Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder

Abstract

Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic resonance imaging study to prospectively evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra-axial fluid detected as early as 6 months and the lack of resolution by 24 months is a hitherto unreported brain anomaly in infants who later develop autism spectrum disorder. This is also the first magnetic resonance imaging evidence of brain enlargement in autism before age 2. These findings raise the potential for the use of structural magnetic resonance imaging to aid in the early detection of children at risk for autism spectrum disorder or other neurodevelopmental disorders.

Moving beyond behaviour-only assessment: Incorporating biomarkers to improve the early detection and diagnosis of autism spectrum disorders

“…Adopting a similar neuroimaging technique, Elison et al (2013) reported associations between the white matter structure of the splenium and visual orienting for typically-developing infants but not for highrisk infants who went on to show behavioural features of ASD. Shen et al (2013) presented consistent results from a study that used magnetic resonance imaging. These authors found that infants diagnosed with ASD at 24 months had signifi cantly greater extra-axial fl uids at 6 -9 months and larger brain volumes at 12 -24 months, compared to infants who did not have a clinical diagnosis of ASD.…”

“…The results of a longitudinal follow-up of these children showed that the ERP measure taken at age 2 was a strong predictor of behavioural outcomes, including language, cognition, and adaptive behaviour. Recent results reported by Shen et al (2013) also indicated that the amount of extra-axial fl uid detected at 6 months predicted the severity of ASD symptoms in infants who received a clinical classifi cation at outcome (24 -36 months). These results provide evidence to suggest that early measures of neurological function may be useful in terms of determining the severity of ASD and predicting later developmental outcomes.…”

“…Several recent studies have used prospective longitudinal designs to investigate brain structure in infants at high familial risk of developing ASD (Elison, Paterson, Wolff, Reznick, Sasson, Gu, et al, 2013;Shen, Nordahl, Young, Wootton-Gorges, Lee, Liston, et al, 2013;Wolff, Hongbin, Guido, Elison, Styner, Gouttard, et al, 2012). Using diffusion tensor imaging, Wolff et al (2012) identifi ed signifi cant qualitative differences in white matter development between high-risk infants who were diagnosed with ASD by 24 months, compared to those who did not receive an ASD diagnosis.…”

Latest findings in autism research: how do they support the importance of early diagnosis and immediate intervention?

“…Given that the acquisition of good quality MRI data requires the individual to remain still in the scanner for an extended period of time (ranging from 10 to 90 minutes), initial studies examined mainly high-functioning adolescents or adults with ASD. More recently however, Nordahl and colleagues [81] have proposed to scan young children during natural sleep without sedation, to better understand when the neurodevelopmental trajectories start to diverge in individuals with autism. They reported great success in these acquisitions from the age of 6 months [82] to 4.5 years old [81].…”

“…More recently however, Nordahl and colleagues [81] have proposed to scan young children during natural sleep without sedation, to better understand when the neurodevelopmental trajectories start to diverge in individuals with autism. They reported great success in these acquisitions from the age of 6 months [82] to 4.5 years old [81]. A summary of the main findings of anatomical differences and alterations in cerebral activity observed in individuals with autism is described below.…”