Guideline on multimodal rehabilitation for patients with post-intensive care syndrome.

BACKGROUND: Intensive Care Unit (ICU) survivors often experience several impairments in their physical, cognitive, and psychological health status, which are labeled as post-intensive care syndrome (PICS). The aim of this work is to develop a multidisciplinary and -professional guideline for the rehabilitative therapy of PICS. METHODS: A multidisciplinary/-professional task force of 15 healthcare professionals applied a structured, evidence-based approach to address 10 scientific questions. For each PICO-question (Population, Intervention, Comparison, and Outcome), best available evidence was identified. Recommendations were rated as "strong recommendation", "recommendation" or "therapy option", based on Grading of Recommendations, Assessment, Development and Evaluation principles. In addition, evidence gaps were identified. RESULTS: The evidence resulted in 12 recommendations, 4 therapy options, and one statement for the prevention or treatment of PICS. RECOMMENDATIONS: early mobilization, motor training, and nutrition/dysphagia management should be performed. Delirium prophylaxis focuses on behavioral interventions. ICU diaries can prevent/treat psychological health issues like anxiety and post-traumatic stress disorders. Early rehabilitation approaches as well as long-term access to specialized rehabilitation centers are recommended. Therapy options include additional physical rehabilitation interventions. Statement: A prerequisite for the treatment of PICS are the regular and repeated assessments of the physical, cognitive and psychological health in patients at risk for or having PICS. CONCLUSIONS: PICS is a variable and complex syndrome that requires an individual multidisciplinary, and multiprofessional approach. Rehabilitation of PICS should include an assessment and therapy of motor-, cognitive-, and psychological health impairments.

Calculation of Prognostic Scores, Using Delayed Imaging, Outperforms Baseline Assessments in Acute Intracerebral Hemorrhage.

Background and Purpose- Patients with intracerebral hemorrhage (ICH) are often subject to rapid deterioration due to hematoma expansion. Current prognostic scores are largely based on the assessment of baseline radiographic characteristics and do not account for subsequent changes. We propose that calculation of prognostic scores using delayed imaging will have better predictive values for long-term mortality compared with baseline assessments. Methods- We analyzed prospectively collected data from the multicenter PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign). We calculated the ICH Score, Functional Outcome in Patients With Primary Intracerebral Hemorrhage (FUNC) Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. The primary outcome was mortality at 90 days. We generated receiver operating characteristic curves for all 3 scores, both at baseline and at 24 hours, and assessed predictive accuracy for 90-day mortality with their respective area under the curve. Competing curves were assessed with nonparametric methods. Results- The analysis included 280 patients, with a 90-day mortality rate of 25.4%. All 3 prognostic scores calculated using 24-hour imaging were more predictive of mortality as compared with baseline: the area under the curve was 0.82 at 24 hours (95% CI, 0.76-0.87) compared with 0.78 at baseline (95% CI, 0.72-0.84) for ICH Score, 0.84 at 24 hours (95% CI, 0.79-0.89) compared with 0.76 at baseline (95% CI, 0.70-0.83) for FUNC, and 0.82 at 24 hours (95% CI, 0.76-0.88) compared with 0.74 at baseline (95% CI, 0.67-0.81) for modified ICH Score. Conclusions- Calculation of the ICH Score, FUNC Score, and modified ICH Score using 24-hour imaging demonstrated better prognostic value in predicting 90-day mortality compared with those calculated at presentation.

Redefining Hematoma Expansion With the Inclusion of Intraventricular Hemorrhage Growth.

Background and Purpose- Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods- Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4-6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results- Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8-54.7) and 82.9% (95% CI, 75.3-88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8-72.1) and specificity of 75.2% (95% CI, 66.8-82.4). Overall accuracy was significantly improved with the revised definition (P=0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31-4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6-65.5]; specificity, 78.3% [95% CI, 40.2-85.1]; aOR, 2.40 [95% CI, 1.23-4.69]). Conclusions- In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

Independent Validation of the Hematoma Expansion Prediction Score: A Non-contrast Score Equivalent in Accuracy to the Spot Sign.

BACKGROUND AND PURPOSE: The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. METHODS: We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. RESULTS: A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4. CONCLUSION: The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Combining Spot Sign and Intracerebral Hemorrhage Score to Estimate Functional Outcome: Analysis From the PREDICT Cohort.

BACKGROUND AND PURPOSE: The intracerebral hemorrhage (ICH) score is the most commonly used grading scale for stratifying functional outcome in patients with acute ICH. We sought to determine whether a combination of the ICH score and the computed tomographic angiography spot sign may improve outcome prediction in the cohort of a prospective multicenter hemorrhage trial. METHODS: Prospectively collected data from 241 patients from the observational PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign) were analyzed. Functional outcome at 3 months was dichotomized using the modified Rankin Scale (0-3 versus 4-6). Performance of (1) the ICH score and (2) the spot sign ICH score-a scoring scale combining ICH score and spot sign number-was tested. RESULTS: Multivariable analysis demonstrated that ICH score (odds ratio, 3.2; 95% confidence interval, 2.2-4.8) and spot sign number (n=1: odds ratio, 2.7; 95% confidence interval, 1.1-7.4; n>1: odds ratio, 3.8; 95% confidence interval, 1.2-17.1) were independently predictive of functional outcome at 3 months with similar odds ratios. Prediction of functional outcome was not significantly different using the spot sign ICH score compared with the ICH score alone (spot sign ICH score area under curve versus ICH score area under curve: P=0.14). CONCLUSIONS: In the PREDICT cohort, a prognostic score adding the computed tomographic angiography-based spot sign to the established ICH score did not improve functional outcome prediction compared with the ICH score.

Do Intracerebral Hemorrhage Nonexpanders Actually Expand Into the Ventricular Space?

BACKGROUND AND PURPOSE: The computed tomographic angiography spot sign as a predictor of hematoma expansion is limited by its modest sensitivity and positive predictive value. It is possible that hematoma expansion in spot-positive patients is missed because of decompression of intracerebral hemorrhage (ICH) into the ventricular space. We hypothesized that revising hematoma expansion definitions to include intraventricular hemorrhage (IVH) expansion will improve the predictive performance of the spot sign. Our objectives were to determine the proportion of ICH nonexpanders who actually have IVH expansion, determine the proportion of false-positive spot signs that have IVH expansion, and compare the known predictive performance of the spot sign to a revised definition incorporating IVH expansion. METHODS: We analyzed patients from the multicenter PREDICT ICH spot sign study. We defined hematoma expansion as ≥6 mL or ≥33% ICH expansion or >2 mL IVH expansion and compared spot sign performance using this revised definition with the conventional 6 mL/33% definition using receiver operating curve analysis. RESULTS: Of 311 patients, 213 did not meet the 6-mL/33% expansion definition (nonexpanders). Only 13 of 213 (6.1%) nonexpanders had ≥2 mL IVH expansion. Of the false-positive spot signs, 4 of 40 (10%) had >2 mL ventricular expansion. The area under the curve for spot sign to predict significant ICH expansion was 0.65 (95% confidence interval, 0.58-0.72), which was no different than when IVH expansion was added to the definition (area under the curve, 0.66; 95% confidence interval, 0.58-0.71). CONCLUSIONS: Although IVH expansion does indeed occur in a minority of ICH nonexpanders, its inclusion into a revised hematoma expansion definition does not alter the predictive performance of the spot sign.

Lack of Early Improvement Predicts Poor Outcome Following Acute Intracerebral Hemorrhage.

OBJECTIVES: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. DESIGN: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). VALIDATION: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). SETTING: Neurocritical and ICUs. PATIENTS: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4-6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2-6, 3-6, 5-6, 6). We employed Youden's J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four-hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden's method showed an optimum cut point at -0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25-7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08-36.66]). All definitions reproduced well in the validation cohort. CONCLUSIONS: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

Imaging of cerebral ischemic edema and neuronal death.

PURPOSE: In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. METHODS: We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. RESULTS: Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ~15 ml/100 g × min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CONCLUSION: CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions.

Perihematomal Edema Is Greater in the Presence of a Spot Sign but Does Not Predict Intracerebral Hematoma Expansion.

BACKGROUND AND PURPOSE: Perihematomal edema volume may be related to intracerebral hemorrhage (ICH) volume at baseline and, consequently, with hematoma expansion. However, the relationship between perihematomal edema and hematoma expansion has not been well established. We aimed to investigate the relationship among baseline perihematomal edema, the computed tomographic angiography spot sign, hematoma expansion, and clinical outcome in patients with acute ICH. METHODS: Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) was a prospective observational cohort study of ICH patients presenting within 6 hours from onset. Patients underwent computed tomography and computed tomographic angiography scans at baseline and 24-hour computed tomography scan. A post hoc analysis of absolute perihematomal edema and relative perihematomal edema (absolute perihematomal edema divided by ICH) volumes was performed on baseline computed tomography scans (n=353). Primary outcome was significant hematoma expansion (>6 mL or >33%). Secondary outcomes were early neurological deterioration, 90-day mortality, and poor outcome. RESULTS: Absolute perihematomal edema volume was higher in spot sign patients (24.5 [11.5-41.8] versus 12.6 [6.9-22] mL; P<0.001), but it was strongly correlated with ICH volume (ρ=0.905; P<0.001). Patients who experienced significant hematoma expansion had higher absolute perihematomal edema volume (18.4 [10-34.6] versus 11.8 [6.5-22] mL; P<0.001) but similar relative perihematomal edema volume (1.09 [0.89-1.37] versus 1.12 [0.88-1.54]; P=0.400). Absolute perihematomal edema volume and poorer outcomes were higher by tertiles of ICH volume, and perihematomal edema volume did not independently predict significant hematoma expansion. CONCLUSIONS: Perihematomal edema volume is greater at baseline in the presence of a spot sign. However, it is strongly correlated with ICH volume and does not independently predict hematoma expansion.

Validation of the 9-Point and 24-Point Hematoma Expansion Prediction Scores and Derivation of the PREDICT A/B Scores.

BACKGROUND AND PURPOSE: Nine- and 24-point prediction scores have recently been published to predict hematoma expansion (HE) in acute intracerebral hemorrhage. We sought to validate these scores and perform an independent analysis of HE predictors. METHODS: We retrospectively studied 301 primary or anticoagulation-associated intracerebral hemorrhage patients presenting <6 hours post ictus prospectively enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus Computed Tomography (PREDICT) study. Patients underwent baseline computed tomography angiography and 24-hour noncontrast computed tomography follow-up for HE analysis. Discrimination and calibration of the 9- and 24-point scores was assessed. Independent predictors of HE were identified using multivariable regression and incorporated into the PREDICT A/B scores, which were then compared with existing scores. RESULTS: The 9- and 24-point HE scores demonstrated acceptable discrimination for HE>6 mL or 33% and >6 mL, respectively (area under the curve of 0.706 and 0.755, respectively). The 24-point score demonstrated appropriate calibration in the PREDICT cohort (χ2 statistic, 11.5; P=0.175), whereas the 9-point score demonstrated poor calibration (χ2 statistic, 34.3; P<0.001). Independent HE predictors included spot sign number, time from onset, warfarin use or international normalized ratio>1.5, Glasgow Coma Scale, and National Institutes of Health Stroke Scale and were included in PREDICT A/B scores. PREDICT A showed improved discrimination compared with both existing scores, whereas performance of PREDICT B varied by definition of expansion. CONCLUSIONS: The 9- and 24-point expansion scores demonstrate acceptable discrimination in an independent multicenter cohort; however, calibration was suboptimal for the 9-point score. The PREDICT A score showed improved discrimination for HE prediction but requires independent validation.

Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant Hematoma Expansion.

BACKGROUND AND PURPOSE: Hematoma expansion in intracerebral hemorrhage is associated with higher morbidity and mortality. The computed tomography (CT) angiographic spot sign is highly predictive of expansion, but other morphological features of intracerebral hemorrhage such as fluid levels, density heterogeneity, and margin irregularity may also predict expansion, particularly in centres where CT angiography is not readily available. METHODS: Baseline noncontrast CT scans from patients enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study were assessed for the presence of fluid levels and degree of density heterogeneity and margin irregularity using previously validated scales. Presence and grade of these metrics were correlated with the presence of hematoma expansion as defined by the PREDICT study on 24-hour follow-up scan. RESULTS: Three hundred eleven patients were included in the analysis. The presence of fluid levels and increasing heterogeneity and irregularity were associated with 24-hour hematoma expansion (P=0.021, 0.003 and 0.049, respectively) as well as increases in absolute hematoma size. Fluid levels had the highest positive predictive value (50%; 28%-71%), whereas margin irregularity had the highest negative predictive value (78%; 71%-85). Noncontrast metrics had comparable predictive values as spot sign for expansion when controlled for vitamin K, antiplatelet use, and baseline National Institutes of Health Stroke Scale, although in a combined area under the receiver-operating characteristic curve model, spot sign remained the most predictive. CONCLUSIONS: Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign.

Telemedical Brain Computed Tomography Misinterpretation by Stroke Neurologists Is Not Associated with Thrombolysis-Related Intracranial Hemorrhage.

BACKGROUND: The Stroke Eastern Saxony Network (SOS-NET) provides telecare for acute stroke patients. Stroke neurologists recommend intravenous thrombolysis based on clinical assessment and cerebral computed tomography (CT) evaluation using Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether ASPECTS misinterpretation by stroke neurologists was associated with thrombolysis-related symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively analyzed consecutive SOS-NET patients treated with thrombolytics from July 2007 to July 2012. Experienced neuroradiologists re-evaluated CT scans blinded to clinical information providing reference standard. We defined ASPECTS underestimation as ASPECTS stroke neurologist--ASPECTS neuroradiologist more than 1 point. Primary outcome was sICH by European Cooperative Acute Stroke Study II criteria. Secondary outcome was unfavorable outcome at discharge defined as modified Rankin Scale scores 3 or more. RESULTS: Of 1659 patients with acute ischemic stroke, thrombolysis was performed in 657 patients. Complete primary outcome and imaging data were available for 432 patients (median age, 75; interquartile range [IQR], 12 years; National Institutes of Health Stroke Scale score, 12 [IQR, 11]; 52.8% women). Nineteen patients (4.4%) had sICH, and 259 patients (60.0%) had an unfavorable outcome at discharge. Interobserver agreement between ASPECTS assessment was fair (κ = .51). ASPECTS underestimation was neither associated with sICH (adjusted odds ratio (OR), 1.32; 95% confidence interval (CI), .36-4.83, P = .68) nor unfavorable outcome (adjusted OR, 1.10; 95% CI, .47-2.54; P = .83). CONCLUSIONS: Despite fair interrater agreement between stroke neurologists and expert neuroradiologists, underestimation of ASPECTS by the former was not associated with thrombolysis-related sICH in our telestroke network.

Therapeutic efficacy of brain imaging in acute ischemic stroke patients.

This article reviews main pathological findings in ischemic stroke patients as imaged with CT, CTA, MRI, and MRA and discusses its clinical effectiveness on different levels: technical, diagnostic accuracy, impact on diagnosis and treatment decisions affecting patient clinical outcome. It emphasizes the importance of detecting ischemic brain tissue damage (infarction) early during a time period when reperfusion therapy may be beneficial and provides evidence that brain tissue hypoattenuation as displayed by non-enhanced CT represents net water uptake (ionic edema) that is highly accurate in defining brain tissue that will not recover with reperfusion whereas MRI is highly sensitive in detecting patterns of ischemic brain tissue even in stages that allow functional recovery.

Venous phase of computed tomography angiography increases spot sign detection, but intracerebral hemorrhage expansion is greater in spot signs detected in arterial phase.

BACKGROUND AND PURPOSE: Variability in computed tomography angiography (CTA) acquisitions may be one explanation for the modest accuracy of the spot sign for predicting intracerebral hemorrhage expansion detected in the multicenter Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study. This study aimed to determine the frequency of the spot sign in intracerebral hemorrhage and its relationship with hematoma expansion depending on the phase of image acquisition. METHODS: PREDICT study was a prospective observational cohort study of patients with intracerebral hemorrhage presenting within 6 hours from onset. A post hoc analysis of the Hounsfield units of an artery and venous structure were measured on CTA source images of the entire PREDICT cohort in a core laboratory. Each CTA study was classified into arterial or venous phase and into 1 of 5 specific image acquisition phases. Significant hematoma expansion and total hematoma enlargement were recorded at 24 hours. RESULTS: Overall (n=371), 77.9% of CTA were acquired in arterial phase. The spot sign, present in 29.9% of patients, was more frequently seen in venous phase as compared with arterial phase (39% versus 27.3%; P=0.041) and the later the phase of image acquisition (P=0.095). Significant hematoma expansion (P=0.253) and higher total hematoma enlargement (P=0.019) were observed more frequently among spot sign-positive patients with earlier phases of image acquisition. CONCLUSIONS: Later image acquisition of CTA improves the frequency of spot sign detection. However, spot signs identified in earlier phases may be associated with greater absolute enlargement. A multiphase CTA including arterial and venous acquisitions could be optimal in patients with intracerebral hemorrhage.

Spot sign number is the most important spot sign characteristic for predicting hematoma expansion using first-pass computed tomography angiography: analysis from the PREDICT study.

BACKGROUND AND PURPOSE: The spot sign score (SSS) provides risk stratification for hematoma expansion in acute intracerebral hemorrhage; however, external validation is needed. We sought to validate the SSS and assess prognostic performance of individual spot characteristics associated with hematoma expansion from a prospective multicenter intracerebral hemorrhage study. METHODS: Two hundred twenty-eight intracerebral hemorrhage patients within 6 hours after ictus were enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study, a multicenter prospective intracerebral hemorrhage cohort study. Patients were evaluated with baseline noncontrast computerized tomography, computerized tomography angiography, and 24-hour follow-up computerized tomography. Primary outcome was significant hematoma expansion (>6 mL or >33%) and secondary outcome was absolute and relative expansion. Blinded computerized tomography angiography spot sign characterization and SSS calculation were independently performed by 2 neuroradiologists and a radiology resident. Diagnostic performance of the SSS and individual spot characteristics were examined with multivariable regression, receiver operating characteristic analysis, and tests for trend. RESULTS: SSS and spot number independently predicted significant, absolute, and relative hematoma expansion (P<0.05 each) and demonstrated near perfect interobserver agreement (κ=0.82 and κ=0.85, respectively). Incremental risk of hematoma expansion among spot-positive patients was not identified for SSS (P trend=0.720) but was demonstrated for spot number (P trend=0.050). Spot number and SSS demonstrated similar area under the curve (0.69 versus 0.68; P=0.306) for hematoma expansion. CONCLUSIONS: Multicenter external validation of the SSS demonstrates that the spot number alone provides similar prediction but improved risk stratification of hematoma expansion compared with the SSS.

Tissue Window in Stroke Thrombolysis study (TWIST): a safety study.

BACKGROUND: Stroke thrombolysis is limited by the "last-seen well" principle, which defines stroke onset time. A significant minority of stroke patients (~15%) awake with their symptoms and are by definition ineligible for thrombolysis because they were "last-seen well" at the time they went to bed implying an interval that is most often greater than three hours. METHODS: A single-centre prospective, safety study was designed to thrombolyse 20 subjects with stroke-on-awakening. Patients were eligible for inclusion if they were last seen well less than 12 hours previously, specifically including those who awoke from sleep with their stroke deficits. They had a baseline computed tomogram (CT) scan with an ASPECTS score greater than 5, no evidence of well-evolved infarction and a CT angiogram / Trans-cranial Doppler ultrasound study demonstrating an intracranial arterial occlusion. Patients fulfilled all other standard criteria for stroke thrombolysis. The primary outcome was safety defined by symptomatic ICH or death. RESULTS: Among 89 screened patients, 20 were treated with thrombolysis. Two patients (10%) died due to massive carotid territory stroke and two patients (10%) died of stroke complications. Two patients (10%) showed asymptomatic intracerebral hemorrhage (ICH) (petechial hemorrhage) and none symptomatic ICH. Reasons for exclusion were: (a) ASPECTS ≤ 5 (29); (b) well-evolved infarcts on CT (19); (c) historical mRS > 2 (17); (d) no demonstrable arterial occlusion or were too mild to warrant treatment (10). CONCLUSIONS: Patients who awake with their deficits can be safely treated with thrombolysis based upon a tissue window defined by NCCT and CTA/TCD.

Does the application of X-ray contrast agents impair the clinical effect of intravenous recombinant tissue-type plasminogen activator in acute ischemic stroke patients?

BACKGROUND AND PURPOSE: Experimental data suggest a negative interaction between x-ray contrast agents and fibrinolytic efficacy of recombinant tissue-type plasminogen activator (rtPA). We hypothesized that the application of a contrast agent before intravenous thrombolysis with rtPA reduces its clinical efficacy in acute ischemic stroke. METHODS: We retrospectively studied consecutive ischemic stroke patients receiving contrast agents for computed tomography angiography before intravenous treatment with rtPA. We compared functional outcomes with an historical control group from the Canadian Alteplase for Stroke Effectiveness Study who did not receive contrast agents before thrombolysis with rtPA. Primary end point was favorable functional outcome at 90 days defined as modified Rankin Scale scores 0 to 2. We performed logistic regression analysis and a propensity score matching analysis to estimate the effect size of contrast agent use as a negative predictor of outcome. RESULTS: We identified 111 patients for the computed tomography angiography and 1119 patients for the control group. Proportions of favorable functional outcome were 47.7% (53/111 patients) for the computed tomography angiography group and 49.5% (542/1094 patients) for the control group (P=0.77). Adjusted probabilities for favorable outcome were 0.48 (95% CI, 0.37-0.58) and 0.51 (95% CI, 0.47-0.54), respectively. Contrast use was associated with reduced odds of favorable outcome (OR, 0.62(;) 95% CI, 0.38-0.99). Propensity score matching suggested a larger effect size (OR, 10.0%; 95% CI, 0.5%-19.3%). CONCLUSIONS: Our study did not show a significant negative clinical effect of x-ray contrast agents applied before intravenous thrombolysis with rtPA. However, to confirm a possible small negative interaction between contrast agents and rtPA, additional experimental and prospective clinical studies are needed.

CT angiographic source images predict outcome and final infarct volume better than noncontrast CT in proximal vascular occlusions.

BACKGROUND AND PURPOSE: Alberta Stroke Programme Early CT Score (ASPECTS) is widely used for assessment of early ischemic changes in acute stroke. We hypothesized that CT angiography source image (CTA-SI) ASPECTS correlates better with baseline National Institutes of Health Stroke Scale score, final ASPECTS and neurological outcomes when compared with noncontrast CT ASPECTS. METHODS: We studied patients presenting with acute ischemic stroke and identified proximal arterial occlusions (internal carotid artery, middle cerebral artery M1, and proximal middle cerebral artery M2) from the Calgary CT Angiography database. CT scans were independently read by 3 observers for baseline noncontrast CT ASPECTS, CT angiography source image ASPECTS, and follow-up ASPECTS. Details of demographics and risk factors were noted. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. RESULTS: We identified 261 patients with proximal occlusions for analysis. We found a better correlation between CT angiography source image ASPECTS and follow-up ASPECTS (Spearman correlation coefficient r=0.65; 95% CI, 0.58 to 0.72; P<0.001) than between noncontrast CT ASPECTS and follow-up CT ASPECTS (r=0.46; 95% CI, 0.36 to 0.55; P<0.001). CT angiography source image ASPECTS correlated better with baseline National Institutes of Health Stroke Scale and 24-hour National Institutes of Health Stroke Scale when compared with noncontrast CT ASPECTS (P<0.001). In an adjusted model including both CT angiography source image ASPECTS and noncontrast CT ASPECTS, CT angiography source image ASPECTS was associated with good outcome (OR, 2.30; 95%, CI, 1.16 to 4.53), whereas noncontrast CT ASPECTS was not (OR, 1.54; 95% CI, 0.84 to 2.82). Among imaging parameters, CT angiography source image ASPECTS was the only independent predictor of good outcome (OR, 2.29; 95% CI, 1.16 to 4.53). CONCLUSIONS: CT angiography source image ASPECTS correlates better with baseline stroke severity, is a better predictor of final infarct extension, and independently predicts neurological outcome than noncontrast CT ASPECTS.

Extent of hypoattenuation on CT angiography source images in basilar artery occlusion: prognostic value in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). METHODS: BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at ≥8 versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0-3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0-2). RESULTS: Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS≥8. Patients with a pc-ASPECTS≥8 more often had a favorable outcome than patients with a pc-ASPECTS<8 (crude RR, 1.7; 95% CI, 0.98-3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS≥8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8-2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5-0.98) and functional independence (RR, 2.0; 95% CI, 1.1-3.8). In post hoc analysis, pc-ASPECTS dichotomized at ≥6 versus <6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2-7.5). CONCLUSIONS: pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.

Malignant profile detected by CT angiographic information predicts poor prognosis despite thrombolysis within three hours from symptom onset.

OBJECTIVE: A malignant profile of early brain ischemia has been demonstrated in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) trial. Patients with a malignant profile had a low chance for an independent functional outcome despite thrombolysis within 3-6 h. We sought to determine whether CT angiography (CTA) could identify a malignant imaging profile within 3 h from symptom onset. METHODS: We studied consecutive patients (04/02-09/07) with anterior circulation stroke who received CTA before intravenous thrombolysis within 3 h. We assessed the Alberta Stroke Program Early CT Score (ASPECTS) on CTA source images (CTASI). Intracranial thrombus burden on CTA was assessed with a novel 10-point clot burden score (CBS). We analyzed percentages independent (modified Rankin Scale score < or =2) and fatal outcome at 3 months and parenchymal hematoma rates across categorized combined CTASI-ASPECTS + CBS score groups where 20 is best and 0 is worst. RESULTS: We identified 114 patients (median age 73 years [interquartile range 61-80], onset-to-tPA time 129 min [95-152]). Among 24 patients (21%) with extensive hypoattenuation on CTASI and extensive thrombus burden (combined score < or =10), only 4% (1/24) were functionally independent whereas mortality was 50% (12/24). In contrast, 57% (51/90) of patients with less affected scores (combined score 11-20) were functionally independent and mortality was 10% (9/90; p < 0.001). Parenchymal hematoma rates were 30% (7/23) vs. 8% (7/88), respectively (p = 0.008). CONCLUSION: CTA identifies a large hyperacute stroke population with high mortality and low likelihood for independent functional outcome despite early thrombolysis.