momto2pandas

Studies do not need to be placebo-controlled to have an impact in the medical community, particularly for children. It helps, but it's not necessary. The process depends on the goal. Both of the avenues you mentioned are used. If the product is already on the market (presuming it's a pharmacological treatment trial), then researchers can just decide what they want to do, design the study, apply for and hopefully get the funding (usually from NIH or some foundation), get approval from an ethics board (IRB), run the study, and publish the results. This process informs the medical community and may influence treatment, but does not lead to the drug being approved by the FDA for treatment of the disease, which in some cases means that insurance companies will call it "experimental" and won't cover it. If, on the other hand, a pharmaceutical company decides to go after marketing approval for a drug - either a drug that is already on the market for other diseases, or one that is still being developed - then there is a specific process they need to follow, with dose-finding trials (what dose do you need to treat that particular disease?), efficacy and safety trials, etc., all with a number and variety (gender, age, race, etc.) of patients that the FDA deems adequate to prove that the drug is safe and effective. If the product is already on the market for something else, the requirements may be less than if it's a brand new product (since a lot of safety issues will already have been explored.) The study designs need to be approved by the FDA and ethics boards, and the pharma company then works with doctors at universities or in the communitty to treat their patients according to the study protocol. The data from all of the studies is then assembled and submitted to the FDA for a determination of whether the drug can be "approved" for marketing for that disease. This smoothes the way to insurance coverage. This process is generally much more definitive, but much more expensive, than drug trials typically initiated by single investigators. If a drug is developed for an "orphan" disease, essentially one that meets criteria for being rare and under-treated, then the process for getting FDA approval is abbreviated and much faster and less expensive. FDA also provides funding to encourage companies to study these diseases, since they are rarely profitable once all of the research costs are taken into account. That's an very abbreviated summary, but that's it in a nutshell. ----- I have to admit, I hadn't given the double-blind side of things much thought and I, like you, would not want my kid to suffer any more than he already has either. But we desperately need more research. I'm pretty far removed from the process, to be honest. Does it take double-blinds for the scientific or medical community to accept results as valid? Or could freshly-diagnosed PANDAS kids not be given abx courses and studied and tracked for changes in their behavioral manifestations and bloodwork before, during and after, without potentially harming someone in the process by giving them a placebo or withholding the intervention? Would such results be considered valid? Or would they, as my psych likes to label much of the stuff I tell him, be considered only "anecdotal evidence." And how does the process work to begin with, do you know? Does a doctor or team of researchers determine a project they'd like to address and then go after funding for it? Or could/would a pharm company itself take an interest in research of a certain kind and commence the research project, from A to Z, on its own? And what about human analogues for the studies, if they must be double-blind: mice or swine or something? Mostly, the gist of my initial query was, would contacting one of the primary abx manufacturers along this vein yield any results?

There are lots of ways of doing studies without placebo controls. These days, ethics guidelines actually prohibit doing placebo-controlled studies where there are existing/alternative treatment options available. It forces researchers to use more clever clinical trial designs, but it is routinely done.

By the way, I don't think that there is any concern about the integrity of the results if they come out of, or are funded by, pharma. I know that's the popular perception and it was my perception before I joined industry as well, but at this point in my experience, having worked for more than a decade in each of academia and industry, I would say that the research done by industry is far and away more reliable than the research done in academia. I will spare you my rant on this topic. :-)

I'm a consultant in the pharma industry who has been doing some research on this topic (I consult or have worked full time as medical director in charge of immunology programs for many of the big players), and so far I don't know of any company that is actually working in this indication. I might be missing something, though, since patents have been submitted for immunological approaches to PANDAS-like syndromes. I am actually supposed to have a meeting next week to talk to a pharma executive in charge of a product that I think would be promising for PANDAS (and who is interested in hearing me out), but I'm going to have to reschedule since I haven't had enough time to prepare slides, etc. (my paid work and 2 [PANDAS] kids, unfortunately, have to take precedence...). I firmly believe that we could get pharma backing for this, and that it would be a great advance. The FDA even provides money and special incentives for companies to do research on "orphan indications," of which this is certainly one. I've developed products for orphan immunology and other indications before, so know how to navigate this process. Unfortunately again, though, the grant deadline is early Feb. I was going to try to submit a proposal on behalf of one of my clients, but simply won't have the time this year.... I've been wanting to try to get the main doctors who treat PANDAS together to go over research ideas and draft up some real proposals for pharma, but again, time has been limiting...

I had that experience too. My son needed emergency dental work on Christmas eve, of all times - he was in screaming pain with toothache. We were worried about the PANDAS but had no choice. As soon as he got off of the dentist's chair, my heart sunk. Huge pupils, huge purple circles, throwing fits all the way home. I spent the next several days wondering if he would ever be the same again. He had already been on Zith prior to the work, and the dentist added 10 days of clindamycin to the zith afterwards. He started to get better after about 4 bad days, and was pretty much back to baseline after 7 days, though a little wobblier than usual. So our vacation was kind of lousy, but at least he was well in time to go back to school with no issues.

sorry to hijack for a minute, but Momto2Pandas, are you sying you had issues until you were treated for TB, and then things started getting better? Yes. We didn't identify the connection immediately, but the anorexia nervosa and tics literally disappeared suddenly at some point during that course of treatment. (I don't remember the exact timing, but I have it all somewhere...). Isoniazid and rifampicin. The mood stuff didn't go away 100% until my thyroid issues were discovered and corrected a bit later, after the TB treatment was over, but they were MUCH MUCH better - I was fully functional at college, etc, after having had to drop out of high school multiple times. Incidentally, I didn't even know that I had TB at the time. I reacted positively to a skin test and then upon follow-up (chest x-ray, etc.) had positive findings for TB. I have no idea how long it had been in there. I had just figured my resp symptoms were allergies, bronchitis, etc., which I suffered from a lot, and of course anorexia nervosa seemed to explain the underweight part.

p.s. During that "chronic" time in my life during my teens, I spent almost 2 years in psychiatric hospitals (5 times, a few months each). Recall that this was the 80's so "PANDAS" wasn't even recognized as more than a one-off thing, and no-one knew anything about treating such one-off cases. I have to say that I am incredibly grateful for that time in my life - that my parents took that very difficult leap to keep me safe until something was figured out by hook or by crook. Not only did that haven buy time for me, but in that setting one spends an enormous amount of time learning strategies to cope. Without having had that, who knows how I would have navigated the up and downs of the years that followed. Those hospitalizations were probably the most important things that have ever happened to me.

I still wonder if it's really a distinction or if we just haven't yet found the right treatments for the "chronic" folks. I was "chronic" (anorexia, bad tics, mood disorders) from about age 13 to age 17 or 18, at which point I was found to have tuberculosis and was treated very aggressively with antibiotics that I had never had before (2 years worth, but I was better PANDAS-wise toward the beginning of that). After that period, I was never chronic again, and I never had been before that period either. My kids have only been episodic so far.

I have to confess that after I was diagnosed with infection-triggered autoimmune neuropsych syndrome, well before PANDAS had been defined and before I could get anyone to prescribe antibiotics consistently even when I wasn't "sick" enough to justify them, I did all kinds of things to get my hands on them. I used to travel to Europe a lot, and I would go around the world while doing so (no extra cost when traveling business class) just to stop in the Bangkok airport and stock up on large quantities of antibiotics with no prescription at their airport pharmacy. I would stock up in Mexico while on vacation. I would go to high-end "make you perfect" cosmetic dermatologists and complain of acne ("I know it's not on my face, but believe me it gets bad unless I have antibiotic X at dose Y....") and get them to prescribe for me. Whatever it took. It's funny to me that now, 20 years later, I can just call up my GP or ped and tell them what's going on and get antibiotics/steroids for me or my kids when I need them without feeling like some kind of a criminal. All that having been said, I did educate myself on possible side effects and kept a close eye on myself. I realized that it wasn't optimal to do what I was doing without medical supervision, but it was that or allow my whole life to go down the tubes at that point, so I did it anyway.

We have been dealing with PANDAS for about 3 years with my ds6, and about a year+ with my ds3.5. And then I've had it for decades. For the first 2.5 years with my older ds, it was ONLY very distinct episodes associated with Strep that would turn on and off abruptly over about 2 weeks. One every several months. Even teachers, parents of other kids, etc. could see exactly the day it started and the day it ended, and he was symptom-free in between. Over the last few months, this pattern still holds, but we've added on more subtle things when he gets other, milder infections or when his best friends get strep. Those last anywhere between 1-4 days, I would say. Those don't have any true OCD, but we see a few tics and a lot of pretty severe moodiness and inattention, large pupils, purple under the eyes, a bunch of allergic skin symptoms, and serious hypersensory stuff. During longer episodes when he's actually gotten physically sick, we see more OCD, tics, etc. in addition to the above. My ds3.5 still only has symptoms when he's actually been clearly sick with a bacterial infection (OCD, defiance, etc. - no tics but some verbal difficulties) and they go away completely with a usual course of antibiotics. Over my life, I started out with distinct episodes as a child, then as a teen it was more continuous with waxing and waning for several years, and then in my 20's it was back to distinct episodes, which eventually became rare (even a few years between) and short, though apparently triggered by a wider variety of things.

The right fish oil supplement has been the single most helpful thing I have used in my decades of dealing with "PANDAS" in myself...but it has to be the right one, with the right ratios. An old psychiatrist of mine from Harvard turned me on to Omegabrite, which is the brand on which the clinical research out of Harvard was done showing positive effects on neuropsych symptoms. They make a big deal out of the exact ratios of EPA/DHA, and my psych felt that this was essential as well. We order it on-line (they have a pediatric formulation as well as an adult one) and it seems to work better than any of the many brands we've tried from drug stores. I also have a number of friends who have reported positive results with these. I think there is a bunch of research cited on their website if you want to look into it.

I think that solidifying/refining the cytokine hypothesis is the key to pharma investment in PANDAS...which, I think, will be the key to lots more research on treatment and etiology. I'm hoping to make strides in this area over the next few months. I've come across some stuff on pro-inflammatory cytokines recently too....I was looking for the possibility that my DH's recent upswing in anxiety could be related to his getting the flu in October... Mental illness as a result of post infectious autoimmunity and or cytokine inflammation....so intriguing...I wish I understood even half of what I read about this stuff. I really do think that once PANDAS becomes more understood, it will open researchers minds to dig more into the infectious aspect of it. Faith, I wanted to mention that strep can also be in the middle ear, but unless there is a perforation, you can't strep test the fluid. It really does seem as if your son is reacting to a viral issue. In my mind, formost in the PANDAS protocol is to try to eliminate strep....but what if it is a viral trigger....then I think you are on the right track to consider anti-virals or supplements that claim to be anti-viral. I was looking into using oil of oregano--but I couldn't find any info about weather it is safe to take with pen vk (my daughter takes this as a prophylaxis). Olive leaf extract is not safe to take with antibiotics because it decreases the effectiveness of the drug. Good Luck ~Karen

My thought was that the two are related and that the pro-inflammatory cytokines increase ICAM-1 along the BBB enabling T-cells to cross. Once across, they get activated by fragments of neuronal tissue and release still more inflammatory cytokines creating a breach in the BBB. This then allows the anti-GM1 which trigger the interference with the basal ganglia signalling. All theory (i.e., 3 pieces of research stitched together without experiment), but seems to fit. I keep having this feeling that once this crossing of the BBB is better understood, we'll have a significant improvement to the understanding and treatment of the Neuropsychiatric aspects of a set of disorders -- i.e., SC, PANDAS, potentially Autism, .... Buster Yes, I have had this thought as well. The effects of cytokines could be both direct neuromodulating effects and "indirect" effects on the BBB that allow all kinds of things to happen. The thing that's making me think that there could be two distinct pathological processes, though, is the fact that we seem to have 2 distinct processes happening in our household as far as the clinical picture, and so far at least one other person is saying the same thing. It seems that many of us science types have done a lot of research. I wonder if we should think about having a little informal mini scientific conference and really hash through ideas critically and brainstorm future directions in research. I'd love to put together slides with all of our ideas and have them critically examined. I'd also still love to do a really good survey to look, among other things, at clusters of symptoms/signs, etc. (e.g. do "hyperimmune" types "look different" than "hypoimmune" types? do different clinical types respond differently to different treatements?) so that we'd have at least that much "data" to work with. It'd be lovely to have the Dr T's, L's, K's, B's, S's, etc. involved. I imagine that there would be interest. The issue is funding, of course. I'd be more than happy to pay my own way and do the prep for free, but paying for everyone else would be something else!

We absolutely see this. Not the full-blown OCD-like stuff, but enough to set off that "look in the eyes" and significant behavior/mood stuff. For us, it generally lasts less time than episodes triggered by actual infections. Also, there at least two, and probably three, in our family with PANDAS, and only my ds6 reacts to exposure in this way. He seems to be the most sensitive to all kinds of triggers.

I like this thinking as well. As far as the clinical presentation, do you feel that the two posited types are different? What do you speculate to be the difference in underlying pathology? I have been thinking about, and would love to put together, a surveymonkey survey to get at some of this. I have a lot of experience in the design of these types of instruments in clinical research and I sure do think it would be useful for PANDAS. I am having a hard time sorting out my family with respect to the two subtypes. I would have to put us into the hypo-immune subset, except that we seem to be hyper-immune when it comes to auto-immunity (like many immune deficiency types) - lots of autoantibodies, atopic symptoms, etc. Steroids have been very helpful clinically, though they have been used only sparingly. One thought I have had: I believe that inflammatory cytokines are elevated both in hyperimmune states and in immune deficiency states (at least in AIDS) - and it's possible that at least a bunch of the process is mediated through those. There is certainly plenty of stuff in the literature about pro-inflammatory cytokines having direct neuromodulating effects that result in psychiatric symptomatology. In my kids, sometimes I wonder if there are two distinct processes going on. There are the overall hypersensitivity (sensory and emotional) and affective lability/irritability/defiance that seem to wax and wane pretty frequently and to respond to a variety of immunological challenges (including allergens), and then there are the distinct, and considerably less frequent, real OCD/tic "flares" that start and stop quite suddenly only with/post infections and that seem to overlay the other symptoms (which also get worse at these times). I have wondered if the background sensory/lability stuff could be cytokine-mediated since it doesn't even seem to require the presence of an infection, and if the distinct OCD-tic episodes could result from a mechanism more similar to the SC model. Has anyone else noticed this distinction?

This could be allergic, as well. Has she been checked for food allergies? Those have caused both sinus issues and bottom rashes for both of my sons.

This is interesting, because I have had the same experiences with strep tests. When my whole family was battling strep back in 2008 (this was when my ds was first diagnosed), everyone else in the family tested positive for strep except for me, and I was the only one with an incredibly raw, red sore throat and all the other strep symptoms. We went through a few rounds of this, and every time I was the symptomatic one, but the only one who tested negative. My doctor finally just said that in his clinical opinion, I definitely had strep, and he told me that the strep test shows false negatives for something like 2-4% of people for some reason, and I was one of those. I figured it must just be something about my throat and their ability to get a good swab. I never had ASO titers taken during those episodes, though, so I don't know what they would have shown.

I also think that there is something to maternal instinct. My husband is not resistant to the idea of PANDAS since he sees it in my kids too (hard to miss), but he doesn't see nearly as much of it as I do - even when we're both around the kids. I realize now that he's not trying to be resistant, he just isn't quite as tuned in to the subtleties of what's normal for the kids and what isn't. For example, I don't think he takes one jot of notice of their bathroom habits, though I know that in the back of my own mind I track all of that stuff on some level and will always be aware of changes. Just wanted to add, too - when I had tics as a kid, it was completely written off as "nervous tics." It was just something that people got or had, like having a mole or something. I think that a lot of that thinking still prevails, but I think that we know better, so please don't second guess yourself! Having gone through the experience of PANDAS as it develops over the course of childhood, I know that even if my DH were totally against it, I would find a way to get my kids seen and treated (or at least followed) despite that. It can get a lot worse rather than better, in the short run, and if I had "known better" but not acted on my kids' behalf because of pressure from my husband, I think that the guilt would do me in. Every relationship is different and this isn't necessarily a recommendation; it's just my perspective...

One thing that I'm not getting from this explanation, though - if it's purely infectious, then why isn't PANDAS more common, and why isn't it always reported in clusters? The assumption must be that there must be some genetic or environmental predisposition involved, no? Although the immune system may not be completely mature until early childhood, even toddlers and young babies generally DO produce immune responses. So it seems that in order for this cascade of events to occur as described, there must be some individual immune failure, not just due to age, to start with. Could be a genetic "flaw" in immunity, or perhaps an overtaxed immune system, premature birth, medication administration....?

That must presume a normally active immune system, no? If one has an immune deficiency in which one fails to produce a proper immune response in the first place or in which one fails to retain immune memory, things would be different, no? Then "enough antiboides to other strains" will never happen. There are certainly adults who have episodes, still, despite tons of strep infections. I can think of a couple who have been in their 70's and 80's. But not 100% immunocompetent. Kim, my father-in-law basically drew me a graph and once the child's body hits the cross over point with their immune system they will not have episodes not even to the S Pyogenes if enough antibodies to other strains exist. -Wendy

I thought about that too! Pediatric Autoimmune Infection-triggered Neuropsychiatric Sydrome (or Disoder) PAIND or PAINS Too negative, but funny how well it fits!

Thanks, Wendy. If it's not too much of a bother, could you tell me what about the PANDAS urinary issues he thinks would be inconsistent with interstitial cystitis? Just curious because there seems to be a correlation between other pediatric-onset anxiety/mood disorders and IC in some clusters. I know very little about urology so don't really know what the difference would be between IC and what we see in PANDAS. I'd love to understand it better.

I was on Yasmin (I think it was called) and it was excellent. On the other hand, the triphasic ones (Triphasil?) were, I believe, disasters.

Haven't seen any research, but in my own experience, the episode I had after my first period was BY FAR the worst of my life - and the longest (of course, I was untreated). Good news is once that one ended, any and all later ones did indeed pale in comparison. I also had the experience that "the pill" can set off problems. In my own experience, some birth control pills were disasters, and others were great. Dr. T told me that he has also seen problems with patients starting on the pill. Incidentally, speaking of hormones, pregnancy/childbirth was probably the best thing that ever happened to me in terms of autoimmune issues, including PANDAS. If I recollect correctly, plenty of data shows the influence of hormones on the immune system and autoimmune conditions, so none of this is a surprise.

My 6 yo ds just had a tooth extraction and we had an ugly flare in follow-up. Those purple-circled, wide-pupiled "mean" eyes and "tantrums" within literally minutes of the procedure - three days before Christmas - made my heart sink. The dentist prescribed clindamycin added onto the Azith he's already on and things luckily got back to normal within 2 days. The dentist said that he is very close to cutting his 6-year molars. Not looking forward to that, although at least now we know that the clindamycin+azith seems to be effective against it. I'm not sure; quite possibly. I guess I could check with the dentist. He's always been a little behind in terms of the maturity of his mouth; he's still housing some of his baby teeth! Is there something about the cutting of the molars we should be aware of? With my child, any oral tissue damage amps up symptoms. Her ped and I think its because she's harboring intracellular strep in her epithelial cells, which is released with tissue damage: cutting teeth, dental surgury, T&A... And the adolescent teeth seem to come with the hormonal development. My daughter had a bad flare recently w/ a double whammy of cutting 4 molars and dental surgery...all timed with the onset of her 1st period. The worst flare of her whole life occurred following T&A surgery. Looking back, her worst times always were thought to be caused by teething pain...before we new about PANDAS, we thought she just had a terrible time with teething.