Pipeline flow diversion of ruptured blister aneurysms of the supraclinoid carotid artery using a single-device strategy.

OBJECTIVE Ruptured blister aneurysms remain challenging lesions for treatment due to their broad, shallow anatomy and thin, fragile wall. Historical challenges with both open microsurgical approaches and intrasaccular endovascular approaches have led to increased use of flow diversion for management of these aneurysms. However, the optimum paradigm, including timing of treatment, use of dual antiplatelet therapy, and number of flow-diverter devices to use remains unknown. The authors describe their experience with ruptured blister aneurysms treated with flow diversion at their institution, and discuss rates of rebleeding and number of devices used. METHODS All patients presenting with subarachnoid hemorrhage from a ruptured blister aneurysm and treated with Pipeline flow diversion were identified. Patient demographic data, clinical status and course, need for external ventricular drain (EVD), timing of treatment, and angiographic details and follow-up were recorded. RESULTS There were 13 patients identified (11 women and 2 men), and 4 had multiple aneurysms. Two aneurysms were treated on initial angiography, with average time to treatment of 3.1 days for the remainder, after discussion with the family and institution of dual antiplatelet therapy. Device placement was technically successful in all patients, with 2 patients receiving 2 devices and the remainder receiving 1 device. There was 1 intraoperative complication, of a wire perforation causing intracerebral hemorrhage requiring decompressive craniectomy. Three patients had required EVD placement for management of hydrocephalus. There was no rebleeding from the target lesion; however, one patient had worsening intraventricular hemorrhage and another had rupture of an unrecognized additional aneurysm, and both died. Of the other 11 patients, 10 made a good recovery, with 1 remaining in a vegetative state. Nine underwent follow-up angiography, with 5 achieving complete occlusion, 2 with reduced aneurysm size, and 2 requiring retreatment for aneurysm persistence or enlargement. There were no episodes of delayed rupture. CONCLUSIONS Pipeline flow diversion is a technically feasible and effective treatment for ruptured blister aneurysms, particularly in good-grade patients without hydrocephalus. Patients with a worse grade on presentation and requiring EVDs may have higher risk for bleeding complications and poor outcome. There was no rebleeding from the target lesion with use of a single device in this series.

General technical considerations for the endovascular management of cerebral aneurysms.

Cerebral aneurysms pose a threat to patients because of their risk of rupture causing subarachnoid hemorrhage, and the goal of treatment is the exclusion of the aneurysm from the circulation to prevent bleeding (in the case of unruptured aneurysms) or rebleeding. This article analyzes the general technical factors associated with the endovascular treatment of cerebral aneurysms. It discusses issues with transarterial access; imaging of aneurysm size, morphology, and regional anatomy to determine the endovascular plan; the techniques for the major endovascular aneurysm devices; and periprocedural management issues to reduce potential treatment-related complications.

Evolving role of endovascular treatment for MCA bifurcation aneurysms: case series of 184 aneurysms and review of the literature.

OBJECTIVE: This study evaluates the role of endovascular therapy for middle cerebral artery (MCA) aneurysms and its evolution over time. We are reporting a large case series of 184 MCA aneurysms and comparative analysis of the literature. METHODS: This was a retrospective review of a prospectively maintained database including all patients with MCA bifurcation aneurysms embolized between 2000 and 2013. There were 184 aneurysms in 166 patients, with 71 ruptured and 113 nonruptured aneurysms. RESULTS: Stent assistance was required in 70 cases (38·0%) and 3 cases (1·6%) required 'Y' stenting. The initial rate of total aneurysm occlusion was 59·8% and at delayed follow up was 90·1%. Seven embolizations resulted in thrombo-embolic complications (3·8%), with no cases of aneurysm re-bleeding, wire perforations, or other hemorrhages. Three patients with ruptured aneurysms died of causes unrelated to the embolization, and none with nonruptured aneurysms died in the follow-up period (total mortality 1·6% at 30 days post-procedure). A total of seven aneurysms (3·9%) required retreatment with an average follow up of 41 months. Prior to dedicated aneurysm stents, 68·8% of patients underwent embolization with the remainder surgically treated. Following the introduction of aneurysm stents in 2002, 92·0% of MCA aneurysms treated were embolized. CONCLUSIONS: During the past decade we have seen a treatment paradigm shift in MCA aneurysm treatment from surgical treatment to endovascular treatment. Developments in 3D angiography, more compliant balloons, dedicated aneurysm stents, complex coils, and antiplatelet therapy regimes have led to this transition for safe and effective management of these patients.

Hemorrhage and risk of further hemorrhagic strokes following cerebral revascularization in Moyamoya disease: A review of the literature.

BACKGROUND: We sought to review the current literature with regards to future risks of hemorrhage following cerebral revascularization in Moyamoya disease (MMD). METHODS: We performed a comprehensive literature review using PubMed to inspect the available data on the risk of hemorrhage after revascularization in MMD. RESULTS: In this review, we identify the risk factors associated with hemorrhage in MMD both before and after cerebral revascularization. We included proposed pathophysiology of the hemorrhagic risk, role of the type of bypass performed, treatment options, and future needs for investigation. CONCLUSIONS: The published cases and series of MMD treatment do show a risk of hemorrhage after treatment with either direct or indirect bypass both in the immediate as well as long-term future. While there are no discernible patterns in the rate of these hemorrhages, there is Class III evidence for the predictive effect of multiple microbleeds on preoperative imaging. Also, whereas revascularization, both direct and indirect, has been shown to reduce ischemic complications from MMD, there is not an association with the risk of hemorrhage after the procedure. Further studies need to be performed to help evaluate what the risk factors are and how to counsel patients as to the long-term outlook of this disease process.

Identification of multiple impurities in a pharmaceutical matrix using preparative gas chromatography and computer-assisted structure elucidation.

Gas chromatography (GC) with a preparative fraction collector (PFC) has been used to facilitate the identification of a number of volatile impurities at major and minor percentage levels in a pharmaceutical matrix by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The trapping process was optimized using liquid sorbents, and the impurities were trapped directly into a deuterated solvent. Challenges related to the pharmaceutical matrix were overcome by derivatization with boron trifluoride in methanol and extraction with heptane, producing the methyl esters of the carboxylic acid impurities and main component. GC coupled to atmospheric pressure chemical ionization mass spectrometry (APCI-MS) with a time-of-flight (TOF) detector was used to acquire accurate mass and isotopic data for the impurities, leading to the determination of their molecular formulas (MF). One dimensional (1D) and two-dimensional (2D) NMR experiments were also acquired to unambiguously determine the impurities' structure. The acquisition time of the latter experiments was minimized by using a high-resolution instrument equipped with a small (1.7 mm) cryogenic probe. The quality of the data was such that the structure of the impurities could be determined semiautomatically by using a computer-assisted structure elucidation (CASE) approach, even though the total amount of one of the isolated impurities was less than 60 nmol.

Miniaturized handheld confocal microscopy for neurosurgery: results in an experimental glioblastoma model.

INTRODUCTION: Recent developments in optical science and image processing have miniaturized the components required for confocal microscopy. Clinical confocal imaging applications have emerged, including assessment of colonic mucosal dysplasia during colonoscopy. We present our initial experience with handheld, miniaturized confocal imaging in a murine brain tumor model. METHODS: Twelve C57/BL6 mice were implanted intracranially with 10(5) GL261 glioblastoma cells. The brains of 6 anesthetized mice each at 14 and 21 days after implantation were exposed surgically, and the brain surface was imaged using a handheld confocal probe affixed to a stereotactic frame. The probe was moved systematically over regions of normal and tumor-containing tissue. Intravenous fluorescein and topical acriflavine contrast agents were used. Biopsies were obtained at each imaging site beneath the probe and assessed histologically. Mice were killed after imaging. RESULTS: Handheld confocal imaging produced exquisite images, well-correlated with corresponding histologic sections, of cellular shape and tissue architecture in murine brain infiltrated by glial neoplasm. Reproducible patterns of cortical vasculature, as well as normal gray and white matter, were identified. Imaging effectively distinguished between tumor and nontumor tissue, including infiltrative tumor margins. Margins were easily identified by observers without prior neuropathology training after minimum experience with the technology. CONCLUSION: Miniaturized handheld confocal imaging may assist neurosurgeons in detecting infiltrative brain tumor margins during surgery. It may help to avoid sampling error during biopsy of heterogeneous glial neoplasms, with the potential to supplement conventional intraoperative frozen section pathology. Clinical trials are warranted on the basis of these promising initial results.

Application of a flexible CO(2) laser fiber for neurosurgery: laser-tissue interactions.

OBJECT: The CO(2) laser has an excellent profile for use in neurosurgery. Its high absorption in water results in low thermal spread, sparing adjacent tissue. Use of this laser has been limited to line-of-sight applications because no solid fiber optic cables could transmit its wavelength. Flexible photonic bandgap fiber technology enables delivery of CO(2) laser energy through a flexible fiber easily manipulated in a handheld device. The authors examined and compared the first use of this CO(2) laser fiber to conventional methods for incising neural tissue. METHODS: Carbon dioxide laser energy was delivered in pulsed or continuous wave settings for different power settings, exposure times, and distances to cortical tissue of 6 anesthetized swine. Effects of CO(2) energy on the tissue were compared with bipolar cautery using a standard pial incision technique, and with scalpel incisions without cautery. Tissue was processed for histological analysis (using H & E, silver staining, and glial fibrillary acidic protein immunohistochemistry) and scanning electron microscopy, and lesion measurements were made. RESULTS: Light microscopy and scanning electron microscopy revealed laser incisions of consistent shape, with central craters surrounded by limited zones of desiccated and edematous tissue. Increased laser power resulted in deeper but not significantly wider incisions. Bipolar cautery lesions showed desiccated and edematous zones but did not incise the pia, and width increased more than depth with higher power. Incisions made without using cautery produced hemorrhage but minimal adjacent tissue damage. CONCLUSIONS: The photonic bandgap fiber CO(2) laser produced reliable cortical incisions, adjustable over a range of settings, with minimal adjacent thermal tissue damage. Ease of application under the microscope suggests this laser system has reached true practicality for neurosurgery.

The metabolic epicenter of supratentorial gliomas: a 1H-MRSI study.

BACKGROUND: Assessing the impact of glioma location on prognosis remains elusive. We approached the problem using multivoxel proton magnetic resonance spectroscopic imaging (1H-MRSI) to define a tumor "metabolic epicenter", and examined the relationship of metabolic epicenter location to survival and histopathological grade. METHODS: We studied 54 consecutive patients with a supratentorial glioma (astrocytoma or oligodendroglioma, WHO grades II-IV). The metabolic epicenter in each tumor was defined as the 1H-MRSI voxel containing maximum intra-tumoral choline on preoperative imaging. Tumor location was considered the X-Y-Z coordinate position, in a standardized stereotactic space, of the metabolic epicenter. Correlation between epicenter location and survival or grade was assessed. RESULTS: Metabolic epicenter location correlated significantly with patient survival for all tumors (r2 = 0.30, p = 0.0002) and astrocytomas alone (r2 = 0.32, p = 0.005). A predictive model based on both metabolic epicenter location and histopathological grade accounted for 70% of the variability in survival, substantially improving on histology alone to predict survival. Location also correlated significantly with grade (r2 = 0.25, p = 0.001): higher grade tumors had a metabolic epicenter closer to the midpoint of the brain. CONCLUSIONS: The concept of the metabolic epicenter eliminates several problems related to existing methods of classifying glioma location. The location of the metabolic epicenter is strongly correlated with overall survival and histopathological grade, suggesting that it reflects biological factors underlying glioma growth and malignant dedifferentiation. These findings may be clinically relevant to predicting patterns of local glioma recurrence, and in planning resective surgery or radiotherapy.

Aura of technology and the cutting edge: a history of lasers in neurosurgery.

In this historical review the authors examine the important developments that have led to the availability of laser energy to neurosurgeons as a unique and sometimes invaluable tool. They review the physical science behind the function of lasers, as well as how and when various lasers based on different lasing mediums were discovered. They also follow the close association between advances in laser technology and their application in biomedicine, from early laboratory experiments to the first clinical experiences. Because opinions on the appropriate role of lasers in neurosurgery vary widely, the historical basis for some of these views is explored. Initial enthusiasm for a technology that appears to have innate advantages for safe resections has often given way to the strict limitations and demands of the neurosurgical operating theater. However, numerous creative solutions to improve laser delivery, power, safety, and ergonomics demonstrate the important role that technological advances in related scientific fields continue to offer neurosurgery. Benefiting from the most recent developments in materials science, current CO(2) laser delivery systems provide a useful addition to the neurosurgical armamentarium when applied in the correct circumstances and reflect the important historical advances that come about from the interplay between neurosurgery and technology.

A generic approach for the determination of residues of alkylating agents in active pharmaceutical ingredients by in situ derivatization-headspace-gas chromatography-mass spectrometry.

A simple, reliable and fast procedure for the simultaneous determination of residues of some common alkylating agents (AAs), such as mesylates, besylates, tosylates and sulfates, employed in drug synthesis, has been developed by in situ derivatization-headspace-gas chromatography-mass spectrometry. Pentafluorothiophenol is used as a derivatizing agent in different water/dimethyl sulfoxide ratios. Compared to former analytical procedures, this approach returns improvements in analysis time, selectivity, analyte stability and method sensitivity (LOD=0.11 microgg(-1) for methyl tosylate). The method exhibits low matrix dependence, excellent accuracy, precision (R.S.D.=2.8-10% range at 1 microgg(-1)) and robustness through the use of deuterated internal standards. Knowledge of the synthetic route allows a targeted approach to the determination of specific AAs since the procedure does not distinguish between acid species. The procedure was successfully applied to different pharmaceutical matrixes, and is particularly suitable for routine analysis with high sample throughput.