Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. METHODS: In a systematic review of OVID MEDLINE-with additional hand-searching of relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5-24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. FINDINGS: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36-0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46-11·60; p<0·0001), antiplatelet use (1·68, 1·06-2·66; p=0·026), and anticoagulant use (3·48, 1·96-6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75-0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95-6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03-0·07). INTERPRETATION: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials. FUNDING: UK Medical Research Council and British Heart Foundation.

Prognosis of post-stroke status epilepticus: Effects of time difference between the two events.

PURPOSE: This study aimed to investigate the prognosis of patients with status epilepticus (SE) following stroke, focusing on the timing of SE after the event and other unexplored variables. METHODS: All consecutive patients experiencing post-stroke SE (PSSE) in our center were included (2011-2016). We analyzed SE- and stroke-related factors in relation to the patients' outcome. RESULTS: 95 patients with PSSE (54 ischemic and 41 hemorrhagic stroke) were analyzed; 40 were women (42.1%) and mean age was 72.7 ±â€¯13.56 years. 51(53.7%) showed prominent motor symptoms, 49(51.6%) needed >2 antiepileptic drugs, and 27(28.4%) required anesthetics. Median duration of SE was 12 h (1-240). Median time from stroke to SE was 15 days (0-532). At discharge, logistic regression identified SE within 72 h after stroke (p = 0.004), baseline mSTESS (p = 0.009), and lesion volume (p = 0.001) as independent factors predicting mortality. Female sex (p = 0.019), SE duration >12 h (p = 0.005), temporal lobe involvement (p = 0.029), and stroke-to-SE time <90 days (p < 0.0001) were independent predictors of functional decline. At long-term follow-up, SE occurring within 72 h after stroke (p = 0.0001), SE duration (p = 0.004), and baseline mSTESS score (p = 0.012) remained as predictive of mortality. CONCLUSIONS: The timing of SE after stroke is associated with different consequences: mortality was higher when SE occurred within the first 72 h after stroke and this risk persisted at follow-up, whereas risk of functional decline was higher when SE occurred during the first 3 months. Other factors such as the mSTESS score and SE duration were associated with outcome at both discharge and long-term follow-up.

High-sensitivity C-reactive protein in high-grade carotid stenosis: risk marker for unstable carotid plaque.

OBJECTIVES: Increasing evidence points to the inflammatory character of atherosclerosis, and several parameters of inflammation have been proposed as cardiovascular risk markers. We analyzed associations among serum high-sensitivity C-reactive protein (hs-CRP) concentrations, carotid plaque structure, and immunocytology, and neurologic symptoms in patients with high-grade carotid stenosis. METHODS: This was a cross-sectional study in a referral center and institutional practice in hospitalized patients. The study included 62 patients with greater than 70% carotid stenosis treated surgically; 58% of patients had symptoms, and 42% did not. Serum hs-CRP concentrations were determined 48 hours before surgery; levels greater than 10 mg/L were considered pathologic. Histopathologic analysis (stable or unstable) and immunohistochemistry (macrophage count, T lymphocytes, activated T lymphocytes) were carried out on the atherosclerotic plaques. RESULTS: Median hs-CRP values were 7.6 mg/L (range, 0-165 mg/L). Median hs-CRP concentrations were higher in patients with unstable plaque (53.2%) than in patients with stable plaque (46.7%): 27.1 mg/L (range, 1.8-165 mg/L) versus 4.1 mg/L (range, 0.3-56 mg/L) (P <.001). Among patients with symptomatic disease, 81% had CRP concentrations significantly higher than CRP concentrations in patients with asymptomatic disease (P <.001). A statistically significant association was found between hs-CRP levels and the presence of macrophages (Spearman rank correlation [rho], 0.61, P <.001) and T lymphocytes in the plaque (Spearman rank correlation [rho], 0.52, P <.001). At logistic regression analysis, neurologic event and macrophages in the plaque were independently associated with unstable plaque. CONCLUSIONS: Increased hs-CRP levels may be related to the presence of macrophages and T lymphocytes in plaque, which is associated with the phenomena of instability that can lead to development of an ischemic event. Thus determination of circulating hs-CRP levels may be a useful additional marker of risk in patients with high-grade carotid stenosis.