Background Remote ischemic conditioning (RIC) is a powerful innate response to transient subcritical ischemia that protects against severe ischemic insults at distant sites. We have previously shown the safety and feasibility of limb RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients, along with changes in neurovascular and cerebral metabolism. In this study we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Methods Neurologic outcome (modified Rankin Scale [mRS]) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent 4 lower-limb conditioning sessions, consisting of 4 five-minute cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. Results The study population consisted of 21 RIC patients and 61 matched controls. There was no significant intergroup difference in age, gender, aneurysm location, clipping versus coiling, Fisher grades, Hunt and Hess grades, or vasospasm. RIC was independently associated with good outcome (OR: 5.17; 95% CI: 1.21–25.02). RIC also showed a trend toward lower incidence of stroke (28.6% vs. 47.5%) and death (4.8% vs. 19.7%). Conclusions Lower-limb RIC following aSAH appears to have a positive effect in the functional outcomes of patients with aSAH. While this effect is consistent with prior preclinical studies, future trials are necessary to conclusively evaluate the effects of RIC for aSAH.

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTR asym at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam ( R 2 = 0.4777, P = 0.0021 ), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury ( R 2 = 0.5334, P = 0.0107 ), and a non-linear correlation with the time from injury to MRI exam ( R 2 = 0.6317, P = 0.0004 ). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.

Background and purpose Remote ischemic conditioning (RIC) is a phenomenon in which short periods of non-fatal ischemia in one tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage (aSAH) undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC. Methods Thirteen patients underwent 4 RIC sessions over 2–12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression (DE) and differential methylation (DM) using an intra-individual paired study design, and then overlapped the DE and DM results for analyses of functional categories and protein-protein interactions. Results We observed 164 DE genes and 3,493 DM CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (P<3.8×10−4) and inflammatory responses (P<1.4×10−4). The cell cycle pathway genes form a significant protein-protein interaction network of tightly co-expressed genes (P<0.00001). Conclusions Gene expression and DNA methylation changes in aSAH patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses.

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ObjectivesReducing variability is integral in quality management. As part of the ongoing Encephaloduroarteriosynangiosis Revascularisation for Symptomatic Intracranial Arterial Stenosis (ERSIAS) trial, we developed a strict anaesthesia protocol to minimise fluctuations in patient parameters affecting cerebral perfusion. We hypothesise that this protocol reduces the intraoperative variability of targeted monitored parameters compared to standard management.DesignProspective cohort study of patients undergoing encephaloduroarteriosynangiosis surgery versus standard neurovascular interventions. Patients with ERSIAS had strict perioperative management that included normocapnia and intentional hypertension. Control patients received regular anaesthetic standard of care. Minute-by-minute intraoperative vitals were electronically collected. Heterogeneity of variance tests were used to compare variance across groups. Mixed-model regression analysis was performed to establish the effects of treatment group on the monitored parameters.SettingTertiary care centre.Participants24 participants: 12 cases (53.8 years±16.7 years; 10 females) and 12 controls (51.3 years±15.2 years; 10 females). Adults aged 30–80 years, with transient ischaemic attack or non-disabling stroke (modified Rankin Scale <3) attributed to 70–99% intracranial stenosis of the carotid or middle cerebral artery, were considered for enrolment. Controls were matched according to age, gender and history of neurovascular intervention.Main outcome measuresVariability of heart rate, mean arterial blood pressure (MAP), systolic blood pressure and end tidal CO2 (ETCO2) throughout surgical duration.ResultsThere were significant reductions in the intraoperative MAP SD (4.26 vs 10.23 mm Hg; p=0.007) and ETCO2 SD (0.94 vs 1.26 mm Hg; p=0.05) between the ERSIAS and control groups. Median MAP and ETCO2 in the ERSIAS group were higher (98 mm Hg, IQR 23 vs 75 mm Hg, IQR 15; p<0.001, and 38 mm Hg, IQR 4 vs 32 mm Hg, IQR 3; p<0.001, respectively).ConclusionsThe ERSIAS anaesthesia protocol successfully reduced intraoperative fluctuations of MAP and ETCO2. The protocol also achieved normocarbia and the intended hypertension.Trial registration numberNCT01819597; Pre-results.