Buster

Hi Elizabeth, I can try to answer the question for you based on the research I did on titers -- but I wasn't quite sure of your question. Rheumatic Heart disease and acute rheumatic fever seem to have a genetic component. Multiple studies have shown that the incidence of ARF when there are rheumatic strains of GABHS is about 3-6%. This seems to be a constant regardless of geography or ethnicity. Most conclude from this that ARF is actually a genetic predisposition. About 30% of those who get ARF get Sydenham's Chorea and about 70% of those get OCD. ASO is affected by lots of different things but most notably cholesterol. There appears to be a binding that occurs between cholesterol and lipids that neutralizes the Streptolycin O toxin (see a 1976 paper by Kaplan : http://jem.rupress.org/content/144/3/754.full.pdf) In addition, tubuculosis, liver disease and other diseases can create false positives in ASO. Anti-DNAseB tends to avoid many of the false-postive issues, but has a pretty high false negative rate. In addition, recent work by Kaplan shows that Anti-DNAseB can fall even with active colonization. So the measurement is really just another indicator and not a perfect diagnostic tool. Buster

Johnsmom, The current research indicates that it is not ASO or AntiDNAseB that cause the exacerbation/goofiness. It's good that your son shows an ASO rise when exposed to strep. Many people even with perfect timing of titers do not show a rise. A good paper by Kaplan shows that even with positive throat culture and perfect timing of blood draws, 46% of subjects presented no ASO rise, 55% presented no Anti-DNAseB rise, and 37% presented no rise of either ASO nor Anti-DNAseB So don't worry if your son didn't have a rise in anti-DNAseB -- most don't. You might be asking if it is that bad a test why do doctors trust it. Well actually they trust the combination (i.e., usually either ASO or AntiDNAse B rise in the majority of cases). However, not always. Anti-DNAse B rises between 4-6 weeks post infection. The fall of antiDNAseB is not well studied and some patients have elevated anti-DNAseB for months/years (despite no culturable strep). Please remember that it is not the absolute value that matters. It is the slope. You have to detect a rise in titers. A single value isn't really useful except to tell you to take another value in a week. Bottom line, if you are worried about dh -- get another draw in a week and see if the titer is rising or falling. If it is falling -- then no worries. If it is rising, then he may have had an infection some 4-6 weeks ago. Buster No, antibody titers are not contagious. But, if your husband has strep (active or carrier state) that can affect your son's ASO titers, because exposure causes the immune system to create antibodies- BUT, ASO titers are not the antibodies that cross react with the basal ganglia to cause PANDAS. I'm sure that antibodies are not contagious. And I'm sure that ASO and antiDnase titers are not the cause of PANDAS. My daughter was (is?) a strep carrier and she never had either of those titers elevated. If your husband's Dnase is elevated, it indicates a past infection (or could be current, but you can"t tell current infections from titer levels). ASO and AntiDnase, IMHO, are the most misinterpreted, confusing tests in this whole PANDAS business.

Hi CSP, It sort of depends on what you are using the antibiotics for. The halflife of keflex is 0.9 hours. This means for a standard dose of 250mg, by 8 hours there's about 0.9 mg left in his system. By 16 hours, 0.003mg. There are other metabolites so the numbers aren't perfectly right -- and different people have different elimination (renal) effectiveness, but generally, the reason for the 4x/day is because the half life is pretty short. You might check with your doctor about alternate dosing. Just checking though, if he's in fire school, does that mean he's doing pretty well at this point? Buster

Peglem, I'm sorry, I should have not been so harsh in my comment regarding the doctors. They are doing the best they can with the available research. I'm just frustrated at some researchers who use provocative titles and have flawed studies. It seems like they we're all doing an experiment with our kids with anti-psych drugs when we can't seem to get funding for testing the effectiveness of antibiotics or IVIG for neuropsych symptoms. I'll revise my earlier post to soften the criticism. Buster

I posted this first on October 5th 2008 in response to a number of papers being released. http://www.latitudes.org/forums/index.php?...st=0#entry26571 Our pediatrician forwarded a set of papers to me from the June issue and October issue of Pediatrics saying "these say PANDAS doesn't exist". That is not what the papers say but it looks like people read abstracts or titles and not papers. I thought I'd spend a moment here about the papers, the methodological flaws and the actual conclusions of the papers in case someone brings any of these up to you: The papers are: Kurlan and Kaplan's June 2008 Pediatrics paper entitled "Streptococcal Infection and Exacerbations of Childhood Tics and Obsessive-Compulsive Symptoms: A Prospective Blinded Cohort Study" http://pediatrics.aappublications.org/content/121/6/1188.long Singer's article in the same journal titled "Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections." http://www.ncbi.nlm.nih.gov/pubmed/18519490 Lin, Kaplan and Leckman's October 2008 paper "Streptococcal upper respiratory tract infections and psychosocial stress predict future tic and obsessive-compulsive symptom severity in children and adolescents with Tourette syndrome and obsessive-compulsive disorder." http://www.ncbi.nlm.nih.gov/pubmed/19833320 The first thing to know is that all of these papers are studying the same set of subjects. There are basic recruitment flaws to all three papers. Problems with the papers The papers have 7 major methodological flaws: The studies are about long-term tic disorders in older kids (11-12) and not about sudden onset PANDAS or symptoms in younger kids (mean age 7.5). This is study about children with long term chronic tics who had onset over 3 years prior. 75% of the subjects in the proported PANDAS group were diagnosed with TS (i.e., had symptoms for > 1 year and no remission for > 3 months). The sample is pulled from the longitudinal study by Kurlan reported in the same issue of Pediatrics. The study did not indicate how many of the children had already hit puberty with the massive hormonal and immune changes that occur. Multiple studies indicate that progestrone and other hormones affect the T helper cell regulatory response. Kirvan and Swedo looked at sudden onset in pre-pubescent children and thus if this was not controlled, this brings even more question into whether the sample is valid. The diagnostic criteria used by Kurlan for his proported PANDAS group is not the same as used by Swedo or Snider. Kurlan used a "clinical course characterized by the abrupt onset of symptoms or by a pattern of dramatic recurrent symptom exacerbations and remission". Swedo used an "Episodic course characterized by acute, severe onset and dramatic symptom exacerbations." (emphasis added) While these sound similar, they are not. Indeed the episodic nature is the key distinguishing element in Swedo's studies as is the severity of the symptoms. Swedo wrote in her May 2003 response to Kurlan, "The episodic, relapasing-remitting course of the PANDAS subgroup is distinctly different from the undulating, waxing-waning course seen in other patients with OCD or tic disorders." In addition, Singer discloses that the average onset was over 4 years prior to his study. Kurlan discloses that the onset was not from documentation, but rather obtained through interviews thus being very prone to recall bias. So it is unclear whether the proported PANDAS subjects met the Episodic course, the severe onset, and the dramatic symptom exacerbations of the Swedo critieria. The subjects exhibited no OCD behavioral changes and are different from Swedo's/Snider's subjects The subjects attributed to be PANDAS subgroup in the Kurlan and Singer studies had a CY-BOCS score that changed only 1.6 [-0.4 to 3.6] (i.e., no change) with controls changing 1.0 [-1.1 to 3.1] (i.e., no change). This is hardly episodic given the baseline CY-BOCS scores and certainly does not indicate remission within the 2 year period but rather the small waxing and waning of OCD symptoms and the limited objective accuracy of the CY-BOCS measure. Swedo subjects often exhibited > 15 points of change in CY-BOCS score. Granted, I have some issues with these studies as well, but this 10 fold difference in CY-BOCS measured exacerbations definitely makes one wonder if these are the same subgroups. The subjects have high tic exacerbations but not OCD exacerbations. It is true that the subjects in the Kurlan/Singer studies had YGTSS-tic exacerbations of 11 pts [4.2-17.9] and certainly this is significant, but most of the other papers on PANDAS focus on the OCD element and less on the tics. So this begs the question about whether the study was more about Tourette's and association with streptococcal pyogenes rather than PANDAS. It also begs the question whether Swedo's criteria should include tic-only exacerbations. It also begs the question whether chronic tics are fundamentally different than onset. The subjects were all on numerous anti-psychotic, alpha-agonists, and mood stabilizers. It is totally unclear what these effects had on the subjects and how these variables were controlled. Did this suppress the OCD response? The blind was broken by informing pediatricians if the children cultured positive for GABHS While this is understandable, it defeats the actual study. PANDAS is thought to be similar in pathogenesis (cause) to Sydenham Chorea where symptoms emerge after untreated streptococcal infection. Multiple studies show that treated GABHS infections lower the incidence of ARF and SC. Given the similar pathogenesis, is it a wonder that treated GABHS would not yield increased exacerbations? This is a long way of saying that I don't see how they can reach any conclusion regarding PANDAS given that their kids don't seem to be PANDAS subjects but rather Tourette's subjects. I have numerous other issues including sampling theory problems, but the key question is how many of the kids in Kurlan's and Singer's studies actually had PANDAS as opposed to being kids with severe Tourettes with the unfortunate waxing/waning of tics associated with Tourette symptoms. Best regards, Buster

Last year I went after the underlying longitudinal study here: http://www.latitudes.org/forums/index.php?...art=#entry26571 I raised the following seven methodological issues: This study is about long-term tic disorders in older kids (11-12) and not about sudden onset PANDAS (mean age 7.5). The sample of children were drawn from a Tourette Subject group where children had tics > 3 years with no remission for > 3 months. The study did not control for puberty The diagnostic criteria used by Kurlan for his purported PANDAS group was not the same as used by Swedo or Snider. The subjects exhibited no OCD behavioral changes over a 2 year period and were very different from Swedo's/Snider's subjects The subjects were all on numerous anti-psychotic, alpha-agonists, and mood stabilizers. The study broke the blind and informed pediatricians if the child was positive for GABHS -- PANDAS (like SC) is a sequelea from untreated GABHS -- not treated GABHS It was a very flawed study. So yes, to actually test these kids, you'd need to get kids who aren't currently on heavy anti-psych meds -- you could then check whether antibiotics or anti-psych better control symptoms. Now that's could be an interesting "placebo" test. Do a double-blind cross over study with anti-psych on one side and antibiotics on the other -- oh wait, one of those is pretty dangerous drug with horrible side effects (including activation and carrying a black label for suicide). Maybe we should be careful about prescribing those to kids. Buster

I responded when this article first came out in http://www.latitudes.org/forums/index.php?...art=#entry49411 Swedo's comments are great. Probably, the most important line in her response however, is the one least likely to be understood. She writes: "In PANDAS, as in the model disorder Sydenham chorea (SC), prompt recognition and treatment of GAS infections is effective in preventing neuropsychiatric sequelae. [4]" What Kurlan, Kaplan, Shrag, ... and others are all missing is that PANDAS is thought to come from "untreated" streptococcal infection. This is the critical piece of information in the pathogenesis and what is so darn annoying about Kurlan, Kaplan, Singer papers. The folks at John Hopkins keep writing about kids "treated" for streptococcal infections rather than looking at a population who present with psychoneurological signs and checking if they have an untreated strep infection. I seriously question the reasoning of these folks -- we know that treating GABHS with antibiotics lowers the incidence of ARF and SC. Duh! So to run an experiment to test the PANDAS pathogenesis you either: 1) get a bunch of kids check them for strep and don't treat them -- yikes, try to get that past an IRB 2) get a bunch of kids with psychoneurologic issues and look for a cause -- what Swedo did You most certainly don't 1) get a bunch of kids, check them for strep, treat them and then complain that you don't see PANDAS correlations! -- What Kurlan, Singer, Kaplan ... have done. Arrggh I hope Swedo keeps hammering this point home. Buster

Well, well, well, she speaks... Did you see the incredibly lame response by Gilbert -- not only did he not respond to the criticism from Swedo, but he decides to cite the equally flawed paper by Singer to try to justify his position. A great point in Swedo's paper is that "treated streptococcal infection" does not lead to ARF or SC or PANDAS. It is the untreated strep infection that is the problem. Finally! Buster

In our case, we had a pretty good idea of what to expect the first 2 weeks. I will say that I am deeply indebted to my dw who was confident and patient while I started to worry that IVIG had just made things worse. The first 2 weeks were very much like watching the last 2 years in fast reverse. Things we hadn't seen for over a year re-emerged. I'm not sure which of the myriad of theories to consider as to why this "reverse symptom" stuff happens, but we can attest it does. The thought that her symptoms would return after a fever 6 months later didn't really occur to us. I think we were just feeling so blessed. We did keep her on prophylactic azith, but as I've written elsewhere, azith just slows a bacterial infection, it doesn't in and of itself kill strep. The illness/fever didn't make us think of strep either, so we think it was likely something else. Buster

Hi Joan Pandas Mom, Yes, after 6 months of no symptoms post IVIG, our daughter got sick again with a fever of 102. We do not think it was GABHS but it is difficult to tell. After the fever, symptoms reemerged following our classic exacerbation pattern of escalation for 2 weeks, plateau for 1 week and fall off for 3 weeks. Unfortunately, her remission was not complete post-illness and held steady at the pre-IVIG baseline. We tried increasing azith and had improvement in mood, but vocal tic, handwriting abnormalities, measurement rituals and eating restriction were now part of her new baseline. We tried a prednisone burst and saw some improvement but these were not sustained post-prednisone. I'm sorry to post this news but wanted folks to know. Absolutely we had 6 months of calm and had our daughter back. We really thought we were done -- frankly this is why I started writing everything up (PANDAS FACT sheet, FAQ post, research summaries, ...) because I thought we were putting this behind us. IVIG was incredibly beneficial -- but (at least in our case) a new infection seems to have retriggered the same reaction. Buster

Yes, my daughter in the worst of her exacerbations (pre-IVIG) had left margin drift issues. She'd start her papers in the center of the page and seemed unable to ever get to the left margin. It was really odd. Then each line would be indented to the right. We are now week 38 -- so she has been 11 weeks post start of exacerbation. 7 weeks post peak of exacerbation and 3 weeks from tail of exacerbation. All of our exacerbations are distinct with a 4 week tail -- and yes, we are now at pre-IVIG level. Our pattern is pretty constant, 2 week ramp, 1 week plateau, 3-4 week fall.

Your child's age at IVIG?: 9 Was your child in exacerbation at the time of IVIG? yes What was the dose? 2g/kg spread over 2 days (i.e., 1g/kg/day) Did your child have immune deficiencies at the time? not exactly. PREVNAR challenge failure, but we didn't revaccinate to test. Post IVIG experiences? week1: headache 2 days, fever 1.5 days. Significant irritability, anger, contamination fears, vocal tic, motor tremor week2: very intense "cycling" of symptoms. Bursts of irritation. Intense but short lived. Lashing out, eating issues, handwriting issues. week 3: Sudden interest in school. Social anxiety falls off dramatically. Handwriting improves. Margins improve. New teacher indicates dd9 is "somewhat defiant at school" week 4: Lots of itching. Dramatic fall off in symptoms. Measurement rituals disappear. Some social concerns - hair, glasses, clothes week 5: calm, quiet -- some social aniety when at large family party week 6: more calm -- no rages for over a week. Penmanship dramatically better week 7: calm -- willingly does homework -- is remembering math facts, spelling is eratic. Very playful. Margins are perfect. week 8: calm, happy -- able to brush teeth alone -- first time in 2 years week 9:calm happy -- enjoys schools, wants to play trumpet, slight handwriting issues still, very slight verbal tic week 10: Playful, teacher and other commenting on change week 11: happy ... until week 27: fever, measurement ritual comes back, food questioning returns, ... ... continued escalation at roughly same baseline as pre-IVIG... until now Was it initially worse or as bad as exacerbation? We were in a medium exacerbation at the time, but I'd say it got worse. It was a weird form though. Days were full of very intense symptoms but each event was short lived. Prior events within a mutli-week exacerbation would go on for hours, this was more like 20 min but lots of different symptoms. The first week we worried we had made her worse. It was seriously like looking at her on fast reverse. I want to stress to you that everyone has slightly different results. I remember hearing about the "turning back pages" and it gave me hope in that first intense week. As a comment, really encourage alignment with your spouse. It helped me that my dw was confident it would get better. First week was tough for us. Buster

It certainly is true that inflammation is a heck of a lot easier to understand than interference with feedback loops. To me, disregulation of dopamine and serotonin makes a lot of sense but only if I phrase it that way rather than talking about phosphorylation :-) Buster

Arggh, yes, I cut and paste and meant to write tyrosine hydroxylase -- catalyst for epinephrine/dopamine and tryptophan hydroxylase -- synthesis of serotonin Sorry about that. I'll go back and edit my post Buster Hey, hey now Mr. Buster , you made me go back and rethink tyrosine hydroxylase (i was looking at skin stuff and you pointed out the connection with CamK and dopamine) now your messing with me throwing tryptophan in here too. So it looks like CaM k activates tyrosine hydrox/ andtryptophan hydrox, correct? Now this speaks of post synaptic density and the hippocampus/forebrain, but still http://www.bioreagents.com/products/produc...?catnbr=MA1-048

In our case Ibubrofen had a noticable improvement. We saw no such improvement on naproxen or acetaminophen. By the way, acetaminophen isn't an NSAID because it isn't anti-inflammatory.

Simple question, I wish I had a simple answer: Cunningham is measuring the ability of antibodies in serum (or CSF) to cause CaM Kinase II activation in neuroblastoma cells. It isn't the amount of CaM Kinase II (which is a protein), but rather the ability of the antibodies to cause state changes in CaM Kinase II that leads to state changes in neuroblastoma cells. The first measurement is about the state change in the CaM Kinase II protein. CaM Kinase II activation affects the presynaptic transmitter release, phosphorylation of tryptophan hydroxylase (think catalyst of serotonin) and tyrosine hydroxylase (think catalyst for precursors of dopamine). In addition, Cunningham was measuring whether antibodies inhibited binding of other chemicals to tubulin, dopamine receptors, or lysoganglioside receptors. This is known interference. It is an independent measurement from CaM Kinase II -- although there may be a correlation between the two. The measurement they are doing checks whether the antibodies bind to the receptors first inhibiting the binding of other chemicals (such as dopamine) to bind to the receptors. http://books.google.com/books?id=az8uSDkB0...nin&f=false Another hard question. What is thought to happen is that children with PANDAS (and SC) generate several unusual antibodies. Kirvan was able to isolate at least three of these antibodies in her studies. These antibodies do not seem to be present in non-PANDAS children -- but it is difficult to run experiments looking for just the single antibody -- so they looked for the effect of the antibody that could be measured. One effect effect they found was CaM Kinase II activation. Only further experiments will demonstrate whether the increased CaM Kinase II activation is exclusively due to the antibodies, whether these antibodies are unique to the genetics of SC and PANDAS kids or whether they are byproducts of something else that is going on. There are some studies indicating localized swelling and this could come from macrophages or T-cells on the brain side of the BBB finding bound antibodies and releasing inflammatory cytokines. Some researchers think the basal ganglia is like a ball of rubberbands where the inflammation causes cross-talk as the rubber-bands slip and this is what's causing confusion and mis-signalling. Cunningham's work is pursuing a slightly different perspective that perhaps it isn't swelling but rather the antibodies actually cause interference by binding to some of the dopamine receptors causing mis-signalling because the real signal can't get through. Hope that helps... Only further research will tell who is right.

This is very true and more than one parent has commented on feeling weirdly happy when their child was diagnosed with PID -- i.e., that they could get a treatment that might help both diseases -- whether related or not.

I'd imagine folks are using "hyperimmune" to be like allergies where some people have very intense antibodies/histamine/inflammatory cytokines response to an antigen -- i.e., react more to one type of antigen. I'd imagine that IgG deficient would be that you don't react to some other types of antigen (such as PREVNAR). There's an expected baseline of background antibodies that most people have and those who don't have these antibodies have a hard time clearing infections. Bottom line, yes, I think you can have an extreme reaction to one type of antigen and a low response to other types of antigens.

This may end up being a really complex thread by the time we're done Not quite -- being lawyer-ly specific, "ASO and Anti-DNAseB measure antibodies to two exotoxins of GABHS. Dual measurements taken 1-2 weeks apart by the same laboratory using the same technique will tell you if the antibodies are rising. Based on current science, only a rising titer is meaningful. The rate of fall or the meaning of a constant titer is not understood. Some individuals have chronically elevated titers with no other symptoms of GABHS. Some individuals have falling titers despite colonized GABHS. Thus a rising ASO and/or Anti-DNAseB can only confirm a prior strep infection and says nothing about whether there is a current infection. Yes ASO and Anti-DNAse B are not anti-neuronal antibodies. Kirvan and Cunningham isolated 3 anti-neuronal antibodies and found one of the 24.3.1 to have significant binding potential with dopamine receptor 2. Yes, but there's a danger in misreading this. IgG is a measurement of the amount of proteins associated with a class of antibodies (the most prevalent) and therefore is a rough estimate of the amount of active antibodies. It is not a measure of B-cells (plasma cells) or T-cells and does not measure the ability of the body to produce antibodies. Absolutely no way to tell without trying to test the concentration -- to an extent that is what Kirvan and Cunningham were doing by testing the concentration of antibodies that bind with certain receptors -- this is known as dilution. They are trying to measure the concentration of a particular type of antibody either in the CSF fluid or in the blood serum. No idea. My first reaction is nothing. Buster

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Hi FiveAm, On the post puberty, no one really knows. By puberty, most kids have strong immune responses to GABHS and other illnesses and the incidence of GABHS drop off significantly. Peak prevalence of GABHS in children is between 5 - 10 years of age. So one of the items being measured could just be less exposure. If you are having creatinine level changes, you should be paying very close attention to whether your child is eating appropriately. Anorexia Nervosa is associated with PANDAS and was the primary scary symptom in our case. Go after this really aggressively as this is absolutely life threatening if your child's body weight is dropping rapidly. Not kidding, this is nothing to mess around with. Onset of Anorexia Nervosa and restrictive eating in children < 10 is extremely rare and almost always medical in cause. Whether Anorexia Nervosa in children between 10-17 is also medical in cause is unknown -- but AN is an OCD manifestation. The obsession can literally kill the child. I don't want to be alarmist and perhaps you were asking a more innocent question (or your child is older), but if this is Anorexia Nervosa or Bolemia get on it immediately. Buster

Hi Jag10, I think this question comes up a lot and I've been debating whether to add it to the FAQ. A number of kids (10% or so) with PANDAS symptoms do seem to have low IgG -- but this could be just a sampling issue - i.e., we're looking for stuff so we're just finding the normal distribution of PID and SID in kids. It's not at all clear whether there is anything causal here. Let me try to explain: PANDAS appears to be the result of three things: a genetic predisposition to an unusual immune response an activation of T-cells that binds with a memory B-cell to create anti-neuronal antibodies a breach of the blood-brain barrier that allows the antibody to reach the basal ganglia These three items are also seen in Sydenham Chorea. The genetic predisposition (1) is pretty clear. About 1% of children exposed to rheumatic strains of GABHS get Sydenham Chorea. This rate seems to be true regardless of ethnicity or geography -- i.e., it's a genetic trait. Kirvan and Cunningham did a good job at isolating the antineuronal antibodies (2) and showing they are elevated in both SC and PANDAS kids. The exotoxins of strep are pretty good at explaining the inflammation that might breach the BBB (3) -- however, there's not a great explanation for why SC happens 6 weeks after the clearance of the GABHS infection -- perhaps this is really the time it takes to create a memory B cell. So what does all this have to do with IgG.... well, IgG levels are more measurement of current antibody levels and the anti-neuronal antibodies are just a drop in the bucket of all the antibodies in the IgG. What seems significant about IgG is that people who have low IgG or low PREVNAR levels have a higher probability that the GABHS infection will last longer and that the GABHS exotoxins will activate the B-cells associated with SC, ARF or PANDAS. This is why doctors treat GABHS with antibiotics, to shorten the time the infection is in the body. So you might be wondering why longer duration of GABHS increases risk of activation... well ... GABHS has really powerful exotoxins that are known as super-antigens. A super-antigen can activate T-cells and B-cells that have nothing to do with the current infection. In particular the B-cells that produce the anti-neuronal antibodies could be activated by one of these super-antigens. There are about 25 of the super-antigens known so far. If you have a predispoisition to creating anti-neuronal antibodies (1) and you have low IgG and aren't able to clear GABHS infection, then the GABHS exotoxins could be triggering the B-cell to create the anti-neuronal antibody (2), the inflammatory cytokines then open the BBB (3). About here, someone is likely to be asking about non-GABHS infections (i.e., PITAND) -- well, yes indeed, another infection could have super-antigens (i.e., activate T-cells that have nothing to do with the infection) and could easily be causing enough inflammation to allow the existing antibodies to cross the BBB (3). Now flipping the whole thing around --- For children who have normal IgG or even hyper-active IgG/IgE -- they seem to be mostly affected by the inflammation. I've been trying to find if anyone has been running cytokine panels and no luck yet. Seems peopel check SED rate, and C-reactive protein, but what we'd really like to know would be IL-1 Beta and other such immuno complexes. Anyway, the high dose IVIG being highly anti-inflammator could just be closing the BBB and thereby breaking the auto-immune cycle allowing the anti-neuronal antibodies in the blood to dissipate -- i.e., high-dose IVIG closes the BBB (#3) and breaks the cycle. That's what I think is going on. Let me know if I should try to write up more here.... I'm wasn't sure if you wanted to know more about asymptomatic strep or were really curious about IgG levels. Buster

It's a little difficult to answer your question based on the numbers I've got. The prevalence of Selective IgG Deficiency seems to be 1 in 10,000--however, the reports are all over the place here and not specific to children. Primary Immune Deficiency is about 1 in 1200 (in the US where we run such tests) but again, no statistics on children. The rate of neuropsychiatric symptoms comorbid with these disorders does not seem to be common enough to be listed as a known symptom. This indicates that PID and SID are likely comorbid rather than causal. What I've seen so far in the reports on this forum is about 10% of the cases reported have true "low" IgG, about 20% have IgG subclass 2 levels at the low end of "normal" -- however, this is extremely selective reporting because folks who have normal results on the test usually don't post. My belief is that PANDAS is a result of three things: a genetic predisposition to an unusual immune response an activation of T-cell that binds with a memory B-cell to create anti-neuronal antibodies a breach of the blood-brain barrier that allows the antibody to reach the basal ganglia The exotoxins of GABHS are superantigens and tend to activate T-cells not specifically oriented toward GABHS. So for individuals with a genetic predisposition (1), the longer GABHS is around, the more likely the wrong T cells and their corresponding B-cells will get activated generating the anti-neuronal antibodies (2) and the exotoxins are quite inflammatory causing (3) the breach of the BBB. For those folks who have trouble clearing streptococcal infections (i.e., have low IgG), they have an increasing the risk for activating the B-cells that create the PANDAS antibodies. Thus low-dose IVIG helps these folks clear strep infections and stay healthy (preventing the PANDAS cycle). For other people who have normal IgG or even hyper-active IgG -- they seem to need help closing the BBB (#3) and thus high-dose IVIG is being used to reduce inflammation. Sorry I can't be more definitive here. Buster

Well, in our case, the dosing was 1g/kg/day which would make 26g for that day. They were dosing 18g and had read that it was .5g/kg/day with 1kg/kg total. So when I looked at the bottle and it said 100ml Gamunex 10% and second bottle was smaller of 80ml and the tag said 18gm total -- it was sort of obvious. Then when the nurse came in and said we need to do a saline flush at the end, I said "you mean Dextrose 5%" and she said "oh, right you are using Gamunex." It was very very busy there but when things are busy, I get a bit hyper vigilant -- I'm sort of protective in a bear sort of way. Buster How do you know?

I'm sure I make the nurses nervous -- I'm sort of a detail guy :-) Just too many stories of screw ups so I check everything. Buster