Background: This study aimed to quantitatively analyse ultra-early brain diffusion-weighted magnetic resonance imaging (DW-MRI) findings to determine the apparent diffusion coefficient (ADC) threshold associated with neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). Methods: This retrospective study included adult survivors of comatose OHCA who underwent DW-MRI imaging scans using a 3-T MRI scanner within 6 h of the return of spontaneous circulation (ROSC). We investigated the association between neurological outcomes and ADC values obtained through voxel-based analysis on DW-MRI. Additionally, we constructed multivariable logistic regression models with pupillary light reflex (PLR), serum neuron-specific enolase (NSE), and ADC values as independent variables to predict poor neurological outcomes. The primary outcome was poor neurological outcome 6 months after ROSC, determined by the Cerebral Performance Category 3–5. Results: Overall, 131 patients (26% female) were analysed, of whom 74 (57%) showed poor neurological outcomes. The group with a poor neurological outcome had lower mean whole brain ADC values (739.1 vs. 787.1 × 10^–6 mm/s) and higher percentages of voxels with ADC below threshold in all ranges (250–1150) (all P < 0.001). The mean whole brain ADC values (area under the receiver operating characteristic curve [AUC] 0.83) and the percentage of voxels with ADC below 600 (AUC 0.81) had the highest sensitivity of 51% (95% confidence interval [CI] 39.4–63.1; cut-off value ≤ 739.2 × 10⁻⁶ mm²/s and > 17.2%, respectively) when the false positive rate (FPR) was 0%. In the multivariable model, which also included PLR, NSE, and mean whole brain ADC values, poor neurological outcome was predicted with the highest accuracy (AUC 0.91; 51% sensitivity). This model showed more accurate prediction and sensitivity at an FPR of 0% than did the combination of PLR and NSE (AUC 0.86; 30% sensitivity; P = 0.03). Conclusions: In this cohort study, early voxel-based quantitative ADC analysis after ROSC was associated with poor neurological outcomes 6 months after cardiac arrest. The mean whole brain ADC value demonstrated the highest sensitivity when the FPR was 0%, and including it in the multivariable model improved the prediction of poor neurological outcomes.

We aimed to investigate intracranial pressure (ICP) changes over time and the neurologic prognosis for out-of-hospital cardiac arrest (OHCA) survivors who received targeted temperature management (TTM). ICP was measured immediately after return of spontaneous circulation (ROSC) (day 1), then at 24 h (day 2), 48 h (day 3), and 72 h (day 4), through connecting a lumbar drain catheter to a manometer or a LiquoGuard machine. Neurological outcomes were determined at 3 months after ROSC, and a poor neurological outcome was defined as Cerebral Performance Category 3–5. Of the 91 patients in this study (males, n = 67, 74%), 51 (56%) had poor neurological outcomes. ICP was significantly higher in the poor outcome group at each time point except day 4. ICP elevation was highest between days 2 and 3 in the good outcome group, and between days 1 and 2 in the poor outcome group. However, there was no difference in total ICP elevation between the poor and good outcome groups (3.0 vs. 3.1; p = 0.476). All OHCA survivors who had received TTM had elevated ICP, regardless of neurologic prognosis. However, the changing pattern of ICP levels differed depending on the neurological outcome.

Background: Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade. Methods: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019–July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007). Results: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 μg/L [interquartile range [IQR], 0.146–0.823 vs 0.754 μg/L [IQR, 0.317–2.228], P = .03). We report a positive correlation between serum S100B and Qa (R² = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556–0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 μg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R² = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629–0.954]) compared with the total cohort. Conclusions: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons.

We investigated prognostic strategies for predicting good outcomes in the early stage of post-cardiac-arrest care using multiple prognostic tests that are available until 24 h after the return of spontaneous circulation (ROSC). A retrospective analysis was conducted on 138 out-of-hospital cardiac-arrest patients who underwent prognostic tests, including the gray–white-matter ratio (GWR-BG), the Glasgow Coma Scale motor (GCS-M) score before sedative administration, and the neuron-specific enolase (NSE) level measured at 24 h after the ROSC. We investigated the prognostic performances of the tests as single predictors and in various combination strategies. Classification and regression-tree analysis were used to provide a reliable model for the risk stratification. Out of all the patients, 55 (44.0%) had good outcomes. The NSE level showed the highest prognostic performance as a single prognostic test and provided improved specificities (>70%) and sensitivities (>98%) when used in combination strategies. Low NSE levels (≤32.1 ng/mL) and high GCS-M (≥4) scores identified good outcomes without misclassification. The overall accuracy for good outcomes was 81.8%. In comatose patients with low NSE levels or high GCS-M scores, the premature withdrawal of life-sustaining therapy should be avoided, thereby complying with the formal prognostication-strategy algorithm after at least 72 h from the ROSC.

We aimed to explore the stratification of physiological factors affecting cerebral perfusion pressure, including arterial oxygen tension, arterial carbon dioxide tension, mean arterial pressure, intracranial pressure (ICP), and blood-brain barrier (BBB) status, with respect to primary or secondary brain injury (PBI or SBI) after out-of-hospital cardiac arrest (OHCA). Among the retrospectively enrolled 97 comatose OHCA survivors undergoing post-cardiac arrest (PCA) care, 46 (47.4%) with already established PBI (high signal intensity (HSI) on diffusion-weighted imaging (DWI) had higher ICP (p = 0.02) and poorer BBB status (p < 0.01) than the non-HSI group. On subgroup analysis within the non-HSI group to exclude the confounding effect of already established PBI, 40 (78.4%) patients with good neurological outcomes had lower ICP at 24 h (11.0 vs. 16.0 mmHg, p < 0.01) and more stable BBB status (p = 0.17 in pairwise comparison) compared to those with poor neurological outcomes, despite the non-significant differences in other physiological factors. OHCA survivors with HSI on DWI showed significantly higher ICP and poorer BBB status at baseline before PCA care than those without HSI. Despite the negative DWI findings before PCA care, OHCA survivors have a cerebral penumbra at risk for potentially leading the poor neurological outcome from unsuppressed SBI, which may be associated with increased ICP and BBB permeability.