Summary Background Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Findings Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19–2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20–1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82–3·29) for intracranial haemorrhage and 1·23 (1·08–1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08–6·72] for intracranial haemorrhage vs 1·47 [1·19–1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36–9·05] vs 1·43 [1·07–1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69–15·81] vs 1·86 [1·23–2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48–84] per 1000 patient-years vs 27 intracranial haemorrhages [17–41] per 10...

Background and Purpose— Plaque inflammation contributes to stroke and coronary events. 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid 18 F-FDG uptake and early recurrent stroke. Methods— We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid 18 F-FDG PET/computed tomography angiography, 18 F-FDG uptake was expressed as maximum standardized uptake value (SUV max ) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUV max with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only. Results— In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUV max was 2.2 (CI, 1.1–4.5; P =0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1–4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98–5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUV max was higher in patients with all recurrence ( P <0.0001) and post-PET recurrence ( P =0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41–3.39; P <0.001) and for post-PET recurrent stroke was 4.57 (CI, 1.5–13.96; P =0.008). Recurrent stroke risk increased across SUV max quartiles (log-rank P =0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59–0.78) and for post-PET recurrence was 0.80 (CI, 0.64–0.96). Conclusions— Plaque inflammation-related 18 F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed, 18 F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.

ObjectiveTo study baseline serum neurofilament light chain (sNfL) levels as a prognostic biomarker in Guillain-Barré syndrome (GBS).MethodsWe measured NfL in serum (98 samples) and cerebrospinal fluid (CSF) (24 samples) of patients with GBS prospectively included in the International GBS Outcome Study (IGOS) in Spain using single-molecule array (SiMoA) and compared them with 53 healthy controls (HCs). We performed multivariable regression to analyse the association between sNfL levels and functional outcome at 1 year.ResultsPatients with GBS had higher NfL levels than HC in serum (55.49 pg/mL vs 9.83 pg/mL, p<0.0001) and CSF (1308.5 pg/mL vs 440.24 pg/mL, p=0.034). Patients with preceding diarrhoea had higher sNfL than patients with respiratory symptoms or no preceding infection (134.90 pg/mL vs 47.86 pg/mL vs 38.02 pg/mL, p=0.016). sNfL levels correlated with Guillain-Barré Syndrome Disability Score and Inflammatory Rasch-built Overall Disability Scale (I-RODS) at every timepoint. Patients with pure motor variant and Miller Fisher syndrome showed higher sNfL levels than patients with sensorimotor GBS (162.18 pg/mL vs 95.50 pg/mL vs 38.02 pg/mL, p=0.025). Patients with acute motor axonal neuropathy cute motor axonal neuropathy had higher sNfL levels than other variants (190.55 pg/mL vs 46.79 pg/mL, p=0.013). sNfL returned to normal levels at 1 year. High baseline sNfL levels were associated with inability to run (OR=1.65, 95% CI 1.14 to 2.40, p=0.009) and lower I-RODS (β −2.60, 95% CI −4.66 to −0.54, p=0.014) at 1 year. Cut-off points predicting clinically relevant outcomes at 1 year with high specificity were calculated: inability to walk independently (>319 pg/mL), inability to run (>248 pg/mL) and ability to run (<34 pg/mL).ConclusionBaseline sNfL levels are increased in patients with GBS, are associated with disease severity and axonal variants and have an independent prognostic value in patients with GBS.