A novel score to estimate thrombus burden and predict intracranial hypertension in cerebral venous sinus thrombosis.

BACKGROUND: Current methods to evaluate the severity of cerebral venous sinus thrombosis (CVST) lack patient-specific indexes. Herein, a novel scoring method was investigated to estimate the thrombus burden and the intracranial pressure (ICP) of CVST. METHODS: In this retrospective study from January 2019 through December 2021, we consecutively enrolled patients with a first-time confirmed diagnosis of CVST by contrast-enhanced magnetic resonance venography (CE-MRV) or computed tomography venography (CTV). In these patients, a comprehensive CVST-Score was established using magnetic resonance black-blood thrombus imaging (MRBTI) to estimate the thrombus burden semi-quantitatively. The relationship between CVST-Score and ICP was explored to assess the potential of using the CVST-score to evaluate ICP noninvasively and dynamically. RESULTS: A total of 87 patients were included in the final analysis. The CVST-Scores in different ICP subgroups were as follows: 4.29±2.87 in ICP<250mmH2O subgroup, 11.36±3.86 in ICP =250-330mmH2O subgroup and 14.99±3.15 in ICP>330mmH2O subgroup, respectively (p<0.001). For patients with ICP ≤330mmH2O, the CVST-Score was linearly and positively correlated with ICP (R2=0.53). The receiver operating characteristic (ROC) curves showed the optimal CVST-Score cut-off values to predict ICP ≥250mmH2O and >330mmH2O were 7.15 and 11.62, respectively (P<0.001). Multivariate analysis indicated CVST-Score as an independent predictor of ICP ≥250mmH2O (odds ratio, 2.15; 95% confidence interval, 1.49-3.10; p<0.001). CONCLUSIONS: A simple and noninvasive CVST-Score can rapidly estimate the thrombus burden and predict the severity of intracranial hypertension in patients with CVST. The CVST-Score can aid in evaluating therapeutic responses and avoiding unnecessary invasive procedures at long-term follow-up.

Efficacy and safety of rivaroxaban in cerebral venous thrombosis: insights from a prospective cohort study.

Rivaroxaban, as a novel oral anticoagulant agent, emerged in thrombosis management. This study aimed to compare the efficacy and safety of once-daily rivaroxaban versus dose-adjusted warfarin for cerebral venous thrombosis treatment in a real-world clinical setting. This is a prospective cohort study based on the real-world clinical data analysis of the patients with imaging-confirmed CVT enrolled from August 2016 through January 2020 and their outcomes were followed up. Patients were grouped according to their treatment strategies: rivaroxaban (15-20 mg daily) or warfarin (dosage-adjusted according to international normalized ratio), which were matched 1:2 on the propensity score. The primary efficacy outcome was recanalization assessed by magnetic resonance venography. Thrombus burden, CVT recurrence and modified Rankin Scale (mRS) were also compared. The safety outcome was major bleeding. Baseline characteristics were well balanced between the 33 patients in rivaroxaban group and 49 in warfarin group after propensity score matching. During 6-month (median) follow-up, 29 patients (87.9%) in rivaroxaban group and 38 patients (77.6%) in warfarin group obtained recanalization (OR, 1.44; 95% CI 0.63-3.30). The thrombus reduction at the 6-month follow-up did not reach statistical difference (p = 0.118). No CVT recurrence was observed in both groups. All patients in rivaroxaban group obtained favorable functional outcomes (mRS = 0-2), whereas in warfarin group, 1 patient remained physically disable (mRS = 3) at the follow-up. No major bleeding events occurred in two groups. Rivaroxaban might have the same or stronger efficacy in facilitating CVT recanalization and preventing CVT recurrence with a lower incidence of bleeding than that of warfarin in Chinese population.

The efficacy and safety of Batroxobin in combination with anticoagulation on cerebral venous sinus thrombosis.

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.

To Predict Visual Deterioration According to the Degree of Intracranial Hypertension in Patients with Cerebral Venous Sinus Thrombosis.

BACKGROUND: Visual damage is one of the most common complications of cerebral venous sinus thrombosis (CVST)-associated intracranial hypertension (IH). This study is aimed at stratifying the risk of IH-induced visual damage in an attempt to predict its deterioration and prevent high-risk patients from irreversible eyesight impairment promptly. METHODS: A total of 94 patients with confirmed diagnosis of CVST were eligible for enrollment in this study. According to cerebrospinal fluid pressure at admission, the involved patients were classified into mild IH (< 250 mmH2O), moderate IH (250-330 mmH2O), and severe IH (≥330 mmH2O) groups. RESULTS: The ratio of visual deterioration in the severe IH group was 75%, which was significantly higher than in either the moderate (44.4%) or the mild groups (14.3%). As regards subjects without visual symptoms at admission, visual deterioration occurred in 9.4 ± 4.5 days after admission in the severe group while it occurred in 30.5 ± 16.8 days in the moderate group (p = 0.024). The conditional inference tree and random forest revealed that severe IH might be considered as an index of visual deterioration. Visual field defect, fading eyesight, and papilledema were significantly worse in patients with severe IH as compared to patients with mild or moderate IH, all p < 0.01. CONCLUSIONS: IH ≥330 mmH2O may be a cut-off value to predict the deterioration of visual damage in CVST, revealing that ophthalmologic interventions should be considered in a timely manner in this condition, particularly when recanalization of cerebral venous sinus cannot be achieved within a short time.

High jugular bulb in patients with non-thrombotic internal jugular venous and transverse sinus stenosis: Clues to pathogenesis.

AIMS: Conventional theories for jugular bulb (JB) formation are insufficient to explain the high proportion of high JB in adult patients. We aimed to study features of high JB in patients with non-thrombotic internal jugular venous stenosis (IJVS) and/or transverse sinus stenosis (TSS) to explore the pathogenesis of high JB formation. METHODS: We retrospectively enrolled consecutive patients with the diagnosis of non-thrombotic IJVS and/or TSS. The relationship between IJVS and/or TSS and high JB was explored. Logistic regression analysis was performed to identify potential independent risk factors for high JB. RESULTS: A total of 228 patients were included in the final analyses. The proportions of IJVS, dominant-side IJVS, and non-TSS in dominant-side high JB subgroup were higher than those in nondominant-side high JB subgroup (83.3% vs. 62.5%, p < 0.001; 72.2% vs. 18.3%, p < 0.001; 43.5% vs. 29.2%, p = 0.02). Heights of JBs on dominant sides in IJVS subgroup and non-TSS subgroup were higher than those in non-IJVS subgroup and TSS subgroup (12.93 ± 2.57 mm vs. 11.21 ± 2.76 mm, p < 0.001; 12.66 ± 2.71 mm vs. 11.34 ± 2.73 mm, p = 0.003). Multivariate logistic regression indicated an independent association between dominant-side IJVS and dominant-side high JB (odds ratio, 29.40; 95% confidence interval, 11.04-78.30; p < 0.001). CONCLUSION: IJVS and asymmetric transverse sinus were independently and positively associated with high JB, especially dominant-side IJVS with dominant-side high JB, indicating a potential hemodynamic relationship between IJVS and high JB formation. Conversely, TTS might impede high JB formation.

Inflammatory Markers Differentiate Cerebral Venous Sinus Thrombosis from Mimics.

Imaging tests always misdiagnose anatomical variants of cerebral sinuses as cerebral venous sinus thrombosis (CVST). Anatomical variants of cerebral sinuses are called CVST mimics. This study aimed to identify the role of inflammatory markers in differentiating CVST from mimics. A total of 146 patients diagnosed as CVST and 93 patients with mimics were recruited in this study. Receiver operating characteristic (ROC) analysis was performed to demonstrate the sensitivity and specificity of inflammatory markers for diagnosing CVST. Rank logistic regression analysis was performed to identify the association of markers to CVST severity and prognosis. CVST presented higher inflammatory reactions compared with mimics, demonstrated by the neutrophil count (5.11 [3.97-6.80] vs. 3.06 [2.34-3.86]), interleukin (IL)-6 (7.42 [3.85-14.22] vs. 2.47 [1.50-4.00]), and neutrophil-to-lymphocyte ratio (NLR; 3.19 [2.18-4.62] vs. 1.66 [1.16-2.22]). ROC analysis showed markers with area under the curve (AUC) >0.8, including IL-6 (optimal cutoff: 3.790; kappa value: 0.499), neutrophil count (3.975; 0.522), and NLR (2.070; 0.476). After propensity score matching, only IL-6 had an AUC >0.8, with an optimal cutoff of 3.060 and a kappa value of 0.636. Ranked logistic regression showed that IL-6 (odds ratio, 95% confidence interval: 1.063, 1.026-1.101; 1.029, 1.009-1.050), cerebrospinal fluid (CSF) immunoglobulin (Ig) A (0.279, 0.110-0.706; 0.398, 0.162-0.974), CSF IgM (22.399, 3.004-167.001; 9.545, 1.382-65.928), and CSF IgG (1.287, 1.124-1.473; 1.232, 1.091-1.392) were independently correlated with the baseline and follow-up mRS. In conclusion, inflammatory markers in CVST were different from those in mimics. These markers, especially IL-6, could not only differentiate CVST from its mimics, but also evaluate CVST severity and prognosis.

Inflammation in Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease that impairs people's wellbeing and quality of life. Inflammation is considered to play an important role in CVT initiation and progression. Several studies have reported the important role of leukocytes, proinflammatory cytokines, and adherence molecules in the CVT-related inflammatory process. Moreover, inflammatory factors exacerbate CVT-induced brain tissue injury leading to poor prognosis. Based on clinical observations, emerging evidence shows that peripheral blood inflammatory biomarkers-especially neutrophil-to-lymphocyte ratio (NLR) and lymphocyte count-are correlated with CVT [mean difference (MD) (95%CI), 0.74 (0.11, 1.38), p = 0.02 and -0.29 (-0.51, -0.06), p = 0.01, respectively]. Moreover, increased NLR and systemic immune-inflammation index (SII) portend poor patient outcomes. Evidence accumulated since the outbreak of coronavirus disease-19 (COVID-19) indicates that COVID-19 infection and COVID-19 vaccine can induce CVT through inflammatory reactions. Given the poor understanding of the association between inflammation and CVT, many conundrums remain unsolved. Further investigations are needed to elucidate the exact relationship between inflammation and CVT in the future.

Low Diastolic Blood Pressure Predicts Good Clinical Outcome in Patients With Cerebral Venous Thrombosis.

Background: Cerebral venous thrombosis (CVT) refers to a stroke subtype characterized by the disturbance of cerebral venous outflow caused by venous thrombosis. Previous studies have reported a range of factors that predict the prognosis of CVT. This study is aimed to find out whether systolic blood pressure (SBP) and diastolic blood pressure (DBP) are suitable as potential indicators of the severity and clinical outcome in CVT patients. Methods: The CVT patients admitted to Xuanwu Hospital from January 2014 to December 2019 were enrolled. The severity of CVT was assessed by the National Institute of Health Stroke Scale (NIHSS) and intracranial pressure (ICP) at the time of admission. The modified Rankin score (mRS) was assessed at 6 months of follow-up. Results: One hundred fifty-six CVT patients were enrolled with a mean age of 35.8 ± 12.8 years. A percentage of 55.8% of the CVT patients recruited were female, and 17.3% were either pregnant or in perinatal period. Headache was the most common symptom. SBP and DBP were not correlated with NIHSS at admission. Furthermore, SBP and DBP had no impact on the disturbance of consciousness, epilepsy, intracranial hemorrhage, and mental disorders. However, SBP and DBP were positively correlated with ICP at admission. SBP > 129.5 mmHg and/or DBP > 77.5 mmHg suggested the presence of intracranial hypertension (IH). Based on current results, SBP was not correlated with mRS at 6 months of follow-up. However, DBP was found to be positively correlated with mRS at 6 months of follow-up. DBP in CVT patients with good prognosis was significantly lower than in those with poor prognosis. DBP > 79.5 mmHg was identified as a cutoff value to predict a poor clinical outcome. A higher mRS and a higher rate of poor clinical outcome were found in CVT patients with SBP > 146 mmHg or DBP > 79.5 mmHg compared to those with SBP ≤ 146 mmHg or DBP ≤ 79.5 mmHg. Conclusion: SBP > 129.5 mmHg and DBP > 77.5 mmHg suggested the presence of IH in CVT patients. DBP > 79.5 mmHg predicted a poor clinical outcome.

Arterial spin labeling-MR may be an alternative to SPECT for evaluating cerebral perfusion in patients with unilateral middle cerebral artery stenosis.

OBJECTIVE: Cerebral blood flow (CBF) mapping of single-photon emission tomography (SPECT) is considered a gold standard for evaluating cerebral perfusion. However, invasiveness, high costs and strict technical requirements can limit its clinical use. We aimed to evaluate the concordance of CBF maps obtained from SPECT and pseudo-continuous arterial spin labeling magnetic resonance (PCASL-MR) imaging for evaluating cerebral perfusion. METHODS: PCASL-MR/SPECT-CBF maps were obtained from 16 eligible patients with unilateral middle cerebral artery stenosis (MCAS). Three slices (basal ganglia, semi-oval center and cerebellum) on both PCASL-MR and SPECT maps were divided into different regions of interest (ROIs) according to the ASPECT criterion, arterial territories, and cerebral hemispheres, respectively. The concordance of the two types of CBF maps and the specificity and sensitivity of PCASL-MR imaging on predicting regional hypoperfusion were calculated. RESULTS: A total of 448 ROIs were divided according to the ASPECT criterion, 192 ROIs partitioned in accordance with arterial territories, and 96 ROIs delineated based on cerebral hemispheres were analyzed. PCASL-MR imaging exhibited 83.78% to 100% sensitivity, 90.19% to 95.83% specificity for detection of hypoperfusion. Qualitative analyses revealed a strong concordance between PCASL-MR and SPECT on reflecting regional cerebral hypoperfusion (Kappa coefficient = 0.662-0.920, p < 0.01). Semi-quantitative analysis by ΔCBF revealed moderate consistency (Spearman correlation coefficient = 0.610-0.571). CONCLUSIONS: Our findings suggest that PCASL-MR may be a promising non-invasive, inexpensive alternative to SPECT for evaluating cerebral perfusion accurately in patients with symptomatic MCAS.

Probable risk factors of internal jugular vein stenosis in Chinese patients-A real-world cohort study.

OBJECTIVES: Extracranial venous anomalies, especially internal jugular vein stenosis (IJVS), have recently received increasing attention, however, its etiologies are uncertain. This study aimed to explore the probable risk factors of IJVS in Chinese PATIENTS AND METHODS: Eligible patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. Probable risk factors were analyzed, including the conditions that may result in IJV wall damage, extraluminal compression, gender and age. RESULTS: A total of 133 patients enrolled in the final analysis, including 73 females and 60 males, the mean age were 54.83 ±â€¯15.25 years. In this IJVS cohort, the top two risks were previous hepatitis B virus (HBV) infection (48.9 %) and osseous compression (41.4 %). The IJVS cohort was divided into two subsets: extraluminal compression and non-compression. In the former, osseous compression (80.9 %) was the top risk factor, other risks including arterial (22.1 %) and lymph node compression (2.9 %). While, in the latter subset, the most common risk factor was previous HBV infection (46.2 %). In addition, cerebral venous sinus thrombosis (CVST) in non-compression subset was more common than that in extraluminal compression subset (21.5 % VS. 2.9 %, p = 0.001). When considered the gender (Male vs. Female), the ratios were 28.3 % vs. 0 % of smoking, p < 0.001, 16.67 % vs. 1.37 % of hyperhomocysteinemia, p = 0.002, and 11.67 % vs. 1.37 % of hyperuricemia, p = 0.023. In the subset with age less than 45 years, the top three risks included CVST (56.25 %), immunological diseases (55.56 %), and hyperhomocysteinemia (50.00 %), while, in the subset with the ages over 60 years, type-2 diabetes (66.66 %), carotid artery compression (53.33 %), previous HBV infection (52.31 %), and osseous compression (49.09 %) were more common than others. CONCLUSION: This study illustrates the probable risks of IJVS may be diverse, in which osseous compression and previous HBV infection may be the top two probable risks of IJVS in Chinese. This is the biggest difference from previous reports based on Caucasian.

Cervical spondylotic internal jugular venous compression syndrome.

AIMS: This study aimed to identify the clinical profiles of cervical spondylosis-related internal jugular vein stenosis (IJVS) comprehensively. METHODS: A total of 46 patients, who were diagnosed as IJVS induced by cervical spondylotic compression were recruited. The clinical manifestations and imaging features of IJVS were presented particularly in this study. RESULTS: Vascular stenosis was present in 69 out of the 92 internal jugular veins, in which, 50.7% (35/69) of the stenotic vessels were compressed by the transverse process of C1, and 44.9% (31/69) by the transverse process of C1 combined with the styloid process. The transverse process of C1 compression was more common in unilateral IJVS (69.6% vs 41.3%, P = 0.027) while the transverse process of C1 combined with the styloid process compression had a higher propensity to occur in bilateral IJVS (52.2% vs 30.4%, P = 0.087). A representative case underwent the resection of the elongated left lateral mass of C1 and styloid process. His symptoms were ameliorated obviously at 6-month follow-up. CONCLUSIONS: This study proposes cervical spondylotic internal jugular venous compression syndrome as a brand-new cervical spondylotic subtype. A better understanding of this disease entity can be of great relevance to clinicians in making a proper diagnosis.

[Establishment of a multiplex ligation-dependent SNP genotyping method and its application in the detection of genes related to chemotherapeutic drugs in breast cancer].

OBJECTIVE: To establish a method for SNP genotyping of multi-genes by allele-specific oligonucleotide probe ligation mediated by a thermostable ligase, and to explore the genetic polymorphisms of drug-metabolizing enzymes in breast cancer patients and their association with chemotherapeutic responses. METHODS: 10 SNP loci of enzyme genes related to chemotherapeutic drugs such as taxanes, anthracyclines and cyclophosphamide were selected, and were genotyped for blood samples from 126 breast cancer patients by the established method. Their correlations with therapeutic responses were retrospectively evaluated. RESULTS: The lower detection limit of genomic DNA by this developed method was 6.25 ng. The fluorescent peak locations of ligation products on ABI PRISM 377 DNA sequencer were accurate and consistent with prospective sizes in bases (Bias range 0.08 - 0.69 bp, x(-) = 0.31 bp, s = 0.18 bp). Same genotyping results were obtained for repeat tests of 8 random samples, which were further confirmed by sequencing analysis. The 10 SNP loci were polymorphic of different frequency in the breast cancer patients. The combinations with GSTP1 genotypes and GSTM1 genotypes were related to anthracycline-based chemotherapy efficacy (P = 0.037), and the low GSTs activity group (GSTP1 variant allele + GSTM1 null) showed the best effects (85.7%). GSTM1 genotypes and their combinations with GSTP1 and/or CYP3A5*3 genotypes were related to taxane-based therapy efficacy (P < 0.05 for all), and both the low GSTs activity group and the drug slow-metabolising group (low GSTs activity group + CYP3A5*3 wild allele) showed better effects (100%). CONCLUSION: The established method is reliable and applicable in multiplex SNPs genotyping of multi-genes. SNPs combination may have a better clinical application value for prediction of chemotherapeutic responses.

Clinical Characteristics and Neuroimaging Findings in Internal Jugular Venous Outflow Disturbance.

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.

Risk factors and predictors of outcomes in 243 Chinese patients with cerebral venous sinus thrombosis: A retrospective analysis.

OBJECTIVES: To investigate the risk factors and predictors of outcomes in a cohort of Chinese patients with cerebral venous sinus thrombosis (CVST), so as to provide a reference for customized clinical decision. PATIENTS AND METHODS: A total of 243 Chinese patients, diagnosed as a first CVST were enrolled in this retrospective study from March 2013 through April 2017. Risk factors and predictors of outcomes for CVST were summarized and analyzed by Chi-square test and logistic regression analysis. RESULTS: Of the 243 cases, obstetric cause (19.8%) was the leading risk factor for CVST, followed by infection (17.7%) and anemia (17.7%). Gender differences in the risk factors for CVST were analyzed, showing that obstetric cause was the top risk factor in female, while hyperhomocysteinemia (22.3%) was the top risk factor in male. In age subgroups, obstetric cause (26.3%) and anemia (17.6%) were more commonly observed in age ≤ 44 years and age > 44 years subgroup, respectively. The ratio of poor outcomes (mRS = 3-6) in this cohort was 23.0%, and central nervous system (CNS) infection was closely related to poor outcomes at discharge (p = 0.023). CONCLUSION: The predominant risk factor for CVST, in this Chinese cohort, may still be obstetric cause in female and hyperhomocysteinemia in male. In addition, CNS infection may predict poor outcomes in CVST patients.

Normobaric oxygen: a novel approach for treating chronic cerebral circulation insufficiency.

Chronic cerebral circulation insufficiency (CCCI) is viewed as an alarming state induced by long-term reduction in cerebral perfusion, which is associated with neurological deficits and high risk of stroke occurrence or recurrence. CCCI accounts for a large proportion of both outpatients and inpatients with cerebrovascular diseases, while management of CCCI remains a formidable challenge to clinicians. Normobaric oxygen (NBO) is an adjuvant hyperoxygenation intervention supplied with one atmosphere pressure (1 ATA =101.325 kPa). A plethora of studies have demonstrated the efficacy of NBO on the penumbra in acute stroke. NBO has been shown to increase the oxygen pressure, raise the intracranial blood flow, protect blood-brain barrier and enhance neuroprotective effects. As similar underlying mechanisms are shared by the penumbra in stroke and the ischemic-hypoxic brain tissues in CCCI, we speculate that NBO may serve as a promising therapeutic strategy for attenuating short-term symptoms or improving long-term clinical outcomes among patients with CCCI. Due to the scant research exploring the efficacy and safety of NBO for treating CCCI so far, both experimental and clinical studies are warranted to verify our hypothesis in the future.

Efficacy of remote ischemic conditioning on improving WMHs and cognition in very elderly patients with intracranial atherosclerotic stenosis.

Our previous study revealed that remote ischemic conditioning (RIC) reduced the incidence of stroke or TIA in octo- and nonagenarians with intracranial atherosclerotic stenosis (ICAS). Herein, we aimed to investigate whether RIC would influence the progression of white matter hyperintensities (WMHs) and cognitive impairment in the same group of patients. Fifty-eight patients with ICAS were randomly assigned in a 1:1 ratio to receive standard medical treatment with RIC (n=30) versus sham-RIC (n=28). The RIC protocol consisted of 5 cycles of alternating 5-min ischemia and 5-min reperfusion applied in the bilateral upper arms twice daily for 300 days. The efficacy outcomes included WMHs change on T2 FLAIR sequences, estimated by the Fazekas scale and Scheltens scale, cognitive change as assessed by the MMSE and MoCA, and some clinical symptoms within 300-day follow-up. Compared with the baseline, RIC treatment significantly reduced Fazekas and Scheltens scores at both 180-day (both p<0.05) and 300-day (both p<0.01) follow-ups, whereas no such reduction was observed in the control group. In the RIC group, Fazekas scores were significantly lower at 300-day follow-up (p<0.001) while Scheltens scores were significantly lower at both 180-day and 300-day follow-ups (both p<0.001), as compared with the control group. There were statistically significant between-group differences in the overall MMSE or MoCA scores, favoring RIC at 180-day and 300-day follow-ups (all p<0.05). RIC may serve as a promising adjunctive to standard medical therapy for preventing the progression of WMHs and ameliorating cognitive impairment in very elderly patients with ICAS.

Batroxobin in combination with anticoagulation may promote venous sinus recanalization in cerebral venous thrombosis: A real-world experience.

AIMS: The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation. METHODS: A total of 31 CVT patients were enrolled in this real-world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times. RESULTS: In the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61-40.7)] and segment-stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69-11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10-635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48-13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90-day follow-up (P > 0.05). CONCLUSIONS: Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit.

Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection.

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.

Impact of seasonal variations on the first ischemic events in patients with moyamoya disease.

OBJECTIVES: This retrospective study aimed to explore the impact of seasonal variations on the first ischemic events in patients with moyamoya disease (MMD). PATIENTS AND METHODS: Based on the first-time ischemic event occurrence, 113 patients, including 84 with cerebral infarction and 29 with transient ischemic attack, who were diagnosed with ischemic MMD were divided into four groups: spring (March-May), summer (June-August), autumn (September-November) and winter (December-February). The incidence of cerebral infarction was considered as the primary parameter. The impact of seasonal variations on the occurrence of cerebral infarction was analyzed by Poisson regression model and seasonal analysis. RESULTS: When summer was set as the reference, patients in summer were more significantly susceptible to develop cerebral infarction as compared with spring (IRR, 0.529, 95%CI, 0.299-0.937, p = 0.03), autumn (IRR, 0.441, 95%CI, 0.240-0.810, p < 0.01) and winter (0.500, 95%CI, 0.279-0.895, p = 0.02). The seasonality of the time series in summer (1.231) was substantially higher than that in the other three seasons (-0.269 in spring, -0.656 in autumn and -0.306 in winter). No discrepancy in either NIHSS or mRS scores at admission was observed among the four seasons. CONCLUSION: Patients with MMD may be more vulnerable to cerebral infarction in summer compared with the other three seasons, and seasonal onset of cerebral infarction does not seem to be associated with the severity of neurological disability at admission.

Understanding jugular venous outflow disturbance.

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.