Micro-Embolic Signals and Dissection: Association or Causation for Stroke? A Systematic Review and Meta-Analysis

<b><i>Background and Objective:</i></b> Although the mechanism of stroke in cervical artery dissection (CAD) has been hypothesized to be embolization rather than hemodynamic compromise, there are a limited number of studies supporting this hypothesis. Detection of micro-embolic signals (MESs) using transcranial Doppler (TCD) helps in understanding the mechanism in these patients. A systematic review and meta-analysis were performed to estimate the prevalence of MES and its association with stroke outcomes in patients with acute stroke/TIA secondary to dissection. <b><i>Methods:</i></b> A comprehensive literature search was conducted for studies before January 26, 2021, in PubMed, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov. Studies were identified that used TCD to detect MES in stroke/TIA patients secondary to CAD. Pooled prevalence was calculated. Entire statistical analysis was conducted in R version 3.6.2. <b><i>Results:</i></b> Eleven studies involving 112 patients (50 MES+, 62 MES−) were included in our meta-analysis. The pooled prevalence of MES among acute stroke/TIA patients secondary to dissection was 46.0% (95% CI 26.0–67.0%). The presence of MES was associated with an increased risk of early ischemic recurrence in patients with CAD. We could not estimate the functional outcome and mortality associated with the presence of MES due to the scarcity of data. <b><i>Conclusions:</i></b> Our meta-analysis showed 46% prevalence of MES in the studies which looked at acute stroke/TIA secondary to CAD using TCD. This finding supports the assumption that embolism may be a major cause of stroke in patients with dissection although this could be determined only in a small population.

Clinical Manifestations and Mechanisms of Autoimmune Disease-Related Multiple Cerebral Infarcts

It is important to investigate the clinical characteristics and identify the stroke mechanisms of patients with autoimmune disease-related stroke, which are necessary for early etiology diagnosis, accurate treatment and preventive strategies. In this article we retrospectively studied eight cases of acute ischemic stroke associated with autoimmune diseases, and without competing conventional stroke etiologies. The characteristics of stroke (clinical and radiological features), the laboratory tests especially serum D-dimer levels (as a marker of hypercoagulable state), and embolic signals on transcranial Doppler were evaluated for all eight patients. High-resolution magnetic resonance imaging (HRMRI), which can help to evaluate vasculitis was performed in four patients. The possible underlying mechanisms of these cases were discussed based on these manifestations. As a result, autoimmune diseases in our study included systemic lupus erythematosus ( n=5), mixed connective tissue disease ( n=1), central nervous system vasculitis ( n=1), and Takayasu arteritis ( n=1). All eight patients presented with acute infarction lesions in ≥2 vascular territories. Most patients presented with numerous small and medium infarction lesions located in the cortical and subcortical areas. Multiple stroke mechanisms were involved in these cases, including hypercoagulability ( n=4), cardiac embolism ( n=1) and vasculitis ( n=3). Embolic signals could be detected on transcranial Doppler in all three stroke mechanisms. In conclusion, our study revealed the characteristics of autoimmune disease-related stroke. For patients with multiple acute cerebral infarcts within non-single arterial territories, autoimmune disease is an important etiology not to be neglected. Multiple stroke mechanisms were involved in these cases.

Circulating Microparticles in Patients with Symptomatic Carotid Disease Are Related to Embolic Plaque Activity and Recent Cerebral Ischaemia

Background and Purpose: In order to assess the association of microparticles derived from activated platelets (PMP) or endothelial cells (EMP) with risk markers for recurrent embolic events in patients with symptomatic carotid artery disease, we studied the associations between PMP/EMP and three risk markers: plaque haemorrhage (PH), micro-embolic signals and cerebral diffusion abnormalities. Methods: Patients with recently symptomatic high-grade carotid artery stenosis (60–99%, 42 patients, 31 men; mean age 75 ± 8 years) and 30 healthy volunteers (HV, 11 men; mean age 56 ± 12 years) were prospectively recruited. Patients were characterised by carotid magnetic resonance imaging (presence of PH [MRI PH]), brain diffusion MRI (cerebral ischaemia [DWI+]) and transcranial Doppler ultrasound (micro-embolic signals [MES+]). PMP and EMP were classified by flow cytometry and expressed as log-transformed counts per microlitre. Results: MES+ patients (n = 18) had elevated PMP (MES+ 9.61 ± 0.57) compared to HV (8.80 ± 0.73; p < 0.0001) and to MES– patients (8.55 ± 0.85; p < 0.0001). Stroke patients had elevated PMP (9.49 ± 0.64) and EMP (6.13 ± 1.0) compared to non-stroke patients (PMP 8.81 ± 0.73, p = 0.026, EMP 5.52 ± 0.65, p = 0.011) and HV (PMP 8.80 ± 0.73, p = 0.007, and EMP 5.44 ± 0.47, p = 0.006). DWI+ patients (n = 16) showed elevated PMP (DWI+ 9.53 ± 0.64; vs. HV, p = 0.002) and EMP (DWI+ 5.91 ± 0.99 vs. HV 5.44 ± 0.47; p = 0.037). Only PMP but not EMP were higher in DWI+ versus DWI– patients (8.67 ± 0.90; p = 0.002). No association was found between PMP and EMP with MRI PH. Conclusions: PMP and EMP were associated with stroke and recent cerebrovascular events (DWI+) but only PMP were also associated with ongoing (MES+) thrombo-embolic activity suggesting a differential biomarker potential for EMP to index cerebral ischaemia while PMP may predict on-going thrombo-embolic activity.