Buster

I re-read Swedo's paper "Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood" and noted that in the study of 29 children, only 2 had tic disorders without OCD http://intramural.nimh.nih.gov/pdn/pubs/pub-5.pdf I then re-read Kurlan's June 2008 Pediatrics paper and discovered that >75% of his kids had been diagnosed with Tourettes, 10% with some chronic tic disorder, 10% with tics not otherwise specified (i.e., 95% of Kurlan's kids had primarily tics). Essentially Swedo was studying OCD and Kurlan is studying Tourettes. Looking at the definitions of OCD and Tourettes Syndrome, TS has a restriction that there is no remission lasting longer than 2 months within a year. This got me wondering whether the reason that the John Hopkins researchers seem to be consistently unable to reproduce Swedo, Kirvan, Dale and Church's results is because they are checking whether PANDAS is a subset of Tourettes rather than whether PANDAS is a subset of OCD. I found out that Singer has just published yet another paper that states that it is comparing non-PANDAS OCD, OCD + chronic tics and OCD + PANDAS . However, looking at his statistics, there are no OCD-only children in the OCD+PANDAS group. In addition, it appears that the OCD+PANDAS group was pulled from kids diagnosed with Tourettes. Thus the group should have been labelled OCD+TS+proportedPANDAS. What I'm getting at is that Kurlan is studying whether PANDAS is a subset of Tourettes rather than whether PANDAS is a subset of OCD. He's using the Tourettes as primary and OCD as secondary rather than having studies of OCD as primary and tics as secondary. So for folks on this forum, were your kids diagnosed with Tourettes or with OCD? Best regards, Buster

Peglem: You might also want to see the paper: http://journals.lww.com/co-neurology/Abstr...isorders.4.aspx Buster

Hi Peglem, I hate to say it, but no, you can't use the Cunningham/Kirvan or Church/Dale tests as diagnostic. The sample sizes are still way too small to establish any norms. In particular, the range of normal on the anti-D2 is quite wide and the mean is elevated -- so it's likely that it's not specific enough to help. Sorry. It might (repeat the might) help add weight to a clinical diagnosis, but really hard to say at this point. In term of the quote from the doctor around D2 receptor item, he was referring to http://www.journals.elsevierhealth.com/per...0109-X/abstract and http://www.nature.com/npp/journal/v32/n1/full/1301199a.html The finding was that there was an effect of SSRI's on D2 receptors but it was unclear whether the seratonine level or the dopamine level was affecting the behavior. Regards, Buster

What a great question.... The most cogent of the responses is: "Your child is suffering from OCD. OCD is a genetic disorder. The vocal tic could be Tourettes Syndrome. TS is thought to occur in about 1% of the population and OCD is thought to affect 2-3% of the population. About 30% of those with TS have OCD." (Note: They don't really know whether OCD is a genetic disorder, but I usually don't argue the point as I think the bulk of the evidence points that way). Okay, thanks, the sky is blue too, so aside from saying it's in the genes, what's happening? "Well, we don't really know. We think OCD is isolated to a dysfunction in the Basal Ganglia and some problem with the dopamine receptor (type 2)." How is it treated? "For OCD, we think that SSRIs and Clinical Behavioral Therapy are the best ways to treat OCD." How do SSRIs work? "Actually we have no idea. We know that the various SSRIs stop absorption (reuptake) of seratonin and it looks like there is a residual effect on dopamine levels. We've found that dopamine levels affect cravings, fear, rituals, ..." So why does CBT work? "We're not sure, but it appears as if additional pathways/receptors get formed when faced with addresing fears." So it is a physiological effect? "We think so." So does CBT work on all OCD and TS cases? "Ah, no. It seems to be more effective on certain forms of OCD." So what if I told you of a recent study that had isolated an antibody that bound with the dopamine receptors interfering with dopmine response? "Your talking about the PANDAS theory..." Why do you call it a theory? "Well, there are lots of studies indicating that the correlation with streptococcal infection is unfounded." Hmm, I've read over 200 papers on PANDAS and only found 2 studies by Dr. Kurlan where he wasn't able to replicate an experiment. Your saying there's a study indicating that OCD is not caused by strep? "It's a controversial diagnosis. I've got to get going." Okay, I guess what I'm really asking is if you ignore the strep side of PANDAS and they find an antibody that interferes with dopamine binding -- would you try to reduce the antibody? "Got to go." I've got to learn not to put data in front of doctors :-) I'm serious that this is about as far as I get in the conversation. --------------- What I was trying to do was separate the association of strep with the antibody from reducing the antibody. What I think is important in Kirvan's studies is that antibody cross-reacts. So lets treat that first and then work our way back to what causes the antibody. I sure think we know, but if the controversy is in the trigger -- lets focus on the treatment and once we get that settled come back to the trigger.

Hi Nevergiveup, Thanks for your words of encouragement and the kind way you phrased your post. I have corresponded with Kaplan and Kurlan with limited success, but have not written to Singer. This is mostly because Singer got his test subjects from Kurlan and it seemed better to focus on Kurlan and then come back and address methodological issues with Singer once selection criteria for subjects got fixed. What is interesting is that from all the data (including the negative ability of Singer to replicate the observation of Church and Dale) it sure looks like the subjects were not the same as PANDAS subjects in other tests. What should have happened was for a test sample to have been sent from Kirvan or Church to Singer so Singer could test his tests. I also found it interesting to read the commentary on Singer's 2004 work at : http://neurology.org/cgi/eletters/65/11/1701 Singer did reply to this, but frankly the best response would have been to ask Church for a sample and verify the efficacy of Singer's tests. Regards, Buster

Hi Dee45, The only real controversy around PANDAS is that Kurlan and Singer have been unable to replicate other people's tests. Unfortunately, this seems to be because they don't actually select kids who have PANDAS. They keep going back to their stock of kids with Tourettes and then make provocative titles for their papers. I wrote up a post about all the things wrong with Kurlan's study (see here) http://www.latitudes.org/forums/index.php?...art=#entry26571 All of Singer's subjects came from Kurlan's study (i.e., they didn't say it, but the studies are linked). Singer says he was counting on Kurlan to get the diagnosis right and Swedo keeps trying to correct Kurlan on how to diagnose, but Kurlan doesn't seem to listen. Just to make this really clear, Kurlan had subjects who had no variance in their OCD symptoms over a 2 year period. If you ask anyone whose kid has PANDAS or look at the Swedo studies, you'll see that those kids have severe changes in OCD +/-20pts in CY-BOCS scores -- not the 1.6 pts of the Kurlan kids. It would be nice if Kurlan would at least reach out to Swedo to confirm a diagnosis or to Kirvan to get a control for his tests before stating anything about PANDAS with the outrageous titles of his papers. Regards, Buster

Hi KG5123, The short summary is that the study is a research study and not a diagnostic test. It probably adds to the weight of other clinical presentations, but there frankly isn't enough data yet to know the specificity/accuracy of the test. What they are showing is that in a prior group of kids, those with SC and PANDAS symptoms had elevated CaM Kinase II activation. So no, the tests can't completely rule out or confirm anything. That's why they're doing additional trials to see what the correlation is with children thought to have SC or PANDAS. Regards, Buster

My dw indicates that I'm not being clear enough.... Unless you revaccinate and look at the levels, then it's not clear what the low levels mean. High levels indicate recent infection or re-innoculation. see "Prevention of Pneumococcal Disease: Recommendations of the Advisory Committee on Immunization Practices" http://www.cdc.gov/mmwr/preview/mmwrhtml/00047135.htm REVACCINATION Duration of Immunity Following pneumococcal vaccination, serotype-specific antibody levels decline after 5-10 years and decrease more rapidly in some groups than others (56,57,61-63), which suggests that revaccination may be indicated to provide continued protection. However, data concerning serologic correlates of protection are not conclusive, which limits the ability to precisely define indications for revaccination based on serologic data alone. I'm not sure I'd revaccinate our dd -- scared enough of everything to mess with anything ... :-) Buster

Okay, a good reference from the original clinical data regarding PREVNAR can be found at http://www.fda.gov/BiologicsBloodVaccines/...s/ucm093833.htm (don't ask me how I found this :-) ) I recommend looking at table 46 on page 59 at http://www.fda.gov/downloads/BiologicsBloo...s/UCM137169.pdf Serotype Pre-dose 3 Post Dose 3 Pre dose 4 Post dose 4 4 0.078 1.46 0.31 2.38 6B 0.327 4.70 1.71 14.45 9V 0.180 1.99 0.57 3.51 14 0.198 4.60 1.45 6.52 18C 0.146 2.16 0.50 3.43 19F 0.374 1.39 0.55 2.07 23F 0.174 1.85 0.44 3.82 What you'll see is that there is a baseline antibody level pre-innoculation and then a 10-12x rise in antibody after innoculation. Each innoculation increases the antibody response. This is the intention of vaccines (i.e., that repeated exposure causes more virulent response by the humoral system). Typically 6B and 14 are active and all the others come out negative (i.e., <0.3ug/ml) in a baseline test unless the subject has recently been exposed to one of the serotypes (i.e., got strep-pneumo). So if your child is not registering a response (i.e. < 0.3 ug/ml) on the antibody test for all but 6B and 14, that could be consistent with a long delay since last exposure. I have lots more papers on the topic -- but the short summary are the papers are about the response of the immune system to exposure. Regards, Buster

Hi Folks, Well, I have a whole bunch of papers on this topic.... There seems to be some disagreement in the papers about how to interpret the tests. Some say that there is supposed be a residual amount of antibodies in the blood, others indicate that you have to reimmunize and then check the antibody levels. A relatively readable paper on hyporesponsiveness is at: http://iai.asm.org/cgi/reprint/76/11/5305 What was interesting in the above paper was the reference that carriage (i.e., nasal colonization) at the time of innoculation might invalidate the innoculation since all B-cells are depleted. When I get home I'll send the papers I got from the Center for Disease Control that provided charts of the antibody levels expected per age group. As far as I can tell, there weren't great studies of the long term protection. But I'll post what I have and what I think the materials mean. Regards, Buster

We saw a difference on ibuprofen and didn't see a difference on Aleve. We can give no explanation for why as both act in remarkably similar ways.

Hi Brian, I really agree with EAMom... I wanted to check on your son's history: If I remember correctly, your son is now 13. In 2007, he was diagnosed with SC with severe twitching/seizure like symptoms and insomnia. He was on ativan and zyrexa that sound like they made him worse rather than better. He was on propholactic amoxicillin to prevent recurrance of SC and over that year the seizures/twitching subsided, but the OCD remained. In June 2008, your local doc recommended stopping amox and by August 2008, your son had significant contamination fears, excessive hand washing and significant restrictive eating. You tried azithromycin for 30 days (I think for a sinus infection), got in touch with Dr. K who switched you to augmentin. In addition you tried a pred burst that showed remarkable improvement (if short lived). In October you went for IVIG, and had significant short term improvement -- but this sort of plateau'd in mid November. In Feb you went for round 2 of IVIG but that was aborted -- then you had a nightmare trying to get it rescheduled. You got blood tests for anti-lysogangliosides and CaM Kinase in May and his rates were consistent with SC again -- sigh. In June and July you got round 2 and round 3 of IVIG in Chicago, but didn't have significant improvement. I'm presuming you are still on augmentin and little else. Looking at the history, it looks like the time he most improved was at the switching time he was on azith and prednisone. Granted you were switching from azith to augmentin at the time, but from the history it looks like the two overlapped. Seems worthwhile to try azith and pred again. Inexpensive, orderable though your docs, ... Wishing the best for you and your family Regards, Buster

I on the other hand want to ask them "and what do you think is the controversy -- are you referring to that research by Kurlan where he proported to have PANDAS kids but none of them had any OCD oscillations in a 2 year study unlike Swedo kids who had +/- 20 pt variances on CY-BOCS scale?" I supposed when you exclude the subjects with the actual disease from your sample, it's not surprising that the sample doesn't differ from the controls. Grrr. 2 years on NIMH money wasted. They could at least have gotten some controls from Swedo.

I read your post and thought about March last year when we were calling our pediatrician because our 7 year old wasn't eating. Our dd was freaking out, thinking she was fat, measuring her arms, looking at herself in the mirror, obsessed with scales. "Just be firmer" our doctor said. We actually tried that -- you'll do anything when your kid's not eating -- surely doctors know. Nothing. We've raised our dd for 7 years and never had an issue. Something was desparately wrong. We went to the pediatrician's office. Our daughter had lost 12% in body weight in 10 days. Right there, in the middle of the exam room, she freaked out. I don't mean a little bit, I mean way off the charts crazy. She was having a full-out psychotic episode with suicidal declarations, "I need to be killed, please kill me, I want to die." It was really, really scary. She was absolutely still, standing, screaming at the top of her lungs, eyes fully dilated, totally psychotic. The doctor came in, tried for a minute to calm her down, and said 'you'll have to go, this is disturbing other patients' -- I couldn't believe it. I still can't. Here's your patient you idiot. This is NOT normal. But they don't deal with mental illness .... I then started calling every psychiatrist I could find -- can you treat a 7 year old with rapid sudden severe eating disorder, measurement rituals, obsessive questioning about food,... I still can't believe the horror of the time. On my 20th call, I reached a psychiatrist who ask (I'm not kidding) did I have a strep test done -- what? I googled 'strep anorexia nervosa' and out popped PANDAS. We were able to reach another pediatrician who got us a bed at the Lucille Packard Children's Hospital Eating Disorders Clinic saying it was the fastest way to get blood work and she would be safe there. We got there (long story) and asked for a strep test -- they thought now we were nuts. The doctors said she had full on OCD and Anorexia Nervosa, but they did humor us and take a culture. Two days later, they were advising us about long term psychiatric care, her culture came back positive (as had her sister's) and everyone was, well, surprised. They started augmentin. I called my wife 18 hours later when "our daughter came back". I'm not kidding, it was as if boom, there she was again. Not all the way back, but recognizable. I truly, truly understand how in the 18th century you'd think she had been possessed. Even then we got "we're an evidence based hospital and there isn't enough evidence to support PANDAS" ... unbelievable. It is a lonely fight and all I can say is trust your gut (and get some tests to back you up). Regards, Buster

I think Kayanne is referring to the post here Discussion about IVIG, PEX and Prednisone

Overall we're doing better. It's been a weird 2 weeks though. Week 1 -- Wild oscillations between elation/joy and rages/frustration. Literally angry one minute and happy the next. It was like seeing prior exacerbations on fast forward. Measurement rituals returned full force. Restrictive eating returned. Contamination fears returned. Separation anxiety really high. Week 2 -- Mixture of calm with wild rages more distance between them. Beginning of week, she was shouting and stuck on how things must be done. Couldn't accept things that were disappointments. Couldn't be reasoned with. She kept saying "listen, listen" but couldn't express what was driving her extreme behavior. She was struggling with writing -- lots of shaking in letter formation. She was full of tears and frustration. By end of week, she's calm again. Hmm... Having some trouble sleeping -- wants to stay up. Week 3 -- started with her being incredibly nice to sister. Her caring side is back. She's drawing again. It seems she has more control over her hands. We'll ask her to draw a house again/write a paragraph and compare to week 1. That's sort of where we are.... By the way, she had fever for 3 days post IVIG. In terms of strep and IVIG -- shouldn't make a difference. The bunch of antibodies you get should take out anything there and those antibodies should be there for 30+ days. It is totally unclear what to do post IVIG, we'll probably keep our dd9 on antibiotics for a while while we check blood levels and sensitivity to strep in others. Regards, Buster

Okay that paper is going to take some time to parse. Wow. How'd you find that one The problem with the Yaddanapudi study is that we're not quite sure if we're reading about symptoms of EAE or about the reaction to the auto-antibodies. It would really help to have an immunology student to bug for a while with questions... I swear if I keep up at this much longer I'm going back and studying immunology Buster

sigh...

Hi folks, The original study was on the D8/17 antibody discovered back in 2001. See http://www.journals.elsevierhealth.com/per...003237/abstract Swedo disclosed in a recent conference on Autism, that the cell line that created the D8/17 antibody died and so the antibody is no longer available. I can't seem to find anyone using D8/17 recently -- so seems to be the case. Sigh. Buster

We actually did a 6 day burst. And then on day 16 (i.e., 10 days from end of burst) we saw noticable improvements (easy interactions with adults, a carefree cheerfulness we hadn't seen in years, lack of separation anxiety). But it was only temporary (i.e., for 3-4 days). Then back to baseline. In terms of IVIG, our local immunologist ordered it and followed Dr. K's protocol. We do not know what will be covered by insurance (if any). Buster

Brief history of PANDAS research from 1976 research to 2009: http://www.latitudes.org/forums/index.php?...ost&p=36300 Regards, Buster

modified on Feb 11, 2012 to include new information on PANS modified on Nov 11, 2011 to include new information on Murphy's clinical studies modified on Aug 12, 2010 to include Hornig's work on passive transfer Hi Folks, I was sorting through my papers on PANDAS and thought I’d package the chronology here and the short summary of each paper in case others are interested in some of the early insights by Husby in 1976, the foundational work by Swedo in 1994-1998, then the recent work on passive transfer in 2009, and now the documentation of what "sudden onset" means by Tanya Murphy in 2011. If you click on the underlined words, you'll be taken to the relevant papers. Dicovery of anti-neural antibodies with GABHS In 1976, Husby found that antibodies to GABHS bonded with neuronal tissue in the caudate nucleus (basal ganglia). He noted that this binding was found for strep of emm-type 6, 11, and 12. He also noted that the reaction did not occur in rabbit brains but only human neural tissue. 46% of sera from 30 children with rheumatic chorea showed IgG antibody reacting with neuronal cytoplasm of human caudate and subthalamic nuclei. The antibody was also detected in 14% of 50 children with active rheumatic carditis. 203 controls showed no such antibody response. In 1977-1979, Husby found these antibodies were pronounced in Huntington’s Chorea and in Sydenham Chorea Acute Rheumatic Fever, Sydenham Chorea and OCD In 1989 Swedo published her study looking at 70 children with OCD over a ten year period where she noted the incredible similarity in symptoms. By 1993, Bronze and Dale published their findings that neural tissue had cross reactivity with antibodies to the M protein from strep emm-type 6. This was essentially a rediscovery of Husby but with the further isolation that the antibodies were to the M protein. In 1994, Swedo published a fascinating paper entitled “Speculations on antineuronal antibody-mediated neuropsychiatric disorders of childhood” where she proposed the hypothesis that neurological abnormalities of childhood may be caused by antineuronal antibodies resulting from a GABHS infection. This seemed to combine Husby’s, Bronze, Dale theories together. PITAND and PANDAS In 1995, Swedo and Allen found 4 children who exhibited sudden onset OCD symptoms coincident with infections. Two of the children had exacerbations coincident with GABHS infections and two with viral infections. Treatment with plasmapherisis, IVIG and prednisone were all found effective. They called this treatable subset of OCD, PITAND (pediatric infection-triggered auto-immune neuropsychiatric disorder). In 1997, Swedo found that the D8/17 marker from Khanna (1989) work on Acute Rheumatic Fever seemed to correlate and support the theory of a distinct genetic pre-disposition for OCD and chorea. She labeled this distinct OCD subgroup PANDAS – in case you wondered where the term came in. IVIG and Plasmaphersis In 1998, Swedo published the landmark paper entitled “Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases.” In which they separated and defined a clinical subgroup of OCD patients. Challenges to the definition came out almost immediately, most notably from Singer and Kurlan who had been studying Tourettes Syndrome and did not think that the definition properly separated the group from children with TS. This has essentially been the argument for the last decade. Singer/Kurlan testing TS kids and Swedo testing the PANDAS subgroup of OCD kids. In 1999, Perlmutter and Swedo conducted a blinded placebo controlled study that demonstrated that IVIG and Plasmapherisis reduced symptoms by some 45 and 50% respectively for the PANDAS subgroup. A later study by Nicolson showed no improvement for OCD and TS patients who did not fit the PANDAS subgroup (i.e., no post-streptococcal exacerbations). Discovery of new antibodies (24.3.1) In 2003, Kirvan and Swedo published the landmark Nature paper entitled “Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea” which pulled together all the above papers into a finding that there were three distinct antibodies that cross-reacted with Lysogangliosides in the brain. In addition, they found one of these antibodies caused significant CaM Kinase II activation in sera. During this time, Dale , Church and others were making similar observations regarding anti-basal ganglia-antibodies (ABGA). However, not all thought the research sufficient. Kurlan, Kaplan and Singer wrote many editorials questioning whether the subgroup was sufficiently distinct. They were consistently unable to repeat Swedo's experiments and questioned therefore whether the diagnostic criteria was strong enough and whether causality was actually shown. Unfortunately, most of their studies were on kids with chronic tics and controlled OCD rather than on children who matched the lightning like onset described by Swedo. This difference in interpreting and applying the PANDAS criteria may explain the divergent findings. Those studying onset seemed to find one finding. Those studying long term non-remitting tics found another. While this should help definition, the unfortunate editorials have instead caused more confusion than clarity. Clarifying the presentation differences of PANDAS (sudden onset, episodic course) In 2004, Swedo responded to Kurlan and Kaplan’s comments explaining the different presentation of PANDAS from traditional OCD in that PANDAS presented with sudden onset and distinct episodes unlike the Tourettes presentation from Kurlan. Curiously, despite this clarification, several longitudinal studies continued to use acute onset or episodic course and used a definition of episodic more consistent with wax/wane than the sawtooth like remission and recurrence described by Swedo. Antibody isolation and Cam Kinase II In 2006, Kirvan and Cunningham published their finding that children from the Swedo studies were distinct from Tourettes and traditional OCD/ADHD patients in that the Sydenham Chorea and PANDAS children had elevated CaM Kinase II activation in their sera. In 2007, Kirvan further showed that Tubulin is a target of the anti-neural antibodies in patients with sydenham chorea. Creation of a mouse model of PANDAS (EAE) and passive transfer In August of 2009 Yaddanapudi showed behavioral abnormalities in a set of mice after innoculation with GABHS. These mice were especially bred to have high T-cell rates and be prone to blood-brain barrier disruption. Yaddanapudi showed that IgG transfered from innoculated mice to non-innoculated mice transferred the behavioral abnormalities. This is known as passive transferance and a key finding for proving auto-antibody effects. Explanation of how the Blood-brain barrier is crossed In November 2009, Bartholomäus et al unlocked a key part of explaining how the blood-brain-barrier can be breached. Using mice similar to Yaddanapudi (i.e., bred to have high T-cell rates and prone to blood-brain barrier disruption), they were able to watch individual T-cells cross the blood-brain-barrier. Once across, the T-cells produced inflammation recruiting other T-cells to the site of the breach. This could explain how antibodies in the blood stream cross the blood-brain barrier which has been the missing element since Husby's initial findings over three decades ago. Th17, Autoimmunity and the blood brain barrier Recently (2010), Wang et al published a remarkable finding that repeated nasal innoculation with live (or dead) GABHS produced Th17 cell response in mice. What was interesting was that mice innoculated with GABHS produced Th1 response, whereas those with just nasal coloniztion produced Th17. Th17 was recently identified in 2006 (see Annunziato et al ) and is highly implicated in auto-immune disorders. In 2007, Kebir et al published the paper "Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation" where it was shown that these Th17 cells are highly pro-inflammatory and promote blood-brain barrier disruption. Perhaps this is the missing link in how auto-antibodies are crossing the blood brain barrier (i.e., GABHS carriage triggers Th17, GABHS infection triggers anti-neuronal antibodies, Th17 disrupts the BBB allowing anti-neuronal antibodies (or B/T-cells) to cross). While this is a mouse model and may not apply to humans, the study is noteworthy because only carriage was needed. This may explain why an apparent "allergic" reaction is seen in some children -- i.e., that only colonization is necessary on subsequent exposure and not infection. Excaberations due to GABHS in acute and chronic cases Two longitudinal studies on children with Tourettes Syndrome (one by Kurlan et al. 2008 and one by Leckman et al 2010 raised questions about whether: the PANDAS criteria was suffienctly narrow to exclude Tourettes patients who just happened to have a coincident strep infection. whether chronic conditions had the same association with GABHS as acute onset Considerable energy was spent on how to define a strep infection and what window should be used to check whether GABHS infections correlated to exacerbations. While these were very well run studies, the exacerbations described (e.g., no change to CYBOC score in 2 years) did not match the reports by Murphy or Swedo. It is possible that the selection criteria was not correctly applied, that the onset phase is distinct from long-term disorders, or that GABHS is merely one of many triggers in established tic disorders. Trying to reconcile the camps In July 2010, a multi-disciplinary workshop on "PANDAS" was held at the National Institude of Health to bring the research perspectives together and compare findings. Clinicians reported a highly coherent set of symptoms that appeared at onset. These findings were compared with the symptoms in the two longitudinal studies on Tourettes children and raised the question of whether the PANDAS criteria was suffienctly narrow to separate patients from Tourette controls. The result of this workshop was the recommendation to: separate the clinical presentation from the etiology/pathogensis (cause) lower the importance of tic symptoms in the defining criteria require acute onset of OCD symptoms in the primary citerion The term "Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)" was chosen to be an umbrella term covering a coherent set of symptoms that could triggered by infection (PITAND and PANDAS) or non-infection triggers. Essentially PANDAS is within PITAND is within PANS. This has the implication that PANDAS criteria would be adjusted to the PANS criteria plus an association with GABHS. Continued clinical studies Several followup studies have focused on the clinical presentation of PANDAS. Murphy in 2011 published a study of 109 subjects (68 controls). Looking only at the clinical presentation, Dr. Murphy concluded that those in the PANDAS group were statistically more likely to: have had definite remissions in neuropsychiatric symptoms; have dramatic onset of symptoms; have definite remissions; show remissions of neuropsychiatric symptoms during antibiotic therapy; have elevated streptococcal titers; have episodes of fever/sore throat at onset/flare up; show positive GAS culture results with symptom onset/flare up; and present with clumsiness In addition, the NIH is repeating the 1998 Perlmutter study and has opened a clinical trial for new patients who exhibit dramatic and rapid onset of symptoms. What I find rather fascinating about all the above is the nice trail of good science leading up to the discovery of the antibodies. The strongest counter evidence to PANDAS is the longitudinal studies that selected cases of chronic tic/Tourettes. One study found a correlation and one did not. While I'm personally frustrated that the reasonable debate in the research community causes confusion and denial of treatment in the clinical setting, it is impressive how quickly progress has been made. Just think, how long from ulcers being thought purely the result of type A behavior/stress and then the finding of Helicobacter pylori? In 1586, Donatus decribes gastic ulcers. In 1913, Rosenow suggests that streptococci produce ulcers. In 1951, Allende notes that penicillin seems to help ulcers. In 1984, NY Times publishes summary of research. Altman states "I've never seen the medical community more defensive or more critical of a story." It's not until 2005 that Warren and Marshall are awarded the Nobel Prize. I appreciate these are different but it reminds me to have patience. Quite a saga. Regards, Buster

Hi PixiesMommy, Started a reply on the lingo here but asked Chemar to move this subtopic to it's own thread. Look here: http://www.latitudes.org/forums/index.php?...ost&p=36261 Regards, Buster

I think our dr. used: 279.9 -- Unspecified disorder of immune mechanism and 348.30 -- Encephalopathy unspecified but not positive -- haven't seen bill yet.

We probably should have pulled this out to its own thread, ... I agree with you that your anti-lysogangliosides are pretty close to the negative controls. There are a couple of possibilities: a ) azithromycin is having an effect on the results -- there are papers that indicate macrolides affect the distribution of the components of CaM Kinase II b ) there's some other element driving elevated CaM Kinase II Did Cunningham offer any more details? Certainly unclear to me how to read those results. Regards, Buster