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Burkholderia cepacia complex emcompasses opportunistic pathogen with various clinical manifestations ranging from no symptoms to severe respiratory infections and septicaemia. Central nervous system infections caused by Burkholderia cepacia complex are rare. We present the first reported case of choroid plexitis caused by Burkholderia cepacia complex following severe coronavirus disease 2019 (COVID-19). A 67-year-old woman who had been previously diagnosed with COVID-19 presented with a mild fever and headache. Gadolinium-enhanced T1-weighted brain magnetic resonance imaging showed contrast effects in the right choroid plexus and encapsulated abscess. Gram staining of cerebrospinal fluid revealed the presence of gram-negative rods. Broad-range polymerase chain reaction amplification of 16S rRNA from the cerebrospinal fluid, followed by sequence analysis, identified Burkholderia cepacia complex; thus, choroid plexitis caused by Burkholderia cepacia complex was diagnosed. After prolonged antimicrobial treatment with a multiantibiotic regimen, the patient recovered completely. This case highlights the importance of long-term therapy with a carefully selected multiantibiotic regimen to achieve complete recovery after Burkholderia cepacia complex infection.
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The choroid plexus (CP), a highly vascularized endothelial-epithelial convolute, is placed in the ventricular system of the brain and produces a large part of the cerebrospinal fluid (CSF). Additionally, the CP is the location of a blood-CSF barrier (BCSFB) that separates the CSF from the blood stream in the CP endothelium. In vitro models of the CP and the BCSFB are of high importance to investigate the biological functions of the CP and the BCSFB. Since the CP is involved in several serious diseases, these in vitro models promise help in researching the processes contributing to the diseases and during the development of treatment options. In this review, we provide an overview on the available models and the advances that have been made toward more sophisticated and "in vivo near" systems as organoids and microfluidic lab-on-a-chip approaches. We go into the applications and research objectives for which the various modeling systems can be used and discuss the possible future prospects and perspectives.
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PURPOSE: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by the destruction of the myelin sheath within the central nervous system. The etiology of MS involves a complex interplay of genetic, environmental, and immunological factors. Recent studies indicated the potential role of the choroid plexus (CP) in the pathogenesis and progression of MS. This systematic review aims to assess existing research on the volume alterations of the CP in MS patients compared to the normal population. METHODS: A comprehensive search was conducted across databases including PubMed, Embase, Scopus, and Web of Science up to June 2024. Data from the included studies were synthesized using a meta-analytical approach with a random-effects model, assessing heterogeneity with the I2 and Tau-squared indices. RESULTS: We included 17 studies in this systematic review. The meta-analysis, which included data from eight studies reporting CP volume relative to TIV, found a statistically significant increase in CP volume in MS patients compared to healthy controls (HCs). The SMD was 0.77 (95% CI: 0.61 to 0.93), indicating a large effect size. This analysis showed no heterogeneity (I² = 0%). A separate meta-analysis was conducted using five studies that reported CP volume as normalized volume, resulting in an SMD of 0.63 (95% CI: 0.2-1.06). CONCLUSION: This study demonstrates an increase in CP volume among MS patients compared to HCs, implying the potential involvement of CP in MS pathogenesis and/or progression. These results show that CP might serve as a radiological indicator in the diagnosis and prognosis of MS.
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Purpose: To illustrate the characteristics of perforating scleral vessels in macular regions between mCNV eyes and contralateral eyes in unilateral mCNV patients. Methods: This was a retrospective study that included patients with unilateral naive mCNV. The study aimed to identify and analyze the distribution of perforating scleral vessels (PSVs) in the macular region of mCNV eyes and contralateral eyes. The central macular choroidal thicknesses (mChT) were measured using optical coherence tomography angiography (OCTA). The grades of myopic atrophic maculopathy (MAM) and macular myopic diffuse chorioretinal atrophy (DCA) were evaluated within groups. The number of PSVs and mChT were compared between contralateral and mCNV eyes based on the grade of DCA. The ROC curves were utilized to explore the diagnostic indexes for mCNV. Results: A total of 102 eyes from 51 patients with unilateral mCNV were included. There was no significance in the severity of MAM or the grade of DCA between mCNV eyes and contralateral eyes (p = 0.074, p = 0.054, respectively). The mean number of PSVs in mCNV eyes was fewer than the contralateral eyes [1.00 (1.00-2.00) vs. 2.00 (0.75-3.00), p = 0.030]. The mChT in mCNV eyes was thinner than the contralateral eyes [36.00 (25.00-53.75) µm vs. 46.00 (31.00-75.25) µm, p = 0.001]. The mean grade of DCA in mCNV eyes was higher than that in contralateral eyes [3.00 (3.00-3.00) vs. 3.00 (2.00-3.00), p = 0.004]. When DCA involved the macular region, there were more PSVs in contralateral eyes than in mCNV eyes [1.50 (1.00-2.00) vs. 2.00 (1.00-3.00), p = 0.042]. Similarly, when DCA involved the foveal region, there were more PSVs in contralateral eyes than in mCNV eyes [1.50 (1.00-2.00) vs. 3.00 (2.00-4.00), p = 0.004]. The grade of DCA and mChT were valuable factors for predicting mCNV eyes (AUC = 0.6566, p = 0.021; AUC = 0.6304, p = 0.029; respectively). When the extent of DCA exceeded the foveal region, the count of PSVs was a good diagnostic factor for predicting mCNV (AUC = 0.7430, p = 0.003). Conclusion: The mean amount of PSVs was significantly lower in the mCNV eyes compared to the contralateral eyes. When the extent of DCA exceeded the foveal region, the count of PSVs was a good diagnostic factor for predicting mCNV. Myopic eyes with a higher grade of DCA and a thinner mChT were more likely to develop mCNV.
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Histopathologic studies of diabetic choroid suggest that diabetic choroidopathy is a key aspect secondary to diabetes. Recently, hyperreflective choroidal foci (HCF) have been introduced as novel optical coherence tomography (OCT) parameter. The aim of this study was to identify and quantify HCF in diabetic subjects with retinopathy, with or without diabetic macular edema (DME). Eighty-five diabetic subjects with different degrees of DR were enrolled: 37 without DME and 48 with DME. All subjects underwent full ophthalmologic examination including spectral domain optical coherence tomography (OCT). OCT images were analyzed to quantify and localize HCF. Each image was analyzed by two independent, masked examiners. OCT images showed that all subjects (100%) had HCF in the different layers of the choroid. The number of HCF was significantly higher in diabetics with DME versus those without DME (p<.0001). HCF showed variable size, shape and location inside the choroid. They were mainly located in choriocapillaris and Sattler's layer, on the edges of blood vessels. The intraobserver and interobserver agreement was almost perfect (ICC >0.9). This study suggests that hyperreflective foci in the choroid of subjects with DR may be accurately identified with structural OCT. Their number significantly increases with the progression of DME. These HCF may represent, as in the retina, a sign of infiltration of inflammatory cells (mainly migrating microglia) into the choroid, according to the hypothesis raised by Jerry Lutty. HCF may confirm in vivo the histopathologic findings suggesting that diabetic choroidopathy may be primarily a neuroinflammatory disorder.
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The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation. We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF. Bi-directional recruitment of monocytes from the periphery and, unexpectedly, macrophages from the CSF to the ChP helped eliminate neutrophils and repair the barrier. Transcriptomic analyses detailed the molecular steps accompanying this process and revealed that ChP epithelial cells transiently specialize to nurture immune cells, coordinating their recruitment, survival, and differentiation as well as regulation of the tight junctions that control the permeability of the ChP brain barrier. Collectively, we provide a mechanistic understanding and a comprehensive roadmap of neuroinflammation at the ChP brain barrier.
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Background: Choroid plexus tumors (CPTs) are rare, potentially aggressive CNS tumors with defined histologic criteria for grading. In recent years, several patients within our practice have demonstrated discordance between the histologic diagnosis and clinical behavior. DNA methylation profiling has emerged as a potential diagnostic adjunct for aiding the clinical approach. Methods: We reviewed the clinical and pathologic data of all CPTs diagnosed at Boston Children's Hospital from 1995 to 2023. All cases with available material (38/48) underwent DNA methylation profiling at NIH/NCI, and the classifier results were correlated with the WHO histologic grade and patient outcomes. Survival information was analyzed using Kaplan-Meier curves. Results: There was good correlation (11/12, 92%) between methylation class and WHO histologic grade for choroid plexus carcinomas (CPC); one histologic CPC grouped with choroid plexus papilloma (CPP) group pediatric (P). Five CPPs grouped with methylation class CPC (5/17, 29%). In the group of atypical CPPs (nâ =â 9), there were two that grouped with methylation class CPC. Survival analysis showed utility of methylation classes in the prediction of biologic behavior. Conclusions: Results indicated that methylation profiling may serve as a valuable tool in the clinical decision-making process for patients with CPTs, providing additional prognostic information compared to WHO histologic grade alone. The value of methylation array analysis is particularly important given the lack of consensus on treatment regimens for CPTs.
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AIM: To report local tumour control, metastasis and survival rates of patients with small choroidal melanoma (CM) after treatment with ruthenium-106 (Ru-106) plaque brachytherapy. METHODS: Retrospective case series of 353 consecutive eyes with small CM (thickness ≤2.5 mm and largest basal diameter ≤16 mm) treated with Ru-106 brachytherapy at the London Ocular Oncology Service, between October 2004 and May 2019. RESULTS: The final cohort included 310 eyes and tumour recurrence was observed in 52 (17%) eyes. Ocular retention rate was 96%. Metastatic disease and tumour-related death occurred in 18 (5.8%) and 12 (3.9%) patients, respectively. Metastases were diagnosed after a median of 54 (54±35; range 3.6-118) months from initial treatment. Kaplan-Meier estimates for tumour recurrence, melanoma-related metastases and survival were 17% (95% CI 13.3% to 22.9%), 4.8% (95% CI 2.6% to 8.5%) and 98% (95% CI 94.4% to 99.1%) at 5 years and 26% (95% CI 18.3% to 35.3%), 16% (95% CI 8.7% to 27.7%) and 92% (95% CI 84.5% to 95.7%) at 10 years, respectively. On multivariable analysis, factors predictive for tumour recurrence included juxtapapillary location, larger plaque and final tumour thickness, and for metastasis exudative retinal detachment. CONCLUSION: Small CMs treated with Ru-106 brachytherapy show recurrence and death rates of 17% and 2% at 5 years and 26% and 8% at 10 years. As small CMs have better prognosis than large tumours, early treatment is the key for better survival outcomes.
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PURPOSE: To evaluate the changes in choroidal thickness 1 year after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) using widefield swept-source optical coherence tomography. METHODS: We retrospectively reviewed 21 patients with CSC who unilaterally underwent half-dose PDT and completed a 12-month follow-up. Choroidal thickness was evaluated before and after PDT within an 18-mm circular grid centered on the fovea subdivided into nine areas in the treated and untreated fellow eyes. RESULTS: All 21 treated eyes showed complete resolution of subretinal fluid at 3 months after PDT, without any recurrence at 12 months. The mean choroidal thickness in all nine areas significantly decreased after PDT at 3 months (P < 0.05) and remained unchanged at 12 months (P < 0.05) compared with that at baseline. However, the subtracted choroidal thickness maps between 3 and 12 months detected significant variations among the cases, classified into an enhanced pattern in 10 eyes (47.6%), an attenuated pattern in six eyes (28.6%), and a stable pattern in five eyes (23.8%). The 21 untreated fellow eyes also showed a decrease in mean choroidal thickness in three of the nine subdivided areas at 12 months (P < 0.05), but this decrease was limited posteriorly. CONCLUSION: The reduction in mean choroidal thickness after half-dose PDT for CSC was extensively maintained for 1 year. However, subclinical hemodynamic changes in the entire choroid occurred longitudinally even in the absence of disease recurrence.
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Indolent nonprogressive multifocal choroidal lesions have been reported to be benign choroidal lymphatic lesions that do not affect the visual function. However, as best known, there are no reports on whether these lesions affect the circulation and function of the retina and choroid. We report a case of indolent nonprogressive multifocal choroidal lesions in which retinal images were available to assess the retinal and choroidal circulation and whether it impacted the retinal function. The patient was a 45-year-old man. Swept-source optical coherence tomography (OCT) showed multiple well-defined, uniform, hyporeflective cavernous lesions in the choroidal layer. Then a diagnosis of indolent nonprogressive multifocal choroidal lesions was made based on the similarity of the features with those reported. OCT angiography showed no blood flow signals in the lesions and reduced blood flow signals in the choroid and choriocapillaris directly above the lesions. Fundus autofluorescence showed retinal pigment epithelial damages that were colocalized with the choroidal lesions. We then performed static visual field testing and multifocal electroretinography (mfERG). The static visual field test showed no decrease in sensitivity in the entire visual field, and mfERG showed no decrease in the amplitudes or implicit times indicating normal retinal function. In indolent nonprogressive multifocal choroidal lesions, the photoreceptor function is preserved but a mild retinal pigment epithelium disorder is present. Thus, the follow-up examinations of indolent nonprogressive multifocal choroidal lesions should include retinal function tests.
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AIM: To evaluate the short-term effects of different sunlight exposure on fundus blood flow perfusion (BFP) after near work. METHODS: In this parallel randomised controlled trial, 81 students aged 7-15 with spherical equivalent refraction between -2.00 and +3.00 diopters were randomly assigned to either a low-illuminance (4k lux) group (N=40) or high-illuminance (10k lux) (N=41). Following 1 hour indoor reading, participants had sunlight exposure matching their group's intensity for 15 minutes. BFPs in the superficial retina, deep retina and choroid were measured at four time points: pre-reading, post-reading, 5th-minute and 15th-minute sunlight exposure. RESULTS: Within the initial 5 minutes of sunlight exposure, the 10k lux group showed a tendency for decreased BFP, particularly in the choroid (superficial retina: -0.2, 95% CI -0.9 to 0.5; deep retina: -0.1, 95% CI -0.6 to 0.4; choroid: -0.4, 95% CI -0.8 to 0.0), while the 4k lux group exhibited an increase (superficial retina: 0.7, 95% CI 0.1 to 1.3; deep retina: 0.3, 95% CI -0.2 to 0.8; choroid: 0.1, 95% CI -0.2 to 0.5). From 5 to 15 minutes, BFP decreased in both groups. At the 5th-minute mark, the 10k lux group exhibited a greater decrease in choroid (10k -0.4 vs 4k 0.1, p=0.051). No significant difference was observed after 15 minutes of exposure. CONCLUSION: Higher illuminance sunlight exposure can restore fundus BFP more rapidly than lower; however, duration remains pivotal. To prevent myopia, continuous sunlight exposure for over 15 minutes is recommended to aid in reinstating the fundus BFP increased by near work. TRIAL REGISTRATION NUMBER: NCT05594732.
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BACKGROUND: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer's disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. METHODS: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aß42, Aß40, Aß42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman's correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aß42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. RESULTS: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aß42 and Aß40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aß42 and Aß40 levels with MMSE scores (19.08% and 36.57%), and Aß42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aß42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aß42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05). CONCLUSIONS: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Plexo Corióideo , Disfunção Cognitiva , Neuroimagem , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/patologia , Feminino , Masculino , Idoso , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/patologia , Estudos Prospectivos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Neuroimagem/métodos , Biomarcadores/líquido cefalorraquidiano , Pessoa de Meia-Idade , Testes Neuropsicológicos , Imageamento por Ressonância Magnética/métodos , Proteínas tau/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidianoRESUMO
OBJECTIVES: The function of choroid plexus is to produce cerebrospinal fluid, which is critical for the glymphatic system function. In this study, we aimed to analyze the differences in choroid plexus volume between patients with obstructive sleep apnea (OSA) and healthy controls, with the goal of discovering the glymphatic system dysfunction in patients with OSA. METHODS: We prospectively enrolled 40 patients with OSA confirmed by polysomnography and 38 age- and sex-matched healthy controls. All participants underwent three-dimensional T1-weighted brain imaging, which was suitable for volumetric analysis. We compared choroid plexus volumes between patients with OSA and healthy controls, and analyzed the association between choroid plexus volume and polysomnographic findings in patients with OSA. RESULTS: Choroid plexus volumes were significantly larger in patients with OSA than in healthy controls (2.311 % vs. 2.096 %, p = 0.005). However, no significant association was detected between choroid plexus volume and polysomnographic findings. CONCLUSION: This study demonstrated enlargement of the choroid plexus in patients with OSA compared with healthy controls. This finding could be related with glymphatic system dysfunction in patients with OSA.
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This study focuses on developing a model for the precise determination of ultrasound image density and classification using convolutional neural networks (CNNs) for rapid, timely, and accurate identification of hypoxic-ischemic encephalopathy (HIE). Image density is measured by comparing two regions of interest on ultrasound images of the choroid plexus and brain parenchyma using the Delta E CIE76 value. These regions are then combined and serve as input to the CNN model for classification. The classification results of images into three groups (Normal, Moderate, and Intensive) demonstrate high model efficiency, with an overall accuracy of 88.56%, precision of 90% for Normal, 85% for Moderate, and 88% for Intensive. The overall F-measure is 88.40%, indicating a successful combination of accuracy and completeness in classification. This study is significant as it enables rapid and accurate identification of hypoxic-ischemic encephalopathy in newborns, which is crucial for the timely implementation of appropriate therapeutic measures and improving long-term outcomes for these patients. The application of such advanced techniques allows medical personnel to manage treatment more efficiently, reducing the risk of complications and improving the quality of care for newborns with HIE.
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Purpose: Blood flow (BF) of the retinal and choroidal vasculatures can be quantitatively imaged using MRI. This study sought to improve methods of data acquisition and analysis for MRI of layer-specific retinal and choroidal BF and then applied this approach to detect reduced ocular BF in a well-established mouse model of glaucoma from both eyes. Methods: Quantitative BF magnetic resonance imaging (MRI) was performed on glaucomatous DBA/2J and normal C57BL/6J mice. Arterial spin labeling MRI was applied to image retinal and choroidal BF using custom-made dual eye coils that could image both eyes during the same scan. Statistics using data from a single eye or two eyes were compared. BF values were calculated using two approaches. The BF rate per quantity of tissue was calculated as commonly done, and the peak BF values of the retinal and choroidal vasculatures were taken. Additionally, the BF rate per retinal surface area was calculated using a new analysis approach to attempt to reduce partial volume and variability by integrating BF over the retinal and choroidal depths. Results: Ocular BF of both eyes could be imaged using the dual coil setup without effecting scan time. Intraocular pressure was significantly elevated in DBA/2J mice compared to C57BL/6J mice (P<0.01). Both retinal and choroidal BF were significantly decreased in DBA/2J mice in comparison to the age-matched normal C57BL/6J mice across all measurements (P < 0.01). From simulations, the values from the integrated BF analysis method had less partial volume effect, and from in vivo scans, this analysis approach also improved power. Conclusion: The dual eye coil setup allows bilateral eye data acquisition, increasing the amount of data acquired without increasing acquisition times in vivo. The reduced ocular BF found using the improved acquisition and analysis approaches replicated the results of previous studies on DBA/2J mice. The ocular hypertensive stress-induced BF reduction found within these mice may represent changes associated with glaucomatous progression.
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The aim of this study was to compare vessel density (VD) in the retina and choroid in eyes with primary open angle glaucoma (POAG), normal tension glaucoma (NTG) and controls. Patients with POAG, NTG and controls underwent OCT scanning of the macula and the disc followed by 6 × 6 mm macula OCT angiography (OCTA) imaging. Global and hemifield VD were recorded for the superficial (SVP) and deep (DVP) vascular plexus and the choriocapillaris (CC). The OCT thickness of the nerve fiber layer (NFL) and ganglion cell layer (GCC) was also measured. Data from 65 POAG, 33 NTG and 40 control eyes matched for age were analyzed. Mean SVP VD was lower in NTG and POAG eyes compared to controls (38.8 ± 5.3, 40.7 ± 6.8 and 48.5 ± 4.0%, p < 0.001). Mean DVP VD was lower in NTG and POAG eyes compared to controls (43.1 ± 6.1, 44.5 ± 7.6 and 48.6 ± 5.8%, p = 0.002). There was no difference in SVP VD or DVP VD between the glaucoma groups (p > 0.050). No difference was noted in CC VD between the groups (68.3 ± 2.3, 67.6 ± 3.7 and 68.5 ± 2.6%, p = 0.287). Lower SVP and DVP VD was seen in eyes with glaucoma compared to normal eyes. NTG and POAG eyes had similar VD loss. Eyes with glaucoma manifested similar CC VD compared to controls.
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BACKGROUND: The choroid plexus (CP) is suggested to be closely associated with the neuroinflammation of multiple sclerosis (MS). Segmentation based on deep learning (DL) could facilitate rapid and reproducible volume assessment of the CP, which is crucial for elucidating its role in MS. PURPOSE: To develop a reliable DL model for the automatic segmentation of CP, and further validate its clinical significance in MS. METHODS: The 3D UX-Net model (3D U-Net used for comparison) was trained and validated on T1-weighted MRI from a cohort of 216 relapsing-remitting MS (RRMS) patients and 75 healthy subjects. Among these, 53 RRMS with baseline and 2-year follow-up scans formed an internal test set (dataset1b). Another 58 RRMS from multi-center data served as an external test set (dataset2). Dice coefficient was computed to assess segmentation performance. Compare the correlation of CP volume obtained through automatic and manual segmentation with clinical outcomes in MS. Disability and cognitive function of patients were assessed using the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). RESULTS: The 3D UX-Net model achieved Dice coefficients of 0.875 ± 0.030 and 0.870 ± 0.044 for CP segmentation on dataset1b and dataset2, respectively, outperforming 3D U-Net's scores of 0.809 ± 0.098 and 0.601 ± 0.226. Furthermore, CP volumes segmented by the 3D UX-Net model aligned consistently with clinical outcomes compared to manual segmentation. In dataset1b, both manual and automatic segmentation revealed a significant positive correlation between normalized CP volume (nCPV) and EDSS scores at baseline (manual: r = 0.285, p = 0.045; automatic: r = 0.287, p = 0.044) and a negative correlation with SDMT scores (manual: r = -0.331, p = 0.020; automatic: r = -0.329, p = 0.021). In dataset2, similar correlations were found with EDSS scores (manual: r = 0.337, p = 0.021; automatic: r = 0.346, p = 0.017). Meanwhile, in dataset1b, both manual and automatic segmentation revealed a significant increase in nCPV from baseline to follow-up (p < 0.05). The increase of nCPV was more pronounced in patients with disability worsened than stable patients (manual: p = 0.023; automatic: p = 0.018). Patients receiving disease-modifying therapy (DMT) exhibited a significantly lower nCPV increase than untreated patients (manual: p = 0.004; automatic: p = 0.004). CONCLUSION: The 3D UX-Net model demonstrated strong segmentation performance for the CP, and the automatic segmented CP can be directly used in MS clinical practice. CP volume can serve as a surrogate imaging biomarker for monitoring disease progression and DMT response in MS patients.
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Plexo Corióideo , Aprendizado Profundo , Progressão da Doença , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente , Humanos , Feminino , Masculino , Adulto , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/patologia , Pessoa de Meia-Idade , Imageamento TridimensionalRESUMO
Increased choroid plexus (CP) volume has been recently implicated as a potential predictor of worse multiple sclerosis (MS) outcomes. The biomarker signature of CP changes in MS are currently unknown. To determine the blood-based biomarker characteristics of the cross-sectional and longitudinal MRI-based CP changes in a heterogeneous group of people with MS (pwMS), a total of 202 pwMS (148 pwRRMS and 54 pwPMS) underwent MRI examination at baseline and at a 5-year follow-up. The CP was automatically segmented and subsequently refined manually in order to obtain a normalized CP volume. Serum samples were collected at both timepoints, and the concentration of 21 protein measures relevant to MS pathophysiology were determined using the Olink™ platform. Age-, sex-, and BMI-adjusted linear regression models explored the cross-sectional and longitudinal relationships between MRI CP outcomes and blood-based biomarkers. At baseline, there were no significant proteomic predictors of CP volume, while at follow-up, greater CP volume was significantly associated with higher neurofilament light chain levels, NfL (standardized ß = 0.373, p = 0.001), and lower osteopontin levels (standardized ß = -0.23, p = 0.02). Higher baseline GFAP and lower FLRT2 levels were associated with future 5-year CP % volume expansion (standardized ß = 0.277, p = 0.004 and standardized ß = -0.226, p = 0.014, respectively). The CP volume in pwMS is associated with inflammatory blood-based biomarkers of neuronal injury (neurofilament light chain; NfL) and glial activation such as GFAP, osteopontin, and FLRT2. The expansion of the CP may play a central role in chronic and compartmentalized inflammation and may be driven by glial changes.
Assuntos
Biomarcadores , Plexo Corióideo , Imageamento por Ressonância Magnética , Esclerose Múltipla , Humanos , Feminino , Masculino , Biomarcadores/sangue , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/patologia , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Proteínas de Neurofilamentos/sangue , Osteopontina/sangue , Proteômica , Proteína Glial Fibrilar Ácida/sangueRESUMO
OBJECTIVE: The objective of this study was to report the results of a bibliometric analysis on the modern corpus of literature pertaining to endoscopic third ventriculostomy (ETV). Prior bibliometrics studies on ETV have focused on highly cited articles, but an advanced bibliometric analysis has not yet been conducted. METHODS: The authors queried the Web of Science (WoS) for (ALL = (endoscopic third ventriculostomy)) OR (ALL = (ETV) AND ALL = (neurosurgery)). Articles or reviews published in English were included. Articles, along with their metadata, were exported. Statistical, bibliometric, and network analyses were performed using the Bibliometrix R package and various Python packages. Reference publication year spectroscopy (RPYS), a method that analyzes the frequency with which references are cited in terms of these references' publication years, was employed to explore the historical roots of the field. RESULTS: Between 1994 and 2023, 1663 documents were identified (1382 articles) from 5457 authors. The mean annual growth rate of publications was 4.9%. International coauthorship increased 4-fold over this time period and was noted for 18.95% of published studies from 2011 to 2023. We observed that Child's Nervous System published the most articles, Journal of Neurosurgery (JNS) articles were cited most frequently, and JNS: Pediatrics articles had the highest impact. Female coauthorship increased from < 1% of published studies before 2000 to 19% by 2022, with an increase in female first authorship from 2% in 2005 to 22% in 2022 and at least 1 female coauthor rising from 3% in 2000 to 68% in 2022. Likewise, minority authorship has increased, as in the early ETV literature > 75% of authors were White while currently only 43% are White. The authors of this study also identified the most prolific authors on the subject. Early in the publication record, etiological and technical terms such as "aqueductal stenosis" and "technical note" predominated. More recently, "complications," "failure," "success," "neuroendoscopy," and "choroid plexus cauterization" were prominent. Utilizing RPYS, the authors identified 32 articles that comprise the foundational articles on ETV, published between 1966 and 2010. CONCLUSIONS: Interest in ETV increased in the 1990s with the advent of advanced endoscopic technologies-particularly digital video. The focus of research has shifted from etiology to outcomes, complication management, and technical mastery.
RESUMO
The brain's neuroreparative capacity after injuries such as ischemic stroke is partly contained in the brain's neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here, we report a mouse genetic tool (the ROSA26iDTR mouse line) for noninvasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss in both aged and young adult brains, accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at 1 mo postablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts (NBs) following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the middle cerebral artery occlusion model of ischemic stroke, NB migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke.