Volume enlargement of the choroid plexus and brain ventricles in drug-naïve, first-episode major depressive disorder.

BACKGROUND: We investigated volumetric alterations in the bilateral choroid plexus (ChP) and brain ventricles of patients during their first episode of major depressive disorder (MDD) prior to antidepressant treatment. METHODS: Seventy-one first-episode drug-naïve patients with MDD and seventy-four healthy control (HC) subjects were recruited. MRI data were obtained, and bilateral ChP and brain ventricle volumes were evaluated using segmentation, based on the adaptive multiscale and expectation maximization method. One-way multivariate analysis of covariance was used to calculate volumetric differences in the bilateral ChP and brain ventricles between the groups, and partial Pearson correlation analyses were used to investigate the relationship between the volumes of the bilateral ChP and brain ventricles. RESULTS: First-episode drug-naïve patients with MDD showed enlarged volumes of the bilateral ChP, bilateral lateral ventricle (LV), and third ventricle compared with HCs. The ChP volume positively correlated with the LV and third ventricle, but not with the fourth ventricle in patients with MDD, whereas it correlated with all four brain ventricles in HCs. We did not observe significant correlations between bilateral ChP volume and brain ventricles, HAMD scores, or symptom severity. LIMITATIONS: Our study populations differed in age and sex and we did not extensively measure the amount of neuroinflammation in the brain or blood, include a functional assessment, nor evaluate other neural comorbidities or neuropsychiatric conditions. CONCLUSIONS: Our study extends the existing research to suggest that illness-related alterations in ChP volume enlargement in first-episode antidepressant-naïve patients with MDD may serve as a trait measure.

Chronic Active Lesions and Larger Choroid Plexus Explain Cognition and Fatigue in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Chronic inflammation may contribute to cognitive dysfunction and fatigue in patients with multiple sclerosis (MS). Paramagnetic rim lesions (PRLs) and choroid plexus (CP) enlargement have been proposed as markers of chronic inflammation in MS being associated with a more severe disease course. However, their relation with cognitive impairment and fatigue has not been fully explored yet. Here, we investigated the contribution of PRL number and volume and CP enlargement to cognitive impairment and fatigue in patients with MS. METHODS: Brain 3T MRI, neurologic evaluation, and neuropsychological assessment, including the Brief Repeatable Battery of Neuropsychological Tests and Modified Fatigue Impact Scale, were obtained from 129 patients with MS and 73 age-matched and sex-matched healthy controls (HC). PRLs were identified on phase images of susceptibility-weighted imaging, whereas CP volume was quantified using a fully automatic method on brain three-dimensional T1-weighted and fluid-attenuated inversion recovery MRI sequences. Predictors of cognitive impairment and fatigue were identified using random forest. RESULTS: Thirty-six (27.9%) patients with MS were cognitively impaired, and 31/113 (27.4%) patients had fatigue. Fifty-nine (45.7%) patients with MS had ≥1 PRLs (median = 0, interquartile range = 0;2). Compared with HC, patients with MS showed significantly higher T2-hyperintense white matter lesion (WM) volume; lower normalized brain, thalamic, hippocampal, caudate, cortical, and WM volumes; and higher normalized CP volume (p from <0.001 to 0.040). The predictors of cognitive impairment (relative importance) (out-of-bag area under the curve [OOB-AUC] = 0.707) were normalized brain volume (100%), normalized caudate volume (89.1%), normalized CP volume (80.3%), normalized cortical volume (70.3%), number (67.3%) and volume (66.7%) of PRLs, and T2-hyperintense WM lesion volume (64.0%). Normalized CP volume was the only predictor of the presence of fatigue (OOB-AUC = 0.563). DISCUSSION: Chronic inflammation, with higher number and volume of PRLs and enlarged CP, may contribute to cognitive impairment in MS in addition to gray matter atrophy. The contribution of enlarged CP in explaining fatigue supports the relevance of immune-related processes in determining this manifestation independently of disease severity. PRLs and CP enlargement may contribute to the pathophysiology of cognitive impairment and fatigue in MS, and they may represent clinically relevant therapeutic targets to limit the impact of these clinical manifestations in MS.

Longitudinal enlargement of choroid plexus is associated with chronic lesion expansion and neurodegeneration in RRMS patients.

BACKGROUND AND OBJECTIVE: We explored dynamic changes in the choroid plexus (CP) in patients with relapsing-remitting multiple sclerosis (RRMS) and assessed its relationship with chronic lesion expansion and atrophy in various brain compartments. METHODS: Fifty-seven RRMS patients were annually assessed for a minimum of 48 months with 3D FLAIR, pre- and post-contrast 3D T1 and diffusion-weighted magnetic resonance imaging (MRI). The CP was manually segmented at baseline and last follow-up. RESULTS: The volume of CP significantly increased by 1.4% annually. However, the extent of CP enlargement varied considerably among individuals (ranging from -3.6 to 150.8 mm3 or -0.2% to 6.3%). The magnitude of CP enlargement significantly correlated with central (r = 0.70, p < 0.001) and total brain atrophy (r = -0.57, p < 0.001), white (r = -0.61, p < 0.001) and deep grey matter atrophy (r = -0.60, p < 0.001). Progressive CP enlargement was significantly associated with the volume and extent of chronic lesion expansion (r = 0.60, p < 0.001), but not with the number or volume of new lesions. CONCLUSION: This study provides evidence of progressive CP enlargement in patients with RRMS. Our findings also demonstrate that enlargement of the CP volume is linked to the expansion of chronic lesions and neurodegeneration of periventricular white and grey matter in RRMS patients.

Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): validation and normative ranges across the adult lifespan.

BACKGROUND: The choroid plexus functions as the blood-cerebrospinal fluid (CSF) barrier, plays an important role in CSF production and circulation, and has gained increased attention in light of the recent elucidation of CSF circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation. Here, we propose three deep learning models that can segment the choroid plexus from commonly-acquired anatomical MRI data and report performance metrics and changes across the adult lifespan. METHODS: Fully convolutional neural networks were trained from 3D T1-weighted, 3D T2-weighted, and 2D T2-weighted FLAIR MRI using gold-standard manual segmentations in control and neurodegenerative participants across the lifespan (n = 50; age = 21-85 years). Dice coefficients, 95% Hausdorff distances, and area-under-curve (AUCs) were calculated for each model and compared to segmentations from FreeSurfer using two-tailed Wilcoxon tests (significance criteria: p < 0.05 after false discovery rate multiple comparisons correction). Metrics were regressed against lateral ventricular volume using generalized linear models to assess model performance for varying levels of atrophy. Finally, models were applied to an expanded cohort of adult controls (n = 98; age = 21-89 years) to provide an exemplar of choroid plexus volumetry values across the lifespan. RESULTS: Deep learning results yielded Dice coefficient = 0.72, Hausdorff distance = 1.97 mm, AUC = 0.87 for T1-weighted MRI, Dice coefficient = 0.72, Hausdorff distance = 2.22 mm, AUC = 0.87 for T2-weighted MRI, and Dice coefficient = 0.74, Hausdorff distance = 1.69 mm, AUC = 0.87 for T2-weighted FLAIR MRI; values did not differ significantly between MRI sequences and were statistically improved compared to current commercially-available algorithms (p < 0.001). The intraclass coefficients were 0.95, 0.95, and 0.96 between T1-weighted and T2-weighted FLAIR, T1-weighted and T2-weighted, and T2-weighted and T2-weighted FLAIR models, respectively. Mean lateral ventricle choroid plexus volume across all participants was 3.20 ± 1.4 cm3; a significant, positive relationship (R2 = 0.54-0.60) was observed between participant age and choroid plexus volume for all MRI sequences (p < 0.001). CONCLUSIONS: Findings support comparable performance in choroid plexus delineation between standard, clinically available, non-contrasted anatomical MRI sequences. The software embedding the evaluated models is freely available online and should provide a useful tool for the growing number of studies that desire to quantitatively evaluate choroid plexus structure and function ( https://github.com/hettk/chp_seg ).

Choroid plexus volume in multiple sclerosis can be estimated on structural MRI avoiding contrast injection.

We compared choroid plexus (ChP) manual segmentation on non-contrast-enhanced (non-CE) sequences and reference standard CE T1- weighted (T1w) sequences in 61 multiple sclerosis patients prospectively included. ChP was separately segmented on T1w, T2-weighted (T2w) fluid-attenuated inversion-recovery (FLAIR), and CE-T1w sequences. Inter-rater variability assessed on 10 subjects showed high reproducibility between sequences measured by intraclass correlation coefficient (T1w 0.93, FLAIR 0.93, CE-T1w 0.99). CE-T1w showed higher signal-to-noise ratio and contrast-to-noise ratio (CE-T1w 23.77 and 18.49, T1w 13.73 and 7.44, FLAIR 13.09 and 10.77, respectively). Manual segmentation of ChP resulted 3.073 ± 0.563 mL (mean ± standard deviation) on T1w, 3.787 ± 0.679 mL on FLAIR, and 2.984 ± 0.506 mL on CE-T1w images, with an error of 28.02 ± 19.02% for FLAIR and 3.52 ± 12.61% for T1w. FLAIR overestimated ChP volume compared to CE-T1w (p < 0.001). The Dice similarity coefficient of CE-T1w versus T1w and FLAIR was 0.67 ± 0.05 and 0.68 ± 0.05, respectively. Spatial error distribution per slice was calculated after nonlinear coregistration to the standard MNI152 space and showed a heterogeneous profile along the ChP especially near the fornix and the hippocampus. Quantitative analyses suggest T1w as a surrogate of CE-T1w to estimate ChP volume.Relevance statement To estimate the ChP volume, CE-T1w can be replaced by non-CE T1w sequences because the error is acceptable, while FLAIR overestimates the ChP volume. This encourages the development of automatic tools for ChP segmentation, also improving the understanding of the role of the ChP volume in multiple sclerosis, promoting longitudinal studies.Key points • CE-T1w sequences are considered the reference standard for ChP manual segmentation.• FLAIR sequences showed a higher CNR than T1w sequences but overestimated the ChP volume.• Non-CE T1w sequences can be a surrogate of CE-T1w sequences for manual segmentation of ChP.

Linking enlarged choroid plexus with plasma analyte and structural phenotypes in clinical high risk for psychosis: A multisite neuroimaging study.

BACKGROUND: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. METHODS: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. RESULTS: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1ß (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. CONCLUSIONS: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.

Enlarged choroid plexus in multiple sclerosis is associated with increased lesion load and atrophy in white matter but not gray matter atrophy.

BACKGROUND: Enlargement of the choroid plexus (CP) is reported to associate with inflammatory activity and contribute to brain atrophy in patients with multiple sclerosis (pwMS). However, a recent study in healthy volunteers (HVTs) has suggested that CP enlargement can be attributed to ventriculomegaly. OBJECTIVES: To clarify the pathological significance of the enlargement of CP in multiple sclerosis (MS). METHODS: A total of 102 pwMS (89 with relapsing-remitting MS and 13 with secondary progressive MS) and 41 HVTs were cross-sectionally evaluated using brain volumetry. The CP volume was compared between disease groups and investigated for the relationships with other brain regional volumes. RESULTS: CP volume was significantly larger in pwMS than in HVTs in the univariate analysis, but not in multivariable analysis. Meanwhile, the CP and lateral ventricle (LV) volumes were significantly correlated. CP enlargement was significantly associated with increased lesion load and cerebral white matter (WM) atrophy, even after adjusting for LV volume. In contrast, multivariable analyses revealed that LV enlargement, but not CP enlargement, was associated with total gray matter (GM) atrophy. CONCLUSION: CP enlargement was closely associated with LV enlargement. After adjusting for LV volume, CP enlargement in pwMS was associated with increased lesion load and WM atrophy but not GM atrophy.

Choroid plexus volume as a marker of retinal atrophy in relapsing remitting multiple sclerosis.

OBJECTIVE: To evaluate choroid plexus (CP) volume as a biomarker for predicting clinical disability and retinal layer atrophy in relapsing remitting multiple sclerosis (RRMS). METHODS: Ninety-five RRMS patients and 26 healthy controls (HCs) underwent 3 T whole brain MRI, expanded disability status scale (EDSS) and optical coherence tomography (OCT). Fully automated intra-retinal segmentation was performed to obtain the volumes of the retinal nerve fiber layer (RNFL), combined ganglion cell layer -inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), total macular volume (TMV) and papillomacular bundle (PMB). Automated segmentation of the CP within the lateral ventricles was performed and the choroid plexus volume (CPV) was normalized by total intracranial volume (TIV). Linear regression analysis and generalized estimating equation (GEE) models were applied to evaluate relationships between nCPV and EDSS, T2 lesion volume, disease duration, and retinal layer volumes, followed by Bonferroni correction analysis for multiple comparisons. RESULTS: RRMS patients had larger tChPV compared to HCs (p < 0.001). After Bonferroni correction, there was a significant positive correlation between tChPV and EDSS (r2 = 0.25, p = 0.0002), disease duration (r2 = 0.30, p = 0.01), and T2 lesion volume (r2 = 0.39, p = 0.0000). A robust negative correlation was found between tChPV and RNFL (p < 0.001), GCIPL (p = 0.003), TMV (p = 0.0185), PMB (p < 0.0001), G (p = 0.04), T(p = 0.0001). CONCLUSIONS: Our findings support the association of tChPV with disability and altered retinal integrity in RRMS.

Fetal choroid plexus arteriovenous malformation, masquerading as a neoplastic lesion.

A woman in her 20s, who was pregnant, underwent a routine antenatal ultrasound revealing organised intraventricular haemorrhage and a vascular area in the left thalamic region. Fetal MRI raised suspicion of arteriovenous malformation (AVM). The baby was delivered at 36 weeks via C-section, and initial brain MRI suggested a possible neoplastic lesion.Cerebral angiography confirmed a large AVM involving the left choroid plexus with arterial feeders from the left anterior and posterior choroidal arteries and a large venous varix draining into the vein of Galen. Both arterial feeders were successfully embolised with Onyx and glue, achieving complete occlusion.Choroid plexus AVMs are rare and often lead to intraventricular or intraparenchymal haemorrhage. Surgical treatment has shown success, but endovascular management is effective, especially for small, deep-seated AVMs, offering a better prognosis.

ChOP-CT: quantitative morphometrical analysis of the Hindbrain Choroid Plexus by X-ray micro-computed tomography.

The Hindbrain Choroid Plexus is a complex, cerebrospinal fluid-secreting tissue that projects into the 4th vertebrate brain ventricle. Despite its irreplaceability in the development and homeostasis of the entire central nervous system, the research of Hindbrain Choroid Plexus and other Choroid Plexuses has been neglected by neuroscientists for decades. One of the obstacles is the lack of tools that describe the complex shape of the Hindbrain Choroid Plexus in the context of brain ventricles. Here we introduce an effective tool, termed ChOP-CT, for the noninvasive, X-ray micro-computed tomography-based, three-dimensional visualization and subsequent quantitative spatial morphological analysis of developing mouse Hindbrain Choroid Plexus. ChOP-CT can reliably quantify Hindbrain Choroid Plexus volume, surface area, length, outgrowth angle, the proportion of the ventricular space occupied, asymmetries and general shape alterations in mouse embryos from embryonic day 13.5 onwards. We provide evidence that ChOP-CT is suitable for the unbiased evaluation and detection of the Hindbrain Choroid Plexus alterations within various mutant embryos. We believe, that thanks to its versatility, quantitative nature and the possibility of automation, ChOP-CT will facilitate the analysis of the Hindbrain Choroid Plexus in the mouse models. This will ultimately accelerate the screening of the candidate genes and mechanisms involved in the onset of various Hindbrain Choroid Plexus-related diseases.

The gut-brain axis: Correlation of choroid plexus volume and permeability with inflammatory biomarkers in Crohn's disease.

BACKGROUND: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD). METHODS: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores. RESULTS: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037). CONCLUSIONS: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans.

The association of CSF biomarkers and cognitive decline with choroid plexus volume in early Parkinson's disease.

OBJECTIVE: This study aims to determine the link between choroid plexus (CP) volume and cognitive decline in patients with early-stage Parkinson's disease (PD) and to test whether pathological proteins in the cerebrospinal fluid (CSF) are involved in the modulation of any detrimental effects from CP volume. METHODS: Data on 95 early-stage PD patients with 5 years of follow-up were collected from the Parkinson's Progression Marker Initiative cohort. The patients were separated into three groups based on tertiles of baseline CP volume. We then used a linear mixed model for longitudinal analysis and conducted path analysis to investigate mediating effects. RESULTS: At baseline, the patients in both the upper and middle tertile group were older and had lower concentrations of CSF Aß1-42 than those in the lowest tertile group. Longitudinal analysis showed that the upper tertile group suffered from a more rapid cognitive decline in the Symbol Digit Modalities test, Hopkins Verbal Learning Test (HVLT)-retention, and HVLT delayed recalled score. Furthermore, path analysis showed that the pathological effects of CP volume on the 5-year decline in memory might be partly mediated by the CSF Aß1-42/αsyn ratio. CONCLUSION: CP enlargement could be an independent risk factor for decreased cognition in patients with early-stage PD, and this risk may be mediated by CSF pathological proteins.

Choroid plexus vascular reactivity in moyamoya: Implications for choroid plexus regulation in ischemic stress.

BACKGROUND AND PURPOSE: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy. METHODS: We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm, repetition time = 2000 ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n = 53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p < .05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories. RESULTS: In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p ≤ .01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population. CONCLUSIONS: Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress.

DPA714 PET Imaging Shows That Inflammation of the Choroid Plexus Is Active in Chronic-Phase Intracerebral Hemorrhage.

PURPOSE: Our aims were to investigate the presence of choroid plexus (CP) inflammation in chronic-phase intracerebral hemorrhage (ICH) patients and to characterize any inflammatory cells in the CP. PATIENTS AND METHODS: An in vivo 18 F-DPA714 PET study was undertaken in 22 chronic-phase ICH patients who were admitted to the First Affiliated Hospital of Fujian Medical University or Tianjin Medical University General Hospital from April 2017 to June 2020. Ten control participants with nonhemorrhagic central nervous system diseases were included. Choroid plexus 18 F-DPA714 uptake was calculated as the average SUVR. To aid the interpretation of the 18 F-DPA714 uptake results at the CP level, Cy5-DPA714 in vivo imaging and immunofluorescence staining were used to show the presence of CP inflammation in an ICH mouse model during the chronic phase (14 weeks after ICH). Then immunofluorescence staining against translocator protein and other specific biomarkers was used to characterize the cells present in the inflamed CP of ICH mice in the chronic phase. RESULTS: PET imaging showed that CP DPA714 SUVRs in chronic-phase ICH patients were higher than in controls (mean CP SUVR ± SD; ICH group: 1.05 ± 0.35; control group: 0.81 ± 0.21; P = 0.006). Immunofluorescence staining of the CP in ICH model mice identified a population of CD45 + immune cells, peripheral monocyte-derived CD14 + cells, CD68 + phagocytes, and CD11b + resident microglia/macrophages expressing translocator protein, possibly contributing to the increased 18 F-DPA714 uptake. CONCLUSIONS: Our study shows that CP DPA714 uptake in chronic-phase ICH patients was higher than that of participants with nonhemorrhagic central nervous system diseases, which means that CP inflammation is still active in chronic-phase ICH patients.

Decreased DTI-ALPS and choroid plexus enlargement in fibromyalgia: a preliminary multimodal MRI study.

PURPOSE: The glymphatic system is a fluid exchange pathway that clears waste products that is crucial for the maintenance of brain homeostasis. However, the exact role it plays in the emergence of fibromyalgia (FM) is still not fully understood. Here, we explored the changes in non-invasive MRI proxy probably related to the glymphatic function in FM patients, and explored brain-behavior relationships. METHODS: A total of 40 participants, consisting of 20 individuals with FM and 20 healthy controls (HCs), were included in the study. The participants underwent structural T1-weighted MRI, diffusion tensor imaging (DTI), and clinical assessment. The data was obtained from an open access dataset. The study compared non-invasive MRI indices, including choroid plexus (CP) volume and DTI analysis along the perivascular space (ALPS), between the FM and HC groups. Furthermore, correlation analysis was conducted to determine the correlation between clinical parameters and both CP volume and DTI-ALPS index. RESULTS: Patients with FM had significantly higher CP volume and a lower DTI-ALPS index than HCs adjusting for age and intracranial volume. Higher CP volume was associated with lower DTI-ALPS index, and longer disease duration. CONCLUSION: Our findings demonstrate aberrant glymphatic function in FM, and that dysfunction in the brain glymphatic system may play a role in the neural mechanisms underlying FM.

Isolated choroid plexus cysts and health and developmental outcomes in childhood and adolescence - A systematic review.

OBJECTIVES: Choroid plexus cysts (CPCs) are incidental findings on ultrasound examination of the fetal brain. It is not known if isolated CPCs are associated with any adverse health or neurodevelopmental outcomes during the life course. This systematic review aimed to collate and synthesize the evidence on whether or not isolated choroid plexus cysts are associated with an increased risk of adverse health or developmental outcomes during childhood and adolescence. METHODS: A search strategy was developed specifically for this study and applied to four electronic databases Medline (Ovid), Embase (Ovid), Web of Science, and Google Scholar. Studies were assessed and selected for inclusion if there was a measurement of CPC (including single or multiple; unilateral or bilateral; isolated or presenting alongside other markers) during the antenatal or early neonatal period (<7 days) with follow-up of children and adolescents for health and developmental outcomes measured at any time from age 1 month onwards. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Due to heterogeneity in the types of outcome measures included and the timing of measurement of outcomes across the studies, it was not possible to pool data across studies and a narrative description of findings was presented. RESULTS: Eight studies (three cohorts and five case series) met the inclusion criteria. Different methods were used for outcome assessment, such as in-person assessment, parent questionnaires, medical records, and telephone interviews with parents. Six studies measured outcomes only once during the specified duration of follow-up; two studies carried out paediatric reviews of the children several times during follow-up. There were no differences in developmental outcomes or physical health between babies with CPCs reported in the three cohort studies, and no abnormalities were detected in the children that were followed up in four of the five case series studies. Most of the included studies were graded as low quality due to the small sample size, high risk of selection bias, unclear definitions of CPC or lack of a comparison group. CONCLUSIONS: The studies conducted to date do not provide evidence of adverse physical health outcomes or neurodevelopmental delays in babies with CPCs. However, most of these studies were small and included a narrow range of outcomes. Further research is needed to explore the relative incidence of outcomes such as ASD, ADHD, epilepsy and educational attainment in children with CPCs.

Tractography Navigated Endoscopic En-Bloc Excision of Pediatric Giant Choroid Plexus Tumor.

Giant choroid plexus (CP) tumors in children pose a formidable surgical challenge due to extensive vascularity/blood loss, tumor size impeding early visualization of the pedicle, hydrocephalus/mass effect distorting cerebral localization, considerable prevalence of atypical tumors and carcinoma demanding excision without tumor spillage, and retraction-associated morbidity. However, total resection of CP papilloma has excellent potential for cure. This is probably the first report in the literature of diffusion tensor imaging navigation-guided tumor pedicle targeting, endoscopic devascularization and division of pedicle followed by en bloc delivery in optimally tackling most of these challenges in a 6-year-old girl presenting with a giant lateral ventricular CP tumor. Giant CP tumors pose a formidable challenge. Extensive vascularity can cause life-threatening blood loss in children.1 Large tumor size makes it impractical during microsurgery to achieve early visualization of pedicle.2 Hydrocephalus and mass effect can distort sulcal anatomy, with potentially devastating deficits.3 Still, prevalence of atypical tumors and carcinoma warrants excision without tumor spillage.4 In Video 1, we demonstrate our "10-D" steps of en-bloc excision, exploiting panoramic visualization of endoscope5: 1. Diagnosis, 2. Diffusion tensor imaging guided pedicle targeting, 3. Design position & exposure, 4. Durotomy, 5. Dissection of sulcus, 6. Delineation of pedicle, 7. Devascularization, 8. Division of pedicle, 9. Delivery of tumor, and 10. Dural & skin closure. The conventional superior parietal lobule approach to get the tumor en-bloc would have been from the posterosuperior direction, where the tumor is likely to conceal the pedicle. The trajectory to first get to the pedicle must be from an anterosuperior direction but will violate corticospinal fibers. Hence entry point was chosen in between, just posterior to the post-central sulcus. To accommodate the 'en-bloc' excision avoiding ventricular seedlings, a 5 cm mini-craniotomy was fashioned centered on the entry point planned in the navigation system. Ventricle was entered perpendicular to the sulcus through the roof of the atrium, with least cortical transgression and avoiding injury to laterally placed optic radiation and speech areas.6 A 30-degree, 4-mm endoscope was inserted anterolateral to the tumor and fixed. The wide-angled vision offered by endoscopes enhancing meticulous dissection is the likely cause of better neurological outcomes, as noted in other ventricular lesions.7 Pedicular attachment of the tumor is coagulated thoroughly and cut, ensuring initial sparing of venous drainage. The draining vein is then coagulated and divided. 'En-bloc' excision is also known in other vascular lesions to decrease the risk of bleeding.8 The angled optics & panoramic visualization helps to identify any possible tumor seedlings.9 This is probably the first report of endoscopic en-bloc excision of a giant choroid plexus tumor in literature.

Normal growth curve of choroid plexus in children: implications for assessing hydrocephalus due to choroid plexus hyperplasia.

OBJECTIVE: Pediatric hydrocephalus requires evaluation while accounting for growth of the intracranial structures, but information on choroid plexus growth in children is lacking. This study aimed to create normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Additionally, the authors aimed to objectively assess the degree of hydrocephalus caused by choroid plexus hyperplasia (CPH) and to examine the impact of surgical procedures. METHODS: This retrospective study analyzed the head CT scans of pediatric patients with minor head trauma treated at Osaka Women's and Children's Hospital between March 2006 and May 2023. The study segmented and calculated intracranial, choroid plexus, and lateral ventricles volumes. The study also calculated the correlation coefficients among these 3 parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters, and mean ± SD values were calculated for each cluster. Growth curves were created by plotting mean values sequentially. Volume obtained from patients with CPH were z-normalized using mean and SD values and compared. RESULTS: A total of 229 CT scans (94 from females) were analyzed, and positive correlations were observed among intracranial volume, choroid plexus volume, and lateral ventricles volume, with the strongest correlation between the choroid plexus and lateral ventricles volumes. The growth rate of intracranial volume was rapid until approximately 20 months of age, while those of choroid plexus volume and lateral ventricles volume increased rapidly until approximately 1 year of age. Subsequently, choroid plexus volume and lateral ventricles volume plateaued at 1.5 ml and 10 ml, respectively. Three patients with CPH were enrolled and quantitatively evaluated on the basis of the z-normalized volume. Notable abnormal volumes of the choroid plexus (range z-normalized values 24.11-51.17) and lateral ventricles (46.78-122.36) were observed. In 2 patients, improvements in the z-normalized values of intracranial volume and lateral ventricles volume were observed after surgical interventions. Additionally, in 1 patient, choroid plexus volume was reduced by approximately 24% (range z-normalized values 51.17-38.93) after bilateral endoscopic plexus coagulation. CONCLUSIONS: This study provides normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Knowledge of these normal values holds the potential for objective assessment of abnormal values associated with hydrocephalus and choroid plexus diseases such as CPH.

Brain-derived subgroups of bipolar II depression associate with inflammation and choroid plexus morphology.

AIM: Elevated inflammation and larger choroid plexus (ChP) volume has been previously identified in mood disorders. Connections between inflammation, ChP, and clinical symptoms in bipolar II depression (BDII-D) are unclear. Data-driven clustering based on neuroanatomical phenotypes may help to elucidate neurobiological associations in BDII-D. METHODS: Inflammatory cytokines, clinical symptoms, and neuroanatomical features were assessed in 150 BDII-D patients. Sixty-eight cortical surface area (SA) and 19 subcortical volumes were extracted using FreeSurfer. The ChP volume was segmented manually using 3D Slicer. Regularized canonical correlation analysis was used to identify significantly correlated components between cortical SA and subcortical volumes (excluding the ChP), followed by k-means clustering to define brain-derived subgroups of BDII-D. Low-grade inflammation was derived by averaging the standardized z scores of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α), which were computed to create a composite z-value score. Partial Pearson correlations followed by multiple comparison correction were conducted to explore associations between inflammation, clinical symptoms, and ChP volume. RESULTS: Subgroup I demonstrated smaller subcortical volume and cortical SA, higher inflammation, and larger ChP volume compared with subgroup II. Greater ChP volume was associated with a higher low-grade inflammation (mean r = 0.289, q = 0.003), CRP (mean r = 0.249, q = 0.007), IL-6 (left r = 0.200, q = 0.03), and TNF-α (right r = 0.226, q = 0.01), while greater IL-1ß was significantly associated with severe depressive symptoms in BDII-D (r = 0.218, q = 0.045). CONCLUSIONS: Neuroanatomically-derived subgroups of BDII-D differed in their inflammation levels and ChP volume. These findings suggest an important role of elevated peripheral inflammation and larger ChP in BDII-D.