Jonathan J. Russin

The Barrow Ruptured Aneurysm Trial: 6-year results.

OBJECT The authors report the 6-year results of the Barrow Ruptured Aneurysm Trial (BRAT). This ongoing randomized trial, with the final goal of a 10-year follow-up, compares the safety and efficacy of surgical clip occlusion and endovascular coil embolization in patients presenting with subarachnoid hemorrhage (SAH) from a ruptured aneurysm. The 1- and 3-year results of this trial have been previously reported. METHODS In total, 500 patients with an SAH met the entry criteria and were enrolled in the study. Of these patients, 471 were randomly assigned to the treatments: 238 to surgical clipping and 233 to endovascular coiling. Six patients who died before treatment and 57 patients with nonaneurysmal SAHs were excluded, leaving a total of 408 patients who underwent clipping (209 assigned) or coiling (199 assigned). Whether to treat patients within the assigned group or to cross over patients to the other group was at the discretion of the treating physician; 38% (75/199) of the patients assigned to coiling were crossed over to clipping and 1.9% (4/209) assigned to clipping were crossed over to coiling. The outcome data were collected by a dedicated nurse practitioner. The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. Six years after randomization, 336 (82%) of 408 patients who had been treated were available for examination. RESULTS On the basis of an mRS score of > 2, and similar to the results at the 3-year follow-up, no significant difference in outcomes (p = 0.24) was detected between the 2 treatment groups. Complete aneurysm obliteration at 6 years was achieved in 96% (111/116) of the clipping group and in 48% (23/48) of the coiling group (p < 0.0001). In the period between the 3- and 6-year follow-ups, 3 additional patients assigned to coiling and none assigned to clipping received retreatment, for overall retreatment rates of 4.6% (13/280) for clipping and 16.4% (21/128) for coiling (p < 0.0001). When aneurysm location was considered, the 6-year results continued to match the previously reported results, with no difference in outcome for anterior circulation aneurysms at most time points. Of the anterior circulation aneurysms assigned to coiling treatment, 42% (70/168) were crossed over to clipping treatment. The outcomes for posterior circulation aneurysms continued to favor coiling. The randomization process was unexpectedly skewed, with 18 of 21 treated aneurysms of the posterior inferior cerebellar artery (PICA) being assigned to clipping, but even when PICA aneurysms were removed from the analysis, outcomes for the posterior circulation aneurysms still favored coiling. CONCLUSIONS Although BRAT was statistically underpowered to detect small differences, these results suggest little difference in outcome between the 2 treatments for anterior circulation aneurysms. This was not the case for the posterior circulation aneurysms, where coil embolization appeared to provide a sustained advantage over clipping. Aneurysm obliteration rates in BRAT were significantly lower and retreatment rates significantly higher in the patients undergoing coiling than in those undergoing clipping. However, despite the fact that retreatment rates were higher after coiling, no recurrent hemorrhages were known to have occurred in patients undergoing coiling in BRAT who were followed up for 6 years. Sufficient questions remain about the relative benefits of the 2 treatment modalities to warrant further well-designed randomized trials.

Postoperative Gamma Knife surgery for benign meningiomas of the cranial base

OBJECT The standard treatment for meningiomas is complete resection, but the proximity of skull base meningiomas to important neurovascular structures makes complete excision of the lesion difficult or impossible. The authors analyzed the mid- and long-term results obtained in patients treated with postresection Gamma Knife surgery (GKS) for residual or recurrent benign meningiomas of the cranial base. METHODS Thirty-six patients with residual or recurrent benign meningiomas of the skull base following one or more surgical procedures underwent GKS. There were 31 women and five men, ranging in age from 22 to 73 years. The median tumor volume was 4.1 ml (range 0.8-20 ml) and the median radiation dose to the tumor margin was 16 Gy (range 15-16 Gy). RESULTS Patients were followed for a median of 81 months (range 30-141 months) after GKS. At the end of the follow-up period, overall neurological improvement was observed in 16 patients (44.4%), whereas the condition in 20 patients (55.6%) was unchanged. One patient suffered transient cerebral edema 6 months after GKS. Based on imaging documentation, a partial response was seen in five patients (13.9%), the disease remained stable in 30 patients (83.3%), and in one patient (2.8%) there was an increase in tumor size. The actuarial progression-free survival rate was 100% at 5 years and 94.7% at 10 years. CONCLUSIONS Gamma Knife surgery was shown to be an excellent adjunct to resection because of its durable rate of tumor control and low toxicity. It should be initially considered along with surgery for the treatment of complex skull base meningiomas.

DNA Methylation in the Malignant Transformation of Meningiomas

Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3–5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways involved in malignant transformation remain to be determined, as does the extent of epigenetic alteration in malignant meningiomas. In this study, we explored the landscape of DNA methylation in ten benign, five atypical and four malignant meningiomas. Compared to the benign tumors, the atypical and malignant meningiomas demonstrate increased global DNA hypomethylation. Clustering analysis readily separates malignant from atypical and benign tumors, implicating that DNA methylation patterns may serve as diagnostic biomarkers for malignancy. Genes with hypermethylated CpG islands in malignant meningiomas (such as HOXA6 and HOXA9) tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stages. Most genes with hypermethylated CpG islands at promoters are suppressed in malignant and benign meningiomas, suggesting the switching of gene silencing machinery from PRC binding to DNA methylation in malignant meningiomas. One exception is the MAL2 gene that is highly expressed in benign group and silenced in malignant group, representing de novo gene silencing induced by DNA methylation. In summary, our results suggest that malignant meningiomas have distinct DNA methylation patterns compared to their benign and atypical counterparts, and that the differentially methylated genes may serve as diagnostic biomarkers or candidate causal genes for malignant transformation.

Three dimensional CT angiography versus digital subtraction angiography in the detection of intracranial aneurysms in subarachnoid hemorrhage

Introduction Ruptured intracranial aneurysms are responsible for over 90% of cases of spontaneous subarachnoid hemorrhage (SAH). Conventional digital subtraction angiography (DSA) remains the gold standard for diagnosing the source of SAH. A prospective study is presented wherein SAH patients underwent three dimensional CT angiography (CTA) prior to DSA in order to assess the specificity and sensitivity of this non-invasive modality to detect aneurysms. Methods 179 consecutive patients with spontaneous SAH presented over 36 months, as identified by screening CT and CTA. Patients with negative CTA findings underwent DSA within 24 h of presentation. All patients who were determined to have angiographically negative SAH underwent follow-up DSA 2 weeks later. Results Of the 179 patients screened by CTA, 13 (7%) were negative for aneurysms or other vascular lesions (arteriovenous malformation or dural fistula) on CTA and underwent DSA. No new lesions were identified on six vessel angiography, resulting in a 0% false negative rate (sensitivity 100%, predictive value 100%). MRI to rule out thrombosed aneurysms and repeat angiography at the 2 week follow-up were negative. Conclusions Sensitivity and specificity were higher than previously reported, suggesting that CTA may be used as an initial screening tool in lieu of DSA. Further studies are necessary to determine if CTA can supplant DSA in ruling out all forms of vascular disease in idiopathic SAH.

Advanced Imaging Modalities in the Detection of Cerebral Vasospasm

The pathophysiology of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is complex and is not entirely understood. Mechanistic insights have been gained through advances in the capabilities of diagnostic imaging. Core techniques have focused on the assessment of vessel caliber, tissue metabolism, and/or regional perfusion parameters. Advances in imaging have provided clinicians with a multifaceted approach to assist in the detection of cerebral vasospasm and the diagnosis of delayed ischemic neurologic deficits (DIND). However, a single test or algorithm with broad efficacy remains elusive. This paper examines both anatomical and physiological imaging modalities applicable to post-SAH vasospasm and offers a historical background. We consider cerebral blood flow velocities measured by Transcranial Doppler Ultrasonography (TCD). Structural imaging techniques, including catheter-based Digital Subtraction Angiography (DSA), CT Angiography (CTA), and MR Angiography (MRA), are reviewed. We examine physiologic assessment by PET, HMPAO SPECT, 133Xe Clearance, Xenon-Enhanced CT (Xe/CT), Perfusion CT (PCT), and Diffusion-Weighted/MR Perfusion Imaging. Comparative advantages and limitations are discussed.

Mechanical Thrombectomy in Acute Stroke: Utilization Variances and Impact of Procedural Volume on Inpatient Mortality

BACKGROUND An increasing number of endovascular mechanical thrombectomy procedures are being performed for the treatment of acute ischemic stroke. This study examines variances in the allocation of these procedures in the United States at the hospital level. We investigate operative volume across centers performing mechanical revascularization and establish that procedural volume is independently associated with inpatient mortality. METHODS Data was collected using the Nationwide Inpatient Sample database in the United States for 2008. Medical centers performing mechanical thrombectomy were identified using International Classification of Diseases, 9th revision codes, and procedural volumes were evaluated according to hospital size, location, control/ownership, geographic characteristics, and teaching status. Inpatient mortality was compared for hospitals performing ≥10 mechanical thrombectomy procedures versus those performing<10 procedures annually. After univariate analysis identified the factors that were significantly related to mortality, multivariable logistic regression was performed to compare mortality outcome by hospital procedure volume independent of covariates. RESULTS Significant allocation differences existed for mechanical thrombectomy procedures according to hospital size (P<.001), location (P<.0001), control/ownership (P<.0001), geography (P<.05), and teaching status (P<.0001). Substantial procedural volume was independently associated with decreased mortality (P=.0002; odds ratio 0.49) when adjusting for demographic covariates. CONCLUSIONS The number of mechanical thrombectomy procedures performed nationally remains relatively low, with a disproportionate distribution of neurointerventional centers in high-volume, urban teaching hospitals. Procedural volume is associated with mortality in facilities performing mechanical thrombectomy for acute ischemic stroke patients. These results suggest a potential benefit for treatment centralization to facilities with substantial operative volume.

Simulation of a high-flow extracranial-intracranial bypass using a radial artery graft in a novel fresh tissue model.

BACKGROUND: Microsurgical vascular anastomosis techniques are technically challenging and used in only a narrow spectrum of neurosurgical procedures. Opportunities for instruction and application have become increasingly rare during standard neurosurgery residencies. OBJECTIVE: To create a neurovascular simulation model that more closely approximates the clinical environment. This article describes a novel surgical model using vascular pressurization in a fresh cadaver to simulate an extracranial-to-intracranial bypass. METHODS: Fresh cadavers were obtained according to the standard operating procedures of the University of Southern California Fresh Tissue Dissection Laboratory. The femoral vessels were cannulated and the entire cadaver pressurized. A high-flow bypass from the common carotid artery to the middle cerebral artery was performed using a radial artery graft. RESULTS: This system has several advantages for neurosurgical simulation. The fresh tissue reproduces intraoperative haptics and anatomy. Extracranial-to-intracranial bypass is a physically demanding procedure and can become fatiguing and frustrating for beginners. This model more closely simulates clinical operative time and conditions. The surgeon is able to rehearse the steps and progression of the operation as opposed to simply focusing on the anastomosis. Surgeon positioning and microscope placement are often difficult for novices. By simulating the operating room conditions, these steps can be practiced, providing experience that can be directly translated to the clinical arena. CONCLUSION: Despite the decrease in frequency, indications for bypass procedures still exist in neurosurgery. The fresh tissue pressurization model offers significant benefits when training neurosurgeons to perform these technically demanding procedures. ABBREVIATIONS: EC-IC, extracranial-intracranial FTDL, Fresh Tissue Dissection Laboratory PVC, polyvinyl chloride

Computed Tomography for Clearance of Cervical Spine Injury in the Unevaluable Patient

OBJECTIVE To review computed tomography (CT) as a stand-alone test for the clearance of cervical spine injury in the unevaluable patient population. METHODS A PubMed database search was performed using a combination of search terms and Medical Subject Headings. Studies that met inclusion criteria were those with unevaluable patient populations suffering blunt trauma who underwent both CT and magnetic resonance imaging (MRI) of the cervical spine. RESULTS Our analysis of 13 articles revealed that a total of 1322 unevaluable patients with a negative CT C-spine who also underwent MRI; 137 of these patients (10%) had positive findings on MRI. Among nine studies with patient management data, a total of 115 patients had positive MRI findings in the setting of a negative CT. Of those 115 patients, 52%, or 60 patients, had changes to their management based on MRI findings. Surgical stabilization was required in three patients, representing 2.5% of the 115 patients with positive MRI findings. The total number of patients in these nine studies who had a negative CT was 855. Therefore, the negative predictive value of a negative CT in this patient population was 92.9% for clinically significant cervical spine injury and 99.6% for cervical spine injury requiring operative intervention. CONCLUSION The evidence supporting CT for the stand-alone evaluation of the cervical spine in the unevaluable patient is insufficient. We contend that a CT of the cervical spine must be supplemented by an additional examination addressing ligamentous instability in this patient population.

Cerebral Vasospasm and Concurrent Left Ventricular Outflow Tract Obstruction: Requirement for Modification of Hyperdynamic Therapy Regimen

BackgroundMedical treatment of arterial vasospasm following aneurysmal subarachnoid hemorrhage (SAH) generally consists of triple H therapy, which frequently relies on inotropic agents in order to increase cardiac output (CO). Patients with concurrent left ventricular outflow tract (LVOT) obstruction may have paradoxical decreases in CO following administration of inotropic pressors, placing them at significant risk for cerebral ischemia and stroke.MethodsThe clinical courses of two patients with SAH-induced arterial vasospasm and underlying left ventricular outflow obstruction are reported. Both patients had hypotension and low cardiac output that were refractory to medical management with triple H therapy. Echocardiography in both patients demonstrated LVOT obstruction secondary to hypertrophic obstructive cardiomyopathy (HOCM).ResultsIntervention in both patients included discontinuation of inotropic agents and maintenance of hypervolemia to a target pulmonary capillary wedge pressure range, resulting in improved cardiac output and mean arterial pressure.ConclusionMedical treatment for cerebral vasospasm with inotropic pressor agents may result in paradoxical decreases in hemodynamic parameters and cerebral perfusion in patients with LVOT obstruction. While HOCM is the most likely structural abnormality to cause this phenomenon, it can be induced by several physiological conditions encountered in the neurocritical care setting. Modifications in triple H therapy regimens may be required in order to optimize cerebral perfusion and prevent cerebral ischemia and stroke in these patients.

Surgical management of skull base tumors

AIM To present a review of the contemporary surgical management of skull base tumors. BACKGROUND Over the last two decades, the treatment of skull base tumors has evolved from observation, to partial resection combined with other therapy modalities, to gross total resection and no adjuvant treatment with good surgical results and excellent clinical outcomes. MATERIALS AND METHODS The literature review of current surgical strategies and management of skull base tumors was performed and complemented with the experience of Barrow Neurological Institute. RESULTS Skull base tumors include meningiomas, pituitary tumors, sellar/parasellar tumors, vestibular and trigeminal schwannomas, esthesioneuroblastomas, chordomas, chondrosarcomas, and metastases. Surgical approaches include the modified orbitozygomatic, pterional, middle fossa, retrosigmoid, far lateral craniotomy, midline suboccipital craniotomy, and a combination of these approaches. The selection of an appropriate surgical approach depends on the characteristics of the patient and the tumor, as well as the experience of the neurosurgeon. CONCLUSION Modern microsurgical techniques, diagnostic imaging, intraoperative neuronavigation, and endoscopic technology have remarkably changed the concept of skull base surgery. These refinements have extended the boundaries of tumor resection with minimal morbidity.