Paediatric Acute-onset Neuropsychiatric Syndrome (PANDAS) misdiagnosed as autism: some implications

Credit: BBC Website 25 January 2019

The BBC website recently ran with an interesting story headed under the title: "Mother's appeal after boy diagnosed with autism when he just needed antibiotics." It was an interesting piece that drew attention once again to an increasingly important condition known as Paediatric Acute-onset Neuropsychiatric Syndrome (PANDAS) also called PANS.

Classically triggered by Streptococcal infections, PANDAS/PANS is typically characterised by quite an abrupt change in behaviour to include things like "clinically significant obsessions, compulsions and/or tics" alongside things like anxiety, sensory issues, aggression and a corresponding loss of academic abilities. Treatment is often multi-disciplinary; but in the most part intervention includes the use of various types of antibiotics clinically indicated to treat strep infections. This also follows a wider research-based thread suggesting that strep infections *might* have some important links to various neuropsychiatric conditions (see here).

The BBC piece specifically focused on how the young boy highlighted was "repeatedly diagnosed as having autism and severe anxiety" and how following a PANDAS diagnosis, and after just two days of antibiotic treatment, the mother of the young boy "felt like Jack was back." I'll also mention that the mum of Jack was herself a medic, a psychiatrist, and so was perhaps more attuned than most people about clinical diagnoses like autism and anxiety. It also emphasises how she kept on questioning...

Mention of the label autism in the BBC story got me thinking about quite a few things. Although still relatively sparse, there are some isolated reports in the peer-reviewed science literature observing that something like PANDAS/PANS can be "misdiagnosed as autism spectrum disorder" [1] in some circumstances. Such a notion complements some still emerging views that: (i) there may be many different routes to a diagnosis of autism (pertinent to the notion of 'the autisms'), (ii) autism is not universally an inborn genetic condition/state/diagnosis present from birth or early infancy, and (iii) autism for some people, is not necessarily a lifelong condition or label or state. Having discussed those views quite a bit on this blog (see here and see here and see here respectively) and noted some 'resistance' in some quarters to them, it is important that stories such as the one about Jack are continually highlighted. Not least because for him at least, his mother's determination and tenacity ultimately led to a new [accurate] diagnosis and subsequent treatment tailored to his particular circumstances. I daresay that other children (and even adults) who perhaps share Jack's clinical picture remain undiagnosed and untreated out there; something which represents a significant health inequality for them and their families. I might also add that the autism-anxiety diagnostic mix discussed in the BBC piece also complements the idea that the word 'comorbidity' may not be entirely accurate for the experience of [some] anxiety in the context of [some] autism (see here).

Jack's story begs the question: just how many people have been diagnosed with autism yet are 'suffering' with undiagnosed PANDAS/PANS? There's a research study there for someone brave enough there; alongside further study on whether elucidating the mechanisms of PANDAS/PANS when seemingly mimicking the signs and symptoms of autism & anxiety *could* be beneficial for at least some other parts of the wider autism spectrum...

Continue questioning and continue investigating seem to be the key lessons, as once again we are reminded that a diagnosis of autism should be a starting point and not 'the finishing line'.

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[1] Goncalves MVM. et al. Pediatric acute-onset neuropsychiatric syndrome (PANS) misdiagnosed as autism spectrum disorder. Immunol Lett. 2018 Nov;203:52-53.

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Gestional exposure to Group B Streptococcus and an autism model

"Overall, these data show for the first time that gestational exposure to GBS [Group B Streptococcus] plays an important role in the generation of neurodevelopmental abnormalities reminiscent of human autism spectrum disorders (ASD)."

I chose to discuss the findings reported by Marie-Julie Allard and colleagues [1] on this blog for various reasons. That this research team already have some research 'form' when it comes to looking at GBS [2] is one; another is the idea that they report "new evidence in favor of the role of a common and modifiable infectious/inflammatory environmental factor in human ASD pathophysiology." With all the focus these days on how there may be some kind of foetal programming going on during the nine months that made us pertinent to the risk of developing autism for some, this line of research also potentially offers up the idea that said programming needn't always be related to the genome we are born with.

GBS infection during pregnancy and birth is not something to be taken lightly. As a primary cause of bacterial infections in newborns, this type of infection can in extreme cases lead to septicaemia (blood poisoning) and also meningitis. This all stems from the fact that around 25-30% of healthy human adults carry this bacteria around in their gut and/or genitourinary tract with no apparent issues for the majority. In rare cases however, infants traversing the birth canal of a mother carrying GBS can come into contact with the bacteria and processes are then set in motion...

Allard et al started with the hypothesis that "GBS-induced gestational infection/inflammation has a deleterious neurodevelopmental impact on uninfected offspring" and set about looking at this potential issue in a rodent model - "a new preclinical rat model" no less. They reported that placentas exposed to GBS "exhibited chorioamnionitis characterized by the presence of Gram-positive cocci and polymorphonuclear cells, with the latter being significantly more prominent in the labyrinth of male offspring." Whilst interesting, this is not necessarily new news. But... when it came to looking at the brain and behaviour of male rat offspring exposed to GBS, there appeared to be a few features potentially "reminiscent of human autism spectrum disorders (ASD)." So: "autistic-like behaviors, such as abnormal social interaction and communication, impaired processing of sensory information and hyperactivity" were noted in this group. The conclusion being that science may have yet another animal model of autism (is this a good or bad thing?) and that GBS-exposed placentas might have implications for offspring developmental outcome.

The previous research paper by this group [2] had already provided some important details pertinent to this line of investigation. "Surprisingly, only male offspring were affected by these combined autistic-like traits" went one of their conclusions on that previous research occasion, insofar as GBS-exposed placentas and their onward effects. They also suggested that there may be some important effects to be had from the "materno-fetal inflammatory response to GBS" coinciding with quite a lot of peer-reviewed data suggesting immune system and inflammatory signalling involvement when it comes to pregnancy and offspring risk of autism (see here and see here).

Stressing that animal models of autism are not necessarily the same as the complexity of autism in it's lived form, the Allard findings are potentially important. Added to something of an important body of research looking at artificial modelling of bacterial infection and its potential importance to offspring outcomes (see here) one can see that the so-called protective cocoon of our mother during the months of our earliest development is not an impenetrable force-field by any stretch of the imagination. Indeed, such an association may go much further than just autism (see here).

Insofar as the 'where next?' in terms of research in this area, well, I might suggest that looking at the rates of offspring autism in women positive or negative to GBS could represent a good research start and perhaps taking things from there. Although there may be some way to go in determining the precise mechanism of GBS exposure in-utero in relation to any possible heightened risk of autism, science might also consider other findings from this research group [3] on how 'intervening' in issues related to inflammation at certain critical periods, might eventually provide some 'protection' for the developing brain...

Oh, and I'll be coming to the paper by Jiang and colleagues [4] in a future post.

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[1] Allard MJ. et al. A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation. Autism Res. 2016 May 25.

[2] Bergeron JD. et al. White matter injury and autistic-like behavior predominantly affecting male rat offspring exposed to group B streptococcal maternal inflammation. Dev Neurosci. 2013;35(6):504-15.

[3] Girard S. et al. IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation. J Immunol. 2010 Apr 1;184(7):3997-4005.

[4] Jiang HY. et al. Maternal Infection during Pregnancy and Risk of Autism Spectrum Disorders: A Systematic Review and Meta-analysis. Brain Behav Immun. 2016 Jun 7. pii: S0889-1591(16)30154-4.

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Allard MJ, Bergeron JD, Baharnoori M, Srivastava LK, Fortier LC, Poyart C, & Sébire G (2016). A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation. Autism research : official journal of the International Society for Autism Research PMID: 27220806