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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The PANDAS hypothesis is supported

PANDAS - pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection - is, as the name suggests, a condition / group of conditions? characterised by bacterial infection, or response to bacteria infection, leading to behavioural / psychiatric presentation(s).

Although fairly widely accepted (at least in the United States) there are some that still question this diagnosis and the idea that infection or response to infection can affect functioning in many more ways than just the somatic. There are, I might add, other examples of this in the clinical literature (see here).

The paper by Sonja Orlovska and colleagues [1] should put a few minds at rest with their 'large-scale' findings that "individuals with a streptococcal throat infection had elevated risks of mental disorders, particularly OCD [obsessive compulsive disorder] and tic disorders"; both key facets of a diagnosis of PANDAS. The additional finding that "nonstreptococcal throat infection was also associated with increased risks, although less than streptococcal infections for OCD and any mental disorder" adds something further to this area.

So, examining one of those oh-so important Scandinavian population registries - this time in Denmark - individuals with "registration of a streptococcal test" were followed up for "a diagnosis of any mental disorder, OCD, or tic disorders." The numbers of participants eventually included were in the hundreds of thousands (+600K) about half of whom at evidence of at least one positive strep test. The authors found that: "Individuals with a positive streptococcal test result had an increased risk of any mental disorder..., particularly of OCD... and tic disorders..., compared with individuals without a streptococcal test."

These are important results. Reiterating the title of this post, the concept of PANDAS is supported by the Orlovska findings. Noting the name Michael Benros on the authorship group of this current paper - someone who has previously explored the possibility that immune function/dysfunction can impact on psychiatry - I daresay that the previous ideas on how infection can affect cognitive abilities for example, (see here) are further extended by this work. Not least that possible identification of bacterial infections as one *cause* of issues such as OCD or tics gets a boost; as does the idea that treating said infections might lead to some rather interesting outcomes. There could also be tie-ups with specific diagnostic labels too (see here)...

To close, there is an election here in Blighty today, so here is party political broadcast for the largest party in the country: The ‘Can’t Be Arsed’ Party. Please exercise your democratic right.

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[1] Orlovska S. et al. Association of Streptococcal Throat Infection With Mental Disorders. JAMA Psychiatry. 2017. May 24.

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Orlovska, S., Vestergaard, C., Bech, B., Nordentoft, M., Vestergaard, M., & Benros, M. (2017). Association of Streptococcal Throat Infection With Mental Disorders JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2017.0995

Tics, OCD and non-coeliac gluten sensitivity: a case report

A curious case report is documented in the paper by Luis Rodrigo and colleagues [1] (open-access) discussing the diagnosis of non-coeliac gluten sensitivity (NCGS) in a young lady "with a long history of 10 years of tics and obsessive compulsive disorder [OCD]." Further, quite a remarkable turn-around in her clinical symptoms was observed following institution of a gluten-free diet (GFD); as the authors note: "One week after the beginning of this diet, the tics diminished notably and the OCD progressively disappeared." They continue: "Within a few months, the tics had entirely stopped and the OCD had almost completely disappeared."

The Rodrigo paper is open-access so no need for me to regurgitate the entire contents to you. I will draw your attention to a few important points though:

• Both her parents were diagnosed with coeliac disease (CD). She carried the 'genetics' of CD - "HLA-DQ8 was positive" - but not the serology of CD - "the anti-transglutaminase tissue antibodies were negative". She was however positive for anti-gliadin antibodies which dissipated as a consequence of gluten removal.
• She was not 'cured' of her tics and OCD. Although rather generalised in their account, the authors talk about "occasional flares" which in some cases correlated with "involuntary transgressions with gluten or periods of exhaustion or illness."
• "She has exhibited a maize intolerance for a year, leading to this having to be excluded from her diet". Although not a large amount of research has been done in this area, there have been previous peer-reviewed rumblings that maize prolamins (specifically zein) might also have pharmcological 'effects' for some with CD [2]. Note the words 'some' and 'CD' in that last sentence.

Of course this is only a case report and whilst interesting and relevant from the N=1 point of view does not necessarily generalise to everyone presenting with tics (or Tourette's syndrome) or OCD. Quite a bit more study is required before this can be determined to be anything but a fluke finding.

I am however interested in this report providing yet another example of the potential extra-intestinal effects of gluten and the promotion of the concept of NCGS. Indeed, the recent paper by Fasano and colleagues [3] perhaps said it best: "Although there is clearly a fad component to the popularity of the GFD, there is also undisputable and increasing evidence for NCGS." One wonders whether this case report might further add to that evidence for the reality of NCGS and indeed, whether labels such as PANS (Pediatric acute-onset neuropsychiatric syndrome) characterised by "rapid onset Obsessive-compulsive disorder (OCD) and/or tics in children and adolescents" may reflect areas ripe for further examination of CD and NCGS related parameters?

So then... Oasis - Stop Crying Your Heart Out.

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[1] Rodrigo L. et al. Tourette Syndrome and Non-Coeliac Gluten Sensitivity. Clinical Remission with
a Gluten-Free Diet: A Description Case. J Sleep Disord Ther 2015, 4:1

[2] Cabrera-Chávez F. et al. Maize prolamins resistant to peptic-tryptic digestion maintain immune-recognition by IgA from some celiac disease patients. Plant Foods Hum Nutr. 2012 Mar;67(1):24, 30.

[3] Fasano A. et al. Non-celiac Gluten Sensitivity. Gastroenterology. 2015 Jan 9. pii: S0016-5085(15)00029-3.

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Huerta M, R. (2015). Tourette Syndrome and Non-Coeliac Gluten Sensitivity. Clinical Remission with a Gluten-Free Diet: A Description Case Journal of Sleep Disorders & Therapy, 04 (01) DOI: 10.4172/2167-0277.1000183