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INTRODUCTION: Sarcomas, a group of neoplasms comprising both tissue and bone soft tissue tumors, has an increasing prevalence in recent years. Prognosis significantly hinges on early detection, and if not detected early, may consequently metastasize. This review will be the first systematic review and meta-analysis characterizing the presentation and progression of brain metastases from bone and soft tissue cancers. METHODS: The PubMed, Scopus, and Web of Science databases were queried to identify studies reporting the incidence of intracranial brain metastases from primary sarcoma to the present. Abstract and full-text screening of 1822 initial articles returned by preliminary search yielded 28 studies for inclusion and data extraction. Qualitative assessment of the studies was conducted in accordance with the Newcastle-Ottawa Scale criteria. Meta-analyses were applied to assess risk factors on outcomes. RESULTS: The average age within the cohort was 27.9 years with a male and female prevalence of 59.1% and 40.9%, respectively. The odds ratio for living status (dead/alive) was calculated for several risk factors - male/female [OR 1.14, 95% CI 0.62, 2.07], single/multiple metastases [OR 0.67, 95% CI 0.35, 1.28], lung metastases/not [OR 1.63, 95% CI 0.85, 3.13], surgery/no surgery [OR 0.49, 95% CI 0.20, 1.21]. The standardized mean differences for duration from diagnoses to metastases were likewise analyzed - male/female [SMD 0.13, 95% CI -0.15, 0.42], single/multiple metastases [SMD 0.11, 95% CI -0.20, 0.42], lung metastases/not [SMD -0.03, 95% CI -0.38, 0.32], surgery/no surgery [SMD 0.45, 95% CI -0.18, 1.09]. The standardized mean differences for duration from metastases to death were analyzed - lung metastases/not [SMD 0.43, 95% CI -0.08, 0.95]. CONCLUSIONS: Our study observed no statistically significant differences in mortality rate among several patient risk factors. Consequentially, there lacks a clear answer as to whether or not an association between mortality rates exists with these patient factors. As such, it is important to continue research in brain-metastasizing sarcomas despite their relative rarity.
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Stroke is a debilitating neurologic condition characterized by an interruption or complete blockage of blood flow to certain areas of the brain. While the primary injury occurs at the time of the initial ischemic event or hemorrhage, secondary injury mechanisms contribute to neuroinflammation, disruption of the blood-brain barrier (BBB), excitotoxicity, and cerebral edema in the days and hours after stroke. Of these secondary mechanisms of injury, significant dysregulation of various immune populations within the body plays a crucial role in exacerbating brain damage after stroke. Pathological activity of glial cells, infiltrating leukocytes, and the adaptive immune system promote neuroinflammation, BBB damage, and neuronal death. Chronic immune activation can additionally encourage the development of neurologic deficits, immunosuppression, and dysregulation of the gut microbiome. As such, immunotherapy has emerged as a promising strategy for the clinical management of stroke in a highly patient-specific manner. These strategies include regulatory T cells (Tregs), cell adhesion molecules, cytokines, and monoclonal antibodies. However, the use of immunotherapy for stroke remains largely in the early stages, highlighting the need for continued research efforts before widespread clinical use.
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Arteriovenous malformations (AVMs) are an anomaly of the vascular system where feeding arteries are directly connected to the venous drainage network. While AVMs can arise anywhere in the body and have been described in most tissues, brain AVMs are of significant concern because of the risk of hemorrhage which carries significant morbidity and mortality. The prevalence of AVM's and the mechanisms underlying their formation are not well understood. For this reason, patients who undergo treatment for symptomatic AVM's remain at increased risk of subsequent bleeds and adverse outcomes. The cerebrovascular network is delicate and novel animal models continue to provide insight into its dynamics in the context of AVM's. As the molecular players in the formation of familial and sporadic AVM's are better understood, novel therapeutic approaches have been developed to mitigate their associated risks. Here we discuss the current literature surrounding AVM's including the development of models and therapeutic targets which are currently being investigated.
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Beyond its neuroprotective role, CSF functions to rid the brain of toxic waste products through glymphatic clearance. Disturbances in the circulation of CSF and glymphatic exchange are common among those experiencing HCP syndrome, which often results from SAH. Normally, the secretion of CSF follows a two-step process, including filtration of plasma followed by the introduction of ions, bicarbonate, and water. Arachnoid granulations are the main site of CSF absorption, although there are other influencing factors that affect this process. The pathway through which CSF is through to flow is from its site of secretion, at the choroid plexus, to its site of absorption. However, the CSF flow dynamics are influenced by the cardiovascular system and interactions between CSF and CNS anatomy. One, two, and three-dimensional models are currently methods researchers use to predict and describe CSF flow, both under normal and pathological conditions. They are, however, not without their limitations. "Rest-of-body" models, which consider whole-body compartments, may be more effective for understanding the disruption to CSF flow due to hemorrhages and hydrocephalus. Specifically, SAH is thought to prevent CSF flow into the basal cistern and paravascular spaces. It is also more subject to backflow, caused by the presence of coagulation cascade products. In regard to the fluid dynamics of CSF, scar tissue, red blood cells, and protein content resulting from SAH may contribute to increased viscosity, decreased vessel diameter, and increased vessel resistance. Outside of its direct influence on CSF flow, SAH may result in one or both forms of hydrocephalus, including noncommunicating (obstructive) and communicating (nonobstructive) HCP. Imaging modalities such as PC-MRI, Time-SLIP, and CFD model, a mathematical model relying on PC-MRI data, are commonly used to better understand CSF flow. While PC-MRI utilizes phase shift data to ultimately determine CSF speed and flow, Time-SLIP compares signals generated by CSF to background signals to characterizes complex fluid dynamics. Currently, there are gaps in sufficient CSF flow models and imaging modalities. A prospective area of study includes generation of models that consider "rest-of-body" compartments and elements like arterial pulse waves, respiratory waves, posture, and jugular venous posture. Going forward, imaging modalities should work to focus more on patients in nature in order to appropriately assess how CSF flow is disrupted in SAH and HCP.