Buster

Thanks, but it's just an Excel graph. It does present, however, the data in a way that makes it easy to see the exacerbations and trend lines.

Dr. Kaplan is a very kind scientist who has devoted a signficant part of his life to the study of streptococcus. He is through and through a scientist first. This means that he accepts field input (what you or others will say), will create a hypothesis and then will try to conduct an experiment to prove the hypothesis by controlling other variables. He is neither for or against PANDAS -- he just thinks a lot of the experiments trying to prove or disprove the hypothesis of PANDAS were not great science. When he says evidence isn't compelling -- he isn't disputing what happened, he's saying there could be lots of explanations and that a good experiment wasn't set up to exclude the anecdotal and prove causality. I'm telling you this so that when you hear him say something you interpret it that he's not arguing with you at all. He's just saying that the evidence is mounting that PANDAS is a distinct entity -- he just doesn't think the current studies have yet supported it. In his own study in 2006 with Kurlan, he was running mostly the laboratory tests. He didn't participate in patient selection or controls. So he is rightly proud of the rigor of the tests but he'll also admit that it neither proves nor disproves the PANDAS theory. He'll use the term "it did not support PANDAS" or something like that. When a researcher is saying something like that -- he's just stating it like it is a number. He's not saying anything about whether PANDAS exists or not (despite his co-author's inflammatory titles), Kaplan is just saying that this particular experiment did not find a hypothesized result and that could be for a ton of different reasons -- back to the drawing board. Bottom line, he's a kind person who will listen. He knows everything about strep and if you want to get him going, ask him "so, why is there asymptomatic carriage in people?" or "why do doctors believe asymptomatic carriage is benign?" Regards, Buster

I'd so love this to be a call-in show... I'd be asking "So let me get this straight, you didn't study sudden onset but rather looked at kids 3+ years after onset of symptoms. You happened to select kids who had no OCD exacerbations over a 2 year window -- that is remarkable and doesn't that tell you that the kids were unlike the kids studied by Swedo?" "Oh, and if I read the study right, you actually treated any strep infection found by telling the kids doctors. It seems the only two available conclusions are either that prompt treatment of streptococcus doesn't lead to PANDAS symptoms or that kids with long term Tourettes matching the PANDAS profile don't have OCD exacerbations." If he goes into his zebra and horse analogy, I'm just going to scream at the computer "would you please just repeat Kirvan's studies before you dig yourself a deeper hole? ...." Buster

Hi mrigsby, If I remember your case right, your son was on augmentin and is testing positive for strep within 4 days of completing the treatment. I suppose the very first question to ask is dosage -- was he taking augmentin once a day? twice a day? Was it 500mg 2x a day? Was it liquid or pill? Have others in the household been tested for strep? I ask because one of the most common reasons someone doesn't clear is that there is another person carrying strep in the house. Also did you change toothbrushes (I'm presuming so). Another reason people don't clear is they just re-infect themselves. Does he tend to mouth something/chew on something? Okay, having now dispensed with all those items... Your ENT is right that most times asymptomatic strep carriers are not treated by doctors -- partially because they aren't complaining and partially because it is sometimes hard to clear them. The usual reason given to clear an asymptomatic carrier is if someone else in the household who is immunocompromised. Clearance is difficult because clearance actually requires the immune system to mount an attack. If your child is not mounting a response, then there's not a lot that just straight antbiotics can do. Have you had your son's IgG, IgM and IgA levels checked? The "red book" recommends clindamycin if amoxicillin/augmentin aren't enough to clear infection. Clindamycin is a smelly, yucky liquid (luckily it comes in a pill form) and is not something you want to be on for any long term duration. We have actually found that azithromycin worked for clearing our second daughter who turned out to be the carrier in our house. If I had a choice, I'd do azith before clindamycin as it is easier to take. The speed with which your son tested positive is slightly odd. For about 5% of kids, they test positive within 10 days after treatment and typically have no ASO or Anti-DNAseB rise. Another 15% have "treatment failure" at 20 days post treatment --they have an ASO and AntiDNAse B rise but reculture positive at 20 days. Technically, only the 5% are considered carriers and only because there was no apparent immunologic response. If you have good clinical observation that leads you to believe your son has PANDAS, then try to clear the carriage. Buster

A basic flowchart of how some of the cases on this board have been diagnosed/treated. http://www.latitudes.org/forums/index.php?showtopic=6688 Buster

Restarted thread with cleaned up version here: http://www.latitudes.org/forums/index.php?showtopic=6688

Here's a cleaned up version of the flowchart pitand_diag2.pdf Buster NOTE: This is not intended to be medical advice, but more a documentation of the steps that many of the patients discussed on this forum have followed...

Here's the type of thing we got by using this type of system over time. And yes I spent way too much time on this....

I can do that -- why do you think Celiac has symptoms similar to PANDAS. I wasn't aware that it had either a tic disorder or OCD. Buster

Thanks for the comments. I get your points, but I'm concerned if we leave the fields without timelines we'll lose the actual benefit of the flow. It was precisely the timelines that I found helpful. Too many people are expecting an immediate change rather than the 2 week effect reported by you and so many others. So, personally, I'd rather keep the time and perhaps add an * that some folks find a longer time. On the 5 day or longer pred burst, I'm basing this more on Dr. K than on Dr. L. I've read the material of Dr. K and he seems to have extremely consistent results here for a large number of cases with a 5 day burst producing results within the 2 week time period. I've tried to track material from Dr. L and been less successful. Perhaps if you are talking with Dr. L you could ask what the average time to impact is. Since pred is not thought to be therapeutic here and has a lot of neg side effects, I'd be very hesitant to just leave it open. With the 10 days vs 5 days -- I'm certainly willing to change it to 5-10 day burst. I like your idea of "healthy" but have to reflect on how it will fit. One of the reasons I did the chart was to see how much rigor can be added to the diagnostic procedure. It's hard to complain about Kurlan or Kaplan's comments on the ambiguity in PANDAS if the diagnostic critieria remains too vague. I realize there are cases like Worried Dad's son and I think a lot about how that could be caught in this cycle. Essentially, I'd like to see how many of the kids already helped on this forum would be caught by such an algorithm. I should stress that the chart is the best that I've found from the material in the literature and controlled trials. I'm sure there are many other tests that folks might run in addition to the ones mentioned. Buster

Helps if I get the URL right. Try the new page again. Sorry about that.

Hi Meg's Mom, Can you check if you were looking at the latest version -- sorry, I might have been updating based on feedback when you posted. Based on Dr. K's interview yesterday, he says he placed about 5-10% on the culture, ASO/Anti-DNase, sore throat, ..., 60-70% on clinical history and 20-30% on the confirmatory affect of prednisone. As such I tried to make it that even if all cultures/titers are negative, you can decide to progress onto antibiotic trials and pred. The tricky part is that doctors will claim there isn't "good evidence" for the trial and so you have to argue the benefit to risk ratio. On CaM Kinase II, yes, 130 would be supportive. The pilot in the Kirvan Nature article was from the patients in Swedo's study. So it is hard to know what the true mid-point is for a broad population. I think that's the whole reason for the research trial. Regards, Buster

I'd recommend the summary at http://www.latitudes.org/forums/index.php?showtopic=6265 and then include copies of some of the referenced papers. The best amongst them are: [Kirvan2006] Kirvan CA, Swedo SE, Kurahara D, Cunningham MW, "Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea". 2006 Autoimmunity 39 (1): 21–9. http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf [Pavone2006] Pavone P, Parano E, Rizzo R, Trifiletti RR (2006). "Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants". J Child Neurol 21 (9): 727-36. http://jcn.sagepub.com/cgi/content/abstract/21/9/727 [Yaddanapudi2009] K Yaddanapudi, M Hornig, R Serge, J De Miranda, A Baghban, G Villar, W I Lipkin Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Molecular Psychiatry August 11, 2009 doi:10.1038/mp.2009.77 http://www.nature.com/mp/journal/vaop/ncur.../mp200977a.html [Moretti2008] Moretti G, Pasquini M, Mandarelli G, Tarsitani L, Biondi M (2008). "What every psychiatrist should know about PANDAS: a review". Clin Pract Epidemol Ment Health 4: 13. http://www.ncbi.nlm.nih.gov/pmc/articles/P...5-0179-4-13.pdf [shet2003]Shet A, Kaplan EL, Johnson DR, Cleary PP, "Immune response to group A streptococcal C5a peptidase in children: implications for vaccine development", J Infect Dis. 2003 Sep 15;188(6):809-17. http://www.journals.uchicago.edu/doi/pdf/10.1086/377700 That should tied him/her over. Buster

Hard to say but probably not. The antibodies are temporary with a 36-45 half-life. I suppose it is possible that the antibody from the donor triggers a T-cell that then bonds with a B-cell that wasn't activated before producing a new set of antibodies that now create a cycle. I doubt it though.

Hi Smarty Jones, let me try to answer the questions you pose. There's not a "proper amount" of antibodies. You basically get a boatload of them. If they aren't used/find anything to bind to, they just keep circulating until they turnover. The halflife of antibodies vary but generally is between 36-45 days. The B cells are still around to make more if need be. It's not known that it actually "retrains" the immune system -- rather it seems to overwhelm the immune system and potentially reactivates T-regulatory cells. The T-regulatory cells suppress the activation of T-cells that would target host cells (at least that is one theory). Another theory is that the antibodies introduced actually find the offending bacteria and mark it for deletion. Once the bacteria (or cell containing the bacteria) is destroyed then there is no longer a trigger for the B-cell that is incorrectly creating antibodies. Finally, a 3rd theory holds that IVIG is very anti-inflammatory (not sure why) and this anti-inflammatory property closes the Blood-brain barrier breaking the cycle of PANDAS. We can attest that it has worked for our daughter on her contamination, OCD and movement disorders. Swedo's studies (see research in essential threads) also has 50 documented cases where the single dose of IVIG/PEX with prophylaxis was sufficient to have sustained results for > 1 year. Nope, it's more that you've got a misfire of a response to an antigen, a failure of regulation of the antibody, and a breach of the blood brain barrier. IVIG helps close the blood-brain barrier, seems to cause regulation of the antibody, and seems to remove the original triggering antigen that the body was having trouble finding/marking. We think so -- although it is possible that the closure of the BBB and the T-reg cells might be enough that simple exposure doesn't cause the significant adverse reaction. Possible on shrinking the basal ganglia -- but current research is that the basal ganglia isn't "swelled" but rather the antibody interferes with cell signalling. THere have been mixed reports about inflammed basal ganglia. In terms of closing the BBB -- yup, that seems to certainly be the case as IVIG is anti-inflammatory and reduced ICAM-1 on the endothelial cells at the BBB. Buster

The test is a research trial. This means they are still trying to determine whether the test has diagnostic usefulness. All indications are that it is a reliable source, but the accuracy/repeatability/specificity is not known. So CaM Kinase II is an additional piece of the puzzle of PANDAS. For many, the CaM Kinase II provides enough confirming evidence that helps move along the process -- however, some doctors use preliminary experimental results and others do not. For example, it was only recently that ANA was correlated with Lupus and even then it is more confirming rather than diagnostic. People with Lupus tend to have elevated ANA -- however everyone with elevated ANA doesn't have Lupus. In terms of why parents do this, it's primarily because we're all looking for any clue or additional puzzle pieces that help us determine the underlying cause. Regards, Buster

Hi Vickie, In our case, we had 4 months without exacerbation over the '08 summer. Then a series of exacerbations with typically 2 months between episodes. We had 3 month break in '09 summer. Post IVIG (August) we are now 5 months from significant exacerbation. Buster

Updated top image to reflect comments

Oh, on the geeky side, Group A strep is almost alway Beta-Hemolytic (meaning it creates completely lyses the cells). Group B can be alpha or gamma hemolytic. This is why GAS and GABHS are used interchangably.

This is due to the work of Kurlan and Kaplan where they published in Pediatrics 2008 the separation of "definite", "probable" and "possible" GABHS infections and told folks that "definite" in their study was a positive throat culture clinical symptoms and a rise in ASO titers in 1-3 weeks post positive culture They chose this extremely limited definition so that no one could argue whether there was or was not a strep infection. Unfortunately, this caused some pediatricians to think this is required rather than the particular choice of that research group. In addition, they chose their kids from children with 3 years + of tic symptoms with no remission. Their purpose (based on sample selection) appears to be to prove that Tourette's kids matching the definition of PANDAS who have symptoms long enough don't have exacerbations cotemporal with GABHS infections. Strangely that isn't what they showed, but the paper is terrible in revealing both the flaw in the paper and the fact that they did find that kids matching the PANDAS subgroup (even from the Tourette's subjects) got more GABHS infections. Sigh Buster

Good point on rule-out. I have to think about where to add that. Perhaps where the other Igg is being tested. I started with a statement in box 7 that ASO won't rise in >46% of cases -- perhaps that is good enough. I also started thinking I'd need to block by time window (i.e, is it within 1 week of exacerbation, 3 weeks, 6 weeks). I also liked the comment about initial versus subsequent. I do see something awfully similar to a hyper-reaction aver a hypo-reaction. Our subsequent exacerbations were more like an allergic reaction (more severe, more immediate) than our initial reaction. I wonder if what is really happening is that the adaptive immune system fails to clear so the humoral system gets involved and now is hyper-responsive. I'll try another revision later today. Buster

That's sort of why I put this down. We have to have an argument (for ourselves and for our doctors) for moving from stage to stage. We could say that we think the high-dose azith or augmentin is anti-inflammatory and on subsequent exacerbation we should treat with an anti-inflammatory. I could even see a jump to a trial of pred to see if it is anti-inflammatory -- but if it is a viral or bacterial trigger suppressing the immune response isn't the best thing to do. Hence I chose a check of the CaM Kinase II scores. The problem is that these scores aren't calibrated enough to know exactly what they mean. Perhaps we could separate the two "stops" and have the first one check the CaM Kinase II and if elevated do a trial of azith to see if positive response. Buster

Hi T.Mom, I actually thought about skipping the whole "check for GABHS" and just jump to box 9 on the presumption that a 30 day trial of antibiotics is WAY safer and cheaper than any anti-psychotic/anti-tic medication that would otherwise be prescribed. I thought about just recommending in box 7 to "get the Cam Kinase II results and if > 160 treat as PANDAS". This would catch the 31%+ of kids who don't have elevated ASO or Anti-DNAseB response -- particularly for difficult to culture sinus infections and cover the docs who don't seem to know how to take a simple throat culture -- couldn't believe the high-false negative rate because the nurses cultured throat rather than tonsils. Sigh. Unfortunately, we don't have enough data yet to know if the Cam Kinase II test can become a diagnostic test. It sure seems promising, but we'll have to wait till the research paper comes out. I'm happy to add another box after box 7 that says "suspected GABHS infection coincident with symptom onset" as a vague placeholder... would that work? The reason I didn't collapse all the boxes is that I consistently see doctors pulling rapid and ASO together and making the very false assumption that the ASO is more accurate than the rapid. It's hard to believe that the ASO is about the same as a coin flip. Buster

Updated based on Vickie's comments

It's a good point. Let me see if I can fix that in the chart. see if revision fixes the problem.