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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IntroductionThe optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism.MethodsIn twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios.ResultsBrain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu.ConclusionsArterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury.

IntroductionHyperglycaemia is detrimental, but maintaining low blood glucose levels within tight limits is controversial in patients with severe traumatic brain injury, because decreased blood glucose levels can induce and aggravate underlying brain injury.MethodsIn 228 propensity matched patients (age, sex and injury severity) treated in our intensive care unit (ICU) from 2000 to 2004, we retrospectively evaluated the influence of different predefined blood glucose targets (3.5 to 6.5 versus 5 to 8 mmol/l) on frequency of hypoglycaemic and hyperglycaemic episodes, insulin and norepinephrine requirement, changes in intracranial pressure and cerebral perfusion pressure, mortality and length of stay on the ICU.ResultsMortality and length of ICU stay were similar in both blood glucose target groups. Blood glucose values below and above the predefined levels were significantly increased in the 3. 5 to 6.5 mmol/l group, predominantly during the first week. Insulin and norepinephrine requirements were markedly increased in this group. During the second week, the incidences of intracranial pressure exceeding 20 mmHg and infectious complications were significantly decreased in the 3.5 to 6.5 mmol/l group.ConclusionMaintaining blood glucose within 5 to 8 mmol/l appears to yield greater benefit during the first week. During the second week, 3.5 to 6.5 mmol/l is associated with beneficial effects in terms of reduced intracranial hypertension and decreased rate of pneumonia, bacteraemia and urinary tract infections. It remains to be determined whether patients might profit from temporally adapted blood glucose limits, inducing lower values during the second week, and whether concomitant glucose infusion to prevent hypoglycaemia is safe in patients with post-traumatic oedema.

Introduction Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined.