MRI May Reveal Infant Brain Anomaly Associated with Autism

Children who were diagnosed with autism spectrum disorder were found to have excessive cerebral spinal fluid and enlarged brains in infancy, according to a recent study by a multidisciplinary team of researchers, raising the possibility that those brain anomalies may serve as potential biomarkers for the early identification of the neurodevelopmental disorder.

The study is the first to track the brain-growth trajectories from infancy in children who later develop autism and the first to associate excessive cerebrospinal fluid during infancy with autism. The study was published online July 9, 2013, in the neurology journal Brain.

“This is the first report of an infant brain anomaly associated with autism that is detectable by using conventional structural MRI [magnetic resonance imaging],” said University of California (UC) Davis MIND Institute (USA ) director of research Dr. David Amaral, who co-led the study. “This study raises the potential of developing a very early method of detecting autism spectrum disorder. Early detection is critical, because early intervention can decrease the cognitive and behavioral impairments associated with autism and may result in more positive long-term outcomes for the child.”

The study was conducted in 55 infants between 6 and 36 months of age, 33 of whom had an older sibling with autism. Twenty-two infants were children with no family history of the disorder. The researchers reported that the brain anomaly was detected substantially more frequently in the high-risk infants who were later diagnosed with autism between 24 and 36 months. Earlier studies by Dr. Sally Ozonoff, the vice chair for research and professor in the department of psychiatry and behavioral sciences, who co-led the study, has shown that the risk of autism is nearly 20 times greater in siblings of children with autism than in the general population. The US Centers for Disease Control and Prevention (Atlanta, GA, USA) puts the overall incidence of autism at one in 88.

The excessive cerebrospinal fluid and enlarged brain volume were identified by intermittently measuring the infant’s brain growth and development using magnetic resonance imaging (MRI), and by routinely evaluation their cognitive, social, communication and motor development. Both the high- and low-risk infants underwent their first MRI scans at six to nine months. The second MRI scans occurred when they were 12 to 15 months old. The third was conducted between 18 and 24 months. The MRI scans were performed while the infants were sleeping naturally, without the need for sedation or anesthesia.

At six months, the researchers began intensive behavioral assessments of the babies’ development. Their parents also periodically completed questionnaires about their infants’ behaviors. These scans were conducted until the infants were 24 to 36 months old, when each child was evaluated as having autism spectrum disorder, other developmental delays, or typical development.

In addition to the 10 children diagnosed with autism, 24% of the high risk, and 13.5% of the low-risk infants were classified as having other developmental delays. Some 45.5% of high-risk and over 86% of low-risk infants were found to be developing normally. The researchers found that by six to nine months of age, the children who developed autism had elevated cerebrospinal fluid levels in the “extra-axial” space above, and surrounding the brain, and that those fluid levels remained abnormally elevated between 18 to 24 months of age. The more fluid during early infancy, the more severe were the child's autism symptoms when diagnosed, the study found.

In the infants who would go on to be diagnosed with autism, the extra-axial fluid volume was, on average, 33% greater at 12 to 15 months and 22% greater at 18 to 24 months, when compared with typically developing infants. At six to nine months, the extra-axial fluid volume was 20 percent greater, when compared with typically developing infants.

The study also provided the first MRI evidence of brain enlargement in autism prior to 24 months. On average, the infants in the study diagnosed with autism had 7% larger brain volumes at 12 months, compared with the typically developing infants. The excessive extra-axial fluid and enlarged brain volume were detected by brain imaging before behavioral signs of autism were evident. “The cause of the increased extra-axial fluid and enlarged brain size is currently unknown,” Dr. Amaral said.

Early diagnosis may be especially beneficial to infants whose older siblings have been diagnosed with autism, but the researchers stressed that this finding must be repeated before it could help in the early ddetection of ASD. The MIND Institute is now working with other research institutions to confirm these findings and to assess how well the potential biomarker can effectively predict a later diagnosis of ASD.

“It is critical to understand how often this brain finding is present in children who do not develop autism, as well,” said Dr. Ozonoff. “For a biomarker to be useful in predicting autism outcomes, we want to be sure it does not produce an unacceptable level of false-positives.”

“If this finding of elevated extra-axial fluid is replicated in a larger sample of infants who develop autism, and it accurately distinguishes between infants who do not develop autism, it has the potential of becoming a noninvasive biomarker that would aid in early detection, and ultimately improve the long-term outcomes of these children through early intervention,” said Mark Shen, UC Davis graduate student and the study’s lead author.


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University of California, Davis MIND Institute