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. 2023 Jul;94(1):182-195.
doi: 10.1002/ana.26648. Epub 2023 Apr 11.

Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Yifei Li  1 , Ying Zhou  1 , Wansi Zhong  1 , Xiao Zhu  1 , Yuping Chen  1 , Kemeng Zhang  1 , Yaode He  1 , Zhongyu Luo  1 , Wang Ran  1 , Jianzhong Sun  2 , Min Lou  1
Affiliations

Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Yifei Li et al. Ann Neurol. 2023 Jul.

Abstract

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. ANN NEUROL 2023;94:182-195.

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