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To develop and validate a prediction model for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) using a temporal unsupervised feature engineering approach, demonstrating improved precision over standard features. 488 consecutive SAH admissions from 2006 to 2014 to a tertiary care hospital were included. Models were trained on 80%, while 20% were set aside for validation testing. Baseline information and standard grading scales were evaluated: age, sex, Hunt Hess grade, modified Fisher Scale (mFS), and Glasgow Coma Scale (GCS). An unsupervised approach applying random kernels was used to extract features from physiological time series (systolic and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation). Classifiers (Partial Least Squares, linear and kernel Support Vector Machines) were trained on feature subsets of the derivation dataset. Models were applied to the validation dataset. The performances of the best classifiers on the validation dataset are reported by feature subset. Standard grading scale (mFS): AUC 0.58. Combined demographics and grading scales: AUC 0.60. Random kernel derived physiologic features: AUC 0.74. Combined baseline and physiologic features with redundant feature reduction: AUC 0.77. Current DCI prediction tools rely on admission imaging and are advantageously simple to employ. However, using an agnostic and computationally inexpensive learning approach for high-frequency physiologic time series data, we demonstrated that our models achieve higher classification accuracy.

The most deadly form of stroke, intracerebral hemorrhage (ICH) continues to puzzle researchers and produce substantial decrements in the quality of patients' lives. Intensive basic research has devised many agents with putative benefit in mitigating the devastating effects of ICH, but these therapies have been largely ineffective in the transition to clinical trials. However, a steady translational pipeline continues to provide new avenues of treatment that may be effective in the management of this condition. In this review, we aim to summarize the array of neuroprotective clinical trials and techniques used in the history of ICH, and delineate the progression of relevant research to date. Furthermore, we provide insight into methods that may allow for better translation of basic science advances into productive clinical trials.

Intracranial arteriovenous malformations (AVMs) are a common cause of stroke in younger patients, and often present as intracerebral hemorrhages (ICH), associated with 10 % to 30 % mortality. Patients who present with a hemorrhage from an AVM should be initially stabilized according to acute management guidelines for ICH. The characteristics of a lesion including its size, location in eloquent tissue, and high-risk features will influence risk of rupture, prognosis, as well as help guide management decisions. Given that rupture is associated with an increased risk of 6 % re-rupture in the year following the initial hemorrhage, versus 1 % to 3 % predicted annual risk in non-ruptured lesions only, definitive treatment is encouraged after ICH stabilization. A rest period of 2 to 6 weeks after hemorrhage is recommended before definitive treatment to avoid disrupting friable parenchyma and the hematoma. Treatment may consist of endovascular embolization, surgical resection, radiosurgery, or a combination of these three interventions based on the lesion.

Introduction: The complement cascade is a critical mediator of the inflammatory response following cerebral ischemia. Recent work has demonstrated that genetic-deficiency of Mannose-binding lectin(MBL) ameliorates reperfusion injury and improves outcome in the acute phase of stroke. The present study sought to further delineate the pathogenic role of MBL in stroke and to examine whether the neuroprotection associated with MBL-deficiency is sustained beyond the acute phase. We hypothesized that genetic MBL deficiency would suppress complement activation and ameliorate reperfusion injury in the acute phase, but that persistent inhibition of complement into the sub-acute phase would serve to abrogate this neuroprotective effect., Methods: The time-course and localization of post-ischemic cerebral MBL and C3 deposition were characterized using both Western-blot and immunohistochemistry. MBL-a/c null(MBL-KO) mice subjected to transient middle cerebral artery occlusion(MCAO) were then employed to investigate the histologic injury and functional outcome associated with genetic MBL deletion at both 24 hours and 7 days., Results: MBL-a/c rapidly deposit on ischemic endothelium and trigger downstream complement activation in the acute phase. Genetic deficiency of MBL abrogates C3 cleavage as well as the sub-acute accumulation of mononuclear cells in the ischemic region. Although MBL-KO mice demonstrate significantly improved outcome at 24 hours, the neuroprotective effect associated with genetic MBL deletion is not sustained., Conclusions: Development of a successful anti-complement neuroprotective strategy will require carefully-tailored inhibition coupled with a greater understanding of the functional effects of complement activation during later phases of stroke recovery.

Dehydroascorbic acid (DHA), a blood-brain barrier transportable form of ascorbic acid, confers robust neuroprotection following murine stroke. In an effort to translate this promising neuroprotective strategy into human clinical trial, we evaluated postischemic DHA administration in a large-animal stroke model. Thirty-six adult male baboons were initially randomized to undergo transorbital craniectomy to induce transient cerebral artery occlusion and to receive postischemic dosing of either 500 mg/kg of DHA or vehicle. Primary outcomes included infarct volume, determined by magnetic resonance imaging, as well as neurological function evaluated on the day of sacrifice. The midpoint interim analysis (n = 9 per cohort) revealed that DHA administration did not significantly improve either infarct volume or neurological function. The study was terminated after a determination of statistical futility. We were unable to confirm a neuroprotective effect for postischemic DHA administration in our large-animal model using a dosing scheme that was previously successful in rodents. Further analysis of the efficacy of DHA administration must thus be undertaken prior to clinical translation.

Background: Safety, feasibility, and efficacy trials in non-human primate stroke models are essential to the evaluation of experimental therapies and their translation to humans. Although Laser Doppler Flowmetry has been successfully employed in rodent stroke to continuously monitor cerebral blood flow, it has not been applied in primate studies. This investigation examined the utility of Laser Doppler Flowmetry in refining an existing baboon model of cerebral ischemia/reperfusion., Method: Continuous Laser Doppler Flowmetry monitoring was used, in non-human primates, to document local cerebral blood flow before, during, and after middle cerebral artery territory occlusion. In each baboon (n = 7) a single Doppler probe was placed into the left frontal cortex through a precoronal burr hole. Correlations between Laser Doppler Flowmetry values and latencies to Motor Evoked Potential dropout were compared using a linear regression model., Findings: Placement of the Laser Doppler probe was easily accomplished in all animals. Laser Doppler Flowmetry tracings accurately documented blood flow changes that occurred with each technical manipulation during the procedure. Laser Doppler confirmed decreased perfusion that coincided both regionally and temporally with vessel occlusion. Depth of ischemia as measured by Laser Doppler Flowmetry was associated with Motor Evoked Potential dropout latencies for individual animals., Conclusions: Continuous, single probe Laser Doppler Flowmetry is a reliable method of documenting perfusion changes following middle cerebral artery territory occlusion in a baboon model of reperfused stroke. This advanced intraoperative monitoring technique may lead to more accurate evaluation of acute stroke therapies in pre-clinical trials.