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

Post-traumatic Winking Induced by Extension of the Hand: A Case Report of a Novel Synkinesis

Several synkinesis syndromes have been reported in the literature. Synkinesis syndromes are rare and are most commonly congenital or follow post-traumatic reinnervation. We describe a novel synkinesis syndrome that developed several months after cervical spinal cord infarction due to a herniated disc in a 29-year-old woman. When the patient overstretched the extensor muscles of the right hand, the right upper eyelid raised automatically and nasal congestion developed. We hypothesize that aberrant reinnervation of the intermediolateral columns of the spinal cord at level C8–T2 by motor neurons of the extensor muscles of the hand occurred

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

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

Endovascular Treatment for Acute Ischemic Stroke in Patients on Oral Anticoagulants: Results from the MR CLEAN Registry

Background and Purpose - The use of oral anticoagulants (OAC) is considered a contra-indication for intravenous thrombolytics as acute treatment of ischemic stroke. However, little is known about the risks and benefits of endovascular treatment in patients on prior OAC. We aim to compare outcomes after endovascular treatment between patients with and without prior use of OAC. Methods - Data of patients with acute ischemic stroke caused by an intracranial anterior circulation occlusion, included in the nationwide, prospective, MR CLEAN Registry between March 2014 and November 2017, were analyzed. Outcomes of interest included symptomatic intracranial hemorrhage and functional outcome at 90 days (modified Rankin Scale score). Outcomes between groups were compared with (ordinal) logistic regression analyses, adjusted for prognostic factors. Results - Three thousand one hundred sixty-two patients were included in this study, of whom 502 (16%) used OAC. There was no significant difference in the occurrence of symptomatic intracranial hemorrhage between patients with and without prior OACs (5% versus 6%; adjusted odds ratio, 0.63 [95% CI, 0.38-1.06]). Patients on OACs had worse functional outcomes than patients without OACs (common odds ratio, 0.57 [95% CI, 0.47-0.66]). However, this observed difference in functional outcome disappeared after adjustment for prognostic factors (adjusted common odds ratio, 0.91 [95% CI, 0.74-1.13]). Conclusions - Prior OAC use in patients treated with endovascular treatment for ischemic stroke is not associated with an increased risk of symptomatic intracranial hemorrhage or worse functional outcome compared with no prior OAC use. Therefore, prior OAC use should not be a contra-indication for endovascular treatment