"specific clinical and neuropsychological dimensions might be related to suicidal behaviors in ASD"

The quote titling this post - "specific clinical and neuropsychological dimensions might be related to suicidal behaviors in ASD [autism spectrum disorder]" - comes from the findings reported by Luisa Weiner and colleagues [1] (open-access). It adds to other recent research talking about how elements of autism *might* associate with suicidality (see here). I should warn you that some of the Weiner findings make for difficult reading.

Authors described a case report of "a 21-year-old male [Mr A] with ASD who attempted suicide twice, in the absence of other psychiatric diagnoses." They detail how, following some quite comprehensive observations, a possible *connection* was noted between his suicidality and "some of the core clinical and neuropsychological features of ASD."

A few important points are highlighted in the Weiner study: "Mr. A. reported that his suicidal thoughts started when he was 18, following an unrequited infatuation with a classmate – the result of a rational decision: he had decided to “fall in love” with her." Things did not however go as he planned, as we are told that: "He started having “obsessive negative thoughts”, and attempted suicide by jumping from a window." He survived but "his suicidal thoughts lingered, characterized by a restrictive, rigid pattern."

Researchers relied on the Beck Depression Inventory (BDI) to rule out depression in this case: his score "was in the normal range (3/63)." This inventory is one of a few that have been described as being "robust in their measurement properties in the general population" [2] but with perhaps more to do in the context of its use in autism. In the absence of depression or rather elevated self-report scores indicative of depression, authors suggest this raises "the question of whether the persistence of suicidal thoughts was associated with ASD-related features."

The Weiner findings have to be placed in the context of other independent research looking at suicidality and autism. First, risk of suicidality is seemingly heightened when autism is diagnosed (see here). Second, although depression - an important variable *linked* to suicidality - is over-represented in relation to autism (see here), questions are still being asked about the impact of depression in relation to suicidality accompanying autism in the context of an often complicated clinical picture (see here). Third, the idea that the features/traits of autism might themselves be independent predictors of suicidality in autism has been discussed on several research occasions (see here and see here and see here).

The culmination of all this work is that quite a lot more research and clinical resources need to be ploughed into looking at suicidality and autism. And, importantly, translating said research into real-world actions to potentially save lives.

If you need someone to talk to, there are organisations out there...

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[1] Weiner L. et al. A case study of suicidality presenting as a restricted interest in autism Spectrum disorder. BMC Psychiatry. 2019; 19: 126.

[2] Cassidy SA. et al. Measurement properties of tools used to assess depression in adults with and without autism spectrum conditions: A systematic review. Autism Res. 2018 May;11(5):738-754.

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Yes, even gait issues accompanying autism should be investigated

In today's post, I'm directing you to the case report published by Valerio Andreozzi and colleagues [1] (open-access). This paper supports the idea that the phrase 'it's just part of their autism' should always be used sparingly (see here) when it comes to the wide range of symptoms that seem to follow or overlap with a diagnosis of autism. And that includes issues with gait or walking (see here).

As I mentioned this was a case report: "An 8-year-old Caucasian boy affected by autism presented with nontraumatic knee pain." He walked with a limp and was presented for further clinical investigation as a result. Things did not run altogether smoothly however as we are told that "Clinical examination was difficult to perform, due to the strong opposition of the autistic child." Clinicians did eventually get some imaging done on his knee which revealed the presence of a rare condition called a posterior cruciate ligament (PCL) ganglion cyst. The authors mention how "only one case of pediatric ganglion cyst of the PCL has been reported in the literature." Surgery was indicated and performed and was successful.

Andreozzi et al talk about some of the hows-and-whys of this condition being noted in this particular patient. There is mention of 'traumatic origin' (no, not the psychobabble version) as being possible as per other mention of this condition in relation to sporting injuries. They also talk about how "children with ASD [autism spectrum disorder] show deficient sensory perception relative to internal or external stimuli... and highly individualized asymmetrical lower extremity angular joint positions during gait..., which may induce tripping or falling and be a cause of repeated trauma over time." Ultimately however, they aren't able to say exactly why this particular condition came to be in this particular patient.

This was a very isolated case and so one shouldn't assume every case of autism being accompanied by gait/walking issues is due to such an issue. It does however reiterate that a diagnosis of autism should not be used as an excuse not to look at other reasons why certain signs and symptoms appear alongside autism. Indeed, when it comes to joint and gait issues appearing alongside autism, there may be quite a few investigations to undertake in this area (see here and see here for example).

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[1] Andreozzi V. et al. Diagnosis and Treatment of a Symptomatic Posterior Cruciate Ganglion Cyst in a Child with Autism. Case Rep Orthop. 2019 Mar 5;2019:9192347.

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NMDAR encephalitis presenting with "behavioral changes and some autistic features"

Anti N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is yet again (see here) the blogging topic today, as I bring the case report published by Yasmin Khundakji and colleagues [1] to your attention. It's an important case report because, in keeping with the primary focus of this blog, the words 'autistic features' also appear in the Khundakji account. This follows quite a bit of other independent research where autism or autistic features has been mentioned in the context of NMDA receptor encephalitis (see here and see here).

The details? "The patient was a healthy girl" ('was' being the operative word). Some time before she was 2 years of age, she experienced some really quite sudden and stark behavioural changes "manifesting as bouts of irritability, aggression, inconsolable crying, and self-mutilatory behavior (self-biting)." A fever brought about various other somatic symptoms, as eye contact was lost and insomnia set in. "In addition, she developed a progressive regression in gross and fine motor skills and an inability to swallow" with seizures following. Things were getting really serious.

Various tests were carried out which in the most part came up within typical reference ranges (including a "brain MRI"). Someone had their suspicions that NMDA receptor encephalitis *might* fit with the presented profile. Lo and behold, following testing a positive result was received albeit "one month later" (samples had to be sent out of country for analysis). Interventions were put in place ("intravenous immunoglobulin (IVIg) and intravenous methylprednisolone... plasma exchange... rituximab") with some being more successful than others. Of particular note: "A dramatic improvement in her social skills and irritability appeared within hours following plasma exchange." Interesting. Things did eventually improve for the young girl at the centre of the Khundakji paper as we are told that: "Apart from mild speech delay, her neurological exam and developmental milestones are normal."

What lessons can be learned from such case reports? How about starting with the idea that rapid onset childhood regression that includes 'autistic features' should always be investigated as a sign of unmet medical need such as a response to infection (see here)? Perhaps also acknowledge that the presentation of autism or autistic features is not a life-long, immutable, set-in-stone scenario for some people (see here and see here and see here)? And as for the effects of plasmapheresis (plasma exchange) on this particular young child linked to a "dramatic improvement in her social skills and irritability", I'm wondering whether there is a research study or two to be designed and conducted on this topic (with due care)?

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[1] Khundakji Y. et al. Anti-NMDA receptor encephalitis in a toddler: A diagnostic challenge. International Journal of Pediatrics and Adolescent Medicine. 2018; 5: 75-77.

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Autism research really needs to study the prevalence and treatment of scurvy in autism

The results published by Melinda Saavedra and colleagues [1] describing another case report where scurvy was [eventually] diagnosed as appearing alongside autism represents yet another 'call to action' on this topic.

I've covered this issue quite a few times before on this blog (see here and see here and see here), and quite frankly it's reached the point where autism research really needs to step up and formally study the prevalence of scurvy in relation to autism. Indeed given the almost universal reports of medical science not initially recognising that scurvy can be no stranger to autism, the time has also come to "announce [to] the pediatrician and other professionals dedicated to primary health care about scurvy as a potential consequence of restrictive diets in children with autism spectrum disorders."

This time around the clinical focus was on a 4 year old boy who was brought to clinical attention as a result of "hip pain and refusal to walk, associated with petechiae and bruising of the lower limbs." The clues were all there that scurvy could be a cause of such symptoms, but it was only when it was revealed that the child had "selective feeding habit" that the penny seemed to finally drop. Indeed: "Levels of Vitamin C in blood were measured and without waiting for results he started treatment with 300 mg per day of ascorbic acid." Lo and behold, his vitamin C results were found to be low, and vitamin C supplementation eventually did the trick. Of vital importance, the pain associated with scurvy also showed improvement and he was discharged from clinical care with a maintenance dose of vitamin C and some nutritional advice.

'Selective feeding patterns', 'picky eating' or whatever you want to call it, is an issue that is not stranger to autism (see here). It's reasonable to assume that where such feeding issues continue into the longer-term, and dependent on what foods are consumed as part of such a restrictive pattern, there are likely to be biological consequences for the person concerned as a function of what nutritional inadequacies follow. Indeed, I daresay that such a pattern follows what is being noticed in connection with other food-related conditions in the longer term (see here). Set in this context, a lot more research and importantly, clinical practice, needs to focus on the hows-and-whys of such behaviours and their remediation. There is no longer any excuse for allowing diseases of the past such as scurvy and also others like rickets, to plague the children of today, vulnerable children of today, where healthy food in most parts of the world, is not in short supply.

Oh, and bear in mind that 'picky eating' might not be the only reason why scurvy might appear alongside autism [2]. We need lots more data.

And also, as I write this [3]...

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[1] Saavedra MJ. et al. Scurvy due to restrictive diet in a child with autism spectrum disorder: case report. Arch Argent Pediatr. 2018 Oct 1;116(5):e684-e687

[2] Hasan Al-Breiki S. et al. Scurvy as the tip of the iceberg. Journal of Dermatology & Dermatologic Surgery. 2014; 18: 46-48.

[3] Caldwell KJ. et al. Child With Autism and a Limp. Ann Emerg Med. 2018 Oct;72(4):493-495.

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"Bowel perforation in chronic idiopathic megarectum and megacolon" and autism: 15 years on...

There was something all-too familiar about the case report detailed by Chukwuebuka Anyaegbuna and colleagues [1]. The description of a young man in his mid-twenties "with autism spectrum disorder" and a "history of chronic constipation" (going back years with "multiple previous admissions") eventually being admitted to intensive care on the basis of a potentially life-threatening bowel state is, unfortunately, nothing new to science and clinical practice (see here).

Bowel issues - both functional and more pathological - are over-represented when it comes to a diagnosis of autism (see here and see here for examples). The specific diagnosis of 'megarectum' detailed in the Anyaegbuna paper in relation to autism had also been noted some 15 years previously [2] in the peer-reviewed science literature. Indeed, the paper by Nadeem Afazal and colleagues [2] looking at over 100 children with autism "who were referred for gastroenterological assessment" showed that constipation was not an infrequent finding for this group. They also reported that many autistic children in their cohort "had moderate/severe loading or acquired megarectum." Their observation that "consumption of milk [was found] to be the strongest predictor of constipation in the autistic group" also chimed with me, as an interested researcher of diet as being a potentially important variable for 'some autism' [3]. And indeed, such an observation also seemingly intersects with other more recent dietary-bowel findings too (see here)...

The Anyaegbuna findings represent the continued failure of autism research and practice to take seriously the issue of bowel problems associated with autism. Stretching back over a period of about twenty years or so, I've noted the various comments from various (typically ill-informed) people protesting that various gastrointestinal (GI) investigations are 'not medically indicated' when it comes to some cases of autism. Some even made jokes about it. It's probably not unreasonable for me to say that set within this atmosphere, there has been a general reluctance to look at such issues for fear of castigation or shaming. There have been some brave research souls (see here and see here) who've kept on looking at bowel issues and autism, but not half as many as there should be. And it is those suffering with such bowel problems who have been let down: please do make sure that you take a good look at the X-rays accompanying the Anyaegbuna report to see what I mean.

Having said all that, I would like to think that things are slowly changing. It's no longer taboo to talk about bowel issues being over-represented in relation to autism. Indeed, we've had study after study all pointing in the same direction: bowel issues are seemingly related to autism, covering both childhood and adulthood. And such bowel issues might have some important effects on behaviour (see here). What we are sadly lacking at the current time however, is a concerted research effort asking 'why'? and 'what can we do to prevent (yes, prevent) such bowel issues occurring rather than just treating them when they occur?'

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[1] Anyaegbuna C. et al. Bowel perforation in chronic idiopathic megarectum and megacolon. BMJ Case Rep. 2018 Aug 20;2018. pii: bcr-2018-225406.

[2] Afzal N. et al. Constipation with acquired megarectum in children with autism. Pediatrics. 2003 Oct;112(4):939-42.

[3] Whiteley P. et al. Nutritional management of (some) autism: a case for gluten- and casein-free diets? Proc Nutr Soc. 2015 Aug;74(3):202-7.

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Functional levels of vitamin D and autistic behaviours?

The paper by Feiyong Jia and colleagues [1] although following a 'case report' methodology provided some interesting reading recently. Based on the idea that maintaining an adequate supply of vitamin D might be rather important on a behavioural level, at least when it comes to 'some' autism, authors provide a route map for some further study.

Including a few notable names previously attached to research looking at a possible connection between vitamin D and autism (see here and see here), Jia et al reported findings for 3 children diagnosed with an autism spectrum disorder (ASD) who "were given vitamin D3 supplementation followed by a long interruption." Alongside looking at serum levels of vitamin D - the sunshine vitamin/hormone - researchers also discussed examination of autistic traits in their small case report population.

They noted that: "the core symptoms of ASD [autism spectrum disorder] fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD." Authors concluded that: "Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD." I'll also direct you to an article about levels of vitamin D and what they might mean (see here) with no medical or clinical advice given or intended.

Keeping in mind that a case report methodology is very good at providing data on individuals but not necessarily great when it comes to information about a wider population, there are some potentially important points to take from the Jia findings. Not least is the idea that screening for something like vitamin D insufficiency or deficiency is something 'under-used' in the current context (and something that has been mentioned in previous peer-reviewed research occasions). More formal, rigorous study of how autistic and other behaviour(s) *might* fluctuate as a function of vitamin D status (indeed, among other potentially important variables) is indicated.

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[1] Jia F. et al. Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report. Nutr Neurosci. 2018 Apr 8:1-4.

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PET scanning as a biomarker for ketogenic diet response in autism? Not quite...

The case report findings reported by Iwona Żarnowska and colleagues [1] provide the blogging fodder today and an interesting idea: could PET imaging - "non-invasive positron emission tomography (PET) with 18 fluoro-deoxyglucose (18FDG PET) of the resting brain" - serve as "a biomarker in identifying individuals with autism who might benefit from the KD [ketogenic diet] due to underlying abnormalities related to glucose hypometabolism"?

'We need more research' is the conclusion reached by authors, who describe a case report of a 6-year old boy who seemed to regress into autism (yes, he regressed - "At the age of 2, he was developmentally on target in motor and cognitive skills, used language for communication, and displayed normal interests, social activities, and behaviours that were appropriate for his age") and was subsequently introduced to a ketogenic diet. The ketogenic diet (KD) has been discussed before on this blog in relation to autism (see here and see here for examples), and how "a very strict, high-fat, low-carbohydrate, adequate-protein and vitamin-supplemented diet with meals distributed evenly throughout the day" seems to have some important effects on behaviour for some.

Indeed, we are told that use of the KD diet for this young man diagnosed with autism and ADHD (attention-deficit hyperactivity disorder) seemed to *correlate* with some important changes to his behavioural presentation. So: "improvements in clinical outcomes were observed as early as 1 month after the classic KD initiation." The sorts of things reported included less hyperactive and aggressive behaviours and some important differences in his scores on schedules such as the CARS (Childhood Autism Rating Scale) focusing on autistic behaviours. Cognitively, there were also some positive changes reported too: "The intellectual development of the patient, as measured by the WISC-R at the age of 7 years and 5 months, also improved his Full Scale IQ increased from 82 to 99..., Verbal Scale IQ increased from 102 to 113..., and Performance Scale IQ increased from 62 to 83." All of this bearing in mind the 'case report' status of this study.

Then to the mention of that word 'biomarker' as PET scanning was conducted "before treatment (baseline study) and 11 months later on the KD (follow-up study)" and results compared. Although no expert on PET (see here for an overview) the aim was to look at glucose and where the glucose-like tracer 'stuck' in terms of parts of the brain. Researchers observed that at baseline, before the KD was put in place, there was evidence of "regional glucose hypometabolism... observed bilaterally in the mesial temporal lobes, basal ganglia, and cerebellum." At follow-up, when the various manifestations of the ketogenic diet had been in place for a year, they reported different findings based on PET scanning: "18F-FDG uptake decreased markedly and diffusely in the whole cerebral cortex with a relatively low reduction in basal ganglia." The authors add that such observations are not a million miles away from similar metabolic changes seen in others when a KD is put in place in relation to the management of epilepsy (a set of conditions where the KD has found a particular usefulness). The shift away from glucose metabolism in those brain areas is thought to represent "a metabolic shift from the utilization of glucose to utilization of ketone bodies as a primary source of energy" a key aim of the ketogenic diet.

Do the Żarnowska live up to their possible 'biomarker' discussions? Erm, I'm afraid not yet they don't. They do make some interesting observations about the use of a ketogenic diet in the context of a single case report including the label autism. They also present some interesting 'brain imaging' data gathered before and after the use of a KD. But as a biomarker? Not on this occasion. Not yet. But don't however discount the potential usefulness of the ketogenic diet in the context of [some] autism however...

To close, of course you know that it's Star Wars Day today. Don't you? 'Penny for your thoughts.'

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[1] Żarnowska I. et al.Therapeutic use of carbohydrate-restricted diets in an autistic child; a case report of clinical and 18FDG PET findings. Metabolic Brain Disease. 2018. April 11.

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On biotin and 'some autism'

Although I've mentioned biotin (vitamin B7) in the context of autism before on this blog (see here), due credit needs to be given to Peter over at the Epiphany blog for more extensive coverage (peer-reviewed based) of this nutrient (see here). Discussing how, within the increasingly large range of conditions that manifest autism or autistic behaviour(s), there may be one or two 'types' of autism that manifest biotin deficiency, there is a pretty obvious course of intervention as and when deficiency is found: supplementation.

And supplementation is exactly what was discussed in the paper by Paul Benke and colleagues [1] reporting on a case report of a young female who presented with "features of autism spectrum disorder, isolated headaches, and episodes of headaches and limb shaking." Alongside those symptoms, authors also discussed a fairly unusual part of her clinical history where "hair and nails did not grow."

Although there are various reasons why hair and nails might not grow - indeed, just about every nutritional deficiency seems to affect something like nail health and growth - biotin was noted as a point of concern in this young lady's clinical picture. Indeed authors noted that: "Administration of biotin restored her nail and hair growth and improved intellectual ability and school performance." They added that use of acetazolamide, more typically indicated for glaucoma and/or epilepsy, seemed to provide some relief from other symptoms: "episodes of headaches, single limb shaking, and loss of consciousness." And before you say it, yes, autism is no protection against the development of headaches (see here).

Bearing in mind this was a single case report yet also acknowledging the tenet: 'if you've met one person, you've met one autistic person', I find descriptions such as this to often be revealing. Other case reports talking about biotinidase deficiency associated with autism [2], where biotinidase is the enzyme responsible for freeing up biotin bound to food (see here), add to the interest in this area. Specifically how some other symptoms - "seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, problems with movement and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection called candidiasis" - associated with biotinidase deficiency are not a million miles away from what has been talked about in some autism literature too (see also the comments section of another post here).

As per my discussions on various other nutrients that seem to be 'deficient' in at least some people on the autism spectrum (see here and see here), the defining message seems to be that post-diagnosis of autism, a screening program needs to be put into place looking at various nutrients in the context of something like eating patterns and behaviours. This could be part of a broader range of screening for something like inborn errors of metabolism that can and do show a connection to some autism (see here) and often (always?) involve nutrients (see here for example). Or could just mirror what is happening in other parts of psychiatry, where physiological parameters are starting to gain some parity with behavioural/developmental/psychiatric ones (see here) mindful of what correcting any deficiency might bring to various aspects of health (see here)...

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[1] Benke PJ. et al. Biotin and Acetazolamide for Treatment of an Unusual Child With Autism Plus Lack of Nail and Hair Growth. Pediatr Neurol. 2018 Feb;79:61-64.

[2] Zaffanello M. et al. A case of partial biotinidase deficiency associated with autism. Child Neuropsychol. 2003 Sep;9(3):184-8.

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The art of the gut microbiome: 'Excretory Wipings' across 45+ years

Excretory Wipings May 18-October 21, 1970 is a piece of art composed by the artist Billy Apple (more accurately known as Billy Apple®). Due to possible copyright issues et al I don't want to show the actual piece on this blog but will describe to you what it comprises: a conceptual art work including toilet paper with erm, traces of a bowel movement provided during that particular period of 1970.

It's probably not everyone's cup of tea when it comes to art, but believe it or not, it might potentially be a rather important research starting point if say you wanted to characterise the gut microbiome past and present. Indeed, that is exactly what the paper by Thilini Jayasinghe and colleagues [1] describes, as they compared the bacterial colonies present in the 1970 sample(s) with a more up-to-date set of samples provided by the same artist in 2016.

Some media interest in the Jayasinghe results can be seen here. In short, three archived samples sourced from the 1970 art piece were compared with three more recent samples sourced exactly 46 years later (2016). Researchers performed 16SrRNA sequencing to "study bacterial phylogeny and taxonomy" [2] and try and find out whether there were similarities/differences in the types of bacteria present and indeed, whether overall bacterial diversity had reduced/stayed the same/increased between the testing periods.

Following this N=1 study, a few details emerged. So: "We observed that 45% of the microbial species were retained over the 45 year interval." Such a finding has to bear in mind that the artist "was suffering from diverticular disease in 2016" and that such a condition may well impact on the type of gut bacteria that is present and/or predominating. Indeed, the authors talk quite a bit about how "the 2016 microbiomes contained significantly higher level of genus Prevotella... which may be related to the observed diverticular disease by having a negative impact on gut immune system." Interestingly too, the word 'butyrate' appears in the Jayasinghe text, as in lower levels of butyrate-producing bacteria being present in the more recent sample. Butyrate is currently going through a period of bacterial 'sainthood' [3] at the moment...

Next: "The diversity of the microbial species from samples taken when Apple was 80 years of age was lower than that from samples when he was 35." Bacterial diversity is something of real interest these days, as more and more people start talking about gut bacterial diversity (and the loss of it) as potentially being related to all-manner of life-enhancing and life-not-so-enhancing correlations. The recent results are framed by the authors in the context of being "consistent with the idea of a drift towards a core microbiome" where ageing seems to play a role in diversity.

Of course, one shouldn't forget that this was a N=1 study and that gut bacterial populations are subject to all-manner of influences pushing and pulling on what bacteria may or may not be present in a longitudinal sense. These latest results say very little outside of what happened to the bacterial profile of Billy Apple® between the testing occasions.

But I'm still intrigued by such findings and the idea that there may be other resources to 'tap into' when it comes to looking either long-term at gut bacterial profiles or indeed, comparing gut bacterial patterns as a function of time and various ages. Y'know, comparing bacterial profiles of various ages in years gone by with similarly aged participants in more modern times, and trying to determine what various factors linked to modern life might have done (or not) to gut bacterial profiles. I don't doubt that some results might be rather interesting and discussion-provoking...

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[1] Jayasinghe TN. et al. Long-term stability in the gut microbiome over 46 years in the life of Billy Apple®. Human Microbiome Journal. 2017; 5-6: 7-10.

[2] Janda JM. & Abbott SL. 16S rRNA Gene Sequencing for Bacterial Identification in the Diagnostic Laboratory: Pluses, Perils, and Pitfalls . Journal of Clinical Microbiology. 2007;45(9):2761-2764.

[3] Canani RB. et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World Journal of Gastroenterology : WJG. 2011;17(12):1519-1528.

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Can a bone marrow transplant really affect psychotic symptoms in schizophrenia?

"Though BMT [bone marrow transplantation] may not be a cure for all cases of schizophrenia, it definitely possesses the potential to manage overall disease severity and improve the quality of life, and this case report is a preliminary demonstration of the safety and efficacy of BMT in treatment-resistant schizophrenia."

So said the findings reported by Tsuyoshi Miyaoka and colleagues [1] (open-access available here) discussing a case report of a young man initially diagnosed with paranoid schizophrenia which was eventually deemed 'treatment-resistant' on the basis of his lack of [positive] response to anti-psychotic medication(s) given for "his auditory hallucinations, suspiciousness, active social avoidance, persecutory delusion, and deterioration in the level of social functioning."

Things unfortunately got worse for this young man we are told, as he was subsequently diagnosed with acute myeloid leukemia - cancer of the white blood cells - setting in motion the initially daunting task of treatment via a bone marrow transplant. As the name suggests, BMT involves the transplantation of bone marrow where stem cells are made. Stem cells are those wonderful cells that give rise to the various types of blood cells we all have among other things. The idea being that a kinda of reboot of white blood cells in this case could potentially treat his leukemia.

Although Miyaoka et al don't actually say how successful the BMT was for his leukemia (the patient was alive 8 years after BMT so I assume successful), they do talk about what happened to his psychotic symptoms following the BMT. So: "Thirty days later, his psychotic symptom had almost disappeared. He was sustained without any neuroleptic treatment and need for any other administration." Indeed, this didn't appear to be any short-term effect neither as "8 years after BMT, the improvements of somatic and psychiatric symptoms are continued, and the patient is very well and there are no residual psychiatric symptoms." In short, things were still going well for this young man both in terms of his past leukemia diagnosis and also psychotic symptoms.

There is always the possibility of "spontaneous improvement without any treatment" as accounting for the psychiatric results presented by the authors. Indeed, I also note that various immunosuppressive medicines were also administered around the time of the BMT to "avoid graft versus host disease (GVHD)" which might also have played some role in light of other research suggestions [2]. One has to be careful not to jump to too many conclusions particularly on the basis of single case reports.

But... it is a potentially important coincidence that use of a BMT came at the same time as the symptom changes noted. I'll also draw your attention to a 'call for case histories' on the topic of "BMT in patients with coincident schizophrenia" made by Sommer and van Bekkum [3] on the back of other work from these authors in relation to "the possibility that schizophrenia may be transmitted" where "a patient... developed severe psychosis after receiving a BM transplant from his schizophrenic brother" [4]. It seems that there may be a two-way process potentially at work when it comes to immune function and schizophrenia.

This is interesting stuff. Framed alongside the idea that schizophrenia might not be a homogeneous condition - think 'the schizophrenias' -  and that at least one 'type' of schizophrenia might have a significant 'immune' component to it (see here for example), one could envisage further investigations on the potential use of BMT in certain cases. I do have to mention safety and the possible side-effects of BMT outside of just GVHD (see here) as being important considerations; added to the invasiveness of BMT.

And whilst we're on this topic, I'd also direct you to some chatter about mice and bone marrow transplants in the context of autism some years back (see here) minus any sweeping generalisations but again, interesting...

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[1] Miyaoka T. et al. Remission of Psychosis in Treatment-Resistant Schizophrenia following Bone Marrow Transplantation: A Case Report. Front Psychiatry. 2017 Sep 21;8:174.

[2] Knight JG. et al. Rationale for a trial of immunosuppressive therapy in acute schizophrenia. Mol Psychiatry. 2007 May;12(5):424-31.

[3] Sommer IE, van Bekkum DW. Call for case histories of BMT in patients with coincident schizophrenia. Bone Marrow Transplantation. 2013;48(6):880.

[4] Sommer IE. et al. Severe chronic psychosis after allogeneic SCT from a schizophrenic sibling. Bone Marrow Transplantation. 2015;50(1):153-154.

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Rare genetic condition manifesting as autism and its management

"We report the case of a young boy with nonverbal autism and intellectual disability, with a rare de novo 1q21.3 microdeletion."

That was the starting point of the article published by Cora Cravero and colleagues [1] (open-access available here). Researchers describe in some detail how a diagnosis of autism spectrum disorder (ASD) was made "on communication and social interaction impairments and restricted, repetitive patterns of behaviour and interests" and what followed: "The patient had early and extreme self-injurious behaviours that led to blindness, complicated by severe developmental regression."

Detailing how "comparative genomic hybridization array identified a de novo 1.4 Mb microdeletion of chromosome 1q21.3" and various associated physiological findings, the Cravero report provides some rather intriguing evidence that the sentence 'science does not know what causes autism' might not necessarily ring true for everyone (see here for other examples). As the authors note: "The 1q21.3 microdeletion seems associated with ID [intellectual disability], dysmorphic features, and early SIB [self-injurious behaviour] and can be a cause of syndromic autism."

One or two particular details are noteworthy in the Cravero findings outside of the idea that the N=1 might be an important concept in relation to the autism spectrum.

First, is the quite extreme effects that self-injurious behaviour (SIB) in the context of autism can have on a person. This child was blinded by their extreme SIB: "intense and repeated mutilations of cheekbones and eyes, culminating in a bilateral blindness at the age of 4 years by intumescent white cataract after numerous surgical complications." As I've mentioned before on this blog, SIB can in some cases lead to some very complicated adverse health outcomes (see here) that are not uncommon to the autism spectrum (see here). There is however a brighter note to add to the SIB experienced by this child as the authors noted that a range of interventions seemed to help alleviate some of the challenging behaviours linked to such actions. I note for example that naltrexone - the opiate antagonist - was utilised to "decrease the endorphin sensation seeking procured by SIB and diminish SIB." This follows something of a resurgence in interest in this medicine (see here) and is music to my own research ears (see here).

Second, is a little detail mentioned about the eating habits of this child: "a diet almost exclusively made up of dairy products." Alongside some accompanying details on how "intestinal transit was altered, with episodes of diarrhoea (false constipation), encopresis, and coprophagia" and I'll just say that this is something I've heard quite a bit down my years of autism research. Alongside the use of lactulose to aid the bowel issues and the anti-opioid effect of naltrexone (yes, the protein in dairy products does break down into opioid-like compounds), I'm wondering whether some of the research I've been involved with down the years looking at casein-free diets might also be relevant too (see here)?

Finally, I need to draw your attention to the increasingly popular idea that regression is a part of quite a few cases of autism (see here). Indeed the pattern of autism + ID particularly being over-represented when it comes to regression in the context of autism (see here) seems to be borne out by the case report detailed by Cravero et al.

It is good to hear that after "a year of hospitalization" the outcomes reported on this child were quite a bit more favourable than where he began. So: "His mood was stable, without tantrums or irritability, and he felt pleasure without crippling stereotypes. The SIB were limited to small low intensity fists against his helmet or his cheekbone, occurring from time to time." Further: "During the best of times he wandered half-days without helmet, smiling and exploring his environment using tactile gestures."

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[1] Cravero C. et al. Management of Severe Developmental Regression in an Autistic Child with a 1q21.3 Microdeletion and Self-Injurious Blindness. Case Rep Psychiatry. 2017;2017:7582780.

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L-methylfolate administration and autism: a case report

I should have really titled this post 'another case report' given yesterday's entry on this blog talking about a case of [untreated] PKU and autistic behaviours/diagnosis. Here I am again talking about another N=1 with autism in mind and specifically the findings reported by Kim Siscoe & David Lohr [1] on how: "L-methylfolate supplementation improved symptoms of aggression and disruptive behavior in a child with autism who tested positive for the C677TT allele of the methyltetrahydrofolate reductase enzyme gene."

First things first. This was a case report; please keep that in mind. Second, I am not a medical doctor and don't provide medical or clinical advice on this blog. Within those caveats I am however very interested in the Siscoe/Lohr observations.

Why? Well, methylene tetrahydrofolate reductase (MTHFR) (gene and enzyme) has featured quite a bit on this blog in light of findings linking gene and enzyme to cases of autism (see here and see here for examples). The idea is that MTHFR serves a primary function in reducing the compound 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate - another name for L-methylfolate -  the reduced and methylated form of folic acid, is an important methyl group donor for the recycling of homocysteine back to methionine utilising vitamin B12 along the way (see here for a nice hand drawn graphic). The implications of disruptions to MTHFR (gene and enzyme) are potentially multiple but include effects on methyl group donor ability (methyl groups potentially linked to things like DNA methylation as part of all that epigenetics jazz that you hear so much about these days) and effects on downstream metabolites such as those related to homocysteine metabolism (see here).

So Siscoe & Lohr present data on what happened when the active form of folate was supplemented following the identified genetic issue with the MTHFR gene potentially affecting typical production of L-methlyfolate.

Where next with this work? Well, it stands to reason that in these days of personalised medicine percolating through to autism research and practice (see here), knowledge about a potential genetic issue identified in [some] cases of autism should be further investigated. We have other examples (see here). I'd like to see larger and more controlled trials of L-methlyfolate supplementation in relation to autism for example, based on screening for issues with the MTHFR gene. I'd like to see a few more biological measures incorporated in such study looking at other aspects of the folate and related cycles too (see here). I'd also like to see more discussion about any long-term implications and/or adverse effects associated with such supplementation along the lines of: should we really be tinkering with mechanisms linked to DNA methylation? Also in relation to some of the other diagnoses associated with issues with MTHFR there is similarly important work emerging [2] which could be quite important in certain instances...

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[1] Siscoe KS. & Lohr WD. L-Methylfolate supplementation in a child with autism and methyltetrahydrofolate reductase, enzyme gene C677TT allele. Psychiatr Genet. 2017 Mar 7.

[2] Roffman JL. et al. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatr. 2017. Mar 14.

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Siscoe, K., & Lohr, W. (2017). L-Methylfolate supplementation in a child with autism and methyltetrahydrofolate reductase, enzyme gene C677TT allele Psychiatric Genetics DOI: 10.1097/YPG.0000000000000170

Presenting with the symptoms of autism and then diagnosed with phenylketonuria (PKU)

The case report from Betül Mazlum and colleagues [1] (open-access available here) illustrates once again that (a) the plural 'autisms' exist (see here) and (b) screening for inborn errors of metabolism (IEM) should be an important part of any autism assessment (see here). Indeed, screening for IEM should really be part of assessments for many different labels...

Detailing a case report wherein a 3-year old child came to clinical attention for "speech delay and social problems", the authors describe how following a diagnosis of "autism according to DSM-IV criteria" further investigations were undertaken. Said investigations included analysis of blood and urine amino acid levels and, voilà, high levels of phenylalanine were detected and a diagnosis of phenylketonuria (PKU) made. Initiation of a low phenylalanine diet (the treatment of choice for PKU) followed and was accompanied by some important [positive] changes to behaviour and cognition. Of particular note to the presentation of autism we are told that: "At 4 months follow-up improvement was noticed in his eye contact, joined attention and speech."

The authors further note: "This case was not at particular risk for PKU at first thought, being born to non-consanguineous parents and during a period when newborn screening with Guthrie test was widely applied in Turkey. Although the child had a heel prick in the hospital where he was delivered, the results are unavailable and therefore whether his sample was analyzed is questionable."

OK, this was a case report and whilst an important 'N=1' is not necessarily generalisable to all autism (or rather all autisms). Insofar as the methods talked about for establishing raised phenylalanine - "Blood and urine amino acid chromatography" - I would have liked to have seen a little more detail in relation to the specific 'chromatography' methods used and any results related to another aromatic amino acid (tyrosine). We don't also have any data on follow-up either (repeat biological testing)...

PKU is an important but quite rare IEM. This is not however the first time that PKU has been linked to autism or the presentation of autistic traits (see here) particularly in cases of 'untreated' PKU. Aside from PKU providing quite a good template for how diet - certain aspects of diet - can affect behaviour and mental state for some (see here) there are other potential implications and 'correlations' on the back of this work. Not least is the intersection between another intervention measure potentially indicated for PKU - tetrahydrobiopterin (sapropterin or BH4) - and research suggesting that the 'mopping up phenylalanine' properties of this compound might be potentially effective for some cases and facets of autism too (see here) based on double-blind, placebo-controlled trial results [2].

"The possibility of a metabolic disorder including PKU should be considered in any child presenting with symptoms of autism, learning or speech problems and PKU should be tested unless the newborn screening results are available." I wouldn't argue with those sentiments [3], allowing for the fact that other correlates should also be considered (see here for example) particularly it seems, when autism appears alongside something like intellectual (learning) disability. The question of whether the quite restrictive low phenylalanine diet typically indicated for PKU might also impact autistic signs and symptoms is something that science still perhaps needs to look into...

Music to close, and how about something lively from The King?

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[1] Mazlum B. et al. A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood. Turk J Pediatr. 2016;58(3):318-322.

[2] Klaiman C. et al. Tetrahydrobiopterin as a treatment for autism spectrum disorders: a double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2013 Jun;23(5):320-8.

[3] Bilder DA. et al. Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study. Mol Genet Metab. 2017 Mar 6. pii: S1096-7192(17)30052-5.

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Mazlum B, Anlar B, Kalkanoğlu-Sivri HS, Karlı-Oğuz K, Özusta Ş, & Ünal F (2016). A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood. The Turkish journal of pediatrics, 58 (3), 318-322 PMID: 28266201

Long terms effects of communication by gesture and autism: a case report

As per previous entries on this blog, I'm not at all adverse to the idea that case reports (the so-called N=1) can offer some important insights into a heterogeneous (dare I say 'plural') condition like autism. Today, I'm once again heading down this route as I bring to your attention the letter from Webster and colleagues [1] talking about a 40 year follow-up note "About a Boy with Autism Taught to Communicate by Gestures when Aged Six."

Harking back to a paper published by some of the authors in 1973 [2] (published in the same journal albeit under a different title name), Webster et al provide some important details on how Geoff, a then 6-year old boy, was taught "a sign-language program" and how "at the time, it seemed to help Geoff and many other children." Fast forward some 40+ years and the authors note that things have changed but at the same time remained pretty much the same for Geoff. So: "Geoff has hung onto the signs taught to him early on" but also: "Geoff now “speaks” as he signs some words. This speech is easier to understand if you see him every day than if you see him only now and then." Indeed his vocabulary, whilst perhaps limited by other standards, does include many important words, mostly signed but some either said verbally or paired verbally with signing. Outside of things like food preferences, I was particularly happy to see that various emotions and states are represented in his vocabulary; never underestimate the power that being able to tell someone that you are 'happy' or 'angry' can bring to a person.

"His communications, both verbal and gestural, are constantly evolving to help him to express his wishes, and he seems very excited when he has made clear his needs or wants and we have understood them." What that sentence tells us is that communication is both a vital bridge and something that should be constantly 'worked on' when it comes to autism [3]. In these days where quite a lot of focus has turned towards the usefulness of early intervention for autism (see here for example), the message that learning is a lifelong thing can often get lost in the noise. I might add that said learning might be made a little easier by the rapid rise in technology [4].

Finally, I think it is important to draw your attention to another aspect of the Webster letter in terms of the use of residential and supported living arrangements and the autism spectrum. In line with the idea that the autism spectrum is truly wide and heterogeneous is the reality that for quite a few people, lifetime residential placement and care are an important part of their lives. Geoff, we are told "adjusted well to the residential setting" and continues to enjoy life in that setting. The authors acknowledge that despite their success in teaching sign to people like Geoff: "we tended to underestimate the long-term services that many of these children, as they grow into adolescence and adulthood, do actually require." I daresay that those sentiments ring as true today as they did 40 years ago.

To close, yet another DC comics film coming soon with an excellent trailer soundtrack...

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[1] Webster CD. et al. Lessons that Linger: A 40-Year Follow-Along Note About a Boy with Autism Taught to Communicate by Gestures when Aged Six. J Autism Dev Disord. 2016. March 28.

[2] Webster CD. et al. Communicating with an autistic boy by gestures. J Autism Child Schizophr. 1973 Oct-Dec;3(4):337-46.

[3] Mulhern T. et al. A systematic review and evaluation of procedures for the induction of speech among persons with developmental disabilities. Dev Neurorehabil. 2016 Apr 8:1-21.

[4] Lorah ER. et al. A Systematic Review of Tablet Computers and Portable Media Players as Speech Generating Devices for Individuals with Autism Spectrum Disorder. J Autism Dev Disord. 2015 Dec;45(12):3792-804.

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Webster, C., Fruchter, D., Dean, J., Konstantareas, M., & Sloman, L. (2016). Lessons that Linger: A 40-Year Follow-Along Note About a Boy with Autism Taught to Communicate by Gestures when Aged Six Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-016-2773-x

Substance use disorder and autism: a case report

Minus any sweeping generalisations, I want to bring your attention to the recent paper by Ashy Rengit and colleagues [1] today, continuing a theme of case reports discussing autism co-occurring with a substance use disorder (SUD). A SUD is generally defined as where the use of one or more substances (drugs) with psychoactive properties leads to significant impairment or distress for a person. Although some people might envisage the use of illicit drugs as being the only way to receiving a diagnosis like SUD, the label also covers more 'everyday' drugs such as problematic alcohol use for example. Indeed, alcohol use disorder (AUD) has its very own category in DSM-5.

I appreciate that this topic is generally neither good dinner-table conversation nor particularly great when it comes to the public image of autism, but as per other discussions overlapping with this topic (see here) it would be folly to ignore it. That some of the characteristics accompanying the diagnosis of autism *might* play a hand in increasing the risk of developing a SUD [2] provides an important message on the value of screening for risk of SUD and where appropriate, educating and intervening early.

Rengit et al provide some useful discussions on the "risk factors which predispose individuals with ASD [autism spectrum disorder] to developing SUD" but I hasten to reiterate that sweeping generalisations are to be avoided, including the ideas of "a positive family history for substance misuse" and the suggestion that autism might be one 'phenotype' "previously reported to be associated with cannabis use" [3] for example.

"It is relaxing in general and provides an amount of happiness" is the explanation offered by Mr. A, the participant under inspection, when it came to explaining his history of alcohol use and abuse. His relationship with alcohol, we are told, began after he graduated from high school and thereafter escalated from "one or two beers per week in solitude" to "hard liquor and wine on a daily basis." There is a familiar theme included in the Rengit paper on how a 'vicious cycle' of anxiety and depression are "perpetuated by his psychosocial limitations" and how combined with chronic worry, a pattern related to his alcohol use may be emerging in conjunction with social circumstances "eliminating his motivation to leave the house." That some of the traditional strategies for overcoming depression and anxiety only previously "showed limited benefit" also provides a rationale for how alcohol might be part and parcel of a self-medication strategy in this case. Similar sentiments have been noted in other research on this topic [4]. I might also bring to your attention the history of suicide attempt(s) reported by the authors as a consequence of "feeling overwhelmed by the new environment and social challenges" that college life brought and how it may also be relevant to discussions on the pathway to SUD in relation to autism. This is particularly relevant to some important discussions recently.

Accepting that different people have different ways and means bringing them to something like a diagnosis of SUD, the Rengit paper brings to light a potentially important but difficult issue linked to some autism. Given the increasing numbers of people being diagnosed with autism (some of them quite late in life) and how in these times of continued austerity many are being left to fend for themselves, one might appreciate that cases of SUD linked to autism are only likely to increase further. This is on top of the idea that certain comorbidity that is over-represented in cases of autism might also increase the chances of something like SUD [5]. That a SUD may further disadvantage people on the autism spectrum not just in terms of health but also in relation to obtaining and sustaining employment for example - "He was also fired from his job for being suspected of being intoxicated" - requires further study and action on both screening vulnerable populations and also managing/treating such issues quickly as and when they occur [6]. Oh, and don't forget the burden of such additional issues on caregivers too [7]...

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[1] Rengit AC. et al. Brief Report: Autism Spectrum Disorder and Substance Use Disorder: A Review and Case Study. J Autism Dev Disord. 2016 Mar 5.

[2] Tabata K. et al. Three cases of alcoholism with autism spectrum disorder. Alcohol Alcoholism. 2014 Sep;49 Suppl 1:i54.

[3] Stringer S. et al. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. Transl Psychiatry. 2016 Mar 29;6:e769.

[4] Clarke T. et al. Substance use disorder in Asperger syndrome: An investigation into the development and maintenance of substance use disorder by individuals with a diagnosis of Asperger syndrome. Int J Drug Policy. 2016 Jan;27:154-63.

[5] Pedersen SL. et al. The Indirect Effects of Childhood ADHD on Alcohol Problems in Adulthood through Unique Facets of Impulsivity. Addiction. 2016 Mar 21.

[6] Kronenberg LM. et al. Personal recovery in individuals diagnosed with substance use disorder (SUD) and co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). Arch Psychiatr Nurs. 2015 Aug;29(4):242-8.

[7] Kronenberg LM. et al. Burden and Expressed Emotion of Caregivers in Cases of Adult Substance Use Disorder with and Without Attention Deficit/Hyperactivity Disorder or Autism Spectrum Disorder. Int J Ment Health Addict. 2016;14:49-63.

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Rengit AC, McKowen JW, O'Brien J, Howe YJ, & McDougle CJ (2016). Brief Report: Autism Spectrum Disorder and Substance Use Disorder: A Review and Case Study. Journal of autism and developmental disorders PMID: 26944591

Can mitochondrial disease be mistaken for chronic fatigue syndrome?

Very possibly, is the answer to the question that titles this post on how the diagnostic borders between mitochondrial disease and chronic fatigue syndrome (CFS) might be blurred. I bring to your attention the case report published by Fernando Galán and colleagues [1] (open-access available here) as an example.

Detailing the experiences of a 30-year old male who "appeared to meet the CDC-1994/Fukuda criteria for CFS [chronic fatigue syndrome]" and for whom 1 year of "cognitive behavioral therapy, graded exercise therapy, and antidepressants" resulted in only 'very slight improvement', authors eventually "considered the possibility of mitochondrial myopathy in this patient."

Screen and you may find, is the primary lesson offered by Galán et al, as "a severe deficiency of activity in complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase) and IV (cytochrome c oxidase) below 42% and 70% of the minimum reference of control value normalized to citrate synthase activity, respectively" is reported. Combined with several variants noted in the mitochondrial genome, and "adult-onset mitochondrial myopathy, with clinical manifestation of peripheral sensory neuropathy, autonomic symptoms, and occipital neuralgia" was the eventual diagnosis. Treatment, consisting of riboflavin (100 mg 3 times per day) and thiamine (300 mg/day) was begun, and coincided with "a marked and sustained improvement." Further clinical improvement was also noted following the use of pregabalin.

In these days of continued questioning about whether the suggested blanket psychological 'treatment' of CFS is actually cutting the scientific mustard (see here) I'm minded to reiterate how Galán et al were able to diagnose a biological reason as to potentially why this man was presenting with the symptoms he was. As far as I'm aware, cognitive behaviour therapy (CBT) is not normally indicated for treating mitochondrial disease and probably why it had such little effect in this case.

Yes this is a single case report and it would certainly be unwise to suggest that every case of CFS or ME is due to mitochondrial issues. That being said, the work from Sarah Myhill and colleagues - 'mitochondria, not hypochondria' - has been discussed before on this blog (see here). Combined with other preliminary results (see here) and I think quite a good case for screening for mitochondrial issues is being formed as and when CFS is diagnosed. Certainly following "the appearance of new symptoms and signs" one might consider putting additional screening resources in place, and indeed probably better to do said screening before any psychosomatic explanations are assumed or acted upon.

Oh, and without medical or clinical advice given or intended, the peer-reviewed literature 'around' this topic also has some other potential 'placebo-controlled' lessons to offer any interested ears (see here)...

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[1] Galán F. et al. Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. J Investig Med High Impact Case Rep. 2015 Sep 24;3(3):2324709615607908.

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Galán F, de Lavera I, Cotán D, & Sánchez-Alcázar JA (2015). Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. Journal of investigative medicine high impact case reports, 3 (3) PMID: 26904705

Allergy symptoms affecting autistic symptoms?

I have quite a bit of time for Harumi Jyonouchi on this blog (see here and see here for example). Not only has Dr Jyonouchi got an eye for some potentially important biological issues associated with at least some cases of autism, she also seems to recognise that behavioural symptoms often seem to go hand-in-hand with other more somatic features as per her work taking gastrointestinal (GI) symptoms into account for example [1].

Another, more recent paper from Dr Jyonouchi caught my eye [2], specifically talking about how "clinicians need to be aware of profound effects of allergy rhinitis on neuropsychiatric symptoms in individuals with limited expressive language." This conclusion comes on the basis of her reporting on two cases - "one with ASD [autism spectrum disorder] and the other with developmental delay, congenital deafness, and other multiple congenital anomalies" - attending a pediatric allergy/immunology clinic for "non-IgE mediated food allergy" and "delayed type food allergy around 4–5 years of age" respectively. In both cases treatment was made using "the second line allergy treatment, omalizmab" (also known as omalizumab), a humanised monoclonal antibody that "inhibits binding of IgE to the IgE receptor expressed on effector cells... and blocks allergen induced immune responses." Normally indicated for patients with 'convincing' IgE-mediated asthma (at least here in Blighty), both children were offered this treatment when first line allergy medications (steroid nasal inhalers, a leukotriene receptor antagonist, and topical ophthalmic solutions for ocular allergy) did not seem to be as effective as they should. Some quite surprising effects are detailed as and when omalizumab was started including a "marked attenuation of their problematic neuropsychiatric symptoms and subsequent improvement in the cognitive development, once respiratory allergy symptoms were under control."

For the child (male, 10 years old) diagnosed with autism, Dr Jyonouchi includes some scores based on the Aberrant Behavior Checklist (ABC) subscales illustrating how correlating with the use of omalizumab, several areas of functioning seemed to improve. Also: "Unfortunately, interruption of omalizmab treatment due to delay in insurance approval, following changes in his insurance coverage, resulted in worsening of his behavioral symptoms in 2015 at 16 years of age. This was again resolved after resuming omalizmab treatment."

Although case reports are particularly interesting in the context of the N=1 with autism in mind (see here) and provide some useful starting points for future research, one has to be slightly cautious in generalising such findings to the larger body of people on the autism spectrum. As I've said many times before on this blog, the growing moves towards pluralising autism (see here) represents one of the more enlightened changes in autism research circles. What this means is that what might be a useful intervention for one person on the autism spectrum, might not necessarily translate to others or all.

That being said, I do find the suggestion of a connection between allergy symptoms and autistic and related symptoms to be a tantalising one. I've previously discussed the idea that allergy and autism (and attention-deficit hyperactivity disorder, ADHD) might eventually show some rather surprising links based on what has been seen in the peer-reviewed science domain (see here and see here) and continues to be discussed [3]. The hints from that research were that more needs to be done and specifically, what happens when allergy and related symptoms are 'treated'; something which the latest Jyonouchi paper has seemingly started to take more seriously.

Music: Weezer - Thank God for Girls.

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[1] Jyonouchi H. et al. Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology. 2005;51(2):77-85.

[2] Jyonouchi H. Marked improvement of neuropsychiatric symptoms following control of allergy symptoms with the use of humanized murine anti-IgE antibody (omalizumab) in 2 patients with severely limited expressive language. Allergy, Asthma & Clinical Immunology. 2015; 11: 38.

[3] Miyazaki C. et al. Allergies in Children with Autism Spectrum Disorder: a Systematic Review and Meta-analysis. Review Journal of Autism and Developmental Disorders. 2015; 2: 374-401.

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Jyonouchi, H. (2015). Marked improvement of neuropsychiatric symptoms following control of allergy symptoms with the use of humanized murine anti-IgE antibody (omalizumab) in 2 patients with severely limited expressive language Allergy, Asthma & Clinical Immunology, 11 (1) DOI: 10.1186/s13223-015-0105-x