Introduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular ... Show moreIntroduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations.Methods and analysis A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after similar to 90 days and includes assessments of the patient's medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including 'OMICs' technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes.Ethics and dissemination The study was approved by the Charite-Universitatsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations.Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx? TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/DRKS00023323. Recruitment started on January 1, 2021. Show less
Background: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT... Show moreBackground: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT through femoral versus alternative arterial access. Methods: In this observational study, we included patients from the MR CLEAN Registry who underwent EVT for acute ischemic stroke in the anterior circulation between 2014 and 2019 in the Netherlands. Patients who underwent EVT through alternative and femoral access were matched on propensity scores in a 1:3 ratio. The primary endpoint was favorable functional outcome (modified Rankin Scale score ≤ 2) at 90 days. Secondary endpoints were early neurologic recovery, mortality, successful intracranial reperfusion and puncture related complications. Results: Of the 5197 included patients, 17 patients underwent EVT through alternative access and were matched to 48 patients who underwent EVT through femoral access. Alternative access was obtained through the common carotid artery (n = 15/17) and brachial artery (n = 2/17). Favorable functional outcome was less often observed after EVT through alternative than femoral access (18% versus 27%; aOR, 0.36; 95% CI, 0.05–2.74). The rate of successful intracranial reperfusion was higher for alternative than femoral access (88% versus 58%), although mortality (59% versus 31%) and puncture related complications (29% versus 0%) were more common after alternative access. Conclusions: EVT through alternative arterial access is rarely performed in the Netherlands and seems to be associated with worse outcomes than standard femoral access. A next step would be to compare the additional value of EVT through alternative arterial access after failure of femoral access. Show less
Hernandez, K.E.R.; Groot, J.H. de; Baas, F.; Stijntjes, M.; Grootendorst-Heemskerk, E.R.M.; Schiemanck, S.K.; ... ; Mugge, W. 2023
Individuals with an upper motor neuron syndrome, e.g., stroke survivors, may have a pathological increase of passive ankle stiffness due to spasticity, that impairs ankle function and activities... Show moreIndividuals with an upper motor neuron syndrome, e.g., stroke survivors, may have a pathological increase of passive ankle stiffness due to spasticity, that impairs ankle function and activities such as walking. To improve mobility, walking aids such as ankle-foot orthoses and orthopaedic shoes are prescribed. However, these walking aids generally limit the range of motion (ROM) of the foot and may therewith negatively influence activities that require a larger ROM. Here we present a new ankle-foot orthosis “Hermes”, and its first experimental results from four hemiparetic chronic stroke patients. Hermes was designed to facilitate active ankle dorsiflexion by mechanically compensating the passive ankle stiffness using a negative-stiffness mechanism. Four levels of the Hermes’ stiffness compensation (0%, 35%, 70% and 100%) were applied to evaluate active ROM in a robotic ankle manipulator and to test walking feasibility on an instrumented treadmill, in a single session. The robotic tests showed that Hermes successfully compensated the ankle joint stiffness in all four patients and improved the active dorsiflexion ROM in three patients. Three patients were able to walk with Hermes at one or more Hermes’ stiffness compensation levels and without reducing their preferred walking speeds compared to those with their own walking aids. Despite a small sample size, the results show that Hermes holds great promise to support voluntary ankle function and to benefit walking and daily activities. Show less
Krivoshein, G.; Bakreen, A.; Maagdenberg, A.M.J.M. van den; Malm, T.; Giniatullin, R.; Jolkkonen, J. 2022
Stroke can be followed by immediate severe headaches. As headaches are initiated by the activation of trigeminal meningeal afferents, we assessed changes in the activity of meningeal afferents in... Show moreStroke can be followed by immediate severe headaches. As headaches are initiated by the activation of trigeminal meningeal afferents, we assessed changes in the activity of meningeal afferents in mice subjected to cortical photothrombosis. Cortical photothrombosis induced ipsilateral lesions of variable sizes that were associated with contralateral sensorimotor impairment. Nociceptive firing of mechanosensitive Piezo1 channels, activated by the agonist Yoda1, was increased in meningeal afferents in the ischemic hemispheres. These meningeal afferents also had a higher maximal spike frequency at baseline and during activation of the mechanosensitive Piezo1 channel by Yoda1. Moreover, in these meningeal afferents, nociceptive firing was active during the entire induction of transient receptor potential vanilloid 1 (TRPV1) channels by capsaicin. No such activation was observed on the contralateral hemi-skulls of the same group of mice or in control mice. Our data suggest the involvement of mechanosensitive Piezo1 channels capable of maintaining high-frequency spiking activity and of nociceptive TRPV1 channels in trigeminal headache pain responses after experimental ischemic stroke in mice. Show less
Background: Acute audiovestibular loss is a neurotologic emergency of which the etiology is frequently unknown. In vestibular neuritis a viral genesis is expected, although there is insufficient... Show moreBackground: Acute audiovestibular loss is a neurotologic emergency of which the etiology is frequently unknown. In vestibular neuritis a viral genesis is expected, although there is insufficient evidence to support viruses as the only possible etiological factor. In sudden deafness, a vascular etiology has been proposed in elderly patients, since cardiovascular risk factors are more frequently present and a higher risk of developing a stroke was seen compared to the general population. So far, very little research has been carried out on vascular involvement in elderly patients with vestibular neuritis. Cardiovascular risk factors have a positive correlation with cerebral small vessel disease, visible as white matter hyperintensities, brain infarctions, microbleeds and lacunes on MRI. The presence of these characteristics indicate a higher risk of developing a stroke. Aim: We investigated whether elderly patients with vestibular neuritis have a higher prevalence of vascular lesions on MRI compared to a control cohort. Materials and Methods: Patients of 50-years and older, diagnosed with vestibular neuritis in a multidisciplinary tertiary referral hospital, were retrospectively reviewed and compared to a control cohort. The primary outcome was the difference in cerebral small vessel disease on MRI imaging, which was assessed by the number of white matter hyperintensities using the ordinal Fazekas scale. Secondary outcomes were the presence of brain infarctions on MRI and the difference in cardiovascular risk factors. Results: Patients with vestibular neuritis (N = 101) had a 1.60 higher odds of receiving a higher Fazekas score than the control cohort (N = 203) (p = 0.048), there was no difference in presence of brain infarctions (p = 1.0). Hyperlipidemia and atrial fibrillation were more common in patients experiencing vestibular neuritis. Conclusion: We found a positive correlation of white matter hyperintensities and VN which supports the hypothesis of vascular involvement in the pathophysiology of vestibular neuritis in elderly patients. Further prospective research is necessary to confirm this correlation. Show less
Vos, E.M.; Geraedts, V.J.; Lugt, A. van der; Dippel, D.W.J.; Wermer, M.J.H.; Hofmeijer, J.; ... ; Wijngaard, I.R. van den 2022
Background: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective... Show moreBackground: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS. Methods: A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included. Results: We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT. Conclusion: Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT. Show less
Background: Endovascular treatment (EVT) is standard of care in anterior circulation large vessel occlusions. In posterior circulation occlusions, data on EVT in isolated posterior cerebral artery ... Show moreBackground: Endovascular treatment (EVT) is standard of care in anterior circulation large vessel occlusions. In posterior circulation occlusions, data on EVT in isolated posterior cerebral artery (PCA) occlusions are limited, although PCA occlusions can cause severe neurological deficit. Objective: To describe in a prospective study the clinical manifestations, outcomes, and safety of EVT in isolated PCA occlusions. Methods: We used data (2014-2017) from the MR CLEAN Registry, a nationwide, prospective cohort of EVT-treated patients in the Netherlands. We included patients with acute ischemic stroke (AIS) due to an isolated PCA occlusion on CT angiography. Patients with concurrent occlusion of the basilar artery were excluded. Outcomes included change in National Institutes of Health Stroke Scale (Delta NIHSS) score, modified Rankin Scale (mRS) score 0-3 after 90 days, mortality, expanded Thrombolysis in Cerebral Infarction (eTICI), and periprocedural complications. Results: Twenty (12%) of 162 patients with posterior circulation occlusions had an isolated PCA occlusion. Median age was 72 years; 13 (65%) were women. Median baseline NIHSS score was 13 (IQR 5-21). Six (30%) patients were comatose. Twelve patients (60%) received IVT. Median Delta NIHSS was -4 (IQR -11-+1). At follow-up, nine patients (45%) had mRS score 0-3. Seven (35%) died. eTICI 2b-3 was achieved in 13 patients (65%). Nine patients (45%) had periprocedural complications. No symptomatic intracranial hemorrhages (sICH) occurred. Conclusions: EVT should be considered in selected patients with AIS with an isolated PCA occlusion, presenting with moderate-severe neurological deficits, as EVT was technically feasible in most of our patients and about half had good clinical outcome. In case of lower NIHSS score, a more conservative approach seems warranted, since periprocedural complications are not uncommon. Nonetheless, EVT seems reasonably safe considering the absence of sICH in our study. Show less
Background: Analyses of the effect of pre-stroke functional levels on the outcome of endovascular therapy (EVT) have focused on the course of patients with moderate to substantial pre-stroke... Show moreBackground: Analyses of the effect of pre-stroke functional levels on the outcome of endovascular therapy (EVT) have focused on the course of patients with moderate to substantial pre-stroke disability. The effect of complete freedom from pre-existing disability (modified Rankin Scale (mRS) 0) versus predominantly mild pre-existing disability/symptoms (mRS 1-2) has not been well delineated. Methods: The HERMES meta-analysis pooled data from seven randomized trials that tested the efficacy of EVT. We tested for a multiplicative interaction effect of pre-stroke mRS on the relationship between treatment and outcomes. Ordinal regression was used to assess the association between EVT and 90-day mRS (primary outcome) in the subgroup of patients with pre-stroke mRS 1-2. Multivariable regression modeling was then used to test the effect of mild pre-stroke disability/symptoms on the primary and secondary outcomes (delta-mRS, mRS 0-2/5-6) compared with patients with pre-stroke mRS 0. Results: We included 1764 patients, of whom 199 (11.3%) had pre-stroke mRS 1-2. No interaction effect of pre-stroke mRS on the relationship between treatment and outcome was observed. Patients with pre-stroke mRS 1-2 had worse outcomes than those with pre-stroke mRS 0 (adjusted common OR (acOR) 0.53, 95% CI 0.40 to 0.70). Nonetheless, a significant benefit of EVT was observed within the mRS 1-2 subgroup (cOR 2.08, 95% CI 1.22 to 3.55). Conclusions: Patients asymptomatic/without disability prior to onset have better outcomes following EVT than patients with mild disability/symptoms. Patients with pre-stroke mRS 1-2, however, more often achieve good outcomes with EVT compared with conservative management. These findings indicate that mild pre-existing disability/symptoms influence patient prognosis after EVT but do not diminish the EVT treatment effect. Show less
Background Higher expanded Treatment In Cerebral Ischemia (eTICI) reperfusion scores after endovascular treatment (EVT) are associated with better outcomes. However, the influence of the number of... Show moreBackground Higher expanded Treatment In Cerebral Ischemia (eTICI) reperfusion scores after endovascular treatment (EVT) are associated with better outcomes. However, the influence of the number of passes on this association is unclear. We aimed to compare outcomes of single-pass good reperfusion (eTICI 2B) with multiple-pass excellent/complete reperfusion (eTICI 2C/3) in daily clinical practice. Methods We compared outcomes of patients in the MR CLEAN Registry with good reperfusion (eTICI 2B) in a single pass to those with excellent/complete reperfusion (eTICI 2C/3) in multiple passes. Regression models were used to investigate the association of single-pass eTICI 2B versus multiple-pass eTICI 2C/3 reperfusion with 90-day functional outcome (modified Rankin Scale (mRS)), functional independence (mRS 0-2), per-procedural complications and safety outcomes. Results We included 699 patients: 178 patients with single-pass eTICI 2B, and 242 and 279 patients with eTICI 2C/3 after 2 and >= 3 passes, respectively. Patients with eTICI 2C/3 after 2 or >= 3 passes did not achieve significantly better functional outcomes compared with patients with single-pass eTICI 2B (adjusted common OR (acOR) 1.06, 95% CI 0.75 to 1.50 and acOR 0.88, 95% CI 0.74 to 1.05 for 90-day mRS, and adjusted OR (aOR) 1.24, 95% CI 0.78 to 1.97 and aOR 0.79, 95% CI 0.52 to 1.22 for functional independence). Conclusions Our results did not show better outcomes for patients who achieved eTICI 2C/3 in multiple, that is, two or more, passes when compared with patients with single-pass eTICI 2B. However, this concerns observational data. Further research is necessary to investigate the per-pass effect in relation to reperfusion and functional outcome. Show less
Voorst, H. van; Kunz, W.G.; Berg, L.A. van den; Kappelhof, M.; Pinckaers, F.M.E.; Goyal, M.; ... ; Majoie, C.B.L.M. 2021
Background The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster... Show moreBackground The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. Methods A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of euro80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. Results EVT administered 1 min faster resulted in a median NMB of euro309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -euro15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. Conclusion One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs. Show less
Objective This qualitative study investigated patients' needs and wishes in relation to patient navigation. Design A qualitative interview study was conducted. Participants were invited to take... Show moreObjective This qualitative study investigated patients' needs and wishes in relation to patient navigation. Design A qualitative interview study was conducted. Participants were invited to take part in three in-depth interviews over a period of 6-12 months. Thematic analysis was used. Setting Interviewees were sought in the Berlin metropolitan area of Germany in academic university hospitals, in rehabilitation clinics and through self-help organisations. Participants The sample consisted of individuals diagnosed with lung cancer (n=20) or stroke (n=20). Results From the perspective of interviewees, patient navigators should function as consistent contact persons, present during the whole care trajectory. Their role would be to guide patients through an often confusing healthcare landscape, offering practical, advisory and emotional assistance corresponding to patients' needs. The study shows that-independent of the disease-participants had similar expectations and needs regarding support from navigators. Conclusion For chronic and complex diseases-as is the case with lung cancer and stroke-it appears less important for navigators to fulfil disease-specific tasks. Rather, they should ensure that patients' more general needs, in relation to social, practical and emotional support, are met in a way that suits their individual wishes. Following these results, patient navigation programmes might be designed to include generic elements, which should then be adapted to the infrastructure in a particular healthcare region and to the particularities of a specific healthcare system. Show less
OBJECTIVE Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and... Show moreOBJECTIVE Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and mortality. Furthermore, they aimed to assess the effectiveness of intravenous alteplase treatment and endovascular treatment (EVT), as well as the best first-line EVT approach in patients with CCE. METHODS The Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry is a prospective, observational multicenter registry of patients treated with EVT for acute ischemic stroke in 16 intervention hospitals in the Netherlands. The association of CCE with functional outcome, reperfusion, and mortality was evaluated using logistic regression models. Univariable comparisons were made to determine the effectiveness of intravenous alteplase treatment and the best first-line EVT approach in CCE patients. RESULTS The study included 3077 patients from the MR CLEAN Registry. Fifty-five patients (1.8%) had CCE. CCE were not significantly associated with worse functional outcome (adjusted common OR 0.71, 95% CI 0.44-1.15), and 29% of CCE patients achieved functional independence. An extended Thrombolysis in Cerebral Infarction score >= 2B was significantly less often achieved in CCE patients compared to non-CCE patients (adjusted OR [aOR] 0.52, 95% CI 0.28- 0.97). Symptomatic intracranial hemorrhage occurred in 8 CCE patients (15%) vs 171 of 3022 non-CCE patients (6%; p = 0.01). The median improvement on the National Institutes of Health Stroke Scale (NIHSS) was 2 in CCE patients versus 4 in non-CCE patients (p = 0.008). CCE were not significantly associated with mortality (aOR 1.16, 95% CI 0.64-2.12). Intravenous alteplase use in CCE patients was not associated with functional outcome or reperfusion. In CCE patients with successful reperfusion, stent retrievers were more often used as the primary treatment device (p = 0.04). CONCLUSIONS While patients with CCE had significantly lower reperfusion rates and less improvement on the NIHSS after EVT, CCE were not significantly associated with worse functional outcome or higher mortality rates. Therefore, EVT should still be considered in this specific group of patients. Show less
Accumulating evidence pinpoints sex differences in stroke incidence, etiology and outcome. Therefore, more understanding of the sex-specific mechanisms that lead to ischemic stroke and aggravation... Show moreAccumulating evidence pinpoints sex differences in stroke incidence, etiology and outcome. Therefore, more understanding of the sex-specific mechanisms that lead to ischemic stroke and aggravation of secondary damage after stroke is needed. Our current mechanistic understanding of cerebral ischemia states that endothelial quiescence in neurovascular units (NVUs) is a major physiological parameter affecting the cellular response to neuron, astrocyte and vascular smooth muscle cell (VSMC) injury. Although a hallmark of the response to injury in these cells is transcriptional activation, noncoding RNAs such as microRNAs exhibit cell-type and context dependent regulation of gene expression at the post-transcriptional level. This review assesses whether sex-specific microRNA expression (either derived from X-chromosome loci following incomplete X-chromosome inactivation or regulated by estrogen in their biogenesis) in these cells controls NVU quiescence, and as such, could differentiate stroke pathophysiology in women compared to men. Their adverse expression was found to decrease tight junction affinity in endothelial cells and activate VSMC proliferation, while their regulation of paracrine astrocyte signaling was shown to neutralize sex-specific apoptotic pathways in neurons. As such, these microRNAs have cell type-specific functions in astrocytes and vascular cells which act on one another, thereby affecting the cell viability of neurons. Furthermore, these microRNAs display actual and potential clinical implications as diagnostic and prognostic biomarkers in ischemic stroke and in predicting therapeutic response to antiplatelet therapy. In conclusion, this review improves the current mechanistic understanding of the molecular mechanisms leading to ischemic stroke in women and highlights the clinical promise of sex-specific microRNAs as novel diagnostic biomarkers for (silent) ischemic stroke. Show less
Research links high blood pressure variability (BPV) with stroke and cerebrovascular disease, however, its association with cognition remains unclear. Moreover, it remains uncertain which BP... Show moreResearch links high blood pressure variability (BPV) with stroke and cerebrovascular disease, however, its association with cognition remains unclear. Moreover, it remains uncertain which BP-derived parameter (ie, variability or mean) holds more significance in understanding vascular contributions to cognitive impairment. We searched PubMed, Embase, PsycINFO, and Scopus and performed a meta-analysis of studies that quantified the association between resting BPV with dementia or cognitive impairment in adults. Two authors independently reviewed all titles, abstracts, and full-texts and extracted data, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Study quality was assessed using the (modified) Newcastle-Ottawa Scale. A multilevel meta-analysis was used, which included effect sizes for both BPV and mean BP, with a combined end point of dementia or cognitive impairment as primary outcome. In the primary analysis, 54 effect sizes were extracted from 20 studies, with a total analytical sample of n=7 899 697. Higher systolic BPV (odds ratio [OR], 1.25 [95% CI, 1.16-1.35]), mean systolic pressure (OR, 1.12 [95% CI, 1.02-1.29]), diastolic BPV (OR, 1.20 [95% CI, 1.12-1.29]), and mean diastolic pressure (OR, 1.16 [95% CI, 1.04-1.29]) were associated with dementia and cognitive impairment. A direct comparison showed that mean BP effect sizes were less strong than BPV effect sizes (OR, 0.92 [95% CI, 0.87-0.97], P<0.01), indicating that the relative contribution of BPV exceeded that of mean BP. Methodological and statistical heterogeneity was high. Secondary analyses were less consistent as to whether BPV and mean BP were differentially associated with dementia subtypes and cognitive domains. Future studies are required to investigate BPV as a target for dementia prevention. Show less
There are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to... Show moreThere are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to focus on germinal matrix-intraventricular hemorrhage (GMH-IVH) and white matter injury. Data about perinatal arterial ischemic stroke (PAIS) or cerebral sinovenous thrombosis (CSVT) in the preterm infant are very limited. In fact, several large cohort studies on neuro-imaging in preterm infants do not even mention neonatal stroke.(1-4) Most studies about PAIS exclude preterm infants.(5) The aim of this review was to provide an update on neonatal stroke in the preterm infant, with a focus on neuro-imaging findings. (c) 2021 The Authors. Published by Elsevier Inc. Show less
Wiegertjes, K.; Jansen, M.G.; Jolink, W.M.T.; Duering, M.; Koemans, E.A.; Schreuder, F.H.B.M.; ... ; Leeuw, F.E. de 2021
Introduction: It is unclear why cerebral small vessel disease (SVD) leads to lacunar stroke in some and to non-lobar intracerebral hemorrhage (ICH) in others. We investigated differences in MRI... Show moreIntroduction: It is unclear why cerebral small vessel disease (SVD) leads to lacunar stroke in some and to non-lobar intracerebral hemorrhage (ICH) in others. We investigated differences in MRI markers of SVD in patients with lacunar stroke or non-lobar ICH.Patients and methods: We included patients from two prospective cohort studies with either lacunar stroke (RUN DMC) or non-lobar ICH (FETCH). Differences in SVD markers (white matter hyperintensities [WMH], lacunes, cerebral microbleeds [CMB]) between groups were investigated with univariable tests; multivariable logistic regression analysis, adjusted for age, sex, and vascular risk factors; spatial correlation analysis and voxel-wise lesion symptom mapping.Results: We included 82 patients with lacunar stroke (median age 63, IQR 57-72) and 54 with non-lobar ICH (66, 59-75). WMH volumes and distribution were not different between groups. Lacunes were more frequent in patients with a lacunar stroke (44% vs. 17%, adjusted odds ratio [aOR] 5.69, 95% CI [1.66-22.75]) compared to patients with a non-lobar ICH. CMB were more frequent in patients with a non-lobar ICH (71% vs. 23%, aOR for lacunar stroke vs non-lobar ICH 0.08 95% CI [0.02-0.26]), and more often located in non-lobar regions compared to CMB in lacunar stroke.Discussion: Although we obserd different types of MRI markers of SVD within the same patient, ischemic markers of SVD were more frequent in the ischemic type of lacunar stroke, and hemorrhagic markers were more prevalent in the hemorrhagic phenotype of non-lobar ICH.Conclusion: There are differences between MRI markers of SVD between patients with a lacunar stroke and those with a non-lobar ICH. Show less
Background Machine learning algorithms hold the potential to contribute to fast and accurate detection of large vessel occlusion (LVO) in patients with suspected acute ischemic stroke. We assessed... Show moreBackground Machine learning algorithms hold the potential to contribute to fast and accurate detection of large vessel occlusion (LVO) in patients with suspected acute ischemic stroke. We assessed the diagnostic performance of an automated LVO detection algorithm on CT angiography (CTA). Methods Data from the MR CLEAN Registry and PRESTO were used including patients with and without LVO. CTA data were analyzed by the algorithm for detection and localization of LVO (intracranial internal carotid artery (ICA)/ICA terminus (ICA-T), M1, or M2). Assessments done by expert neuroradiologists were used as reference. Diagnostic performance was assessed for detection of LVO and per occlusion location by means of sensitivity, specificity, and area under the curve (AUC). Results We analyzed CTAs of 1110 patients from the MR CLEAN Registry (median age (IQR) 71 years (60-80); 584 men; 1110 with LVO) and of 646 patients from PRESTO (median age (IQR) 73 years (62-82); 358 men; 141 with and 505 without LVO). For detection of LVO, the algorithm yielded a sensitivity of 89% in the MR CLEAN Registry and a sensitivity of 72%, specificity of 78%, and AUC of 0.75 in PRESTO. Sensitivity per occlusion location was 88% for ICA/ICA-T, 94% for M1, and 72% for M2 occlusion in the MR CLEAN Registry, and 80% for ICA/ICA-T, 95% for M1, and 49% for M2 occlusion in PRESTO. Conclusion The algorithm provided a high detection rate for proximal LVO, but performance varied significantly by occlusion location. Detection of M2 occlusion needs further improvement. Show less
Smit, J.M.; Simon, J.; Mahdiui, M. el; Szaraz, L.; Rosendael, P.J. van; Kolassvary, M.; ... ; Bax, J.J. 2021
Background: The left atrial appendage (LAA) has been regarded as an important source of cardiac thrombus formation and appears important in the contribution to thromboembolism in patients with... Show moreBackground: The left atrial appendage (LAA) has been regarded as an important source of cardiac thrombus formation and appears important in the contribution to thromboembolism in patients with atrial fibrillation (AF). Our aim was to evaluate the relationship between LAA morphology and previous stroke or transient ischemic attack in 2 large and distinct patient cohorts with and without known AF. Methods: The study population consisted of patients with and without drug-refractory AF who underwent computed tomography before transcatheter AF ablation or clinically indicated for suspected coronary artery disease. The computed tomography data were used for volumetric assessment of the left atrium and LAA and to determine LAA morphology. The LAA was classified by 3 readers in consensus as chicken wing, swan, cauliflower, or windsock, based on predefined morphology classification criteria. Results: In total, 1813 patients (mean age 59 +/- 11 years, 42% female) who underwent computed tomography were included in this analysis (908 patients with AF and 905 patients without known AF). Swan LAA morphology was independently associated with prior stroke/transient ischemic attack in the overall study population (odds ratio, 3.40, P<0.001), and in patients with (odds ratio, 2.88, P=0.012) and without known AF (odds ratio, 3.96, P=0.011). Conclusions: Swan morphology of the LAA is independently associated with prior stroke or transient ischemic attack in patients with known AF, as well as in patients not previously diagnosed with AF. Show less
Background Approximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We... Show moreBackground Approximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We aimed to quantify the importance of predictors of poor functional outcome despite successful reperfusion. Methods We analyzed patients from the MR CLEAN Registry between March 2014 and November 2017 with successful reperfusion (extended Thrombolysis In Cerebral Infarction >= 2B). First, predictors were selected based on expert opinion and were clustered according to acquisition over time (ie, baseline patient factors, imaging factors, treatment factors, and postprocedural factors). Second, several models were constructed to predict 90-day functional outcome (modified Rankin Scale (mRS)). The relative importance of individual predictors in the most extensive model was expressed by the proportion of unique added chi(2) to the model of that individual predictor. Results Of 3180 patients, 1913 (60%) had successful reperfusion. Of these 1913 patients, 1046 (55%) were functionally dependent at 90 days (mRS >2). The most important predictors for mRS were baseline patient factors (ie, pre-stroke mRS, added chi(2) 0.16; National Institutes of Health Stroke Scale score at baseline, added chi(2) 0.12; age, added chi(2) 0.10), and postprocedural factors (ie, symptomatic intracranial hemorrhage (sICH), added chi(2) 0.12; pneumonia, added chi(2) 0.09). The probability of functional independence for a typical stroke patient with sICH was 54% (95% CI 36% to 72%) lower compared with no sICH, and 21% (95% CI 4% to 38%) for pneumonia compared with no pneumonia. Conclusion Baseline patient factors and postprocedural adverse events are important predictors of poor functional outcome in successfully reperfused patients with ischemic stroke. This implies that prevention of postprocedural adverse events has the greatest potential to further improve outcomes in these patients. Show less
Cardioaortic embolism to the brain accounts for approximately 15-30% of ischaemic strokes and is often referred to as 'cardioembolic stroke'. One-quarter of patients have more than one cardiac... Show moreCardioaortic embolism to the brain accounts for approximately 15-30% of ischaemic strokes and is often referred to as 'cardioembolic stroke'. One-quarter of patients have more than one cardiac source of embolism and 15% have significant cerebrovascular atherosclerosis. After a careful work-up, up to 30% of ischaemic strokes remain 'cryptogenic', recently redefined as 'embolic strokes of undetermined source'. The diagnosis of cardioembolic stroke remains difficult because a potential cardiac source of embolism does not establish the stroke mechanism. The role of cardiac imaging-transthoracic echocardiography (TTE), transoesophageal echocardiography (TOE), cardiac computed tomography (CT), and magnetic resonance imaging (MRI)-in the diagnosis of potential cardiac sources of embolism, and for therapeutic guidance, is reviewed in these recommendations. Contrast TTE/TOE is highly accurate for detecting left atrial appendage thrombosis in patients with atrial fibrillation, valvular and prosthesis vegetations and thrombosis, aortic arch atheroma, patent foramen ovale, atrial septal defect, and intracardiac tumours. Both CT and MRI are highly accurate for detecting cavity thrombosis, intracardiac tumours, and valvular prosthesis thrombosis. Thus, CT and cardiac magnetic resonance should be considered in addition to TTE and TOE in the detection of a cardiac source of embolism. We propose a diagnostic algorithm where vascular imaging and contrast TTE/TOE are considered the first-line tool in the search for a cardiac source of embolism. CT and MRI are considered as alternative and complementary tools, and their indications are described on a case-by-case approach. Show less
