Sunday, 28 October 2012

Cerebral palsy and autism

I seem to keep saying this but one of the many important things about autism is that the diagnosis of autism has not yet been found to be protective against other conditions occurring alongside. This is probably not new news to many as per the comorbities which have been, and continue to be found in cases of autism; recognised even by official guidance on autism (see here).

Importantly however in recent times, more attention is being directed to the overlap of autism with other conditions and how those other conditions might potentially further inform sub-groups (endophenotypes) within the autism spectrum in terms of aetiology and pathology. I'm specifically thinking of the 'significantly over-represented' paper published earlier this year (2012) as a prime example.

Enter then another paper by Pål Surén and colleagues* looking at the overlap between autism spectrum conditions, ADHD, epilepsy and cerebral palsy and reportedly finding a "significant burden of disease associated with neurologic and neurodevelopmental disorders in children".

I'm not specifically going to discuss Surén's paper in excruciating detail because the results really don't need me complicating them. What however I am interested in is the body of work in the peer-reviewed arena suggesting a link between the presence of autism and one comorbidity detailed in their paper, cerebral palsy, and what, if anything, we can draw from such an association.

Perhaps best to first describe what cerebral palsy (CP) is (and isn't). The UK charity Scope have quite a good description of CP (here) alongside more detailed information being available. Basically, CP is a catch-all term for a group of conditions primarily affecting movement and resulting in physical disability. The brain is a central organ to CP (hence the name cerebral palsy) and in particular how certain adverse factors whether inborn or during pregnancy and/or the neonatal period may affect brain development. That being said, the mechanisms of brain disturbances linked to CP is still a work in progress and new-ish ideas are still emerging about things like inflammation for example, being potentially linked to CP (see this study by Marlow and colleagues**) and indeed some familiar themes on food and gut hyperpermeability*** when extended to other parts of the body.

Whilst issues with movement is a core symptom of CP, there are a variety of other presentations that also seem to be evident in children with CP. So learning disability, epilepsy and sensory issues have all been noted, as well as more physical issues such as functional bowel problems like constipation. Without wishing to make bridges where none might be required, I was struck by how much overlap in peripheral features there is between CP and cases of autism.

So then to some of the links (or not) between CP and autism:

  • Estimated prevalence rates of CP are slightly difficult to interpret bearing in mind that factors such as twin/multiple births are seen as risk factors. Figures from the US report an estimated prevalence of CP of about 0.3%. This paper by Glinianaia and colleagues**** suggested an estimated prevalence rate of 0.2% for singletons and 1.1% in multiple UK births, with birth weight also being a potential modifying risk factor. That multiple birth link with CP also seems to hold where an autism link perhaps doesn't (see here).
  • In terms of the overlap between autism and CP, Mouridsen and colleagues***** confirmed that there seems to be an over-representation of CP in cases of autism compared to non-autism controls as per the findings of other datasets (herehereherehere and here - phew!). Of the limited studies done on the presentation of autism and CP, preliminary results suggest that the severity of core autistic symptoms may also be adversely influenced by the two conditions appearing alongside each other (here).
  • Although the brain is undoubtedly implicated in CP, there is still some debate about the precise areas of the brain involved in the different presentations of the condition. Current thought is that different areas of the brain may be involved in individual cases of CP according to how symptoms present. The link between brain and autism is an equally complex relationship made even more complicated by the wide range of abilities/disabilities noted across different cases. I could tentatively suggest a link to brain areas involved with motor control given the overlap (yes, motor issues have been mentioned in cases of autism) between the conditions. Indeed, ataxic CP has been linked to issues with the cerebellum; the cerebellum being a favourite target for some autism research also as per the recent consensus paper by Fatemi and colleagues******. I hasten to add that I am by no means reducing both conditions down to just one area of the brain however. 
  • Interestingly, infections such as cytomegalovirus (CMV), previously linked to the onset of autism (here) have also been overlapped with CP (here). Maternal infection and fever during pregnancy has also been associated with an increased risk of offspring CP as per the results of this study****** and some familiar names to autism research. Again without making too many unwarranted connections, the recent CHARGE results spring to mind as a possible comparator.
  • The immune system and CP... how long have you got? To take one example, those dastardly IL-6 cytokines rear their head in cases of CP both from a genetics point of view (here) and possibly tied into increasing amounts of circulating IL-6 (here). Other patterns of cytokine presentation have also been reported alongside coagulation anomalies (here). Need I say anymore about IL-6 (and other cytokines) and autism?

There are other instances of 'overlap' between autism and CP but I am wary of listing all of them because of the risk of falling into the trap of just reciting research and actively looking for connections. Taking the model of autoimmunity and the presence of one autoimmune condition potentially raising the risk of other autoimmune conditions appearing/being diagnosed, I think we might be looking at a similar process here with regards to the various connections being made between autism and CP - be they structural brain issues, infections, immune function or others.

What this and other investigations reiterate is that the links noted between autism and a wide variety of other conditions form an important part of the research landscape and potential clues as to the underlying nature of the condition. Accepting the current stance that both CP and autism are categorised as 'lifelong conditions' the very preliminary shared links between intervention strategies such as HBOT for CP and HBOT for autism (no endorsement given or intended) makes me wonder about the need for some more detailed investigation.

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Surén P. et al. Autism spectrum disorder, ADHD, epilepsy, and cerebral palsy in Norwegian children. Pediatrics. June 2012.
DOI: 10.1542/peds.2011-3217

** Marlow N. et al. Characteristics of children with cerebral palsy in the ORACLE children study. Developmental Medicine & Child Neurology. 2012; 54: 640-646.

*** Stenberg R. et al. Increased prevalence of antibodies against dietary proteins in children and young adults With cerebral palsy. Journal of Pediatric Gastroenterology & Nutrition. September 2012.

**** Glinianaia SC. et al. Cerebral palsy rates by birth weight, gestation and severity in North of England, 1991-2000 singleton births. Archives of Disease in Childhood. 2011; 96: 180-185.

***** Mouridsen SE. et al. A longitudinal study of epilepsy and other central nervous system diseases in individuals with and without a history of infantile autism. Brain & Development. 2011; 33: 361-366.

****** Fatemi SH. et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum. 2012; 11: 777-807.

******* Grether JK. & Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA. 1997; 278: 207-211.

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ResearchBlogging.org Surén P, Bakken IJ, Aase H, Chin R, Gunnes N, Lie KK, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Øyen AS, & Stoltenberg C (2012). Autism spectrum disorder, ADHD, epilepsy, and cerebral palsy in Norwegian children. Pediatrics, 130 (1) PMID: 22711729