Matthew T. Bender

P2Y12 hyporesponse (PRU>200) is not associated with increased thromboembolic complications in anterior circulation Pipeline

Introduction Recent reports suggest that thromboembolic complications are associated with Pipeline embolization device (PED) placement cluster in P2Y12 hyporesponders. Objective To evaluate the role of P2Y12 hyporesponse in PED placement by retrospectively reviewing a single-center series of patients. Methods We retrospectively reviewed an institutional review board-approved database of patients with an aneurysm at a single institution and identified all patients with a measured P2Y12 reaction unit (PRU)>200 who had undergone anterior circulation PED placement. Events such as transient ischemic attack, stroke, and hemorrhage were identified as well as demographic and procedural details. Results Fifty-two patients with a PRU >200 had undergone anterior circulation PED placement. Four patients had prior subarachnoid hemorrhage (SAH) (8%) and 11 aneurysms (21%) had been previously treated. The average aneurysm size was 7.6u2005mm (±6.2). PED thrombosis occurred intraprocedurally in three patients, none of whom developed neurological deficits after abciximab administration. Treatment of all patients was successful and 48 procedures (92%) had no complications. One patient had a major stroke (2%) with permanent hemiparesis. There were three minor complications (6%): one minor stroke with a visual field cut, one 10u2005cc intracranial hemorrhage with transient left lower extremity weakness, and one transient neurological deficit not verified by imaging. No deaths or cases of SAH occurred. Conclusions P2Y12 hyporesponse (PRU>200) is not associated with increased periprocedural complications in a contemporary series of patients undergoing anterior circulation PED placement. Titration of antiplatelet medications to P2Y12 >200 remains unindicated and may increase the risk of hemorrhagic complications.

Effectiveness of Repeat Glycerol Rhizotomy in Treating Recurrent Trigeminal Neuralgia

BACKGROUNDnPercutaneous glycerol rhizotomy (GR) is used to treat trigeminal neuralgia (TN), with satisfactory pain relief lasting 2 to 3 years in most patients after the first intervention. The efficacy of subsequent GRs, however, has not been studied.nnnOBJECTIVEnTo compare the pain relief and durability achieved by the first GR with those obtained after subsequent GRs in a retrospective cohort of TN patients.nnnMETHODSnBetween 1998 and 2010, 548 patients with TN underwent 708 GRs. After exclusions, 430 initial GRs (GR1) and 114 subsequent GRs (GR2+) were compared in terms of initial pain relief, durability, sensory change, and complications. Durability was assessed by determining median time to treatment failure for all GRs achieving complete pain relief without medications (n = 375: 264 failures, 111 censored). Predictors of initial pain relief were assessed by logistic regression, and predictors of failure were assessed by Cox regression analysis.nnnRESULTSnAfter GR1, pain relief results were as follows: 285 patients (66%) were pain free without medications, 26 (6%) were pain free with medications, 66 (15%) improved, and 53 (12%) were unchanged. After GR2+, results were as follows: 90 patients (79%) were pain free without medications, 6 (5%) were pain free with medications, 7 (6%) improved, and 11 (10%) were unchanged (P = .03). Median time to treatment failure was 26 months after GR1 and 25 months after GR2+ (P = .34). On multivariate analysis, prior GR was a positive predictor of initial pain relief (odds ratio, 2.067; 95% confidence interval, 1.243-3.437; P = .005) and had no effect on durability.nnnCONCLUSIONnTN patients experienced greater pain relief and equivalent durability after GR2+ beyond the initial treatment.

Endovascular flow diversion for treatment of anterior communicating artery region cerebral aneurysms: a single-center cohort of 50 cases

Background Flow diversion represents a novel but definitive treatment for recurrent and difficult-to-coil aneurysms of the anterior communicating artery (ACoA) region, of which reports are limited. Objective To determine the effectiveness of the Pipeline embolization device (PED) in treating aneurysms in the ACoA region. Methods We retrospectively reviewed an IRB-approved database of patients with an aneurysm at a single institution for patients with ACoA or A1–A2 aneurysms treated with PED. Data analyzed included demographics, aneurysm characteristics, procedural details, follow-up results, and outcomes. Results A total of 50 procedures were performed on 41 patients, including seven patients who underwent bilateral ‘H-pipe’ PED placement. The average age was 56u2005years and 46% of the patients were female. The average aneurysm size was 4.5u2005mm, and two large (>10u2005mm) aneurysms were treated. The vessel of origin was either the ACoA (26 aneurysms, 63%) or the A1–A2 junction (15 aneurysms, 37%). Eighteen patients (44%) had prior subarachnoid hemorrhage and 20 had previously been treated either with clipping (6 aneurysms, 15%) or coiling (14 aneurysms, 34%). Procedural success was achieved in 48/50 cases (96%) and two cases were aborted. Coils were deployed adjunctively in two cases (4%). Procedural outcomes included no deaths, one major ischemic stroke (2%), and two patients with intracranial hemorrhage (4%). Complete aneurysm occlusion was achieved in 81% of patients at 6u2005months and 85% of patients at last follow-up digital subtraction angiography. Conclusions The PED can be used safely and effectively in the treatment of aneurysms of the ACoA region. This represents a good alternative treatment option to microsurgical clipping and endovascular coiling.

A Glutamate Receptor Antagonist, S-4-Carboxyphenylglycine (S-4-CPG), Inhibits Vasospasm After Subarachnoid Hemorrhage in Haptoglobin 2 to 2 Mice

BACKGROUNDnVasospasm contributes to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Glutamate concentrations increase after SAH and correlate with vasospasm in experimental SAH. The haptoglobin (Hp) 2-2 genotype is associated with higher risk of vasospasm after SAH. We tested the efficacy of (S)-4-carboxyphenylglycine (S-4-CPG), a metabotropic glutamate receptor inhibitor, for the treatment of vasospasm after SAH in Hp 2-2 and Hp 1-1 mice.nnnOBJECTIVEnTo evaluate the effect on vasospasm and neurobehavioral scores after SAH of systemic S-4-CPG, as well as its toxicity, and phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in Hp 2-2 mice.nnnMETHODSnWestern blot was used to assess changes in VASP phosphorylation in response to glutamate with and without S-4-CPG. A pharmacokinetics study was done to evaluate S-4-CPG penetration through the blood-brain barrier in vivo. Toxicity was assessed by administering increasing S-4-CPG doses. Efficacy of S-4-CPG assessed the effect of S-4-CPG on lumen patency of the basilar artery and animal behavior after SAH in Hp 1-1 and Hp 2-2 mice. Immunohistochemistry was used to evaluate the presence of neutrophils surrounding the basilar artery after SAH.nnnRESULTSnExposure of human brain microvascular endothelial cells to glutamate decreased phosphorylation of VASP, but glutamate treatment in the presence of S-4-CPG maintains phosphorylation of VASP. S-4-CPG crosses the blood-brain barrier and was not toxic to mice. S-4-CPG treatment significantly prevents vasospasm after SAH. S-4-CPG administered after SAH resulted in a trend toward improvement of animal behavior.nnnCONCLUSIONnS-4-CPG prevents vasospasm after experimental SAH in Hp2-2 mice. S-4-CPG was not toxic and is a potential therapeutic agent for vasospasm after SAH.

Percutaneous Procedures for the Treatment of Trigeminal Neuralgia.

Three major percutaneous procedures are currently used to treat trigeminal neuralgia (TN). Percutaneous balloon compression, glycerol rhizotomy, and radiofrequency thermocoagulation interrupt afferent pain fibers by injury to the trigeminal nerve root or ganglion. Each is capable of offering immediate and durable pain relief. Each is associated with relatively low, but variable rates of complications. Patient heterogeneity, technical variation, and nonstandard outcomes plague the existing outcomes literature and limit comparisons of treatments. Rendering treatment selection a function of individual physician preference and practice patterns. Randomized, prospective trials are needed; in the meantime, percutaneous rhizotomy remains an excellent treatment for selected patients.

Small Aneurysms Account for the Majority and Increasing Percentage of Aneurysmal Subarachnoid Hemorrhage: A 25-Year, Single Institution Study

BACKGROUNDnProspective studies of unruptured aneurysms have shown very low rates of rupture for small aneurysms (<10 mm) and suggested that the risk of treatment outweighs benefit. However, common clinical practice shows that patients with aneurysmal subarachnoid hemorrhage (aSAH) frequently have small aneurysms.nnnOBJECTIVEnTo investigate trends in size and location of ruptured aneurysms over a 25-yr period.nnnMETHODSnA prospective, Institutional Review Board-approved database of all patients presenting to our institution with aSAH from 1991 to 2016 was analyzed. Cerebral angiography identified the source of hemorrhage. Patients with nonaneurysmal etiologies were excluded.nnnRESULTSnComplete data were available for 1306/1562 patients (84%) with aSAH from 1991 to 2016. The average age was 53 yr and 72% of patients were female. The average size of ruptured aneurysms over 25 yr was 8.0 mm. The average size of ruptured aneurysms decreased steadily with each 5-yr interval from 10.1 mm (1991-1996) to 6.6 mm (2012-2016; P < .001). Overall, very small aneurysms (<5 mm) were responsible for aSAH in 41% of patients. The percentage of very small ruptured aneurysms rose from 29% during the initial 5-yr period (1991-1996) to 50% in the most recent period. Likewise, the percentage of ruptured aneurysms that were 5 to 9 mm rose from 26% to 34% (P < .001). In the past 5 yr, aneurysms <10 mm accounted for 84% of aSAH. Vessel of origin (P = .097) and aneurysm location (P = .322) did not vary with time.nnnCONCLUSIONnRuptured small and very small aneurysms represent a majority and increasing share of aSAH. Identification and prophylactic treatment of these aneurysms remains an important clinical role for cerebrovascular neurosurgery.

Use of a next-generation multi-durometer long guide sheath for triaxial access in flow diversion: experience in 95 consecutive cases

Background Intracranial access techniques in modern neurointerventions have shifted towards more robust access platforms. The long guide sheath is one of the building blocks of triaxial systems used in intracranial embolizations. Here we present our experience with the AXS Infinity LS long sheath in the triaxial platform for the implantation of the Pipeline embolization device (PED). Methods We retrospectively identified patients who underwent PED Flex treatment with the AXS Infinity LS at a single institution. Procedural data collected included parent artery tortuosity, patient demographics, vasodilator use, aneurysm characteristics, equipment utilized, and catheter-related complications. Results A total of 95 cases were completed using the AXS Infinity LS for the triaxial platform foundation in PED Flex treatment of cerebral aneurysms. Mean patient age was 56.2±12.2 years (range 21–86). Average aneurysm size was 6.9±6.2u2009mm (range 1–38). There were 89 anterior circulation cases (94%) and 6 posterior circulation cases (6%). Significant cervical ICA tortuosity was present in 11/89 (12%) and moderate to severe cavernous ICA tortuosity was present in 29/89 (33%). Mean fluoroscopy time was 40.0±19.8u2009min. In 14/95 cases (15%), vasospasm prophylaxis or treatment with intra-arterial verapamil infusion was performed. Catheter access-related complications included asymptomatic iatrogenic dissection in one case (1%) from the distal intracranial catheter and groin hematoma in one case (1%). No parent vessel wall abnormalities were visualized in the region of the Infinity long sheath on final control angiography in all 95 cases. Conclusion The AXS Infinity LS is the newest long guide sheath available for modern neurointerventional procedures. We have shown its utility in augmenting the triaxial access platform in PED Flex cases by providing enhanced distal tip trackability with added support in the aortic arch and proximal great vessels.

Use of the 0.027-inch VIA microcatheter for delivery of Pipeline Flex: a technical note

Background The Pipeline Embolization Device (PED; Medtronic Neurovascular, Irvine, California, USA) is designed for delivery through a 0.027″ microcatheter. Challenges with the second-generation PED Flex include limited support from the Marksman microcatheter for consistent resheathing and transmission of push forces for device delivery. The VIA27 (Sequent Medical/MicroVention Terumo, Tustin, California, USA) is an alternative 0.027″ microcatheter originally designed for intrasaccular flow diverter delivery. Here we describe our experience with the VIA27 in the delivery of PED Flex. Methods We retrospectively identified patients who underwent PED Flex treatment with the VIA27 microcatheter at our institution. Patient demographics, aneurysm characteristics, equipment utilized, and procedural details were documented. Results A total of 127 cases were completed using the VIA27 microcatheter for PED Flex implantation. Mean patient age was 56.8±12.4u2005years (range 21–86u2005years). All but one of the cases were treatments for intracranial aneurysms. Average aneurysm size was 6.5±6u2005mm (range 2–38u2005mm). Of the 127 cases, 120 (95%) were anterior circulation cases and 7 (6%) were posterior circulation cases. Significant cervical internal carotid artery (ICA) tortuosity was present in 33/120 cases (28%). Moderate to severe cavernous ICA tortuosity was present in 54/120 cases (45%). Mean fluoroscopy time was 34.1±22.7u2005min. Large diameter PED devices (4.5–5u2005mm) were used in 42/127 cases (33%). Balloon post-processing of the PED was used in 15/127 cases (12%) to improve vessel wall apposition of the PED. Conclusions The VIA27 is a microcatheter capable of successful PED Flex delivery in neurointervention. We have shown its utility in enhancing both resheathing and push for optimal PED Flex implantation. The VIA27 microcatheter may be a useful and safe adjunct to the traditional Marksman microcatheter in PED Flex treatment of the cerebrovasculature.

Shifting Treatment Paradigms for Ruptured Aneurysms from Open Surgery to Endovascular Therapy Over 25 Years

BACKGROUNDnSince the introduction of Gugliemi detachable coils in the early 1990s, major clinical studies have supported an increasing role for coil embolization of ruptured aneurysms. We assessed aneurysm location and treatment modality in aneurysmal subarachnoid hemorrhage (aSAH) over the past 25 years.nnnMETHODSnA prospective, institutional review board-approved aneurysm database was screened for patients presenting with aSAH from 1991 to 2016. Microsurgical and endovascular capabilities were present throughout. All patients underwent cerebral angiography prior to treatment.nnnRESULTSnData were available for 1306/1562 patients (83.6%) presenting with aSAH from 1991-2016. 72% were female, with average age 52.8 years, and average aneurysm size 8.0 mm. The most common vessel of origin was the anterior cerebral artery (37.3%), internal carotid artery (33.3%), and middle cerebral artery (14.6%). Posterior circulation accounted for 14.8% of the aneurysms. Open surgery was performed for 72.4% of aneurysms, endovascular treatment for 22.0%, and 5.7% were not treated. There was an increase in aneurysms treated by endovascular methods over 5-year intervals: 3.0% (1991-1996), 13.4% (1997-2001), 17.2% (2002-2006), 24.3% (2007-2011), and 41.9% (2012-2016). Posterior circulation aneurysms led this trend, increasing from 9.1% endovascular to 71.4%. Endovascular treatment increased from 2.9% and 1.4% of anterior cerebral artery and internal carotid artery aneurysms to 39.6% and 40.7%, respectively, in the most recent 5-year interval. By comparison, endovascular methods remained less commonly used for middle cerebral artery aneurysms (0% initially, now 22.0%).nnnCONCLUSIONSnEndovascular treatment of ruptured intracranial aneurysms has steadily increased over the past 25 years at our major academic institution. This is consistent with positive data from clinical trials, advances in endovascular technology, and increasing experience of endovascular specialists.

Iulius Casserius and the First Anatomically Correct Depiction of the Circulus Arteriosus Cerebri (of Willis)

The circulus arteriosus cerebri is the arterial anastomotic circle at the base of the brain, now better known as the circle or polygon of Willis. The British physician and anatomist Thomas Willis (1621-1675) was the first to demonstrate the physiologic function and observe the clinical significance of the circulus. It has been overlooked, however, that the first accurate depiction of the circulus was provided by the Paduan anatomist Giulio Cesare Casseri (Iulius Casserius) (1552-1616) in two engravings published posthumously in multiple formats, including the Tabulae anatomicae LXXIIX (1627). Casserius was the fifth of the six Vesalian anatomists at the University of Padua, Italy, which was the site of the most important discoveries in anatomy in the 16th and 17th centuries. Here we review the life of Casserius, his rise from servant to Girolamo Fabrizio DAcquapendente (Fabricius) (1533-1619) to Professor of Surgery at the University of Padua, his research in comparative anatomy, and his depiction of the circulus arteriosus cerebri. Although previous authors have commented on Casseriuss portrayal of the circulus arteriosus in Table 10 of Tabulae anatomicae LXXIIX, none have discussed Figure 2 of Table 9. This is important because whereas the anterior communicating artery complex is depicted clearly in one table, the accurate course of the posterior communicating arteries is shown in the other. Together, Tables 9 and 10 represent a sophisticated, sequential dissection, which deserves recognition as the first accurate portrayal of the arterial anastomosis at the base of the brain.