"abnormally high extra-axial cerebrospinal fluid (CSF) volume" and autism

"Increased extra-axial CSF [cerebrospinal fluid] volume is a reliable brain anomaly that has now been found in three independent cohorts, comprising both high-risk and normal-risk children with autism spectrum disorder."

So concluded the findings reported by Mark Shen and colleagues [1] following their study results - "case-control MRI study" results - enquiring whether "increased extra-axial CSF volume is found in a large, independent sample of children diagnosed with autism spectrum disorder, whether extra-axial CSF remains abnormally increased beyond infancy, and whether it is present in both normal-risk and high-risk children with autism."

This latest study from Shen et al follows a research theme [2], a quite long running research theme [3] by all accounts, observing that extra-axial CSF volume might be important to at least some autism. Increased extra-axial CSF volume is described as a brain anomaly insofar as representing a larger than expected volume of cerebrospinal fluid 'coating' the brain, or at least filling the extra-axial space sitting on top and around the brain. It's perhaps not surprising that this work has also included the words 'brain enlargement' in discussions given the physical effect that such increased volume might have.

This latest chapter in the extra-axial CSF volume research comes from a familiar research initiative - the UC Davis MIND Institute Autism Phenome Project - "a longitudinal analysis of children diagnosed with autism spectrum disorder and age-matched typically developing children." The Autism Phenome Project (APP) has already been discussed a few times on this blog for various research reasons (see here and see here). The APP also has something of an interest in brain enlargement appearing alongside regression too (see here). This time around "159 children with autism spectrum disorder (132 male, 27 female) and 77 with typical development (49 male, 28 female) underwent MRI scans." Researchers were looking at extra-axial CSF volume as well as things like brain volume and head circumference. Alongside, various other behavioural measures and questionnaires on things like sleep were included.

"The autism spectrum disorder group had an average of 15·1% more extra-axial CSF than controls after accounting for differences in brain volume, weight, age, and sex." Further: "Both extra-axial CSF volume... and brain volume... uniquely contributed to enlarged head circumference in the autism spectrum disorder group." Authors also reported that: "Increased extra-axial CSF volume was associated with greater sleep disturbances... and lower non-verbal ability."

As per the opening quote to this post, this is not the first time that some of those findings have been reported in the science arena and I very much doubt that it will be the last time either. The authors also talk about such MRI findings in light of "normal risk (ie, from simplex families) or high risk (ie, from multiplex families)" for autism and applying "a previously validated machine learning algorithm based on extra-axial CSF volume, brain volume, age, and sex" but I'd like to see a lot more data before venturing further into these aspects. Not least, data covering the question of 'why?'. From the previous studies in this area, some hypotheses have been put forward, for example: "[as] CSF circulates through the developing brain, it removes inflammatory cytokines and proteins secreted by neurons that can otherwise accumulate and have a pathological effect on brain development." Such a hypothesis needs further research but is perhaps complementary to other discussions about 'neuroinflammation' in the context of autism (see here).

We await further investigations.

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[1] Shen MD. et al. Extra-axial cerebrospinal fluid in high-risk and normal-risk children with autism aged 2-4 years: a case-control study. Lancet Psychiatry. 2018 Sep 27. pii: S2215-0366(18)30294-3.

[2] Shen MD. et al. Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism. Biol Psychiatry. 2017 Aug 1;82(3):186-193.

[3] Shen MD. et al. Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder. Brain. 2013;136(9):2825-2835.

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