Perivascular Spaces Research Articles

The association between structural connectivity and anti-seizure medication response in patients with temporal lobe epilepsy.

This study aimed to investigate the differences in structural connectivity and glymphatic system function between patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and healthy controls. Additionally, we analyzed the association between structural connectivity, glymphatic system function, and antiseizure medication (ASM) response. We retrospectively enrolled patients with TLE and HS and healthy controls who underwent diffusion tensor imaging at our hospital. We assessed structural connectivity in patients with TLE and HS and healthy controls by calculating network measures using graph theory and evaluated glymphatic system function using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Patients with TLE and HS were categorized into two groups: ASM poor and good responders. We enrolled 55 patients with TLE and HS and 53 healthy controls. Of the 55 patients with TLE and HS, 39 were ASM poor responders, and 16 were ASM good responders. The assortativity coefficient in patients with TLE and HS was higher than that in healthy controls (0.004 vs. -0.007, p = 0.004), and the assortativity coefficient in ASM poor responders was lower than that in ASM good responders (-0.001 vs. -0.197, p = 0.003). The DTI-ALPS index in patients with TLE and HS was lower than that in healthy controls (1.403 vs. 1.709, p < 0.001); however, the DTI-ALPS index did not differ between ASM poor and good responders (1.411 vs. 1.385, p = 0.628). The DTI-ALPS index had a significant negative correlation with age in patients with TLE and HS (r = -0.267, p = 0.049). We confirmed increased assortativity coefficient in structural connectivity and decreased DTI-ALPS index in patients with TLE and HS compared with healthy controls. Additionally, we demonstrated an association between decreased assortativity coefficient in structural connectivity and ASM poor response in patients with TLE patients and HS. This study investigates the relationship between brain connectivity changes and glymphatic system function with antiseizure medication response in patients with temporal lobe epilepsy and hippocampal sclerosis. The research reveals that these patients show altered brain connectivity and glymphatic function compared to healthy individuals. A key finding is the strong link between a specific connectivity measure (assortativity coefficient) and antiseizure medication response, providing valuable insights that could influence epilepsy treatment and future research directions.

T2 MRI visible Perivascular Spaces in Parkinson`s Disease: clinical significance and association with polysomnography measured sleep.

Poor sleep quality might contribute to the risk and progression of neurodegenerative disorders via deficient cerebral waste clearance functions during sleep. In this retrospective cross-sectional study, we explore the link between enlarged perivascular spaces (PVS), a putative marker of sleep-dependent glymphatic clearance, with sleep quality and motor symptoms in Parkinson`s disease (PD) patients. T2-weighted MRI images of 20 patients and 17 healthy control subjects were estimated visually for PVS in the basal ganglia (BG) and centrum semiovale (CSO). The patient group additionally underwent a single-night polysomnography. Readouts included polsyomnographic sleep features and slow-wave activity (SWA), a quantitative EEG marker of sleep depth. Associations between PVS counts, PD symptoms (MDS-UPDRS scores) and sleep parameters were evaluated using correlation and regression analyses. Intra- and inter-rater reproducibility was assessed with weighted Cohen`s kappa coefficient. BG and CSO PVS counts in both patients and controls did not differ significantly between groups. In patients, PVS in both brain regions were negatively associated with SWA (1-2Hz) (BG: r(15)=-0.58, padj=0.015 and CSO: r(15)=-0.6, padj=0.015). Basal ganglia PVS counts were positively associated with motor symptoms of daily living (IRR=1.05, CI [1.01, 1.09], p=0.007, padj=0.026) and antidepressant use (IRR=1.37, CI [1.05, 1.80], p=0.021, padj=0.043) after controlling for age. Centrum Semiovale PVS counts in patients were positively associated with a diagnosis of REM sleep behaviour disorder (IRR=1.39, CI [1.06 , 1.84]), p=0.018, padj=0.11). These results add evidence that sleep deterioration may play a role in impairing glymphatic clearance via altered perivascular function, potentially contributing to disease severity in PD patients.

Microangiopathy in temporal lobe epilepsy with diffusion MRI alterations and cognitive decline

White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05–0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorβ and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE.

Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease.

Previous studies have suggested that enlarged perivascular spaces (EPVSs) are potential radiological markers of cerebral ischemia in moyamoya disease (MMD). However, serial changes in EPVSs after surgical revascularization have not yet been clarified. We aimed to elucidate the postoperative changes in EPVSs in adult patients with MMD, clinical and radiological factors affecting the number of EPVSs, and the degree of postoperative changes. We counted the EPVSs in the centrum semiovale in each hemisphere on a T2-weighted MRI performed before surgery. EPVSs were quantified 3months and 2years after combined bypass surgery in surgically treated patients and compared with the number of EPVSs before surgery. We performed multivariate logistic regression analysis to identify the clinical and radiological factors associated with the number of EPVSs. This study included 120 hemispheres of 65 adults with MMD. Older age (P < 0.01), posterior cerebral artery (PCA) involvement (P < 0.01), and cerebral blood flow (CBF) impairment (P = 0.02) were significantly associated with a large number of EPVSs. The number of EPVSs markedly decreased at 3months and 2years after surgery compared with that before surgery (P < 0.01). PCA involvement (P = 0.04) and CBF impairment (P = 0.02) were independent predictors of the regression of EPVSs after surgery. The number of EPVSs in the centrum semiovale was closely associated with age, PCA involvement, and CBF impairment in adult patients with MMD, which remarkably regressed after surgical revascularization, especially in the hemispheres with PCA involvement and CBF impairment. EPVSs are reversible radiological markers reflecting impaired cerebral hemodynamics in adult patients with MMD.

A bibliometric analysis of cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is a significant contributor to both stroke and dementia. While numerous studies on CSVD have been published, herein, we have conducted a bibliometric examination of the literature on CSVD, revealing its hot spots and emerging patterns. We used the Web of Science Core Collection as our primary database and conducted a literature search from January 2008 to January 2023. CiteSpace, VOSviewer, online bibliometric platform, and R-bibliometrix were employed to conduct bibliometric analysis and network visualization, including the number of publications, countries, institutions, journals, citations, authors, references, and keywords. A total of 4891 publications on CSVD were published in 790 journals by 19,066 authors at 3,862 institutions from 84 countries. The United States produced the most written works and had a significant impact in this field of study. The University of Edinburgh had the highest publication count overall. The journal with the most publications and co-citations was Stroke. Wardlaw, Joanna was the most prolific author and commonly cited in the field. The current areas of research interest revolved around "MRI segmentation" and "Enlarged perivascular spaces in the basal ganglia." We conducted a bibliometric analysis to examine the advancements, focal points, and cutting-edge areas in the field of CSVD to reveal potential future research opportunities. Research on CSVD is currently rapidly advancing, with a consistent rise in publications on the topic since 2008. At the same time, we identified leading countries, institutions, and leading scholars in the field and analyzed journals and representative literature. Keyword co-occurrence analysis and burst graph emergence detection identified MRI segmentation and Basal ganglia enlarged perivascular spaces as the most recent areas of research interest.

Glymphatic System Assessment Using DTI-ALPS in Age-Dependent Neurodegenerative Diseases

Introduction. Dysfunction of the glymphatic system glymphatic system of the brain is considered a pathogenetic factor in some age-dependent neurodegenerative diseases, including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and normal pressure hydrocephalus (NPH). The innovative method for calculating DTI-ALPS (Diffusion Tensor Image Analysis ALong the Perivascular Space) allows non-invasive assessment of the glymphatic system status using magnetic resonance imaging (MRI). The aim of the study is to compare DTI-ALPS in patients with AD, DLB, PD, and NPH and to evaluate its potential use as a biomarker of the glymphatic system status in these diseases. Materials and methods. The study included 116 subjects: 32 patients with AD, 15 patients with DLB, 31 patients with PD, 11 patients with NPH, and 27 healthy volunteers. Cognitive testing was performed for patients in the main groups using the Montreal Cognitive Assessment (MoCA) score. All subjects underwent diffusion tensor imaging (DTI) of the brain. DTI-ALPS was then calculated. Results. DTI-ALPS index significantly differed across groups (p 0.001). Patients with AD, DLB, and NPH had a significantly lower DTI-ALPS index on both sides compared to the PD group and healthy volunteers (p 0.01). Analysis of the entire sample showed a direct correlation between MoCA score and DTI-ALPS index (p 0.05). Conclusion. This is the first comparison of DTI-ALPS across such a broad range of age-dependent neurodegenerative diseases. Since our DTI-ALPS results were comparable to previously reported data, we believe that this parameter can be used as an indirect marker of the glymphatic system status.

Immunohistochemical Expression of Tenascin-C in Canine Meningiomas.

In humans, tenascin-C (TN-C) expression has been detected in more aggressive neoplasms of the central nervous system, such as gliomas and meningiomas. No study has analyzed the immune expression of TN-C in canine meningioma. The current study aimed to investigate the immunohistochemical distribution of TN-C in different grades of canine meningiomas. Twenty-one cases of canine meningioma (12 grade I, 6 grade II, and 3 grade III) were analyzed. All samples were examined by immunohistochemistry with the following antibodies: TN-C, epithelial membrane antigen (EMA), Ki-67, pan-cytokeratin (Pan CK), and vimentin. The histopathological diagnosis of meningioma was reinforced with the positive labeling of vimentin (moderate to strong) and EMA (mild to moderate) in neoplastic cells in most cases, independently of its grade or subtype. The immunoreactivity of TN-C was irregular: mild in grade I, moderate in grade II, and moderate to severe in grade III neoplasms. Usually, immune positivity was observed in the stroma and perivascular space in all subtypes. In addition, the concentric whorls of neoplastic cells were labeled positive in some psammomatous and transitional meningiomas. The reaction to TN-C was more significant in grade II and III tumors. The immunohistochemical findings of the current study suggest that TN-C can act as a stromal marker, mainly in grade II or III meningiomas.

Factors associated with the distribution of brain metastases in lung cancer: a retrospective study.

The distribution of brain metastases (BMs) in patients with lung cancer may be associated with the primary tumor-related factors and cerebral small vascular diseases (CSVDs). The aim of this study was to investigate the potential effects of the above factors on the distribution of BMs. A total of 5,788 lesions in 823 patients with BMs from lung cancer were enrolled. The numbers of BMs and CSVDs in 15 brain regions were determined. CSVDs include recent small subcortical infarcts (RSSIs), perivascular spaces, and lacunes of presumed vascular origin (LPVOs). We collected the number of CSVDs, and primary tumor-related factors (including clinical and imaging features) in lung cancer patients with BMs. Univariate and multivariate linear regression were utilized to analyze the potential influence of the above factors on the number of BMs in 15 brain regions. In addition, we performed subgroup analyses of all patients with adenocarcinoma (AD), female patients with AD, male patients with AD, and patients with small cell lung cancer. Univariate linear regression analyses showed that bone metastasis, adrenal metastasis, RSSIs, and LPVOs were associated with the number of BMs in over half of the examined brain regions. Only the independent association of LVPOs persisted in the multivariate linear regression analyses, and similar phenomenon was found in the subgroup analyses. In conclusion, the distribution of BMs in lung cancer patients appears to be associated with the presence of LVPOs, while primary tumor-related factors have less influence.

Alterations in the DTI-ALPS index and choroid plexus volume are associated with clinical symptoms in participants with narcolepsy type 1

BackgroundNarcolepsy type 1 (NT1) is a sleep disorder characterized by excessive daytime sleepiness accompanied by cataplexy. Sleep disorders have been shown to affect the glymphatic system. This study aimed to evaluate changes in the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and choroid plexus (CP) volume in NT1 participants, and to further explore their clinical significance. MethodsWe prospectively enrolled participants diagnosed with NT1 based on cerebrospinal fluid hypocretin-1 concentration and multiple sleep latency tests at our hospital. All participants underwent MRI to allow analysis of the DTI-ALPS index and CP volume. We subsequently performed correlation analyses between the DTI-ALPS index, CP volume, and important clinical parameters, including the Epworth Sleepiness Scale (ESS) score, Narcolepsy Severity Scale (NSS) score, stage rapid eye movement sleep (REM) ratio, stage 1 non-REM (N1) ratio, stage 2 non-REM (N2) ratio, and stage 3 non-REM (N3) ratio, among the NT1 participants. Inter-group and correlation analyses of DTI-ALPS index and CP volume were performed using age, sex, body mass index, and lateral ventricle volume as covariates. ResultsThis study enrolled 41 NT1 participants and 42 healthy controls (HC). The DTI-ALPS index of NT1 participants was significantly lower than HC (1.444±0.119 vs.1.661±0.135, P<0.001), while the CP volume of NT1 participants was significantly larger than those of HC (0.831±0.146 vs. 0.645±0.137, P<0.001). The DTI-ALPS index was negatively correlated with both the ESS (PFDR-corrected<0.001) and NSS scores (PFDR-corrected=0.010), but positively correlated with the Stage N3 ratio (PFDR-corrected=0.033). The CP volume of NT1 participants was positively correlated with ESS (PFDR-corrected=0.047) and NSS scores (PFDR-corrected=0.047), but negatively correlated with the stage N3 ratio (PFDR-corrected=0.047). ConclusionOur study suggests that the DTI-ALPS index was lower and CP volume was larger in NT1 participants. The DTI-ALPS index and CP volume in the NT1 participants were related to disease severity and sleep structure. These findings may provide new insights into the mechanisms underlying NT1.

Quantification of T-Cell Receptor Excision Circles (TRECs).

Aging is a natural process that compromises the immune system's functionality increasing the risk of infectious, tumors, and autoimmune diseases. The thymus involution is an age-dependent process characterized by decreased cellularity, peripheral lymphocyte infiltration into the perivascular space, and expansion of adipose tissue. All those modifications hamper the functionality of the organ and lead to a decline of naïve T-cell production with a shrinking of the T-cell repertoire. Thymus atrophy is described in several disorders including autoimmune diseases. The quantification of T-cell receptor excision circles (TRECs) in recent thymus emigrants is a standard procedure to investigate the thymic function. In this chapter, we discuss the methodology used to quantify this molecule in peripheral blood mononuclear cells and isolated CD4+ and CD8+ T cells.

A brain-wide solute transport model of the glymphatic system.

Brain waste is largely cleared via diffusion and advection in cerebrospinal fluid (CSF). CSF flows through a pathway referred to as the glymphatic system, which is also being targeted for delivering drugs to the brain. Despite the importance of solute transport, no brain-wide models for predicting clearance and delivery through perivascular pathways and adjacent parenchyma existed. We devised such a model by upgrading an existing model of CSF flow in the mouse brain to additionally solve advection-diffusion equations, thereby estimating solute transport. We simulated steady-state transport of 3 kDa dextran injected proximal to the perivascular space (PVS) of the middle cerebral artery, mimicking in vivo experiments. We performed a sensitivity analysis of 11 biological properties of PVSs and brain parenchyma by repeatedly simulating solute transport with varying parameter values. Parameter combinations that led to a large total pressure gradient, poor CSF perfusion or a steep solute gradient were deemed unrealistic. Solute concentrations in parenchyma were most sensitive to changes in pial PVS size, as this parameter linearly affects volume flow rates. We also found that realistic transport requires both highly permeable penetrating PVSs and high-resistance parenchyma. This study highlights the potential of brain-wide models to provide insights into solute transport processes.

Seven-tesla magnetic resonance imaging of the nervus terminalis, olfactory tracts, and olfactory bulbs in COVID-19 patients with anosmia and hypogeusia.

Linking olfactory epithelium to the central nervous system are cranial nerve 1, the olfactory nerve, and cranial nerve "0," and the nervus terminalis (NT). Since there is minimal expression of angiotensin-converting enzyme-2 (ACE-2) in the olfactory nerve, it is unclear how SARS-CoV-2 causes anosmia (loss of smell) and hypogeusia (reduction of taste). In animal models, NT expresses ACE-2 receptors, suggesting a possible SARS-CoV-2 viral entry site in humans. The purpose of this study was to determine whether ultra-high-field 7 T magnetic resonance imaging (MRI) could visualize the NT, olfactory bulbs (OB), and olfactory tract (OT) in healthy controls and COVID-19 anosmia or hypogeusia and to qualitatively assess for volume loss and T2 alterations. In this study, 7 T MRI was used to evaluate the brain and olfactory regions in 45 COVID-19 patients and 29 healthy controls. Neuroimaging was qualitatively assessed by four board-certified neuroradiologists who were blinded to outcome assignments: for the presence or absence of NT; for OB, OT, and brain volume loss; and altered T2 signal, white matter T2 hyperintensities, microhemorrhages, enlarged perivascular spaces, and brainstem involvement. NT was identifiable in all COVID-19 patients and controls. T2 hyperintensity in the NT, OB, and OT in COVID-19 patients with anosmia or hypogeusia was statistically significant compared to controls and COVID-19 patients without anosmia or hypogeusia. On 7 T MRI, NT was radiographically identifiable, adjacent to OB and OT. In COVID-19 anosmia and hypogeusia, T2 hyperintensity of NT, OB, and OT was statistically significant compared to COVID-19 patients without anosmia or hypogeusia and controls. The NT may be a potential entry site for SARs-CoV-2 and may play a role in the pathophysiology of COVID-19 anosmia.

Waste clearance shapes aging brain health.

Brain health is intimately connected to fluid flow dynamics that cleanse the brain of potentially harmful waste material. This system is regulated by vascular dynamics, the maintenance of perivascular spaces, neural activity during sleep, and lymphatic drainage in the meningeal layers. However, aging can impinge on each of these layers of regulation, leading to impaired brain cleansing and the emergence of various age-associated neurological disorders, including Alzheimer's and Parkinson's diseases. Understanding the intricacies of fluid flow regulation in the brain and how this becomes altered with age could reveal new targets and therapeutic strategies to tackle age-associated neurological decline.

Early Improvement in Interstitial Fluid Flow in Patients With Severe Carotid Stenosis After Angioplasty and Stenting.

This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS). We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values. In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001). An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

Dose-dependent Effect of Current Smoking on Enlarged Perivascular Space Identified on Brain MRI.

Cerebral small-vessel disease (CSVD) is a common cause of cognitive decline and stroke. Several studies have shown that smoking is a risk factor for CSVD progression. However, the extent to which smoking exacerbates CSVD lesions remains unclear. In this study, we aimed to clarify the association between total smoking exposure and the severity of CSVD in healthy participants. We analyzed the data of participants aged ≥ 50 years who underwent brain screening. The participants' age, sex, body mass index, alcohol consumption history, and medical history (hypertension, diabetes mellitus, and dyslipidemia) were investigated. Smoking status was assessed in pack-years, and smokers were classified as current or past smokers. CSVD findings on magnetic resonance imaging were used to evaluate the severity of periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), and enlarged perivascular spaces (EPVSs). The EPVSs were measured in the basal ganglia and centrum semiovale regions. Multivariable ordinal logistic regression analyses were performed to evaluate the effect of smoking, adjusted for the participants' baseline characteristics. A total of 2,137 participants were included in this study. The mean age of the participants was 58.7 years. The mean pack-years were 20.5 for past smokers and 26.8 for current smokers. Among current smokers, increased pack-years were significantly associated with a high EPVS burden in the basal ganglia (odds ratio: 1.14, 95% confidence interval: 1.00-1.28), whereas no such significant association was found for past smokers. No statistically significant association was found between pack-years and the risks of PVH, DSWMH, or EPVS in the centrum semiovale. Current smoking was associated with a dose-dependent risk of EPVS in the basal ganglia in healthy participants.

Glymphatic dysfunction in multiple sclerosis and its association with disease pathology and disability.

The role of the glymphatic system in multiple sclerosis (MS)-related disability remains underexplored. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a non-invasive method to assess glymphatic function. To evaluate glymphatic function in MS patients with lower and higher disability. This study included 118 MS patients who underwent structural, diffusion-weighted imaging, and clinical assessment. The participants were divided into lower (MS-L, n = 57) and higher disability (MS-H, n = 61) subgroups. Brain parenchymal fraction (BPF), lesion load (LL), and DTI-ALPS index were measured. Subgroup differences and correlations between DTI-ALPS index and other measures were explored. Logistic regression was performed to evaluate BPF, LL, and DTI-ALPS index in classifying lower and higher disability patients. Significant differences in DTI-ALPS index between MS-H and MS-L (d = -0.71, false discovery rate-corrected p-value (p-FDR) = 0.001) were found. The DTI-ALPS index correlated significantly with disease duration (rp = -0.29, p-FDR = 0.002) and EDSS (rsp = -0.35, p-FDR = 0.0002). It also showed significant correlations with BPF and LL. DTI-ALPS index and LL were significant predictors of disability subgroup (DTI-ALPS: odds ratio (OR) = 1.77, p = 0.04, LL: OR = 0.94, p = 0.02). Our findings highlight DTI-ALPS index as an imaging biomarker in MS, suggesting the involvement of glymphatic impairment in MS pathology, although further research is needed to elucidate its role in contributing to MS-related disability.

Glymphatic System Dysfunction in Congenital Sensorineural Hearing Loss: A DTI-ALPS Study

The neural mechanisms underlying congenital sensorineural hearing loss (CSNHL) remain elusive. This study evaluated the function of the glymphatic system in children with CSNHL compared to normal-hearing children using the DTI-ALPS approach, which utilizes diffusion tensor imaging along the perivascular space. Twenty-six children with CSNHL and 30 age- and sex-matched healthy controls (HCs) with normal hearing thresholds were recruited. The DTIALPS index was calculated for each group. We analyzed the discrepancies in the DTI-ALPS index between patients with CSNHL and healthy controls. Additionally, Spearman's correlation analysis was performed to investigate the relationship between the DTI-ALPS index and age in children with CSNHL. Significant differences in the DTI-ALPS index were observed between the two groups. Compared with HCs, the DTI-ALPS index in CSNHL patients was significantly lower (1.49388±0.11441 vs. 1.61402±0.15430, p=0.002). In addition, diffusivity along the z-axis in the association fiber (Dzzassoc) index was significantly higher in the CSNHL group than in the HC group (0.00041±0.00006 vs. 0.00036±0.00004, p=0.003). Furthermore, we discovered a noteworthy downward correlation between the DTI-ALPS index and age in children with CSNHL (rho = -0.544, p=0.005). In this present study, glymphatic system activity in CSNHL children was investigated for the first time using the DTI-ALPS index. A significant decrease in glymphatic system function was detected in CSNHL children, which correlated well with age. The DTI-ALPS index could serve as a valuable biomarker for tracking disease progression and treatment in CSNHL and unraveling the neural mechanisms of early hearing deprivation in children with CSNHL.

Enlarged brain perivascular spaces correlate with blood plasma osmolality in the healthy population: A longitudinal study

Enlarged perivascular spaces (EPVS) are increasingly recognized as an MRI detectable feature of neuroinflammatory processes and age-related neurodegenerative changes. Understanding perivascular characteristics in healthy individuals is crucial for their applicability as a reference for pathological changes. Limited data exists on the EPVS load and interhemispheric asymmetry in distribution among young healthy subjects. Despite the known impact of hydration on brain morphometric studies, blood plasma osmolality's effect on EPVS remains unexplored.This study investigated the influence of age, total intracranial volume (TIV), and blood plasma osmolality on EPVS characteristics in 59 healthy adults, each undergoing MRI and osmolality assessment twice within 14.8 months (mean ± 4 months). EPVS analysis was conducted in the centrum semiovale using high-resolution automated segmentation, followed by an optimization algorithm to enhance EPVS segmentation accuracy. Linear Mixed Effects model was used for the statistical analysis, which unveiled significant inter-individual variability in EPVS load and inter-hemispheric asymmetry. EPVS volume increased with age, higher TIV and lower blood plasma osmolality levels. Our findings offer valuable insights into EPVS characteristics among the healthy population, establishing a foundation to further explore age-related and pathological changes.

Causal effect of air pollution on the risk of brain health and potential mediation by gut microbiota

ObjectiveEpidemiologic investigations have examined the correlation between air pollution and neurologic disorders and neuroanatomic structures. Increasing evidence underscores the profound influence of the gut microbiota on brain health. However, the existing evidence is equivocal, and a causal link remains uncertain. This study aimed: to determine if there is a causal connection between four key air pollutants, and 42 neurologic diseases, and 1325 distinct brain structures; and to explore the potential role of the gut microbiota in mediating these associations. MethodsUnivariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) models were deployed to estimate the causal impact of air pollutants (including particulate matter [PM] with aerodynamic diameters <2.5 μm [PM2.5], and <10 μm [PM10]; PM2.5 absorbance; and nitrogen oxides [NOx]) on brain health through various Mendelian randomization methodologies. Lastly, the mediating role of the gut microbiome in the connections between the identified pollutants and neurologic diseases and brain structures was systematically examined. ResultsThe potential causal associations of PM2.5, PM2.5 absorbance, PM10, and exposure to NOx, with the risks of intracerebral hemorrhage, hippocampal perivascular spaces, large artery strokes, generalized epilepsy with tonic-clonic seizures, Alzheimer’s disease, multiple sclerosis, anorexia nervosa, post-traumatic stress disorder (PTSD), and 420 brain structures, were investigated by UVMR analysis. Following adjustment for air pollutants by MVMR analysis, the genetic correlations between PM10 exposure and PTSD and multiple sclerosis remained significant and robust. Importantly, we observed that phylum Lentisphaerae may mediate the association between PM10 and multiple sclerosis. Additionally, PM2.5 absorbance with a greater risk of reduced thickness in the left anterior transverse temporal gyrus of Heschl and a decreased area in the right sulcus intermedius primus of Jensen, mediated by genus Senegalimassilia and genus Lachnospiraceae UCG010, respectively. Finally, we provided evidence that Clostridium innocuum and genus Ruminococcus2 may partly mediate the causal effect of NOx on altered thickness in the left transverse temporal cortex and area in the right sulcus intermedius primus of Jensen, respectively. ConclusionThis study established a genetic connection between air pollution and brain health, implicating the gut microbiota as a potential mediator in the relationship between air pollution, neurologic disorders, and altered brain structures.

Transport of β-amyloid from brain to eye causes retinal degeneration in Alzheimer's disease.

The eye is closely connected to the brain, providing a unique window to detect pathological changes in the brain. In this study, we discovered β-amyloid (Aβ) deposits along the ocular glymphatic system in patients with Alzheimer's disease (AD) and 5×FAD transgenic mouse model. Interestingly, Aβ from the brain can flow into the eyes along the optic nerve through cerebrospinal fluid (CSF), causing retinal degeneration. Aβ is mainly observed in the optic nerve sheath, the neural axon, and the perivascular space, which might represent the critical steps of the Aβ transportation from the brain to the eyes. Aquaporin-4 facilitates the influx of Aβ in brain-eye transport and out-excretion of the retina, and its absence or loss of polarity exacerbates brain-derived Aβ induced damage and visual impairment. These results revealed brain-to-eye Aβ transport as a major contributor to AD retinopathy, highlighting a new therapeutic avenue in ocular and neurodegenerative disease.