A-Hyun Cho

Safety and efficacy of MRI-based thrombolysis in unclear-onset stroke. A preliminary report

Background: Standard selection criteria for thrombolysis typically exclude patients with acute ischemic stroke with unclear onset. Multimodal MRI screening may be able to identify those with a favorable benefit-risk ratio for thrombolysis. We aimed to evaluate the safety and efficacy of MRI-based thrombolysis in unclear-onset stroke (UnCLOS). Methods: We reviewed the thrombolysis database registries from 3 medical centers in Korea. Subjects received thrombolysis with intravenous tissue plasminogen activator (tPA) or combined intravenous tPA and intra-arterial urokinase within 3 h, or intra-arterial urokinase within 6 h from symptom detection. For patients with UnCLOS, MRI-specific eligibility criteria (i.e. positive perfusion-diffusion mismatch and absence of well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions) were applied. Rates of immediate and 5-day recanalization, early neurological improvement and symptomatic intracranial hemorrhage (ICH) within 48 h after treatment and 3-month modified Rankin Scale (mRS) scores were compared between patients with UnCLOS and those with clear-onset stroke (CLOS). Results: 32 patients with UnCLOS and 223 patients with CLOS were included. Baseline characteristics were comparable between the two groups, except that the proportion of MRI screening was higher, and detection-to-door time and door-to-needle time were longer in the UnCLOS group (p < 0.01). Rates of recanalization (immediate, 81.3 vs. 63.1%; delayed, 80.6 vs. 69.1%), early neurological improvement (on day 1, 46.9 vs. 35.9%; on day 7, 50.0 vs. 49.3%), symptomatic ICH (6.3 vs. 5.8%) and 3-month outcome (mRS 0–1, 37.5 vs. 35.0%; mRS 0–2, 50.0 vs. 49.3%) did not differ between the UnCLOS and CLOS groups. Conclusion: These preliminary results suggest that thrombolysis based on MRI criteria may safely be applied to acute stroke patients with unclear onset.

Rapid appearance of new cerebral microbleeds after acute ischemic stroke

Background: It is unknown whether the development of cerebral microbleeds (MBs), small areas of signal loss on T2*-weighted gradient-echo imaging (GRE), follows a slow or a rapid process. We hypothesized that MBs may develop rapidly after certain critical events, such as strokes, and investigated the frequency, location, and factors associated with the formation of new MBs after acute ischemic stroke. Methods: We retrospectively examined 237 consecutive acute ischemic stroke patients who underwent MRI within 24 hours and follow-up MRI during the week after symptom onset. We defined new MBs as MBs that newly appeared on follow-up GRE outside the infarcted area. We examined the association of new MBs with demographics, risk factors, laboratory data, baseline MBs, and small vessel disease (SVD; leukoaraiosis and lacunar infarctions). Results: Seventy-five patients (31.6%) had baseline MBs, and 30 (12.7%) developed new MBs. Multiple logistic regression analysis indicated that the presence of baseline MBs (odds ratio [OR] 5.72, 95% confidence interval [CI] 2.12–15.42, p = 0.001) and severe SVD (OR 2.94, 95% CI 1.12–7.77, p = 0.03) independently predicted the development of new MBs. Of the 56 new MBs, 29 (51.8%) appeared in the lobar location, 17 (30.4%) appeared in the deep location, and 10 (17.9%) appeared in the infratentorial location. Conclusions: This study suggests that new microbleeds (MBs) can develop rapidly after acute ischemic stroke. Baseline MBs and severe small vessel disease are predictors for the development of new MBs. Further studies will be needed to investigate the clinical implications and mechanisms of these findings.

Stroke awareness decreases prehospital delay after acute ischemic stroke in korea

BackgroundDelayed arrival at hospital is one of the major obstacles in enhancing the rate of thrombolysis therapy in patients with acute ischemic stroke. Our study aimed to investigate factors associated with prehospital delay after acute ischemic stroke in Korea.MethodsA prospective, multicenter study was conducted at 14 tertiary hospitals in Korea from March 2009 to July 2009. We interviewed 500 consecutive patients with acute ischemic stroke who arrived within 48 hours. Univariate and multivariate analyses were performed to evaluate factors influencing prehospital delay.ResultsAmong the 500 patients (median 67 years, 62% men), the median time interval from symptom onset to arrival was 474 minutes (interquartile range, 170-1313). Early arrival within 3 hours of symptom onset was significantly associated with the following factors: high National Institutes of Health Stroke Scale (NIHSS) score, previous stroke, atrial fibrillation, use of ambulance, knowledge about thrombolysis and awareness of the patient/bystander that the initial symptom was a stroke. Multivariable logistic regression analysis indicated that awareness of the patient/bystander that the initial symptom was a stroke (OR 4.438, 95% CI 2.669-7.381), knowledge about thrombolysis (OR 2.002, 95% CI 1.104-3.633) and use of ambulance (OR 1.961, 95% CI 1.176-3.270) were significantly associated with early arrival.ConclusionsIn Korea, stroke awareness not only on the part of patients, but also of bystanders, had a great impact on early arrival at hospital. To increase the rate of thrombolysis therapy and the incidence of favorable outcomes, extensive general public education including how to recognize stroke symptoms would be important.

Impaired kidney function and cerebral microbleeds in patients with acute ischemic stroke

Background: We investigated the association between the presence of cerebral microbleeds and poor kidney function in patients with acute ischemic stroke. Methods: We retrospectively examined consecutive acute ischemic stroke patients who underwent gradient echo MRI. The presence of cerebral microbleeds on gradient echo MRI was independently interpreted. The number and location of microbleeds were assessed. Demographics including age, sex, risk factors, and stroke subtype were obtained. Kidney function was estimated by measuring glomerular filtration rate (GFR) with the modification of diet in renal disease method. Results: Of the 152 patients included, 45 (29.6%) patients had cerebral microbleeds on gradient echo MRI. The cerebral microbleeds were most commonly located in deep or infratentorial location (27/45 [60%]). Hypertension, presence of leukoaraiosis, old age, and low GFR were associated with the presence of cerebral microbleeds (p = 0.064, <0.001, 0.014, and <0.001). The mean GFR levels were lower in patients with cerebral microbleeds (65.15 ± 22.54 vs 78.82 ± 19.11 mL/min/1.73 m2). After the adjustment of risk factors, age, and sex, low GFR levels were associated with the presence of cerebral microbleeds (odds ratio, 3.85; 95% confidence interval, 1.52 to 9.76, p = 0.004). Conclusion: Impaired kidney function is associated with the presence of cerebral microbleeds in acute ischemic stroke.

Is 15 mm Size Criterion for Lacunar Infarction Still Valid? A Study on Strictly Subcortical Middle Cerebral Artery Territory Infarction Using Diffusion-Weighted MRI

Background and Purpose: The ‘lacunar hypothesis’ has been challenged, since small (diameter <15 mm) subcortical infarcts can be produced by middle cerebral artery disease (MCAD) or cardioembolism (CE), while a larger infarct can occur without evidence of MCAD or CE. We sought to assess whether the lacunar hypothesis based on size is still valid. Methods: We studied 118 patients who were admitted within 72 h after stroke onset and had acute deep subcortical MCA territory infarcts detected by diffusion-weighted MRI, and who had undergone angiography (mostly MR angiography). Stroke mechanisms were arbitrarily categorized regardless of lesion size: (1) MCAD when there was a corresponding MCA lesion; (2) internal carotid artery disease (ICAD) when there was a significant (>50%) ipsilateral ICAD; (3) CE when there was emboligenic heart disease without MCAD or ICAD, and (4) small vessel disease (SVD) when there was neither CE nor MCAD. SVD was further divided into definite SVD (dSVD, longest diameter <15 mm) or probable SVD (pSVD, longest diameter ≧15 mm). Results: Seventy-three patients (62%) had SVD, of which 38 (32%) had pSVD and 35 (30%) dSVD. Thirty-three patients (28%) had MCAD, five (4%) CE, and seven (6%) ICAD. The infarct diameter in MCAD was not larger than in SVD (p = 0.35), and there was no difference in clinical features or risk factors between MCAD and SVD, or between pSVD and dSVD. CE was distinguished from SVD by its larger size and cortical symptoms. Conclusions: There are no clinical and lesion-size differences between MCAD and SVD, suggesting that there seems to be no rationale for the 15 mm size criterion for lacunar or small-vessel infarction.

Reperfusion Therapy in Unclear-Onset Stroke Based on MRI Evaluation (RESTORE) A Prospective Multicenter Study

Background and Purpose— Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke. Methods— This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch >20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries. Results— Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5 ± 10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14–4.49). Conclusions— In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.

Focal Fluid-Attenuated Inversion Recovery Hyperintensity Within Acute Diffusion-Weighted Imaging Lesions Is Associated With Symptomatic Intracerebral Hemorrhage After Thrombolysis

Background and Purpose— We investigated whether focal hyperintensity on fluid-attenuated inversion recovery image within acute infarcts is associated with symptomatic intracerebral hemorrhage (SICH) after thrombolysis. Methods— Patients with acute ischemic stroke who underwent MRI screening before thrombolysis were enrolled. The presence of focal fluid-attenuated inversion recovery hyperintensity within acute infarcts did not preclude thrombolysis. SICH was defined as hemorrhagic transformation with any neurological decline (SICH-1) or with an increase in National Institutes of Health Stroke Scale of ≥4 (SICH-2) within 48 hours. Results— Among 88 included patients, focal fluid-attenuated inversion recovery hyperintensity within acute infarct lesions was observed in 27 (30.7%) patients. Multivariate analysis showed that focal fluid-attenuated inversion recovery hyperintensity was independently associated with SICH-1 (OR, 13.64; 95% CI, 1.51 to 123.28) and SICH-2 (OR, 10.44; 95% CI, 1.11 to 98.35). Conclusion— The presence of focal fluid-attenuated inversion recovery hyperintensity within acute infarcts may increase the risk of symptomatic intracerebral hemorrhage after thrombolysis.

MRI evidence of reperfusion injury associated with neurological deficits after carotid revascularization procedures

Background and purpose:  Some patients develop major neurological complications after carotid revascularization procedures, despite the lack of new infarcts or classical hyperperfusion syndrome.

White Matter Hyperintensity in Ischemic Stroke Patients: It May Regress Over Time

Background and Purpose White matter hyperintensities (WMH) are frequently observed on MRI in ischemic stroke patients as well as in normal elderly individuals. Besides the progression of WMH, the regression of WMH has been rarely reported. Thus, we aimed to investigate how WMH change over time in patients with ischemic stroke, particularly focusing on regression. Methods We enrolled ischemic stroke patients who underwent brain MRI more than twice with at least a 6 month time-interval. Based on T2-weighted or FLAIR MRI, WMH were visually assessed, followed by semiautomatic volume measurement. Progression or regression of WMH change was defined when 0.25 cc increase or decrease was observed and it was also combined with visible change. A statistical analysis was performed on the pattern of WMH change over time and factors associated with change. Results A total of 100 patients were enrolled. Their age (mean±SD) was 67.5±11.8 years and 63 were male. The imaging time-interval (mean) was 28.0 months. WMH progressed in 27, regressed in 9 and progressed in distinctive regions and regressed in others in 5 patients. A multiple logistic regression model showed that age (odds ratio[OR] 2.51, 90% confidence interval[CI] 1.056-5.958), male gender (OR 2.957, 95% CI 1.051-9.037), large vessel disease (OR 1.955, 95% CI 1.171-3.366), and renal dysfunction (OR 2.900, 90% CI 1.045-8.046) were associated with progression. Regarding regression, no significant factor was found in the multivariate analysis. Conclusions In 21.5% of ischemic stroke patients, regression of WMH was observed. WMH progression was observed in a third of ischemic stroke patients.

Coexisting Carotid Atherosclerosis in Patients with Intracranial Small- or Large-Vessel Disease

Background and Purpose The coexistence of carotid atherosclerosis in ischemic stroke patients with small-vessel disease (SVD) or intracranial large-vessel disease (ICLVD) was investigated using carotid duplex ultrasonography, and whether its coexistence affected the clinical prognosis was determined. Methods Ischemic stroke patients with SVD or ICLVD were enrolled (n=103). Risk factors, demographic data, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained for all of the subjects. Early neurological progression was defined by an increase in NIHSS score during the first 7 days. Carotid ultrasonography was performed to measure the intima-media thickness (IMT) and carotid plaques. Results Among the 103 patients who were retrospectively enrolled in this study (56 with SVD and 47 with ICLVD), 66 (64.1%) had an atherosclerotic plaque and 23 (22.3%) had increased IMT. Increased IMT was observed more frequently in ICLVD than in SVD [15/47 (31.9%) vs. 8/56 (14.3%), p=0.032]. An atherosclerotic plaque was observed on subsequent carotid ultrasonographic examination in 28 (50%) of the 56 patients whose computed tomography angiography scans of the neck vessels were interpreted as normal. There was no association between presence of atherosclerotic change and early neurologic progression (p=0.94). Conclusions A coexisting atherosclerotic plaque or increased IMT was observed in 71.8% of patients with SVD or ICLVD. Whether the coexistence of carotid atherosclerotic change with either of these conditions affects the clinical prognosis remains to be elucidated.