Mitochondrial dysfunction may be central to the pathophysiology of traumatic brain injury (TBI) and often can be recognized cytologically by changes in mitochondrial ultrastructure. This study is the first to broadly characterize and quantify mitochondrial morphologic alterations in surgically resected human TBI tissues from three contiguous cortical injury zones. These zones were designated as injury center (Near), periphery (Far), and Penumbra. Tissues from 22 patients with TBI with varying degrees of damage and time intervals from TBI to surgical tissue collection within the first week post-injury were rapidly fixed in the surgical suite and processed for electron microscopy. A large number of mitochondrial structural patterns were identified and divided into four survival categories: normal, normal reactive, reactive degenerating, and end-stage degenerating profiles. A tissue sample acquired at 38 hours post-injury was selected for detailed mitochondrial quantification, because it best exhibited the wide variation in cellular and mitochondrial changes consistently noted in all the other cases. The distribution of mitochondrial morphologic phenotypes varied significantly between the three injury zones and when compared with control cortical tissue obtained from an epilepsy lobectomy. This study is unique in its comparative quantification of the mitochondrial ultrastructural alterations at progressive distances from the center of injury in surviving TBI patients and in relation to control human cortex. These quantitative observations may be useful in guiding the translation of mitochondrial-based neuroprotective interventions to clinical implementation.
Accurate prognostication of outcomes following traumatic brain injury (TBI) affects not only the aggressiveness of intervention and therapeutic decision-making, but also the clinicians' ability to provide reliable expectations. To investigate the relative ability of clinicians to accurately predict a patient's outcomes when compared to point of care prognostic models, we surveyed clinical providers of 86 patients with moderate-severe TBI at admission, day 3, and day 7 post-injury for a patient's predicted functional outcome at six months and mortality. The predicted mortality and functional outcomes were compared to actual occurrence of 14 day mortality and functional outcomes at six months. A prognostic score was then calculated utilizing the Corticoid Randomization After Significant Head Injury (CRASH) and International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) models and categorized as high, intermediate, and low likelihood of mortality or poor functional outcome and compared to clinical predictions. Overall, clinicians of varying backgrounds showed an accurate prediction of survival (87.2-97.4%) but struggled in prognosticating poor functional outcomes (24.3-36.6%). These values did not statistically improve over 7 days. Stratified CRASH (87.2%) and IMPACT (84.9%) accuracy rates were statistically better than clinical judgment alone in predicting functional outcomes (p<0.0001). Prognostic models calculated at admission showed to be potentially useful in conjunction with clinical judgment in accurately predicting both survival and six month functional outcomes.
There is no gold standard for the diagnosis of mTBI. BAM screening is a useful diagnostic adjunct in patients with mTBI and may facilitate decision making. An abnormal BAM reading adds significance to LOC as a predictor of a new abnormality on head CT. In our study, opting not to CT scan patients with a normal BAM signal would have missed no new CT findings and no patients who required medical intervention for TBI, at a cost savings of $202,950.
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