Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion.

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.

Development of Broad-Spectrum Nanobodies for the Therapy and Diagnosis of SARS-CoV-2 and Its Multiple Variants.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evaded the efficacy of previously developed antibodies and vaccines, thus remaining a significant global public health threat. Therefore, it is imperative to develop additional antibodies that are capable of neutralizing emerging variants. Nanobodies, as the smallest functional single-domain antibodies, exhibit enhanced stability and penetration ability, enabling them to recognize numerous concealed epitopes that are inaccessible to conventional antibodies. Herein, we constructed an immune library based on the immunization of alpaca with the S1 subunit of the SARS-CoV-2 spike protein, from which two nanobodies, Nb1 and Nb2, were selected using phage display technology for further characterization. Both nanobodies, with the binding residues residing within the receptor-binding domain (RBD) region of the spike, exhibited high affinity toward the S1 subunit. Moreover, they displayed cross-neutralizing activity against both wild-type SARS-CoV-2 and 10 ο variants, including BA.1, BA.2, BA.3, BA.5, BA.2.75, BF.7, BQ.1, EG.5.1, XBB.1.5, and JN.1. Molecular modeling and dynamics simulations predicted that both nanobodies interacted with the viral RBD through their complementarity determining region 1 (CDR1) and CDR2. These two nanobodies are novel tools for the development of therapeutic and diagnostic countermeasures targeting SARS-CoV-2 variants and potentially emerging coronaviruses.

The proteomic analysis uncovers the cellular responses to the African swine fever virus membrane proteins p54, p17, and pB117L.

African swine fever virus (ASFV) infection causes African swine fever (ASF), a highly contagious and fatal disease that poses severe threat to swine production. To gain insights into the host responses to ASFV, we generated recombinant adenovirus Ad5 expressing viral membrane proteins p54, p17, and pB117L individually and infected an alveolar cell line, 3D4/21, with these recombinant viruses. Then, the cell lysates were analyzed using label-free quantification proteomic analysis method. A total of 2158 differentially expressed proteins (DEPs) were identified, of which 817, 466, and 875 proteins were from Ad5-p54-, Ad5-p17-, Ad5-pB117L-infected 3D4/21 cells, respectively. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed distinct yet interconnecting patterns of protein interaction networks. Specifically, the Ad5-p54 virus infection enriched the DEPs primarily involved in the metabolic pathways, endocytosis, adherens junction, and SNARE interactions in vesicular transport. The Ad5-p17 virus infection enriched the DEPs in endocytosis, ubiquitin-mediated proteolysis, N-Glycan biosynthesis, and apoptosis, while the Ad5-pB117L virus infection enriched the DEPs in metabolic pathways, endocytosis, oxidative phosphorylation, and focal adhesion. In summary, these results provide a comprehensive proteinomics analysis of the cellular responses to three ASFV membrane proteins, thus facilitating our understanding of ASFV pathogenesis.

Effect of collateral circulation in patients with multiple craniocervical artery stenoses.

Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long-term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro-basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743-0.857, p < 0.001; Tan scores: OR: 0.478, 95% CI: 0.336-0.679, p < 0.001). Meanwhile, the collateral circulation scores were significantly associated with the recurrence of AIS within 3 years (rLMC scores: OR: 0.926, 95% CI: 0.860-0.997, p = 0.042; Tan scores: OR: 0.467, 95% CI: 0.306-0.712, p < 0.001). Most associations remained significant in the subgroup of patients with VBA stenosis. Favorable collateral circulation in multiple craniocervical artery stenosis patients reduced long-term ischemic event recurrence. Stratifying treatment risks is essential for optimizing outcomes.

Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke.

Synaptotagmin III (Syt3) is a Ca2+-dependent membrane-traffic protein that is highly concentrated in synaptic plasma membranes and affects synaptic plasticity by regulating post-synaptic receptor endocytosis. Here, we show that Syt3 is upregulated in the penumbra after ischemia/reperfusion (I/R) injury. Knockdown of Syt3 protects against I/R injury, promotes recovery of motor function, and inhibits cognitive decline. Overexpression of Syt3 exerts the opposite effects. Mechanistically, I/R injury augments Syt3-GluA2 interactions, decreases GluA2 surface expression, and promotes the formation of Ca2+-permeable AMPA receptors (CP-AMPARs). Using a CP-AMPAR antagonist or dissociating the Syt3-GluA2 complex via TAT-GluA2-3Y peptide promotes recovery from neurological impairments and improves cognitive function. Furthermore, Syt3 knockout mice are resistant to cerebral ischemia because they show high-level expression of surface GluA2 and low-level expression of CP-AMPARs after I/R. Our results indicate that Syt3-GluA2 interactions, which regulate the formation of CP-AMPARs, may be a therapeutic target for ischemic insults.

GluA1 Degradation by Autophagy Contributes to Circadian Rhythm Effects on Cerebral Ischemia Injury.

The mechanisms of many diseases, including central nervous system disorders, are regulated by circadian rhythms. The development of brain disorders such as depression, autism, and stroke is strongly associated with circadian cycles. Previous studies have shown that cerebral infarct volume is smaller at night (active phase) than during the day (inactive phase) in ischemic stroke rodent models. However, the underlying mechanisms remain unclear. Increasing evidence suggests that glutamate systems and autophagy play important roles in the pathogenesis of stroke. Here, we report that GluA1 expression was decreased and autophagic activity was increased in active-phase male mouse models of stroke compared with the inactive-phase models. In the active-phase model, induction of autophagy decreased the infarct volume, whereas inhibition of autophagy increased the infarct volume. Meanwhile, GluA1 expression was decreased following activation of autophagy and increased following inhibition of autophagy. We used Tat-GluA1 to uncouple p62, an autophagic adapter, from GluA1 and found that this blocked the degradation of GluA1, an effect similar to that of inhibition of autophagy in the active-phase model. We also demonstrated that knock-out of the circadian rhythm gene Per1 abolished the circadian rhythmicity of the volume of infarction and also abolished GluA1 expression and autophagic activity in wild-type (WT) mice. Our results suggest an underlying mechanism by which the circadian rhythm participates in the autophagy-dependent regulation of GluA1 expression, which influences the volume of infarction in stroke.SIGNIFICANCE STATEMENT Circadian rhythms affect the pathophysiological mechanisms of disease. Previous studies suggested that circadian rhythms affect the infarct volume in stroke, but the underlying mechanisms remain largely unknown. Here, we demonstrate that the smaller infarct volume after middle cerebral artery occlusion/reperfusion (MCAO/R) during the active phase is related to lower GluA1 expression and activation of autophagy. The decrease in GluA1 expression during the active phase is mediated by the p62-GluA1 interaction, followed by direct autophagic degradation. In short, GluA1 is the substrate of autophagic degradation, which mainly occurs after MCAO/R during the active phase but not the inactive phase.

Daridorexant for the treatment of insomnia disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Daridorexant is a novel dual orexin receptor antagonist that has shown efficacy as a treatment for insomnia in multiple randomized clinical trials. However, the efficacy and safety of daridorexant for treatment of insomnia disorder has not been characterized comprehensively in the literature. Therefore, we performed a meta-analysis of available studies. We performed a meta-analysis to systematically evaluate the efficacy and safety of daridorexant for treatment of insomnia disorder. METHODS: MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials were systematically searched up to February 2022. Relative risk and standard mean difference were used to evaluate clinical outcomes. RESULTS: We pooled 2271 patients from 4 randomized clinical trials, and evaluated efficacy endpoints. We found that 50 mg of daridorexant was superior to placebo for 4 efficacy outcomes including wake time after sleep onset, latency to persistent sleep, subjective total sleep time, and Insomnia Daytime Symptoms and Impacts Questionnaire domain score (P < .05). In addition, there were no significant differences (P > .05) in adverse events between daridorexant and placebo. CONCLUSIONS: Different dosages of daridorexant were tested for treatment of insomnia; however, 5 and 10 mg are not available because of issues of suboptimal effectiveness. Daridorexant showed better efficacy and safety for treatment of insomnia disorder at doses of 25 and 50 mg.

Scalp block for postoperative pain after craniotomy: A meta-analysis of randomized control trials.

Background: Postoperative pain after craniotomy is an important clinical concern because it might lead to brain hyperemia and elevated intracranial pressure. Considering the side effects of opioid, several studies have been conducted to investigate the effect of local anesthetics, especially the scalp block, on postoperative pain. However, the strength of evidence supporting this practice for postoperative pain after craniotomy was unclear and the best occasion of scalp block was also not identified. Therefore, we conducted a meta-analysis to evaluate the efficacy, safety, and the best occasion of scalp block for postoperative pain after craniotomy. Methods: PubMed, Embase, and the Cochrane Library databases from database inception to October 10, 2021 were searched for all randomized controlled trials evaluating the effect of scalp block on postoperative pain after craniotomy. Data were assessed by StataMP 16 software. Results: A total of 12 studies were included. A random-effect model was used to analyze all data. Patients under scalp block earned fewer scores than the non-scalp block group in visual analogue scale at the very early period (MD = -1.97, 95% CI = -3.07 to -0.88), early period (MD = -1.84, 95% CI = -2.95 to -0.73) and intermediate period (MD = -1.16, 95% CI = -1.84 to -0.49). Scalp block could also significantly prolong the time of the first request of rescue analgesia and reduce the use of additional analgesics without a significant difference in the incidence of complications. Subgroup analysis showed there was no significant difference in analgesia effect between pre-incision scalp block and post-incision scalp block in all periods. Conclusion: Scalp block could lead to lower pain intensity scores, more time of the first request of rescue analgesia, and fewer analgesic drugs applied in the first 12 h after craniotomy. There was no significant difference between pre-incision and post-incision scalp block in the occurrence and severity of postoperative pain.

Repetitive transcranial magnetic stimulation combined with respiratory muscle training for pulmonary rehabilitation after ischemic stroke-A randomized, case-control study.

Respiratory muscle weakness often occurs after stroke, which can lead to pulmonary dysfunction (PD). Pulmonary dysfunction prolongs the length of hospital stay and increases the risk of death. In a prospective, randomized, case-control study, we used musculoskeletal ultrasonography (MSUS), and pulmonary function tester to objectively evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with respiratory muscle training (RMT) in the treatment of PD in patients with acute ischemic stroke. Sixty-two stroke patients with PD were recruited and eventually 60 patients participated in this study. The control group was treated with RMT, and the treatment group was treated with rTMS on the basis of RMT. Treatment occurred five times a week for 8 weeks. Before and after treatment, diaphragmatic thickness (DT), diaphragmatic thickening fraction (DTF) and diaphragmatic mobility (DM) in patients, bilateral chest wall were measured by MSUS. Meanwhile, FVC, FEV1, FEV1/FVC, PEF, and MVV tested by pulmonary function tester was used to evaluate the improvement of lung functional. activities of daily living (ADL) was used as an objective criterion to evaluate the overall functional recovery of patients before and after treatment. After treatment, DT, DTF, and DM values improved significantly in both the affected and unaffected sides. The FVC, FEV1, FEV1/FVC, PEF, MVV, and ADL were all increased after the treatment. Combined treatment showed a stronger increase than that by RMT treatment alone. The study preliminarily shows that rTMS and RMT could improve lung functional after acute ischemic stroke.

Association of concomitant headache with hypoperfusion in ischemic stroke: A multimodal CT-based study.

Previous investigations indicate that vessel wall elasticity may contribute to the occurrence of an ischemic stroke-associated headache. In this prospective study, the association between radiologic parameters of intracranial hemodynamic changes and concomitant headaches during the early phase of ischemic stroke was examined. Consecutive patients with acute ischemic stroke (AIS) from the First Affiliated Hospital of Soochow University were recruited and divided into two groups according to their questionnaire results and the International Classification of Headache Disorder 3 criteria. Baseline data, including stroke sub-types and neurological function, at admission and discharge were collected. Non-contrast computed tomography (CT), CT angiography, and CT perfusion were performed to assess intracranial hemodynamic changes. Multiple adjusted logistic models were used and possible confounding factors were included in sequential models. A total of 190 patients with AIS (93 headaches and 97 non-headache) were recruited. There were significant differences between the two groups in gender, hypertension, Alberta stroke program early CT score, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Furthermore, rCBV (adjusted odds ratio [OR] 0.160; 95% confidence interval [CI], 0.055-0.461; p < 0.001) and rCBF (adjusted OR, 0.309; 95% CI, 0.113-0.844; p < 0.05) were significantly associated with concomitant headache during the early phase of AIS in fully adjusted models. After adjusting for sociodemographic characteristics and other confounding factors, p values for the ORs were robust and intensified. Patients with lower rCBV and rCBF tended to experience the concomitant headache during the early phase of AIS. Regional hypoperfusion and microcirculation might play an important role in this separate clinical entity.

MicroRNA-133b-3p Targets Purinergic P2X4 Receptor to Regulate Central Poststroke Pain in Rats.

Central poststroke pain (CPSP) is a neuropathic pain syndrome that usually occurs after cerebrovascular accidents. Currently, the pathogenesis of CPSP is not fully understood. Purinergic P2X4 receptor (P2X4R) is implicated in neuropathic pain including CPSP. Herein, we demonstrated that the levels of microRNA-133b-3p (miR-133b-3p), which targets P2X4R transcripts, were significantly downregulated in the ventral posterolateral nucleus of the thalamus (VPL), cerebrospinal fluid (CSF), and plasma of CPSP rats. The expression levels of miR-133b-3p negatively correlated with the severity of allodynia. Genetic knockdown of P2X4R in the VPL protected CPSP rats against allodynia. Similarly, genetic overexpression of miR-133b-3p in the VPL reversed the allodynia established in CPSP rats via downregulation of P2X4R expression. Treatment using gabapentin in CPSP rats significantly restored the decreased miR-133b-3p expression in the VPL, CSF, and plasma and blocked allodynia in CPSP rats. The administration of an miR-133b-3p inhibitor into the VPL abolished the antiallodynic activity of gabapentin. This mechanism was associated with P2X4R expression and involved the endogenous opioid system. Human patients with CPSP showed decreased plasma levels of miR-133b-3p compared with those of control participants. Logistic regression analysis of our patient cohort showed that determining plasma levels of miR-133b-3p may be useful for CPSP diagnosis and treatment.

High serum complement component C4 as a unique predictor of unfavorable outcomes in diabetic stroke.

Previous studies demonstrated that diabetic stroke patients had a poor prognosis and excess complement system activation in the peripheral blood. In this study, the association of serum complement levels with the prognosis of diabetic stroke was examined. Patients with acute ischemic stroke were recruited and were divided into two groups according to their history of diabetes. Baseline data on the admission, including C3 and C4 were collected. Neurologic function at discharge was the primary outcome and was quantified by the National Institutes of Health Stroke Scale (NIHSS). A total of 426 patients with acute ischemic stroke (116 diabetic strokes and 310 non-diabetic strokes) were recruited in this study. There were significant differences between the two groups in hypertension, coronary disease, triglyceride, high-density lipoprotein cholesterol, fasting blood sugar, C4, and mortality rates. Furthermore, the values of complement protein levels were divided into tertiles. In the diabetic stroke group, serum C4 level at the acute phase in the upper third was independently associated with NIHSS score at discharge and concurrent infection. These associations were not significant in non-diabetic stroke. High serum C4 level at admission, as a unique significant predictor, was associated with unfavorable clinical outcomes in the diabetic stroke, independently of traditional risk factors.

Calcitonin Gene-Related Peptide Monoclonal Antibody Versus Botulinum Toxin for the Preventive Treatment of Chronic Migraine: Evidence From Indirect Treatment Comparison.

Background: The previously approved botulinum toxin and nowadays promising calcitonin gene-related peptide (CGRP) monoclonal antibody have shown efficacy for preventing chronic migraine (CM). However, there is no direct evidence for their relative effectiveness and safety. In this study, we conducted an indirect treatment comparison to compare the efficacy and safety of CGRP monoclonal antibody with botulinum toxin for the preventive treatment of chronic migraine. Methods: Up to August 31, 2020, we systematically searched PubMed, Embase, and Cochrane Library Central Register of Controlled Trials (Central). Weighted mean difference (WMD) and relative risk (RR) were used to evaluate clinical outcomes. Indirect treatment comparison (ITC) software was used to conduct indirect treatment comparison. Results: Ten studies were pooled with 6,325 patients in our meta-analysis. Both botulinum toxin and CGRP monoclonal antibody demonstrated favorable efficacy in the change of migraine days, headache days, HIT-6 score, and 50% migraine responder rate compared with placebo. In indirect treatment comparison, CGRP monoclonal antibody was superior to botulinum toxin in the frequency of acute analgesics intake (WMD = -1.31, 95% CI: -3.394 to 0.774, p = 0.02113), the rate of treatment-related adverse events (AEs) (RR = 0.664, 95% CI: 0.469 to 0.939, p = 0.04047), and the rate of treatment-related serious adverse events (RR = 0.505, 95% CI: 0.005 to 46.98, p < 0.001). Conclusion: For chronic migraine patients, CGRP monoclonal antibody was slightly better than botulinum toxin in terms of efficacy and safety. In the future, head-to-head trials would be better to evaluate the efficacy and safety between different medications in the prevention of chronic migraine.

Recent advances in the protective role of hydrogen sulfide in myocardial ischemia/reperfusion injury: a narrative review.

Hydrogen sulfide (H2S) is recognized to be a novel mediator after carbon monoxide and nitric oxide in the organism. It can be produced in various mammalian tissues and exert many physiological effects in many systems including the cardiovascular system. A great amount of recent studies have demonstrated that endogenous H2S and exogenous H2S-releasing compounds (such as NaHS, Na2S, and GYY4137) provide protection in many cardiovascular diseases, such as ischemia/reperfusion injury, heart failure, cardiac hypertrophy, and atherosclerosis. In recent years, many mechanisms have been proposed and verified the protective role exhibited by H2S against myocardial ischemia/reperfusion injury, and this review is to demonstrate the protective role of exogenous and endogenous H2S on myocardial ischemia/reperfusion injury.

P2X4R Contributes to Central Disinhibition Via TNF-α/TNFR1/GABAaR Pathway in Post-stroke Pain Rats.

Central post-stroke pain (CPSP) is a disabling condition in stroke patients. It is a type of neuropathic pain for which the mechanism and relevant drug pathways remain unknown. Inflammatory response and central disinhibition have been suggested recently. Our previous research has shown targeting P2X4 receptors (P2X4R) may be effective in the treatment of CPSP, but the downstream pathway of the P2X4R has not been studied. In this study, we found the increase in tumor necrosis factor alpha (TNF-α) level and endocytosis of surface gamma-aminobutyric acid a receptors (GABAaR) in CPSP, and these effects were inhibited by blocking P2X4R. Furthermore, antagonizing TNF-α can increase surface GABAaR expression and mechanical pain threshold. Meanwhile, knocking down TNFR1 but not TNFR2 reversed the endocytosis of surface GABAaR and alleviated mechanical allodynia. Thus, the neuropathic pain was mediated, in part, through P2X4R/TNF-α/TNFR1/GABAaR signaling, which was induced after stroke. PERSPECTIVE: P2X4R regulates the pathophysiological mechanism of CPSP through central disinhibition mediated by TNF-α/TNFR1. Our results suggest that modulation of P2X4R-TNF-α/TNFR1-GABAaR signaling could provide a new therapeutic strategy to treat CPSP.

TMEM175 mediates Lysosomal function and participates in neuronal injury induced by cerebral ischemia-reperfusion.

As the main organelles for the clearance of damaged proteins and damaged organelles, the function of lysosomes is crucial for maintaining the intracellular homeostasis of long-lived neurons. A stable acidic environment is essential for lysosomes to perform their functions. TMEM175 has been identified as a new K+ channel that is responsible for regulating lysosomal membrane potential and pH stability in neurons. This study aimed to understand the role of TMEM175 in lysosomal function of neurons and neuronal injury following cerebral ischemia-reperfusion (I/R). A middle-cerebral-artery occlusion/reperfusion (MCAO/R) model was established in adult male Sprague-Dawley rats in vivo, and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic ischemia-reperfusion (I/R) injury in vitro. We found that the protein level of TMEM175 decreased after cerebral I/R injury and that TMEM175 overexpression ameliorated MCAO/R-induced brain-cell death and neurobehavioral deficits in vivo. Furthermore, these results were recapitulated in cultured neurons. Acridine orange (AO) staining, as well as LysoSensor Green DND-189, cathepsin-B (CTSB), and cathepsin-D (CTSD) activities, showed that TMEM175 deficiency inhibited the hydrolytic function of lysosomes by affecting lysosomal pH. In contrast, TMEM175 upregulation reversed OGD/R-induced lysosomal dysfunction and impaired mitochondrial accumulation in cultured neurons. TMEM175 deficiency induced by cerebral I/R injury leads to compromised lysosomal pH stability, thus inhibiting the hydrolytic function of lysosomes. Consequently, lysosomal-dependent degradation of damaged mitochondria is suppressed and thereby exacerbates brain damage. Exogenous up-regulation of TMEM175 protein level could reverse the neuronal lysosomal dysfunction after ischemia-reperfusion.

Temporal Patterns of Vertigo and Migraine in Vestibular Migraine.

Vestibular migraine (VM) is a multidisciplinary disease under exploration. Multiple temporal patterns of vertigo and migraine make it difficult to diagnose VM, and their effect on the clinical features of VM is still unclear. Here we investigated the clinical features of VM under three temporal patterns. 172 VM patients were enrolled in this study and divided into three groups: 86 patients in group A had an earlier onset of migraine than vertigo, 35 patients in group B had an earlier onset of vertigo than migraine, and 51 patients in group C had concurrent vertigo and migraine. No significant difference was found among three groups regarding types, intensity and accompanying symptoms of the vestibular attack. Patients in group C presented higher frequency and longer duration of vertigo than group A and B, while patients in group A presented lower frequency and shorter duration of headaches than group B and C. Additionally, the frequency, duration, intensity and accompanying symptoms of headache in group A decreased significantly after the onset of vertigo, especially in women around menopause. We hypothesized that vestibular stimulation could inhibit the trigeminal pain pathway, while painful trigeminal stimulation could excite the vestibular system. Our findings may contribute to the clinical identification of VM and further clarification of its pathogenesis.

Alterations in Regional Homogeneity Assessed by fMRI in Patients with Migraine Without Aura.

The aim of this study was to investigate the alterations in regional homogeneity assessed by fMRI in patients with migraine without aura (MWoA). Fifty-six eligible MWoA patients and 32 matched healthy volunteers were enrolled in this study. MWoA patients were divided into three groups according to the headache days per month within 3 months: infrequent episodic migraine (IEM) group, frequent episodic migraine (FEM) group, and chronic migraine (CM) group. Data collection and rest-state fMRI examination were performed in all cases. The ReHo method was used to analyze the blood oxygen level dependent (BLOD) signals of the adjacent voxels in the brain regions of each patient, and the consistency of their fluctuations in the sequences of same time. Compared with normal controls, ReHo values of bilateral thalami, right insula and right middle temporal gyrus increased and both precentral gyri decreased in the IEM group; ReHo values of bilateral thalami and the right middle temporal gyrus increased; ReHo values of both anterior cingulate cortex, precentral gyri and putamen decreased in the FEM group. Compared with control group, ReHo values of left olfactory cortex, right hippocampus, parahippocampal gyrus, suboccipital gyrus and precuneus increased, both precentral gyri, precuneus, putamen and anterior cingulate cortex decreased in the CM group. Compared with IEM group, ReHo values of both putamen, left middle frontal gyrus, right superior frontal gyrus increased, and the left precuneus decreased in the FEM group. Compared with FEM group, ReHo values of left olfactory and left precuneus increased, and the right superior frontal gyrus, insula, middle temporal gyrus, thalami, both superior temporal gyri decreased in the CM group. In the IEM group, the changes of function focus on the regions associated with coding, conduction and regulation of pain signals. In the FEM group, functional alterations mainly concentrated on the regions associated with pain regulation and emotion cognition. In the CM group, the changes focus on the regions related to spatial attention and cognition, affective disorders and pain feedback, which may be associated with migraine production, development and chronification.