Amie W. Hsia

Distal hyperintense vessels on FLAIR: An MRI marker for collateral circulation in acute stroke?

Background: Hyperintense vessels (HV) on fluid-attenuated inversion recovery imaging are frequently observed in acute ischemic stroke patients. However, the exact mechanism and clinical implications of this sign have not yet been clearly defined. The features of HV and its relevance to other imaging factors are presented here. Methods: Prominence and location of HV were documented in 52 consecutive patients with middle cerebral artery (MCA) territory infarction, before treatment with IV recombinant tissue plasminogen activator. Pretreatment ischemic lesion volume, perfusion lesion volume, and vessel occlusion were determined in addition to recanalization status and ischemic lesion volume on follow-up imaging. NIH Stroke Scale (NIHSS) was used as a measure of clinical severity. Results: HV distal to arterial occlusion was observed in 73% of patients; more frequent in proximal than distal MCA occlusion patients. Among the 38 patients with proximal MCA occlusion, initial perfusion lesion volume was comparable among patients with different grade distal HV. However, patients with more prominent distal HV had smaller initial, 24-hour, and subacute ischemic lesion volumes and lower initial NIHSS scores. Conclusions: The presence of distal hyperintense vessels before thrombolytic treatment is associated with large diffusion–perfusion mismatch and smaller subacute ischemic lesion volumes in patients with proximal middle cerebral artery occlusion. DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GRE = gradient recalled echo; HV = hyperintense vessels; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; rt-PA = recombinant tissue plasminogen activator; TE = echo time; TI = inversion time; TIMI = thrombolysis in myocardial infarction; TR = repetition time.

Racial differences in microbleed prevalence in primary intracerebral hemorrhage

Background: Primary intracerebral hemorrhage is two to three times more common in many racial populations, including black patients. Previous studies have shown that microbleeds, identified on gradient echo MRI (GRE), are present in 50–80% of patients with primary ICH. The objective of this study was to compare, by race, the rates, risk factors, and topography of microbleeds in patients hospitalized for primary ICH. Methods: Patients diagnosed with primary ICH at two metropolitan stroke centers were included. Clinical and neuroimaging data were recorded for each patient. Analyses were performed to compare baseline characteristics as well as imaging findings by race. Results: A total of 87 patients met inclusion criteria (42 black subjects, 45 white subjects). The black cohort was younger (p < 0.001), and had a greater rate of hypertension (p = 0.001), but not other vascular risk factors. Microbleeds were more prevalent in the black population, with 74% of blacks having one or more microbleeds compared to 42% of whites (p = 0.005). The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%, p = 0.106). When adjusting for age, hypertension, and alcohol use, race was an independent predictor of microbleeds (OR 3.308, 95% CI 1.144–9.571, p = 0.027). Conclusions: These pilot data suggest that significant racial differences exist in the frequency and topography of microbleeds in patients with primary ICH. Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression, as well as possible therapeutic strategies, particularly in medically underserved populations.

Screening with MRI for Accurate and Rapid Stroke Treatment: SMART

Objective: The objective of this study was to demonstrate the feasibility of timely multimodal MRI screening before thrombolysis in acute stroke patients. Methods: Quality improvement processes were initiated in 2013 to reduce door-to-needle (DTN) time at the 2 hospitals where the NIH stroke team provides clinical care. Acute ischemic stroke (AIS) patients who received IV tissue plasminogen activator (tPA) ≤4.5 hours from last known normal were identified. Demographic and clinical characteristics and timing metrics were analyzed comparing the time periods before, during, and after the quality improvement processes. Results: There were 157 patients treated with IV tPA for AIS during 2012–2013, of whom 135 (86%) were screened with MRI. DTN time was significantly reduced by 40% during this period from a median of 93 minutes in the first half of 2012 to 55 minutes in the last half of 2013 (p < 0.0001) with a significant 4-fold increase in the proportion of treated patients with DTN time ≤60 minutes from 13.0% to 61.5%, respectively (p < 0.00001). Improvement in DTN time was associated with reduced door-to-MRI time, and there were no differences in demographic or clinical characteristics (p = 0.21–0.76). Conclusions: It is feasible and practical to consistently and rapidly deliver IV tPA to AIS patients within national benchmark times using MRI as the routine screening modality. The processes used in the SMART (Screening with MRI for Accurate and Rapid Stroke Treatment) Study to reduce DTN time have the potential to be widely applicable to other hospitals.

Racial Disparities in Tissue Plasminogen Activator Treatment Rate for Stroke A Population-Based Study

Background and Purpose— Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. Methods— Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. Results— Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). Conclusions— In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

Negative Diffusion-Weighted Imaging After Intravenous Tissue-Type Plasminogen Activator is Rare and Unlikely to Indicate Averted Infarction

Background and Purpose— Some patients treated with intravenous (IV) tissue-type plasminogen activator (tPA) have negative diffusion-weighted imaging (DWI) on follow-up imaging. Without a visible infarct, there may be uncertainty as to whether the patient was having a stroke that was averted by tPA or whether the symptoms had not been cerebrovascular in origin. We evaluated patients presenting with suspected acute stroke with a positive DWI lesion before IV tPA to determine the probability of finding a negative DWI up to 48 hours after treatment. Methods— We included patients from the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) project who had acute MRI screening with a positive DWI lesion before IV tPA treatment and had follow-up MRI up to 48 hours later. Experienced readers interpreted all acute and follow-up MRIs looking for ischemic lesions on DWI. Results— There were 231 patients who met study inclusion criteria, of which 225 patients (97.4%) had a persistent positive DWI corresponding to the acute stroke lesion on all follow-up imaging. Four patients (1.7%) had transient DWI lesion reversal with positive DWI on subsequent follow-up imaging. There were only 2 cases (0.9%) of complete DWI lesion reversal on all follow-up imaging. Conclusions— Averted infarction after IV tPA is rare, occurring in 0.9% of patients with pretreatment positive DWI evidence of acute ischemia. For IV tPA-treated patients who have a negative DWI on follow-up imaging, a cause other than acute stroke should be explored.

Visual Perfusion–Diffusion Mismatch Is Equivalent to Quantitative Mismatch

Background and Purpose— The concept of stroke MRI mismatch based on qualitative evaluation of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) has been applied in clinical practice for several years. The benefit of MRI in providing pathological evidence of ischemia before thrombolytic treatment has been demonstrated. The purpose of this study is to determine the reliability of the qualitative method and compare it with quantitative mismatch measurement in thrombolytic-treated patients. Methods— Patients (n=70) were selected from the Lesion Evolution of Stroke and Ischemic On Neuroimaging (LESION) database if they: (1) were treated with intravenous recombinant tissue plasminogen activator; (2) had a pretreatment MRI with evaluable DWI and PWI; and (3) had acute ischemic lesion volume >10 mL on DWI as determined by core imaging laboratory measurements. Quantitative mismatch was defined as a difference of >50 mL between abnormal mean transit time and DWI volumes. Sample characteristics and postdischarge modified Rankin Scale for the positive mismatch patients were compared between the subgroups identified by qualitative versus quantitative methods. Results— Patient characteristics and thrombolytic outcomes (sex, age, National Institutes of Health Stroke Scale, mismatch volume, and modified Rankin Scale) did not differ for mismatch patients identified by qualitative versus quantitative methods. Qualitative mismatch selection among neurologists had a high sensitivity (0.82), specificity (0.80), accuracy (0.81), and positive predictive value (0.88) compared with quantitative measurements. Conclusions— We observed that qualitative evaluation of mismatch identified the same thrombolytic-treated patients compared with retrospective quantitative mismatch measurements.

Reperfusion Half-Life. A Novel Pharmacodynamic Measure of Thrombolytic Activity

Background and Purpose— We hypothesized that the probability of reperfusion can be modeled by an exponential decay (ie, half-life) function and that this reperfusion half-life is decreased by thrombolytic treatment. Methods— Serial perfusion MRI scans were evaluated for evidence of reperfusion in intravenous tissue plasminogen activator-treated (n=45) and untreated (n=103) patients. The cumulative probability of reperfusion for each group was fit with exponential decay functions. The resulting reperfusion half-life (ie, the time it takes half the sample to reperfuse) was calculated. Results— In untreated patients, a monoexponential decay function fit the data well (R2=0.95) with a half-life of 29.1 hours. In tissue plasminogen activator-treated patients, the data were best fit with a biexponential decay function (R2=0.99) that had a fast and a slow component. The fast component is attributable to tissue plasminogen activator therapy and has a half-life of 0.71 hours, whereas the slow component was similar to that of the untreated group. Approximately 3.5 hours after the start of treatment, the effect of tissue plasminogen activator on the probability of reperfusion was negligible. Conclusion— The probability of reperfusion can be well described by the reperfusion half-life. Determination of the fast component reperfusion half-life may be an approach to compare the relative potency of different thrombolytic agents.

Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia

Background and Purpose— Animal models of acute cerebral ischemia have demonstrated that diffuse blood–brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. Methods— Acute stroke patients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. Results— Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). Conclusions— This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator.

Methodology for a community-based stroke preparedness intervention: the Acute Stroke Program of Interventions Addressing Racial and Ethnic Disparities Study.

Background and Purpose— Acute stroke education has focused on stroke symptom recognition. Lack of education about stroke preparedness and appropriate actions may prevent people from seeking immediate care. Few interventions have rigorously evaluated preparedness strategies in multiethnic community settings. Methods— The Acute Stroke Program of Interventions Addressing Racial and Ethnic Disparities (ASPIRE) project is a multilevel program using a community-engaged approach to stroke preparedness targeted to underserved black communities in the District of Columbia. This intervention aimed to decrease acute stroke presentation times and increase intravenous tissue-type plasminogen activator utilization for acute ischemic stroke. Results— Phase 1 included (1) enhancement of focus of emergency medical services on acute stroke; (2) hospital collaborations to implement and enrich acute stroke protocols and transition District of Columbia hospitals toward primary stroke center certification; and (3) preintervention acute stroke patient data collection in all 7 acute care District of Columbia hospitals. A community advisory committee, focus groups, and surveys identified perceptions of barriers to emergency stroke care. Phase 2 included a pilot intervention and subsequent citywide intervention rollout. A total of 531 community interventions were conducted, reaching >10 256 participants; 3289 intervention evaluations were performed, and 19 000 preparedness bracelets and 14 000 stroke warning magnets were distributed. Phase 3 included an evaluation of emergency medical services and hospital processes for acute stroke care and a year-long postintervention acute stroke data collection period to assess changes in intravenous tissue-type plasminogen utilization. Conclusions— We report the methods, feasibility, and preintervention data collection efforts of the ASPIRE intervention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00724555.Background and Purpose Acute stroke education has focused on stroke symptom recognition. Lack of education about stroke preparedness and appropriate actions may prevent people from seeking immediate care. Few interventions have rigorously evaluated preparedness strategies in multiethnic community settings.

Association between neurologic improvement with decline in blood pressure and recanalization in stroke

IMPORTANCE Patients with stroke often have a decline in blood pressure after thrombolysis. Neurologic improvement could result from recanalization or better collateral flow despite persistent occlusion. We hypothesized that neurologic improvement with concurrent decline in blood pressure may be a clinical sign of recanalization after intravenous tissue plasminogen activator. OBSERVATIONS Patients treated with intravenous tissue plasminogen activator at Suburban Hospital, Bethesda, Maryland, and MedStar Washington Hospital Center, Washington, DC, from 1999 to 2009 were included in the study if they had pretreatment and 24-hour magnetic resonance angiographic scans, National Institutes of Health Stroke Scale scores at those times, and proximal middle cerebral artery occlusion demonstrated prior to treatment. The recanalization status on 24-hour magnetic resonance angiography was classified as none, partial, or complete. Seventeen patients met study criteria. On 24-hour magnetic resonance angiography, 3 patients had no recanalization, 8 had partial recanalization, and 6 had complete recanalization. At 24 hours after thrombolysis, neurologic improvement with concurrent decline in systolic blood pressure of 20 mm Hg or greater was seen in 4 patients with partial recanalization, 4 patients with complete recanalization, and none of the patients with no recanalization. CONCLUSIONS AND RELEVANCE Neurologic improvement with concurrent decline in systolic blood pressure of 20 mm Hg or greater after intravenous tissue plasminogen activator may be a clinical sign of recanalization. This observation needs confirmation in a larger cohort.