Clinical Features, Diagnosis and Treatment of Narcolepsy
Section snippets
History
Narcolepsy, from the Greek words “narco,” meaning numbness, stupor, or stiffness, and “lepsy,” meaning fit or seizure, literally translates to mean a fit of stupor or stiffness. The attacks of stupor were identified as sleep episodes. Narcolepsy was originally described by Gelineau in 1880 as a disorder involving excessive sleepiness and sleep attacks associated with a variety of emotional states. He also described episodes of falls or astasia, which were later termed cataplexy. Westphal, in
Clinical features
Narcolepsy is a disorder of the central nervous system for which there is no known cure. The effects of narcolepsy are largely manifested during periods of wakefulness. Narcolepsy is described as a syndrome consisting of excessive daytime sleepiness (EDS) (including periods of irresistible sleep), cataplexy, sleep paralysis, and hypnagogic hallucinations; additional features include automatic behaviors and fragmented or disrupted nighttime sleep.
Narcolepsy typically begins with the symptom of
Epidemiology
Narcolepsy can begin in infancy (rarely) or as late as old age, but most commonly before age 25 years, and usually in the first 2 decades of life.5 It affects men and women equally; however, some studies indicate a slightly greater prevalence in men.6 Although the exact number of patients with narcolepsy is not known with certainty, it is by definition a rare disorder, affecting approximately 1 in 2000 people in the United States. Although there is a greater incidence of narcolepsy among
Genetics
Many studies suggest a genetic influence to narcolepsy. An early study by Kessler and colleagues15 identified 9 patients with narcolepsy and 17 patients with EDS among first-degree relatives of 50 narcoleptic probands. Guilleminault and colleagues16 showed that 40% of probands (out of a clinic population of 334 unrelated patients with narcolepsy) had at least 1 family member with an isolated daytime sleepiness complaint and 6% had a positive family history of narcolepsy. Mignot17 reported that
Pathophysiology
The pathophysiology of narcolepsy with cataplexy has recently been better understood with the discovery of the neuropeptide hypocretin.23, 24 Hypocretin-containing neurons are located in the perifornical and lateral hypothalamus where they project widely to communicate with numerous brain nuclei including those responsible for the regulation of sleep and alertness. Current evidence suggests that most cases of narcolepsy with cataplexy are associated with loss of hypocretin-containing
Diagnosis
There are 3 main types of narcolepsy: narcolepsy with cataplexy, narcolepsy without cataplexy, and secondary narcolepsy (Box 1). Narcolepsy with cataplexy is defined as excessive sleepiness that occurs for at least 3 months and is associated with definite cataplexy. The diagnosis may be confirmed by polysomnography followed by a MSLT.37 Alternatively, a low CSF hypocretin level (≤110 pg/mL or one-third of mean normal control values) is diagnostic.26 The polysomnography should confirm at least 6
Pediatric considerations
Generally speaking, narcolepsy is rare in children less than 5 years of age. In a meta-analysis of 235 patients, Challamel and colleagues38 reported that 4.6% of the patients were younger than 5 years of age at the time of the diagnosis. Furthermore, it is difficult to identify narcolepsy symptoms in preschool children as they are not able to provide an accurate history of cataplexy, hypnagogic hallucinations, or sleep paralysis, and many normal children in this age group take habitual naps
Differential diagnosis
The individual symptoms of narcolepsy are also seen in other disorders and can be a normal phenomenon in certain circumstances (eg, sleep deprivation). Table 1 lists some other disorders associated with narcolepsy symptoms.
Treatment
There is no known cure for narcolepsy and therefore treatment is targeted at symptom management. Even with optimum management, EDS and cataplexy are seldom completely controlled.
Nonpharmacologic management should be initiated in all patients. Patient education is an important component of any treatment plan for narcolepsy. Good sleep habits with avoidance of sleep deprivation and/or irregular sleep patterns should be emphasized. The scheduling of short naps (15–20 minutes) 2 to 3 times per day
Narcolepsy and Obstructive Sleep Apnea
EDS is a common symptom in narcolepsy and obstructive sleep apnea. When both disorders are present in the same patient, it poses a diagnostic and treatment challenge. The frequency of this co-occurrence and its clinical significance is not known. From the prevalence of obstructive sleep apnea's alone (about 4% of the general population8), it is likely that this co-occurrence is not uncommon. Sleep apnea may be seen more frequently with narcolepsy.63 The pathogenesis for obstructive sleep apnea
Summary
Narcolepsy is characterized by EDS, cataplexy, sleep paralysis, and hypnagogic/hypnapompic hallucinations. It is currently believed to be caused by a deficiency in hypocretin-producing neurons in the lateral hypothalamus. Diagnosis is by the presence of appropriate clinical symptoms and confirmation by a polysomnogram followed by an MSLT. The MSLT shows a short sleep latency (≤8 minutes) and 2 or more sleep onset REM periods. In patients with cataplexy, CSF hypocretin levels are typically less
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