Chronic cerebral circulation insufficiency (CCCI) may not be an independent disease; rather, it is a pervasive state of long-term cerebral blood flow insufficiency caused by a variety of etiologies, and considered to be associated with either occurrence or recurrence of ischemic stroke, vascular cognitive impairment, and development of vascular dementia, resulting in disability and mortality worldwide. This review summarizes the features and recent progress of CCCI, mainly focusing on epidemiology, experimental research, pathophysiology, etiology, clinical manifestations, imaging presentation, diagnosis, and potential therapeutic regimens. Some research directions are briefly discussed as well.
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.
Extracranial venous abnormalities, especially jugular venous outflow disturbance, were originally viewed as nonpathological phenomena due to a lack of realization and exploration of their feature and clinical significance. The etiology and pathogenesis are still unclear, whereas a couple of causal factors have been conjectured. The clinical presentation of this condition is highly variable, ranging from insidious to symptomatic, such as headaches, dizziness, pulsatile tinnitus, visual impairment, sleep disturbance, and neck discomfort or pain. Standard diagnostic criteria are not available, and current diagnosis largely depends on a combinatory use of imaging modalities. Although few researches have been conducted to gain evidence-based therapeutic approach, several recent advances indicate that intravenous angioplasty in combination with stenting implantation may be a safe and efficient way to restore normal blood circulation, alleviate the discomfort symptoms, and enhance patients' quality of life. In addition, surgical removal of structures that constrain the internal jugular vein may serve as an alternative or adjunctive management when endovascular intervention is not feasible. Notably, discussion on every aspect of this newly recognized disease entity is in the infant stage and efforts with more rigorous designed, randomized controlled studies in attempt to identify the pathophysiology, diagnostic criteria, and effective approaches to its treatment will provide a profound insight into this issue.
Despite decades of formidable exploration, multi-organ ischemia-reperfusion injury (IRI) encountered, particularly amongst elderly patients with clinical scenarios, such as age-related arteriosclerotic vascular disease, heart surgery and organ transplantation, is still an unsettled conundrum that besets clinicians. Remote ischemic conditioning (RIC), delivered via transient, repetitive noninvasive IR interventions to distant organs or tissues, is regarded as an innovative approach against IRI. Based on the available evidence, RIC holds the potential of affording protection to multiple organs or tissues, which include not only the heart and brain, but also others that are likely susceptible to IRI, such as the kidney, lung, liver and skin. Neuronal and humoral signaling pathways appear to play requisite roles in the mechanisms of RIC-related beneficial effects, and these pathways also display inseparable interactions with each other. So far, several hurdles lying ahead of clinical translation that remain to be settled, such as establishment of biomarkers, modification of RIC regimen, and deep understanding of underlying minutiae through which RIC exerts its powerful function. As this approach has garnered an increasing interest, herein, we aim to encapsulate an overview of the basic concept and postulated protective mechanisms of RIC, highlight the main findings from proof-of-concept clinical studies in various clinical scenarios, and also to discuss potential obstacles that remain to be conquered. More well designed and comprehensive experimental work or clinical trials are warranted in future research to confirm whether RIC could be utilized as a non-invasive, inexpensive and efficient adjunct therapeutic intervention method for multi-organ protection.
Objective We aimed to evaluate the safety and effectiveness of short‐term remote ischemic postconditioning ( RIPC ) in acute stroke monkey models. Methods Acute stroke monkeys were allocated to four groups based on the number of limbs exposed to RIPC . RIPC was initiated by 5‐min cuff inflation/deflation cycles of the target limb(s) for 5–10 bouts. Vital signs, skin integrity, brain MRI , and serum levels of cardiac enzymes (myoglobin, creatine kinase [ CK ], CK ‐muscle/brain [ CK ‐ MB ]), one inflammatory marker (high‐sensitivity C‐reactive protein [hs CRP ], and one endothelial injury marker (von Willebrand factor [ vWF ]) were assessed. Spetzler scores were used to assess neurological function. Results No significant differences in vital signs or local skin integrity were found. Short‐term RIPC did not reduce infarct volume under any condition at the 24th hour after stroke. However, neurological function improved in multi‐limb RIPC compared with sham and single‐limb RIPC at the 30th day follow‐up after stroke. Myoglobin, CK , and CK ‐ MB levels were reduced after multi‐limb RIPC , regardless of the number of bouts. Moreover, multi‐limb RIPC produced a greater diminution in CK ‐ MB levels, whereas two‐limb RIPC was more effective in reducing serum CK levels at the 24th hour after stroke. hs CRP increased after 5 bouts of multi‐limb RIPC before decreasing below baseline and single‐limb RIPC levels. Serum vWF was decreased at later time points after RIPC in all RIPC groups. Conclusions Stroke monkeys in hyperacute stage may benefit from short‐term RIPC ; however, whether this intervention can be translated into clinical use in patients with acute ischemic stroke warrants further study.
Cerebral venous sinus thrombosis (CVST) is an uncommon subtype of stroke with highly variable clinical presentation. Although anticoagulation with heparin and/or warfarin remains the standard treatment for CVST, treatment failure is still common. This study aims to evaluate the safety and efficacy of Batroxobin in combination with anticoagulation on CVST control. In this retrospective study, a total of 61 CVST patients were enrolled and divided into Batroxobin (n = 23) and control (n = 38) groups. In addition to the same standard anticoagulation in control, patients in the treatment group received Batroxobin 5 BU intravenous infusion (10 BU for the first time) every other day, for a total of three infusions. A higher recanalization rate was found in Batroxobin group (adjusted OR [95% CI] of 2.5 [1.1-5.0], p = 0.028) compared to the control group, especially in patients with high levels of fibrinogen (adjusted OR [95% CI] of 4.7 [1.4-16.7], p = 0.015). Statistically significant differences between the two groups were seen regarding the levels of thrombin time, fibrinogen and D-dimer at each cut-off time point (all p < 0.01). Compared with baseline, NIHSS scores at discharge showed significant improvement in the Batroxobin group [0(0, 4.25)-5(2, 11), p = 0.036]. No significant difference in mRS scores was found between the two groups at discharge or at 6-month outpatient follow-up (all p > 0.05). Additionally, Batroxobin did not increase the risk of intracranial hemorrhage. We conclude that Batroxobin is a potentially safe and effective adjunct therapeutic agent promoting CVST recanalization especially in patients with high level of fibrinogen.
Background Normobaric oxygen (NBO) has received considerable attention due to controversial data in brain protection in patients with acute stroke. This study aims to analyze current data of NBO on brain protection as used in the clinic. Methods We searched for and reviewed relevant articles and references from Pubmed, Medline, Embase, Cochrane, and Clincialtrials.gov that were published prior to October 2017. Data from prospective studies were processed using RevMan5.0 software, provided by Cochrane collaboration and transformed using relevant formulas. Results A total of 11 prospective RCT studies including 6366 patients with acute stroke (NBO group, 3207; control group, 3159) were enrolled in this analysis. △NIHSS represented the values of NIHSS at 4, 24 h, or 7 days post-stroke minus baseline NIHSS. Compared to controls, there was a minor trend toward NBO benefits in short-term prognostic indices, as indicated by decreased ΔNIHSS at our defined time points. By contrast, NBO decreased Barthel Index scores between 3 and 7 months, and increased death rates at 3, 6 months, and 1 year, whereas, modified Rankin Scale scores between 3 and 6 months were unchanged. Conclusions The existing trends toward benefits revealed in this meta-analysis help us appreciate the promising value of NBO, although current evidence of NBO on improving clinical outcomes of stroke is insufficient. Well-designed multi-center clinical trials are encouraged and urgently needed to further explore the efficacy of NBO on brain protection.
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