Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure.

Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's.

Endovascular intervention for the treatment of epistaxis: cone beam CT review of anatomy, collateral, and treatment implications/efficacy.

Epistaxis is common, impacting more than half the population, and can require procedural intervention in approximately 10% of cases. With an aging population and increasing use of antiplatelets and anticoagulants, severe epistaxis is likely to increase in frequency significantly over the next two decades. Sphenopalatine artery embolization is rapidly becoming the most common type of procedural intervention. The efficacy of endovascular embolization is dependent on a refined understanding of the anatomy and collateral physiology of this circulation as well as the impact of temporizing measures such as nasal packing and inflation of a nasal balloon. Likewise, safety is dependent on a detailed appreciation of collateralization with the internal carotid artery and ophthalmic artery. Cone beam CT imaging has the resolution to enable a clear visualization of the anatomy and collateral circulation associated with the arterial supply to the nasal cavity, in addition to assisting with hemorrhage localization. We present a review of epistaxis treatment, a detailed description of anatomic and physiologic considerations informed by cone beam CT imaging, and a proposed protocol for sphenopalatine embolization for which there is currently no standard.

Papillary glioneuronal tumor presenting with low-pressure hydrocephalus from intraventricular spread: Case Report.

Papillary glioneuronal tumors are a rare and typically benign entity with pathological and radiographic complexity. Presentation can mimic other neoplasms, making diagnosis more challenging. The literature to date describes the clinical understanding, diagnostic, therapeutic, and prognostic characteristics of this limited number of patients. In this article, we report an unusual case of a glioneuronal tumor with multifocal presentation, normal pressure hydrocephalus-like symptoms, and large peritumoral parenchymal cysts, which guided the surgical approach. This unusual presentation has not previously been reported and adds valuable information to the clinical recognition and management literature.

Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge.

Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.

Artificial intelligence aneurysm measurement tool finds growth in all aneurysms that ruptured during conservative management.

BACKGROUND: Cerebral aneurysm rupture is associated with high rates of morbidity and mortality. Detecting aneurysms at high risk of rupture is critical in management decision making. Rupture risk has traditionally been associated with size-measured as a maximum dimension. However, aneurysms are morphologically dynamic, a characteristic ignored by large prospective aneurysm risk studies. Manual measurement is challenging and fraught with error. We used an artificial intelligence (AI) measurement tool to study aneurysms that ruptured during conservative management to detect changes in size not appreciated by manual linear measurement. METHODS: A single practice database with >5000 aneurysms was queried. Patients followed conservatively for an unruptured aneurysm were identified using appropriate diagnosis codes. This cohort was screened for subsequent rupture using procedure codes. Only patients with two vascular imaging studies before rupture were included. RESULTS: Five patients met the criteria. All patients had aneurysm enlargement, two of which were not detected from manual linear measurements, including adjudication and analysis, during a multidisciplinary neurovascular conference in a high volume practice. Maximum dimension increased at a minimum of 1.8% (range 1.8-63.3%) from the first scan to the last, and aneurysm volume increased at a minimum of 5.9% (5.9-385.5%), highlighting the importance of volumetric measurement. CONCLUSIONS: AI-enabled volumetric measurements are more sensitive to changes in size and detected enlargement in all aneurysms that ruptured during conservative management. This finding has major implications for clinical practice and methods used for interval aneurysm measurement in patients being conservatively followed.

Recurrent Primary Intrasellar Paraganglioma.

We describe a case of an 81-year-old male presenting with bitemporal visual field defects and blurry vision in the right eye. The patient was found to have a recurrent primary paraganglioma in the sellar and suprasellar region requiring a repeat transsphenoidal endoscopic resection. Immunohistochemical examination confirmed paraganglioma with the classic zellballen appearance which stained positive for chromogranin, synaptophysin, and S-100 in the periphery. Paragangliomas (PGLs) in the sella turcica are a rare entity; only 19 cases have ever been reported in the literature. PGLs in the sellar region are often misdiagnosed or diagnosed in a delayed fashion. Earlier diagnosis of this locally aggressive tumor and meticulous debulking can prevent morbidity secondary to the tumor's compressive effects. This report highlights the effectiveness of surgical interventions in treatment of paragangliomas. More research is still needed to determine the need for adjuvant therapies such as radiation.

Initial Experience Using Intraoperative Magnetic Resonance Imaging During a Trans-Sulcal Tubular Retractor Approach for the Resection of Deep-Seated Brain Tumors: A Case Series.

BACKGROUND: Treatment of deep-seated subcortical intrinsic brain tumors remains challenging and may be improved with trans-sulcal tubular brain retraction techniques coupled with intraoperative magnetic resonance imaging (iMRI). OBJECTIVE: To conduct a preliminary assessment of feasibility and efficacy of iMRI in tubular retractor-guided resections of intrinsic brain tumors. METHODS: Assessment of this technique and impact upon outcomes were assessed in a preliminary series of brain tumor patients from 2 centers. RESULTS: Ten patients underwent resection with a tubular retractor system and iMRI. Mean age was 53.2 ± 9.0 yr (range: 37-61 yr, 80% male). Lesions included 6 gliomas (3 glioblastomas, 1 recurrent anaplastic astrocytoma, and 2 low-grade gliomas) and 4 brain metastases (1 renal cell, 1 breast, 1 lung, and 1 melanoma). Mean maximal tumor diameter was 2.9 ± 0.95 cm (range 1.2-4.3 cm). The iMRI demonstrated subtotal resection (STR) in 6 of 10 cases (60%); additional resection was performed in 5 of 6 cases (83%), reducing STR rate to 2 of 10 cases (20%), with both having tumor encroaching on eloquent structures. Seven patients (70%) were stable or improved neurologically immediately postoperatively. Three patients (30%) had new postoperative neurological deficits, 2 of which were transient. Average hospital length of stay was 3.4 ± 2.0 d (range: 1-7 d). CONCLUSION: Combining iMRI with tubular brain retraction techniques is feasible and may improve the extent of resection of deep-seated intrinsic brain tumors that are incompletely visualized with the smaller surgical exposure of tubular retractors.

Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial.

BACKGROUND: Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1-4 brain metastases. METHODS: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. DISCUSSION: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03398694 (registration date: January 12, 2018).

Denosumab Treatment for a Residual Giant Cell Tumor of the Clivus: A Case Report and Review of the Literature.

BACKGROUND: Giant cell tumors (GCTs) are a locally aggressive primary bone neoplasm of osteoclast-like cells. These lesions largely occur in the epiphyses of long bones, but there have been rare reports of occurrence in the pelvis, spine, or skull. Of those located in the skull, involvement of the clivus has been rarely reported. CASE DESCRIPTION: We present a case of an 18-year-old woman presenting with a third nerve palsy, found to have a lytic lesion of the upper clivus that was primarily treated with endoscopic endonasal resection. Her third nerve palsy resolved postoperatively, and subsequent histopathologic analysis revealed a GCT. Six-month postoperative magnetic resonance imaging (MRI) revealed progression of residual disease for which she was treated with adjuvant denosumab. This treatment resulted in a significant decrease in the tumor size. She subsequently underwent proton beam radiation. At 1-year postsurgery, the patient's MRI remained stable after completing denosumab and proton therapy. She was neurologically intact and had no issues from her treatment. CONCLUSIONS: Denosumab has demonstrated anti-GCT efficacy. In combination with proton therapy, it has the potential to spare a young, vulnerable population from adverse long-term effects of traditional adjuvant radiation therapy. To our knowledge, this is the first report of the use of denosumab in the treatment of GCT of the clivus in the United States.

Intraoperative angiography via the popliteal artery: a useful technique for patients in the prone position.

OBJECTIVE Intraoperative angiography can be a valuable tool in the surgical management of vascular disorders in the CNS. This is typically accomplished via femoral artery puncture; however, this can be technically difficult in patients in the prone position. The authors describe the feasibility of intraoperative angiography via the popliteal artery in the prone patient. METHODS Three patients underwent intraoperative spinal angiography in the prone position via vascular access through the popliteal artery. Standard angiography techniques were used, along with ultrasound and a micropuncture needle for initial vascular access. Two patients underwent intraoperative angiography to confirm the obliteration of dural arteriovenous fistulas. The third patient required unexpected intraoperative angiography when a tumor was concerning for a vascular malformation in the cervical spine. RESULTS All 3 patients tolerated the procedure without complication. The popliteal artery was easily accessed without any adaptation to typical patient positioning for these prone-position cases. This proved particularly beneficial when angiography was not part of the preoperative plan. CONCLUSIONS Intraoperative angiography via the popliteal artery is feasible and well tolerated. It presents significant benefit when obtaining imaging studies in patients in a prone position, with the added benefit of easy access, familiar anatomy, and low concern for catheter thrombosis or kinking.

Pediatric Pontine Cavernous Malformations: The Presigmoid, Posterior Petrosal Approach.

BACKGROUND: Brainstem cavernous malformations (cavernomas) in children have a high risk of hemorrhage and neurological deterioration. This risk is magnified if the child has a genetic predisposition for cavernoma formation. The surgical management is challenging and carries a significant risk of morbidity. OBJECTIVE: To describe the feasibility of a posterior petrosal approach to brainstem cavernomas in a pediatric population. METHODS: A single institution operative experience with this technique was reviewed; 2 cases were identified and are technically described here with supportive figures and illustrations, as well as a focused literature review. RESULTS: Two pediatric cases with multiple symptomatic hemorrhages from large expanding pontine cavernomas were identified. Both cavernomas were resected through a presigmoid posterior petrosal approach. While this approach is well described in the adult literature for ventral brainstem lesions, its description for the treatment of pontine cavernomas in the pediatric populations is scarce. CONCLUSION: This study demonstrates the utility and feasibility of the posterior petrosal approach in two pediatric patients at different points in cranial base development.

Technology that achieves the Triple Aim: an economic analysis of the BrainPath™ approach in neurosurgery.

BACKGROUND: The Triple Aim is defined as: improving the patient experience of care, improving the health of populations, and reducing the per capita cost of health care. The purpose of this analysis was to evaluate the economic value of a new neurosurgical technique, the BrainPath™ approach, for use in patients with subcortical tumors and intracerebral hemorrhage (ICH). METHODS: Inpatient length of stay (LOS) data were collected for ICH and brain tumor surgical patient cases between August 2013 and November 2015. Patient cases were separated into two groups; BrainPath approach (n = 28) and conventional techniques, such as craniotomy, (n = 208). The average intensive care unit (ICU) LOS was calculated for each group by diagnosis-related group and compared between groups. RESULTS: The new surgical technology resulted in surgical intervention in 14 ICH cases which otherwise would have been medically managed due to the hemorrhage location or size of the ICH. A reduction in ICU LOS was seen in this group. Based on the variable direct cost per day in the neuro critical care unit at this academic medical center, 14 patient cases incurred ~ US$210,000 less in direct ICU costs. Surgical resection was possible in two tumor patient cases which would have been biopsied, rather than surgically resected, also due to location of the abnormalities. A total net value of > US$329,000 is attributable to the analyzed approach over a 28-month period. CONCLUSION: This analysis shows positive economic value for the new technology group when ICU LOS and reimbursement are considered against equipment costs, thus achieving Triple Aim objectives.

The Safety and Feasibility of Image-Guided BrainPath-Mediated Transsulcul Hematoma Evacuation: A Multicenter Study.

BACKGROUND: Subcortical injury resulting from conventional surgical management of intracranial hemorrhage may counteract the potential benefits of hematoma evacuation. OBJECTIVE: To evaluate the safety and potential benefits of a novel, minimally invasive approach for clot evacuation in a multicenter study. METHODS: The integrated approach incorporates 5 competencies: (1) image interpretation and trajectory planning, (2) dynamic navigation, (3) atraumatic access system (BrainPath, NICO Corp, Indianapolis, Indiana), (4) extracorporeal optics, and (5) automated atraumatic resection. Twelve neurosurgeons from 11 centers were trained to use this approach through a continuing medical education-accredited course. Demographical, clinical, and radiological data of patients treated over 2 years were analyzed retrospectively. RESULTS: Thirty-nine consecutive patients were identified. The median Glasgow Coma Scale (GCS) score at presentation was 10 (range, 5-15). The thalamus/basal ganglion regions were involved in 46% of the cases. The median hematoma volume and depth were 36 mL (interquartile range [IQR], 27-65 mL) and 1.4 cm (IQR, 0.3-2.9 cm), respectively. The median time from ictus to surgery was 24.5 hours (IQR, 16-66 hours). The degree of hematoma evacuation was ≥90%, 75% to 89%, and 50% to 74% in 72%, 23%, and 5.0% of the patients, respectively. The median GCS score at discharge was 14 (range, 8-15). The improvement in GCS score was statistically significant ( P < .001). Modified Rankin Scale data were available for 35 patients. Fifty-two percent of those patients had a modified Rankin Scale score of ≤2. There were no mortalities. CONCLUSION: The approach was safely performed in all patients with a relatively high rate of clot evacuation and functional independence.

Minimally Invasive Transsulcal Resection of Intraventricular and Periventricular Lesions Through a Tubular Retractor System: Multicentric Experience and Results.

BACKGROUND: Conventional approaches to deep-seated cerebral lesions range from biopsy to transcortical or transcallosal resection. Although the former does not reduce tumor burden, the latter are more invasive and associated with greater potential for irreparable injury to normal brain. Disconnection syndrome, hemiparesis, hemianesthesia, or aphasia is not uncommon after such surgery, especially when lesion is large. By contrast, the transsulcal parafascicular approach uses naturally existing corridors and a tubular retractor to minimize brain injury. METHODS: A retrospective review of patients undergoing minimally invasive transsulcal parafascicular resection of ventricular and periventricular lesions, across 5 independent centers, was conducted. RESULTS: Twenty patients with lesions located in the lateral ventricle (n = 9), the third ventricle (n = 6) and periventricular region (n = 4) are described in this report. Average age was 64 years (8 male/12 female). The average depth from cortical surface was 4.37 cm. A 13.5-mm-diameter tubular retractor (BrainPath [NICO Corporation, Indianapolis, Indiana, USA]) of differing lengths was used, aided by neuronavigation. Gross total resection was obtained in 17 patients. Pathologies included colloid cyst, subependymoma, glioma, meningioma, central neurocytoma, lymphoma, and metastasis. Three patients experienced transient morbidity: memory loss (2), hemiparesis (1). One patient died 3 months postoperatively as a result of unrelated pulmonary illness. Follow-up ranged from 6 to 27 months (average, 12 months). CONCLUSIONS: This technique is safe and effective for the treatment of intraventricular and periventricular lesions. Surgery-related morbidity is minimal and often transient. Lesions are satisfactorily resected and residuum occurs only when the neoplasm involves vital structures. The tubular retractor minimizes trauma to brain incident in the surgeon's path.

Lateral supracerebellar infratentorial approach for microsurgical resection of large midline pineal region tumors: techniques to expand the operative corridor.

Pineal region tumors pose certain challenges in regard to their resection: a deep surgical field, associated critical surrounding neurovascular structures, and narrow operative working corridor due to obstruction by the apex of the culmen. The authors describe a lateral supracerebellar infratentorial approach that was successfully used in the treatment of 10 large (> 3 cm) midline pineal region tumors. The patients were placed in a modified lateral decubitus position. A small lateral suboccipital craniotomy exposed the transverse sinus. Tentorial retraction sutures were used to gently rotate and elevate the transverse sinus to expand the lateral supracerebellar operative corridor. This approach placed only unilateral normal structures at risk and minimized vermian venous sacrifice. The surgeon achieved generous exposure of the caudal midline mesencephalon through a "cross-court" oblique trajectory, while avoiding excessive retraction on the culmen. All patients underwent the lateral approach with no approach-related complication. The final pathological diagnoses were consistent with meningioma in 3 cases, pilocytic astrocytoma in 3 cases, intermediate grade pineal region tumor in 2 cases, and pineoblastoma in 2 cases. The entire extent of these tumors was readily reachable through the lateral supracerebellar route. Gross-total resection was achieved in 8 (80%) of the 10 cases; in 2 cases (20%) near-total resection was performed due to adherence of these tumors to deep diencephalic veins. Large midline pineal region tumors can be removed through a unilateral paramedian suboccipital craniotomy. This approach is simple, may spare some of the midline vermian bridging veins, and may be potentially less invasive and more efficient.

Posterior interhemispheric transfalcine transprecuneus approach for microsurgical resection of periatrial lesions: indications, technique, and outcomes.

OBJECT: Surgical exposure of the peritrigonal or periatrial region has been challenging due to the depth of the region and overlying important functional cortices and white matter tracts. The authors demonstrate the operative feasibility of a contralateral posterior interhemispheric transfalcine transprecuneus approach (PITTA) to this region and present a series of patients treated via this operative route. METHODS: Fourteen consecutive patients underwent the PITTA and were included in this study. Pre- and postoperative clinical and radiological data points were retrospectively collected. Complications and extent of resection were reviewed. RESULTS: The mean age of patients at the time of surgery was 39 years (range 11-64 years). Six of the 14 patients were female. The mean duration of follow-up was 4.6 months (range 0.5-19.6 months). Pathology included 6 arteriovenous malformations, 4 gliomas, 2 meningiomas, 1 metastatic lesion, and 1 gray matter heterotopia. Based on the results shown on postoperative MRI, 1 lesion (7%) was intentionally subtotally resected, but ≥ 95% resection was achieved in all others (93%) and gross-total resection was accomplished in 7 (54%) of 13. One patient (7%) experienced a temporary approach-related complication. At last follow-up, 1 patient (7%) had died due to complications of his underlying malignancy unrelated to his cranial surgery, 2 (14%) demonstrated a Glasgow Outcome Scale (GOS) score of 4, and 11 (79%) manifested a GOS score of 5. CONCLUSIONS: Based on this patient series, the contralateral PITTA potentially offers numerous advantages, including a wider, safer operative corridor, minimal need for ipsilateral brain manipulation, and better intraoperative navigation and working angles.

Analysis of the tortuosity of the internal carotid artery in the cavernous sinus.

BACKGROUND: The morphology of the internal carotid artery at the skull base is important in radiologic interpretation, surgery, and more recently, endovascular interventional and diagnostic procedures. Therefore, a thorough knowledge of the shape of the carotid siphon can be important in the clinical realm. METHODS: In this study, we evaluated the shape of the carotid siphon from a lateral perspective on cerebral angiography. These shapes were then correlated to the Lang and Reiter classification. RESULTS: Types A, B, and C were distributed as follows: type A 12 (30%), B 16 (40%), 12 (30%). There was no significant difference (p > 0.05) in patient ages between the three types (type A 54.6 ± 14.2 years, type B 55.1 ± 14.9 years, and type C 52.7 ± 16.9 years). Normalized for gender disproportion, there was no significant gender predominance for any type (type A female:male = 1.4:1; type B female:male = 1.1:1; type C female:male = 0.7:1). CONCLUSIONS: Such a classification scheme with additional application in another group might be of use to future studies aimed at the morphology of the cavernous part of the internal carotid artery.

Endoscopic endonasal resection of skull base chondrosarcomas: technique and early results.

OBJECT: The authors of this study sought to report the technique and early clinical outcomes of a purely endonasal endoscopic approach for resection of petroclival chondrosarcomas. METHODS: Between 2010 and 2014, 8 patients (4 men and 4 women) underwent endonasal endoscopic operations to resect petroclival chondrosarcomas at 2 institutions. The patients' mean age was 44.8 years (range 30-64 years). One of the patients had previously undergone radiation therapy and another a staged craniotomy. Using volumetric software, an independent neuroradiologist assessed the extent of the resections on MRI scans taken immediately after surgery and at the 3-month follow-up. Immediate complications and control of symptoms were also recorded. In addition, the authors reviewed the current literature on surgical treatment of chondrosarcoma. RESULTS: The mean preoperative tumor diameter and volume were 3.4 cm and 9.8 cm(3), respectively. Six patients presented with cranial neuropathies. Endonasal endoscopic surgery achieved > 95% resection in 5 of the 8 patients and < 95% resection in the remaining 3 patients. One of the 6 neuropathies resolved, and the remaining 5 partially improved. One instance of postoperative CSF leakage required a reoperation for repair; no other complications associated with these operations were observed. All of the patients underwent adjuvant radiotherapy. CONCLUSIONS: According to the authors' experience, the endoscopic endonasal route is a safe and effective approach for the resection of appropriately selected petroclival chondrosarcomas.

Endoscopic endonasal transplanum transtuberculum resection of a large solid choroid plexus papilloma of the third ventricle.

Choroid plexus papilloma (CPP) is a highly vascular solid or mixed solid-cystic tumor. Previously described resection techniques for the more common solid CPP in the third ventricle have all been through the transcranial route. The authors review the literature and describe a patient who, to their knowledge, is the first successful resection of a large, completely solid CPP of the third ventricle through an entirely endoscopic, extended transphenoidal approach. Using modern neuroendoscopic methods and closure techniques, a gross total resection was accomplished and a successful closure without postoperative cerebrospinal fluid leak was achieved despite the presence of preoperative hydrocephalus. For appropriately selected lesions, an extended endonasal skull base resection can be performed successfully for vascular tumors despite the presence of preoperative hydrocephalus.