title: Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital of Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Baumann
authors.forename: Esther
authors.initials: E
authors.lastname: Werth
authors.forename: Reto
authors.initials: R
authors.lastname: Stocker
authors.forename: Silke
authors.initials: S
authors.lastname: Ludwig
authors.forename: Claudio L
authors.initials: CL
authors.lastname: Bassetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000523:psychology*; D005260:Female; D023261:Glasgow Outcome Scale; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D000068797:Orexins; D017286:Polysomnography; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D012307:Risk Factors; D020178:Sleep Disorders, Circadian Rhythm / Q000134:cerebrospinal fluid / Q000209:etiology*
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins