Showing posts with label febrile illness. Show all posts
Showing posts with label febrile illness. Show all posts

Monday, 14 January 2019

"Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood"

I want to bring the findings reported by Julie Dreier and colleagues [1] to your attention today and their observation that: "Children with epilepsy and febrile seizures-with and without concomitant epilepsy-are at increased risk of developing a broad range of psychiatric disorders in later life."

Researchers report results based on the examination of one of those ever-so-impressive Scandinavian population registries that have moved science forward in many, many different areas (see here for example). This time around it was the Danish National Patient Register and the inclusion of data from "1 291 679 individuals... born in Denmark and followed up in our population cohort (approximately 15 million person-years)." Over 43,000 individuals showed a history of febrile seizure - "fits that can happen when a child has a fever" - and over 10,000 had epilepsy. Likewise: "83 735 (6%) cohort members were identified with at least one of the psychiatric disorders of interest" including substance abuse disorders, schizophrenia, mood disorder, anxiety, and personality disorder.

Results: "The risk of any psychiatric disorder was raised in individuals with a history of febrile seizures..., epilepsy..., or both disorders." The magnitude of the risk was categorised as statistically significant in terms of elevation but ranged from between a 10-50% increased risk. Further: "Excess risk of psychiatric illness associated with childhood seizures was present across a range of different disorders, most notably schizophrenia but also anxiety and mood disorders." Authors also opine that further research is needed on this topic with regards to mechanisms pertinent to identifying "potential options for prevention."

Although some caution is always required when one variable (epilepsy) is solely correlated with another (history of recorded psychiatric diagnosis), I am interested in the Dreier findings. I'm interested not only because of the *association* being made between a condition that often has life-changing effects on other often life-changing diagnoses but also because this *association* complements other links being made with epilepsy. I speak of the various studies linking epilepsy to diagnostic labels such as autism and attention-deficit hyperactivity disorder (ADHD) of course (see here and see here for examples) whilst pointing out that ADHD and autism are not to be categorised as mental health conditions. Such links between epilepsy and neurodevelopmental diagnoses are all the more interesting because the presence of labels such as autism and ADHD are also known to manifest elevations in other psychiatric diagnoses such as mood disorder, anxiety and schizophrenia (see here and see here and see here for examples). It's not therefore unreasonable to suspect that there may be some 'over-arching' themes when it comes to epilepsy/febrile seizures 'linking' with various developmental and psychiatric diagnoses.

Minus any sweeping generalisations and being careful how I phrase this, one area that requires a lot more investigation is the neurological effect that epilepsy in particular can have. I speak of the idea that seizures can, in some cases, affect the physical nature of the brain [2] and the question of whether such 'damage' might also then affect the presentation of behaviour akin to the signs and symptoms of a neurodevelopmental or psychiatric diagnosis. I know this is not a particularly palatable line of thinking but it does require further scientific exploration. This is also pertinent to the Dreier study focusing in on childhood seizures and by inference, possible effects on the developing brain. Another area of further investigation is whether the presentation of epilepsy or seizures *might* be part-and-parcel of various syndromes also presenting with neurodevelopmental and/or psychiatric features? We do have some examples of this already (see here) and, given that various genetic syndromes are quite regularly being identified day-by-day, it's another area that could yield some important data.

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[1] Dreier JW. et al. Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood: a Danish nationwide cohort study. Lancet Child Adolesc Health. 2018 Dec 6. pii: S2352-4642(18)30351-1.

[2] Bronen RA. et al. The Status of Status: Seizures Are Bad for Your Brain's Health. American Journal of Neuroradiology. 2000; 21: 1782-1783.

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Monday, 10 April 2017

"Predisposition" to autoimmunity and inflammatory activation linked to autistic regression?

The paper by Ori Scott and colleagues [1] provides some very welcome interest in the concept of regression in relation to autism. As I've indicated quite a few times on this blog, regression accompanying cases of autism has [finally] been accepted by the research community at large (see here for example) but there is still some way to go with regards to the hows-and-whys of regression. There are some clues (see here) but more data is required. What the evidence available so far suggests is that sweeping generalisations about autism exclusively occurring/appearing during very early infancy or even before, are probably not as accurate as many people might realise (see here)...

So, starting from the idea that autistic regression might have an important 'immune-related' component to it, the authors set about reviewing the medical charts/records of some 240 children diagnosed with an autism spectrum disorder (ASD). A small but significant proportion of the cohort presented with an "autistic regression variant". Researchers looked at various potentially important facets of those medical charts in relation to things like "febrile illness preceding initial parental concern" (in relation to autistic features) and "possible non-immune precipitants such as pregnancy and postnatal complications." Another important feature of the study was to look-see whether various autoimmune disease/conditions were a feature of the immediate family in regressing and non-regressing cases.

Results: well, febrile illness did seem to be quite a lot more apparent in those children who experienced autistic regression. Indeed the figures went something like 30% in those with autistic regression and 0% in those without. Wow. Researchers also reported that rates of autoimmune disease in the immediate family were quite a bit higher in the regression group compared with non-regressing participants (33% vs. 12%). Further: "Type 1 diabetes and autoimmune thyroiditis were both more common in families with children with autistic regression." The authors conclude: "Our findings suggest that predisposition to autoimmunity, and immune/inflammatory activation, may be associated with autistic regression."

Accepting that this was research based on chart reviews (and indeed chart reviews in 2014) and the relatively small group numbers presenting with autistic regression, these are potentially important findings. Familial autoimmune conditions/disease *correlating* with autism is by no means a new thing (see here). Type 1 diabetes - the one where the pancreas don't produce any insulin as a result of the body failing to recognise self as self - has some history in relation to offspring autism risk (see here). Autoimmune thyroiditis, or at least some of the biological markers of this disease, also has some research history (see here). Interestingly, autoimmune thyroid disease also might have some connection to cases of depression too (see here) which could pose some intriguing questions in relation to the body of research talking about antidepressant use being potentially important to offspring autism too (see here). It would be a brave person to say there is no possibility of a connection between these and other familial autoimmune conditions and offspring autism...

The febrile illness stats produced by Scott and colleagues in relation to the regression group are really very interesting. Febrile illness denoting fever and corresponding symptoms in relation to autism onset is an area crying out for further research. Yes, febrile illness can affect onset of things like seizures and/or epilepsy and it would be rather intriguing to see whether this might play a role in the onset of some autism bearing in mind the epilepsy connection posed so far (see here). But more than that are the numerous voices talking about fever being a facet of symptoms onset under quite a few circumstances [2]. The words 'post-encephalitic' spring to mind and with it, quite a bit more scientific inquiry being indicated. And there is also another area that might benefit from some additional scrutiny in relation to developmental regression 'plus' other factors accompanying cases of autism [3]...

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[1] Scott O. et al. Clinical clues for autoimmunity and neuroinflammation in patients with autistic regression. Dev Med Child Neurol. 2017 Apr 6.

[2] Mankoski RE. et al. Etiologies of autism in a case-series from Tanzania. J Autism Dev Disord. 2006 Nov;36(8):1039-51.

[3] Poling JS. et al. Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol. 2006 Feb;21(2):170-2.

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ResearchBlogging.org Scott O, Shi D, Andriashek D, Clark B, & Goez HR (2017). Clinical clues for autoimmunity and neuroinflammation in patients with autistic regression. Developmental medicine and child neurology PMID: 28383115