Yuka Terasawa

Large Ischemic Lesions on Diffusion-Weighted Imaging Done Before Intravenous Tissue Plasminogen Activator Thrombolysis Predicts a Poor Outcome in Patients With Acute Stroke

Background and Purpose— MRI is useful for detecting early ischemic lesions before administration of tissue plasminogen activator in patients with hyperacute ischemic stroke. However, it is unclear whether early ischemic change seen on diffusion-weighted imaging (DWI) can be used to predict patient outcomes. Methods— Consecutive patients with anterior circulation ischemic stroke treated with tissue plasminogen activator within 3 hours of stroke onset were prospectively studied. The National Institutes of Health Stroke Scale score was obtained before and 7 days after tissue plasminogen activator administration. MRI, including DWI, was done before tissue plasminogen activator thrombolysis. The relationship between the DWI Alberta Stroke Programme Early CT Score (ASPECTS) and patients’ outcomes was assessed. Results— The subjects consisted of 49 consecutive patients with stroke (27 males; mean age, 72.9±10.3 years). The median (range) of the baseline DWI ASPECTS value was 9 (3–10). Dramatic improvement was seen in one of 8 patients with an ASPECTS ≤5 compared with 21 of 41 patients with a DWI ASPECTS >5 (P=0.0592). On the other hand, worsening was noted more frequently in patients with a DWI ASPECTS ≤5 (3 of 8 patients) than in patients with an ASPECTS >5 (4 of 41 patients; P=0.0753). Bad outcome was seen more frequently in patients with a DWI ASPECTS ≤5 (6 of 8 patients) than in patients with a DWI ASPECTS >5 (2 of 41 patients; P<0.0001). Multivariate logistic regression analysis demonstrated that a DWI ASPECTS ≤5 was the only independent predictor of a bad outcome (OR, 33.4; 95% CI, 2.7 to 410.8; P=0.0062). Conclusion— DWI ASPECTS appears to be a reliable tool for predicting bad outcome. Patients with a DWI ASPECTS >5 should be considered eligible for tissue plasminogen activator therapy.

Relation of Atrial Fibrillation to Glomerular Filtration Rate

Although both atrial fibrillation (AF) and decreasing glomerular filtration rate (GFR) are strongly related to advanced age and share common associated vascular risk factors, few studies have explored the relation between AF and GFR. From residents (age >or=40 years) in Kurashiki City, a total of 41,417 subjects (median age 72 years; 13,956 men) were enrolled in the Kurashiki City Annual Medical Survey from May to December 2006. The estimated overall prevalence of AF was 1.6% (2.8% in the low-GFR tertile, 1.2% in the middle tertile, and 0.9% in the high tertile, p <0.001). After all subjects were categorized into age tertiles (age thresholds 68 and 76 years), AF was identified in 0.9% in the low-GFR tertile, 0.6% in the middle tertile, and 0.5% in the high tertile in the low-age tertile (p = 0.018); 2.6% in the low-GFR tertile, 1.2% in the middle tertile, and 1.1% in the high tertile in the middle-age tertile (p <0.001); and 3.9% in the low-GFR tertile, 2.4% in the middle tertile, and 1.7% in the high tertile in the high-age tertile (p <0.001). The odds ratio for AF adjusted for age, gender, vascular risk factors, cardiac disease, and hemoglobin was 1.91 (95% confidence interval 1.54 to 2.38, p <0.001) for the low-GFR tertile versus the high tertile and 1.12 (95% confidence interval 0.88 to 1.42, p = 0.364) for the middle-GFR tertile versus the high tertile. The prevalence of AF gradually increased with decreasing GFR. In conclusion, AF appears to be associated with decreasing GFR.

Hemorrhagic transformation of ischemic brain tissue after t-PA thrombolysis as detected by MRI may be asymptomatic, but impair neurological recovery

BACKGROUND AND PURPOSE Symptomatic intracranial hemorrhages are typically clinically catastrophic and occur more frequently with tissue plasminogen activator (t-PA) therapy compared to without t-PA therapy. However, it has been unclear whether asymptomatic intracranial hemorrhage has clinical implications. METHODS Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. Patients with symptomatic hemorrhages were excluded from the study. To identify the presence of early recanalization and intracranial hemorrhage, as well as to measure infarction volume, MRI examinations, including diffusion-weighted imaging, T2(), FLAIR, and MRA, were performed before and 1 h, 24 h, and 5-7 days after t-PA thrombolysis. At the same time, serial NIHSS scores were obtained. The independent predictors of dramatic recovery were determined using multivariate logistic regression analysis. RESULTS 51 patients were enrolled in the present study. 22 patients (H group) had an asymptomatic hemorrhage. The NIHSS score of the Non-H group decreased, but that of the H group did not (11.5+/-6.5 vs. 17.1+/-6.5 at baseline, and 4.5+/-6.8 vs. 14.3+/-7.6 at 7 days; P=0.0073 for ANOVA). Asymptomatic hemorrhage was more frequently seen in non-dramatic improvement group than in dramatic improvement group (65.5% vs. 13.6%, P=0.0002). On multivariate logistic regression analysis using the variables that had a P<0.1 on univariate analysis (AF, baseline NIHSS score, glucose, the presence of asymptomatic hemorrhage, ICA occlusion, early recanalization 1 h after t-PA infusion, and infarction volume 7 days after t-PA therapy), early recanalization (OR: 11.33; 95%CI: 1.064-120.704; P=0.044) and infarction volume <100 cm(3) (OR: 13.56; 95%CI: 1.020-180.125; P=0.048) were independent factors for dramatic improvement, while asymptomatic hemorrhage (OR: 0.03; 95%CI: 0.002-0.537; P=0.016) was an independent negative factor. CONCLUSION Asymptomatic hemorrhage was an independent negative factor for dramatic improvement. Asymptomatic hemorrhage after t-PA thrombolysis may be associated with neurological recovery.

Neurological deterioration in small vessel disease may be associated with increase of infarct volume

BACKGROUND AND PURPOSE The mechanism of neurological deterioration in small vessel disease is unclear. We examined the relationship between neurological deterioration and change of infarct volume in acute small vessel disease. METHODS We studied consecutive patients with acute supratentorial small vessel disease. Patients were classified into two groups (D: group with deterioration, N: group with no deterioration). We performed serial MRI studies, measured infarct volumes using NIH Image, and calculated the changes in infarct volume (Delta volume) between initial and follow-up diffusion-weighted imaging (DWI). RESULTS Seventy-two patients (44 males, 68+/-11 years of age) were enrolled. Fifteen patients exhibited neurological deterioration (group D) and 57 patients did not (group N). Initial infarct volume was 0.66 cm3 in group D and 0.45 cm3 in group N (p=0.025). Infarct volumes on follow-up DWI were 1.41 cm3 and 0.72 cm3, respectively (p=0.001). The Delta volume in group D was larger than that in group N (0.76 cm3 vs 0.27 cm3, p=0.001). In order to differentiate D from N group, sensitivity specificity analysis yielded a cut-off value of Delta volume of 0.5 cm3 for differentiation of the two groups, which exhibited a sensitivity of 80% and specificity of 84%. Multivariate logistic regression analysis demonstrated that increase in infarct volume of over 0.5 cm3 (odds ratio; 18.0, 95% CI; 1.4 to 270, p=0.027) was independently associated with neurological deterioration in patients with acute small vessel disease. CONCLUSIONS Enlargement of infarct volume may contribute to neurological deterioration in acute small vessel disease.

Could clinical diffusion-mismatch determined using DWI ASPECTS predict neurological improvement after thrombolysis before 3 h after acute stroke?

Background Clinical-diffusion mismatch (CDM) between stroke severity and volume of diffusion-weighted imaging (DWI) lesions seems to predict penumbra. The Alberta Stroke Program Early CT Score on DWI (DWI ASPECTS) is a simple score for identifying ischaemic lesions. The authors examined whether CDM using DWI ASPECTS can predict neurological improvement in patients with acute stroke treated with intravenous tissue plasminogen activator (t-PA). Methods The authors enrolled consecutive patients with anterior circulation stroke treated with intravenous t-PA. The authors calculated a cut-off value for CDM using DWI ASPECTS. After excluding a group of patients with mild symptoms (National Institutes of Health Stroke Scale (NIHSS) score <8), the authors divided the patients into two groups by presence or not of CDM (a positive group (P-CDM) and a negative group (N-CDM)). The authors then compared clinical characteristics including NIHSS score and modified Rankin Scale at 90 days after intravenous t-PA. Results Seventy-one patients (male 41, mean age 74 years) were enrolled. DWI ASPECTS was linearly related to DWI lesion volume. The authors defined CDM as NIHSS scores ≥8 and DWI ASPECTS ≥7. The P-CDM group had 35 patients (61%) and the N-CDM group 22 patients (39%). NIHSS scores on admission were 15 (median) in P-CDM and 20 in N-CDM (p=0.004). NIHSS scores after intravenous t-PA improved in P-CDM but were unchanged in N-CDM (7 vs 20 at 7 days, p=0.033 on ANOVA). A favourable outcome at 90 days, defined as modified Rankin scale 0–3, was found in 46% of P-CDM patients and 14% of N-CDM patients (p=0.020). Conclusion CDM determined using DWI ASPECTS may be associated with neurological improvement in patients treated with intravenous t-PA.

The Presence of a Right-to-Left Shunt Is Associated With Dramatic Improvement After Thrombolytic Therapy in Patients With Acute Ischemic Stroke

Background and Purpose— The efficacy of pharmacological thrombolysis using tissue plasminogen activator depends on the relative fibrin content of the thrombus. We investigated whether patients with stroke with a right-to-left shunt (RLS), whose embolic source was associated with fibrin-rich thrombus formed in the venous system, were more likely to improve dramatically after thrombolytic therapy than those without RLS. Methods— Patients with acute stroke treated with tissue plasminogen activator were assessed prospectively to determine the clinical factors associated with “dramatic improvement” after tissue plasminogen activator administration. “Dramatic improvement” was defined as a ≥10-point reduction in the total National Institutes of Health Stroke Scale score or a total National Institutes of Health Stroke Scale score of 0 or 1 at 7 days. The presence of an RLS was determined using contrast transcranial Doppler within 6 hours of stroke onset. Results— Forty-four patients (26 males; mean age; 73.0±10.7 years; baseline National Institutes of Health Stroke Scale score,13.4±6.6) were enrolled. Twenty-one patients had dramatic improvement (D group). Contrast transcranial Doppler demonstrated an RLS in 17 (35.4%) patients. On multivariate logistic regression analysis using hyperlipidemia, atrial fibrillation, RLS, DWI-ASPECTS (>8), baseline National Institutes of Health Stroke Scale score (<10), and glucose (<120 mg/dL) as variables with a P<0.1 on univariate analysis, RLS (OR, 5.9; CI,1.3 to 27.3; P=0.022) was the only independent factor associated with dramatic improvement. Conclusion— The presence of an RLS on contrast transcranial Doppler was an independent factor associated with dramatic improvement after tissue plasminogen activator administration.

Heart failure may be associated with the onset of ischemic stroke with atrial fibrillation: A brain natriuretic peptide study

BACKGROUND AND PURPOSE Congestive heart failure is a risk factor for ischemic stroke. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. We hypothesized that heart failure was associated with the onset of ischemic stroke patients with atrial fibrillation (AF). METHODS Between June 2006 and December 2007, we prospectively enrolled consecutive acute ischemic stroke patients with AF within 24 h of onset. Plasma BNP was measured twice, on admission and on days 28 or at discharge. As a control, we measured plasma BNP of chronic phase of stroke outpatients with AF. We investigated whether plasma BNP was elevated in the acute phase of stroke. RESULTS One hundred and nine patients (58 females; mean age, 76.3 years) were enrolled in the present study. Mean+/-SD of NIHSS score on admission and mRS score at discharge were 12.6+/-8.3 and 3.7+/-1.8, respectively. The interval from stroke onset to plasma BNP measurement on admission was 6.8+/-6.3 h. Moreover, follow up BNP was measured at mean of 26+/-9 days after stroke onset. The plasma BNP level in the acute phase of stroke was significantly higher than that of the subacute phase of stroke (median (interquartile range, IQR) 299.0 (176.8-469.5) vs. 149.5 (68.1-347.0) pg/ml, p<0.001). There was no significant difference in plasma BNP level between the subacute phase of stroke and control group (median (IQR) 149.5 (68.1-347.0) vs. 165.0 (64.6-224.0) pg/ml, p=0.543). CONCLUSION Plasma BNP was elevated in the acute phase of stroke. Heart failure may be associated with the onset of ischemic stroke patients with AF.

Contrast Transcranial Doppler Can Diagnose Large Patent Foramen Ovale

Background: Contrast transesophageal echocardiography (c-TEE) and contrast transcranial Doppler (c-TCD) are useful diagnostic tools for detecting right-to-left shunts (RLS). However, the diagnostic accuracy of c-TCD for patent foramen ovale (PFO) remains uncertain. We investigated the relationship between the size of PFO determined by c-TEE and c-TCD findings and assessed the detectable rate of RLS by c-TCD. Methods: We assessed RLS three times using simultaneous c-TCD and c-TEE in 107 patients (321 examinations). We classified all of ultrasound examinations into three groups by size according to microbubbles on c-TEE, such as no PFO (0 microbubble), small PFO (1–29 microbubbles) and large PFO (≥30 microbubbles). We also calculated the number of microembolic signals (MES) on c-TCD and evaluated the association between PFO size on c-TEE and MES count on c-TCD. Results: In the present study, c-TEE detected RLS in 105 (33%; small PFO, n = 78; large PFO, n = 27), and c-TCD detected RLS in 49 (15%) of 321 examinations. Among 78 examinations with small PFO, MES were found in only 19 (24%) on c-TCD. In contrast, of all 27 examinations with large PFO, MES were found on c-TCD. Also, c-TCD were able to detect MES in 3 of 216 examinations among the no-PFO group. When ≥2 MES on c-TCD was established as the cutoff to predict large PFO on c-TEE, the sensitivity, specificity and accuracy were 96.3, 96.8, and 96.9%, respectively. Conclusion: When two or more MES were determined by c-TCD, large PFO could be accurately diagnosed.

Recanalization between 1 and 24 hours after t-PA therapy is a strong predictor of cerebral hemorrhage in acute ischemic stroke patients

BACKGROUND AND PURPOSE Intravenous administration of tissue plasminogen activator (t-PA) can improve clinical outcomes in patients with acute ischemic stroke. The most important complication of t-PA therapy is intracerebral hemorrhage (ICH). The aim of this study was to use serial MRI studies to identify independent predictors of symptomatic and asymptomatic ICH after t-PA therapy. METHODS Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. To identify the presence of recanalization in the occluded arteries and the presence of ICH, MRI, including diffusion weighted imaging (DWI), T2*, and magnetic resonance angiography (MRA), was performed before and 1 h, 24 h, and 5-7 days after t-PA thrombolysis. The independent predictors of ICH were determined using multivariate logistic regression analysis. RESULTS 41 patients (21 males, 20 females; mean age, 73.2+/-10.7 years) were enrolled, and 19 ICHs (1 symptomatic, 18 asymptomatic) were observed on T2*. The initial MRA demonstrated occluded brain arteries in 31 patients (75.6%), of which follow-up MRA at 1 h, 24 h, and 5-7 days after t-PA therapy revealed recanalization in 48.4%, 80.0%, and 90.0% of patients, respectively. The frequency of recanalization within 1 h after t-PA therapy did not differ between ICH and No-ICH groups, but the ICH group had more frequent recanalization between 1 h and 24 h after t-PA than the No-ICH group (50.0% vs. 4.5%, P=0.001). The ICH group had arterial fibrillation (AF) more frequently than the No-ICH group (78.9% vs. 27.3%, P=0.001). Compared to the No-ICH group, the NIHSS score was higher (16.4+/-5.7 vs. 11.5+/-6.5, P=0.011) and the ASPECTS-DWI value (a normal DWI has an ASPECTS-DWI value of 11 points) was lower (7.3+/-2.4 vs. 8.9+/-1.9, P=0.019) in the ICH group. Multivariate logistic regression analysis demonstrated that the presence of recanalization between 1 and 24 h after the end of t-PA infusion (OR: 20.2; CI: 1.0-340.9; P=0.037) was the only independent predictor of ICH. CONCLUSION Recanalization of occluded arteries between 1 and 24 h but not within 1 h after t-PA infusion should be independently associated with symptomatic and asymptomatic ICH after t-PA therapy.

Reversible diffusion-weighted lesion in a TIA patient without arterial recanalization: A case report

A 70-year-old man with right hemiparesis (NIHSS score 15) was admitted to our hospital 1 h after onset. Diffusion-weighted imaging (DWI) revealed a hyperintense lesion in the left corona radiata and magnetic resonance angiography (MRA) revealed occlusion of the left middle cerebral artery (MCA). At 2.5 h after onset, his neurological deficits dramatically improved (with NIHSS score change from 15 to 2). Immediately thereafter, follow-up MRI revealed that the hyperintense lesion on DWI had disappeared, though the left MCA occlusion remained. By the end of follow-up MRI examination, his neurological deficits had completely disappeared. We report here the patient with transient ischemic attack with a reversible ischemic lesion on DWI without early arterial recanalization.