Background Intracerebral hemorrhage (ICH) remains the deadliest form of stroke worldwide, inducing neuronal death through a wide variety of pathways. Therapeutic hypothermia (TH) is a robust and well studied neuroprotectant widely used across a variety of specialties. Aims This review summarizes results from preclinical and clinical studies to highlight the overall effectiveness of TH to improve long-term ICH outcomes while also elucidating optimal protocol regimens to maximize therapeutic effect. Summary of Review A systematic review was conducted across three databases to identify trials investigating the use of TH to treat ICH. A random-effects meta-analysis was conducted on preclinical studies, looking at neurobehavioral outcomes, blood brain barrier breakdown (BBB), cerebral edema, hematoma volume, and tissue loss. Several mixed-methods meta-regression models were also performed to adjust for variance and variations in hypothermia induction procedures. 21 preclinical studies and 5 human studies were identified. The meta-analysis of preclinical studies demonstrated a significant benefit in behavioral scores (ES=-0.43, p=0.02), cerebral edema (ES=1.32, p=0.0001), and BBB (ES=2.73, p=<0.00001). TH was not found to significantly affect hematoma expansion (ES=-0.24, p=0.12) or tissue loss (ES=0.06, p=0.68). Clinical study outcome reporting was heterogeneous, however there was recurring evidence of TH-induced edema reduction. Conclusions The combined preclinical evidence demonstrates that TH reduced multiple cell death mechanisms initiated by ICH, yet there is no definitive evidence in clinical studies. The cooling strategies employed in both preclinical and clinical studies were highly diverse, and focused refinement of cooling protocols should be developed in future preclinical studies. The current data for TH in ICH remains questionable despite the highly promising indications in preclinical studies. Definitive randomized controlled studies are still required to answer this therapeutic question.
Background. Intracerebral hemorrhage (ICH) accounts for 10–20% of all strokes and is associated with high morbidity and mortality. Recent studies have identified serum biomarkers as a means to improve outcome prognostication in poor grade ICH patients. Poor prognosis of ICH patients and complex pathophysiology of the disease necessitate prognostic serum biomarkers to help guide treatment recommendations. Objective. The objective is to systematically review all biomarkers used to predict long-term functional outcome in patients with spontaneous intracerebral hemorrhage. Results. We identified 36 studies investigating the predictive utility of 50 discrete biomarkers. Data from 4865 ICH patients were reviewed. Inflammatory biomarkers (11/50) were most often studied, followed by oxidative (8/50), then neuron and astrocyte-specific (7/50). S100 calcium binding protein B, white blood cell count, and copeptin were the most often studied individual biomarkers. The prognostic utility of 23 biomarkers was analyzed using receiver operating characteristic curves. Area under the curve (AUC) values for all available biomarkers except neutrophil/lymphocyte ratio were acceptable. Twenty of the 23 biomarkers were characterized by at least one excellent AUC value. Vascular endothelial growth factor, glial fibrillary astrocyte protein, and S100 calcium binding protein B were characterized by outstanding AUC. Conclusions. We identified the inflammatory and neuron and astrocyte-specific biomarker categories as having the greatest number of significant individual biomarker predictors of long-term outcome. Further investigation utilizing cross-validation of prediction models in a second independent group and blinded assessment of outcomes for the predictive utility of biomarkers in patients with ICH is warranted.
Intracerebral hemorrhage (ICH) is a devastating form of stroke associated with a 40% mortality rate at 30 days and a 75% functional dependence rate at 6 months. The role of surgery to treat ICH remains controversial. Preclinical studies suggest minimally invasive clot evacuation following ICH may benefit patients by mitigating primary and secondary brain injury.1 2 In this video, we report the operative technique used in minimally invasive surgicsopic evacuation following ICH (video 1). We demonstrate our presurgical approach using preoperative volumetric imaging loaded onto a stereotactic guidance system. Evacuation of intraparenchymal and intraventricular components of a hemorrhage are shown under direct surgiscopic vision using the Aurora System (Integra LifeSciences, Princeton, NJ, USA). Hemostasis is achieved when actively bleeding vessels are directly cauterized and irrigation of the clot cavity yields no fresh blood. Pre- and postevacuation radiographic differences illustrate the mitigation of clot burden in an elderly patient.Video 1
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