Cerebral revascularization after the Carotid Occlusion Surgery Study: what candidates remain, and can we do better?

OBJECTIVECerebral revascularization for carotid occlusion was previously a mainstay procedure for the cerebrovascular neurosurgeon. However, the 1985 extracranial-intracranial bypass trial and subsequently the Carotid Occlusion Surgery Study (COSS) provided level 1 evidence via randomized controlled trials against bypass for symptomatic atherosclerotic carotid occlusion disease. However, in a small number of patients optimal medical therapy fails, and some patients with flow-limiting stenosis develop a perfusion-dependent neurological examination. Therefore it is necessary to further stratify patients by risk to determine who may most benefit from this intervention as well as to determine perioperative morbidity in this high-risk patient population.METHODSA retrospective review was performed of all revascularization procedures done for symptomatic atherosclerotic cerebrovascular steno-occlusive disease. All patients undergoing revascularization after the publication of the COSS in 2011 were included. Perioperative morbidity and mortality were assessed as the primary outcome to determine safety of revascularization in this high-risk population. All patients had documented hypoperfusion on hemodynamic imaging.RESULTSAt total of 35 revascularization procedures were included in this review. The most common indication was for patients with recurrent strokes, who were receiving optimal medical therapy and who suffered from cerebrovascular steno-occlusion. At 30 days only 3 perioperative ischemic events were observed, 2 of which led to no long-term neurological deficit. Immediate graft patency was good, at 94%. Long term, no further strokes or ischemic events were observed, and graft patency remained high at 95%. There were no factors associated with perioperative ischemic events in the variables that were recorded.CONCLUSIONSCerebral revascularization may be done safely at high-volume cerebrovascular centers in high-risk patients in whom optimal medical therapy has failed. Further research must be done to develop an improved methodology of risk stratification for patients with symptomatic atherosclerotic cerebrovascular steno-occlusive disease to determine which patients may benefit from intervention. Given the high risk of recurrent stroke in certain patients, and the fact that patients fail medical therapy, surgical revascularization may provide the best method to ensure good long-term outcomes with manageable up-front risks.

Outcomes after coverage of lenticulostriate vessels by flow diverters: a multicenter experience.

OBJECTIVE: With the increasing use of flow diversion as treatment for intracranial aneurysms, there is a concomitant increased vigilance in monitoring complications. The low porosity of flow diverters is concerning when the origins of vessels are covered, whether large circle of Willis branches or critical perforators. In this study, the authors report their experience with flow diverter coverage of the lenticulostriate vessels and evaluate their safety and outcomes. METHODS: The authors retrospectively reviewed 5 institutional databases of all flow diversion cases from August 2012 to June 2018. Information regarding patient presentation, aneurysm location, treatment, and outcomes were recorded. Patients who were treated with flow diverters placed in the proximal middle cerebral artery (MCA), proximal anterior cerebral artery, or distal internal carotid artery leading to coverage of the medial and lateral lenticulostriate vessels were included. Clinical outcomes according to the modified Rankin Scale were reviewed. Univariate and multivariate analyses were performed to establish risk factors for lenticulostriate infarct. RESULTS: Fifty-two patients were included in the analysis. Postprocedure cross-sectional images were available in 30 patients. Two patients experienced transient occlusion of the MCA during the procedure; one was asymptomatic, and the other had a clinical and radiographic ipsilateral internal capsule stroke. Five patients had transient symptoms without radiographic infarct in the lenticulostriate territory. Two patients experienced in-stent thrombosis, leading to clinical MCA infarcts (one in the ipsilateral caudate) after discontinuing antiplatelet therapy. Discontinuation of dual antiplatelet therapy prior to 6 months was the only variable that was significantly correlated with stroke outcome (p < 0.01, OR 0.3, 95% CI 0-0.43), and this significance persisted when controlled for other risk factors, including age, smoking status, and aneurysm location. CONCLUSIONS: The use and versatility of flow diversion is increasing, and safety data are continuing to accumulate. Here, the authors provide early data on the safety of covering lenticulostriate vessels with flow diverters. The authors concluded that the coverage of these perforators does not routinely lead to clinically significant ischemia when dual antiplatelet therapy is continued for 6 months. Further evaluation is needed in larger cohorts and with imaging follow-up as experience develops in using these devices in more distal circulation.

Hemorrhage associated with ventriculoperitoneal shunt placement in aneurysmal subarachnoid hemorrhage patients on a regimen of dual antiplatelet therapy: a retrospective analysis.

OBJECTIVE: Intracranial stenting and flow diversion require the use of dual antiplatelet therapy (DAPT) to prevent in-stent thrombosis. DAPT may significantly increase the risk of hemorrhagic complications in patients who require subsequent surgical interventions. In this study, the authors sought to investigate whether DAPT is a risk factor for hemorrhagic complications associated with ventriculoperitoneal (VP) shunt placement in patients with aneurysmal subarachnoid hemorrhage (aSAH). Moreover, the authors sought to compare VP shunt complication rates with respect to the shunt's location from the initial external ventricular drain (EVD) site. METHODS: Patients with aSAH who presented to the authors' institution from July 2009 through November 2016 and required VP shunt placement for persistent hydrocephalus were included. The rates of hemorrhagic complications associated with VP shunt placement were compared between patients who were on a regimen of DAPT (aspirin and clopidogrel) for use of a stent or flow diverter, and patients who underwent microsurgical clipping or coiling only and were not on DAPT using a backward stepwise multivariate analysis. Rates of radiographic hemorrhage and infection-related VP shunt revision were compared between patients who underwent VP shunt placement along the same track and those who underwent VP shunt placement at a different site (contralateral or posterior) from the initial EVD. RESULTS: A total of 443 patients were admitted for the management of aSAH. Eighty of these patients eventually required VP shunt placement. Thirty-two patients (40%) had been treated with stent-assisted coiling or flow diverters and required DAPT, whereas 48 patients (60%) had been treated with coiling without stents or surgical clipping and were not on DAPT at the time of VP shunt placement. A total of 8 cases (10%) of new hemorrhage were observed along the intracranial proximal catheter of the VP shunt. Seven of these hemorrhages were observed in patients on DAPT, and 1 occurred in a patient not on DAPT. After multivariate analysis, only DAPT was significantly associated with hemorrhage (OR 31.23, 95% CI 2.98-327.32; p = 0.0001). One patient (3%) on DAPT who experienced hemorrhage required shunt revision for hemorrhage-associated proximal catheter blockage. The remaining 7 hemorrhages were clinically insignificant. The difference in rates of hemorrhage between shunt placement along the same track and placement at a different site of 0.07 was not significant (6/47 vs 2/32, p = 0.46). The difference in infection-related VP shunt revision rate was not significantly different (1/47 vs 3/32, p = 0.2978). CONCLUSIONS: This clinical series confirms that, in patients with ruptured aneurysms who are candidates for stent-assisted coiling or flow diversion, the risk of clinically significant VP shunt-associated hemorrhage with DAPT is low. In an era of evolving endovascular therapeutics, stenting or flow diversion is a viable option in select aSAH patients.

The use of alternatives to clopidogrel in flow-diversion treatment with the Pipeline embolization device.

OBJECTIVEThromboembolic complications continue to be encountered with Pipeline embolization devices (PEDs) despite routine clopidogrel/aspirin antiplatelet therapy. This study examined the safety and efficacy of prasugrel in the management of clopidogrel-resistant patients treated for cerebral aneurysms.METHODSFour hundred thirty-seven consecutive patients were identified between January 2011 and May 2016. Patients allergic, or having less than 30% platelet inhibition, to a daily 75-mg dose of clopidogrel received 10 mg of prasugrel daily (n = 20) or 90 mg of ticagrelor twice daily (n = 2). The mean (± SD) follow-up duration was 15.8 ± 12.4 months. The primary outcome was the modified Rankin Scale (mRS) score registered before discharge and at each follow-up visit. To control confounding, multivariable mixed-effects logistic regression and propensity score conditioning were used.RESULTSTwenty-six (5.9%) of 437 patients presented with a subarachnoid hemorrhage (SAH). The mean patient age was 56.3 years, and 62 were women (14.2%). One of the 7 patients lost to follow-up received prasugrel. One patient was allergic to clopidogrel and prasugrel simultaneously. All patients receiving prasugrel or ticagrelor (n = 22) had an mRS score ≤ 2 on their latest follow-up visit (mean score 0.67 ± 1.15). In a multivariate analysis, clopidogrel did not affect the mRS score on last follow-up (p = 0.14). Multivariable logistic regression showed that clopidogrel was not associated with an increased long-term recurrence rate (OR 0.17, 95% CI 0.01-2.70, p = 0.21), an increased thromboembolic complication rate (OR 0.46, 95% CI 0.12-1.67, p = 0.24), or an increased hemorrhagic event rate (OR 0.39, 95% CI 0.91-1.64, p = 0.20). None of the patients receiving prasugrel or ticagrelor died or suffered a long-term recurrence or a hemorrhagic event; only 1 patient suffered from mild aphasia subsequent to a thromboembolic event. Three patients taking clopidogrel died during the study: 2 from acute SAH and 1 from intraparenchymal hemorrhage. Clopidogrel was not associated with an increased mortality rate (OR 2.18, 95% CI 0.11-43.27, p = 0.61). The same associations were present in propensity score-adjusted models.CONCLUSIONSIn a cohort of patients treated with PEDs, prasugrel (10 mg/day) was a safe alternative to clopidogrel-resistant or clopidogrel-allergic patients, or nonresponders.

Laboratory assessments of therapeutic platelet inhibition in endovascular neurosurgery: comparing results of the VerifyNow P2Y12 assay to thromboelastography with platelet mapping.

OBJECTIVEInhibition of platelet aggregation is vital to preventing thromboembolic complications related to stent placement in endovascular neurosurgery, but excessive inhibition potentiates hemorrhagic complications. Recent evidence suggests an ideal inhibition range of 70-150 P2Y12 response units (PRU) as measured on the VerifyNow assay, which relies on photometric measurements of platelet aggregation. Thromboelastography (TEG) with platelet mapping (PM) is an alternative assay that directly measures clot formation and mechanical strength. This study compares the results of PRU to TEG-PM.METHODSPatients with simultaneous or near-simultaneous PRU and TEG-PM results who underwent cervical carotid artery stenting, intracranial stent-assisted aneurysm coiling, or flow diversion at the authors' institution between August 2015 and November 2016 were identified. PRU results were compared with the TEG maximal amplitude (MA) attributable to adenosine diphosphate (ADP) activity (MA-ADP) as measured by TEG-PM. Platelet inhibition was considered therapeutic for MA-ADP values < 50 mm or PRU < 194. The Pearson correlation coefficient was calculated, and the sensitivity and specificity of PRU were calculated assuming that the results of TEG-PM reflected the true degree of platelet inhibition.RESULTSTwenty-three patients were identified with a total of 37 matched sets of TEG-PM and PRU. Three of these pairs were excluded due to anemia outside of the PRU manufacturer's recommended range. The Pearson correlation coefficient for these values was 0.50 (p = 0.0026). The prevalence of clopidogrel nonresponders determined by TEG-PM (9%) matched reported rates (5%-12%); PRU demonstrated much higher prevalence (39%). For detecting a therapeutic level of platelet inhibition, PRU demonstrated a sensitivity of 0.59, specificity of 0.50, positive predictive value of 0.95, and negative predictive value of 0.07. Ideal inhibition was concordant in only 25% of observations in which at least one of the results was ideal.CONCLUSIONSAgreement between TEG-PM and PRU regarding the degree of platelet inhibition is poor. PRU likely overestimates clopidogrel resistance, as 93% of patients with PRU > 194 demonstrate a therapeutic level of platelet inhibition on TEG.

Whole blood aggregometry prior to Pipeline embolization device treatment of intracranial aneurysms: defining an optimal platelet inhibition cutoff value for clopidogrel.

OBJECTIVEDual antiplatelet therapy is required for the treatment of intracranial aneurysms with the Pipeline embolization device (PED). Platelet function testing (PFT) is often used to assess the efficacy of the antiplatelet regimen prior to PED placement. The optimal impedance values for whole blood aggregometry in this setting have not been defined.METHODSA retrospective review of a prospectively maintained database was performed for the years 2011-2015 to identify patients with intracranial aneurysms treated with the PED who underwent pretreatment PFT using whole blood aggregometry. Antiplatelet therapy was not altered based on PFT results; all patients remained on standard doses of aspirin and clopidogrel. Clinical, radiographic, and laboratory data were analyzed to identify the optimal cutoff impedance value for clopidogrel responsiveness using the receiver operating characteristic curve and Youden's index.RESULTSForty-nine patients underwent 53 endovascular procedures for the treatment of 76 aneurysms using the PED. The majority of these aneurysms were located in the anterior circulation (90.8%) and affected the internal carotid artery (89.5%). Patients in 30 procedures (56.6%) were identified as clopidogrel responders based on the manufacturer cutoff value (< 6 Ω). Thromboembolic complications occurred in 13 (24.5%) procedures; patients in 6 (11.3%) cases were symptomatic and those in 3 (5.7%) cases had ischemic strokes. Eleven of the 13 (84.6%) thromboembolic complications occurred in clopidogrel nonresponders. An impedance value of ≥ 6 Ω was independently associated with thromboembolic complications. The optimal electrical impedance value was identified as ≥ 6 Ω (sensitivity 84.6%, specificity 70.0%, area under the curve 0.77) for identifying clopidogrel nonresponders.CONCLUSIONSThromboembolic complications are more common following PED placement in patients who do not respond adequately to clopidogrel. Clopidogrel nonresponders can be identified using pretreatment whole blood aggregometry. The optimal cutoff value to categorize a patient as a clopidogrel nonresponder when using whole blood aggregometry is ≥ 6 Ω.

Dual antiplatelet therapy in aneurysmal subarachnoid hemorrhage: association with reduced risk of clinical vasospasm and delayed cerebral ischemia.

OBJECTIVE Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories involving platelet activation have been postulated as potential explanations of the development of clinical vasospasm and DCI. However, the effects of dual antiplatelet therapy (DAPT; aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients. METHODS Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into 2 groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the 2 groups, utilizing univariate and multivariate logistic regression. RESULTS Of 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (OR 0.244, CI 95% 0.097-0.615, p = 0.003) and DCI (OR 0.056, CI 95% 0.01-0.318, p = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% vs 2%, p = 0.9). CONCLUSIONS The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.

Timing and nature of in-house postoperative events following uncomplicated elective endovascular aneurysm treatment.

OBJECT: Most patients with asymptomatic intracranial aneurysms treated with endovascular methods are closely observed overnight in an intensive care unit setting for complications, including ischemic and hemorrhagic stroke, cardiac dysfunction, and groin access complications. The purpose of this study was to analyze the timing, nature, and rate of in-house postoperative events. METHODS: Patients who underwent endovascular treatment or retreatment of unruptured cerebral aneurysms from March 2002 to June 2012 were identified from a prospective case log and their medical records were reviewed. The presentation, patient characteristics, aneurysm size and location, and method of endovascular treatment of each cerebral aneurysm were recorded. Patients with adverse intraprocedural events including perforation and thromboembolism were excluded from this analysis. Overnight postprocedural monitoring was performed in a neurological intensive care unit or postanesthesia care unit for all patients, with discharge planned for postoperative Day 1. Postprocedural events occurring during hospitalization were categorized as intracranial hemorrhage, ischemic stroke, groin hematoma resulting in additional treatment or prolonged hospital stay, retroperitoneal hematoma, and cardiac events. The time from the completion of the procedure to event discovery was recorded. RESULTS: A total of 687 endovascular treatments of unruptured cerebral aneurysms were performed. Nine treatments were excluded from our analysis due to intraprocedural events. Endovascular procedures included coiling alone, stent-assisted coiling, balloon-assisted coiling, balloon-assisted embolization with a liquid embolic agent, and placement of a flow diversion device with or without coiling. Twenty-seven treatments (4.0%) resulted in postprocedural complications: 3 intracranial hemorrhages, 6 ischemic strokes, 4 cardiac events, 5 retroperitoneal hematomas, and 9 groin hematomas. The majority (20 [74.0%]) of these 27 complications were detected within 4 hours from the procedure. These included 1 hemorrhage, 4 ischemic strokes, 4 cardiac events, 2 retroperitoneal hematomas, and 9 groin hematomas. All cardiac events and groin hematomas were detected within 4 hours. Four (14%) of the 27 complications were detected between 4 and 12 hours, 1 (3.7%) between 12 and 24 hours, and 2 (7.4%) more than 24 hours after the procedure. The complications detected more than 4 hours from the conclusion of the procedure included 2 minor intracranial hemorrhages causing headache and resulting in no permanent deficits, 2 mild ischemic strokes, and 3 asymptomatic retroperitoneal hematomas identified by falling hematocrit levels that required no further intervention or treatment. CONCLUSIONS: The large majority of significant postprocedural events after uncomplicated endovascular aneurysm intervention occur within the first 4 hours; these events become less frequent with increasing time. Transfer to a floor bed after 4-12 hours for further observation is reasonable to consider in some patients.