Endothelial cell (EC) dysfunction is known to contribute to cerebral aneurysm (CA) pathogenesis. Evidence shows that damage or injury to the EC layer is the first event in CA formation. The mechanisms behind EC dysfunction in CA disease are interrelated and include hemodynamic stress, hazardous nitric oxide synthase (NOS) activity, oxidative stress, estrogen imbalance, and endothelial cell-to-cell junction compromise. Abnormal variations in hemodynamic stress incite pathological EC transformation and inflammatory zone formation, ultimately leading to destruction of the vascular wall and aneurysm dilation. Hemodynamic stress activates key molecular pathways that result in the upregulation of chemotactic cytokines and adhesion molecules, leading to inflammatory cell recruitment and infiltration. Concurrently, oxidative stress damages EC-to-EC junction proteins, resulting in interendothelial gap formation. This further promotes leukocyte traffic into the vessel wall and the release of matrix metalloproteinases, which propagates vascular remodeling and breakdown. Abnormal hemodynamic stress and inflammation also trigger adverse changes in NOS activity, altering proper EC mediation of vascular tone and the local inflammatory environment. Additionally, the vasoprotective hormone estrogen modulates gene expression that often suppresses these harmful processes. Crosstalk between these sophisticated pathways contributes to CA initiation, progression, and rupture. This review aims to outline the complex mechanisms of EC dysfunction in CA pathogenesis.

OBJECTIVE Awake surgery has previously been found to improve patient outcomes postoperatively in a variety of procedures. Recently, multiple groups have investigated the utility of this modality for use in spine surgery. However, few current meta-analyses exist comparing patient outcomes in awake spinal anesthesia with those in general anesthesia. Therefore, the authors sought to present an updated systematic review and meta-analysis investigating the utility of spinal anesthesia relative to general anesthesia in lumbar procedures. METHODS Following a comprehensive literature search of the PubMed and Cochrane databases, 14 clinical studies were included in our final qualitative and quantitative analyses. Of these studies, 5 investigated spinal anesthesia in lumbar discectomy, 4 discussed lumbar laminectomy, and 2 examined interbody fusion procedures. One study investigated combined lumbar decompression and fusion or decompression alone. Two studies investigated patients who underwent discectomy and laminectomy, and 1 study investigated a series of patients who underwent transforaminal lumbar interbody fusion, posterolateral fusion, or decompression. Odds ratios, mean differences (MDs), and 95% confidence intervals were calculated where appropriate. RESULTS A meta-analysis of the total anesthesia time showed that time was significantly less in patients who received spinal anesthesia for both lumbar discectomies (MD −26.53, 95% CI −38.16 to −14.89; p = 0.00001) and lumbar laminectomies (MD −11.21, 95% CI −19.66 to −2.75; p = 0.009). Additionally, the operative time was significantly shorter in patients who underwent spinal anesthesia (MD −14.94, 95% CI −20.43 to −9.45; p < 0.00001). Similarly, when analyzing overall postoperative complication rates, patients who received spinal anesthesia were significantly less likely to experience postoperative complications (OR 0.29, 95% CI 0.16–0.53; p < 0.0001). Furthermore, patients who received spinal anesthesia had significantly lower postoperative pain scores (MD −2.80, 95% CI −4.55 to −1.06; p = 0.002). An identical trend was seen when patients were stratified by lumbar procedures. Patients who received spinal anesthesia were significantly less likely to require postoperative analgesia (OR 0.06, 95% CI 0.02–0.25; p < 0.0001) and had a significantly shorter hospital length of stay (MD −0.16, 95% CI −0.29 to −0.03; p = 0.02) and intraoperative blood loss (MD −52.36, 95% CI −81.55 to −23.17; p = 0.0004). Finally, the analysis showed that spinal anesthesia cost significantly less than general anesthesia (MD −226.14, 95% CI −324.73 to −127.55; p < 0.00001). CONCLUSIONS This review has demonstrated the varying benefits of spinal anesthesia in awake spine surgery relative to general anesthesia in patients who underwent various lumbar procedures. The analysis has shown that spinal anesthesia may offer some benefits when compared with general anesthesia, including reduction in the duration of anesthesia, operative time, total cost, and postoperative complications. Large prospective trials will elucidate the true role of this modality in spine surgery.

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Protein arginine methylation is a common post-translational modification that plays a pivotal role in cellular regulation. Protein arginine methyltransferases (PRMTs) catalyze the modification of target proteins by adding methyl groups to the guanidino nitrogen atoms of arginine residues. Protein arginine methylation takes part in epigenetic and cellular regulation and has been linked to neurodegenerative diseases, metabolic diseases, and tumor progression. Aberrant expression of PRMTs is associated with the development of brain tumors such as glioblastoma and medulloblastoma. Identifying PRMTs as plausible contributors to tumorigenesis has led to preclinical and clinical investigations of PRMT inhibitors for glioblastoma and medulloblastoma therapy. In this review, we discuss the role of arginine methylation in cancer biology and provide an update on the use of small molecule inhibitors of PRMTs to treat glioblastoma, medulloblastoma, and other cancers.