Buster

Good catches. I'll have to think about where to put the antibiotic question. I got a new question that came in around "how long after starting antibiotics should I expect a response?" -- tough question. I'll absolutely extend the time link on the note regarding steroid burst. What I was trying to position was that long-term predinsone has really high risks and that all the efficacy studies are only on more the "break the cycle" or "diagnosis" approach. Latimer seems to be doing more the "break the cycle" whereas Dr. K seems to use more the "diagnostics" use. In terms of the strep re-test, the studies by Kaplan which have false negative reports cover 14-21 days from end of treatment. There were a small % of patients who were negative at 14 days but then postiive at 21 days. I'll pull the study, but my memory is 6%. So the safer margin is at 21 days (or logically 1 month from detection of positive culture). Thanks for review and comments, I'll take one more crack at the FAQ in an hour. Buster

edited base post with some of the new questions.

I recommend this flow chart: http://www.latitudes.org/forums/index.php?showtopic=6688

Wow, I most assuredly don't agree with her there. If I can nudge you in any way, I'd really encourage you to do the test. It's essentially the only lab test that at least indicates a direction (given all the problems with GABHS cultures and blood work). Otherwise you are just left with the clinical symptoms (which are really tough in your son's case). Yes, the research test might come back negative, but wow, wouldn't that help your comfort one way or the other? It is totally possible that it isn't PANDAS, but it seems you'd want to rule out the others. What I think you've indicated is that SSRIs did not seem to stabilize mood. This seems really consistent with other reports on this panel and in Murphy's report where they saw greater activation on SSRI's -- I don't think it is exactly the dose, but rather that if the antibodies are interfering with dopamine receptors, then that SSRI is acting like turning up the volume on your TV show and then the antibody comes along like a loud commercial. What I'm getting at is it's like the body can't quite get the dopamine regulated because there is actually something interfering with the receptors (not with the dopamine itself). This, in my opinion, is why there is activation on SSRIs -- you're adding dopamine to an unregulated baseline -- you'll still get the peaks and valleys but with higher peaks (and higher valleys) -- meaning disinhibition occurs. I'm presuming you've had the MRI for ADEM and checked for demylination. Have you had a functional MRI -- such as during an episode so that can see what is triggering? I can see that Dr. L might have a profile now for PANDAS kids.... I just was listening though to Dr. K talking about the spectrum from Autism on one side to chorea on the other. Yes, it might be something else, but wow, I'm really surprised that she's pointing you in a new direction rather than completing the few tests that might help. Did you ever run a prednisone burst ? You also mentioned Omnicef -- did you ever try the other macrolides such as azith. Not recommending just wondering how you ended up on Omnicef and how you ended up on the oscillation pattern (i.e., 5 on 5 off). I know you are seeking some closure and direction and I'm probably just adding more weight, but I just don't know understand which of the symptoms has given Dr. L the confidence to redirect you as it's definitely not obvious from what you wrote. Best regards Buster

wornoutmom, Your post made me so sad. I'd be okay if it posted why you felt that your son had some other diagnosis, but what you posted was indicating you were largely back to a non-diagnosis. I hate to disagree with Dr. L, but I have to say that PANDAS kids absolutely have good and bad days. It is exactly the sawtooth effect that so distinguished the disease for Dr. K and Dr. Swedo. Did you ever run the CaM Kinase II results? It certainly seemed you had exacerbations associated with illness and that would perfectly correlate with high auto-antibodies with some BBB imparement. So did you ever have significant remission on long term antibiotics? Did you have significant remission on prednisone? Sigh. I know you followed the flowchart at http://www.latitudes.org/forums/index.php?showtopic=6688 how did you fall out? Best regards and thinking of you, Buster

A couple of things: Carriage is usually shorthand for "asymptomatic carriage" and is defined as having a positive throat culture for > 14 days and not having an immunologic response A rising titer (of ASO or AntiDNAse B ) is an indication of a prior GABHS infection, but to find the rising titer you must do two draws 1-2 weeks apart (i.e., have a baseline againt which to measure). Most doctors don't have the two titers and use the "Upper Limit of Normal" ULN as a baseline measurement. Statistically, this works out to be a good indicator for kids with strong immunologic responses on first draw -- however, with only a single draw, you do not know if the titer is rising or falling. The titer can rise even if there is no present GABHS infection. ASO rises in 46% of people 1-4 weeks post initial-infection. AntiDNAseB rises 6-8 weeks post initial-infection. In 31% of people neither ASO nor AntiDNAseB rise despite a positive throat culture. A constant titer is meaningless. If significantly elevated it is possible that there is a recurrent infection but there is no reliable study indicating how to interpret a constant titer. To be safe, most doctors treat an elevated titer as if it were rising and in the absence of positive throat swab will inquire about a possible sinus, vaginal or skin infection. A falling titer is also not really helpful. The rate of fall of titers is not studied. In many, AntiDNAseB can stay elevated for months. In general, trust the throat culture first. Bottom line, I have no idea how the doctor would have called you a carrier as you only had a single measurement and no postiive culture. Regards, Buster

I've put a copy of the file temporarily at pandas_treatment_log.xls until Dr. T posts his fileserver name. Buster

That does seem to be the case for many of Dr. K's patients and seems to be the case for us. So far, the single IVIG was the cross-over between continued motion abnomalities, mood lability, contamination fears, fine motor tremors.... It did take 14 days until we saw a positive effect, and then we saw another slight bump in the 16th week. But every day seems better. Trying not to jinx ourselves, but so far so good. Buster

Are you asking about the effect of long-term antibiotics? or the justification of using antibiotics for minimizing the severity of GABHS triggered auto-immune responses? The efficacy in PANDAS diagnosed children? or a "how does it work" question? I have papers on all of these items. Buster As for articles on long-term abx efficacy, I'd love to see those, also. Hopefully seomone here will be able to chime in. Scientific American Mind can be purchased at most of the larger, national bookstores; we got our last copy at Barnes & Noble. You can also purchase issues on-line; I think the cost is $7.95/per, or something like that.

We're at 27 weeks post IVIG and almost all symptoms pre-IVIG have disappeared. Our dd9 had anorexia nervosa, hallucinations, suicidal statements, measurement rituals, significant defiance, compulsions, movement disorders, fine motor issues, ... These symptoms are absent. We still have a small amount of social anxiety -- but this seems an underlying condition and is not inhibitory. You should make sure that you really think the symptoms are auto-immune in nature. If not, then IVIG will probably not help a lot. We had a couple of "bumps" most notably the first 2 weeks and then at week 16 week we had a flare. We were not able to isolate what happened at 16 weeks, but it lasted 5 days and is now gone again. Bottom line, we're in good space now. Can't tell you the prognosis yet, but we seem to fall in the camp that a single dose was sufficient. To others, the most notable change is the absense of the movement disorder. To us, the most significant change is everything else (the lack of compulstions, the lack of defiance, the improvement to fine motor skills, the decline of separation anxiety, ...). Regards, Buster

Let me translate. If your doctor did an IgM test, then the test came back positive and your child had mycoplasma pseumonia within last 4-6 weeks.

Ha, funny, ... Problem is we don't know the lab standards or which test was done. Call your lab/doctor and ask what the normal ranges are. If it was the IgM then see: https://www.labcorp.com/wps/portal/!ut/...2fshowDetail.do Test Number: 163212 CPT Code: 86738 Specimen: Serum Volume: 1 mL Minimum Volume: 0.5 mL Container: Red-top tube or gel-barrier tube Storage Instructions: Maintain specimen at room temperature. Causes for Rejection: Hemolysis; lipemia; gross bacterial contamination Reference Interval: Negative: <770 units/mL Use: Aid in the diagnosis of atypical pneumonia and Stevens-Johnson syndrome by providing laboratory support for a Mycoplasma pneumoniae infection. Results must be interpreted in light of each patient's history, physical examination, and other diagnostic findings. Limitations: The absorbent used in this assay removes as much as 15 mg/mL of human IgG, but the presence of residual IgG in individuals with hypergammaglobulinemia may affect results adversely. Methodology: Enzyme immunoassay (EIA) Additional Information: Low positive results (770-950 units/mL) are presumptive evidence of acute or recent infection. It is recommended that the test be repeated on a fresh specimen one to two weeks later to assure reactivity. Specific IgM may persist for several months after initial infection or be absent during reinfection. References: Ali NJ, Sillis M, Andrews BE, et al, ”The Clinical Spectrum and Diagnosis of Mycoplasma pneumoniae Infection,” Q J Med, 1986, 58:227, 241. 3737868 Levy M, Shear NH, ”Mycoplasma pneumoniae Infections and Stevens-Johnson Syndrome: Report of Eight Cases and Review of the Literature,” Clin Pediatr (Phila), 1991, 30(1):42-9 (review).1899814

Your doctor or the lab should be able to provide reference ranges and interpretation. You can read more about the IgM test (presumingthat's what you had) here. Type in Mycoplasma IgM in the menu. https://www.labcorp.com/wps/portal/!ut/...2fshowDetail.do Test Number: 163212 CPT Code: 86738 Specimen: Serum Volume: 1 mL Minimum Volume: 0.5 mL Container: Red-top tube or gel-barrier tube Storage Instructions: Maintain specimen at room temperature. Causes for Rejection: Hemolysis; lipemia; gross bacterial contamination Reference Interval: Negative: <770 units/mL Use: Aid in the diagnosis of atypical pneumonia and Stevens-Johnson syndrome by providing laboratory support for a Mycoplasma pneumoniae infection. Results must be interpreted in light of each patient's history, physical examination, and other diagnostic findings. Limitations: The absorbent used in this assay removes as much as 15 mg/mL of human IgG, but the presence of residual IgG in individuals with hypergammaglobulinemia may affect results adversely. Methodology: Enzyme immunoassay (EIA) Additional Information: Low positive results (770-950 units/mL) are presumptive evidence of acute or recent infection. It is recommended that the test be repeated on a fresh specimen one to two weeks later to assure reactivity. Specific IgM may persist for several months after initial infection or be absent during reinfection. References: Ali NJ, Sillis M, Andrews BE, et al, ”The Clinical Spectrum and Diagnosis of Mycoplasma pneumoniae Infection,” Q J Med, 1986, 58:227, 241. 3737868 Levy M, Shear NH, ”Mycoplasma pneumoniae Infections and Stevens-Johnson Syndrome: Report of Eight Cases and Review of the Literature,” Clin Pediatr (Phila), 1991, 30(1):42-9 (review).1899814

If you have "hidden" strep somewhere in the body, would the ASO & DNASE titers show it? Not necessarily. Depends on timing and where the strep is located. ASO does not rise for skin strep. Also some 31+% of children won't have a rising titer despite a positive culture and perfect timing of blood test.

Hi Kcdc3, I was reading your previous posts . How long were you on continuous antibiotics? I couldn't tell from previous posts. How many days in a row were you taking azith? Buster

So very, very glad to get your news. Yeah!

<double post>

For those pursuing this train of thought, I just ran across this paper in Sept 2009 Journal of Pediatric Neurology. I haven't yet read full article . Buster http://www.pedneur.com/article/S0887-8994(...0210-0/abstract Pathogenesis of Neurologic Manifestations of Mycoplasma pneumoniae Infection Mitsuo Narita, MD Mycoplasma pneumoniae has been associated with various neurologic manifestations, but exactly how the organism can cause such a wide variety of diseases is a long-standing mystery. In this respect, although pneumonia has been considered the hallmark of Mycoplasma pneumoniae infection, emerging accumulations of data have revealed that the infection can cause a number of extrapulmonary manifestations even in the absence of pneumonia. The importance of host immune response in the pathomechanism of pneumonia has been established, but the pathomechanisms of extrapulmonary manifestations remain largely unknown. For this review, extrapulmonary manifestations due to M. pneumoniae infection were classified into three categories: a direct type, in which locally induced cytokines must play a role; an indirect type, in which immune modulation such as autoimmunity must play a role; and a vascular occlusion type, in which vasculitis or thrombosis (either or both, and with or without systemic hypercoagulable state) must play a role. This classification was then applied within a literature review for neurologic manifestations. Most neurologic manifestations due to M. pneumoniae infection could be reasonably classified into and explained by one of the three types of pathomechanisms.

Hi Wendy, Just a quick note that I share your perspective on the 100% and give thanks every day for the first psychiatrist who wondered if we had tested for strep. I also feel terrible for the children (and their parents) who are coping with OCD and haven't found treatment that works. I still recall March 2008 googling "strep, anorexia nervosa and OCD" and out pops PANDAS. I remember how surprised I was that the doctors were willing to prescribe Lexapro, Ativan, Klonopin and wouldn't give us antibiotics without positive culture. Thank goodness, she was positive and showed significant improvement 20 hrs after starting antibiotics. There were a lot of variables at that time so we systematically started removing variables to figure out what was going on. The folks in the hospital were trying to explain that we would need to give long-term psychiatric care and possible institutionalization of our daughter. There was no way we could accept this. It just didn't make sense. This wasn't some slow progression, this was a light switch effect -- absolutely wacky behavior. There had to be a tumor, a medical reason. A cause. So I too agree, get the tests, check the family with throat cultures, help turn the Cunningham tests into a diagnostic test, write letters to the NIMH to fund more research... but most importantly trust your gut. Don't give up searching for a cure. Each story where children get better is a joy. I hope that we find the right diagnostic steps to help doctors who doubt PANDAS be like the doctors who didn't believe that Sydenham Chorea is caused by antibodies to strep. Buster

Well, actually, you want to check whether the clinical symptoms are consistent with the symptoms of PANDAS. For example, did your child have daytime urinary frequency? Were the symptoms sudden onset? etc. Then, yes, you would want to check whether the family members have strep. The main reason is that strep does tend to ping-pong in a family. It's an easy test although important to be done by someone who knows how to take a throat culture. You can certainly just start with your potential PANDAS child, but at least in our case, other family members were good indicators that we had strep in the house. The ASO blood test has only a 46% accuracy and then only when taken within 1-4 weeks of a likely strep infection. Outside of that window, its value is limited. Strangely that's even a stronger reason to have them checked. Most kids of school age get strep once every two years. That's a really reasonable concern and a reason some people get either a home strep test or go to a clinic. You can certainly get all of them at once. The real problem is that most doctors think the ASO is definitive -- it's not. In addition, most doctors don't know you have to check titer direction (meaning two draws). Further most doctors don't know the timing interval for ASO and AntiDNAseB (sigh, makes you wonder what they learn in school). You are absolutely correct and if the doctor isn't well informed, that's exactly what they'll do. Yes, you can execute the tests as a group and that is often better since they have different time windows. However, don't let a doctor tell you that a negative ASO overrides a positive throat culture!

Hmm, not exactly. The groups are divided into those with OCD only, those with OCD and tics and those presenting with only tics. In addition, often the tics are vocal (although certainly many have motor tics or motion abnormalties too). There certainly are specific blood tests but they only add weight to the PANDAS or PITAND diagnosis, they aren't in and of themselves conclusive. Again, I refer you to the flow chart and the other documents as they are pretty explicit on the tests and the confidence intervals.

That's actually what Swedo did: In 1994, Swedo selected a pediatric subset of the "infection triggered auto-immune neuropsychiatric disorder" (PITAND). Then in 1998, she started looking at the subset of PITAND where the infection was strep (I suppose it could have been called PSTAND but PANDAS stuck). For the last 12 years she's been fighting just to show that even this subset is distinct and should be treated differently from patients who have OCD/tics without the autoimmune component. This is why she ran the trial with Nicolson in 2000 called "An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations." That study was a parallel to the Perlmutter 1999 study. In Nicolson it was shown that kids with OCD who did not have exacerbations associated with infections did not get better on PEX. In Perlmutter it was shown that kids with OCD exacerbations associated with infections did get better on PEX and IVIG. There were a bunch of case studies inbetween. What I'm trying to highlight is that Swedo probably got the trouble with the TS crowd because she included tics as her critieria rather than showing OCD symptoms post-strep, then broadening to OCD + tics post strep, then broadening to tic only post strep, then broadening to non-strep infections, ... Buster I think there should be an overall grouping of PIAND (Post Infectious Autoimmune Neuropsychiatric Disorder) with sub-categories that delineate the triggering infections.

Take a quick look through the flowchart at: http://www.latitudes.org/forums/index.php?showtopic=6688 and the overview document/FAQ sheets at: http://www.latitudes.org/forums/index.php?showtopic=6265 and http://www.latitudes.org/forums/index.php?showtopic=6266 Best regards, Buster

Updated flowchart to add mycoplasma pneumonia test at ASO draw. Buster

Frankly, I'd say no. Elevated Cam Kinase II is correlated with PANDAS and SC but is not shown to be definitive for PANDAS. There 's just not enough data yet to say whether there are other things that can cause elevated Cam Kinase II (hence the research trial) -- or how repeatable the tests are -- or that just because you have the potential in the blood serum that it will cross the BBB. CaM Kinase II should still be treated as just another piece of the puzzle. I liked Dr. K's comment on the AutismOne podcast where he said that antibodies to strep exotoxins count for him about 5-10%, clinical signs count a lot, response to prednisone burst is confirmatory for him. So he puts most of his weight on the clinical signs. Regards, Buster