Seizure outcome in patients with cavernous malformation after early surgery.

OBJECTIVE: To describe seizure outcome and complications in patients with cavernous malformations (CM) undergoing early versus late surgery. METHODS: A database was created for all CM patients who presented with seizure referred to the neurosurgical clinic at an academic center. A telephone survey and chart review were conducted to evaluate for preoperative and postoperative seizure frequency. Postoperative seizure-free outcome of patients who had ≤2 preoperative seizures versus those that had >2 preoperative seizures was compared. RESULTS: A total of 35 CM patients were included for analysis. Nineteen patients had ≤2 preoperative seizures and 16 patients had >2 preoperative seizures, six of them drug resistant for over two years. Among the ≤2 seizure group, 15 had only a single seizure before surgical resection. 94.7% of patients with ≤2 preoperative seizures and 62.5% of patients with >2 preoperative seizures were seizure free one year following surgical resection (p = 0.019). 78.9% of patients with ≤2 preoperative seizures and 25% of patients with >2 preoperative seizures were able to wean off AEDs (p < 0.001). Among those patients who had a single preoperative seizure, 100% of patients were seizure free at one year. CONCLUSIONS: Early surgical resection for CM patients who present after a CM-related seizure is an effective, well tolerated treatment and has good chance to offer seizure freedom without the need for long-term antiepileptic medications. Outcome for patients operated with only one or two preoperative seizures may lead to better results than patients who delay the procedure.

Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma.

BACKGROUND: Despite initial treatment with high-dose methotrexate-based regimens, many patients with primary central nervous system lymphoma (PCNSL) relapse and die from their disease. No standard of care exists at progression or relapse, but chemotherapy and in some cases radiation are usually used. Pemetrexed is a multitargeted antifolate, similar to methotrexate, but with a broader spectrum of activity. Because methotrexate is an integral part of PCSNL treatment, the authors assessed the antitumor activity and safety of pemetrexed in recurrent PCNSL. METHODS: Patients with relapsed/refractory PCNSL were enrolled in this trial. Treatment consisted of pemetrexed 900 mg/m(2) given every 3 weeks with low-dose dexamethasone, folate, and B12 supplementation. Each cycle was 6 weeks, and follow-up imaging was done before each new cycle. Treatment was continued until complete remission, progression, or toxicity. RESULTS: Eleven patients were treated, with a median age of 69.8 years and Karnofsky performance status of 70%; 10 of 11 patients had failed prior high-dose methotrexate. The median number of pemetrexed cycles given was 5, with an associated overall response rate of 55% and disease control rate of 91%. The 6-month progression-free survival (PFS) was 45%, median PFS was 5.7 months, and median overall survival was 10.1 months. Toxicities were primarily hematologic and infectious. CONCLUSIONS: Pemetrexed has single-agent activity in relapsed/refractory PCNSL. Toxicities were seen likely because of the higher than standard dose used. Further investigation of this agent or other multitargeted antifolates in PCNSL is warranted to determine optimal dose and efficacy in a more homogeneous population.

Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging--pilot study.

PURPOSE: To derive a magnetic resonance (MR)-based imaging metric that reflects local perfusion changes resulting from the administration of angiogenic-inhibiting chemotherapy in patients with recurrent glioblastoma multiforme (GBM). MATERIALS AND METHODS: In this retrospective Institutional Review Board-approved HIPAA-compliant study, 16 patients (12 men, four women; mean age, 51.8 years + or - 15.1 [standard deviation]) with recurrent GBM received bevacizumab every 3 weeks (15 mg per kilogram of body weight) as part of a clinical trial. Baseline MR images were acquired, and follow-up images were acquired every 6 weeks thereafter until tumor progression or death. Imaging included perfusion and T1-weighted contrast material-enhanced MR imaging. Perfusion images were analyzed both with and without correction for contrast material leakage. The volumes of interest were selected as enhancing voxels on T1-weighted contrast-enhanced MR images. Relative cerebral blood volume (rCBV) maps were created from analysis of MR perfusion images. The volumes of interest were used to calculate the following parameters: size, mean rCBV, mean leakage coefficient K(2), and hyperperfusion volume (HPV), which is the fraction of the tumor with an rCBV higher than a predetermined threshold. Percent change in each parameter from baseline to first follow-up was compared with time to progression (TTP) by using a Cox proportional hazards model with calculation of hazard ratios. RESULTS: The most significant hazard ratio was seen with a DeltaHPV cutoff of rCBV greater than 1.00 (hazard ratio, 1.077; 95% confidence interval: 1.026, 1.130; P = .002). The only significant ratios greater than one were those that resulted from perfusion calculated as mean rCBV and DeltaHPV. The ratios were also higher after correction for leakage. CONCLUSION: This pilot study derived an imaging metric (HPV) that reflects local perfusion changes in GBMs. This metric was found to show a significantly improved correlation to TTP as compared with more commonly used metrics.

4D radial acquisition contrast-enhanced MR angiography and intracranial arteriovenous malformations: quickly approaching digital subtraction angiography.

BACKGROUND AND PURPOSE: The current gold standard for imaging intracranial AVMs involves catheter-based techniques, namely cerebral digital subtraction angiography (DSA). However, DSA presents some procedural risks to the patient. Unfortunately, AVM patients usually undergo multiple DSA exams throughout their diagnostic and therapeutic course, significantly increasing their procedural risk exposure. As such, high-quality noninvasive imaging is desired. We hypothesize that 4D radial acquisition contrast-enhanced MRA approximates the vascular architecture and hemodynamics of AVMs compared to conventional angiography. METHODS: Thirteen consecutive AVM patients were assessed by 4D radial acquisition contrast-enhanced MRA and DSA. The 4D rCE-MRA images were independently assessed regarding the location, nidal size, Spetzler-Martin grade, and identification of arterial feeders, drainage pattern, and any other vascular anomalies. RESULTS: 4D rCE-MRA correctly depicted the size, venous drainage pattern, and prominent arterial feeders in all cases. Spetzler-Martin grade was correctly determined between reviewers and between the different imaging modalities in all cases except 1. The nidus size was in good correlation between the reviewers, where r=0.99, P<0.000001. There was very good agreement between reviewers regarding the individual scans (kappa=0.63 to 1), whereas the agreement between the DSA and 4D rCE-MRA images was also good (kappa=0.61 to 0.85). CONCLUSIONS: We have developed a 4D radial acquisition contrast-enhanced MRA sequence capable of imaging intracranial AVMs approximating that of DSA. Image analysis demonstrates equivalency in terms of grading AVMs using the Spetzler-Martin grading scale. This 4D rCE-MRA sequence has the potential to avoid some applications of DSA, thus saving patients from potential procedural risks.

Genomics of human intracranial aneurysm wall.

BACKGROUND AND PURPOSE: The pathogenesis of intracranial aneurysms (IAs) remains elusive. Most studies have focused on individual genes, or a few interrelated genes or products, at a time in human IA. However, a broad view of pathologic mechanisms has not been investigated by identifying pathogenic genes and their interaction in networks. Our study aimed to analyze global gene expression patterns in the IA wall. METHODS: To our knowledge, our group was the first to perform Illumina microarray analysis on human IA via comparison of aneurysm wall and superficial temporal artery tissues from 6 consecutive patients. We adopted stringent statistical criteria to the individual genes; genes with a false discovery rate <0.01 and >2-fold change were selected as differentially expressed. To identify the overrepresented biologic pathways with the differentially expressed genes, we performed hypergeometric testing of the genes selected by relaxed criteria of P<0.01 and fold change >1.5. RESULTS: There are 326 distinct differentially expressed genes between IA and superficial temporal artery tissues (>2-fold change) with a false discovery rate <0.01. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways revealed the most impacted functional pathways: focal adhesion, extracellular matrix receptor interaction, and cell communication. Analysis of the Gene Ontology also supported the involvement of another 2 potentially important pathways: inflammatory response and apoptosis. CONCLUSIONS: The differentially expressed genes in the aneurysm wall may shed light on aneurysm pathobiology and provide novel targets for therapeutic intervention. These data will help generate hypotheses for future studies.

Radial sliding-window magnetic resonance angiography (MRA) with highly-constrained projection reconstruction (HYPR).

Sufficient temporal resolution is required to image the dynamics of blood flow, which may be critical for accurate diagnosis and treatment of various intracranial vascular diseases, such as arteriovenous malformations (AVMs) and aneurysms. Highly-constrained projection reconstruction (HYPR) has recently become a technique of interest for high-speed contrast-enhanced magnetic resonance angiography (CE-MRA). HYPR provides high frame rates by preferential weighting of radial projections while maintaining signal-to-noise ratio (SNR) by using a high SNR composite. An analysis was done to quantify the effects of HYPR on SNR, contrast-to-noise ratio (CNR), and temporal blur compared to the previously developed radial sliding-window technique using standard filtered backprojection or regridding methods. Computer simulations were performed to study the effects of HYPR processing on image error and the temporal information. Additionally, in vivo imaging was done on patients with angiographically confirmed AVMs to measure the effects of alteration of various HYPR parameters on SNR as well as the fidelity of the temporal information. The images were scored by an interventional radiologist in a blinded read and were compared with X-ray digital subtraction angiography (DSA). It was found that with the right choice of parameters, modest improvements in both SNR and dynamic information can be achieved as compared to radial sliding-window MRA.

Acute symptomatic cerebellar tonsillar herniation following intraoperative lumbar drainage.

Complications of tonsillar herniation associated with lumbar drainage have been reported in the literature. However, acutely symptomatic tonsillar herniation after intraoperative lumbar drainage is rare. The following case illustrates the risk associated with cerebrospinal fluid (CSF) drainage in the setting of tonsillar herniation. The use of lumbar drainage during cranial surgery is a common practice for reducing intracranial pressure and enhancing exposure, but is not without complications. In addition to the complications of the insertion procedure itself, the change in pressure gradient between the intracranial and the suboccipital compartments is of key importance. The authors present the case of a patient who underwent a subtemporal craniotomy for resection of mesial temporal cavernous malformation with intraoperative lumbar drainage. The patient had a preexisting, asymptomatic 4-mm Chiari malformation and progressive neurological deficits resulting from further cerebellar tonsillar herniation in the early postoperative period developed, which required a lumbar blood patch, decompressive suboccipital craniectomy, and C-1 laminectomy with duroplasty. After placement of the lumbar drain and subsequent CSF drainage, the change in CSF pressure gradient above and below the foramen magnum probably led to the herniation. Unfortunately, the patient has lasting neuropathic pain and cervical cord signal changes on MR images.

Posterior fossa arteriovenous malformations.

Arteriovenous malformations (AVMs) of the posterior fossa are complex neurovascular lesions that are less common than their supratentorial counterparts, accounting for < 15% of all AVMs. The majority of patients with these lesions present with intracranial hemorrhage, a factor that has been consistently shown to increase one's risk for subsequent bleeding. Studies have additionally shown a posterior fossa or deep AVM location to portend a more aggressive natural history. The authors reviewed the literature on posterior fossa AVMs, finding their annual rupture rates to be as high as 11.6%, an important factor that underscores the importance of aggressive treatment of lesions amenable to intervention as therapeutic options and results continue to improve.

Coil embolization of posttraumatic pseudoaneurysm of the ophthalmic artery causing subarachnoid hemorrhage. Case report.

The authors report a unique case of subarachnoid hemorrhage caused by a traumatic pseudoaneurysm of the ophthalmic artery, which was successfully treated with coil embolization. Clinical and imaging features, as well as the relevant literature, are described.

Advances in the radiosurgical treatment of large inoperable arteriovenous malformations.

Radiosurgery has proven useful in the treatment of small arteriovenous malformations (AVMs) of the brain. However, the volume of healthy tissue irradiated around large lesions is rather significant, necessitating reduced radiation doses to avoid complications. As a consequence, this can produce poorer obliteration rates. Several strategies have been developed in the past decade to circumvent dose-volume problems with large AVMs, including repeated treatments as well as dose, and volume fractionation schemes. Although success on par with that achieved in lesions smaller than 3 ml remains elusive, improvements over the obliteration rate, the complication rate or both have been reported after conventional single-dose stereotactic radiosurgery (SRS). Radiosurgery with a marginal dose or peripheral dose < 15 Gy rarely obliterates AVMs, yet most lesions diminish in size posttreatment. Higher doses may then be reapplied to any residual nidi after an appropriate follow-up period. Volume fractionation divides AVMs into smaller segments to be treated on separate occasions. Doses > 15 Gy irradiate target volumes of only 5-15 ml, thereby minimizing the radiation delivered to the surrounding brain tissue. Fewer adverse radiological effects with the use of fractionated radiosurgery over standard radiosurgery have been reported. Advances in AVM localization, dose delivery, and dosimetry have revived interest in hypofractionated SRS. Investigators dispensing >or= 7 Gy per fraction minimum doses have achieved occlusion with an acceptable number of complications in 53-70% of patients. The extended latency period between treatment and occlusion, about 5 years for emerging techniques (such as salvage, staged volume, and hypofractionated radiotherapy), exposes the patient to the risk of hemorrhage during that period. Nevertheless, improvements in dose planning and target delineation will continue to improve the prognosis in patients harboring inoperable AVMs.