The initial acute phase response predicts long-term stroke recovery.

Indicators of an acute phase response (APR) in acute ischemic stroke have been shown to correlate with infarct size and predict stroke recurrence. In this study, we examined how well the APR indicators predicted long-term stroke recovery compared with standard clinical predictors of recovery. Plasma levels of interleukin-6 (IL-6), fibrinogen, white blood cells (WBCs), and serum albumin were measured within 4+/-2 days of onset in 131 stroke patients who were free of apparent infections. Standard clinical predictors included initial National Institutes of Health Stroke Scale (NIHSS), infarct size on computed tomography (CT), and Glasgow scale. The individual correlations with 6-month Glasgow outcome were IL-6, 0.42; fibrinogen, 0.24; WBC, 0.35; albumin, 0.47; NIHSS, 0.53; infarct size, 0.19; and initial Glasgow, 0.57. (all P<.005). Multiple regression analysis yielded an adjusted R(2) of .31 for the APR indicators, compared with .38 for the clinical variables. These results indicate that the initial APR is highly correlated with 6-month stroke recovery and that this correlation approaches that observed with standard clinical predictors.     

Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth.

BACKGROUND AND PURPOSE: More effective imaging methods are needed to overcome the limitations of CT in the investigation of treatments for acute ischemic stroke. Diffusion-weighted MRI (DWI) is sensitive in detecting infarcted brain tissue, whereas perfusion-weighted MRI (PWI) can detect brain perfusion in the same imaging session. Combining these methods may help in identifying the ischemic penumbra, which is an important concept in the hemodynamics of acute stroke. The purpose of this study was to determine whether combined DWI and PWI in acute (<24 hours) ischemic stroke can predict infarct growth and final size. METHODS: Forty-six patients with acute ischemic stroke underwent DWI and PWI on days 1, 2, and 8. No patient received thrombolysis. Twenty-three patients underwent single-photon emission CT in the acute phase. Lesion volumes were measured from DWI, SPECT, and maps of relative cerebral blood flow calculated from PWI. RESULTS: The mean volume of infarcted tissue detected by DWI increased from 46.1 to 75.6 cm(3) between days 1 and 2 (P<0.001; n=46) and to 78.5 cm(3) after 1 week (P<0.001; n=42). The perfusion-diffusion mismatch correlated with infarct growth (r=0. 699, P<0.001). The volume of hypoperfusion on the initial PWI correlated with final infarct size (r=0.827, P<0.001). The hypoperfusion volumes detected by PWI and SPECT correlated significantly (r=0.824, P<0.001). CONCLUSIONS: Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.     

Interleukin-12 in acute ischemic stroke patients

Cytokines are important mediators of stroke-induced immunological/inflammatory reaction which contributes to brain infarct progression as well as to the disease severity and outcome. The aim of the study was to evaluate the levels of the proinflammatory and immunomodulatory cytokine interleukin-12 (IL-12) in serum of acute ischemic stroke patients, and to investigate the relation between these levels and demographic, laboratory, neuroimaging, and clinical data. The study comprised 23 first-ever ischemic stroke patients and 15 age- and sex-matched controls. Blood sampling for the determination of IL-12 and such peripheral markers of inflammation as erythrocyte sedimentation rate (ESR) and leukocyte count, together with cranial CT were performed within 24 h of stroke, while neurological and functional deficits were estimated, respectively, with the Scandinavian Stroke Scale (SSS) and Barthel Index (BI) within the same period and two weeks later. Stroke patients displayed significantly higher serum IL-12 levels in comparison with controls. The serum IL-12 levels in stroke patients correlated significantly with the ESR values, the volume of early brain CT hypodense areas, and with the SSS and BI scores calculated within both studied times. The results indirectly suggest that IL-12 may play a role in the pathophysiology of ischemic stroke.     

A predictive risk model for outcomes of ischemic stroke

BACKGROUND AND PURPOSE: The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome. The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone. The purpose of this study was to determine the multivariable relationship between infarct volume, 6 clinical variables, and 3-month outcomes in ischemic stroke patients. METHODS: Included in the study were 256 eligible patients from the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS). Six clinical variables and 1-week infarct volume were the prespecified predictor variables. The National Institutes of Health Stroke Scale, Barthel Index, and Glasgow Outcome Scale were the outcomes. Multivariable logistic regression techniques were used to develop the model equations, and bootstrap techniques were used for internal validation. Predictive performance of the models was assessed for discrimination with receiver operator characteristic (ROC) curves and for calibration with calibration curves. RESULTS: The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves. The areas under the ROC curves were statistically greater (P<0.001) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability. CONCLUSIONS: Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients. Demonstration of this relationship with acute clinical variables and 1-week infarct information supports future attempts to predict 3-month outcome with all acute variables.     

Reduced severity of strokes in patients with silent brain infarctions

Background: Silent brain infarctions (SBIs), leukoaraiosis (LA), and microbleeds (MBs) are ischaemic silent radiologic abnormalities that act as predictors of subsequent strokes. This study investigated the independent effect of silent radiologic abnormalities on initial stroke severity and short‐term outcome. Methods: A consecutive series of patients who had their first ischaemic stroke within 72 h of symptom onset were included. Demographic and clinical characteristics were collected on admission, and magnetic resonance imaging was performed to evaluate the ischaemic lesion, SBI, LA, and MB. Factors potentially associated with lower initial stroke severity (admission NIH Stroke Scale 0–5) and good short‐term outcome (discharge NIH Stroke Scale 0–5, modified Rankin Scale 0–1) were validated by multivariate analysis. Results: Silent brain infarctions were noted in 82 (45%) of the 182 patients. Although there were no statistically significant differences in stroke subtypes and lesion location, univariate analysis revealed that patients with SBI had reduced stroke severity (P = 0.005) and infarction volume (P = 0.001). After adjusting for covariates, the presence of SBI was independently associated with lower stroke severity and good short‐term outcome when the NIH Stroke Scale was used as dependent variable (OR 3.368, 95% CI 1.361–8.332, P = 0.009; OR 3.459, 95% CI 1.227–9.755, P = 0.019, respectively). However, the presence of SBI lost significance when the discharge‐modified Rankin Scale was used as dependent variable (P = 0.058). Conclusion: Amongst silent radiologic abnormalities, SBI was the only predictor of reduced stroke severity and infarct volume. Silent brain infarction deserves more attention in evaluating stroke severity.     

Infarct volume on apparent diffusion coefficient maps correlates with length of stay and outcome after middle cerebral artery stroke

BACKGROUND: Diffusion-weighted MRI (DWI) can depict acute ischemia based on decreased apparent diffusion coefficient (ADC) values. ADC maps, unlike DWI (which have contributions from T2 properties), solely reflect diffusion properties. Recent studies indicate that severity of neurological deficit corresponds with degree of ADC alteration. PURPOSE: To determine whether infarct volume on ADC maps correlates with length of hospitalization and clinical outcome in patients with acute ischemic middle cerebral artery (MCA) stroke. STUDY POPULATION: Forty-five consecutive patients with acute (3 SDs below the average ADC value of a contralateral control region. Infarct volume was correlated with length of hospitalization and 6-month outcome assessed with Glasgow Outcome Scale (GOS), Modified Rankin Score (mRS), Barthel Index (BI) and a dichotomized outcome status with favorable outcome defined as GOS 1, mRS or=95. RESULTS: Infarct volume on ADC maps ranged from 0.2 to 187 cm(3) and was significantly correlated with length of hospitalization (p < 0.001, r = 0.67). Furthermore, ADC infarct volume was significantly correlated with GOS (r = 0.73), mRS (r = 0.68), BI (r = 0.67) and outcome status (r = 0.65) (each p < 0.001). Multiple logistic regression revealed a statistically significant correlation between ADC infarct volume and outcome status (p < 0.05), but none for Canadian Neurological Scale score, age and gender (p >0.05 each). CONCLUSION: Infarct volume measured by using a quantitative definition for infarcted tissue on ADC maps correlated significantly with length of hospitalization (as a possible surrogate marker for short-term outcome) and functional outcome after 6 months. ADC infarct volume may provide prognostic information for patients with acute ischemic MCA stroke.     

Correlation between serum neuron specific enolase and functional neurological outcome in patients of acute ischemic stroke

Context:

The use of biomarkers to predict stroke prognosis is gaining particular attention nowadays. Neuron specific enolase (NSE), which is a dimeric isoenzyme of the glycolytic enzyme enolase and is found mainly in the neurons is one such biomarker.

Aims:

This study was carried out on patients of acute ischemic stroke with the aims to determine the correlation between NSE levels on the day of admission with infarct volume, stroke severity, and functional neurological outcome on day 30.

Materials and Methods:

Seventy five patients of acute ischemic stroke admitted in the Department of Medicine were included in the study. Levels of NSE were determined on day 1 using the human NSE ELISA kit (Alpha Diagnostic International Texas 78244, USA). Volume of infarct was measured by computed tomography (CT) scan using the preinstalled software Syngo (version A40A) of Siemen''s medical solutions (Forchheim, Germany). Stroke severity at admission was assessed using Glasgow coma scale (GCS) and functional neurological outcome was assessed using modified Rankin scale (mRS) on day 30.

Statistical Analysis Used:

Statistical analysis was performed using the SPSS software for windows version 15.0 (SPSS).

Results:

A positive correlation was found between concentration of NSE on day 1 and infarct volume determined by CT scan (r = 0.955, P < 0.001). A strong negative correlation was found between GCS at presentation and concentration of NSE on day 1 (r = −0.806, P < 0.001). There was a positive correlation between NSE levels at day 1 and functional neurological outcome assessed by mRS at day 30 (r = 0.744, P < 0.001).

Conclusions:

Serum levels of NSE in first few days of ischemic stroke can serve as a useful marker to predict stroke severity and early functional outcome. However, larger studies with serial estimation of NSE are needed to establish these observations more firmly.Key Words: Glasgow coma scale, infarct volume, ischemic stroke, modified Rankin scale, neuron specific enolase     

Prognostic value of plasma HMGB1 in ischemic stroke patients with cerebral ischemia-reperfusion injury after intravenous thrombolysis

BackgroundTo investigate the value of plasma high mobility group box protein 1 (HMGB1) in evaluating the prognosis of cerebral ischemia-reperfusion injury (CIRI) in ischemic stroke patients.Methods132 ischemic stroke patients were recruited. Before and after thrombolytic therapy at 2 h, 6 h, 12 h, 24 h, and 36 h, the Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) were recorded. The Modified Rankin scale (mRS) was used to assess the prognosis at 3 months.ResultsThe NIHSS score, GCS score and plasma HMGB1 level peaked at 6 h after thrombolytic therapy, and plasma HMGB1 level was positively correlated with infarct volume and NIHSS score, and negatively correlated with GCS score. Plasma HMGB1 level at 6 h had the highest value in identifying patients with poor unfavorable functional outcome after 3 months, with a sensitivity of 86.8% and a specificity of 74.0%. Logistic regression results showed that plasma HMGB1 had a strong association with unfavorable functional outcome [odds ratio (OR) =1.621, P<0.001]. After adjusting for infarct volume and NIHSS score did not attenuate the association (OR=1.381, P=0.005). Finally, we found that plasma HMGB1 at 6 h had the highest value in identifying patients with non-survival after 3 months (χ²=28.655, P<0.001). Logistic regression results showed that plasma HMGB1 had a strong association with non-survival (OR=2.315, P<0.001). After adjusting for infarct volume and NIHSS score did not attenuate the association (OR=2.013, P<0.001).ConclusionPlasma HMGB1 exerts a good predictive value for CIRI in ischemic stroke patients, and its increased expression is correlated with worse prognosis.     

Susceptibility-weighted imaging predicts infarct size and early-stage clinical prognosis in acute ischemic stroke

Susceptibility-weighted imaging (SWI) is a non-invasive technique that can reveal venous structures and iron in the brain. This retrospective study evaluated SWI, relative to other imaging techniques, for determining cerebral infarct size and early-stage clinical prognosis in patients with acute ischemic stroke. Within 3 days after onset, 22 patients with acute ischemic stroke underwent SWI, diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), fluid-attenuated inversion recovery (FLAIR), and magnetic resonance angiography (MRA). At least 7 days after onset, the patients also underwent cranial FLAIR or computed tomography (CT). The severity of neurological damage was adjudged with NIHSS (National Institutes of Health Stroke Scale) scores. The imaged cranial lesions were evaluated according to ASPECTS (Alberta Stroke Program Early CT Score). The SWI-ASPECTS significantly correlated with mean transit time (MTT)-ASPECTS (Spearman’s test, r?=?0.662, P?=?0.001) in evaluating ischemic penumbra and significantly correlated with the FLAIR and CT-ASPECTS (Spearman’s test, r?=?0.765, P?<?0.001) in predicting infarct size. SWI is feasible for the early evaluation of cerebral infarct size and clinical prognosis of patients with acute cerebral infarction. SWI is a useful predictor of early infarct growth and early-stage outcome.     

Influence of pretreatment MRI parameters on clinical outcome, recanalization and infarct size in 49 stroke patients treated by intravenous tissue plasminogen activator

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome (p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion (p=0.009), and in patients with larger pretreatment PWI (p=0.001) and DWI (p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion (p=0.02) and a delayed time to peak (TTP) on pretreatment PWI (p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume (p=0.025). Recanalization was associated with a lower final infarct size (p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.