S Hussain

Transcranial Laser Therapy in Acute Stroke Treatment Results of Neurothera Effectiveness and Safety Trial 3, a Phase III Clinical End Point Device Trial

Background and Purpose— On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. Methods— We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ⩽24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included. Results— The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0–2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705–1.488). Conclusions— Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.

Mycotic aneurysm detection rates with cerebral angiography in patients with infective endocarditis

Background Cerebral angiography remains the gold standard for the detection of mycotic aneurysms, and it has been estimated that ruptured mycotic aneurysms result in 5% of the neurological complications of patients with infective endocarditis (IE). Objective To determine the diagnostic yield of cerebral angiography in the above patient population and to assess patient factors that might suggest greater or lesser utility. Methods We retrospectively reviewed 168 patients who underwent cerebral angiography with a diagnosis of IE or infected left ventricular assist device at the Cleveland Clinic between January 2003 and March 2010 in accordance with institutional review board guidelines. Chart and imaging review was performed. Results 15/168 patients (8.9%) had mycotic aneurysms; 93.3% (14/15) of the patients with mycotic aneurysms presented with CNS hemorrhage and 66.7% (10/15) had acute ischemic findings. Of the 15 patients with mycotic aneurysms on angiography, seven underwent CT angiography and six underwent MR angiography, which showed mycotic aneurysms in three (42.9%) and two cases (one of which was questionable; 33.3%), respectively. Conclusions Patients with IE or similar sources of central bacterial emboli are prone to neurovascular complications. Approximately 9% of patients with IE at our institution who undergo cerebral angiography have mycotic aneurysms. Presentation with hemorrhage appears to be more predictive of aneurysm, as approximately 22% of patients with IE and hemorrhage were found to have an aneurysm compared with only 1% when hemorrhage was absent. Thus, patients with IE presenting with intracranial hemorrhage should undergo vascular imaging, preferably with cerebral angiography.

ASPECTS discrepancies between CT and MR imaging: analysis and implications for triage protocols in acute ischemic stroke.

Background Optimal imaging triage for intervention for large vessel occlusions remains unclear. MR-based imaging provides ischemic core volumes at the cost of increased imaging time. CT Alberta Stroke Program Early CT Score (ASPECTS) estimates are faster, but may be less sensitive. Objective To assesses the rate at which MRI changed management in comparison with CT imaging alone. Methods Retrospective analysis of patients with acute ischemic stroke undergoing imaging triage for endovascular therapy was performed between 2008 and 2013. Univariate and multivariate analyses were performed. Multivariate logistic regression was used to evaluate the effect of time on disagreement in MRI and CT ASPECTS scores. Results A total of 241 patients underwent both diffusion-weighted imaging (DWI) and CT. Six patients with DWI ASPECTS ≥6 and CT ASPECTS <6 were omitted, leaving 235 patients. For 47 patients, disagreement between the two modalities resulted in different treatment recommendations. The estimated probability of disagreement was 20.0% (95% CI 15.4% to 25.6%). In a multivariate logistic regression, CT ASPECTS >7 (p=0.004) and admission National Institutes of Health Stroke Scale (NIHSS) score <16 (p=0.008) were simultaneously significant predictors of agreement in ASPECTS. The time between modalities was a marginally significant predictor (p=0.080). Conclusions The study suggests that patients with NIHSS scores at admission of <16 and patients with CT ASPECTS >7 have a higher likelihood of agreement between CT and DWI based on an ASPECTS cut-off value of 6. Additional MRI for triage in patients with NIHSS at admission of >16, and ASPECTS of 6 or 7 may be more likely to change management. Unsurprisingly, patients with low CT ASPECTS had good correlation with MRI ASPECTS.

P-022 Flow Diversion in the Posterior Circulation: A Single Center Experience and Literature Review

Introduction Flow diverters have been increasingly utilised for the treatment of large intracranial aneurysms, predominantly in the anterior circulation. There is limited data available on the safety and efficacy of this treatment approach for posterior circulation aneurysms, which often times have limited therapeutic options and unfavorable natural history. Objective The goal of this study is to present our posterior circulation flow diverter experience in comparison with recent studies. We also discuss the potential role of platelet inhibition testing, adjunctive coiling and the relevance of aneurysm type in clinical outcome. Methods This is a retrospective review of 6 patients with 7 aneurysms (5 saccular, 2 fusiform) in posterior circulation vessels, treated with flow diverter technology. We compare our results to available studies in the current literature. Results Pre-procedure platelet inhibition testing was routinely utilised. The average largest aneurysm diameter was 19.5 mm, and aneurysm length was up to 52 mm. None of the aneurysms were acutely ruptured, but one patient had a history of prior subarachnoid haemorrhage. Locations included 3 basilar artery, 3 distal vertebral artery and 1 posterior cerebral artery aneurysms. An average of 2 flow diverters were placed successfully in all patients. Adjunctive coiling was utilised in 3 (42.9%) cases. Imaging and clinical follow up was available in all 7 cases, ranging from 3.5 to 25 months (mean 10.1 months). Complete angiographic occlusion was seen in 3 out of 7 cases (42.9%), and another 3 aneurysms 42.9%) had decreased residual filling on follow-up. The one remaining patient had no clinical complications and no change in aneurysm filling initially after the procedure, but developed in-stent thrombosis with large brainstem stroke at 4.5 months, a week after he self-discontinued his dual antiplatelet therapy. Other clinical events included one patient with a periprocedural stroke with moderate residual deficits, and 2 other patients with a small periprocedural stroke with complete recovery. One of the latter 2 patients developed acute intraprocedural in-stent thrombosis with transient symptoms, which was rapidly treated, and had no significant long-term clinical consequences. There was no death, distal parenchymal haemorrhage or delayed aneurysm rupture. Overall 4 out of 6 patients, or 5 of 7 cases (71%), had good clinical outcome (mRS 0–1), all with saccular type aneurysms. Conclusion Posterior circulation flow diversion carries risks, but may represent a reasonable treatment option in carefully selected patients with high-risk aneurysms, which otherwise have and poor natural history and no optimal treatment strategy. Further data is necessary to assess the role of flow diversion in the posterior circulation. Disclosures G. Toth: None. M. Bain: None. S. Hussain: None. S. Moskowitz: None. P. Rasmussen: 1; C; ev3/Codman. 2; C; Codman. 4; C; Penumbra. 6; C; Blockade Medical. T. Masaryk: None. F. Hui: None.

Fibromuscular Dysplasia and Its Neurologic Manifestations: A Systematic Review

Importance Data on neurologic manifestations of fibromuscular dysplasia (FMD) are rare, and current knowledge remains limited. Objectives To present a comprehensive review of the epidemiologic characteristics, management, and prognosis of the neurologic manifestations associated with cerebrovascular FMD (ie, involving cervical or intracranial arteries) and to guide future research priorities. Evidence Review References were identified through searches of PubMed from inception to December 2017 using both the medical subject headings and text words. Additional sources were also identified by reviewing reference lists of relevant articles and through searches of the authors’ personal files. Selected articles described at least 1 clinical or radiologic feature and/or outcome of cerebrovascular FMD. Isolated case reports could be included if they described interesting or noteworthy manifestations of FMD. Findings A total of 84 relevant references were identified. Diagnosis of cerebrovascular FMD is based on the appearance of alternating arterial dilatation and constriction (“string of beads”) or of focal narrowing, with no sign of atherosclerotic or inflammatory lesions. Although the diagnosis is easily apparent on results of radiographic imaging, making a diagnosis can be challenging in children or individuals with atypical phenotypes, such as purely intracranial FMD and arterial diaphragm. Involvement of multiple arteries is common, and there is increased incidence of cervical artery dissection and intracranial aneurysms. A variant in the PHACTR1 gene has been associated with FMD as well as cervical artery dissection and migraine, although less than 5% of cases of FMD are familial. Headaches, mainly of the migraine type, are observed in up to 70% of patients with FMD. Cerebrovascular FMD is mostly asymptomatic, but the most frequent neurologic manifestations include transient ischemic attack and ischemic stroke, notably in the presence of associated cervical artery dissection. Other conditions associated with FMD include subarachnoid hemorrhage and, rarely, intracranial hemorrhage. Management relies on observational data and expert opinion. Antiplatelet therapy is considered reasonable to prevent thromboembolic complications. Endovascular therapy is typically restricted to cases with symptomatic stenosis despite optimal medical therapy or in those with rupture of an intracranial aneurysm. Conclusions and Relevance Longitudinal cohort studies of individuals of multiple ethnicities with biosampling are needed to better understand the risk factors, pathophysiological features, and outcomes of FMD. Patient advocacy groups could assist researchers in answering patient-centered questions regarding FMD.

E-049 Accuracy of non-invasive and invasive imaging in identifying ica occlusion: a comparative study in 65 patients

Introduction Internal carotid artery (ICA) occlusion is often encountered in acute stroke patients with reported prevalence of approximately 24% [1]. Such occlusion is usually defined preprocedural on non-invasive imaging (CT or MR angiography “CTA/MRA”) if available or intraprocedural during endovascular stroke treatment (digital subtraction angiography “DSA”). However, there is discrepancy between the site of the ICA occlusion on CTA/MRA compared to DSA [2] and even to findings on endovascular intervention (i.e. catheterization of the ICA). On imaging, a tapered narrowing of the ICA, the so-called “flame-shaped” occlusion is commonly seen [3, 4]. ICA pseudo-occlusion is therefore defined as non- opacification of the ICA on CTA/MRA but presence of flow on DSA. In our study we aim to examine the accuracy of different imaging modalities in accurately localizing the site of the ICA dissection, compared to direct catheterization of the ICA. Methods We performed a retrospective analysis of acute stroke patients undergoing endovascular stroke treatment who exhibited ICA occlusion in 4 participating centers between January 2015 and March 2017. All patients had imaging studies (CTA or MRA), diagnostic DSA and endovascular intervention. Patients’ demographics and comorbidities were noted. Images were reviewed by the interventional team in their respective center for the following parameters; extent of ICA occlusion (proximal contrast opacification cutoff and distal appearance of contrast opacification) and “flame shaped” pattern of ICA occlusion on imaging (CTA/MRA/DSA) as well as level of contrast opacification and pattern of ICA occlusion (“flame shaped”, “stump” occlusion or intraluminal defect) during the endovascular intervention. Results A total of 65 patients satisfied the inclusion criteria. The mean age was 70 years (standard deviation “SD” 13). There were 33 (51%) males and 32 (49%) females. Sixty (92%) patients had hypertension, 49 (75%) had hyperlipidemia, 23 (35) had coronary artery disease and 18 (28%) patients had diabetes mellitus. Flame- shaped occlusion pattern of the ICA was present in 12 (18%%) of patients on CTA/MRA and in 19 (29%) on DSA. Only 2 (3%) patients had ICA dissection though. During the ICA catheterization the site of the occlusion was at the common carotid artery in 1 (2%) patient, ICA origin in 13 (43%), cervical ICA in 28 (43%), petrous ICA in 2 (3%), cavernous ICA in 3 (5%), supracliniod ICA in 11 (17%), communicating segment ICA in 2 (3%) and ICA T-segment in 5 (8%) patients, while 29/57 (51%) of patients had “stump” ICA occlusion pattern, 13/57 (23%) had a “flame shaped” occlusion, 11/57 (19%) had a filling defect in the ICA and 4 (7%) patients had delayed opacification of the ICA. Conclusion Our result suggests that there is a lack of correlation between the imaging findings of carotid occlusion on imaging compared with catheter angiography of the ICA during the intervention in acute stroke treatment. Thus, endovascular catheterization of the ICA is often required for the exact characterization and localization of the carotid occlusion and to determine if a dissection is the underlying pathology in such cases. Disclosures A. El Mekabaty: None. Q. Hao: None. E. Cheng-Ching: None. S. Hussain: None. A. Spiotta: None. F. Hui: None.

O-009 ASPECTS Scores and DWI Volume: How well do they correlate?

Recent trials for the management of large vessel occlusion for acute ischemic stroke have demonstrated better outcomes for intervention over IV tPA alone. Ideal imaging triage remains uncertain, however CT only paradigms, volumetric paradigms, penumbral paradigms and collateral paradigms have been proposed and used. The volumetric exclusion criteria employed in EXTEND-IA and SWIFT-PRIME may have contributed to mRS 0–2 rates of 71% and 60% respectively. One of the appeals of MR estimation of irreversible “core” infarct is that it is the most accurate readily available modality. CT ASPECTS is more widely available, but may underestimate the volume of core. Statistical methods The Pearson correlation coefficient was used to assess the amount of linear correlation between ASPECTS and DWI volume. The DWI volume values observed within each ASPECT score were then summarized. An empirical receiver operating characteristic (ROC) curve was used to summarize the accuracy of using ASPECTS to predict DWI volume less than 70 cc. The operating point furthest from the chance diagonal was selected as the optimal ASPECTS threshold and 95% Agresti-Coull confidence intervals were calculated for the sensitivity and specificity at this cut point. Results DWI ASPECTS and DWI volume had a strong negative correlation (r = –0.76; 95% CI: –0.67, – 0.82), though there was a fair amount of variability in DWI volume within a given DWI ASPECT score. CT ASPECTS and DWI volume had a moderate negative correlation (r = –0.50; 95% CI: – 0.36, –0.62), though there was considerable variability in DWI volume for a given CT ASPECT score. In this sample, there were 105 patients with DWI volume < 70 cc and 27 with volume ≥ 70 cc. The area under the ROC curve for predicting DWI volume < 70 cc was 0.93 for DWI ASPECTS and 0.81 for CT ASPECTS. The ASPECTS thresholds which maximized the overall rate of correct classification were 5 and 8 for DWI and CT, respectively. When DWI ASPECTS > 5 was considered positive for DWI volume < 70, the estimated sensitivity and specificity were 0.88 (92/105; 95% CI: 0.80, 0.93) and 0.85 (23/27; 95% CI: 0.67, 0.95), respectively. When CT ASPECTS > 8 was considered positive for DWI volume < 70, the estimated sensitivity and specificity were 0.64 (67/105; 95% CI: 0.54, 0.72) and 0.85 (23/27; 95% CI: 0.67, 0.95), respectively.Abstract O-009 Figure 1 Disclosures F. Hui: None. J. Bullen: None. S. John: None. G. Toth: None. S. Hussain: None.

E-029 Flow Diverter Treatment of a Ruptured Anterior Cerebral Artery Blister Aneurysm

Introduction “Blister” type aneurysms (BA) are rare, atypical vascular lesions with fragile wall, broad base, difficult visualisation on imaging and high risk of rupture. Endovascular treatment of these aneurysms remains very challenging. While neck-remodelling with balloons and stents, or open surgery are available options, fragility of the thin aneurysm wall and lack of a true neck make treatment very high risk. The use of flow diverters is a possible alternative, but only limited data is available on this new therapeutic modality for BA treatment. Objective We report a case of flow diverter placement allowing successful endovascular treatment of a ruptured “blister” aneurysm on the anterior cerebral artery (ACA). We review currently available literature on this topic. Methods A 60-year-old female presented with extensive subarachnoid haemorrhage (SAH) from a left A1 segment 2.7 mm BA. An EVD was placed a day before intervention. The patient was loaded on aspirin and clopidogrel approximately 6 hours before the procedure. Adequate platelet response was confirmed by platelet aggregometry. Under general anaesthesia, a standard microcatheter and intermediate catheter were used to access the left ACA. The microcatheter was advanced into the left A2 segment, carefully passing the affected vessel portion and aneurysm neck. Slow deployment of the device was achieved without complications. A single device was used. For comparison and review, we searched the literature via standard online resources for flow diverter treatment of blister type aneurysms. Results Successful placement of the flow diverter device resulted in excellent neck coverage and wall opposition. Immediate stagnation in the small aneurysm lumen was seen. Further follow-up angiograms at 3 and 7 days demonstrated complete occlusion of the aneurysm lumen. The patient’s EVD was removed on postoperative day 7 while continuing antiplatelet agents without any complications. The patient made a good neurologic recovery. There are very few cases of ruptured BA flow diverter treatments currently published, none in smaller ACA vessels. Conclusion We effectively treated an acutely ruptured BA in the ACA with a flow diverter device. Although peri-procedural management in the acute SAH period can be challenging due to the obligatory use of dual antiplatelet therapy, flow diverter treatment is now a potential therapeutic alternative for high-risk blister type aneurysms, even in smaller vessels. To our knowledge, this is the first report of a ruptured BA flow diverter treatment in ACA vessels. Disclosures G. Toth: None. M. Bain: None. S. Hussain: None. F. Hui: None. P. Rasmussen: 1; C; ev3. 4; C; Penumbra, Blockade Medical. 6; C; ev3, Penumbra, Possis Medrad, Codman Neurovascular. Abstract E-029 Figure 1

P-023 MR Diffusion for Stroke Triage: When is it most useful?

Introduction MR Diffusion Weighted Imaging is known to be very sensitive to acute ischaemic change and probably represents one of the best clinically available methods to estimate the size of an ischaemic core. CT is more widely available, is faster, but may be relatively insensitive. Given that sensitivities vary even as ischaemic core is changing, there may be periods during which MR and CT may agree more or less as the infarct progresses. Methods The institutional database for MRI was queried to select patients that underwent MRI and CT during the triage process for acute ischaemic stroke. Patient data was collected and CT and MR ASPECTS scores were assessed for agreement and variance as a function of time from symptom onset. Results 71 patients were found with complete data and having MRI and CT within 60 minutes. 32 females (45.1%), mean age 70.7 years (range26–95). The mean time of MRI after LSW was 362.5 minutes (range 72 minutes to 22.3hours). The mean time between CT and MRI 38.2 min (range 4–60 minutes, 91% > 20 minutes. When using a theoretical discriminator of ASPECTS score 8 or greater for intervention, we found that MR and CT had a higher frequency of disagreement among patients with MRIs 3–6 hours after LKW compared with patients 6 hours (29.3% vs 10%, p=0.049). In patients with CT ASPECTS 7 or less, there were no disagreements with MR Diffusion. In patients with CT ASPECTS 8 or greater, there were 14/41 disagreements (34.2%) p<0.001. Conclusions Based on this data, there is some cause to believe that MRI may be more useful during an intermediate period and less useful early in the time course of a stroke as well as in the late course of an acute stroke. Abstract P-023 Table 1 Frequency of Disagreement in patient Management Using Cutpoint of 7 Abstract P-023 Figure 1 Difference between CT and MR ASPECTS Disclosures F. Hui: 3; C; Penumbra, Microvention. D. Wisco: None. N. Obuchowski: None. E. Cheng-Ching: None. K. Uchino: None. S. Hussain: None.

P-017 Intermediate catheters: experience, cost and complication rates at two high volume centers

Introduction Stable access to target lesions is foundational to endovascular therapy, be it in hemorrhagic or ischemic disease. Continued evolution in access technology has resulted in next generation catheters that afford improved trackability, as well as distal and proximal support. Neuron guide catheter family and the Concentric Outreach Distal Access Catheter fall into this category of hybrid catheters. Both families of devices possess overlapping characteristics allowing operators to achieve a more stable proximal access complex. Methods A retrospective review of 608 cases in which an intermediate catheter was used during 2008–2010 at Cleveland Clinic (Cleveland, OH) and throughout 2010 at Emory University Hospital (Atlanta, GA) was conducted, and the cases classified by indication. Catheter placement, distal most location and related complications were recorded and experience summarized. We also review the differences in the catheters and the rationale for catheter selection, as well as relative costs for each approach. Results A total of 311 Neuron 053, 166 Neuron 070, 36 DAC 3.9 Fr, 61 DAC 4.3 Fr, and 34 DAC 5.2 Fr catheters were deployed. Of these, 459 placements were in the anterior circulation, 130 in the posterior circulation, 11 in the external carotid artery, and eight were used intravenously. Abstract P-017 table 1 summarizes the clinical scenarios where the catheters were used, Abstract P-017 table 2 the distal most placements, Abstract P-017 table 3 the complications and Abstract P-017 table 4 the estimated costs for a typical catheter selection. Complication rates were 9/131 (6.9%) for the DAC catheter group, 16/311 (5.1%) for the Neuron 053 group, and 14/166 (8.4%) for the Neuron 070 group with p=0.37, χ2 test Abstract P-017 table 5.Abstract P-017 Table 1 Clinical scenarios Catheter # Cases Aneurysm Stroke AVM AVS ICAD Tumor Epi Venous DX Spasm Sac DAC 131 24 42 31 8 21 3 0 1 0 1 0 Neuron 053 311 162 16 25 12 73 6 2 1 1 7 6 Neuron 070 166 117 22 11 3 5 1 0 0 3 0 4 AVM, Arteriovenous Malformation; AVS, Arteriovenous Shunts, including Cavernous Carotid Fistulae and Dural Arteriovenous shunts; ICAD, Intracranial Stenoses including in stent restenoses; Epi, Epistaxis; Venous, Sinus Thrombosis; DX, Diagnostic Procedures including Balloon Test Occlusions; Spasm, Vasospasm; Sac, Vessel Sacrifice.Abstract P-017 Table 2 Distal most placement Catheter # Cases Cervical ICA Petrous ICA Cav/Com SupraClin ICA M1/A1 M2/A2 Vert Basilar PCA SCA/PICA/AICA ECA Vein DAC 131 0 0 34 58 6 13 3 6 1 2 5 Neuron 053 311 7 91 113 1 2 84 1 0 1 7 4 Neuron 070 166 17 109 18 0 0 20 0 0 0 2 0Abstract P-017 Table 3 Complication rates Catheter # Cases # Complications DAC 131 9 (6.9%) Neuron 053 311 16 (5.1%) Neuron 070 166 14 (8.4%) p=0.37, χ2 testAbstract P-017 Table 4 Relative costs Combination Cost 6F Sheath, SL-10, 6F Envoy, Synchro-2 microwire 1 6F Sheath, 6F Envoy, DAC, SL-10, Synchro-2 microwire 1.43 6F Sheath, Neuron 053, SL-10, Synchro-2 microwire 1.15* Based on prices available at Cleveland Clinic.Abstract P-017 Table 5 Complications DAC Neuron 053 Neuron 070 # Cases 131 311 166 # Complications 9 (6.9%) 16 (5.1%) 14 (8.4%) Air embolus 1 (0.8%) 0 (0.0%) 0 (0.0%) Dissection 2 (1.6%) 2 (0.6%) 1 (0.6%) Inadvertant embolization 3 (2.4%) 0 (0.0%) 3 (1.8%) Extravasation/Perforation 2 (1.6%) 6 (1.8%) 4 (2.4%) Intraparenchymal hemorrhage 1 (0.8%) 2 (0.6%) 0 (0.0%) Clot-on-coil 0 (0.0%) 2 (0.6%) 2 (1.2%) Parent vessel compromise 0 (0.0%) 4 (1.2%) 2 (1.2%) Distal stroke 0 (0.0%) 0 (0.0%) 2 (1.2%) Conclusion Next generation access catheters possess characteristics that blend qualities of traditional microcatheters and guide catheters. These “intermediate catheters” represent a class of access devices that allow for better catheter support, and allow for multi-axial access techniques. The utility of these catheters must be balanced against costs. The increased procedural complexity involved in using multi-axial techniques should also be a consideration, but judicious application should prove beneficial to patients. There is no statistically significant difference in complication rates when using these catheters as well as comparable complication rates when compared to historical complication rates quoted to patients.