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Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study
Open accessAbstract
Sleep-wake disturbances (SWD) are common after traumatic brain injury (TBI). In acute TBI, we recently found decreased CSF levels of hypocretin-1, a wake-promoting neurotransmitter. In the present study, we aimed to delineate the frequency and clinical characteristics of post-traumatic SWD, to assess CSF hypocretin-1 levels 6 months after TBI, and to identify risk factors for posttraumatic SWD. A total of 96 consecutive patients were enrolled within the first 4 days after TBI. Six months later, out of 76 TBI patients, who did not die and who did not move to foreign countries, we included 65 patients (86%, 53 males, mean age 39 years) in our study. Patients were examined using interviews, questionnaires, clinical examinations, computed tomography of the brain, laboratory tests (including CSF hypocretin-1 levels, and HLA typing), conventional polysomnography, maintenance of wakefulness and multiple sleep latency tests (MSLT) and actigraphy. Potential causes of post-traumatic SWD were assessed according to international criteria. New-onset sleep-wake disturbances following TBI were found in 47 patients (72%): subjective excessive daytime sleepiness (EDS; defined by the Epworth Sleepiness Scale > or = 10) was found in 18 (28%), objective EDS (as defined by mean sleep latency < 5 min on MSLT) in 16 (25%), fatigue (daytime tiredness without signs of subjective or objective EDS) in 11 (17%), post-traumatic hypersomnia 'sensu strictu' (increased sleep need of > or = 2 h per 24 h compared to pre-TBI) in 14 (22%) patients and insomnia in 3 patients (5%). In 28 patients (43% of the study population), we could not identify a specific cause of the post-traumatic SWD other than TBI. Low CSF hypocretin-1 levels were found in 4 of 21 patients 6 months after TBI, as compared to 25 of 27 patients in the first days after TBI. Hypocretin levels 6 months after TBI were significantly lower in patients with post-traumatic EDS. There were no associations between post-traumatic SWD and severity or localization of TBI, general clinical outcome, gender, pathological neurological findings and HLA typing. However, post-traumatic SWD correlated with impaired quality of life. These results suggest that sleep-wake disturbances, particularly EDS, fatigue and hypersomnia are common after TBI, and significantly impair quality of life. In almost one out of two patients, post-traumatic SWD appear to be directly related to the TBI. An involvement of the hypocretin system in the pathophysiology of post-traumatic SWD appears possible. Other risk factors predisposing towards the development of post-traumatic SWD were not identified.
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“Patients with mild TBI still experience sleep disorders,59,60 and show decreased orexin in the CSF,56,57”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [57]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Injury to ascending arousal pathways from the brainstem may contribute, but recent findings suggest a key role for the neuropeptides hypocretin-1 and -2 (also known as orexin-A and -B).2,4,5”
From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [2]
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“Even after 6 months recovery, many TBI patients with EDS have persistently low hypocretin-1 levels.2”
From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [2]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Coma and obtundation are common during the acute period, but even after 6 months recovery, 43% of patients have symptoms of sleep disorders.2,3”
From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [2]
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“25/27 patients had low levels of CSF hypocretin after acute injury (1–4 days post-injury).”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [57]
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“Hypocretin levels 6 months after TBI were significantly lower in patients with post-traumatic excessive daytime sleepiness.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [57]
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“Low CSF hypocretin levels, as defined as less than 320 pg/mL, were found in 4 of 21 patients 6 months after TBI.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [57]
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“Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood.”
From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [2]
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“In a prospective study of 65 TBI patients, 1 in 4 patients reported excessive daytime sleepiness (EDS) irrespective of the location or severity of the head trauma.2”
From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [2]
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Citations
Cites
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MethodMaas, A. I. R., Hukkelhoven, C. W. P. M., Marshall, L. F., & Steyerberg, E. W. (2005) · Neurosurgery · doi:10.1227/01.neu.0000186013.63046.6b · Cited by 943
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ResultThe diagnosis of head injury requires a classification based on computed axial tomography.
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Lumba‐Brown, A., Yeates, K. O., Sarmiento, K., Breiding, M. J., Haegerich, T. M., Gioia, G. A., Turner, M., Benzel, E. C., Suskauer, S. J., Giza, C. C., et al. (2018) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2018.2853 · Cited by 603
Mathias, J. L., & Alvaro, P. K. (2012) · Sleep Medicine · doi:10.1016/j.sleep.2012.04.006 · Cited by 506
Evidence‐Based Recommendations for the Assessment and Management of Sleep Disorders in Older Persons
Bloom, H. G., Ahmed, I., Alessi, C. A., Ancoli‐Israel, S., Buysse, D. J., Kryger, M. H., Phillips, B. A., Thorpy, M. J., Vitiello, M. V., & Zee, P. C. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02220.x · Cited by 464
Sleep disturbance and melatonin levels following traumatic brain injury
Shekleton, J. A., Parcell, D. L., Redman, J. R., Phipps‐Nelson, J., Ponsford, J. L., & Rajaratnam, S. M. W. (2010) · Neurology · doi:10.1212/wnl.0b013e3181e0438b · Cited by 248
REM Sleep Instability – A New Pathway for Insomnia?
Riemann, D. W., Spiegelhalder, K., Nissen, C., Hirscher, V., Baglioni, C., & Feige, B. (2012) · Pharmacopsychiatry · doi:10.1055/s-0031-1299721 · Cited by 254
Metadata
- Authors
- Baumann, C. R., Werth, E., Stocker, R., Ludwig, S., & Bassetti, C. L.
- Affiliations
- University Hospital Zurich (CH)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05-29
- Volume
- 130
- Issue
- 7
- Pages
- 1873-1883
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2145062984
- Cited by
- 380
- References
- 53
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 12 · 2023: 9 · 2022: 21 · 2021: 15 · 2020: 19 · 2019: 24 · 2018: 34 · 2017: 20 · 2016: 30 · 2015: 32 · 2014: 26 · 2013: 35 · 2012: 22
- FWCI
- 17.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, sleep-wake disturbances, orexin-A, cerebrospinal fluid, excessive daytime sleepiness, insomnia, fatigue, risk factors, HLA typing, multiple sleep latency test, actigraphy, polysomnography, HLA-DR
- MeSH terms
- Orexins, Adolescent, Adult, Aged, Brain Injuries, Female, Humans, Male, Middle Aged, Neuropeptides, Prognosis, Prospective Studies, Quality of Life, Risk Factors, Polysomnography, Sleep Disorders, Circadian Rhythm, Glasgow Outcome Scale, Intracellular Signaling Peptides and Proteins
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