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Increased extra-axial cerebrospinal fluid volume may predict autism
After examination of three independent cohorts, researchers found that extra-axial cerebrospinal fluid volume was higher in children with autism spectrum disorder from 6 months through to age 3 years, regardless of familial risk.
“The presence of increased extra-axial CSF in infancy had previously been considered to be benign because it had not been associated with a clinical syndrome,” Mark D. Shen, PhD, from the department of psychiatry at University of North Carolina, Chapel Hill, and colleagues wrote. “Several outstanding questions remained from the previous studies, which used the infant sibling study design in which the participants were at high familial risk for autism because they had an older sibling with autism spectrum disorder.”
Researchers examined whether a large, independent sample of children with ASD had increased extra-axial CSF volume, whether extra-axial CSF remains abnormally increased beyond infancy and whether this occurred in both normal-risk and high-risk children with autism in a case-control MRI study.
Using a previously validated machine learning algorithm, the investigators compared children with ASD — comprising both normal-risk and high-risk infants — and typically developing children aged 2 to 4 years in measures of extra-axial CSF volume, brain volume, head circumference, sleep issues and familial risk status derived from MRI and behavioral assessments.
In total, 159 young children with ASD and 77 typically developing children underwent MRI scans. Shen and colleagues discovered that the ASD group had an average of 15.1% more extra-axial CSF than the typically developing group after accounting for differences in brain volume, weight, age and sex (P = .007; Cohen’s d = 0.39). Subgroups of 132 normal-risk and 27 high-risk children with ASD had nearly identical extra-axial CSF volumes (P = .78), with both groups demonstrating significantly greater volumes than controls.
The researchers found that both extra-axial CSF volume (P = .004) and brain volume (P < .0001) uniquely contributed to enlarged head circumference in children with autism (P = .04). Higher extra-axial CSF volume was linked to greater sleep disturbances (P = .03) and lower non-verbal ability (P = .04), the results showed.
With positive predictive value of 83% (95% CI, 76.2-88.3) and an accuracy of 78%, the machine learning algorithm correctly predicted 133 of 159 children with ASD (sensitivity = 84%; 95% CI, 76.7-88.8) and 50 of 77 children without ASD (specificity = 65%; 95% CI, 53.1-75.2).
“The findings of our study ... suggest that increased extra-axial CSF is a potential stratification marker for a biologically meaningful subtype in autism spectrum disorder,” the researchers wrote. “Clinicians should be aware that the increased extra-axial CSF volume might not be benign, and its presence should signal the need for careful monitoring and developmental screening. Earlier detection might ultimately lead to earlier behavioral intervention, which appreciably improves a child’s long-term outcomes.” – by Savannah Demko
Disclosure: Shen reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.