Buster

Hi NeverGiveUp, Were the symptoms different and escalating? The accuracy/senstivity of the tests is not known (i.e., variances seen as high as +/- 10%) so your two numbers above could both represent a true result of 150. Cunningham's lab rechecked our serum and on same serum we got 183 one time and 170 another. Regards, Buster P.S. We did test ANA and they've been normal.

Sorry about that. I put too many things in the explanation :-(. I revised the post, see if it makes more sense now . I'll post material on Treg separately. Regards, Buster

We have heard it more as "turning back the pages" and in our case this accurately expresses what was happening. We keep a daily journal and plot symptoms from the week. Since IVIG, it has been like flipping backwards through the journal. Symptoms that were there over 6 months ago have suddenly emerged and then passed just as quickly. The only remaining symptoms are: a slight verbal tic some social anxiety some separation anxiety Even these are now substantially reduced. Regards, Buster

-edit, wrong post

(revised) There are a couple explanations that seem to make sense to me on the "turning back pages" Inflammation? There is a theory that the anti-neuronal antibody causes inflammation of the basal ganglia. Under this theory, PEX reduces the antibody causing the inflammation, IVIG has significant anti-inflammatory effects and might get rid of the antibody, and prednisone has strong immunosuppresent behavior. So the theory here would be that as the inflammation goes down and the symptoms that emerged on the way up re-emerge on the way down. Concentration of antibody? A second explanation is that PEX and IVIG reduce the concentration of anti-neuronal antibodies in the blood and PEX, IVIG and prednisone all three are anti-inflammatory and help close the Blood Brain Barrier (i.e., preventing any remaining antibodies from getting to the neurons). So with fewer antibodies getting to the brain, eventually the antibodies stop binding to the dopamine receptors and the proper signals can get through. This is similar to having a lot of static on a radio and then having that static removed. So turning back the pages could be either a result of reduced inflammation or a result in the concentration of the anti-neuronal antibodies. What for me is interesting is that prednisone seems to have such an effect -- this seems to imply that inflammation (particularly of the BBB) is part of what is going on. I'll add a separate post about Treg cells as I think I confused folks enough with the above :-) Regards, Buster

Keeping our fingers crossed too... You're about 4 weeks behind us.... Wishing you the best, Buster

Hi Faith, I'm not sure what to say... there seems to be three camps: 1) PANDAS -- exacerbations of OCD and tics are related to auto-immune problem where an antibody is initially created in response to a GABHS infection. Unlike SC, the antibody does not appear to interfere with joints or heart muscle but rather interferes with neuronal tissue if there is a breach in the blood brain barrier. 2) chronic tic disorder -- probably isn't this since you have said there is a vocal tic. 3) Tourette Syndrome -- motor and vocal tic for > 12 m with no remission for > 3 months 4) TS/OCD -- Tourette Syndrome with comorbid OCD or Obsessive/Compulsive Symptoms 5) PANDAS triggered TS/OCD -- Tourette Syndrome that has a temporal association with GABHS (huge debate) Seems like your child falls into the 3, 4 or 5 category. Now #5 has huge amount of debate with Singer being on one side and a number of others being on the other. The key question is whether PANDAS left untreated becomes #4 or #5. This sure has a bunch of researchers having conflicting results. Kivan in her 2006 study indicated that controls with classic tics had lower CaM Kinase II activation and low anti-lysogangliosides and were distinguished from kids with Sydenham Chorea or PANDAS who had high anti-lysogangliosides and high CaM Kinase II. The key question is that if symptoms don't seem to improve on antibiotics and don't seem to get worse with GABHS infection are they unrelated to GABHS or are the antibodies so intense that a temporary addition of GABHS or relief from GABHS doesn't change the impact on the basal ganglia. Singer seems to be set to prove #5 doesn't exist, but unfortunately he keeps making comments about #1 (even if he doesn't study those kids). So if you are barking at trees... Probably the big item is to look at 4 and 5 and decide how you treat the symptoms while you look for a cause. In #5, prophylatic antibiotics should help prevent subsequent infection -- but keeping up the prophylaxis is difficult. One missed dose and your child is not protected for 3 more days. In #4, the OCD is usually not debilitating (at least from what I read), so treatment for tics seems what most choose. I'd then get the Kirvan blood test just to get some clue whether #4 or #5. Hope that helps, Buster

FANTASTIC. We have been thinking about your family and just hoping for a post and I am sooo glad to hear the news. So, let me try something and see if this works... I don't have papers that say this (so this is my personal belief)... 1. The recommended dosage for Azith or Augmentin are all based on kids with healthy immune systems that can recognize the strep and find the GABHS that is hiding behind the Hyaluronic acid capsule. However, strep can go intracellular and as such can reburst sometime in the future. If your immune system can't "take out" the strep, then the GABHS will just keep multiplying and the B-cells keep generating the "wrong" antibodies (i.e., the one targeting the GlcNAc, but never quite latch onto the right stuff for the macrophages and killer cells to find. 2. Penicillin and augmentin and all that stuff only stops rapidly multiplying GABHS -- but suppose it isn't rapidly multiplying but slowly multiplying -- then you have more an more strep, more and more antibodies and more and more symptoms. 3. Now Kurlan is showing that with chronic strep, ASO numbers actually fall as if the body basically gets used to the streptolycin O over time. 4. But that says nothing about the concentration of 24.3.1 or the other anti-lysogangliosides and we also know that the super-antigens also seem to cause a breakdown of the BBB 5. So a perfect storm -- we've got strep in the bloodstream slowly growing or in a biostatic state -- neither getting bigger or less. We've got T-cells and B-cells maxed out and depleted trying to create "the right antibodies" but they keep creating these GlcNAc ones rather than something that actually takes out Strep.... So what happens if we then up the antibiotics... Well in the case of Augmentin it turns from just slowing down the strep (bacterialstatic) to being bacterialcidal -- at high enough dosage it literally does "kill" the extracellular strep. If there is enough out there then even the intracellular strep when it bursts will run into a whole lot of augmentin and not create more problems. If you can keep this up long enough the 24.3.1 should drop off and the CaM Kinase II number should come down ... hope, hope, hope.... I know the above isn't "proven" but what I think is happening with PEX is removal of the faulty antibody -- but it won't get rid of underlying streap. IVIG brings in a whole bunch of other antibodies that should "self-regulate" if the B and T-cells aren't depleted. But if the strep is still lingering and the B/T-cells are depleted then I could see why IVIG wouldn't help -- there just wouldn't be any more cells to do more attacks.... I'm sure some immunologist is saying "Jeez, that's not how it works at all" but that's my best explanation at this point... :-) Best regards, Buster

Based solely on our observation of behavior of our child. We've been monitoring and plotting symptoms for the last 72 weeks. These symptoms for us were: * contamination fears * complex measurement rituals * movement disorders (particularly poor handwriting and tremors) * vocal tics * raging and emotional lability * lashing out and hitting behavior * restrictive eating * body image/morphology issues (in a 7 year old) * OCD questioning and rituals * social anxiety * separation anxiety The severity of these symptoms has episodes but the baseline kept creeping up over the year until we were at approximately 50% of the all time peak -- particularly noticable were the movement disorders, the vocal tic, social anxiety and the contamination fears. Post IVIG (albeit the first 2 weeks were very concerning), the movement disorder, social anxiety and contamination fears are gone. We notice a slight vocal tic still but it is incredibly mild. Regards, Buster

Totally agree! (of course I better since EAMom is my dw) We still did, however, have the episodes and escalations even with the baseline change. The problem wasn't the recognition of the exacerbation, the problem was that the remission never got back down. I don't know if over the prior year it was just the frequency of exposure (since her sister had 5 strep infections plus the one you had) or whether her immune system just got more sensitive or that the CaM Kinase II just never dissipated. For some strange reason, in our dd the antibodies didn't seem to just disappear after 4-6 weeks -- they most certainly went down but a basic baseline kept creeping up. With IVIG, the baseline reset to 0 again. Buster

Faith, let me see if I can clear this up... Look for an episodic course As far as we know, PANDAS seems very similar to Sydenham Chorea and is looking less and less like chronic tic disorders or Tourette Syndrome. What I'm getting at is that tics that are there relatively constant without cessation probably are not the episodic course characteristic of PANDAS and Sydenham Chorea. I say probably, because we don't really know. It's auto-antibodies and a breach of the BBB The best research I've found is Kirvan's 2006 work where she isolated antibody 24.3.1 and found that this antibody cross-reacted with lysogangliosides and appears to interfere (through CaM Kinase II activation) with neuronal signalling in the brain. 24.3.1 seems to get produced by the B-cell/T-cells in some kids in response to a strep infection -- however, what is odd about 24.3.1 is that it targets GlcNAc (a carbohydrate that is exposed on the surface of the GABHS cell wall). The only problem with this is that GlcNAc is also exposed on other cell walls so this little antibody can cause some problems and attach where it shouldn't -- particularly if it attached to the basal ganglia. Now the good news is that it doesn't look like it causes any cell death or demylination -- yeah. But it does seem to interfere -- like a cellphone interfering with the radio. So now, what about colonization, infection .... I have no idea if your kid has PANDAS... if you are seeing a correlation of really severe exacerbations and when that happens your kid has a positive throat culture -- and then during quiescence your kid has a negative throat culture, then this is a good indication of PANDAS. If instead you have slow waxing and waning of symptoms (i.e., no abrupt onset or symptom remission) then that probably doesn't meet Swedo's criteria. If it is PANDAS, then all that is technically required is elevated auto-antibodies in the blood stream (such as 24.3.1) and some break down in the blood brain barrier. Intense fear or stress, infection (viral or bacterial) or high blood pressure are all capable of causing a breach of the BBB. Once the auto-antibodies cross, then it is thought that they interfere with the basal ganglia. So what does antibiotics have to do with the above... Well, the auto-antibodies have a half-life (i.e., they seem to dissipate at around 4-6 weeks after GABHS is treated). Now for most kids, they can overcome strep on their own (14 days without antibiotics) however, some kids are able to stay colonized for a while. This means that the B-cells stay activated producing more antibodies until eventually the B-cells stop and the whole cycle stops. The benefit of antibiotics is that they stop the GABHS sooner (i.e., 2 days versus 14 days) and thus there's less antigens and thus less antibodies. So now all the way back to your child.... Being on antibiotics doesn't "do" anything except make it harder for the GABHS to get a foothold. Antibiotics don't stop tics or stop antibodies. The antibodies are there in response to the antigen. When the antibiotics slow the antigens the immune system comes along and wipes out the antigens -- but still there will be left over antibodies that will hang out for a while (again typically 4 weeks). Once again, if you aren't seeing that correlation (i.e., you don't see a postiive throat culture correlated with a very explosive or high ramp in symptoms) then it is certainly possible that something other than SC or PANDAS is going on. It is this episodic nature that is the hallmark of PANDAS. Is colonization enough? Now there's been considerable debate about whether colonization is enough to set off a PANDAS kids' immune system or whether infection is actually required. I don't know. All the studies are being conservative and so are checking correlation with infection demonstrated with rising titers or with sore throats -- but this undoubtedly is too conservative and is missing a number of cases. In our case, our daughter ramping symptoms meant to take her sister to the doctor for a throat culture. 7/8 times her sister was positive for strep. She was a canary for us. So for us, it sure seemed that colonization was all that was necessary -- not all out infection. We ended up plotting symptoms daily for 75 weeks while we tried to figure out this crazy thing. Hope this helps -- the point is that episodic course of symptom severity is key. Correlation with a positive throat culture is great as a diagnostic tool. Getting cunningham tests sure seems to help as a puzzle piece (although it is not a diagnostic test). Best regards, Buster

Well, no. About 40% of children who have positive throat cultures exhibit no rise of either ASO or AntiDNAse B. See "A little bit about ASO" at http://www.latitudes.org/forums/index.php?...art=#entry25312 According to current research, about 5% of children are likely carriers. Thus 35% of children have infections but for reasons not known don't seem to mount ASO or anti-DNAse B responses. Depending on how much you want to know here, post again and I'll send a followup. I'm not sure what to say here. In our case a positive throat culture is what we go by. For some reason I just can't figure, doctors seem to like ASO and AntiDNAse B test but they are basically irrelevant if you have a positive throat culture. ASO and AntiDNAse B can be used if you missed the window for getting a throat culture. PANDAS is not a response to ASO or AntiDNAse B. PANDAS appears to be a response to another antibody that interferes with neuronal cells. In Kirvan's work, she isolates auto-antibody 24.3.1 that interferes with lysoganglioside GM1. I posted a bunch of info on this in other threads. Bottom line, go for the throat culture -- don't worry about the rest unless you really truly need some other evidence and you missed the window for a throat culture. Current medical practice is that a positive throat culture is a presumptive infection. Regards, Buster

I originallly posted this at http://www.latitudes.org/forums/index.php?...art=#entry25680 There seems to be a good amount of confusion about how antibiotics work. Just remember that antibiotics don't kill strep, they slow it down. Some antibiotics are bacteriostatic (like macrolides that slow replication) and some are bacteriacidal (like pennicilin that weaken cell walls). But the point is that antibiotics just slow down an infection and rely on the immune system to mount enough macrophages to surround and destroy invaders or take out infected cells. In addition, there seems to be a good amount of confusion between colonization (what a culture finds) and infection (what titers track). Now most times colonization of GABHS leads to an infection, but not always. For GABHS there are four major phases: adhesion colonization invasion infection Adhesion is about how the bacteria attaches itself to the skin or to a mucosal lining -- i.e., how does the strep keep from getting wiped away. There was lots of study on this between 1970 and 2000 with the result that they think it is a combination of protein M, lipoteichoic acid and protein F. Colonization has to do with growth. It is not really clear what causes the limiting of colonization in carriers. Certainly some have shown that other bacteria/flora in the throat compete for various building block material so one bacteria can interfere with another bacteria's growth. On p.68 of Dr. Kaplan's book "Streptococcal Pharyngitis" http://books.google.com/books?id=YiYY86j9A...F0ih6D5yurBrejg Dr. Kaplan makes some very interesting observations that the streptococcal progenes cells seem to stop producing M protein in those with carriage. Kaplan observed that the mechanisms that produced the "symbiotic relationship with the human host have not been identified." Invasion has to do with penetration of the epithilial cells. There are two types of invasion: extra-cellular invasion and intra-cellular invasion. In extra-cellular invasion, the streptococcal pyogenes release a spreading factor (e.g., hyaluronidase) that destroys connective tissue and streptokinase (which indirectly destroys fibrin and prevents blood clotting). In addition, the strep produces stretolysin O which acts to kill phagocytes. Hyaluronic acid capsule also acts as a cloaking mechanism for GABHS which prevent phagocytes (i.e, those cells that detect antigens) from recognizing GABHS. On intracellular strep, Kurlan notes in the above reference that GABHS produces M1 proteins have the ability to penetrate cells. There's a great picture of invasive intracellular strep in the 2000 paper by Cunningham. Again the exact mechanism by which invasion occurs isn't known but it appears that certain emm-types of GABHS can penetrate cells like a virus. So the theory about carriers was that they had "adhesion and colonization without invasion" -- meaning that if you did a throat culture you'd certainly get streptococcal pyogenes, but that for reasons not known, the strep hadn't penetrated/invaded. This state has been declared to be benign, but actually no one knows this. The strep is most certainly producing streptolysin O, streptolysin S, hyaluronidase, streptokinase, ... however, these seem either to not penetrate past the epithilial layer or for some reason the immune system doesn't mount a response to these antigens. Kaplan refers to this as an unexplained enigma. Infection, on the other hand, is what happens when the invasion overwhelms the immune system's ability to keep up the wall of defense. During infection, the growth continues unchecked and antibiotics help by either stopping reproduction of the strep or by weakening the actual cell wall of the strep (penicillin). In addition many of the macrolides are immunomodulating and shift the production of Th1 versus Th2 cells. The Th2 get the stuff extracellular and Th1 gets the stuff that is intracellular (if it can find it). So essentially, antibiotics stem the flow, the immune system builds up a response and then overwhelms the bacteria (if it can find it all). Breaks in skin, tooth extractions, dental work, ... all enable rapid invasion and infection since the protection of the epithilial cells is broken and the bacteria can get right into the blood stream and reproduce rapidly. In addition, the subsequent exposures to strep (or its exotoxins) seem to be much more severe and so the recommendation is for prophilaxis antibiotics for ARF and SC individuals. So, why are carriers resistant to antibiotics? Well, it isn't clear that they are. It seems that there is a class of carriers who are only colonized (i.e., have no other symptoms of strep -- no ASO titers, no Anti-DNAse rise, no sore throat, ...). For this class of carriers, its really, really hard for the antibiotic to reach the colonized strep since it is really on the surface of the skin (or just on the surface of the tonsils) and not invasive. For people who has some invasion (i.e., its gotten into the blood stream), there may still be a problem with antibiotics getting to the surface colonization. In addition, if the strep has gone intracellular, then the antibiotic has to hang out until the cells burst otherwise the whole thing just starts all over again. Another Wrinkle Just to throw an entirely weird wrinkle on this, the recent Kurlan paper shows that ASO titers drop after long exposure to strep (even if the strep is untreated) -- indicating either the strep is changing in what it produces or that the body gets used to the Streptolycin O (sort of getting used to bee stings) and stops mounting such a defense. This sure raises questions about the effectiveness of ASO as a strep selection tool. Regard, Buster

frustration

I know, I know... I sort of went into retreat for a while -- even with all the data we had, it was hard to go through IVIG. Lots of worries about blood products and all the things we just don't know yet. Those first two weeks post-IVIG were the worst. I really started to worry we had just made things worse. I do think the mini-longitudinal data is really interesting. I realize it is totally anecdotal at this point but still, the shift from 183 to 119 somehow was really comforting. I also want to stress that not everything is back to "normal." There's still a slight verbal tic -- a sort of irregular breathing. There also remains some separation anxiety. It's unclear to me whether these are learned behaviors i.e., now comfortable habits rather than obsessions/compulsions. Hard to say and we'll just have to see. But all the true obsessional items and complex movement/measurement rituals are gone. Wishing everyone on this forum some quiet time, Buster

Hi Folks, Thanks to all who have sent questions regarding our dd9. We remain in good shape two months post IVIG. I will say that our initial 2 weeks were quite unnerving as all symptoms got suddenly much, much worse. It was like watching the last year on fast reverse. Symptoms came and went but interestingly in reverse order with the earliest symptoms being the last to leave. Week 1: significant escalation of symptoms, movement disorders, tremor, contamination fears, vocal tic, very irritable Week 2: continued escalation of symptoms. Very intense but short lived. Interestingly like watching last 6 months on fast reverse. Angry, lashing out, eating issues, handwriting issues. Week 3: school starts. She's interested in school and handwriting has improved. Margins are much better. School teacher indicates dd9 is somewhat defiant in class. Week 4: lots of itchiness. slight food restriction. dramatic fall off of symptoms. concerns about wearing glasses in public, measurement compulsions disappear Week 5: calm, quiet -- some social anxiety when at a large family party Week 6: more calm -- no rages for a week Week 7: calm -- willingly does homework -- is remembering math facts, spelling is eratic, getting along well with sister Week 8: calm, happy -- able to brush teeth alone -- first time in 2 years. Week 9: calm, happy -- enjoys school, likes trumpet, some handwriting issues still, very slight verbal tic It's really odd having relative calm in the house again. It's not 100% "normal" but most assuredly better than anytime in the past year (probably 95%). She still has a slight verbal tic and some underlying social anxiety, but all other symptoms are gone. On the CaM Kinase, we ran a mini-longitudinal study here. Our dd9 was at: 183% not in exacerbation (April), 253% during exacerbation (June), and at 170.5% on post prednisone burst (Aug). and 119% at 6 weeks postIVIG (Sept) It is still very much a research topic what the above means, but CaM Kinase II did seem to correlate with symptom severity. Best regards, Buster

Hi Melanie, They don't really know why IVIG works. There was a study by Swedo that IVIG on non-PANDAS OCD didn't really have an effect. Similar studies on Tourettes Syndrome didn't seem to have benefit (although the data seems mixed). One thought is that IVIG has a byproduct of being a really strong anti-inflammatory -- so it might just close the blood-brain-barrier. It's also possible it drops inflammatory cytokines by doing a bit of a reset on the immune system -- the bottom line is no one really knows. Regards, Buster

Hi Peglam, We have a couple of theories. According to Kirvan's 2003 paper, it appears that three of the antibodies interfere with lyso-gangliosides, but only one of them causes CaM Kinase II activation. So it could be that there was a shift in concentration of the anti-lyso-gangliosides, it is also very possible that 640 is really very close to 1280 (i.e., I chose only one time constant to report). It's possible that there's something else in the blood serum (such as another unidentified antibody) that causes CaM Kinase II activation. It's hard to say. With respect to your second question, I don't think it needs to be an active strep infection, just that the antibodies are in the blood. I've been thinking that the anti-lysogangliosides probably drop at the same rate as other antibodies (i.e., around 4-6 weeks). So after the antigen is removed, the symptoms should abate over that time. I'm sure in some people the rate drops faster, in others slower. We'll just have to see what the research discovers... We're unfortunately at the fore-front of the disease and have to wait for research to explain in the lab what we observe in the field :-) Regards, Buster

Hi folks, Just to remind everyone, we don't yet know what real normals are on the tests yet -- or what symptoms are tied to which antibodies (if at all). PANDAS is thought to have a pathogenesis similar to Sydenham Chorea and to be caused by the combination of three events: the creation of an antibody to GABHS that cross-reacts with neuronal tissue a genetic pre-disposition that does not suppress the antibody a break-down in the blood brain barrier that allows the antibody to reach neuronal tissue Just because we have the antibody in the blood that could cross react with neuronal tissues doesn't mean it will. Essentially you need all 3 elements to get an exacerbation. It is my belief that the break-down of the blood brain barrier is the dominant reason we see exacerbations (i.e., it is the last straw). So what we see with Prednisone and likely with IVIG (and maybe even with azithromycin) is closing of the blood brain barrier by reducing inflammation of the endothelial cells. We've drawn titers 3 times: once when we were in a calm quiescent state once during an exacerbation (pre-prednisone) once post-prednisone CaM Kinase II was 185% in the calm, 253% in the exacerbation and 170% post-predinsone. So it does look like CaM Kinase II is correlated with exacerbation as per Kirvan. We also noticed that anti-Tubulin was elevated in the exacerbation. Prednisone did seem to lower anti-D1, anti-D2 and anti-Tubulin, but strangely didn't have an effect on anti-Lysoganglioside. We're not sure yet why the anti-Lysoganglioside didn't drop... Here's our numbers: quiescent: anti-Lyso: 1280 anti-Tubulin: 1000 anti-D1: 8000 anti-D2: 16000 CaM Kinase II: 183% [*] exacerbation (pre-pred): anti-Lyso: 640 anti-Tubulin: 4000 anti-D1: 8000 anti-D2: 16000 CaM Kinase II: 253% [*] 3 weeks post-pred (quiescent) anti-Lyso: 1280 anti-Tublin:2000 anti-D1: 4000 anti-D2: 8000 CaM Kinase II: 170% Regards, Buster

Hi Kim, Was the strep isolated at the initial event (i.e., a culture). I ask because a cough is usually exclusionary to strep throat. However, you are right, some coughs and certainly sniffing and tongue clicks can be vocal tics. You mentioned OCD symptoms, which ones did she have? How severe? Were they at the same time as the cough or just later during the kindergarten episode? You mentioned Prozac -- how long was she on it -- I see she improved over 2 months while on Prozac but wasn't sure how long you kept her on the SSRI. PANDAS is considered a sub-group of OCD and/or tics (meaning to have PANDAS your child would typically have a DSM-IV diagnosis of OCD or a diagnosis of a tic disorder). Since PANDAS is primarily defined by the onset and by the abrupt severity of episodic symptoms, this makes it more difficult to identify if there is not significant differences between convalescent state and exacerbation state. Changes of > 20pts in YGTSS or > 15 pts in CYBOCS scores are common for PANDAS kids. In terms of treatments, our dd9 had remarkable improvement after 10 days of azithromcyin. Later, we found that her symptoms corresponded to her sister having strep (i.e., our dd9 was a canary for strep in our dd6). I mention this, because it is likely good to check the family for strep when trying to isolate the cause of an exacerbation. We have kept our daughter on propholactic antibiotics but it took having our psychiatrist, rheumatologist, letters from experts, ... to convince our pediatrician to overcome her reticence to antibiotics. In our case we did try several antibiotics because we frankly had no other explanation for the "demonic possession" of our child who was quiet literally incapacitated by OCD requiring hospitalization due to the severity of her condition. Wishing you the best and hope you'll reply with more details, Regards, Buster

Hi Meg, Good catch on Sokol's work. Since our child had AN, I was very interested in Sokol's work, but the work was not picked up after Dr. Sokol's effort. This coupled with the demise of the D8/17 marker makes it hard to know what to do with the papers. I hope that another researcher will pick up the thread and resurrect the research. Regards, Buster

Hi Colleen, I found one paper where Prozac seemed to change the type of Cam Kinase II activation (see http://www.nature.com/npp/journal/v32/n12/abs/1301378a.html). Not sure if this will affect results or not and have asked the lab about it. I searched for affect of long term azith and I didn't find anything that indicated it affected these results. I think that's still a research area that would need to be controlled for. In terms of anti-dopamine, as best I can tell, those values would fall into normal range -- presuming you sent D1 and then D2. Regards, Buster

That's a really excellent question.... In Kirvan and Cunningham's 2006 papers it appears the controls were: * non-PANDAS OCD (6) * non-PANDAS tics (Tourettes, CTD and tics NOS) - (10) * non-PANDAS ADHD - (10) * non-PANDAS without neuropsych issues (i.e., normal) - (5) Regards, Buster

Putting our numbers here too: non-exacerbation: Anti-lyso: 1280 Anti-tubulin: 1000 Anti-D1: 8000 anti-D2: 16000 CamKinase II: 183% Exacerbation: Anti-lyso: 640 anti-tubulin: 4000 anti-D1: 8000 anti-D2: 16000 CamKinase II: 253% Regards, Buster

Hi Folks, I'll try to offer some explanation here based upon what's written in Kirvan and Cunningham's paper, but you might want to contact the lab for a full explanation. First, these are research tests and as such shouldn't be used as diagnostic because the whole purpose of the research test is to determine whether there is an association between measurements and symptoms. So, treat the tests as just one of the pieces in the puzzle we're all trying to figure out. At this point, the tests are compared against a group of controls but remember the sample size is REALLY small (like 30+ controls) so true "normals" aren't really known. The theory in PANDAS is that one or more antibodies are produced that interfere with normal signalling in the brain. Kirvan and Cunningham isolated several antibodies in their work and together these are referred to anti-lysogangliosides. The test they run is to add the blood serum to neuroblastoma cells and then check if adding a tagged ganglioside binds with the cells. If it doesn't, then it is assumed that the serum used up all the binding spots. This isn't perfectly accurate but hopefully good enough for explanation. Similar tests are done for binding to dopamine 1 and 2 receptors. Essentially, they are looking to see if the serum interferes with dopamine binding. Then tubulin is a a protein that acts as a dimmer that self-regulates a number of properties in messaging (way too simple explanation, but think of it as part of a feedback loop). So anti-tubulin is thought to inhibit the ability of tubulin to "dim"/regulate certain cell properties. Kirvan found that this interference with tubulin occurred in Sydenham Chorea kids. Finally, CaM Kinase II activation... well, essentially, this is complicated, but take it that it affects the barrier of endothelial cells and is thought to regulate signalling in synapses -- some neurologist is right now cringing at my explanation. Something in the blood is causing the activation, but this isn't in itself a problem. What is thought to be an issue is if the blood-brain-barrier is opened, then some of what's in the blood crosses into the spinal fluid and can interfere with brain chemistry and signalling particularly in the area of the Basal Ganglia. So, summarizing: * anti-lysogangliosides check whether something in blood serum is interfering with the binding of GM1 -- competing for binding sites * anti-d1 checks whether something in the blood serum is interfering with binding at dopamine receptor 1 sites * anti-d2 checks if interference with dopamine receptor 2 sites * anti-tubulin checks whether interference with tubulin binding * CaM Kinase II checks whether the enzyme is "turning on" causing signalling In Kirvan's studies, high anti-lysogangliosides and high CaM Kinase II were associated with SC and PANDAS and high anti-tubulin was associated with SC. Again, I'm not a doctor and this isn't my specialty, but the above is my understanding and you might want to check with the lab how to interpret the result. Regards, Buster