Neuroaxonal Injury May Mediate the Association Between Hyperglycemia and Prognosis in Spontaneous Subarachnoid Hemorrhage.

Hyperglycemia during early brain injury (EBI) period after spontaneous subarachnoid hemorrhage (SAH) is associated with poor outcome, but the underlying physiopathology is unknown. This study assessed if hyperglycemia during EBI is associated with markers of neuroaxonal injury and whether these biomarkers partially account for the association between hyperglycemia and poor clinical outcome. Ninety-two SAH patients admitted within 24 h of bleeding onset were prospectively included. Glucose levels were measured at arrival and every 6 h for 72 h. Serum neurofilament light chain (NFL) levels were measured at 72 h. Functional outcome was assessed with the modified Rankin Scale (mRS) at 90 days (poor outcome, mRS > 2). The association between glucose metrics, NFL levels, and clinical outcome was assessed with univariate and multivariate analyses. Mediation analysis was performed to examine the potential chain in which NFL may mediate the relationship between glucose and functional outcome. Higher glucose and NFL levels during EBI were associated with poor clinical outcome in adjusted analysis. NFL levels were associated with older age, higher initial severity, and higher glucose levels during EBI period. In adjusted mediation analyses, the association between glucose and clinical outcome was significantly mediated by NFL levels. The mediator NFL explained 25% of the association between glucose during EBI period and poor functional outcome at 90 days. In SAH, the association between glucose levels during EBI and poor clinical outcome might be significantly mediated by NFL levels. The link between hyperglycemia and poor clinical outcome might be explained in part through secondary neuroaxonal injury.

Effects of Achieving Rapid, Intensive, and Sustained Blood Pressure Reduction in Intracerebral Hemorrhage Expansion and Functional Outcome.

BACKGROUND AND OBJECTIVES: The time taken to achieve blood pressure (BP) control could be pivotal in the benefits of reducing BP in acute intracerebral hemorrhage (ICH). We aimed to assess the relationship between the rapid achievement and sustained maintenance of an intensive systolic BP (SBP) target with radiologic, clinical, and functional outcomes. METHODS: Rapid, Intensive, and Sustained BP lowering in Acute ICH (RAINS) was a multicenter, prospective, observational cohort study of adult patients with ICH <6 hours and SBP ≥150 mm Hg at 4 Comprehensive Stroke Centers during a 4.5-year period. Patients underwent baseline and 24-hour CT scans and 24-hour noninvasive BP monitoring. BP was managed under a rapid (target achievement ≤60 minutes), intensive (target SBP <140 mm Hg), and sustained (target stability for 24 hours) BP protocol. SBP target achievement ≤60 minutes and 24-hour SBP variability were recorded. Outcomes included hematoma expansion (>6 mL or >33%) at 24 hours (primary outcome), early neurologic deterioration (END, 24-hour increase in NIH Stroke Scale score ≥4), and 90-day ordinal modified Rankin scale (mRS) score. Analyses were adjusted by age, sex, anticoagulation, onset-to-imaging time, ICH volume, and intraventricular extension. RESULTS: We included 312 patients (mean age 70.2 ± 13.3 years, 202 [64.7%] male). Hematoma expansion occurred in 70/274 (25.6%) patients, END in 58/291 (19.9%), and the median 90-day mRS score was 4 (interquartile range, 2-5). SBP target achievement ≤60 minutes (178/312 [57.1%]) associated with a lower risk of hematoma expansion (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.23-0.77), lower END rate (aOR 0.43, 95% CI 0.23-0.80), and lower 90-day mRS scores (aOR 0.48, 95% CI 0.32-0.74). The mean 24-hour SBP variability was 21.0 ± 7.6 mm Hg. Higher 24-hour SBP variability was not related to expansion (aOR 0.99, 95% CI 0.95-1.04) but associated with higher END rate (aOR 1.15, 95% CI 1.09-1.21) and 90-day mRS scores (aOR 1.06, 95% CI 1.04-1.10). DISCUSSION: Among patients with acute ICH, achieving an intensive SBP target within 60 minutes was associated with lower hematoma expansion risk. Rapid SBP reduction and stable sustention within 24 hours were related to improved clinical and functional outcomes. These findings warrant the design of randomized clinical trials examining the impact of effectively achieving rapid, intensive, and sustained BP control on hematoma expansion. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in adults with spontaneous ICH and initial SBP ≥150 mm Hg, lowering SBP to <140 mm Hg within the first hour and maintaining this for 24 hours is associated with decreased hematoma expansion.

Computed tomography perfusion as an early predictor of malignant cerebral infarction.

INTRODUCTION: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks. MATERIALS AND METHODS: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F-score was calculated as an indicator of precision and sensitivity. RESULTS: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F-score 0.52, Youden's index 6), than with perfusion-based measures: relative cerebral blood volume threshold <40% (AUC 0.87, F-score 0.71, Youden's index 34 mL) or relative cerebral blood flow threshold <35% (AUC 0.87, F-score 0.62, Youden's index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS. DISCUSSION AND CONCLUSION: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment.

Aneurysmal subarachnoid haemorrhage: Volumetric quantification of the blood distribution pattern to accurately predict the ruptured aneurysm location.

BACKGROUND: In spontaneous subarachnoid haemorrhage (SAH) accurate determination of the bleeding source is paramount to guide treatment. Traditionally, the bleeding pattern has been used to predict the aneurysm location. Here, we have tested a software-based tool, which quantifies the volume of intracranial blood and stratifies it according to the regional distribution, to predict the location of the ruptured aneurysm. METHODS: A consecutive series of SAH patients admitted to a single tertiary centre between 2012-2018, within 72 h of onset, harbouring a single intracranial aneurysm. A semi-automatized method of blood quantification, based on the relative density increase, was applied to initial non-contrast CTs. Five regions were used to define the bleeding patterns and to correlate them with aneurysm location: perimesencephalic, interhemispheric, right/left hemisphere and intraventricular. RESULTS: 68 patients were included for analysis. There was a strong association between the distribution of blood and the aneurysm location (p < 0.001). In particular: ACom and interhemispheric fissure (p < 0.001), MCA and ipsilateral hemisphere (p < 0.001), ICA and ipsilateral hemisphere and perimesencephalic cisterns (p < 0.001), PCom and hemispheric, perimesencephalic and intraventricular (p = 0.019), and PICA and perimesencephalic and intraventricular (p < 0.001). The internal diagnostic value was high (AUROC ≥ 0.900) for these locations. CONCLUSION: Regional automatised volumetry seems a reliable and objective tool to quantify and describe the distribution of blood within the subarachnoid spaces. This tool accurately predicts the location of the ruptured aneurysm; its use may be prospectively considered in the emergency setting when speed and simplicity are attained.

Influence of Hospital Type on Outcomes of Patients With Acute Spontaneous Intracerebral Hemorrhage: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Whether the outcome of patients with spontaneous intracerebral hemorrhage (ICH) differs depending on the type of hospital where they are admitted is uncertain. The objective of this study was to determine influence of hospital type at admission (telestroke center [TSC], primary stroke center [PSC], or comprehensive stroke center [CSC]) on outcome for patients with ICH. We hypothesized that outcomes may be better for patients admitted to a CSC. METHODS: This is a multicenter prospective observational and population-based study of a cohort of consecutively recruited patients with ICH (March 2020-March 2022). We included all patients with spontaneous ICH in Catalonia (Spain) who had a pre-ICH modified Rankin scale (mRS) score of 0-3 and who were admitted to the hospital within 24 hours of onset. We compared patients admitted to a TSC/PSC (n = 641) or a CSC (n = 1,320) and also analyzed the subgroup of patients transferred (n = 331) or not transferred (n = 310) from a TSC/PSC to a CSC. The main outcome was the 3-month mRS score obtained by blinded investigators. Outcomes were compared using adjusted ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI for a shift in mRS scores. A propensity score matching (PSM) analysis was performed for the subgroup of transferred patients. RESULTS: Relevant data were obtained from 1961 of a total of 2,230 patients, with the mean (SD) age of 70 (14.1) years, and 713 (38%) patients were women. After adjusting for confounders (age, NIH Stroke Scale score, intraventricular hemorrhage, hematoma volume, and pre-ICH mRS score), type of hospital of initial admission (CSC vs TSC/PSC) was not associated with outcome (adjusted common OR 1.13, 95% CI 0.93-1.38). A PSM analysis indicated that transfer to a CSC was not associated with more favorable outcomes (OR 0.77, 95% CI 0.55-1.10; p = 0.16). DISCUSSION: In this population-based study, we found that, after adjusting for confounders, hospital types were not associated with functional outcomes. In addition, for patients who were transferred from a TSC/PSC to a CSC, PSM indicated that outcomes were similar to nontransferred patients. Our findings suggest that patient characteristics are more important than hospital characteristics in determining outcome after ICH. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03956485.