What's new in TS

[kim]

This neurologist has a daughter with TS. The first part was kind of uninteresting. Diagnostic criteria, etc.

 

What was interesting, was the genetic identification, that he has worked on. That info is right near the end. I wish the chart was more clear.

 

If anyone listerns/watches, can you figure out, what the headings say at the top of the chart? It's blury, and I can't read it. He identifies genes that are responsible for cells involved in infection.

 

http://www.ucdmc.ucdavis.edu/mindinstitute...vents.html#2005

 

What’s New in Tourette’s

 

Presenter: Frank Sharp, M.D.

 

Affiliation: UC Davis M.I.N.D. Institute

 

Date: August 5, 2005

[kim]

I have listened to this several times (struggling to understand)

 

I'm tempted to burn this, or at least the last part, and take it to any future Dr.s. It's so good to see that someone is looking in the direction of the immune system. I guess this man really may be interested in getting some real answers, since his daughter and his best friends son, both have TS.

 

It was confusing, because I couldn't read the charts and you couldn't tell what he was pointing at while he was talking.

 

What I was able to come up with so far (I think) is that he tested over 100 kids. Some had epilesy, daily chonic headache etc. He said in kids with TS, he found 8 genes that identified the TS kids. Ok, that part was easy...but, then he goes on to say, that when he looked at those genes, some were low expressers, some were high, and there were a few, that were very high.

 

He says that NK (natural killer) and CD8 cells were high in the whole group (again, I think that's what he's saying, it may have been 1/2 of the group) I have also, done a little reading on IL 24, which in the same family as IL 10.

 

He talks about PANDAS a little. Seems to think that it truly exists, but in a small %. Then he talks about NK and CD8 usually being elevated in the presence of a virus. He says the explaination could be, that it is just their genetic makeup (high expressors of these genes), or there may be a virus involved. He talks about a subset of autistic kids having this same profile.

 

He says that there are estimates as high as 1 of 50 people affected by TS/chronis tics reported in Europe, talks about problems with executive functioning (a lack of focus and organization) and how this can be the most debilitating part of the syndrome, for some. Is sounds like this is a big problem for his daughter. Then he points out, how important reseach is, with such high estimates of people affected. Yipeeeee

 

He says that the autoimmunity link has never been studied. He mentions RA and lupus, graves, etc. If I remember right, he mentions recent connection to restless leg syndrome.

 

This article was helpful....looking at NK and CD8

 

http://www.hhmi.org/cgi-bin/askascientist/...%2Fans_026.html

 

He does mention B cells (make antibodies), neutrophils...kill bacteria, and gene expression in different subset of ts, completely different from every other kid.

[faith]

Kim,

thanks for all that. I couldn't seem to get this started on my computer. Have to get my technical hubby to help...

 

You know, I just feel compelled to say, while its great that someone is advocating theories and research into this, and this seems to be really great information, although complicated, its interesting that the ball only seems to get rolling when it is a parent who has children affected by this, and I guess luckily, some have a scientific background, and can delve much further into it. But if they were not affected by this, would they still be on the other side of the fence? ... Think about all the research and progress that gets started because these people have children or loved ones and are directly affected by some illness or disorder (look at autism) .... we really are the strongest army!

 

Faith

[kim]

yes, Faith, I agree that these things are starting to be looked at more closely because of the sheer # of people affected. Sadly, it's become prevelent enough that it's drawing attention from people who more than likely would have continued to ignore, if it didn't affect them personally.

 

This is a newer study with immune markers discussed again.

 

http://www.ncbi.nlm.nih.gov/sites/entrez?d...l=pubmed_docsum

 

Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study.

[Chemar]

Hi Kim

for some reason that keeps freezing my computer, so I am basing my comment only on what I have read here

 

re the virus idea for TS ................

My husband, his dad, and my youngest son ALL mamnifest TS. Three generations of males in a row.

My oldest son has no TS symptoms. Neither do I. Nor did my husband's mom.

How would a virus explain this clearly hereditary occurrance?

And what of the genetic work already documented for TS

Why would males have such a higher incidence of TS if it is viral??

 

as I did not actually watch this lecture, I obviously may have totally missed the points being made, so apologize up front if I am misunderstanding the premise.

 

Now the immuno issues I can understand as it does seem that is a major factor in TS.

 

and yes, the comments on the most being achieved when parents get active....absolutely agreed....in my own reference frame....if Bonnie Grimaldi hadnt done research to help her own child, and if she hadnt freely shared her plan on the web all those years ago......I would not have found the help I so desperately needed for my son!

[kim]

Cheri,

 

Due to time constraints and the complexity of these issues, which I obviously am not capable of understanding, I'm just going to post here what I find, to see if we can piece anything together, a little at a time.

 

Let's say that in a case where there is such a clear picture of family history (possibly another subset) that it is a genetically inherited dysreguation in T regulatory cells, for what ever reason.

 

This part of your question, had me completely stumped. I am aware of the theory that estrogen is protective in a situation where mercury/thimerosal is thought to cause immune system dysregulation, but had no idea, how it may apply, if mercury exposure was not the suspect.

 

Why would males have such a higher incidence of TS if it is viral??

 

But, look at this.

 

http://www.sciencedirect.com/science?_ob=A...7b0cafa3743a7b3

 

Estrogen (E2) upregulates the FoxP3 gene that marks regulatory CD4+CD25+ T cells (Treg cells). However, E2 also inhibits the ability of antigen presenting cells (APC) to activate T cells.

 

I don't think that it is a specific virus, which might trigger a problem (what Dr. Sharp referred to in the lecture) but possibly any viral infection, that could trigger neuro problems, in a genetically susceptable subset? If estrogen is involved in the Treg process, couldn't that account for the higher incidence in males, even when looking at previous generations, which wouldn't necessarly be exposed to things that could be triggering a higher incidence, at a younger age, in our current generation?

[kim]

Cheri,

 

I walked away, and had to come back and google Tregs+dopamine (thinking about your question, regarding "previous TS research").

 

I haven't even begun to think this through, but it sure looked interesting

 

http://bloodjournal.hematologylibrary.org/...tract/109/2/632

 

CD4+CD25+ regulatory T lymphocytes (Tregs) are specialized T cells playing a key role in the control of immune homeostasis. Here, we show that human Tregs constitutively express tyrosine hydroxylase (TH, EC 1.14.16.2 [EC] ), the rate-limiting enzyme in the synthesis of catecholamines, and contain substantial amounts of dopamine, norepinephrine, and epinephrine, which are released upon treatment with reserpine.

[bmom]

I googled the Mind Institute and the Neurologist that spoke on this. It looks like he was granted money in 2006 to do more research. Sounds like he was going to be researching the autoimmunity angle as well. $300,000 for the next 5 years. I am half tempted to call there and say so how is this going? Just glad someone is working on it and considering the autoimmune angle. I did speak with a DO who also thinks this is an autoimmune angle that I saw on this board a long time ago. His name is Dr. Louis Kaplan. He says that he called the TSA to tell them of his research years ago and they poo-pood him. Has anyone heard of him and his research? He seems to be retired now as he is in his 80's but is trying to right a paper about his research.

[michele]

Kim,

Our DAN said estrogen plays a huge part in tic related disorders and autoimmune attacks. He looked at me and said something about my bone structure being petite at five foot four and my long hair and soft features and said it is common for these kids to have mom's who are more masculine. That the mom's have more testosterone. I do have to shave everyday though! I wonder if ethnicity plays a role. I am Italian. Yesterday someone asked about the role of race? He talked about the protective nature of estrogen for shots and mercury exposure. Told me not to give him Tylenol because it depletes estrogen. I never knew this before. Also said there was a connection to my mercury fillings and exposure during prenatal. Maybe this is old stuff to you but I find it very interesting about the tie into immune system dysregulation and what you are discussing. Also our neurologist mentioned a possible tie to immune disorders and tics. Said it is bad becuse kids are always getting ill at a young age. Just my two cents. Your mind is much more technical then mine. Thanks for getting me thinking.

 

Michele

Cheri,

 

Due to time constraints and the complexity of these issues, which I obviously am not capable of understanding, I'm just going to post here what I find, to see if we can piece anything together, a little at a time.

 

Let's say that in a case where there is such a clear picture of family history (possibly another subset) that it is a genetically inherited dysreguation in T regulatory cells, for what ever reason.

 

This part of your question, had me completely stumped. I am aware of the theory that estrogen is protective in a situation where mercury/thimerosal is thought to cause immune system dysregulation, but had no idea, how it may apply, if mercury exposure was not the suspect.

 

Why would males have such a higher incidence of TS if it is viral??

 

But, look at this.

 

http://www.sciencedirect.com/science?_ob=A...7b0cafa3743a7b3

 

Estrogen (E2) upregulates the FoxP3 gene that marks regulatory CD4+CD25+ T cells (Treg cells). However, E2 also inhibits the ability of antigen presenting cells (APC) to activate T cells.

 

I don't think that it is a specific virus, which might trigger a problem (what Dr. Sharp referred to in the lecture) but possibly any viral infection, that could trigger neuro problems, in a genetically susceptable subset? If estrogen is involved in the Treg process, couldn't that account for the higher incidence in males, even when looking at previous generations, which wouldn't necessarly be exposed to things that could be triggering a higher incidence, at a younger age, in our current generation?

[faith]

Michele,

interesting about the estrogen/tetosterone -- did you mean the doctor thought kids with tics (or other issues?) would have more tetosterone and you "don't" fit that description? I fit your description as well (5'2", small feminine featuures and italian). I also would not say my son was overly filled with tetosterone, he is small boned and also has soft facial features. So does that mean we are opposite of what the doc said?

 

Faith

[kim]

I have been reading my eyeballs right out of my head, on this subject. Almost, have to push them back in to try to sleep

 

I can't seem to wait for the good Dr. to complete his studies!

 

I have psorisis on my elbow, and the back of my head. We have parents who have talked about RA, lupus, restless legs, etc. I'm positive injecting kids with multiple vaxes, not to mention the questions surrounding thimerosal have played a part in all of this. The effects of aluminum (one article talked about injecting alum into one arm, the antigen into the other, and getting a heightened immune response THEY KNOW that alum heightens an arm of the immune system, and that it can play a role in allergic disease. Then, there is the issue of genetic susceptability. Also, the measles virus being found (vax strain, not wild) in the intestines of some children, is almost as controversial as the thimerosal scandal.

 

So, I keep reading

 

Appanrently, NK cells are usually found, where there is virus, but....I had to see what I could find regarding strep. This sentence caught my attention.

 

NK cell deficient mutant mice were also more resistant to S. pyogenes than were the corresponding control mice Wonder if it applies to kids too?

 

This is a copy of an email that I sent to a friend, this morning.

 

I haven't gotten the book, that you recomm. yet. I'm still limping along with cellular biology for dummies, 101. There is something that I would like you to look at though. In the lecture that I emailed to you (where the subset of TS kids showed high expression of NK cells), I was curious how NK cells may fit into a strep situation. I found this study, where they looked at the incidence of sepsis, induced by strep. It looked like NK cells were detrimental, in a strep situation. When they stripped mice of NK cells, they had less problems. Hummm. If there are a subset of kids, who are high expressers of NK cells, the inflammatory problems that are discussed in this study, could apply to brain tissue too, no?

 

If you just skip to the disscussion part, at the end, you can probably get the jist, of it.

 

Abstact

http://www.journals.uchicago.edu/cgi-bin/r...:10.1086/428501

 

Natural killer (NK) cells are critical components of the innate immune system and have been implicated in the pathogenesis of septic shock. In the present study, the relative contribution of NK cells to the development of Streptococcus pyogenes induced septic shock was investigated in a mouse model of group A streptococcal infection that resembles the development of this condition in humans. C3H/HeN mice were depleted of NK cells by in vivo administration of antiasialo ganglio-N-tetraosylceramide antibodies and then were examined for their response to infection with S. pyogenes. NK cell depleted mice exhibited increased survival times and slower development of disease during group A streptococcal infection than did nondepleted control mice. The augmented resistance to S. pyogenes observed in NK cell depleted mice was associated with serum levels of proinflammatory cytokines such as interferon-, interleukin (IL)12, and IL-6 during the early phase of infection that were much lower than those detected in nondepleted control mice. NK cell deficient mutant mice were also more resistant to S. pyogenes than were the corresponding control mice. We conclude that NK cells, by amplifying the inflammatory response, significantly contribute to the progression of S. pyogenes induced septic shock.

 

I think this is the full PDF

 

http://www.journals.uchicago.edu/JID/journ...8/33148.web.pdf

Contribution of Natural Killer Cells

to the Pathogenesis of Septic Shock Induced

by Streptococcus pyogenes in Mice

[bmom]

Kim, most of what you have posted is over my head. I am glad that you are involved because I just cant seem to get it. I called UCDavis and spoke to Dr. Sharp-I really didn't think I would get him, but it was his direct line. I wasn't even sure what to say when he answered and he was very nice yet I wouldn't suggest calling as not to overwhelm him. Anyway, he said he had 2 children with tourettes- I thought he only had one, but he said 2. He also said someone had emailed him about magnesium recently and he had someone checking on this. He is still looking into the virus route and the few studies that have been done with autoimmune drugs haven't had many results yet.

[bmom]

He also said that he is still working on the virus idea. The thought that it starts as a virus of somesort, but becomes something else. It reminded me of Michelle where it was strep induced at first, yet now has continued. I told him we all appreciate the research he is doing.

[kim]

bmom,

 

You are so proactive! I had to laugh, thinking of how nerve wrecking, it would have been to get him on the line. Poor man, would have never gotten off the phone, if it would have been me who would have gotten him.

 

I think there is an email address, for him somewhere. Everyone, will have to keep their eyes peeled for any info, on his work.

 

Thank you so much, for posting his remarks!

 

kim

[kim]

Just thought of another one.

 

My sons best friend all the way back from preschool (now 14) has had two incidence of tics. Mouth stretching and wrist shaking.

 

One flair was after mono, the other after chicken pox. VIRUS