Long-term morphological changes of symptomatic lacunar infarcts and surrounding white matter on structural MRI

The contributing studies were funded by the Chief Scientist Office of the Scottish Executive (grant 217 NTU R37933), the Wellcome Trust (grants 075611 and WT088134/Z/09/A), and Row Fogo Charitable Trust. The imaging was performed at the Brain Research Imaging Centre Edinburgh, which is supported by the SINAPSE (Scottish Imaging Network, A Platform for Scientific Excellence) collaboration and the Chief Scientist Office of the Scottish Government (http://www.bric.ed.ac.uk/). This work was supported by European Union Horizon 2020 (EU H2020), PHC- 03 to 15, project No. 666881, SVDs@Target, and the Fondation Leducq Transatlantic Network of Excellence for Study of Perivascular Spaces in Small Vessel Disease, ref No. 16 CVD 05. Dr Loos was supported by the Dutch Alzheimer Foundation.Peer reviewedPublisher PD

Estimating the Magnitude of Genetic Factors by Calculating the Genetic Relative Risk of Stroke in First-Ever Lacunar Stroke Patients

BACKGROUND: Positive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke. METHODS: By questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated. PRINCIPAL FINDINGS: We collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45-3.53) for overall first-degree relatives, 4.52 (95%CI 3.61-5.65) for patients' parents and 2.10 (95%CI 1.63-2.69) for patients' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size. CONCLUSIONS: We found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke

Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension

Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a “total SVD score” was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0–4) in each patient. Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function remained significant after adjustment for age, sex, education, anxiety and depression score, potential vascular risk factors, patient group, and baseline cognitive performance. Conclusion: Our study shows that a total SVD score can predict cognitive decline, specifically in executive function, over 4 years in hypertensive patients. This emphasizes the importance of considering total brain damage due to SVD

Prediction of final infarct volume from native CT perfusion and treatment parameters using deep learning

CT Perfusion (CTP) imaging has gained importance in the diagnosis of acute stroke. Conventional perfusion analysis performs a deconvolution of the measurements and thresholds the perfusion parameters to determine the tissue status. We pursue a data-driven and deconvolution-free approach, where a deep neural network learns to predict the final infarct volume directly from the native CTP images and metadata such as the time parameters and treatment. This would allow clinicians to simulate various treatments and gain insight into predicted tissue status over time. We demonstrate on a multicenter dataset that our approach is able to predict the final infarct and effectively uses the metadata. An ablation study shows that using the native CTP measurements instead of the deconvolved measurements improves the prediction.Comment: Accepted for publication in Medical Image Analysi

Equal performance of aspiration and stent retriever thrombectomy in daily stroke treatment

BACKGROUND: Mechanical thrombectomy with stent retrievers has proved to be safe and effective in endovascular treatment of acute ischemic stroke. Direct aspiration has shown revascularization rates comparable to those of stent retrievers in the recent ASTER and COMPASS trials. However, the efficacy of aspiration in routine clinical practice has not yet been shown. OBJECTIVE: To show that aspiration has clinical and technical outcomes equal to those of stent retriever thrombectomy in daily clinical practice. METHODS: We analysed data of patients with a large vessel occlusion of the anterior circulation registered in the Dutch MR CLEAN Registry between March 2014 and June 2016. Primary outcome was functional outcome measured with the modified Rankin Scale (mRS) score. Secondary outcomes were reperfusion grade, periprocedural complication rate, and procedure duration. Association of treatment technique with functional outcome was estimated with univariable and multivariable ordinal logistic regression analysis and expressed as a common OR (cOR) for a shift towards better outcome on the mRS. RESULTS: As first-line treatment, 207 of 1175 patients (17.6%) were treated with direct aspiration, and 968 (82.4%) by a stent retriever. We observed no differences in functional outcome (adjusted cOR=1.020 (95% CI 0.68 to 1.52)) and periprocedural complications. Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b) was similar. Duration of the procedure was shorter with aspiration (57 min (IQR 35-73) vs 70 min (IQR 47-95), p<0.0001). CONCLUSION: Direct aspiration shows clinical outcomes equal to those of stent retriever thrombectomy in our large multicenter real-life cohort. We found no difference in complication rates and shorter procedure times for aspiration

A Comprehensive View on MRI Techniques for Imaging Blood-Brain Barrier Integrity

The blood-brain barrier (BBB) is the interface between the blood and brain tissue, which regulates the maintenance of homeostasis within the brain. Impaired BBB integrity is increasingly associated with various neurological diseases. To gain a better understanding of the underlying processes involved in BBB breakdown, magnetic resonance imaging (MRI) techniques are highly suitable for noninvasive BBB assessment. Commonly used MRI techniques to assess BBB integrity are dynamic contrast-enhanced and dynamic susceptibility contrast MRI, both relying on leakage of gadolinium-based contrast agents. A number of conceptually different methods exist that target other aspects of the BBB. These alternative techniques make use of endogenous markers, such as water and glucose, as contrast media. A comprehensive overview of currently available MRI techniques to assess the BBB condition is provided from a scientific point of view, including potential applications in disease. Improvements that are required to make these techniques clinically more easily applicable will also be discussed.</p

Aspiration Versus Stent Retriever Thrombectomy for Posterior Circulation Stroke

BACKGROUND AND PURPOSE: Whereas a clear benefit of endovascular treatment for anterior circulation stroke has been established, randomized trials assessing the posterior circulation have failed to show efficacy. Previous studies in anterior circulation stroke suggest that advanced thrombectomy devices were of great importance in achieving clinical benefit. Little is known about the effect of thrombectomy techniques on outcomes in posterior circulation stroke. In this study, we compare first-line strategy of direct aspiration to stent retriever thrombectomy for posterior circulation stroke. METHODS: We analyzed data of patients with a posterior circulation stroke who were included in the Multicentre Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry between March 2014 and December 2018, a prospective, nationwide study, in which data were collected from consecutive patients who underwent endovascular treatment for ischemic stroke in the Netherlands. We compared patients who underwent first-line aspiration versus stent retriever thrombectomy. Primary outcome was functional outcome according to the modified Rankin Scale. Secondary outcomes were reperfusion grade, complication rate, and procedure duration. Associations between thrombectomy technique and outcome measures were estimated with multivariable ordinal logistic regression analyses. RESULTS: Overall, 71 of 205 patients (35%) were treated with aspiration, and 134 (65%) with stent retriever thrombectomy. Patients in the aspiration group had a lower pc-ASPECTS on baseline computed tomography, and general anesthesia was more often applied in this group. First-line aspiration was associated with better functional outcome compared with stent retriever thrombectomy (adjusted common odds ratio for a 1-point improvement on the modified Rankin Scale 1.94 [95% CI, 1.03-3.65]). Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2B) was achieved more often with aspiration (87% versus 73%, P=0.03). Symptomatic hemorrhage rates were comparable (3% versus 4%). Procedure times were shorter in the aspiration group (49 versus 69 minutes P<0.001). CONCLUSIONS: In this retrospective nonrandomized cohort study, our findings suggest that first-line aspiration is associated with a shorter procedure time, better reperfusion, and better clinical outcome than stent retriever thrombectomy in patients with ischemic stroke based on large vessel occlusion in the posterior circulation

Repeated Endovascular Thrombectomy in Patients With Acute Ischemic Stroke: Results From a Nationwide Multicenter Database

Background and Purpose- Patients with acute ischemic stroke treated with endovascular thrombectomy may be treated with repeat endovascular thrombectomy (rEVT) in case of recurrent large vessel occlusion. Data on safety and efficacy of these interventions is scarce. Our aim is to report on frequency, timing, and outcome of rEVT in a large nation-wide multicenter registry. Methods- In the Netherlands, all patients with endovascular thrombectomy have been registered since 2002 (MR CLEAN Pretrial registry, MR CLEAN Trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], and MR CLEAN Registry). We retrospectively reviewed these databases for anterior circulation rEVT cases. Patient characteristics, procedural data, and functional outcome (modified Rankin Scale at 90 days) were analyzed. Results- Of 3928 patients treated between 2002 and 2017, 27 (0.7%) underwent rEVT. Median time between first and second procedure was 78 (1-1122) days; 11/27 patients were re-treated within 30 days. Cardioembolism was the most common etiology (18 patients [67%]). In 19 patients (70%), recurrent occlusion occurred ipsilateral to previous occlusion. At 90 days after rEVT procedure, 44% of the patients had achieved functional independence (modified Rankin Scale score of 0-2), and 33% had died. Adverse events were 2/27 (7.4%) intracranial hemorrhage, 1/27 (3.7%) stroke progression, and 1/27 (3.7%) pneumonia. Conclusions- In this large nationwide cohort of patients with acute ischemic stroke treated with endovascular thrombectomy, rEVT was rare. Stroke cause was mainly cardio-embolic, and most recurrent large vessel occlusions in which rEVT was performed occurred ipsilateral. Although there probably is a selection bias on repeated treatment in case of recurrent large vessel occlusion, rEVT appears safe, with similar outcome as in single-treated cases

Acute Endovascular Treatment of Patients With Ischemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO.Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24–48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO.Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (resp. mean −5 vs. mean −1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (−4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00).Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD

Posttreatment Ischemic Lesion Evolution Is Associated With Reduced Favorable Functional Outcome in Patients With Stroke

BACKGROUND AND PURPOSE: Ischemic lesion volume can increase even 24 hours after onset of an acute ischemic stroke. In this study, we investigated the association of lesion evolution with functional outcome and the influence of successful recanalization on this association. METHODS: We included patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) who received good quality noncontrast CT images 24 hours and 1 week after stroke onset. The ischemic lesion delineations included infarct, edema, and hemorrhagic transformation. Lesion evolution was defined as the difference between the volumes measured on the 1-week and 24-hour noncontrast CTs. The association of lesion evolution with functional outcome was evaluated using unadjusted and adjusted logistic regression. Adjustments were made for baseline, clinical, and imaging parameters that were associated P<0.10) in univariate analysis with favorable functional outcome, defined as modified Rankin Scale score of ≤2. Interaction analysis was performed to evaluate the influence of successful recanalization, defined as modified Arterial Occlusion Lesion score of 3 points, on this association. RESULTS: Of the 226 patients who were included, 69 (31%) patients achieved the favorable functional outcome. Median lesion evolution was 22 (interquartile range, 10–45) mL. Lesion evolution was significantly inversely correlated with favourable functional outcome: unadjusted odds ratio, 0.76 (95% CI, 0.66–0.86; per 10 mL of lesion evolution; P<0.01) and adjusted odds ratio: 0.85 (95% CI, 0.72–0.97; per 10 mL of lesion evolution; P=0.03). There was no significant interaction of successful recanalization on the association of lesion evolution and favorable functional outcome (odds ratio, 1.01 [95% CI, 0.77–1.36]; P=0.94). CONCLUSIONS: In our population, subacute ischemic lesion evolution is associated with unfavorable functional outcome. This study suggests that even 24 hours after onset of stroke, deterioration of the brain continues, which has a negative effect on functional outcome. This finding may warrant additional treatment in the subacute phase