Approach

The diagnosis of narcolepsy is based on history followed by polysomnography (PSG) and a multiple sleep latency test (MSLT).

For full international classification of sleep disorders (ICSD) diagnostic criteria for narcolepsy type 1 and type 2, see  Diagnostic criteria.[1]

History

Virtually all patients with narcolepsy have excessive daytime sleepiness (EDS). Patients may also report chronic fatigue or tiredness and memory problems. There may be a history of poor performance at work or of car accidents. The Epworth Sleepiness Scale (ESS) can be used for evaluating EDS.[73][74][75]​ People with untreated narcolepsy typically have ESS scores of ≥15.

People with narcolepsy are also prone to sleep attacks, which manifest as a high propensity to fall asleep in inappropriate situations several times a day.[76][77] This can take place during monotonous, sedentary activity; post-prandially; or when fully involved in a task. Episodes may last a few minutes to longer than 1 hour.[78][79] Patients may report low physical or mental energy, a frequent correlate of sleep disorders; poor memory and concentration, which may show progressive deterioration, frequently being attributed to ageing; reduced work capabilities including inattention and inability to sustain repetitive tasks; and car accidents due to sleepiness and overt dozing.

Most (but not all) people with narcolepsy type 1 have cataplexy (generalised muscle weakness leading to partial or complete collapse), which can be present at the time of the diagnosis or appear within 3 to 5 years after the perceived onset of sleepiness.[16] Narcolepsy type 2 is not associated with cataplexy.[1]​ Cataplexy is most frequently triggered by emotional stimuli such as laughter, excitement, or anger.[5] Speech may be impaired, vision may be blurred, and respiration may become irregular during an attack. A complete loss of muscle tone can lead to collapse and the risk of head trauma or bone fractures. Status cataplecticus is a rare manifestation of cataplexy, characterised by prolonged cataplexy that lasts for hours.[5] Patients often fall asleep after a cataplectic attack. People often report hypnagogic hallucinations (visual or auditory perceptions on falling asleep) or hypnopompic hallucinations (visual or auditory perceptions on awakening).

Many people with narcolepsy also report sleep paralysis, which may be accompanied by hypnopompic hallucinations and a feeling of suffocation. It is sometimes difficult to differentiate these from anxiety attacks. In anxiety, inexplicable fear is often the initial event, followed by inability to move.

There may be a history of disturbed night-time sleep, or of other sleep disorders, such as obstructive sleep apnoea (OSA), periodic limb movement disorder of sleep, and rapid eye movement (REM) sleep behaviour disorder, which are more common with narcolepsy.[1][80]​ It is important to diagnose comorbid sleep disorders, as they may contribute to EDS, and therapy differs.[5] Patients with narcolepsy have frequent sleep-onset REM sleep periods or REM intrusions into wakefulness. This may be elicited from the history as dreams during transitions from sleep to waking and vice versa, dreams during short daytime naps, and difficulty in differentiating such dream episodes from reality.

There may be a family history of sleep disorders, or a history of central nervous system trauma or infection.

Clinical examination

Usually normal, except in patients with narcolepsy due to a medical condition, in which case clinical signs of the underlying condition may be elicited (e.g., obesity in Prader-Willi syndrome, hepatomegaly in Niemann-Pick disease, and paresis in multiple sclerosis).

Diagnostic tests

Although narcolepsy (with or without cataplexy) is sometimes diagnosed clinically, a definitive diagnosis requires further diagnostic testing.[1][81][82]​​​​

PSG and MSLT

The first investigation in people with suspected narcolepsy is an overnight PSG, which is generally followed by MSLT.[83] It is strongly recommended that the MSLT be preceded by at least 1 week of actigraphic recording with a sleep log or diary to clarify if the results could be confounded by insufficient sleep, shift work, or another circadian sleep disorder.[1] PSG ascertains sleep quality before the MSLT and can identify alternative or co-existing causes of EDS, such as OSA, periodic limb movement disorder of sleep, or REM sleep behaviour disorder.[1][80][82]​​​​​​ The PSG may be normal, but often shows snoring, frequent awakenings, mildly reduced sleep efficiency, reduced sleep latency (<10 minutes), periods of REM sleep within the first 15 minutes of sleep, and REM fragmentation by multiple spontaneous arousals.

An MSLT is performed only if the PSG performed the night before shows >6 hours of total sleep time.[84] In general, the naps of patients with narcolepsy contain periods of REM sleep. A mean sleep latency of ≤8 minutes plus 2 or more sleep-onset REM periods (SOREMPs) is diagnostic for narcolepsy.[1][84] By contrast, healthy subjects usually fall asleep in 10 to 15 minutes.[85]

However, there are a number of weaknesses in the ability of the MSLT to definitively diagnose narcolepsy, and other factors, such as sex, age, shift work, and medicine use, may also affect SOREMPs.[86][87]​ Therefore, if there is a strong suspicion of narcolepsy, repetition of the MSLT is required.[86]​ The MSLT is not appropriate for diagnosing narcolepsy in shift workers unless they have resumed a normal circadian pattern.[1]

Other tests

Human leukocyte antigen (HLA) typing may be useful in certain situations, because the majority of the patients with narcolepsy are HLA-DQB1*0602 positive, but this is not diagnostic for narcolepsy. HLA typing may be considered if lumbar puncture is being contemplated to measure cerebrospinal fluid (CSF) hypocretin-1 levels, since any patient who is HLA-negative is very likely to have normal hypocretin-1 levels.[1]

Low CSF hypocretin-1 levels (110 picograms/mL or less than one third of mean values obtained in normal subjects with the same standardised assay) are a diagnostic marker for narcolepsy type 1 in patients with EDS.[1] However, this requires a lumbar puncture, which is painful for patients, and is usually indicated only if MSLT results are uninterpretable or equivocal due to poor sleep efficiency (e.g., concurrent sleep disorders) or MSLT is not suitable (e.g., shift worker, or an inability to discontinue psychoactive drugs with REM sleep suppressive action.[1][88][89]​​​ CSF hypocretin levels are not affected by sleep deprivation, circadian disturbance, disordered breathing, or medicine use or discontinuation, but may be lowered in some seriously ill patients.[1]

The maintenance of wakefulness test (MWT) may be indicated when the inability to remain awake constitutes a safety risk.[84] 

Actigraphy can be used for monitoring the nocturnal arousals/limb movements or to document the circadian patterns.[90]

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