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.
Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery.
Background: Injury is a major global health problem, causing >5,800,000 deaths annually and widespread disability largely attributable to neurotrauma. 89% of trauma deaths occur in low- and middle-income countries (LMICs), however data on neurotrauma epidemiology in LMICs is lacking. In order to support neurotrauma surveillance efforts, we present a review and analysis of data dictionaries from national registries in LMICs. Methods: We performed a scoping review to identify existing national trauma registries for all LMICs. Inclusion/exclusion criteria included articles published since 1991 describing national registry neurotrauma data capture methods in LMICs. Data sources included PubMed and Google Scholar using the terms "trauma/neurotrauma registry" and country name. Resulting registries were analyzed for neurotrauma-specific data dictionaries. These findings were augmented by data from direct contact of neurotrauma organizations, health ministries, and key informants from a convenience sample. These data were then compared to the WHO minimum dataset for injury (MDI) from the international registry for trauma and emergency care. Results: We identified 15 LMICs with 16 total national trauma registries tracking neurotrauma-specific data elements. Among these, Cameroon had the highest concordance with the MDI, followed by Colombia, Iran, Myanmar and Thailand. The MDI elements least often found in the data dictionaries included helmet use, and alcohol level. Data dictionaries differed significantly among LMICs. Common elements included Glasgow Coma Score, mechanism of injury, anatomical site of injury and injury severity scores. Limitations included low response rate in direct contact methods. Conclusion: Significant heterogeneity was observed between the neurotrauma data dictionaries, as well as a spectrum of concordance or discordance with the MDI. Findings offer a contextually relevant menu of possible neurotrauma data elements that LMICs can consider tracking nationally to enhance neurotrauma surveillance and care systems. Standardization of nationwide neurotrauma data collection can facilitate international comparisons and bidirectional learning among health care governments.
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