Narcolepsy Diagnosis
Diagnosis
- Identify all symptoms that suggest narcolepsy
- Presence of both excessive daytime sleepiness & cataplexy highly suggest narcolepsy
- Obtain structured sleep history
- Determine whether main complaint is sleepiness or fatigue
- Timing, quantity & quality of sleep
- Snoring or difficulty in breathing
- Relevant medication or drug use including alcohol intake
- According to DSM-5 criteria, narcolepsy is the daily occurrence of uncontrollable need to sleep, daytime lapses or napping for at least 3 times per week for the past 3 months with the presence of any of the following:
- Cataplexy episodes, that occur at least a few times in a month, can be defined as either:
- Occurrence in patients with long-standing disease of sudden bilateral loss of muscle tone with intact consciousness for a few seconds to minutes triggered by laughter or joking
- Presence of unprovoked grimaces or jaw-opening episodes with tongue thrusting or global hypotonia without any obvious emotional triggers in children or adult patients within the past 6 months
- Inadequate hypocretin as measured using cerebrospinal fluid hypocretin-1 immunoreactivity values (≤1/3 of values obtained in healthy individuals tested using the same assay or ≤110 pg/mL). Low CSF levels should not be due to acute brain injury, inflammation or infection
- Nocturnal sleep polysomnography shows ≤15 minutes of rapid eye movement sleep latency or a multiple sleep latency test of ≤8 minutes mean sleep latency & ≥2 sleep-onset rapid eye movement periods
- Cataplexy episodes, that occur at least a few times in a month, can be defined as either:
- Based on DSM-5 criteria, narcolepsy can be subclassified as:
- Narcolepsy without cataplexy but with hypocretin deficiency if the patient has low CSF hypocretin-1 levels& positive results in polysomnography/multiple sleep latency test but there is no cataplexy
- Narcolepsy with cataplexy but without hypocretin deficiency if the patient has normal CSF hypocretin-1levels but with cataplexy & positive results in polysomnography/multiple sleep latency test, this is a rare type of narcolepsy
- Autosomal dominant cerebellar ataxia, deafness, & narcolepsy if the patient has narcolepsy at the age of 30-40 years (late-onset) with low or intermediate CSF hypocretin-1 levels, deafness, cerebellar ataxia, & eventually dementia caused by exon 21 DNA (cytosine-5)-methyltransferase-1 mutations
- Autosomal dominant narcolepsy, obesity & type 2 diabetes if the patient has narcolepsy, obesity, & type 2 diabetes & low CSF hypocretin-1 levels associated with a mutation in the myelin oligodendrocytes glycoprotein gene
- Narcolepsy secondary to another medical condition if the patient has narcolepsy due to medical conditions that cause infectious (eg, Whipple’s disease, sarcoidosis), traumatic or tumoral destruction of hypocretin neurons
- Severity of narcolepsy based on DSM-5 criteria can be classified as:
- Mild if cataplexy occurs <1/week, the need for naps is only once or twice per day, & with less disturbing nocturnal sleep
- Moderate if cataplexy occurs once daily or every few days, with daily need for multiple naps, & with disturbed nocturnal sleep
- Severe if the patient has multiple attacks of drug-resistant cataplexy daily, almost constant sleepiness, &disturbed nocturnal sleep
Evaluation
Diagnostic Exams
- Confirm the diagnosis, determine severity & exclude other sleep disorders
Polysomnography (PSG)
- Overnight test for concurrent sleep disorders
- Helps to exclude other conditions that produce sleepiness such as obstructive sleep apnea, periodic limb movement disorder & rapid eye movement (REM) sleep behavior disorders
- Accurately documents fragmented sleep patterns with a normal amount of rapid eye movement sleep but a pattern of sleep-onset rapid eye movement
- A short latency rapid eye movement sleep can be an evidence for narcolepsy esp if multiple sleep latency test (MSLT) results are vague
Multiple Sleep Latency Test (MSLT)
- Helps to confirm the diagnosis
- Useful in determining the severity of daytime sleepiness
- Performed one day after the nocturnal polysomnography
- ≤8 minutes of MSLT & ≥2 sleep-onset REM (SOREM) periods indicate pathological sleepiness in narcolepsy
- Narcoleptics usually fall asleep & enter rapid eye movement sleep within 15 minutes of sleep onset
Maintenance of Wakefulness Test (MWT)
- Objective test that measures the ability to resist falling asleep
- Narcoleptics usually have short sleep latencies in maintenance of wakefulness test
- This test does not necessarily confirm diagnosis but only indicates that the patient is sleepy
Assessment
Epworth Sleepiness Scale
- Subjective test in which patients are asked to rate their level of sleepiness in normal daytime situations
- Total score of ≥11 suggests a high probability of sleep disturbance
- Most commonly used index of sleepiness in adults
- A 7-point scale that quantifies subjectively the sleepiness of the patient throughout the day
Laboratory Tests
Cerebrospinal Fluid Hypocretin
- Absence of low levels of cerebrospinal fluid hypocretin-1 can confirm the presence of narcolepsy with cataplexy
- ≤110 pg/mL CSF hypocretin-1 level has a high positive predictive value of 94%
- Most accurate diagnostic technique
- Its use in narcolepsy without cataplexy needs to be determined
- Normal levels of CSF hypocretin-1 have been found in narcolepsy without cataplexy & idiopathic hypersomnia
Human Leukocyte Antigen (HLA) Testing
- The clinical use of HLA subtype DQB1*0602 & DQA1*0602 is limited because of genetic variation
- Should not be used for the diagnosis of narcolepsy without cataplexy
Imaging
Magnetic Resonance Imaging (MRI)
- Useful in patients with atypical symptoms or focal findings on neurological exam to identify structural lesions of the brainstem & diencephalon which can cause narcolepsy
Classification
Types of Narcoplepsy
Narcolepsy w/ cataplexy
- ≥3 months of excessive daytime sleepiness
- Presence of definitive history of cataplexy
- May be confirmed by:
- Polysomnography to rule out other causes of disrupted nocturnal sleep & demonstrating at least 6 hours of sleep followed by multiple sleep latency test showing ≤8 minutes of sleep latency & ≥2 SOREM; or
- ≤110 pg/mL CSF hypocretin-1 level
Narcolepsy without cataplexy
- ≥3 months of excessive daytime sleepiness
- No cataplexy or questionable/atypical cataplexy-like episodes
- Must be confirmed by polysomnography & multiple sleep latency test
Narcolepsy caused by a medical condition
- ≥3 months of excessive daytime sleepiness
- Significant underlying medical or neurologic condition accounts for the daytime sleepiness
- Presence of definitive history of cataplexy; or
- Positive polysomnography & multiple sleep latency test when cataplexy or questionable/atypical cataplexy-like episode is not present
- <110 pg/mL CSF hypocretin-1 level (or 30% of normal control values) if there is absence of cataplexy or negative polysomnography & multiple sleep latency test