Sex differences in clot, vessel and tissue characteristics in patients with a large vessel occlusion treated with endovascular thrombectomy.

INTRODUCTION: To improve our understanding of the relatively poor outcome after endovascular treatment (EVT) in women we assessed possible sex differences in baseline neuroimaging characteristics of acute ischemic stroke patients with large anterior vessel occlusion (LVO). PATIENTS AND METHODS: We included all consecutive patients from the MR CLEAN Registry who underwent EVT between 2014 and 2017. On baseline non-contrast CT and CT angiography, we assessed clot location and clot burden score (CBS), vessel characteristics (presence of atherosclerosis, tortuosity, size, and collateral status), and tissue characteristics with the Alberta Stroke Program Early Computed Tomography Score (ASPECTS). Radiological outcome was assessed with the extended thrombolysis in cerebral infarction score (eTICI) and functional outcome with the modified Rankin Scale score (mRS) at 90 days. Sex-differences were assessed with multivariable regression analyses with adjustments for possible confounders. RESULTS: 3180 patients were included (median age 72 years, 48% women). Clots in women were less often located in the intracranial internal carotid artery (ICA) (25%vs 28%, odds ratio (OR) 0.85;95% confidence interval: 0.73-1.00). CBS was similar between sexes (median 6, IQR 4-8). Intracranial (aOR 0.73;95% CI:0.62-0.87) and extracranial (aOR 0.64;95% CI:0.43-0.95) atherosclerosis was less prevalent in women. Vessel tortuosity was more frequent in women in the cervical ICA (aOR 1.89;95% CI:1.39-2.57) and women more often had severe elongation of the aortic arch (aOR 1.38;95% CI:1.00-1.91). ICA radius was smaller in women (2.3vs 2.5 mm, mean difference 0.22;95% CI:0.09-0.35) while M1 radius was essentially equal (1.6vs 1.7 mm, mean difference 0.09;95% CI:-0.02-0.21). Women had better collateral status (⩾50% filling in 62%vs 53% in men, aOR 1.48;95% CI:1.29-1.70). Finally, ASPECT scores were equal between women and men (median 9 in both sexes, IQR 8-10vs 9-10). Reperfusion rates were similar between women and men (acOR 0.94;95% CI:0.83-1.07). However, women less often reached functional independence than men (34%vs 46%, aOR 0.68;95% CI:0.53-0.86). DISCUSSION AND CONCLUSION: On baseline imaging of this Dutch Registry, men and women with LVO mainly differ in vessel characteristics such as atherosclerotic burden, extracranial vessel tortuosity, and collateral status. These sex differences do not result in different reperfusion rates and are, therefore, not likely to explain the worse functional outcome in women after EVT.

Development and validation of a prediction model for failure of the transfemoral approach of endovascular treatment for large vessel occlusion acute ischemic stroke.

INTRODUCTION: Extracranial vascular characteristics determine the accessibility of the large vessel intracranial occlusion for endovascular treatment (EVT) in acute ischemic stroke. We developed and validated a prediction model for failure of the transfemoral approach to aid clinical decision making regarding EVT. METHODS: A prediction model was developed from data of patients included in the Dutch multicenter MR CLEAN Registry (March 18th 2014 until June 15th 2016) with penalized logistic regression. Predictor variables were available prior to the EVT procedure and included age, hypertension and extracranial vascular characteristics assessed on baseline CTA. The prediction model was internally validated, temporally validated within a second MR CLEAN Registry cohort (June 15th 2016 until November 1st 2017) and updated by re-estimating the coefficients using the combined cohort. RESULTS: Failure of the transfemoral approach occurred in 7% of patients, in both cohorts (derivation cohort: n=887, median age 71 years, interquartile range [IQR] 60-80, 52% men; validation cohort: n=1111, median age 73 years, IQR 62-81, 51% men). The prediction model had a c-statistic of 0.81 (95%CI: 0.76-0.86) in the derivation cohort, 0.69 (95%CI: 0.62-0.75) at temporal validation, and 0.75 (95%CI: 0.71-0.79) in the final prediction model, with the following penalized ß-coefficients for predictors age (per decade): 0.26, hypertension: -0.16, severe aortic arch elongation: 1.45, bovine aortic arch: 0.44, elongation of the supra-aortic arteries: 0.72, cervical ICA elongation: 0.44, and high-grade stenosis of the cervical ICA: 0.78. CONCLUSION: Our prediction model showed good performance for prediction of failure to reach the intracranial occlusion by the transfemoral approach.

The prognostic value of extracranial vascular characteristics on procedural duration and revascularization success in endovascularly treated acute ischemic stroke patients.

Introduction: Vascular anatomy might affect endovascular treatment success in acute ischemic stroke patients with large vessel occlusion. We investigated the prognostic value of extracranial vascular characteristics on procedural time and revascularization success in patients with large vessel occlusion in the anterior cerebral circulation. Patients and methods: We included 828 patients endovascularly treated within 6.5 hours of symptom onset from the Dutch MR CLEAN-Registry. We evaluated aortic arch configuration, stenosis and tortuosity of supra-aortic arteries, and internal carotid arteries (ICAs) on pre-intervention CTA. We constructed logistic prediction models for outcome variables procedural duration (≥60 minutes) and non-successful revascularization (extended thrombolysis in cerebral infarction (eTICI) of 0-2A) using baseline characteristics and assessed the effect of extracranial vascular characteristics on model performance. Results: Cervical ICA tortuosity and stenosis ≥99% improved prediction of long procedural duration compared with baseline characteristics from area under the curve of 0.61 (95% CI: 0.57-0.65) to 0.66 (95% CI: 0.62-0.70) (P < 0.001). Cervical ICA tortuosity was significantly associated with non-successful recanalization. Prediction of non-successful revascularization did not improve after including aortic arch elongation, acute take-off angle, aortic variant, origin stenosis of supra-aortic arteries, and cervical ICA tortuosity, with an area under the curve of 0.63 (95% CI: 0.59-0.67) compared with 0.59 (95% CI: 0.55-0.63) (P = 0.11). Conclusion: Extracranial vascular characteristics have additional prognostic value for procedural duration, but not for revascularization success, compared with baseline characteristics. Performance of both prediction models is limited in patients treated for large vessel occlusion.

CT Angiography of the Heart and Aorta in TIA and Ischaemic Stroke: Cardioembolic Risk Sources and Clinical Implications.

BACKGROUND: Cardiac emboli are important causes of (recurrent) ischaemic stroke. Aorta atherosclerosis might also be associated with an increased risk of stroke recurrence. This study aimed to evaluate the yield and clinical implications of CT-angiography (CTA) of the heart and aorta in the diagnostic workup of transient ischaemic attack (TIA) or ischaemic stroke. METHODS: CTA of the heart and aortic arch was performed in TIA/ischaemic stroke patients, in addition to routine diagnostic workup. Occurrence of cardioembolic (CE) risk sources and complex aortic plaques were assessed. Implications of cardiac CTA for therapeutic management were evaluated RESULTS: Sixty-seven patients were included (TIA n = 33, ischaemic stroke n = 34) with a mean age of 68 years (range 51-89) and median NIHSS of 0 (interquartile range 0-2). CE risk sources were detected in 29 (43%) patients. An intracardiac thrombus was present in 2 patients (3%; TIA 0%; ischaemic stroke 6%). Medium/low-risk CE sources included mitral annular calcification (9%), aortic valve calcification (18%) and patent foramen ovale (18%). Complex aortic plaque was identified in 16 patients (24%). In two patients with an intracardiac thrombus, therapeutic management changed from antiplatelet to oral anticoagulation. CONCLUSIONS: CTA of the heart and aorta has a high yield for detection of embolic risk sources in TIA/ischaemic stroke, with clinical consequences for 6% of ischaemic stroke patients. Implementation of CTA of the heart and aorta in the acute stroke setting seems valuable, but cost-effectiveness of this approach remains to be determined.

Stroke progression and clinical outcome in ischemic stroke patients with a history of migraine.

BACKGROUND: Patients with migraine might be more susceptible of spreading depolarizations, which are known to affect vascular and neuronal function and penumbra recovery after stroke. We investigated whether these patients have more severe stroke progression and less favorable outcomes after recanalization therapy. METHODS: We included patients from a prospective multicenter ischemic stroke cohort. Lifetime migraine history was based on the International Classification of Headache Disorders II criteria. Patients without confirmed migraine diagnosis were excluded. Patients underwent CT angiography and CT perfusion <9 h of onset and follow-up CT after three days. On admission, presence of a perfusion deficit, infarct core and penumbra volume, and blood brain barrier permeability (BBBP) were assessed. At follow-up we assessed malignant edema, hemorrhagic transformation, and final infarct volume. Outcome at three months was evaluated with the modified Rankin Scale (mRS). We calculated adjusted relative risks (aRR) or difference of means (aB) with regression analyses. RESULTS: We included 600 patients of whom 43 had migraine. There were no differences between patients with or without migraine in presence of a perfusion deficit on admission (aRR: 0.98, 95%CI: 0.77-1.25), infarct core volume (aB: -10.8, 95%CI: -27.04-5.51), penumbra volume (aB: -11.6, 95%CI: -26.52-3.38), mean blood brain barrier permeability (aB: 0.08, 95%CI: -3.11-2.96), malignant edema (0% vs. 5%), hemorrhagic transformation (aRR: 0.26, 95%CI: 0.04-1.73), final infarct volume (aB: -14.8, 95%CI: 29.9-0.2) or outcome after recanalization therapy (mRS > 2, aRR: 0.50, 95%CI: 0.21-1.22). CONCLUSION: Elderly patients with a history of migraine do not seem to have more severe stroke progression and have similar treatment outcomes compared with patients without migraine.

Treatment and imaging of intracranial atherosclerotic stenosis: current perspectives and future directions.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is a common cause of stroke worldwide. It results in ischemic stroke due to different mechanisms including artery-to-artery embolism, in situ thrombo-occlusion, occlusion of perforating arteries, and hemodynamic failure. In this review, we present an overview of current treatment and imaging modalities in intracranial atherosclerotic stenosis. METHODS: PubMed was searched for relevant articles in English that evaluated the treatment and imaging of intracranial atherosclerotic stenosis (ICAS). RESULTS: Aggressive medical management, consisting of dual antiplatelet therapy and intensive risk factor management, is important in patients with ICAS because of a substantial risk of recurrent stroke, approximately 20% in the first year, in patients on aspirin or warfarin alone. Recent trials have suggested that, aggressive medical therapy results in better outcome as compared with intracranial stenting. However, the question remains what the optimal treatment strategy would be in patients with recurrent strokes in the setting of failed aggressive medical therapy. Moreover, controversy exists whether a subgroup of patients with symptomatic ICAS could benefit from intracranial stenting if selection is based on radiological evidence of hemodynamic failure. With regard to imaging, transcranial Doppler ultrasound and magnetic resonance angiography are useful screening tests for exclusion of ICAS, but need confirmation by other imaging modalities when stenosis is suggested. Computed tomography angiography has a high positive and negative predictive value for detection of intracranial luminal stenosis of 50% or higher, but performs worse than digital subtraction angiography with regard to establishing the exact degree of luminal stenosis. Novel imaging techniques including high-resolution CT and MRI better identify plaque characteristics than conventional imaging methods. CONCLUSIONS: Currently, aggressive medical management remains the standard of care for patients with ICAS. Further research is needed to identify high-risk subgroups and to develop more effective treatments for ICAS patients.

Cortical Venous Filling on Dynamic Computed Tomographic Angiography: A Novel Predictor of Clinical Outcome in Patients With Acute Middle Cerebral Artery Stroke.

BACKGROUND AND PURPOSE: Venous flow in the downstream territory of an occluded artery may influence patient prognosis after ischemic stroke. Our aim was to study cortical venous filling (CVF) in a time-resolved manner with dynamic computed tomographic angiography and to assess the relationship with clinical outcome. METHODS: Patients with a proximal middle cerebral artery occlusion underwent noncontrast CT and whole-brain CT perfusion/dynamic CT angiography within 9 hours after stroke-onset. We defined poor outcome as a modified Rankin Scale score of ≥3. Association between the extent and velocity of CVF and poor outcome at 3 months was analyzed with Poisson-regression. Prognostic value of optimal CVF (maximum opacification of cortical veins) in addition to age, stroke severity, treatment, Alberta Stroke Program Early CT score, cerebral blood flow, and collateral status was assessed with logistic regression and summarized with the area under the curve. RESULTS: Eighty-eight patients were included, with a mean age of 67 years. By combining the extent and velocity of optimal CVF, we observed a decreased risk of poor outcome in patients with good and fast optimal CVF, risk ratio of 0.5 (95% confidence interval, 0.3-0.7). Extent and velocity of optimal CVF had additional prognostic value (area under the curve, 0.88; 95% confidence interval, 0.77-0.98; P<0.02) compared with a model without CVF information. CONCLUSIONS: The combination of extent and velocity of optimal CVF, as assessed with dynamic CT angiography, is useful to identify patients with acute middle cerebral artery stroke at higher risk of poor clinical outcome at 3-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl/trialreg and http://www.clinicaltrials.gov. Unique identifier: NTR1804 and NCT00880113, respectively.

Impact of Collateral Status Evaluated by Dynamic Computed Tomographic Angiography on Clinical Outcome in Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: Status of collateral circulation is a strong predictor of outcome after acute ischemic stroke. Our aim was to compare the predictive value of strategies for collateral blood flow assessment with dynamic computed tomographic angiography (CTA) and conventional single-phase CT angiography. METHODS: Patients with a proximal middle cerebral artery occlusion underwent noncontrast CT, single-phase CTA and whole brain CT perfusion/dynamic CTA within 9 hours after stroke onset. We defined poor outcome as a score on the modified Rankin Scale score of ≥3. The association between collateral score and clinical outcome at 3 months was analyzed with Poisson regression. The prognostic value of collateral scoring with dynamic CTA and single-phase CTA in addition to age, stroke severity, and noncontrast CT was assessed with logistic regression and summarized with the area under the curve. RESULTS: Seventy patients were included, with a mean age of 68 years. We observed an increased risk of poor outcome in patients with poor collaterals on single-phase CTA (risk ratio, 1.8; 95% confidence interval, 1.0-3.1) and on dynamic CTA (risk ratio, 2.0; 95% confidence interval, 1.5-2.7). The prediction of poor clinical outcome by means of collateral adjustment was better with dynamic CTA (area under the curve, 0.84; likelihood ratio test P<0.01) than by single-phase CTA (area under the curve, 0.80; likelihood ratio test P=0.33). CONCLUSIONS: Collateral assessment with dynamic CTA better predicts clinical outcome at 3 months than single-phase conventional CTA. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl/trialreg. Unique identifier: NTR1804. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00880113.