Start, Stop, Continue? The Benefit of Overlapping Intravenous Thrombolysis and Mechanical Thrombectomy : A Matched Case-control Analysis from the German Stroke Registry.

OBJECTIVE: Here we compare the procedural and clinical outcome of patients undergoing thrombectomy with running thrombolysis to matched controls with completed intravenous therapy and an only marginally overlapping activity. METHODS: Patients from 25 sites in Germany were included, who presented with an acute ischemic stroke. Patients' baseline characteristics (including ASPECTS, NIHSS and mRS), grade of reperfusion, and functional outcome 24 h and at day 90 after intervention were extracted from the German Stroke Registry (n = 2566). In a case-control design we stepwise matched the groups due to age, sex and time to groin puncture and time to flow restoration. RESULTS: In the initial cohort (overlap group n = 864, control group n = 1702) reperfusion status (median TICI in overlap group vs. control group: 3 vs. 2b), NIHSS after 24 h, early neurological improvement parameters, mRS at 24 h and at day 90 were significantly better in the overlap group (p < 0.001) with a similar risk of bleeding (2.9% vs. 2.4%) and death (18% vs. 22%). After adjustment mRS at day 90 still showed a trend for lower disability scores in the overlap group (3 IQR 1-5 vs. 3 IQR 1-6, p = 0.09). While comparable bleeding risk could be maintained (4% in both groups), there were significantly more deaths in the control group (18% vs. 30%, p = 0.006). CONCLUSION: The presented results support the approach of continuing and completing a simultaneous administration of intravenous thrombolysis during mechanical thrombectomy procedures.

Further Development of Combined Techniques Using Stent Retrievers, Aspiration Catheters and BGC : The PROTECTPLUS Technique.

PURPOSE: First pass complete (mTICI 3) reperfusion must be regarded as the ultimate goal in mechanical thrombectomy (MT) in patients suffering from an emergent large vessel occlusion (ELVO). With this in mind a technical modification of the previously published PROTECT (PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy) approach, the PROTECTPLUS technique was evaluated. Under proximal flow arrest using a balloon guide catheter (BGC), a stent retriever was only partially inserted into a large-bore aspiration catheter. This construction was subsequently retracted as a unit into the BGC with aspiration both at the aspiration catheter and at the BGC. METHODS: A case-control study was performed comparing the PROTECT technique with the PROTECTPLUS technique with respect to the technical and procedural parameters. Patients n = 165 (101 PROTECT, 64 PROTECTPLUS) with ELVO of either the terminus of the internal carotid artery or the proximal middle cerebral artery were included. RESULTS: Using the PROTECTPLUS resulted in a higher rate of first pass complete reperfusions (59.4% vs. 27.7%, p < 0.001) as compared with PROTECT. The PROTECTPLUS also led to shorter procedure times (21 min vs. 37 min, p = 0.001) and higher rates of overall complete reperfusion (73.5% vs. 49.5%, p = 0.014) compared to PROTECT. CONCLUSION: The PROTECTPLUS technique is a promising technical modification to further optimize endovascular stroke treatment.

The Atherosclerosis Risk Variant rs2107595 Mediates Allele-Specific Transcriptional Regulation of HDAC9 via E2F3 and Rb1.

Background and Purpose- Genome-wide association studies have identified the HDAC9 (histone deacetylase 9) gene region as a major risk locus for atherosclerotic stroke and coronary artery disease in humans. Previous results suggest a role of altered HDAC9 expression levels as the underlying disease mechanism. rs2107595, the lead single nucleotide polymorphism for stroke and coronary artery disease resides in noncoding DNA and colocalizes with histone modification marks suggestive of enhancer elements. Methods- To determine the mechanisms by which genetic variation at rs2107595 regulates HDAC9 expression and thus vascular risk we employed targeted resequencing, proteome-wide search for allele-specific nuclear binding partners, chromatin immunoprecipitation, genome-editing, reporter assays, circularized chromosome conformation capture, and gain- and loss-of-function experiments in cultured human cell lines and primary immune cells. Results- Targeted resequencing of the HDAC9 locus in patients with atherosclerotic stroke and controls supported candidacy of rs2107595 as the causative single nucleotide polymorphism. A proteomic search for nuclear binding partners revealed preferential binding of the E2F3/TFDP1/Rb1 complex (E2F transcription factor 3/transcription factor Dp-1/Retinoblastoma 1) to the rs2107595 common allele, consistent with the disruption of an E2F3 consensus site by the risk allele. Gain- and loss-of-function studies showed a regulatory effect of E2F/Rb proteins on HDAC9 expression. Compared with the common allele, the rs2107595 risk allele exhibited higher transcriptional capacity in luciferase assays and was associated with higher HDAC9 mRNA levels in primary macrophages and genome-edited Jurkat cells. Circularized chromosome conformation capture revealed a genomic interaction of the rs2107595 region with the HDAC9 promoter, which was stronger for the common allele as was the in vivo interaction with E2F3 and Rb1 determined by chromatin immunoprecipitation. Gain-of-function experiments in isogenic Jurkat cells demonstrated a key role of E2F3 in mediating rs2107595-dependent transcriptional regulation of HDAC9. Conclusions- Collectively, our findings imply allele-specific transcriptional regulation of HDAC9 via E2F3 and Rb1 as a major mechanism mediating vascular risk at rs2107595.

Functional Outcome Following Stroke Thrombectomy in Clinical Practice.

Background and Purpose- Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of endovascular treatment reperfusion rates and functional outcome on a countrywide scale. Methods- Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0-2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders. Results- Median age was 75 years (interquartile range, 64-82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10-19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio [OR], 1.06; 95% CI, 1.05-1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03-1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08-1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15-1.39), alteplase use (OR, 1.49; 95% CI, 1.08-2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45-1.96). Conclusions- High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Thrombocytopenia and declines in platelet counts: predictors of mortality and outcome after mechanical thrombectomy.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) has well-known risk factors. The role of platelets in patients treated using mechanical thrombectomy (MT) has not been studied. The aim of this study was to study if there is an association of initial thrombocytopenia (TP) and a decline of platelets counts (DPC) with the clinical outcomes, mortality and intracranial hemorrhage (ICH) rates in AIS patients treated with MT. MATERIALS AND METHODS: In a case-control study consecutive MT-stroke patients were analyzed. A multivariate logistic regression model was used to test for good clinical outcome (mRS 90 days <= 2) and mortality adjusting for age, initial NIHSS, pretreatment with tPA, statins and platelet inhibitors, occlusion site, time from symptom onset to recanalization, initial TP (< 150 × 109/L) and DPC (> 26%). Additionally, rates of ICH were compared. RESULTS: Of 294 patients included, 9.6% had an initial TP and 23.8% a DPC > 26%. The mortality rate in patients with normal platelet counts was 26.1% vs. 48.3% (p = 0.002) in patients with initial TP with an aOR of 3.47 (CI 1.28-9.4, p = 0.005). No difference regarding the rate of good clinical outcome (p = 0.204) and ICH (p = 0.18) was observed. A DPC of more than 26% during the first 5 days of hospitalization predicted the rate of mortality (aOR 2.4 CI 1.14-5.04, p = 0.021) and the chances of a good clinical outcome (aOR 0.291 CI 0.128-0.666, p = 0.003) without significant differences of ICH rates (p = 0.735). CONCLUSION: In AIS patients treated with MT an initial TP was independently associated with higher mortality rates and a marked DPC with higher mortality rates as well as poorer clinical outcomes.

Hippocampus subfield volumetry after microsurgical or endovascular treatment of intracranial aneurysms-an explorative study.

BACKGROUND: To study hippocampus subfield volumes in patients after microsurgical clipping (MC) and/or endovascular coiling (EC) of intracranial aneurysms. METHODS: Hippocampus subfield volumetry was performed using FreeSurfer v6.0 in 51 patients (35 females, mean age 54.9 ± 11.9 years, range 24-78 years). Visual inspection of image and segmentation quality was performed prior to statistical analyses. Multiple regression analysis, controlled for age, sex, and side of treatment, was used to assess the impact of prior MC and history of subarachnoid haemorrhage (SAH) on hippocampus subfield volumes (cornu ammonis (CA)-2/3, CA-4, subiculum). Partial correlation analyses were used to assess effect of multiple treatments on hippocampus subfield volumes. RESULTS: Prior MC was significantly associated with lower hippocampal subfield volumes in MC patients for right and left CA-2/3 (ß = -22.32 [-40.18, -4.45]; p = 0.016 and ß = -20.03 [-39.38, -0.68]; p = 0.043) and right CA-4 (ß = -17.00 [-33.86, 0.12]; p = 0.048). History of SAH was not significantly associated with hippocampal subfield volumes. We observed a higher disease burden in the MC cohort. The number of aneurysms correlated with right-sided hippocampal subfield volumes while the number of treatment interventions did not. CONCLUSION: In this explorative study, we found that history of MC was significantly associated with lower volumes in distinct hippocampal subfields, which may be a consequence of a more extensive treatment. This could indicate specific atrophy of CA-2/3 after MC and should motivate hippocampal subfield assessment in larger cohorts.

Automated Calculation of the Alberta Stroke Program Early CT Score: Feasibility and Reliability.

Background The Alberta Stroke Program Early CT Score (ASPECTS) evaluation is a qualitative method to evaluate focal hypoattenuation at brain CT in early acute stroke. However, interobserver agreement is only moderate. Purpose To compare ASPECTS calculated by using an automatic software tool to neuroradiologist evaluation in the setting of acute stroke. Materials and Methods For this retrospective study, consensus ASPECTS were defined by two neuroradiologists based on baseline noncontrast CTs collected from January 2017 to December 2017 from patients with an occlusion in the middle cerebral artery and from an additional cohort of patients suspected of having stroke and no large vessel occlusion. Imaging data from both baseline and follow-up CT was evaluated for the consensus reading. After 6 weeks, the same two neuroradiologists again determined ASPECTS by using only the baseline CT. For comparison, ASPECTS was also calculated from baseline CT images by using a commercially available software (RAPID ASPECTS). Both methods were compared by using weighted κ statistics. Results CT scans from 100 patients with middle cerebral artery occlusion (44 women [mean age ± standard deviation, 75 years ± 14] and 56 men [mean age, 71 years ± 14]) and 52 patients suspected of having stroke and no large vessel occlusion (19 women [mean age, 69 years ± 18] and 33 men [68 years ± 15]) were evaluated. Neuroradiologists showed moderate agreement with the consensus score (κ = 0.57 and κ = 0.56). Software analysis showed substantial agreement (κ = 0.9) with the consensus score. Software analysis showed a substantial agreement (κ = 0.78) after greater than 1 hour between symptom onset and imaging, which increased to high agreement (κ = 0.92) in the time window greater than 4 hours. The neuroradiologist raters did not achieve comparable results to the software until the time interval of greater than 4 hours (κ = 0.83 and κ = 0.76). Conclusion In acute stroke of the middle cerebral artery, the Alberta Stroke Program Early CT score calculated with automated software had better agreement than that of human readers with a predefined consensus score. © RSNA, 2019 Online supplemental material is available for this article.

Vertebral Artery Patency and Thrombectomy in Basilar Artery Occlusions.

Background and Purpose- Factors influencing recanalization success in basilar artery occlusions are largely unknown. Preliminary evidence has suggested that flow arrest in the vertebral artery contralateral to the catheter bearing vertebral artery may facilitate recanalization. The aim of this analysis was to assess the impact of anatomic variations and flow conditions on recanalization success in basilar artery occlusion treated with mechanical thrombectomy. Methods- Consecutive basilar artery occlusions treated with second-generation thrombectomy devices at a single-center were retrospectively analyzed. Baseline patients' characteristics, occlusion length, collateral circulation, underlying stenosis, incomplete occlusions, and patency of the vertebral arteries were analyzed with regards to recanalization success. Aplastic or hypoplastic vertebral artery contralateral to the catheter position was defined as contralateral low flow condition. Logistic regression analysis was used to examine the association between anatomic variations and flow conditions in relation to complete recanalization and the modified Rankin Scale score while controlling for several potentially confounding variables. Clinical impact was evaluated using the modified Rankin Scale score of ≤3. Results- One hundred fifteen patients were included (mean age 71.5±12.8, m:f=2:1, median National Institutes of Health Stroke Scale =15, interquartile range =10-22). Complete recanalization was more often observed in patients with contralateral low flow conditions (80.6% versus 50.0%), which remained an independent predictor of complete recanalization in multivariable analysis (adjusted odds ratio, 5.81; 95% CI, 1.97-17.19). Patients with complete posterior recanalization had lower in-hospital mortality (16.4% versus 41.7%) and more often achieved modified Rankin Scale score of ≤3 (49.4% versus 8.3%), even after adjusting for potential confounders (adjusted odds ratio, 15.93; 95% CI, 1.42-179.00). Conclusions- Contralateral low flow condition (vertebral artery aplasia or hypoplasia) seems to be an independent factor for fewer distal emboli and complete recanalization in basilar artery occlusion patients treated by modern endovascular devices. Complete recanalization reflecting the absence of peri-interventional clot fragmentation brings clear clinical benefit. Further studies are warranted to evaluate the need for contralateral flow modulation or ipsilateral balloon guide catheter during posterior circulation thrombectomy in patients with bilaterally patent vertebral arteries.

Endovascular Stroke Treatment on Single-Plane vs. Bi-Plane Angiography Suites : Technical Considerations and Evaluation of Treatment Success.

INTRODUCTION: Endovascular stroke therapy is mostly available in comprehensive stroke centers with state of the art bi-plane angiography suites. The aim of the present study was to analyze if it is justifiable to treat patients with alternative x­ray machines in the case of capacity constraints, or if it is mandatory to refer patients in such cases. Secondly, we wanted to draw conclusions for the feasibility of different logistic approaches in stroke treatment, such as a "helistroke" concept. METHODS: This was a retrospective dual center analysis of all patients treated on a single-plane angiography suite between 2009 and 2017. A propensity scored matching analysis at a 1:3 ratio was performed with patients treated on a bi-plane angiography suite to receive homogeneous groups. RESULTS: A total of 42 patients were treated on a single-plane angiography suite and were compared to 126 patients treated on a bi-plane angiography suite. No significant differences in technical parameters, procedure times, recanalization success and complications could be detected. Also, there was no difference in the clinical outcome between the two groups. The only significant difference was the higher amount of radiation dose used on the bi-plane angiography machines to achieve the final results (205,660 mGy × cm2 vs. 114,565 mGy × cm2; p < 0.001). DISCUSSION: In an era of an ever-changing stroke infrastructure and an increasing demand in thrombectomy procedures, it is feasible and safe for experienced neurointerventionalists to perform endovascular stroke procedures on single-plane angiography units.

Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology.

Background and Purpose- Intracranial thrombi can be characterized according to their permeability as measured by contrast agent penetration. Thrombus composition and its associated pathogenesis are important factors affecting treatment and secondary prevention. We aimed to explore the histopathologic factors explaining the heterogeneity of thrombus permeability measures and evaluated potential correlations with stroke pathogenesis. Methods- Thrombus densities were measured in thin-slice noncontrast computed tomography and automatically aligned computed tomographic angiography images of 133 patients with large-vessel occlusions of the middle cerebral artery. Change in thrombus attenuation (Δt) and corrected void fraction (ε; attenuation increase corrected for contralateral artery densities) were calculated. First, these thrombus perviousness measures were correlated with histological thrombus components (especially fractions of fibrin-platelet accumulation and red blood cells) and stroke pathogenesis (n=32). For validation, an association between perviousness and pathogenesis was assessed in a second, independent cohort (n=101). Results- Thrombus perviousness estimates were correlated with both fibrin/platelets fractions (Δt: r=0.43, P=0.016/ε: r=0.45, P=0.01) and inversely with red blood cells counts (Δt: r=-0.46, P=0.01/ε: r=-0.49, P=0.006). In the first cohort, Δt was substantially higher in samples from patients with cardioembolic stroke pathogenesis as compared with noncardioembolic-derived thrombi ( P=0.026). In the validation cohort, thrombus perviousness measures differed significantly between cardioembolic (Δt: median [ interquartile range]=12.53 [8.70-17.90]; ε: median [interquartile range]=0.054 [0.036-0.082]) and noncardioembolic thrombi (Δt: median [interquartile range]=3.2 [2.17-6.44], P<0.001; ε: median [interquartile range]=0.020 [0.011-0.027], P<0.001) and were associated with pathogenesis (Δt: ß=0.45, P=0.016/ε: ß=83.6, P=0.013) in a binary logistic regression model. Conclusions- Permeable thrombi showed a strong correlation with lower fractions of red blood cells counts and more fibrin/platelets conglomerations, concurrent with an association with cardioembolic origin. This novel information about thrombus perviousness may be valuable as a new and simple to acquire imaging marker for identifying stroke pathogenesis using early and readily available imaging.

Worse endovascular mechanical recanalization results for patients with in-hospital onset acute ischemic stroke.

OBJECTIVE: Strokes with onset inside the hospital account for approximately 2-17% of all acute ischemic strokes. The few existing studies addressing these in-hospital strokes lack a thorough analysis of patients who underwent endovascular mechanical thrombectomy-the state of the art therapy for acute strokes due to large vessel occlusions. The objective of the study was to evaluate the efficacy and safety of mechanical revascularization therapy in in-hospital stroke patients. METHODS: In a single-center case-control study, a propensity score-matched analysis in a 1:2 ratio with the covariates sex, age, type of occluded large vessel, i.v. thrombolysis, and National Institutes of Health Stroke Scale prior to endovascular mechanical thrombectomy was performed. All identified in-hospital stroke patients between 2010 and 2017 were matched to two consecutive out-of-hospital stroke patients. RESULTS: 27 in-hospital strokes were compared to 54 out-of-hospital strokes. After propensity score matching, the baseline characteristics were well balanced between these groups. The times for symptom onset to alarm, symptom onset to imaging, symptom onset/alarm to start of recanalization and symptom onset to final recanalization respectively were faster in in-hospital stroke patients. In contrast, the recanalization procedure itself took significantly longer in in-house patients and had a significantly lower rate of technical success resulting in significantly worse clinical outcomes. CONCLUSION: The recognition, assessment and pre-interventional procedures of patients with in-hospital strokes and subsequent mechanical thrombectomy are favorable. Nevertheless, in-hospital stroke patients display inferior recanalization results and poorer clinical outcomes. Furthermore, we find mechanical thrombectomy seems safe for treatment of in-hospital strokes.

Presence of the Posterior Communicating Artery Contributes to the Clinical Outcome After Endovascular Treatment of Patients with MCA Occlusions.

PURPOSE: In patients with acute occlusions of the middle cerebral artery, the collaterals play an important role in infarct growth and potentially on clinical outcome. As the primary collateral pathway, the posterior cerebral artery with the posterior communicating artery (PComA) is important. We analyzed the influence of the presence of an ipsilateral PComA on infarct growth and clinical outcome. METHODS: We included 101 patients with M1 occlusions and subsequent endovascular treatment and differentiated patients without an ipsilateral PComA from those with an ipsilateral PComA. RESULTS: There was no difference in the rate of successful recanalizations and procedural parameters between both groups. Of the patients with an existing PComA, 51% showed an excellent clinical outcome (90d mRS < 2), but only 28% of the patients without PComA had an excellent clinical outcome (p = 0.02). The presence of an ipsilateral PComA was independently associated with the rate of excellent clinical outcome (aOR 3.9, 95% CI 1.2-9.8; p = 0.021) and lower infarct volume (38 ± 8 cm3 vs. 78 ± 13 cm3, p = 0.032). CONCLUSION: The presence of an ipsilateral PComA is a predictor for excellent clinical outcome independently from the technical success of mechanical recanalization. This finding provides insights into the changes of circulation in patients suffering from an acute stroke and underlines the importance of collateralization.

PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy - evaluation of a double embolic protection approach in endovascular stroke treatment.

PURPOSE: Stent retriever-based mechanical thrombectomy (MT) for emergent large vessel occlusions (ELVO) is often complicated by thrombus fragmentation causing distal embolization and embolization to new vascular territories. Well-established embolic protection approaches include proximal flow arrest and distal aspiration techniques during stent retriever maneuvers. Aiming at the reduction of thrombus fragmentation during MT we evaluated a technical approach combining proximal balloon occlusion together with direct thrombus aspiration during MT: the PROTECT technique. METHODS: We performed a case-control study comparing the PROTECT technique with sole distal aspiration during MT regarding technical and procedural parameters, n=200 patients with ELVO of either the terminus of the internal carotid artery or the proximal middle artery were included. RESULTS: PROTECT resulted in a shorter procedure time (29 vs 40 min; P=0.002), in a higher rate of successful recanalizations (100% vs 78%; P=0.001) and a higher rate of complete reperfusions (70% vs 39%; P<0.001) compared with sole distal aspiration during MT. CONCLUSION: The PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Pathogenic ischemic stroke phenotypes in the NINDS-stroke genetics network.

BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.