Introduction The Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) trial showed efficacy of intra-arterial (IA) treatment in ...acute ischemic stroke (AIS). We studied the evolution of IA treatment for AIS and its effects on clinical outcome and recanalization in The Netherlands in the pre-MR CLEAN era. Methods Data on 517 patients with AIS treated with IA therapy were collected retrospectively from all intervention centers in The Netherlands from 2002 to the start of participation in the MR CLEAN trial. Clinical outcome was measured by means of the modified Rankin Scale score and recanalization with the Thrombolysis in Cerebral Infarction Scale. Results IA therapy was first used in patients with basilar artery occlusion. Over the years, there was a gradual increase in the number of anterior circulation strokes treated. There was a shift in applied therapies from primary IA therapy to combined intravenous and IA therapy and from IA thrombolysis to mechanical thrombectomy. Time from symptom onset to treatment decreased. Recanalization rates gradually increased. At the same time, there was a trend toward more favorable outcomes after 3 months and fewer deceased patients both at discharge and after 3 months. However, none of these changes reached statistical significance. Conclusion The treatment approach used in the MR CLEAN trial was the result of an evolution of practise in the preceding years, with gradual improvement in technical and clinical outcomes.
Introduction About 15% of patients with transient ischemic attack (TIA) or minor ischemic stroke have functional impairment after 3 months. We studied the role of whole brain computed tomography ...perfusion (WB-CTP) in the emergency diagnosis of TIA or minor stroke in predicting disability at 3 months. Methods We included patients with ongoing symptoms of a TIA or minor stroke with a National Institutes of Health Stroke Scale (NIHSS) score less than 4 who were evaluated with noncontrast CT (NCCT), CT angiography (CTA), and WB-CTP within 24 hours of symptom onset. Patients treated with thrombolysis or a premorbid modified Rankin Scale (mRS) score greater than 1 were excluded. The association between clinical or imaging features and disability (mRS score ≥2) at 3 months was analyzed with Poisson regression. Potential additional prognostic value of WB-CTP was assessed with logistic regression. Results We included 115 patients in 2012 to 2013. Median age was 68 years, and 66% were men. At 3 months, 20 patients (17%) were disabled. NIHSS score on admission (relative risk RR, 3.6; 95% confidence interval CI, 1.4-9.3), female sex (RR, 2.4; 95% CI, 1.1-5.3), early ischemic changes on NCCT (RR, 5.0; 95% CI, 2.6-9.9), extracranial or intracranial vessel stenosis ≥50% on CTA (RR, 3.0; 95% CI, 1.4-6.4), and perfusion abnormalities on WB-CTP (RR, 11.4; 95% CI, 4.6-28.2) were associated with disability at 3 months. In multivariable analysis, the relation between perfusion abnormalities and poor outcome remained essentially the same. WB-CTP showed prognostic value in addition to proved clinical and imaging predictors of disability. Conclusions WB-CTP is useful to identify patients with TIA or minor ischemic stroke at high risk of functional impairment at 3-month follow-up.
Summary Background Previous work suggests that impairments of cerebrovascular flow or reactivity might be early markers of cerebral amyloid angiopathy (CAA). Hereditary cerebral haemorrhage with ...amyloidosis–Dutch type (HCHWA-D) is a genetic form of CAA that can be diagnosed before the onset of clinical symptoms by DNA testing. We aimed to investigate whether haemodynamic measures are decreased in presymptomatic and symptomatic HCHWA-D mutation carriers compared with healthy controls. Methods In this case-control study, we included presymptomatic and symptomatic HCHWA-D mutation carriers diagnosed through genetic testing and recruited through the HCHWA-D patient association (Katwijk, Netherlands) and the outpatient clinic of the Department of Neurology of the Leiden University Medical Center (Leiden, Netherlands), and healthy controls. We measured regional cerebral blood flow (rCBF) using pseudo-continuous arterial spin labelling. Quantitative flow was measured by phase-contrast magnetic resonance angiography of the cerebropetal vessels. Vascular reactivity was established by measuring changes in blood-oxygen-level-dependent (BOLD) signal after visual stimulation. Data from presymptomatic and symptomatic individuals were compared with healthy controls using mixed-model regression analysis. Findings Between May 15, 2012, and December 22, 2015, we investigated cross-sectional imaging data from 27 HCHWA-D mutation carriers (12 presymptomatic and 15 symptomatic) and 33 healthy controls. Compared with controls, symptomatic HCHWA-D carriers had significantly decreased cortical grey matter rCBF in the occipital lobe (mean difference −11·1 mL/100 g per min, 95% CI −2·8 to −19·3; uncorrected p=0·010) and decreased flux in the basilar artery (mean difference −0·9 mL/s, 95% CI −1·5 to −0·2; uncorrected p=0·019). However, we noted no changes in rCBF and flux in presymptomatic carriers compared with controls. Vascular reactivity was significantly decreased in the occipital lobe in both presymptomatic (mean BOLD change 1·1% SD 0·5, mean difference −0·4% change, 95% CI −0·7 to −0·2; p=0·001; mean time to baseline 10·1 s SD 7·6, mean difference 4·6 s, 95% CI 0·4 to 8·8; p=0·032) and symptomatic carriers (mean BOLD change 0·4% SD 0·1, mean difference −0·9%, 95% CI −1·1 to −0·6; p<0·0001; mean time to baseline 20·3 s SD 8·4, mean difference 13·1 s, 95% CI 9·4 to 16·9; p<0·0001) compared with controls; however, the difference in mean time to peak was only significant for symptomatic carriers (mean difference 12·2 s, 95% CI 8·6 to 15·9; p<0·0001). Interpretation Our findings suggest that determination of vascular reactivity might be a useful biomarker for early detection of vascular amyloid pathology in sporadic CAA, and a biomarker of efficacy in future intervention trials. Our data indicate that vascular reactivity measurements might be useful for differential diagnosis in dementia to determine the vascular component. Funding USA National Institutes of Health.
Summary Background Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke ...Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods MR CLEAN was a randomised, controlled, open-label, phase 3 trial of intra-arterial treatment in patients (aged ≥18 years from the Netherlands) with proximal arterial occlusion of the anterior circulation, given intra-arterial treatment within 6 h of stroke onset. The primary outcome was 90 day modified Rankin Scale (mRS) score. We estimated the intra-arterial treatment effect for all patients in MR CLEAN who had ASPECTS graded by using multivariable ordinal logistic regression analysis (a proportional odds model) to calculate the adjusted common odds ratio for a shift towards a better functional outcome according to the mRS for intra-arterial treatment and usual care than for usual care alone. We entered an interaction term into the model to test for interaction with prespecified ASPECTS subgroups: 0–4 (large infarct) versus 5–7 (moderate infarct) versus 8–10 (small infarct). MR CLEAN is registered with the Netherlands Trial Registry, number NTR1804, and the ISRCTN Registry, number ISRCTN10888758. Findings 496 patients—232 (47%) in the intra-arterial treatment and usual care group and 264 (53%) in the usual care alone group—were included in the analysis. We noted no significant difference in intra-arterial treatment effect between the ASPECTS subgroups according to 90 day ordinal mRS (adjusted common odds ratio interaction term relative to ASPECTS 8–10: ASPECTS 0–4: 0·79 95% CI 0·20–3·19, p=0·740; and ASPECTS 5–7: 1·02 0·44–2·35, p=0·966). Intra-arterial treatment did not cause a significant increase in the proportion of patients with at least one serious adverse event in any of the ASPECTS subgroups (ASPECTS 0–4: eight 73% of 11 patients in treatment and usual care group vs 11 58% of 19 in usual care alone group, p=0·42; ASPECTS 5–7: 32 59% of 54 vs 19 49% of 39, p=0·31; ASPECTS 8–10: 70 42% of 167 vs 82 40% of 206; p=0·68). For death within 7 days or within 30 days and hemicraniectomy, the differences between the intra-arterial treatment and usual care versus usual care alone groups were not significant by ASPECTS subgroups. A significantly higher proportion of patients had recurrent ischaemic stroke in the intra-arterial treatment plus usual care group than in the usual care alone group in the ASPECTS 8–10 subgroup (eight 5% vs one <1%; p=0·007). Interpretation Contrary to findings from previous studies suggesting that only patients with non-contrast CT ASPECTS of more than 7 benefit from intra-arterial treatment, data from this study suggest that patients with ASPECTS 5–7 should be treated. Further evidence is needed for patients with ASPECTS 0–4, for whom treatment might yield only marginal absolute benefit. Funding Dutch Heart Foundation, AngioCare, Medtronic/Covidien/EV3, Medac/Lamepro, Penumbra, Stryker, and Top Medical.
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