Merel J A Luitse

Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis

BACKGROUND Since the early 1980s, imaging techniques have enabled population-based studies of intracerebral haemorrhage. We aimed to assess the incidence, case fatality, and functional outcome of intracerebral haemorrhage in relation to age, sex, ethnic origin, and time period in studies published since 1980. METHODS From PubMed and Embase searches with predefined inclusion criteria, we identified population-based studies published between January, 1980, and November, 2008. We calculated incidence and case fatality. Incidences for multiple studies were pooled in a random-effects binomial meta-analysis. Time trends of case fatality were assessed with weighted linear-regression analysis. FINDINGS 36 eligible studies described 44 time periods (mid-year range 1983-2006). These studies included 8145 patients with intracerebral haemorrhage. Incidence did not decrease between 1980 and 2008. Overall incidence was 24.6 per 100 000 person-years (95% CI 19.7-30.7). Incidence was not significantly lower in women than in men (overall incidence ratio 0.85, 95% CI 0.61-1.18). Using the age group 45-54 years as reference, incidence ratios increased from 0.10 (95% CI 0.06-0.14) for people aged less than 45 years to 9.6 (6.6-13.9) for people older than 85 years. Median case fatality at 1 month was 40.4% (range 13.1-61.0) and did not decrease over time, and was lower in Japan (16.7%, 95% CI 15.0-18.5) than elsewhere (42.3%, 40.9-43.6). Six studies reported functional outcome, with independency rates of between 12% and 39%. Incidence of intracerebral haemorrhage per 100 000 person-years was 24.2 (95% CI 20.9-28.0) in white people, 22.9 (14.8-35.6) in black people, 19.6 (15.7-24.5) in Hispanic people, and 51.8 (38.8-69.3) in Asian people. INTERPRETATION Incidence of intracerebral haemorrhage increases with age and has not decreased between 1980 and 2006. Case fatality is lower in Japan than elsewhere, increases with age, and has not decreased over time. More data on functional outcome are needed. FUNDING Netherlands Heart Foundation.

Diabetes, hyperglycaemia, and acute ischaemic stroke

Diabetes and ischaemic stroke often arise together. People with diabetes have more than double the risk of ischaemic stroke after correction for other risk factors, relative to individuals without diabetes. Multifactorial treatment of risk factors for stroke-in particular, lifestyle factors, hypertension, and dyslipidaemia-will prevent a substantial number of these disabling strokes. Hyperglycaemia occurs in 30-40% of patients with acute ischaemic stroke, also in individuals without a known history of diabetes. Admission hyperglycaemia is associated with poor functional outcome, possibly through aggravation of ischaemic damage by disturbing recanalisation and increasing reperfusion injury. Uncertainty surrounds the question of whether glucose-lowering treatment for early stroke can improve clinical outcome. Achievement of normoglycaemia in the early stage of stroke can be difficult, and the possibility of hypoglycaemia remains a concern. Phase 3 studies of glucose-lowering therapy in acute ischaemic stroke are underway.

Prediction of outcome in patients with suspected acute ischaemic stroke with CT perfusion and CT angiography: the Dutch acute stroke trial (DUST) study protocol

BackgroundPrediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated.Methods/designThe DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0–2 represents good outcome, and a score of 3–6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests.DiscussionThis study will provide insight in the added prognostic value of CTP and CTA parameters in outcome prediction of acute stroke patients. The prediction models that will be developed in this study may help guide future treatment decisions in the acute stage of ischaemic stroke.

Fever After Aneurysmal Subarachnoid Hemorrhage Relation With Extent of Hydrocephalus and Amount of Extravasated Blood

Background and Purpose— Fever after aneurysmal subarachnoid hemorrhage is associated with poor outcome. Because hydrocephalus and extravasated blood may influence thermoregulation, we determined whether these factors increase the risk for fever after subarachnoid hemorrhage. Methods— Fever within 14 days (subdivided into infectious and noninfectious) was defined as a mean daily body temperature above 38.0°C for at least 2 consecutive days in a prospectively collected cohort of 194 patients with subarachnoid hemorrhage. Hazard ratios were calculated to assess the impact of hydrocephalus (bicaudate index) and cisternal and intraventricular blood (Hijdra score) on the occurrence of fever. Adjusted hazard ratios were calculated in one multivariate model, including other possible confounding factors. Results— Infectious fever occurred in 34% of patients and noninfectious fever in 9%. Adjusted hazard ratios of intraventricular blood were 2.2 (95% CI, 1.3 to 3.8) for any fever, 2.4 (95% CI, 1.3 to 4.4) for infectious fever, and 2.0 (95% CI, 0.7 to 5.9) for noninfectious fever. Adjusted hazard ratios of cisternal blood and hydrocephalus for infectious and noninfectious fever ranged from 0.6 to 1.5, all with wide CIs. Conclusion— Intraventricular blood is an independent risk factor for the development of fever. In this study, noninfectious fever was rare and not related to extravasated blood or hydrocephalus.

Symptomatic internal carotid artery occlusion: a long-term follow-up study

Background Information on outcome of patients with occlusion of the internal carotid artery (ICA) is limited by the short duration of follow-up and lack of haemodynamic studies on the brain. Methods The authors prospectively investigated 117 consecutive patients with transient or moderately disabling cerebral or retinal ischaemia associated with ICA occlusion between September 1995 and July 1998, and followed them until June 2008. The authors determined the risk of recurrent ischaemic stroke and other vascular events and prognostic factors, including collateral pathways and transcranial Doppler CO2 reactivity. Results Patients (mean age 61±9 years; 80% male) were followed for a median time of 10.2 years; 22 patients underwent endarterectomy for contralateral ICA stenosis and 16 extracranial/intracranial bypass surgery. Recurrent ischaemic stroke occurred in 23 patients, resulting in an annual rate of 2.4% (95% CI 1.5 to 3.6). Risk factors for recurrent ischaemic stroke were age (HR 1.07, 1.02 to 1.13), cerebral rather than retinal symptoms (HR 8.0, 1.1 to 60), recurrent symptoms after documented occlusion (HR 4.4, 1.6 to 12), limb-shaking transient ischaemic attacks at presentation (HR 7.5, 2.6 to 22), history of stroke (HR 2.8, 1.2 to 6.7) and leptomeningeal collaterals (HR 5.2, 1.5 to 17) but not CO2 reactivity (HR 1.01, 0.99 to 1.02). The composite event of any vascular event occurred in 57 patients, resulting in an annual rate of 6.4% (95% CI 4.9 to 8.2). Conclusion The prognosis of patients with transient ischaemic attack or minor stroke and ICA occlusion depends on age, several clinical factors and the presence of leptomeningeal collaterals. The long-term risk of recurrent ischaemic stroke is much lower than that of other vascular events.

The Prognostic Value of CT Angiography and CT Perfusion in Acute Ischemic Stroke.

Background: CT angiography (CTA) and CT perfusion (CTP) are important diagnostic tools in acute ischemic stroke. We investigated the prognostic value of CTA and CTP for clinical outcome and determined whether they have additional prognostic value over patient characteristics and non-contrast CT (NCCT). Methods: We included 1,374 patients with suspected acute ischemic stroke in the prospective multicenter Dutch acute stroke study. Sixty percent of the cohort was used for deriving the predictors and the remaining 40% for validating them. We calculated the predictive values of CTA and CTP predictors for poor clinical outcome (modified Rankin Scale score 3-6). Associations between CTA and CTP predictors and poor clinical outcome were assessed with odds ratios (OR). Multivariable logistic regression models were developed based on patient characteristics and NCCT predictors, and subsequently CTA and CTP predictors were added. The increase in area under the curve (AUC) value was determined to assess the additional prognostic value of CTA and CTP. Model validation was performed by assessing discrimination and calibration. Results: Poor outcome occurred in 501 patients (36.5%). Each of the evaluated CTA measures strongly predicted outcome in univariable analyses: the positive predictive value (PPV) was 59% for Alberta Stroke Program Early CT Score (ASPECTS) ≤7 on CTA source images (OR 3.3; 95% CI 2.3-4.8), 63% for presence of a proximal intracranial occlusion (OR 5.1; 95% CI 3.7-7.1), 66% for poor leptomeningeal collaterals (OR 4.3; 95% CI 2.8-6.6), and 58% for a >70% carotid or vertebrobasilar stenosis/occlusion (OR 3.2; 95% CI 2.2-4.6). The same applied to the CTP measures, as the PPVs were 65% for ASPECTS ≤7 on cerebral blood volume maps (OR 5.1; 95% CI 3.7-7.2) and 53% for ASPECTS ≤7 on mean transit time maps (OR 3.9; 95% CI 2.9-5.3). The prognostic model based on patient characteristics and NCCT measures was highly predictive for poor clinical outcome (AUC 0.84; 95% CI 0.81-0.86). Adding CTA and CTP predictors to this model did not improve the predictive value (AUC 0.85; 95% CI 0.83-0.88). In the validation cohort, the AUC values were 0.78 (95% CI 0.73-0.82) and 0.79 (95% CI 0.75-0.83), respectively. Calibration of the models was satisfactory. Conclusions: In patients with suspected acute ischemic stroke, admission CTA and CTP parameters are strong predictors of poor outcome and can be used to predict long-term clinical outcome. In multivariable prediction models, however, their additional prognostic value over patient characteristics and NCCT is limited in an unselected stroke population.

Hyperglycemia in aneurysmal subarachnoid hemorrhage : a potentially modifiable risk factor for poor outcome

Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) occurs frequently and is associated with delayed cerebral ischemia (DCI) and poor clinical outcome. In this review, we highlight the mechanisms that cause hyperglycemia after aSAH, and we discuss how hyperglycemia may contribute to poor clinical outcome in these patients. As hyperglycemia is potentially modifiable with intensive insulin therapy (IIT), we systematically reviewed the literature on IIT in aSAH patients. In these patients, IIT seems to be difficult to achieve in terms of lowering blood glucose levels substantially without an increased risk of (serious) hypoglycemia. Therefore, before initiating a large-scale randomized trial to investigate the clinical benefit of IIT, phase II studies, possibly with the help of cerebral blood glucose monitoring by microdialysis, will first have to improve this therapy in terms of both safety and adequacy.

Predictive Value of Thrombus Attenuation on Thin-Slice Non-Contrast CT for Persistent Occlusion after Intravenous Thrombolysis

Background: In stroke erythrocyte-rich thrombi are more sensitive to intravenous thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have higher density on non-contrast CT (NCCT). We investigated the relationship between thrombus density and recanalization and whether persistent occlusions can be predicted by Hounsfield unit (HU) measurements. Methods: In 88 IV-rtPA-treated patients with intracranial ICA or MCA occluding thrombus and follow-up imaging, thrombus and contralateral vessel attenuation measurements were performed on thin-slice NCCT. Mean absolute and relative HU were compared between patients with persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade 0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted for stroke subtype, clot burden score, occlusion site and time to thrombolysis) odds ratios for persistent occlusion were calculated. Additional prognostic value for persistent occlusion was estimated by adding HU measurements to the area under the curve (AUC) of known determinants and calculating optimal cut-off values. Results: Patients with persistent occlusion (n = 19) had significant lower mean HU (absolute 52.2 ± 9.5, relative 1.29 ± 0.20) compared to recanalization (absolute 63.1 ± 10.7, relative 1.54 ± 0.23, both p < 0.0001). Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6-6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per 0.20 relative HU decrease. Attenuation measurements significantly increased the AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative HU). Cut-off values of <56.5 absolute HU and <1.38 relative HU showed optimal predictive values for persistent occlusion. Conclusions: Thrombus density is related to recanalization rate. Lower absolute and relative HU are independently related to persistent occlusion and HU measurements significantly increase discriminative performances of known recanalization determinants.

Admission Hyperglycaemia and Cerebral Perfusion Deficits in Acute Ischaemic Stroke

Introduction: Hyperglycaemia (HG) occurs in 30-40% of the patients with acute ischaemic stroke and is associated with larger infarct size and poor functional outcome. It is unknown whether HG is also associated with larger perfusion deficits in the acute stage of ischaemic stroke. As perfusion computed tomography (CT) is a reliable technique to determine the infarct core and ischaemic penumbra, we aimed to determine if patients with acute ischaemic stroke and HG have larger perfusion deficits or infarct cores on admission perfusion CT than patients with normoglycaemia (NG). Methods: We identified 80 consecutive patients (mean age 69 ± 11 years, 58% men) with acute supratentorial non-lacunar ischaemic stroke in whom CT showed a perfusion deficit within 24 h after stroke onset. The size of the total perfusion deficit area (mean transit time of >145% compared to the contralateral hemisphere) and the infarct core area (cerebral blood volume of <2.0 ml/100 g) at the level of the basal ganglia (level 1) and at the level of the corona radiata (level 2) were compared between patients with HG (admission glucose ≥7.0 mM) and patients with NG with a MANOVA. Clinical outcome [modified Rankin Scale (mRS) score] after 6 months was correlated to glucose levels at admission. Results: Admission HG was present in 33 of the 80 patients (41%). A perfusion deficit was present in 79 (40% HG) patients at level 1 and 75 (43% HG) at level 2. The total area with a perfusion deficit (level 1 HG 22.1 ± 11.3 and NG 23.3 ± 12.3 cm2; level 2 HG 27.1 ± 12.3 and NG 25.4 ± 12.0 cm2) and the proportion of the infarct core (level 1 HG 31 ± 30% and NG 25 ± 22%; level 2 HG 33 ± 27% and NG 26 ± 23%) did not differ significantly between the groups. HG was associated with worse outcome (mRS ≥3) at 6 months (OR 2.6, 95% CI 0.72-9.1). Conclusions: As compared to patients with NG, patients with HG did not have larger perfusion deficits in the acute stage of ischaemic stroke. Nevertheless, functional outcome was worse in patients with HG, which means that poor clinical outcome in stroke patients with HG could not be explained by a larger perfusion deficit in the acute stage. Therefore, our study suggests that there might be a window of opportunity for glucose-lowering therapy in the future.

Permeable Thrombi Are Associated With Higher Intravenous Recombinant Tissue-Type Plasminogen Activator Treatment Success in Patients With Acute Ischemic Stroke

Background and Purpose— Preclinical studies showed that thrombus permeability improves recombinant tissue-type plasminogen activator (r-tPA) efficacy. We hypothesize that thrombus permeability estimated from radiological imaging is associated with improved recanalization after treatment with intravenously administered r-tPA (r-tPA) and with better functional outcome. Methods— We assessed thrombus attenuation increase (TAI) in patients from the Dutch Acute Stroke Study with an occlusion of an intracranial artery on computed tomographic angiography. Patients were included within 9 hours after the stroke onset. After dichotomization of TAI as pervious or impervious, logistic regressions analyses were performed to estimate associations of intravenous r-tPA therapy with complete recanalization and with favorable functional outcome (modified Rankin Scale score of ⩽2). Results— Three hundred eight patients matched the inclusion criteria. The median TAI was 20.1 (interquartile range, 8.5–37.8) Hounsfield unit (HU). We found a significant increase in the odds of complete recanalization with increasing TAI for patients treated with intravenous r-tPA (P=0.030). One hundred thirty-one (42%) thrombi were classified as pervious with TAI of ≥23 HU. In patients with a pervious thrombus, complete recanalization was more frequent after treatment with intravenous r-tPA than after conservative treatment (odds ratio, 6.26; 95% confidence interval, 2.4–16.8; P<0.001). In patients with an impervious thrombus, the effect of intravenous r-tPA was not significant (odds ratio, 1.4; 95% confidence interval, 0.5–4.1; P=0.47). Favorable outcome was more common in patients with a pervious thrombi than without (odds ratio, 2.1; 95% confidence interval, 1.3–3.4; P=0.001). Conclusions— Thrombus perviousness, as measured on computed tomography in the acute stage of ischemic stroke, is strongly associated with recanalization after intravenous r-tPA treatment and with favorable functional outcome.