C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. Methods: This prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. Results: Two hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 µg/L [520-2075] vs 1220 µg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. Conclusion: Two widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

Stroke phenotype in cannabis users among young adults with ischemic stroke.

BACKGROUND AND PURPOSE: Incidence of ischemic stroke in young adults has been steadily increasing over the past 20 years. One hypothesis to explain this phenomenon is the increase in the use of illicit drugs, including cannabis. However, the mechanisms and the clinical presentation of ischemic stroke associated with cannabis use are unclear. The objective of this study was to describe the phenotype of ischemic stroke in cannabis users compared to nonusers among a population of young adults with a first-ever ischemic stroke. METHODS: Patients aged 18-54 years consecutively hospitalized in a university department of neurology for a first-ever ischemic stroke from January 2017 to July 2021 were included. Drug use over the past year was assessed by a semistructured interview, and the stroke phenotype was described using the ASCOD classification. RESULTS: A total of 691 patients, including 78 of 691 (11.3%) cannabis users, were included. Cannabis use was independently associated with potential A1 (odds ratio [OR] = 3.30, 95% confidence interval [CI] = 1.45-7.5, p = 0.004) and uncertain A2 (OR = 13.1, 95% CI = 2.89-59.4, p < 0.001) atherosclerotic cause of stroke after adjustment for vascular risk factors including tobacco and other drug use. Moreover, the association of atherosclerosis and cannabis use was significant for frequent (OR = 3.13, 95% CI = 1.07-8.6, p = 0.030) and daily cannabis use (OR = 4.43, 95% CI = 1.40-13.4, p = 0.008), but not for occasional use. CONCLUSIONS: We found a significant, independent, and graded association of cannabis use with the atherosclerotic stroke phenotype.

Cryptogenic Ischemic Stroke in Migraine: Role of Patent Foramen Ovale.

Introduction: Migraine with aura (MWA) has been associated with cryptogenic ischemic stroke (CIS) after adjustment for the presence of a patent foramen ovale (PFO) assessed by a transcranial Doppler. This study aimed at evaluating the association of MWA with causal PFO assessed by Transesophageal echocardiography (TEE) in CIS. Methods: Patients aged 18-54 years consecutively treated for first acute ischemic stroke in a university hospital stroke unit, between January 2017 and December 2019, were included in this cross-sectional study. Associations between migraine subtypes and PFO were tested for all PFO, possibly causal PFO (PFO with large shunt and/or atrial septal aneurysm [ASA]), and the probably causal PFO subset (large shunt and/or ASA, plus risk of paradoxical embolism [RoPE] score ≥ 7). We adjusted the association between migraine subtypes and possibly causal PFO, which included the probably causal subset for age, sex, large artery atherosclerosis, and small vessel disease. Results: A total of two hundred and two patients with CIS were included, of whom 42/202 (20%) had MWA, 32/202 (15%) had migraine without aura, and 128/202 (63%) had no migraine. MWA was associated with possibly causal PFO (OR = 4.0, 95%CI [1.78-9.3], P < 0.001) and with probably causal PFO (OR = 5.4, 95%CI [2.37-13], P < 0.001). In a multinomial logistic regression analysis, MWA remained associated with possibly causal PFO (OR = 3.24, 95% CI [1.45-7.2], P = 0.004). Conclusion: In a young adult population with CIS, MWA was strongly associated with possibly causal PFO, i.e., with a large shunt or combined with an interatrial septal aneurysm.

Migraine and large artery atherosclerosis in young adults with ischemic stroke.

INTRODUCTION: Migraine is a risk factor for ischemic stroke, but the mechanisms of stroke associated with migraine are debated. The aim of this study was to investigate the association between migraine and large artery atherosclerosis (LAA) in young adults with ischemic stroke. METHODS: Patients aged between 18 and 54 years consecutively treated for first acute ischemic stroke in a university hospital stroke unit between January 2017 and December 2019 were included in this cross-sectional study. Migraine status was systematically assessed by the same headache specialist. Stenotic and nonstenotic LAA of extracranial and intracranial cerebral arteries were evaluated and graded using the ASCOD (atherosclerosis, small-vessel disease, cardiac pathology, other causes, dissection) criteria. We adjusted the association between migraine and LAA for traditional risk factors. RESULTS: A total of 415 patients were included (mean age [standard deviation], 43.9 [8.7] years; 258/415 [62.2%] men). Migraine with aura (MWA) was diagnosed in 76 patients, and migraine without aura (MWoA) in 68 patients. Patients with migraine had fewer traditional cardiovascular risk factors. Stenotic LAA (10/144 [6.9%] vs. 42/271 [15.5%]; p < 0.001) and LAA of any grade (35/144 [24.3%] vs. 138/271 [50.9%]; p < 0.001) were significantly less frequent in patients with migraine than in patients without migraine, respectively. Multivariable analysis adjusting for age, sex, overweight, tobacco use, hypertension, diabetes, and hyperlipidemia showed a negative association between migraine and LAA of any grade (odds ratio [OR] = 0.44, 95% confidence interval [CI: 0.254-0.78], p = 0.005). This negative association was found for both MWoA (OR = 0.42, 95% CI [0.204-0.88], p = 0.020) and MWA (OR = 0.47, 95% CI [0.228-0.96], p = 0.037) compared to no migraine. CONCLUSION: In this study of young adults with ischemic stroke, migraine had a negative association with LAA. This negative association was independent of traditional vascular risk factors and was found for both MWA and MWoA.

Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)-Comparison With ISCVT Cohort.

Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown. Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort. Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al. Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients. Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.

Atrial fibrillation and migraine with aura in young adults with ischemic stroke.

BACKGROUND: Migraine is associated with an increased risk of ischemic stroke. The associations are stronger in migraine with aura than in migraine without aura, in women than in men, and in younger subjects. However, the mechanisms by which migraine might increase the risk of ischemic stroke are debated. METHODS: We analysed the associations between migraine without aura and migraine with aura and the causes of ischemic stroke in patients aged 18-54 years treated consecutively in a university hospital stroke center. RESULTS: A total of 339 patients (mean/SD age 43.8/8.8 years, 62.83% male) were included. Migraine with aura was diagnosed in 58 patients, and migraine without aura in 54 patients. Patients with migraine with aura were younger and had fewer traditional cardiovascular risk factors than patients with no migraine. Migraine with aura was strongly associated with atrial fibrillation (odds ratio, 5.08; 95% confidence interval, 1.24-21.92; p = 0.011) and negatively associated with atherosclerosis (odds ratio, 0.29; 95% confidence interval, 0.05-0.97; p = 0.033) and small vessel disease (odds ratio, 0.13; 95% confidence interval, 0.00-0.87; p = 0.022). No other cause of stroke was significantly associated with migraine. The most common cause of stroke was atherosclerosis in no-migraine patients, dissection in migraine without aura patients and patent foramen ovale in migraine with aura patients. Atrial fibrillation was, together with dissection, the second leading cause of stroke in migraine with aura patients, accounting for 10.34% of cases in this subgroup. CONCLUSION: We showed that atrial fibrillation was a common cause of ischemic stroke in young adults with migraine with aura.

Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial.

While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up. We enrolled patients aged 18-70 years less than 2 weeks following moderate-severe ischemic carotid stroke. Patients were randomized 2:1 to receive intravenous MSCs or not. Primary outcomes assessed feasibility and safety. Secondary outcomes assessed global and motor recovery. Passive wrist movement functional MRI (fMRI) activity in primary motor cortex (MI) was employed as a motor recovery biomarker. We compared "treated" and "control" groups using as-treated analyses. Of 31 enrolled patients, 16 patients received MSCs. Treatment feasibility was 80%, and there were 10 and 16 adverse events in treated patients, and 12 and 24 in controls at 6-month and 2-year follow-up, respectively. Using mixed modeling analyses, we observed no treatment effects on the Barthel Index, NIHSS, and modified-Rankin scores, but significant improvements in motor-NIHSS (p = 0.004), motor-Fugl-Meyer scores (p = 0.028), and task-related fMRI activity in MI-4a (p = 0.031) and MI-4p (p = 0.002). Intravenous autologous MSC treatment following stroke was safe and feasible. Motor performance and task-related MI activity results suggest that MSCs improve motor recovery through sensorimotor neuroplasticity. ClinicalTrials.gov Identifier NCT00875654.