Epilepsy caused by antibodies

[KarenB]

http://www.epilepsy.com/newsletter/...0dbd17-Epilepsy_News_4_24_13&utm_medium=email

This just out from the Epilepsy Therapy Project.

A large study has discovered that 11% of epilepsy patients "had antibodies to one or more antigens:
■Voltage-gated potassium channel
■ Complex protein
■ Glycine receptors
■ Glutamic acid decarboxylase (GAD)
■ NMDA receptors "

This group of patients also tends to have seizures that are resistant to epilepsy meds.

The article states that immune-based meds may need to be considered.

 

[JaneC]

Thanks for this Karen. I'm very interested in a possible link between epilepsy and the immune system due to the large prevalence of autoimmune conditions in our family history - MS, thyroid disease, colitis, diabetes.

The difficult to treat bit doesn't apply with my daughter but I'll be keeping an eye on research into this in any case x

 

[Nakamova]

Yes, there have been other studies linking seizures to inflammation in the brain -- and since inflammation can be a result of autoimmune response, that makes the connection seem even more likely.

 

[Cint]

As I've posted before, I had epilepsy first. After prescribing AED's did I start having hypothyroid, plus it runs in my family. Then the depression set in. And after prescribing a drug for depression, the Type 1 diabetes came along. No one else in my immediate family has diabetes. Or epilepsy. But depression and bi-polar is big time!

I am one of those E patients who is resistant to meds. That's why I had an unsuccessful brain surgery and I just had my 3rd VNS surgery.

So my question is: How do we know whether my E is due to a bad autoimmune system or is my autoimmune disorder caused by E and/or AED's?

 

[JaneC]

Nak, I had a brief OMG! minute there based on the increased risk of my children having MS due to the familial link. And then I remembered my daughter had a clear MRI the day before her abnormal EEG

Cint that's an interesting question, although one I don't have an answer to. From what I've read about MS, some people with MS have seizures as a result but otherwise no clear link seems to have been established (yet).

It's also interesting what you say about depression and bipolar illness being common in your family, given the fact that so many drugs developed as AEDs are now used for mental health issues.

 

[qtowngirl]

I am one of those E patients who is resistant to meds. That's why I had an unsuccessful brain surgery and I just had my 3rd VNS surgery.

onder:
surgery is usually the option for those who are resistant to meds, rather than meds being the reason a surgery is unsuccessful.
just for those cint who may be new to the forum, thought i'd mention. to me it reads just as is instead of how you meant. that's why you had brain surgery (unsuccessful) and just had 3rd vns.

 

[Cint]

onder:
surgery is usually the option for those who are resistant to meds, rather than meds being the reason a surgery is unsuccessful.
just for those cint who may be new to the forum, thought i'd mention. to me it reads just as is instead of how you meant. that's why you had brain surgery (unsuccessful) and just had 3rd vns.

:agree: It does sound a bit confusing. Thanks for a reasonable explanation. And because of the brain surgery, I suffer from aphasia (finding words). So sometimes what I'm trying to say and what I do say may not make total sense.

 

[KarenB]

Cint -- I just read an article about depression and temporal lobe epilepsy -- I think it was in that same issue of the Epilepsy Therapy Project newsletter linked above. We all know that certain seizure meds can induce depression, but as I recall, sometimes depression can precede the epilepsy, and I think the article said something about using depression as a diagnostic symptom for temporal lobe epilepsy.

And...certain meds, like Depakote (Valproic Acid), can damage the liver/spleen/pancreas, which can affect insulin production and cause diabetes.

But I am personally intrigued with this whole link between immune disorders/allergies and epilepsy. Jon also has very difficult to control epilepsy -- right now it is, thank God!! Most meds don't work at all, and I've wondered if that was because his seizures are due to some sort of immune response rather than a brain thing. I do know that he's had seizures that appeared to be triggered by eating a food he was apparently allergic to (eggplant).

I'd like to do more research on those antigens above, to see what they are, exactly.

 

[qtowngirl]

:agree: It does sound a bit confusing. Thanks for a reasonable explanation. And because of the brain surgery, I suffer from aphasia (finding words). So sometimes what I'm trying to say and what I do say may not make total sense.

no worries, it gets the best of us. lol in a few months time you may be having to sort out for everyone what i'm saying!! good times.

 

[KarenB]

Perhaps someone who has a better scientific mind that I do can help me out. I decided to look up the 5 "antigens" above to which 11% of people with epilepsy have antibodies to.

But from what I can understand...a voltage gated potassium channel is...part of the body(?)...so...does that mean that...someone can be allergic to...themselves? That can't be right...I must not be understanding this correctly.

 

[KarenB]

Still working through this potassium channel thing...but...there's apparently a type of encephalitis with seizures associated with Voltage gated postassium channel antibody disorders...these disorders can cause seizures, along with abnormal EEG's and MRI's (temporal lobe), sleep disorders, and a whole lot of other stuff that I'll have to look up because I don't know what they mean.

"Most cases respond favorably to immunosuppression with plasma exchange, intravenous immunoglobulin or pulse intravenous methylprednisolone, usually followed by oral steroids."

http://www.ncbi.nlm.nih.gov/pubmed/20816272

 

[KarenB]

OK, working more on just what a voltage-gated potassium channel is...and working through some aricles and textbooks
http://neuro.med.harvard.edu/faculty/documents/yellenMovingParts.pdf

It's a type of ion channel located within the plasma membrane of cells -- a sort of water-filled tunnel that allows (in this case potassium) to pass through -- other ion channels allow sodium, etc. to pass through.

So...if I'm understanding this correctly...these potassium channels exist in many of the cells of the body. And...ion channels are important parts of the nervous system

Voltage-gated ion channels produce electrical signalling in neurons and other excitable cells. So, the channels allow sodium to enter the cells and potassium to exit, keeping everything in electrical balance...

...so...if I'm understanding this correctly...if the potassium channel is disrupted somehow...then the electrical balance is all off...and this can lead to problems with the neurological system.

 

[KarenB]

I just had a "well...duh..." moment. Everyone else probably already knows this, but in answer to my question above about whether a person can be allergic to themselves...or part of themselves...that apparently is precisely what autoimmune disease is...an allergic type of reaction to one's own cells and tissues. So...yes...apparently, one can actually be allergic to parts of their own cells, including potassium channels.

Just wondering...those of you with epilepsy that doesn't respond well to meds...maybe Cint could weigh in...have you ever had occasion to be treated with steroids for some condition...and...if so...did it have an effect on your seizures...good or bad?

 

[KarenB]

I just came across this intriguing case study of a man with voltage-gated potassium channel antibody-associated encephalopathy
http://bjp.rcpsych.org/content/189/2/182.full

He was originally diagnosed with psychogenic non-epileptic seizures (which were later discovered to be real frontal lobe seizures. He also developed panic attacks, delusions, and hallucinations. A 24 hour EEG came back normal. He developed marked insomnia. His psychological state got so bad he had to be admitted for some time. Finally, after 3 months, he was found to be positive for voltage gated potassium channels, and was successfully treated with steroids and plasma exchange (the latter brought dramatic improvement).

 

[Cint]

Just wondering...those of you with epilepsy that doesn't respond well to meds...maybe Cint could weigh in...have you ever had occasion to be treated with steroids for some condition...and...if so...did it have an effect on your seizures...good or bad?

I only had to be treated with an inhalant for asthma that contains a cortico-steroid. It didn't seem to interfere with my seizure meds or seizures. I've never taken prednisone, the steroid my son often had to take growing up because of his hard-to-control asthma.

 

[Haffgus]

Thanks Karen for sharing the article. My 15 year-old has had type 1 diabetes for 8 years. She has thyroid antibodies, although normal thyroid function. Diagnosed with generalized epilepsy in January and currently on Depakote and weaning off Keppra. Hoping the Depakote will work as the Keppra didn't.

 

[KarenB]

Thanks Cint -- it seems that in the case of some seizures that are antibody related -- that immune treatment can be successful -- but the one article indicated that steroid treatment offered some temporary relief, but that plasma exchange worked a dramatic improvement.

Haffgus -- how did they happen to find that your daughter had thyroid antibodies? I wonder if even though the antibodies aren't affecting her thyroid (yet) if the autoimmune stuff (isn't diabetes 1 also autoimmune?) is the cause of her seizures?

Depakote has a lot of different actions, so is successful for lots of seizure types. It didn't really help our son until he went on the Ketogenic Diet, and then we weren't sure if it was the medication or the diet that was doing the trick. We had to wean off the Depakote because it began to cause liver damage, and he remained seizure free on just the diet for about 6 months.

 

[Haffgus]

Type 1 diabetes is an autoimmune disease. We see her endocrinologist every three months, and she gets blood tested annually for other autoimmune diseases as she is at a much higher risk of having another autoimmune disease. Most common are thyroid and celiac. We have known for five years that she has thyroid antibodies and therefore will most likely eventually become hypothyroid. Her neurologist says the epilepsy is unrelated to the diabetes, which is why I found the article you posted very interesting.

 

[KarenB]

Our Jonathan developed hypothyroid this past year (it was diagnosed at the same time that he had the bad relapse in seizures). He was having thyroid testing done every year or two (he has Down Syndrome, so more likely to have hypothyroid) before that, and it always came back normal. It has been well controlled with meds; however, can't help but wonder if there's a relationship to the seizures (docs say no). His fasting blood glucose levels have also been a little high recently (pre-diabetes range), which is unusual for a child on the Ketogenic diet. One specialist thought he might be developing Type 1 diabetes, but controlled by the diet. At this point, his pediatrician and endocrinologist are just monitoring that to see if it gets any higher. Type 2 diabetes runs in the family, but no one has Type 1. It's possible that the Depakote he was on damaged his pancreas along with the liver, and that may have affected his insulin/blood glucose.

(Make sure your daughter is getting her liver enzymes checked every month or two, since she's on Depakote).

 

[KarenB]

Continuing to work my way down that list of 5 allergens. The 2nd one is complex protein.

The medical dictionary defines this as a protein that contains a simple protein and at least one molecule of another substance, as a glycoprotein, lipoprotein, nucleoprotein, or hemoglobin.

Glycoprotein = proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains. Examples: mucin (found in mucus), antibodies (immunoglobulin), connective tissue (collagen), hormones (such as thyroid stimulating)

lipoprotein = a molecule made from protein and fat, bound to the proteins, which allow fats to move through the water inside and outside cells, and emulsify fat molecules, and transport cholesterol and triglycerides

nucleoprotein = a protein and a nucleic acid (DNA or RNA). Harnessed by many viruses.

hemoglobin = protein in red blood cells that carries oxygen