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Unknown onset ischemic strokes in patients last-seen-well >4.5 h: differences between wake-up and daytime-unwitnessed strokes.

ABSTRACT: Patients with unknown time of stroke onset (UOS) represent around one-third of ischemic stroke patients. These are patients with wake-up stroke (WUS) or daytime-unwitnessed stroke (DUS), often presenting outside the time-window for reperfusion therapy. UOS patients presenting between 4.5 and 12 h after time of last-seen-well were included. Clinical and imaging characteristics were compared between WUS and DUS patients. Good functional outcome was defined as a modified Rankin scale of ?2 at follow-up. Sixty-one UOS patients were included: 42 WUS and 19 DUS patients. Stroke severity at presentation was mild to moderate with a median National Institutes of Health Stroke Scale of 5 in WUS and 6 in DUS patients. Time between last-seen-well and presentation at the hospital was shorter in patients with DUS compared to WUS (506 vs 362 min, p < 0.01). CT imaging results were similar, with a median Alberta Stroke Program Early CT Score of 10 for both WUS and DUS patients. After correction for age and NIHSS at presentation, no difference in good functional outcome was found between WUS (52%) and DUS (22%). In patients with unknown onset ischemic strokes presenting between 4.5 and 12 h after time of last-seen-well, clinical and radiological features were in large part similar between WUS and DUS. The outcome in the overall cohort was rather poor despite a favorable neuroimaging profile at presentation. These findings underscore the need for clinical trials in patients in whom stroke onset time is unknown.

SUBMITTER: Dekker L

PROVIDER: S-EPMC5565646 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Unknown onset ischemic strokes in patients last-seen-well >4.5 h: differences between wake-up and daytime-unwitnessed strokes.

Dekker Luuk L Hund Hajo H Lemmens Robin R Boiten Jelis J van den Wijngaard Ido I

Acta neurologica Belgica 20170812 3

Patients with unknown time of stroke onset (UOS) represent around one-third of ischemic stroke patients. These are patients with wake-up stroke (WUS) or daytime-unwitnessed stroke (DUS), often presenting outside the time-window for reperfusion therapy. UOS patients presenting between 4.5 and 12 h after time of last-seen-well were included. Clinical and imaging characteristics were compared between WUS and DUS patients. Good functional outcome was defined as a modified Rankin scale of ≤2 at follo ...[more]

PMID: 28803427

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Project description:Background: rt-PA for ischemic stroke in the unknown or extended time window beyond the first 4. 5 h after symptom onset is safe and effective for certain patients after selection by multimodal neuroimaging. However, the evidence for this approach comes mainly from patients with anterior circulation stroke (ACS), while the data on posterior circulation stroke (PCS) are scarce. Methods: Ischemic stroke patients treated with IV-thrombolysis in the unknown or extended time window between January 2011 and May 2019 were identified from an institutional registry. The patients were categorized into PCS or ACS based on clinico-radiological findings. We analyzed the hemorrhagic complications, clinical and imaging efficacy outcomes, and mortality rates by comparing the PCS and ACS patient groups. Adjusted outcome analyses were performed after propensity score matching for the relevant factors. Results: Of the 182 patients included, 38 (20.9%) had PCS and 144 (79.1%) had ACS. Symptomatic acute large vessel occlusion (LVO) was present in 123 patients on admission [27 (22.0%) PCS and 96 (78.0%) ACS]. The score on the National Institutes of Health Stroke Scale (NIHSS), the time from last seen normal, and the door-to-needle times were similar in PCS and ACS. In patients with LVO, the NIHSS score was lower [8 (5-15) vs. 14 (9-18), p = 0.005], and infarction visible on follow-up imaging was less common [70.4 vs. 87.5%; aRD, -18.9% (-39.8 to -2.2%)] in the PCS patient group. There was a trend toward a lower risk for intracranial hemorrhage (ICH) following intravenous thrombolysis in PCS vs. ACS, without reaching a statistical significance [5.3 vs. 16.9%; aRD, -10.4% (-20.4 to 4.0%)]. The incidence of symptomatic ICH [according to the ECASS III criteria: 2.6 vs. 3.5%; aRD, -2.9% (-10.3 to 9.2%)], efficacy outcomes, and mortality rates were similar in PCS and ACS patients. Conclusions: In this real-world clinical cohort, the safety and the efficacy of rt-PA for ischemic stroke in the unknown or extended time window did not show relevant differences between PCS and ACS, with a trend toward less hemorrhagic complications in PCS. The findings reconfirm the clinician in the usage of rt-PA beyond the first 4.5 h also in selected patients with PCS.

Project description:BackgroundThe optimal dose of tenecteplase vs. alteplase for acute ischemic stroke (AIS) has yet to be established. Therefore, we included the latest randomized controlled trials (RCT) to assess the efficacy and safety of different doses of tenecteplase vs. alteplase for AIS within 4.5 hours of symptom onset.MethodsLiterature was searched in PubMed, Cochrane Library, Embase, Web of Science, and clinical trial registries until February 12, 2023. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using Bayesian network meta-analysis (NMA). Treatments were ranked based on efficacy and safety using the surface under the cumulative ranking curve (SUCRA).ResultsEleven RCTs with 5,475 patients were included. Tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg had significantly higher rates of excellent functional outcome (tenecteplase: OR, 1.85; 95% CrI, 1.44-2.37; alteplase: OR, 1.60; 95% CrI, 1.29-1.97) and good functional outcome (tenecteplase: OR, 1.54; 95% CrI, 1.19-1.98; alteplase: OR, 1.40; 95% CrI, 1.14-1.74) than placebo, despite an increased risk of symptomatic intracranial hemorrhage. Furthermore, the NMA (OR, 1.16; 95% CrI, 1.01-1.33) and the pairwise meta-analysis (OR, 1.16; 95% CI, 1.02-1.33; P = 0.03) indicated that tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg in excellent functional outcome. Alteplase 0.9 mg/kg (OR, 2.54; 95% CrI, 1.45-8.08) significantly increased the risk of any intracranial hemorrhage compared with placebo. SUCRA results demonstrated that tenecteplase 0.25 mg/kg ranked first and tenecteplase 0.4 mg/kg ranked last in efficacy outcomes.ConclusionsThe NMA indicated that tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg are safe and significantly improve clinical outcomes in patients with AIS within 4.5 h of symptom onset. Furthermore, tenecteplase 0.25 mg/kg provides more benefit and has the potential to replace alteplase 0.9 mg/kg in AIS treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/index.php, identifier: CRD42022343948.

Dataset Information

Unknown onset ischemic strokes in patients last-seen-well >4.5 h: differences between wake-up and daytime-unwitnessed strokes.

Publications

Unknown onset ischemic strokes in patients last-seen-well >4.5 h: differences between wake-up and daytime-unwitnessed strokes.

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