Gary M. Nesbit

Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke Results of the MERCI Trial

Background and Purpose— The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. Methods— We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. Results— Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score ≤2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Conclusions— A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.

Perfusion-CT Assessment of Infarct Core and Penumbra: Receiver Operating Characteristic Curve Analysis in 130 Patients Suspected of Acute Hemispheric Stroke

Background and Purpose— Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. Methods— One hundred and thirty patients with symptoms suggesting hemispheric stroke ≤12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. Results— The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml×100 g−1. Conclusion— In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.

Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumours

Ferumoxtran‐10 (Combidex®), a dextran‐coated iron oxide nanoparticle, provides enhancement of intracranial tumours by magnetic resonance (MR) for more than 24 h and can be imaged histologically by iron staining. Our goal was to compare ferumoxtran imaging and histochemistry vs. gadolinium enhancement in malignant brain tumours on preoperative and postoperative MR. Methods: Seven patients with primary and metastatic malignant tumours underwent MR imaging with gadolinium and ferumoxtran both pre‐ and postoperatively. Normalized signal intensities on the ferumoxtran‐enhanced scans were determined in representative regions of interest. Resected tissue from six ferumoxtran patients and from three patients who did not receive ferumoxtran was assessed for localization of iron in tumour and reactive brain. Results: All malignant tumours (all of which enhanced by gadolinium MR) showed ferumoxtran accumulation with T1 and T2 signal changes, even using a 0.15 T intraoperative MR unit in one patient. Iron staining was predominantly in reactive cells (reactive astrocytes and macrophages) and not tumour cells. In five of the seven patients, including two patients who showed additional lesions, areas enhancing with ferumoxtran but not with gadolinium were observed. Comparison of the pre‐ and postoperative MR revealed residual ferumoxtran‐enhancing areas in four of seven cases. Conclusion: In malignant tumours, ferumoxtran may show areas of enhancement, even with a 0.15 T intraoperative MR, that do not enhance with gadolinium. Ferumoxtran‐enhancing lesions have persistent increased T1 signal intensity for 2–5 days, which may provide advantages over gadolinium for postoperative imaging. Histochemistry for iron shows uptake of ferumoxtran in reactive cells (astrocytes and macrophages) rather than tumour cells.

Clinical and angiographic outcomes, with treatment data, for patients with cerebral aneurysms treated with Guglielmi detachable coils: a single-center experience.

OBJECTIVE The purpose of this report is to provide the most detailed treatment and outcome data currently available in the literature, to allow for the further evaluation of Guglielmi detachable coils (GDC) as an appropriate treatment option for patients with cerebral aneurysms. METHODS During a period of 4.5 years, 74 patients with intracerebral aneurysms were treated with GDC in the Department of Neurosurgery at Oregon Health Sciences University. A comprehensive retrospective and prospective analysis of these patients was performed, to assess the overall angiographic and clinical outcomes for these patients. RESULTS Seventy-seven aneurysms were treated, with an average angiographic follow-up period of 1.4 years. Initially, 40% of aneurysms exhibited complete (100%) occlusion, 52% near complete (90-99%) occlusion, and 8% incomplete (<90%) occlusion. The average clinical follow-up period was 2.2 years. For unruptured aneurysms, 85% of patients returned to independent status. Of patients of Hunt and Hess Grade I/II status, 81% were independent; of patients of Grade III status, 100% were independent; and, of patients of Grade IV/V status, 50% were independent. The procedure-related morbidity rate was 9.1%, with a 7.8% risk of death from aneurysm perforation, stroke, or delayed hemorrhage. No completely occluded aneurysm hemorrhaged after GDC treatment (follow-up period, 1.9 yr). Of near complete occlusions, 2.6% hemorrhaged after embolization, at a rate of 1.4%/yr (follow-up period, 1.9 yr). CONCLUSION This study details long-term clinical outcomes after GDC treatment and describes factors affecting the need for retreatment. Although complete anatomic cure was not obtained in all cases and the long-term protection from subarachnoid hemorrhage remains to be determined, these data indicate that GDC are a safe and efficacious treatment for cerebral aneurysms.

Safety and Efficacy of Percutaneous Transluminal Angioplasty for Intracranial Atherosclerotic Stenosis

BACKGROUND AND PURPOSE Percutaneous transluminal angioplasty (PCTA) is increasingly used to treat extracerebral arterial stenosis. The present study evaluates the safety and efficacy of PCTA treatment of symptomatic intracranial atherosclerotic stenosis. METHODS A series of 22 vessels in 17 patients were treated with PCTA. All patients had recurrent neurological symptoms referable to the stenotic vessel despite optimal medical therapy. Critical (> 70%) arterial stenosis was confirmed by angiogram, and angioplasty was performed with a 3.0- to 3.5-mm Stealth balloon. RESULTS The average preangioplasty stenosis (North American Symptomatic Carotid Endarterectomy Trial criteria) was 72 +/- 8% (mean +/- SD), with a significant improvement seen after angioplasty; the best angiographic stenosis (after healing of intimal injury, if any) was 43 +/- 24% (P < .001). Overall PCTA was successful in 82% of the vessels. There were two strokes during angioplasty for a 30-day morbidity rate of 9.1% per treated vessel and 11.7% per case. The other 15 patients were clinically evaluated at 3 and 6 months; all cases were without further events. Restenosis was evaluated in 8 patients (12 vessels) with an angiogram at 6 months showing further improvement compared with the initial post-PCTA stenosis (51 +/- 10% versus 37 +/- 21% [P = .05]). CONCLUSIONS PCTA may be a beneficial therapy in selected cases of symptomatic intracranial atherosclerotic stenosis. Further study using a randomized trial is needed.

Rotational Vertebral Artery Occlusion: A Mechanism of Vertebrobasilar Insufficiency

OBJECTIVE Symptomatic dynamic changes in blood flow secondary to vertebral artery compression with rotational head motion are evaluated in a series of patients as a cause for posterior circulation transient ischemic attacks. These cases are classic examples of rotational vertebral artery occlusion and allow for the discussion of the anatomic basis, angiographic features, and treatment options. ILLUSTRATIVE CASES In our series, symptoms of vertebrobasilar insufficiency were reproducible with rotational head movement. Compression of the vertebral artery was demonstrated angiographically. The correct site of occlusion of the vertebral artery was apparent only by dynamic angiography with progressive head rotation. All of the patients presented in the illustrative cases had occlusion at the C2 level; however, one patient had been previously misdiagnosed and another had an additional site of occlusion. The anatomic course of the vertebral artery is described in addition to the sites of rotational occlusion. CONCLUSION Rotational vertebral occlusion is an important cause of vertebrobasilar symptoms, which may lead to permanent neurological deficit if left undiagnosed. Dynamic angiography is the established method of diagnosis. Great care must be taken to avoid misdiagnosing the site of occlusion or missing a second occlusive site. For this reason, it is crucial to have a thorough understanding of the anatomic course of the vertebral artery and the muscular and tendinous insertions, which may cause rotational occlusion. The decision for treatment must be based on the site of occlusion as well as the assessment of the patient as a surgical candidate. A review of the literature reveals that surgical treatment is effective and must be considered to avoid further morbidity.

The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study.

OBJECTIVEFerumoxytol, an iron oxide nanoparticle that targets phagocytic cells, can be used in magnetic resonance imaging of malignant brain tumors and can be administered as a bolus, allowing dynamic imaging. Our objectives were to determine the optimum time of delayed contrast enhancement of ferumoxytol, and to compare ferumoxytol and gadolinium contrast agents for magnetic resonance angiography and perfusion. METHODSTwelve patients with malignant brain tumors underwent serial magnetic resonance imaging multiple times up to 72 hours after ferumoxytol injection at both 1.5 and 3-T. The enhancement time course was determined for ferumoxytol and compared with a baseline gadolinium scan. Perfusion, time-of-flight and dynamic magnetic resonance angiography and T1-weighted scans were compared for the two agents. RESULTSThe lesions were detectable at all field strengths, even with an intraoperative 0.15-T magnet. Maximal ferumoxytol enhancement intensity was at 24 to 28 hours after administration, and the enhancing volume subsequently expanded with time into a non-gadolinium-enhancing, high T2-weighted signal region of tumor-infiltrated brain. Dynamic studies were assessed with both agents, indicating early vascular leak with gadolinium but not with ferumoxytol. CONCLUSIONOur most important finding was that gadolinium leaks out of blood vessels early after injection, whereas ferumoxytol stays intravascular in the “early” phase, thereby increasing the accuracy of tumor perfusion assessment. As a magnetic resonance imaging contrast agent, ferumoxytol visualizes brain tumors at all field strengths evaluated, with delayed enhancement peaking at 24 to 28 hours after administration.

High-resolution Three-dimensional Magnetic Resonance Angiography and Three-dimensional Spoiled Gradient-recalled Imaging in the Evaluation of Neurovascular Compression in Patients with Trigeminal Neuralgia: A Double-blind Pilot Study

OBJECTIVE:To assess the value of high-resolution three-dimensional (3D) time-of-flight (TOF) magnetic resonance (MR) angiography and gadolinium (Gad)-enhanced 3D spoiled gradient-recalled imaging in the visualization of neurovascular compression in patients with trigeminal neuralgia. METHODS:Forty-eight patients with unilateral trigeminal neuralgia underwent high-resolution 3D TOF MR angiography. After administration of a contrast agent, a 3D spoiled gradient-recalled sequence (3D Gad) was run. Images were reviewed by a radiologist blinded to clinical details. All patients underwent microvascular decompression surgery. Microdissection of the trigeminal nerve and compressing vessels was videotaped during surgery and reviewed by surgeons uninvolved in patient care. Results from neuroradiological studies were then compared with findings on operative videotapes. RESULTS:MR angiography in combination with 3D Gad imaging identified surgically verified neurovascular contact in 42 of 46 (91%) symptomatic nerves. The offending vessel (artery, vein) was correctly identified in 31 of 41 cases (sensitivity, 76%; specificity, 75%). Neurovascular compression was observed in 71% of asymptomatic nerves with a trend toward greater compression severity on the symptomatic nerve (P < 0.09). Agreement between the direction of neurovascular contact defined by 3D TOF MR angiography and 3D Gad and findings at surgery was good (&kgr; = 0.78; 95% confidence interval, 0.61–0.94). CONCLUSION:Double-blind assessment of surgical and neuroradiological findings confirms that neurovascular compression can be visualized with good sensitivity in patients with trigeminal neuralgia by 3D TOF MR angiography in combination with Gad-enhanced 3D spoiled gradient-recalled sequences. Anatomic relationships defined by this method can be useful in predicting surgical findings.

Radiologic correlates of symptom-based diagnostic criteria for chronic rhinosinusitis.

OBJECTIVE In 1997, the Task Force on Rhinosinusitis (TFR) set forth symptom-based diagnostic guidelines for chronic rhinosinusitis (CRS). In the present study, we examined radiologic correlates of the TFR diagnostic criteria for rhinosinusitis. STUDY DESIGN AND SETTING One hundred twenty-five consecutive patients undergoing computed tomography (CT) scans of the sinuses were studied at Oregon Health and Science University. Patients were evaluated prospectively with a questionnaire based on the TFR criteria, and their CT scans were graded according to the Lund-Mackay scoring system. RESULTS Of the 125 patients, 115 met the symptom criteria for CRS. However, 40 of 115 had negative scans (Lund-McKay score, 0) despite meeting the diagnostic criteria for rhinosinusitis. Of 115, 75 had positive scans (Lund-McKay score, >1). Of the 10 patients who had negative diagnoses for rhinosinusitis, 9 had a positive CT scan. The Kappa coefficient was -0.103 (+/-95% confidence interval, -0.201 to -0.004), indicating poor agreement between CRS positivity and CT positivity. The sensitivity of TFR criteria for detecting a positive scan was 89%, but the specificity was poor at only 2%. CONCLUSION AND SIGNIFICANCE Based on these pilot data, it appears that the specificity and predictive value of the current TFR criteria may not be adequate to serve as a diagnostic standard for rhinosinusitis. Additional validating data may provide guidance for improving the sensitivity and specificity of symptom-based diagnostic instruments for rhinosinusitis.

Proximal junctional acute collapse cranial to multi-level lumbar fusion: a cost analysis of prophylactic vertebral augmentation

BACKGROUND CONTEXT Limited data are available regarding incidence of proximal junctional acute collapse after multilevel lumbar spine fusion. There are no data regarding the cost of prophylactic vertebral augmentation adjacent to long lumbar fusions compared with the costs of performing revision fusion surgery for patients suffering with this complication. PURPOSE To perform a cost analysis of prophylactic vertebral augmentation for prevention of proximal junctional acute collapse after multilevel lumbar fusion. STUDY DESIGN Retrospective chart review and cost analysis. PATIENT SAMPLE All female patients older than 60 years undergoing extended lumbar fusions were reviewed to establish the incidence of proximal junctional acute collapse. OUTCOME MEASURES Cost estimates for two-level vertebroplasty, two-level kyphoplasty, and revision instrumented fusion were calculated using billing data and cost-to-charge ratios. METHODS Cost comparisons of prophylactic vertebral augmentation versus extension of fusion for patients suffering from proximal junctional acute collapse were performed. RESULTS Twenty-eight female patients older than 60 years underwent lumbar fusions from L5 or S1 extending to the thoracolumbar junction (T9-L2). Fifteen of the 28 patients had prophylactic vertebroplasty cranial to the fused segment. Proximal junctional acute collapse requiring revision surgery occurred in 2 of the 13 patients (15.3%) treated without prophylactic vertebroplasty. None of the 15 patients undergoing cement augmentation experienced this complication. Assuming a 15% decrease in the incidence of proximal junctional acute collapse, the estimated cost to prevent a single proximal junctional acute collapse was