Influence of Lipid Profiles on the Risk of Hemorrhagic Transformation after Ischemic Stroke: Systematic Review

Background: It has been suggested that low cholesterol levels might be associated with an increased risk of hemorrhagic transformation (HT) in patients with acute cerebral ischemia. We systematically reviewed the literature to determine the influence of lipid profiles on the HT risk. Methods: We searched PubMed from 1966 and EMBASE from 1980 for studies that investigated the association between lipid profiles and HT. We performed a meta-analysis (weighted mean difference method) for the comparison between presence and absence of HT (all or symptomatic) for total, low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol, and triglycerides. Results: Eight studies investigating 1,763 patients were eligible, but none was designed specifically to address this question. All studies recruited acute stroke patients selected on the presumed cause of cerebral ischemia or treatment received. The meta-analysis showed that: (i) patients with all HT had lower LDL cholesterol levels (p = 0.008) but no difference in HDL cholesterol levels (p = 0.066), total cholesterol (p = 0.129) and triglycerides (p = 0.900); (ii) patients with symptomatic HT had lower total cholesterol levels (p = 0.035) but did not differ in LDL (p = 0.056) and HDL cholesterol (p = 0.138) and triglyceride (p = 0.851) levels. Conclusion: HT is associated with baseline total and LDL cholesterol levels, but the mechanism of this association needs to be explored to identify preventive strategies

The Behavioral and Cognitive Executive Disorders of Stroke: The GREFEX Study.

BACKGROUND: Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. METHODS: 237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. RESULTS: Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. CONCLUSIONS: This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.

PURPOSE The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements

Factors Associated with Poststroke Fatigue: A Systematic Review

Background. Poststroke fatigue (PSF) is a frequent, disabling symptom that lacks a consensual definition and a standardized evaluation method. The (multiple) causes of PSF have not been formally characterized. Objective. To identify factors associated with PSF. Method. A systematic review of articles referenced in MEDLINE. Only original studies having measured PSF and potentially associated factors were included. Data was extracted from articles using predefined data fields. Results. Although PSF tends to be more frequent in female patients and older patients, sociodemographic factors do not appear to have a major impact. There are strong associations between PSF and emotional disturbances (such as depression and anxiety). PSF may also be linked to attentional disturbances (mainly slowing in processing speed). The literature data have failed to demonstrate a clear impact of the type and severity of stroke. It has been suggested that PSF results from alterations in the frontothalamostriatal system and/or inflammatory processes. Pain, sleep disorders, and prestroke fatigue also appeared to be associated with PSF. Implications. A better understanding of PSF may improve stroke patient care and facilitate the development of effective treatments

Incidence and predictors of late seizures in intracerebral hemorrhages

Background and Purpose: To identify incidence and predictors of late seizures (LS, occurring >1 week of stroke) in a cohort of patients with intracerebral hemorrhage (ICH). Methods: Prospective cohort of consecutive adults with spontaneous ICH. Incidence and predictors were identified with Cox regression. We included multivariate analyses on MRI biomarkers (global cortical atrophy, leukoaraiosis, brain microbleeds). Results: Our study population consisted of 325 patients: 54% men, median age 70 years (interquartile range, 58-79). During 778 person-years of follow-up, the incidence rate was 4 new cases/100 person-years (95% confidence interval, 3-6). The median delay between ICH and LS was 9 months (interquartile range, 3-23). The only factor independently associated with the occurrence of LS was a cortical involvement of the ICH (hazard ratio, 2.8; 95% confidence interval, 1.3-6.1). Concerning MRI biomarkers, multivariate analyses found lobar brain microbleeds to be associated with LS (hazard ratio, 2.4; 95% confidence interval, 1.1-5.4), especially if >= 3 (hazard ratio, 2.7; 95% confidence interval, 1.1-6.8). LS were associated with a worse functional outcome after 3 years of follow-up (P=0.009). Conclusions: LS frequently occur >9 months after ICH onset, imposing a long-term follow-up. The association of lobar brain microbleeds with the risk of LS might suggest a link with the underlying vasculopathy (cerebral amyloid angiopathy)

Which factors influence the resort to surrogate consent in stroke trials, and what are the patient outcomes in this context?

International audienceBACKGROUND:The provision of informed consent is a prerequisite for inclusion of a patient in a clinical research project. In some countries, the legislation on clinical research authorizes a third person to provide informed consent if the patient is unable to do so directly (i.e. surrogate consent). This is the case during acute stroke, when the symptoms may prevent the patient from providing informed consent and thus require a third party to be approached. Identification of factors associated with the medical team's decision to resort to surrogate consent may (i) help the care team during the inclusion process and (ii) enable the patient's family circle to be better informed (and thus feel less guilty) about providing surrogate consent.METHODS:Patients included in the BIOSTROKE cohort (initially dedicated to the analysis of factors influencing stroke severity) were divided into two groups: those having provided informed consent directly and those for whom a third party (such as a family member) had provided surrogate consent. We compared the groups in terms of the initial clinical characteristics (age, gender, type of stroke, severity on the National Institutes of Health Stroke Scale (NIHSS), pre-stroke cognitive status according to the Informant Questionnaire on Cognitive Decline in the Elderly, and the stroke's aetiology) and the functional and cognitive impairments (according to the NIHSS, the modified Rankin score (mRS) and the Mini Mental State Examination) on post-stroke days 8 and 90.RESULTS:Three hundred and ninety five patients were included (mean ± SD age: 67 ± 15 years; 53% males). Surrogate consent had been obtained in 228 cases, and 167 patients had provided consent themselves. The patients included with surrogate consent were likely to be older and more aphasic, with a pre-existing cognitive disorder and more severe stroke (relative to the patients having provided consent). In terms of recovery, the patients included with surrogate consent had a worse functional prognosis (day 90 mRS ≥3: 57.6%, compared with 16.8% in patients having provided consent themselves; p < 0.0001) and a worse cognitive prognosis (day 90 MMS < 24: 15.4% and 4.8%, respectively; p < 0.002). The mortality rate was significantly higher in the surrogate consent group.CONCLUSIONS:We found that in addition to age, aphasia and stroke severity, pre-stroke cognitive status is a factor that should prompt the care team to consider requesting surrogate consent for participation in a clinical study. Given that the unfavourable outcome in patients with surrogate consent is often due to their initial clinical state (rather than inclusion in a trial per se), the issue of the family's feelings of guilt (and how to avoid these feelings) should be further addressed

Early-onset delirium after spontaneous intracerebral hemorrhage

Objective This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage. Methods We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia. Results The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3-35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32-3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13-2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01-2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00-2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60-2.87). Conclusion Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up

External validation of the MRI-DRAGON score: early prediction of stroke outcome after intravenous thrombolysis.

The aim of our study was to validate in an independent cohort the MRI-DRAGON score, an adaptation of the (CT-) DRAGON score to predict 3-month outcome in acute ischemic stroke patients undergoing MRI before intravenous thrombolysis (IV-tPA).We reviewed consecutive (2009-2013) anterior circulation stroke patients treated within 4.5 hours by IV-tPA in the Lille stroke unit (France), where MRI is the first-line pretherapeutic work-up. We assessed the discrimination and calibration of the MRI-DRAGON score to predict poor 3-month outcome, defined as modified Rankin Score >2, using c-statistic and the Hosmer-Lemeshow test, respectively.We included 230 patients (mean ±SD age 70.4±16.0 years, median [IQR] baseline NIHSS 8 [5]-[14]; poor outcome in 78(34%) patients). The c-statistic was 0.81 (95%CI 0.75-0.87), and the Hosmer-Lemeshow test was not significant (p = 0.54).The MRI-DRAGON score showed good prognostic performance in the external validation cohort. It could therefore be used to inform the patient's relatives about long-term prognosis and help to identify poor responders to IV-tPA alone, who may be candidates for additional therapeutic strategies, if they are otherwise eligible for such procedures based on the institutional criteria