Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment

Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment

Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment

Regionally Altered Immunosignals of Surfactant Protein-G, Vascular and Non-Vascular Elements of the Neurovascular Unit after Experimental Focal Cerebral Ischemia in Mice, Rats, and Sheep

The surfactant protein-G (SP-G) has recently been discovered in the brain and linked to fluid balance regulations. Stroke is characterized by impaired vessel integrity, promoting water influx and edema formation. The neurovascular unit concept (NVU) has been generated to cover not only ischemic affections of neurons or vessels but also other regionally associated cells. This study provides the first spatio-temporal characterization of SP-G and NVU elements after experimental stroke. Immunofluorescence labeling was applied to explore SP-G, vascular and cellular markers in mice (4, 24, and 72 h of ischemia), rats (24 h of ischemia), and sheep (two weeks of ischemia). Extravasated albumin indicated vascular damage within ischemic areas. Quantifications revealed decreasing SP-G signals in the ischemia-affected neocortex and subcortex. Inverse immunosignals of SP-G and vascular elements existed throughout all models. Despite local associations between SP-G and the vasculature, a definite co-localization was not seen. Along with a decreased SP- G-immunoreactivity in ischemic areas, signals originating from neurons, glial elements, and the extracellular matrix exhibited morphological alterations or changed intensities. Collectively, this study revealed regional alterations of SP-G, vascular, and non-vascular NVU elements after ischemia, and may thus stimulate the discussion about the role of SP-G during stroke

Regionally Altered Immunosignals of Surfactant Protein-G, Vascular and Non-Vascular Elements of the Neurovascular Unit after Experimental Focal Cerebral Ischemia in Mice, Rats, and Sheep

The surfactant protein-G (SP-G) has recently been discovered in the brain and linked to fluid balance regulations. Stroke is characterized by impaired vessel integrity, promoting water influx and edema formation. The neurovascular unit concept (NVU) has been generated to cover not only ischemic affections of neurons or vessels but also other regionally associated cells. This study provides the first spatio-temporal characterization of SP-G and NVU elements after experimental stroke. Immunofluorescence labeling was applied to explore SP-G, vascular and cellular markers in mice (4, 24, and 72 h of ischemia), rats (24 h of ischemia), and sheep (two weeks of ischemia). Extravasated albumin indicated vascular damage within ischemic areas. Quantifications revealed decreasing SP-G signals in the ischemia-affected neocortex and subcortex. Inverse immunosignals of SP-G and vascular elements existed throughout all models. Despite local associations between SP-G and the vasculature, a definite co-localization was not seen. Along with a decreased SP- G-immunoreactivity in ischemic areas, signals originating from neurons, glial elements, and the extracellular matrix exhibited morphological alterations or changed intensities. Collectively, this study revealed regional alterations of SP-G, vascular, and non-vascular NVU elements after ischemia, and may thus stimulate the discussion about the role of SP-G during stroke

Regionally Altered Immunosignals of Surfactant Protein-G, Vascular and Non-Vascular Elements of the Neurovascular Unit after Experimental Focal Cerebral Ischemia in Mice, Rats, and Sheep

The surfactant protein-G (SP-G) has recently been discovered in the brain and linked to fluid balance regulations. Stroke is characterized by impaired vessel integrity, promoting water influx and edema formation. The neurovascular unit concept (NVU) has been generated to cover not only ischemic affections of neurons or vessels but also other regionally associated cells. This study provides the first spatio-temporal characterization of SP-G and NVU elements after experimental stroke. Immunofluorescence labeling was applied to explore SP-G, vascular and cellular markers in mice (4, 24, and 72 h of ischemia), rats (24 h of ischemia), and sheep (two weeks of ischemia). Extravasated albumin indicated vascular damage within ischemic areas. Quantifications revealed decreasing SP-G signals in the ischemia-affected neocortex and subcortex. Inverse immunosignals of SP-G and vascular elements existed throughout all models. Despite local associations between SP-G and the vasculature, a definite co-localization was not seen. Along with a decreased SP-G-immunoreactivity in ischemic areas, signals originating from neurons, glial elements, and the extracellular matrix exhibited morphological alterations or changed intensities. Collectively, this study revealed regional alterations of SP-G, vascular, and non-vascular NVU elements after ischemia, and may thus stimulate the discussion about the role of SP-G during stroke

Feasibility, Safety, and Outcome of Endovascular Recanalization in Childhood Stroke

This cohort study examines the use of endovascular recanalization in pediatric patients with arterial ischemic stroke and clinical outcomes. Importance Randomized clinical trials have shown the efficacy of thrombectomy of large intracranial vessel occlusions in adults; however, any association of therapy with clinical outcomes in children is unknown. Objective To evaluate the use of endovascular recanalization in pediatric patients with arterial ischemic stroke. Design, Setting, and Participants This retrospective, multicenter cohort study, conducted from January 1, 2000, to December 31, 2018, analyzed the databases from 27 stroke centers in Europe and the United States. Included were all pediatric patients (<18 years) with ischemic stroke who underwent endovascular recanalization. Median follow-up time was 16 months. Exposures Endovascular recanalization. Main Outcomes and Measures The decrease of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score from admission to day 7 was the primary outcome (score range: 0 [no deficit] to 34 [maximum deficit]). Secondary clinical outcomes included the modified Rankin scale (mRS) (score range: 0 [no deficit] to 6 [death]) at 6 and 24 months and rate of complications. Results Seventy-three children from 27 participating stroke centers were included. Median age was 11.3 years (interquartile range [IQR], 7.0-15.0); 37 patients (51%) were boys, and 36 patients (49%) were girls. Sixty-three children (86%) received treatment for anterior circulation occlusion and 10 patients (14%) received treatment for posterior circulation occlusion; 16 patients (22%) received concomitant intravenous thrombolysis. Neurologic outcome improved from a median PedNIHSS score of 14.0 (IQR, 9.2-20.0) at admission to 4.0 (IQR, 2.0-7.3) at day 7. Median mRS score was 1.0 (IQR, 0-1.6) at 6 months and 1.0 (IQR, 0-1.0) at 24 months. One patient (1%) developed a postinterventional bleeding complication and 4 patients (5%) developed transient peri-interventional vasospasm. The proportion of symptomatic intracerebral hemorrhage events in the HERMES meta-analysis of trials with adults was 2.79 (95% CI, 0.42-6.66) and in Save ChildS was 1.37 (95% CI, 0.03-7.40). Conclusions and Relevance The results of this study suggest that the safety profile of thrombectomy in childhood stroke does not differ from the safety profile in randomized clinical trials for adults; most of the treated children had favorable neurologic outcomes. This study may support clinicians' practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence. Question Is endovascular treatment in pediatric patients (<18 years) associated with ischemic stroke and the clinical outcome? Findings In this cohort study including 73 children, endovascular recanalization appeared to be safe with positive outcomes in a real-world setting (proportion of successful recanalization, 87%). The study findings suggest that neurologic outcomes of the children were mostly favorable and comparable with those noted in adult trials. Meaning This study appears to support the level of evidence in favor of endovascular recanalization in children with acute, large-vessel occlusion; a higher strength of recommendation may contribute to clinical outcome in children affected by arterial ischemic stroke

Does Device Selection Impact Recanalization Rate and Neurological Outcome? An Analysis of the Save ChildS Study

Background and Purpose-The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods-The Save ChildS cohort study (January 2000-December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients (<18 years), diagnosed with arterial ischemic stroke who underwent endovascular recanalization. Patients were grouped into first-line contact aspiration (A Direct Aspiration First Pass Technique [ADAPT]) and non-ADAPT groups as well as different stent retriever size groups. Associations with baseline characteristics, recanalization rates (modified Treatment in Cerebral Infarction), complication rates, and neurological outcome parameters (Pediatric National Institutes of Health Stroke Scale after 24 hours and 7 days; modified Rankin Scale and Pediatric Stroke Outcome Measure at discharge, after 6 and 24 months) were investigated. Results-Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4x20 mm (widthxlength) was the most frequently chosen size (36 patients =61%). A first- line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions-Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection

Cost-Effectiveness of Endovascular Thrombectomy in Childhood Stroke: An Analysis of the Save ChildS Study

Background and Purpose The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. Methods In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient sub-group with unsuccessful recanalization was used to model the standard of care group. For model -ing of lifetime estimates, pediatric and adult input parameters were obtained from the current lit- erature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. Results The model results yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to$169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. Conclusions EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke

Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke An Analysis of the Save ChildS Study

Objective To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct. Methods A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct. Results Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population. Conclusions Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct. Classification of Evidence This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe