Somatic Variants in SVIL in Cerebral Aneurysms.

Background and Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Results: Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. Discussion: We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Orbital reconstruction for tumor-associated proptosis: quantitative analysis of postoperative orbital volume and final eye position.

OBJECTIVE: Surgical resection of sphenoid wing tumors and intraorbital pathology carries the dual goal of appropriately treating the target pathology as well as correcting proptosis. Residual proptosis following surgery can lead to cosmetic and functional disability. The authors sought to quantitatively assess the effect of orbital volume before and after reconstruction to determine the optimal strategy to achieve proptosis correction. METHODS: All surgeries involving orbital wall reconstruction for orbital or intracranial pathology that preoperatively resulted in proptosis between 2007 and 2017 were reviewed. Proptosis was measured by the exophthalmos index (EI): the ratio of the distance of the anterior limit of each globe to a line drawn between the anterior limit of the frontal processes of the zygomas, comparing the pathological eye to the normal eye. Postoperative radiographic measurements were taken at least 60 days after surgery to allow surgical swelling to abate. The orbit contralateral to the pathology was used as an internal control for normal anatomical orbital volume. Cases with preoperative EI < 1.10, orbital exenteration, or enucleation were excluded. RESULTS: Twenty-three patients (16 females and 7 males, with a mean age of 43.6 ± 22.8 years) were treated surgically for tumor-associated proptosis. Nineteen patients harbored meningiomas (11 en-plaque; 8 sphenoid wing), and one patient each harbored an orbital schwannoma, glomangioma, arteriovenous malformation, or cavernous hemangioma. Preoperative EI averaged 1.28 ± 0.10 (range 1.12-1.53). Median time to postoperative imaging was 19 months. Postoperatively, the EI decreased to a mean of 1.07 ± 0.09. Greater increases in size of the reconstructed orbit were positively correlated with greater quantitative reductions in proptosis (p < 0.01). Larger volume of soft tissue pathology was also associated with achieving greater proptosis correction (p < 0.01). Residual exophthalmos (defined as EI > 1.10) was present in 8 patients, while reconstruction in 2 patients resulted in clinically asymptomatic enophthalmos (defined as EI < 0.95). Tumor invasion into the superior orbital fissure sinus was associated with residual proptosis (p = 0.04). CONCLUSIONS: Proptosis associated with intracranial and orbital pathology represents a surgical challenge. The EI is a reliable and quantitative assessment of proptosis. For orbital reconstruction in cases of superior orbital fissure involvement, surgeons should consider rebuilding the orbit at slightly larger than anatomical volume.

Obliteration of a metameric spinal arteriovenous malformation (Cobb syndrome) using combined endovascular embolization and surgical excision.

Cobb syndrome represents the concurrent findings of a metameric spinal vascular malformation and a cutaneous vascular malformation within several dermatomes of each other. This rare entity engenders many difficult decisions with respect to appropriate therapeutic management. Historically, surgical excision carried a high morbidity, and conservative management without intervention was preferred. More recently, several cases of endovascular embolization have been reported with good success. The authors describe the case of a 17-year-old boy who presented with a right gluteal angioma and was found to have a spinal arteriovenous malformation. Multiple embolizations failed to prevent neurological deterioration, and the patient eventually became wheelchair dependent. Surgical excision of the malformation led to partial recovery of neurological function, and at the latest follow-up, 52 months postoperatively, the patient was able to ambulate independently. This case demonstrates the successful treatment of a patient with Cobb syndrome with surgical excision after multiple refractory embolizations. A multidisciplinary approach, which balances the patient's current neurological function against the risks and potential gains from any interventional and surgical procedure, is recommended.

Postoperative resolution of abnormal blood vessels related to a nerve root hemangioblastoma.

To our knowledge, there are currently no published reports that describe the postoperative evolution of abnormal blood vessels associated with spinal nerve root hemangioblastomas. We present a patient with a hemangioblastoma that was completely resected. Follow-up imaging revealed complete resolution of the abnormal blood vessels. We hypothesize that complete resection of spinal nerve root hemangioblastomas eliminates the venous hypertension and allows for regression of the dilated vascular network. Persistent dilated vessels should be followed closely for residual tumors.

Lumbar microdiscectomy and microendoscopic discectomy.

Lumbar microdiscectomy, which relies on the operating microscope for visualization, was first described in the late 1970s. This operation is considered the gold standard procedure for patients who require surgery for symptomatic lumbar disc herniation causing radiculopathy that has not improved with conservative measures. A new approach to the management of symptomatic lumbar disc herniation, microendoscopic discectomy, was introduced in 1997. This operation utilizes a tubular retractor system and a microendoscope for visualization rather than the operating microscope. As it is a new procedure, long-term outcomes have not yet been established for this operation. However, recent literature suggests that microendoscopic discectomy may be as effective as the traditional lumbar microdiscectomy in relieving radiculopathy. This article describes the operative techniques and outcomes reported in the literature for both lumbar microdiscectomy and microendoscopic discectomy.