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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]
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.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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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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In the citing paper
“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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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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