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Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

In traumatic brain injury (TBI), diffuse axonal injury (DAI) accounts for a significant portion of intra-axial injury. Past studies have shown diffusion-weighted magnetic resonance imaging (DWI) to be sensitive in detecting visible DAI lesions; however, diffuse lesions are frequently not seen on imaging. In this study, we focused on detecting nonvisible, quantifiable diffusion changes using an apparent diffusion coefficient (ADC) map. Findings were correlated to injury using admission Glasgow Coma Scale (GCS) and to long-term outcome using Glasgow Outcome Score (GOS) at 6-12 months after injury. Thirty-seven adults with TBI (mean age 32 yrs, range 18-70 yrs) were studied in addition to 35 age-matched controls. DWI was performed using single-shot echo planar technique (TR/TE = 4,000/110 milliseconds; 5 mm thick). Twenty-eight regions of interest (ROI) were manually drawn on the corresponding ADC maps in predetermined locations and ADC values were recorded. All ROIs excluded visibly abnormal areas on the T2-weighted images. Brain regions were categorized into 5 zones: peripheral gray matter, peripheral white matter, deep gray matter, deep white matter, and posterior fossa. Admission GCS score was dichotomized into “severe” (3-8) or “mild/moderate” (9-15) injury. The GOS was dichotomized into “poor” (1-3) or “good” outcome (4-5). Statistical analysis was performed using the ANOVA method with Scheffe and Tukey HSD post hoc comparisons. In the ROIs, DWI was able to detect greater abnormalities than conventional MRI. Mean ADC values in all brain zones were significantly different between subjects and controls ( p ≤ .05). When comparing zones, the “severe” injury GCS category had significantly higher mean ADC values than the controls ( p ≤ .05). In the posterior fossa, the “severe” injury group had significantly different mean ADC values than the “mild/moderate” injury group ( p = .034). When focusing on the GOS, the “good” outcome group had significantly higher mean ADC values when compared to controls ( p ≤ .05). In the deep gray matter, the “good” and “poor” outcome groups showed a significant mean ADC difference ( p = .0001). This study concludes that ADC maps can be used to detect nonvisible DAI, which is frequently not seen, and that injuries in the deep gray matter can be used to predict outcome in adult TBI patients.

Traumatic brain injury (TBI) is a common cause of death and disability. Predicting prognosis for these patients is often difficult. We studied injuries detected by different radiological modalities and organized by brain regions in a group of adult TBI patients. These findings were correlated with patient Glasgow Outcome Scores (GOS) at 6 to 12 months after injury. The three modalities studied were computed tomography (CT), T2-weighted magnetic resonance imaging (T2), and fluid-attenuated inversion recovery (FLAIR) MRI. Injuries in 16 brain regions (organized into three zones) were analyzed to determine whether geographic distribution of damage was predictive of outcome. The purpose of this study was to identify which modality and region(s) of injury best predict long-term outcome. The patient population consisted of 39 adults (mean age 35.3 yrs; range 18-68 yrs) who were admitted to Loma Linda University Medical Center between February 2001 and May 2003. CT, T2, and FLAIR images were obtained for each patient as well as their GOS score at 6 to 12 months post-TBI. Intraparenchymal lesions were traced, counted, and measured using a semi-automated computer software program ( Image Pro Plus ) and confirmed by a board-certified neuroradiologist (K.A.T.). The traced lesions were converted to lesion volumes based on slice thickness and pixel size. The brain was artificially divided into 16 anatomical regions, which were additionally grouped into three zones (superficial, deep, and posterior fossa). The GOS results were dichotomized into good outcomes (GOS = 4-5) and poor outcomes (GOS = 1-3). Statistical analysis was performed using parametric tests, including one- and two-way ANOVA tests with Scheffe post hoc comparisons. The extent of injuries detected by T2 and FLAIR images were significantly different between good and poor groups while injuries on CT did not differ. Injuries on FLAIR were most correlated with outcome among the three modalities. No single brain zone injury was a stronger predictor of outcome among the three. However, injuries in the brain stem (BS), frontal white matter (FWM), and thalamus (THAL) were the strongest predictors of outcome among the individual brain regions. The study results conclude that FLAIR is superior to CT and T2-weighted MRI for prognostic determination and injuries in the BS, FWM, and THAL are most predictive of outcome in adults with TBI.

High resolution susceptibility weighted imaging (SWI) is a more sensitive imaging modality to detect diffuse hemorrhagic axonal injury than conventional T2-weighted gradient-recalled echo sequences. There is some evidence that traumatic injuries to deeper brain structures may be related to the long term neurologic outcome. In this study, hemorrhagic lesions were analyzed for volume and anatomical distribution to determine the relationship between regional injury and level of disability measured by the Glasgow Outcome Score (GOS) at 6 months or greater. 76 adult patients presenting with traumatic brain injury were imaged with SWI sequences along with a standard magnetic resonance imaging protocol. SWI scans were imported into computer software (Image Pro Plus, Media Cybernetics Inc.) to measure the area of each hypointense lesion. The volume was extrapolated by multiplying effective slice thickness by area. Each lesion was assigned an anatomical region out of 16 possible locations such as frontal or parietal lobes, as well as categories for deeper brain structures such as basal ganglia or corpus callosum. The GOS was determined on 47 of these patients at 6 months or greater. Hemorrhagic volumes were compared to GOS in each brain region individually and to grouped regions that differentiated more superficial locations from deeper brain structures. Significance was reported at p ≤ 0.05. Mean hemorrhage volume was significantly higher in patients with poor outcomes (GOS of 1 to 3) when compared to those with good outcomes (GOS 4-5) in the grouped category including the thalamus, basal ganglia, and corpus callosum. There were non-significant trends of higher volumes with poor outcomes in the grouped category that included frontal, parietal, temporal, and occipital regions as well as the category that combined brain stem and cerebellum. Results showed 9 of the 16 locations demonstrating higher volumes of hemorrhagic lesions in patients with poor outcome. The increased sensitivity of SWI allows for detection of lesions that may not be observed in other modalities. Deep brain structures such as the thalamus, basal ganglia, and corpus callosum may be important in predicting long term outcome as represented by the significantly higher lesion volumes in patients with a GOS of 1-3 indicating death, vegetative state, or severe disability. This supports what has previously been reported and may be of use in tailoring a rehabilitative treatment plan.