Baseline Cerebral Small Vessel Disease Is Not Associated with Gait Decline After Five Years

Background Cerebral small vessel disease (SVD) is cross-sectionally associated with gait disturbances, however, the relation between baseline SVD and gait decline over time is uncertain. Furthermore, diffusion tensor imaging (DTI) studies on gait decline are currently lacking. Objective To investigate the association between baseline imaging SVD markers and gait decline. Methods In 2006, 310 participants from the RUN DMC cohort, a prospective cohort with older adults aged 50–85 years with SVD, were included. Gait variables were assessed using a computerized walkway during baseline and follow-up. Linear and logistic regression analyses were used to investigate the relation between imaging measures and gait decline and incident gait impairment (speed ≤ 1.0 m/s). Tract-based spatial statistics (TBSS) was used to identify possible differences in DTI measures of white matter tracts between participants with and without incident gait impairment. Results Mean age was 63.3 years (SD: 8.4) and mean follow-up duration 5.4 years (SD: 0.2). No significant associations between imaging measures and gait decline were found. TBSS analysis revealed no significant differences in DTI measures between participants with and without incident gait impairment after additional adjustment for SVD. In sub-analyses, a high total WMH volume (OR: 2.8 for highest quartile, 95% CI: 1.1–7.1) and high infratentorial WMH volume (OR: 1.8 per SD increase, 95% CI: 1.1–2.9) were associated with an increased 5-year risk of gait impairment, although this was not significant after correction for multiple testing. Conclusion Baseline imaging SVD markers were not associated with gait decline or incident gait impairment after 5 years. Future studies should investigate if SVD progression is related to gait deterioration

Cerebral small vessel disease and incident parkinsonism: The RUN DMC study

Objective: To investigate the relation between baseline cerebral small vessel disease (SVD) and the risk of incident parkinsonism using different MRI and diffusion tensor imaging (DTI) measures. Methods: In the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, a prospective cohort study, 503 elderly participants with SVD and without parkinsonism were included in 2006. During follow-up (2011-2012), parkinsonism was diagnosed according to UK Brain Bank criteria. Cox regression analysis was used to investigate the association between baseline imaging measures and incident all-cause parkinsonism and vascular parkinsonism (VP). Tract-based spatial statistics analysis was used to identify differences in baseline DTI measures of white matter (WM) tracts between participants with VP and without parkinsonism. Results: Follow-up was available from 501 participants (mean age 65.6 years; mean follow-up duration 5.2 years). Parkinsonism developed in 20 participants; 15 were diagnosed with VP. The 5-year risk of (any) parkinsonism was increased for those with a high white matter hyperintensity (WMH) volume (hazard ratio [HR] 1.8 per SD increase, 95% confidence interval [CI] 1.3-2.4) and a high number of lacunes (HR 1.4 per number increase, 95% CI 1.1-1.8) at baseline. For VP, this risk was also increased by the presence of microbleeds (HR 5.7, 95% CI 1.9-16.8) and a low gray matter volume (HR 0.4 per SD increase, 95% CI 0.2-0.8). Lower fractional anisotropy values in bifrontal WM tracts involved in movement control were observed in participants with VP compared to participants without parkinsonism. Conclusions: SVD at baseline, especially a high WMH volume and a high number of lacunes, is associated with incident parkinsonism. Our findings favor a role of SVD in the etiology of parkinsonism

Spirits, Ghosts, Atmospheres of Capital

To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association (GWA) studies (N=10,768 from European ancestry enrolled in pregnancy/birth cohorts) and followed up three lead signals in six replication studies (combined N=19,089). Rs7980687 on chromosome 12q24 (P=8.1×10(−9)), and rs1042725 on chromosome 12q15 (P=2.8×10(−10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P=3.8×10(−7) for rs7980687, P=1.3×10(−7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P=3.9×10(−6)). SNPs correlated to the 17q21 signal show genome-wide association with adult intra cranial volume(2), Parkinson’s disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons