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Risk of epilepsy in autism tied to age, intelligence

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Laura Geggel
19 August 2013

Electrical storm: About half of people with autism have unusual electrical brain waves even when they don’t have epilepsy.

Children with autism who are older than 13 years and have low intelligence are at the greatest risk of having epilepsy, says one of the largest epidemiological studies on the issue to date1.

Children are typically diagnosed with epilepsy after having at least two seizures — uncontrolled surges of electrical activity in the brain. About 2 percent of the general population has epilepsy2. Most studies peg its prevalence among people with autism at 30 percent.

The new study, published 4 July in PLoS One, breaks down this prevalence by age. It finds that among children with autism, up to 12.5 percent of children aged 2 to 17 have epilepsy. The rate is largely driven by epilepsy in children aged 13 to 17, who have more than double that prevalence.

The study also found that low intelligence — defined as having an intelligence quotient (IQ) below 70 — is associated with a cluster of symptoms seen in people who have both epilepsy and autism. The symptoms include difficulty with daily living, poor motor skills and language ability, regression and social impairment.

Many of the previous studies on epilepsy in autism are based on small numbers or bias the sample by recruiting participants from clinics specializing in epilepsy, says Eric Morrow, assistant professor of biology at Brown University in Providence, Rhode Island, and lead investigator on the new study.

To eliminate this bias, the study tapped four large American autism databases, with 5,815 children in total, and found that 289 of them have epilepsy.

"There is a new style of research in autism now emerging, which is trying to build larger and larger datasets," Morrow says. "The overriding thing that we're all trying to contend with in autism is the huge heterogeneity."

The new study's large numbers give credence to its findings, but other researchers point out that the datasets — the 2007 National Survey of Children's Health and three genetic databases, the Autism Consortium, the Autism Genetic Resource Exchange and the Simons Simplex Collection, a dataset run by SFARI.org's parent organization — are not intended to investigate epilepsy rates.

Dataset variety:

The Simons Simplex Collection, for example, designed to find genetic differences in people with autism, excludes people who have fragile X syndrome and most people with autism who have an IQ below 75. Both of those groups are known to have high rates of epilepsy. As such, the registry records an epilepsy prevalence of only 2.9 percent, the lowest among the four datasets.

The other three datasets yield average epilepsy rates of 12.5 percent, 7 percent and 5 percent, respectively. The 2007 National Survey of Children's Health, a phone-based survey, may have the highest rate because it relied on parent reports for the autism diagnoses and did not verify them with any tests. 

"Before, the ranges were all over the place," says Orrin Devinsky, director of the New York University Comprehensive Epilepsy Center, who was not involved in the study. "I think this study gives values that make sense and probably, in part, may reflect some aspects of the patient populations that they were taken from."

Most children develop epilepsy during the first three years of life. But children with autism show a second spike in epilepsy in early adolescence. This makes age an important factor when studying prevalence, Morrow says.

"If you're going to measure the prevalence of a particular condition, in this case, epilepsy, you want to know whether you're through the age of risk," Morrow says.

Although the exact prevalence of epilepsy varies among the four datasets, each shows the same trend of greater prevalence with age.

When the rates are broken down by age, in the three genetic datasets, about 10 percent of children aged 13 and older have epilepsy. That rate jumps to 26 percent in the 2007 National Survey of Children's Health.

"The older the participant, the greater the percentage of epilepsy, at least in the first two decades [of life]," Morrow says.

A smaller study of 101 children with autism, published 20 July in the Journal of Autism and Developmental Disorders, found that those who have repetitive behavior or aggressive conduct are also more likely to have unusual electrical activity in their brains than those who do not show such behaviors3. The results are less pronounced in children with autism who do not have intellectual disability.

Other studies have found an association between epilepsy and low intelligence in children with autism.

"It's not that surprising that if you have more global disruption in the form of a lower IQ and autism, you'd be at higher risk for having epilepsy," says Elliott Sherr, professor of neurology and pediatrics at the University of California, San Francisco, who was not involved in the study.

In addition to intellectual disability, many children with autism have co-occurring conditions such as language delay or attention deficit hyperactivity disorder, which can make it challenging to diagnose epilepsy.

"It can be very difficult to separate out what's a language problem, what's an attention problem and what's a problem related to autism from what's a seizure," Devinsky says.

Given that epilepsy may affect about one-third of children with autism, he says, "one of the issues for the future is to come up with more standardized criteria of what is epilepsy, specifically in the autism population, which has not been done."

News and Opinion articles on SFARI.org are editorially independent of the Simons Foundation.

References:

1: Viscidi E.W. et al. PLoS One 8, e67797 (2013) PubMed

2: Tuchman R. and I. Rapin Lancet Neurol. 1, 352-358 (2002) PubMed

3: Mulligan C.K. and D.A. Trauner J. Autism Dev. Disord. Epub ahead of print (2013) PubMed

Comments

Name: Steve White
20 August 2013 - 2:43AM

Truly I don't know a thing about this topic but there was a finding several years back of a very high percentage of autistic patients, I think children, having antibodies to one of their own brain cells. Maybe Purkinje? The study was out of UC Davis by some of the same folks who are prominent researchers in the maternal antibody area.
If I remember right it was a class of brain cell involved in making some type of neurotransmitter, and disruption of that neurotransmitter was known to cause seizures.
The percentage of patients who had this auto antibody was less than 30% of autistics so it would not account for all cases but it might account for all or a very high percentage of those who developed epilepsy over time. (seems to me many auto immune conditions get worse in adolescence don't they?)

Fingers crossed I don't think this is relevant to my child but does anyone know where that research went? Seemed to me maybe 1 or 2% of controls but 20% of autistics had this antibody.

Name: Steve White
20 August 2013 - 3:02AM

I should have gone and looked at this more before writing anything.

I got it all wrong in regards to the research at UC Davis. They found antibodies to "GABAergic interneurons" in about 20% of their study participants.

It as another group with the Purkinje cells.

And there are other groups with other autoantibody findings.

It seems like a very active area of research although this article does not mention the topic, can the author please comment on theories of why epilepsy develops so often in adolescence?

Name: ASDDad
20 August 2013 - 7:54AM

Fetal programming during pregnancy / development through a viral / bacterial insult.Leading to seizure susceptibility in later life.

Name: Steve White
20 August 2013 - 3:41PM

Thanks for comment I am going to research this a bit. Our kid's autism is maternal antibody related and I have not heard of that being tied with epilepsy but not knowing, it's still worrisome.

Name: Anonymous
21 August 2013 - 6:47AM

Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats

http://www.jneurosci.org/content/28/27/6904.long

Name: Steve White
21 August 2013 - 4:19PM

Thanks very much for the citation. I can only read abstracts for the most part but that sounds potentially huge.
I noticed that paper was from 2008 if I read it right, is there something on behavioral abnormalities induced by the same treatments?

Name: Steve White
21 August 2013 - 4:40PM

I saw a recent citation from Ann. Neur which I guess means Annals of Neurology, this about mice not rats and implicating IL 6. I copied the entire abstract and will try to Paste it here but paired down, but you can find it at PubMed:

Ann Neurol. 2013 Mar 21. doi: 10.1002/ana.23898. [Epub ahead of print]

Maternal immune activation promotes hippocampal kindling epileptogenesis in mice.

Pineda E, Shin D, You SJ, Auvin S, Sankar R, Mazarati A.


Source

Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.

Name: Steve White
21 August 2013 - 4:45PM

One more quick comment- I don't know if it's tied to epilepsy or not but the folks up at MIND Institute and UC Davis Med School did a study finding IL-6 levels correlated with behavioral symptom severity. I was at a conference (HELP group in LA, very good conference for layman, in the fall) and asked Dr. Judy Van de Water if this indicated IL-6 should be knocked down in patients, she was not willing to say that at the time but the study quoted above makes me wonder. I have no reason to think it's really relevant to my kid though he was supposed to have had elevated IL-6, so I did not really pursue it but maybe it's very important for some kids. But immune suppression is dangerous.

Name: Anonymous
22 August 2013 - 2:16PM

http://www.epilepsy.com/newsletter/aug12/epilepsy_antibodies

archneur.jamanetwork.com/article.aspx?articleid=1149705

Name: john
7 October 2013 - 5:50PM

this is cool

Name: Jennifer Taylor
13 November 2013 - 10:57AM

My daughter was first diagnosed with Epilepsy as an infant, but we never knew she had Autism until her seizures returned at age 14. She was seizure-free and med-free for over 10 years. After her seizures came back, she was diagnosed with Asperger's and has always had it. She's high-functioning and that is why it was missed. However, have these studies taken into consideration the increase in the hormone level for teens? Her tonic-clonic seizures always seemed to have a connection with her cycles. We are treating her Epilepsy with 2 secondary seizure meds and progesterone and it seems to be working. She has had no tonic-clonic seizure for over a year and she is now 16. I hope more studies are done on this.

Name: Annde15
13 December 2013 - 11:51PM

My son is 13 and is mainstreamed at school. He does well but has a language disability. I remember when he was less then two years old having two what I think were episodes. Complaints from sitter of starring into space was happening too. Doctor said he was fine. Now at 13 he's having episodes of headaches and seeing red then black and having to sit. I'm thinking something is happening again so off to the docs for a work up after 10 years of doing well. Keeping my fingers crossed!

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