This study provides Class II evidence that BOLD-CVR identifies CCD in patients with symptomatic unilateral cerebrovascular steno-occlusive disease.

Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) contributes to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. The aim of this study was to investigate the clinical and pathophysiological association between cerebrospinal fluid hemoglobin (CSF-Hb) and SAH-SBI. In a cohort of 47 patients, we collected daily CSF-samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between spectrophotometrically determined CSF-Hb and SAH-SBI. The accuracy of CSF-Hb to monitor for SAH-SBI markedly exceeded that of established methods (AUC: 0.89 [0.85-0.92]). Temporal proteome analysis revealed erythrolysis accompanied by an adaptive macrophage response as the two dominant biological processes in the CSF-space after aneurysm rupture. Ex-vivo experiments on the vasoconstrictive and oxidative potential of Hb revealed critical inflection points overlapping CSF-Hb thresholds in patients with SAH-SBI. Selective depletion and in-solution neutralization by haptoglobin or hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.

Crossed cerebellar diaschisis (CCD) in internal carotid artery (ICA) stroke refers to attenuated blood flow and energy metabolism in the contralateral cerebellar hemisphere. CCD is associated with an interruption of cerebro-cerebellar tracts, but the precise mechanism is unknown. We hypothesized that in patients with ICA occlusions, CCD might indicate severe hemodynamic impairment in addition to tissue damage. Duplex sonography and clinical data from stroke patients with unilateral ICAO who underwent blood oxygen-level-dependent MRI cerebrovascular reserve (BOLD-CVR) assessment were analysed. The presence of CCD (either CCD+ or CCD−) was inferred from BOLD-CVR. We considered regions with negative BOLD-CVR signal as areas suffering from hemodynamic steal. Twenty-five patients were included (11 CCD+ and 14 CCD−). Stroke deficits on admission and at 3 months were more severe in the CCD+ group. While infarct volumes were similar, CCD+ patients had markedly larger BOLD steal volumes than CCD− patients (median [IQR] 122.2 [111] vs. 11.6 [50.6] ml; p < 0.001). Furthermore, duplex revealed higher peak-systolic flow velocities in the intracranial collateral pathways. Strikingly, posterior cerebral artery (PCA)-P2 velocities strongly correlated with the National Institute of Health Stroke Scale on admission and BOLD-CVR steal volume. In patients with strokes due to ICAO, the presence of CCD indicated hemodynamic impairment with larger BOLD-defined steal volume and higher flow in the ACA/PCA collateral system. Our data support the concept of a vascular component of CCD as an indicator of hemodynamic failure in patients with ICAO.

INTRODUCTION Reliable preoperative identification of patients at high risk for early postoperative complications occurring within 24 h (EPC) of intracranial tumor surgery can improve patient safety and postoperative management. Statistical analysis using machine learning algorithms may generate models that predict EPC better than conventional statistical methods. OBJECTIVE To train such a model and to assess its predictive ability. METHODS This cohort study included patients from an ongoing prospective patient registry at a single tertiary care center with an intracranial tumor that underwent elective neurosurgery between June 2015 and May 2017. EPC were categorized based on the Clavien-Dindo classification score. Conventional statistical methods and different machine learning algorithms were used to predict EPC using preoperatively available patient, clinical, and surgery-related variables. The performance of each model was derived from examining classification performance metrics on an out-of-sample test dataset. RESULTS EPC occurred in 174 (26%) of 668 patients included in the analysis. Gradient boosting machine learning algorithms provided the model best predicting the probability of an EPC. The model scored an accuracy of 0.70 (confidence interval [CI] 0.59-0.79) with an area under the curve (AUC) of 0.73 and a sensitivity and specificity of 0.80 (CI 0.58-0.91) and 0.67 (CI 0.53-0.77) on the test set. The conventional statistical model showed inferior predictive power (test set: accuracy: 0.59 (CI 0.47-0.71); AUC: 0.64; sensitivity: 0.76 (CI 0.64-0.85); specificity: 0.53 (CI 0.41-0.64)). CONCLUSION Using gradient boosting machine learning algorithms, it was possible to create a prediction model superior to conventional statistical methods. While conventional statistical methods favor patients’ characteristics, we found the pathology and surgery-related (histology, anatomical localization, surgical access) variables to be better predictors of EPC.

Background In patients with steno‐occlusive disease, recent findings suggest that hemodynamic alterations may also be associated with crossed cerebellar diaschisis (CCD) rather than a functional disruption alone. Purpose To use a quantitative multiparametric hemodynamic MRI to gain a better understanding of hemodynamic changes related to CCD in patients with unilateral anterior circulation stroke. Study Type Prospective cohort study. Population Twenty‐four patients (25 datasets) with symptomatic unilateral anterior circulation stroke. Field Strength/Sequence 3T/two sequences: single‐shot (echo‐planar imaging) EPI sequence and T2* gradient echo perfusion‐weighted imaging study. Assessment The presence of CCD was inferred from the cerebellar asymmetry index (CAI) of the blood oxygenation‐level dependent cerebrovascular reactivity (BOLD‐CVR) exam, which was calculated from the mean BOLD‐CVR and standard deviation of the CAI of the healthy control group. For all perfusion‐weighted (PW)‐MRI parameters, the cerebellar and middle cerebral artery (MCA) territory asymmetry indices were calculated. Statistical Tests Independent Student's t‐test to compare the variables from the CCD positive(+) and CCD negative(–) groups and analysis of covariance (ANCOVA) to statistically control the effect of covariates (infarct volume and time since ischemia onset). Results CCD was present in 33% of patients. In the MCA territory of the affected hemisphere, BOLD‐CVR was significantly more impaired in the CCD(+) group as compared to the CCD(–) group (mean BOLD‐CVR ± SD [%BOLD signal/ΔmmHgCO2]: –0.03 ± 0.12 vs. 0.11 ± 0.13, P < 0.05). Moreover, the mean transit time (MTT) (asymmetry index (%) CCD(+) vs. CCD(–): 28 ± 23 vs. 4 ± 11, P < 0.05) and time to peak (TTP) (10 ± 10 vs. 2 ± 5, P < 0.05) in the MCA territory of the affected hemisphere were significantly prolonged, while cerebral blood volume was, on average, increased in the CCD(+) group (25 ± 15 vs. 4 ± 19, P < 0.05). Data Conclusion Our findings show that, in patients with symptomatic unilateral anterior circulation stroke, CCD is associated with hemodynamic impairment in the ipsilateral MCA territory, which further supports the concept of a vascular component of CCD. Level of Evidence 3 Technical Efficacy Stage 3

BACKGROUND The Barrow Neurological Institute (BNI) score, measuring maximal thickness of aneurysmal subarachnoid hemorrhage (aSAH), has previously shown to predict symptomatic cerebral vasospasms (CVSs), delayed cerebral ischemia (DCI), and functional outcome. OBJECTIVE To validate the BNI score for prediction of above-mentioned variables and cerebral infarct and evaluate its improvement by integrating further variables which are available within the first 24 h after hemorrhage. METHODS We included patients from a single center. The BNI score for prediction of CVS, DCI, infarct, and functional outcome was validated in our cohort using measurements of calibration and discrimination (area under the curve [AUC]). We improved it by adding additional variables, creating a novel risk score (measure by the dichotomized Glasgow Outcome Scale) and validated it in a small independent cohort. RESULTS Of 646 patients, 41.5% developed symptomatic CVS, 22.9% DCI, 23.5% cerebral infarct, and 29% had an unfavorable outcome. The BNI score was associated with all outcome measurements. We improved functional outcome prediction accuracy by including age, BNI score, World Federation of Neurologic Surgeons, rebleeding, clipping, and hydrocephalus (AUC 0.84, 95% CI 0.8-0.87). Based on this model we created a risk score (HATCH—Hemorrhage, Age, Treatment, Clinical State, Hydrocephalus), ranging 0 to 13 points. We validated it in a small independent cohort. The validated score demonstrated very good discriminative ability (AUC 0.84 [95% CI 0.72-0.96]). CONCLUSION We developed the HATCH score, which is a moderate predictor of DCI, but excellent predictor of functional outcome at 1 yr after aSAH.

The results of recent randomized clinical trials narrow the indication for cerebral bypass in the setting of ischemic cerebrovascular disease. However, cerebral bypass is still very useful for managing complex intracranial aneurysms (not amenable to selective clipping or endovascular therapies) and is the only treatment option for managing symptomatic patients with Moyamoya vasculopathy and impaired brain hemodynamics.

The clinical significance of ipsilateral thalamic diaschisis (ITD) occurring after stroke is unknown. To characterize ITD, we investigate its hemodynamic, structural, and clinical implications. A single-institution prospective cross-sectional study was conducted using 28 symptomatic cerebrovascular steno-occlusive patients undergoing both BOLD-CVR and Diamox-challenged 15(O)-H2O-PET. Follow-up was at least three months. In addition, 15 age-matched healthy subjects were included. ITD was diagnosed based on a BOLD-CVR thalamic asymmetry index (TAI) > +2 standard deviations from healthy subjects. Cerebral blood flow differences were assessed using a PET-based TAI before and after Diamox challenge. Thalamic volume masks were determined using Freesurfer. Neurological status at symptom onset and after three months was determined with NIHSS and mRS scores. ITD was diagnosed in 15 of 28 (57%) patients. PET-TAI before and after Diamox challenge were increased in patients with ITD, indicating an ipsilateral thalamic blood flow decrease. Patients with ITD exhibited a marked ipsilateral thalamic volume decrease as compared to patients without ITD and healthy subjects. Furthermore, patients with ITD had worse NIHSS and mRS at symptom onset and after three months follow-up, even after adjustment for stroke volume. The presence of ITD is characterized by thalamic volume reduction, reduced thalamic blood flow, and worse neurological performance unrelated to stroke volume.