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.

New and expanding ventricular hemorrhage predicts poor outcome in acute intracerebral hemorrhage.

OBJECTIVE: To describe the relationship between intraventricular hemorrhage (IVH) expansion and long-term outcome and to use this relationship to select and validate clinically relevant thresholds of IVH expansion in 2 separate intracerebral hemorrhage (ICH) populations. METHODS: We used fractional polynomial analysis to test linear and nonlinear models of 24-hour IVH volume change and clinical outcome with data from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT)-ICH study. The primary outcome was poor clinical outcome (modified Rankin Scale [mRS] score 4-6) at 90 days. We derived dichotomous thresholds from the selected model and calculated diagnostic accuracy measures. We validated all thresholds in an independent single-center ICH cohort (Massachusetts General Hospital). RESULTS: Of the 256 patients from PREDICT, 127 (49.6%) had an mRS score of 4 to 6. Twenty-four-hour IVH volume change and poor outcome fit a nonlinear relationship, in which minimal increases in IVH were associated with a high probability of an mRS score of 4 to 6. IVH expansion ≥1 mL (n = 53, sensitivity 33%, specificity 92%, adjusted odds ratio [aOR] 2.68, 95% confidence interval [CI] 1.11-6.46) and development of any new IVH (n = 74, sensitivity 43%, specificity 85%, aOR 2.53, 95% CI 1.22-5.26) strongly predicted poor outcome at 90 days. The dichotomous thresholds reproduced well in a validation cohort of 169 patients. CONCLUSION: IVH expansion as small as 1 mL or any new IVH is strongly predictive of poor outcome. These findings may assist clinicians with bedside prognostication and could be incorporated into definitions of hematoma expansion to inform future ICH treatment trials.

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.

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.

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.

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.

Location of intracerebral haemorrhage predicts haematoma expansion.

INTRODUCTION: The role of intracerebral haemorrhage location in haematoma expansion remains unclear. Our objective was to assess the effect of lobar versus non-lobar haemorrhage on haematoma expansion and clinical outcome. PATIENTS AND METHODS: We analysed data from the prospective PREDICT study where patients with intracerebral haemorrhage presenting to hospital under 6 h of symptom onset received baseline computed tomography (CT), CT angiogram, 24 h follow-up CT, and 90-day mRS. Intracerebral haemorrhage location was categorised as lobar versus non-lobar, and primary outcomes were significant haematoma expansion (>6 ml) and poor clinical outcome (mRS > 3). Multivariable regression was used to adjust for relevant covariates. The primary analysis population was divided by spot sign status and the effect of haemorrhage location was compared to haematoma expansion in exploratory post hoc analysis. RESULTS: Among 302 patients meeting the inclusion criteria, lobar haemorrhage was associated with increased haematoma expansion >6 ml (p = 0.003), poor clinical outcome (p = 0.011) and mortality (p = 0.017). When adjusted for covariates, lobar haemorrhage independently predicted significant haematoma expansion (aOR 2.2 (95% CI: 1.1-4.3), p = 0.021) and poor clinical outcome (aOR 2.6 (95% CI: 1.2-5.6), p = 0.019). Post hoc analysis showed that patients who were spot sign negative had a higher degree of haematoma expansion with baseline lobar haemorrhage (lobar 26% versus deep 11%; p = 0.01). No significant associations were observed in spot-positive patients (lobar 52% versus deep 47%; p = 0.69). DISCUSSION AND CONCLUSION: Haematoma expansion is more likely to occur with lobar intracerebral haemorrhage and haemorrhage location is associated with poor clinical outcome. As expansion is a promising therapeutic target, hemorrhage location may be helpful for prognostication and as a selection tool in future ICH clinical trials.

CT-angiography source images indicate less fatal outcome despite coma of patients in the Basilar Artery International Cooperation Study.

Background Coma is associated with poor outcome in patients with basilar artery occlusion. Aims We sought to assess whether the posterior circulation Acute Stroke Prognosis Early CT Score and the Pons-Midbrain Index applied to CT angiography source images predict the outcome of comatose patients in the Basilar Artery International Cooperation Study. Methods Basilar Artery International Cooperation Study was a prospective, observational registry of patients with acute basilar artery occlusion with 48 recruiting centers worldwide. We applied posterior circulation Acute Stroke Prognosis Early CT Score and Pons-Midbrain Index to CT angiography source images of Basilar Artery International Cooperation Study patients who presented with coma. We calculated adjusted risk ratios to assess the association of dichotomized posterior circulation Acute Stroke Prognosis Early CT Score (≥8 vs. <8) and Pons-Midbrain Index (<3 vs. ≥3) with mortality and favourable outcome (modified Rankin Scale score 0-3) at one month. Results Of 619 patients in the Basilar Artery International Cooperation Study registry, CT angiography source images were available for review in 158 patients. Among these, 78 patients (49%) presented with coma. Compared to non-comatose patients, comatose patients were more likely to die (risk ratios 2.34; CI 95% 1.56-3.52) and less likely to have a favourable outcome (risk ratios 0.44; CI 95% 0.24-0.80). Among comatose patients, a Pons-Midbrain Index < 3 was related to reduced mortality (adjusted RR 0.66; 95% CI 0.46-0.96), but not to favourable outcome (adjusted RR 1.19; 95% CI 0.39-3.62). Posterior circulation Acute Stroke Prognosis Early CT Score dichotomized at ≥ 8 vs. <8 was not significantly associated with death (adjusted RR 0.70; 95% CI 0.46-1.05). Conclusion In comatose patients with basilar artery occlusion, the extent of brainstem ischemia appears to be related to mortality but not to favourable outcome.

Collateral state and the effect of endovascular reperfusion therapy on clinical outcome in ischemic stroke patients.

PURPOSE: Clinically successful endovascular therapy (EVT) in ischemic stroke requires reliable noninvasive pretherapeutic selection criteria. We investigated the association of imaging parameters including CT angiographic collaterals and degree of reperfusion with clinical outcome after EVT. METHODS: In our database, we identified 93 patients with large vessel occlusion in the anterior circulation treated with EVT. Besides clinical data, we assessed the baseline Alberta Stroke Program Early CT score (ASPECTS) on noncontrast CT (NCCT) and CT angiography (CTA) source images, collaterals (CT-CS) and clot burden score (CBS) on CTA and the degree of reperfusion after EVT on angiography. Three readers, blinded to clinical information, evaluated the images in consensus. Data-driven multivariable ordinal regression analysis identified predictors of good outcome after 90 days as measured with the modified Rankin Scale. RESULTS: Successful angiographic reperfusion (OR 26.50; 95%-CI 9.33-83.61) and good collaterals (OR 9.69; 95%-CI 2.28-59.27) were independent predictors of favorable outcome along with female sex (OR 0.35; 95%-CI 0.14-0.85), younger age (OR 0.88; 95%-CI 0.83-0.92) and higher NCCT ASPECTS (OR 2.54; 95%-CI 1.01-6.63). Outcome was best in patients with good collaterals and successful reperfusion, but there was no statistical interaction between collaterals and reperfusion. CONCLUSIONS: CTA-collateral status was the strongest pretherapeutic predictor of favorable outcome in ischemic stroke patients treated with EVT. CTA-collaterals are thus well suited for patient selection in EVT. However, the independent effect of reperfusion on outcome tended to be stronger than that of CTA-collaterals.

Ultraearly hematoma growth in active intracerebral hemorrhage.

OBJECTIVE: To determine the association of ultraearly hematoma growth (uHG) with the CT angiography (CTA) spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH). METHODS: We analyzed data from 231 patients enrolled in the multicenter Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT study. uHG was defined as baseline ICH volume/onset-to-CT time (mL/h). The spot sign was used as marker of active hemorrhage. Outcome parameters included significant hematoma expansion (>33% or >6 mL, primary outcome), rate of hematoma expansion, early neurologic deterioration, 90-day mortality, and poor outcome. RESULTS: uHG was higher in spot sign patients (p < 0.001) and in patients scanned earlier (p < 0.001). Both uHG >4.7 mL/h (p = 0.002) and the CTA spot sign (p = 0.030) showed effects on rate of hematoma expansion but not its interaction (2-way analysis of variance, p = 0.477). uHG >4.7 mL/h improved the sensitivity of the spot sign in the prediction of significant hematoma expansion (73.9% vs 46.4%), early neurologic deterioration (67.6% vs 35.3%), 90-day mortality (81.6% vs 44.9%), and poor outcome (72.8% vs 29.8%), respectively. uHG was independently related to significant hematoma expansion (odds ratio 1.06, 95% confidence interval 1.03-1.10) and clinical outcomes. CONCLUSIONS: uHG is a useful predictor of hematoma expansion and poor clinical outcomes in patients with acute ICH. The combination of high uHG and the spot sign is associated with a higher rate of hematoma expansion, highlighting the need for very fast treatment in ICH patients.

Small intracerebral hemorrhages have a low spot sign prevalence and are less likely to expand.

BACKGROUND: Hematoma expansion is a major predictor of morbidity and mortality after intracerebral hemorrhage (ICH). Both baseline hematoma volume and the CT-angiogram (CTA) spot sign predict hematoma expansion. Because the CTA spot sign may represent foci of active hemorrhage, we hypothesized that patients with smaller baseline hematoma volumes are less likely to be spot sign positive, and therefore less likely to expand. AIM: We sought to validate our prior finding that small hematomas are unlikely to expand, and to determine the relationship between baseline hematoma volume, spot sign status, and risk of hematoma expansion. METHODS: Data were from the prospective PREDICT ICH study. Patients presenting within 6 h of symptom onset with completed baseline CT, CTA, and follow-up CT were included. Baseline hematoma volume was categorized a priori (<3 mL, 3-10 mL, 10-20 mL, >20 mL). The primary outcome was significant hematoma expansion (≥6 mL, ≥12.5 mL or ≥33%) and secondary outcomes were early neurological worsening, good clinical outcome (modified Rankin Scale 0-3), and mortality at 90 days. RESULTS: Among 315 patients meeting the inclusion criteria, baseline hematoma volume category predicted absolute hematoma expansion (p < 0.001), spot sign prevalence (p < 0.001), early neurologic worsening (p = 0.002), clinical outcome (p < 0.001), and mortality (p < 0.001). Very small hematomas (<3 mL) were unlikely to be spot positive (7.7%), unlikely to expand (2.6%), and were associated with a 73% chance of good clinical outcome. Spot sign appeared to be most predictive of expansion in the 3-10 mL baseline hematoma volume category. CONCLUSION: Very small hematomas are unlikely to expand and have a low spot sign prevalence. Hemostatic therapy trials may be best targeted at hemorrhages >3 mL in volume.

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.

Time dependence of reliability of noncontrast computed tomography in comparison to computed tomography angiography source image in acute ischemic stroke.

There is no consensus on how the reliability and predictive ability of noncontrast computed tomography (NCCT) and computed tomography angiography source image (CTASI) change over time from acute ischemic stroke onset. We hypothesized that the reliability for detecting early ischemic changes (EIC) would be lower in early time periods and that changes identified on CTASI would be more reliable across examiners than changes identified on NCCT. To address this, we compared the relationships between CTASI, NCCT, and final infarct in patients with initial computed tomography (CT) imaging at different time points after stroke onset. Patients with acute ischemic stroke with proximal anterior circulation occlusions (internal carotid artery, middle carotid artery M1, proximal M2) from Calgary CT Angiography (CTA) database were studied. The cohort was categorized in four groups based on time from stroke onset to baseline NCCT/CTA: 0-90 mins (n = 69), 91-180 mins (n = 88), 181-360 mins (n = 46), and >360 mins (n = 58). Median scores of NCCT-Alberta Stroke Program Early CT Score (ASPECTS), CTASI ASPECTS, and follow-up ASPECTS among different time categories were compared. To determine reliability, a subsample of NCCT brain and CTASI were interpreted at separate sessions weeks apart by two neuroradiologists and two stroke neurologists in random order. Median and mean ASPECTS ratings on NCCT and CTASI were higher than final ASPECTS in each time category (P < 0·001 for all comparisons). CTASI ASPECTS was lower than NCCT ASPECTS in each time category, and differences were significant at 0-90 mins and 91-180 mins (P < 0·001). The least agreement among readers was in detection of EIC on NCCT brain in the ultra-early phase (<90 mins) [intraclass correlation coefficient (ICC) = 0·48. By contrast, there was excellent agreement on EIC on CTASI regardless of time period (ICC = 0·87-0·96). Using ASPECTS methodology, CTASI is more reliable than NCCT at predicting final infarct extent particularly in the early time windows.