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Abstract Objective To delineate the structural connectome alterations in patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs). Background The pathogenesis of migraine chronification remains elusive, with structural brain network changes potentially playing a key role. However, there is a paucity of research employing graph theory analysis to explore changes in the whole brain structural networks in patients with CM and EM. Methods The individual structural brain connectome of 60 patients with CM, 34 patients with EM, and 39 healthy control participants were constructed by using deterministic diffusion-tensor tractography. Graph metrics including global efficiency, characteristic path length, local efficiency, clustering coefficient, and small-world parameters were evaluated to describe the topologic organization of the white matter structural networks. Additionally, nodal clustering coefficient and efficiency were considered to assess the regional characteristics of the brain connectome. A graph-based statistic was used to assess brain network properties across the groups. Results Graph theory analysis revealed significant disruptions in the structural brain networks of CM patients, characterized by reduced global efficiency, local efficiency, and increased characteristic path length compared to HCs. Additionally, CM patients exhibited significantly lower local efficiency than EM patients. Notably, the CM group demonstrated marked reductions in local clustering coefficient and nodal local efficiency in the frontal and temporal regions compared with the healthy control group and EM group. Nodal local efficiency can effectively distinguish CM from EM and HCs. Moreover, the disrupted topologic efficiency was significantly associated with attack frequency and MIDAS score in patients with migraine after Bonferroni correction. Conclusion Decreased structural connectivity in the frontal and temporal regions may serve as a neuroimaging marker for migraine chronification and disease progression, providing valuable insights into the pathophysiology of chronic migraine.

Abstract Background New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH. Methods The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features. Results T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression. Conclusions Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.

Abstract Background The brain functional network topology in new daily persistent headache (NDPH) is not well understood. In this study, we aim to assess the cortical functional network topological characteristics of NDPH using non-invasive neural signal recordings. Methods Resting-state magnetoencephalography (MEG) was used to measure power fluctuations in neuronal oscillations from distributed cortical parcels in 35 patients with NDPH and 40 healthy controls (HCs). Their structural data were collected by 3T MRI. Functional connectivity (FC) of neural networks from 1 to 80 Hz frequency ranges was analyzed with topographic patterns and calculated network topological parameters with graph theory. Results In the delta (1–4 Hz) and beta (13–30 Hz) bands, the lateral occipital cortex and superior frontal gyrus FC were increased in NDPH groups compared to HCs. Graph theory analysis revealed that the NDPH had significantly increased global efficiency in the delta band and decreased nodal clustering coefficient (left medial orbitofrontal cortex) in the theta (4–8 Hz) band. The clinical characteristics had a significant correlation with network topological parameters. Age at onset of patients showed a positive correlation with global efficiency in the delta band. The degree of depression of patients showed a negative correlation with the nodal clustering coefficient (left medial orbitofrontal cortex) in the theta band. Conclusion The FC and topology of NDPH in brain networks may be altered, potentially leading to cortical hyperexcitability. Moreover, medial orbitofrontal cortex is involved in the pathophysiological mechanism of depression in patients with NDPH. Increased FC observed in the lateral occipital cortex and superior frontal gyrus during resting-state MEG could serve as one of the imaging characteristics associated with NDPH.

Abstract Background Preliminary evidence suggests that several headache disorders may be associated with glymphatic dysfunction. However, no studies have been conducted to examine the glymphatic activity in migraine chronification. Purposes To investigate the glymphatic activity of migraine chronification in patients with episodic migraine (EM) and chronic migraine (CM) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Methods In this cross-sectional study, patients with EM, CM, and healthy controls (HCs) were included. All participants underwent a standard brain magnetic resonance imaging (MRI) examination. Bilateral DTI-ALPS indexes were calculated for all participants and compared among EM, CM, and HC groups. Correlations between the DTI-ALPS index and clinical characteristics were analyzed. Results A total of 32 patients with EM, 24 patients with CM, and 41 age- and sex-matched HCs were included in the analysis. Significant differences were found in the right DTI-ALPS index among the three groups (p = 0.011), with CM showing significantly higher values than EM (p = 0.033) and HCs (p = 0.015). The right DTI-ALPS index of CM group was significantly higher than the left DTI-ALPS index (p = 0.005). And the headache intensity was correlated to DTI-ALPS index both in the left hemisphere (r = 0.371, p = 0.011) and in the right hemisphere (r = 0.307, p = 0.038), but there were no correlations after Bonferroni correction. Conclusions Glymphatic system activity is shown to be increased instead of impaired during migraine chronification. The mechanism behind this observation suggests that increased glymphatic activity is more likely to be a concomitant phenomenon of altered vascular reactivity associated with migraine pathophysiology rather than a risk factor of migraine chronification.

Abstract Background Amygdala, an essential element of the limbic system, has served as an important structure in pain modulation. There is still a lack of clarity about altered cerebral perfusion of amygdala in migraine. This study aimed to investigate the perfusion variances of bilateral amygdala in episodic migraine (EM) and chronic migraine (CM) using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). Methods Twenty-six patients with EM, 55 patients with CM (33 CM with medication overuse headache (MOH)), and 26 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL MR imaging to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The CBF and aCBV values in the bilateral amygdala were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. Results Compared with HC participants, patients with CM were found to have increased CBF and aCBV values in the left amygdala, as well as increased CBF values in the right amygdala (all P 0.05). In patients with CM, the increased perfusion parameters of bilateral amygdala were positively correlated with MIDAS score after adjustments for age, sex, and body mass index (BMI). Conclusion Hyperperfusion of bilateral amygdala might provide potential hemodynamics evidence in the neurolimbic pain network of CM.

Abstract Background New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. The pathogenesis of NDPH remains unclear, and there are few white matter imaging studies related to NDPH. The purpose of this study was to investigate the micro-structural abnormalities of white matter in NDPH and provided insights into the pathogenesis of this disease based on tract-based spatial statistics (TBSS). Methods Twenty-one patients with NDPH and 25 healthy controls (HCs) were included in this study. T1 structural and diffusion magnetic resonance imaging (MRI) were acquired from all participants. Differences in the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between patients with NDPH and HCs were investigated using TBSS analysis. Results Significantly decreased FA, increased MD and RD were found in patients with NDPH compared to HCs. White matter regions overlaid with decreased FA, increased MD and RD were found in 16 white matter tracts from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas and Johns Hopkins University White-Matter Tractography Atlas. Specifically, these white matter regions included the right anterior thalamic radiation (ATR), body of the corpus callosum (BCC), bilateral cingulum, left hippocampal cingulum (CGH), left corticospinal tract (CST), forceps major, fornix, left inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), left posterior limb of the internal capsule (PLIC), right retrolenticular part of the internal capsule (RPIC), splenium of the corpus callosum (SCC), right superior longitudinal fasciculus (SLF) and left uncinate fasciculus (UF). After Bonferroni correction, there were no correlations between the FA, MD, AD and RD values and the clinical characteristics of patients with NDPH (p > 0.05/96). Conclusion The results of our research indicated that patients with NDPH might have widespread abnormalities in the white matter of the brain.

Abstract Objective To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.

Objective Treatment of syncope in older adults places a burden on healthcare systems. We used five risk stratification tools to predict short-term adverse outcomes in older patients with syncope. Methods This was a retrospective analysis of patients with syncope (age ≥60 years) in the emergency department of an urban academic hospital. The data were evaluated using the Risk Stratification of Syncope in the Emergency Department (ROSE), San Francisco Syncope Rule (SFSR), FAINT, Canadian Syncope Risk Score (CSRS), and Boston Syncope Criteria (BSC) tools. Sensitivity, specificity, accuracy, positive and negative predictive value (NPV), and positive and negative likelihood ratios of each tool were calculated and compared for adverse events within 1 month. Results In total, 221 patients (average age 75.6 years) were analyzed. Fifty-nine patients (26.7%) had experienced an adverse event within 1 month. For the ROSE, SFSR, FAINT, CSRS and BSC tools, sensitivities were 81.3%, 76.3%, 93.2%, 71.2%, and 94.9%, specificities were 88.3%, 87.7%, 56.8%, 71.6%, and 67.3%, and NPVs were 92.9%, 91.0%, 95.8%, 87.2%, and 97.3%, respectively. Conclusion The five assessed tools could be useful for physicians in screening older patients with syncope for the risk of short-term adverse events, according to the patient’s actual situation.

Abstract Background New daily persistent headache (NDPH) is a rare but debilitating primary headache disorder that poses a significant burden on individuals and society. Despite its clinical importance, the underlying pathophysiological mechanisms of NDPH remain unclear. In this study, we aimed to investigate the brain structural changes and neural activity patterns in patients with NDPH using multimodal brain imaging analysis of structural magnetic resonance imaging (sMRI) combined with magnetoencephalography (MEG). Methods Twenty-eight patients with NDPH and 37 healthy controls (HCs) were recruited for this study, and their structural and resting-state data were collected by 3.0 Tesla MRI and MEG. We analyzed the brain morphology using voxel-based morphometry and source-based morphometry. In each brain region, MEG sensor signals from 1 to 200 Hz were analyzed using an adapted version of Welch's method. MEG source localization was conducted using the dynamic statistical parametric mapping, and the difference of source distribution between patients with NDPH and HCs was examined. Results Our results revealed significant differences in the regional grey matter volume, cortical thickness, and cortical surface area between the two groups. Specifically, compared with HCs, patients with NDPH showed a significant decrease in cortical thickness of the left rostral cortex in the middle frontal gyrus, decreased cortical surface area of the left fusiform gyrus, decreased grey matter volume of the left superior frontal gyrus and the left middle frontal gyrus, and increased grey matter volume of the left calcarine. Furthermore, the power of the whole brain, bilateral frontal lobes, and right temporal lobe in the NDPH group were higher than that in HCs in the ripple frequency band (80-200 Hz). Functional and structural analysis suggested that there were structural changes and abnormal high frequency cortical activity in both frontal and temporal lobes in patients with NDPH. Conclusion Our findings indicated that patients with NDPH have abnormalities in brain morphology, such as cortical area, cortical thickness, and grey matter volume, accompanied by abnormal cortical neural activity. Brain structural changes in the frontotemporal cortex and abnormalities in cortical ripple activity may be involved in the pathogenesis of NDPH.

Abstract Background and purpose The pathogenesis of new daily persistent headache (NDPH) is not fully understood. We aim to map aberrant functional connectivity (FC) in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). Methods Brain structural and functional MRI data were acquired from 29 patients with NDPH and 37 well-matched healthy controls (HCs) in this cross-sectional study. Region of interest (ROI) based analysis was used to compare FC between patients and HCs, with 116 brain regions in the automated anatomical labeling (AAL) atlas were defined as seeds. The correlations between aberrant FC and patients’ clinical characteristics, and neuropsychological evaluation were also investigated. Results Compared with HCs, patients with NDPH showed increased FC in the left inferior occipital gyrus, right thalamus and decreased FC in right lingual gyrus, left superior occipital gyrus, right middle occipital gyrus, left inferior occipital gyrus, right inferior occipital gyrus, right fusiform gyrus, left postcentral gyrus, right postcentral gyrus, right thalamus and right superior temporal gyrus. There were no correlation between FC of these brain regions and clinical characteristics, neuropsychological evaluation after Bonferroni correction (p > 0.05/266). Conclusions Patients with NDPH showed aberrant FC in multiple brain regions involved in perception and regulation of emotion and pain. Trial registration ClinicalTrials.gov Identifier: NCT05334927.

Abstract Background New daily persistent headache (NPDH) is a rare primary headache that is highly disabling. The pathophysiology of NDPH is still unclear, and we aimed to reveal the underlying mechanism of NDPH through functional magnetic resonance imaging (fMRI) analysis. Methods In this cross-sectional study, thirty patients with NDPH and 30 healthy controls (HCs) were recruited. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the GE 3.0 T system. We performed ReHo, ALFF (conventional band: 0.01–0.08 Hz, slow-5: 0.01–0.027 Hz, slow-4: 0.027–0.073 Hz) and seed-based to the whole brain functional connectivity (FC) analysis in the NDPH and HC groups. The sex difference analysis of ReHo, ALFF, and FC values was conducted in the NDPH group. We also conducted Pearson’s correlation analysis between ReHo, ALFF, FC values and clinical characteristics (pain intensity, disease duration, HIT-6, GAD-7, PHQ-9, and PSQI scores). Results Both increased ReHo (PFWE-corr = 0.012) and ALFF values (0.01–0.08 Hz, PFWE-corr = 0.009; 0.027–0.073 Hz, PFWE-corr =0.044) of the left middle occipital gyrus (MOG_L) were found in the NDPH group compared to the HC group. There was no significant difference in FC maps between the two groups. Compared to the HC group, no difference was found in ReHo (p = 0.284), ALFF (p = 0.246), and FC (p = 0.118) z scores of the MOG_L in the NDPH group. There was also no sex difference in ReHo (p = 0.288), ALFF (p = 0.859), or FC z score (p = 0.118) of the MOG_L in patients with NDPH. There was no correlation between ReHo, ALFF, FC z scores and clinical characteristics after Bonferroni correction (p

Abstract Background The definitive pathogenic mechanisms underlying chronic migraine (CM) remain unclear. Mounting evidence from functional and structural magnetic resonance imaging (MRI) studies suggests that the caudate nucleus (CN) plays a role in the cognitive, sensory, and emotional integration of pain information in patients with migraine. However, evidence concerning the role played by CN in CM patients is limited. Here, we used the CN as the seed to explore patterns of functional connectivity (FC) among healthy controls (HCs), patients with episodic migraine (EM), and patients with CM. Methods We included 25 HCs, 23 EM patients, and 46 CM patients in this study. All participants underwent resting-state functional MRI scans on a GE 3.0T MRI system. We performed seed-based FC analyses among the three groups using the bilateral CNs as seeds. We also compared the subgroups of CM (with and without medication overuse headache, males and females) and performed Pearson’s correlation analyses between FC values and the clinical features of CM patients. Results FC values between the right CN and five clusters (mainly involved in emotion, cognition, and sensory-related brain regions) were higher in CM patients than in HCs. Compared to EM patients, enhanced FC values between the bilateral precuneus, left anterior cingulate gyrus, right middle cingulate cortex, right lingual gyrus, and right CN were shown in the CM patients. There were no significant differences between CM patients with and without MOH, males and females. FC values between the bilateral calcarine cortex, lingual gyrus, and right CN were positively correlated with body mass index. Moreover, right CN-related FC values in the left calcarine cortex and right lingual gyrus were inversely correlated with visual analogue scale scores for headaches. Conclusion Our results revealed abnormal right CN-based FC values in CM patients, suggesting dysfunction of brain networks associated with pain perception and multi-regulation (emotion, cognition, and sensory). Aberrant FC of the CN can provide potential neuroimaging markers for the diagnosis and treatment of CM.

Abstract Background and purpose New daily persistent headache (NDPH) and chronic migraine (CM) are two different types of headaches that might involve vascular dysregulation. There is still a lack of clarity about altered brain perfusion in NDPH and CM. This study aimed to investigate the cerebral perfusion variances of NDPH and CM using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). Methods Fifteen patients with NDPH, 18 patients with CM, and 15 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL-MRI to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The automated anatomical labeling atlas 3 (AAL3) was used to parcellate 170 brain regions. The CBF and aCBV values in each brain region were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. Results Compared with HC participants, patients with NDPH were found to have decreased CBF and aCBV values in multiple regions in the right hemisphere, including the right posterior orbital gyrus (OFCpost.R), right middle occipital gyrus (MOG.R), and ventral anterior nucleus of right thalamus (tVA.R), while patients with CM showed increased CBF and aCBV values presenting in the ventral lateral nucleus of left thalamus (tVL.L) and right thalamus (tVL.R) compared with HCs (all p

Abstract Background The pathogenesis of migraine chronification remains unclear. Functional and structural magnetic resonance imaging studies have shown impaired functional and structural alterations in the brains of patients with chronic migraine. The cerebellum and periaqueductal gray (PAG) play pivotal roles in the neural circuits of pain conduction and analgesia in migraine. However, few neurotransmitter metabolism studies of these migraine-associated regions have been performed. To explore the pathogenesis of migraine chronification, we measured gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the dentate nucleus (DN) and PAG of patients with episodic and chronic migraine and healthy subjects. Methods Using the MEGA-PRESS sequence and a 3-Tesla magnetic resonance scanner (Signa Premier; GE Healthcare, Chicago, IL, USA), we obtained DN and PAG metabolite concentrations from patients with episodic migraine (n = 25), those with chronic migraine (n = 24), and age-matched and sex-matched healthy subjects (n = 16). Patients with chronic migraine were further divided into those with (n = 12) and without (n = 12) medication overuse headache. All scans were performed at the Beijing Tiantan Hospital, Capital Medical University. Results We found that patients with chronic migraine had significantly lower levels of GABA/water (p = 0.011) and GABA/creatine (Cr) (p = 0.026) in the DN and higher levels of Glx/water (p = 0.049) in the PAG than healthy controls. In all patients with migraine, higher GABA levels in the PAG were significantly associated with poorer sleep quality (GABA/water: r = 0.515, p = 0.017, n = 21; GABA/Cr: r = 0.522, p = 0.015, n = 21). Additionally, a lower Glx/Cr ratio in the DN may be associated with more severe migraine disability (r = -0.425, p = 0.055, n = 20), and lower GABA/water (r = -0.424, p = 0.062, n = 20) and Glx/Water (r = -0.452, p = 0.045, n = 20) may be associated with poorer sleep quality. Conclusions Neurochemical levels in the DN and PAG may provide evidence of the pathological mechanisms of migraine chronification. Correlations between migraine characteristics and neurochemical levels revealed the pathological mechanisms of the relevant characteristics.

Abstract Nocturnal trough systolic blood pressure (NTSBP) and Time Point of Nocturnal Trough Systolic Blood Pressure (T‐NTSBP) were important parameters of nocturnal blood pressure, the predictive values of which are unclear for stroke outcome. This study aimed to examine the relationship between NTSBP/T‐NTSBP and stroke outcome. The authors used data from a nationwide ambulatory blood pressure monitoring cohort study conducted in China, which recruited 2348 ischemic stroke and transient ischemic attack (TIA) patients. NTSBP was defined as the lowest SBP during nighttime (22:00–6:00), and T‐NTSBP was defined as the corresponding time point of NTSBP. The associations between NTSBP/T‐NTSBP and stroke outcome (stroke recurrence and combined vascular event [CVE]) at 90 days or 1 year were analyzed using cox regression models. According to NTSBP classified by quartile, hazard ratio (HR) with 95% confidence interval (CI) for NTSBP quartile 4 (>129 mm Hg) was 2.727 (1.148–6.478) for CVE at 90‐day, compared with quartile 1 (≤102 mm Hg). However, an attenuated association between NTSBP and CVE was observed at 1 year. In addition, we observed the group of T‐NTSBP at 4:00–6:00 had a lowest CVE incidence at 90 days among four groups (22:00–23:59, 00:00–1:59 2:00–3:59, 4:00–6:00). After multivariable adjustment, T‐NTSBP was significantly associated with CVE incidence at 90 days (T‐NTSBP at the 4:00–6:00 versus the 22:00–23:59 group: HR, 0.433; 95%CI, 0.190–0.986), independent of NTSBP and average nocturnal SBP. Both of NTSBP and T‐NTSBP were important predictors for short‐term cardiovascular risk in ischemic stroke and TIA patients.

Background: Multifocal atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than single artery affected. Triglyceride-rich lipoprotein (TRL) has been implicated in the early development of atherosclerosis.However, evidence on the effect of remnant cholesterol, a major atherogenic component of TRL, on multifocal atherosclerosis in Chinese health asymptomatic subjects is insufficient. This study aimed to investigate the association of remnant cholesterol with intra- and extra-cranial atherosclerosis in Chinese population. Methods: This study enrolled 3665 participants (median age 52.31 years) from the Asymptomatic Polyvascular Abnormalities Community study. Parameters of intra- and extra-cranial atherosclerosis includes intracranial artery stenosis (ICAS), carotid plaque, carotid artery stenosis (CAS), and carotid hypertrophy (intima-media thickness >0.9 mm). Logistic regression was used to assess these associations. Results: The prevalence of vascular atherosclerosis significantly increased with increasing remnant cholesterol quartiles (P for trend

Background and Purpose: QT dispersion (QTd) abnormalities are widely documented in stroke patients. This study aims to investigate the association between QTd and clinical outcomes in IS patients.Methods: IS patients registered in the Blood Pressure and Clinical Outcome in transient ischemic attack (TIA) or IS (BOSS) registry between 2012 and 2014 within 24 h of onset were analyzed. In this prospective observational study, we identified 1,522 IS cases with adequate electrocardiographic evaluations to assess QTd after the index stroke. Patients were classified into four groups based on the quartile of QTd, with the lowest group as the reference. The primary stroke outcome was defined as a modified Rankin Scale score ≥3 at 1-year. Multiple logistic regressions were utilized to investigate the association between QTd and outcome events.Results: The mean QTd across all cases was 57 ms (40–83). Functional dependency or death was documented in 214 (14.98%) cases at 1 year. After adjusting for confounders, the prevalence of death and major disability (mRS ≥ 3) showed significant differences according to the quartile of QTd, with the risk of death and major disability (mRS ≥ 3) at 1 year being significantly higher for patients in Q4 than for those in Q1 (adjusted OR = 1.626, 95% CI:1.033–2.560). However, there were no significant correlation between QTd and the event outcomes at 1 year.Conclusions: QTd was associated with poor functional outcomes at 1 year. QTd is a useful surrogate marker for adverse functional prognosis, which might help to stratify risk in patients with acute IS.

Background: The mechanism of obesity paradox in stroke is not clear. This study aimed to investigate whether uric acid (UA) contributes to obesity-stroke outcome paradox.Material and Methods: The study cohort consisted of 1,984 IS patients recruited in the ACROSS-China study. Serum UA and BMI were measured at admission. Low and high BMI groups were defined by the threshold of 24, and low and high UA by the age- and sex-specific median. Poor outcomes were defined as modified Rankin scale score ≥3 in 1 year after onset.Results: UA was significantly and positively correlated with BMI. Lower levels of UA and BMI were significantly associated with higher risk of poor outcomes. Incidence of the poor outcome was 34.5, 29.4, 27.7, and 23.5% in the BMI/UA groups of low/low, high/low, low/high and high/high, respectively, with p = 0.001 for trend. The association between low UA and poor outcome was significant in lower BMI groups (odds ratio = 1.36, p = 0.006 in quartile 1 and 1.28, p = 0.021 in quartile 2), but the odds ratios were not significant in the BMI quartile 3 and 4 groups, with p = 0.038 for trend. The adverse effect of lower UA was significant in males, but not in females, with p = 0.006 for sex difference.Conclusions: These findings suggest that low UA and low BMI have a joint effect on poor outcomes in IS patients. Across BMI categories, uric acid is differentially associated with functional outcome after stroke. This effect of low UA in the low BMI groups may be one of the mechanisms underlying the obesity-stroke paradox of the outcome in IS patients.

The white matter disease spectrum is associated with many genetic diseases, including AARS2, CADASIL, ALD, and others. In this study, to determine the novel alanyl-tRNA synthetase 2 mutation implicated in white matter disease, several families with an autosomal recessive inheritance pattern of white matter disease were analyzed by whole-exome sequencing. Variants were prioritized according to their rarity and pathogenic variants in genes already known to be associated with leukodystrophies and were confirmed by Sanger sequencing using standard protocols. We identified 5 rare variants (c.452T>C chr6:44279256 p.M151T, c.1871G>A chr6:44272054 p.W624X, c.802A>G chr6:44278128 p.M268V, c.1703-1704del chr6:-44272430-44272431 p.Q568fs, and c.179C>A chr6-44280882 p.P60H) with varying expression in 4 independent Chinese families with leukodystrophy. These single nucleotide variants (SNVs), or deletion mutations, each induced a frameshift, causing a missense mutation in alanyl-tRNA synthetase 2. These findings suggested that all mutations might contribute to the development of leukodystrophy in the examined family members. Combined with previous findings, our data confirmed that the novel mutations are located in leukodystrophy-related risk genes. We also summarized all the alanyl-tRNA synthetase 2 mutations related to the onset of leukodystrophies in adults.

Background and objective: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the best known and the most common monogenic small vessel disease (SVD). Cognitive impairment is an inevitable feature of CADASIL. Total SVD score and global cortical atrophy (GCA) scale were found to be good predictors of poor cognitive performance in community-dwelling adults. We aimed to estimate the association between the total SVD score, GCA scale and the cognitive performance in patients with CADASIL.Methods: We enrolled 20 genetically confirmed CADASIL patients and 20 controls matched by age, gender, and years of education. All participants underwent cognitive assessments to rate the global cognition and individual domain of executive function, information processing speed, memory, language, and visuospatial function. The total SVD score and GCA scale were rated.Results: The CADASIL group performed worse than the controls on all cognition measures. Neither global cognition nor any separate domain of cognition was significantly different among patients grouped by total SVD score. Negative correlations between the GCA score and cognitive performance were observed. Approximately 40% of the variance was explained by the total GCA score in the domains of executive function, information processing speed, and language. The superficial atrophy score was associated with poor performance in most of the domains of cognition. Adding the superficial atrophy score decreased the prediction power of the deep atrophy score on cognitive impairment alone.Conclusions: The GCA score, not the total SVD score, was significantly associated with poor cognitive performance in patients with CADASIL. Adding the superficial atrophy score attenuated the prediction power of the deep atrophy score on cognitive impairment alone.

Glycyl-tRNA synthetase (GARS) gene mutations have been reported to be associated with Charcot-Marie-Tooth disease 2D and distal hereditary motor neuropathy type V (dHMN-V). In this study, we report a novel GARS mutation in a Chinese family with dHMN-V. Clinical, electromyogram, genetic, and functional data were explored. The proband was an 11-year-old girl presented with progressive distal limb muscle weakness and atrophy due to peripheral motor neuropathy for 1 year. Another five members from three successive generations of the family showed similar symptoms during their first to second decades and demonstrated an autosomal dominant inheritance. The results of genetic testing revealed a novel c.383T>G mutation in the GARS gene in the affected individuals, showing apparent genetic cosegregation. Further bioinformatic analyses showed that the c.383T > G mutation resulted in L128R alteration in the second functional protein domain, and the mutation site was well conserved among different species. In silico analysis predicted that this mutation probably affected protein function. In vitro, this GARS mutation led to a different protein localization pattern than that of the wild-type enzyme. The study found a novel GARS mutation of c.383T > G causing dHMN-V with subcellular localization abnormity in a genetic cosegregation family. These findings broaden the mutational spectrum of GARS.