Plexus Volume Research Articles

Choroid Plexus Volume Change-A Candidate for a New Radiological Marker of MS Progression.

(1) Background: Multiple sclerosis (MS) is an auto-immune, chronic, neuroinflammatory, demyelinating disease that affects mainly young patients. This progressive inflammatory process causes the chronic loss of brain tissue and results in a deterioration in quality of life. To monitor neuroinflammatory process activity and predict the further development of disease, it is necessary to find a suitable biomarker that could easily be used. In this research, we verify the usability of choroid plexus (CP) volume, a new MS biomarker, in the monitoring of the progression of multiple sclerosis disease. (2) Methods: A single-center, prospective study with three groups of patients was conducted based on the following groups: MS patients who received experimental cellular therapy (Treg), treatment-naïve MS patients and healthy controls. (3) Results: This study concludes that there is a correlation between the CPV/TIV (choroid plexus/total intracranial volume) ratio and the progress of multiple sclerosis disease-patients with MS (MS + Treg) had larger volumes of choroid plexuses. CPV/TIV ratios in MS groups were constantly and significantly growing. In the Treg group, patients with relapses had larger plexuses in comparison to the group with no relapses of MS. A similar correlation was observed for the GD+ group (patients with postcontrast enhancing plaques) compared against the non-GD group (patients without postcontrast enhancing plaques). (4) Conclusion: Choroid plexus volume, due to its immunological function, correlates with the inflammatory process in the central nervous system. We consider it to become a valuable radiological biomarker of MS activity.

Association between choroid plexus volume and cognition in Parkinson disease.

The choroid plexus (CP) clears harmful metabolites from the central nervous system as part of the glymphatic system. We investigated the association of CP volume (CPV) with baseline and longitudinal cognitive decline in patients with Parkinson disease (PD). We retrospectively reviewed the medical records of 240 patients with newly diagnosed PD who had undergone detailed neuropsychological tests and high-resolution T1-weighted structural magnetic resonance imaging during the initial assessment. The CPV of each patient was automatically segmented, and the intracranial volume ratio was used in subsequent analyses. The relationship between CPV and baseline composite scores of each cognitive domain was assessed using multivariate linear regression analyses. A Cox proportional hazards model was used to compare the risk of dementia conversion with CPV. CPV negatively correlated with composite scores of the frontal/executive function domain (β = -0.375, p = 0.002) after adjusting for age, sex, years of education, and parkinsonian symptom duration. The Cox regression model revealed that a larger CPV was associated with a higher risk of dementia conversion (hazard ratio [HR] = 1.509, p = 0.038), which was no longer significant after adjusting for the composite scores of the frontal/executive function domain. A mediation analysis demonstrated that the effect of CPV on the risk of dementia conversion was completely mediated by frontal/executive function (direct effect: HR = 1.203, p = 0.396; indirect effect: HR = 1.400, p = 0.015). Baseline CPV is associated with baseline frontal/executive function, which subsequently influences dementia conversion risk in patients with PD.

Association of Choroid Plexus Volume With Serum Biomarkers, Clinical Features, and Disease Severity in Patients With Frontotemporal Lobar Degeneration Spectrum.

Choroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study we investigated ChP volume in a large cohort of frontotemporal lobar degeneration (FTLD) spectrum patients to explore a possible link between ChP volume and other disease-specific biomarkers. Participants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL) and serum phosphorylated-Tau181 (p-Tau181), cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models (GMM) algorithm. Three-hundred and sixteen patients within FTLD spectrum were included in this study, specifically 135 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD), 75 primary progressive aphasia (PPA), 46 progressive supranuclear palsy (PSP), 60 corticobasal syndrome (CBS). In addition, 82 age-matched healthy subjects were recruited as controls (HC). ChP volume was significantly larger in FTLD patients compared with HC, across the clinical subtype. Moreover, we found a significant difference in ChP volume between HC and patients stratified for disease-severity based on CDRplus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioural deficits, as well as with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from FTLD patients better than other previously identified brain structure volumes. Considering the clinical, pathological, and genetic heterogeneity of the disease, ChP could represent a potential biomarker across the FTLD spectrum, especially at the early stage of disease. Further longitudinal studies are needed to establish its role in disease onset and progression. This study provides Class III evidence that choroid plexus volume, as measured on MRI scan, can assist in differentiating patients with FTLD from healthy controls, and in characterizing disease severity.

Relationship between the tau protein and choroid plexus volume in Alzheimer's disease.

Tau protein accumulation in the brain is thought to be one of the causes of Alzheimer's disease (AD). Recent studies found that the choroid plexus (CP) has a role in β-amyloid and tau protein clearance in the brain. We evaluated the relationships between CP volume and the ß-amyloid and tau protein depositions. Participants were 20 patients with AD and 35 healthy subjects who underwent MRI and PET scanning using the ß-amyloid tracer 11C-PiB and the tau/inflammatory tracer 18F-THK5351. We computed the volume of the CP and estimated the relationships between the CP volume and ß-amyloid and tau protein/inflammatory deposition by Spearman's correlation test. The CP volume was significantly positively correlated with both the standardized uptake value ratio (SUVR) of 11C-PiB and the SUVR of 18F-THK5351 in all participants. The CP volume was also significantly positively correlated with the SUVR of 18F-THK5351in patients with AD. Our data suggested that the volume of the CP was a good biomarker for the evaluation of tau deposition and neuroinflammation.

Increased apparent blood flow and volume of the choroid plexus in the Alzheimer’s Disease patients

BackgroundRecent works suggested the association between the dysfunctional glymphatic system and Alzheimer's Disease, which shows as alternated cerebrospinal fluid production. It is believed that the choroid plexus is the major site of CSF production conventionally and the choroid plexus blood flow is related to the production rate directly. Therefore, we investigated the choroid plexus perfusion in AD patients using arterial spin labeling (ASL) and MRI retrospectively.Method21 AD patients (15 males, 76.1±5.7 years), 36 MCI patients (20 males, 72.6±7.9 years), and 88 healthy controls (40 males, 74.8±8.0 years) from the ADNI3 were included in this study. The lateral choroid plexus regions were segmented automatically based on a 3D U‐net deep learning method, which has been demonstrated with higher accuracy compared to the Freesurfer. In addition, the gray matter mask was segmented from the T1 weighted images using SPM12, and it was used to transfer the ASL and M0 images to the T1 weighted image space. Relative cerebral blood flow was quantified by first dividing the ASL image with its smoothed M0 image (a Gaussian filter with the sigma of 4 pixels), and then normalizing the mean signal of the choroid plexus region with the mean of the gray matter region. The gray matter mask was chosen as the region with a probability higher than 0.5.ResultIn the nonparametric Mann‐Whitney U test, the choroid plexus volume of the AD patients (1.58±0.40ml) was significantly larger (p = 0.036) than that of the healthy controls (1.41±0.39). In addition, the AD patients (0.85±0.30) showed significantly higher (p = 0.017) relative perfusion of the choroid plexus regions than the healthy controls (0.70±0.20).ConclusionThe enlarged volume and increased blood flow of the choroid plexus may suggest the over‐compensation of CSF production in AD patients. However, further investigation is required to separate the blood flow and CSF signal in ASL at the choroid plexus region.

Influence of Cardiorespiratory Fitness and MRI Measures of Neuroinflammation on Hippocampal Volume in Multiple Sclerosis Patients (S27.007)

<h3>Objective:</h3> To investigate whether higher cardiorespiratory fitness (CRF) may limit the detrimental effects of neuroinflammation on hippocampal volume in the main multiple sclerosis (MS) clinical phenotypes. <h3>Background:</h3> The hippocampus is a clinically-relevant brain region that is characterized by neuroplasticity and neurogenesis also in adults. Neuroinflammation and CRF may specifically influence hippocampal integrity, thus modulating the processes promoting neurogenesis and neuroprotection that contribute to the preservation of functions. <h3>Design/Methods:</h3> Brain structural MRI scans and maximum oxygen consumption (VO₂max), a proxy of CRF, were acquired from 81 MS patients (27 relapsing-remitting [RR] and 54 progressive [P]), and 47 age- and sex-matched healthy controls (HC). White matter T2-hyperintense lesion volume (T2-LV) and choroid plexus volume (CPV) were quantified as neuroinflammatory measures. Associations of T2-LV, CPV and CRF with normalized brain (NBV), gray matter (NGMV), thalamic (NTV) and hippocampal volumes were assessed using linear regression analysis. Stepwise hierarchical regression models were used to evaluate the independent contribution of demographic, clinical, T2-LV, CPV and VO₂max in explaining the aforementioned volumes. <h3>Results:</h3> In MS, higher T2-LV was significantly associated with lower global and regional brain volumes (standardized-β from −0.706 to −0.356, p≤0.009), except for NGMV (p=0.105). Higher CPV was significantly associated only with lower NBV and NTV in both RRMS and PMS patients (standardized-β from −0.545 to −0.290, p≤0.045). Higher VO₂max was significantly associated only with higher normalized hippocampal volume only in RRMS patients (standardized-β=0.448, p=0.013). Using stepwise hierarchical regression models, T2-LV in both RRMS (ΔR²=0.124, p=0.043) and PMS patients (ΔR²=0.095, p=0.028) and VO₂max only in RRMS patients (ΔR²=0.153, p=0.014) were found to explain a significant portion of hippocampal volume variance. <h3>Conclusions:</h3> By exerting beneficial neurotrophic effects, a higher CRF may have a specific neuroprotective role for the hippocampus, mainly in the early phases of MS. <b>Disclosure:</b> Mr. Morozumi has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Albergoni has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Elisabetta Pagani has nothing to disclose. Alessandro Meani has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Choroid plexus volume is enlarged in clinically isolated syndrome patients with optic neuritis

Objectives: We investigated choroid plexus (CP) volume in patients presenting with optic neuritis (ON) as a clinically isolated syndrome (CIS), compared to a cohort with established relapsing–remitting multiple sclerosis (RRMS) and healthy controls (HCs). Methods: Three-dimensional (3D) T1, T2-FLAIR and diffusion-weighted sequences were acquired from 44 ON CIS patients at baseline, 1, 3, 6 and 12 months after the onset of ON. Fifty RRMS patients and 50 HCs were also included for comparison. Results: CP volumes was larger in both ON CIS and RRMS groups compared to HCs, but not significantly different between ON CIS and RRMS patients (analysis of covariance (ANCOVA) adjusted for multiple comparisons). Twenty-three ON CIS patients who converted to clinically definite MS (MS) demonstrated CP volume similar to RRMS patients, but significantly larger compared to HCs. In this sub-group, CP volume was not associated with the severity of optic nerve inflammation or long-term axonal loss, not with brain lesion load. A transient increase of CP volume was observed following an occurrence of new MS lesions on brain magnetic resonance imaging (MRI). Interpretation: Enlarged CP can be observed very early in a disease. It transiently reacts to acute inflammation, but not associated with the degree of tissue destruction.

Choroid plexus volume as a proxy of neuroinflammation in depression

IntroductionChoroid plexus (CP) is a physiological barrier, producing cerebrospinal fluid (CSF), neurotrophic, and inflammatory factors. It’s also involved in the neuro-immune axis, facilitating the interplay between central and peripheral inflammation, allowing trafficking of immune cells. Coherently, CP enlargement has been found in psychiatric diseases characterized by inflammatory signature. Although CP volume correlates with central microglia activation in major depressive disorder (MDD), it’s never been directly associated with peripheral markers in mood disorders.ObjectivesExamine CP volume in mood disorders and healthy controls (HC) in relation to clinical features and peripheral inflammatory markers.MethodsCP volume was extracted with FreeSurfer in 72 HC and 152 age- and sex-matched depressed patients: 79 BD and 73 MDD. Plasma analytes in patients were collected through immunoassay technology (Bioplex). We tested for the effect of age by group on CP volume. Then we focused on the interaction between illness duration and diagnosis in predicting CP volume. After testing the effect of specific analytes by diagnosis, we calculated moderated moderation models (SPSS, PROCESS) setting each analyte as independent variable, CP volume as predicted variable and illness duration and diagnosis as moderators. We get the effects’ significance with the likelihood ratio statistic, always controlling for age, sex, and intracranial volume.ResultsPatients were comparable in illness duration and severity. CP volume is differentially distributed through groups (right: p=0.04; left: p&lt;0.01), with higher volumes in the clinical groups. Age by group significantly predict right CP volume (p=0.01). Also, duration of illness differently predicts right CP volume in MDD and BD (p=0.03) (Figure1). Then, given the significant interaction effect of IL13 (p=0.02) and IL1ra (p=0.01) in predicting right CP, we run the moderated moderation model. Longer illness duration has an effect in strengthening the opposite predicting value of IL1ra (ΔR2=0.03, p&lt;0.01) on right CP volume in MDD and BD (Figure2).Image:Image 2:ConclusionsOur findings propose CP as a proxy of inflammation in depression, being significantly predicted by peripheral immune markers in MDD and BD. In particular, the signature of inflammation in depression, could represent the neurotoxic load of the disease over the illness, with a worse effect in BD, with possible disruption of brain barriers permeability and an opposite effect of tightening and central segregation in MDD. Further analyses are needed to better elucidate this neurobiological mechanisms across mood disorders.Disclosure of InterestNone Declared

Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus.

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.

Crosstalk across barriers: choroid plexus volume affects white matter integrity in bipolar depression

Crosstalk across barriers: choroid plexus volume affects white matter integrity in bipolar depression

Enlarged choroid plexus related to cortical atrophy in multiple sclerosis.

To investigate the correlation between choroid plexus volume and whole brain morphology in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Fifty-one patients with MS, 42 patients with NMOSD, and 56 healthy controls (HC) were recruited. The morphological changes in choroid plexus and whole brain tissue were compared between three groups and the correlations between choroid plexus volume and brain atrophy were further investigated. The longitudinal alterations of brain morphology in 25 MS and 20 NMOSD patients were compared. Compared to the HC group, the choroid plexus volumes were increased in the MS group (p < 0.001) but not in the NMOSD group (p > 0.05). Compared to the HC group, the MS group showed reduced cortex thickness, deep gray matter volume, and increased ventricle system volume, and the NMOSD group showed increased third ventricle volume (all p < 0.05, false discovery rate corrected). In the MS group, there were widespread correlations between enlarged choroid plexus volume and reduced cerebral cortex thickness (p < 0.05, r = -0.292~-0.538, false discovery rate corrected). The interval time was not significantly different between the MS (median: 1.37 years) and NMOSD group (median: 1.25 years) (p > 0.05). In MS, compared with the baseline, the right hippocampus and nucleus accumbens volumes were decreased in long follow-up, and bilateral lateral ventricle volumes were increased both in short and long follow-up (all p < 0.05, false discovery rate corrected). The enlarged choroid plexus related to reduced cortical thickness and progressive local brain atrophy are shown in MS patients, but not obvious in NMOSD patients. • MS and NMOSD have different altered patterns in choroid plexus volume and brain atrophy. • The enlarged choroid plexus related to brain atrophy is shown in MS patients, but not obvious in NMOSD patients. • Progressive local brain atrophy is shown in MS patients, but not obvious in NMOSD patients.

Choroid plexus volume is associated with levels of CSF proteins predominantly expressed by the choroid plexus in non‐demented individuals with AD pathophysiology.

AbstractBackgroundThe choroid plexus (CP) is a structure located inside the brain ventricles and is responsible for the production of cerebrospinal fluid (CSF), transport of proteins across the epithelium to the CSF and clearance of proteins from the CSF. The CP undergoes changes with aging, which are exacerbated in Alzheimer's disease (AD) and could alter CP functioning. Nonetheless, the relation between CP functioning and AD pathophysiology is still unclear. Here, we investigated the association of CP volume with levels of CSF proteins predominantly expressed by the CP and amyloid positivity in non‐demented individuals.MethodWe included 235 individuals with normal cognition (NC) or mild cognitive impairment (MCI) from the European EMIF‐AD MBD study (49% women, mean age 67.9 (SD 7.9) years). Based on CSF Aβ1‐42 (A, data‐driven cut‐offs) and p‐tau (T, center‐specific cut‐offs), individuals were classified as cognitively normal with normal A and T (controls, n=54). Based on CSF Aβ1‐42, individuals with NC or MCI were classified as amyloid‐positive (CN A+, n=61; MCI A+, n=67). CSF proteomic data were centrally generated using TMT mass spectrometry and 5 CSF proteins with predominant expression in the CP were selected based on the Protein Atlas, Harmonizome and literature (TTR, MFRP, SLC5A5, FOLR1, SOD3). CP and hippocampal volumes on MRI were quantified using FreeSurfer. We used non‐parametric (Spearman) partial correlations corrected for age, gender and total intracranial volume (TIV).ResultLower Aβ42 levels were associated with higher CP volume in MCI (Figure 1). Higher levels of CP predominant expressed proteins were generally associated with increased CP volume in persons with amyloid positivity, in both preclinical and prodromal AD (Table 1). Lower Aβ42 levels were associated with lower hippocampal volume in MCI (Figure 2). Lower hippocampal volumes were associated with higher CP volumes in MCI (Figure 3). Nonetheless, hippocampal volume and the levels of CP predominant expressed proteins were generally not correlated (Table 2).ConclusionOur findings suggest that CP volume is associated with levels of proteins predominantly expressed by the CP in predementia stages of AD. This would suggest CP dysfunction in early AD. This is important for future research and AD treatment development.

Differences in the choroid plexus volume and microstructure are associated with body adiposity.

The choroid plexus (CP) is a cerebral structure located in the ventricles that functions in producing most of the brain’s cerebrospinal fluid (CSF) and transporting proteins and immune cells. Alterations in CP structure and function has been implicated in several pathologies including aging, multiple sclerosis, Alzheimer’s disease, and stroke. However, identification of changes in the CP remains poorly characterized in obesity, one of the main risk factors of neurodegeneration, including in the absence of frank central nervous system alterations. Our goal here was to characterize the association between obesity, measured by the body mass index (BMI) or waist circumference (WC) metrics, and CP microstructure and volume, assessed using advanced magnetic resonance imaging (MRI) methodology. This cross-sectional study was performed in the clinical unit of the National Institute on Aging and included a participant population of 123 cognitively unimpaired individuals spanning the age range of 22 – 94 years. Automated segmentation methods from FreeSurfer were used to identify the CP structure. Our analysis included volumetric measurements, quantitative relaxometry measures (T 1 and T 2), and the diffusion tensor imaging (DTI) measure of mean diffusivity (MD). Strong positive associations were observed between WC and all MRI metrics, as well as CP volume. When comparing groups based on the established cutoff point by the National Institutes of Health for WC, a modest difference in MD and a significant difference in T 1 values were observed between obese and lean individuals. We also found differences in T1 and MD between obese and overweight individuals as defined using the BMI cutoff. We conjecture that these observations in CP volume and microstructure are due to obesity-induced inflammation, diet, or, very likely, dysregulations in leptin binding and transport. These findings demonstrate that obesity is strongly associated with a decline in CP microstructural integrity. We expect that this work will lay the foundation for further investigations on obesity-induced alterations in CP structure and function.

Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy.

ObjectivesRecent studies suggested that the expansion of long‐standing multiple sclerosis (MS) lesions and an enlargement of choroid plexus may be linked to chronic inflammation and microglial activation. We investigated the potential association between plexus volume and subsequent lesion expansion in patients with relapsing‐remitting MS.MethodsPre‐ and post‐gadolinium 3D‐T1, 3D FLAIR and diffusion tensor images were acquired from 49 patients. Choroid plexus (CP) volume (normalised by Total Intracranial Volume, TIV) and lesion activity were analysed between baseline and 48 months. In addition, plexus volume was measured in 40 healthy controls of similar age and gender.ResultsBaseline CP/TIV ratio was significantly larger in RRMS patients compared to normal controls (p < 0.001). CP/TIV ratio remained stable in RRMS patients during follow‐up period. There was a strong correlation between baseline CP/TIV ratio and subsequent rate of chronic lesion expansion (p < 0.001), which was stronger in close proximity to CSF. A cut‐off of 98 × 10−5 CP/TIV ratio predicted future lesion expansion with a sensitivity of 85% and specificity of 76%. CP/TIV ratio larger than a cut‐off was associated with >8‐fold increased risk of chronic lesion expansion. Baseline CP/TIV ratio was also associated with change in Mean Diffusivity (MD) inside of chronic lesions. Furthermore, baseline CP/TIV ratio significantly correlated with central brain atrophy. There was, however, no correlation between CP/TIV ratio and volume of new lesions.InterpretationOur data demonstrate that baseline CP/TIV ratio predicts subsequent expansion of chronic periventricular MS lesions and associated tissue damage within and outside of chronic lesions.

Mind over what matters: How training in emotional self-regulation can strengthen the immune response in lonely elders

Patients with treatment-resistant schizophrenia (TRS) suffer severe, long-term psychotic symptoms and chronic stress. Salivary kynurenic acid (KYNA) and choroid plexus were evidenced to relate to psychological stress. We hypothesized that TRS patients would have higher salivary KYNA levels than patients who respond to antipsychotics (NTRS) and healthy controls (HC), and increased salivary KYNA levels are associated with clinical phenotypes and choroid plexus volume. A total of 66 HC participants, 53 patients with TRS and 46 with NTRS were enrolled. Salivary KYNA levels were measured by liquid chromatography-tandem mass spectrometry, choroid plexus volume by magnetic resonance imaging, and cognitive functions with the MATRICS Consensus Cognitive Battery. The TRS group had significantly higher salivary KYNA levels than the NTRS group (p = 0.003), who in turn had higher salivary KYNA than HC (p = 0.02). Higher salivary KYNA levels were associated with larger choroid plexus volume (r = 0.48, p = 0.004); lower attention/vigilance (r = -0.44, p = 0.004), verbal learning (r = -0.44, p = 0.004), total MCCB score (r = -0.42, p = 0.005); and a higher total PANSS score (r = 0.48, p = 0.004) in TRS patients. An enlarged choroid plexus also related to worse attention/vigilance (r = -0.39, p = 0.03), verbal learning (r = -0.55, p = 0.001), total MCCB score (r = -0.41, p = 0.02) and clinical symptoms (r = 0.48, p = 0.004) in TRS patients only. We conclude that elevated salivary KYNA levels and associated choroid plexus enlargement are clinically relevant indicators of TRS, with salivary KYNA being particularly valuable as a peripheral marker. Our findings should benefit TRS research and benefit the improvement of personalized treatment.

Elevated salivary kynurenic acid levels related to enlarged choroid plexus and severity of clinical phenotypes in treatment-resistant schizophrenia

Patients with treatment-resistant schizophrenia (TRS) suffer severe, long-term psychotic symptoms and chronic stress. Salivary kynurenic acid (KYNA) and choroid plexus were evidenced to relate to psychological stress. We hypothesized that TRS patients would have higher salivary KYNA levels than patients who respond to antipsychotics (NTRS) and healthy controls (HC), and increased salivary KYNA levels are associated with clinical phenotypes and choroid plexus volume. A total of 66 HC participants, 53 patients with TRS and 46 with NTRS were enrolled. Salivary KYNA levels were measured by liquid chromatography-tandem mass spectrometry, choroid plexus volume by magnetic resonance imaging, and cognitive functions with the MATRICS Consensus Cognitive Battery. The TRS group had significantly higher salivary KYNA levels than the NTRS group (p = 0.003), who in turn had higher salivary KYNA than HC (p = 0.02). Higher salivary KYNA levels were associated with larger choroid plexus volume (r = 0.48, p = 0.004); lower attention/vigilance (r = -0.44, p = 0.004), verbal learning (r = -0.44, p = 0.004), total MCCB score (r = -0.42, p = 0.005); and a higher total PANSS score (r = 0.48, p = 0.004) in TRS patients. An enlarged choroid plexus also related to worse attention/vigilance (r = -0.39, p = 0.03), verbal learning (r = -0.55, p = 0.001), total MCCB score (r = -0.41, p = 0.02) and clinical symptoms (r = 0.48, p = 0.004) in TRS patients only. We conclude that elevated salivary KYNA levels and associated choroid plexus enlargement are clinically relevant indicators of TRS, with salivary KYNA being particularly valuable as a peripheral marker. Our findings should benefit TRS research and benefit the improvement of personalized treatment.

Choroid Plexus Volume and Permeability at Brain MRI within the Alzheimer Disease Clinical Spectrum.

Background Mounting evidence suggests that the choroid plexus (CP) plays an important role in the pathophysiology of Alzheimer disease (AD), but its imaging profile in cognitive impairment remains unclear. Purpose To evaluate CP volume, permeability, and susceptibility by using MRI in patients at various stages of cognitive impairment. Materials and Methods This retrospective study evaluated patients with cognitive symptoms who underwent 3.0-T MRI of the brain, including dynamic contrast-enhanced (DCE) imaging and quantitative susceptibility mapping (QSM), between January 2013 and May 2020. CP volume was automatically segmented using three-dimensional T1-weighted sequences; the volume transfer constant (ie, Ktrans) and fractional plasma volume (ie, Vp) were determined using DCE MRI, and susceptibility was assessed using QSM. The effects of CP volume, expressed as the ratio to intracranial volume, on cognition were evaluated using multivariable linear regression adjusted for age, sex, education, apolipoprotein E ε4 allele status, and volumetric measures. Results A total of 532 patients with cognitive symptoms (mean age, 72 years ± 9 [SD]; 388 women) were included: 78 with subjective cognitive impairment (SCI), 158 with early mild cognitive impairment (MCI), 149 with late MCI, and 147 with AD. Among these, 132 patients underwent DCE MRI and QSM. CP volume was greater in patients at more severe stages (ratio of intracranial volume × 103: 0.9 ± 0.3 for SCI, 1.0 ± 0.3 for early MCI, 1.1 ± 0.3 for late MCI, and 1.3 ± 0.4 for AD; P < .001). Lower Ktrans (r = -0.19; P = .03) and Vp (r = -0.20; P = .02) were negatively associated with CP volume; susceptibility was not (r = 0.15; P = .10). CP volume was negatively associated with memory (B = -0.67; standard error of the mean [SEM], 0.21; P = .01), executive function (B = -0.90; SEM, 0.31; P = .01), and global cognition (B = -0.82; SEM, 0.32; P = .01). Conclusion Among patients with cognitive symptoms, larger choroid plexus volume was associated with severity of cognitive impairment in the Alzheimer disease spectrum. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Chiang in this issue.

Choroid Plexus Volume in Multiple Sclerosis vs Neuromyelitis Optica Spectrum Disorder: A Retrospective, Cross-sectional Analysis.

Background and ObjectivesThe choroid plexus has been shown to play a crucial role in CNS inflammation. Previous studies found larger choroid plexus in multiple sclerosis (MS) compared with healthy controls. However, it is not clear whether the choroid plexus is similarly involved in MS and in neuromyelitis optica spectrum disorder (NMOSD). Thus, the aim of this study was to compare the choroid plexus volume in MS and NMOSD.MethodsIn this retrospective, cross-sectional study, patients were included by convenience sampling from 4 international MS centers. The choroid plexus of the lateral ventricles was segmented fully automatically on T1-weighted MRI sequences using a deep learning algorithm (Multi-Dimensional Gated Recurrent Units). Uni- and multivariable linear models were applied to investigate associations between the choroid plexus volume, clinically meaningful disease characteristics, and MRI parameters.ResultsWe studied 180 patients with MS and 98 patients with NMOSD. In total, 94 healthy individuals and 47 patients with migraine served as controls. The choroid plexus volume was larger in MS (median 1,690 µL, interquartile range [IQR] 648 µL) than in NMOSD (median 1,403 µL, IQR 510 µL), healthy individuals (median 1,533 µL, IQR 570 µL), and patients with migraine (median 1,404 µL, IQR 524 µL; all p < 0.001), whereas there was no difference between NMOSD, migraine, and healthy controls. This was also true when adjusted for age, sex, and the intracranial volume. In contrast to NMOSD, the choroid plexus volume in MS was associated with the number of T2-weighted lesions in a linear model adjusted for age, sex, total intracranial volume, disease duration, relapses in the year before MRI, disease course, Expanded Disability Status Scale score, disease-modifying treatment, and treatment duration (beta 4.4; 95% CI 0.78–8.1; p = 0.018).DiscussionThis study supports an involvement of the choroid plexus in MS in contrast to NMOSD and provides clues to better understand the respective pathogenesis.

Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I.

To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls. Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4-5years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.

Choroid Plexus Volume Predicts Expansion of Chronic Lesions and Associated Brain Atrophy in Multiple Sclerosis

Choroid Plexus Volume Predicts Expansion of Chronic Lesions and Associated Brain Atrophy in Multiple Sclerosis