Outcomes in transcranial microsurgery versus extended endoscopic endonasal approach for primary resection of adult craniopharyngiomas.

OBJECTIVE Craniopharyngiomas have historically been resected via transcranial microsurgery (TCM). In the last 2 decades, the extended endoscopic endonasal (transtuberculum) approach to these tumors has become more widely accepted, yet there remains controversy over which approach leads to better outcomes. The purpose of this study is to determine whether differences in outcomes were identified between TCM and extended endoscopic endonasal approaches (EEEAs) in adult patients undergoing primary resection of suprasellar craniopharyngiomas at a single institution. METHODS A retrospective review of all patients who underwent resection of their histopathologically confirmed craniopharyngiomas at the authors' institution between 2005 and 2015 was performed. Pediatric patients, revision cases, and patients with tumors greater than 2 standard deviations above the mean volume were excluded. The patients were divided into 2 groups: those undergoing primary TCM and those undergoing a primary EEEA. Preoperative patient demographics, presenting symptoms, and preoperative tumor volumes were determined. Extent of resection, tumor histological subtype, postoperative complications, and additional outcome data were obtained. Statistical significance between variables was determined utilizing Student t-tests, chi-square tests, and Fisher exact tests when applicable. RESULTS After exclusions, 21 patients satisfied the aforementioned inclusion criteria; 12 underwent TCM for resection while 9 benefitted from the EEEA. There were no significant differences in patient demographics, presenting symptoms, tumor subtype, or preoperative tumor volumes; no tumors had significant lateral or prechiasmatic extension. The extent of resection was similar between these 2 groups, as was the necessity for additional surgery or adjuvant therapy. CSF leakage was encountered only in the EEEA group (2 patients). Importantly, the rate of postoperative visual improvement was significantly higher in the EEEA group than in the TCM group (88.9% vs 25.0%; p = 0.0075). Postoperative visual deterioration only occurred in the TCM group (3 patients). Recurrence was uncommon, with similar rates between the groups. Other complication rates, overall complication risk, and additional outcome measures were similar between these groups as well. CONCLUSIONS Based on this study, most outcome variables appear to be similar between TCM and EEEA routes for similarly sized tumors in adults. The multidisciplinary EEEA to craniopharyngioma resection represents a safe and compelling alternative to TCM. The authors' data demonstrate that postoperative visual improvement is statistically more likely in the EEEA despite the increased risk of CSF leakage. These results add to the growing evidence that the EEEA may be considered the approach of choice for resection of select confined primary craniopharyngiomas without significant lateral extension in centers with experienced surgeons. Further prospective, multiinstitutional collaboration is needed to power studies capable of fully evaluating indications and appropriate approaches for craniopharyngiomas.

Incidence, epidemiology, and treatment of aneurysmal subarachnoid hemorrhage in 12 midwest communities.

Only 8 studies have investigated the incidence and epidemiology of aneurysmal subarachnoid hemorrhage (aSAH) in the United States. This is the first investigation in Indiana, which has some of the highest rates of tobacco smoking and obesity in the nation. The authors prospectively identified 441 consecutive patients with aSAH from 2005 to 2010 at 2 hospitals where the majority of cases are treated. Incidence calculations were based on US Census populations. Epidemiologic variables included demography; risk factors; Hunt and Hess scale; Fisher grade; number, location, and size of aneurysms; treatment type; and complications. Overall incidence was 21.8 per 100,000 population. Incidence was higher in women, increased with age, and did not vary by race. One third to half of patients were hypertensive and/or smoked cigarettes at the time of ictus. Variations by count were partially explained by Health Factor and Morbidity Rankings. Complications varied by treatment. These findings deviate from estimates that 6-16 per 100,000 people in the United States will develop aSAH and are double the incidence in a Minnesota population between 1945 and 1974. The results also deviate from the worldwide estimate of 9.0 aSAHs per 100,000 person-years. The predictive value of variations in Health Factor and Morbidity Rankings implicates the importance of future research on multivariate biopsychosocial causation of aSAH.

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.

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.

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.

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.

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.

Technical video: Onyx-18 embolization of spinal epidural arteriovenous Fistula using the scepter-Mini balloon catheter.

Spinal arteriovenous fistulas (AVFs) account for approximately 70% of all vascular spinal malformations and commonly develop in the lateral epidural space at the epidural /radicular venous junction. The fistula is located close to the spinal nerve root where a radiculomeningeal artery shunts to a radicular vein. Increased venous pressure leads to decreased spinal venous drainage and venous congestion causing progressive myelopathy, bowel/bladder incontinence and erectile dysfunction. Treatment consists of surgical occlusion of the intradural vein, or endovascular embolization, which has a reported success rate of 25%-75%.1 Endovascular failure can occur with inadequate embolic penetration of the nidus and the proximal segment of the draining vein, or premature reflux of the liquid embolic agent.The use of a dual-lumen balloon microcatheter offers advantage in these cases given the ability to push liquid embolysate more distally during balloon inflation. The Scepter Mini is a new dimethyl-sulfoxide (DMSO)-compatible dual-lumen balloon microcatheter with a distal-tip outer diameter of 1.6 Fr and a nominal balloon diameter of 2.2 mm, facilitating atraumatic navigation and safer balloon inflation. Limited neurointerventional experience using the Scepter Mini in predominantly cerebrovascular cases has reported favorable navigability and flow arrest2, 3 Although Onyx is rarely used for spinal AVF embolization, success has been reported considering the well-known favorable experience in cerebral cases.1, 4, 5We present one of the first cases of Onyx embolization of a spinal dural AVF through a Scepter Mini in a patient with progressively worsening lower extremity sensorimotor dysfunction. Operators should be aware of radiculomedullary arteries arising at the same level or at adjacent levels to avoid unintentional Onyx migration during balloon inflation.

The Use of a Pipeline Embolization Device for Treatment of a Ruptured Dissecting Middle Cerebral Artery M3/M4 Aneurysm: Challenges and Technical Considerations.

Prompt, effective treatment is necessary following aneurysmal subarachnoid hemorrhage to prevent recurrent rupture, which is thought to double mortality. Atypical ruptured aneurysms, such as blister or dissecting pseudoaneurysms, or those that are unusually distal in the middle cerebral artery (MCA) are challenging to treat with either open or endovascular options, though the pipeline embolization device (PED) has shown promise in multiple case series. We present a case of a ruptured dissecting pseudoaneurysm in the distal MCA (distal M3/proximal M4) prefrontal division in an healthy young patient (<60 years) successfully treated with a PED. The PED was chosen both as the only vessel sparing option in the young patient as well as for its potential as a vessel sacrifice tool if the pseudoaneurysm was felt to be incompletely treated, which in this case was not necessary-though would have leveraged the thrombogenicity of the device as a therapeutic advantage.

Use of Adenosine to Facilitate Localization and Repair of Internal Carotid Artery Injury during Skull Base Surgery: A Case Report and Literature Review.

BACKGROUND: Internal carotid artery (ICA) injuries represent a rare, potentially fatal complication of endoscopic endonasal skull base surgery (EESBS). The use of adenosine to induce transient hypotension and facilitate management of high-flow, high-pressure arterial lesions has been well-documented in neuro-endovascular literature. A similar setting in which adenosine-induced hypotension may prove beneficial is during the management of major vascular injury encountered during EESBS. METHODS: A case of ICA injury and subsequent repair during EESBS is presented. RESULTS: A 74-year-old female underwent endoscopic transsphenoidal resection for a recurrent pituitary adenoma. During suprasellar resection, the right cavernous ICA was inadvertently injured resulting in brisk bleeding. Immediate vascular tamponade was applied, and a crushed muscle graft was obtained. Two intravenous doses of adenosine were administered in quick succession to produce transient hypotension and facilitate repair of the injury with the graft. Neurovascular imaging revealed a small pseudoaneurysm which remained stable throughout the postoperative course. The patient underwent definitive stent embolization of the pseudoaneurysm 1 month following discharge. CONCLUSION: Prompt repair of ICA injury during EESBS is crucial, but often limited by poor visualization. Adenosine-induced hypotension has demonstrated great efficacy as an adjuvant in neurovascular clipping of intracranial aneurysms and remains a valuable tool for the endoscopic skull-base surgeon as well. In cases with high risk for ICA injury, adenosine should be readily available.

Endovascular treatment and radiographic follow-up of proximal traumatic intracranial aneurysms in adolescents: case series and review of the literature.

PURPOSE: Traumatic intracranial aneurysms are rare lesions that are relatively more common in the pediatric population. Proximal traumatic aneurysms occur near the skull base. Direct surgical repair of these lesions is difficult due to the anatomically confined area, clinical status of a head injury patient, and the transmural nature of the injury. These lesions often lack a definable neck or wall suitable for clipping. While the indications and capabilities of endovascular treatment continue to expand, there are unanswered questions about the durability of treatment, especially in young patients. There are few reports examining the radiographic outcomes of endovascular treatment specifically for traumatic intracranial aneurysms. Therefore, we examined our experience treating these rare proximal lesions in an adolescent population. METHODS: A retrospective review of prospectively collected data from 2000-2008 in a large, multidisciplinary neurovascular and trauma center was performed. RESULTS: Three pediatric patients received endovascular treatment for traumatic intracranial aneurysms near the skull base. All patients had successful obliteration of their lesion without vessel sacrifice; however, two patients required multiple procedures for coil compaction or refilling of the aneurysm. There were no complications or ischemic events related to treatment. Follow-up imaging ranged from 6 months to 3.5 years. CONCLUSIONS: Traumatic intracranial aneurysms at the skull base can be successfully treated with endovascular methods; however, close follow-up is necessary.

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.

Trans-zygomatic middle cranial fossa approach to access lesions around the cavernous sinus and anterior parahippocampus: a minimally invasive skull base approach.

PURPOSE: Exposure of the cavernous sinus or anterior parahippocampus often involves a wide exposure of the temporal lobe and mobilization of the temporalis muscle associated with temporal lobe retraction. The authors present a cadaveric study to illustrate the feasibility, advantages and landmarks necessary to perform a trans-zygomatic middle fossa approach to lesions around the cavernous sinus and anterior parahippocampus. METHODS: The authors performed bilateral trans-zygomatic middle fossae exposures to reach the cavernous sinus and parahippocampus in five cadavers (10 sides). We assessed the morbidity associated with this procedure and compared the indications, advantages, and disadvantages of this method versus more extensive skull base approaches. A vertical linear incision along the middle portion of the zygomatic arch was extended one finger breadth inferior to the inferior edge of the zygomatic arch. Careful dissection inferior to the arch allowed preservation of facial nerve branches. A zygomatic osteotomy was followed via a linear incision through the temporalis muscle and exposure of the middle cranial fossa floor. RESULTS: A craniotomy along the inferolateral temporal bone and middle fossa floor allowed extradural dissection along the middle fossa floor and exposure of the cavernous sinus including all three divisions of the trigeminal nerve. Intradural inspection demonstrated adequate exposure of the parahippocampus. Exposure of the latter required minimal or no retraction of the temporal lobe. CONCLUSIONS: The trans-zygomatic middle fossa approach is a simplified skull base exposure using a linear incision, which may avoid the invasivity of more extensive skull base approaches while providing an adequate corridor for resection of cavernous sinus and parahippocampus lesions. The advantages of this approach include its efficiency, ease, minimalism, preservation of the temporalis muscle, and minimal retraction of the temporal lobe.

A Systematic Review of Sellar and Parasellar Brown Tumors: An Analysis of Clinical, Diagnostic, and Management Profiles.

OBJECTIVE: To systematically review and analyze clinical, diagnostic, and management trends in sellar and parasellar brown tumors reported in existing literature. METHODS: In this systematic review, PubMed, Ovid MEDLINE, Scopus, and Google Scholar databases were searched for reported cases of sellar/parasellar brown tumors. Relevant titles and abstracts were screened in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles meeting inclusion criteria were subjected to data extraction, summarization, and analysis. A rare case of parasellar brown tumor was also presented. RESULTS: Eight reports (including the current report) were eligible for inclusion. Mean patient age was 42.75 years. Reported symptoms included visual disturbances (n = 6), headache (n = 5), fatigue (n = 3), nausea/vomiting (n = 2), chest pain (n = 1), neck pain (n = 1), and dysphagia (n = 1). In cases where computed tomography findings were provided (n = 6), lesions were noted to be expansile and lytic. Lesions were hyperintense on T2-weighted magnetic resonance imaging (66.7%) and demonstrated contrast enhancement (83.3%). Histology unanimously showed multinucleated giant cells in a fibrovascular connective tissue stroma. Dramatic symptom resolution was noted in all patients who underwent resection of the sellar/parasellar brown tumor (n = 4; 50%). CONCLUSIONS: Sellar/parasellar brown tumors are a rare, tertiary manifestation of hyperparathyroidism and can be elusive to diagnose. Diagnosis requires a high index of clinical suspicion in addition to comprehensive biochemical testing, imaging, and histopathologic analysis. Surgical extirpation is favored in cases where the lesion is causing compressive symptoms, or if it is unresponsive to management of hyperparathyroidism.

Neurosurgical Management of Self-Inflicted Cranial Crossbow Injury.

BACKGROUND: Although gun-related penetrating traumatic brain injuries make up the majority of cranial missile injuries, low-velocity penetrating injuries present significant clinical difficulties that cannot necessarily be identically managed. Bow hunting is an increasingly popular pastime, and a crossbow allows a unique mechanism to cause a self-inflicted cranial injury with a large, low-velocity projectile. Historically, arrow removal is described in an operating room setting, which provides limited knowledge of the location of vascular injury in the setting of postremoval hemorrhage, and may represent an inefficient use of operating room availability. CASE DESCRIPTION: Two patients presented after self-inflicted cranial crossbow injuries. Both were neurologically salvageable. Initial assessment with computed tomography angiography allowed triage into likely or unlikely vascular injury. Arrow removal was performed in a radiology setting rather than in the operating room to allow immediate postremoval imaging to localize hemorrhage. While an operating room was on standby, neither patient required neurosurgical operative intervention. Both patients made a good recovery with no further injury caused by arrow removal. CONCLUSIONS: We describe a novel approach to retained cranial arrow removal in a radiologic, rather than operative, setting and describe its relative benefits over traditional removal in the operating room.

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.

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.

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.

Effects of distance and transport method on intervention and mortality in aneurysmal subarachnoid hemorrhage.

OBJECTIVE Most patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) initially present to a hospital that lacks a neurosurgical unit. These patients require interhospital transfer (IHT) to tertiary facilities capable of multidisciplinary neurosurgical intervention. Yet, little is known about the effects of IHT on the outcomes of patients suffering from aSAH. In this study, the authors examined the effects of IHT and transport method on the timing of treatment, rebleed rates, and overall outcomes of patients who have experienced aSAH. METHODS A retrospective review of medical records identified all consecutive patients who presented with aSAH at an outside hospital and subsequently underwent IHT to a tertiary aneurysm care center and patients who initially presented directly to a tertiary aneurysm care facility between 2008 and 2015. Demographic, operative, radiological, hospital of initial evaluation, transfer method, and outcome data were retrospectively collected. RESULTS The authors identified 763 consecutive patients who were evaluated for aSAH at a tertiary aneurysm care facility either directly or following IHT. For patients who underwent IHT and after accounting for these patients' clinical variability and dichotomizing the patients into groups transferred less than 20 miles and more than 20 miles, the authors noted a significant increase in mortality rates: 7% (< 20 miles) and 18.8% (> 20 miles) (p = 0.004). The increased mortality rate was partially explained by an increased rate of initial presentation to an accredited stroke center in patients undergoing IHT of less than 20 miles (p = 0.000). The method of transport (ground or air ambulance) was found to have significant effect on the patients' outcomes as measured by the Glasgow Outcome Scale score (p = 0.021); patients who underwent ground transport demonstrated a higher likelihood of discharge to home (p = 0.004). The increased severity of presentation in the patient cohort undergoing IHT by air as defined by the Glasgow Coma Scale score, a need for an external ventricular drain, Hunt and Hess grade, and intubation status at presentation did not result in increased mortality when compared with the ground cohort (p = 0.074). In addition, there was an 8-hour increase in duration of time from admission to treatment for the air cohort as compared with the ground cohort (p = 0.054), indicating a potential for further improvement in the overall outcome of this patient group. CONCLUSIONS Aneurysmal SAH remains a challenging neurosurgical disease process requiring highly coordinated care in tertiary referral centers. In this study, the overall distance traveled and the transport method affected patient outcomes. The time from admission to treatment should continue to improve. Further analysis of IHT with a focus on patient monitoring and treatment during transport is warranted.

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).