Clifford J. Eskey

Preliminary Experience with Onyx Embolization for the Treatment of Intracranial Dural Arteriovenous Fistulas

BACKGROUND AND PURPOSE: Onyx was recently approved for the treatment of pial arteriovenous malformations, but its use to treat dural arteriovenous fistulas (DAVFs) is not yet well established. We now report on the treatment of intracranial DAVFs using this nonadhesive liquid embolic agent. MATERIALS AND METHODS: We performed a retrospective analysis of 12 consecutive patients with intracranial DAVFs who were treated with Onyx as the single treatment technique at our institution between March 2006 and February 2007. RESULTS: A total of 17 procedures were performed in 12 patients. In all of the cases, transarterial microcatheterization was performed, and Onyx-18 or a combination of Onyx-18/Onyx-34 was used. Eight patients were men. The mean age was 56 ± 12 years. Nine patients were symptomatic. There was an average of 5 feeders per DAVF (range, 1–9). Cortical venous reflux was present in all of the cases except for 1 of the symptomatic patients. Complete resolution of the DAVF on immediate posttreatment angiography was achieved in 10 patients. The remaining 2 patients had only minimal residual shunting postembolization, 1 of whom appeared cured on a follow-up angiogram 8 weeks later. The other patient has not yet had angiographic follow-up. Follow-up angiography (mean, 4.4 months) is currently available in 9 patients. There was 1 angiographic recurrence (asymptomatic), which was subsequently re-embolized with complete occlusion of the fistula and its draining vein. There was no significant morbidity or mortality. CONCLUSION: In our experience, the endovascular treatment of intracranial DAVFs with Onyx is feasible, safe, and highly effective with a small recurrence rate in the short-term follow-up.

Normal variation of vertebral artery on CT angiography and its implications for diagnosis of acquired pathology.

Purpose CT angiography (CTA) is rapidly becoming a popular tool for the evaluation of cerebrovascular diseases. Noninvasive diagnosis of vertebral artery pathology using CTA relies in part on diminished vertebral artery size or eccentric position relative to the transverse foramen. However, normal variation of the vertebral artery on CT has not been systematically described. Method Patients younger than 40 years who underwent CTA for reasons other than evaluation of vertebral artery disease were studied. Area measurements of the vertebral artery and the transverse foramen were performed by three radiologists. Variance component analysis was performed. Results There is marked variation in the size of the vertebral artery relative to the transverse foramen, with the vertebral artery occupying 8–85% of the foramen. In many patients, marked asymmetry in relative vertebral artery size and position was observed. This asymmetry would often vary markedly from level to level within the same patient. Conclusion Vertebral artery size and position in the transverse foramina vary markedly in normal young subjects. These normal variations must be considered when evaluating vertebral artery pathology on CT angiograms.

Tumor Bed Dynamics After Surgical Resection of Brain Metastases: Implications for Postoperative Radiosurgery

PURPOSE To analyze 2 factors that influence timing of radiosurgery after surgical resection of brain metastases: target volume dynamics and intracranial tumor progression in the interval between surgery and cavity stereotactic radiosurgery (SRS). METHODS AND MATERIALS Three diagnostic magnetic resonance imaging (MRI) scans were retrospectively analyzed for 41 patients with a total of 43 resected brain metastases: preoperative MRI scan (MRI-1), MRI scan within 24 hours after surgery (MRI-2), and MRI scan for radiosurgery planning, which is generally performed ≤1 week before SRS (MRI-3). Tumors were contoured on MRI-1 scans, and resection cavities were contoured on MRI-2 and MRI-3 scans. RESULTS The mean tumor volume before surgery was 14.23 cm3, and the mean cavity volume was 8.53 cm3 immediately after surgery and 8.77 cm3 before SRS. In the interval between surgery and SRS, 20 cavities (46.5%) were stable in size, defined as a change of ≤2 cm3; 10 cavities (23.3%) collapsed by >2 cm3; and 13 cavities (30.2%) increased by >2 cm3. The unexpected increase in cavity size was a result of local progression (2 cavities), accumulation of cyst-like fluid or blood (9 cavities), and nonspecific postsurgical changes (2 cavities). Finally, in the interval between surgery and SRS, 5 cavities showed definite local tumor progression, 4 patients had progression elsewhere in the brain, 1 patient had both local progression and progression elsewhere, and 33 patients had stable intracranial disease. CONCLUSIONS In the interval between surgical resection and delivery of SRS, surgical cavities are dynamic in size; however, most cavities do not collapse, and nearly one-third are larger at the time of SRS. These observations support obtaining imaging for radiosurgery planning as close to SRS delivery as possible and suggest that delaying SRS after surgery does not offer the benefit of cavity collapse in most patients. A prospective, multi-institutional trial will provide more guidance to the optimal timing of cavity SRS.

A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme

Purpose Irinotecan is a cytotoxic agent with activity against gliomas. Thalidomide, an antiangiogenic agent, may play a role in the treatment of glioblastoma multiforme (GBM). To evaluate the combination of thalidomide and irinotecan, we conducted a phase II trial in adults with newly-diagnosed or recurrent GBM. Patients and methods Thalidomide was given at a dose of 100 mg/day, followed by dose escalation every 2 weeks by 100 mg/day to a target of 400 mg/day. Irinotecan was administered on day 1 of each 3 week cycle. Irinotecan dose was 700 mg/m2 for patients taking enzyme-inducing anticonvulsants and 350 mg/m2 for all others. The primary endpoint was tumor response, assessed by MRI. Secondary endpoints were toxicity, progression-free survival, and overall survival. Results Twenty-six patients with a median age of 55 years were enrolled, with fourteen evaluable for the primary outcome, although all patients were included for secondary endpoints. One patient (7%) exhibited a partial response after twelve cycles, and eleven patients (79%) had stable disease. The intention to treat group with recurrent disease included 16 patients who had a 6-month PFS of 19% (95% CI: 4–46%) and with newly-diagnosed disease included 10 patients who had a 6-month PFS of 40% (95% CI: 12–74%). Gastrointestinal (GI) toxicity was mild, but six patients (23%) experienced a venous thromboembolic complication. Two patients had Grade 4 treatment-related serious adverse events that required hospitalization. There were no treatment-related deaths. Conclusion The combination of irinotecan and thalidomide has limited activity against GBM. Mild GI toxicity was observed, but venous thromboembolic complications were common.

Platelet function inhibitors and platelet function testing in neurointerventional procedures

Over the past decade there has been a growing use of intracranial stents for the treatment of both ischemic and hemorrhagic cerebrovascular disease, including stents to assist in the remodeling of the neck of aneurysms as well as the use of flow diverting devices for aneurysm treatment. With this increase in stent usage has come a growing need for the neurointerventional (NI) community to understand the pharmacology of medications used for modifying platelet function, as well as the testing methodologies available. Platelet function testing in NI procedures remains controversial. While pre-procedural antiplatelet assays might lead to a reduced rate of thromboembolic complications, little evidence exists to support this as a standard of care practice. Despite the routine use of dual antiplatelet therapy (DAT) with aspirin and a P2Y12 receptor antagonist (such as clopidogrel, prasugrel, or ticagrelor) in most neuroembolization procedures necessitating intraluminal reconstruction devices, thromboembolic complications are still encountered.1–3 Moreover, DAT carries the risk of hemorrhagic complications, with intracerebral hemorrhage (ICH) being the most potentially devastating.4 ,5 Light transmission aggregometry (LTA) is the gold standard to test for platelet reactivity, but it is usually expensive and may not be easily obtainable at many centers. This has led to the development of point-of-care assays, such as the VerifyNow (Accumetrics, San Diego, California, USA), which correlates strongly with LTA and can reliably measure the degree of P2Y12 receptor inhibition.6–9 VerifyNow results are reported in P2Y12 reaction units (PRUs), with a lower PRU value corresponding to a higher level of P2Y12 receptor inhibition and, presumably, a lower probability of platelet aggregation, and a higher PRU value corresponding to a lower level of P2Y12 receptor inhibition and, hence, a higher chance of platelet activation and aggregation. While aspirin resistance is perhaps less common, clopidogrel resistance may be more challenging as …

Vertebral augmentation: report of the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery

Vertebroplasty and kyphoplasty are minimally invasive image-guided procedures that involve the injection of cement (typically polymethylmethacrylate (PMMA)) into a vertebral body. Kyphoplasty involves inflation of a balloon tamp to create a cavity within the vertebral body into which cement is subsequently injected. The majority of these vertebral augmentation procedures are performed to relieve back pain from osteoporotic or cancer-related vertebral compression fractures and to reinforce the vertebral body with neoplasm or vascular tumor. The primary goal of vertebroplasty and kyphoplasty is to reduce back pain and to improve patients functional status, and the secondary goal is stabilization of a vertebra weakened by fracture or neoplasia. ### Osteoporotic vertebral fractures Osteoporosis is a common disease that causes significant morbidity and incurs a significant healthcare cost to the community. The major osteoporotic fractures involve the hip, vertebra, proximal humerus and distal forearm; the lifetime osteoporotic fracture risk at age 50 is approximately one in two women and one in five men.1 The lifetime incidence of symptomatic osteoporotic vertebral fractures in women at age 50 is estimated at 10–15%1; once a vertebral fracture occurs, there is a 20% risk of another vertebral fracture within 12 months.2 Most osteoporotic vertebral compression fractures are asymptomatic or result in minimal pain; only a third of vertebral fractures result in medical attention.3 Conservative medical therapy is therefore appropriate for the vast majority of vertebral compression fractures since most acute back pain symptoms are mild and subside over a period of 6–8 weeks as the fracture heals. The goals of conservative therapy are pain reduction (with analgesics and/or bed rest), improvement in functional status (with orthotic devices and physical therapy) and prevention of future fractures (with vitamin D, calcium supplementation and antiresorptive agents). However, conservative treatment for those with severe pain or limitation of function is not benign. It …

Invasive interventional management of post-hemorrhagic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

Current clinical practice standards are addressed for the invasive interventional management of post-hemorrhagic cerebral vasospasm (PHCV) in patients with aneurysmal subarachnoid hemorrhage. The conclusions, based on an assessment by the Standards Committee of the Society of Neurointerventional Surgery, included a critical review of the literature using guidelines for evidence based medicine proposed by the Stroke Council of the American Heart Association and the University of Oxford, Centre for Evidence Based Medicine. Specifically examined were the safety and efficacy of established invasive interventional therapies, including transluminal balloon angioplasty (TBA) and intra-arterial vasodilator infusion therapy (IAVT). The assessment shows that these invasive interventional therapies may be beneficial and may be considered for PHCV—that is, symptomatic with cerebral ischemia and refractory to maximal medical management. As outlined in this document, IAVT may be beneficial for the management of PHCV involving the proximal and/or distal intradural cerebral circulation. TBA may be beneficial for the management of PHCV that involves the proximal intradural cerebral circulation. The assessment shows that for the indications described above, TBA and IAVT are classified as Class IIb, Level B interventions according to the American Heart Association guidelines, and Level 4, Grade C interventions according to the University of Oxford Centre for Evidence Based Medicine guidelines.

Computed tomography angiography: improving diagnostic yield and cost effectiveness in the initial evaluation of spontaneous nonsubarachnoid intracerebral hemorrhage.

OBJECT Computed tomography angiography (CTA) is increasingly used as a screening tool in the investigation of spontaneous intracerebral hemorrhage (ICH). However, CTA carries additional costs and risks, necessitating its judicious use. The authors hypothesized that subsets of patients with nontraumatic, nonsubarachnoid ICH are unlikely to benefit from CTA as part of the diagnostic workup and that particular patient risk factors may be used to increase the yield of CTA in the detection of vascular sources. METHODS The authors performed a retrospective analysis of 1376 patients admitted to Dartmouth-Hitchcock Medical Center with ICH over an 8-year period. Patients with subarachnoid hemorrhage, hemorrhagic conversion of ischemic infarcts, trauma, and known prior malignancy were excluded from the analysis, resulting in 257 patients for final analysis. Records were reviewed for medical risk factors, hemorrhage location, and correlation of CTA findings with final diagnosis. Multiple logistic regression analysis was used to investigate the combined effects of baseline variables of interest. Model selection was conducted using the stepwise method with p = 0.10 as the significance level for variable entry and p = 0.05 the significance level for variable retention. RESULTS Computed tomography angiography studies detected vascular pathology in 34 patients (13.2%). Patient characteristics that were associated with a significantly higher likelihood of identifying a structural vascular lesion as the source of hemorrhage included patient age younger than 65 years (OR = 16.36, p = 0.0039), female sex (OR = 14.9, p = 0.0126), nonsmokers (OR = 103.8, p = 0.0008), patients with intraventricular hemorrhage (OR = 9.42, p = 0.0379), and patients without hypertension (OR = 515.78, p < 0.0001). Patients who were older than 65 years of age, with a history of hypertension, and hemorrhage located in the cerebellum or basal ganglia were never found to have an identified structural source of hemorrhage on CTA. CONCLUSIONS Patient characteristics and risk factors are important considerations when ordering diagnostic tests in the workup of nonsubarachnoid, nontraumatic spontaneous ICH. Although CTA is an accurate diagnostic examination, it can usually be omitted in the workup of patients with the described characteristics. The use of this algorithm has the potential to increase the yield, and thus the safety and cost effectiveness, of this diagnostic tool.

Optimizing computed tomography to reduce artifacts from titanium aneurysm clips: an in vitro study. Technical note.

OBJECT At many institutions digital subtraction angiography remains the standard imaging procedure for the postoperative evaluation of patients following placement of a cerebral aneurysm clip largely because of the artifacts produced by the clip on computed tomography (CT). The authors evaluated the effect of various imaging parameters on the quality of 3D reconstructions from CT scans while imaging a phantom to optimize the CT angiograms. METHODS Using multidetector CT scanners with submillimeter detector collimation (0.625 mm), the authors scanned a silicone phantom with attached commercial aneurysm clips. Slice thickness, reconstruction overlap, kilovolt level, milliampere level, and pitch were varied. Neuroradiologists, who were blinded to the scanning parameters, rated the reconstructions for image quality and artifact reduction. RESULTS Images of the titanium clip using 140 kV and 380 mA with 0.625-mm overlapping reconstructed slices provided excellent 3D visualization of both the clip and the aneurysm model, even when using two adjacent clips. CONCLUSIONS Overlapping reconstructions combined with thin-section acquisition can provide detailed images of titanium clips and surrounding tissues without the use of low-pitch values.

Magnetic resonance imaging/magnetic resonance angiography fusion technique for intraoperative navigation during microsurgical resection of cerebral arteriovenous malformations

OBJECT Microsurgical resection of arteriovenous malformations (AVMs) is facilitated by real-time image guidance that demonstrates the precise size and location of the AVM nidus. Magnetic resonance images have routinely been used for intraoperative navigation, but there is no single MRI sequence that can provide all the details needed for characterization of the AVM. Additional information detailing the specific location of the feeding arteries and draining veins would be valuable during surgery, and this detail may be provided by fusing MR images and MR angiography (MRA) sequences. The current study describes the use of a technique that fuses contrast-enhanced MR images and 3D time-of-flight MR angiograms for intraoperative navigation in AVM resection. METHODS All patients undergoing microsurgical resection of AVMs at the Dartmouth Cerebrovascular Surgery Program were evaluated from the surgical database. Between 2009 and 2011, 15 patients underwent surgery in which this contrast-enhanced MRI and MRA fusion technique was used, and these patient form the population of the present study. RESULTS Image fusion was successful in all 15 cases. The additional data manipulation required to fuse the image sets was performed on the morning of surgery with minimal added setup time. The navigation system accurately identified feeding arteries and draining veins during resection in all cases. There was minimal imaging-related artifact produced by embolic materials in AVMs that had been preoperatively embolized. Complete AVM obliteration was demonstrated on intraoperative angiography in all cases. CONCLUSIONS Precise anatomical localization, as well as the ability to differentiate between arteries and veins during AVM microsurgery, is feasible with the aforementioned MRI/MRA fusion technique. The technique provides important information that is beneficial to preoperative planning, intraoperative navigation, and successful AVM resection.