Sleep-wake disturbances in hospitalized patients with traumatic brain injury: association with brain trauma but not with an abnormal melatonin circadian rhythm

Study Objectives: To test whether the sleep-wake cycle disruption in patients hospitalized with traumatic brain injury (TBI) (1) is also found in patients with traumatic injuries other than TBI (non-TBI) and (2) is associated with a weaker or abnormal circadian clock signal. Methods: Forty-two non-mechanically ventilated and non-sedated patients hospitalized for moderate-to-severe TBI were compared to 34 non-TBI patients. They wore wrist actigraphs for 9.4 +/- 4.2 days, starting 19.3 +/- 12.6 days post-injury. Of these, 17 TBI and 14 non-TBI patients had their urine collected every hour for 25 hours, starting 18.3 +/- 12.3 days post-injury. We calculated urinary 6-sulfatoxymelatonin concentration to obtain total 24-hour excretion, excretion onset, offset, duration, amplitude, and acrophase. Using Student's t-tests, we compared groups on actigraphy (daytime activity ratio, nighttime total sleep time, and fragmentation index) and melatonin variables. We investigated associations between melatonin and actigraphy variables using Pearson's correlations. Results: TBI patients had poorer daytime activity ratio (TBI: 77.5 +/- 9.4%; non-TBI: 84.6 +/- 6.9%), shorter nighttime total sleep time (TBI: 353.5 +/- 96.6 min; non-TBI: 421.2 +/- 72.2 min), and higher fragmentation index (TBI: 72.2 +/- 30.0; non-TBI: 53.5 +/- 23.6) (all p-values < 0.01). A melatonin rhythm was present in both groups, and no group differences were found on melatonin variables. No associations were found between melatonin and actigraphy variables in TBI patients. Conclusion: Moderate-to-severe TBI patients have more serious sleep-wake disturbances than non-TBI patients hospitalized in the same environment, suggesting that the brain injury itself alters the sleep-wake cycle. Despite their deregulated 24-hour sleep-wake cycle, TBI patients have a normal circadian clock signal.