A daily temperature rhythm in the human brain predicts survival after brain injury
Rzechorzek, Nina M
Thrippleton, Michael J
Chappell, Francesca M
The CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators
O'Neill, John S
Oxford University Press (OUP)
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Rzechorzek, N. M., Thrippleton, M. J., Chappell, F. M., Mair, G., Ercole, A., Cabeleira, M., The CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators, et al. (2022). A daily temperature rhythm in the human brain predicts survival after brain injury. Brain https://doi.org/10.1093/brain/awab466
Patients undergo interventions to achieve a ‘normal’ brain temperature; a parameter that remains undefined for humans. The profound sensitivity of neuronal function to temperature implies the brain should be isothermal, but observations from patients and non-human primates suggest significant spatiotemporal variation. We aimed to determine the clinical relevance of brain temperature in patients by establishing how much it varies in healthy adults. We retrospectively screened data for all patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury High Resolution Intensive Care Unit Sub-Study. Only patients with direct brain temperature measurements without targeted temperature management were included. To interpret patient analyses, we prospectively recruited 40 healthy adults (20 males, 20 females, 20-40 years) for brain thermometry using magnetic resonance spectroscopy. Participants were scanned in the morning, afternoon, and late evening of a single day. In patients (n=114), mean brain temperature (38.5±0.8°C) exceeded body temperature (37.5±0.5°C, P<0.0001) and ranged from 32.6 to 42.3°C. Of 100 patients eligible for brain temperature rhythm analysis, 25 displayed a daily rhythm, and the brain temperature range decreased in older patients (P=0.018). In healthy participants, mean brain temperature (38.5±0.4°C) exceeded oral temperature (36.0±0.5°C) and was 0.36°C higher in luteal females relative to follicular females and males (P=0.0006 and P<0.0001, respectively). Temperature increased with age, most notably in deep brain regions (0.6°C over 20 years, P=0.0002), and varied spatially by 2.41±0.46°C with highest temperatures in the thalamus. 1 Brain temperature varied by time of day, especially in deep regions (0.86°C, P=0.0001), and was lowest at night. From the healthy data we built HEATWAVE—a chronotype-controlled 4-dimensional map of human brain temperature. Testing the clinical relevance of HEATWAVE in patients, we found that lack of a daily brain temperature rhythm increased the odds of death in intensive care 21-fold (P=0.016), whilst absolute temperature maxima or minima did not predict outcome. A warmer mean brain temperature was associated with survival (P=0.035) however, and ageing by 10 years increased the odds of death 11-fold (P=0.0002). Human brain temperature is higher and varies more than previously assumed—by age, sex, menstrual cycle, brain region, and time of day. This has major implications for temperature monitoring and management, with daily brain temperature rhythmicity emerging as one of the strongest single predictors of survival after brain injury. We conclude that daily rhythmic brain temperature variation—not absolute brain temperature—is one way in which human brain physiology may be distinguished from pathophysiology.
The prospective study was funded by a Medical Research Council Clinician Scientist Fellowship awarded to N.M.R. (MR/S022023/1). J.S.O.N. is supported by the Medical Research Council (MC_UP_1201/4). Some of the data contributing to the retrospective analysis were obtained in the context of CENTER-TBI, a large collaborative project (EC grant 602150) supported by the European Union’s 7th Framework program (FP7/2007-2013). Additional funding for patient data collection was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA). M.J.T. acknowledges funding from the NHS Lothian Research and Development Office.
European Commission (602150)
External DOI: https://doi.org/10.1093/brain/awab466
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333415
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/