Cytotoxic Edema Associated with Hemorrhage Predicts Poor Outcome after Traumatic Brain Injury

Abstract

Magnetic resonance imaging (MRI) is used rarely in the acute evaluation of traumatic brain injury (TBI) but may identify findings of clinical importance not detected by computed tomography (CT). We aimed to characterize the association of cytotoxic edema and hemorrhage, including traumatic microbleeds, on MRI obtained within hours of acute head trauma and investigated the relationship to clinical outcomes. Patients prospectively enrolled in the Traumatic Head Injury Neuroimaging Classification study (NCT01132937) with evidence of diffusion-related findings or hemorrhage on neuroimaging were included. Blinded interpretation of MRI for diffusion-weighted lesions and hemorrhage was conducted, with subsequent quantification of apparent diffusion coefficient (ADC) values. Of 161 who met criteria, 82 patients had conspicuous hyperintense lesions on diffusion-weighted imaging (DWI) with corresponding regions of hypointense ADC in proximity to hemorrhage. Median time from injury to MRI was 21 (10-30) h. Median ADC values per patient grouped by time from injury to MRI were lowest within 24 h after injury. The ADC values associated with hemorrhagic lesions are lowest early after injury, with an increase in diffusion during the subacute period, suggesting transformation from cytotoxic to vasogenic edema during the subacute post-injury period. Of 118 patients with outcome data, 60 had Glasgow Outcome Scale Extended scores £6 at 30/90 days postinjury. Cytotoxic edema on MRI (odds ratio [OR] 2.91 [1.32-6.37], p = 0.008) and TBI severity , p = 0.005) were independent predictors of outcome. These findings suggest that in patients with TBI who had findings of hemorrhage on CT, patients with DWI/ADC lesions on MRI are more likely to do worse.

Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury

“…Acute glibenclamide administration after contusional TBI is likely needed for maximal benefit on hematoma and cytotoxic edema—in mice, both processes approached their “worst” values within 3 hours after CCI. Although both cytotoxic and vasogenic edema are clinically seen in TBI ( 30 , 32 ), recent work confirmed that cytotoxic edema was acute (24 hr) and associated with unfavorable outcome ( 31 ).…”

“…T1-post gadolinium images were obtained at 7 days. Sequences included multiplanar T 1 - and T 2 -weighted anatomical imaging for volumetric analyses (hematoma and edema); multiecho quantitative T 2 relaxometry (quantitative vasogenic edema), multiplanar diffusion/quantitative apparent diffusion coefficient (ADC, quantitative cytotoxic edema), and postgadolinium T 1 -weighted images (BBB integrity) (30–32, 46–48) (Supplemental Methods, http://links.lww.com/CCM/H260). Aside from the contusion, regions of interest (ROIs) included ipsilateral and contralateral cortex, hippocampus, corpus callosum, and thalamus.…”

“…In TBI, these endophenotypes have a variable spatiotemporal evolution with distinct prognostic implications. Cellular/cytotoxic edema develops acutely and is considered highly deleterious to outcome, whereas vasogenic edema is often more space-occupying/compressive with extracellular fluid/plasma protein extravasation (30–33). The two subtypes may require different treatment targets and/or warrant adjustments in dose or timing of the same treatment.…”

Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response

“…Traumatic brain injury affects more than 69 million people worldwide every year (Dewan et al, 2018), leading to chronic comorbidities such as sleep disorders, neuroendocrine dysregulation, post-traumatic epilepsy, or psychiatric problems (Bramlett and Dietrich, 2015). Some of the candidate mechanisms to induce these comorbidities include edema, focal lesions with tissue loss and subdural hemorrhage (van Asch et al, 2010;Jha et al, 2019;Turtzo et al, 2021). Yet, these mechanisms are not present in mild TBI (mTBI), which affects 75% of TBI survivors.…”

Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy

“…However, the environment of TBI lesions is responsive to insults. Various factors can be released leading to neuroinflammation, oxidative stress, and cytotoxic edema [ 16 , 17 , 18 , 19 , 20 ]. These pathological conditions could influence grafted stem cells, including NSCs and mesenchymal stem cells.…”