Association between household size and risk of incident dementia in the UK Biobank study.

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

An NIR-IIb emissive transmembrane voltage nano-indicator for the optical monitoring of electrophysiological activities in vivo.

In vivo transmembrane-voltage detection reflected the electrophysiological activities of the biological system, which is crucial for the diagnosis of neuronal disease. Traditional implanted electrodes can only monitor limited regions and induce relatively large tissue damage. Despite emerging monitoring methods based on optical imaging have access to signal recording in a larger area, the recording wavelength of less than 1000 nm seriously weakens the detection depth and resolution in vivo. Herein, a Förster resonance energy transfer (FRET)-based nano-indicator, NaYbF4:Er@NaYF4@Cy7.5@DPPC (Cy7.5-ErNP) with emission in the near-infrared IIb biological window (NIR-IIb, 1500-1700 nm) is developed for transmembrane-voltage detection. Cy7.5 dye is found to be voltage-sensitive and is employed as the energy donor for the energy transfer to the lanthanide nanoparticle, NaYbF4:Er@NaYF4 (ErNP), which works as the acceptor to achieve electrophysiological signal responsive NIR-IIb luminescence. Benefiting from the high penetration and low scattering of NIR-IIb luminescence, the Cy7.5-ErNP enables both the visualization of action potential in vitro and monitoring of Mesial Temporal lobe epilepsy (mTLE) disease in vivo. This work presents a concept for leveraging the lanthanide luminescent nanoprobes to visualize electrophysiological activity in vivo, which facilitates the development of an optical nano-indicator for the diagnosis of neurological disorders.

Altered neurovascular coupling in migraine without aura.

Neurovascular coupling (NVC) provides new insights into migraine, a neurological disorder impacting over one billion people worldwide. This study compared NVC and cerebral blood flow (CBF) in patients with migraine without aura (MwoA) and healthy controls. About 55 MwoA patients in the interictal phase and 40 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging and arterial spin-labeling perfusion imaging scans. The CBF and resting-state neuronal activity indicators, including the amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC), were calculated for each participant. The global and regional NVCs were assessed using cross-voxel CBF-neuronal activity correlations and CBF/neuronal activity ratios. Patients with MwoA showed increased CBF/ALFF ratios in the left media, superior and inferior frontal gyri, and anterior cingulate gyrus, increased CBF/DC ratios in the left middle and inferior frontal gyri, and increased CBF/ReHo ratios in the right corpus callosum and right posterior cingulate gyrus. Lower CBF/ALFF ratios in the right rectal gyrus, the left orbital gyrus, the right inferior frontal gyrus, and the right superior temporal gyrus were also found in the MwoA patients. Furthermore, the CBF/ALFF ratios in the inferior frontal and superior temporal gyri were positively correlated with the Headache Impact Test scores and Hamilton anxiety scale scores in the MwoA patients. These findings provide evidence for the theory that abnormal NVC contributes to MwoA.

Simultaneous ischemic regions targeting and BBB crossing strategy to harness extracellular vesicles for therapeutic delivery in ischemic stroke.

Extracellular vesicles (EVs) derived from adipose-derived stem cells (ADSC-EVs) hold great promise for ischemic stroke treatment, but their therapeutic efficacy is greatly limited due to insufficient targeting ability. Previous reports focused on single ischemic targeting or blood-brain barrier (BBB) penetration, precise delivery to the brain parenchyma has not been fully considered. This study leveraged the targeting ability of RGD peptide and the cell penetrating ability of Angiopep-2 peptide to deliver ADSC-EVs precisely to the impaired brain parenchyma. We found that dual-modified EVs (RA-EVs) significantly enhanced the transcellular permeability across BBB in vitro, and not only targeted ischemic blood vessels but also achieved rapid accumulation in the ischemic lesion area after intravenous administration in vivo. RA-EVs further decreased the infarct volume, apoptosis, BBB disruption, and neurobehavioral deficits. RNA sequencing revealed the molecular regulation mechanism after administration. These findings demonstrate that dual-modification optimizes brain parenchymal targeting and highlights the significance of recruitment and penetration as a previously unidentified strategy for harnessing EVs for therapeutic delivery in ischemic stroke.

Near Infrared Emissive Lanthanide Luminescence Nanoparticle Used in Early Diagnosis and Brain Temperature Detection for Ischemic Stroke.

Ischemic stroke (IS) is one of the most dangerous medical conditions resulting in high mortality and morbidity. The increased brain temperature after IS is closely related to prognosis, making it highly significant for the early diagnosis and the progression evaluation of IS. Herein, a temperature-responsive near infrared (NIR) emissive lanthanide luminescence nanoparticle is developed for the early diagnosis and brain temperature detection of IS. After intravenous injection, the nanoparticles can pass through the damaged blood-brain barrier of the ischemic region, allowing the extravasation and enrichment of nanoparticles into the ischemic brain tissue. The NIR luminescence signals of the nanoparticles are used not only to judge the location and severity of the cerebral ischemic injury but also to report the brain temperature variation in the ischemic area through a visualized way. The results show that the designed nanoparticles can be used for the early diagnosis of ischemic stroke and minimally invasive temperature detection of cerebral ischemic tissues in transient middle cerebral artery occlusion mice model, which is expected to make the clinical diagnosis of ischemic stroke more rapid and convenient, more accurately evaluate the state of brain injury in stroke patients and also guide stroke hypothermia treatment.

Altered resting-state effective connectivity of trigeminal vascular system in migraine without aura: A spectral dynamic causal modeling study.

BACKGROUND: The trigeminal vascular system is an important part of the anatomical and physiological basis of migraine. The effective connectivity (EC) among the regions of interest (ROIs) in the trigeminal vascular system involved in migraine without aura (MWoA) remains unclear. METHODS: In this cross-sectional study, 48 patients (mean [SD] age 38.06 [10.35] years; male, 14/48 [29%]) with MWoA during the interictal phase and 48 healthy controls of similar age and sex (mean [SD] age 38.96 [10.96] years; male, 14/48 [29%]) underwent resting-state functional magnetic resonance imaging (fMRI). Dynamic causal modeling analysis was conducted to investigate directional EC among ROIs in the trigeminal vascular system including the bilateral brainstem, the primary somatosensory cortex (S1), the thalamus, and the insula. RESULTS: Compared with the healthy control group, MWoA represented significantly reduced EC from the left brainstem (Brainstem.L) to the left insula (MWoA: mean [SD] -0.16 [0.36]; healthy controls: mean [SD] 0.11 [0.41]; Pcorrected = 0.021), reduced EC from the Brainstem.L to the right insula (MWoA: mean [SD] -0.15 [0.39]; healthy controls: mean [SD] 0.03 [0.35]; Pcorrected = 0.021), and decreased EC from the left thalamus (Thalamus.L) to the Brainstem.L (MWoA: mean [SD] -0.13 [0.56]; healthy controls: mean [SD] 0.10 [0.45]; Pcorrected = 0.021). Altered EC parameters were not significantly correlated with MWoA clinical data. CONCLUSION: These results further provide increasing evidence that disturbed homeostasis of the trigeminovascular nociceptive pathway is involved in the pathophysiological mechanisms of migraine. Patients with MWoA exhibited a regional interaction distinct from healthy controls in the neural pathway of the Bilateral Insula-Brainstem.L-Thalamus.L, which may shed light on the future understanding of brain mechanisms for MWoA. Future brain-based interventions are suggested to consider the dysregulation in the Bilateral Insula-Brainstem.L-Thalamus.L circuits.

Effect of the serum 25-hydroxyvitamin D level on risk for short-term residual dizziness after successful repositioning in benign paroxysmal positional vertigo stratified by sex and onset age.

Objective: A low serum 25-hydroxyvitamin D (25(OH)D) level is relevant to both the occurrence and recurrence of benign paroxysmal positional vertigo (BPPV). However, whether it also contributes to residual dizziness (RD) after successful repositioning maneuvers is unknown. Therefore, this study aimed to explore the correlation between the serum 25(OH)D level and short-term RD severity in patients with BPPV after successful repositioning maneuvers. Methods: In total, 251 patients with BPPV after successful repositioning were enrolled and prospectively followed up for 1 week (W1). Serum 25(OH)D values were detected by chemiluminescence immunoassay at enrollment (W0). In addition, we explored the relationship between 25(OH)D values at baseline and RD severity at W1 in different subgroups stratified by sex and onset age (early-onset, ≤50 years; late-onset, >50 years). Results: The serum 25(OH)D level of female patients was significantly lower than that of male patients (15.9 ± 6.8 vs. 19.8 ± 6.6 ng/ml, p < 0.001). Its level also decreased in early-onset patients compared to late-onset ones (15.3 ± 5.9 vs. 18.0 ± 7.3 ng/ml, p = 0.003). In addition, early-onset female patients had lower 25(OH)D values than late-onset female patients (14.0 ± 5.5 vs. 17.1 ± 7.2 ng/ml, p = 0.004). However, this difference was not observed between early- and late-onset male patients. Among early-onset female patients, the 25(OH)D values of the moderate-to-severe RD group were lower than those of the minor or no RD group (10.9 ± 3.3 vs. 14.7 ± 5.7 vs. 15.0 ± 5.9 ng/ml, p = 0.046). Multivariate analysis found that decreased 25(OH)D values were related to the occurrence of moderate-to-severe RD in early-onset female patients (OR = 0.801; p = 0.022). This effect did not exist in late-onset female or male patients with BPPV. Conclusions: Age and sex differences in serum 25(OH)D levels exist in patients with BPPV. A decreased 25(OH)D level in early-onset female patients may increase the odds of moderate-to-severe RD 1 week after successful repositioning maneuvers.

Microstructural Differences of the Cerebellum-Thalamus-Basal Ganglia-Limbic Cortex in Patients with Somatic Symptom Disorders: a Diffusion Kurtosis Imaging Study.

Somatic symp tom disorders (SSDs) are a group of psychiatric disorders characterized by persistent disproportionate concern and obsessive behaviors regarding physical conditions. Currently, SSDs lack effective treatments and their pathophysiology is unclear. In this paper, we aimed to examine microstructural abnormalities in the brains of patients with SSD using diffusion kurtosis imaging (DKI) and to investigate the correlation between these abnormalities and clinical indicators. Diffusion kurtosis images were acquired from 30 patients with SSD and 30 healthy controls (HCs). Whole-brain maps of multiple diffusion measures, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), mean kurtosis (MK), radial kurtosis (RK), and axial kurtosis (AK), were calculated. To analyze differences between the two groups, nonparametric permutation testing with 10,000 randomized permutations and threshold-free cluster enhancement was used with family-wise error-corrected p values < 0.05 as the threshold for statistical significance. Then, the correlations between significant changes in these diffusion measures and clinical factors were examined. Compared to HCs, patients with SSD had significantly higher FA, MK, and RK and significantly lower MD and RD in the cerebellum, thalamus, basal ganglia, and limbic cortex. The FA in the left caudate and the pontine crossing tract were negatively correlated with disease duration; the MD and the RD in the genu of the corpus callosum were positively correlated with disease duration. Our findings highlight the role of the cerebellum-thalamus-basal ganglia-limbic cortex pathway, especially the cerebellum, in SSDs and enhance our understanding of the pathogenesis of SSDs.

Oculomotor impairments in de novo Parkinson's disease.

Objective: Reliable electrophysiological indicators are urgently needed in the precise evaluation of Parkinson's disease (PD). It is still elusive whether oculomotor performance is impaired or has clinical value in early PD. This study aims to explore oculomotor performance in newly diagnosed, drug-naïve PD and its correlation with clinical phenotype. Methods: Seventy-five patients with de novo PD, 75 patients with essential tremor (ET), and 46 gender-and age-matched healthy controls (HCs) were included in this cross-sectional study. All subjects underwent oculomotor test via videonystagmography. Visually guided saccade latency, saccadic accuracy and gain in smooth pursuit eye movement (SPEM) at three frequencies of the horizontal axis were compared among the three groups. Patients with PD also received detailed motor and non-motor evaluation by serial scales. The association between key oculomotor parameters and clinical phenotypes were explored in PD patients. Results: Both de novo PD and ET patients showed prolonged saccadic latency and decreased saccadic accuracy relative to HCs. SPEM gain in PD was uniformly reduced at each frequency. SPEM gain at 0.4 Hz was also decreased in ET compared with HCs. However, there was no significant difference of oculomotor parameters between de novo PD and ET patients. Furthermore, prolonged saccadic latency was correlated with long disease duration, whereas decreased SPEM gain was associated with severe motor symptoms in de novo PD patients. Conclusion: Ocular movements are impaired in de novo, drug naïve PD patients; these changes could be indicators for disease progression in PD.

Post-operative neutrophil-to-lymphocyte ratio and outcome after thrombectomy in acute ischemic stroke.

Background: Neutrophil to lymphocyte ratio (NLR) is a novel inflammatory marker to predict adverse cardiovascular events. However, there is a lack of data on hemorrhagic transformation (HT) and neurological outcome after mechanical thrombectomy in acute ischemic stroke (AIS). We investigated whether NLR before and after thrombectomy for patients with AIS was associated with HT and neurological outcomes. Methods: We performed a retrospective analysis of consecutive patients with anterior circulation AIS who underwent thrombectomy. HT was evaluated by CT within 24 h after thrombectomy. Clinical data had been collected retrospectively; laboratory data were extracted from our electronic hospital information system. NLR was obtained at admission (NLR1) and immediately after thrombectomy (NLR2). The main outcomes were post-interventional intracranial hemorrhage and unfavorable functional status (modified Rankin scale scores of 3-6) 3 months post-stroke. Results: A total of 258 patients with AIS, according to the NIHSS (median 14), were included. NLR2 was higher in patients who developed HT after thrombectomy and unfavorable neurological outcomes 3 months post-stroke (p < 0.001) than in those without HT or favorable outcomes, even after correction for co-factors [Odds Ratio (OR) 1.35 for HT, 95% confidence interval (CI)1.16-1.57, p < 0.001, and 1.85 for unfavorable outcome, 95%CI 1.57-2.17, p < 0.001]. The optimal cutoff value for the NLR2 as an indicator for auxiliary diagnosis of HT and the unfavorable outcome was 8.4 and 8.8, respectively. Conclusion: NLR immediately after thrombectomy is a readily available biomarker of HT and neurological outcomes in patients with AIS.

Clinical and cVEMP Evaluation Predict Short-Term Residual Dizziness After Successful Repositioning in Benign Paroxysmal Positional Vertigo.

Objective: Residual dizziness (RD) is a frequent symptom with unknown pathogenesis, often complained about by the patients with benign paroxysmal positional vertigo (BPPV), even after a successful canalith repositioning procedure (CRP). This study aims to quantitatively evaluate the short-term RD severity and its risk factors in patients with BPPV after successful CRPs. Methods: In total two hundred and twenty patients with BPPV after successful CRPs (W0) were prospectively followed up for 1 week (W1). Besides demographics and serial neuropsychological assessments (including dizziness handicap inventory-DHI, etc.), patients also received cervical/ocular vestibular evoked myogenic potential (c/oVEMP) evaluation. RD was defined as patients with dizziness or imbalance, dizziness visual analog scale (VAS) >1, and without positional vertigo or nystagmus at W1. Demographic, clinical, and VEMPs differences were compared among the three groups: patients with minor (dizziness VAS 1-3) and moderate-to-severe RD (dizziness VAS > 3) and without RD. Results: The total frequency of RD at W1 was 49.1% (n = 108), with 32.3% (n = 71) minor, and 16.8% (n = 37) moderate-to-severe RD. Logistic regression analyses revealed that RD was closely associated with DHI status (OR = 2.101, P = 0.008) at W0, this effect was not present for minor RD. In addition to DHI score > 30 (OR = 4.898, P < 0.001) at W0, bilateral cVEMP absence (OR = 4.099, P = 0.005) was also an independent influential factor of moderate-to-severe RD. Conclusion: Our study highlights the importance of RD quantified evaluation. DHI score >30 and bilateral cVEMP absence could increase the risk of short-term moderate-to-severe RD.

Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke When Multiple Passes Are Required and Associated Risk Factors.

INTRODUCTION: This study aimed to evaluate the outcomes of mechanical thrombectomy for acute ischemic stroke when multiple passes are required and to identify the associated risk factors. METHODS: Consecutive patients with acute ischemic stroke treated with mechanical thrombectomy at the Neurology Department of Ninth People's Hospital and the Neurosurgery Department of Xinhua Hospital of Shanghai Jiao Tong University School of Medicine from 2013 to 2018 were included. Patients were divided into 2 groups: those who received ≤2 passes and those who received >2 passes. Outcomes of the 2 groups were compared. Multivariate linear regression was used to determine factors associated with the need for >2 passes. All patient data were reviewed retrospectively. RESULTS: A total of 122 patients were included, of whom 83 patients required ≤2 passes and 39 patients required >2 passes. After adjusting for sex, atrial fibrillation history, smoking history, and involvement of middle cerebral artery and internal cerebral artery, the National Institutes of Health Stroke Scale (NIHSS) score was associated with a 1.08-times greater risk of >2 passes (95% confidence interval [CI]: 1.01-1.17), and internal carotid artery with a 5.13-times greater risk of >2 passes (95% CI: 1.02-25.69). Having more than 2 passes was associated with significantly higher 7-day (25.6% vs. 6%), 90-day mortality rates (34.2% vs. 16%) and a significantly lower recanalization rate (66.7% vs. 89.2%). CONCLUSION: Needing more than 2 passes during mechanical thrombectomy is associated with poorer outcomes. Higher preprocedural NIHSS scores and internal carotid artery thrombi are associated with more than 2 passes.

Significant Structural Alterations and Functional Connectivity Alterations of Cerebellar Gray Matter in Patients With Somatic Symptom Disorder.

Objective: Recent studies have revealed a strong association between the cerebellum and psychiatric disorders. However, the structural changes in the cerebellar regions and functional connectivity (FC) patterns in patients with somatic symptom disorder (SSD) have not been elucidated. Methods: Thirty-seven patients with SSD (29 drug-naive and 8 medicated patients) and 37 sex- and age-matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging scans. The spatially unbiased infratentorial (SUIT) cerebellar atlas-based voxel-based morphometry was used to investigate the changes in cerebellar regional gray matter (GM). Seed-based FC was further computed to explore the pattern of abnormal FC across the whole brain. Correlations were calculated to investigate the relationship between cerebellar structural (and FC) changes and clinical characteristics. Results: After controlling for age, sex, total intracranial volume, medication, and mean FD covariates, all patients with SSD had increased mean GM volume (GMV) in the posterior lobules of the cerebellum bilaterally when compared with HCs, specifically, in the bilateral cerebellar crura I and II. Patients with SSD showed significantly stronger FC between the right crura I and II and bilateral precuneus inferior parietal region, and postcentral gyrus, extending to the superior parietal lobe, cingulate gyrus, and the white matter subgyral. In addition to the two clusters, right lingual gyrus was also a surviving cluster with significantly higher FC. Partial correlation analysis revealed that the degree of regional GMV increases in the two significant clusters and the Hamilton Depression Scale (HAMD) score was negatively correlated. Moreover, the FC of right crura I and II with the left parietal lobe and right lingual gyrus were also negatively associated with the HAMD score. Conclusions: SSD exhibited significant microstructural changes and changes in FC pattern in the posterior cerebellar lobe. These results shed new light on the psychological and neural substrates of SSD and may serve as a potential treatment target for SSD based on the cerebellar area.

Effects of exosomal miRNAs in the diagnosis and treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Exosomes are extracellular vesicles secreted by a variety of cells, and they participate in intercellular communication by transferring microRNA (miRNA) and other substances. Among the various internal and external factors involved in the occurrence and development of AD, exosome-derived miRNAs have become essential in the pathogenesis and treatment of AD. As nanocarriers of miRNA, exosomes are expected to become an important tool in the pathogenesis, diagnosis, and treatment of AD. This article reviews the roles of exosomal miRNAs in the pathophysiological process, diagnostic biomarkers and treatment of AD.

Disrupted White Matter Functional Connectivity With the Cerebral Cortex in Migraine Patients.

Background: In attempts to understand the migraine patients' overall brain functional architecture, blood oxygenation level-dependent (BOLD) signals in the white matter (WM) and gray matter (GM) were considered in the current study. Migraine, a severe and multiphasic brain condition, is characterized by recurrent attacks of headaches. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both WM and GM. It is feasible to explore the functional interactions between WM tracts and GM regions in migraine. Methods: Forty-eight migraineurs without aura (MWoA) and 48 healthy controls underwent resting-state functional magnetic resonance imaging. Pearson's correlations between the mean time courses of 48 white matter (WM) bundles and 82 gray matter (GM) regions were computed for each subject. Two-sample t-tests were performed on the Pearson's correlation coefficients (CC) to compare the differences between the MWoA and healthy controls in the GM-averaged CC of each bundle and the WM-averaged CC of each GM region. Results: The MWoAs exhibited an overall decreased average temporal CC between BOLD signals in 82 GM regions and 48 WM bundles compared with healthy controls, while little was increased. In particular, WM bundles such as left anterior corona radiata, left external capsule and bilateral superior longitudinal fasciculus had significantly decreased mean CCs with GM in MWoA. On the other hand, 16 GM regions had significantly decreased mean CCs with WM in MWoA, including some areas that are parts of the somatosensory regions, auditory cortex, temporal areas, frontal areas, cingulate cortex, and parietal cortex. Conclusion: Decreased functional connections between WM bundles and GM regions might contribute to disrupted functional connectivity between the parts of the pain processing pathway in MWoAs, which indicated that functional and connectivity abnormalities in cortical regions may not be limited to GM regions but are instead associated with functional abnormalities in WM tracts.

Clinical and Oculomotor Correlates With Freezing of Gait in a Chinese Cohort of Parkinson's Disease Patients.

Accumulating evidence suggests that freezing of gait (FOG) is a unique gait disturbance in Parkinson's disease (PD), and its pathophysiology is not fully elucidated. The present study aims to investigate the clinical and oculomotor associations with FOG in Chinese PD patients. From Jan 2017 to Dec 2019, a total of 210 PD patients were consecutively registered for FOG evaluation based on item-3 of the Freezing of Gait Questionnaire (FOGQ). We explored the demographic, motor, and non-motor symptom differences in FOG positive (PD+FOG, n = 45) vs. negative (PD-FOG, n = 165) group. In addition, 40 PD patients and 37 healthy controls (HC) also underwent oculomotor test via videonystagmography (VNG). Visually guided saccade (VGS) latency, saccade accuracy and gain in smooth pursuit eye movement (SPEM) at three frequencies of horizontal axis were compared among PD+FOG (n = 20), PD-FOG (n = 20), and HC (n = 37). Compared with PD-FOG, PD+FOG had longer disease duration, more severe motor symptoms, lower cognitive scores, more severe depressive and autonomic impairments, as well as higher daily levodopa equivalent dosage. FOG occurred more frequently in patients with wearing-off. VNG subgroup analysis demonstrated that PD+FOG had prolonged saccade latency and decreased saccade accuracy relative to PD-FOG or HC. SPEM gain at 0.1 and 0.2 Hz was also decreased in PD+FOG compared with HC. Furthermore, prolonged saccade latency was correlated with higher FOGQ scores in PD patients. Our results verify that PD with FOG patients suffer from more severe motor and non-motor symptoms, indicating more extensive neurodegeneration. Prolonged saccade latency could be a practical oculomotor parameter both for identification and progression of FOG in PD.

Blood Pressure Variability during Angiography in Patients with Ischemic Stroke and Intracranial Artery Stenosis.

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge.

Disrupted functional connectivity between sub-regions in the sensorimotor areas and cortex in migraine without aura.

BACKGROUND: Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. METHODS: Forty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions. RESULTS: We found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities. CONCLUSION: In patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.

DNA Methylation Analysis Identifies Differentially Methylated Sites Associated with Early-Onset Intracranial Atherosclerotic Stenosis.

AIM: Studies have suggested that genetic and environmental factors do not account for all risks and mechanisms of intracranial atherosclerotic stenosis (ICAS). DNA methylation may play a role in the progression of ICAS. METHODS: DNA methylation profiles of peripheral blood leucocytes from 7 patients with early-onset ICAS and 7 perfectly matched controls were interrogated for the first time using the Illumina Infinium Human MethylationEPIC BeadChip. Afterward, functional analysis for differentially methylated genes was conducted. In addition, pyrosequencing verification was performed in an independent cohort comprising 21 patients with early-onset ICAS and 21 age- and gender-matched controls. RESULTS: A total of 318 cytosine-phosphate-guanine sites were found to be differentially methylated based on the established standards. Functional analysis annotated differentially methylated sites to atherosclerosis-related processes and pathways, such as the negative regulation of hydrolase activity (GO 0051346), type II diabetes mellitus (KEGG hsa04930), and the insulin signaling pathway (KEGG hsa04910). In addition, a differentially methylated site was also validated, cg22443212 in gene Rnf213, which showed significant hypermethylation in patients with early-onset ICAS compared with controls 59.56% (49.77%, 88.55%) vs. 44.65% (25.07%, 53.21%), respectively; P=0.010). Receiver operating characteristic curve analysis showed that the area under the curve value of cg22443212 was 0.744 (95% confidence interval, 0.586-0.866; P=0.002). CONCLUSIONS: We revealed that altered DNA methylation may play a role in the occurrence and development of ICAS. These results provided new epigenetic insights into ICAS.

Altered Spontaneous Activity and Functional Connectivity in the Posterior Pons of Patients With Migraine Without Aura.

The brainstem has been discussed as the main player in the pathogenesis of migraine. Dysfunctional brainstem nuclei and their abnormal connections to other key brain centers may contribute to headache and other symptoms of migraine. In the present study, 32 patients with migraine without aura (MWoA) and 32 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI scans. We used masked independent analysis (mICA) to investigate whether patients with MWoA exhibited abnormal brainstem nuclei-cortical functional connectivity (FC). The mICA can suppress adjacent physiological noise and prevent results from being driven by the much stronger signals of the surrounding structures. Regional homogeneity (ReHo) was used to investigate whether the brainstem regions with abnormal FC to other brain areas exhibited abnormal regional neuronal activity. Patients with MWoA showed significantly weaker FC between the posterior pons and the left superior parietal lobule, the left middle temporal gyrus, and the left middle frontal gyrus. Furthermore, patients with MWoA exhibited significantly decreased ReHo values in the posterior pons compared with HCs, and the posterior pons ReHo value was significantly negatively correlated with HIT-6 scores in the MWoA group. Patients with MWoA exhibited functional abnormalities in the posterior pons and weakened connections between the posterior pons and several key cortical brain areas involved in pain processing during the resting state. PERSPECTIVE: This study provided increased evidence that the pons is involved in the pathophysiological mechanism of migraine, and weakened connections suggest that the touch and pain sensation of migraine sufferers may not be properly relayed to cortical processing areas, which may be associated with the pathogenesis of MWoA.