Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for immunosuppressive treatment

Cerebral amyloid angiopathy (CAA) is a common but often asymptomatic disease, characterized by deposition of amyloid in cerebral blood vessels. We describe the successful treatment of CAA encephalopathy with dexamethasone in a patient with CAA-related inflammation causing subacute progressive encephalopathy and seizures, which is an increasingly recognized subtype of CAA. The two pathological subtypes of CAA-related inflammation are described and a review of the literature is performed concerning immunosuppressive treatment of CAA-related inflammation with special attention to its pathological subtypes. Immunosuppressive therapy appears to be an appropriate treatment for CAA encephalopathy

Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry

Background and Purpose—Collateral circulation status at baseline is associated with functional outcome after ischemic stroke and effect of endovascular treatment. We aimed to identify clinical and imaging determinants that are associated with collateral grade on baseline computed tomography angiography in patients with acute ischemic stroke due to an anterior circulation large vessel occlusion. Methods—Patients included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n=500) and MR CLEAN Registry (n=1488) were studied. Collateral status on baseline computed tomography angiography was scored from 0 (absent) to 3 (good). Multivariable ordinal logistic regression analyses were used to test the association of selected determinants with collateral status. Results—In total, 1988 patients were analyzed. Distribution of the collateral status was as follows: absent (7%, n=123), poor (32%, n=596), moderate (39%, n=735), and good (23%, n=422). Associations for a poor collateral status in a multivariable model existed for age (adjusted common odds ratio, 0.92 per 10 years [95% CI, 0.886–0.98]), male (adjusted common odds ratio, 0.64 [95% CI, 0.53–0.76]), blood glucose level (adjusted common odds ratio, 0.97 [95% CI, 0.95–1.00]), and occlusion of the intracranial segment of the internal carotid artery with occlusion of the terminus (adjusted common odds ratio 0.50 [95% CI, 0.41–0.61]). In contrast to previous studies, we did not find an association between cardiovascular risk factors and collateral status. Conclusions—Older age, male sex, high glucose levels, and intracranial internal carotid artery with occlusion of the terminus occlusions are associated with poor computed tomography angiography collateral grades in patients with acute ischemic stroke eligible for endovascular treatment

Acute Endovascular Treatment of Patients With lschemic 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 (raw 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

Collateral status and recanalization after endovascular treatment for acute ischemic stroke

Background: Successful recanalization and good collateral status are associated with good clinical outcomes after endovascular treatment (EVT) for acute ischemic stroke, but the relationships among them are unclear. Objective: To assess if collateral status is associated with recanalization after EVT and if collateral status modifies the association between successful recanalization and functional outcome. Methods: We retrospectively analyzed data from the MR CLEAN Registry, a multicenter prospective cohort study of patients with a proximal anterior occlusion who underwent EVT in the Netherlands. We determined collateral status with a previously validated four-point visual grading scale and defined successful recanalization as an extended Thrombolysis in Cerebral Infarction score ≥2B. Functional outcome was determined using the modified Rankin Scale score at 90 days. We assessed, with multivariable logistic regression models, the associations between (1) collateral status and successful recanalization, (2) successful recanalization and functional outcome, (3) collateral status and functional outcome. An interaction of collateral status and successful recanalization was assessed. Subgroup analyses were performed for patients treated with intravenous thrombolysis. Results: We included 2717 patients, of whom 1898 (70%) had successful recanalization. There was no relationship between collateral status and successful recanalization (adjusted common OR (95% CI) of grades 1, 2, and 3 vs 0: 1.19 (0.82 to 1.72), 1.20 (0.83 to 1.75), and 1.10 (0.74 to 1.63), respectively). Successful recanalization (acOR (95% CI): 2.15 (1.84 to 2.52)) and better collateral grades (acOR (95% CI) of grades 1, 2, and 3 vs 0: 2.12 (1.47 to 3.05), 3.46 (2.43 to 4.92), and 4.16 (2.89 to 5.99), respectively) were both associated with a shift towards better functional outcome, without an interaction between collateral status and successful recanalization. Results were similar for the subgroup of thrombolysed patients. Conclusions: Collateral status is not associated with the probability of successful recanalization after EVT and does not modify the association between successful recanalization and functional outcome

Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry

Background and Purpose - Collateral circulation status at baseline is associated with functional outcome after ischemic stroke and effect of endovascular treatment. We aimed to identify clinical and imaging determinants that are associated with collateral grade on baseline computed tomography angiography in patients with acute ischemic stroke due to an anterior circulation large vessel occlusion. Methods - Patients included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n=500) and MR CLEAN Registry (n=1488) were studied. Collateral status on baseline computed tomography angiography was scored from 0 (absent) to 3 (good). Multivariable ordinal logistic regression analyses were used to test the association of selected determinants with collateral status. Results - In total, 1988 patients were analyzed. Distribution of the collateral status was as follows: absent (7%, n=123), poor (32%, n=596), moderate (39%, n=735), and good (23%, n=422). Associations for a poor collateral status in a multivariable model existed for age (adjusted common odds ratio, 0.92 per 10 years [95% CI, 0.886-0.98]), male (adjusted common odds ratio, 0.64 [95% CI, 0.53-0.76]), blood glucose level (adjusted common odds ratio, 0.97 [95% CI, 0.95-1.00]), and occlusion of the intracranial segment of the internal carotid artery with occlusion of the terminus (adjusted common odds ratio 0.50 [95% CI, 0.41-0.61]). In contrast to previous studies, we did not find an association between cardiovascular risk factors and collateral status. Conclusions - Older age, male sex, high glucose levels, and intracranial internal carotid artery with occlusion of the terminus occlusions are associated with poor computed tomography angiography collateral grades in patients with acute ischemic stroke eligible for endovascular treatment

Impact of single phase CT angiography collateral status on functional outcome over time: Results from the MR CLEAN Registry

Background: Collateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent. Methods: We included consecutive patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry (March 2014-June 2016) with an anterior circulation large vessel occlusion undergoing EVT. Functional outcome was measured on the modified Rankin Scale (mRS) at 90 days. We investigated the association between collaterals and mRS in the MR CLEAN Registry with ordinal logistic regression and if this association was time dependent with an interaction term. Additionally, we determined modification of EVT effect by collaterals compared with MR CLEAN controls, and also investigated if this was time dependent with multiplicative interaction terms. Results: 1412 patients were analyzed. Functional independence (mRS score of 0-2) was achieved in 13% of patients with grade 0 collaterals, in 27% with grade 1, in 46% with grade 2, and in 53% with grade 3. Collaterals were significantly associated with mRS (adjusted common OR 1.5 (95% CI 1.4 to 1.7)) and significantly modified EVT benefit (P=0.04). None of the effects were time dependent. Better collaterals corresponded to lower mortality (P<0.001), but not to lower rates of symptomatic intracranial hemorrhage (P=0.14). Conclusion: In routine clinical practice, better collateral status is associated with better functional outcome and greater treatment benefit in EVT treated acute ischemic stroke patients, independent of time to treatment. Within the 6 hour time window, a substantial proportion of patients with absent and poor collaterals can still achieve functional independence

Association between thrombus composition and stroke etiology in the MR CLEAN Registry biobank

Purpose: The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice. Methods: The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification. Results: The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00–1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00–1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar. Conclusion: Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin

Association between thrombus composition and stroke etiology in the MR CLEAN Registry biobank

Purpose: The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice. Methods: The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification. Results: The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00–1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00–1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar. Conclusion: Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin

Impact of single phase CT angiography collateral status on functional outcome over time:results from the MR CLEAN Registry

Background Collateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent. Methods We included consecutive patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry (March 2014-June 2016) with an anterior circulation large vessel occlusion undergoing EVT. Functional outcome was measured on the modified Rankin Scale (mRS) at 90 days. We investigated the association between collaterals and mRS in the MR CLEAN Registry with ordinal logistic regression and if this association was time dependent with an interaction term. Additionally, we determined modification of EVT effect by collaterals compared with MR CLEAN controls, and also investigated if this was time dependent with multiplicative interaction terms. Results 1412 patients were analyzed. Functional independence (mRS score of 0-2) was achieved in 13% of patients with grade 0 collaterals, in 27% with grade 1, in 46% with grade 2, and in 53% with grade 3. Collaterals were significantly associated with mRS (adjusted common OR 1.5 (95% CI 1.4 to 1.7)) and significantly modified EVT benefit (P=0.04). None of the effects were time dependent. Better collaterals corresponded to lower mortality (P Conclusion In routine clinical practice, better collateral status is associated with better functional outcome and greater treatment benefit in EVT treated acute ischemic stroke patients, independent of time to treatment. Within the 6 hour time window, a substantial proportion of patients with absent and poor collaterals can still achieve functional independence