Increased Cerebrospinal Fluid on Infant MRI's Might Be A Predictor of Autism

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Highlights:

• Autism spectrum disorders (ASD's) are diagnosed on an average at about 3 to 4 years of age based on behavioral impairments.
• Earlier diagnosis is essential to initiate appropriate interventions that improve the long-term prognosis for the child.
• The research team has shown that increased cerebrospinal fluid (CSF) in infants detected by magnetic resonance imaging (MRI) could predict autism risk at 6 months.

Children diagnosed with autism at 2 years age had significantly higher amounts of cerebrospinal fluid (CSF) at 6 months and 12 months compared to normal children according to a study led by Joseph Piven, MD belonging to UNC School of Medicine.

Reason for the Study

Autism spectrum disorders (ASDs) are developmental disorders associated with impaired social and communication skills, associated with repetitive behavioral patterns.

‘Cerebrospinal Fluid imaging of infants could help predict autism risk earlier in order to initiate necessary interventions sooner so that long term outcomes are better for the child’

Studies have shown that early diagnosis of autism and initiation of interventions help in decreasing the impairments and improves the longterm outlook for the child.

However at present, there are no biological markers to predict the risk of autism in infants early and typically diagnosis is made on an average at around 4 years due to impaired behavioral patterns. Studies have shown that babies who have an older sibling diagnosed with ASD might be at an increased risk of being diagnosed with autism.

There are indications that biological differences such as larger head size at 4 to 6 months of age and alterations in the organization of white matter might predict autism diagnosis later. However, it is not clear whether MRI can detect clinically significant structural variations in infants at higher risk for ASD and if these are associated with development of ASD.

The aim of the study was to determine if any consistently observable MRI findings as early as 6 months might differentiate infants who develop ASD from normal development or occurrence of other developmental delays.

Details and Findings of the Study

The present study included 343 children, of which 221 were at increased risk for development of autism because they had an older sibling diagnosed with autism. Forty-seven of these children went on to be diagnosed with autism at 24 months. MRI's were taken at ages 6, 12 and 24 months.

• The MRI's of the 6-month-olds who were diagnosed with autism showed 18 percent more CSF compared to the 6-month-olds that did not develop autism. The amount of CSF remained elevated even at 12 months and 24 months.
• Infants who developed severe autism had even more (24 percent higher) CSF at 6 months compared to children who were not diagnosed with ASD
• Higher amounts of CSF at 6 months was associated with a greater impairment of gross motor skills such as head and limb control.

"The CSF is easy to see on standard MRIs and points to a potential biomarker of autism before symptoms appear years later," said Piven, co-senior author of the study. According to Thomas E. Castelloe Distinguished Professor of Psychiatry, and director of the Carolina Institute for Developmental Disabilities (CIDD). "We also think this finding provides a potential therapeutic target for a subset of people with autism."

Newly Discovered Role of the CSF

Until recently it was believed that the CSF was a protective cushion between the brain and the skull. Scientists recently found that the CSF acts to filter out inflammatory proteins and other by-products of brain metabolism. This is then replaced by formation of new CSF four times a day in children as well as adults.

The findings of the study suggest that faulty CSF flow could be one of the causes for autism risk, possibly by affecting the developing brain.

"We know that CSF is very important for brain health, and our data suggest that in this large subset of kids, the fluid is not flowing properly," said Mark Shen, PhD, CIDD postdoctoral fellow and first author of the study. "We don't expect there's a single mechanism that explains the cause of the condition for every child. But we think improper CSF flow could be one important mechanism."

In 2013, Shen co-led a similar study of CSF in infants at UC Davis, and worked with David Amaral, PhD, co-senior author of the current study. Using MRIs, they found significantly higher amounts of CSF in babies that went on to develop autism. They acknowledged the study was small; it involved 55 babies and 10 went on to be diagnosed with autism. A larger study was needed to substantiate the findings which led to the current study.

Conclusion

The authors found that CSF predicted with nearly 70 percent accuracy, the risk for autism development. Although not a perfect predictor, the differences are easily observable on MRI and this could be used by child specialists as an additional tool for diagnosing autism risk early and for possible intervention.

References:

1. Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC3754460/)

Source: Medindia

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