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  • Author or Editor: Christopher Michael x
  • Journal of Neurosurgery x
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John S. Norris, Taufik A. Valiante, M. Christopher Wallace, Robert A. Willinsky, Walter J. Montanera, Karel G. terBrugge and Michael Tymianski

Object. The authors sought to establish prospectively whether there is a simple relationship between radiological features of brain arteriovenous malformation (AVM) hemodynamics and a patient's clinical presentation.

Methods. Thirty-one consecutive patients with AVMs underwent cerebral angiography at 3.8 frames/second during each standardized injection of contrast material. Contrast dilution curves were derived from the image sequences by using regions of interest (ROIs) traced on arteries feeding and veins draining the AVM nidus. Angiographic parameters were then analyzed in a blinded fashion. These parameters included the times required to reach the peak contrast density, the contrast decay time, and fractions thereof, in the ROI for each vessel. The authors determined whether these parameters, the arteriovenous transit time, and/or AVM size were related to patients' presentation with hemorrhage (11 patients), seizure (11 patients), or other clinical symptoms (nine patients). Statistically significant results were found only in analyses of arterial phase times to reach peak contrast density. Analyses of venous parameters, AVM size, and nidus transit time showed trends but no statistical significance. Arterial filling with contrast material was significantly slower in patients presenting with hemorrhage (mean 50%, 80%, and 100% of time to peak ± standard error [SE] = 1.19 ± 0.13, 1.97 ± 0.18, and 3.04 ± 0.34 seconds, respectively) compared with patients presenting with seizures (mean 50%, 80%, and 100% of time to peak ± SE = 0.80 ± 0.12, 1.32 ± 0.18, and 1.95 ± 0.29 seconds, respectively) according to analysis of variance (p < 0.05) and post-hoc t-tests (p < 0.05) for each parameter. Patients who presented with other symptoms had intermediate arterial filling times.

Conclusions. These simple hemodynamic parameters, which can be obtained without added risk to the patient, may help identify a subset of individuals in whom AVMs pose a higher risk of future hemorrhage and who may therefore warrant more expeditious treatment.

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Christopher Nutting, Michael Brada, Lucy Brazil, Ahmen Sibtain, Frank Saran, Charlotte Westbury, Anne Moore, David G. T. Thomas, Daphne Traish and Susan Ashley

Object. This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma.

Methods. This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy.

Conclusions. The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

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Eugene S. Flamm, Harold P. Adams Jr., David W. Beck, Richard S. Pinto, John R. Marler, Michael D. Walker, John C. Godersky, Christopher M. Loftus, José Biller, David J. Boarini, Chris O'Dell, Karla Banwart and Gail Kongable

✓ A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction.

No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.

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Zeev Feldman, Malcolm J. Kanter, Claudia S. Robertson, Charles F. Contant, Christopher Hayes, Michael A. Sheinberg, Cynthia A. Villareal, Raj K. Narayan and Robert G. Grossman

✓ The traditional practice of elevating the head in order to lower intracranial pressure (ICP) in head-injured patients has been challenged in recent years. Some investigators argue that patients with intracranial hypertension should be placed in a horizontal position, the rationale being that this will increase the cerebral perfusion pressure (CPP) and thereby improve cerebral blood flow (CBF). However, ICP is generally significantly higher when the patient is in the horizontal position. This study was undertaken to clarify the issue of optimal head position in the care of head-injured patients. The effect of 0° and 30° head elevation on ICP, CPP, CBF, mean carotid pressure, and other cerebral and systemic physiological parameters was studied in 22 head-injured patients. The mean carotid pressure was significantly lower when the patient's head was elevated at 30° than at 0° (84.3 ± 14.5 mm Hg vs. 89.5 ± 14.6 mm Hg), as was the mean ICP (14.1 ± 6.7 mm Hg vs. 19.7 ± 8.3 mm Hg). There was no statistically significant change in CPP, CBF, cerebral metabolic rate of oxygen, arteriovenous difference of lactate, or cerebrovascular resistance associated with the change in head position. The data indicate that head elevation to 30° significantly reduced ICP in the majority of the 22 patients without reducing CPP or CBF.

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Christopher D. Duntsch, Qihong Zhou, Himangi R. Jayakar, James D. Weimar, Jon H. Robertson, Lawrence M. Pfeffer, Lie Wang, Zixiu Xiang and Michael A. Whitt

Object. The purpose of this study was to evaluate both replication-competent and replication-restricted recombinant vesicular stomatitis virus (VSV) vectors as therapeutic agents for high-grade gliomas by using an organotypic brain tissue slice—glioma coculture system.

Methods. The coculture system involved growing different brain structures together to allow neurons from these tissues to develop synaptic connections similar to those found in vivo. Rat C6 or human U87 glioma cells were then introduced into the culture to evaluate VSV as an oncolytic therapy. The authors found that recombinant wild-type VSV (rVSV-wt) rapidly eliminated C6 glioma cells from the coculture, but also caused significant damage to neurons, as measured by a loss of microtubule-associated protein 2 immunoreactivity and a failure in electrophysiological responses from neurons in the tissue slice. Nonetheless, pretreatment with interferon beta (IFNβ) virtually eliminated VSV infection in healthy tissues without impeding any oncolytic effects on tumor cells. Despite the protective effects of the IFNβ pretreatment, the tissue slices still showed signs of cytopathology when exposed to rVSV-wt. In contrast, pretreatment with IFNβ and inoculation with a replication-restricted vector with its glycoprotein gene deleted (rVSV-ΔG) effectively destroyed rat C6 and human U87 glioma cells in the coculture, without causing detectable damage to the neuronal integrity and electrophysiological properties of the healthy tissue in the culture.

Conclusions. Data in this study provide in vitro proof-of-principle that rVSV-ΔG is an effective oncolytic agent that has minimal toxic side effects to neurons compared with rVSV-wt and therefore should be considered for development as an adjuvant to surgery in the treatment of glioma.

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Zachary A. Seymour, Penny K. Sneed, Nalin Gupta, Michael T. Lawton, Annette M. Molinaro, William Young, Christopher F. Dowd, Van V. Halbach, Randall T. Higashida and Michael W. McDermott


Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004–2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages.


All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed.


Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9–68 years). The median modified radiosurgery-based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose ≥ 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97–16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant).


VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to ≤ 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure.

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Christopher J. Balamucki, Volker W. Stieber, Thomas L. Ellis, Stephen B. Tatter, Allan F. DeGuzman, Kevin P. McMullen, James Lovato, Edward G. Shaw, Kenneth E. Ekstrand, J. Daniel Bourland, Michael T. Munley, Michael Robbins and Charles Branch


Gamma Knife surgery (GKS) is a treatment option for patients with refractory typical trigeminal neuralgia (TN), TN with atypical features, and atypical types of facial pain. The Gamma Knife’s 201 60Co sources decay with a half-life of 5.26 years. The authors examined whether the decrease in dose rate over 4.6 years between Co source replacements affected the control rates of facial pain in patients undergoing GKS.


The authors collected complete follow-up data on 239 of 326 GKS procedures performed in patients with facial pain. Patients were classified by their type of pain. The isocenter of a 4-mm collimator helmet was targeted at the proximal trigeminal nerve root, and the dose (80–90 Gy) was prescribed at the 100% isodose line. Patients reported the amount of pain control following radiosurgery by answering a standardized questionnaire.

Eighty percent of patients experienced greater than 50% pain relief, and 56% of patients experienced complete pain relief after GKS. Neither dose rate nor treatment time was significantly associated with either the control rate or degree of pain relief. A significant association between the type of facial pain and the pain control rate after GKS was observed (p < 0.001; Pearson chi-square test).

In their statistical analysis, the authors accounted for changes in prescription dose over time to prevent the dose rate from being a confounding variable. There was no observable effect of the dose rate or of the treatment duration within the typical period to source replacement.


Patients with facial pain appear to receive consistent treatment with GKS at any time during the first half-life of the Co sources.

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Chad W. Washington, Gregory J. Zipfel, Michael R. Chicoine, Colin P. Derdeyn, Keith M. Rich, Christopher J. Moran, DeWitte T. Cross and Ralph G. Dacey Jr.


The purpose of aneurysm surgery is complete aneurysm obliteration while sparing associated arteries. Indocyanine green (ICG) videoangiography is a new technique that allows for real-time evaluation of blood flow in the aneurysm and vessels. The authors performed a retrospective study to compare the accuracy of ICG videoangiography with intraoperative angiography (IA), and determine if ICG videoangiography can be used without follow-up IA.


From June 2007 through September 2009, 155 patients underwent craniotomies for clipping of aneurysms. Operative summaries, angiograms, and operative and ICG videoangiography videos were reviewed. The number, size, and location of aneurysms, the ICG videoangiography and IA findings, and the need for clip adjustment after ICG videoangiography and IA were recorded. Discordance between ICG videoangiography and IA was defined as ICG videoangiography demonstrating aneurysm obliteration and normal vessel flow, but post-IA showing either an aneurysmal remnant and/or vessel occlusion requiring clip adjustment.


Thirty-two percent of patients (49 of 155) underwent both ICG videoangiography and IA. The post-ICG videoangiography clip adjustment rate was 4.1% (2 of 49). The overall rate of ICG videoangiography–IA agreement was 75.5% (37 of 49) and the ICG videoangiography–IA discordance rate requiring post-IA clip adjustment was 14.3% (7 of 49). Adjustments were due to 3 aneurysmal remnants and 4 vessel occlusions. These adjustments were attributed to obscuration of the residual aneurysm or the affected vessel from the field of view and the presence of dye in the affected vessel via collateral flow. Although not statistically significant, there was a trend for ICG videoangiography–IA discordance requiring clip adjustment to occur in cases involving the anterior communicating artery complex, with an odds ratio of 3.3 for ICG videoangiography–IA discordance in these cases.


These results suggest that care should be taken when considering ICG videoangiography as the sole means for intraoperative evaluation of aneurysm clip application. The authors further conclude that IA should remain the gold standard for evaluation during aneurysm surgery. However, a combination of ICG videoangiography and IA may ultimately prove to be the most effective strategy for maximizing the safety and efficacy of aneurysm surgery.

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Alim P. Mitha, Benjamin Reichardt, Michael Grasruck, Eric Macklin, Soenke Bartling, Christianne Leidecker, Bernhard Schmidt, Thomas Flohr, Thomas J. Brady, Christopher S. Ogilvy and Rajiv Gupta


Imaging of intracranial aneurysms using conventional multidetector CT (MDCT) is limited because of nonvisualization of features such as perforating vessels, pulsatile blebs, and neck remnants after clip placement or coil embolization. In this study, a model of intracranial saccular aneurysms in rabbits was used to assess the ultra-high resolution and dynamic scanning capabilities of a prototype flat-panel volumetric CT (fpVCT) scanner in demonstrating these features.


Ten New Zealand white rabbits underwent imaging before and after clipping or coil embolization of surgically created aneurysms in the proximal right carotid artery. Imaging was performed using a prototype fpVCT scanner, a 64-slice MDCT scanner, and traditional catheter angiography. In addition to the slice data and 3D views, 4D dynamic views, a capability unique to fpVCT, were also created and reviewed. The images were subjectively compared on 1) 4 image quality metrics (spatial resolution, noise, motion artifacts, and aneurysm surface features); 2) 4 posttreatment features reflecting the metal artifact profile of the various imaging modalities (visualization of clip or coil placement, perianeurysmal clip/coil anatomy, neck remnant, and white-collar sign); and 3) 2 dynamic features (blood flow pattern and aneurysm pulsation).


Flat-panel volumetric CT provided better image resolution than MDCT and was comparable to traditional catheter angiography. The surface features of aneurysms were demonstrated with much higher resolution, detail, and clarity by fpVCT compared with MDCT and angiography. Flat-panel volumetric CT was inferior to both MDCT and angiography in terms of image noise and motion artifacts. In fpVCT images, the metallic artifacts from clips and coils were significantly fewer than those in MDCT images. As a result, clinically important information about posttreatment aneurysm neck remnants could be derived from fpVCT images but not from MDCT images. Time-resolved dynamic sequences were judged slightly inferior to conventional angiography but superior to static MDCT images.


The spatial resolution, surface anatomy visualization, metal artifact profile, and 4D dynamic images from fpVCT are superior to those from MDCT. Flat-panel volumetric CT demonstrates aneurysm surface features to better advantage than angiography and is comparable to angiography in metal artifact profile. Even though the temporal resolution of fpVCT is not quite as good as that of angiography, fpVCT images yield clinically important anatomical information about aneurysm surface features and posttreatment neck remnants not attainable with either angiography or MDCT images.