Early Phase Of Acute Ischemic Stroke Research Articles

Association of concomitant headache with hypoperfusion in ischemic stroke: A multimodal CT-based study.

Previous investigations indicate that vessel wall elasticity may contribute to the occurrence of an ischemic stroke-associated headache. In this prospective study, the association between radiologic parameters of intracranial hemodynamic changes and concomitant headaches during the early phase of ischemic stroke was examined. Consecutive patients with acute ischemic stroke (AIS) from the First Affiliated Hospital of Soochow University were recruited and divided into two groups according to their questionnaire results and the International Classification of Headache Disorder 3 criteria. Baseline data, including stroke sub-types and neurological function, at admission and discharge were collected. Non-contrast computed tomography (CT), CT angiography, and CT perfusion were performed to assess intracranial hemodynamic changes. Multiple adjusted logistic models were used and possible confounding factors were included in sequential models. A total of 190 patients with AIS (93 headaches and 97 non-headache) were recruited. There were significant differences between the two groups in gender, hypertension, Alberta stroke program early CT score, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Furthermore, rCBV (adjusted odds ratio [OR] 0.160; 95% confidence interval [CI], 0.055-0.461; p < 0.001) and rCBF (adjusted OR, 0.309; 95% CI, 0.113-0.844; p < 0.05) were significantly associated with concomitant headache during the early phase of AIS in fully adjusted models. After adjusting for sociodemographic characteristics and other confounding factors, p values for the ORs were robust and intensified. Patients with lower rCBV and rCBF tended to experience the concomitant headache during the early phase of AIS. Regional hypoperfusion and microcirculation might play an important role in this separate clinical entity.

Focus on blood pressure levels and variability in the early phase of acute ischemic stroke with hypertension and carotid stenosis.

To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single‐center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP < 140 mm Hg and DBP < 90 mm Hg), Group 2: (SBP: 140–159 mm Hg and or DBP: 90–99 mm Hg), and Group 3: (SBP ≥160 mm Hg and/or DBP ≥100 mm Hg) according to the guidelines. The associations of mean BP levels and variability with outcomes (recurrent stroke, all‐cause death and the composite cardiovascular events) at 6 months were analyzed by Cox proportional hazard models. The associations of BP variability with BP levels and cerebral blood flow (CBF) were analyzed by linear regression and generalized additive models. Both for primary and secondary outcome, more events occurred in Group 1 compared with Group 2, while no significant difference was found in Group 3 with higher BP levels. Lower systolic BP variability showed better prognosis and higher CBF. The associations were more significant in patients with CAS ≥50%. BP variability exhibited a linear negative relationship with BP levels. In the early phase of AIS with hypertension and CAS, maintaining low blood pressure variability may be important to improve outcomes while low BP levels (SBP/DBP < 140/90 mm Hg) were harmful, especially in those patients with CAS ≥ 50%.

Intracranial Hemorrhage After Reperfusion Therapies in Acute Ischemic Stroke Patients.

Reperfusion therapies are the mainstay of acute ischemic stroke (AIS) treatments and overall improve functional outcome. Among the established complications of intravenous (IV) tissue-type plasminogen activator (tPA), intracranial hemorrhage (ICH) is by far the most feared and has been extensively described by seminal works over the last two decades. Indeed, IV tPA is associated with increased odds of any ICH and symptomatic ICH responsible for increased mortality rate during the first week after an AIS. Despite these results, IV tPA has been found beneficial in several pioneering randomized trials and improves functional outcome at 3 months. Endovascular therapy (EVT) combined with IV tPA for AIS patients consecutive to an anterior circulation large-vessel occlusion does not increase ICH occurrence. Of note, EVT following IV tPA leads to significantly higher rates of early reperfusion than with IV tPA alone, with no difference in ICH, which challenges the paradigm of reperfusion as a major prognostic factor for ICH complications. However, several blood biomarkers (glycemia, platelet and neutrophil count), clinical factors (age, AIS severity, blood pressure management, diabetes mellitus), and neuroradiological factors (cerebral microbleeds, infarct size) have been identified as risk factors for ICH after reperfusion therapy. In the years to come, the ultimate goal will be to further improve either reperfusion rates and functional outcome, while reducing hemorrhagic complications. To this end, various approaches being investigated are discussed in this review, such as blood-pressure control after reperfusion or the use of new antiplatelet agents as an adjunct to IV tPA and exhibit reduced hemorrhagic potential during the early phase of AIS.

Early microvascular cerebral blood flow response to head-of-bed elevation is related to outcome in acute ischemic stroke.

Previously, microvascular cerebral blood flow (CBF) response to a mild head-of-bed (HOB) elevation has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS). We have hypothesized that early CBF response is related to the functional outcome. Patients with a non-lacunar AIS in the anterior circulation were monitored by DCS to measure relative CBF (ΔrCBF) on the frontal lobes bilaterally during a 0°-30° HOB elevation at early (≤ 12) or late (> 12) hours from symptom onset. National Institutes of Health Stroke Scale (NIHSS) scores were recorded at baseline at 24 and at 48h. Functional outcome was measured by the modified Rankin Scale (mRS) at 3months. Thirty-eight (n = 38) AIS patients [baseline NIHSS = 19 (interquartile range: 16, 21)] were studied. ΔrCBF decreased similarly in both hemispheres (p = 0.4) when HOB was elevated and was not associated with baseline and follow-up NIHSS scores or patient demographics. At the early phase (n = 17), a lower or paradoxical ΔrCBF response to HOB elevation was associated with an unfavorable functional outcome (mRS > 2) in the ipsilesional (but not in the contralesional) hemisphere (p = 0.010). ΔrCBF response in the late acute phase was not related to mRS. Early CBF response to mild HOB elevation in the ipsilesional hemisphere is related to functional outcome. Further studies may enable optical monitoring at the bedside to individualize management strategies in the early phase of AIS.

Abstract WP243: Randomized Clinical Trial Evaluating the Safety and Feasibility of Intensive Lowering of Blood Pressure in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis and Assessed using CT Perfusion Imaging

Introduction: Uncertainty persists over the optimal management of blood pressure (BP) in the early phase of acute ischemic stroke (AIS). This study aims to determine the safety and effects of intensive BP lowering on cerebral blood flow and functional outcomes in AIS patients treated with intravenous thrombolysis. Methods: In a randomized controlled trial, AIS patients with a systolic BP of 160-180mmHg were randomized to early intensive BP lowering (systolic target range 140-160mmHg) or guideline-based BP management (systolic range 160-180mmHg) during first 72-hours using primarily intravenous labetalol. All study subjects underwent CT perfusion at baseline, 24 and 72-hours post-randomization to evaluate change in cerebral hemodynamics. Clinical outcome was assessed using a dichotomized modified Rankin scale (scores 0-1 as excellent outcome versus scores 2-6 as poor outcome) at 90 days. Results: Of the 48 recruited patients, 25 (52%) were assigned to the early intensive BP lowering arm and 23 (48%) to the guideline-based BP management arm. Excellent functional outcome at 90 days were similar in the 2 arms- 56% in the early intensive BP lowering arm and 61% in the standard therapy arm. There were no significant differences in the baseline, 24 and 72-hour CT perfusion cerebral hemodynamic parameters or symptomatic intracranial hemorrhage between the 2 study arms. Conclusions: In the early phase of AIS, intensive BP lowering appears to be a safe strategy. Large randomized controlled trials are needed to confirm our study findings.

Persistent Leukocytosis—Is this a Persistent Problem for Patients with Acute Ischemic Stroke?

In the setting of acute ischemic stroke (AIS), leukocytosis has been shown to be an indicator of inflammatory response. Although leukocytosis on admission has been shown to correlate with initial stroke severity in AIS patients, no work has been done to assess if there are differences in transient or persistent leukocytosis in patients without infection. The objective of this study is to determine the clinical significance of persistent versus transient leukocytosis during the early phase of AIS. Patients who presented with AIS to our center within 48hours of symptom onset between July 2008 and June 2010 were retrospectively identified by chart review. Patients were included if they had leukocytosis on admission (defined as white blood cell count >11,000/μL based on laboratory reference range values). A logistic regression model was used to evaluate persistent leukocytosis (leukocytosis 48hours after admission) as a predictor of several outcome measures, including good functional outcome (discharge modified Rankin Scale score of 0-2). Marginal effects were used to estimate the probability of poor functional outcome. Of the 438 patients screened, 49 had leukocytosis on admission and of those 24 (49%) had persistent leukocytosis. NIHSS score correlated significantly with persistence of leukocytosis (r=.306; P=.0044). More people with transient leukocytosis (leukocytosis lasting <48hours) had a good functional outcome (44% versus 16%; P=.006). After adjusting for baseline NIHSS score, persistent leukocytosis was not a significant independent predictor of good functional outcome, but showed an association (OR, 2.5; 95% CI, .562-10.7; P=.2322). Persistent leukocytosis after adjusting for age and NIHSS score at admission is associated with a poor functional outcome, but it is not statistically significant (OR, 2.43; 95% CI, .59-9.87; P=.2151). After controlling for age and NIHSS score on admission, for patients with persistent leukocytosis, the probability of having poor functional outcome at discharge was increased by 16 percentage points. Persistent leukocytosis is associated with higher baseline NIHSS scores. Persistent leukocytosis is tightly linked with baseline stroke severity and is associated with poor patient outcomes. Our study found that patients with persistent leukocytosis are more likely to present with severe strokes and maintain a high NIHSS score at 24hours after admission, unlike patients without leukocytosis or patients with transient leukocytosis. Furthermore, it appears that persistent leukocytosis outside the setting of aninfection negatively impacts the short-term functional outcome of AIS patients.Identifying patients with persistent leukocytosis could help to prognosticate and target patients that may benefit from future anti-inflammatory interventions.

Abstract W P32: Association of Low Cerebral Blood Volume With Negative FLAIR Hyperintensity in Acute Ischemic Stroke

Objective: FLAIR hyperintensity is being used in clinical trials as a surrogate imaging biomarker for stroke onset time to test the safety of thrombolysis. Studies have shown that patients with negative and positive FLAIR hyperintensity overlap at similar time points from stroke onset in the early phase of acute ischemic stroke (AIS). Hyperintensity on FLAIR MRI likely represents increased tissue water content. We sought to determine if cerebral blood volume (CBV) mediates FLAIR hyperintensity in the early phase of AIS. Methods: AIS patients seen in 2012 were included in the study if i) onset time was known, ii) an MRI with perfusion was performed within 12 hours of onset time, iii) had imaging confirmed vascular occlusion of ICA, M1, or M2. Following co-registration of raw perfusion images with FLAIR, CBV maps were generated using PMA ASIST™ software. Two raters blinded to clinical information separately evaluated the DWI, FLAIR and CBV maps and measured the signal intensity ratio (SIR) for the brightest region on FLAIR normalized by homologous contra-lateral tissue. The SIR was similarly measured for CBV in same region. FLAIR negative was defined as SIR&lt;1.15, “Low CBV” was defined as CBV SIR &lt;0.5. Results: One hundred eighty two patients were screened and 30 met all study criteria; 21 women, with mean age of 71 (± 16) years and median NIHSS 18 (IQR 9-22). Using linear regression analysis, CBV SIR was associated with FLAIR SIR (p &lt;0.049). In the 0-3hr time window, overall CBV was not associated with FLAIR hyperintensity. However, in the 3-7.5hr time window, patients with negative FLAIR were more likely to have low CBV and conversely, patients with positive FLAIR were more likely to have normal CBV. Conclusion: CBV likely mediates FLAIR hyperintensity in 3-7.5hr of stroke onset but it has less impact on FLAIR hyperintensity in the first 3 hours of AIS. Low CBV could be a potential surrogate imaging biomarker in addition to FLAIR hyperintensity in the early phase of AIS.

Microvascular Imaging in Acute Ischemic Stroke

Microvascular imaging (MVI), a new ultrasound technology, is used to analyze brain perfusion at the patient's bedside. This study aims to evaluate the diagnostic and prognostic value of MVI in patients with acute ischemic stroke (AIS). Nineteen patients suffering from AIS (mean age, 70.9 ± 12.2 years; 47% female; mean NIHSS-score, 12 ± 8) were investigated within the first 12 hours after symptom onset. We used the iU22 (Philips) system (S5-1 probe; low-mechanical index; depth, 13 cm), and 2 bolus injections of an ultrasound contrast agent (2.4 mL SonoVue per injection). The area of maximal perfusion deficit (AMPD) was compared with infarction on follow-up cranial computed tomography (CT) and NIHSS score 24 hours after stroke onset. Of 19 patients, 15 patients (79%) had sufficient insonation conditions. Of these patients, 12 had infarctions. The sensitivity and specificity of detecting infarctions with ultrasound perfusion imaging were 91% and 67%, respectively. A significant correlation existed between the AMPD and NIHSS score at 24 hours after symptom onset (P= .023), and with occlusion of the internal carotid artery (P= .005). Performing bedside MVI in the early phase of AIS provides information on brain parenchyma perfusion and prognosis of AIS.