Objective: This study aims to evaluate protective effects of brief repetitive bilateral arm ischemic preconditioning (BAIPC) on stroke recurrence in patients with symptomatic atherosclerotic intracranial arterial stenosis (IAS). Methods: A total of 68 consecutive cases with symptomatic IAS, diagnosed by imaging, were enrolled in this prospective and randomized study. All patients received standard medical management. Patients in the BAIPC group (n = 38) underwent 5 brief cycles consisting of bilateral upper limb ischemia followed by reperfusion. The BAIPC procedure was performed twice daily over 300 consecutive days. Incidence of recurrent stroke and cerebral perfusion status in BAIPC-treated patients were compared with the untreated control group (n = 30). Results: In the control group, incidence of recurrent stroke at 90 and 300 days were 23.3% and 26.7%, respectively. In the BAIPC group, incidence of recurrent stroke was reduced to 5% and 7.9% at 90 and 300 days (p < 0.01), respectively. The average time to recovery (modified Rankin Scale score 0–1) was also shortened by BAIPC. Cerebral perfusion status, measured by SPECT and transcranial Doppler sonography, improved remarkably in BAIPC-treated brain than in control (p < 0.01). Conclusion: This study provides a proof-of-concept that BAIPC may be an effective way to improve cerebral perfusion and reduce recurrent strokes in patients with IAS. Further investigation of this therapeutic approach is warranted as some patients were excluded after randomization.

Background and purpose: Stroke is a leading cause of death and acquired disability in adults today. Inflammation plays an important role in the pathophysiology of stroke. The peripheral neutrophil-to-lymphocyte ratio (NLR) is an important global inflammatory indicator becoming more mainstream in stroke care. This meta-analysis aims to evaluate the relationship between the baseline NLR and acute ischemic and hemorrhagic stroke, as well as define the clinical significance of NLR in subtypes of ischemic stroke. Methods: This meta-analysis was registered in PROSPERO with the number CRD42018105305. We went through relevant articles from PubMed Central (PMC) and EMBASE. Prospective and retrospective studies were included if related to baseline NLR levels prior to treatment in patients with ischemic or hemorrhagic stroke. Studies were identified up until April 2019. The cutoff value for NLR and the sources of odds ratios (ORs)/risk ratios (RRs) were measured. Modified Rankin Scale (mRS) was used to investigate the outcomes during clinical follow-up. Predefined criteria were used to evaluate the risk of bias in eligible studies. P-values < 0.05 were considered statistically significant. STATA version 14.0 (STATA, College Station, TX) was used in all statistical analyses. Results: Thirty-seven studies with 43,979 individuals were included in the final analysis. Higher NLR levels were correlated with increased risk of ischemic stroke (ORs/RRs = 1.609; 95% CI = 1.283–2.019), unfavorable functional outcome at 3 months (ORs/RRs = 1.851; 95% CI = 1.325–2.584), and increased mortality in patients with ischemic stroke (ORs/RRs = 1.068; 95% CI = 1.027–1.111). While in terms of hemorrhagic stroke (including SAH and ICH), elevated NLR levels only had deleterious effects on mortality (ORs/RRs = 1.080; 95% CI = 1.018–1.146). Conclusions: Baseline NLR level is a promising predictor of the clinical outcomes in both ischemic and hemorrhagic stroke. In addition, elevated NLR is also associated with a high risk of ischemic stroke occurrence. However, future studies are needed to demonstrate the underlying mechanisms and further explain this association.

Background and Purpose—: We aimed to evaluate the efficacy of remote ischemic conditioning (RIC) in patients with cerebral small-vessel disease. Methods—: Thirty patients with cerebral small-vessel disease–related mild cognitive impairment were enrolled in this prospective, randomized controlled study for 1 year. Besides routine medical treatment, participants were randomized into the experimental group (n=14) undergoing 5 cycles consisting of ischemia followed by reperfusion for 5 minutes on both upper limbs twice daily for 1 year or the control group (n=16) who were treated with sham ischemia–reperfusion cycles. The primary outcome was the change of brain lesions, and secondary outcomes were changes of cognitive function, plasma biomarkers, and cerebral hemodynamic parameters both at baseline and at the end of 1-year follow-up. Results—: Compared with pretreatment, the post-treatment white matter hyperintensities volume in the RIC group was significantly reduced (9.10±7.42 versus 6.46±6.05 cm ³ ; P =0.020), whereas no significant difference was observed in the sham-RIC group (8.99±6.81 versus 8.07±6.56 cm ³ ; P =0.085). The reduction of white matter hyperintensities volume in the RIC group was more substantial than that in sham group (−2.632 versus −0.935 cm ³ ; P =0.049). No significant difference was found in the change of the number of lacunes between 2 groups (0 versus 0; P =0.694). A significant treatment difference at 1 year on visuospatial and executive ability was found between the 2 groups (0.639 versus 0.191; P =0.048). RIC showed greater effects compared with sham-RIC on plasma triglyceride (−0.433 versus 0.236 mmol/L; P =0.005), total cholesterol (−0.975 versus 0.134 mmol/L; P <0.001), low-density lipoprotein (−0.645 versus −0.029 mmol/L; P =0.034), and homocysteine (−4.737 versus −1.679 µmol/L; P =0.044). Changes of the pulsation indices of middle cerebral arteries from the baseline to 1 year were different between the 2 groups (right: −0.075 versus 0.043; P =0.030; left: −0.085 versus 0.043; P =0.010). Conclusions—: RIC seems to be potentially effective in patients with cerebral small-vessel disease in slowing cognition decline and reducing white matter hyperintensities. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01658306.