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BackgroundWhile memantine has been considered a promising drug for migraine prevention, no conclusive evidence exists comparing its efficacy with other migraine-preventive medications. This network meta-analysis (NMA) aimed to access the effectiveness and acceptability of memantine and other guideline-recommended prophylactic agents for migraine.MethodsWe searched the Cochrane Register of Controlled Trials, Embase, PubMed, and ClinicalTrials databases from their inception to 1 June 2024. Randomized placebo-controlled trials (RCTs) examining the pharmacological prevention of adult migraine patients were included. The primary efficacy outcome was the change in migraine days, and the primary safety outcome was withdrawal due to adverse events. Secondary outcomes included 50% response rates and frequency of any adverse events. The analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsThirty-eight RCTs, including a total of 13,223 participants, were analyzed. Our analysis showed that memantine demonstrated the second-largest reduction in migraine days [standardized mean difference (SMD): −0.83; 95% confidence interval (CI): −1.26, −0.41 compared with placebo] and the highest 50% response rates [odds ratio (OR): 5.58, 95% CI: 1.31 to 23.69] in all studied interventions. Moreover, among all interventions, memantine appeared to show the lowest dropout rate and moderate frequency of adverse events. However, its confidence intervals contained null values.ConclusionThis study provides prioritisation evidence for memantine in migraine prevention, as memantine can significantly decrease the frequency of migraine attacks, improves response rates, and fair acceptability. These beneficial effects were not inferior to currently recommended pharmacological regimens. However, due to the lack of long-term efficacy and safety data, as well as few direct comparisons with active control agents, the estimates of memantine may be overly optimistic. Clinicians should interpret the findings of current NMA cautiously and apply them in a relatively conservative manner.

Background and purposePrevious studies have shown that human herpes simplex virus (HSV) infection may be associated with the onset of headache or migraine. We aimed to investigate the association between HSV infection and severe headache or migraine.Materials and methodsThe cross-sectional data on 5,730 participants aged 20–49 years were obtained from the 1999–2004 National Health and Nutrition Examination Survey (NHANES). We used weighted logistic regression analysis to assess the association between HSV infection (HSV-1 gG-1 and HSV-2 gG-2) and severe headache or migraine, and performed subgroup analyses.ResultsOur study found that women, higher education, higher body mass index, better family conditions, smoking and alcohol consumption were all associated with severe headaches or migraines. After adjusting for confounding factors such as sex, age, race, and education, HSV-2 (+) was still significantly associated with severe headache or migraine (OR = 1.22, 95%CI:1.03–1.46, p = 0.0443). In subgroup analyses, we found that participants with HSV-1 (−) and HSV-2 (+) were also significantly associated with severe headache or migraine (OR = 1.41, 95%CI:1.04–1.91, p = 0.0281).ConclusionHSV-2 gG-2(+) was significantly associated with severe headache or migraine.

BackgroundMigraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes.MethodsWe conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables. Summary statistics for migraine were obtained from 3 databases: the International Headache Genetics Consortium (IHGC), UK Biobank, and FinnGen study. MR analyses were performed per outcome database for each exposure and subsequently meta-analyzed. Reverse MR analysis was performed to determine whether migraine were risk factors for immune diseases. In addition, we conducted a genetic correlation to identify shared genetic variants for these two associations.ResultsNo significant causal relationship was found between immune diseases and migraine and its subtypes. These results were robust with a series of sensitivity analyses. Using the linkage disequilibrium score regression method (LDSC), we detected no genetic correlation between migraine and immune diseases.ConclusionThe evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated.

Abstract Background Migraine is a common disabling neurological disorder with severe physical and psychological damage, but there is a lack of convenient and effective non-invasive early prediction methods. This study aimed to develop a new series of non-invasive prediction models for migraine with external validation. Methods A total of 188 and 94 subjects were included in the training and validation sets, respectively. A standardized professional questionnaire was used to collect the subjects' 9-item traditional Chinese medicine constitution (TCMC) scores, Pittsburgh Sleep Quality Index (PSQI) score, Zung's Self-rating Anxiety Scale and Self-rating Depression Scale scores. Logistic regression was used to analyze the risk predictors of migraine, and a series of prediction models for migraine were developed. Receiver operating characteristic (ROC) curve and calibration curve were used to assess the discrimination and calibration of the models. The predictive performance of the models were further validated using external datasets and subgroup analyses were conducted. Results PSQI score and Qi-depression score were significantly and positively associated with the risk of migraine, with the area of the ROC curves (AUCs) predicting migraine of 0.83 (95% CI:0.77–0.89) and 0.76 (95% CI:0.68–0.84), respectively. Eight non-invasive predictive models for migraine containing one to eight variables were developed using logistic regression, with AUCs ranging from 0.83 (95% CI: 0.77–0.89) to 0.92 (95% CI: 0.89–0.96) for the training set and from 0.76 (95% CI: 0.66–0.85) to 0.83 (95% CI: 0.75–0.91) for the validation set. Subgroup analyses showed that the AUCs of the eight prediction models for predicting migraine in the training and validation sets of different gender and age subgroups ranged from 0.80 (95% CI: 0.63–0.97) to 0.95 (95% CI: 0.91–1.00) and 0.73 (95% CI: 0.64–0.84) to 0.93 (95% CI: 0.82–1.00), respectively. Conclusions This study developed and validated a series of convenient and novel non-invasive prediction models for migraine, which have good predictive ability for migraine in Chinese adults of different genders and ages. It is of great significance for the early prevention, screening, and diagnosis of migraine.

Abstract Background Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been directly compared. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of various intranasal agents for the treatment of acute migraine in adult patients. Methods The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to 15 August 2023. Randomized controlled trials (RCTs) using intranasal agents (no restrictions on dose, formulation, dosing regimen or timing of the first dose) to treat adult patients with acute migraine were included. The primary efficacy endpoint was pain freedom at 2 h, and the primary safety endpoint was adverse events (AEs). The analysis process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Nineteen studies (21 RCTs, 9738 participants) were included. Compared to the placebo, 5 mg of zolmitriptan using a conventional liquid nasal spray device was the most effective for pain freedom at 2 h [odds ratio (OR): 4.67, 95% confidence interval (CI): 3.43 to 6.43] and 24 h (OR: 5.49, 95% CI: 3.58 to 8.42) among all the interventions. Butorphanol nasal spray 1 mg was the most effective (OR: 8.62, 95% CI: 1.11 to 66.92) for pain freedom at 1 h, but with low-quality evidence. DFN-02 presented the highest freedom from nausea (OR: 4.95, 95% CI: 1.29 to 19.01) and phonophobia (OR: 5.36, 95% CI: 1.67 to 17.22) at 2 h, albeit with lower odds of achieving complete pain freedom. ROX-828 showed the highest improvement in freedom from photophobia at 2 h (OR: 4.03, 95% CI: 1.66 to 9.81). Dihydroergotamine nasal spray was significantly associated with the highest risk of AEs (OR: 9.65, 95% CI: 4.39 to 21.22) and was not recommended for routine use. Zavegepant nasal spray demonstrated the lowest risk of AEs (OR: 2.04, 95% CI: 1.37 to 3.03). The results of sensitivity analyses for the primary endpoints (pain freedom at 2 h and AEs) were generally consistent with those of the base case model. Conclusions Compared with other new intranasal-specific therapies in treating migraine attacks, zolmitriptan nasal spray 5 mg was the most effective agent for pain freedom at 2 h. Zavegepant nasal spray 10 mg had the fewest adverse side effects.

ObjectiveTo assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG).Methods28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed.ResultsThe frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy.ConclusionsAbnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.

Abstract Background The atherogenic index of plasma (AIP) is an important alternative metabolic biomarker of atherosclerosis and cardiovascular diseases. Nevertheless, the correlation between the AIP and carotid atherosclerosis is unknown among the general population. Methods A total of 52,380 community residents, aged ≥ 40 years who underwentcervical vascular ultrasound from December 2017 to December 2020 in Hunan China, were selected for retrospective analysis. The AIP was calculated as a logarithmically converted ratio of triglycerides (TG) to high-density lipoprotein-cholesterol (HDL-C). The participants were divided into AIP quartile groups (Q1-Q4). Logistic regression models and restricted cubic spline analyses were used to examine the association of the AIP with carotid atherosclerosis. Stratified analyses were applied to control for confounding factors. The incremental predictive value of the AIP was further assessed. Results After adjusting for traditional risk factors, an increased AIP was associated with a higher rate of carotid atherosclerosis (CA), increased carotid intima-media thickness (CIMT), and plaques [odds ratio, OR (95% confidence interval, CI): 1.06 (1.04, 1.08), 1.07 (1.05, 1.09), and 1.04 (1.02, 1.06) per 1-SD increase in the AIP, respectively]. Compared with those participants in the quartile 1 group, those in the quartile 4 group had a greater risk of CA [OR 1.18, 95% CI (1.12, 1.25)], increased CIMT [OR 1.20, 95% CI (1.13, 1.26)], and plaques [OR 1.13, 95% CI (1.06, 1.19)]. However, we did not observe an association between the AIP and stenosis [0.97 (0.77, 1.23), p for trend = 0.758]. Restricted cubic spline analyses also showed a cumulative increase in the risk of CA, increased CIMT, and plaques but not stenosis severity (> 50%) with an increase of the AIP. Subgroup analyses showed that a more significant association between the AIP and the prevalence of increased CA was detected in younger subjects (aged

IntroductionThis study aimed to study the therapeutic effects of ofatumumab in patients with myasthenia gravis (MG) in addition to the immunomodulatory effects on peripheral follicular T helper (Tfh) cells and T helper type 17 (Th17) cells.MethodsThirty-one patients with anti-acetylcholine receptor (AChR) antibody-positive MG were included in this study. At weeks 0, 1, 2, and 4, an initial dose of 20 mg of ofatumumab was injected subcutaneously, with a 2-month follow-up after completing this first cycle. At baseline, 1 month, and 3 months, we assessed the Quantitative MG (QMG), 15-item MG-Quality of Life (MG-QOL15), and MG-Activities of Daily Living (MG-ADL) scales and measured the frequencies of Tfh, Th17, and B cells and the levels of anti-AChR antibody, IL-6, IL-21, and IL-17 in the peripheral blood.ResultsAt 1 month and 3 months, the QMG, MG-QOL15, and MG-ADL scores were all significantly reduced. At 3 months, doses of prednisone were reduced by an average of 37%. Decreased frequencies of Tfh and Th17 cells, depletion of B cells, and reduced levels of IL-6, IL-21, and IL-17 were all observed at 1 month or 3 months.DiscussionTherefore, the therapeutic effect of ofatumumab could be detected after one cycle of treatment, which was maintained for 2 months. The immunomodulatory effect of ofatumumab during the observation period may involve depletion of B cells, reduction of Tfh and Th17 cells frequencies, and reduced levels of IL-6, IL-21, and IL-17. The findings provide novel data for the potential application of ofatumumab in MG.

BackgroundSeveral easily and inexpensively measured indicators of visceral adiposity dysfunction are currently available, but it remains unclear whether they are correlated with stroke risk in the community-dwelling population. We aimed to examine the longitudinal association of the triglyceridemic-waist phenotypes, the triglyceride glucose (TyG) index, as well as TyG-related indicators with stroke risk.MethodsIn this study, we conducted a prospective cohort study in Hunan, a region located in Central China, where the prevalence of stroke is relatively high. We included a total of 20185 subjects aged ≥40 years between November 2017 and December 2018. Triglyceride glucose-body mass index (TyG-BMI) and triglyceride glucose-waist circumference (TyG-WC) were calculated as multiplying TyG index by BMI and WC, respectively. Triglyceride waist phenotypes were categorized into four phenotypes: HTGW (elevated triglyceride and enlarged WC), NTNW (normal triglyceride and normal WC); HTNW (high triglyceride and normal WC), and NTGW (normal triglyceride and enlarged WC). We constructed a multivariable Cox regression model to assess the association between these novel lipid indicators and the risk of stroke. Subgroup analysis was conducted to test the robustness of our research findings. ROC curve was used for assessing the predictive ability of different stroke risk indices.ResultsAfter 2 years of follow- up, 135 participants experienced new stroke events. After adjusting for potential confounders, we found that participants with HTGW had higher likelihood of stroke (HR: 1.96, 95% CI: 1.21 to 3.16). However, we did not find significant associations for HTNW (HR: 1.42, 95% CI: 0.91 to 2.21) and NTGW (HR: 1.09, 95% CI 0.67 to 1.78). when compared to participants in the first TyG quartile, those in the fourth TyG quartile were associated with a 2.06-fold (95% CI: 1.22, 3.50) risk of stroke. Each 1-SD increase in TyG, TyG-BMI, and TyG-WC was associated with a higher risk of stroke, with adjusted HRs of 1.34 (95% CI: 1.11 to 1.61), 1.35 (95% CI: 1.14 to 1.59), and 1.23 (95% CI: 1.04 to 1.46), respectively. In subgroup analyses, those positive relationships appeared to be stronger among male participants with lower levels of physical activity and smoking.ConclusionHTGW, along with higher levels of TyG and TyG-related indicators, were found to be associated with an elevated risk of stroke. HTGW and these novel lipid indicators might be reliable indicators to identify populations at elevated risk of stroke.

Abstract The precise detection and interpretation of pathogenic DYSF variants are sometimes challenging, largely due to rare deep‐intronic splice‐altering variants. Here, we report on the genetic diagnosis of a male patient with dysferlinopathy. He remained genetically unsolved after routine exonic detection approaches that only detected a novel heterozygous frameshift variant (c.407dup, p.Thr137Tyrfs*11) in DYSF exon 5. Via muscle‐derived DYSF mRNA studies, we identified a novel deep‐intronic DYSF variant in the other allele (c.1397 + 649C > T), which causing in‐frame alterations in DYSF mRNA and protein structure and confirmed his genetic diagnosis of dysferlinopathy. Our study emphasizes the potential role of undetected deep‐intronic splice‐altering variants in monogenic diseases.

Giant cell arteritis (GCA) is a kind of systemic vasculitis affecting individuals over 50 years old and is often the cause of new-onset headaches in older adults. Patients with GCA sometimes have rheumatic polymyalgia (PMR). The diagnosis of GCA generally depends on clinical manifestation, elevated erythrocyte sedimentation rate (ESR) or C-reactive protein, and positive imaging findings commonly obtained by ultrasound or temporal artery biopsy. In this study, we report a case of an 83-year-old woman with a new-onset headache and an elevated ESR. The result of the temporal artery ultrasound did not distinguish between vasculitis and atherosclerosis. The F18-fluorodeoxyglucose positron emission tomography and computed tomography (18F FDG PET-CT) were performed and suggested large vessel vasculitis with temporal artery involvement. In addition, polyarticular synovitis and bursitis were also revealed. Finally, the diagnosis of secondary headache attributed to CGA complicated with PMR was established. The patient experienced remission of symptoms after glucocorticoid therapy. PET can become a powerful tool for diagnosis and differential diagnosis when the ultrasound result is ambiguous and a biopsy is not obtained.

BackgroundAnxiety and depression are the most common psychiatric comorbidities in migraine, but their impact on the risk of developing migraine and their gender and age differences are unclear, and research on their associations with migraine-related burdens are limited.ObjectiveTo systematically explore the association between anxiety and depression with migraine and migraine-related burdens, including the risk of developing migraine, as well as migraine frequency, severity, disability, headache impact, quality of life and sleep quality.MethodsA total of 170 migraineurs and 85 sex-and age-matched healthy control subjects were recruited consecutively for this study. Anxiety and depression were assessed using Zung’s Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS), respectively. Logistic regression and linear regression analyses were used to explore the associations between anxiety and depression with migraine and its burdens. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SAS score and SDS score on migraine and its severe burdens.ResultsAfter adjusting for confounders, anxiety and depression remained significantly associated with an increased risk of developing migraine, with odds ratios of 5.186 (95% CI:1.755–15.322) and 3.147 (95% CI:1.387–7.141), respectively. Meanwhile, there were significant additive interactions between the association of anxiety and depression with the risk of developing migraine in gender and age (P for interaction

ObjectiveThe aim of the study was to investigate the clinical, neuropsychological, and regional cerebral blood flow (rCBF) perfusion changes in patients with neuropsychiatric symptoms caused by nitrous oxide (N2O) abuse.MethodsA total of 16 patients with neuropsychiatric symptoms caused by nitrous oxide abuse were recruited for this study. The study was carried out in the withdrawal phase of N2O abuse. A 925–1110 MBq 99mTc-ECD was administered intravenously. SPECT/CT images were collected with a low-energy and high-resolution collimator. The region uptake statistics of different brain regions of interest between patients with N2O abuse and normal people of the databases for younger subjects from the Scenium DB Comparison software were calculated automatically.ResultsThe clinical manifestations of the 16 patients with neuropsychiatric symptoms were mood lability, anxiety, hallucination, delusion, agitation, confusion, and other psychiatric symptoms. In addition, 15 of the patients also complained of memory decline; 14 patients manifested numbness or paresthesia; 14 patients developed limb weakness, and their motor impairments were more severe in the lower limbs than in the upper limbs; and eight patients had urinary and defecation disturbances. In the neuropsychological examination, the BPRS score was 54.69 ± 11.48, the HAMD score was 30.00 ± 11.06, the HAMA score was 18.06 ± 5.77, the MMSE score was 28.06 ± 2.29, and the MoCA score was 25.06 ± 3.40. SPECT showed hypoperfusion in the frontal and temporal lobes, which is consistent with the clinical findings.ConclusionThis was the first study to demonstrate the obvious effect of N2O abuse on CBF in patients with neuropsychiatric symptoms. CBF perfusion imaging is helpful to detect the changes in the local brain functional activity in patients with N2O abuse.

BackgroundThe relationship between sleep and migraine is well known to be bidirectional. However, few studies have systematically assessed the association between sleep quality and the risk of developing migraine, and its gender and age differences are unclear. And there is currently limited evidence on the associations between sleep quality and migraine-related burdens.ObjectiveThe objectives of this study were to: (1) explore the association between sleep quality and the risk of developing migraine, and its gender and age differences; (2) investigate the associations between sleep quality and the total pain burden, severity, disability, headache impact, quality of life, anxiety, and depression of migraine patients.MethodsThis study consecutively enrolled 134 migraine patients and 70 sex- and age-matched healthy control subjects. Sleep quality was assessed through the Pittsburgh Sleep Quality Index (PSQI). Logistic regression and linear regression analyses were used to explore the associations between sleep quality with the risk of developing migraine and the migraine-related burdens.ResultsThe prevalence of poor sleep quality in migraine patients was significantly higher than that in subjects without migraine (P < 0.001). After adjusting for various confounding factors, the risk of migraine with poor sleep quality remained 3.981 times that of those with good sleep quality. The subgroup analysis showed that there were significant additive interactions between poor sleep quality and the risk of migraine in gender, age, and education level (P for interaction < 0.05), and the stronger correlations were found in females, populations with ages more than 35 years old, and with lower education levels. In addition, multivariate linear regression analysis showed that poor sleep quality was significantly and independently associated with the total pain burden, severity, headache impact, quality of life, anxiety, and depression in migraine patients (P trend < 0.05).ConclusionPoor sleep quality was significantly independently associated with an increased risk of developing migraine and the migraine-related burdens. Strengthening PSQI assessment is valuable for the early prevention and treatment of migraine patients.

Background and PurposeDiagnosing cervical artery dissection (CAD) is still a challenge based on the current radiographic criteria. This study aimed to assess the value of three-dimensional high-resolution magnetic resonance imaging (3D HRMRI) in the detection of the signs of CAD and its diagnosis.Materials and MethodsPatients with CAD from January 2016 to January 2021 were recruited from our 3D HRMRI database. The signs of dissection (intramural hematomas, intimal flap, double lumen), length and location of the dissection, thickness of the intramural hematoma, intraluminal thrombus, and percentage of dilation of the outer contour of the dissection on 3D HRMRI were assessed.ResultsFourteen patients with 16 CADs, including 12 carotid CADs and 4 vertebral CADs, were finally diagnosed in this study. On 3D HRMRI, intramural hematomas were detected in 13/16 (81.3%) lesions with high sensitivity (100%) and high specificity (100%). Intimal flaps were found in 9/16 (56.3%) lesions with moderate sensitivity (64.3%) and high specificity (88.9%). Double lumen signs were observed in 4/16 (25.0%) lesions with high sensitivity (80.0%) and high specificity (100%). In addition, concomitant intraluminal thrombus were detected in 4/16 (25.0%) lesions with high sensitivity (80.0%) and high specificity (100%). The mean length of dissection was (25.1 ± 13.7) mm. The mean thickness of the intramural hematoma was (4.3 ± 2.3) mm. The mean percentage of dilation for the outer contour of the dissection was (151.3 ± 28.6)%.ConclusionThe 3D HRMRI enables detection of the dissecting signs, such as intramural hematoma, intimal flap, double lumen, and intraluminal thrombus with high sensitivity and specificity, suggesting a useful, and non-invasive tool for definitively diagnosing CAD.

Intracranial atherosclerotic stenosis is one of the main causes of ischemic stroke and transient ischemic attack. High-resolution magnetic resonance imaging allows us to directly observe the intracranial artery wall, accurately assess the condition of the vascular wall, and quantitatively analyze the vascular wall and intracranial atherosclerotic plaque load. We report a case of acute cerebral infarction with left middle cerebral artery stenosis. During the first 3 weeks, the patient was treated with aspirin 100 mg and clopidogrel 75 mg daily. Afterwards, the patient continued to be given aspirin, and cilostazol 100 mg twice daily was given instead of clopidogrel. After 24 months of follow-up, we observed a significant reversal of intracranial atherosclerotic plaque using high-resolution MRI (HR-MRI) and discussed the advantages of HR-MRI in evaluating drug therapy for intracranial atherosclerotic plaque.

Abstract Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO ( http://www.crd.york.ac.uk/PROSPERO ), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Citation Index Expanded) for relevant studies up to 31 May 2019. We included clinical trials which compared efficacy outcomes (measured by National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) and safety outcomes (such as death and adverse effects) between the stem cell-based therapies and control in ischemic stroke. We performed random effect meta-analysis using Review Manager 5.3. Our review included nine randomized controlled trials (RCTs) and seven non-randomized studies (NRSs), involving 740 participants. Stem cell-based therapies were associated with better outcomes measured by NIHSS (mean difference (MD) − 1.63, 95% confidence intervals (CI) − 2.73 to − 0.53, I 2 =60%) and BI (MD 14.68, 95% CI 1.12 to 28.24, I 2 = 68%) in RCTs, and by BI (MD 6.40, 95% CI 3.14 to 9.65, I 2 = 0%) in NRSs. However, the risk of bias was high and the efficacy outcomes of RCTs were high heterogeneity. There was no significant difference in mortality between the stem cell group and the control group. Fever, headache, and recurrent stroke were the most frequently reported adverse effects. Our review shows that stem cell-based therapies can improve the neurological deficits and activities of daily living in patients with ischemic stroke.

ObjectivesThis study analyzed differences in the mean cerebral blood flow (mCBF) and arterial transit time (ATT) of the anterior and posterior circulations between patients with intracranial atherosclerotic stenosis (ICAS) and control subjects. We also investigated the correlation between ATT and mCBF in the two groups, and evaluated whether the blood flow velocity of the extracranial carotid/vertebral arteries can influence mCBF.MethodsA total of 32 patients with ICAS were prospectively enrolled at the Radiology Department of the China-Japan Friendship Hospital between November 2020 and September 2021. All patients had extensive arterial stenosis, with 17 having cerebral arterial stenosis in the anterior circulation and 15 in the posterior circulation. Thirty-two healthy subjects were enrolled as a control group. Enhanced arterial spin labeling (eASL) imaging was performed using a 3.0-T GE magnetic resonance imaging scanner, and all patients underwent carotid and vertebral Doppler ultrasound examinations. CereFlow software was used for post-processing of the eASL data, to obtain cerebral perfusion parameters such as mCBF and ATT. Independent samples t-tests were used to analyze and compare mCBF and ATT of the anterior circulation (frontal lobe, parietal lobe, and insula) and posterior circulation (occipital lobe, cerebellum) between the patient and control groups. The relationships of ATT and mCBF in the two groups were evaluated with Pearson’s correlation. The blood flow velocity of the extracranial internal carotid/vertebral arteries, including the peak systolic velocity (PSV), end diastolic velocity (EDV), mean PSV (mPSV), and mean EDV (mEDV), was compared between the control and study groups using t-tests. Multiple linear regression analysis was then applied to determine the factors associated with mCBF in the two groups.ResultsThe mCBFs of the anterior and posterior circulations in the patient group were lower than those of the control group. The ATTs in the patient group were all significantly longer than those of the control group (p < 0.05). Except for the insula in the control group, significant correlations were found between ATT and mCBF in all other investigated locations in the two groups (p < 0.05). The blood flow velocity of the extracranial internal carotid/vertebral arteries differed significantly between the control and patient groups (p < 0.05). The multiple linear regression analysis revealed that in patients with ICAS, mPSV of the vertebral arteries and local ATT correlated with mCBF of the occipital lobes and the cerebellum, respectively (p < 0.05). In contrast, there was no significant correlation within the anterior circulation (frontal lobes, parietal lobes, and insula).ConclusionThere was a significant relationship between ATT and mCBF in patients with ICAS. Extracranial blood flow may influence intracranial hemodynamics in the posterior circulation in patients with ICAS. The maintenance of extracranial blood flow is of great significance in the preservation of intracranial hemodynamics.

ObjectivesTo evaluate the difference between low-molecular-weight heparin (LMWH) and aspirin in preventing early neurological deterioration (END) and recurrent ischemic stroke (RIS), post-recovery independence, and safety outcomes in acute ischemic stroke.Materials and MethodsWe performed systematic searches of the PubMed, Embase, Web of Science, and Cochrane Library databases for full-text articles of randomized controlled trials (RCTs) of LMWH vs. aspirin in the early management of acute ischemic stroke. Information on study design, eligibility criteria, baseline information, and outcomes was extracted. Synthesized relative risks (RRs) with 95% confidence intervals (CIs) are used to present the differences between the two treatments based on fixed-effects models.ResultsFive RCTs were retrieved from the online databases. The results showed no significant difference in efficacy outcomes between the two groups among unselected patients. Subgroup analysis showed that LMWH was significantly related to a lower incidence of END events [relative risk (RR): 0.44, 95% confidence interval (CI): 0.35–0.56] and reduced occurrence of RIS during treatment (OR: 0.34, 95% CI: 0.16–0.75) in non-cardioembolic stroke. LMWH significantly increased the number of patients with a modified Rankin scale (mRS) score of 0–1 at 6 months in patients with large-artery occlusive disease (LAOD) (RR: 0.50, 95% CI: 0.27–0.91). LMWH had a similar effect on symptomatic intracranial hemorrhage (sICH) and major extracranial hemorrhage during treatment to that of aspirin, except that LMWH was related to an increased likelihood of extracranial hemorrhage.ConclusionsIn patients with acute non-cardioembolic ischemic stroke, especially that with large-artery stenosis, LMWH treatment significantly reduced the incidence of END and RIS, and improved the likelihood of independence (mRS 0–1) at 6 months compared with those with aspirin treatment. LMWH was related to an increased likelihood of extracranial hemorrhage among all patients; however, the difference in major extracranial hemorrhage and sICH was not significant. Choosing the appropriate patients and paying attention to the start time and duration of treatment are very important in the use of anticoagulation.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier CRD42020185446.

Abstract Background Two-dimensional high-resolution MRI (2D HRMRI) faces many technical challenges for fully assessing morphologic characteristics of inherent tortuous basilar arteries. Our aim was to investigate remodeling mechanisms and plaque distribution in symptomatic patients with basilar artery stenosis on three-dimensional (3D) HRMRI. Methods Forty-six consecutive patients with symptomatic basilar artery atherosclerotic stenosis on MRA (70–99%) were enrolled. The remodeling index (RI) was the ratio of vessel area at the maximal-lumen-narrowing (MLN) site to reference vessel area. RI ≥ 1.05 was defined as positive remodeling (PR), RI ≤ 0.95 as negative remodeling (NR), and 0.95 < RI < 1.05 as intermediate remodeling (IR). The remodeling patterns were divided into two groups (PR and non-PR [NR and IR]). The cross-sectional and longitudinal distribution of BA plaques were evaluated. Results Two patients were excluded because of poor-quality images. Images of 44 patients were available for measurements. PR was found in 23 (52.3%) patients, and non-PR in 21 (47.7%) patients. At the MLN sites, vessel area, wall area, plaque size and percentage of plaque burden of PR group were significantly greater than non-PR group (p < .001). Most plaques (90.9%) of the 44 patients were located at the dorsal, left and right walls. For the longitudinal distribution of plaque, 8 (18.2%) and 36 (81.8%) plaques were located in BA proximal and distal to AICA, respectively. Most plaques (68.2%) were eccentrically distributed. Conclusions 3D HRMRI with postprocessing multiple planar reconstruction is able to evaluate the remodeling pattern and plaque distribution of basilar artery atherosclerotic stenosis, which might be used to guide intracranial intervention.

The floating plaque in carotid artery is an uncommon condition that can be detected by a duplex ultrasonography scan and is a high-risk factor for embolic cerebrovascular disease. The histopathological features of floating plaque in carotid artery vary. To the best of our knowledge, there is still considerable controversy about the treatment of floating carotid plaque. In this case, the floating carotid plaque was located in the edge of atherosclerotic plaque in common carotid artery, pathological finding following carotid endarterectomy confirmed that the mobile substances were formed by the contents of the plaque protruding into the carotid lumen after the rupture of the fibrous cap, without mural thrombus. This pathological change was different from those of the mobile substances, which were commonly considered as mural thrombotic substances of ulcer plaque caused by the ruptures of fibrous cap of vulnerable plaque. According to pathological differences, we investigated pathogenesis of ischemic cerebrovascular disease caused by floating carotid plaque and possible treatments.

Atherosclerosis is a chronic inflammatory disease caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a critical factor at all stages of atherosclerosis progression. Proinflammatory cytokines accelerate atherosclerosis progression, while anti-inflammatory cytokines ameliorate the disease. Accordingly, strategies to inhibit immune activation and impede immune responses towards anti-inflammatory activity are an alternative therapeutic strategy to conventional chemotherapy on cardiocerebrovascular outcomes. Since a number of Chinese medicinal plants have been used traditionally to prevent and treat atherosclerosis, it is reasonable to assume that the plants used for such disease may suppress the immune responses and the resultant inflammation. This review focuses on plants that have immunomodulatory effects on the production of inflammatory cytokine burst and are used in Chinese traditional medicine for the prevention and therapy of atherosclerosis.

The C1q complement/TNF-related protein (CTRP) superfamily, which includes the adipokine adiponectin, has been shown in animal models to have positive metabolic and cardiovascular effects. We sought to investigate circulating CTRP1, CTRP9, CTRP12 and CTRP13 concentrations in persons with type 2 diabetes mellitus (T2DM), with age and BMI matched controls, and to examine the effects of a 2 hour 75g oral glucose tolerance test (OGTT) on serum CTRP1, CTRP9, CTRP12 and CTRP13 levels in persons with T2DM.Cross-sectional study [newly diagnosed T2DM (n = 124) and control (n = 139) participants]. Serum CTRP1, CTRP9, CTRP12 and CTRP13 were measured by ELISA.Systolic and diastolic blood pressure, total cholesterol (TCH), Low-density lipoprotein (LDL)-cholesterol, triglycerides, TCH/High-density lipoprotein (HDL) ratio, triglycerides/HDL ratio, glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), C-reactive protein and endothelial lipase were significantly higher, whereas leptin and adiponectin were significantly lower in T2DM participants. Serum CTRP1 were significantly higher and CTRP12 significantly lower in T2DM participants. Age, diastolic blood pressure, glucose and CTRP12 were predictive of serum CTRP1; leptin was predictive of serum CTRP9; glucose and CTRP1 were predictive of serum CTRP12; endothelial lipase was predictive of serum CTRP13. Finally, serum CTRP1 were significantly higher and CTRP12 significantly lower in T2DM participants after a 2 hour 75g OGTT.Our data supports CTRP1 and CTRP12 as potential novel biomarkers for the prediction and early diagnosis of T2DM. Furthermore, pharmacological agents that target CTRP1 and CTRP12 could represent a new strategy in the treatment of T2DM.

Objective: Unknown etiology. Background: Spinal cord arteriovenous fistula that only manifests as lower back pain is easily misdiagnosed as myofasciitis, lumbar spondylosis, and other diseases, and incorrect treatment such as glucocorticoid blockade might be given, leading to worsening of the condition. Case Report: We analyze the clinical characteristics of a patient with spinal dural arteriovenous fistula who presented with chronic-onset low back pain. A patient with spinal dural arteriovenous fistula presented with chronic-onset low back pain as the only symptom, and was misdiagnosed as having myofasciitis. We assessed the paraclinical data, clinical reasoning, and course of treatment. The patient was an elderly man with low back pain for 1 year. He was diagnosed with myofasciitis in a local hospital and received local blocking treatment using glucocorticoid, and left lower-limb weakness appeared after that. After he was admitted to our hospital, enhanced thoracic and lumbar magnetic resonance imaging and selective spinal angiography were performed, and the results indicated the diagnosis of spinal dural arteriovenous fistula. After surgical treatment, the low back pain and lower-limb weakness were alleviated, and the patient is still under follow-up. Conclusions: The possibility of spinal dural arteriovenous fistula should not be overlooked among patients with chronic low back pain, and caution should be taken when using glucocorticoids for treatment of chronic low back pain. [ABSTRACT FROM AUTHOR]