Proximal Middle Cerebral Artery Occlusion Research Articles

Abstract TP45: Analysis of FLAIR Hyperintense Vessels by the Different Phase of Multiphase CTA in Acute MCA Occlusion

Background: It is well known that hyperintense vessels (HV) on fluid-attenuated inversion recovery (FLAIR) image suggest slow collateral flow in case of large arterial occlusion. Multiphase CT angiography (CTA) is an imaging technique that provides time-resolved images of pial arteries. We analyzed the correlation of HVs on FLAIR image with collateral vessels on the different phases of multiphase CTA. Methods: FLAIR images and multiphase CTA was analyzed in 7 patients with proximal MCA occlusion. We counted the number of discrete FLAIR HVs distal to the occlusion site and investigated whether the FLAIR HVs could be seen at the same area in different phases of multiphase CTA. Results: The mean duration between symptom onset and acquisition of multiphase CTA was 5.6 hours and mean duration between CTA and MRI was 0.6 hour. A total 32 FLAIR HVs were observed in 7 patients. Of these, 13 HVs were observed in the 1 st phase CTA, 25 HVs in the 2 nd phase, and 26 HVs in the 3 rd phase. Six HVs were not observed in all three phases of CTA. Conclusions: In cases of acute proximal MCA occlusion, the collateral vessels shown as FLAIR HVs are more frequently observed in the late phase of multiphase CTA. Fig 1. A 74-year-old man with acute occlusion of left middle cerebral artery. FLAIR image (A) shows 3 discrete HVs at left temporoparietal area. These FLAIR HVs are most clearly seen at 3 rd phase contrast enhanced CTA (D) B, C: 1 st and 2 nd phase contrast enhanced CTA

Abstract WP52: ASPECTS and eASPECTS Correlation With Baseline and Final Infarct Volume in Acute Ischemic Stroke Thrombectomy Patients

Alberta Stroke Program Early CT score (ASPECTS) is widely used as cut-off point to indicate thrombolysis therapy in acute ischemic stroke. Its role in predicting patients likely to benefit from endovascular therapy has not been defined yet. ASPECTS presents a poor interrater reliability, and an automated software (eASPECTS) has been recently created to solve this limitation. Our aim was to evaluate correlation between ASPECTS measured by neurorradiologists, eASPECTS and cerebral blood volume (CBV) lesion, as well as to determine the impact of ASPECTS and eASPECTS on final infarct in thrombectomy patients. Methods: Consecutive patients with acute intracranial ICA and proximal MCA (M1) occlusion who underwent endovascular thrombectomy were included. ASPECTS and e-ASPECTS on basal non-contrast CT were evaluated. Admission infarct core was measured on CBV in CT perfusion. We assessed time from symptom onset to neuroimaging evaluation and recanalization (TICI 2b-3) after thrombectomy. Infarct volume was measured on 24-hour control CT. Results: We included 214 patients (88% with MCA occlusion). Median NIHSS was 18 (IQR 14-20) and mean time from symptom onset to CT was 194.11±154.34 min. Complete recanalization rate was 80.84%. Median ASPECTS was 9 (IQR 8-10) and median eASPECTS 9 (IQR 7.75-10), mean CBV infarct core was 55.29±90cc. Correlation (r s ) between ASPECTS and eASPECTS was 0.44 (p<0.01). ASPECTS/eASPECTS and CBV presented a significant correlation only after 180 min of symptom onset (r s =-0.44, p<0.01 / r s =-0.26, p<0.05). Both ASPECTS and eASPECTS (r s =-0.40 and -0.43) correlated with 24h infarct volume in patients with complete recanalization (p<0.01). A logistic regression analysis showed that both ASPECTS (OR 0.56, p<0.01, CI 0.43-0.72) and eASPECTS (OR 0.57, p<0.01, CI 0.44-0.73) predicted independently low final infarct volume, together with recanalization (OR 4.6, p=0.03, CI 1.69-2.34). Conclusions: Correlation of ASPECTS and eASPECTS with CBV was time-dependent as both measurements correlated with CBV when time to CT was>180 min. Both ASPECTS and eASPECTS predicted infarct volume after thrombectomy.

Abstract 63: Collaterals in Thrombectomy for MCA Occlusion: Mapping the Collaterome in the Trevo Retriever Registry

Background: The delay and dispersion of collateral circulation to the MCA territory is readily available prior to endovascular thrombectomy for acute ischemic stroke (AIS). Factors associated with collateral grade have never been established in such an extensive population, reflecting diverse subjects from around the world. Largescale data from the Trevo Retriever Registry enables mapping of the MCA collaterome for the first time. Methods: The Imaging and Angiography Core Lab of the Trevo Retriever Registry independently conducted prospective evaluation of angiography in more than 1,500 subjects. Collaterals were systematically scored using ASITN grade prior to thrombectomy. Descriptive statistics detailed the distribution of collateral grades and analyses with demographic, imaging and clinical variables to explore key associations with routinely acquired registry data. Results: 890 subjects (68.5 ± 15.1 years; 54.6% women; baseline NIHSS median 15 (10-19)) with AIS due to MCA occlusion had angiography of collateral circulation centrally adjudicated. Proximal M1 MCA occlusion was noted in 671/890 (75.4%). Collateral grade prior to thrombectomy included grade 4 or most robust collaterals in 38/890 (4.3%), 3 in 294/890 (33.0%), 2 in 467/890 (52.5%), 1 in 80/890 (9%) and 0 or none in 11/890 (1.2%). Baseline collaterals at angiography and pre-procedure ASPECTS were closely correlated (r=0.439, p<0.001) with more modest correlation between collateral grade and CTP/DWI (rrCBF<30% or ADC<620) infarct core (r=-0.31, n=391; p<0.001) or CTP/PWI (Tmax>6s) hypoperfusion at-risk (r=-0.10, n=391; p=0.043) volumes. First pass mTICI≥2b occurred in 553/858 (64.5%) with final mTICI≥2b in 824/890 (92.6%). Collateral grade prior to thrombectomy (each 1-point increment, after adjustment for other predictors) was strongly associated (OR 1.38 95%CI (1.12-1.7), p=0.002) with good clinical outcomes (mRS 0-2) at 90 days. Conclusions: Largescale mapping of collaterals prior to MCA thrombectomy reveals marked variation in the extent and functional impact of the collaterome. The preponderance of partial perfusion in the downstream ischemic territory prompts the need to investigate and leverage the protective nature of the collaterome in AIS.

The UCP2-866G/A Polymorphism Could be Considered as a Genetic Marker of Different Functional Prognosis in Ischemic Stroke After Recanalization.

Recent studies based on experimental animal models of stroke have suggested that uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is thought to regulate energy metabolism and reduce reactive oxygen species generation, provides protection against reperfusion damage. We aimed to investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which enhances its transcriptional activity, is associated with functional prognosis in patients with embolic ischemic stroke after early recanalization. We investigate a hospital-based prospective cohort of patients with acute ischemic stroke due to occlusion of the middle cerebral artery diagnosed by transcranial Doppler who obtained a partial/complete recanalization 24h after administration of intravenous thrombolysis. The main end point of the study was functional independence defined as modified Rankin Scale 0-2 on day 90. A total of 80 patients were enrolled. The UCP2-866G/A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism technique (14 genotype A/A (18%), 45 genotype A/G (56%) and 21 genotype G/G (26%). The percentage of patients with good functional outcome at 3months was significantly higher in patients harboring the A/A genotype than in those with A/G or G/G genotypes (85 vs 41%, p=0.01). The A/A genotype was found to be an independent marker of good prognosis after adjustment for secondary variables (age, sex, glucose level, NIHSS score at baseline, complete recanalization and early neurological improvement) in a logistic regression analysis (OR 0.05, 95% CI 0.01-0.48, p=0.01). Our results suggest that the AA genotype of UCP2-866 may predict a better functional outcome in ischemic stroke after recanalization of proximal MCA occlusion.

Clinical outcome prediction after thrombectomy of proximal middle cerebral artery occlusions by the appearance of lenticulostriate arteries on magnetic resonance angiography: A retrospective analysis

Post-ischemic vasodynamic changes in infarcted brain parenchyma are common and range from hypo- to hyperperfusion. In the present study, appearance of the lenticulostriate arteries (LSAs) on postinterventional 3T time-of-flight (TOF)-MRA suggestive for altered post-stroke vasodynamics following thrombectomy was investigated. Patients who underwent thrombectomy for a proximal MCA occlusion and for whom postinterventional 3T TOF-MRA (median at day 3) was available, were included in this retrospective analysis (n=98). LSA appearance was categorized into presence (LSA-sign+) or absence (LSA-sign−) of vasodilatation in the ischemic hemisphere. Functional outcome was determined using the modified Rankin scale (mRS). LSA-sign+ was observed in 64/98 patients. Hypertension (adjusted OR: 0.171, 95% CI: 0.046–0.645) and preinterventional IV rtPA (adjusted OR: 0.265, 95% CI: 0.088–0.798) were associated with absence of the LSA-sign+. In multivariate logistic regression, LSA-sign+ was associated with substantial neurologic improvement (adjusted OR: 10.18, 95% CI: 2.69–38.57) and good functional outcome (discharge-mRS ≤ 2, adjusted OR: 7.127, 95% CI: 1.913–26.551 and day 90 mRS ≤ 2, adjusted OR: 3.786, 95% CI: 1.026–13.973) after correcting for relevant confounders. For all clinical endpoints, model fit improved when including the LSA-sign term (p<0.05). Asymmetrical dilatation of LSAs following successful thrombectomy indicates favorable neurologic and mid-term functional outcomes. This may indicate preserved cerebral blood flow regulatory mechanisms.

Isolated Striatocapsular Infarcts after Endovascular Treatment of Acute Proximal Middle Cerebral Artery Occlusions: Prevalence, Enabling Factors, and Clinical Outcome.

Striatocapsular infarcts (SCIs) are defined as large subcortical infarcts involving the territory of more than one lenticulostriate artery. SCI without concomitant ischemia in the more distal middle cerebral artery (MCA) territory [isolated SCI (iSCI)] has been described as a rare infarct pattern. The purpose of this study was to assess the prevalence of iSCI in patients treated with endovascular thrombectomy (ET), to evaluate baseline and procedural parameters associated with this condition, and to describe the clinical course of iSCI patients. A retrospective analysis of 206 consecutive patients with an isolated MCA occlusion involving the lenticulostriate arteries and treated with ET was performed. Baseline patient and procedural characteristics and ischemic involvement of the striatocapsular and distal MCA territory [iSCI, as opposed to non-isolated SCI (niSCI)] were analyzed using multivariate logistic regression models. Prevalence of iSCI was assessed, and clinical course was determined with the rates of substantial neurological improvement and good functional short- and mid-term outcome (discharge/day 90 Modified Rankin Scale ≤2). iSCI was detected in 53 patients (25.7%), and niSCI was detected in 153 patients (74.3%). Successful reperfusion [thrombolysis in cerebral infarction (TICI) 2b/3] [adjusted odds ration (aOR) 8.730, 95% confidence interval (95% CI) 1.069-71.308] and good collaterals (aOR 2.100, 95% CI 1.119-3.944) were associated with iSCI. In successfully reperfused patients, TICI 3 was found to be an additional factor associated with iSCI (aOR 5.282, 1.759-15.859). Patients with iSCI had higher rates of substantial neurological improvement (71.7 vs. 37.9%, p < 0.001) and higher rates of good functional short- and mid-term outcome (58.3 vs. 23.7%, p < 0.001 and 71.4 vs. 41.7%, p < 0.001). However, while iSCI patients, in general, had a more favorable outcome, considerable heterogeneity in outcome was observed. High rates of successful reperfusion (TICI 2b/3) and in particular, complete reperfusion (TICI 3) are associated with iSCIs. The high prevalence of iSCI in successfully reperfused patients with good collaterals corroborates previous concepts of iSCI pathogenesis. iSCI, once considered a rare pattern of cerebral ischemia, is likely to become more prevalent with increases in endovascular stroke therapy. This may have implications for patient rehabilitation and pathophysiological analyses of ischemic damage confined to subcortical regions of the MCA territory.

Dexpramipexole improves bioenergetics and outcome in experimental stroke.

Dexpramipexole, a drug recently tested in patients with amyotrophic lateral sclerosis (ALS,) is able to bind F1Fo ATP synthase and increase mitochondrial ATP production. Here, we have investigated its effects on experimental ischaemic brain injury. The effects of dexpramipexole on bioenergetics, Ca2+ fluxes, electrophysiological functions and death were evaluated in primary neural cultures and hippocampal slices exposed to oxygen-glucose deprivation (OGD). Effects on infarct volumes and neurological functions were also evaluated in mice following proximal or distal middle cerebral artery occlusion (MCAo). Distribution of dexpramipexole within the ischaemic brain was evaluated by means of mass spectrometry imaging. Dexpramipexole increased mitochondrial ATP production in cultured neurons or glia and reduces energy failure, prevents intracellular Ca2+ overload and affords cytoprotection when cultures are exposed to OGD. This compound also counteracted ATP depletion, mitochondrial swelling, anoxic depolarization, loss of synaptic activity and neuronal death in hippocampal slices subjected to OGD. Post-ischaemic treatment with dexpramipexole, at doses consistent with those already used in ALS patients, reduced brain infarct size and ameliorated neuroscore in mice subjected to transient or permanent MCAo. Notably, the concentrations of dexpramipexole reached within the ischaemic penumbra equalled those found neuroprotective in vitro. Dexpramipexole, a compound able to increase mitochondrial F1Fo ATP-synthase activity reduced ischaemic brain injury. These findings, together with the excellent brain penetration and favourable safety profile in humans, make dexpramipexole a drug with realistic translational potential for the treatment of stroke. This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

Revascularization of tandem occlusions in acute ischemic stroke: review of the literature and illustrative case.

OBJECTIVE Tandem occlusions continue to represent a major challenge in patients with acute ischemic stroke (AIS). The anterograde approach with proximal to distal revascularization as well as the retrograde approach with distal to proximal revascularization have been reported without clear consensus or standard guidelines. METHODS The authors performed a comprehensive search of the PubMed database for studies including patients with carotid occlusions and tandem distal occlusions treated with endovascular therapy. They reviewed the type of approach employed for endovascular intervention and clinical outcomes reported with emphasis on the revascularization technique. They also present an illustrative case of AIS and concurrent proximal cervical carotid occlusion and distal middle cerebral artery occlusion from their own experience in order to outline the management dilemma for similar cases. RESULTS A total of 22 studies were identified, with a total of 790 patients with tandem occlusions in AIS. Eleven studies used the anterograde approach, 3 studies used the retrograde approach, 4 studies used both, and in 4 studies the approach was not specified. In the studies that reported Thrombolysis in Cerebral Infarction (TICI) grades, an average of 79% of patients with tandem occlusions were reported to have an outcome of TICI 2b or better. One study found good clinical outcome in 52.5% of the thrombectomy-first group versus 33.3% in the stent-first group, as measured by the modified Rankin Scale (mRS). No study evaluated the difference in time to reperfusion for the anterograde and retrograde approach and its association with clinical outcome. The patient in the illustrative case had AIS and tandem occlusion of the internal carotid and middle cerebral arteries and underwent distal revascularization using a Solitaire stent retrieval device followed by angioplasty and stent treatment of the proximal cervical carotid occlusion. The revascularization was graded as TICI 2b; the postintervention National Institutes of Health Stroke Scale (NIHSS) score was 17, and the discharge NIHSS score was 7. The admitting, postoperative, and 30-day mRS scores were 5, 1, and 1, respectively. CONCLUSIONS In stroke patients with tandem occlusions, distal to proximal revascularization represents a reasonable treatment approach and may offer the advantage of decreased time to reperfusion, which is associated with better functional outcome. Further studies are warranted to determine the best techniques in endovascular therapy to use in this subset of patients in order to improve clinical outcome.

Hemorrhagic Transformations after Thrombectomy: Risk Factors and Clinical Relevance

Background: Hemorrhagic transformation (HT) is a major complication of acute ischemic stroke, potentially associated with clinical deterioration. We attempted to identify risk factors and evaluated clinical relevance of minor and major HTs following endovascular thrombectomy (ET) in isolated middle cerebral artery (MCA) occlusions. Methods: This is a retrospective single-center analysis of 409 patients with isolated MCA occlusion treated with ET. Patients' and procedural characteristics, severity of HT according to the European Cooperative Acute Stroke Study criteria, and clinical outcomes were analyzed. Multivariate logistic regression models with standard retention criteria (p < 0.1) were used to determine risk factors and clinical relevance of HT. Results are shown as adjusted OR (aOR) and respective 95% CIs. Good neurologic short-term outcome was defined as National Institutes of Health Stroke Scale (NIHSS) score <5 at the day of discharge. Results: Of 299 patients included, hemorrhagic infarction (HI) was detected in 87 patients, while 13 patients developed parenchymal hematoma (PH). Higher age (aOR 0.970, 95% CI 0.947-0.993, p = 0.012), eligibility for intravenous recombinant tissue plasminogen activator (IV rtPA; aOR 0.512, 95% CI 0.267-0.982, p = 0.044), and complete recanalization (TICI 3, aOR 0.408, 95% CI 0.210-0.789, p = 0.008) were associated with a lower risk of HI. Risk factors for HI included higher admission NIHSS score (aOR 1.080, 95% CI 1.010-1.153, p = 0.024) and higher admission glucose levels (aOR 1.493, 95% CI 1.170-1.904, p = 0.001). Further, female sex tended to be associated with a lower risk of HI (aOR 0.601, 95% CI 0.316-1.143, p = 0.121), while a statistical trend was observable for proximal MCA occlusion (aOR 1.856, 95% CI 0.945-3.646, p = 0.073) and a history of hypertension (aOR 2.176, 95% CI 0.932-5.080, p = 0.072) to increase risk of HI. Longer intervals from symptom onset to first digital subtraction angiography runs (aOR 1.013, 95% CI 1.003-1.022, p = 0.009), lower preinterventional Alberta Stroke Program Early CT score (aOR 0.536, 95% CI 0.307-0.936, p = 0.028) and wake-up stroke (aOR 18.540, 95% CI 1.352-254.276, p = 0.029) were associated with PH. Both, PH and HI were independently associated with lower rates of good neurologic outcome (aOR 0.086, 95% CI 0.008-0.902, p = 0.041 and aOR 0.282, 95% CI 0.131-0.606, p = 0.001). Conclusion: Risk of HI following MCA occlusion and subsequent ET is mainly determined by factors influencing infarct severity. Good recanalization results seem to be protective against subsequent HI. Our results support the notion that occurrence of PH after ET is time dependent and risk increases with more extensive early ischemic damage. Both, HI and PH do not seem to be facilitated by bridging therapy with IV rtPA or the use of oral anticoagulants, but were independently associated with more severe neurologic disability. These results support the notion that HI is not a “benign” imaging sign.

Elevated body temperature in ischemic stroke associated with neurological improvement.

Some studies suggest that high body temperature within the first few hours of ischemic stroke onset is associated with improved outcome. We hypothesized an association between high body temperature on admission and detectable improvement within 6-9hours of stroke onset. Consecutive ischemic stroke patients with NIHSS scores obtained within 3hours and in the interval 6-9hours after stroke onset were included. Body temperature was measured on admission. A total of 315 patients with ischemic stroke were included. Median NIHSS score on admission was 6. Linear regression showed that NIHSS score 6-9hours after stroke onset was inversely associated with body temperature on admission after adjusting for confounders including NIHSS score <3hours after stroke onset (P<.001). The same result was found in patients with proximal middle cerebral occlusion on admission. We found an inverse association between admission body temperature and neurological improvement within few hours after admission. This finding may be limited to patients with documented proximal middle cerebral artery occlusion on admission and suggests a beneficial effect of higher body temperature on clot lysis within the first three hours.

Stroke Lesions in a Large Upper Limb Rehabilitation Trial Cohort Rarely Match Lesions in Common Preclinical Models

Background. Stroke patients with mild-moderate upper extremity motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. Laboratory-based investigators use lesioning techniques for similar goals. Objective. To determine whether stroke lesions in an upper extremity rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. Methods. Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. Results. Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, <1% had lesions resembling proximal middle cerebral artery or surface vessel occlusion models. Preclinical models of subcortical white matter injury best resembled the ICARE population (33%). Intracranial hemorrhage participants had small (median 12.5 mL) lesions that best matched the capsular hematoma preclinical model. Conclusions. ICARE subjects are not representative of all stroke patients, but they represent a clinically and scientifically important subgroup. Compared with lesions in general stroke populations and widely studied animal models of recovery, ICARE participants had smaller, more subcortically based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models.

Abstract TMP89: Collaterals and Reperfusion Mediate Blood Pressure Changes in Acute Ischemic Stroke

Background: The pathophysiology and optimal management of blood pressure changes in acute ischemic stroke remain unknown. Blood pressure guidelines do not consider patient-specific or serial data on dynamic blood pressure readings. We investigated continuous blood pressure data during endovascular therapy for acute stroke to discern changes associated with collaterals, recanalization and reperfusion. Methods: Continuous monitoring blood pressure data was collected in consecutive cases of endovascular therapy for acute ischemic stroke due to ICA or proximal MCA occlusion. Angiography details were independently analyzed to document site of arterial occlusion, baseline collateral grade, time of device deployments, time of recanalization, time of final reperfusion, final AOL recanalization and final TICI reperfusion. Statistical analyses correlated instantaneous and serial blood pressure changes with these angiographic parameters. Results: 80 patients (median age 73 years; 33 women) were studied. Arterial lesions included 37 ICA and 41 proximal M1 MCA occlusions. Collateral grade prior to intervention included 2 ASITN grade 4, 26 grade 3, 23 grade 2, 6 grade 1 and 0 grade 0. oTICI2C reperfusion scores after thrombectomy included 2 TICI 3 (100%), 22 TICI 2C (90-99%), 25 TICI o2B (67-89%), 9 TICI m2B (50-66%), 19 TICI 2A (&lt;50%) and 3 TICI 0/1. More robust collateral grade was associated with greater reperfusion scores (r=0.32, p=0.028). The change in blood pressure (ΔBP) from earliest BP to time of recanalization was mean 59% of ΔBP during the entire procedure. Better collaterals were associated with lower BP prior to recanalization (r=-0.377, p=0.012). Lower BP prior to recanalization was linked with greater TICI reperfusion (r=-0.242, p=0.050). Higher TICI reperfusion scores were also associated with a greater drop or ΔBP at the time of recanalization (r=0.269, p=0.031). AOL recanalization was not related to ΔBP. Conclusions: Collaterals and reperfusion, but not recanalization, mediate blood pressure changes in acute ischemic stroke. Prospective, precision medicine stroke studies should leverage patient-specific, real-time data on continuous blood pressure with imaging correlates to define BP goals of future in-hospital management.

Abstract WMP24: CT Angiography Collateral Gradient Mapping: Validation of a Novel Imaging Technique in Acute Ischemic Stroke

Background: CT angiography (CTA) is routinely acquired in acute ischemic stroke, providing data on extent of collaterals yet current techniques compromise either spatial or temporal resolution. We developed and validated a novel imaging technique from standard or single-phase CTA to discriminate both the spatial and temporal blood flow features in leptomeningeal collaterals. Methods: Consecutive acute ischemic stroke patient data, including single-phase CTA (sCTA) followed immediately by digital subtraction angiography (DSA), in the setting of ICA or proximal MCA occlusions were analyzed. Three-dimensional (3D) reconstruction and surface mapping of collateral flow gradients on sCTA was performed. Quantitative output of flow gradients in individual collateral vessels was correlated with DSA ASITN collateral grade. Results: 75 consecutive cases of acute stroke due to ICA or proximal MCA occlusion were analyzed with contemporaneous sCTA and DSA. Automatic post-processing of collateral gradient maps and generation of quantitative data output followed 3D reconstruction and segmentation of sCTA. sCTA collateral gradient mapping was feasible in all cases, compared to limitations in availability of DSA collateral grades. Poor collateral status on DSA (ASITN 0-1) was evident as limited extent and color-mapped gradients on sCTA. In contrast, sCTA gradient mapping provided more detailed distinction between subjects of intermediate or partial DSA collaterals (ASITN 2) and also amongst complete, but delayed DSA collaterals (ASITN 3). sCTA gradient mapping provided quantitative data on the delay of collateral flow in individual cortical vessels. Conclusions: CTA collateral gradient mapping can routinely provide detailed data on both the extent and delay of collaterals, using standard sCTA acquisition. This novel imaging technique may provide key information to distinguish the wide variability of ASITN grades 2-3, most commonly encountered in acute stroke.

Abstract WMP15: A Simple Tool to Predict Target Mismatch in Ischemic Stroke Patients with Anterior Circulation Occlusion

Introduction: The efficacy of endovascular thrombectomy in an extended time window for acute ischemic stroke patients with Target Mismatch (TM) on perfusion imaging was shown in a recent study and the ongoing DEFUSE-3 trial is studying thrombectomy in a 6-16 hour window for TM patients. A limitation of TM is that perfusion imaging is not widely available. We sought to identify a tool to predict TM based on clinical factors and CT angiogram (CTA) imaging, which is available at most hospitals. Methods: We reviewed acute ischemic stroke patients from 2010-2014 with proximal middle cerebral artery occlusion, CTA and CT perfusion (CTP) at hospital admission. TM was identified on CTP using the Olea Sphere volumetric analysis software with Bayesian deconvolution. TM was defined by the DEFUSE-3 criteria. ASPECTS was derived from the non-contrast CT head and the CTA source images (CTA-ASPECTS). Two collateral scores were derived from CTA source images. Results: 61 patients met inclusion criteria. The mean±SD age was 61±18 years and 61% were male. Mean NIH Stroke Scale (NIHSS) was 14.1±8.0 and median (IQR) follow-up modified Rankin Scale was 3 (1,6). TM was present in 35/61 (57%), who had lower mRS at follow-up (z=3.5, p&lt;0.001). The predictor variables are shown in Table 1. The best combination of predictors was CTA-ASPECTS &gt;4 and NIHSS &lt;16, which had a sensitivity of 80% and specificity of 85% for TM (Figure 1). Discussion: We report a reliable, accessible, and clinically useful tool for predicting TM. This score warrants further study as a tool to guide transfer decisions from primary or secondary stroke centers to tertiary centers where endovascular intervention would be possible for selected patients.

Abstract 62: Sanguinate TM Opens Collaterals, Improves Reperfusion and Decreases Infarct in Hypertensive Rats

Background: The PEGylated cell-free carboxyhemoglobin gas exchanger Sanguinate TM (SG) has multiple beneficial actions that may improve stroke outcome including anti-inflammatory, vasodilatory and oxygen delivery capacity. We investigated the ability of SG to improve infarction in spontaneously hypertensive rats (SHR) that are known to have vasoconstricted pial collaterals and poor stroke outcome. Methods: SHR were treated IV with SG (8 ml/kg; n=8) or vehicle (Lactated Ringer’s; n=6) plus tPA (0.9 mg/ml) after 30 min of proximal middle cerebral artery occlusion (MCAO) by filament occlusion. Pial collateral and reperfusion flow were measured for 2 hrs of occlusion and 2 hrs reperfusion using dual laser Doppler probes in the core (Bregma -2mm, lateral +4mm) and collateral (Bregma +2mm, lateral +3mm) territories. Collateral openings (number and duration (min)) were assessed off cerebral blood flow (CBF) tracings, defined as independent of changes in blood pressure (Fig. 1; arrows show openings). Infarction was measured using triphenyltetrazolium chloride (TTC). Animals were anesthetized with chloral hydrate and ventilated to maintain blood gases within normal ranges. Results: Vehicle-treated SHR had incomplete reperfusion and poor collaterals that was improved by SG. During MCAO, SG increased the number of collateral openings from 1.0±0.8 to 3.1±0.8 (p=0.03) and duration of openings from 6.0±5.8 to 35.4±9.8 min (p=0.04; Fig. 2). Reperfusion CBF was -43±6% of baseline in vehicle-treated, but only -7±19% of baseline in SG-treated animals. Improved collateral and reperfusion flow with SG was associated with decreased infarct volume vs. vehicle (28.8±3.2% vs. 18.8±2.3%; p&lt;0.05). The presence of tPA had no effect in either group. Conclusions: Smaller infarction with early SG treatment may be related to its ability to open constricted collaterals in SHR and improve reperfusion. Thus, SG may be able to extend the time window for endovascular or tPA treatment.

Abstract TP45: Predictors for Good Collaterals in 857 Patients With Acute Ischemic Stroke and Proximal Middle Cerebral Artery Occlusion

Background: Good collaterals in acute ischemic stroke (AIS) correlate with smaller infarct size, improved outcome, and better recanalization rates after revascularisation treatments. Given that the variables determining collateral circulation are poorly understood, we aimed to identify predictors of good collaterals in a large series of AIS with middle cerebral artery (MCA) occlusion. Methods: In the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 2003 to 2016, we identified all AIS with MCA occlusion (M1 or proximal M2) on CT angiography (CTA) performed within 24 hours. Collaterals were graded from 0 (absent) to 3 (100% or more) and classified as good (grades 2 and 3) or poor. We correlated collateral status with various clinical, metabolic and radiological variables in a univariate, then multivariate regression analyses (MVA). Results: Of the 2’027 patients with AIS involving the MCA and good quality CTA during the study period, 857 met the inclusion criteria. Median age was 72.3±20.5 years, 48.4% were females, and median admission NIHSS was 16±9. Younger age (OR=0.99, confidence interval (CI) 0.98-0.99) and lower NIHSS on admission (OR=0.92, CI=0.90-0.94) were significantly associated with good collaterals. Hyperglycemia (OR=0.94, CI=0.88-0.99) and higher creatininemia (OR=0.99, CI=0.99-1) correlated with poor collaterals. The distribution of vascular risk factors was similar. Radiologically, good collateral status was predicted by higher ASPECTS score (OR=1.31, CI=1.24-1.40), absence of a hyperdense MCA sign (OR=0.60, CI=0.46-0.79), lower clot burden (OR=1.18, CI=1.12-1.24) and absence of proximal intracranial arterial pathology (OR=0.44, CI=0.33-0.58). MVA results will be presented. Conclusion: Good collaterals are associated with lower age and lower NIHSS, whereas high blood glucose and creatinine values predicted poor collaterals. On neuroimaging, minor early ischemic changes, lower clot burden and distal site of vascular occlusion correlated with good collaterals. These data may predict stroke outcome in certain patients, explain futile recanalisation, and help select patients for late or aggressive recanalisation treatments independently of time windows.

Abstract 178: Infarct Growth Rate Depends on Collateral Status in Acute Ischemic Stroke Patients

Introduction and Hypothesis: Multiple studies have demonstrated no statistically significant association between time after stroke onset and initial infarct volume. Factors other than time may play a role in infarct growth. We sought to investigate association between collateral status and infarct growth rate in acute ischemic stroke (AIS) patients. Methods: We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who had DWI within 8 hours of stroke onset. Collateral status was categorized into three groups: poor (none or minimal), intermediate (present but &lt; contralateral side) and good (≥ contralateral side). DWI lesion volumes were measured and infarct growth rate was calculated using MRI time after stroke onset. Mann-Whitney test and correlation coefficient were used for statistical analysis. Results: In our 130 patients, 62 female (48%), the average values (mean±SD) were: age 70 ± 17 years, NIHSS 16 ± 6, DWI volume 59 ± 65 mL, time after stroke onset 4 ± 2 hours, and infarct growth rate 17 ± 23 mL/hour. 19 (14.6%) had poor, 75 (57.7%) had intermediate, and 36 (27.7%) had good collaterals. Infarct growth rate and DWI lesion volume were significantly increased with decreased collateral quality (p&lt;0.0004 for all group comparisons). Patients with good collaterals were younger (p=0.004 and p=0.018 compared to poor and intermediate groups respectively) and had lower NIHSS scores (p&lt; 0.001). Time after stroke onset, gender, or occlusion site (ICA vs MCA) were not significantly different among different collateral groups. There was no correlation between time and DWI volume (r2=0.02, p=0.8) or collateral status (r2=0.05, p=0.6). There was significant correlation between collateral status and infarct growth (r2=-0.6,p&lt;0.0001). Conclusion: AIS patients with good collaterals have small initial DWI lesion volumes and slower infarct growth rates. These patients may be candidates for treatment options outside traditional time windows.

Abstract TP40: Prediction of a Small DWI Lesion Using Single Phase Collateral Score and Noncontrast CT ASPECT Score

Introduction and Hypothesis: Small initial DWI lesion volume (≤70 mL) is a strong predictor of favorable outcome post i IA thrombectomy and has been used for patient selection in multiple clinical trials. We sought to investigate if collateral and/or CT ASPECT scores could predict a small DWI lesion volume. Methods: We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who underwent DWI within 8 hours of stroke onset. DWI lesion volumes were dichotomized to small (≤70mL) and large (&gt;70ml). Collateral vessels were categorized to 5 groups: 0=none, 1=minimal, 2=less than 50%, 3=more than 50%, 4=equal and 5=more than the contralateral side. Logistic regression, ROC curve analyses and weighted Kappa test were performed. Results: In 130 patients, 62 female (48%), the average values (mean±SD) were: age 70±17 years, NIHSS 16±6, DWI volume 59±65 mL, time after stroke onset 4.4±1.8 hours, CT ASPECT score 6±2 and collateral score 3±1. Time, age, gender, or occlusion site (ICA vs MCA) were not independent predictors of a small DWI volume with p values all &gt;0.05. Collateral score (OR 6.32, P&lt;0.0001), CT ASPECT score (OR 2.37, P&lt;0.0001), and NIHSS (OR 0.87, P&lt;0.0003) significantly contributed to prediction of a small DWI volume. ROC curve analysis with both ASPECT and collateral scores contributing to predicted probabilities showed an AUC of 0.93. The AUC was 0.88 and 0.85 for collateral and ASPECT scores alone respectively. Collateral score ≥3 with ASPECT ≥9 yields specificity of 97.4% and sensitivity of 48.9% while collateral score ≥4 alone provides specificity of 97.4% and sensitivity of 38.9%, missing approximately 16% and 43% of potential candidates for IA therapy based on a DWI lesion volume &lt; 70 mL respectively. Inter-rater agreements between two neuroradiologists were k=0.53 (41.5% agreement) for collateral and k=0.53 (32.3% agreement) for ASPECT scores. Conclusion: Collateral score alone or combined with ASPECTS can predict a small DWI lesion volume with high specificity. However, sensitivity is relatively low and inter-rater agreement is fair. These findings should be considered when DWI is not available to select patients for IA therapy.

Computed tomography–based quantification of lesion water uptake identifies patients within 4.5 hours of stroke onset: A multicenter observational study

Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours, the time window of thrombolysis. Perfusion CT was used to identify ischemic brain tissue, and its density was measured in native CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. The optimal cutoff value of water uptake distinguishing stroke onset within and beyond 4.5 hours was calculated in patients with proximal middle cerebral artery occlusion (derivation cohort) with known time of symptom onset. The so-derived cutoff value was validated in a prospective cohort from other stroke centers. Of 178 patients of the derivation cohort, 147 (82.6%) had CT within 4.5 hours. Percentage water uptake was significantly lower in patients with stroke onset within compared to beyond 4.5 hours. The area under the receiver operating characteristic curve for distinguishing these patient groups according to percentage water uptake was 0.999 (95% confidence interval = 0.996-1.000, p < 0.001) with an optimal cutoff value of 11.5%. Applying this cutoff to the validation cohort of 240 patients, sensitivity was 98.6%, specificity 90.5%, positive predictive value 99.1%, and negative predictive value 86.4%. Quantification of brain water uptake identifies stroke patients with symptom onset within 4.5 hours with high accuracy and may guide the decision to use thrombolysis in patients with unknown time of stroke onset. Ann Neurol 2016;80:924-934.

A stress-related explanation to the increased blood pressure and its course following ischemic stroke

BackgroundA hypertensive response after ischemic stroke is frequent, yet its pathophysiology is unknown. Mechanisms related to local ischemic damage, major vascular occlusion, and psychological stress due to acute illness have been proposed. We assessed the natural course of blood pressure (BP) within the first 24 h in groups of ischemic stroke patients with different characteristics. We hypothesized that a consistent BP reduction, regardless of stroke location, time window from debut to admission and presence of persistent vascular occlusion, would favor a stress-related mechanism as an important cause of the hypertensive response after ischemic stroke.MethodsIschemic stroke patients (n=1067) were prospectively registered, and BP was measured on admission and <3 h, 3–6 h, 6–12 h and 12–24 h after admission. Patients were categorized according to the location of diffusion-weighted imaging (DWI) lesions (cortical, large subcortical, mixed cortico-subcortical, lacunar, cerebellar, brain stem or multiple), time window (admitted within or after 6 h of symptom onset) and presence of persistent proximal middle cerebral artery (MCA) occlusion versus normal findings on magnetic resonance angiography (MRA) at 24 h.ResultsA reduction in systolic BP and diastolic BP from baseline to 12–24 h was found across all DWI locations except for diastolic BP in cerebellar (P=0.072) lesions. Apart from diastolic BP in patients with normal MRA findings at 24 h (P=0.060), a significant fall in systolic BP and diastolic BP at 12–24 h was registered, irrespective of whether patients were admitted within 6 h or after 6 h of stroke onset or had persistent MCA occlusion versus normal MRA findings.ConclusionWe found a relatively consistent decline in BP within 24 h after admission across different stroke locations in patients admitted within or after 6 h of stroke onset and in patients with persistent MCA occlusion. Our findings suggest that a systemic factor such as psychological stress may be an important contributor to the frequently elevated BP on admission in patients with ischemic stroke.