Congenital rubella, autism and remote stroke

Case reports. I know they rank pretty low in the order of what counts as objective scientific evidence [1] despite their often interesting findings. That being said, when it comes to a diagnosis like autism, with all its associated heterogeneity and elevated risk of various comorbidity probably better encapsulated in a more 'plural autisms' understanding, case reports can offer something of an important view into the many and varied ways in which someone might arrive on the autism spectrum and their subsequent individual experiences. A focus on the N=1 if you like...

The case report from Jill and George Hutton [2] (open-access) describing how the "diagnosis of congenital rubella was recognized more than ten years after the birth" of their male infant subject and how "congenital rubella is linked to both autism and ischemic brain injury" provides some rather interesting details for science and practice. The paper is open-access but a few pointers might be useful:

• The paper describes a boy delivered at 38 weeks to a "USA born physician at 30 years of age mostly working at a busy, urban, county hospital with a large immigrant population". Mum had been vaccinated against rubella at least once some decades earlier (possibly with a booster 7-8 years before giving birth). "She was non-immune to rubella at her first prenatal visit at 10 weeks gestation" but at delivery showed immunity to rubella suggesting intervening exposure. The authors reported the detail about 'large immigrant population' because of the issue of risk of transmission from those "emigrating from countries with absent or suboptimal national vaccination programs" [3].
• Her son "met all motor milestones, but was delayed in speech and exhibited social anxiety" during early infancy. He had a single seizure at 18 months (febrile seizure). He was eventually diagnosed with autism between 5-7 years old.
• An MRI was fortuitously offered at 10 years old with findings "most consistent with a remote stroke". The authors conclude that: "As causes of stroke were eliminated, the diagnosis of congenital rubella as a unifying diagnosis of autism and stroke became more probable."

I was drawn to talk about this paper for various reasons.

First is the continuing association between viral/bacterial exposures during pregnancy and offspring behavioural outcomes (see here). As per the research of people such as Stella Chess, mentioned in the Hutton article, discussing autism presenting in cases of congenital rubella [4] and reporting that "a high rate of autism and a high rate of recovery were observed" there is potentially so much more to see in this area of autism research. In-utero rubella exposure, by the way, is not the only infective agent linked to the presentation of autism for some (see here).

Second were some of the details reported by the Huttons on their young participant and in particular, the idea that congenital rubella may 'unify' the findings of stroke + autism. Pediatric stroke has been looked at with infectious disease in mind before [5]. The research literature in the area of stroke and autism is however not exactly straight-forward. It would be easy to say that stroke had a deleterious effect on the brain which then 'lead' to autism as per other research in this area [6], but this perhaps rather simplifies an all-too-likely more complex relationship. Certainly, I would like to see a little more investigation done on this topic and in particular the delayed manifestations of congenital rubella [7] as and when appropriate to a diagnosis of autism or autism spectrum disorder [8]. If and when this connection is further established, one could also reasonably ask about intervention strategies and whether autistic symptoms could be ameliorated in any way in this group? Remember those words from Chess: "a high rate of recovery was observed"...

Finally, the question is raised about the role of vaccination in preventing congenital rubella and possible knock-on effects for offspring development including autism-related outcomes. In a previous post on the talking point that is vaccination and autism (see here) I discussed some data which suggested that rubella vaccination may very well have "prevented hundreds, and perhaps thousands, of ASD [autism spectrum disorder] cases from 2001 through 2010 in the US." [9] The Hutton paper kinda overlaps with such discussions alongside detailing the issue of waning immunity [10]. I might add that analysis of the biology of individual responses (or not) to rubella vaccination [11] and even transmission from previous vaccinees [12] in light of other data is perhaps also implied in any future work in this area.

What the Hutton paper serves to reiterate is that there may be many potential paths towards a diagnosis of autism or ASD. Receipt of said diagnosis should also perhaps be a starting point for further inquiry rather than an endpoint...

Music: Blur - Out Of Time.

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[1] Nissen T. & Wynn R. The clinical case report: a review of its merits and limitations. BMC Res Notes. 2014 Apr 23;7:264.

[2] Hutton J. & Hutton GJ. Congenital Rubella with Autism and Evidence of a Remote Stroke. J Vaccines Vaccin 2014, 5:6

[3] Fang J. et al. Case report: congenital rubella syndrome: a rare but persistent concern in the United States. J Perinatol. 2013 Nov;33(11):899-902.

[4] Chess S. Follow-up report on autism in congenital rubella. J Autism Child Schizophr. 1977 Mar;7(1):69-81.

[5] Salih MA. et al. Infectious and inflammatory disorders of the circulatory system as risk factors for stroke in Saudi children. Saudi Med J. 2006 Mar;27 Suppl 1:S41-52.

[6] Weir K. & Salisbury DM. Acute onset of autistic features following brain damage in a ten-year-old. J Autism Dev Disord. 1980 Jun;10(2):185-91.

[7] Sever JL. et al. Delayed Manifestations of Congenital Rubella. Clin Infect Dis. 1985; 7 (Supplement 1): S164-S169.

[8] Hwang SJ. & Chen YS. Congenital rubella syndrome with autistic disorder. J Chin Med Assoc. 2010 Feb;73(2):104-7.

[9] Berger BE. et al. Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination--United States, 2001-2010. BMC Public Health. 2011 May 19;11:340.

[10] Just M. et al. Duration of immunity after rubella vaccination: a long-term study in Switzerland. Rev Infect Dis. 1985 Mar-Apr;7 Suppl 1:S91-4.

[11] Kennedy RB. et al. Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination. Hum Genet. 2014 Nov;133(11):1407-17.

[12] Wilkins J. et al. Transmission of rubella vaccine virus from vaccinees to contacts. Calif Med. 1971 Nov;115(5):16-22.

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George J Hutton, J. (2014). Congenital Rubella with Autism and Evidence of a Remote Stroke Journal of Vaccines & Vaccination, 05 (06) DOI: 10.4172/2157-7560.1000258