Test Id : ORXNA
Orexin-A/Hypocretin-1, Spinal Fluid
Useful For
Suggests clinical disorders or settings where the test may be helpful
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.
Highlights
Orexin-A (hypocretin-1) is a neuropeptide involved in the sleep/wake cycle in humans. An abnormally low concentration of orexin-A (hypocretin-1) in cerebrospinal fluid (CSF) indicates type I narcolepsy.
Cerebrospinal fluid 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.
Method Name
A short description of the method used to perform the test
Radioimmunoassay (RIA)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Hypocretin
Orexin
Hypocretin-1
Orexin-A
Specimen Type
Describes the specimen type validated for testing
CSF
Ordering Guidance
Orexin-A (hypocretin-1) deficiency is the hallmark of narcolepsy type 1. The diagnostic criteria for type 1 narcolepsy include the presence of cataplexy and/or measured cerebrospinal fluid 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
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: Plain vial with no additives
Specimen Volume: 1.5 mL
Pediatric Volume: 0.5 mL
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.
Forms
If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
0.5 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| CSF | Frozen (preferred) | 120 days | |
| Ambient | 72 hours | ||
| Refrigerated | 7 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
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.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 (human leukocyte antigen) complex DQB1 *0602. However, while almost all individuals with narcolepsy exhibit this particular HLA complex, it is not specific for the presence of narcolepsy type 1. 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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Normal individuals: >200 pg/mL
Previous literature has defined cerebrospinal fluid orexin-A/hypocretin-1 concentrations of 110 pg/mL or below as being consistent with narcolepsy type 1-(Mignot E. Arch Neurol. 2002:59;1553-1562). Concentrations between 111 pg/mL and 200 pg/mL are considered intermediate and have limited diagnostic utility for narcolepsy, as they may be representative of other neurological disorders. Concentrations above 200 pg/mL are considered normal.
Interpretation
Provides information to assist in interpretation of the test results
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 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 (< or =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.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Several factors contribute in the decision to measure orexin in cerebrospinal fluid (CSF). Orexin deficiency in HLA (human leukocyte antigen) DQB1*0602-negative patients is rare. This test may be considered for the diagnosis of narcolepsy type 1, after HLA positivity is shown, if a clinical multiple sleep latency test is negative or unavailable due to potential confounding circumstances. It may also be considered if there is suspicion that cataplexy is of psychogenic origin.
Orexin (hypocretin-1) concentrations between 111 pg/mL and 200 pg/mL are considered intermediate and have limited diagnostic utility for type 1 narcolepsy, as they may be representative of other neurological disorders.
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.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. A recommended time period before collection cannot be made because it will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held and assayed after the radioactivity has sufficiently decayed. This will result in a test delay.
In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. Caution should be used in interpretation of results and the laboratory should be alerted if the result does not correlate with the clinical presentation.
Supportive Data
In an in-house Mayo Clinic study utilizing this assay on cerebrospinal fluid (CSF) from 100 individuals without type 1 narcolepsy, all samples (100%) exhibited orexin (hypocretin-1) concentrations higher than the 200 pg/mL normal threshold (mean value of 531pg/mL + or - 89). Additionally, all 6 out of 6 patients with confirmed type 1 narcolepsy had measured CSF concentrations below 110 ng/mL by this assay (mean value of <50 pg/mL).
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Bourgin P, Zeitzer JM, Mignot E. CSF hypocretin-1 assessment in sleep and neurological disorders. Lancet Neurol. 2008;7(7):649-662. doi:10.1016/S1474-4422(08)70140-6
2. Mignot E, Lammers GJ, Ripley B, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002;59(10):155-162. doi:10.1001/archneur.59.10.1553
3. Sateia MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest. 2014;146(5):1387-1394. doi:10.1378/chest.14-0970
4. Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007;369(9560):499-511. doi:10.1016/S0140-6736(07)60237-2
5. Ripley B, Overeem S, Fujiki N, et al. CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Neurology. 2001;57(12):2253-2258. doi:10.1212/wnl.57.12.2253
6. Liblau RS, Vassalli A, Seifinejad A, Tafti M. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy. Lancet Neurol. 2015;14(3):318-328. doi:10.1016/S1474-4422(14)70218-2
7. Keating G, Bliwise DL, Saini P, Rye DB, Trotti LM. Hypocretin measurement: shelf age of radioimmunoassay kit, but not freezer time, influences assay variability. Scand J Clin Lab Invest. 2017;77(5):390-393. doi:10.1080/00365513.2017.1325928
8. Sahni AS, Carlucci M, Malik M, Prasad B. Management of excessive sleepiness in patients with narcolepsy and OSA: Current challenges and future prospects. Nat Sci Sleep. 2019;11:241-252. Published 2019 Oct 23. doi:10.2147/NSS.S218402
Method Description
Describes how the test is performed and provides a method-specific reference
The orexin-A (hypocretin-1) cerebrospinal fluid assay is a competitive radioimmunoassay. Orexin-A (hypocretin-1) in the patient sample competes with labeled (125)I orexin-A/hypocretin-1 for a limited number of primary antibody binding sites during a 24-hour incubation. Antibody-bound orexin-A/hypocretin-1 is separated from the unbound portion by a goat-anti-rabbit secondary antibody. Centrifugation brings down the heavy antibody complexes while unbound antigen remains in solution and is discarded. The competitive binding to the anti-peptide between endogenous orexin-A/hypocretin-1 and labeled peptide allows for the determination of orexin-A/hypocretin-1 concentration. This is done by measuring bound labeled peptide as a function of orexin-A/hypocretin-1 concentration in a prepared calibration curve.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Twice monthly (Second and fourth Monday)
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
83519
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| ORXNA | Orexin-A/Hypocretin-1, CSF | 91670-0 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 604230 | Orexin-A/Hypocretin-1, CSF | 91670-0 |