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HelpTest ID ORXNA Orexin-A/Hypocretin-1, Spinal Fluid
Advisory Information
Orexin-A (hypocretin-1) deficiency is the hallmark of narcolepsy type 1. The diagnostic criteria for type 1 narcolepsy includes the presence of cataplexy and/or measured cerebrospinal fluid (CSF) orexin-A/hypocretin-1 concentrations less than or equal to 110 pg/mL. Alternative testing for narcolepsy type 1 includes mean latency of 8 minutes in the clinical multiple sleep latency test, with evidence of sleep-onset rapid eye movement periods and cataplexy.
Specimen Required
Patient Preparation: Patient should not have recently received radioisotopes, either therapeutically or diagnostically, due to potential assay interference.
Collection Container/Tube: Sterile vial
Submission Container/Tube: CSF in plain vial with no additives
Specimen Volume: 1.5 mL
Pediatric Volume: 0.5 mL minimum volume
Collection Instructions:
1. Obtain aliquot from second collection vial (preferred, not required).
2. Hemolyzed specimens will give false-positive results. Specimens should be centrifuged to remove any red cells prior to shipping.
Useful For
Aiding in the diagnosis and differentiation of type 1 narcolepsy from other causes of hypersomnolence
This assay is not intended for use as a screening test.
Method Name
Radioimmunoassay (RIA)
Reporting Name
Orexin-A/Hypocretin-1, CSFSpecimen Type
CSFSpecimen Minimum Volume
0.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| CSF | Frozen | 120 days |
Clinical Information
Narcolepsy affects 0.02% to 0.05% of the population and the onset of symptoms often occurs in adolescence. Orexin (also known as orexin-A or hypocretin-1) is a neuropeptide produced in the hypothalamus and is involved in the sleep/wake cycle in humans. Impairment of orexin production and orexin-modulated neurotransmission is associated with narcolepsy with cataplexy (episodes of muscle weakness in response to emotional stimuli). An abnormally low concentration of orexin-A/hypocretin-1 in cerebrospinal fluid (CSF) is indicative of what is termed type 1 narcolepsy.
Survey of the literature reveals that approximately 85% to 95% of randomly selected individuals with type 1 narcolepsy and typical cataplexy, exhibit low (<110 pg/mL) CSF orexin (hypocretin-1) concentrations.(1) In one large study, the sensitivity of this cutoff was found to be 87% with a specificity of 99%.(2) Orexin deficiency and type 1 narcolepsy are closely associated with HLA complex DQB1 *0602. It is estimated that only 1 in 500 HLA DQB1*0602-negative individuals exhibit low CSF orexin concentrations. CSF concentrations have been found to almost always be above 200 pg/mL in healthy individuals and those with non-type 1-narcoleptic sleep disorders such as narcolepsy type 2 and idiopathic hypersomnia.
Reference Values
Normal individuals should be >200 pg/mL
Previous literature has defined CSF orexin-A/hypocretin-1 concentrations of ≤ 110 pg/mL as being consistent with narcolepsy type 1 - (Mignot E: Arch Neurol 2002:59;1553-1562). Concentrations between 111 to 200 pg/mL are considered intermediate and have limited diagnostic utility for narcolepsy, as they may be representative of other neurological disorders. Concentrations of >200 pg/mL are considered normal.
Interpretation
The diagnostic criteria for type 1 narcolepsy in the International Classification of Sleep Disorders (3) include the presence of hypersomnia, cataplexy (episodes of muscle weakness in response to emotional stimuli) and/or measured cerebrospinal fluid (CSF) orexin (hypocretin-1) concentrations less than or equal to 110 pg/mL.
Orexin (hypocretin-1) CSF concentrations have been classified into 3 categories in the literature. They include low (≤110 pg/mL), which is indicative of type 1 narcolepsy; intermediate (ranges between 111-200 pg/mL); and normal (>200 pg/mL). Previous studies have shown that 106 of 113 patients with clinically defined type 1 narcolepsy exhibited low (<110 pg/mL) orexin concentrations. In another study, all 48 healthy individuals exhibited orexin (hypocretin-1) CSF concentrations above 200 pg/mL.
In the periodic hypersomnia disorder of Kleine-Levin syndrome, the CSF orexin levels may be low during the sleepy periods, with return to normal when individuals are not sleepy.
Clinical Reference
1. Bourgin P, Zeitzer JM, Mignot E: CSF hypocretin-1 assessment in sleep and neurological disorders. Lancet Neurol 2008 Jul;7(7):649-62.doi:10.1016/S1474-4422(08)70140-6. Review
2. Mignot E, Lammers GJ, Ripley B, Okun M, et al: The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002 Oct;59(10):155-62. PubMedPMID: 12374492
3. Sateia MJ: International classification of sleep disorders-third edition: highlights and modifications. Chest 2014 Nov;146(5):1387-1394. doi: 10.1378/chest.14-0970. Review
4. Dauvilliers Y, Arnulf I, Mignot E: Narcolepsy with cataplexy. Lancet 2007;369:499-5112
5. Ripley B, Overeem S, Fujiki N, Nevsimalova S, et al: CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Neurology 2001 Dec 26;57(12):2253-2258. PubMed PMID: 11756606
Day(s) and Time(s) Performed
Third Tuesday of every month; 8 a.m.
Analytic Time
3 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.CPT Code Information
83519
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| ORXNA | Orexin-A/Hypocretin-1, CSF | 91670-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 604230 | Orexin-A/Hypocretin-1, CSF | 91670-0 |
Forms
If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.