Boundary and vulnerability estimation of the internal borderzone using ischemic stroke lesion mapping.

Distinction between deep and superficial middle cerebral artery (MCA) territories and their junctional vascular area (the internal borderzone or IBZ) constitutes a predictor of stroke patient outcome. However, the IBZ boundaries are not well-defined because of substantial anatomical variance. Here, we built a statistical estimate of the IBZ and tested its vulnerability to ischemia using an independent sample. First, we used delineated lesions of 122 patients suffering of chronic ischemic stroke grouped in deep, superficial and territorial topographies and statistical comparisons to generate a probabilistic estimate of the IBZ. The IBZ extended from the insular cortex to the internal capsule and the anterior part of the caudate nucleus head. The IBZ showed the highest lesion frequencies (~30% on average across IBZ voxels) in our chronic stroke patients but also in an independent sample of 87 acute patients. Additionally, the most important apparent diffusion coefficient reductions (-6%), which reflect stroke severity, were situated within our IBZ estimate. The IBZ was most severely injured in case of a territorial infarction. Then, our results are in favour of an increased IBZ vulnerability to ischemia. Moreover, our probabilistic estimates of deep, superficial and IBZ regions can help the everyday spatial classification of lesions.

Monitoring of biological response to clopidogrel after treatment for non-cardioembolic ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Biological response to clopidogrel prescribed after a non-cardioembolic ischemic stroke or transient ischemic attack (TIA) has been little studied. The aim of our study (AAPIX) was to assess this response and investigate the agreement between different biological assays in revealing poor responders. METHODS: Patients hospitalized following a non-cardioembolic ischemic stroke or transient ischemic attack (TIA) and prescribed clopidogrel were consecutively included from September 2013 to November 2015 in the Stroke Center of Saint-Etienne Hospital. Blood was drawn after 5 to 8 days of standard-dose clopidogrel. Light transmission aggregometry (LTA) and flow cytometric assays, using vasodilator-stimulated phosphoprotein [VASP] and CD62P, were accomplished for all patients. Transmission electron microscopy (TEM) was performed for a poor clopidogrel-responder and for a patient with discordant platelet assay results (platelet reactivity index (PRI) >50% and maximum platelet aggregation <70%), after activation with adenosine diphosphate (ADP) 10 µM. RESULTS: 72 patients were included. According to LTA, VASP assay and CD62P test results, 65%, 71% and 0% of patients, respectively, had a low response to clopidogrel, indicating poor agreement between these assays. Images of ADP-activated platelet samples from a patient manifesting a low response to clopidogrel and from a patient with discordant platelet assay results showed an ultrastructural pattern typical of activation and a state of slight activation, respectively. CONCLUSIONS: Platelet function results obtained using different assays for patients having experienced a non-cardioembolic ischemic stroke or TIA were discordant. Transmission electron microscopy could be useful in certain clinical contexts when platelet function assay results disagree.

Who should undergo a comprehensive cognitive assessment after a stroke? A cognitive risk score.

OBJECTIVE: To validate the ability of a specifically developed cognitive risk score to identify patients at risk of poststroke neurocognitive disorders (NCDs) who are eligible for a comprehensive cognitive assessment. METHODS: After assessing 404 patients (infarct 91.3%) in the Groupe de Réflexion pour l'Evaluation Cognitive VASCulaire (GRECogVASC) cross-sectional study with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network battery 6 months after stroke, we used multivariable logistic regression and bootstrap analyses to determine factors associated with NCDs. Independent, internally validated factors were included in a cognitive risk score. RESULTS: Cognitive impairment was present in 170 of the 320 patients with a Rankin Scale score ≥1. The backward logistic regression selected 4 factors (≥73% of the permutations): NIH Stroke Scale score on admission ≥7 (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.29-4.3, p = 0.005), multiple strokes (OR 3.78, 95% CI 1.6-8, p = 0.002), adjusted Mini-Mental State Examination (MMSEadj) score ≤27 (OR 6.69, 95% CI 3.9-11.6, p = 0.0001), and Fazekas score ≥2 (OR 2.34, 95% CI 1.3-4.2, p = 0.004). The cognitive risk score computed with these 4 factors provided good calibration, discrimination (overoptimism-corrected C = 0.793), and goodness of fit (Hosmer-Lemeshow test p = 0.99). A combination of Rankin Scale score ≥1, cognitive risk score ≥1, and MMSEadj score ≥21 selected 230 (56.9%) of the 404 patients for a comprehensive assessment. This procedure yielded good sensitivity (96.5%) and moderate specificity (43%; positive predictive value 0.66, negative predictive value 0.91) and was more accurate (p ≤ 0.03 for all) than the sole use of screening tests (MMSE or Montréal Cognitive Assessment). CONCLUSION: The GRECogVASC cognitive risk score comprises 4 easily documented factors; this procedure helps to identify patients at risk of poststroke NCDs who must therefore undergo a comprehensive assessment. CLINICALTRIALSGOV IDENTIFIER: NCT01339195.

Role of platelet α2-adrenoreceptor in biological low response to Clopidogrel for patients with non cardioembolic ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Low biological response to Clopidogrel prescribed after non cardioembolic ischemic stroke or transient ischemic attack (TIA) is a major clinical problem and could explain the recurrence of vascular events. Platelet α2-adrenoreceptors are involved in the high residual platelet reactivity in stable coronary artery disease patients on dual antiplatelet therapy. In the present study we investigated the impact of platelet α2-adrenoreceptors on ADP-induced platelet aggregation and on ADP-induced platelet membrane CD62P (P-selectin) expression, a marker of platelet activation on blood samples from patients hospitalized at the acute phase of a non cardioembolic ischemic stroke or TIA. METHODS: 72 consecutive patients were prospectively recruited over the course of two years in a monocentric study. Patients received a daily 75 mg-dose of Clopidogrel. ADP-induced platelet aggregation was measured alone, with low dose epinephrine or with atipamezole, a selective α blocker of α2-adrenoreceptors, by Light Transmittance Aggregometry (LTA). Platelet membrane expression of P-selectin was measured by flow cytometry with either ADP alone or combined with epinephrine. RESULTS: Epinephrine at low dose stimulated ADP-induced platelet membrane expression of CD62P whereas Atipamezole significantly inhibited 10 µM ADP-induced platelet aggregation. CONCLUSIONS: Our study showed the role of platelet α2-adrenoreceptors in biological low response to Clopidogrel for patients hospitalized for a non-cardioembolic ischemic stroke or TIA. Atipamezole could improve the status of biological response to Clopidogrel.

Prevalence of Poststroke Neurocognitive Disorders Using National Institute of Neurological Disorders and Stroke-Canadian Stroke Network, VASCOG Criteria (Vascular Behavioral and Cognitive Disorders), and Optimized Criteria of Cognitive Deficit.

BACKGROUND AND PURPOSE: The prevalence of poststroke neurocognitive disorder (NCD) has yet to be accurately determined. The primary objective of the present study was to optimize operationalization of the criterion for NCD by using an external validity criterion. METHODS: The GRECOG-VASC cohort (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) of 404 stroke patients with cerebral infarct (91.3%) or hemorrhage (18.7%) was assessed 6 months poststroke and 1003 healthy controls, with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network standardized battery. Three dimensions of the criterion for cognitive impairment were systematically examined by using the false-positive rate as an external validity criterion. Diagnosis of mild and major NCD was based on the VASCOG criteria (Vascular Behavioral and Cognitive Disorders). The mechanisms of functional decline were systematically assessed. RESULTS: The optimal criterion for cognitive impairment was the shortened summary score (ie, averaged performance for action speed, executive functions, and language) because it was associated with the highest (P=0.0001) corrected true-positive rate (43.5%) and a false-positive rate ≤5%. Using this criterion, the mean (95% confidence interval) prevalence of poststroke NCD was 49.5% (44.6-54.4), most of which corresponded to mild NCD (39.1%; 95% confidence interval, 34.4-43.9) rather than dementia (10.4%; 95% confidence interval, 7.4-13.4). CONCLUSIONS: This study is the first to have optimized the operationalization of the criterion for poststroke cognitive impairment. It documented the prevalence of poststroke NCD in the GRECOG-VASC cohort and showed that mild cognitive impairment accounts for 80% of the affected patients. Finally, the method developed in the present study offers a means of harmonizing the diagnosis of NCD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01339195.

Brain magnetic resonance imaging findings in cryptogenic stroke patients under 60 years with patent foramen ovale.

PURPOSE: To compare magnetic resonance imaging (MRI) brain feature in cryptogenic stroke patients with patent foramen ovale (PFO), cryptogenic stroke patients without PFO and patients with cardioembolic stroke. MATERIALS AND METHODS: The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients' medical records and imaging data. The patients' medical files were retrospectively reviewed in accordance with human subject research protocols. Ninety-two patients under 60 years of age were included: 15 with cardioembolic stroke, 32 with cryptogenic stroke with PFO and 45 with cryptogenic stroke without PFO. Diffusion-weighted imaging of brain MRI was performed by a radiologist blinded to clinical data. Univariate, Fischer's exact test for qualitative data and non-parametric Wilcoxon test for quantitative data were used. RESULTS: There was no statistically significant difference found between MRI features of patients with PFO and those with cardioembolic stroke (p<.05). Patients without PFO present more corticosubcortical single lesions (p<.05) than patients with PFO. Patients with PFO have more often subcortical single lesions larger than 15mm, involvement of posterior cerebral arterial territory and intracranial occlusion (p<.05) than patients with cryptogenic stroke without PFO. CONCLUSION: Our study suggests a cardioembolic mechanism in ischemic stroke with PFO.

[Intracranial hemorrhages: epidemiology and implication of antithrombotic therapy]. / Hémorragies intracrâniennes : épidémiologie et implication des traitements antithrombotiques.

OBJECTIVE: Intracranial hemorrhage (ICH) is an antithrombotic treatment complication. Our study's goal is to assess the proportion of ICH occurring while the patient is on antithrombotic treatment. The secondary goal is to assess the proportion of "avoidable" ICH (anticoagulant overdosage, debatables indications). METHODS: We conducted a descriptive epidemiological single-center study of ICH during 2 years. We analyzed the type of ICH, the type of antithrombotic treatment, the level of anticoagulation and the relevance of antithrombotic treatment indication. RESULTS: Of the 400 patients admitted for an ICH, 131 (33%) were treated by antithrombotic therapy: oral anti-vitamin K anticoagulants (VKA) in 14.1% of cases and antiplatelet agents in 15.1%. Of VKA patients, overdosage rate was 30.2%. The indication of antithrombotic therapy was debatable in 18.3% of cases. CONCLUSION: Our study highlights the frequency of ICH occurring on antithrombotic therapy and the significant proportion of "avoidable" ICH.

[What are the crucial factors affecting the time to admission of patients with suspected stroke to the emergency department?]. / Quels sont les facteurs influençant les délais d'admission des patients arrivant aux urgences pour une suspicion d'accident vasculaire cérébral.

OBJECTIVE: To analyse the factors influencing the time of admission of patients presenting an acute ischaemic stroke (AIS) to the emergency department. PATIENTS AND METHODS: Between May 2006 and July 2007, all patients with suspected stroke admitted to the emergency department were included. Patients' characteristics and the nature and timing of the events following symptom detection were recorded in the emergency department. The symptoms observed, the person telephoning for help, the person or establishment contacted, the measures implemented (attendance of a physician, medical or paramedical intervention) and the means of transport to the hospital were noted. The overall population was analysed descriptively and patients admitted within 3 hours of symptom onset (group I) were compared with those admitted after a longer interval (group II). The final diagnosis of AIS was confirmed on patient discharge. The results were expressed as the mean (± SD) or median (interquartile range), Mann-Whitney and Chi(2) tests being used to analyse differences between the two groups (threshold of statistical significance: P<0.05). RESULTS: Among the 678 patients admitted with suspected stroke, 536 were diagnosed as having experienced an AIS, 65 a haemorrhagic stroke, 3 a cerebral venous thrombosis and 74 an event other than an acute neurovascular event. The results therefore concern 536 patients (median age: 75 years), of whom 166 (31%, group I) were admitted within 3 hours of symptom onset and 370 after a longer interval (group II). The median time between symptom onset and the call for help was 15 min (1-26) in group I and 300 min (60-960) in group II (P<0.0001). The median times to intervention of a physician (the patient's regular general practitioner, the physician on duty, or the SMUR [Mobile Emergency and Resuscitation Service] physician) ranged from 10 to 60 min. Median transport times ranged from 30 to 120 min depending on the type of transport employed. The two groups differed significantly with regard to intervention of a physician before admission to the emergency department (40% of patients in group I vs. 72% in group II, P<0.0001), initial call to the emergency medical call centre ("15" in France) (42% vs. 17%, P<0.001), presence of a relative or other person at the time of functional symptom onset (58% vs. 39%, P<0.01), and immediate transport to hospital without medical intervention (49 vs. 11%). Finally, irrespective of the time to hospital admission, 12% of the patients studied were eligible for intravenous thrombolysis. CONCLUSION: In the event of a suspected stroke, these results favour contacting the emergency medical call centre and immediate transfer of the patient to an appropriate hospital establishment without waiting for prior medical intervention.