Buster

Hi Everyone, I apologize for going quiet for the last month. I wanted to followup and let people know a couple things about what's been happening with our dd. Short summary is that in October, we started to notice symptoms returning and discovered the following week that dd's sister cultured positive for strep (at least we have a good canary for strep now). Her sister's strep seemed to have an effect even though dd was on propholaxis azithromycin. According to scientists/doctors we contacted, strep can recolonize even while on antibiotic. Antibiotic will slow invasion, but the antibiotics rely on the host's immune response. After clearing sister, dd got significantly better but then started to have exacerbations two weeks later. We thought sister wasn't cleared, but she was culture negative. So either strep was still going around school or we were having a reminant effect in dd. Symptoms have mostly disappeared again (although verbal tic/groan remains). Last time this took 1 month to disappear after other symptoms. 1) October 10th: noticed dd's symptoms returning, measurement ritual, fine motor tremor, some eating restriction 2) October 17th: started sucking on things, won't wash hands, stomach hurts, not eating 3) October 20th: sister cultures positive for strep (GABHS), start treatment for strep 4) October 22st: dd is grumpy won't wear glasses, anxious 5) October 29th: dd back to normal 6) November 5th: dd still normal 7) November 12th: dd still normal, slight motion tremor 9) November 15th: slight verbal tic -- sort of like a groan, fine motor function issues 10) November 17th: sister is culture negative for strep (but lots of strep at school) 11) November 26th: aggitated, a measurement ritual is back, shakiness in fine motor function, added advil to night meds 12) December 3rd: seems back to normal, slight fine motor function issue and verbal groan/tic. All other symptoms gone. Regards, Buster

Hi Pat, I agree the adult cuffs are tough to use on kids. Typical BP's for children are located at http://www.nhlbi.nih.gov/guidelines/hypert...n/child_tbl.pdf . I wasn't sure of Gaby's age but it looks fine (i.e., in 30th percentile or so). Yup we give a couple of probiotics. We haven't observed a yeast problem.

Hi Pandas_Denmark, I posted a reply to Pmoreno separately, but yes, our dd did have odd visual distortions. She said hers were like rainbows you see on bubbles. That sort of odd irridesence. In checking with a number of doctors there were a lot of explanations. She could have been having ocular migraines because she wasn't eating. She could have had low-blood pressure because she was dehydrated. Both are certainly possible. Our dd described them as ghosts and became quite scared of them. Even saw them coming out of the tap water and had severe contamination fears. This dissipated when she got on antibiotics. We ask her every so often whether she has a headache or has seen the spots. Nothing so far. Regards, Buster

Hi Pat, Regarding floaters: There can be several explanations and it sounds worth a trip to the doctor to get your child's blood pressure checked and ketone level checked -- is she eating all right? For blood pressure, I highly recommend checking both standing and then checking resting after 5 min. They do this for folks with heart problems, but if your daughter isn't getting enough fluids (i.e., is dehydrated) she too could be having rapidly changing blood pressure. Strangely enough floaters can be low blood pressure -- it will show up as flashes or bits of light. You can also get them from high-blood pressure but they show up slightly differently. Finally there are occular migraines -- i.e., no distinct headache but rather a blurred ring that expands or widens to the edge of the eye. If your daughter can describe them better, perhaps one of us will recognize the symptom, but I'd still recommend checking blood pressure. For example, baths can actually lower blood pressure substantially, perhaps that's the effect. Does it happen more when she is lying down? It turns out that our dd had something she called "ghosts" and she'd see them coming out of the faucet during the absolute worst of the episodes. I asked her about these during her symptom free time and she said they were very odd, like rainbows you see on a bubble -- sort of irridescent and yes, she was scared of them and thought she was seeing ghosts. We don't know exactly what caused our dd's symptoms. The opthamalogist thought it likely that it was starvation during her whole anorexia nervosa phase. She hasn't had the symptoms since recovery and anti-biotics. Regards, Buster

Two weeks ago, our dd started exhibiting odd behavior once again. She's been on propholactic antibiotics since she got out of the hospital in March (7 months ago). We're seeing some of her measurement rituals return, some of her odd motion tremors and some restriction in her eating (similar to how she was in early February). This is by no means of the same magnitude as her symptoms in February, but it is also not the absence of symptoms that we've been blessed with for the past 4 months. Low and behold we received strep notifications from her school and ended up taking her sister to the doctor to check for strep. Sure enough her sister cultured positive -- way positive. So we're treating her sister to eradicate her strep and are hoping our dd's symptoms subside. We sort of knew this might happen -- i.e., that despite propholaxis our dd could have exacerbations due to exposure to strep. Even in the case of penicillin (which is bacteriacidal) it only supresses rapid growth and still relies on the body's immune system to get the bulk of the infection. Azithromycin stops the production of a protein, but similarly relies on the body's immune system to get the infection. So in the face of some strep, out come the antibodies and if the Swedo/Kirvan reports are correct, we'll have some cross-reaction/inflammation before the strep is wiped out. So we're seeing a low-level version of symptoms. We're worried it'll get worse and hope it disappears again when her sister is cleared, but we'll have to see. Sigh.... Buster

Our dd also had frequent headaches during the PANDAS episodes. We ended up asking her one day whether her head hurt and she replied "almost all the time". We asked her why she didn't tell us and she said, "you never asked." Sigh. We tried some advil to relieve pain and that helped a lot. She could then sleep. We then told her to tell us if she had other headaches. She also seemed to have occular migraines (saw odd shapes). This is more likely due to malnutrition during the time but could also be linked with the headaches. Buster

Hi all, I was wondering if anyone has seen dyslexia or dysgraphia with their PANDAS child. Regards, Buster

The following is a May 2008 summary article about PANDAS. It is pretty complete and nicely balanced indicating what was found to date and also where experiments failed to replicate results. The bibliography is also quite good. HTTP version at http://www.pubmedcentral.nih.gov/articlere...id=18495013 PDF is located at: http://www.pubmedcentral.nih.gov/picrender...mp;blobtype=pdf Regards, Buster

Hi Worried Dad, The clavulanate in Augmentin works by binding to bacterial beta-lactamase and thus stop the enzymes from breaking down the amoxicillin molecule. Clavulanate itself has no significant antibacterial activity; it merely helps to prevent amoxicillin from being broken down by bacteria enzymes that would otherwise be resistant to it. Essentially, clavulanate "augments" the activity of amoxicillin. Here's a reference about the role of beta-lactamase producing bacteria and bacterial interference in streptococcal tonsillitis http://www.ncbi.nlm.nih.gov/sites/entrez?d...;indexed=google More info on clavulanate is located at: http://bacteria.emedtv.com/amoxicillin-and...-potassium.html Regards, Buster

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Hi Pat, No, our dd hasn't been through IVIG. We had a horrible feb-june and are now in a holding pattern and a bit concerned about changing any meds. It is such a relief from the storm that the past 3 months of calm is very healing for all of us. We're not thrilled with staying on antibiotics, but as long as her symptoms stay in remission, we'll keep on this routine.. I noticed that you mentioned that your dd has a twin. Are they identical twins? Regards, Buster

Hi Myrose, What an awful experience you and your dd have been through. I absolutely understand your concern. We are in a similar holding situation. Right now my dd is stable (i.e., no symptoms) on azithromycin and Prozac (after a horrible feb-june). At this point, we are pretty sure any strep is now gone and the azithromycin is acting either as as a propholaxis dose (i.e., inhibiting recolonization/infection) or as an immunomodulator/anti-inflammatory. We don't quite know, but we are concerned about taking her off of it with strep going around the school. Having weathered such a storm it is really tough to change anything. We have decided to just stay with our current medications for a while, so the whole family has some time to heal. We're not sure what we will do longer term. I was reading through your other posts and I didn't see whether your dd ever had a negative culture. I saw the positive culture in Feb and presumably the ASO titers were drawn 1-4 weeks later (i.e., March). Given the horrible experience your daughter had with blood draw, no wonder she doesn't want to repeat. One option might be just a skin swab. Our daughter was positive in throat and perianal for GABHS. Perhaps the skin one would be less scary (although it may not show anything). Interestingly, I've just run across a couple papers indicating that skin GABHS infections don't generate ASO responses. I thought this fascinating. Our daughter too had significant stuffed up nose. It was so bad that she used to try to blow her nose and was getting a number of nose bleeds. I'd sure be interested to find out if others ran into this. We tried antihistamines (chlorotrimaton) and that seemed to have a good effect. I don't know how to give any advice here except to commisserate. If I run across anything I'll certainly send it on. Did your doctor indicate, by the way, why Topamax? For OCD, Topamax has been used in conjunction with SSRI's but I hadn't seen it used alone. Was it primarily for the tics? Regards, Buster

Hi Linda, Our dd has not had IVIG and we are currently holding on propholaxis antibiotics. Her symptoms subsided on azithromycin. Many others on this forum have had IVIG when their symptoms either did not resolve or got worse. It is our hope that IVIG won't be necessary. regards, Buster

Hi Myrose, I think the main item would be what's the relationship you have with the folks you are sending the email to. If they think they've got your child's situation under control, then they're going to be really hesitant to change anything -- even antibiotics. So if you're not in the middle of an exacerbation, it's going to be really hard (in my opinion) to sway a doctor without at least a really great track history associating prior exacerbations with positive strep cultures. If they don't see such a relationship, they aren't going to act. 1. Are you seeing current exacerbations? If not, then even if it were PANDAS it is highly unlikely you'd find any evidence of strep if the last exacerbation was > 8 weeks ago. Depending on when was the last exacerbation, all residuals of strep can be gone. If you are in an exacerbation, was a throat culture done ? 2. Are you thinking of propholaxis antibiotics? This is going to be tough to get without some evidence that your child's symptoms are temporally linked with a streptococcal infection. We gratefully had a positive strep culture in the middle of a really bad exacerbation which allowed us to treat with antibiotics and see the improvement. From your previous posts, it sounded like your child was doing well at the moment. Is there something that is motivating you to want to change medication? Is it mostly a concern about a followup exacerbation? I know none of us want to go through another round, but it's really tough to get propholaxis antibiotics without some evidence. If you have a followup exacerbation, then I most certainly would recommend a throat culture. That should be enough evidence to get antibiotics. At that point you can debate which one and do all the followup. I know this is a horrible position -- waiting and worrying, but unless you have a great track history with the doctor and they have some evidence, they are really unlikely to put your child on propholaxis. You are more than welcome to cut and paste what I posted into an email. I think all you will be doing is setting up the foundation for a followup conversation if you get another exacerbation. Regards, Buster

Hi Colleen, Can you provide a bit more history? EAMom is absolutely right that there are strains of strep that do not grow in air and thus have to be specially cultured with a puncture rather than surface wipe. There are also strains of strep that produce an uncharacteristic growth pattern that can easily be missed if the test itself was for group A Beta-Haemolyitic strep. However, these are very rare and it sounds like you had other ways of confirming strep infection. For odd cultures: http://icmr.nic.in/ijmr/ijmr_supp/4.pdf For interference for GABHS: http://archotol.ama-assn.org/cgi/reprint/125/5/552.pdf For intracellular strep: http://jmm.sgmjournals.org/cgi/reprint/49/6/499.pdf Of course the Kaplan papers are also quite good if you'd like me to repost those. Regards, Buster

Hi Pat, I haven't studied this area of IVIG symptoms and their progression. The best I've found so far is section 9 of http://www.emedicine.com/med/topic3546.htm where they outline all the really awful stuff that can follow with IVIG. Hearing your dd's symptoms, you definitely should talk with your doctor/neurologist about what you are seeing. There is a rare form of aseptic meningitis that has been associated with IVIG http://www.annals.org/cgi/content/full/121/4/259 that can drive such extreme behavioral changes. It wasn't clear from your post whether the emotional lability was there before IVIG or seemed to be result. Are you treating the headache and nausea with anything? I'll keep looking, ... Best wishes and thoughts, Buster

Hi Chemar, I had originally intended the "PANDAS research for your doubting doctor" and the "a little bit about ASO titers" to be a form of PANDAS and GABHS summary that I wish I had found several months ago. I'd sure like to see (and would be happy to contribute) to an essential thread that has references to the key papers (and their findings). The discussions are excellent but I also think some reference material or a FAQ would be great. Is there a way to put out a post, collect discussion and then nominate the post to the sticky state if it proves useful to enough folks? Every day I'm running across more material and would dearly love to share interesting papers I've run across with others who are also struggling with this wacky disease. Best regards, Buster

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Well, this is not really well understood. Kaplan did a great study on "failure rates" http://www.journals.uchicago.edu/doi/pdf/10.1086/320745 when he was comparing efficacy of different antibiotics. What is extremely interesting in his study was on page 3 where there is a graph of the followup. Here he shows that the subjects were treated with azithromycin and clarithromycin. 10% had positive throat cultures at 13-19 days after treatment, 18% had positive throat culture at 28-39 days. His purpose in Figure 1 was to show that clarithromycin was effective at clearing strep -- but this also indicates that 5-10% of folks will have false negatives and will re-colonize with strep even if "negative" at 2 weeks. I thought this was a good experiment and write up. Buster

Hi Chemar, Do you have a reference for any study with such CY-BOCS scores? The studies I have seen show the more gradual wax/wane with changes in CYBOCS in the +/- 3-4 pts rather than the 15 pt changes. Regards, Buster

I asked because we noted significant exacerbations following dental cleaning/tooth extractions in our dd. Similarly ARF and SC patients are put on propholaxis antibiotics when having cleaning because any carriage in the throat can easily be introduced into the blood stream causing rapid growth from the release bacteria. Your write up certainly seems to show a strong correlation to improvement on antibiotics. I don't know any advice to give you here except keep up the vigilance and throat cultures. Please note that even on antibiotics, recolonization can occur from a family member. We discovered in our household that dd's sister was an asymptomatic strep carrier and it appears that dd was getting recolonized until we eradicated strep in her sister. This is most assuredly not a controlled study, but given you son's sensitivity, you might want to consider . Regards, Keith

Hi Myrose, The actual criteria you want to look at is "Episodic course characterized by acute, severe onset and dramatic symptom exacerbations." It isn't the "suddenness" but rather the severity and the episodic course. While almost all with OCD or tics have good and bad days, the pattern in PANDAS is quite different from the "waxing and waning" seen in chronic OCD or chronic tics. Instead the symptoms increase with sharp exacerbations rather than a gradual rise. While these might be more severe PANDAS cases, Swedo and Snider's cases had +/- 15 pts of CY-BOCS score differences during an episode. Typical waxing/waning is more like 1-4 pts of CY-BOCS changes (i.e. no new symptoms but rather intensity of existing conditions). Regards, Buster

What about Kurlan's June 2008 Pediatrics article? I've gotten a bunch of questions regarding Kurlan's June 2008 article in Pediatrics that is titled: "Streptococcal Infection and Exacerbations of Childhood Tics and Obsessive-Compulsive Symptoms: A Prospective Blinded Cohort Study" and 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://pediatrics.aappublications.org/cgi/...ract/121/6/1198 These papers are very recent and even our pediatrician sent us links about them saying that "New research shows PANDAS doesn't exist." This is not what these papers show. I've probably never been so annoyed in my life. First and foremost, I should compliment the authors on a very careful study. However, they basically blew it on their sample of children and seem to have selected Tourette's children with > 3 years of continuous tics with no exacerbations in OCD as their proported PANDAS group. So the science was probably good, but they weren't testing the hypothesis they intended to test. Problems with the Kurlan and the Singer Studies I think the paper is fundamentally flawed with 6 major issues. This study is about long-term tic disorders in older kids (11-12) and not about sudden onset PANDAS (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? 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. 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. in re-reading this post, I realize I should soften my criticism by saying how very impressed I was to see the size of the Kurlan study and Singer study and that the data set they collected is undoubtedly very helpful. Think of it, 40 kids being bleed every 4 weeks for 2 years with no immediate benefit. The study is impressive in scope, the data undoubtedly valuable, but the claims are definitely questionable. Okay, now onto Singer's conclusions (or non-conclusions)-- about antibody interaction with neuronal tissue So the good news is they tried to repeat Kirvan's 2006 work on cross-reactivity of an antibody with idiotype of GlcNAc. However, their sample set again, didn't have PANDAS kids (at least no episodic courses of OCD exacerbations), so they found that there wasn't cross-reactivity difference between their controls and their sample of proported PANDAS kids. What conclusion can you draw from that. Most certainly not the conclusion that seems to be drawn from folks not reading the actual paper. This stuff gets me soooo irritated. Best regards, Buster

Best summary papers on PANDAS Swedo's 1998 landmark paper: http://ajp.psychiatryonline.org/cgi/reprint/155/2/264.pdf Feitosa de Olvieira did a nice job summarizing research in 2007: http://www.scielo.br/scielo.php?script=sci...=en&nrm=iso Mell's 2007 summary: http://pediatrics.aappublications.org/cgi/...t/full/116/1/56 (although I couldn't find a free version of this) Exellent summary of GABHS Cunningham wrote an outstanding paper summarizing the literature http://cmr.asm.org/cgi/reprint/13/3/470 Kaplan wrote a very good paper on intracellular strep: http://www.journals.uchicago.edu/doi/pdf/10.1086/508773 Best summary papers on IVIG and Plasma Exhange The best study that I've found about IVIG was Perlmutter's 1999 Lancet report: http://intramural.nimh.nih.gov/pdn/pubs/pub-5.pdf where there was a demonstrated improvement of both IVIG and Plasma Exchange over Placebo in the decline of OCD symptoms. The followup actually offered IVIG to those who had placebo and again these had good results. There was a followup study on IVIG for OCD for non-PANDAS kids by Orvidas and Slattery (2001) that showed no improvement for non-PANDAS kids. I sure wish they had just repeated Perlmutter's test. Incredibly, despite this begging for a followup experiment, there has been no followup study to test efficacy of IVIG on PANDAS vs non-PANDAS cases. Indeed the current NIMH site warns that IVIG should only be considered for severe cases and if anything recommends against it till there is more research (but hasn't funded any) -- grr. There is a very good paper on "Evidence for the presence of streptococcal-superantigen-neutralizing antibodies in normal polyspecific immunoglobulin G" http://iai.asm.org/cgi/content/abstract/64/12/5395 where the author notes that IVIG seems to neutralize two of the superantigens of streptococcal infections. The exact mechanism of neutralization is not known. Best summary papers on Azithromycin vs Penicillin as treatment There also hasn't been a followup to Swedo's azith vs pen study -- which seems incredible given the efficacy of both pen and azith. Swedo even comments that they had expected azithromycin to be a control in her study and hadn't expected it to work as well as the penicillin. There are several studies on certain strains of strep being able to go intracellular (i.e, where penicillin can't reach). Kaplan wrote an excellent paper on the efficacy of macrolides on getting intracellular strep in 2005 http://www.journals.uchicago.edu/doi/pdf/10.1086/508773. At the same time there are numerous papers on resistance by strep (GABHS) to macrolides. For example, http://www.journals.uchicago.edu/doi/pdf/10.1086/432480 and http://www.journals.uchicago.edu/doi/abs/10.1086/320745 So it is a bit of a hit/miss. If penicillin can reach the strep, then it remains the preferred bactericidal option; however, many doctors prefer Augmentin or Cephalosporins (e.g. Keflex) as these have higher clinical efficacy. Theory of why IVIG, Plasmapheresis, Prednisone, Azithromycin and Penicillin all seem to work The best research I've found comes from Kirvan and Cunningham (see http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf). Kirvan and Cunningham have isolated several anti-nerual antibodies that seem to be produced PANDAS children that interfere with neural tissue and cause faulty neuronal signalling. Note: these are NOT anti-streptolycin-O (ASO) or Anti-DNAse-B antibodies. Kirvan and Cunningham isolated three anti-host antibodies that target a carbohydrate on the streptococcus cell wall. Unfortunately, this carbohydrate sequence is very similar to receptors on neural cells and so the antibody can bind with neural tissue and interfere with neuronal signalling. The antibody is produced during a strep infection and remembered by a B-cell. When a subsequent strep infection comes along, the B-cell recreates the antibody and replicates it to go after the strep. Unfortunately, the faulty antibody binds with other cells other than just the strep. In most people, a T-cell regulator notices the faulty antibody and stops the faulty antibody from replicating. In PANDAS and Sydeham Chorea, the regulation doesn't seem to happen. So, in some ways, PANDAS and Sydeham Chorea are thought to be due to a deficiency in T-cell regulation. As therapy, plasmapherisis is thought to work by removing the antibody. Penicillin works by killing off the bacteria that causes the body to massively replicate the antibody. Azithromycin does something similar and seems to have anti-inflammatory and immunomodulating effects (i.e., slows the bacteria, slows the creation of lots of antibodies and helps to keep the blood brain barrier closed). In the case of IVIG, the belief is that the T-regulator cells get reset and begin to suppress the faulty antibody. The exact mechanism for this is not understood. In addition, IVIG tends to have excellent anti-inflammatory effects and this may also have significant effect by closing the blood-brain barrier (if open) and reducing inflammation of the basal ganglia. The biggest complaint about the theory is "how did the antibody cross the blood-brain barrier?" There are lots of theories on this as well. One is that the exotoxins from the strep are affecting the blood-brain barrirer http://www.neurology.org/cgi/content/abstract/54/7/1433. Another holds that perhaps inflammation (from the strep infection or some other source) is keeping the blood brain barrier open. Strong anti-inflammatories (such as prednisone) and IVIG have been found to close the blood brain barrier in other diseases. It is possible that the anti-inflammatory effect and closing the blood brain barrier is why IVIG works for PANDAS kids - whereas Plasmapherisis removes the faulty antibody so an open BBB wouldn't matter. Stress (epinephrine), infection, inflammation can all cause openings in the blood brain barrier, but the exact mecahnism is not known for PANDAS. Best regards, Buster

I wish I knew too! At this point, I've been tracking the papers on D8/17 and it has been mixed. It is at least an anomoly in the B Lymphocyte and seems the show up in PANDAS, SC and ARF patients. How this marker corresponds with activation on B cells or whether there is some flaw in binding due to this and the MyD88 TLR is just unknown. I'll keep digging though. I'll go back and re-read Kirvan's paper again, but my understanding was that the antibody was attacking GlcNAc (i.e., that was the idiotype) and thus causing the attack on host self. It is not known how the antibody is crossing the blood brain barrier. I ran into a very interesting paper on epinephrine affecting BBB and allowing antibodies and drugs to pass. Perhaps there has to be a very frightening event/stress marker that lines up with the strep allowing the antibodies to cross. Just don't know.... Thanks, Buster