Background: The ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) has been identified as a potential predictor of malignant edema formation in patients with acute... Show moreBackground: The ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) has been identified as a potential predictor of malignant edema formation in patients with acute ischemic stroke. Aims: We aimed to evaluate the added value of the CSF/ICV ratio in a model to predict malignant edema formation in patients who underwent endovascular treatment. Methods: We included patients from the MR CLEAN Registry, a prospective national multicenter registry of patients who were treated with endovascular treatment between 2014 and 2017 because of acute ischemic stroke caused by large vessel occlusion. The CSF/ICV ratio was automatically measured on baseline thin-slice noncontrast CT. The primary outcome was the occurrence of malignant edema based on clinical and imaging features. The basic model included the following predictors: age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT score, occlusion of the internal carotid artery, collateral score, time between symptom onset and groin puncture, and unsuccessful reperfusion. The extended model included the basic model and the CSF/ICV ratio. The performance of the basic and the extended model was compared with the likelihood ratio test. Results: Malignant edema occurred in 40 (6%) of 683 patients. In the extended model, a lower CSF/ICV ratio was associated with the occurrence of malignant edema (odds ratio (OR) per percentage point, 1.2; 95% confidence interval (CI) 1.1-1.3, p < 0.001). Age lost predictive value for malignant edema in the extended model (OR 1.1; 95% CI 0.9-1.5, p = 0.372). The performance of the extended model was higher than that of the basic model (p < 0.001). Conclusions: Adding the CSF/ICV ratio improves a multimodal prediction model for the occurrence of malignant edema after endovascular treatment. Show less
Aim To investigate whether there is a topographical and temporal pattern of index and recurrent intracerebral hemorrhages (ICH) in Dutch-type hereditary Cerebral Amyloid Angiopathy (D-CAA) to... Show moreAim To investigate whether there is a topographical and temporal pattern of index and recurrent intracerebral hemorrhages (ICH) in Dutch-type hereditary Cerebral Amyloid Angiopathy (D-CAA) to increase our understanding on CAA-related ICH development. Methods We included patients with DNA confirmed D-CAA or a history with >= 1 lobar ICH and >= 1 first-degree relative with D-CAA. Topographical pattern was studied by location (proportion frontal/parietal/temporal/occipital; infra/supratentorial and occurrence ratios relative to lobe volume) and volume of index and recurrent ICHs were determined on CT. Temporal pattern was examined by time between recurrent ICHs was retrieved from medical records. Results We included 72 patients with D-CAA (mean age at index ICH 55 years) with in total 214 ICH. The median follow-up time was 7 years (range 0.8 to 28 years). All ICH were lobar and supratentorial. The index ICH was most frequently located in the occipital lobe (34% vs. 22% in the other three lobes; with index ICH occurrence ratios relative to lobe volume of 1.9 for occipital, 1.0 for temporal, 1.2 for parietal, and 0.5 for frontal, p = 0.001). In 16/47 (34%) patients with multiple ICH, the second ICH was located in the same lobe as the index ICH. The median time-interval between subsequent ICH was #1-2 ICH 27 months, #2-3 ICH 14 months, and #3-4 ICH 7 months (p = 0.6) There was no difference in volume between index and recurrent ICHs. Conclusions We found that index and recurrent ICHs in D-CAA have a preference for the occipital lobe and are least frequent in the frontal lobe, which adds to the existing knowledge of histopathological studies on amyloid load in CAA. Surprisingly, there was no acceleration in time nor gradual increase of hematoma volume between subsequent ICHs. Show less
Background Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke. We assessed whether the effect of endovascular treatment is modified by brain... Show moreBackground Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke. We assessed whether the effect of endovascular treatment is modified by brain atrophy in patients with acute ischemic stroke due to large vessel occlusion. Methods We used data from MR CLEAN, a multicenter trial including patients with acute ischemic stroke due to anterior circulation large vessel occlusion randomized to endovascular treatment plus medical care (intervention) versus medical care alone (control). We segmented total brain volume (TBV) and intracranial volume (ICV) on baseline non-contrast computed tomography (n = 410). Next, we determined the degree of atrophy as the proportion of brain volume in relation to head size (1 - TBV/ICV) x 100%, analyzed as continuous variable and in tertiles. The primary outcome was a shift towards better functional outcome on the modified Rankin Scale expressed as adjusted common odds ratio. Treatment effect modification was tested using an interaction term between brain atrophy (as continuous variable) and treatment allocation. Results We found that brain atrophy significantly modified the effect of endovascular treatment on functional outcome (P for interaction = 0.04). Endovascular treatment led to larger shifts towards better functional outcome in the higher compared to the lower range of atrophy (adjusted common odds ratio, 1.86 [95% CI: 0.97-3.56] in the lowest tertile vs. 1.97 [95% CI: 1.03-3.74] in the middle tertile vs. 3.15 [95% CI: 1.59-6.24] in the highest tertile). Conclusion Benefit of endovascular treatment is larger in the higher compared to the lower range of atrophy, demonstrating that advanced atrophy should not be used as an argument to withhold endovascular treatment. Show less
Background Recent studies suggest that superficially located cerebellar intracerebral hemorrhage (ICH) and microbleeds might point towards sporadic cerebral amyloid angiopathy (CAA). Aims We... Show moreBackground Recent studies suggest that superficially located cerebellar intracerebral hemorrhage (ICH) and microbleeds might point towards sporadic cerebral amyloid angiopathy (CAA). Aims We investigated the proportion of cerebellar ICH and asymptomatic macro- and microbleeds in Dutch-type hereditary CAA (D-CAA), a severe and essentially pure form of CAA. Methods Symptomatic patients with D-CAA (defined as >= 1 symptomatic ICH) and presymptomatic D-CAA mutation-carriers were included. We assessed magnetic resonance imaging scans for symptomatic (cerebellar) ICH and asymptomatic cerebellar macro- and microbleeds according to the STRIVE-criteria. Location was assessed as superficial-cerebellar (cortex, vermis or juxta-cortical) or deep-cerebellar (white matter, pedunculi cerebelli and gray nuclei). Results We included 63 participants (mean age 58 years, 60% women, 42 symptomatic). In total, the 42 symptomatic patients with D-CAA had 107 symptomatic ICH (range 1-7). None of these ICH were located in the cerebellum. Six of 42 (14%, 95%CI 4-25%) symptomatic patients and none of the 21 (0%, 95%CI 0-0%) presymptomatic carriers had >= 1 asymptomatic cerebellar macrobleed(s). All macrobleeds were superficially located. Cerebellar microbleeds were found in 40 of 63 (64%, 95%CI 52-76) participants (median 1.0, range 0-159), 81% in symptomatic patients and 29% in presymptomatic carriers. All microbleeds were strictly or predominantly superficially (ratio superficial versus deep 15:1) located. Conclusions Superficially located asymptomatic cerebellar macrobleeds and microbleeds are common in D-CAA. Cerebellar microbleeds are already present in the presymptomatic stage. Despite the high frequency of cerebellar micro and macrobleeds, CAA pathology did not result in symptomatic cerebellar ICH in patients with D-CAA. Show less
BackgroundEarly prediction of malignant infarction may guide treatment decisions. For patients who received endovascular treatment, the risk of malignant infarction is unknown and risk factors are... Show moreBackgroundEarly prediction of malignant infarction may guide treatment decisions. For patients who received endovascular treatment, the risk of malignant infarction is unknown and risk factors are unrevealed.AimsThe objective of this study is to estimate the incidence of malignant infarction after endovascular treatment in patients with an occlusion of the anterior circulation, to identify independent risk factors, and to establish a model for prediction.MethodsWe analyzed patients who received endovascular treatment for a large vessel occlusion in the anterior circulation within 6.5 h after symptom onset, included in the Dutch MR CLEAN Registry between March 2014 and June 2016. We compared patients with and without malignant infarction. Candidate predictors were incorporated in a multivariable binary logistic regression model. The final prediction model was established using backward elimination. Discrimination and calibration were evaluated with the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow test.ResultsOf 1445 patients, 82 (6%) developed malignant infarction. Independent predictors were lower age, higher National Institutes of Health Stroke Scale (NIHSS), lower alberta stroke program early CT score (ASPECTS), internal carotid artery occlusion, lower collateral score, longer times from onset to groin puncture, and unsuccessful reperfusion. The AUROC of a prediction model combining these features was 0.83 (95% confidence interval (CI): 0.79-0.88) and the Hosmer-Lemeshow test indicated appropriate calibration (P = 0.937).ConclusionThe risk of malignant infarction after endovascular treatment started within 6.5 h of stroke onset is approximately 6%. Successful reperfusion decreases the risk. A prediction model combining easily retrievable measures of age, ASPECTS, collateral status, and reperfusion shows good discrimination between patients who will develop malignant infarction and those who will not. Show less
Koemans, E.A.; Voigt, S.; Rasing, I.; Jolink, W.M.T.; Harten, T.W. van; Grond, J. van der; ... ; Wermer, M.J.H. 2021
Background and aimTo investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary... Show moreBackground and aimTo investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH).MethodsWe performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T-2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features.ResultsWe included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging.ConclusionWhereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA. Show less
BackgroundThe Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer... Show moreBackgroundThe Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading.AimsWe present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology.MethodsWe included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0-2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors.ResultsIn total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58-88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome.ConclusionqTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score. Show less
Background and aimIn acute ischemic stroke, under- or overestimation of body weight can lead to dosing errors of recombinant tissue plasminogen activator with consequent reduced efficacy or... Show moreBackground and aimIn acute ischemic stroke, under- or overestimation of body weight can lead to dosing errors of recombinant tissue plasminogen activator with consequent reduced efficacy or increased risk of hemorrhagic complications. Measurement of body weight is more accurate than estimation of body weight but potentially leads to longer door-to-needle times. Our aim was to assess if weight modality (estimation of body weight versus measurement of body weight) is associated with (i) symptomatic intracranial hemorrhage rate, (ii) clinical outcome, and (iii) door-to-needle times.MethodsConsecutive patients treated with intravenous thrombolysis between 2009 and 2016 from 14 hospitals were included. Baseline characteristics and outcome parameters were retrieved from medical records. We defined symptomatic intracranial hemorrhage according to the European Cooperative Acute Stroke Study (ECASS)-III definition and clinical outcome was assessed with the modified Rankin Scale. The association of weight modality and outcome parameters was estimated with regression analyses.ResultsA total of 4801 patients were included. Five hospitals used measurement of body weight (n = 1753), six hospitals used estimation of body weight (n = 2325), and three hospitals (n = 723) changed from estimation of body weight to measurement of body weight during the study period. In 2048 of the patients (43%), measurement of body weight was used and in 2753 (57%), estimation of body weight. In the measurement of body weight group, an inbuilt weighing bed was used in 1094 patients (53%) and a patient lift scale in 954 patients (47%). In the estimation of body weight group, policy regarding estimation was similar. Estimation of body weight was not associated with increased symptomatic intracranial hemorrhage risk (adjusted odds ratio = 1.16; 95% confidence interval 0.83-1.62) or favorable outcome (adjusted odds ratio = 0.99; 95% confidence interval 0.82-1.21), but it was significantly associated with longer door-to-needle times compared to measurement of body weight using an inbuilt weighing bed (adjusted B = 3.57; 95% confidence interval 1.33-5.80) and shorter door-to-needle times compared to measurement of body weight using a patient lift scale (-3.96; 95% confidence interval -6.38 to -1.53).ConclusionWe did not find evidence that weight modality (estimation of body weight versus measurement of body weight) to determine recombinant tissue plasminogen activator dose in intravenous thrombolysis eligible patients is associated with symptomatic intracranial hemorrhage or clinical outcome. We did find that estimation of body weight leads to longer door-to-needle times compared to measurement of body weight using an inbuilt weighing bed and to shorter door-to-needle times compared to measurement of body weight using a patient lift scale. Show less
Charidimou, A.; Frosch, M.P.; Salman, R.A.; Baron, J.C.; Cordonnier, C.; Hernandez-Guillamon, M.; ... ; Int CAA Assoc 2019
Rationale To prevent recurrent venous thrombotic events after acute cerebral venous or dural sinus thrombosis, guidelines recommend long-term oral anticoagulation with vitamin K antagonists. Non... Show moreRationale To prevent recurrent venous thrombotic events after acute cerebral venous or dural sinus thrombosis, guidelines recommend long-term oral anticoagulation with vitamin K antagonists. Non-vitamin K oral anticoagulant experience in cerebral venous or dural sinus thrombosis is limited to case reports and series.Aim To compare dabigatran with dose-adjusted warfarin in patients with cerebral venous or dural sinus thrombosis for the prevention of recurrent venous thrombotic event.Sample size One hundred and twenty patients.Methods and design This study is a phase III, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded endpoint adjudication. Patients with acute cerebral venous or dural sinus thrombosis after 5-15 days of treatment with parenteral heparin are randomized to either dabigatran etexilate 150mg twice daily or dose-adjusted (international normalized ratio 2-3) warfarin (24 weeks).Study outcome The primary endpoint is a composite of patients with new venous thrombotic event (recurring cerebral venous or dural sinus thrombosis, deep venous thrombosis of any limb, pulmonary embolism, and major bleeding (International Society on Thrombosis and Hemostasis definition)) during the treatment period. Statistics will be descriptive (number and frequencies).Study timelines Inclusion started in December 2016. Final results are expected by the end of 2018.Discussion This exploratory trial is the first to compare vitamin K with non-vitamin K antagonists in cerebral venous or dural sinus thrombosis. It will provide evidence to guide physicians and patients in choosing oral anticoagulants to prevent venous thrombotic event after acute cerebral venous or dural sinus thrombosis. ClinicalTrials.gov number: NCT02913326. Show less
