspected, testing is required to confirm the diagnosis. The patient should undergo all-night polysomnographic (PSG) testing, followed by a daytime multiple sleep latency test (MSLT). Measurement of CSF hypocretin can be diagnostic but is performed mainly in the research setting and is not common in the clinical setting, said Dr. Thorpy.

Patients with narcolepsy typically fall asleep in an average of less than 8 minutes during the nap opportunities of the MSLT. They also have at least two sleep-onset REM periods. “A new change in the diagnostic classification is that a sleep-onset REM period on the preceding night’s PSG can count as one of the two sleep-onset REM periods required for diagnosis,” said Dr. Thorpy.

“In the case of type 1 narcolepsy, the history is usually pretty clear, and the MSLT is usually positive, in the sense that it is consistent with a narcolepsy pattern,” said Thomas E. Scammell, MD, professor of neurology at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. “The PSG is also important, because other factors that disrupt the patient’s nighttime sleep (such as obstructive sleep apnea and periodic limb movements) must be ruled out, especially in type 2 narcolepsy,” said Dr. Scammell.


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