Mild-to-Moderate Hypothermia for Management of Severe Traumatic Brain Injury in China: History, Current Status, and Future

Use of therapeutic hypothermia to treat patients with severe traumatic brain injury was described more than 50 years ago. Unexpected improvement in some of these patients was attributed to hypothermia, but none of the early studies systematically evaluated the efficacy of hypothermia, and many patients were thought to have been harmed by the treatment, particularly when cooled below 30°C or when cooled for longer than 48 hours. Recent investigations have found that therapeutic moderate hypothermia (32–34°C) for relatively brief durations can improve histological and behavioral outcome following experimental brain injury. Cooling to this degree and duration has not been implicated as a cause for the cardiac arrhythmias, coagulation abnormalities, or infections attributed to hypothermia in the earlier studies. These laboratory investigations also defined several neurochemical mechanisms through which hypothermia may limit secondary brain injury and brain swelling. Four clinical trials of therapeutic moderate hypothermia were completed during the past three years; each detected a beneficial effect from cooling patients with severe traumatic brain injury to 32 to 34°C for up to 48 hours. In the largest of these studies, therapeutic moderate hypothermia was shown to cause a significant improvement in neurological outcomes 3, 6, and 12 months after injury for those patients with an initial Glasgow Coma Scale score of 5 to 7. The improvement in outcome for these patients was associated with a hypothermia-induced reduction of intracranial pressure and cerebrospinal fluid levels of interleukln-1β and glutamate.

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Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury

Frontiers in Neurology ◽

10.3389/fneur.2021.729184 ◽

2021 ◽

Vol 12 ◽

Author(s):

Frederick A. Zeiler ◽

Yasser Iturria-Medina ◽

Eric P. Thelin ◽

Alwyn Gomez ◽

Jai J. Shankar ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Management Strategies ◽

Current Status ◽

Data Sets ◽

Omics Data ◽

Mortality And Morbidity ◽

Daunting Task ◽

Severe Tbi

Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the “one-treatment fits all” approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex “-omics” data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.

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