Evidence for an autoimmune aetiology of epilepsy?

With a title like that, I was bound to post about the paper by Mei-Sing Ong and colleagues [1] and their suggestion that: "Epilepsy and autoimmune disease frequently co-occur; patients with either condition should undergo surveillance for the other".

Capo di Noli @ Wikipedia 

United under the umbrella that is autism spectrum comorbidity (even possible phenotypes), I've talked quite a bit on this blog about epilepsy / seizure disorders (see here) and autoimmune conditions (see here), and how coexistence alongside the presentation of autism may be a potential route towards some overlapping or shared genetic or biochemical pathways being involved. It is indeed a coincidence that one of the authors on the Ong paper - Isaac Kohane - is one and the same with some autism [comorbidity] research in mind.

The Ong paper details the results of a a survey of health insurance claims in the US where authors "examined the relationship between epilepsy and 12 autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease". They reported that the risk of epilepsy was higher amongst those people with an autoimmune condition - all 12 of the autoimmune conditions looked at - and particularly when it came to risk for children. More chatter about this study can be found here.

Looking through many of those autoimmune conditions examined by Ong, the first thing that struck me was that many of those conditions have been talked about in research circles in the context of autism. Bowel conditions such as ulcerative colitis and Crohn's disease have certainly seen their fair share of discussion (see here) alongside the possibility of other bowel disease presentation in cases (see here). Coeliac (celiac) disease and autism... well, don't get me started. Antiphospholipid syndrome, or at least anti-phospholipid antibodies, have also been talked about in the context of autism too (see here). I could go on and on and on; reiterating that a diagnosis of autism is seemingly protective of nothing when it comes to other health issues, and quite a few of those health issues tend to fall into the autoimmune domain.

The next thing that struck me about that list of autoimmune conditions and indeed, how they might link into something like epilepsy, was the issue of food, and in particular gluten. Now, I'm not trying to make any sweeping generalisations here or anything like that, but outside of the classical relationship between coeliac disease and gluten, there is quite a bit of emerging evidence that gluten may be implicated in so much more including some overlap with autism. Don't believe me? Well, take type 1 diabetes as one example and papers like the one by Marietta and colleagues [2] on gluten modulating the incidence of type 1 diabetes (at least in mice). The paper by Sildorf and colleagues [3] even went as far as reporting on how a gluten-free diet was associated with clinical remission without insulin therapy for one boy with type 1 diabetes, bearing in mind no clinical or medical advice is given or intended from me on this issue. At this point I might also drop in a note about the various research being done on epilepsy, some epilepsy, and the use of a ketogenic diet (high fat, low carbohydrates which I assume impacts on gluten intake) as potentially being relevant here too.

Alessio Fasano, who has been mentioned on this blog before, summarised the possibility of a connection between gluten (gliadin) and type 1 diabetes quite nicely in one of his papers [4]. Indeed, following on from that paper and the notion that "loss of intestinal barrier function is necessary to develop autoimmunity", the question emerges: does the association between autoimmune diseases and epilepsy also suggest that gut permeability (a.k.a leaky gut) might be a feature of some cases of epilepsy? I don't want to get too bogged down with answering that question aside from reiterating that following on from the observations of Ong et al if it was eventually confirmed that there may be an autoimmune component to at least some cases of epilepsy, autism and particularly those cases of autism accompanied by a diagnosis of epilepsy, may very well represent one of the next stages in the evolution of this research topic.

Music to close. It's been a while since I've linked to an Elvis song, so here's Viva Las Vegas.

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[1] Ong MS. et al. Population-Level Evidence for an Autoimmune Etiology of Epilepsy. JAMA Neurol. 2014 Mar 31.

[2] Marietta EV. et al. Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome. PLoS One. 2013 Nov 13;8(11):e78687.

[3] Sildorf SM. et al. Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. BMJ Case Rep. 2012 Jun 21;2012.

[4] Visser J. et al. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009 May;1165:195-205.

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Ong MS, Kohane IS, Cai T, Gorman MP, & Mandl KD (2014). Population-Level Evidence for an Autoimmune Etiology of Epilepsy. JAMA neurology PMID: 24687183