Capillary Index Score in the Interventional Management of Stroke trials I and II.

BACKGROUND AND PURPOSE: The Capillary Index Score (CIS) is a simple angiography-based scale for assessing viable tissue in the ischemic territory. We retrospectively applied it to Interventional Management of Stroke (IMS) trials I and II to evaluate the predictive value for good outcomes. METHODS: CIS was calculated from pretreatment diagnostic cerebral angiograms blinded to outcome. IMS I and II diagnostic cerebral angiogram images of sufficient quality were reviewed and CIS calculated for treated subjects with internal carotid artery or M1 occlusion. CIS scoring (0-3) was dichotomized into favorable (f CIS; 2 or 3) and poor (p CIS; 0 or 1). Modified thrombolysis in cerebral infarction score 2b or 3 was considered good revascularization. CIS and modified thrombolysis in cerebral infarction scores were compared with good outcome, defined as modified Rankin Scale score≤2 at 90 days. RESULTS: Twenty-eight of 161 subjects met the inclusion criteria. Thirteen (46%) had f CIS. Good clinical outcome was significantly different between the 2 CIS groups (62% for f CIS versus 7% for p CIS; P=0.004). Good reperfusion correlated to good outcome (P=0.04). No significant differences in time to intravenous or intra-arterial treatment were identified between f CIS and p CIS groups (P>0.25). CONCLUSIONS: A f CIS was found in ≈50% of subjects and was a virtual prerequisite for good outcome in this study subgroup of IMS I and II. We call this the 50% barrier.

Addition of hyperacute MRI AIDS in patient selection, decreasing the use of endovascular stroke therapy.

BACKGROUND AND PURPOSE: The failure of recent trials to show the effectiveness of acute endovascular stroke therapy (EST) may be because of inadequate patient selection. We implemented a protocol to perform pretreatment MRI on patients with large-vessel occlusion eligible for EST to aid in patient selection. METHODS: We retrospectively identified patients with large-vessel occlusion considered for EST from January 2008 to August 2012. Patients before April 30, 2010, were selected based on computed tomography/computed tomography angiography (prehyperacute protocol), whereas patients on or after April 30, 2010, were selected based on computed tomography/computed tomography angiography and MRI (hyperacute MRI protocol). Demographic, clinical features, and outcomes were collected. Univariate and multivariate analyses were performed. RESULTS: We identified 267 patients: 88 patients in prehyperacute MRI period and 179 in hyperacute MRI period. Fewer patients evaluated in the hyperacute MRI period received EST (85 of 88, 96.6% versus 92 of 179, 51.7%; P<0.05). The hyperacute-MRI group had a more favorable outcome of a modified Rankin scale 0 to 2 at 30 days as a group (6 of 66, 9.1% versus 33 of 140, 23.6%; P=0.01), and when taken for EST (6 of 63, 9.5% versus 17 of 71, 23.9%; P=0.03). On adjusted multivariate analysis, the EST in the hyperacute MRI period was associated with a more favorable outcome (odds ratio, 3.4; 95% confidence interval, 1.1-10.6; P=0.03) and reduced mortality rate (odds ratio, 0.16; 95% confidence interval, 0.03-0.37; P<0.001). CONCLUSIONS: Implementation of hyperacute MRI protocol decreases the number of endovascular stroke interventions by half. Further investigation of MRI use for patient selection is warranted.

Heterogeneity of efficacy and safety of antiplatelet therapy in cardiovascular and cerebrovascular disease.

The beneficial effects of antiplatelet therapy for secondary prevention in patients with prior cardiovascular or cerebrovascular events, including stroke, transient ischemic attack, and myocardial infarction, have been demonstrated repeatedly over the past decade. It is increasingly apparent that pathophysiologic differences between patients with different types of prior vascular events have an important effect on treatment outcomes. Several large, important trials of antiplatelet therapies, including MATCH, CHARISMA, ESPRIT, and TRITON-TIMI 38, underscore the heterogeneity of the efficacy and safety of antiplatelet agents in patients with recent cerebrovascular disease, compared with patients with recent acute coronary syndromes. Trial data therefore support an individualized approach to antithrombotic therapy for secondary vascular-event prevention that is appropriate for any probable future vascular events and actively reduces the impact of modifiable risk factors common to all vascular events. The potential for benefit in reducing recurrent vascular events must be weighed against the increased risk of bleeding and of patient non-responsiveness to treatment. A number of other factors also need to be considered, including drug interactions, patient compliance, and adverse-effect profiles. Overall, there is now a substantial body of clinical trial evidence that supports the need to carefully individualize antiplatelet therapy and other risk-reducing strategies on the basis of each patient's pathology and specific needs.

Quantitative perihematomal blood flow in spontaneous intracerebral hemorrhage predicts in-hospital functional outcome.

BACKGROUND AND PURPOSE: Few data on xenon computed tomography-based quantitative cerebral blood flow (CBF) in spontaneous intracerebral hemorrhage have been reported. We correlated perihematomal CBF in a retrospective series of 42 subacute spontaneous intracerebral hemorrhage patients undergoing xenon computed tomography with in-hospital discharge status and mortality. METHODS: We calculated 3 area-weighted mean CBF values: (1) within the computed tomography-visible rim of perihematomal edema, (2) within a 1-cm marginal radius around the hematoma, and (3) all cortical regions of interest immediately adjacent to the hematoma. Primary outcomes were in-hospital mortality and discharge status (ordinally as 0=home, 1=acute rehabilitation, 2=nursing home, 3=death). Discharge status was used as a surrogate for in-hospital functional outcome. RESULTS: Median hematoma volume was 14.4 cm(3) (range, 2 to 70). Median perihematomal (low-attenuation rim) CBF was 21.9 cm(3).100 g(-1).min(-1) (range, 6.1 to 81.1), and the median 1-cm marginal radius CBF was 26.8 cm(3).100 g(-1).min(-1) (range, 10.8 to 72.8). The median regional cortical CBF was 26.7 cm(3).100 g(-1).min(-1) (range, 6.9 to 72.6). Eight patients had 1-cm marginal radius or regional cortical CBF values <20 cm(3).100 g(-1).min(-1). Hematoma volume (odds ratio [OR], 1.68 per 10-cm(3) volume; P=0.036) and intraventricular hemorrhage (OR, 1.88 per grade of intraventricular hemorrhage; P=0.036) predicted mortality. Two CBF measures, hydrocephalus, and IVH predicted poor in-hospital functional outcome in bivariate analysis. Each CBF measure (OR, 0.34 to 0.43; P<0.001 to 0.003) and intraventricular hemorrhage (OR, 3.42; P<0.001) predicted in-hospital functional outcome in multivariable analyses. CONCLUSIONS: Most spontaneous intracerebral hemorrhage patients lack perihematomal penumbra. Perihematomal CBF independently predicts in-hospital discharge status but not in-hospital mortality. Further studies are warranted to determine whether perihematomal CBF predicts long-term functional outcomes.

Secondary stroke prevention with antiplatelet therapy with emphasis on the cardiac patient: a neurologist's view.

The prevention of secondary vascular events is of paramount importance in patients with a history of stroke or transient ischemic attack (TIA). Most cardiologists are aware of the benefits of clopidogrel plus aspirin versus those of other antiplatelet regimens in patients with acute coronary syndrome. Using a representative post-stroke patient as an example, this article reviews data evaluating the effectiveness of antiplatelet regimens in preventing secondary vascular events in stroke and TIA patients. These results differ from those seen in clinical trials of acute coronary syndrome patients. Clinical studies provide little evidence that clopidogrel, with or without aspirin, is more efficacious in this setting than aspirin alone. Moreover, the increased risk of bleeding episodes with clopidogrel and aspirin in combination probably outweighs any small reductions in secondary event risk. In contrast, extended-release dipyridamole (ER-DP) plus aspirin reduces secondary stroke risk to a significantly greater extent (23% relative risk reduction) than aspirin alone. Currently available clinical trial data support the use of ER-DP plus aspirin, but not clopidogrel plus aspirin, to prevent secondary vascular events after stroke or TIA.

Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The natural history of perihematomal edema in human hyperacute spontaneous intracerebral hemorrhage (ICH) has not been well described. METHODS: This study was a secondary analysis of a previously reported prospective, population-based study of hematoma growth in 142 patients with spontaneous ICH. Patients were first imaged within 3 hours of onset, then 1 and 20 hours later. We excluded patients with anticoagulant use (n=7), underlying aneurysm/vascular malformation (n=9), trauma (n=1), incomplete data (n=20), infratentorial ICH (n=17), and no consent (n=2), leaving an overall study population of 86 patients. From this overall group we further excluded patients with intraventricular extension (n=38), subsequent surgery (n=5), or death (n=2) before 20-hour postbaseline CT. This second, "restricted" analysis group of 41 patients was relatively devoid of clinical or radiological variables likely to confound edema measurement. Absolute and relative edema volumes (edema volume divided by hematoma volume) were descriptively summarized. Correlations between baseline edema volumes and relevant clinical and radiological variables were then performed. RESULTS: Overall, median absolute edema volume increased from 6.93 to 14.4 cm(3) during the first 24 hours after ICH, and median relative edema volume increased from 0.47 to 0.81. In the restricted group, median absolute edema volume was 7.4 cm(3) at baseline and 11.0 cm(3) at 24 hours after ICH, and median relative edema volume increased from 0.55 to 0.81. Baseline relative edema volume was significantly negatively correlated with subsequent change in relative edema volume from baseline to 20-hour CT (r=0.57, P=0.0002) but was not significantly correlated with other clinical and radiological variables, including hematoma volume or change in hematoma volume. CONCLUSIONS: Perihematomal edema volume increases by approximately 75% during the first 24 hours after hyperacute spontaneous ICH. Patients with the least amounts of baseline relative edema volume were most likely to develop significant additional amounts of edema during the first 24 hours after spontaneous ICH.

Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Little is known about the relationship between perihematomal edema in spontaneous intracerebral hemorrhage (ICH) and outcome. The purpose of this study was to determine whether absolute or relative edema volume (edema volume divided by hematoma volume) predicts mortality or functional outcome in patients with hyperacute spontaneous ICH. We hypothesized that increasing baseline relative edema volume is associated with greater probability of poor functional outcome. METHODS: This was a secondary analysis of a prospective, population-based study of hematoma growth in 142 patients with spontaneous ICH. Patients were imaged within 3 hours of onset, then 1 and 20 hours later. Our primary analysis excluded patients with anticoagulant use (n=7), underlying aneurysm/vascular malformation (n=9), trauma (n=1), incomplete data (n=20), infratentorial ICH (n=17), intraventricular extension (n=38), and no consent (n=2). We analyzed whether associations existed between baseline edema volumes or other clinical/radiological variables and either 12-week modified Rankin Scale score >2 or 30-day mortality. Secondary analyses used 20-hour CT scan data, all patients with supratentorial ICH, and 12-week Barthel Index score <85. RESULTS: By multivariable logistic regression analysis, baseline relative edema was the strongest independent predictor of functional outcome and was associated with lesser odds of poor 3-month functional outcome (odds ratio, 0.09 per 1.0-unit [100%] increase; 95% CI, 0.01 to 0.64; P=0.016) and 12-week Barthel Index score <85 (odds ratio, 0.12; 95% CI, 0.02 to 0.91; P=0.039) but did not predict mortality. Secondary analyses confirmed this result. Absolute edema volume predicted neither mortality nor functional outcome. CONCLUSIONS: Relative edema is strongly predictive of functional outcome in patients with hyperacute supratentorial spontaneous ICH without intraventricular extension.

The cortical ischemic core and not the consistently present penumbra is a determinant of clinical outcome in acute middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Patient selection for acute stroke therapy based on physiology rather than on time may lead to expansion of the therapeutic window, improved outcomes, and fewer side effects than currently achieved. This approach requires early determination of both irreversible (core) and reversible (penumbra) ischemia in acute stroke. METHODS: Using established perfusion thresholds, we characterized the relationship among core, penumbra, and brain tissue perfused above penumbral thresholds (non-core/non-penumbra [NC/NP]) in 36 patients with middle cerebral artery (MCA) stem occlusion who underwent quantitative cerebral blood flow (CBF) assessment with xenon-enhanced CT within 6 hours of symptom onset. RESULTS: While great variability in the mean+/-SD percentage of core (37.6+/-18.7) and NC/NP (30.3+/-16.6) was observed, the percentage of penumbra was relatively constant from individual to individual, constituting approximately one third of the cortical MCA territory (32.1+/-7). In univariable and multivariable analyses, percent core and not percent penumbra was significantly associated with outcome. CONCLUSIONS: In acute MCA occlusion, penumbra is consistently present within a relatively narrow range, despite great variability in the size of core. This may explain why the core and not the penumbra is the main determinant of outcome in our group of patients. Recanalization therapy in acute MCA occlusion should ideally be guided by diagnostic methods capable of rapidly and reliably identifying irreversible ischemia.

Hypercholesterolemia, HMG-CoA reductase inhibitors, and risk of intracerebral hemorrhage: a case-control study.

BACKGROUND AND PURPOSE: Several studies have demonstrated an association between hypocholesterolemia and intracerebral hemorrhage (ICH). We tested the hypothesis that hypercholesterolemia or use of HMG-CoA reductase inhibitors (statin) agents, or both, are associated with ICH. METHODS: This study was part of the preplanned midway analysis of an ongoing, population-based, case-control study of the genetic and environmental risk factors of hemorrhagic stroke. Conditional stepwise logistic regression modeling was used to determine if self-reported hypercholesterolemia or statin use, or both, were independent risk factors for ICH. RESULTS: Between December 1, 1997, and June 30, 2000, 188 cases of ICH and 366 age-, race-, and gender-matched controls were enrolled. Hypercholesterolemia and statin use were less common among cases than controls: 25% versus 38% (P=0.003) and 9% versus 17% (P=0.03), respectively. Hypercholesterolemia with statin use was associated with less risk of ICH (OR=0.30; P=0.0008) in multivariable analysis after controlling for alcohol use, hypertension, previous stroke, first-degree relative with ICH, education level, and apolipoprotein E alleles. CONCLUSIONS: Hypercholesterolemia was associated with a lower risk of ICH. We have not found an increased risk of ICH with the widespread use of statins in our population. Given the lack of cholesterol levels in the current study, further studies are needed to determine if lower cholesterol levels secondary to statin use bear the same risk as low cholesterol levels for ICH.

Therapeutic basilar artery occlusion for management of medically refractory basilar artery stenosis: case report.

OBJECTIVE AND IMPORTANCE: To describe a novel therapeutic approach (endovascular basilar artery occlusion) to a notoriously difficult-to-manage clinical condition (actively symptomatic high-grade basilar artery stenosis) on the basis of assessment of the patient-specific mechanism of disease. CLINICAL PRESENTATION: An 81-year-old woman presented with recurrent episodes of brainstem ischemia refractory to aggressive medical therapy. Cerebral angiography revealed a high-grade proximal basilar artery stenosis. On the basis of clinical presentation and angiographic findings, the pathogenesis of this complex of symptoms was thought to be embolic rather than hemodynamic. INTERVENTION: Endovascular coil occlusion of the basilar artery was used, with excellent outcome (cessation of ischemic symptoms and independent level of functioning at 1 yr). CONCLUSION: Successful endovascular management of intracranial occlusive disease requires understanding of the mechanism responsible for the patient's symptoms.

Intra-arterial thrombolysis for acute ischemic stroke.

Intra-arterial thrombolysis, administered within six hours of symptoms onset, has been shown in a randomized, prospective, multicenter trial and in several nonrandomized case series to be beneficial in acute ischemic stroke caused by occlusion of the middle cerebral artery or its major divisions. Benefit has been reported in a relatively small number of nonrandomized case series beyond the six-hour time window in basilar artery occlusion. Although intra-arterial thrombolysis appears to be an effective and relatively safe form of therapy for certain patients with acute ischemic stroke, better outcomes and fewer side effects than currently reported are to be desired. Whether this will be achieved in part by a better selection of patients based on physiologic rather than chronologic criteria, by achieving higher and faster recanalization rates (through combined use of intra-arterial and intravenous therapy or through use of mechanical clot-dissolution devices), or by combining thrombolysis with neuroprotectant strategies remains to be established by future trials.