Association Between Carotid-Cerebral Pulse Wave Velocity and Acute Ischemic Stroke: Clinical Trial Protocol

BackgroundPulse wave velocity is commonly regarded as the most effective and noninvasive indicator for evaluating arterial stiffness, while increased arterial stiffness is known to be related to atherosclerosis, which has been proved to play a significant role on the onset of acute ischemic stroke. However, it is still only used in the assessment of central and peripheral arteries. Our previous studies have found that carotid-cerebral pulse wave velocity measured using transcranial Doppler may be a promising method for the assessment of human cerebral arterial stiffness. This trial was designed to examine the association between carotid-cerebral pulse wave velocity and acute ischemic stroke.MethodsIn a single-center, single-arm, prospective clinical trial, patients with acute ischemic stroke who had anterior circulation infarcts confirmed by magnetic resonance imaging are eligible to receive measurement of carotid-cerebral pulse wave velocity, which is measured in the supine position with transcranial Doppler that using 2-MHz and 4-MHz ultrasound probes by 2 experienced operators. Subjects will be received follow-up for 1 year. Vascular and nonvascular death at follow-up will be assessed as primary outcomes. Secondary outcomes include intracerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack, recurrence or aggravation of ischemic stroke.ConclusionThis trial will be the first to evaluate carotid-cerebral pulse wave velocity in patients with acute ischemic stroke using transcranial Doppler. The results may provide more valuable theoretical basis for the prevention, treatment, and prognosis of acute ischemic stroke.     

The Changing Effect of Blood Pressure on Stroke Outcomes Through Acute to Subacute Stage of Ischemic Stroke

BackgroundThis study explored the associations of blood pressure (BP) with various stroke outcomes and investigated their changes by the elapsed time after stroke onset.MethodsPatients who arrived within 48 hours of stroke onset between April 2008 and September 2014 were consecutively enrolled. For 10 days of hospitalization, all measured systolic BP (SBP) was summarized into mean at acute (first 3 days) and subacute stage (afterward to 7 days) for each patient. Coprimary outcomes were unfavorable outcome (modified Rankin Scale >2) at discharge and time to composite cardiovascular event of stroke, myocardial infarction, and vascular death for 1-year follow-up. Adjusted odds ratios (AOR) through SBP_mean in both acute and subacute stages were interpolated using restricted cubic spline technique and adopted logistic regression models with predetermined covariates. The adjusted hazard ratios for cardiovascular event by SBP_mean in both stages were interpolated.ResultsThe study enrolled 3723 subjects (mean age, 66.7 ± 13.2 years old and median baseline National Institute of Health Stroke Scale score, 3). SBP_mean in both stages showed linear trends for risks of unfavorable outcome, while the increase of AOR was observed explicitly in acute stage rather than subacute stage, especially in higher values. In contrast, SBP_mean demonstrated the U-shaped associations with cardiovascular event in subacute stage rather than acute stage.ConclusionsIn ischemic stroke, association patterns of BP would be different depending on stroke outcomes. The risky interval of BP would be changed by the elapsed time after stroke onset.     

Serum Retinoic Acid Level and The Risk of Poststroke Cognitive Impairment in Ischemic Stroke Patients

Background: Retinoic acid (RA), an active metabolite of vitamin A, possesses enormous protective effects on vascular systems. It may also be positively related to good functional outcome after ischemic stroke. However, whether circulating RA concentration is associated with poststroke cognitive impairment (PSCI) remains unclear. This study aimed to detect the association between RA level and PSCI among patients with first-ever acute ischemic stroke. Methods: Two hundred and 61 consecutive patients were prospectively recruited during March 2018 and March 2019. Serum RA concentration was measured at admission for all patients. We also performed cognitive function examination using the Montreal Cognitive Assessment (MoCA) at admission and at every follow-up visit. Patients with MoCA score less than 26 were identified as developing PSCI. Results: The median serum RA level was 2.0 ng/mL (interquartile range, 1.1-3.2 ng/mL) after admission. Patients diagnosed as PSCI at admission, 1-month and 3-month were 53 (20.3%), 91 (34.6%), and 141 (54.0%), respectively. Univariate analysis showed that reduced RA level was correlated with PSCI at 3-month (P = .003), but not at admission (P = .416) and 1-month poststroke (P = .117). After adjusting for all potential confounders, the odds ratio for the lowest tertile of RA, compared with the highest tertile, was 1.97 (95% confidence interval, 1.01-3.83, P = .046) for PSCI at 3 months. Furthermore, multiple-adjusted spline regression model further confirmed the dose-response relationships between RA level and 3-month PSCI (P < .001). Conclusions: Decreasing serum RA level might be associated with 3-month PSCI in ischemic stroke patients.     

Thrombolysis Following Heparin Reversal With Protamine Sulfate in Acute Ischemic Stroke: Case Series and Literature Review

IntroductionAdministering intravenous IV tissue plasminogen activator (tPA) is the recommended standard of care in acute ischemic stroke (AIS), although it is not recommended to administer intravenous thrombolysis with tPA following heparin reversal with protamine sulfate in patients with AIS.MethodsWe describe a case series of three patients and the most comprehensive literature review published to date in this specific subset of AIS patients undergoing thrombolysis following heparin reversal with protamine sulfate. The literature review was based on a scoping review methodology performed on four databases; PubMed, CINAHL, Web of Science, and Cochrane Library. All sources were searched from the inauguration of the database until February 2019. A total of six articles involving eight patients were identified.ResultsThe primary safety outcome of no symptomatic intracranial hemorrhage (sICH) was met in all eleven patients, although only seven cases had a good functional outcome at 3 months.ConclusionsIn appropriately selected AIS patients, coagulopathy correction appears to be safe from an sICH standpoint and may be beneficial. However, given the potential for bias with observational databases, case reports and case series, extreme caution is warranted in applying these results to routine clinical practice.     

Clinical and Radiological Difficulties to Detect Isolated MCA Dissection before Intravenous tPA Therapy

A 64-year-old woman was admitted to our hospital 48 minutes after sudden onset of dysphasia and right hemiplegia. Head computed tomography revealed small infarcts in the left putamen and 4-dimensional computed tomography angiography depicted high-degree stenosis in the left middle cerebral artery and delayed filling of the contrast media in the left middle cerebral artery territory. The patient underwent intravenous tissue plasminogen activator treatment. On day 5 of hospitalization, the patient underwent conventional cerebral angiography, revealing internal carotid artery to middle cerebral artery dissection. Fortunately, subarachnoid hemorrhage as an adverse effect did not occur, although iv-tPA was administered without detecting middle cerebral artery dissection.     

Safety and Efficacy of Repeated Thrombolysis with Alteplase in Early Recurrent Ischemic Stroke: A Systematic Review

Background and Aim: The current American Heart Association guidelines for the management of acute ischemic stroke advise against the use of intravenous (IV) alteplase in patients with recurrent stroke occurring within 90 days of their index event. Following these guidelines strictly, patients having early recurrent ischemic stroke would be unable to avail of this reperfusion strategy that has been proven to confer superior clinical outcomes. While some registry-based studies have demonstrated the safety of IV alteplase in this subgroup of patients, data on the repeated use of the drug are lacking. Thus, we aim to determine the safety and efficacy of repeated thrombolysis in patients with early recurrent ischemic strokes. Methods: The following electronic databases were searched for relevant studies: the Cochrane Central Register for Controlled Trials by The Cochrane Library, MEDLINE by PubMed, Health Research and Development Information Network, Scopus, and ClinicalTrials.gov. Data on symptomatic intracranial hemorrhage, 90-day clinical outcomes, systemic hemorrhage and allergic reactionswere synthesized. Results: Ten articles with 33 patients in total were included in our review. One patient developed symptomatic intracranial hemorrhage after the second reperfusion attempt and subsequently died from pneumonia. Another died from spontaneous rupture of previously unidentified infrarenal aortic aneurysm. Six of the 13 patients with available follow-up data had good clinical outcomes (Modified Rankin Score 0-2). There were no allergic reactions and other drug-related adverse events noted. Conclusions: Repeated IV alteplase can be safe and efficacious in patients who have early recurrent ischemic stroke. Larger studies, trials, or registry-based data are needed to ascertain the encouraging findings of our review.