Endothelial pyroptosis-driven microglial activation in choroid plexus mediates neuronal apoptosis in hemorrhagic stroke rats.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with alarmingly high rates of disability and mortality, and current therapeutic options are suboptimal. A critical component of ICH pathology is the initiation of a robust inflammatory response, often termed "cytokine storm," which amplifies the secondary brain injury following the initial hemorrhagic insult. The precise sources and consequences of this cytokine-driven inflammation are not fully elucidated, necessitating further investigation. METHODS: To address this knowledge gap, our study conducted a comprehensive cytokine profiling using Luminex® assays, assessing 23 key cytokines. We then employed single-cell RNA sequencing and spatial transcriptomics at three critical time points post-ICH: the hyperacute, acute, and subacute phases. Integrating these multimodal analyses allowed us to identify the cellular origins of cytokines and elucidate their mechanisms of action. RESULTS: Luminex® cytokine assays revealed a significant upregulation of IL-6 and IL-1ß levels at the 24-h post-ICH time point. Through the integration of scRNA-seq and spatial transcriptomics in the hemorrhagic hemisphere of rats, we observed a pronounced activation of cytokine-related signaling pathways within the choroid plexus. Initially, immune cell presence was sparse, but it surged 24 h post-ICH, particularly in the choroid plexus, indicating a substantial shift in the immune microenvironment. We traced the source of IL-1ß and IL-6 to endothelial cells, establishing a link to pyroptosis. Endothelial pyroptosis post-ICH induced the production of IL-1ß and IL-6, which activated microglial polarization characterized by elevated expression of Msr1, Lcn2, and Spp1 via the NF-κB pathway in the choroid plexus. Furthermore, we identified neuronal populations undergoing apoptosis, mediated by the Lcn2-SLC22A17 pathway in response to IL-1ß and IL-6 signaling. Notably, the inhibition of pyroptosis using VX-765 significantly mitigated neurological impairments. CONCLUSIONS: Our study provides evidence that endothelial pyroptosis, characterized by the release of IL-1ß and IL-6, triggers microglial polarization through NF-κB pathway activation, ultimately leading to microglia-mediated neuronal apoptosis in the choroid plexus post-ICH. These findings suggest that targeted therapeutic strategies aimed at mitigating endothelial cell pyroptosis and neutralizing inflammatory cytokines may offer neuroprotection for both microglia and neurons, presenting a promising avenue for ICH treatment.

Elevated peripheral inflammation is associated with choroid plexus enlargement in independent sporadic amyotrophic lateral sclerosis cohorts.

BACKGROUND: Using neuroimaging techniques, growing evidence has suggested that the choroid plexus (CP) volume is enlarged in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, the CP has been suggested to play an important role in inflammation-induced CNS damage under disease conditions. However, to our knowledge, no study has investigated the relationships between peripheral inflammation and CP volume in sporadic ALS patients. Thus, in this study, we aimed to verify CP enlargement and explore its association with peripheral inflammation in vivo in independent ALS cohorts. METHODS: Based on structural MRI data, CP volume was measured using Gaussian mixture models and further manually corrected in two independent cohorts of sporadic ALS patients and healthy controls (HCs). Serum inflammatory protein levels were measured using a novel high-sensitivity Olink proximity extension assay (PEA) technique. Xtreme gradient boosting (XGBoost) was used to explore the contribution of peripheral inflammatory factors to CP enlargement. Then, partial correlation analyses were performed. RESULTS: CP volumes were significantly higher in ALS patients than in HCs in the independent cohorts. Compared with HCs, serum levels of CRP, IL-6, CXCL10, and 35 other inflammatory factors were significantly increased in ALS patients. Using the XGBoost approach, we established a model-based importance of features, and the top three predictors of CP volume in ALS patients were CRP, IL-6, and CXCL10 (with gains of 0.24, 0.18, and 0.15, respectively). Correlation analyses revealed that CRP, IL-6, and CXCL10 were significantly associated with CP volume in ALS patients (r = 0.462 ∼ 0.636, p < 0.001). CONCLUSION: Our study is the first to reveal a consistent and replicable contribution of peripheral inflammation to CP enlargement in vivo in sporadic ALS patients. Given that CP enlargement has been recently detected in other brain diseases, these findings should consider extending to other disease conditions with a peripheral inflammatory component.

Choroid plexus volumes in patients with transient global amnesia: A retrospective study.

Increased choroid plexus (ChP) volume is well known to be associated with glymphatic system dysfunction. This study aimed to investigate glymphatic system function in patients with transient global amnesia (TGA) compared to healthy controls through ChP volumes measurements. We retrospectively enrolled patients with TGA from our hospital, as well as healthy controls. This was retrospectively observational study followed STROBE guideline. All participants underwent brain magnetic resonance imaging, including three-dimensional T1-weighted imaging. We analyzed and compared ChP volumes between patients with TGA and healthy controls and investigated the relationship between ChP volumes and clinical characteristics in patients with TGA. We enrolled 44 patients with TGA and 47 healthy controls. Among the 44 patients with TGA, 38 experienced a single TGA event, while 6 had recurrent TGA events. ChP volumes did not significantly differ between patients with TGA and healthy controls (2.140% vs 2.089%, P = .568). However, ChP volumes were higher in patients with a single TGA event compared to those with recurrent events (2.204% vs 1.740%, P < .013). We observed a significant positive correlation between ChP volumes and age in patients with TGA (R = 0.282, P = .007). ChP volumes were not associated with the duration of amnesia in patients with TGA (R = 0.187, P = .274). We find no differences in the glymphatic system function, as demonstrated by ChP volume for the first time. This study also found a significant correlation between ChP volume and age in patients with TGA, indicating that aging influences glymphatic system function.

Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.

BACKGROUND: Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll-like receptor 4/nuclear factor-kappa B/Na+/K+/2Cl-cotransporter 1(TLR4/NF-κB/NKCC1) signal pathway in the development of hydrocephalus. METHOD: Hydrocephalus was induced in adult rats (8 weeks) by intracisternal kaolin injection, then pyrrolidinedithiocarbamate (PDTC) and bumetanide were administrated to the rats mode. Then the rat model was evaluated, and ventricular volume was calculated at different time points. Then CPE, cortex, preventricular tissue, and CSF were obtained. Protein expressions of TLR-4, NKCC/serine-threonine STE20/SPS1-related, proline-alanine-rich kinase (SPAK), pNKCC1, pSPAK, GFAP, AQP1, and AQP4 were measured by RT-PCR, western blot, and immunofluorescence (IF) stains in CPE, respectively. RESULT: Our data showed that inflammation factors tumor necrosis factor-(TNF-α), interleukin 18(IL-18), and glial fibrillary acidic protein (GFAP) concentrations were significantly higher in the model group than in controls. The TLR4/NF-κB/NKCC1 signal pathway were actived by NF-κB-p65, NKCC1, pNKCC1- pSPAK complex, and Aquaporin1 (AQP1) high expression. PDTC and bumetanide use can help regular TLR4/NF-κB/NKCC1 expression and reduced AQP1 expression by down-regulate NF-B-p65 and inhibiting NKCC1, respectively. As a result, the treatment groups alleviated CPE abnormal secretion and ventricle enlargement. CONCLUSION: These results confirmed that the inflammatory reaction contributes TLR4/NF-κB/NKCC1 mediated CPE abnormal secretion and consequent hydrocephalus. Regulation of TLR4/NF-κB/NKCC1 and AQP1 can prevent this process. Our study provides a strong rationale for further exploring alleviating CPE abnormal secretion as a therapeutic perspective of hydrocephalus.

Choroid Plexus Volume in Pediatric-Onset Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Recent studies suggest that the choroid plexus (CP) may function as a site of access of inflammatory cells into the CNS in multiple sclerosis (MS). Pediatric-onset MS (POMS) is characterized by a high inflammatory burden, as evidenced by a high relapse rate and volume of T2 lesions, making patients with POMS an informative population to evaluate choroid plexus volume (CPV). The objectives of the study were (1) to evaluate CPV at symptom onset in participants with POMS compared with healthy controls (HCs); (2) to evaluate changes in CPV in the first year of disease in participants with POMS; and (3) to evaluate associations between CPV, brain volumes, relapse activity, and disability in participants with POMS. METHODS: Baseline 1.5T MRI scans were acquired from 23 participants with POMS and 23 age-matched and sex-matched HCs; 18 participants with POMS also had 12-month follow-up MRI scans. The CP of the lateral ventricles was segmented manually. CP and brain structure volumes were normalized for total intracranial volume. The number of relapses, T2 and gadolinium-enhancing T1 lesion counts, and Expanded Disability Status Scale (EDSS) scores at 12 months were also analyzed. Baseline CPVs were compared between groups using the Wilcoxon exact test, and CPV change from baseline to 12 months in participants with POMS was compared using the Wilcoxon signed-rank test. The relationship between CPV and brain volumetric measures, T2 lesion volumes, lesion count, number of relapses, and EDSS scores was assessed through Spearman correlation. RESULTS: The median normalized CPV was 1.51 × 10-3 (interquartile range [IQR]: 1.32-1.76) in POMS baseline scans and 1.21 × 10-3 (IQR: 1.1-1.47) in HC scans (p = 0.001). CPV did not significantly change at 12 months in the 18 participants with POMS with follow-up scans (p = 0.352). CPV in participants with POMS and HCs correlated with lateral ventricular volume (p = 0.012 for both groups) but did not correlate with brain and T2 lesion volumes or lesion count at baseline, nor with relapse activity or EDSS scores at 12 months in participants with POMS. DISCUSSION: CPV measured at baseline is greater in participants with POMS than in HCs. Baseline CPV did not predict higher disease activity or worse neurologic outcomes over 1 year. While higher CPV may be an early feature of inflammation in MS, its strong correlation with ventricular volumes could also reflect enlargement secondary to the mechanical attachment of CP to the ventricular wall.

Carotid artery vascular stenosis causes the blood-CSF barrier damage and neuroinflammation.

BACKGROUND: The choroid plexus (ChP) helps maintain the homeostasis of the brain by forming the blood-CSF barrier via tight junctions (TJ) at the choroid plexus epithelial cells, and subsequently preventing neuroinflammation by restricting immune cells infiltration into the central nervous system. However, whether chronic cerebral hypoperfusion causes ChP structural damage and blood-CSF barrier impairment remains understudied. METHODS: The bilateral carotid stenosis (BCAS) model in adult male C57BL/6 J mice was used to induce cerebral hypoperfusion, a model for vascular contributions to cognitive impairment and dementia (VCID). BCAS-mediated changes of the blood-CSF barrier TJ proteins, apical secretory Na+-K+-Cl- cotransporter isoform 1 (NKCC1) protein and regulatory serine-threonine kinases SPAK, and brain infiltration of myeloid-derived immune cells were assessed. RESULTS: BCAS triggered dynamic changes of TJ proteins (claudin 1, claudin 5) accompanied with stimulation of SPAK-NKCC1 complex and NF-κB in the ChP epithelial cells. These changes impacted the integrity of the blood-CSF barrier, as evidenced by ChP infiltration of macrophages/microglia, neutrophils and T cells. Importantly, pharmacological blockade of SPAK with its potent inhibitor ZT1a in BCAS mice attenuated brain immune cell infiltration and improved cognitive neurological function. CONCLUSIONS: BCAS causes chronic ChP blood-CSF damage and immune cell infiltration. Our study sheds light on the SPAK-NKCC1 complex as a therapeutic target in neuroinflammation.

Choroid plexus enlargement correlates with periventricular pathology but not with disease activity in radiologically isolated syndrome.

BACKGROUND: Choroid plexus (ChP) enlargement is an emerging radiological biomarker in multiple sclerosis (MS). OBJECTIVES: This study aims to assess ChP volume in a large cohort of patients with radiologically isolated syndrome (RIS) versus healthy controls (HC) and explore its relationship with other brain volumes, disease activity, and biological markers. METHODS: RIS individuals were included retrospectively and compared with HC. ChPs were automatically segmented using an in-house automated algorithm and manually corrected. RESULTS: A total of 124 patients fulfilled the 2023 RIS criteria, and 55 HCs were included. We confirmed that ChPs are enlarged in RIS versus HC (mean (±SD) normalized ChP volume: 17.24 (±4.95) and 11.61 (±3.58), respectively, p < 0.001). Larger ChPs were associated with more periventricular lesions (ρ = 0.26; r2 = 0.27; p = 0.005 for the correlation with lesion volume, and ρ = 0.2; r2 = 0.21; p = 0.002 for the correlation with lesion number) and lower thalamic volume (ρ = -0.38; r2 = 0.44; p < 0.001), but not with lesions in other brain regions. Conversely, ChP volume did not correlate with biological markers. No significant difference in ChP volume was observed between subjects who presented or did not have a clinical event or between those with or without imaging disease activity. CONCLUSIONS: This study provides evidence that ChP volume is higher in RIS and is associated with measures reflecting periventricular pathology but does not correlate with biological, radiological, or clinical markers of disease activity.

Choroid plexitis caused by Burkholderia cepacia complex after COVID-19.

Burkholderia cepacia complex (BCC) encompasses opportunistic pathogen with various clinical manifestations ranging from no symptoms to severe respiratory infections and septicemia. Central nervous system infections caused by BCC are rare. To the best of our knowledge, we present the first reported case of choroid plexitis caused by BCC after severe 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 ribosomal RNA from the cerebrospinal fluid, followed by sequence analysis, identified BCC; thus, choroid plexitis caused by BCC 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 BCC infection.

Serum Biomarker Signatures of Choroid Plexus Volume Changes in Multiple Sclerosis.

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.

Enhanced choroid plexus segmentation with 3D UX-Net and its association with disease progression in multiple sclerosis.

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.

Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer's continuum.

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.

Choroid plexus volumes and auditory verbal learning scores are associated with conversion from mild cognitive impairment to Alzheimer's disease.

PURPOSE: Mild cognitive impairment (MCI) can be the prodromal phase of Alzheimer's disease (AD) where appropriate intervention might prevent or delay conversion to AD. Given this, there has been increasing interest in using magnetic resonance imaging (MRI) and neuropsychological testing to predict conversion from MCI to AD. Recent evidence suggests that the choroid plexus (ChP), neural substrates implicated in brain clearance, undergo volumetric changes in MCI and AD. Whether the ChP is involved in memory changes observed in MCI and can be used to predict conversion from MCI to AD has not been explored. METHOD: The current study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to investigate whether later progression from MCI to AD (progressive MCI [pMCI], n = 115) or stable MCI (sMCI, n = 338) was associated with memory scores using the Rey Auditory Verbal Learning Test (RAVLT) and ChP volumes as calculated from MRI. Classification analyses identifying pMCI or sMCI group membership were performed to compare the predictive ability of the RAVLT and ChP volumes. FINDING: The results indicated a significant difference between pMCI and sMCI groups for right ChP volume, with the pMCI group showing significantly larger right ChP volume (p = .01, 95% confidence interval [-.116, -.015]). A significant linear relationship between the RAVLT scores and right ChP volume was found across all participants, but not for the two groups separately. Classification analyses showed that a combination of left ChP volume and auditory verbal learning scores resulted in the most accurate classification performance, with group membership accurately predicted for 72% of the testing data. CONCLUSION: These results suggest that volumetric ChP changes appear to occur before the onset of AD and might provide value in predicting conversion from MCI to AD.

Volumetric Changes in the Choroid Plexus Associated with Spontaneous Intracranial Hypotension in Patients with Spinal CSF Leak.

BACKGROUND AND PURPOSE: The choroid plexus contains specialized ependymal cells responsible for CSF production. Recent studies have demonstrated volumetric and perfusion changes in the choroid plexus with age and neurodegenerative disorders, however, volumetric changes in the choroid plexus in low pressure states is not known. The purpose of this study is to evaluate volumetric differences in choroid plexus size in patients with spontaneous intracranial hypotension (SIH) resultant from spinal CSF leaks compared with healthy controls. MATERIALS AND METHODS: This was a retrospective, institutional review board-approved study. Patients with MRI evidence of SIH and a spinal CSF leak diagnosed on myelography and subsequently confirmed at surgery were included in this study. All patients included in this study including age-matched healthy controls had a brain MRI performed on a either a 1.5 or 3T scanner with acquisition of 3D T1 postcontrast (eg, BRAVO, MPRAGE, etc). In all patients, the trigonum ventriculi volume, in the atria of the lateral ventricles, was contoured by using Visage-7 segmentation tools on the volumetric postcontrast T1 sequence. A basic 2-tailed t test was used to compare choroid plexus volumes between the 2 groups. RESULTS: Thirty-four patients were included with 17 patients with SIH with spinal CSF leak and 17 healthy control patients who were age- and sex-matched. The mean age of patients was 45 years, standard deviation 14 years. The mean volume of the choroid plexus for patients with SIH with spinal CSF leak was 1.2 cm3 (standard deviation = 0.26) compared with 0.63 cm3 (standard deviation = 0.31) in the control group (P < .0001). CONCLUSIONS: Results of this study demonstrate a higher choroid plexus volume in patients with SIH with spinal CSF leak compared with age- and sex-matched healthy controls. This likely reflects compensatory mechanisms to counteract intracranial hypotension by increasing CSF production as well as increased vascularity of the choroid plexus through expansion of the intracranial blood pool.

Cytological features of ependymal and choroid plexus tumours.

Ependymal and choroid plexus tumours arise in anatomically related regions. Their intraoperative differential diagnosis is large and depends on factors such as age, tumour site and clinical presentation. Squash cytology can provide valuable information in this context. Cytological features of conventional ependymomas, subependymomas and myxopapillary ependymomas as well as choroid plexus tumours are reviewed and illustrated. Differential diagnostic considerations integrating morphological and clinical information are discussed.

Choroid plexus enlargement in patients with obstructive sleep apnea.

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.

Glymphatic dysfunction mediates the influence of choroid plexus enlargement on information processing speed in patients with white matter hyperintensities.

Glymphatic dysfunction has been correlated with cognitive decline, with a higher choroid plexus volume (CPV) being linked to a slower glymphatic clearance rate. Nevertheless, the interplay between CPV, glymphatic function, and cognitive impairment in white matter hyperintensities (WMHs) has not yet been investigated. In this study, we performed neuropsychological assessment, T1-weighted three-dimensional (3D-T1) images, and diffusion tensor imaging (DTI) in a cohort of 206 WMHs subjects and 43 healthy controls (HCs) to further explore the relationship. The DTI analysis along the perivascular space (DTI-ALPS) index, as a measure of glymphatic function, was calculated based on DTI. Severe WMHs performed significantly worse in information processing speed (IPS) than other three groups, as well as in executive function than HCs and mild WMHs. Additionally, severe WMHs demonstrated lower DTI-ALPS index and higher CPV than HCs and mild WMHs. Moderate WMHs displayed higher CPV than HCs and mild WMHs. Mini-Mental State Examination, IPS, and executive function correlated negatively with CPV but positively with DTI-ALPS index in WMHs patients. Glymphatic function partially mediated the association between CPV and IPS, indicating a potential mechanism for WMHs-related cognitive impairment. CPV may act as a valuable prognostic marker and glymphatic system as a promising therapeutic target for WMHs-related cognitive impairment.

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2.

Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2-induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21-encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2-induced neuropathogenesis.

Choroid plexus enlargement is associated with future periventricular neurodegeneration in multiple sclerosis.

BACKGROUND: The choroid plexus (CP), located within the ventricles of the brain and the primary producer of cerebrospinal fluid, has been shown to be enlarged in patients with multiple sclerosis (MS) and linked to periventricular remyelination failure. Atrophied T2-lesion volume (aT2-LV), a promising neurodegenerative imaging marker in progressive MS (PMS), reflects the volume of periventricular lesions subsumed into cerebrospinal fluid over the follow-up. METHODS: In a cohort of 143 people with relapsing-remitting MS (RRMS) and 53 with PMS, we used 3T magnetic resonance imaging (MRI) to quantify CP volume (CPV) at baseline and aT2-LV over an average of 5.4 years of follow-up. Partial correlations, adjusting for age and sex, and linear regression analyses were used to assess the relationships between imaging measures. RESULTS: In both cohorts, CPV was associated with aT2-LV in both the RRMS group (r = 0.329, p < 0.001) as well as the PMS group (r = 0.522, p < 0.001). In regression analyses predicting aT2-LV, ventricular volume (final adjusted R2 = 0.407, p < 0.001) explained additional variance beyond age, sex, and T2-lesion volume in the RRMS group while CPV (final adjusted R2 = 0.446, p = 0.009) was retained in the PMS group. CONCLUSION: Findings from this study suggest that the CP enlargement is associated with future neurodegeneration, with a particularly relevant role in PMS.

Choroid plexus imaging in multiple sclerosis management - a systematic review.

INTRODUCTION: Multiple sclerosis (MS) is a central nervous system (CNS) disease associated with inflammation, demyelination, and neurodegeneration. It affects more than 2 million people globally, and usually occurs in young adults, three-quarters of whom are women. Importantly, accurate diagnosis and treatment are essential, as this disease can lead to the rapid development of disability. The choroid plexus (CP) is a structure widely known as the main cerebrospinal fluid source. However, it is also involved in immune cell trafficking to the cerebrospinal fluid, which is increased in different neurological disorders, particularly those associated with neuroinflammation. As MS is generally thought to be caused by an autoimmune process, it has been suggested that the choroid plexus may play a significant role in its pathogenesis, manifesting via changes in imaging characteristics. MATERIAL AND METHODS: Although research regarding this topic has been very limited, the results of the available studies appear promising. To further investigate this subject, we performed a systematic literature review according to the PRISMA 2020 guidelines. The PubMed and Embase databases were searched for relevant articles, and after thorough analysis, 16 studies were included in our review. RESULTS: CP volume was significantly increased in MS patients compared to healthy individuals. Furthermore, some studies found that CP enlargement occurs even before a definite diagnosis. Moreover, a few articles reported correlations between CP volume and brain atrophy, or even disease severity. CONCLUSIONS: Our findings show that CP imaging has the potential to become a novel and valuable tool in multiple sclerosis management.