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Choroid plexus and perivascular space enlargement in neuropsychiatric systemic lupus erythematosus

Molecular Psychiatry (2023)Cite this article

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Abstract

Choroid plexus (CP) enlargement is proposed as a marker of neuroinflammation in immune-mediated conditions. CP involvement has also been hypothesized in the immunopathology of systemic lupus erythematosus (SLE). We investigated whether CP enlargement occurs in SLE patients and its association with neuropsychiatric involvement. Additionally, we explored abnormalities along the glymphatic system in SLE patients through enlarged perivascular space (PVS) quantification. Clinical assessment and 3 Tesla brain dual-echo and T1-weighted MRI scans were obtained from 32 SLE patients and 32 sex and age-matched healthy controls (HC). CPs were manually segmented on 3D T1-weighted sequence and enlarged PVS (ePVS) were assessed through Potter’s score. Compared to HC, SLE patients showed higher normalized CP volume (nCPV) (p = 0.023), with higher CP enlargement in neuropsychiatric SLE (NPSLE) (n = 12) vs. non-NPSLE (p = 0.027) patients. SLE patients with antiphospholipid antibodies (APA) positivity (n = 18) had higher nCPV compared to HC (p = 0.012), while APA negative ones did not. SLE patients also had higher Potter’s score than HC (p < 0.001), with a tendency towards a higher number of basal ganglia ePVS in NPSLE vs. non-NPSLE patients. Using a random forest analysis, nCPV emerged as a significant predictor of NPSLE, together with T2-hyperintense white matter (WM) lesion volume (LV) and APA positivity (out-of-bag AUC 0.81). Our findings support the hypothesis of a role exerted by the CP in SLE physiopathology, especially in patients with neuropsychiatric involvement. The higher prevalence of ePVS in SLE patients, compared to HC, suggests the presence of glymphatic system impairment in this population.

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Fig. 1: Choroid plexus segmentation and between-group comparison.
Fig. 2: Enlarged perivascular space identification and Potter’s score distribution.
Fig. 3: Random forest informative predictors of neuropsychiatric involvement in patients with systemic lupus erythematosus (SLE).

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The anonymized dataset used and analysed during the current study is available from the corresponding author on reasonable request.

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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Mor Gueye, Paolo Preziosa, Monica Margoni, Alessandro Meani, Massimo Filippi & Maria A. Rocca

  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Mor Gueye, Paolo Preziosa, Monica Margoni, Lucia Moiola, Massimo Filippi & Maria A. Rocca

  3. Vita-Salute San Raffaele University, Milan, Italy

    Paolo Preziosa, Patrizia Rovere-Querini, Angelo A. Manfredi, Massimo Filippi & Maria A. Rocca

  4. Unit of Immunology, Rheumatology, Allergy and Rare Diseases & Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Giuseppe A. Ramirez & Angelo A. Manfredi

  5. Unit of General Medicine and Advanced Care, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Enrica P. Bozzolo

  6. Unit of Internal Medicine & Division of Immunology, Transplantation and Infectious diseases, IRCCS Ospedale San Raffaele, Milan, Italy

    Valentina Canti & Patrizia Rovere-Querini

  7. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

  8. Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

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  1. Mor Gueye
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Prof. Rocca and Prof Filippi had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. -Concept and design: Preziosa, Rocca, Filippi. -Acquisition, analysis, or interpretation of data: All authors. -Drafting of the manuscript: Gueye, Preziosa, Margoni, Meani, Rocca, Filippi. -Critical revision of the manuscript for important intellectual content: All authors. -Statistical analysis: Meani. -Supervision: Rocca.

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Correspondence to Maria A. Rocca.

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Gueye, M., Preziosa, P., Ramirez, G.A. et al. Choroid plexus and perivascular space enlargement in neuropsychiatric systemic lupus erythematosus. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02332-4

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