Background and Purpose—: There is some controversy on the association of the National Institutes of Health Stroke Scale (NIHSS) score to predict arterial occlusion on MR arteriography and CT arteriography in acute stroke. Methods—: We analyzed NIHSS scores and arteriographic findings in 2152 patients (35.4% women, mean age 66±14 years) with acute anterior or posterior circulation strokes. Results—: The study included 1603 patients examined with MR arteriography and 549 with CT arteriography. Of those, 1043 patients (48.5%; median NIHSS score 5, median time to clinical assessment 179 minutes) showed an occlusion, 887 in the anterior (median NIHSS score 7/0–31), and 156 in the posterior circulation (median NIHSS score 3/0–32). Eight hundred sixty visualized occlusions (82.5%) were located centrally (ie, in the basilar, intracranial vertebral, internal carotid artery, or M1/M2 segment of the middle cerebral artery). NIHSS scores turned out to be predictive for any vessel occlusions in the anterior circulation. Best cut-off values within 3 hours after symptom onset were NIHSS scores ≥9 (positive predictive value 86.4%) and NIHSS scores ≥7 within >3 to 6 hours (positive predictive value 84.4%). Patients with central occlusions presenting within 3 hours had NIHSS scores <4 in only 5%. In the posterior circulation and in patients presenting after 6 hours, the predictive value of the NIHSS score for vessel occlusion was poor. Conclusions—: There is a significant association of NIHSS scores and vessel occlusions in patients with anterior circulation strokes. This association is best within the first hours after symptom onset. Thereafter and in the posterior circulation the association is poor.

Background and Purpose—: Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. Methods—: In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. Results—: One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5–2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0–5.0) compared with 7.9% (95% confidence interval, 7.2–8.7) in ischemic strokes. Conclusions—: In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. Among these factors collaterals as seen on angiography were of special interest. Forty-four patients were included in this analysis. They had all received endovascular therapy and at least minimal reperfusion was achieved. Their penumbra was assessed with perfusion- and diffusion-weighted imaging. Perfusion-weighted imaging volumes were defined by circular singular value decomposition deconvolution maps (T_max > 6 s) and results were compared with volumes obtained with non-deconvolved maps (time to peak > 4 s). Loss of penumbral volume was defined as difference of post- minus pretreatment diffusion-weighted imaging volumes and calculated in per cent of pretreatment penumbral volume. Correlations between baseline characteristics, reperfusion, collaterals, time to reperfusion and penumbral volume loss were assessed using analysis of covariance. Collaterals (P = 0.021), reperfusion (P = 0.003) and their interaction (P = 0.031) independently influenced penumbral tissue loss, but not time from magnetic resonance (P = 0.254) or from symptom onset (P = 0.360) to reperfusion. Good collaterals markedly slowed down and reduced the penumbra loss: in patients with thrombolysis in cerebral infarction 2 b-3 reperfusion and without any haemorrhage, 27% of the penumbra was lost with 8.9 ml/h with grade 0 collaterals, whereas 11% with 3.4 ml/h were lost with grade 1 collaterals. With grade 2 collaterals the penumbral volume change was −2% with −1.5 ml/h, indicating an overall diffusion-weighted imaging lesion reversal. We conclude that collaterals and reperfusion are the main factors determining loss of penumbral tissue in patients with middle cerebral artery occlusions. Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatment.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140–720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22–2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82]; P =0.02). Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

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: β −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

Objective A reperfusion quality of thrombolysis in cerebral infarction (TICI)≥2b has been set as the therapeutic angiography target for interventions in patients with acute ischaemic stroke. This study addresses whether the distinction between TICI2b and TICI3 reperfusions shows a clinically relevant difference on functional outcome. Methods A systematic literature review and meta-analysis was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to test the primary hypothesis that TICI2b and TICI3 reperfusions are associated with different rates of modified Rankin Scale (mRS) ≤2 at day 90. Secondary endpoints included rates of haemorrhagic transformations, mortality and excellent functional outcome (mRS ≤1). Summary estimates of ORs (sOR) with 95% CI were calculated using the inverse variance heterogeneity model accounting for multiple true effect sizes. Results Fourteen studies on 2379 successfully reperfused patients were included (1131 TICI3, 1248 TICI2b). TICI3 reperfusions were associated with higher rates of functional independence (1.74, 95% CI 1.44 to 2.10) and excellent functional outcomes (2.01, 95% CI 1.60 to 2.53), also after including adjusted estimates. The safety profile of patients with TICI3 was superior, as demonstrated by lower rates of mortality (sOR 0.59, 95% CI 0.37 to 0.92) and symptomatic intracranial haemorrhages (sOR 0.42, 95% CI 0.25 to 0.71). Conclusion TICI3 reperfusions are associated with superior outcome and better safety profiles than TICI2b reperfusions. This effect seems to be independent of time and collaterals. As reperfusion quality is the most important modifiable predictor of patients’ outcome, a more conservative definition of successful therapy and further evaluation of treatment approaches geared towards achieving TICI3 reperfusions are desirable.