"a pooled ASD prevalence of 6.3% in individuals with epilepsy"

The quote heading this short-ish post came from the findings reported by Lauren Strasser and colleagues [1] who systematically reviewed and meta-analysed the collected data pertinent to "the prevalence and risk factors for autism spectrum disorder (ASD) in epilepsy."

Bearing in mind that epilepsy is quite a comprehensive term, authors estimated that some 6-7% of those diagnosed with epilepsy or a condition manifesting epilepsy will also present with an ASD. Further that specific types of epilepsy might confer a specific risk for ASD: "When divided by type, the risks of ASD for general epilepsy, infantile spasms, focal seizures, and Dravet syndrome were 4.7%, 19.9%, 41.9%, and 47.4% respectively."

The relationship between autism and epilepsy has been known about for many years (see here). We know for example, that age and intellectual functioning level play a role in the risk of developing epilepsy in the context of autism but are careful with sweeping generalisations (see here). We also know that a growing number of genetic conditions manifest both as autism or autistic traits and epilepsy (see here for example). We even have 'colliding' research areas talking about options for treating some 'difficult to treat' cases of epilepsy as perhaps also impacting on some of the features of autism too (see here) (with no medical or clinical advice given or intended).

What's also being recognised a little more in the peer-reviewed research literature and beyond is that being diagnosed with certain types of epilepsy also potentially impacts on the risk of autism or ASD also being diagnosed or presenting with 'significant' autistic traits (see here and see here). This to me has quite a few important implications, not least that this data "may help clinicians in early screening and diagnosis of ASD in this population." It also cements the relationship between autism and epilepsy / epilepsy and autism and further asks whether for some people at least, 'comorbidity' in relation to the presence of both terms should be replaced with something rather more core and fundamental?

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[1] Strasser L. et al. Prevalence and risk factors for autism spectrum disorder in epilepsy: a systematic review and meta-analysis. Dev Med Child Neurol. 2017 Nov 9.

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Cannabidiol for drug-resistant seizures in Dravet syndrome

"Cannabis drug cuts seizures in children with severe epilepsy in trial" went one of the headlines referencing the results published by Orrin Devinsky and colleagues [1]. Accompanied by an editorial talking about 'real data, at last' [2] on how a chemical component of cannabis - cannabidiol - might be rather useful for some forms of drug-resistant seizures in Dravet syndrome, there is quite a bit of enthusiasm about these latest findings added to other results from this authorship group (see here). The trial details for their latest results can also be found on the ClinicalTrials.gov website (see here).

Dravet syndrome is something that I had previously heard of in light of some connections being made with the presentation of autism or autistic features [3]. Indeed, in these days of the plural autisms (see here) and adherence to the old 'we don't know what causes autism' mantra (see here), there is still quite a bit more investigation needed on autism appearing alongside known genetic or metabolic conditions and what this might mean for prevalence estimates of autism for example.

Dravet syndrome (DS) - also called severe myoclonic epilepsy in infancy (SMEI) - is primarily characterised by a severe type of epilepsy present in early infancy that continues accompanied by a progressive decline of other developmental functions. Such a regression accompanying seizures has attracted some autism researchers' attention (see here) in view of the clinical profile of DS not being a million miles away from that seen in other instances of autistic regression (see here). This also bearing in mind that autism and epilepsy are also not unstrange bedfellows (see here).

In the latest study Devinsky et al set about testing the possible effectiveness of cannabidiol in cases of DS under the gold-standard - double-blind, placebo-controlled - conditions. Some 120 children and young adults diagnosed with DS were randomly allocated to receive "either cannabidiol oral solution [GWP42003-P] at a dose of 20 mg per kilogram of body weight per day or placebo" over a 14 week period. I should also mention that this was pharmaceutical grade cannabidiol. Researchers primarily focused on seizure frequency between the two groups but did also look at important issues such as the instances and types of adverse events (AEs).

As per the headlines, the results suggested that cannabidiol did seem to be quite effective at reducing the frequency of seizures in the treated group compared to controls. Over 40% of those in receipt of the active medication showed at least a 50% decrease in seizure frequency over the course of study. Perhaps a little worrying were the observations that around a quarter of those in receipt of the placebo also showed a similar pattern of reduction (and why this finding just escaped statistical significance for the group taking the active medicine). Results also showed a pattern of possible 'super-responders' to cannabidiol intervention: "The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo."

But then there were the AEs also identified. So: "Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group." This also is a bit of worry, particularly if cannabidiol is something that needs to be constantly taken to maintain any seizure-reducing effects.

On the whole these are interesting findings in need of greater research scrutiny. I will reiterate that this was a controlled study using pharmaceutical grade cannabidiol, so one has to be careful not to assume that either the findings or the intervention will be successful or available to the general population. This is a particularly important point in these days of talk about medicinal cannabis use and condition such as epilepsy (see here) for example.

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[1] Devinsky O. et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020.

[2] Berkovic SF. annabinoids for Epilepsy - Real Data, at Last. N Engl J Med. 2017 May 25;376(21):2075-2076.

[3] Li BM. et al. Autism in Dravet syndrome: prevalence, features, and relationship to the clinical characteristics of epilepsy and mental retardation. Epilepsy Behav. 2011 Jul;21(3):291-5.

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Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S, & Cannabidiol in Dravet Syndrome Study Group. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. The New England journal of medicine, 376 (21), 2011-2020 PMID: 28538134