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Augmented reality (AR) technology has played an increasing role in cerebrovascular neurosurgery over the last two decades. Hence, we aim to evaluate the technical and educational value of head-mounted (HM) AR in cerebrovascular procedures.This is a single-center retrospective study of patients who underwent open surgery for cranial and spinal cerebrovascular lesions between April and August 2022. In all cases, the Medivis Surgical AR platform and HoloLens 2 were used for preoperative and intraoperative (pre-incision) planning. Surgical plan adjustment due to the use of HMAR and subjective educational value of the tool were recorded.33 patients and 35 cerebrovascular neurosurgical procedures were analyzed. Procedures included: 12 intracranial aneurysm (IA) clippings, six brain and one spinal arteriovenous malformation (AVM) resections, two cranial dural arteriovenous fistula (DAVF) obliterations, three carotid endarterectomies (CEA), two extracranial-intracranial direct bypasses, two encephaloduroangiosynostosis (EDAS) for Moyamoya disease, one biopsy of superficial temporal artery (STA), two microvascular decompressions (MVD), two cavernoma resections, one combined IA clipping and EDAS for Moyamoya disease and one percutaneous feeder catheterization for AVM embolization. Minor changes in the surgical plan were recorded in 16/35 procedures (45.7%). Subjective educational value was scored as: "very helpful" for cranial, spinal AVMs, and CEAs; "helpful" for IA, DAVFs, direct bypass, EDAS, and STA-biopsy; and "not helpful" for cavernoma resection and MVD.HMAR can be used in cerebrovascular neurosurgery as an adjunctive tool that might influence surgical strategy, enable 3-dimensional understanding of complex anatomy, and provide great educational value in selected cases.

Background Vertebral-venous fistulas (VVFs) are rare. Scarce literature exists to guide our understanding and management. We report our experience and propose a classification based on flow, feeder number, and involvement of accessible veins. Additionally, we include a practical treatment approach. Methods Retrospective chart and imaging review of cerebrovascular arteriovenous fistulas treated in our center between July 2013 and April 2022. We reviewed patient demographics, presentation, imaging, treatment strategies, and outcomes. Results Nine patients with VVFs were identified, six were females. Ages ranged between 38–83 years. There were six high-flow and three low-flow. Most VVFs originated at the level of V3. Additional feeders from the internal carotid artery, external carotid artery, and/or subclavian artery were present in four cases (two were high-flow). Four cases had multiple arterial feeders. All cases were symptomatic. Origin was spontaneous in eight and iatrogenic in one case. Most common presenting symptoms were pain (7) and pulsatile tinnitus (4). Neurological deficits were present in two cases (1 high- and 1 low-flow). Four cases were treated with vertebral artery segmental sacrifice alone, three required multiple transarterial embolizations with or without VA sacrifice, one case had single transvenous approach, and one was treated with single targeted transarterial embolization. One patient had a minor transient neurological complication. No treatment-related mortality was seen. Conclusion Treatment of high-flow and symptomatic low-flow VVFs is feasible and safe. Our classification and treatment approach might help guide patient selection and choice of endovascular approach. However, our approach warrants further validation with a larger number of patients.

Background Intracranial pseudoaneurysms (PSAs) are associated with high rupture and mortality rates and have traditionally been treated by parent vessel sacrifice. There has been recent interest in using flow-diverting devices for treatment of these complex lesions while preserving flow through the parent artery. The objective of this study is to examine the safety and efficacy of these devices in the treatment of intracranial PSA. Methods We performed a multi-institutional retrospective study of intracranial PSAs treated with the Pipeline Embolization Device (PED) between 2014 and 2017 at 7 institutions. Complications and clinical and radiographic outcomes were reviewed. Results A total of 19 patients underwent PED placement for intracranial PSA. Iatrogenic injury and trauma comprised most etiologies in our series. The mean pseudoaneurysm diameter was 8.8 mm, and 18 of 19 PSAs (95%) involved the internal carotid artery (ICA). Multiple PEDs were deployed in a telescoping fashion in 7 patients (37%). Of the 18 patients with follow up imaging, 14 (78%) achieved complete pseudoaneurysm obliteration and 2 achieved near-complete obliteration (11%). Two patients (11%) were found to have significant pseudoaneurysm progression on short-term follow-up and required ICA sacrifice. No patients experienced new neurologic deficits or deterioration secondary to PED placement. No patients experienced bleeding or rebleeding from PSA. Conclusions In well-selected patients, the use of flow-diverting stents may be a feasible alternative to parent vessel sacrifice. Given the high morbidity and mortality associated with PSA, we recommend short- and long-term radiographic follow-up for patients treated with flow-diverting stents.

Background and Purpose— Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods— STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0–2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results— Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P =0.001) and distal access catheter (83/235 [35%]; P =0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P P =0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P =0.007) and distal access catheter (113/218 [52%]; P =0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions— BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Objectives To examine outcome of bilateral extracranial to intracranial (EC-IC) bypass surgeries for a Down syndrome patient with hard-to-treat epilepsy and moyamoya. Materials and methods Superficial temporal arteries were anastamosed using an indirect bypass technique to middle cerebral arteries bilaterally to help limit perfusion deficits and seizure controls. Results Two superficial temporal to middle cerebral artery indirect bypass surgeries were performed within 3 months. Post-revascularization improvements included seizure control, gait, perfusion, wakefulness, language and quality of life. Conclusion In patients with Down syndrome and moyamoya, improvements in seizure control and quality of life may occur with EC-IC bypass procedures., Highlights • Moyamoya blood flow compromises can be seen in Down syndrome. • Both moyamoya and Down syndrome are associated with Epilepsy. • If moyamoya related perfusion worsens, so can seizure control. • We report bilateral indirect extracranial to intracranial bypass surgeries in a Down syndrome patient with moyamoya. • The surgeries markedly improved seizure control and quality of life.

Acute and subacute carotid occlusion represents a challenging clinical scenario. Treatment paradigms are shifting towards being more aggressive with revascularization. In patients with a symptomatic occlusion and a favorable infarct burden, revascularization should be considered. Multiple imaging modalities, including DUS, CTA, MRI, perfusion imaging, and traditional catheter angiography should be used to draw a comprehensive picture of the patient’s intracranial perfusion and reserve at the time of presentation. Questions regarding the superiority of open versus endovascular treatment, angioplasty and stenting versus angioplasty alone, and proximal-to-distal versus distal-to-proximal treatment order have yet to be answered.

Supplemental Digital Content is available in the text., Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P

Background and Purpose— Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. Methods— STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. Results— A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab–adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. Conclusions— This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Complications from anterior approaches to the cervical spine are uncommon with normal anatomy. However, variant anatomy might predispose one to an increased incidence of injury during such procedures. We hypothesized that left vertebral arteries that arise from the aortic arch instead of the subclavian artery might take a more medial path in their ascent making them more susceptible to iatrogenic injury. Fifty human adult cadavers were examined for left vertebral arteries having an aortic arch origin and these were dissected along their entire cervical course. Additionally, two radiological databases of CTA and arteriography procedures were retrospectively examined for cases of aberrant left vertebral artery origin from the aortic arch over a two-year period. Two cadaveric specimens (4%) were found to have a left vertebral artery arising from the aortic arch. The retrospective radiological database analysis identified 13 cases (0.87%) of left vertebral artery origin from the aortic arch. Of all cases, vertebral arteries that arose from the aortic arch were much more likely to not only have a more medial course (especially their preforaminal segment) over the cervical vertebral bodies but also to enter a transverse foramen that was more cranially located than the normal C6 entrance of the vertebral artery. Spine surgeons who approach the anterior cervical spine should be aware that an aortic origin of the left vertebral artery is likely to be closer to the midline and less protected above the C6 vertebral level. Clin. Anat. 30:811-816, 2017. © 2017Wiley Periodicals, Inc.

Objective Posterior circulation strokes account for over one quarter of all ischemic strokes. The frequency of vertebral artery origin stenosis (VAOS) in patients with vertebrobasilar insufficiency (VBI) has been estimated to be as high 26%–32%, and VAOS is the direct cause of posterior circulation strokes in 9% of patients. This association could have a significant genetic component. This study examines the feasibility of the internal thoracic artery (ITA) as a donor vessel for revascularization in patients with VAOS. Methods Ten sides from 5 fresh-frozen white cadaveric necks derived from 3 women and 2 men were used in this study. The mean age of the cadavers at death was 77.2 years (range, 68–88 years). The subclavian artery, vertebral artery, and ITA were dissected. The length and diameter (proximal and distal) of the V1 segment and the length and diameter of the ITA were recorded. Finally, the ITA was transposed to the V1 segment of the vertebral artery (VA1). Results The mean length of the VA1 and its diameter at the proximal and distal parts were 35.51 and 3.69 mm, respectively. The mean length and diameter of the ITA were 26.53 and 3.27 mm, respectively. Rerouting the ITA to the VA1 was feasible without tension on all sides. Conclusions This study indicates that the ITA is anatomically and hemodynamically an excellent option for bypass surgery in a VAOS scenario. We present convincing and reproducible data to aid neurosurgeons in choosing the procedure best suited to their patients.

Appropriate management of adult gliomas requires an accurate histopathological diagnosis. However, the heterogeneity of gliomas can lead to misdiagnosis and undergrading, especially with biopsy. We evaluated the role of preoperative relative cerebral blood volume (rCBV) analysis in conjunction with histopathological analysis as a predictor of overall survival and risk of undergrading. We retrospectively identified 146 patients with newly diagnosed gliomas (WHO grade II–IV) that had undergone preoperative MRI with rCBV analysis. We compared overall survival by histopathologically determined WHO tumor grade and by rCBV using Kaplan–Meier survival curves and the Cox proportional hazards model. We also compared preoperative imaging findings and initial histopathological diagnosis in 13 patients who underwent biopsy followed by subsequent resection. Survival curves by WHO grade and rCBV tier similarly separated patients into low, intermediate, and high-risk groups with shorter survival corresponding to higher grade or rCBV tier. The hazard ratio for WHO grade III versus II was 3.91 (p = 0.018) and for grade IV versus II was 11.26 (p

BACKGROUND AND PURPOSE: MR imaging–guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue. The goal of this study was to describe MR imaging findings pre- and post-ventralis intermedius nucleus lesioning by MR imaging–guided focused sonography as a treatment for essential tremor and to determine whether there was an association between these imaging features and the clinical response to MR imaging–guided focused sonography. MATERIALS AND METHODS: Fifteen patients with medication-refractory essential tremor prospectively gave consent; were enrolled in a single-site, FDA-approved pilot clinical trial; and were treated with transcranial MR imaging–guided focused sonography. MR imaging studies were obtained on a 3T scanner before the procedure and 24 hours, 1 week, 1 month, and 3 months following the procedure. RESULTS: On T2-weighted imaging, 3 time-dependent concentric zones were seen at the site of the focal spot. The inner 2 zones showed reduced ADC values at 24 hours in all patients except one. Diffusion had pseudonormalized by 1 month in all patients, when the cavity collapsed. Very mild postcontrast enhancement was seen at 24 hours and again at 1 month after MR imaging–guided focused sonography. The total lesion size and clinical response evolved inversely compared with each other (coefficient of correlation = 0.29, P value = .02). CONCLUSIONS: MR imaging–guided focused sonography can accurately ablate a precisely delineated target, with typical imaging findings seen in the days, weeks, and months following the treatment. Tremor control was optimal early when the lesion size and perilesional edema were maximal and was less later when the perilesional edema had resolved.

Object Intravenous sodium nitrite has been shown to prevent and reverse cerebral vasospasm in a primate model of subarachnoid hemorrhage (SAH). The present Phase IIA dose-escalation study of sodium nitrite was conducted to determine the compound's safety in humans with aneurysmal SAH and to establish its pharmacokinetics during a 14-day infusion. Methods In 18 patients (3 cohorts of 6 patients each) with SAH from a ruptured cerebral aneurysm, nitrite (3 patients) or saline (3 patients) was infused. Sodium nitrite and saline were delivered intravenously for 14 days, and a dose-escalation scheme was used for the nitrite, with a maximum dose of 64 nmol/kg/min. Sodium nitrite blood levels were frequently sampled and measured using mass spectroscopy, and blood methemoglobin levels were continuously monitored using a pulse oximeter. Results In the 14-day infusions in critically ill patients with SAH, there was no toxicity or systemic hypotension, and blood methemoglobin levels remained at 3.3% or less in all patients. Nitrite levels increased rapidly during intravenous infusion and reached steady-state levels by 12 hours after the start of infusion on Day 1. The nitrite plasma half-life was less than 1 hour across all dose levels evaluated after stopping nitrite infusions on Day 14. Conclusions Previous preclinical investigations of sodium nitrite for the prevention and reversal of vasospasm in a primate model of SAH were effective using doses similar to the highest dose examined in the current study (64 nmol/kg/min). Results of the current study suggest that safe and potentially therapeutic levels of nitrite can be achieved and sustained in critically ill patients after SAH from a ruptured cerebral aneurysm. Clinical trial registration no.: NCT00873015 (ClinicalTrials.gov).

Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor.From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability).Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001).In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).

Object Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube. Methods and Results In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance. Conclusions The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

Magnetic resonance–guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

Object Transcranial MR-guided focused ultrasound surgery (MRgFUS) is evolving as a treatment modality in neurosurgery. Until now, the trigeminal nerve was believed to be beyond the treatment envelope of existing high-frequency transcranial MRgFUS systems. In this study, the authors explore the feasibility of targeting the trigeminal nerve in a cadaveric model with temperature assessments using computer simulations and an in vitro skull phantom model fitted with thermocouples. Methods Six trigeminal nerves from 4 unpreserved cadavers were targeted in the first experiment. Preprocedural CT scanning of the head was performed to allow for a skull correction algorithm. Three-Tesla, volumetric, FIESTA MRI sequences were performed to delineate the trigeminal nerve and any vascular structures of the cisternal segment. The cadaver was positioned in a focused ultrasound transducer (650-kHz system, ExAblate Neuro, InSightec) so that the focus of the transducer was centered at the proximal trigeminal nerve, allowing for targeting of the root entry zone (REZ) and the cisternal segment. Real-time, 2D thermometry was performed during the 10- to 30-second sonication procedures. Post hoc MR thermometry was performed on a computer workstation at the conclusion of the procedure to analyze temperature effects at neuroanatomical areas of interest. Finally, the region of the trigeminal nerve was targeted in a gel phantom encased within a human cranium, and temperature changes in regions of interest in the skull base were measured using thermocouples. Results The trigeminal nerves were clearly identified in all cadavers for accurate targeting. Sequential sonications of 25–1500 W for 10–30 seconds were successfully performed along the length of the trigeminal nerve starting at the REZ. Real-time MR thermometry confirmed the temperature increase as a narrow focus of heating by a mean of 10°C. Postprocedural thermometry calculations and thermocouple experiments in a phantom skull were performed and confirmed minimal heating of adjacent structures including the skull base, cranial nerves, and cerebral vessels. For targeting, inclusion of no-pass regions through the petrous bone decreased collateral heating in the internal acoustic canal from 16.7°C without blocking to 5.7°C with blocking. Temperature at the REZ target decreased by 3.7°C with blocking. Similarly, for midcisternal targeting, collateral heating at the internal acoustic canal was improved from a 16.3°C increase to a 4.9°C increase. Blocking decreased the target temperature increase by 4.4°C for the same power settings. Conclusions This study demonstrates focal heating of up to 18°C in a cadaveric trigeminal nerve at the REZ and along the cisternal segment with transcranial MRgFUS. Significant heating of the skull base and surrounding neural structures did not occur with implementation of no-pass regions. However, in vivo studies are necessary to confirm the safety and efficacy of this potentially new, noninvasive treatment.

OBJECTIVE In appropriate candidates, the treatment of medication-refractory mesial temporal lobe epilepsy (MTLE) is primarily surgical. Traditional anterior temporal lobectomy yields seizure-free rates of 60%–70% and possibly higher. The field of magnetic resonance–guided focused ultrasound (MRgFUS) is an evolving field in neurosurgery. There is potential to treat MTLE with MRgFUS; however, it has appeared that the temporal lobe structures were beyond the existing treatment envelope of currently available clinical systems. The purpose of this study was to determine whether lesional temperatures can be achieved in the target tissue and to assess potential safety concerns. METHODS Cadaveric skulls with tissue-mimicking gels were used as phantom targets. An ablative volume was then mapped out for a “virtual temporal lobectomy.” These data were then used to create a target volume on the InSightec ExAblate Neuro system. The target was the amygdala, uncus, anterior 20 mm of hippocampus, and adjacent parahippocampal gyrus. This volume was approximately 5cm3. Thermocouples were placed on critical skull base structures to monitor skull base heating. RESULTS Adequate focusing of the ultrasound energy was possible in the temporal lobe structures. Using clinically relevant ultrasound parameters (power 900 W, duration 10 sec, frequency 650 kHz), ablative temperatures were not achieved (maximum temperature 46.1°C). Increasing sonication duration to 30 sec demonstrated lesional temperatures in the mesial temporal lobe structures of interest (up to 60.5°C). Heating of the skull base of up to 24.7°C occurred with 30-sec sonications. CONCLUSIONS MRgFUS thermal ablation of the mesial temporal lobe structures relevant in temporal lobe epilepsy is feasible in a laboratory model. Longer sonications were required to achieve temperatures that would create permanent lesions in brain tissue. Heating of the skull base occurred with longer sonications. Blocking algorithms would be required to restrict ultrasound beams causing skull base heating. In the future, MRgFUS may present a minimally invasive, non-ionizing treatment of MTLE.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel combination of technologies that is actively being realized as a noninvasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological use. A combined search of PubMed and MEDLINE was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real time, it allows monitored provision of treatment location and energy deposition; is noninvasive, thereby limiting or eliminating disruption of normal tissue; provides focal delivery of therapeutic agents; enhances radiation delivery; and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early-phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact.

Object Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18–36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated. Methods Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0–2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy. Results The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033). Conclusions Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10–36 hours after surgery despite prolonged and severe hypercortisolism.

Object Intratumoral hypoxia is believed to be exhibited in high-grade gliomas. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion to hypoxic tissues. In this research, the authors use oxygen-sensitive PET studies to evaluate the extent of hypoxia in vivo in a glioblastoma model and the effect of TSC on the baseline oxygenation of the tumor. Methods The C6 glioma cells were stereotactically implanted in the right frontal region of rat brains. Formation of intracranial tumors was confirmed on MR imaging. Animals were injected with Copper(II) diacetyl-di(N4-methylthiosemicarbazone) (Cu-ATSM) and then either TSC or saline (6 rats each). Positron emission tomography imaging was performed, and relative uptake values were computed to determine oxygenation within the tumor and normal brain parenchyma. Additionally, TSC or saline was infused into the animals, and carbonic anhydrase 9 (CA9) and hypoxia-inducing factor–1α (HIF-1α) protein expression were measured 1 day afterward. Results On PET imaging, all glioblastoma tumors demonstrated a statistically significant decrease in uptake of Cu-ATSM compared with the contralateral cerebral hemisphere (p = 0.000002). The mean relative uptake value of the tumor was 3900 (range 2203–6836), and that of the contralateral brain tissue was 1017 (range 488–2304). The mean relative hypoxic tumor volume for the saline group and TSC group (6 rats each) was 1.01 ± 0.063 and 0.69 ± 0.062, respectively (mean ± SEM, p = 0.002). Infusion of TSC resulted in a 31% decrease in hypoxic volume. Immunoblot analysis revealed expression of HIF-1α and CA9 in all tumor specimens. Conclusions Some glioblastomas exhibit hypoxia that is demonstrable on oxygen-specific PET imaging. It appears that TSC lessens intratumoral hypoxia on functional imaging. Further studies should explore relative hypoxia in glioblastoma and the potential therapeutic gains that can be achieved by lessening hypoxia during delivery of adjuvant treatment.

The treatment of high-flow vein of Galen aneurysmal malformations (VGAM) remains a therapeutic challenge for the neurosurgeon and the neurointerventionalist, as it is associated with high morbidity and mortality rates despite recent advances in open cranial surgery and interventional neuroradiology. A 37-year-old patient presented with a history of non-specific headaches. He had a history of heart failure since birth that was caused by an untreated VGAM. Intravenous boluses of adenosine were injected as an attempt to slow down the arteriovenous shunting of a VGAM prior to endovascular treatment. Adenosine can be a very useful adjunct in patients with extremely high arteriovenous shunting. n-butyl cyanoacrylate (n-BCA) should be the embolic material of choice due to its quick polymerization and adhesive properties.

Background and Purpose— The effects of aneurysm treatment modality (clipping or coiling) on the incidence of cerebral vasospasm and infarction after subarachnoid hemorrhage have not been clearly defined. We hypothesized that there may be a difference in angiographic and clinical vasospasm, cerebral infarction, and clinical outcome between patients undergoing clipping compared to coiling. Methods— A retrospective, exploratory analysis of 413 patients randomized into the CONSCIOUS-1 trial was conducted. Patients underwent baseline and follow-up catheter angiography and computed tomography, as well as clinical assessments. Radiology end points were adjudicated by central blinded review, and angiographic vasospasm was quantified by measurements of arterial diameters on catheter angiography. The effect of method of aneurysm treatment (clipping [n=199] or coiling [n=214]) on angiographic vasospasm, delayed ischemic neurological deficit, cerebral infarction, and clinical outcome was analyzed using univariate and multivariate logistic regression. Propensity matching was used to adjust for differences in baseline risk factors between clipped and coiled patients. Results— In all patients and the propensity-matched subset, aneurysm coiling was associated with a significantly reduced risk of angiographic vasospasm and delayed ischemic neurological deficit compared to clipping. Cerebral infarction and clinical outcome were not associated with clipping or coiling. Conclusions— In this exploratory analysis, aneurysm coiling was associated with less angiographic vasospasm and delayed ischemic neurological deficit than surgical clipping, whereas no effect on cerebral infarction or clinical outcome was observed. Whether this is attributable to differences in baseline risk factors between clipped and coiled patients or a true difference cannot be proven here.

Object The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS). Methods Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm3 at the time of GKS, and a mean prescription dose of 21.9 Gy was used. Results After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career. Conclusions Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

Astroblastomas are exceedingly rare central nervous system tumors. Surgical resection is the standard initial treatment for astroblastomas. Still, some astroblastomas that have been completely resected recur. The optimal treatment for these lesions is unclear. There are no previous reports of the use of Gamma Knife radiosurgery in the treatment of astroblastomas. The patient is a 58 year old woman who had undergone resection of a left parieto-occipital tumor at an outside hospital in 2002, with repeat resection for recurrences in 2005 and 2007. Pathologic analysis at the Mayo Clinic demonstrated the tumor to be a low-grade astroblastoma. Repeat imaging in 2008 again demonstrated recurrence, and the patient was referred to our center for Gamma Knife radiosurgery. Pre and post-contrast T1 stereotactic MR images were obtained and imported into the treatment planning system for the Gamma Knife Perfexion. Two foci of tumor consistent with the patient's known left parietal astroblastoma were identified. A prescription dose of 18.00 Gy to the 50% isodose was delivered, and 16 isocenters were used. Follow-up imaging 17 months post-radiosurgery demonstrated a decrease in tumor size. Gamma Knife radiosurgery represents a useful treatment modality for recurrent astroblastomas. While surgical resection of low grade astroblastomas can be curative, Gamma Knife radiosurgery may be beneficial in cases where gross total resection is not feasible.

Object Trigeminal neuralgia is believed to be related to vascular compression of the affected nerve. Radiosurgery has been shown to be reasonably effective for treatment of medically refractory trigeminal neuralgia. This study explores the rate of occurrence of MR imaging–demonstrated vascular impingement of the affected nerve and the extent to which vascular impingement affects pain relief in a population of trigeminal neuralgia patients undergoing Gamma Knife radiosurgery (GKRS). Methods The authors performed a retrospective analysis of 106 cases involving patients treated for typical trigeminal neuralgia using GKRS. Patients with or without single-vessel impingement on CISS MR imaging sequences and with no previous surgery were included in the study. Pain relief was assessed according to the Barrow Neurological Institute (BNI) pain intensity score at the last follow-up. Degree of impingement, nerve diameter preand post-impingement, isocenter placement, and dose to the point of maximum impingement were evaluated in relation to the improvement of BNI score. Results The overall median follow-up period was 31 months. Overall, a BNI pain score of 1 was achieved in 59.4% of patients at last follow-up. Vessel impingement was seen in 63 patients (59%). There was no significant difference in pain relief between those with and without vascular impingement following GKRS (p > 0.05). In those with vascular impingement on MR imaging, the median fraction of vessel impingement was 0.3 (range 0.04–0.59). The median dose to the site of maximum impingement was 42 Gy (range 2.9–79 Gy). Increased dose (p = 0.019) and closer proximity of the isocenter to the site of maximum vessel impingement (p = 0.012) correlated in a statistically significant fashion with improved BNI scores in those demonstrating vascular impingement on the GKRS planning MR imaging Conclusions Vascular impingement of the affected nerve was seen in the majority of patients with trigeminal neuralgia. Overall pain relief following GKRS was comparable in those with and without evidence of vascular compression on MR imaging. In subgroup analysis of those with MR imaging evidence of vessel impingement of the affected trigeminal nerve, pain relief correlated with a higher dose to the point of contact between the impinging vessel and the trigeminal nerve. Such a finding may point to vascular changes affording at least some degree of relief following GKRS for trigeminal neuralgia.

OBJECTIVE. This article reviews the physical principles of MRI-guided focused ultra-sound and discusses current and potential applications of this exciting technology. CONCLUSION. MRI-guided focused ultrasound is a new minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors.

Vascular diseases of the cerebral circulation represent a complex and diverse spectrum of pathology. Within the cerebrovascular field, there have been numerous recent advances in patient diagnosis, evaluation, imaging analysis, medical therapies, microsurgical treatments, and minimally invasive therapeutic modalities. These improvements have been driven by research developments from in vitro, in vivo, translational, and clinical studies. We review and add to the primary literature concerning this special issue. Stroke is a major cause of morbidity and mortality. Although intravenous tissue plasminogen activator has been a validated medical therapy in patients with acute ischemic stroke, there are many patients who fail to meet the defined time window for treatment. Neuroprotective agents for acute stroke could provide a major therapeutic advantage for many patients. In this issue, H.-K. Liew et al. demonstrate that “Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury.” Further studies are indicated to better define potential alternative medical therapies in acute ischemic stroke patients. Although earlier randomized clinical trials (RCTs) challenged the use of endovascular therapy in acute cerebrovascular occlusion [1–3], refinements in patient selection and three recent RCTs have validated the benefit of endovascular mechanical thrombectomy, preferably with retrievable stents (i.e., stentrievers), in patients with large vessel occlusion [4, 5]. Limitations of prior RCTs of endovascular stroke intervention included the use of earlier generation thrombectomy devices. In this issue, O. Ozdemir et al. provide us with “Predictors of a Good Outcome after Endovascular Stroke Treatment with Stent Retrievers”. Long-term follow-up in the International Study of Unruptured Intracranial Aneurysms (ISUIA) [6] and the International Subarachnoid Hemorrhage Aneurysm Trial (ISAT) has validated both microsurgical clipping and endovascular coiling in the treatment of ruptured and unruptured aneurysms [7]. As these outcomes are based on patients who were primarily treated during the 1990s, they may be based on antiquated means of patient evaluation and treatment. Recently, there have been many advances in medical therapies, imaging, microsurgical treatment, and endovascular therapies for cerebral aneurysms [8]. In the current issue, N. Ajiboye et al. provide us with an update on “Unruptured Cerebral Aneurysms: Evaluation and Management.” Cerebral vasospasm continues to be a leading cause of morbidity and mortality following aneurysm rupture. Recent RCTs have not provided us with further therapeutic strategies [9]. Perhaps refinements in patient evaluation and selection will improve patient outcomes. S. H. Sheen et al. provide a protocol on “Intravenous Flat-Detector Computed Tomography Angiography for Symptomatic Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage.” These new imaging modalities may yield a less invasive means for the evaluation and treatment of patients with aneurysmal subarachnoid hemorrhage. Recent RCTs and prospective cohort studies have challenged current management strategies for unruptured cerebral arteriovenous malformations (AVMs), but these analyses have not been without limitations [10, 11]. When indicated, current AVM interventions include microsurgery, radiosurgery, and embolization. These therapeutic options are also often used individually or as part of a multimodality approach. In this issue N. Ajiboye et al. provide us with an update through “Cerebral Arteriovenous Malformations: Evaluation and Management.” Additionally, S. Peschillo et al. provide us with a review on treatment options in “Brain AVMs: An Endovascular, Surgical, and Radiosurgical Update.” Neurovascular diseases are a heterogeneous group of disorders that are often associated with poor clinical outcomes. S. Tabuchi provides us with a review on “Auditory Dysfunction in Patients with Cerebrovascular Disease” and A. Y. Lu et al. provide us with an assessment of “Hemifacial Spasm and Neurovascular Compression.” Although the majority of neurovascular diseases are primarily arterial pathologies, cerebral venous diseases may also incur significant morbidity. To round out this issue, we provide an update and review of “Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results.” Although cerebrospinal fluid diversion has been a mainstay of treatment in patients with idiopathic intracranial hypertension (IIH) refractory to medical therapy, recent advances in endovascular therapies have provided an effective alternative treatment option. Specifically, venous sinus stenting has been shown to provide durable neurological improvement in IIH patients with venous sinus stenosis and a significant physiologic pressure gradient. Further studies regarding associated complications, neurological outcomes, and radiographic results are necessary. Improvements in clinical evaluation, imaging, and treatment will lead to better outcomes in patients with neurovascular disease. Although there continue to be many advances in neurovascular disease, these options must be carefully assessed and compared to existing modalities to ascertain the best practices for our patients. Within this compilation of studies, we hope to elucidate areas of uncertainty, recent developments, and clinical necessity. Robert M. Starke Stephen J. Monteith Andrew M. Southerland R. Webster Crowley Nohra Chalouhi Dale Ding David M. Hasan Aaron S. Dumont

We analysed 166 cases of paediatric central nervous system tumour presenting to Auckland City and Starship Children’s Hospital, New Zealand, between 1995 and 2004. The purpose of this study was to perform an audit of paediatric neurosurgical practice in the upper North Island of New Zealand with the objective of assessing patient presentation, demographics, and modality and efficacy of therapy. The overall incidence of central nervous system tumours was 3.42/100,000/year. The incidence rate of medulloblastoma for Maori was over double that for European New Zealanders. Tumour clearance was attempted in 81.3% of patients. Some type of adjunct therapy was received by 45.2% of patients. Overall, 60.8% of patients had satisfactory or good results. Survival rates for pilocytic astrocytoma and ependymoma were consistent with previous studies. Survival data for medulloblastoma demonstrate improved outcomes with complete resection of tumour and with a specialist paediatric neurosurgeon compared with general neurosurgeons. Recent management changes have led to improved outcomes.

Object. Charcot-Marie-Tooth (CMT) disease is a collection of related genetic disorders affecting peripheral nerves with an incidence of one in every 2500 individuals. A diagnosis of CMT disease has classically relied on a medical history, examination, and measurement of nerve conduction velocities. Advancements in genetic testing and magnetic resonance (MR) imaging techniques may provide clinicians with a more precise diagnostic armamentarium. The authors investigated MR neurography as a possible method to characterize CMT subtypes. Methods. The authors performed MR neurography to evaluate sciatic nerves in the mid-thigh area of seven patients with genetically defined subtypes of CMT, one patient with chronic inflammatory demylinating polyneuropathy, and one patient without neuropathy. The authors correlate their findings with normal nerve conduction velocities (NCVs) and present their results as a descriptive case series. Although MR neurography could not be used to distinguish subtypes of CMT disease on nerve area or fascicle number, it appears to characterize phenotypic features and disease progression noninvasively in patients with some subtypes. Conclusions. In conjunction with NCV measurements, MR neurography may be useful in the diagnosis of CMT neuropathies and in monitoring disease progression.

✓ The purpose of this article is to raise awareness of spontaneous spinal hematomas that develop after administration of low-molecular-weight heparin therapy. The authors describe four patients in whom these hematomas developed without precipitating events while receiving a treatment dose of enoxaparin (Clexane) (∼1 mg/kg). Spontaneous spinal hematomas (not related to trauma, surgery, or lumbar puncture) are a rare clinical entity. Several causes have been identified, including acquired and congenital clotting abnormalities and underlying vascular lesions. Aspirin, warfarin, tissue plasminogen activator, and heparin have all been implicated in causing spinal hematomas. Concerns regarding the use of low-molecular-weight heparin agents in neuraxis anesthesia have been well documented. Their possible contribution to nontraumatic spinal hematomas has been less well described. The authors believe that low-molecular-weight heparin agents present a small but significant risk of spinal hematoma. This should be considered when prescribing therapy because such a complication may be catastrophic.

Despite advances in surgical and endovascular techniques, fusiform aneurysms remain a therapeutic challenge. Introduction of flow-diverting stents has revolutionized the treatment of aneurysms with wide necks and of complex morphology. The authors report their experience with the endovascular treatment of fusiform aneurysms using the Pipeline Embolization Device.A retrospective review of 146 patients with cerebral aneurysms treated with the Pipeline Embolization Device between June 2011 and January 2013 was performed. Twenty-four patients were identified as having fusiform aneurysms. Twenty-four aneurysms in these 24 patients were treated. The mean patient age was 59 years. There were 9 men and 15 women. Angiographic and clinical data (including the modified Rankin Scale [mRS] score) were recorded at the time of treatment and at follow-up. The aneurysms were located in the internal carotid artery in 8 patients (33.3%), middle cerebral artery in 8 patients (33.3%), anterior cerebral artery in 1 patient (4%), and vertebrobasilar circulation in 7 patients (29%). The aneurysms were smaller than 10 mm in 3 patients, 10-25 mm in 16 patients, and larger than 25 mm in 5 patients. The mean largest dimension diameter was 18 mm.Stent deployment was successful in all cases. The minor procedural morbidity was 4% (1 case). Morbidity and mortality related to aneurysm treatment were 4.2% and 4.2%, respectively. The mean mRS scores preoperatively and at clinical follow-up (median 6.0 months, mean 6.9 months) were 0.71 and 1.2, respectively (91.7% presented with an mRS score of 2 or better, and 79.2% had an mRS score of 2 or better at the 6.0-month follow-up). At clinical follow-up, 82.6% of patients were stable or had improved, 13.0% worsened, and 4.2% had died. Twenty-two (91.7%) of 24 patients had follow-up angiography available (mean follow-up time 6.3 months); 59% had excellent angiographic results (95% or complete occlusion), 31.8% had complete aneurysm occlusion, 27.3% had greater than 95% aneurysm occlusion, 18.2% had a moderate decrease in size (50%-95%), 4.5% had a minimal decrease in size (50%), 13.6% had not changed, and 4.5% had an increase in size.This series demonstrates that endovascular treatment of fusiform cerebral aneurysms with flow diversion was a safe and effective treatment. Procedural complications were low. Long-term morbidity and mortality rates were acceptable given the complex nature of these lesions.

A 34-year-old woman presented with a rapid onset of meningitic symptoms. Cerebrospinal fluid (CSF) from a lumbar puncture revealed a leucocytosis with a preponderance of monocytes, elevated protein and reduced glucose. Herpes simplex virus (HSV) type II was subsequently confirmed by polymerase chain reaction (PCR) of CSF. The patient's level of consciousness deteriorated and a CT scan revealed hydrocephalus. The patient required placement of an external ventricular drain for 5 days; however, she made a full recovery without specific antiviral therapy. This is the first reported case of hydrocephalus secondary to isolated HSV type II meningitis.

Background Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept. Methods The transcranial effectiveness of MRgFUS was tested ex vivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and sonicated in vivo with one 5-second pulse of 700 W through a bone window or with 3000 W when treated through an ex vivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images. Results In both in vivo porcine blood clot through a craniectomy model and the porcine clot in an ex vivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue. Conclusions Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an in vivo porcine model of ICH and in 2 ex vivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.

This paper reviews the current intraoperative imaging tools that are available to assist neurosurgeons in the treatment of intracerebral hemorrhage (ICH). This review shares the authors' experience with each modality and discusses the advantages, potential limitations, and disadvantages of each. Surgery for ICH is directed at blood clot removal, reduction of intracranial pressure, and minimization of secondary damage associated with hematoma breakdown products. For effective occlusion and safe obliteration of vascular anomalies associated with ICH, vascular neurosurgeons today require a thorough understanding of the various intraoperative imaging modalities available for obtaining real-time information. Use of one or more of these modalities may improve the surgeon's confidence during the procedure, the patient's safety during surgery, and surgical outcome. The modern techniques discussed include 1) indocyanine green–based video angiography, which provides real-time information based on high-quality images showing the residual filling of vascular pathological entities and the patency of blood vessels of any size in the surgical field; and 2) intraoperative angiography, which remains the gold standard intraoperative diagnostic test in the surgical management of cerebral aneurysms and arteriovenous malformations. Hybrid procedures, providing multimodality image-guided surgeries and combining endovascular with microsurgical strategies within the same surgical session, have become feasible and safe. Microdoppler is a safe, noninvasive, and reliable technique for evaluation of hemodynamics of vessels in the surgical field, with the advantage of ease of use. Intraoperative MRI provides an effective navigation tool for cavernoma surgery, in addition to assessing the extent of resection during the procedure. Intraoperative CT scanning has the advantage of very high sensitivity to acute bleeding, thereby assisting in the confirmation of the extent of hematoma evacuation and the extent of vascular anomaly resection. Intraoperative ultrasound aids navigation and evacuation assessment during intracerebral hematoma evacuation surgeries. It supports the concept of minimally invasive surgery and has undergone extensive development in recent years, with the quality of ultrasound imaging having improved considerably. Image-guided therapy, combined with modern intraoperative imaging modalities, has changed the fundamentals of conventional vascular neurosurgery by presenting real-time visualization of both normal tissue and pathological entities. These imaging techniques are important adjuncts to the surgeon's standard surgical armamentarium. Familiarity with these imaging modalities may help the surgeon complete procedures with improved safety, efficiency, and clinical outcome.

Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18-36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated.Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0-2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy.The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033).Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10-36 hours after surgery despite prolonged and severe hypercortisolism.

BACKGROUND AND PURPOSE As magnetic resonance-guided focused ultrasound (MRgFUS) sonothrombolysis relies on mechanical rather than thermal mechanisms to achieve clot lysis, thermometry is not useful for the intraoperative monitoring of clot breakdown by MRgFUS. Therefore, the purpose of this study was to evaluate the optimum imaging sequence for sonothrombolysis. METHODS In vitro blood drawn from 6 healthy volunteers was imaged using T1, T2 spin-echo, and T2 gradient-echo (GRE) sequences both before and after sonication using an Insightec ExAblate 4000 FUS transducer. Signal intensities of the three MR imaging sequences were measured and normalized to background signal for each time point. Representative samples of the pre- and postsonication clot were also sent to pathology for hematologic analysis. RESULTS After sonication, the clot in the treatment tube was fully lysed as evidenced by physical and hematologic evaluation. The difference between pre- and postsonicated normalized signal intensity ratios demonstrated statistical significance only on T2 and GRE sequences (P < .001). However, significant blooming artifact limited interpretation on all GRE images. CONCLUSION T2 is the most appropriate sequence for the evaluation of mechanical MRgFUS sonothrombolysis of an in vitro clot. These findings are consistent across the oxidative states of clot up to 48 hours.

Neurovascular diseases compromise a heterogeneous group of disorders with a broad spectrum of phenotypes. Recent advances include greater understanding of both the genetic links and the basic mechanisms underlying the pathophysiology of cerebrovascular diseases. Improvements in neurovascular disease therapies have risen both from cell cultures and animal models of disease. Additionally, developments in technology have resulted in improvements in diagnosis, including a variety of advances in vascular imaging, medical therapies, and surgical and endovascular therapies. Recent randomized clinical trials have also helped to refine patient selection and optimal treatment modalities. Stroke is a leading cause of morbidity and mortality. Three recent trials have challenged the use of endovascular therapy in acute cerebrovascular occlusion [1]. Limitations of these studies included lack of large vessel occlusions in many patients and the use of older thrombectomy devices. In the recent edition, S. Hann et al. demonstrate the benefits of next generation thrombectomy devices in clot removal. For patients with significant intracranial disease, recent trials have demonstrated that best medical therapy results in improved outcomes over intracranial stenting [2]. For patients who have failed best medical therapy, the optimal treatment options remain unclear. D. Ding et al. review potential options in the current edition, including balloon-mounted stents that may offer an effective alternative to self-expanding stents with lower rates of in-stent stenosis [3]. Cerebral arteriovenous malformations (AVMs) consist of an abnormal tangle of blood vessels that shunt blood directly from arteries to veins without an intervening capillary bed. The molecular mechanisms behind their development, progression, and hemorrhage remain incompletely defined, and further critical work is indicated for both risk stratification and the potential development of an alternative medical therapy. Recent studies have highlighted the altered role of Notch signaling pathway in AVMs [4], and the in vivo study by J. Tu and N. F. Jufri adds to the literature by demonstrating that wall shear stress likely contributes to AVM angiogenesis through activation of Notch. Further studies are necessary to determine how altered gene expression in critical vascular genes likely contributes to AVM instability and hemorrhage. Recent trials have challenged aggressive treatment of AVM patients at low risk for hemorrhage [5]. For patients with high risk features, intervention may be necessary. R. Dalyai et al. review clinical outcomes following radiosurgery with embolization in large AVMs. Similarly, the molecular mechanisms underlying cerebral aneurysm formation and rupture remain unclear [6]. It has been known for some time that female gender is a significant risk factor for both aneurysm formation and subarachnoid hemorrhage. J. Tu et al. reviewed the role of estrogen receptors in signaling mechanisms in human cerebral vascular endothelial cells which may help to provide a preventative therapy for aneurysm progression. A number of trials have recently addressed the role of endovascular therapy in cerebral aneurysms [7]. For mycotic aneurysms, the optimal therapy is incompletely defined, and this area is eloquently reviewed by M. Zanaty et al. Following aneurysm rupture, vasospasm is a significant cause of morbidity and mortality. A number of preventative and treatment measures may be beneficial, including alterations in cerebral blood flow dynamics as assessed by D. K. Kung et al. and the efficacy of intra-arterial nimodipine as tested by S. Ott et al. Neurovascular diseases are often associated with devastating outcomes. Progression from in vitro, in vivo, translational, and clinical studies has led to many new developments. Additionally, developments in technology have improved treatment outcomes. Although there have been numerous advances in treatment for neurovascular diseases, there remain many areas of uncertainty. Through this collection of papers, we hope to highlight areas of uncertainty, recent advances, and future clinical necessity. Robert M. Starke Stephen J. Monteith Nohra Chalouhi Dale Ding Ricky Medel David Hasan Aaron S. Dumont

The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS).Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm(3) at the time of GKS, and a mean prescription dose of 21.9 Gy was used.After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career.Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

Penetrating head injury from nailguns has become increasingly recognised due to their frequent use in the construction industry and home. We report a New Zealand case series of 12 penetrating nailgun head injuries, the largest of its type, detailing presentation, management, risk factors and outcomes. Recommendations based on these factors are provided, suggesting a minimal surgical approach and an individually case-assessed need for antibiotic prophylaxis and anti-epileptic drugs. Prognostic factors on initial imaging are discussed. The majority of injuries, despite being visually impressive, are associated with minimal neurological impairment.