Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism

Abstract

Background We previously reported that infants who developed ASD had increased CSF in the subarachnoid space (i.e., extra-axial CSF) from 6–24 months of age (1). We attempt to confirm and extend this finding in a larger, independent sample. Methods A longitudinal MRI study of infants at-risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months; 221 were high-risk for ASD because of an older sibling with ASD; 122 were low-risk with no family history of ASD. Forty-seven infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. Results Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared to both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen’s d=0.54). Extra-axial CSF volume remained elevated through 24 months (d=0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6–24 months (24% greater at 6 months, d=0.70; 15% greater at 24 months, d=0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. Conclusions This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

A novel framework for the local extraction of extra-axial cerebrospinal fluid from MR brain images

“…Consistent with our previous global EA-CSF report, 3 we see a larger negative change in local EA-CSF from 6 to 12 months as compared to from 12 to 24 months. As shown in Figure 3 (c), several regions show statistically significant local EA-CSF changes (p < 0.05) including right posterior cingulate gyrus, right cuneus, right superior occipital gyrus, right middle occipital gyrus, left angular gyrus and left middle frontal gyrus.…”

“…EA-CSF enlargement is believed to provide an early sign that CSF is not filtering and draining when it should; which can provide an early biomarker detection of children at risk for neurodevelopmental disorders (e.g., autism spectrum disorder (ASD)). Shen et al 2,3 indicated that the amount of EA-CSF detected as early as 6 months was predictive of more severe ASD symptoms at 24 month. A quantitative protocol was developed to objectively measure the volume of the total EA-CSF in each participants’ magnetic resonance (MR) brain scan.…”

Autism spectrum disorder: advances in diagnosis and evaluation

“…Also in the IBIS high risk cohort (n=59), a functional connectivity MRI based machine learning algorithm applied at 6 months of age had a 81% sensitivity and 100% specificity for the diagnosis of ASD 79. Increased extra-axial cerebral spinal fluid volume at 6 months of age correlated with motor function at 6 months and was associated with a diagnosis of ASD at 24 months (80% sensitivity and 67% specificity) 80. ASD related connectivity differences mapped to functional networks underlying joint attention skills at 12 months and 24 months 81.…”

Anatomy‐guided joint tissue segmentation and topological correction for 6‐month infant brain MRI with risk of autism

“…These findings demonstrate the brain differences between autism and controls in the first postnatal year, before the behavioral symptoms appearing (Sowell and Bookheimer, 2012), implying that it is possible to identify brain biomarkers of ASD in the very early stage for early diagnosis and intervention. For example, in (Shen et al, 2017), it was revealed that ASD causes an extra-axial fluid and is characterized by excessive CSF over the frontal lobes at 6-9 months of age, which raises the possibility that those brain anomalies may serve as potential biomarkers for early identification of ASD.…”