CSF hypocretin/orexin levels in narcolepsy and other neurological conditions
Abstract
Objective To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders. Methods A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years). Results As previously reported, CSF hypocretin-1 levels were undetectably low ( Conclusions Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.
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In Ripley et al. 2001, one patient had CSF collected 7 months after injury but still had low levels of orexin.
“One of the patients had CSF collected 7 months after injury but still had low levels of orexin.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [51]
In Ripley et al. 2001, patients with neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis had normal orexin levels.
“patients with neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis had normal orexin levels”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [51]
In Ripley et al. 2001, six out of seven patients with craniocerebral trauma demonstrated low levels of orexin.
“Six out of seven patients with craniocerebral trauma in the Ripley et al. 2001 study demonstrated low levels of orexin.51”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [51]
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Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury
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CSF hypocretin-1 levels are normal in multiple-system atrophy
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Self-citationEffects of Traumatic Brain Injury on the Orexin/Hypocretin System
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- Authors
- Ripley, B., Overeem, S., Fujiki, N., Nevsimalova, S., Uchino, M., Yesavage, J., Di Monte, D., Dohi, K., Melberg, A., Lammers, G. J., Nishida, Y., Roelandse, F. W. C., Hungs, M., Mignot, E., & Nishino, S.
- Affiliations
- Leiden University (NL)
- From the Stanford University Center for Narcolepsy (Drs. Fujiki, Hungs, Mignot, and Nishino, and B. Ripley), Palo Alto, CA; Department of Neurology and Clinical Neurophysiology (Dr. Lammers, S. Overeem, and F.W.C. Roelandse), Leiden University Medical Center, Leiden, the Netherlands; Department of Neurology (Dr. Nevsimalova), 1st Medical Faculty, Charles University, Prague, Czech Republic; Department of Neurology (Drs. Uchino and Nishida), Kumamoto University, School of Medicine, Kumamoto, Japan;...
- ORCID
- Venue
- Neurology
- Published
- 2001-12-26
- Volume
- 57
- Issue
- 12
- Pages
- 2253-2258
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2054088581
- Cited by
- 415
- References
- 1
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 5 · 2023: 10 · 2022: 12 · 2021: 8 · 2020: 8 · 2019: 10 · 2018: 11 · 2017: 10 · 2016: 17 · 2015: 13 · 2014: 14 · 2013: 19 · 2012: 18
- FWCI
- 13.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k01mh001600-04, 5r01ns027710-12)
- National Institute of Mental Health (MH-40041, MH 01600)
- National Institute of Neurological Disorders and Stroke (NS-23724, NS 33797, NS27710)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- orexin-A, orexin, narcolepsy, cerebrospinal fluid, Guillain-Barré syndrome, hypothalamic dysfunction, blood-brain barrier, head trauma, Alzheimer's disease, Parkinson's disease, multiple sclerosis, diagnostic biomarkers
- MeSH terms
- Orexins, Carrier Proteins, Humans, Narcolepsy, Nervous System Diseases, Neuropeptides, Radioimmunoassay, Sensitivity and Specificity, Intracellular Signaling Peptides and Proteins
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