Background and Aims: The DAWN and DEFUSE-3 trials demonstrated the benefit of late endovascular treatment (EVT) in acute ischemic stroke (AIS) patients. We aimed to identify indipendent predictors for late EVT eligibility according to trials and to more liberal criteria. Moreover, we compared the clinical outcome of patients treated with late EVT and fulfilling each set of selection criteria. Material and Methods: In the ASTRAL registry (2003-2017), we calculated the proportion of late (6-24 hours) EVT eligibility according to trials and to more liberal criteria (the latter including M2 occlusion, lower NIHSS on admission, and using ASPECTS for core volume estimation). We searched for clinical and radiological variables associated with late EVT eligibility using a multivariate regression. We also analysed functional independence (modified Rankin Scale (mRS) 0-2) at 3 months for patients treated with late EVT. Results: Out of 925 late arriving AIS patients with complete data, 2.5% were eligible with DAWN, 5.1% with DEFUSE-3 and 11.1% with liberal criteria. Variables associated with late EVT eligibility are shown in Table 1. Functional independence was achieved in 6/14 (42.9%) of the trial-eligible, and in 11/27 (40.7%) of the liberal-eligible patients treated with EVT. After adjustment for age, NIHSS, vigilance impairment, ASPECTS and acute glucose, DEFUSE-3-like patients showed better outcome than DAWN-like and liberal criteria selected patients (OR 4.45; 95%CI 1.11-17.85). Conclusion: Among late arriving AIS patients, only 5% were eligible for late EVT based on trials criteria. Radiological variables were stronger than clinical predictors to identify DAWN and DEFUSE-3 patients. In the small cohort of effectively treated patients, satisfying DEFUSE-3 was associated with the most favourable outcome.
Background Limited observational data are available on endovascular treatment in acute ischemic stroke due to cervical artery dissection. Three studies comparing endovascular treatment with standard medical therapy or intravenous thrombolysis in cervical artery dissection-related acute ischemic stroke did not demonstrate superiority of endovascular treatment. Efficacy and the choice of endovascular treatment technique in this setting remain to be established. Aims To assess the potential efficacy and safety of endovascular treatment compared to intravenous thrombolysis alone or to no revascularization treatment in our center. Methods We selected all consecutive patients with cervical artery dissection-related acute ischemic stroke and intracranial occlusion from the Acute STroke Registry and Analysis of Lausanne between 2003 and 2017. We compared clinical and neuroimaging data of patients treated by endovascular treatment versus patients receiving intravenous thrombolysis or patients without revascularization treatment. Safety analysis included symptomatic intracranial hemorrhage, major radiological hemorrhages (parenchymal hematoma 1, parenchymal hematoma 2, and subarachnoid hemorrhage) and mortality within seven days. We assessed favorable clinical outcome (modified Rankin Scale 0-2) at three months using a binary logistic regression model. Results Of the 109 patients included, 24 had endovascular treatment, 38 received intravenous thrombolysis alone, and 47 had no revascularization treatment. Endovascular treatment patients had a higher rate of recanalization at 24 h. Major radiological hemorrhages occurred more often in endovascular treatment patients (all with bridging therapy) than in patients without revascularization treatment (p = 0.026), with no differences in symptomatic intracranial hemorrhage or mortality within seven days. Favorable clinical outcome at three months did not differ between groups (endovascular treatment versus intravenous thrombolysis p = 0.407; endovascular treatment versus no revascularization treatment p = 0.580). Conclusions In this single-center cohort of cervical artery dissection-related acute ischemic stroke with intracranial occlusion, endovascular treatment with prior intravenous thrombolysis may increase the risk of major radiological but not symptomatic intracranial hemorrhage. Despite the lack of clear superiority in our cohort, endovascular treatment should currently not be withheld in these patients.
Background and aims Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. Methods In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan–Meier product limit method. Results In 772 patients (median NIHSS: 6 (interquartile range: 3–12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27–2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73–1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44–1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05–2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2–48.6) vs. 36.6% (27.8–47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5–50.0) vs. 34.0% (26.0–43.6) respectively; log-rank test: 4.54, p = 0.033). Conclusions Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.
Oral anticoagulation with vitamin K antagonists (VKA) was the cornerstone of stroke prevention in atrial fibrillation (AF). This review article presents the state of the art, with regard to the treatment options developed over the past few years, the new oral anticoagulants (NOAC). A search in PubMed for relevant published studies has been performed. Dabigatran and apixaban were superior to warfarin to reduce stroke risk or systemic embolism ; dabigatran, rivaroxaban and edoxaban were non-inferior. All NOAC are globally non-inferior to warfarin for stroke prevention in non-valvular AF and they have a superior safety profile, with a reduced intracranial bleeding risk. They are now the first choice for treatment.Les antagonistes de la vitamine K (AVK) ont été pendant longtemps la référence comme prévention de l’accident vasculaire cérébral (AVC) chez les patients souffrant de fibrillation auriculaire (FA). Cet article de revue propose une mise à jour des options thérapeutiques développées ces dernières années, à savoir les nouveaux anticoagulants oraux (NACO). Une recherche des études pertinentes a été effectuée dans PubMed. Il apparaît ainsi que le dabigatran et l’apixaban sont supérieurs à la warfarine pour réduire les AVC et les embolies systémiques ; le dabigatran, le rivaroxaban et l’édoxaban sont non inférieurs. Tous les NACO sont donc globalement non inférieurs à la warfarine pour prévenir les AVC dans la FA non valvulaire et ils ont un profil de sécurité supérieur, avec un moindre risque d’hémorragie intracrânienne. Ils représentent maintenant le traitement de premier choix.
The impact of prior statin use on outcomes after thrombolysis is unclear. We evaluated outcomes of patients treated by IV, intra-arterial (IA) thrombolysis, or combined therapy, according to prior statin use.We analyzed data from a patient registry (606 patients) and conducted a systematic review.We identified 11 previous studies (6,438 patients) that evaluated the effect of statin use on outcomes after IV thrombolysis (8 studies), IA thrombolysis (2 studies), or a single/combined approach (1 study). In our registry and in most of the retrieved studies, statin users had more risk factors and concomitant antiplatelet treatment than nonstatin users. Regardless of treatment strategy, prior statin use was not associated with favorable outcome (adjusted odds ratio [OR] 1.36; 95 confidence interval [CI] 0.86-2.16), symptomatic intracranial hemorrhage (sICH) (OR 0.57; 95% CI 0.22-1.49), or recanalization (OR 1.87; 95% CI 0.69-5.03). In meta-analysis, prior statin use was not associated with favorable outcome (crude OR 0.99; 95% CI 0.88-1.12), but was associated with an increased risk of sICH (crude OR 1.55; 95% CI 1.23-1.95). However, when the available multivariable associations were combined (5 studies), the effect of prior statin use on risk of sICH was not significant (OR 1.31; 95% CI 0.97-1.76).These results suggest no beneficial or detrimental effect of prior statin use in acute stroke patients treated by IV thrombolysis, IA thrombolysis, or combined therapy, although the numbers of patients treated by IA thrombolysis or combined therapy are too small to exclude an effect.
Background: The increasing number of patients eligible for endovascular therapy (EVT) could be a potential source of fatigue for the stroke management team leading to poor outcome. We sought to investigate the association between EVT start time in acute ischemic stroke (AIS) and long-term neurological outcome.Methods: In this retrospective cohort study, 1,558 cases treated by EVT from January 2012 to December 2018 were analysed using stroke registries from two tertiary stroke centres. The primary endpoint was the score on the the modified Rankin Scale (mRS) at 90 days. A proportional odds model was used to calculate the common odds ratio (OR) as a measure of the likelihood that the intervention at a given EVT start time would lead to lower scores on the mRS than at other EVT start times. Secondary endpoints were EVT start-to-recanalisation time, modified treatment in cerebral ischemia score, number of EVT passes and rate of symptomatic intracranial haemorrhage. Findings: Symptom onset-to-EVT start time was significantly higher and use of IV tPA significantly lower between 10:20-11:34 (P<0·004 and P=0·012, respectively). The primary endpoint favored EVT start times in the morning at 08:00-10:20 and 10:20-11:34 (OR, 0·53; 95% confidence interval (CI), 0·37-0·75; P<0·001; OR, 0·62; 95% CI, 0·44-0·87; P=0·006, respectively), while it disfavored EVT start times at the end of the working day at 15:55-17:15 (OR, 1·47; 95% CI, 1·03-2·09; P=0·033) and 18:55-20:55 (OR, 1·54; 95% CI, 1·07-2·22; P=0·020). No statistical difference was observed in the secondary endpoints between any time periods.Interpretation: EVT for AIS in the morning leads to better long-term neurological outcome, despite having a statistically longer symptom onset-to-EVT start time, while EVT at the end of the work day leads to poorer long-term neurological outcome. Neither difference in baseline factors, standard workflow and technical efficacy metrics could be identified as potential mediators of this effect.Funding Statement: The authors stated: No funding was provided for this study.Declaration of Interests: The authors certify that they have no affiliations with any financial or non-financial interest in the subject matter or materials discussed in this manuscript.Ethics Approval Statement: The study was approved by the local institutional review board of each hospital under the auspices of the Swiss ethics committees for research involving humans (Swissethics). No informed consent was required according to the legislation.
Information about rivaroxaban plasma level (RivLev) may guide treatment decisions in patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) taking rivaroxaban.In a multicenter registry-based study (Novel Oral Anticoagulants in Stroke Patients collaboration; ClinicalTrials.gov: NCT02353585) of patients with stroke while taking rivaroxaban, we compared RivLev in patients with AIS and ICH. We determined how many AIS patients had RivLev ≤ 100ng/ml, indicating possible eligibility for thrombolysis, and how many ICH patients had RivLev ≥ 75ng/ml, making them possibly eligible for the use of specific reversal agents. We explored factors associated with RivLev (Spearman correlation, regression models) and studied the sensitivity and specificity of international normalized ratio (INR) thresholds to substitute RivLev using cross tables and receiver operating characteristic curves.Among 241 patients (median age = 80 years, interquartile range [IQR] = 73-84; median time from onset to admission = 2 hours, IQR = 1-4.5 hours; median RivLev = 89ng/ml, IQR = 31-194), 190 had AIS and 51 had ICH. RivLev was similar in AIS patients (82ng/ml, IQR = 30-202) and ICH patients (102ng/ml, IQR = 51-165; p = 0.24). Trough RivLev(≤137ng/ml) occurred in 126/190 (66.3%) AIS and 34/51 (66.7%) ICH patients. Among AIS patients, 108/190 (56.8%) had RivLev ≤ 100ng/ml. In ICH patients, 33/51 (64.7%) had RivLev ≥ 75ng/ml. RivLev was associated with rivaroxaban dosage, and inversely with renal function and time since last intake (each p < 0.05). INR ≤ 1.0 had a specificity of 98.9% and a sensitivity of 25.7% to predict RivLev ≤ 100ng/ml. INR ≥ 1.4 had a sensitivity of 59.3% and specificity of 90.1% to predict RivLev ≥ 75ng/ml.RivLev did not differ between patients with AIS and ICH. Half of the patients with AIS under rivaroxaban had a RivLev low enough to consider thrombolysis. In ICH patients, two-thirds had a RivLev high enough to meet the eligibility for the use of a specific reversal agent. INR thresholds perform poorly to inform treatment decisions in individual patients. Ann Neurol 2018;83:451-459.
<i>Background:</i> Mannitol infusion is widely used in clinical practice to reduce perilesional edema in intracerebral hemorrhage (ICH), though no controlled studies have yet provided evidence of its effects on clinical outcome or on cerebral blood flow impairment following the event. The aim of our study was to evaluate blood flow velocity changes in the middle cerebral arteries (MCA) after a mannitol bolus in patients with ICH. <i>Methods:</i> Transcranial Doppler bilateral monitoring was performed for 90 min in 20 patients with ICH, during 100 ml mannitol bolus i.v. administration. The MCA mean flow velocities (MFVs) and pulsatility index (PI) were recorded. <i>Results:</i> When the ‘healthy’ and the ‘affected’ hemispheres were compared, we observed higher MCA MFV and lower PI on the affected side than on the contralateral side, both at baseline and during the experiment. After the mannitol bolus, we observed a significant MFV increase, starting at the end of the infusion and lasting longer than 60 min in the MCA on the affected side alone. The PI increased after mannitol administration on the healthy side alone. <i>Conclusions:</i> A single bolus of mannitol modified cerebral hemodynamics in our patients with ICH, increasing flow velocities on the affected MCA. This effect may be a consequence of reduced edema in the perilesional areas. The increased PI on the unaffected side may be indicative of preserved pulsatility in the healthy hemisphere.
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