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Background & Purpose: Children were excluded from the recent positive mechanical thrombectomy trials and the literature on endovascular therapy in this population needs to be built. We report here case series of pediatric patients who received mechanical thrombectomy at our institution. Methodology: Our prospectively collected UCLA acute stroke database from 2000 to present was retrospectively reviewed. Only patients Results: All five patients (ages 2-15) suffered an embolic stroke. Three of them had congenital heart disease and one had repeated episodes of syncope and bradycardia. No risk factors other than PFO were identified in the fifth patient. Occlusion sites were ICA-M1 (n=2), M1 (n=2), and M1-M2 (n=1). IV tPA was used in one case. Time from last known well to reperfusion ranged from 3h to 9h 28min and the patients’ initial collaterals were scored between grades 2 - 3. AOL score of 3 was achieved in all cases, TICI 2a in two and TICI 2b in three cases. Merci was used in two cases, Penumbra, Solitaire and Mindframe Capture were used each in one case. One patient developed intracerebral hemorrhage that required hemicraniectomy. The PedNIHSS score at discharge ranged from 0 to 8 and the Ped-mRS score up-to 90 days ranged from 0 to 4, with 80% of children having Ped-mRS ≤ 3. Conclusion: Mechanical thrombectomy may be a safe and feasible treatment option in pediatric stroke patients with large vessel occlusion.

Background and Purpose: The SWIFT PRIME trial demonstrated superior outcomes in patients presenting with disabling acute ischemic stroke (AIS) who underwent endovascular therapy vs. intravenous tissue plasminogen activator (t-PA) alone. We sought to understand the relationship between functional independence and time to reperfusion in study patients assigned to thombectomy. Methods: SWIFT PRIME is a global, multi-center, prospective, randomized, open, blinded endpoint study comparing functional outcomes in AIS subjects treated with either IV t-PA alone or IV t-PA in combination with Solitaire stent retriever device. Among patients in whom substantial reperfusion (TICI 2b/3) was achieved, we analyzed the effect onindependent outcome (mRS 0-2) of time from stroke onset to reperfusion (OTR) and from qualifying imaging to reperfusion Results: Among 83 patients undergoing thrombectomy, substantial reperfusion was achieved in 73 (88%). A marked effect of OTR was noted (Figure 1A). The rate of functional independence was 87% if reperfusion was achieved 150 minutes from symptoms onset. The absolute rate of good outcomes decreased by 10% over the next 60 minutes of delay in OTR and by 15% with every 60 minute delay there-after. Faster post-arrival workflow speed improved outcomes among patients presenting directly to study hospitals (Figure 1B). Conclusions: Speed of reperfusion is a dominant determinant of functional outcome among patients treated with stent retrievers. In the early period after, every 6 minute delay in reperfusion causes 1 more out of 100 treated patients to not achieve functional independence.

Background and Purpose: Timely recanalization in large vessel occlusive disease is essential to achieving good outcomes in patients with AIS. As such, the SWIFT PRIME study design incorporated aggressive time metrics and real time direct feedback. We systemically investigated variables affecting the time spent during discrete patient process steps including patient transport, selection and treatment delivery in patients treated in the SWIFT PRIME trial. Methods: Data was analyzed from the SWIFT PRIME trial, a global, multi-center, prospective, randomized, open, blinded endpoint (PROBE) IDE study comparing functional outcomes in AIS subjects treated with either IV t-PA alone (93 patients) or IV t-PA in combination with Solitaire device (93 patients). Each patient enrollment was analyzed for workflow and direct feedback was provided to the enrolling site. Results: The median time from Emergency Department (ED) arrival to groin puncture was 90 minutes (interquartile range [IQR], 69 - 120) and ED arrival to reperfusion time was 139 minutes (IQR, 108 - 169). The median ED to imaging start time was 16 minutes (IQR, 10-23.5), puncture to device deployment was 24 minutes (IQR, 18-33), and device deployment to reperfusion was 8 minutes (IQR, 5-23). The association between time intervals and baseline characteristics of the patient, mode of arrival at the endovascular-capable hospital and procedural characteristics was evaluated with multivariate negative binomial regression using a logarithmic link function (Figure). Conclusions: Detailed attention to workflow with iterative feedback and aggressive time goals leads to a highly efficient workflow. Future steps for improvement include faster triage and transport of patients to endovascular capable centers as well as advancements in treating patients with difficult anatomical features.

Background: Recent patient series have shown IV tPA to more often lyse cerebral thrombi when started sooner after symptom onset in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). This association has been attributed to less fibrin-cross-linking and less compaction of thrombi. We sought to determine if this phenomenon would make endovascular thrombectomy less often needed among AIS-LVO patients treated hyperacutely with IV tPA. Methods: In a prospectively maintained registry, we identified patients receiving IV tPA at 2 academic medical centers from March 2005 - May 2015. Inclusion criteria were: 1) LVO seen on CTA or MRA before (or early during) infusion of IV tPA and 2) follow-up vessel imaging within 6h of IV tPA initiation, using CT, MR or catheter angiogram. Degree of thrombus lysis with IV tPA alone was rated using the arterial occlusive lesion (AOL) Scale. Results: Among the 166 patients, average age was 72.4 (±13.4), 52.4% were female and pretreatment NIHSS was 13.9 (±8.4). Onset to needle time (OTN) was median 105 min (IQR 79-129) and door to needle time 44 min (27-65). Initial vessel imaging modality was MRA in 68.7% and CTA in 31.3%. Early post-tPA vessel imaging modality was catheter angiogram in 63.8%, MRA in 33.7% and CTA in 2.4%. Time from tPA initiation to recanalization assessment was faster when post-tPA vessel imaging was catheter angiogram vs MRA/CTA, 72 min (45.5-116.5) vs 232 min (185-283), p Discussion: Among large vessel acute ischemic stroke patients, the rate of complete recanalization with IV tPA alone is only 1 in 6, and faster OTN time is not associated with increased recanalization. All AIS-LVO patients should proceed to thrombectomy as swiftly as possible.

Background: The majority of patients enrolled in SWIFT PRIME had CT perfusion imaging immediately prior to randomization; 34 patients were randomized following a diffusion and perfusion MRI. Methods: Patients with MCA (M1) and distal carotid occlusions were randomized to treatment with tPA alone vs. tPA + Solitaire stent retriever. The primary outcome was the distribution of the mRS at 90 days. The same automated software (RAPID) was used for both MRI and CTP patients to identify patients with the Target mismatch profile for enrollment. Results: MRI selection was performed in 34 patients; CTP in 139. Mean age was 71 years (MRI) vs. 68 years (CTP), p=0.08; baseline NIHSS was 17 in both groups. Target mismatch profile was present in 95% (MRI) vs. 83% (CTP), p=0.3. Median time from ER arrival to randomization was 69 min (MRI) vs. 67 min (CTP), p=0.61. A higher percentage of the MRI group was transferred from an outside hospital (59% vs. 35%, p=0.02) and therefore the time from stroke onset to randomization was longer in the MRI group (236 minutes vs. 179 minutes, p=0.003.) Baseline median ischemic core volumes were similar in the MRI vs. CTP group (7 ml vs. 5 ml); baseline perfusion lesions were larger in the MRI group (133 ml vs. 97 ml, P=0.01) Reperfusion rates (> 90%/TICI 3) did not differ in the Solitaire treated patients in the MRI (94%) vs. CTP (85%) groups, p=0.7. The primary efficacy analysis (distribution of mRS at 90 days) demonstrated a statistically significant benefit in both the MRI (p=0.02) and CTP subgroups (p=0.01). Among MRI selected patients, mRS 0-2 at 90 days occurred in 63% of the Solitaire group vs. 33% of the tPA alone group (ARR 30%, p=0.17) and infarct growth was reduced (17 ml vs. 50 ml, p=0.089). CTP selected patients had mRS 0-2 rates at 90 days of 60% in the Solitaire group vs. 40% tPA alone (ARR 20%, p=0.025) and a reduction in infarct growth (14 vs. 27 ml, p=0.047). Conclusions: Although MRI selected patients in SWIFT PRIME were slightly older and treated longer after symptom onset, they demonstrated a statistically significant benefit on the primary efficacy endpoint. Reductions in infarct growth and rates of favorable clinical outcomes in the MR subgroup were also comparable to those seen in the CT perfusion subgroup.

Introduction: Mechanical thrombectomy (MT) improves clinical outcome of patients with acute ischemic stroke (AIS) and a large vessel occlusion. Approximately 90% of patients in the recent MT trials received intravenous thrombolysis (IVT) prior to MT. Aim: To determine if IVT in combination with MT is superior to MT alone in patients with AIS and a large vessel occlusion. Methods: A patient-level pooled analysis of the STAR and SWIFT studies, two large multicenter prospective studies on MT for AIS was utilized. Using multivariate logistic regression analysis, we compared mRS at follow-up, reperfusion rates, and complication rates (intracerebral hemorrhage and emboli to uninvolved territories) between patients who underwent MT following IVT, to those who underwent only MT. An independent core laboratory scored all radiological outcomes. Results: Of 291 included patients, 160 (55%) underwent MT following IVT, and 131 (45%) underwent only MT. Of the patients treated with IVT, 116 were IVT failures (full tpa dose) and 44 received bridging therapy (mean tpa dose 0.62 mg/kg). Patients who received IVT less often had atrial fibrillation (33 vs. 47 %, p=0.016) and diabetes (14 vs. 24%, p=0.023), and had a lower mean ASPECTS (8.1 vs. 8.5, p=0.031) compared to thos who underwent only MT. There was no difference in baseline NIHSS (both median 17) or location of the occlusion between groups. We did not find a statistically significant association between use of IVT in addition to MT vs. MT alone for any of the outcomes. There were trends towards a lower risk of symptomatic intracerebral hemorrhage (adjusted OR 0.12, 95% CI 0.01-1.13), a higher risk of vasospasm (adjusted OR 1.81, 95% CI 0.86-3.80), and a higher chance of mRS 0-2 (adjusted OR 1.60, 95% CI 0.86-3.80) in patients who received MT following IVT, compared to MT alone. Conclusions: We observed no statistically significant benefit or harm for the use of IVT in addition to MT in patients with AIS and a large vessel occlusion.

Background: Previous randomized trials of endovascular therapy for stroke have shown better rates of functional independent outcome (mRS 0-2 at 90 days) with earlier initiation of endovascular therapy. In these trials no information was available to assess the volume of salvageable brain tissue prior to intervention or tissue reperfusion post- intervention. We sought to determine the associations between times to treatment, mismatch volume, reperfusion rates and functional independent outcome (FIO) in patients with the Target mismatch (TMM) profile in SWIFT PRIME. Methods: Patients with TMM on CT or MR perfusion, as determined by an automated software package (RAPID), were included in the analysis. We compared the rate of FIO and factors associated with FIO in patients randomized early (3h) from stroke symptom onset (SSO). Age, NIHSS, core volume, mismatch volume and successful reperfusion at 27 h (>90% reduction in perfusion lesion volume on CT or MR Perfusion) were included in univariate and a multivariate logistic regression analysis. Results: A total of 131/195 patients had TMM. FIO was 62.3% (33/53) in the early vs. 43.6% (34/78) in the late group, p=0.0498. In the Solitaire arm, FIO was 72.4% (21/29) in early group vs. 55.0% (22/40) in the late group. In the tPA arm FIO was 50.0% (12/24) in the early group vs. 31.6% (12/38) in the late group. There was no significant difference in age, baseline NIHSS, core volume, or mismatch volume among the overall early vs late groups but successful reperfusion at 27h occurred in 76% of the early vs. 55% of the late group (p Conclusions: Earlier lytic and stent-retriever thrombectomy interventions are associated with higher rate of FIO in patients with Target mismatch profiles in SWIFT Prime trial. This improved outcome is likely due to higher reperfusion rates that are achieved with earlier intervention, suggesting greater responsiveness of less organized and less compacted thrombi to fibrinolysis and potentially stent retrieval.

Background: Five recent trials demonstrated benefit of endovascular treatment (ET) for large-vessel ischemic stroke. But, while all were positive, the trials differed in their estimates of benefit magnitude. We tested whether trial differences in rate and speed of successful accounted for their variations in effect size estimates. Methods: We analyzed all 5 recent positive endovascular stroke trials, MR CLEAN, ESCAPE, EXTEND-IA, REVASCAT, and SWIFT-PRIME. An expanded analysis also included the 2 prior neutral trials, IMS-3 and MR RESCUE. Linear regression and correlation coefficients probed variable relations. Results: Among the 5 positive trials, rates of substantial reperfusion ranged from 59%-88% and OTR from 241-355 minutes. Independent functional outcome rates ranged in the endovascular arms from 32.6% to 71.4%, and in the control arms from 19.1% to 40.0%. Absolute differences in functional independence between treatment arms ranged from 13.5% - 31.4%. In the 2 neutral trials, reperfusion rates were lower, OTR longer, and outcome differences much less. Linear regression demonstrated very strong relation of both trial reperfusion rate and trial reperfusion speed to trial magnitude of treatment benefit (Figure). Across all 7 trials, the correlation between reperfusion rate and treatment effect size was r= 0.98, and between reperfusion speed and treatment effect size was r=0.85. Among just the 5 positive trials, reperfusion rate correlation with treatment effect size was r=0.87, and between reperfusion speed and treatment effect size was r=0.89. Conclusion: Achievement of successful reperfusion and speed of reperfusion are potent determinants of the degree of benefit with endovascular reperfusion therapy, and account for more than three-quarters of the variation in degree of treatment benefit in the 5 recent positive thrombectomy trials. To maximize patient benefit from endovascular intervention, open arteries fully and fast.

Purpose: Ischemic stroke patients with low cerebral blood volume (CBV), low apparent diffusion coefficient (ADC) and increased microvascular permeability (K2) have increased risk of parenchymal hemorrhage (PH) after recanalization therapies. We have developed a predictive model to examine the risk of PH following revascularization therapies using combined MR perfusion and diffusion biomarkers. Methods: Voxel-based values of rCBV, K2, and ADC from the infarction core were obtained using pre-treatment MRI data from patients enrolled in the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) clinical trial. Using histogram analyses the 10 th and 90 th percentile values were calculated for the rCBV, ADC, and K2 variables for each patient. The associations between PH and extreme values of CBV (10%rCBV), ADC (10%ADC), and K2 (90%K2) in each patient were assessed in univariate and multivariate analyses. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting PH. Results: In 83 patients included in this analysis, 20 (24%, 13 PH1, 7 PH2) developed PH. Univariate analysis showed significantly lower 10%rCBV and 10%ADC values and significantly higher 90%K2 values in patients with PH. After controlling for age, baseline NIHSS, infarct volume, and status of recanalization, multivariate logistic regression analysis identified 10%rCBV (p=0.002) and 90%K2 (p=0.03), but not 10%ADC (p=0.07), as independent predictors of PH. For 10%RCBV, ROC analysis showed the greatest AUC (0.87) at a threshold < 0.45 with sensitivity/specificity of 95%70%. For 90%K2, the greatest AUC (0.75) was obtained at a threshold of > 0.27 with sensitivity/specificity of 90%/60%. In a separate model, a combined K2-rCBV classifier remained the single independent predictor of PH (OR=33). Conclusion: Our results suggest that combined increased permeability and decreased rCBV derived from MR perfusion can be used for risk stratification in patients with AIS before undergoing revascularization therapies.

Background: Larger infarct size at presentation as determined by ASPECTS is associated with reduced likelihood of good outcome in acute ischemic stroke. However, infarct volume alone explains only a modest fraction (∼30%) of the variation in stroke outcome. Incorporating the relative eloquence of each ASPECTS region may improve the predictive power. Methods: In the combined database of the SWIFT and STAR trials, we identified patients treated with the Solitaire stent retriever. Using the 24hr CT scan, a multivariate linear regression was used to determine the relative contribution of each ASPECTS region, separately in each hemisphere, to freedom from disability (mRS 0-2) at 90 days. The coefficients from the regression were used to create an Eloquence-weighted ASPECTS score (EL-ASPECTS), which was compared against the original in predicting outcome based on the presentation CT scan. Results: Among 254 patients treated with ET, average age was 68, 64% were female, and NIHSS was mean 16 (SD +/- 5). Mean ASPECTS at presentation was 8.2 and 6.4 at 24 hrs. The most commonly involved ASPECTS regions were the lentiform nuclei (70%), insula (55%), and caudate (52%). In multivariate analysis, for the right hemisphere on 24hr CT, preservation of M1 (OR 1.6) and M4 (OR 1.2) regions were most strongly predictive of good outcome. For the left hemisphere on 24 hr CT, preservation of M3 (OR 2.6), and M5 (OR 2.5) and involvement of M2 (OR -1.9) were most predictive. Eloquence weights were assigned to all 20 R/L ASPECTS regions to create EL-ASPECTS. EL-ASPECTS, compared with original ASPECTS, demonstrated improved discrimination for independent functional outcome for right hemisphere (C-statistic 0.78 vs. 0.69), left hemisphere (0.78 vs. 0.72), and all stroke patients (0.76 vs. 0.70). On presentation CTs, multivariate analyses including age and presentation NIHSS demonstrated EL-ASPECTS but not original ASPECTS was predictive of good clinical outcome (OR 1.65, p Conclusions: Incorporation of regional weighting into ASPECTS improves the ability to predict who will achieve independent functional outcomes with endovascular therapy in acute ischemic stroke.

BackgroundEndovascular reperfusion techniques are a promising intervention for acute ischemic stroke (AIS). Prior studies have identified markers of initial injury (arrival NIH stroke scale (NIHSS) or infarct volume) as predictive of outcome after these procedures. We sought to define the role of collateral flow at the time of presentation in determining the extent of initial ischemic injury and its influence on final outcome.MethodsDemographic, clinical, laboratory, and radiographic data were prospectively collected on a consecutive cohort of patients who received endovascular therapy for acute cerebral ischemia at a single tertiary referral center from September 2004 to August 2010.ResultsHigher collateral grade as assessed by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading scheme on angiography at the time of presentation was associated with improved reperfusion rates after endovascular intervention, decreased post-procedural hemorrhage, smaller infarcts on presentation and discharge, as well as improved neurological function on arrival to the hospital, discharge, and 90 days later. Patients matched by vessel occlusion, age, and time of onset demonstrated smaller strokes on presentation and better functional and radiographic outcome if found to have superior collateral flow. In multivariate analysis, lower collateral grade independently predicted higher NIHSS on arrival.ConclusionsImproved collateral flow in patients with AIS undergoing endovascular therapy was associated with improved radiographic and clinical outcomes. Independent of age, vessel occlusion and time, in patients with comparable ischemic burdens, changes in collateral grade alone led to significant differences in initial stroke severity as well as ultimate clinical outcome.

OBJECTIVE: To introduce the utilization of a swine arteriovenous malformation (AVM) model for stereotactic radiosurgery research and to describe the morphological changes in the vessels after radiation. METHODS: The model was created in six animals by creation of a right-sided carotid-jugular fistula. Pre- and postsurgical hemodynamic evaluation was performed. The left rete was radiated in four animals; two animals were not radiated. All animals were sacrificed 4 months after surgery, and the bilateral retia were obtained at autopsy. RESULTS: There were no procedure-related complications. A pressure gradient of 20 mmHg across the nidus was obtained after surgery. The peak velocity in the arterial feeder increased from 18.5 to 83 cm/s. Microscopic examination of the control animals showed intimal hyperplasia and disrupted internal elastic lamina, similar to human AVMs. The radiated retia showed more prominent intimal hyperplasia. This was confirmed by histometric studies showing greater luminal occlusion in radiated specimens. Adventitial fibrosis was prominent in the radiated retia and was absent in the control animals. Immunohistochemical studies showed proliferating smooth muscle cells in the intima. The adventitial fibrosis consisted of smooth muscle cells surrounded by collagen Type IV extracellular matrix. CONCLUSION: The nidus component and high-flow vasculopathy make this an attractive model for stereotactic radiosurgery research. Histology of the radiated models is similar to those described in radiated human AVMs. Further studies of the model are warranted to gain a better understanding of the cellular and molecular events in AVM vessels after stereotactic radiosurgery.

The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome. We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2∗-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome. A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13–13.59; P

Objective: To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL). Methods: We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions. Results: Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0–2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7–7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8–10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8–2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0–1; OR 2.2, 95% CI 1.0–4.7). Conclusions: The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

Recent randomized clinical trials have shown the benefit of stent retrievers for endovascular intervention in patients with acute ischemic stroke. The Solitaire 2 FR 4×40 device was developed to address longer clots as well as procedural difficulties. This study was undertaken to evaluate the safety of the new device in a swine model at 0, 30, and 90 days as well as its in vitro effectiveness. There were no significant differences in the overall animal health, tissue injury, hemorrhagic or thrombogenic events related to device usage. Based on the comparison at multiple time points, the Solitaire 2 4×40 device was similar in safety and usability to the Solitaire 2 4×20 device. Due to the additional length of the device, the Solitaire 2 4×40 device may in fact provide a number of additional technical benefits in the neurothrombectomy treatment of ischemic stroke.

Background: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. Methods: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. Results: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. Conclusions: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

Object Treatment of patients presenting with poor-grade (Hunt and Hess Grade IV or V) subarachnoid hemorrhage (SAH) is controversial. Endovascular coil embolization has been considered a valuable therapeutic alternative to surgical clip placement for this kind of patient. The aim of the present study was to evaluate immediate and long-term angiographic and clinical outcomes in patients with poor-grade SAH treated by endovascular embolization. Methods One hundred eleven patients with Hunt and Hess Grade IV or V SAH were treated with endovascular embolization at the University of California at Los Angeles Medical Center between October 1990 and December 2004. Eighty patients harbored Grade IV hemorrhages and 31 patients had Grade V ones. Immediate and long-term anatomical and clinical outcomes were evaluated in all patients. Long-term clinical outcome assessments were based on follow-up data obtained over an average of 32 months posttherapy. Technical complications occurred in 15 patients (13.5%). Immediate complete aneurysm occlusion was observed in 51.4% of aneurysms. Angiographic, long-term follow-up review revealed aneurysm recanalization in 16.2% of cases. Thirty-nine patients (35.1%) demonstrated a favorable long-term clinical outcome. The overall mortality rate in this patient series was 32.4%. The mortality rate associated with vasospasm was significantly higher in patients with Grade IV SAHs than in those with Grade V hemorrhages. Conclusions The results of this study demonstrate a valuable contribution of endovascular therapy of ruptured intracranial aneurysms in patients with Hunt and Hess Grade IV or V SAH. This technique was successful in decreasing repeated aneurysm rupture and in enabling aggressive medical management during the acute phase of SAH. This is particularly important in patients with Grade IV SAH because of their potential for obtaining higher physical and functional recoveries.

OBJECTIVE: Giant intracranial aneurysms present unique therapeutic intricacies. The purpose of this study was to evaluate the anatomic and hemodynamic characteristics of these lesions and the current endovascular and combined surgical and endovascular techniques available for their treatment. METHODS: A review of the literature and the personal experiences of the authors with endovascular treatment of giant aneurysms are presented. This review included anatomic and hemodynamic features and analysis of the diverse endovascular techniques that have been reported for the management of these aneurysms. RESULTS: Anatomic features that create particular challenges in the therapeutic approach of giant aneurysms include size, shape (saccular, fusiform, serpentine), neck dimensions, branch involvement, intraluminal thrombosis, and location. Hemodynamic characteristics that affect endovascular treatment are lateral or terminal aneurysm type of flow and embolic material placement (inflow versus outflow aneurysmal region). The current endovascular therapeutic approaches include parent artery occlusion, trapping, endosaccular embolization with or without adjunctive techniques such as balloon-assisted or stent placement, and combined surgical and endovascular approaches, mainly with surgical revascularization and endovascular occlusion. CONCLUSION: Although there are a wide variety of endovascular therapeutic options for the treatment of giant intracranial aneurysms, none of the current techniques is completely successful and free of complications in the management of these complex lesions. A detailed and individualized analysis of each case in conjunction with sufficient understanding of the anatomy and hemodynamics of a particular aneurysm should guide the therapeutic decision. Further research advances will assist in elucidating the factors predisposing to genesis, progression, and aggressive clinical manifestations of these giant lesions.

Objective: To determine the frequency of early neurologic deterioration with infarct expansion (ENDIE) and poor outcomes among ischemic stroke patients not treated with reperfusion therapies because of rapidly improving or mild symptoms (RIMS) and to study the predictive value of hyperacute MRI in these patients. Methods: We identified consecutive patients with symptoms of acute stroke undergoing multimodal MRI within 6 hours of onset without evidence of hemorrhage on imaging. Medical records were reviewed for evidence of early neurologic deterioration within 48 hours. All deteriorating patients had repeat MRI to ascertain causes of worsening. Poor outcome was defined as a discharge modified Rankin Scale (mRS) score of ≥3. Results: We identified 74 patients with stroke symptoms ≤6 hours from onset. Forty had RIMS, and 39 did not receive reperfusion therapies because of RIMS. Among these 39, 4 experienced ENDIE, and 8 were discharged with mRS score of ≥3. Eight of the 39 patients had large-vessel occlusions on MR angiography. Three of 8 patients with large-vessel occlusion as against only one of 31 patients without occlusion had ENDIE (odds ratio [OR] 18, 95% CI 1.6 to 209, p = 0.02). Four of 8 patients with large-vessel occlusion as against 4 of 31 patients without occlusion had a discharge mRS score of ≥3 (OR 7, 95% CI 1.2 to 38, p = 0.04). Conclusions: About 10% of patients eligible for acute reperfusion therapy excluded on the basis of mild or rapidly improving symptoms show early neurologic deterioration with infarct expansion within 48 hours, and about 20% show poor outcome at discharge. Persisting large-vessel occlusion substantially increases the risk of early worsening and poor functional outcome.

Background and Purpose— Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management. Methods— This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke. Results— The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. “Red” clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another. Conclusions— Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.

Object The Matrix detachable coil is a new bioactive, bioabsorbable coil used in the endovascular embolization of intracranial aneurysms. It has a platinum core covered with a bioactive, bioabsorbable polymer (polyglycolic acid/lactide). The authors report on their initial midterm clinical experience with the first-generation Matrix detachable coil. Methods One hundred twelve patients harboring 118 aneurysms were treated using Matrix coils. Forty-nine aneurysms (41.5%) were associated with acute subarachnoid hemorrhage (SAH). Twenty-four lesions (49%) were harbored by patients with Hunt and Hess Grade I, 11 (23.4%) by patients with Grade II, eight (16.3%) by those with Grade III, and six (12.2%) by those with Grade IV. Four aneurysms (3.4%) were harbored by patients who had presented with nonacute SAH. Sixty-five aneurysms (55%) were unruptured. Fifty-seven lesions (48.3%) were small with a small neck, 29 (24.6%) were small with a wide neck, 30 (25.4%) were large, and two (1.7%) were giant. All patients were followed up to obtain angiography and clinical outcome data. Technical complications occurred in six patients: two thromboembolic complications and four aneurysm perforations. Of these six patients, the status of two deteriorated because of aneurysm perforation and another two because of thrombus formation (morbidity 3.6%). There were five deaths—one due to rerupture after embolization. Angiography follow-up studies of 87 aneurysms were obtained. Seventy aneurysms demonstrated progressive occlusion or a stable neck (80.5%), and 17 had some degree of recanalization (19.5%). The aneurysms originally diagnosed as a neck remnant showed a 15% rate of recanalization. Conclusions Matrix coils can be delivered into aneurysms with technical complications similar to those encountered using GDCs. Midterm anatomical outcomes to date have shown moderate improvement in the recanalization rate when compared with those realized using the GDC system. Because of the increased friction associated with the first-generation Matrix coil, the packing density in most aneurysms was less than that achieved with GDCs. Prolonged angiography follow-up evaluations are needed to document long-term efficacy.

OBJECTIVE: Stereotactic radiosurgery is an established, effective treatment for brain arteriovenous malformations. The mechanisms of vessel occlusion in arteriovenous malformations has not been extensively evaluated. To better understand these mechanisms, we report histopathological changes in the swine rete mirabile after stereotactic radiosurgery. METHODS: Thirty-five swine were used, 15 as nonradiated controls and 20 as radiated. Two in the control group and five in the radiated group were sacrificed before the study endpoint. Tissue was obtained from 13 nonradiated (4 at 3 mo, 5 at 6 mo, 4 at 9 mo) and 15 radiated swine (2 at 3 mo, 3 at 6 mo, 10 at 9 mo) for histological, immunohistochemical, and morphometric analysis. RESULTS: Radiated vessels showed increasing intimal hyperplasia over the follow-up period. Histometrical analysis confirmed this with evidence of progressive luminal narrowing over the follow-up period. Immunohistochemical analysis showed intimal cells to be proliferating smooth muscle cells with surrounding extracellular collagen Type IV. Adventitial fibrosis composed of collagen Type IV was also seen with smooth muscle cells interspersed within the collagen matrix. The nonradiated animals showed no intimal hyperplasia or change in the appearance or size of the vessels over the same follow-up period. Adventitial fibrosis was minimal in the nonradiated animals. CONCLUSION: The vessels show an intimal response to radiation with progressive occlusion caused by migrating, proliferating smooth muscle cells, a likely source of the extracellular collagen in the intima. Cytokine mediated pathways likely produce these morphological changes. Future studies will be directed toward elucidating these underlying molecular mechanisms.

Object. The aim of this study was to determine whether computerized tomography (CT) angiography could be used to identify and characterize aneurysms of the posterior circulation and guide optimal treatment selection, and how data obtained using this method compared with intraoperative findings. Methods. Patients suspected of harboring brain aneurysms underwent CT angiography and digital subtraction (DS) angiography; the results were prospectively interpreted by blinded independent evaluators. All patients with posterior circulation aneurysms were consecutively enrolled in the study. After treatment, neurosurgeons and endovascular therapists evaluated the ability of CT and DS angiography to demonstrate features of the lesions important for triage between treatment options (Wilcoxon signed-rank test) and to allow for coil or clip preselection and complete treatment planning (McNemar test of proportions), while using intraoperative findings as the basis of truth. In 242 patients overall, CT angiography detected 38 aneurysms and two aneurysmal blisters in 32 patients. The sensitivity of CT angiography in revealing posterior circulation aneurysms was 100% compared with DS angiography, with no false-positive results. Furthermore, CT angiography was sufficient as the sole study at triage for 65% of the posterior circulation aneurysms (26 of 40 lesions; p < 0.001), including 62% of the complex lesions (p < 0.001), and permitted coil or clip preselection in 74% of treated cases (20 of 27 cases; p < 0.002). Results of CT angiography revealed information about mural calcification and intraluminal thrombus not available on DS angiography, which affected patient care. Conclusions. In this study population, CT angiography was comparable to DS angiography in the detection and characterization of aneurysms of the posterior circulation. Computerized tomography angiography was used successfully to triage patients between endovascular and neurosurgical treatment options in a significant proportion of cases and permitted treatment planning in more than 70% of treated cases.

Stroke is the third most common cause of death in the United States following heart disease and cancer. Following the success of thrombolysis for myocardial infarction in the early 1990s, major trials for evaluation of this new therapeutic approach for ischemic stroke were initiated. The majority of ischemic strokes are due to occlusion of a cerebral vessel by a blood clot. Occlusion of a cerebral blood vessel leads to a core of infracted tissue surrounded by a relatively hypoperfused but viable brain tissue (the ischemic penumbra), which can be potentially salvaged by rapid recanalization of the target vessel. The underlying rationale for introduction of thrombolytic drugs is the lysis of an obliterating thrombus and reestablishment of blood flow. In this article we review the major intravenous thrombolysis trials leading to approval of intravenous recombinant tissue plasminogen activator, the only FDA approved treatment available today for acute ischemic stroke.

Ischemic stroke is a major cause of morbidity and mortality. Despite the fact that it is the third most common cause of death in the United States, there is only one FDA approved treatment for patients. This is Intravenous recombinant tissue plasminogen activator given within 3 hours of symptom onset. Furthermore, despite the approval of this drug, it has been underutilized in the community. The limited time window of 3 hours disqualifies many patients from receiving the drug. In addition, fears of intracranial hemorrhage have resulted in underutilization of the drug in the community setting. Efforts to increase the time window to treatment include utilization of the intraarterial route for delivery of thrombolytic drug and interventional mechanical strategies to revascularize intracranial vessels. In this report we review the major intraarterial thrombolysis trials and review the mechanical strategies being developed to treat patients with acute ischemic stroke.

Introduction/purpose The efficacy of endovascular stroke treatment is highly time-dependent. Thus optimizing systems of care to deliver appropriate treatment as swiftly as possible is a key goal of stroke care providers. We aim to analyze timeliness of treatment in a large endovascular cohort by assessing 1) real-world time metrics of care delivery, 2) specific causes of delays to treatment, and 3) time lost due to interhospital transfer. Materials and methods The STRATIS registry is a prospective, multicenter study of patients with large vessel occlusion (LVO) treated with the Solitaire Stentriever within 8 hours of onset. Subjects were separated by direct presentation (direct group) vs. interhospital transfer to the enrollling hospital (transfer group), and further characterized by the use of IV tPA (IVT) or mechanical thrombectomy alone (MT). Total alarm-to-revascularization time measured overall performance of the system of care. We also calculated a hypothetical ‘bypass’ scenario by comparing the door-to-tPA times for the two groups and adding the transfer time to the direct group for an extremely conservative estimate of additional travel time. Results A total of 688 subjects were analyzed. Median times from stroke onset to revascularization for direct vs. transfer patients in the MT-alone subgroup were 238.5 and 325.0 minutes respectively, and in the IVT plus MT were 192.0 and 305.5 minutes respectively (Figure 1). Median alarm-to-revascularization times for direct vs. transfer patients in the MT subgroup were 189 and 264 minutes respectively (75 minute difference; p = 0.0001), and in IVT were 169 and 268 respectively (99 minute difference; p Conclusion Time to revascularization is much slower for patients requiring interhospital transfer. The delay is accounted for by the time between imaging and departure, which is when treatment decisions and transfer arrangements are made, and should be a target for improvement. An important consideration for many regional systems is whether certain stroke patients should bypass the nearest hospital to go directly to an endovascular center. We created a conservative model of such a scenario, which suggests that successful revascularization would be achieved 99 minutes earlier by bypass. This may have significant implications for regional stroke systems of care. Disclosures M. Froehler: 2; C; Medtronic Neurovascular. 6; C; Site PI (Large, Liberty, SCENT, Feat, Barrel, Atlas, Rhapsody, Positive, Sep 3D) payment to institution. M. Aziz-Sultan: 2; C; Medtronic Neurovascular. 6; C; Expert Witness - BMC. R. Jahan: 1; C; Medtronic Neurovascular. 2; C; Medtronic Neurovascular. R. Klucznik: 3; C; Medtronic Neurovascular. J. Saver: 2; C; Medtronic Neurovascular, Stryker, Neuravia, Cognition Medical, Boehringer Ingelheim (prevention only). O. Zaidat: 2; C; Medtronic Neurovascular. D. Yavagal: 2; C; Medtronic Neurovascular. 6; C; ESCAPE trial DSCMB member. N. Mueller-Kronast: 2; C; Medtronic Neurovascular.

Background and Purpose— The middle cerebral artery (MCA) “dot” sign consists of hyperdensity of an arterial structure, seen as a dot in the sylvian fissure. The MCA dot sign has been proposed to indicate thrombosis of M2 or M3 MCA branches, analogous to the hyperdense middle cerebral artery (HMCA) sign indicating M1 thrombosis. The MCA dot sign has not been validated previously against the gold standard of conventional cerebral angiography. Methods— Noncontrast CT scans and immediately subsequent cerebral angiograms from 54 acute stroke patients within 8 hours of symptom onset were analyzed. CT films were inspected for the MCA dot sign and HMCA sign. Vascular findings on CT were compared with findings at angiography. Results— Mean patient age was 71 years; median National Institutes of Health Stroke Scale score was 16.5. Mean time from symptom onset to CT was 125 minutes, and that from CT to angiography was 117 minutes. All patients had arterial occlusion at angiography. Of the anterior circulation occlusions, M1 occlusions were noted in 28 patients, isolated M2 in 15, and isolated M3 in 4. One definite MCA dot sign was observed in 16.7% of patients, and an HMCA sign was observed in 13.9%. MCA dot sign performance in predicting the presence of M2 or M3 clot at angiography was as follows: sensitivity 38%, specificity 100%, positive predictive value 100%, negative predictive value 68%, and overall accuracy 73%. Conclusions— The MCA dot sign is a highly specific and moderately sensitive indicator of acute thrombus in the M2/M3 MCA branches, as validated by catheter angiography. The MCA dot sign is a useful additional acute stroke CT marker.

Neuroimaging is an important part of the assessment of patients with hyperacute stroke. As new treatments that may reverse cerebral ischemia have been developed, the role of neuroimaging has changed from simply anatomic depiction of early infarction to identification, by means of physiologic (rather than simply anatomic) information, of regions that are at risk for infarction. The goal of such imaging techniques is to monitor successes and complications of recently developed treatments such as thrombolysis.

Background and Purpose— Identifying core, irreversibly infarcted tissue and salvageable penumbral tissue is crucial to informed, physiologically guided decision making regarding thrombolytic and other interventional therapies in acute ischemic stroke. Pretreatment perfusion MRI offers promise as a means to differentiate core from penumbral tissues. Methods— Diffusion-perfusion MRIs were performed before treatment and on day 7 in patients undergoing successful vessel recanalization with intra-arterial thrombolytic therapy. Perfusion maps of the time to peak of the residue function (T max ) were generated after deconvolution of an arterial input function. Initial perfusion abnormalities and final infarct regions were outlined by hand. Posttreatment images were coregistered to the pretreatment study. Voxel-by-voxel and volume analyses were performed to identify thresholds of perfusion abnormalities that best predict core, irreversibly infarcted tissue. Results— Fourteen patients (4 men, 10 women) with vessel recanalization were studied. Mean age was 73 years, and median entry National Institutes of Health Stroke Scale score was 12. Mean time from symptom onset to start of intra-arterial infusion was 245 minutes and to recanalization was 338 minutes. With a voxel-by-voxel analysis, T max ≥6 and ≥8 seconds (sensitivity, 71% and 53%; specificity, 63% and 80%) correlated most highly with day 7 final infarct. With a volume analysis, T max ≥6 and ≥8 seconds ( r 2 =0.704 and r 2 =0.705) correlated most highly with day 7 final infarct. Conclusions— Perfusion-weighted imaging measures of ischemia severity accurately differentiate irreversibly injured core from penumbral, salvageable tissue. The best threshold for identifying core infarcted tissue is adjusted T max of ≥6 to 8 seconds.

BackgroundIn light of recent positive trial data for endovascular therapy in acute ischemic stroke (AIS), stent retriever use by practitioners without prior experience with these devices may become more common.ObjectiveTo assess the safety and efficacy of thrombectomy for AIS using Solitaire for patients treated in the roll-in period of the Solitaire With the Intention For Thrombectomy (SWIFT) trial, which represented the first clinical use of the device for these interventionalists.MethodsProspectively collected demographic, clinical, and angiographic data on patients treated in the initial roll-in and subsequent randomized phases of the SWIFT study were collected and analyzed. Key statistical analyses were validated by an independent external statistician.ResultsPatients in the roll-in period achieved equivalently high rates of reperfusion (55%) compared with those treated with the device in the randomized phase (61%). Rates of adverse events were comparable (13% vs 9%). Rates of good neurological outcome were equivalent between the roll-in and randomized patients treated with Solitaire (63% vs 58%). Including the roll-in patients strengthened the conclusions of the study, that reperfusion rates without symptomatic hemorrhage with Solitaire were greater than with Merci (59% vs 24%, pConclusionsThrombectomy in AIS using the Solitaire stent retriever device can be performed safely and effectively when used by experienced neurointerventionalists without previous experience with the device.Trial registration numberThe SWIFT study is registered with ClinicalTrials.gov, number NCT 01054560.

BACKGROUND: Faster time from onset to recanalization (TTR) in acute ischemic stroke using endovascular therapy (ET) has been associated with better outcome. However, prior studies have analyzed only dichotomized disability outcomes, which may underestimate the full effect of treatment. METHODS: In the combined databases of the SWIFT and STAR trials, we identified patients treated with the Solitaire FR stent retriever with achievement of substantial reperfusion (TICI 2b-3). A multivariate linear regression model was used to assess factors associated with TTR. RESULTS: Among 195 patients treated with ET with TICI2b-3 reperfusion, average age was 68, 62% were female, NIHSS was 16, and premorbid mRS was 0 in 71% and 1 in 16%. Target occlusion location was ICA in 14% and M1 in 71%, and 56% received IV tPA. Median TTR was 304 min (IQR 198-436). Shorter TTR was associated with improved median 90-day mRS (1.4 vs. 2.3 vs. 3.3, for TTR groups of 124-240 vs. 241-360 vs. 361-648, p CONCLUSIONS: Analysis of disability over the entire outcome range demonstrates a marked effect of shorter time to reperfusion upon improved clinical outcome, substantially higher than simple binary metrics. These findings emphasize the importance of accelerating endovascular reperfusion therapy.

Background: Previous studies have shown an association between reperfusion and good clinical outcome, but it is unknown if this association differs depending on the site of the arterial occlusive lesion (AOL). We pooled individual patient data from prospective endovascular stroke studies to assess this. Methods: We included data from the endovascular arm of IMS III, a trial of intravenous (IV) thrombolysis alone versus IV thrombolysis and endovascular treatment; SWIFT, a trial comparing the Solitaire with the Merci device; STAR, a cohort study of patients treated with the Solitaire device; and DEFUSE 2, a cohort study of patients who received endovascular therapy. We compared the strength of the associations between reperfusion and clinical outcomes in patients with ICA, M1 and M2/3/4 (M2+) occlusions. The primary outcome was good functional outcome at day 90 defined as a modified Rankin Scale 0-2. Secondary outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH). Results: 710 Patients were included in the analysis. The site of the AOL was ICA in 161, M1 in 389, and M2+ in 160 patients (M2=131, M3=23 and M4=6). The association between reperfusion and good functional outcome was stronger for patients with ICA occlusions (45% vs 19%; OR 3.5, 95%CI 1.7-7.2) and M1 occlusions (58% vs 18%; OR 6.2, 95%CI 3.8-10.2) than for patients with M2+ occlusions (53% vs 45%; OR 1.4, 95%CI 0.8-2.6) (p for difference in ORs=0.003). Mortality was reduced with reperfusion in patients with ICA (39% vs 18%; OR 0.4, 95%CI 0.2-0.7) and M1 occlusions (30% vs 10%; OR 0.3, 95%CI 0.2-0.5), but not in patients with M2+ occlusions (15% vs 15%; OR 1.0, 95%CI 0.4-2.3). Reperfusion was associated with fewer incidences of sICH without evidence of an interaction with AOL (OR 0.3, 95%CI 0.2-0.6). Conclusion: The association between endovascular reperfusion and improved clinical outcomes is more profound in patients with ICA and M1 occlusions than in patients with M2+ occlusions. This differential response to reperfusion has important implications for the design and power calculations of endovascular stroke trials.

We report a case of primary mucocutaneous histoplasmosis in an immunocompetent individual. The patient, a 61-year-old woman, presented with a non-healing ulcer on the lateral border of her tongue. Excisional biopsy of the lesion was consistent with histoplasmosis and no evidence of pulmonary or disseminated infection was found. Although mucocutaneous infection has been well-described as a manifestation of disseminated disease, especially in immunocompromised individuals, oral infections in immunocompetent patients are rare.

Object. Middle cerebral artery (MCA) aneurysms can be difficult to detect and characterize. The authors describe the utility and impact of helical computerized tomography (CT) angiography for the evaluation of aneurysms in this location, and compare this modality with digital subtraction (DS) angiography and intraoperative findings. Methods. Two hundred fifty-one patients with suspected cerebral aneurysms underwent CT angiography. Two-dimensional multiplanar reformatted images and three-dimensional CT angiograms were examined by two independent readers in a blinded fashion. Results were compared with findings on DS angiograms to determine the relative efficacy of these modalities in the detection and characterization of aneurysms. Questionnaires completed by neurosurgeons and endovascular therapists were used to determine the impact of CT angiograms on aneurysm management. Twenty-eight patients harboring 31 MCA aneurysms and 26 patients without aneurysms were identified using CT angiography. The sensitivity of CT angiography and DS angiography for MCA aneurysms was 97%; both techniques showed 100% specificity. In 76% of evaluations, the CT angiography studies provided information not available on DS angiography examinations. For the characterization of aneurysms, CT angiography was rated superior (72%) or equal (20%) to DS angiography in 92% of cases evaluated (p < 0.001). Computerized tomography angiography was evaluated as the only study needed for patient triage in 82% of cases (p < 0.001), and as the only study needed for treatment planning in 89% of surgically treated (p < 0.001) and in 63% of endovascularly treated cases (p < 0.001). The information acquired on CT angiograms changed the initial treatment plan in 24 (67%) of these 36 complex lesions (p < 0.01). The aneurysm appearance intraoperatively was identical or nearly identical to that seen on CT angiograms in 17 (89%) of 19 of the surgically treated cases. Conclusions. Computerized tomography angiography has unique advantages over DS angiography and is a viable alternative to the latter modality in the diagnosis, triage, and treatment planning in patients with MCA aneurysms.

The vascular anatomy of the spinal cord is reviewed. This serves as a basis not only to understand the pathophysiology of spinal cord vascular malformations but also to logically classify these lesions. Imaging studies required to identify and categorize these vascular malformations are also described.

✓ The authors present the case of a 69-year-old man who suffered from bilateral cortical venous hypertension due to a brain pial arteriovenous malformation (AVM) with a high-flow fistula. The AVM became complicated by the development of a high-grade stenosis of the posterior superior sagittal sinus (SSS). A comparison of cerebral angiograms obtained at different times revealed that the severe SSS stenosis had developed within a 5-year period and was located distal to the nidus of the left parietal AVM nidus, away from the entrance of the dominant superior superficial cortical draining vein into the SSS. The high-flow fistula was occluded with detachable coils and the AVM nidus was further embolized with acrylic. The SSS stenosis was mechanically dilated by means of balloon angioplasty and stent placement. This case provides angiographic evidence to support the hypothesis that a pial arteriovenous fistula in an adult can cause high-flow occlusive venopathy in a major sinus within a relatively short time and that this acquired high-flow occlusive venopathy can develop at an atypical location distant from the nidus of the AVM.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma and can have a variety of clinical and histological manifestations, including erythrodermic, pustular, bullous, hypo/hyperpigmented, and verrucous forms. We describe a case of a 59-year-old woman who presented with verrucous hyperkeratotic plaques on her distal fingertips, dorsal feet, and areolae that were subsequently biopsied and shown to be mycosis fungoides. This case highlights one of the many atypical manifestations of MF and underscores the need to have a high clinical suspicion for the disease.

The authors report on the histologic and immunohistochemical analyses of a cerebral aneurysm embolized with platinum coils and with the longest observation period. A 58-year-old woman presenting with subarachnoid hemorrhage due to ruptured basilar top aneurysm was treated with Guglielmi detachable coils (GDC) 22 years ago. She was the 15th case since the GDC was introduced. After she died of unrelated causes, an autopsy and thorough histologic examination were performed. Gross examination revealed no adhesion between the aneurysm wall and the surrounding brain tissue. Histologic and immunohistochemical analyses demonstrated that the cavity of the aneurysm was filled with homogeneous collagenous fibrous tissue, while the neck was completely covered by a dense collagenous neointima and a smooth muscle cell layer. The unique histologic results of this case may contribute to a better understanding of the long-term evolution of the healing process in intracranial aneurysms successfully treated with the GDC.

Background and Purpose—Collaterals at angiography before endovascular therapy were analyzed to ascertain the effect on a novel end point of successful revascularization without symptomatic hemorrhage in the Solitaire FR With the Intention for Thrombectomy (SWIFT) study.Methods—Collateral grade (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology) on baseline angiography was independently assessed, blind to other data, with statistical analyses delineating the relationship with clinical, laboratory, and imaging parameters.Results—Angiographic data on collaterals were available in 119 of 144 subjects (mean age, 67±12 years; 52% woman; median National Institutes of Health Stroke Scale, 18 [range, 8–28]). Worse collaterals were noted in subjects with elevated baseline blood glucose (P=0.013) and those with elevated baseline systolic blood pressure (P=0.039). Multivariate predictors of partial or worse collaterals included absence of prior hypertension (odds ratio, 4.049,P=0.012), smoking history (odds ratio, 3.822;P=0.013), and higher blood glucose (odds ratio, 1.017;P=0.022). Collaterals were strongly related to Alberta Stroke Program Early CT Score (ASPECTS) at baseline (0–1: median 8 [3–10]; 2–9 [5–10]; 3–9 [7–10]; 4–9 [8–10];PPP=0.019), better median National Institutes of Health Stroke Scale at day 7/discharge (PPP=0.021.Conclusions—Better collaterals were associated with lower glucose, lower blood pressure, smaller baseline infarcts in SWIFT, and greater likelihood of successful revascularization without hemorrhage and good clinical outcomes.Clinical Trial Registration—URL:http://www.clinicaltrials.gov. Unique identifier: NCT01054560.

Background The ideal population of patients for endovascular therapy (ET) in acute ischemic stroke remains undefined. Recent ET trials have moved towards selecting patients with proximal middle cerebral artery (MCA) or internal carotid artery occlusions, which will likely leave a gap in our understanding of the treatment outcomes of M2 occlusions. Objective and methods To examine the presentation, treatment, and outcomes of M2 compared with M1 MCA occlusions in patients undergoing ET by assessing comprehensive MRI, angiography, and clinical data. Results We found that M2 occlusions can lead to massive strokes defined by hypoperfused and infarcted volumes as well as death or moderate to severe disability in nearly 50% of patients at discharge. Compared with M1 occlusions, M2 occlusions achieved similar Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization rates, with significantly less hemorrhage. M2 occlusions presented with smaller infarct and hypoperfused volumes and had smaller final infarct volumes regardless of recanalization. TICI 2b/3 recanalization of M2 occlusions was associated with smaller infarct volumes compared with TICI 0–2a recanalization, as well as less infarct expansion, in patients who received IV tissue plasminogen activator as well as those that did not. Successful reperfusion of M2 occlusions was associated with improved discharge modified Rankin scale. Conclusions If suitable as targets of ET, M2 occlusions should be given the same consideration as M1 occlusions.

Object. The goal of this study was to evaluate the utility of volume-rendered helical computerized tomography (CT) angiography in patients with intracranial aneurysms. The authors compared the abilities of CT angiography, digital subtraction (DS) angiography, and three-dimensional time-of-flight magnetic resonance (MR) angiography to characterize aneurysms.Methods. Helical CT angiography was performed in 45 patients with suspected intracranial aneurysms by using volume-rendered multiplanar reformatted (MPR) images. Digital subtraction angiography was performed using biplane angiography. These studies and those performed using MR angiography were interpreted in a blinded manner. Two neurosurgeons and two interventional neuroradiologists independently graded the utility of CT angiography with respect to aneurysm characterization.Fifty-five aneurysms were detected. Of these, 48 were evaluated for treatment. Computerized tomography angiography was judged to be superior to both DS and MR angiography in the evaluation of the arterial branching pattern at the aneurysm neck (compared with DS angiography, p = 0.001, and with MR angiography, p = 0.007), aneurysm neck geometry (compared with DS angiography, p = 0.001, and with MR angiography, p = 0.001), arterial branch incorporation (compared with DS angiography, p = 0.021, and with MR angiography, p = 0.001), mural thrombus (compared with DS angiography, p < 0.001), and mural calcification (compared with DS angiography, p < 0.001, and with MR angiography, p < 0.001). For surgical cases, CT angiography had a significant impact on treatment path (p = 0.001), operative approach (p = 0.001), and preoperative clip selection (p < 0.001). For endovascular cases, CT angiography had an impact on treatment path (p < 0.02), DS angiography study time (p = 0.01), contrast agent usage (p = 0.01), and coil selection (p = 0.02). Computerized tomography angiography provided unique information about 39 (81%) of 48 aneurysms, especially when compared with DS angiography (p = 0.003). The sensitivity and specificity of CT angiography compared with DS angiography was 1. The sensitivity and specificity of CT and DS angiography studies compared with operative findings were 0.98 and 1, respectively.Conclusions. Computerized tomography angiography is equal to DS angiography in the detection and superior to DS angiography and MR angiography in the characterization of brain aneurysms. Information contained in volume-rendered CT angiography images had a significant impact on case management.

Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra-arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion-weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8-38 cm3) and decreased to 10 cm3 (95% CI, 3-17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2-16 cm3) at baseline to 1 cm3 (95% CI, 0.4-2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality.

Primary central nervous system lymphoma (PCNSL) usually presents with clinical and neuroimaging findings consistent with single or multiple intracranial mass lesions. On cranial magnetic resonance imaging (MRI), such lesions are nearly always contrast enhancing, reflecting disruption of the blood-brain barrier at the site of tumor nodules. We describe 2 cases from the UCLA Medical Center who developed a rapidly progressive dementia due to extensive gray and white matter cerebral lesions involving much of the brain. In the patient who came to autopsy, widely infiltrating, focally necrotic B-cell plasmacytoid lymphoma was noted throughout the cerebral neuraxis. MRI findings in case 2 were consistent with diffuse lymphomatous brain infiltration without mass lesions, which was biopsy proven. We conclude that PCNSL may occur in a diffusely infiltrating form which may occur without MRI evidence of mass lesions or blood-brain barrier compromise. We refer to this entity as ‘lymphomatosis cerebri’ and add it to the differential diagnosis of a rapidly progressive dementia.

Background: Combined IV TPA and catheter-based reperfusion is an emerging treatment strategy for acute ischemic stroke. Both patient care and clinical trial design would be enhanced by delineation of which patients rapidly respond to IV TPA alone, before endovascular therapy can be initiated. Methods: In a prospectively maintained registry of patients treated under a general policy of combined IV TPA and endovascular therapy, we analyzed subjects with MRA/CTA-confirmed anterior circulation occlusions prior to IV TPA start. Results: Among 118 patients meeting study entry criteria, age was mean 71.5 (SD 14.5), 53.0% were female, and baseline NIHSS was 14.4 (SD 7.1). Confirmed sites of occlusion prior to IV TPA were internal cerebral artery (ICA) in 22.9%, M1 segment of middle cerebral artery (MCA) in 50.0%, and M2-3 in 27.1%. Among patients undergoing catheter cerebral angiography, median time from start of IV TPA to diagnostic catheter angiogram was 75 mins (IQR 50-113). A total of 48 (40.7%) patients achieved partial or complete recanalization (AOL 2-3) of the initial target artery with IV TPA alone (partial in 22 (18.6%) and complete in 26 (22.2%)); an additional 44 (37.3%) achieved partial or complete recanalization after endovascular therapy. Recanalization rates after IV TPA alone varied by target occlusion site: ICA - 22.2%, M1 - 40.7%, and M2-3 - 56.2%. In multivariate logistic regression analysis, independent predictors of recanalization with IV TPA alone were: M2-3 clot location, OR 3.04 (95% CI 1.20-7.73, p=0.019) and TOAST etiology large-artery atherosclerosis, OR 0.14 (CI 0.04-0.50, p = 0.003). Good outcome (mRS ≤ 3) rates at 3 months were 76.6% among recanalizers with IV TPA alone and 47.5% among recanalizers after both IV TPA and catheter therapy. Conclusions: When combined IV-endovascular treatment is pursued, recanalization with IV TPA alone occurs in 4 out of 10 patients before catheter therapy is started, is more common with more distal clot location, and is associated with a high rate of excellent clinical outcomes.