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.