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.

Symptomatic intracranial arterial stenosis (SIAS) is very common in octo-and nonagenarians, especially in the Chinese population, and is likely the most common cause of stroke recurrence worldwide. Clinical trials demonstrate that endovascular treatment, such as stenting, may not be suitable for octogenarians with systemic diseases. Hence, less invasive methods for the octogenarian patients are urgently needed. Our previous study (unique identifier: NCT01321749) showed that repetitive bilateral arm ischemic preconditioning (BAIPC) reduced the incidence of stroke recurrence by improving cerebral perfusion (confirmed by single photon emission computed tomography and transcranial Doppler sonography) in patients younger than 80 years of age; however, the safety and effectiveness of BAIPC on stroke prevention in octo-and nonagenarians with SIAS are still unclear. The objective of this study was to evaluate the safety and effectiveness of BAIPC in reducing stroke recurrence in octo-and nonagenarian patients with SIAS. Fifty-eight patients with SIAS were enrolled in this randomized controlled prospective study for 180 consecutive days. All patients enrolled in the study received standard medical management. Patients in the BAIPC group (n=30) underwent 5 cycles consisting of bilateral arm ischemia followed by reperfusion for 5 min each twice daily. Those in the control group (n=28) underwent sham-BAIPC twice daily. Blood pressure, heart rate, local skin status, plasma myoglobin, and plasma levels of thrombotic and inflammatory markers were documented in both groups before beginning the study and for the first 30 days. Finally, the incidences of stroke recurrence and magnetic resonance imaging during the 180 days of treatment were compared. Compared with the control, BAIPC had no adverse effects on blood pressure, heart rate, local skin integrity, or plasma myoglobin, and did not induce cerebral hemorrhage in the studied cohort. BAIPC reduced plasma high sensitive C-reactive protein, interleukin-6, plasminogen activator inhibitor-1, leukocyte count, and platelet aggregation rate and elevated plasma tissue plasminogen activator (all p<0.01). In 180 days, 2 infarctions and 7 transient ischemic attacks were observed in the BAIPC group compared with 8 infarctions and 11 transient ischemic attacks in the sham BAIPC group (p<0.05). BAIPC may safely inhibit stroke recurrence, protect against brain ischemia, and ameliorate plasma biomarkers of inflammation and coagulation in octo-and nonagenarians with SIAS. A multicenter trial is ongoing.Clinical Trial Registration: www.clinicaltrials.gov, unique identifier: NCT01570231.

Recently, internal jugular vein stenosis (IJVS) is gaining increasing attention from clinical researchers due to a series of confounding symptoms that impair the quality of life in affected individuals but cannot be explained by other well-established causes. In this study, we aimed to elucidate the clinical features, neuroimaging characteristics and pathogenesis of IJVS, and explore their possible correlations, in attempt to provide useful clues for clinical diagnosis and treatment. Forty-three eligible patients with unilateral or bilateral IJVS confirmed by contrast-enhanced magnetic resonance venography of the brain and neck were enrolled in this study. Magnetic resonance imaging along with magnetic resonance angiography or computed tomography angiography was applied to identify the radiological pattern of parenchymal or arterial lesions. Cerebral perfusion and metabolism were evaluated by single-photon emission computed tomography (SPECT). Of the 43 patients (46.0 ± 16.0 years old; 30 female), 14 (32.6%) had bilateral and 29 had unilateral IJVS. The common clinical symptoms at admission were tinnitus (60.5%), tinnitus cerebri (67.6%), headache (48.8%), dizziness (32.6%), visual disorders (39.5%), hearing impairment (39.5%), neck discomfort (39.5%), sleep disturbance (60.5%), anxiety or depression (37.5%) and subjective memory decline (30.2%). The presence of bilateral demyelination changes with cloudy-like appearance in the periventricular area and/or centrum semiovale was found in 95.3% (41/43) patients. SPECT findings showed that 92.3% (24/26) patients displayed cerebral perfusion and metabolism mismatch, depicted by bilaterally and symmetrically reduced cerebral perfusion and increased cerebral glucose consumption. IJVS may contribute to alterations in cerebral blood flow and metabolism, as well as white matter lesion formation, all of which may account for its clinical manifestations.

Background and Purpose-Ethanol consumption is inversely associated with the risk of ischemic stroke, suggesting a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified ethanol as a possible treatment for acute ischemic stroke. Methods-Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Five sets of experiments were conducted: to determine the dose-response effect of ethanol on brain infarction and functional outcome; to determine whether combining ethanol and hypothermia produces synergistic neuroprotection; to determine the therapeutic windows of opportunity for ethanol in stroke; to test whether ethanol promotes intracerebral hemorrhage in a hemorrhagic or ischemic stroke or after administration of thrombolytics; and to test the affect of ethanol on hypoxia-inducible factor-1␣ protein expression. Results-Ethanol at 1.5 g/kg reduced infarct volume and behavioral dysfunction when administered at 2, 3, or 4 hours after middle cerebral artery occlusion. The protective effect of ethanol was not improved when paired with hypothermia. Ethanol did not promote cerebral hemorrhage in hemorrhagic or ischemic stroke in combination with recombinant tissue-type plasminogen activator or urokinase. Ethanol treatment (1.5 g/kg) increased protein levels of hypoxiainducible factor-1␣ at 3 hours postreperfusion. Conclusions-Ethanol exerts a strong neuroprotective effect when administered up to 4 hours after ischemia, increases expression of hypoxia-inducible factor-1␣, and does not promote intracerebral hemorrhage when used with thrombolytics. Ethanol is a potential neuroprotectant for acute ischemic stroke. (Stroke. 2012;43:205-210.)

Background The detection of somatic mutations in cell-free DNA (cfDNA) from liquid biopsy has emerged as a non-invasive tool to monitor the follow-up of cancer patients. However, the significance of cfDNA clinical utility remains uncertain in patients with brain tumors, primarily because of the limited sensitivity cfDNA has to detect real tumor-specific somatic mutations. This unresolved challenge has prevented accurate follow-up of glioma patients with non-invasive approaches. Methods Genome-wide DNA methylation profiling of tumor tissue and serum cell-free DNA of glioma patients. Results Here, we developed a non-invasive approach to profile the DNA methylation status in the serum of patients with gliomas and identified a cfDNA-derived methylation signature that is associated with the presence of gliomas and related immune features. By testing the signature in an independent discovery and validation cohorts, we developed and verified a score metric (the “glioma epigenetic liquid biopsy score” or GeLB) that optimally distinguished patients with or without glioma (sensitivity: 100%, specificity: 97.78%). Furthermore, we found that changes in GeLB score reflected clinicopathological changes during surveillance (e.g., progression, pseudoprogression or response to standard or experimental treatment). Conclusions Our results suggest that the GeLB score can be used as a complementary approach to diagnose and follow up patients with glioma.

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Remote ischemic conditioning (RIC) confers protection on major organs from hypoxic/ischemic injuries; however, its impacts on attention network function and blood oxygen levels in unacclimatized adults exposed to high altitudes have yet to be elucidated. In this study, we recruited 120 healthy male volunteers, of which one was exposed to high altitude and the other was exposed to low altitude. The two cohorts were further divided into RIC and sham control groups. The attentional network test (ANT) was performed to evaluate cognitive function before and after RIC treatment. Other outcomes such as heart rate, blood pressure, blood oxygen saturation, cerebral tissue oxygenation index (CTOI), and cerebrovascular hemodynamic indices were also evaluated. Prior to RIC treatment, there were no significant differences in orienting or executive function between the treatment and control arms of either cohort. Alerting function was significantly lower in the highaltitude cohort than in the low-altitude cohort. There were significant reductions in both blood oxygen and CTOI in the high-altitude cohort relative to the low-altitude cohort, while the pulse index (PI) of the former cohort was significantly increased. After RIC treatment, there was a significant difference in alerting function between the high-altitude RIC group and its associated control. The CTOI of the treatment group increased from 60.39±3.40% to 62.78±4.40%, and blood oxygenation also improved. Furthermore, this group showed a significant reduction in its PI. Exposure to high-altitude environments had a significant impact on alerting function, blood oxygen, CTOI, and PI. RIC ameliorated changes in attentional function, as well as blood oxygen and CTOI, suggesting that it potentially alters cerebrovascular compliance upon exposure to high altitude.