Choroid Plexus Volume in Multiple Sclerosis vs Neuromyelitis Optica Spectrum Disorder

Müller, Jannis; Sinnecker, Tim; Wendebourg, Maria Janina; Schläger, Regina; Kühle, Jens; Schädelin, Sabine; Benkert, Pascal; Derfuss, Tobias; Cattin, Philippe C.; Jud, Christoph; Spieß, Florian; Amann, Michael; Lincke, Therese; Baraković, Muhamed; Cagol, Alessandro; Tsagkas, Charidimos; Parmar, Katrin; Pröbstel, Anne‐Katrin; Reimann, Sophia; Asseyer, Susanna; Duchow, Ankelien; Brandt, Alexander U.; Ruprecht, Klemens; Hadjikhani, Nouchine; Fukumoto, Shoko; Watanabe, Mitsuru; Kitajima, Masaki; Matsushita, Takuya; Isobe, Noriko; Kira, Jun‐ichi; Kappos, Ludwig; Wuerfel, Jens; Granziera, Cristina; Paul, Friedemann; Yaldizli, Özgür

doi:10.1212/nxi.0000000000001147

Cited by 45 publications

(45 citation statements)

References 34 publications

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“…This implies that plexus enlargement may occur early in the course of MS, which is also supported by recent study of Ricigliano et al which demonstrated enlarged choroid plexus even at presymtomatic stage of the disease. 12,25 Stability of plexus and its weak association with baseline lesion volume (as was also observed in a recent study by M€ uller et al 24 ) and with the volume and severity of new lesions implies that, at least in our cohort, increased plexus size relates to a pathogenesis that is discrete from acute inflammatory demyelination, supporting, therefore, the notion that different mechanisms are likely to be responsible for acute and smouldering inflammation. 1,2,15,26,27 The essential role of the choroid plexus in maintaining the blood-CSF barrier and modulation of inflammatory cells trafficking into the central nervous system has recently attracted the attention of MS researchers.…”

Section: Figure 6 Analysis Of Association Between Plexus Volume and C...supporting

confidence: 87%

“…Stability of plexus and its weak association with baseline lesion volume (as was also observed in a recent study by Müller et al 24 1,2,15,26,27 …”

Section: Discussionsupporting

confidence: 76%

“…In accordance with recently published studies, we found a significantly larger volume of choroid plexus (as measured by CP/TIV ratio) in our cohort of RRMS patients compared to normal controls. 24…”

Section: Discussionmentioning

confidence: 99%

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

Klistorner

Barnett

Parratt

et al. 2022

Ann Clin Transl Neurol

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Objectives Recent 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. Methods Pre‐ 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. Results Baseline 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. Interpretation Our 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.

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Section: Figure 6 Analysis Of Association Between Plexus Volume and C...supporting

confidence: 87%

“…Stability of plexus and its weak association with baseline lesion volume (as was also observed in a recent study by Müller et al 24 1,2,15,26,27 …”

Section: Discussionsupporting

confidence: 76%

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

Klistorner

Barnett

Parratt

et al. 2022

Ann Clin Transl Neurol

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“…Recently, choroid plexus (CP) volume has been suggested as a reliable marker of neuroinflammation in several neurological disorders, including MS10–12 and Alzheimer’s disease 13. These highly vascularised structures, which extend along the floor of the lateral ventricles and the roof of the third and fourth ventricles, play a key role in the homoeostasis of the blood–cerebrospinal fluid (CSF) barrier and immune regulation within the central nervous system (CNS) 14.…”

Section: Introductionmentioning

confidence: 99%

“…In vivo MRI studies demonstrated that, compared with healthy controls (HC), patients with adult MS had higher CP volume,10–12 which was significantly associated with relapse rate,10 11 the severity of clinical disability10 and number and volume of brain T2-hyperintense and gadolinium-enhancing WM lesions,10–12 especially in patients with a relapsing–remitting (RR) course 11…”

Section: Introductionmentioning

confidence: 99%

Choroid plexus enlargement in paediatric multiple sclerosis: clinical relevance and effect of sex

Margoni

Gueye

Meani

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundChoroid plexus (CP) enlargement has been suggested as a reliable marker of neuroinflammation in adult multiple sclerosis (MS). We investigated CP volume in patients with paediatric MS compared with matched healthy controls (HC), possible sex-related effect, and the associations with clinical and structural MRI variables.MethodsBrain 3.0 T dual-echo and three-dimensional (3D) T1-weighted sequences were selected retrospectively from 69 patients with paediatric MS and 23 age-matched and sex-matched HC. CP volume was manually obtained from 3D T1-weighted scans by two expert raters.ResultsCP segmentation was highly reproducible (intraobserver agreement: rater I=0.963, rater II=0.958; interobserver agreement=0.968). Compared with HC, patients with paediatric MS showed higher normalised CP volume (p<0.001). Both female and male patients with paediatric MS showed higher normalised CP volume compared with sex-matched HC (women: p<0.001 and men: p=0.021), with a significant disease×sex interaction (p=0.040). In patients with MS, a higher normalised CP volume was significantly associated with higher brain lesional volume (β=0.252, p=0.017), larger lateral ventricle volume (β=0.470, false discovery rate (FDR)-p<0.001), lower normalised brain volume (β=−0.413, FDR-p=0.002) and lower normalised thalamic volume (β=0.291, FDR-p=0.046). No associations with disease duration, Expanded Disability Status Scale score, normalised cortical and white matter volumes were found (FDR-p≥0.172). A significant effect of the disease in the negative association between normalised volumes of CP and thalami was observed (FDR-p=0.046).ConclusionsCP enlargement occurs in paediatric MS, suggesting its early involvement in the pathophysiology of the disease. The higher CP volume, which is found especially in female patients, supports the hypothesis of sex-related differences occurring already in paediatric MS.

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Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Zhou

Zhong

et al. 2023

Annals of Neurology

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Objective: Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear. Methods: This retrospective study included 2 prospective 3.0-T magnetic resonance imaging (MRI) cohorts. In cohort 1, patients with indications for lumbar puncture underwent 3-dimensional T1-weighted sequence (3D-T1) before and at 39 hours after intrathecal administration of contrast agent (glymphatic MRI). In cohort 2, patients with WMH were enrolled from the CIRCLE study and had a median follow-up time of 1.4 years. WMH and CP of the lateral ventricles were automatically segmented on T2 fluid-attenuated inversion recovery (FLAIR) and 3D-T1, respectively. CP volume was expressed as a ratio to intracranial volume. Glymphatic clearance was measured as signal percentage change from baseline to 39 hours at 8 brain locations based on glymphatic MRI in the first cohort, or as noninvasive diffusion tensor image analysis along the perivascular space (DTI-ALPS) index based on DTI in the second cohort. Results: In cohort 1, a total of 52 patients were included. Higher CP volume was correlated with slower glymphatic clearance rate in all brain locations. In cohort 2, a total of 197 patients were included. Baseline CP volume was positively associated with WMH volume and its growth. Furthermore, DTI-ALPS index partially mediated the association of CP with both WMH load and growth. Interpretations: Enlarged CP volume could be an indicator for larger growth of WMH, potentially involving impaired glymphatic clearance function. The exploration of CP may provide a novel perspective to clarify the mechanism of WMH pathogenesis, as well as other glymphatic-related disorders.

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Choroid Plexus Volume in Multiple Sclerosis vs Neuromyelitis Optica Spectrum Disorder

Cited by 45 publications

References 34 publications

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

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

Choroid plexus enlargement in paediatric multiple sclerosis: clinical relevance and effect of sex

Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

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