Thomas Kucinski

Effect of Intravenous Thrombolysis on MRI Parameters and Functional Outcome in Acute Stroke <6 Hours

Background and Purpose— The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. Methods— In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). Results— We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13;P =0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%;P <0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P =0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (≤3 hours or 3 to 6 hours) (univariate analysis: mRS ≤2, P =0.017; mRS ≤1, P =0.023). Age (P =0.003), thrombolytic therapy at 0 to 6 hours (P =0.01), recanalization (P =0.016), lesion volume on day 7 (P =0.001), and initial National Institutes of Health Stroke Scale score (P =0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P =0.024) but not final infarct volume. Conclusions— In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.

Stroke Magnetic Resonance Imaging Is Accurate in Hyperacute Intracerebral Hemorrhage: A Multicenter Study on the Validity of Stroke Imaging

Background and Purpose— Although modern multisequence stroke MRI protocols are an emerging imaging routine for the diagnostic assessment of acute ischemic stroke, their sensitivity for intracerebral hemorrhage (ICH), the most important differential diagnosis, is still a matter of debate. We hypothesized that stroke MRI is accurate in the detection of ICH. To evaluate our hypotheses, we conducted a prospective multicenter trial. Methods— Stroke MRI protocols of 6 university hospitals were standardized. Images from 62 ICH patients and 62 nonhemorrhagic stroke patients, all imaged within the first 6 hours after symptom onset (mean, 3 hours 18 minutes), were analyzed. For diagnosis of hemorrhage, CT served as the “gold standard.” Three readers experienced in stroke imaging and 3 final-year medical students, unaware of clinical details, separately evaluated sets of diffusion-, T2-, and T2*-weighted images. The extent and phenomenology of the hemorrhage on MRI were assessed separately. Results— Mean patient age was 65.5 years; median National Institutes of Health Stroke Scale score was 10. The experienced readers identified ICH with 100% sensitivity (confidence interval, 97.1 to 100) and 100% overall accuracy. Mean ICH size was 17.3 mL (range, 1 to 101.5 mL). The students reached a mean sensitivity of 95.16% (confidence interval, 90.32 to 98.39). Conclusions— Hyperacute ICH causes a characteristic imaging pattern on stroke MRI and is detectable with excellent accuracy. Even raters with limited film-reading experience reached good accuracy. Stroke MRI alone can rule out ICH and demonstrate the underlying pathology in hyperacute stroke.

Transient Ischemic Attacks Before Ischemic Stroke: Preconditioning the Human Brain? A Multicenter Magnetic Resonance Imaging Study

Background and Purpose— We investigated whether transient ischemic attacks (TIAs) before stroke can induce tolerance by raising the threshold of tissue vulnerability in the human brain. Methods— Sixty-five patients with first-ever ischemic territorial stroke received diffusion- and perfusion-weighted MRI within 12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in T2, apparent diffusion coefficient (ADC) maps and perfusion maps, and cerebral blood flow and cerebral blood volume values were compared between patients with and without a prodromal TIA. Results— Despite similar size and severity of the perfusion deficit, initial diffusion lesions tended to be smaller and final infarct volumes were significantly reduced (final T2: 9.1 [interquartile range, 19.7] versus 36.5 [91.2] mL; P =0.014) in patients with a history of TIA (n=16). This was associated with milder clinical deficits. Conclusions— The beneficial effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous neuroprotection in the human brain.

Outcome and Symptomatic Bleeding Complications of Intravenous Thrombolysis Within 6 Hours in MRI-Selected Stroke Patients: Comparison of a German Multicenter Study With the Pooled Data of ATLANTIS, ECASS, and NINDS tPA Trials

Background and Purpose— We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials. Methods— Patients were examined by perfusion-weighted and diffusion-weighted imaging ≤6 hours. Within 3 hours, patients were treated according to Second European-Australasian Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA was performed based on MRI findings. Favorable outcome was assessed after 90 days using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral bleeding complications were assessed on follow-up MRI or computed tomography. Data were compared with the pooled placebo and pooled tPA patients of the ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke (NINDS) tPA trials. Results— From 174 MRI-selected tPA patients, 62% (n=108) were treated in ≤3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40% [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI-selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and 1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392). Conclusions— This study supports that it is safe and effective to expand the time window for IV-tPA up to 6 hours in patients with tissue at risk as defined by MRI.

Aggressive Therapy With Intravenous Abciximab and Intra-Arterial rtPA and Additional PTA/Stenting Improves Clinical Outcome in Acute Vertebrobasilar Occlusion Combined Local Fibrinolysis and Intravenous Abciximab in Acute Vertebrobasilar Stroke Treatment (FAST): Results of a Multicenter Study

Background and Purpose— A combined therapy of local recombinant tissue plasminogen activator (rtPA) fibrinolysis and intravenous Abciximab platelet inhibition with additional percutaneous transluminal angioplasty (PTA)/stenting may improve recanalization and neurological outcome in patients with acute vertebrobasilar occlusion. Methods Combined FAST therapy consisted on intravenous bolus of Abciximab (0.25 mg/kg) followed by a 12-hour infusion therapy (0.125 &mgr;g/kg per minute) and low-dose intra-arterial rtPA (median dosage: 20 mg, FAST cohort: N=47). The results were compared with a retrospective cohort, treated by intraarterial rtPA monotherapy (median dosage: 40 mg, rtPA cohort, N=41). Additional PTA/stenting was performed in case of severe residual stenosis. Recanalization success was classified according to the Trials in Myocardial Infarction (TIMI) criteria: TIMI0/1, failed recanalization; TIMI2/3, successful recanalization. Bleeding complications were evaluated according to severe extracerebral hemorrhage (ECH), asymptomatic intracerebral hemorrhage (AIH), and symptomatic intracerebral hemorrhage (SIH). Results— Overall bleeding rate was higher under the combined therapy, but the SIH rate did not differ (FAST versus rtPA: ECH, 3% versus 0%; AIH, 32% versus 22%; SIH 13% versus 12%). Additional PTA/stenting was performed in 14 (FAST) versus 5 (rtPA) patients. TIMI2/3 recanalization rate was similar (FAST, 72%; rtPA, 68%), but TIMI3 rate was remarkably higher under combined therapy (FAST, 45%; rtPA, N=22%). Neurologic outcome appeared better under combined therapy (FAST versus rtPA: favorable outcome rate: 34% versus 17%) with a significantly lower mortality rate (FAST versus rtPA: 38% versus 68%; P=0.006). These results were consistent for embolic and atherothrombotic occlusions. Conclusion Combined therapy of intravenous Abciximab and half dose intra-arterial rtPA with additional PTA/stenting appears to improve neurologic outcome in acute vertebrobasilar occlusion despite an increase of overall bleeding complications.

Predictors of Apparent Diffusion Coefficient Normalization in Stroke Patients

Background and Purpose— We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. Methods— Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). Results— Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. Conclusions— ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include “tissue at risk.”

Leukoaraiosis Is a Risk Factor for Symptomatic Intracerebral Hemorrhage After Thrombolysis for Acute Stroke

Background and Purpose— The aim of the study was to evaluate whether leukoaraiosis (LA) is a risk factor for symptomatic intracerebral hemorrhage (sICH) in patients treated with thrombolysis for acute stroke. Methods— In this retrospective, multicenter analysis, we evaluated data from acute anterior circulation stroke patients (n=449; <6 hours after symptom onset) treated with thrombolysis. All patients had received standard magnetic resonance imaging evaluation before thrombolysis, including a high-quality T2-weighted sequence. For the analysis, LA in the deep white matter was dichotomized into absent or mild versus moderate or severe (corresponding to Fazekas scores of 0 to 1 versus 2 to 3). Results— The rate of sICH was significantly more frequent in patients with moderate to severe LA of the deep white matter (n=12 of 114; 10.5%) than in patients without relevant LA (n=13 of 335; 3.8%), corresponding to an odds ratio of 2.9 (95% CI, 1.29 to 6.59; P=0.015). In a logistic-regression analysis (including age, National Institutes of Health Stroke Scale score at presentation, and type of thrombolytic treatment), LA remained a significant independent risk factor (odds ratio, 2.9; P=0.03). Conclusions— LA of the deep white matter is an independent risk factor for sICH after thrombolytic treatment for acute stroke.

Prediction of Malignant Middle Cerebral Artery Infarction by Early Perfusion- and Diffusion-Weighted Magnetic Resonance Imaging

Background and Purpose— We tested the hypothesis that early diffusion- and perfusion-weighted MRI (DWI and PWI, respectively) allows the prediction of malignant middle cerebral artery (MCA) infarction (MMI). Methods— Thirty-seven patients with acute MCA infarction and proximal vessel occlusion (carotid-T, MCA main stem) were studied by DWI, PWI, and MR angiography within 6 hours of symptom onset. Eleven patients developed MMI, defined by decline of consciousness and radiological signs of space-occupying brain edema. Lesion volumes were retrospectively defined as apparent diffusion coefficient <80% (ADC<80%) and time to peak >+4 seconds (TTP>+4s) compared with the unaffected hemisphere. ADC decrease within the infarct core (ADCcore) and relative ADC within the ADC<80% lesion (rADClesion) were measured. Neurological deficit at admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). Results— Patients with MMI showed larger ADC<80% (median, 157 versus 22 mL; P <0.001) and TTP>+4s (208 versus 125 mL; P <0.001) lesion volumes, smaller TTP/ADC mismatch ratio (1.5 versus 5.5; P <0.001), lower ADCcore values (290 versus 411 mm2/s; P <0.001), lower rADClesion (0.60 versus 0.66; P =0.001), higher frequency of carotid-T occlusion (64% versus 15%; P =0.006), and higher NIHSS score at admission (20 versus 15; P =0.001). Predictors of MMI were as follows for sensitivity and specificity, respectively: ADC<80% >82 mL, 87%, 91%; TTP>+4s >162 mL, 83%, 75%; TTP/ADC mismatch ratio <2.4, 80%, 79%; ADCcore <300 mm2/s, 83%, 85%; rADClesion <0.62, 79%, 74%; and NIHSS score at admission ≥19, 96%, 72%. Conclusions— Quantitative analysis of early DWI and PWI parameters allows the prediction of MMI and can help in the selection of patients for aggressive tissue-protective therapy.

Outcome and Severe Hemorrhagic Complications of Intravenous Thrombolysis With Tissue Plasminogen Activator in Very Old (≥80 Years) Stroke Patients

Background and Purpose— Information on safety and efficacy of intravenous thrombolysis with tissue plasminogen activator (tPA) (IV-tPA) in very old acute ischemic stroke (AIS) patients is scarce. We studied outcome and severe hemorrhagic complications in patients aged 80 and older. Methods— We analyzed data of AIS patients, treated with IV-tPA, in 3 German stroke centers. Neurologic deficit on admission was assessed using the National Institutes of Health Stroke Scale (NIHSS). Outcome was assessed after 90 days using the Modified Rankin Scale (MRS), and favorable outcome was defined as a MRS score of 0 to 1. Severe intracerebral bleeding complications were assessed on follow-up magnetic resonance imaging or cranial computed tomography. Data were compared between patients <80 years of age and patients aged ≥80 years. Results— A total of 228 patients were treated with IV-tPA; 38 (16%) were 80 years or older. There was no difference in NIHSS on admission or onset to treatment time between younger and older patients. Less patients ≥80 years of age achieved a favorable outcome (26.3 versus 46.8%, P=0.021), and mortality was higher in older patients (21.1 versus 5.3%, P=0.004). There was no difference in the rate of parenchymal hemorrhage (6.3%<80 years versus 5.3%≥80 years, P=1.000) and symptomatic intracerebral hemorrhage (2.6%<80 years versus 2.6%≥80 years, P=1.000) between both groups. Conclusion— There is no increase in severe intracerebral hemorrhage after IV-tPA in very old patients, but outcome is worse as compared with younger patients. There is no evidence to exclude ischemic stroke patients from thrombolysis based on a predefined age threshold.

Endovascular therapy of acute vertebrobasilar occlusion: early treatment onset as the most important factor.

In view of the poor prognosis for patients with acute intracranial vertebrobasilar occlusion (VBO), factors were sought that predict survival and good neurologic outcome after acute endovascular treatment by means of local intra-arterial fibrinolysis (LIF) and percutaneous transluminal angioplasty (PTA). LIF was performed in 83 patients with angiographically established acute VBO. A significant residual stenosis after LIF was treated by additional PTA in 8 patients. The types of occlusion were classified as either embolic occlusion (EO) or atherothrombotic occlusion (AO). Outcome was evaluated after 3 months by the Barthel Index (BI) as favorable (BI >90), unfavorable (BI <90) or death and compared for each of 3 diagnostic or treatment variables: recanalization success, occlusion type and time to treatment. Four fibrinolytic treatment modes [urokinase, low-dose and high-dose recombinant tissue-type plasminogen activator (rt-PA), rt-PA + Lys-plasminogen] were also analyzed. The outcome was favorable in 19 patients (23%), unfavorable in 14 (17%) and 50 died (60%). Recanalization was successful in 54 patients (66%). The neurologic outcome was better in recanalized than in nonrecanalized patients (favorable outcome: 30 vs. 10%, mortality: 54 vs. 72%; p = 0.118). The neurologic outcome was better in EO than in AO (favorable outcome: 31 vs. 17%, mortality: 47 vs. 70%, p = 0.112). Under combined treatment by LIF and PTA in 8 patients with AO, 4 survived, 3 with a favorable outcome (38%). Early treatment onset (≤6 h) led to a significantly better neurologic outcome than delayed treatment onset (>6 h; favorable outcome: 36 vs. 7%, mortality: 52 vs. 70%, p = 0.005). Although no statistically significant differences were found between the types of fibrinolytic agents, treatment with rt-PA and Lys-plasminogen tended toward better results. Early treatment onset proved to be the most important factor for successful endovascular therapy in acute VBO, whereas recanalization and presence of an embolic occlusion also tended toward better results. Additional PTA may be a promising therapy in cases of significant residual stenosis after LIF.