Intro

[michele]

Wow Buster,

I think that was the best explanation to this whole PANDAS I have ever read. It really does make sense too. Your thinking process is so incredible. Also the links are great. Dr.'s only go by research and I like the way you have pieced the puzzle together.

 

Have you tried the IVIG yet for your daughter? Are you going with Dr. K or working with him now? I just wondered if you think she is a good candidate for IVIG and if it has worked for her? At what point do you think it is best to try it? Only if the child is having a severe reaction to strep and PANDAS? I know your daughter has had a rough time of it. My six year old son is pretty stable on the Omnicef/cefdinir and Abilify for now. However, I do worry long term what the complications from the drug and the effects of the repeat PANDAS episodes. Since we have been on long term antibiotics for over a year my son has only had mild PANDAS symptoms from exposure to strep. He does have the emotional behaviors that don't seem to go away now but the meds are keeping him stable. When he gets exposed to people with strep he has meltdowns that last for a few weeks and a few tics but not anything that is horrible. He just gets so stuck on an idea or like and it is hard to turn him off of it other then to give in because he just goes on and on. I am worried that is a symptom of Bipolar and wonder if that is another symptom of the PANDAS or if the two are also related? As soon as he gets what he has been badgering us about he is onto something else. It is a bad cycle. The psych said to just stop giving in and buying him things. He is so convincing after a few weeks of constant hounding that I start to feel bad depriving him of something that he thinks about constantly. The past few weeks it has been a football helmet he wanted. He searched them online for hours, then he started asking every neighbor on the block for one. When I didn't get him one a few weeks ago he cried the whole car ride home and in the store and kicked and screamed. It has to be a mild form of OCD. Well yesterday I saw they were on sale at Target so I bought him it and told him I will give him it to him for his report card being good. He is having so much fun with it though he runs around and dances in it and acts out a football game. He is so cute. He put it on the first thing in the morning. He gets so excited. It is hard to not give in to that kind of enthusiasm.

 

Michele

To date has there ever been a study saying IVIG or azith is the best treatment for PANDAS?

 

The best study that I've found about IVIG was Perlmutter's 1999 Lancet report: http://intramural.nimh.nih.gov/pdn/pubs/pub-5.pdf where there was a demonstrated improvement of both IVIG and Plasma Exchange over Placebo in the decline of OCD symptoms. The followup actually offered IVIG to those who had placebo and again these had good results. There was a followup study on IVIG for OCD for non-PANDAS kids by Orvidas and Slattery (2001) that showed no improvement for non-PANDAS kids. I sure wish they had just repeated Perlmutter's test.

 

Incredibly, despite this begging for a followup experiment, there has been no followup study to test efficacy of IVIG on PANDAS vs non-PANDAS cases. Indeed the current NIMH site warns that IVIG should only be considered for severe cases and if anything recommends against it till there is more research (but hasn't funded any) -- grr.

 

There also hasn't been a followup to Swedo's azith vs pen study -- which seems incredible given the efficacy of both pen and azith. Swedo even comments that they had expected azithromycin to be a control in her study and hadn't expected it to work as well as the penicillin. There are several studies on certain strains of strep being able to go intracellular (i.e, where penicillin can't reach). Kaplan wrote an excellent paper on the efficacy of macrolides on getting intracellular strep in 2005 http://www.journals.uchicago.edu/doi/pdf/10.1086/508773.

 

At the same time there are numerous papers on resistance by strep (GABHS) to macrolides. For example,

http://www.journals.uchicago.edu/doi/pdf/10.1086/432480

and

http://www.journals.uchicago.edu/doi/abs/10.1086/320745

 

So it is a bit of a hit/miss. If penicillin can reach the strep, then it remains the preferred bactericidal option.

 

Now as to why is any of this working at all... well, that's really what's been on my mind for the last 2 months. Plasma Exchange removes antibodies. IVIG puts in antibodies. Penicillin is bactericidal to fast growing bacteria. Azithromycin is bacteriostatic to slow growing bacteria. Why should all of these show some efficacy (anecdotally or in clinical trials).

 

My best explanation is that PANDAS kids create an antibody with an idiotype for GlcNAc (see Kirvan 2006: http://www.csus.edu/bios/faculty/Kirvan/Ki...JNI_article.pdf ). I think most people suppress this antibody through either a T cell regulator or a B cell regulator (see http://content.jci.org/articles/view/37099).

 

The IVIG theory was about the introduction of an IgG antibody that was attacking the strep http://iai.asm.org/cgi/content/full/66/5/2279 . However, if so, why would also plasmapheresis work?

 

What seems to make the most sense is that the IgG is bringing in an anti-antibody (call it Fred) that attacks the GlcNAc idiotype antibody and prevents it from replicating. Thus IVIG works because it adds the regulatory antibody. Plasmapheresis works because it removes a bunch of the bad antibody. The exacerbations happen in PANDAS kids because the strep is active, the antibody replicates, attacks the strep (and neuronal tissue) and then declines in the blood stream as the strep is wiped out. I think azithromycin works by attacking any intracellular strep http://www.journals.uchicago.edu/doi/pdf/10.1086/508773 and also shifting the immune response (Th2 to Th1) thereby suppressing the replication of the antibody to the GlcNAc. I think this is also why prednisone seems to work (a strong immunosuppresant). Of course this is all just a theory.

 

As to why amoxicillin works, I think it just gets rid of the strep. After a period of time, the body stops replicating the antibody and the immune system settles down (we hope). In my dd case, I think we needed additional help to supress the immune response and reduce inflammation so azith worked better -- but without a clincial trial it is just anecdotal evidence.

 

 

Best regards,

 

Buster

[EAMom]

Hi Michele,

 

I think Buster (my dh) was thinking about sending Dr. K. an e-mail but hasn't contacted him yet. We are pretty familiar with him through Diana and I believe Diana has already shown Dr. K. some of Buster's other ideas.

 

Right now our PANDAS dd is just about 100% on the 250mg/Az (and 10mg prozac), so we're kind of waiting to see how she does this school year with exposure to strep/other illnesses. Of course there are concerns over the ramifications of long term Azithromycin. On the other hand, we don't know if IVIG is completely without perils...for example whether it will introduce some antibody or something which could have a bad effect 30-40 years down the road. In general, IVIG is given to really sick kids (cancer, HIV) and I don't know if there are any studies to show it's safety very long term. Every once in a while, we see a motion or a behavior (for example, if dd overeacts to something) and we wonder "is that the PANDAS breaking through?" But for the most part, dd is doing really well, so we are waiting to see what happens.

 

Despite my concerns about long term Azithromycin or IVIG, I do have more concern about the effect of repeat PANDAS episodes on children (on their brains, but also on their experiences in school, life).

 

EAMom

 

PS...(not that my children are completely unspoiled or perfectly behaved!) An idea of what to do when you ds "begs" for stuff... if your child decides he really wants something you could have him "work" towards his goal. He can earn $$ by doing extra chores, good behavior in school, etc. This is what we did when our youngest (5years old, not the one with pandas) really wanted a guinea pig. She did chores around the house, etc and finally had the $20 needed to adopt the little guy from the animal shelter (ha ha...of course I still had to construct the cage! buy supplies, etc...but I like him too). That way your child is "earning" what he wants he wants, not so much begging and you giving in. The difference is that dd was kept bugging me to do chores instead of just continuously bugging me to get a guinea pig. And if she/he finally goes long enough and earns enough $$$ then you know they really wanted it and probably deserve it/have earned it. Maybe it will also teach them something about the value of $$$?

[amy s]

Buster, this is absolutely excellent info and all the studies are great.