Buster

Reply to Fuelforall moved here: http://www.latitudes.org/forums/index.php?showtopic=8252

I agree with LLM, take him in for a strep test. You might want them to take a urine sample to check for a bladder infection too. It is unlikely to be positive given the symptoms you mention. Do you have other siblings in the house? If you can it would be great to get them also tested. At our house, symptom exacerbation was correlated with sister getting strep - i.e., symptoms showed up before colonization or infection in dd. Exposure seemed sufficient. Regards, Buster

Hi Brandy, PANDAS is thought to be caused by three things: a genetic predisposition to an abnormal immune reaction the creation of antineuronal antibodies as a response to an antigen (i.e. GABHS) ability of the antineuronal antibodies to cross the BBB (e.g., due to inflammation or high blood pressure or ...) The exact mechanism in #3 is not known, but inflammation seems the most likely culprit. Abnormal levels of eosinophils are common in those with allergies (and asthma) and these cells degranulate to release an array of cytotoxic granuals and inflammatory cytokines ( IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, and TNF alpha). If the anti-neuronal antibodies are still in the blood stream (they seem to have a half-life of 28 days), then eosiniophils and other diseases that increase inflammation of the endothelial cells can allow these to cross the BBB. This is why symptom exacerbation could be due to other sources of BBB inflammation -- not because they produce the antineuronal antibodies (i.e., not #2), but rather because they allow the antineuronal antibodies to cross the BBB. So to your question about antibiotics. Some antibiotics (such as macrolides) are anti-inflammatory and immunomodulating. They tend to shift the immune reaction from Th2 to Th1 response reducing inflammation (i.e., address #2 above). Azithromycin falls in this camp. There have been reports on this forum that high-dose augmentin is also anti-inflammatory but I don't have a good reference study there. What might be happening (just a guess) is that augmentin is acting to stop residual spread of a GABHS infection, reduce the superantigens that creates significant inflammation, and by treating this underlying trigger, reduces the antineuronal antibody production such that there isn't anything in the blood to cross the BBB. It is important to remember that antibiotics don't kill GABHS, they essentially prevent rapid spread of bacteria so that the bodies immune system can eradicate the bacteria. If your child's exacerbations don't seem to correlate with GABHS/mycoplamsa infections/exposures then probably other treatments might work better. For those who do have correlation with GABHS exposure/infection, antibiotics seem to keep the severity of symptoms in check. More research is needed to know for sure, but that's what we think at this point. Buster

Hi Karmen, The CaM Kinase II is consistent with the range other PANDAS children have had. At this point, there isn't enough data to say that high CaM Kinase II is exclusive to SC or PANDAS. However, if you have other clinical reasons to suspect PANDAS then the high range would lend more weight to the diagnosis. The anti-D1 was just barely elevated (i.e., one dilution out of normal). Otherwise the other values are in range. Has your child had significant symptom changes with infection? Do antibiotics help him with his "brain bully". Wishing you the best. Buster

They probably ran the wrong test or were checking for SLE. Anti DNA DS is a test for Lupus. It is not the same as AntiDNAseB. ASO rises between 1-4 weeks after a strep infection in about 54% of children. AntiDNAseB rises between 6-8 weeks after a strep infection in about 45% of children. The 4/23 would fall within the timeline for a rising ASO on 5/10. If the actual infection was the week of 4/23, you'd be at the limit of AntiDNAse B now but you certainly can check. Risperdone modulates dopamine essentially smoothing out spikes. Did your doctor prescribe this for tics or for bipolar or for some other condition? It sounds however, like it has been helpful in your case. I ask because in about 10% of cases Risperdone itself causes tremors in hands, headaches and insomnia. So I guess I'm checking if the tics preceeded the medication. How old is your child? Therapy generally requires insight to be effective. Buster

There is a ton going on in your post. Starting with the CaM Kinase II, I think peglem was another case with extraordinarily high CaM Kinase II but normal results on everything else. I too was confused here as I thought that the antibodies isolated by Cunningham (such as 24.3.1) were also anti-lysogangliosides. However, it appears that there are other antibodies in the serum that can cause CaM Kinase II activation that aren't anti-lysoganglioside. I'd recommend writing to Dr. Cunningham to ask about it if you are concerned. PANDAS is really diagnosed by clinical symptoms. The elevated CaM Kinase II appears to be significant at separating cases (based on the research by Kirvan and Cunningham), but the anti-lyso, anti-tubulin, anti-D1, and anti-D2 are not yet correlated. My guess is there is something else in the serum (i.e., another antibody) that is causing the elevated CaM Kinase II and this is just not one of the antibodies tested for by the other 4 tests. Regards, Buster

Chorea typically refers to writhing motions. In terms of choreiform movements, these refer to fine piano playing movements when a child is put in a stressed stance with arms extended, eyes closed and tongue exposed. More info can be found here http://books.google.com/books?id=l9wtYZ_iC...ed=0CCAQ6AEwBw#

Do you have a link to that paper? My daughter's psychiatrist is interested in PANDAS in a let's-see-how-this-all-turns-out kind of way and I think that study would be something she'd like to see. Not that anybody can get a ybocs score on my kid, but she does have other patients. Here's one you can use [Murphy2004] Murphy TK, Muhammad S, Soto O, et al. "Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics", Biological Psychiatry, Volume 55, Issue 1, Pages 61-68, January 2004 http://www.journals.elsevierhealth.com/per...0704-2/abstract

I'm presuming you got your answer -- I'm curious if you got a throat culture during the flair up. You seem to be running blood work but I didn't see any cultures. Presuming you had the tests run by the same laboratory, the ASO would indicate that somewhere around Feb 27th-May 1st your child had a strep infection. There's only a single measurement of of AntiDNAse B so the single result is not clear whether it was rising or falling. The High IgG value of Mycoplasma AB would indicate that your child did have mycoplasma pneumonia in the past, but it's not clear whether this is a recent infection (due to the low IgM). Buster

Apparently dosing above 1.5 g/kg is highly anti-inflammatory. In terms of tics (or OCD), no easy way to know between #2 (immune supressive) and #3 (anti-inflammatory). IVIG is just too blunt a treatment to discern. Prednisone also affects both #2 and #3. Dr. K uses prednisone burst as a check to see if IVIG might be effective (i.e., if prednisone is effective, IVIG is likely more effective). Buster

Hi Tapiash Well PANDAS is thought to be caused by three things: a genetic predisposition to an abnormal immune response an immune response to GABHS that produces anti-neuronal antibodies a breach of the blood-brain barrier that exposes the anti-neuronal antibodies to neuronal tissue In PITANDS replace GABHS in #2 with some other antigen. When your doctor is referring to anti-inflammatories and immuno-modulation, they are taking about addressing #2 and #3. Anti-inflammatories can help address #3, and immunomodulation can help address #2. Azithromycin is both an antibiotic and is immunomodulating. In addition to suppressing growth of gram positive bacteria (such as GABHS) it also shifts something called the Th2->Th1 response. Essentially this changes whether the body produces stuff that goes after bacteria or stuff that goes after infected cells. Curiously this shift also affects inflammation. Other anti-inflammatories are things like Advil - or Non-Steroid Anti-Inflammatories. Predisone is a steroid anti-inflammatory and immunomodulating. IVIG in high enough dosage is also immunomodulating, immunosuppressive and anti-inflammatory. Your doctor should be able to explain the rationale for any treatment and it sounds like you have one well informed. Let me know if this just creates more questions. Buster

Hi Fuelforall, Can you post your actual numbers? The antilysogangliosides should have tapped out at 1280 -- at least the way that Cunningham usually runs the tests. She's testing in dilutions of 1/2 -- so 10,20,40,80,160,320,640,1280 Similarly on anti-D1 she's testing (I think), 125, 250, 500, 1000, 2000, 4000, 8000, 16000 In general, no, IVIG does not directly address the anti-lysogangliosides. However, they may be affected by IVIG. IVIG is a very broad treatment having lots of effects -- it is not a precise treatment. From the literature, IVIG is thought to have 3 main effects: IVIG at larger doses is highly anti-inflammatory -- if the tic/OCD are due to antibodies crossing the blood-brain barrier, IVIG could help close the BBB IVIG brings new antibodies that can block T-cell activation -- this is sometimes called regulatory -- it is immuno suppressive IVIG also adds new antibodies that can mark bacteria/cells. This is helpful if your own body can't recognize the disease (can create the antibody). #3 is really more around people who can't raise a response to certain antigens. #2 suppresses a response. #1 reduces inflammation. What Cunningham has published on is the reduction of CaM Kinase II post PEX/IVIG -- she hasn't published on the anti-lysogangliosides yet. Essentially, we don't know what the antiD2, anti-D1 or anti-lysoganglioside #'s mean yet. Cunningham tests are more confirmatory rather than diagnostic at this point. Buster

You're making me blush - but thanks for the kind comments -- y'all can stop now. My purpose in writing the article was to overcome some of the information that was in a previous article that was based mostly on the out-of-date NIMH website. Hope others will write papers too and get more color to the disease out there. The item that I'm finding time and time again when talking with various researchers is that they have never heard of the +17 pt change in CY-BOCs scores in the OCD symptoms of PANDAS -- I point them to Snider's early papers and they are a bit surprised. In our case we definitely had the jump from slightly nervous kid to full on psychosis. Buster

Hi Peglem, As always, you have great questions. In 2003, Kirvan and Cunningham isolated 3 antibodies in Sydenham Chorea children. These are known as 24.3.1, 31.1.1, and of course 37.2.1. What was unusual about these monoclonal antibodies is that they bonded with lysoganglioside GM1. Kirvan and Cunningham \ showed that these antibodies were absent in convalescent serum, but present during exacerbation. It also turns out that 24.3.1 not only bonded with lysoganglioside GM1 -- but also was sufficient to cause CaM Kinase II activation. Kirvan was sure it was just 24.3.1 because she had gotten rid of all the other material that wasn't 24.3.1. In the current test that Dr. Cunningham is running, I don't believe she isolates the three antibodies but rather is checking the broader category of any antibody (or substance) in the blood serum interacting with the lysoganglioside substrate. An unusual property of 24.3.1 is that it is targeting the GlcNAC epitype (i.e., the carbohydrate on the cell surface of GABHS). However, your point is really valid, do we know that GABHS is the only trigger of 24.3.1? The answer is no. That causality is not shown. So we don't know why 24.3.1 emerges, but there is good evidence it is present in SC and PANDAS children after a strep infection and not in controls. That is not causality, just co-existant. When Dr. Cunningham is running the ELISA, she isn't doing the full antibody isolation, but rather using the serum in the manner of my post. This means there is a potential that something else in the serum is causing the reaction, but I and others have contacted Dr. Cunningham about this and so far none of the things we've mentioned seem to affect the results. I was probably the one starting the question on whether kids on SSRI have higher anti-D2. It made sense to me especially since kid's serum could have elevated serotonin levels. I asked Dr. Cunningham about this and she was checking this and the impact azith might have. I don't know the outcome of that check. Best regards, Buster Do they know what it is in the serum that is interfering w/ the bonding? I mean, how do they know its from strep and not something else? And wasn't there a correlation between kids on SSRIs having high antiD2? Could the SSRIs be interfering with the dopamine receptor, instead of an antibody? I hope I'm asking that right.

Hi Tenacity, Your point is a good one. It was hard to know where to draw the line in the article between the personal experience, the clincial symptoms, and explaining the known and projected pathophysiology. In our case we had exacerbations with Fifth's disease and recently with a fever with unknown cause (likely viral), but it was hard to weave into the article. What I hope other parents will do is help get their stories out there. Kaplan says routinely, "observe in the field explain in the lab". This is really the power of writing up the stories and sharing them with folks like Diana P. and others where they can get the stories in front of the researcher -- sort of the "see there's more here than you thought." I've started a couple times to write up a PITAND fact sheet (to parallel the PANDAS fact sheet) but haven't finished it yet. I keep hoping for some breakthrough in pathophysiology research that I can add into the write up. Regards, Buster

That was exactly why I wrote that part. Many researchers say that because there isn't any carditis it isn't life threatening -- actually Kurlan uses the word "benign" -- arggh. Clearly never lived with one going through this. My point was we already know that untreated rheumatic strains of GABHS cause acute rheumatic fever. There is no debate on this. So why on earth are we putting kids at risk who culture positive for strep? Buster

Hi Tapiash, I can try to explain the titers, but what they mean isn't quite known yet. Dr. Cunningham is running what is known as Competitive Inhibition ELISAs -- this is a fancy term for seeing who gets there first. While not perfectly the same, this is sort of similar to what happened when you did titration experiments in high-school chemistry. What they do is take a substrate of a chemical like a "lysoganglioside". And then have a known quantity of a chemical that changes colors when it binds to the lysoganglioside. They choose the concentration of this chemical to create a pronounced change in the tube. If there was none of your serum added, and only the chemical added, the tube would change colors. Now they take your serum and start diluting it by powers of 2 into each tube. In this way they have very weak concentrations and very strong concentrations. They first add this "diluted serum" and then try to add the "color change chemical". Since the diluted serum is already bonded to the lysogangliosides there's no room for the color changing chemical to attach and so the color doesn't change. They keep diluting the concentration of serum until there's a color change. So the number being reported is the amount of dilution needed before the serum didn't "interfere" with the color change. So 640 and 1280 are just one dilution away. So too are 8000 and 16000. Generally they don't look closer. In terms of your numbers, the serum interfered a bit with lysogangliosides (slightly elevated), was within norm for tubulin, was slightly elevated for anti-D1, and normal for D2. Beyond that, we don't know a lot more. Probably more than you ever wanted to know and not what you actually wanted to know... Buster

I wrote an article for the Latitudes online newletter to provide a parent's perspective on PANDAS. Sheila was kind enough to forward me the link to an external website that picked up on the article. The external website asked Sheila for rights to repost the article. I like that it both linked back to the ACN forum and made the article available at this URL. http://www.foodsmatter.com/asd_autism/misc...les/pandas.html Buster

A month ago, Kim posted Swedo's reply to Gilbert and Kurlan's letter about Zebras and Horses (see http://www.latitudes.org/forums/index.php?...art=#entry65250 ) I've been fuming since then... Not about Swedo's reply, but rather why those trying to disprove the PANDAS hypothesis forget that it is untreated streptococcal infections that give rise to Sydenham Chorea and acute rheumatic fever. Experiments on treated streptococcal infection show that antibiotics are effective in preventing/minimizing severity of recurrance -- hello, that's why they do prophylaxis for patients with Acute Rheumatic Fever... So a question, and I'm serious, is this really not understood? I just can't believe that folks are running 2 year longitudinal studies and failing to control for whether someone is treated or not for streptococcal infection. It still amazes me that they broke the blind and told the pediatrician whether the child had strep -- rather than having that be an independent check by the pediatrician. Buster

Here's one I put together where I tried to keep it simple... http://pandasdad.home.comcast.net/what%20is%20pandas.pdf I also strongly recommend the school nurse news article: http://www.schoolnursenews.org/BackIssues/.../pandas0903.pdf Somewhere around here I have a more technical presentation with all the references and documentation as per the PANDAS fact sheet. But I think the above ones are effective. See if this helps. Buster

Hi Isabel, This paper is unusual for several reasons. This was an institutional study that happened to be sampling children for GABHS infection and detected an outbreak of an epidemic that did not cause symptoms of strep throat. This meant 47 of 50 children had culturable strep, but the children did not have a rise in ASO or Anti-DNAse B. This result could be treated two ways. Either colonization is all that happened (i.e., no infection), or an infection occcured and the bacteria did not produce significant amounts of Streptolycin O or DNAse B. The result was surprising because instead of only 20% of the children getting "asymptomatic carriage" 80% had asymptomatic carriage. What was also surprising was that while the culture revealed that strain was one that is normally invasive (M-11), none of the children (barring one) had antibodies to that particular strain -- i.e., it doesn't look like the colonized M-11 actually invaded. However further study showed that there were antibodies to another strain derived from a common parent of M-11 (how they figured this out is not disclosed). This other strain lacks the M-protein. Other researchers had found this type specific antibody to the "base" type seemed to only occur in those with carriage and not in those with symptomatic response. This seems to indicate that some transformation to the M strain occurred in each child . Another interesting item was that when the M-11 strain was isolated it produced very little streptolysin O but produced significant amount of DNAseB. There was clearly something odd about the strain or something that was keeping the strain in check. Kaplan had found in other studies that other bacteria in the throat could hold strains of GABHS in check, he also found that in certain individuals, the M-protein is not replicated (i.e., the strain changes type within a person with carriage -- a form of mutation). It's unclear whether that was occuring in this case. Perhaps the most interesting comment in the paper is the sentence around "benign pharyngeal acquisition". They write "Despite increasing evidence for the occurrence of "benign" pharyngeal acquisition of Streptococcus and the absence of an association of nonpurulent complications with this entity in contrast to the high risk of such complications with symptomatic disease [2, 3, 5, 14, 15, 27-29], it is premature, at this stage of our knowledge, to use these data as a basis for not treating patients with mild streptococcal pharyngitis." What this says is that there is a lack of evidence that carriage is actually benign. Kaplan says this too in his paper about carriage being an enigma. Furthermore the authors of this paper highlight that in studies of recent increases in acute rheumatic fever, many who got the disease had no recollection of a preceeding sore throat. I realize that the above is probably more than most want to know, but: The bottom line is that if you get a positive throat culture, treat it. Buster

Could be a lot of things. It's possible he's gotten a viral infection of some sort. Prednisone essentially makes you more susceptible to such stuff. His immune system should be back by now so it's probably fighting it off -- if that's what it was.

Hi Jag10, Well, yes, I do collect data and stare at it thinking it will tell me something -- most times it doesn't Based on Shep and Kurlan, the absolute value of any of the titers is not as important as the direction. Since most people do not have an initial value to compare against, they use what is called the upper limit of normal as if that was one of your prior readings. Let me try by analogy, have you known anyone who gets big welts to a mosquito bite whereas others have only a small bump? Well, that's sort of what is happening here. Some have huge reactions to the exotoxin DANse-B and others don't. Some people produce tons of antibodies (3000 IU per ml) while others don't. This is why kurlan uses direction -- i.e., by analogy is there a bump. He doesn't look at the height, just that it got bigger or smaller. Hope the analogy works. Buster

Well, sort of. ASO is neutralized by certain lipids. GABHS on the skin does not tend to cause an ASO response as the Streptolycin O is neutralized by the skin. There seems to be some concern in your post about the higher Anti-DNAseB levels. If they are rising then there was likely an infection in the prior 8 weeks. If they are falling then who knows. If they are constant -- no one knows. Only a rising titer is informative. Generally a throat culture is preferable to taking blood titers. Use of blood titers is really to confirm a prior suspected strep infection in the prior 1-8 weeks. Are you concerned that your dh is still positive? The odd are that his titers are falling from a prior infection. Buster

Hi folks, thought I'd jump in for a moment. You probably are both right. PITAND doesn't require an initial streptococcal infection based on the definition from Allen and Swedo in 1994. However, they basically didn't study it and started restricting their study to anything that seemed repeatable and found that GABHS was correlated with the OCD symptoms seen. What's a bit unusual about GABHS is that it produces super antigens -- these things can trigger immune reactions from T and B cells that weren't specifically targeting the antigen. Other bacterical infections can do this too. GABHS has 17+ known exotoxins -- other bacteria have a bunch of them too. So what might be going on is that there is a humoral B-memory cell that is waiting around for neuronal tissue and gets activated accidentally by one of these infections and with a bit of inflammation is able to find some actual neuronal tissue and a feedback loop starts. Now on the question of titers -- the study by Kurlan and Wannamaker indicates that ASO and AntiDNAseB titers fall at radically different rates in people. Some people the values will return to undetectable levels and some people will retain a background of antibodies. There is no good research on why this happens. Most children under the age of 12 will have 1 strep infection every 2-3 years. yes, some will escape, but if you are in a district like ours, the notices come home almost weekly in the winter with 5-6 kids per class getting wiped out. Labs have different values of "normal". For example in one study, kids not suspected of GABHS strep in the 5-10 year range, had 48% had titers below 100 6.8% had titers of 100 10.6% between 101-125 7.6% between 126-156, 22.1% between 157-195 and 4.5% in 196-244 The bottom line is that most tests cannot test for memory B-cells that would show a prior exposure to streptococcal infection. Certainly ASO and AntiDNAse B do not test this but rather whether there are active antibodies not the potential of remembered antibodies. This is why if you are checking for resistance to PREVNAR vaccines or other stuff, you have to essentially re-expose (like with a revaccine) and then check levels to see if the memory B-cells took. You can't use negative ASO or AntiDNAseB to make a statement about prior strep. After an infection they can return to zero or in 33% of cases never rise in the first place. Let me know if that doesn't make sense. Buster