Intra-Arterial Thrombolysis is Associated with Delayed Reperfusion of Remaining Vessel Occlusions following Incomplete Thrombectomy.

BACKGROUND AND PURPOSE: Intra-arterial thrombolytics may be used to treat distal vessel occlusions, which cause incomplete reperfusion following mechanical thrombectomy. Because immediate reperfusion after intra-arterial thrombolytics occurs rarely, the aim of this study was to assess the delayed effect of intra-arterial thrombolytics using follow-up perfusion imaging. MATERIALS AND METHODS: We included patients from a prospective stroke registry (February 2015 to September 2022) who had undergone mechanical thrombectomy and had incomplete reperfusion (expanded TICI 2a-2c) and available 24 hour perfusion imaging. Perfusion imaging was rated as delayed reperfusion if time-sensitive perfusion maps did not show wedge-shaped delays suggestive of persisting occlusions corresponding to the post-mechanical thrombectomy angiographic deficit. Patients treated with intra-arterial thrombolytics were compared with controls using multivariable logistic regression and inverse probability of treatment weighting matching for baseline differences and factors associated with delayed reperfusion. RESULTS: The median age of the final study population (n = 459) was 74 years (interquartile range, 63-81 years), and delayed reperfusion occurred in 61% of cases. Patients treated with additional intra-arterial thrombolytics (n = 40) were younger and had worse expanded TICI scores. After matching was performed, intra-arterial thrombolytics was associated with higher rates of delayed reperfusion (adjusted OR = 2.7; 95% CI, 1.1-6.4) and lower rates of new infarction in the residually hypoperfused territory after mechanical thrombectomy (adjusted OR = 0.3; 95% CI, 0.1-0.7). No difference was found in the rates of functional independence (90-day mRS, 0-2; adjusted OR = 1.4; 95% CI, 0.4-4.1). CONCLUSIONS: Rescue intra-arterial thrombolytics is associated with delayed reperfusion of remaining vessel occlusions following incomplete mechanical thrombectomy. The value of intra-arterial thrombolytics as a potential therapy for incomplete reperfusions after mechanical thrombectomy should be assessed in the setting of randomized controlled trials.

Risks of Undersizing Stent Retriever Length Relative to Thrombus Length in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Results regarding the association of thrombus length, stent retriever length, and recanalization success in patients with acute ischemic stroke are inconsistent. We hypothesized that the ratio of thrombus length to stent retriever length may be of particular relevance. MATERIALS AND METHODS: Patients with acute ischemic stroke undergoing stent retriever thrombectomy at our institution between January 2010 and December 2018 were reviewed retrospectively. Thrombus length was assessed by measuring the susceptibility vessel sign on SWI using a 1.5T or 3T MR imaging scanner. Multivariable logistic regression models were used to determine the association between thrombus length, stent retriever length, and thrombus length/stent retriever length ratio with first-pass recanalization, overall recanalization, and embolization in new territories. Results are shown as adjusted ORs with 95% CIs. Additional mediation analyses were performed to test for indirect effects on first-pass recanalization and overall recanalization success. RESULTS: The main analysis included 418 patients (mean age, 74.9 years). Increasing stent retriever length was associated with first-pass recanalization. Decreasing thrombus length and lower thrombus length/stent retriever length ratios were associated with first-pass recanalization and overall recanalization. Thrombus length and stent retriever length showed no association with first-pass recanalization or overall recanalization once thrombus length/stent retriever length ratio was factored in, while thrombus length/stent retriever length ratio remained a significant factor in both models (adjusted OR, 0.316 [95% CI, 0.112-0.892]; P = .030 and adjusted OR, = 0.366 [95% CI, 0.194-0.689]; P = .002). Mediation analyses showed that decreasing thrombus length and increasing stent retriever length had a significant indirect effect on first-pass recanalization mediated through thrombus length/stent retriever length ratio. The only parameter associated with embolization in new territories was an increasing thrombus length/stent retriever length ratio (adjusted OR, 5.079 [95% CI, 1.332-19.362]; P = .017). CONCLUSIONS: Information about thrombus and stent length is more valuable when combined. High thrombus length/stent retriever length ratios, which may raise the risk of unsuccessful recanalization and embolization in new territories, should be avoided by adapting stent retriever selection to thrombus length whenever possible.

SWI Susceptibility Vessel Sign in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The frequency and clinical significance of the susceptibility vessel sign in patients with acute ischemic stroke remains unclear. We aimed to assess its prevalence in patients with acute ischemic stroke undergoing mechanical thrombectomy and to analyze its association with interventional and clinical outcome parameters in that group. MATERIALS AND METHODS: Six hundred seventy-six patients with acute ischemic stroke and admission MR imaging were reviewed retrospectively. Of those, 577 met the eligibility criteria for further analysis. Imaging was performed using a 1.5T or 3T MR imaging scanner. Associations between baseline variables, interventional and clinical outcome parameters, and susceptibility vessel sign were determined with multivariable logistic regression models. Results are shown as adjusted ORs with 95% CIs. RESULTS: The susceptibility vessel sign was present in 87.5% (n = 505) of patients and associated with tandem occlusion (adjusted OR, 3.3; 95% CI, 1.1-10.0; P = .032) as well as successful reperfusion, defined as an expanded TICI score of ≥2b (adjusted OR, 2.4; 95% CI, 1.28-4.6; P = .007). The susceptibility vessel sign was independently associated with functional independence (mRS ≤ 2: adjusted OR, 2.1; 95% CI, 1.1-4.0; P = .028) and lower mortality (adjusted OR, 0.4; 95% CI, 0.2-0.7; P = .003) at 90 days, even after adjusting for successful reperfusion. The susceptibility vessel sign did not influence the number of passes performed during mechanical thrombectomy, the first-pass reperfusion, or the risk of peri- or postinterventional complications. CONCLUSIONS: The susceptibility vessel sign is an MR imaging phenomenon frequently observed in patients with acute ischemic stroke and is associated with successful reperfusion after mechanical thrombectomy. However, superior clinical functional outcome and lower mortality noted in patients showing the susceptibility vessel sign could not be entirely attributed to higher reperfusion rates.

Fatal intracranial haemorrhage occurring after oral anticoagulant treatment initiation for secondary stroke prevention in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: In this pooled analysis of seven multicentre cohorts potential differences were investigated in the incidence, characteristics and outcomes between intracranial haemorrhages (ICHs) associated with the use of non-vitamin K antagonist oral anticoagulants (NOAC-ICH) or with vitamin K antagonists (VKA-ICH) in ischaemic stroke patients after oral anticoagulant treatment initiation for atrial fibrillation (AF). METHODS: Data from 4912 eligible AF patients who were admitted in a stroke unit with ischaemic stroke or transient ischaemic attack and who were treated with either VKAs or NOACs within 3 months post-stroke were included. Fatal ICH was defined as death occurring during the first 30 days after ICH onset. A meta-analysis of available observational studies reporting 30-day mortality rates from NOAC-ICH or VKA-ICH onset was additionally performed. RESULTS: During 5970 patient-years of follow-up 71 participants had an ICH, of whom 20 were NOAC-ICH and 51 VKA-ICH. Patients in the two groups had comparable baseline characteristics, except for the higher prevalence of kidney disease in VKA-ICH patients. There was a non-significant higher number of fatal ICH in patients with VKAs (11 events per 3385 patient-years) than in those with NOACs (three events per 2623 patient-years; hazard ratio 0.32, 95% confidence interval 0.09-1.14). Three-month functional outcomes were similar (P > 0.2) in the two groups. The meta-analysis showed a lower 30-day mortality risk for patients with NOAC-ICH compared to VKA-ICH (relative risk 0.70, 95% confidence interval 0.51-0.95). CONCLUSIONS: Non-vitamin K oral anticoagulants for intracranial haemorrhages and VKA-ICH occurring during secondary stroke prevention of AF patients have comparable baseline characteristics and outcomes except for the risk of fatal ICH within 30 days, which might be greater in VKA-ICH.

Fast-track versus long-term hospitalizations for patients with non-disabling acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to assess the feasibility and safety of fast-track hospitalizations in a selected cohort of patients with stroke. METHODS: Patients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion-weighted imaging were included. Neurological deficits of the included patients were non-disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared - fast-track hospitalizations (≤72 h) and long-term hospitalizations (>72 h). The primary end-point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3-6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW). RESULTS: Amongst the 521 patients who met the inclusion criteria, fast-track hospitalizations were performed in 79 patients (15%). In the fast-track group, seven patients (8.9%) met the primary end-point, compared to 37 (8.4%) in the long-term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42-2.34, P = 0.88]. After weighting for IPTW, the odds of the primary end-point remained similar between the two arms (ORIPTW 1.27, 95% CI 0.51-3.16, P = 0.61). The costs of fast-track hospitalizations were lower, on average, by $4994. CONCLUSIONS: Fast-track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long-term hospitalizations.

Management of patients with stroke treated with direct oral anticoagulants.

Since their market approval, direct oral anticoagulants (DOACs) are being increasingly used for stroke prevention in patients with atrial fibrillation. However, the management of DOAC-treated patients with stroke poses several challenges for physicians in everyday clinical practice, both in the acute setting and in long-term care. This has spurred extensive research activity in the field over the past few years, which we review here.

Serum neurofilament light chain in patients with acute cerebrovascular events.

BACKGROUND AND PURPOSE: Serum neurofilaments are markers of axonal injury. We addressed their diagnostic and prognostic role in acute ischemic stroke (AIS) and transient ischemic attack (TIA). METHODS: Nested within a prospective cohort study, we compared levels of serum neurofilament light chain (sNfL) drawn within 24 h from symptom onset in patients with AIS or TIA. Patients without magnetic resonance imaging on admission were excluded. We assessed whether sNfL was associated with: (i) clinical severity on admission, (ii) diagnosis of AIS vs. TIA, (iii) infarct size on admission magnetic resonance diffusion-weighted imaging (MR-DWI) and (iv) functional outcome at 3 months. RESULTS: We analyzed 504 patients with AIS and 111 patients with TIA. On admission, higher National Institutes of Health Stroke Scale (NIHSS) scores were associated with higher sNfL: NIHSS score < 7, 13.1 pg/mL [interquartile range (IQR), 5.3-27.8]; NIHSS score 7-15, 16.7 pg/mL (IQR, 7.4-34.9); and NIHSS score > 15, 21.0 pg/mL (IQR, 9.3-40.4) (P = 0.01). Compared with AIS, patients with TIA had lower sNfL levels [9.0 pg/mL (95% confidence interval, 4.0-19.0) vs. 16.0 pg/mL (95% confidence interval, 7.3-34.4), P < 0.001], also after adjusting for age and NIHSS score (P = 0.006). Among patients with AIS, infarct size on admission MR-DWI was not associated with sNfL, either in univariate analysis (P = 0.15) or after adjusting for age and NIHSS score on admission (P = 0.56). Functional outcome 3 months after stroke was not associated with sNfL after adjusting for established predictors. CONCLUSIONS: In conclusion, among patients admitted within 24 h of AIS or TIA onset, admission sNfL levels were associated with clinical severity on admission and TIA diagnosis, but not with infarct size on MR-DWI acquired on admission or functional outcome at 3 months.

Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined. METHODS: In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)]. CONCLUSION: Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. METHODS: In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m2 ) from underweight (<18.5 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (≥30 kg/m2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. RESULTS: Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. CONCLUSION: In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH.

New ischaemic brain lesions in cervical artery dissection stratified to antiplatelets or anticoagulants.

BACKGROUND AND PURPOSE: To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow-up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment. METHODS: This prospective observational study included consecutive CAD patients with ischaemic or non-ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow-up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion-weighted imaging (DWI), intracerebral bleeds (ICBs) by paramagnetic-susceptible sequences. Outcome measures were any new DWI lesions or ICBs on follow-up MRI scans. Kaplan-Meier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant). RESULTS: Sixty-eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow-up MRI scans was 5 (3-10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30-day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01-30.93)], occlusion of the dissected vessel [4.09 (1.24-13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70-26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32-3.15)] or on functional 6-month outcome [1.27 (0.41-3.94)]. No new ICBs were observed. CONCLUSION: New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials.

Simple variables predict miserable outcome after intravenous thrombolysis.

BACKGROUND AND PURPOSE: To test the predictability of miserable outcome amongst ischaemic stroke patients receiving intravenous thrombolysis (IVT) based on a simple variables model (SVM) and to compare the model's predictive performance with that of an existing score which includes imaging and laboratory parameters (DRAGON). METHODS: The SVM consists of the parameters age, independence before stroke, normal Glasgow coma verbal score, able to lift arms and able to walk. In a derivation cohort (n = 1346) and a validation cohort (n = 638) of consecutive IVT-treated stroke patients, the probability estimated by SVM and the observed occurrence of miserable 3-month outcome (modified Rankin score 5-6) were compared. The performances of SVM and the DRAGON score were compared. The area under the receiver operating curve (AUC) (95% confidence interval, CI) and the bootstrapping approach were used to compare the predictive performance. RESULTS: The AUCs to predict miserable outcome in the derivation cohort were 0.807 (95% CI 0.774-0.838) using the SVM and 0.822 (0.790-0.850) using the DRAGON score (P = 0.3). For the validation cohort, AUCs were 0.786 (0.742-0.829) for the SVM and 0.809 (0.774-0.845) for the DRAGON score (P = 0.23). Only one patient with an SVM probability of >70% for miserable outcome in either cohort had a good outcome whilst 83% had a miserable outcome. An online SVM calculator to estimate the probability of miserable outcome for individual patients is available under http://www.unispital-basel.ch/SVM-Tool. CONCLUSION: The SVM was similar in accuracy to the DRAGON score for predicting miserable outcome after IVT. As these simple variables are available already at the pre-hospital stage, the SVM may facilitate and accelerate pre-hospital triage of patients at high risk for miserable outcome after IVT towards endovascular treatment.