Endovascular Therapy or Medical Management Alone for Isolated Posterior Cerebral Artery Occlusion: A Multicenter Study.

BACKGROUND: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown. METHODS: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0-2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage, and early neurological deterioration. RESULTS: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63-82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4-10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66-1.01]; P=0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95-1.43]; P=0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35-4.67]; P=0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64-3.84]; P<0.0001). CONCLUSIONS: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial.

BACKGROUND: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. METHODS: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. FINDINGS: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). INTERPRETATION: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. FUNDING: Medtronic and University Hospital Bern.

Magnetic Resonance Imaging or Computed Tomography for Suspected Acute Stroke: Association of Admission Image Modality with Acute Recanalization Therapies, Workflow Metrics, and Outcomes.

OBJECTIVE: To examine rates of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), door-to-needle (DTN) time, door-to-puncture (DTP) time, and functional outcome between patients with admission magnetic resonance imaging (MRI) versus computed tomography (CT). METHODS: An observational cohort study of consecutive patients using a target trial design within the nationwide Swiss-Stroke-Registry from January 2014 to August 2020 was carried out. Exclusion criteria included MRI contraindications, transferred patients, and unstable or frail patients. Multilevel mixed-effects logistic regression with multiple imputation was used to calculate adjusted odds ratios with 95% confidence intervals for IVT, MT, DTN, DTP, and good functional outcome (mRS 0-2) at 90 days. RESULTS: Of the 11,049 patients included (mean [SD] age, 71 [15] years; 4,811 [44%] women; 69% ischemic stroke, 16% transient ischemic attack, 8% stroke mimics, 6% intracranial hemorrhage), 3,741 (34%) received MRI and 7,308 (66%) CT. Patients undergoing MRI had lower National Institutes of Health Stroke Scale (median [interquartile range] 2 [0-6] vs 4 [1-11]), and presented later after symptom onset (150 vs 123 min, p < 0.001). Admission MRI was associated with: lower adjusted odds of IVT (aOR 0.83, 0.73-0.96), but not with MT (aOR 1.11, 0.93-1.34); longer adjusted DTN (+22 min [13-30]), but not with longer DTP times; and higher adjusted odds of favorable outcome (aOR 1.54, 1.30-1.81). INTERPRETATION: We found an association of MRI with lower rates of IVT and a significant delay in DTN, but not in DTP and rates of MT. Given the delays in workflow metrics, prospective trials are required to show that tissue-based benefits of baseline MRI compensate for the temporal benefits of CT. ANN NEUROL 2022;92:184-194.

Relevance of National Institutes of Health Stroke Scale subitems for best revascularization therapy in minor stroke patients with large vessel occlusion: An observational multicentric study.

BACKGROUND AND PURPOSE: The best management of acute ischemic stroke patients with a minor stroke and large vessel occlusion is still uncertain. Specific clinical and radiological data may help to select patients who would benefit from endovascular therapy (EVT). We aimed to evaluate the relevance of National Institutes of Health Stroke Scale (NIHSS) subitems for predicting the potential benefit of providing EVT after intravenous thrombolysis (IVT; "bridging treatment") versus IVT alone. METHODS: We extracted demographic, clinical, risk factor, radiological, revascularization and outcome data of consecutive patients with M1 or proximal M2 middle cerebral artery occlusion and admission NIHSS scores of 0-5 points, treated with IVT ± EVT between May 2005 and March 2021, from nine prospectively constructed stroke registries at seven French and two Swiss comprehensive stroke centers. Adjusted interaction analyses were performed between admission NIHSS subitems and revascularization modality for two primary outcomes at 3 months: non-excellent functional outcome (modified Rankin Scale score 2-6) and difference in NIHSS score between 3 months and admission. RESULTS: Of the 533 patients included (median age 68.2 years, 46% women, median admission NIHSS score 3), 136 (25.5%) initially received bridging therapy and 397 (74.5%) received IVT alone. Adjusted interaction analysis revealed that only facial palsy on admission was more frequently associated with excellent outcome in patients treated by IVT alone versus bridging therapy (odds ratio 0.47, 95% confidence interval 0.24-0.91; p = 0.013). Regarding NIHSS difference at 3 months, no single NIHSS subitem interacted with type of revascularization. CONCLUSIONS: This retrospective multicenter analysis found that NIHSS subitems at admission had little value in predicting patients who might benefit from bridging therapy as opposed to IVT alone. Further research is needed to identify better markers for selecting EVT responders with minor strokes.

Importance of Delayed Reperfusions in Patients With Incomplete Thrombectomy.

BACKGROUND: There is paucity of data regarding the effects of delayed reperfusion (DR) on clinical outcomes in patients with incomplete reperfusion following mechanical thrombectomy. We hypothesized that DR has a strong association with clinical outcome in patients with incomplete reperfusion after mechanical thrombectomy (expanded Thrombolysis in Cerebral Infarction, 2a-2c). METHODS: Single-institution's stroke registry retrospective analysis of patients admitted from February 2015 to December 2020. DR was defined as the absence of any perfusion delay on ≈24-hour contrast-enhanced follow-up perfusion imaging, whereas persistent perfusion deficit denotes a perfusion delay corresponding to the catheter angiographic deficit directly after the intervention. The association of perfusion outcome (DR versus persistent perfusion deficit) with the occurrence of new infarcts and 90-day functional independence (modified Rankin Scale score 0-2) was evaluated using logistic regression analyses. Comparison of predictive accuracy was evaluated by calculating area under the curve for models with and without perfusion outcome. RESULTS: In 566 patients (mean age 74, 49.6% female), new infarcts in the incomplete reperfusion areas were less common in DR versus persistent perfusion deficit patients (small punctiform: 17.1% versus 25%, large confluent: 7.9% versus 63.2%; P=0.001). After adjustment for confounders, DR was a strong predictor of functional independence (adjusted odds ratio, 2.37 [95% CI 1.34-4.23]). There was a significant improvement in predictive accuracy of functional independence when perfusion outcome was added to expanded Thrombolysis in Cerebral Infarction alone (area under the curve 0.57 versus 0.62, P=0.01). CONCLUSIONS: Occurrence of DR is closely associated with tissue outcome and functional independence. DR may be an independent prognostic parameter, suggesting it as a potential outcome surrogate for medical rescue therapies.

Endovascular Treatment for Acute Ischemic Stroke With or Without General Anesthesia: A Matched Comparison.

BACKGROUND: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain. METHODS: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias. RESULTS: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42-2.16]; P<0.001), the coarsened exact matching (n=332-524, using multiple imputations of missing values; OR, 1.60 [1.08-2.36]; P=0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20-2.15]; P=0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59-4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30-3.75]), dependency or death (OR, 1.42 [0.91-2.23]), or mortality (OR, 1.65 [0.94-2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76-5.04]), dependency or death (OR, 1.49 [1.07-2.07]), and mortality (OR, 1.65 [1.11-2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73-4.29]). CONCLUSIONS: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Perfusion Imaging and Clinical Outcome in Acute Minor Stroke With Large Vessel Occlusion.

BACKGROUND: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy. METHODS: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume). RESULTS: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P=0.03. However, mismatch volume modified the effect of bridging on clinical outcome (Pinteraction=0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only (Pinteraction=0.002). CONCLUSIONS: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

OBJECTIVE: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS: This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: ß -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). INTERPRETATION: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.

Association of diabetes mellitus and admission glucose levels with outcome after endovascular therapy in acute ischaemic stroke in anterior circulation.

BACKGROUND AND PURPOSE: We aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice. METHODS: Consecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared. RESULTS: We included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR]adjusted  = 0.61, p = 0.023) and worse 3-month functional outcome (modified Rankin Scale [mRS] = 0-2: 31.3% vs. 48%, ORadjusted  = 0.59, p = 0.004; death: 38.9% vs. 24.1%, ORadjusted  = 1.75, p = 0.002; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.52, p = 0.005; death: ORadjusted  = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (padjusted  = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3-month functional outcome (mRS = 0-2: 28.3% vs. 50.4%, ORadjusted  = 0.52, p < 0.0001; death: 40.4% vs. 22.4%, ORadjusted  = 1.80, p = 0.001; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.38, p < 0.0001; death: ORadjusted  = 2.39, p < 0.0001). If analysis was additionally adjusted for DM, 3-month functional outcome remained significantly worse in patients with AH (mRS = 0-2: ORadjusted  = 0.58, p = 0.004; death: ORadjusted  = 1.57, p = 0.014; mRS shift: padjusted  = 0.004). DM independently predicted recurrent/progressive in-hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in-hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J-shaped. CONCLUSIONS: Hyperglycaemia more than DM was associated with worse 3-month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging.

Association of the COVID-19 outbreak with acute stroke care in Switzerland.

BACKGROUND AND PURPOSE: In Switzerland, the COVID-19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020. METHODS: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3-month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019. RESULTS: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13-April 26 of the years 2018-2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07). CONCLUSIONS: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained.

Treatment and Outcome in Stroke Patients With Acute M2 Occlusion and Minor Neurological Deficits.

BACKGROUND AND PURPOSE: Treatment in stroke patients with M2 segment occlusion of the middle cerebral artery presenting with mild neurological deficits is a matter of debate. The main purpose was to compare the outcome in patients with a minor stroke and a M2 occlusion. METHODS: Consecutive intravenous thrombolysis (IVT) eligible patients admitted to the Bernese stroke center between January 2005 and January 2020 with acute occlusion of the M2 segment and National Institutes of Health Stroke Scale score ≤5 were included. Outcome was compared between IVT only versus endovascular therapy (EVT) including intra-arterial thrombolysis and mechanical thrombectomy (MT; ±IVT) and between IVT only versus MT only. RESULTS: Among 169 patients (38.5% women, median age 70.2 years), 84 (49.7%) received IVT only and 85 (50.3%) EVT (±IVT), the latter including 39 (45.9%) treated with MT only. Groups were similar in sex, age, vascular risk factors, event cause, or preevent independency. Compared with IVT only, there was no difference in favorable outcome (modified Rankin Scale score, 0-2) for EVT (adjusted odds ratio, 0.96; adjusted P=0.935) or for MT only (adjusted odds ratio, 1.12; adjusted P=0.547) groups. Considering only patients treated after 2015, there was a significantly better 3-month modified Rankin Scale shift (adjusted P=0.032) in the EVT compared with the IVT only group. CONCLUSIONS: Our study demonstrates similar effectiveness of IVT only versus EVT (±IVT), and of IVT only versus MT only in patients with peripheral middle cerebral artery occlusions and minor neurological deficits and indicates a possible benefit of EVT considering only patients treated after 2015. There is an unmet need for randomized controlled trials in this stroke field, including imaging parameters, and more sophisticated evaluation of National Institutes of Health Stroke Scale score subitems, neurocognition, and quality of life neglected by the standard outcome scales such as modified Rankin Scale and National Institutes of Health Stroke Scale score.

Bridging May Increase the Risk of Symptomatic Intracranial Hemorrhage in Thrombectomy Patients With Low Alberta Stroke Program Early Computed Tomography Score.

BACKGROUND AND PURPOSE: Whether intravenous thrombolysis (IVT) increases the risk for symptomatic intracranial hemorrhage (sICH) in patients treated with mechanical thrombectomy (MT) is a matter of debate. Purpose of this study was to evaluate the extent of early ischemia as a possible factor influencing the risk for sICH after IVT+MT versus direct MT. METHODS: An explorative analysis of the BEYOND-SWIFT (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy) multicenter cohort was performed. We hypothesized that the sICH risk between IVT+MT versus direct MT differs across the strata of Alberta Stroke Program Early CT Scores (ASPECTS). For this purpose, all patients with ICA, M1, and M2 vessel occlusions and available noncontrast computed tomography or diffusion-weighed imaging ASPECTS (n=2002) were analyzed. We used logistic regression analysis in subgroups, as well as interaction terms, to address the risk of sICH in IVT+MT versus direct MT patients across the ASPECTS strata. RESULTS: In 2002 patients (median age, 73.7 years; 50.7% women; median National Institutes of Health Stroke Scale score, 16), the overall rate of sICH was 6.5% (95% CI, 5.5%-7.7%). Risk of sICH differed across ASPECTS groups (9-10: 6.3%; 6-8: 5.6% and ≤5 9.8%; P=0.042). With decreasing ASPECTS, the risks of sICH in the IVT+MT versus the direct MT group increased from adjusted odds ratio of 0.61 ([95% CI, 0.24-1.60] ASPECTS 9-10), to 1.72 ([95% CI, 0.69-4.24] ASPECTS 6-8) and 6.31 ([95% CI, 1.87-21.29] ASPECTS ≤5), yielding a positive interaction term (1.91 [95% CI, 1.01-3.63]). Sensitivity analyses regarding diffusion-weighed imaging versus noncontrast computed tomography ASPECTS did not alter the primary observations. CONCLUSIONS: The extent of early ischemia may influence relative risks of sICH in IVT+MT versus direct MT patients, with an excess sICH risk in IVT+MT patients with low ASPECTS. If confirmed in post hoc analyses of randomized controlled trial data, IVT may be administered more carefully in patients with low ASPECTS eligible for and with direct access to MT.

Symptomatic internal carotid artery stenosis in the presence of a persistent primary hypoglossal artery.

OBJECTIVES: Anatomic variations of the extracranial carotid artery are rare. Persistent primitive hypoglossal artery appears with a reported incidence between 0.03% and 0.2%. We report a case of recurrent transient ischemic attacks originating from proximal internal carotid artery stenosis associated with ipsilateral persistent primitive hypoglossal artery and give a review of the existing literature. METHODS: A 78-year-old patient with a medical history of two previous transient ischemic attacks consulted our emergency department with an acute left hemispheric stroke. Intravenous thrombolysis permitted complete resolution of symptoms. Concurrent Computed Tomography (CT) and Magnetic Resonance (MR) angiography revealed an unstable plaque causing 50% stenosis of the left internal carotid artery with a persistent primitive hypoglossal artery dominantly perfusing the posterior circulation, and bilateral hypoplastic vertebral arteries. RESULTS: Uneventful carotid artery stenting using a proximal protection device was performed, and the patient was discharged after 12 days. Six months follow-up was uneventful with a patent stent in the internal carotid artery. CONCLUSIONS: Treatment of symptomatic carotid artery stenosis in the presence of persistent primitive hypoglossal artery is challenging. Management should be driven by patients' co-morbidities, the anatomical localization of the lesions and local expertise. In the case of a high origin of the persistent primary hypoglossal artery, carotid artery stenting with the use of a proximal cerebral protection device is probably the preferred and simplest approach.

Influence of inferior petrosal sinus drainage symmetry on detection of adenomas in Cushing's syndrome.

BACKGROUND: Asymmetric inferior petrosal sinuses (IPS) are not infrequently encountered during bilateral IPS sampling. There is little data on whether IPS symmetry influences success in predicting the adenoma side in patients with ACTH-dependent Cushing's syndrome (CS). OBJECTIVE: To assess the influence of IPS drainage patterns on detection of an adenoma in CS. METHODS: Retrospective single-center cohort analysis reviewing records of patients with CS and negative MRI findings who subsequently underwent BIPSS. RESULTS: BIPSS was performed in 38 patients with a mean age of 45±15 years. The overall technical success rate was 97% for bilateral cannulation. Asymmetric IPS were observed in 11 (39%) patients with Cushing's disease (CD). A side-to-side ACTH ratio was not significantly different between patients with symmetric outflow and those with asymmetric outflow at baseline (8.6±2.7 versus 16.4±6.0; P=0.45), but ratios were significantly different after ovine corticotropin-releasing hormone (oCRH) stimulation (6.0±2.5 versus 35.7±22.5; P=0.03). BIPSS correctly predicted the side of the adenoma in 25 (96%) patients with CD. Prediction was better when the venous outflow was symmetric (100%) rather than asymmetric (93%), although the difference was not significant (P=0.42). Remission from CS was achieved in 32 patients (87%), independent of the symmetry of IPS. CONCLUSIONS: Bearing in mind the sample size of this audit, asymmetric IPS at least do not seem to diminish the accuracy of diagnosis of ACTH-dependent CS, nor do they influence the clinical outcome.

[Intracerebral haemorrhage - acute event and chronic disease]. / Die intrazerebrale Hirnblutung: Akutes Ereignis und chronische Erkrankung.

Intracerebral haemorrhage - acute event and chronic disease Abstract. Intracerebral hemorrhage accounts for 10-15% of all strokes and approximately 1'500-2'000 patients per year in Switzerland. Acute treatment by multi-disciplinary experts at certified stroke units and stroke centers is important to provide optimal care. A simple ABC-care bundle (revert anticoagulation, control blood pressure, inform neurosurgeon) decreases poor outcome. Despite a high mortality, one third of patients are functionally independent after intracerebral hemorrhage contradicting widespread pessimism. About 80% of all intracerebral hemorrhage are attributable to different types of cerebral small vessel disease. Relative and absolute risks of recurrent hemorrhage and ischemic stroke differ significantly. Patients with intracerebral hemorrhage are vascular high-risk patients with chronic cerebrovascular disease. Long-term outpatient management should include neurovascular specialists to deal with important decisions (blood pressure management, antithrombotic therapy including anticoagulation, specialized neurorehabilitation to improve neurocognitive deficits, therapy of possible complications such as epilepsy) to provide optimal and individual care to patients. Currently ongoing randomized controlled trials will provide important results in the next years further improving treatment of intracerebral hemorrhage.

Effect of Pre- and In-Hospital Delay on Reperfusion in Acute Ischemic Stroke Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Post hoc analyses of randomized controlled clinical trials evaluating mechanical thrombectomy have suggested that admission-to-groin-puncture (ATG) delays are associated with reduced reperfusion rates. Purpose of this analysis was to validate this association in a real-world cohort and to find associated factors and confounders for prolonged ATG intervals. METHODS: Patients included into the BEYOND-SWIFT cohort (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the Solitaire FR With the Intention for Thrombectomy; https://www.clinicaltrials.gov; Unique identifier: NCT03496064) were analyzed (n=2386). Association between baseline characteristics and ATG was evaluated using mixed linear regression analysis. The effect of increasing symptom-onset-to-admission and ATG intervals on successful reperfusion (defined as Thrombolysis in Cerebral Infarction [TICI] 2b-3) was evaluated using logistic regression analysis adjusting for potential confounders. RESULTS: Median ATG was 73 minutes. Prolonged ATG intervals were associated with the use of magnetic resonance imaging (+19.1 [95% CI, +9.1 to +29.1] minutes), general anesthesia (+12.1 [95% CI, +3.7 to +20.4] minutes), and borderline indication criteria, such as lower National Institutes of Health Stroke Scale, late presentations, or not meeting top-tier early time window eligibility criteria (+13.8 [95% CI, +6.1 to +21.6] minutes). There was a 13% relative odds reduction for TICI 2b-3 (adjusted odds ratio [aOR], 0.87 [95% CI, 0.79-0.96]) and TICI 2c/3 (aOR, 0.87 [95% CI, 0.79-0.95]) per hour ATG delay, while the reduction of TICI 2b-3 per hour increase symptom-onset-to-admission was minor (aOR, 0.97 [95% CI, 0.94-0.99]) and inconsistent regarding TICI 2c/3 (aOR, 0.99 [95% CI, 0.97-1.02]). After adjusting for identified factors associated with prolonged ATG intervals, the association of ATG delay and lower rates of TICI 2b-3 remained tangible (aOR, 0.87 [95% CI, 0.76-0.99]). CONCLUSIONS: There is a great potential to reduce ATG, and potential targets for improvement can be deduced from observational data. The association between in-hospital delay and reduced reperfusion rates is evident in real-world clinical data, underscoring the need to optimize in-hospital workflows. Given the only minor association between symptom-onset-to-admission intervals and reperfusion rates, the causal relationship of this association warrants further research. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064.

Endovascular Stroke Treatment and Risk of Intracranial Hemorrhage in Anticoagulated Patients.

Background and Purpose- We aimed to determine the safety and mortality after mechanical thrombectomy in patients taking vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Methods- In a multicenter observational cohort study, we used multiple logistic regression analysis to evaluate associations of symptomatic intracranial hemorrhage (sICH) with VKA or DOAC prescription before thrombectomy as compared with no anticoagulation. The primary outcomes were the rate of sICH and all-cause mortality at 90 days, incorporating sensitivity analysis regarding confirmed therapeutic anticoagulation. Additionally, we performed a systematic review and meta-analysis of literature on this topic. Results- Altogether, 1932 patients were included (VKA, n=222; DOAC, n=98; no anticoagulation, n=1612); median age, 74 years (interquartile range, 62-82); 49.6% women. VKA prescription was associated with increased odds for sICH and mortality (adjusted odds ratio [aOR], 2.55 [95% CI, 1.35-4.84] and 1.64 [95% CI, 1.09-2.47]) as compared with the control group, whereas no association with DOAC intake was observed (aOR, 0.98 [95% CI, 0.29-3.35] and 1.35 [95% CI, 0.72-2.53]). Sensitivity analyses considering only patients within the confirmed therapeutic anticoagulation range did not alter the findings. A study-level meta-analysis incorporating data from 7462 patients (855 VKAs, 318 DOACs, and 6289 controls) from 15 observational cohorts corroborated these observations, yielding an increased rate of sICH in VKA patients (aOR, 1.62 [95% CI, 1.22-2.17]) but not in DOAC patients (aOR, 1.03 [95% CI, 0.60-1.80]). Conclusions- Patients taking VKA have an increased risk of sICH and mortality after mechanical thrombectomy. The lower risk of sICH associated with DOAC may also be noticeable in the acute setting. Improved selection might be advisable in VKA-treated patients. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064. Systematic Review and Meta-Analysis: CRD42019127464.

Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0-5.

Background and Purpose- If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0-5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0-5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods- Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration-URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0-3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0-2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results- Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0-5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363-12.961), functional independence (aOR, 5.583; 95% CI, 1.964-15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083-0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062-0.887). The mortality-reducing effect remained in patients with ASPECTS 0-4 (aOR, 0.167; 95% CI, 0.056-0.499). Sensitivity analyses did not change the primary results. Conclusions- In patients presenting with ASPECTS 0-5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.

Survival and Outcome After Poor-Grade Aneurysmal Subarachnoid Hemorrhage in Elderly Patients.

Background and Purpose- Whether maximal treatment should be offered to elderly patients suffering from poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is controversial. The survival of patients in this subgroup beyond the usual outcome measurements 6 to 12 months after aSAH is unclear. The purpose of this study is to provide survival and outcome data to support clinicians making decisions on treatment for this subgroup of patients. Methods- We performed a retrospective analysis of the Bernese SAH database for poor-grade (World Federation of Neurosurgical Societies grade IV and V) elderly patients (age ≥60 years) suffering from aSAH admitted to our institution from 2005 to 2017. Patients were divided into 3 age groups (60-69, 70-79, and 80-90 years). Survival analysis was performed to estimate mean survival and hazard ratios for death. Binary logarithmic regression was used to estimate the odds ratio for favorable (modified Rankin Scale score of 0-3) and unfavorable (modified Rankin Scale score of 4-6) outcome. Results- Increasing age was associated with an increasing risk of death after aSAH. The hazard ratio increased by 6% per year of age ( P<0.001; hazard ratio, 1.06; 95% CI, 1.03-1.09) and 76% per decade ( P<0.001; hazard ratio, 1.76; 95% CI, 1.35-2.29). Mean survival was 56.3±8 months (patients aged 60-69 years), 31.6±7.6 months (70-79 years), and 7.6±5.8 months (80-90 years). Unfavorable outcomes 6 to 12 months after aSAH were strongly related to older age. The odds ratio increased by 11% per year of age ( P<0.001; odds ratio, 1.11; 95% CI, 1.05-1.18) and 192% per decade ( P<0.001; odds ratio, 2.92; 95% CI, 1.63-5.26). Conclusions- Risk for death and unfavorable outcome increases markedly with older age in elderly patients with poor-grade aSAH. Despite a high initial mortality, treatment resulted in a reasonable proportion of favorable outcomes up to 79 years of age and only a small number of patients who were moderately or severely disabled 6 to 12 months after aSAH. Mean survival and proportion of favorable outcomes decreased markedly in patients older than 80 years.

Rates and Quality of Preinterventional Reperfusion in Patients With Direct Access to Endovascular Treatment.

Background and Purpose- Preinterventional reperfusion before endovascular treatment (ET) is a benefit of bridging with intravenous tPA (tissue-type plasminogen activator). However, detailed data on reperfusion quality and rates of obviating ET in a cohort of patients with immediate access to ET is lacking. Purpose of this analysis was to evaluate prevalence and quality of preinterventional reperfusion in mothership patients. Methods- All mothership patients (n=627) from a prospective registry subjected to angiography with an intention to perform ET were reviewed. Preinterventional change of occlusion site (COS) was categorized into COS with Thrombolysis in Cerebral Infarction (TICI) 0/1, COS with TICI ≥2a, COS with TICI ≥2b, and COS with perfusion worsening. Predictors and clinical relevance were evaluated using multivariable logistic regression and results are displayed as adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95% CI). Results- Prevalence of COS in all patients was 10.7% (95% CI, 8.3%-13.1%), subdividing into 2.7% COS with TICI 0/1, 6.2% COS with ≥TICI 2a (including 2.9% with TICI ≥2b), and 1.8% COS with perfusion worsening. Factors related to COS with ≥TICI 2a were intravenous tPA (aOR, 11.98; 95% CI, 4.5-31.6), cardiogenic thrombus origin (aOR, 2.3; 95% CI, 1.1-4.6), and thrombus length (aOR per 1 mm increase 0.926; 95% CI, 0.87-0.99). Additional ET was performed despite COS with ≥TICI 2a in 51.3%. COS with ≥TICI 2a showed a tendency for favorable outcomes (modified Rankin Scale, ≤2; aOR, 2.65; 95% CI, 0.98-7.17). Rates of COS with ≥TICI 2a were particularly low in internal carotid artery and proximal M1 occlusions (2.2%; 95% CI, 0.9%-5%), where intravenous tPA was associated with perfusion worsening (aOR, 4.33; 95% CI, 1.12-16.80). Conclusions- Prevalence of preinterventional reperfusion is non-negligible in patients with direct access to ET and is clearly favored by intravenous tPA treatment. However, it is often incomplete and often requires additional ET. Preinterventional reperfusion of internal carotid artery and proximal M1 occlusions is rare and usually of low quality, where intravenous tPA may also promote perfusion worsening.