Buster

Hi MomMd, Which titers are you checking? Are you checking the anti-GM1 titers or ASO or ...? Buster quote name='mom md' date='Jun 1 2009, 07:52 PM' post='33644'] PEX has less risk of blood infections (never been a case report) because it is just albumin being transfused, as opposed to IVIG which is pooled antibody. PEX is more invasive though, it requires a central line and a PICU stay for 3-4 days. We checked the titers before we decided on PEX just to see if the azith had brought the titers down because he was still having so many symptoms. The nice thing about the PEX is we can check his levels through the process and make sure they get cleared.

See http://www.latitudes.org/forums/index.php?...amp;mode=linear Kirvan and Cunningham have isolated 3 auto-antibodies that they believe separate TS, PANDAS and SC and have shown that CaM Kinase II activation is different between an exacerbation in PANDAS and tics/non-PANDAS OCD. Singer was supposedly trying to replicate this study in his 2008 Pediatric paper, but was not successful. Looking at his criteria, it appears that he chose children with chronic tics (> 3 years without remission) rather than those with episodic OCD courses (i.e., I think his study was more about TS than about PANDAS). I appreciate your question around waxing and waning and want to go back to Swedo's comment in her 2004 response to Kurlan that the episodic course of PANDAS is nothing like the unfortunate waxing and waning associated with TS or non-PANDAS OCD. On the CYBOCS score, Kirvan, Cunningham, Swedo, ... were all seeing differences of 15 pts in severity on CYBOCS. Kurlan and Singer saw differences of 3 points mean -- i.e., a 5 to 1 difference. This, in my opinion, is the difference in episodic versus wax/wane. If you have primarily tics, I don't know if the studies will be helpful. I haven't studied that area as much because the scariest part for us was our dd OCD. I'll check. An episode for us last 5 weeks from initial exacerbation. Behavioral changes the first 2 weeks, we then get a movement disorder around the 9th day, then a verbal tic (a grunt) on the 12-14th day. The behavioral items clear around this time but the tic and movement items remain. The movement disorder is a weird measurement ritual -- hard to describe but our daughter seems oblivious that it is happening. The verbal tic is the last to go so it's there a good 3 weeks before we notice its absence. This is what we mean by episodic -- a period of 4-5 weeks going from nothing to significant back to nothing. The height of an exacerbation is still small compared to where we were a year ago, but it's clear when she's in an exacerbation. Regards, Buster

Kayanne, Oh that is so annoying.... I hate it when doctors misuse studies. That's some "expert" you've got. The study that the doctor was likely referring to was Swedo's own 1999 study that was entitled "A Pilot Study of Penicillin Prophylaxis for Neuropsychiatric Exacerbations Triggered by Streptococcal Infections. BIOL PSYCHIATRY: 1999;45:1564–1571 ." http://intramural.nimh.nih.gov/pdn/pubs/pub-6.pdf The conclusion of the paper says, "Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size." (emphasis added) When Swedo talks about this study, she says the compliance (whether someone took the drug each day) was poor. The problem with penicillin is if you miss even a single dose you are not protected for 24 hours. Swedo set about to fix this study in 2005, where she did achieve prophylaxis with two antibiotics showing their efficacy. "Antibiotic Prophylaxis with Azithromycin or Penicillin for Childhood-Onset Neurospychiatric Disorders Biol Psychiatry 2005; 57: 788-792" http://intramural.nimh.nih.gov/pdn/pubs/pub-9.pdf This is known as an active placebo affect. Clearly your doctor did not actually read either study. I've placed links to both papers here in case you'd like to give him the actual references to read.... Also, I recommend reading the Kirvan and Cunningham's material that I cite here: http://www.latitudes.org/forums/index.php?showtopic=4785 I'd like to also underscore EAMom's comment that there are no actual studies that anti-psychotic drugs or CBT are effective with PANDAS. I can imagine conducting studies to test whether these methods work, but it's sort of amazing that doctors are willing to prescribe these untested, often offlabel, and non-blinded methods while ignoring the actual evidence-based research. Not sure what else to say except thank goodness you had a pediatrician who had read something about PANDAS. Best Regards, Buster

So was that 2 gm/kg dosing? Buster

Please take this poll if your child had IVIG (with or without a dose of prednisone)... Buster

Hi KimDeL, I was asking about the Clonidine because it generally is given to lower blood pressure by binding to noepinephrine. It was a bit surprising to see in the list of meds. It is used for Tourettes and ADHD, but I was wondering why your doctor prescribed it. On the steroids, I was asking because of the Clonidine. There is one treatment I had seen where steroids were used to lower B-cell activation and Clonidine was used to minimize blood-brain-barrier disruption due to high-blood presure. Something maybe to consider here is that azith does a lot more than just be an antibiotic. It is immunomodulating (shifting Th2 response to Th1 response) and anti-inflammatory. Amoxicillin does not have these two properties. Hard to say what was going on. Glad to hear about Kawasaki's being ruled out. Buster

Yup. I certainly would try to prevent another sentinal event. In the ideal world, I'd: give the prednisone check that the anti-neural antibodies are declining get the IVIG keep her on narrow-band antibiotics verify that the anti-neural antibodies are still low 6 months out (or even better check after a sibling gets strep) If I saw no exacerbations and the anti-neural antibodies remained low despite potential reculture I might really start to think it was a long term cure :-) Best, Buster

Claire, I only wish I knew the answer to your question. We're going through the same dilemma ourselves. We haven't pursued any of the treatments yet as dd's symptoms are largely controlled on azith and so we've been in a holding pattern trying to figure out what to do and blessing the momentary calm. IVIG makes me nervous because it is a blood product (i.e., who knows what's in it) and I can't quite get why it should work (see my caveat below, I've got a clue now). Plasmapherisis I understand, but think it is at best a short term fix because the B-cells are still there and can reactivate. I'm also not thrilled about opening a central line. Plasmapherisis + antibiotics makes sense to me (remove the serum antibodies and protect against another B-cell trigger on presumption that strep is the trigger and not some other GlcNAc carbohydrate). Unfortunately there aren't great studies here. Prednisone, I understand (suppress the B-cell activation, reduce inflammatory cytokines). This could be working by stopping leakage across BBB or by suppressing B-cells. There are a lot of side effects and I agree with you that I don't want dd on it for any length of time. So, with all that said, we're leaning towards IVIG this summer with an initial burst of Prednisone (i.e., essentially following Dr. K's protocol). We're trying to get a local immunologist to do it, but if not, we'll be on a flight to Chicago. What is swaying me to this unknown is: Dr. K's apparent success with IVIG -- many on this forum have found significant help there A really interesting paper by Aharon Kessel in 2007 called "Intravenous Immunoglobulin Therapy Affects T Regulatory Cells by Increasing Their Suppressive Function". You can get a copy of the paper at http://www.jimmunol.org/cgi/reprint/179/8/5571 . I'm trying to track down peer reviews of this paper now. What Aharon is showing is that there really may be something to IVIG resetting T regulatory cells. If true, this may provide long term suppression of the B-cell activation by stopping the anti-host antibodies. I'd be super interested in your (and others) opinion on the paper and I wonder if Dr. Latimer would comment on it? So bottom line, I don't have a recommendation. In our personal situation our dd's symptoms are drastically reduced on azith (we think for the immunomodulating (Th2->Th1 shift) and antiinflammatory (BBB) properties. At the moment, we have the luxury of time, but every time we get a flare up we worry that her baseline isn't resetting. We also worry that her struggle with math and handwritting is tied to CaM Kinase II activation and that we should do something more... Take it that we're stressing about this too. Best regards, Buster

Hi MomMD, Thanks for posting on your conversation with Dr. Leckmann. I've been tracking his work (or more precisely his student's work on T-cell regulation). I think that is partially true. The anti-neural antibodies are in the blood stream and if Kirvan is right, they are targeting GlcNAc which is a fairly common carbohydrate in the body and just happens to be on the exterior cell wall of the GABHS. Since the monoclonal antibody doesn't seem to be binding to other sources of GlcNAc but only to Tubulin and neural tissue, there's probably something unusual about the chain itself. In Kirvan's JNI paper, she shows that CaM Kinase II activation is reduced in the case of convalescent PANDAS and SC patients in 15 of the 16 patients. This indicates that by removing the initial antigen (presumably GABHS) the antibodies reduce and the B-cells stop replicating the antibody. If the blood-brain barrier opens in the convalescent state then the concentration is low and unlikely to cause CaM Kinase II activation. This seems to warrant keeping triggers from coming -- just to keep the antibody concentration low. In 4 of the 16 cases, the antibodies were still high in convalesence so that a disruption of the BBB would have then just let the already active antibodies in. So, it seems in both cases, lowering (and keeping low) the anti-neural antibodies would be the goal and hopefully reseting the B-cell to stop making the wrong antibody. Long way of saying, I'd still try to remove the antigen and keep the B-cells from producing antibodies if possible. Part of me is worried that the Neural cells themselves will be considered antigens by these anti-neurall antibodies and thus you don't need the external trigger. However, I'm hopeful that is not the case -- i.e., that the seminal event requires an external infection. But I agree with you that periodic pred or IVIG or PeX might be required. Hoping Leckmann publishes before 2011. Regards, Buster

Hi Bronxmom2, The paper I was referring to about PANDAS and the effectiveness of IVIG and Plasma Exchage was: Perlmutter's 1999 Lancet report: http://intramural.nimh.nih.gov/pdn/pubs/pub-5.pdf I didn't see it in your list. It's a great paper. Another one you might like to see (i.e., if you're into historical landmarks) is Gannar Husby's paper "Antibodies Reacting with Cytoplasm of SubThalamic and Caudate Nuclei Neruons in Chorea and Acute Rheumatic Fever" at http://jem.rupress.org/cgi/reprint/144/4/1094 . This amazing paper from 1976 (yes 1976) is the oldest I've found and I think it was lost in the literature until Cunningham found it in her work on Pathogenesis of group A streptococcal infections. Husby lays out the whole autoimmune theory that was later found by Swedo and the antiboidies isolated by Kirvan. At this point, it would be fair to say there has been 33 years of research on this :-) The paper I was citing in my other post was : http://linkinghub.elsevier.com/retrieve/pi...887899405005436 which compares effectiveness of the various treatments on SC kids -- with 1 month and 1 year followups. Buster

Hi EAMom, Your point above is excellent and I too have been fascinated by Kirvan's 3b figure. I sure wish someone else had replicated this study. A slight difficulty in the 3b figure is that Kirvan was taking kids with acute PANDAS (i.e., in exacerbation) and comparing them with non-PANDAS OCD, Tics and ADHD kids. If I replot the convalescent kids (taking data from figure 2a and plotting it in figure 3a), it shows that the PANDAS kids in convalescence look a lot like Non-PANDAS kids. Out of the 16 kids, only 4 kids maintained high CaM Kinase II activation in the convalescent state . What's interesting about this is that for 75% of the kids, the antibodies reduced with symptom decline. For 25%, the antibodies remained at same or elevated levels. This makes me think that there are two things going on: for some, the convalescent state comes from a reduction of the auto-antibodies for others, perhaps the blood brain barrier has closed preventing the auto-antibodies from crossing into CSF As far as I could tell, Kiran didn't have CSF matches to Serum in this 2006 study. This means we can't look at the question of whether the decline in symptoms is tied to a decline in CSF auto-antibodies independently of the amount of auto-antibodies in serum. I went back to her 2003 Nature article and while the data sets are undoubtedly disjoint (i.e., can't link the results), the Nature article (figure 4 d) seems to support the hypothesis that it is the amount of auto-antibodies in the CSF and not the Serum auto-antibodies. This even more supports the notion that there are two independent triggering events: in one, the auto-antibodies are removed and another sentinel event is required to raise the auto-antibodies in the second, the auto-antibodies are in the serum, but can't get to the CSF So for some people, they need both the strep infection and a break down of blood brain barrier due to infection, stress, .... In others they need only the break down of the blood brain barrier because the B-cells are already stuck maintaining a high set of auto-antibodies. I'll keep digging and see if I can get anything from Husby's paper on this. He did work on this topic back in 1976. Regards, Buster

Hi KimDeL, wow, there's a lot in here... I wasn't sure what med was for what symptom from the post. You mentioned Zoloft and Clonadine but was this for treating the tics or was there some other condition being treated? Has your doctor ruled out Kawasakis Disease? http://www.aocd.org/skin/dermatologic_dise...is-disease.html I agree with P.Mom here that what you might be seeing is just the response to strep and it doesn't have anything to do with the medication. Of course there could be a cross reaction. I can say that in our case (i.e., with our dd) our symptoms are pretty time driven. We see the following: dd is on propholaxis antibiotic we observe a ramp in separation anxiety and some defiance we culture sister and sister comes back positive for GABHS we treat sister at 5-7 days after starting treatment, dd has a vocal tic and movement/measurement rituals two weeks later movement/measurement rituals disappear we culture sister and sister comes back negative for GABHS (i.e., we check that we cleared sister) one to two weeks later vocal tic disappears so full cycle is 3-4 weeks until we're back to baseline. So checking on your chronology: He had a sore throat and azithromycin was prescribed. You had increased peeling/tics a week later At three weeks from starting azith (2 weeks from completing) you took him to the doctor and a throat culture came back positive for strep -- i.e., strain was not stopped with azith Right? Has he ever been on steroids over the past 2 years? Regards, Buster

I got a number of questions regarding my comment above so let me try to explain what is thought to be going on. The streptococcal infection is thought to be a seminal event or initial trigger that produces the anti-neural antibodies. These anti-neural antibodies are then circulating in blood serum at some concentration. If the strep is destroyed (antibiotics or otherwise), then most of the antibodies disappear because the triggering antigen is gone. It is likely, however, that the antibody is remembered by the B-cells for future use. Now a subsequent strep exposure occurs. The B-cell "remembers" the antibody and produces it to attack the strep. It replicates and rebuilds a concentration of antibodies in the serum. On the presumption that these anti-neural antibodies can't touch anything but neural tissue, all is fine as long as the blood brain barrier is closed (i.e., the anti-neural antibody can't get to the brain tissue). Suppose now the blood brain barrier opens (due to illness, trama, infection, disease, genetic predisposition, ....). Now the circulating antibodies can interact with neural tissue and signal it found what it was looking for. This signal generally causes inflammation and more antibodies to be produced. Hence the auto-immune problem. So there are really two ways that the antibody concentration grow: * Another strep infection or exposure occurs and so the B-memory cell triggers up more antibodies * the antibodies in the serum find what they are looking for and announce the need to replicate more antibodies The key is clearly the blood brain barrier. As long as the antibodies are stuck in serum, nothing happens (provided they only cross-react with neural tissue). If the blood brain barrier opens, then inflammation, replication and odd signalling can occur. So, while Strep is likely the seminal event, other infections can open the Blood Brain Barrier and an exacerbation can occur. Note, the above is a theory and not yet proven. Kirvan and Cunningham have isolated the antibody, but not explained the crossing. Leckman has demonstrated some interesting findings on T-cell regulation but not shown that deficiency in PANDAS. Regards, Buster

Hi DcMom, In terms of the research, I wasn't quoting any of Leckman's work. Leckman seems to be working on the theory that T-cell regulation is messed up and so the anti-host antibody isn't properly supressed. Other auto-immune diseases treated with IVIG tend to be multi-dosing. What I mean is that for some diseases IVIG adds in suppression of host-attacking antibodies... however, over time, this suppression antibody gets all used up and you need more of them. In PANDAS, Dr. K and Dr. Leckman seem to think that there is a disfunction of the T-regulators and that IVIG does a reset on the immune system and helps the body relearn how to separate host attacking from foreign body attacking. If this "lesson" is learned then a single IVIG may suffice. As far as I know, no one has studied the long term effects of IVIG and whether it is a cure of the disease or just a cure of the symptom. There's good anecdotal evidence from Swedo's studies that the single dosage was sufficient, but I couldn't find second experiments that supported that theory. Dr. K probably has the best anecdotal evidence -- even if not blinded. At this point there just doesn't seem to be enough data to say one way or the other... Buster

Hi MomtoTaylor, Acutally there is good research on using prednisone as a diagnostic technique. However, the research is on Sydeham Chorea and not on PANDAS itself. see http://linkinghub.elsevier.com/retrieve/pi...887899405005436 for a double blind placebo controlled study on Prednisone and its effect for SC. There is good research that PANDAS has similar antibodies to SC but at different concentration (see papers by Kirvan and Cunningham http://www.csus.edu/bios/faculty/Kirvan/Ki...JNI_article.pdf ). I should stress that these antibodies are not the ASO or Anti-DNAse-B antibodies we see in a lot of posts but are instead anti-neural antibodies known as 24.3.1, 31.1.1, and 37.2.1. There's good papers here by Church, Dale, Kirvan and Cunningham. Now having said all that, our immunologist isn't a big fan of using Prednisone in this way as Pred has all sorts of side effects itself and there is some debate whether it would be predictive of a response to IVIG. I'm not sure what to say here except that Dr. K has seen more kids with PANDAS than probably anyone else. Prednisone likely carries less danger than IVIG and can help separate a case that would respond to anti-inflammatory or may be caused by an overactive immune system. I think this is why Dr. K uses it. Hope the above links help. Regards, Buster

Reading through a bunch of recent papers I now understand Dr. Swedo's comment at a recent Autism Conference that based on recent research "the controversy around PANDAS should be over." Over the past several months I've spent a good amount of time reviewing papers on molecular mimicry and the auto-immune aspects of PANDAS. I thought I'd post what I learned and also request comments from others who've been tracking this. I started this with the post "PANDAS research for your doubting doctor" http://www.latitudes.org/forums/index.php?showtopic=3911 because I found that a lot of the doctors were really ill informed about the research on PANDAS. One of the most significant papers is by Kirvan and Cunningham in the July 2003 issue of Nature Medicine (a very prestigous journal) about "Mimicry and auto-antibody mediated neuronal signalling" http://www.nature.com/nm/journal/v9/n7/pdf/nm892.pdf . They also published a 2006 paper in the Journal of Neuroimmunology http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf on "Antibody-mediated neuronal cell signaling in behavior and movement disorders". Finally Kirvan in 2007 published a paper on "Tubulin Is a Neuronal Target of Autoantibodies in Sydenham’s Chorea." What they found was the following: They were able to isolate three auto-antibodies that were created in response to Group A B-Hemolytic Streptococcal infections in patients with Sydeham Chorea and PANDAS. Now these auto-antibodies have nothing to do with ASO or Anti-DNAse B or those tests. I really want to underscore this because so much attention is often paid to ASO and Anti-DNAse B, but it appears neither of those antibodies have anything to do with PANDAS (except confirm whether you once had a strep infection -- and even then with a 33% false negative rate -- see A little bit about ASO titers and More about ASO ). These newly discovered antibodies (which go by the names 24.3.1, 31.1.1, and 37.2.1) cross-react with a lysoganglioside in the brain. By cross-react, what they mean is that if those antibodies are present, they bind with neural tissue in a similar manner to one of the brain's own chemicals. In addition, they discovered that if the antibody exists in enough concentration, it can signal neuronal activity (i.e., make a muscle move or stimulate a thought/action). This is a really significant finding and could explain a lot of the tics and behavioral abnormalities. The only party I have found who tried to replicate Kirvan's experiment was Kurlan and Singer in their June 2008 Pediatrics report. However, Kurlan and Singer ran their experiments on Tourettes kids with waxing and waning tics and not PANDAS kids with episodic OCD symptoms (see Problems with Kurlan Paper). It looks like Cunningham and Kirvan's results apply only to PANDAS OCD and not to Tourettes or non-PANDAS OCD. In reading through reviews of the Kirvan paper, it appears the biggest complaint is that Kirvan and Cunningham have not described how the antibody in blood serum crosses the blood brain barrier and gets into central spinal fluid (CSF). For this to occur, there has to be some breakdown of the blood-brain barrier. Tracking this down, there are a number of interesting reports where streptococcal infections themselves can interfere with the blood brain barrier -- http://www.neurology.org/cgi/content/abstract/54/7/1433 . In addition, there are papers that epinephrine (from fear or stress) causes a breakdown of the barrier. In addition, inflammation (such as that produced during an immune response to an infection) can cause a breakdown in the barrier. What's interesting about this item around inflammation is that prednisone and IVIG are both big anti-inflammatories and immunosuppressors. So they could be closing the blood brain barrier and reducing the replication of the pro-inflammatory cytokines and auto-antibodies. So folks, have you run across papers that show PANDAS OCD kids have an open blood brain barrier (other than the observation that something is getting to the brain ?) What is interesting to me about Kirvan and Cunningham's papers is that it provided significant supporting evidence of Swedo's original 1994 theory and explained why Plasmapherisis would work (removes the auto-antibody), why Prednisone would work (suppresses the auto-antibody and reduces inflammation of blood brain barrier), why IVIG would work (high anti-inflammatory impact and IgG has been found to have B and T cell suppressors that would supress certain auto-antibodies). Comments? Other papers? Regards, Buster

Hi Sarah, Not sure what to say to Dr. Sanker except that it's a shame he's so busy that he can't read research papers. The disease he probably likes is ADEM (Acute disseminated encephalomyelitis). It's a pretty scary disease that has a positive side of seeming to be a single incident. For some reason, neurologists have an easier time accepting the unexplained occurance of ADEM and prescribing IVIG for treatment than they do with an explanation of an antibody reaction to an exotoxin of GABHS. If you'd like to help Dr. Sanker's education, you might drop off a copy of Dale's paper http://qjmed.oxfordjournals.org/cgi/reprint/96/3/183 Which compares ADEM, PANDAS and SC. It's an excellent paper and worth the read. Regards, Buster

Hi Julie, I'm not sure there is a great answer to your question. The current research indicates that the ASO and AntiDNAse B antibodies are not the problem. A rising titer in either of them indicates a prior strep infection, but a falling titer or stable titer does not seem to mean a lot (even if elevated). In most people, propholatic antibiotics do keep titers low by reducing the spread of any bacteria that invades to the blood stream -- however, if the person is really "allergic" to an exotoxin of strep, there can still be very high/elevated responses since propholatic antibiotics reduce the spread but not the existance of strep. The best research I've found thus far indicates that the likely culprit in PANDAS is a very different monoclonal antibody that targets GlcNAc (a carbohydrate) (see research by Kirvan and Cunningham). For reasons not understood, this antibody crosses the blood brain barrier and causes inflamation and/or interferes with dopamin reception in the basal ganglia (at least that's the theory). The thought is that IVIG interferes with the creation of this antibody or the new IgG identifies it as autoimmune and suppresses the antibody. Unfortunately, there doesn't seem to be any way to test for this antibody so the objective of prophylactic antibiotics is to try to minimize re-infection even if recolonization occurs. Colonization means that the bacteria is growing on the skin or throat. Infection means that the bacteria has invaded the blood stream. Regards, Buster

Azithromycin (except Zmax - the time released version) can be taken with or without food, but food reduces stomach upset. Zmax should be taken on an empty stomach 1 hour before eating. Azithromycin (except Zmax) should not be taken at the same time as aluminum- or magnesium- based antacids, such as Mylanta or Maalox because antacids will bind the azithromycin and prevent it from being absorbed from the intestine. Regards, Buster

Hi folks, Here's a fair article about how macrolides work: http://books.google.com/books?id=UCnIBIVKv...esult#PPA182,M1 The short summary is that macrolides (such as azithromycin) affects the RNA's ability to copy a protein. So this doesn't technically kill the step, but rather stops it from replicating. Essentially macrolides rely on your immune system to find the tagged cells and wipe out those cells. Azithromycin and other macrolides hold the replication in check. Now a thing to note is that it looks like azithromycin is stopping other rapidly replicating proteins too. So it is possible it isn't the strep, but some other inhibited copy procedure. I'm still looking into whether azithromycin supresses the copying of certain antibodies. If anyone runs across something here, I'd sure be interested. There are a lot of theories about what causes macrolide resistance, but the short summary is that the copying happens in resistant strains whereas it isn't copied in non-resistant strains. They aren't sure whether something keeps the macrolide from binding/interfering or whether the interference only works on certain protein strains. Buster

Some information on ASO and AntiDNAseB titers An intro to ASO and AntiDNAse B: http://www.latitudes.org/forums/index.php?...st=0#entry29305 Some followup comments regarding "what's normal" http://www.latitudes.org/forums/index.php?...art=#entry29305

I've gotten a lot of questions regarding ASO titers and there seems to be some confusion about titers and PANDAS. Hope the following helps: 1) Is PANDAS a reaction to elevated ASO or AntiDNAseB titers? The research indicates no. ASO and AntiDNAseB are responses (antibodies) to exotoxins from Group A Beta-Hemolytic Streptococci. PANDAS is thought to be a reaction to another antibody that's created in response to the streptococci. The theory from Cunningham and Kirvan is that there is a monoclonal antibody that is created that targets a particular carbohydrate sequence on the streptococci. This monoclonal antibody is supressed in most people but for some reason it is not supressed in PANDAS kids. 2) What amount of streptococcus is necessary to cause a detectable rise in ASO and AntiDNAseB? This is unknown. Some people respond with high antibody counts while others have low counts. It is just not understood. Studies in 2003 by Shet and Kaplan indicate that ASO rises in 53% of patients with culturable strep, AntiDNAseB rises in 45% of patients with culturable strep, and either ASO or AntiDNAseB rises in 60% of patients with culturable strep (i.e., 40% don't have such a rise). 3) Does an elevated ASO or AntiDNAseB indicate a persistant strep infection? Apparently not. Some people keep high AntiDNAseB for years. The rate of fall is just not known. 4) Is a high ASO or AntiDNAseB bad? It is unclear, it indicates the body is still producing antibodies to antigens from strep, but PANDAS is likely related to a different antibody and it is not at all clear if the rise/fall of this antibody is linked to the ASO or AntiDNAseB titer. 5) Is there a test for this antibody associated with PANDAS? Not yet. There remains considerable debate about the antibody and whether the antibody causes inflammation or just interference with basal ganglia function. Swedo and others thought the debate over PANDAS would end when the antibody was discovered. Unfortunately, others have not properly repeated Kirvan and Cunningham's experiment and others have had difficulty correctly identifying PANDAS patients. Regards, Buster

Michele, First, I'm sorry that my post was not helpful to your doctor. I have to admit that I too would be skeptical of material off an internet site without doing my own research and cross checking sources. It is very unfortunate that your doctor seems unwilling to see if the material has validity and worse that your doctor seems not to do his/her own research. With some, you might be more effective by getting the underlying papers on PANDAS rather than giving them the summary material (i.e., hand them Madeline Cunningham's paper, Kirvan's paper, Swedo's landmark paper, Kaplan's strep papers, ... we could create for you an extremely good bibliography of the papers we rely on). This is called the "thump" effect. It's the walk in with "here's my papers on this disease, can you tell me what data you are relying on?" Now it is possible that your doctor has read Kurlan's or Singer's papers that came out in Pediatrics June 2008. These papers which use the same underlying data set have, by some, been said to be proof that PANDAS doesn't exist. They absolutely, positively do not say that. But they did show that a group of kids with long term TS, who were likely post-pubescent at time of study (e.g., 13-16), did not have a correlation with strep infections when using a particular definition of a strep infection and a particular measurement criteria. The studies say nothing about onset and nothing about treatment or effectiveness. There are many, many flaws in the studies, but frankly, I think the Kurlan study (that Singer uses his data from) has done more damage to PANDAS kids and their parents than provided any benefit. If your doctor brings up either study, you might need rebuttal arguments -- please see my post at:Kurlan and Singer's Papers At the end of the day, you might find it easier to just get another doctor who will at least look at the literature. As concerned parents, we scour research journals spending endless hours trying to correlate reports on a disease that has been only recognized in the last decade. We too worry about "do no harm" and are constantly trading off the diagnostic benefit versus the harm of every test. I have no good answer to you except to find a doctor who will also spend time researching what's wrong with your child and you can trust with the treatment of your child. Best wishes and thoughts, Buster We did not see completely back to normal results with our dd but a definate huge improvement up and above anything we had seen in a very long time. We saw results beginning on day two but I am not sure that is very common. using

Danuta, We too had the same experience as you for our 7.5 year old. After very bad sudden onset OCD (Anorexia Nervosa, ritual movements, questioning rituals, ...) for 4 months (Feb-June), her symptoms resolved with dramatic improvement after 2 weeks on azithromycin. She was then symptom free for 3 months (thank goodness) with a minor flare up in October. We took her asymptomatic sister in who cultured positive for strep. Once we got her sister treated (used Azith on sister), symptoms resolved once more and we're back at baseline. It might be worthwhile to move the conversation to PANDAS forum. We too are in the "what's next" phase wondering what to do and yet grateful for these periods of calm after a terrible storm. Buster

We tried 3 months of Amox with no effect. Augmentin seemed to help but we had trouble clearing dd's sister of strep on Augmentin. Azith helped dramatically in June. DD's sister caught strep again in October and was cleared again on Azith. Some folks have success with cephalosporins.