Combined thrombolysis with abciximab and rtPA in patients with middle cerebral artery occlusion.

BACKGROUND: In patients with acute middle cerebral artery (MCA) occlusion, recanalization rates with intravenous (IV) recombinant tissue plasminogen activator (rtPA) are limited. Aim- We evaluated the feasibility and safety of combined IV thrombolysis with abciximab and reduced dose rtPA in a 3- to 6-h time window. METHODS: We prospectively (March 2002 to February 2005) studied patients with symptomatic MCA occlusion on computed tomography (CT) angiography and absence of major early ischemic changes (EIC) on non-contrast CT (NCCT) within 3-6 h from symptom onset. Patients were treated with IV abciximab and half-standard dose rtPA. Outcome parameters were symptomatic intracerebral hemorrhage (sICH), early clinical improvement and functional independence at discharge (modified Rankin Scale score < or = 2). RESULTS: Of 13 patients, mean age was 62 +/- 11 years, onset-to-treatment time 4.8 +/- 0.9 h and median baseline National Institutes of Health Stroke Scale score 11 (interquartile range 6.5-13.5). sICH occurred in one patient (8%). We observed early clinical improvement in four patients (31%). Six patients (46%) were functionally independent at discharge. CONCLUSIONS: In patients with acute symptomatic MCA occlusion and absence of major EIC on NCCT, combined IV thrombolysis with abciximab and half-standard dose rtPA was feasible and seemed to be safe if applied within 3-6 h from symptom onset.

[Computed tomography in acute ischemic stroke. Current developments compared with stroke MRI]. / Computertomographie beim akuten Schlaganfall. Aktuelle Entwicklungen im Vergleich mit dem Schlaganfall-MRT.

Modern multimodal acute stroke computed tomography (CT) includes noncontrast cranial CT (NCT), CT angiography (CTA), and CT perfusion imaging (CTP). Compared to stroke MRI, NCT is faster and easier. Multimodal CT can determine acute stroke etiology: Is arterial occlusion or intracerebal hemorrhage present? How extensive are the perfusion disturbance and infarct core, respectively? The information from NCT is sufficient for making acute stroke thrombolysis decisions within 4.5 h from symptom onset. The therapeutic effect of CTA and CTP--as well as acute stroke MRI--on improved functional outcome has still not been established.

[Reliability of quantifying vascular white matter brain lesions -- a contribution to reproducible quantitative diagnosis]. / Reliabilität der Quantifizierung von vaskulären Läsionen der weissen Hirnsubstanz -- ein Beitrag zur replizierbaren quantitativen Diagnostik.

PURPOSE: Microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The "experience-based" evaluation is insufficient. Rating scales may contribute to reproducible quantification. MATERIALS AND METHODS: In MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). RESULTS: As to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. CONCLUSION: The rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age-associated physiological vs. pathological size of the WML can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics.

Multimodal Computed Tomography Based Definition of Cerebral Imaging Profiles for Acute Stroke Reperfusion Therapy (CT-DEFINE): Results of a Prospective Observational Study.

PURPOSE: To prospectively evaluate the prognostic impact of multimodal computed tomography-based imaging in ischemic stroke patients potentially eligible for reperfusion therapy. METHODS: Anterior circulation stroke patients underwent non-contrast CT (NCCT), CT-angiography, and CT-perfusion within 12 h from symptom-onset. Patients could be treated with intravenous-tissue plasminogen activator (IV-tPA), endovascular or combined reperfusion therapies. Cerebral imaging profiles (IP) were NCCT-Alberta Stroke Program Early CT Score (ASPECTS) > 7 (IP1); NCCT-ASPECTS > 5 and proximal occlusion on CT-angiography (IP2); CT-perfusion mismatch between cerebral blood volume (CBV)-ASPECTS, and cerebral blood flow (CBF)-ASPECTS ≥ 2 (IP3). Favorable outcome was defined as modified Rankin Scale ≤ 2 at 3 months. RESULTS: Of 102 included patients, 62 (61%) received any reperfusion therapy. In IP2 and IP3, favorable outcome was more frequent in patients with reperfusion therapy than in those without; however, this did not reach statistical significance (IP2: 39% vs 15%, p = 0.26; IP3: 50% vs 17 %; p = 0.31). No difference was seen in IP1 (58% vs 58%, p = 1.0). In IP2, patients with IV-tPA alone achieved better functional outcome (50% vs 11%, p = 0.03) and lower mortality (0% vs 28%, p = 0.045) than those without. CONCLUSIONS: Our results suggest a benefit with imaging profile selection based upon the combination of a small-to-moderate-sized infarction and a visible intracranial occlusion in patients receiving IV-tPA. Reperfusion therapy may be futile in patients without proven vessel occlusion.

Outcome Differences between Intra-Arterial Iso- and Low-Osmolality Iodinated Radiographic Contrast Media in the Interventional Management of Stroke III Trial.

BACKGROUND AND PURPOSE: Intracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III). MATERIALS AND METHODS: We reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model. RESULTS: Of baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol. CONCLUSIONS: While data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation.

The Alberta Stroke Program Early CT Score in clinical practice: what have we learned?

The introduction of brain imaging with computed tomography revolutionised the treatment of patients with acute ischaemic stroke. With the visual differentiation of haemorrhagic stroke from ischaemic stroke, thrombolytic therapy became feasible. The Alberta Stroke Program Early CT Score was devised to quantify the extent of early ischaemic changes in the middle cerebral artery territory on noncontrast computed tomography. With its systematic approach, the score is simple and reliable. However, the assessment of early ischaemic changes and Alberta Stroke Program Early CT scoring require training. The Alberta Stroke Program Early CT Score is a strong predictor of functional outcome. Furthermore, the effectiveness of intraarterial thrombolysis in patients with middle cerebral artery occlusion shows effect modification by the Alberta Stroke Program Early CT Score. This review summarises the Alberta Stroke Program Early CT Score methodology. We illustrate current knowledge regarding Alberta Stroke Program Early CT Score applied to clinical trials and comment on how Alberta Stroke Program Early CT Score may facilitate clinical treatment decision making and future trial design. Moreover, we introduce a modification of the Alberta Stroke Program Early CT Score methodology that disregards isolated cortical swelling, i.e. focal brain swelling without associated parenchymal hypoattenuation, as early ischaemic changes in the Alberta Stroke Program Early CT Score system.

CT angiography source images predict final infarct extent in patients with basilar artery occlusion.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) is a 10-point grading system to quantify ischemic changes in the posterior circulation. We analyzed whether pc-ASPECTS on CT angiography (CTA) source images (CTASI) predicted the final infarct extent and hemorrhagic transformation (HT) rate in patients with basilar artery occlusion. MATERIALS AND METHODS: A pc-ASPECTS score of 10 indicates absence of visible ischemic changes in the posterior circulation, and pc-ASPECTS score of 0 indicates ischemic changes in the midbrain, pons, and bilateral thalami, posterior circulation territories, and cerebellar hemispheres. We retrospectively studied patients with basilar artery occlusion on CTA within 24 hours from symptom onset. We applied pc-ASPECTS to noncontrast CT (NCCT), CTASI, and follow-up images by 3-reader-consensus and assessed HT on follow-up images. We calculated Spearman correlation coefficients and performed linear regression analysis. Final infarct extent and HT rates were compared across dichotomized CTASI pc-ASPECTS groups (>/= 8 vs < 8). RESULTS: Among 43 patients, median (range) onset to CTA time was 5.0 hours (range, 0.7-24 hours). Pc-ASPECTS on CTASI (r = 0.75; P < .001) but not NCCT (r = 0.29; P = .063) correlated with pc-ASPECTS on follow-up scans. Linear regression demonstrated a significant positive relationship between pc-ASPECTS on CTASI and follow-up scans (R(2) = 0.58; P < 01). Median follow-up pc-ASPECTS was lower in patients with a CTASI pc-ASPECTS < 8 compared with patients with a CTASI pc-ASPECTS of 8 or more, respectively (P < .001). HT rates were 27.3% vs 9.5%, respectively (P = .24). None of 8 patients without thrombolysis had HT on follow-up scans. CONCLUSIONS: The extent of hypoattenuation on CTASI predicts the final infarct extent in patients with basilar artery occlusion.