Parasagittal dural volume correlates with cerebrospinal fluid volume and developmental delay in children with autism spectrum disorder

Nivedita Agarwal; Giulia Frigerio; Gloria Rizzato; Tommaso Ciceri; Elisa Mani; Fabiola Lanteri; Massimo Molteni; Roxana O Carare; Letizia Losa; Denis Peruzzo

doi:10.1038/s43856-024-00622-8

Parasagittal dural volume correlates with cerebrospinal fluid volume and developmental delay in children with autism spectrum disorder

Commun Med (Lond). 2024 Oct 4;4(1):191. doi: 10.1038/s43856-024-00622-8.

Authors

Nivedita Agarwal¹, Giulia Frigerio², Gloria Rizzato², Tommaso Ciceri^{3

4}, Elisa Mani⁵, Fabiola Lanteri⁵, Massimo Molteni⁵, Roxana O Carare^{6

7}, Letizia Losa², Denis Peruzzo³

Affiliations

¹ Diagnostic Imaging and Neuroradiology Unit, IRCCS Scientific Institute E. Medea, Bosisio Parini, Lecco LC, Italy. [email protected].
² Diagnostic Imaging and Neuroradiology Unit, IRCCS Scientific Institute E. Medea, Bosisio Parini, Lecco LC, Italy.
³ Neuroimaging Unit, IRCCS Scientific Institute E. Medea, Bosisio Parini, Lecco LC, Italy.
⁴ Department of Information Engineering, University of Padua, Padua, Italy.
⁵ Child Psychopathology Unit, IRCCS Scientific Institute E. Medea, Bosisio Parini, Lecco LC, Italy.
⁶ Faculty of Medicine, University of Southampton, Southampton, UK.
⁷ University of Medicine, Pharmacy, Science, and Technology, Targu-Mures, Romania.

Abstract

Background: The parasagittal dura, a tissue that lines the walls of the superior sagittal sinus, acts as an active site for immune-surveillance, promotes the reabsorption of cerebrospinal fluid, and facilitates the removal of metabolic waste products from the brain. Cerebrospinal fluid is important for the distribution of growth factors that signal immature neurons to proliferate and migrate. Autism spectrum disorder is characterized by altered cerebrospinal fluid dynamics.

Methods: In this retrospective study, we investigated potential correlations between parasagittal dura volume, brain structure volumes, and clinical severity scales in young children with autism spectrum disorder. We employed a semi-supervised two step pipeline to extract parasagittal dura volume from 3D-T2 Fluid Attenuated Inversion Recovery sequences, based on U-Net followed by manual refinement of the extracted parasagittal dura masks.

Results: Here we show that the parasagittal dura volume does not change with age but is significantly correlated with cerebrospinal fluid (p-value = 0.002), extra-axial cerebrospinal fluid volume (p-value = 0.0003) and severity of developmental delay (p-value = 0.024).

Conclusions: These findings suggest that autism spectrum disorder children with severe developmental delay may have a maldeveloped parasagittal dura that potentially perturbs cerebrospinal fluid dynamics.

Plain language summary

Cerebrospinal fluid (CSF) is produced in the brain. It is a medium of transport for neural growth factors and waste products. CSF is drained out of the brain through multiple pathways, one of them being the recently identified parasagittal dura (PSD) which also plays a role in the immune system within the brain. We estimated the PSD volume in children with autism spectrum disorder (ASD) and found the volume was associated with the amount of CSF in the brain. We also found that the PSD volume is smaller in children who have severe forms of developmental delay. Our findings suggest problems in the development of the PSD could have in impact on brain development and waste removal in children with ASD. More research in this area could enable a better understanding of the underlying causes of ASD.