Buster

Hi Vickie, Yes, this is intended to capture the "steps" that people take -- i.e., how did they reach a conclusion -- whether PID or non-PANDAS or likely PANDAS. With respect to the steroid burst, it's being used here as a diagnostic tool. There are severe adverse reactions for long term treatment with prednisone (see issues discussed in treatment of MS and Lupus) and as far as I know there is only one controlled study of pred for SC and none on pred for PANDAS. Buster

I'm sort of hoping folks will have read the Signs and Symptoms list at: http://www.latitudes.org/forums/index.php?showtopic=6265 which includes the list: Obsessions (e.g., preoccupation with a fixed idea or an unwanted feeling, often accompanied by symptoms of anxiety) Compulsions (e.g., an irresistible impulse to act, regardless of the rationality of the motivation) Choreiform movements (e.g., milk-maid grip, fine finger playing movements in stressed stance) Emotional lability (e.g.,irritability, sudden unexplainable rages, fight or flight behaviors) (66%) Personality changes (54%) Age inappropriate behaviors particularly regressive bedtime fears/rituals (50%) Separation anxiety (46%) Oppositional defiant disorder (40%) Tactile/sensory defensiveness (40%) Hyperactivity, impulsivity, fidgetiness, or inability to focus (40%) Major Depression (36%) Marked deterioration in handwriting or math skills. (26%) Daytime urinary frequency/enuresis (12%) Anorexia (particularly fear of choking, being poisoned, contamination fears, fear of throwing up) Buster

I thought I'd try to capture the steps folks have been taking in trying to diagnose PANDAS. Please check it over... Probably folks have lots of suggestions to improve, but thought this was a good start EDITED ** Modified : http://pandasdad.home.comcast.net/pandas_diag2.pdf Buster NOTE: This is not intended to be medical advice, but more a documentation of the steps that many of the patients discussed on this forum have followed...

No idea. I've wondered about this too. One of our children seems to get this hot flash episode -- practically melting in the middle of the floor complaining of being hot and only calming with a shower. It seemed so similar to an older person with a hot flash -- the sudden intense feeling of heat. Our pediatrician asked us to check heart rate when it happens and to see if it is in the middle of an anxiety attack. Neither seems to be the case. They indicated if it keeps up we might want to have thyroid/andrenal checked. It is curious. In our case, our dd is not having a mini-fever. Buster

"Carriage is an enigma" -- so says Dr. Ed Kaplan in his paper 1980 paper http://www.sciencedirect.com/science?_ob=A...92d1da34fbe59d6 There are several odd things about the carriage state. The first is it seems that the M-protein is affected in patients with chronic GABHS colonization. When these cells are moved to non-carriage individuals, the M-protein re-emerges. So something weird is happening there. Also in carriage individuals there seems to be competition from other throat flora that seems to keep the GABHS in check. Finally, there seems to be some IgA problem that prevents the colonization from being easily cleared. Carriage seems to create a low-grade infection that doesn't cause a huge ASO or Anti-DNAse response because only a small amount of the GABHS ever invades the blood stream. In PANDAS, a hyper sensitivity is thought to occur where that "small amount" is enough and so it isn't at all clear that carriage is benign. Although Swedo and others have primarily studied children who did not have carriage (i.e., those mounting a high ASO response). Now with respect to the typhoid Mary comment -- those with Carriage are actually just a lot less contageous -- there seems to be a bunch of differnet reasons. They tend not to have a large amount of mucous build up, they don't tend to cough/sneeze out the bacteria, and the bacteria itself seems to have certain mutation that is suppressing several of the factors that cause improved binding/adhesion (namely the M protein). So absolutely a carrier in the house can infect others, but it is not the same as having someone with full on strep (which tends to spread easily). Buster

Since you have the positive strep cultures, you really shouldn't be getting any blood work for strep exotoxin antigens. You might be getting blood work for other stuff, but you already have the positive on strep.

So far on the forum, we seem to find that prednisone (a very specific type of steroid that is highly anti-inflammatory and immunosuppressant) provides only temporary relief. While prednisone does calm the immune system, if the original triggers are around (virus, bacteria, auto-immune) then when the prednisone is stopped the B-cells will reactivate and release more antibodies. If the original trigger is gone, then prednisone can be effective at breaking an inflammation cycle. Buster P.S. And prednisone isn't anything to mess around with. It has lots of nasty side effects if someone is on it for any prolonged period. It is not the same thing as the anabolic-androgenic steroids (fake testosterone) you were referring to. Prednisone is a very specific synthetic corticosteroids that mimic the action of cortisol (cortoisone) -- prednisone is a immunosuppressent and anti-inflammatory.

Hi Melanie, There are a couple of theories here. PANDAS is thought to be caused by three things: an immune response that generates an anti-neuronal antibody a failure of the T-reg cells to suppress the anti-neuronal antibody a breach of the blood-brain barrier such that the anti-neuronal antibody reaches neuronal tissue So prednisone slows down the production of antibodies (what peglem wrote) what affects #1 and acts a bit like #2. In addition, prednisone is highly anti-inflammatory (by reducing inflammatory cytokines) and thus can close #3. Given that advil also seems to work and that IVIG seems to work (but the antibodies seem to stay high based on our anecdotal experience). I think it is fundamentally #3 at play -- prednisone temporarily is closing the BBB. Buster

Hi Austin Mom, wecome to the forum. Lexapro led to activation in our daughter. Apparently Lexapro is actually offlabel for children (i.e., not well tested) and due to its very short half life it seems to have very significant problems especially if you miss a dose. Increasing lexapro made our child worse. While it was difficult to separate Lexapro from PANDAS, her behavior sure matched Akathesia. Lexapro does have some rather nasty withdrawl symptoms and it happens very quickly. Within 24 hours of stopping Lexapro, our daughter definitely got the classic flu-like symptoms and the zapping feeling. There's a nice study by [Murphy2006]Murphy TK, Storch EA, Strawser MS, "Selective serotonin reuptake inhibitor-induce behavioral activation in the PANDAS subtype", Primary Psychiatry, 2006;13(8):87-89, http://mbldownloads.com/0806PP_Murphy.pdf In terms of long-term treatment with antibiotics, we did this for 72 weeks (i.e., about 1.5 years). Without a doubt the antibiotics helped a lot, but our daughter never really "reset" back to full remission. After each episode, she got better, but not back to the same behavior pre exacerbation. She had 6 exacerbations over the 72 weeks -- each exacerbation lasting 4-5 weeks (i.e., 27 weeks were in exacerbations). By the end of this she was up 20 points in symptoms. This baseline change and the re-emergence of restrictive eating (she had symptoms of anorexia nervosa in a 7 year old) made us consider IVIG. Our belief is that if there was more spacing between activations/exacerbations, she would have done fine on the prophylactic antibiotics. Best regards, Buster

I actually think there is a lot here. We were reading papers that Progesterone seems to shift Th2 to Th1 response (similar to the immunomodulation by azithromycin). Buster

I really encourage you to get the other papers in the write up I did here. http://www.latitudes.org/forums/index.php?showtopic=6265 And yes, this is one of my favorite articles. Buster

I have to agree with all the others. The demanding defiant, cognitive inflexibility was very pronounced with our daughter -- it just had to be a certain way. Couldn't rationalize it. Couldn't see that it was odd. By the way, I mention this last one because usually they say that folks with OCD recognize that their demand is odd. That was not the case with our daughter. Technically OCD in kids doesn't require the self awareness. Buster

Realistically, you can probably only get to #1 on this list. I'd use [Perlmutter1999]Perlmutter SJ, Leitman SF, Garvey MA, "Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood", Lancet 1999; 354 : 1153 – 58 http://intramural.nimh.nih.gov/pdn/pubs/pub-5.pdf as the starting point. Then add Kessel http://www.jimmunol.org/cgi/reprint/179/8/5571 and probably Kirvan: [Kirvan2006] Kirvan CA, Swedo SE, Kurahara D, Cunningham MW, "Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea". 2006 Autoimmunity 39 (1): 21–9. http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf Not sure if Dr. T can offer anything on 2-5. Oh, by the way, if anyone throws Singer or Kurlan at you, you can use their recent reply in http://pediatrics.aappublications.org/cgi/...22/5/1157-a.pdf that says "We are unable to fully disagree with the conclusion of Alvarenga et al that “GABHS may still have a major role in PANDAS,” because as we pointed out, our study was designed to examine the relationship between acute GABHS infection and exacerbations of PANDAS but not the onset of PANDAS." They studied kids with long term tics (> 3 years). Did not study children with signfiicantly varying OCD presentation. It bugs me a lot that those guys can pull Tourettes kids and then try to draw some conclusion about PANDAS rather than just usign the money to check the experiments of Kirvan. Sigh. Buster

Actually we have four... 181 -- not in exacerbation 253 -- in an exacerbation and pre-prednisone burst 170.5 -- not in exacerbation and post prednisone burst 119 -- post IVIG Buster

Hi Misty, Wow, a lot going on... Let me see if I got it straight... at 6, he was diagnosed with everything from ADHD to Tourettes to OCD at 7, you discovered that he had chronic sinusitus. He had strep throat 5 times. He was hospitalized 3 times (including having tubes added) at 9, he developed significant ticcing and odd movement disorders at 12, he has significant fine motor impairment (handwriting), defiant behavioral issues, odd laughter, and is walking on edge of shoes Have you asked him about his walking on edge of shoes? Many kids with OCD do this to avoid too much contact with the floor. It's actually a contamination fear manifesting as a compulsion. Another explanation might be a form of chorea. Another might be a form of dystonia. If he does a pushup against a wall, is his body twisted or symmetric? Can he do a regular pushup? Some of the defiance could be activation from Prozac. The dilated pupils could also be akathesia. Hard to tell from the description. What psych meds is he on now? Of course all the symptoms may just be manifestations of PANDAS. I guess the real question is what do you want your ENT to do? It sounds like you got the prescription for prednisone. You have some concern that the strep may not be gone. You also may also be seeking a longer supply of antibiotics or have a concern that the chronic strep is due to the strep going intracellular. If you really feel the augmentin didn't do anything, I'd suggest switching to azithromycin and seeing if the strep is intracellular. You could always hand him the Kaplan paper http://www.journals.uchicago.edu/doi/pdf/10.1086/508773 that shows how strep can go intracellular and that macrolides can help. Usually doctors don't much like being handed papers... however, you could read through http://www.latitudes.org/forums/index.php?showtopic=6265 and offer to send him any information/papers if he'd like. For ENT folks, they tend to like the strep papers. For immunologists, they tend to like the Kirvan papers. Wishing you the very best and let us know how your visit goes. Buster

Repost if this doesn't quite explain it... PANDAS is thought to be caused by an antibody that interferes with the dopamine receptors in the brain. I think of PANDAS like setting the volume on your TV for your favorite show and then a commercial hits and the volume is suddenly ear splitting loud, you reset for the commercial and now it is too soft for your show. Think of that happening all the time, it's really hard to keep the volume just right. Again it isn't that the volume is too loud or too soft -- it's sort of both -- it's not equalized or regulated. Maybe not the best analogy -- but I hate commercials . Weaning off Prozac is sort of like that commercial interuption on its own. It takes about 3 weeks to reduce 30 mg of Prozac to 10 mg. NorFluoxetine has a half-life of ~14days. This means at 14 days the effect is like taking 15 mg. At 28 days, the effect is like taking 7mg, etc. In general, your child will stabilize to the new dosage level in 30 days from when you dropped the dose. During the weaning, it is fairly common to have aggitation, irritation and motor difficulties. This is essentially from the body trying to re-regulate the changing amount of dopamine needed to transmit a signal. Yes, it is changing slowly but it still takes time to adjust. Bottom line is that weaning can be a complicating factor with PANDAS because both are messing with the perceived amount of dopamine. If it has been < 30 days since your child has been on a stable dose of Prozac, you'll have to wait it out to see what the new baseline is. Prozac doesn't exactly interfere with treating PANDAS, but rather Prozac and PANDAS are both messing with the same neurotransmitters. Buster

where is the post? Number three post within this topic Here's the paper reference: [Pavone2006] Pavone P, Parano E, Rizzo R, Trifiletti RR (2006). "Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants". J Child Neurol 21 (9): 727-36. http://jcn.sagepub.com/cgi/content/abstract/21/9/727 "Chronic PANDAS Rather than the characteristic explosive onset typical of PANDAS, in which parents can often point to the day and even hour when symptoms began, many patients with tics and/or obsessive-compulsive disorder have a much more gradual onset and chronic course, with waxing and waning of symptoms over the course of days to weeks. D8/17 antibodies have been demonstrated in patients with PANDAS16,17 and patients with chronic tic disorders.5,6,125–129 Anti–basal ganglia antibodies had also been demonstrated in patients with tic disorders and/or obsessive-compulsive disorder, well before the PANDAS concept was proposed, and strongly confirmed in a recent large study.130 Could some patients with less explosive onset of Tourette syndrome/obsessive-compulsive disorder have a more persistent streptococcal infection? We recently found evidence of a streptococcal carrier state in 72% of patients with Tourette syndrome–obsessive-compulsive disorder surveyed over a 3-year period (Trifiletti, manuscript in preparation), some 3- to 10-fold higher than the general population. We propose that this group be called ‘‘chronic PANDAS.’’ Chronic PANDAS might prove to be much more common than classic PANDAS."

If I take the definition of Chronic to be Trifilleti's and Pavone's definition (i.e., gradual onset, carrier state, more tics than OCD), then I don't think my daughter would qualify. Her symptoms remitted with antibiotics -- but came back when antibiotics were discontinued. In addition, her exacerbations were linked to strep in the house. Once treated it remitted. Looking at case histories, it seems like those with tics definitely take longer to remit. Buster Hey Michael -- I'm not sure, but I think we qualify as "chronic." Son diagnosed with OCD at 6, waxes and wanes (or exacerbations) throughout the last 6 years and only moved on to PANDAS about 4 months ago. We are about to begin our third month-long dose of abx, and we ARE seeing improvement . . . slow, saw-toothed, but improvement nonetheless. I think you're right though . . . I feel like these are "tougher nuts to crack," maybe because the duration of their illness (and early mis-diagnosis) has permitted the strep to go intracellular? Maybe because the brain has taken on some more permanent configurations or accommodations during the illness prior to abx intervention? Maybe because the associated behaviors have become more ingrained over the extended time period, so even once the physical issues are addressed, it takes longer to turn back the clock on the learned behaviors? I'll be interested in hearing what Buster has to say, also!

There's a lot in your post. I guess the first thing I should say is that we didn't see the impact of the prednisone until 10 days after the burst (i.e. the 14th day from the start). It was a very significant remission of symptoms. You mentioned that you had shifted from 30mg Prozac (2009) down to 10mg (2010). I was wondering when you got down to 10mg. Prozac has a very long half-life and while it is self-weaning the withdrawl can be clouding some things. An item to consider is that it is possible you were getting activation from the Prozac when you were essentially removing the interference with dopamine by treating the PANDAS. I can write more here, but the short question is when were you doing the Prozac withdrawl relative to the Augmentin trial. Buster

We charted our daughter on 11 variables each rated 0-9. 1-3 there, but barely 4-6 meant pronounced event but not constant 7-9 meant huge impact, disabling or unable to function These were: separation anxiety social anxiety emotional lability lashing out/hitting/biting restrictive eating/skipping meals contamination fears/hallucinations demanding defiance OCD measurement rituals OCD repetitive questioning large motion movement abnormality illegible handwriting/fine motor tremor (includes dropping things/clumsiness) An exacerbation would be a jump of +15 points (typically 2 or more items going from nothing to severe). I'm not sure our cut off is useful to anyone else, but it is what we used. The rise was over 3 days and lasted typically 4 weeks. Buster

Folks just a warning. The maximum daily dosage for clavulanic acid is 600 mg for adults and 10 mg/kg body weight for children. Typical Augmentin is 500/125 (meaning 500 of amoxicillin and 125 mg of Clavulanic Acid). If this was taken twice a day (i.e., 250 mg of Clavulanic Acid) then you need to weigh at least 55 lbs. If you are prescribed a higher amount then you need the XR formulation which is typically of the form 1000/62.5 which is 1000 mg of Augmentin and 62.5 mg clavulanic acid.

Michael, I am so sorry to hear your news. My heart dropped when I read it as I remember vividly our own challenge when we were scared for our daughter and for others in the family. I'm glad he and you are safe. Thinking of you and your whole family. Buster

I laughed at this too. I read so many papers over the past 80 months that I forget that antilysogangliosides aren't dinner conversations for everyone. I'm embarrassed to say they are now at our house. It really is my goal to make the material accessible to anyone -- so please send me an IM or post if it's not making sense.

Flow Cytometry is a mechanism of taking blood cells and dropping them one by one in front of a laser that then scatters light in a particular pattern for each type of cell. (It's actually totally cool). By adding special flourescently modified antibodies to the sample you can get these antibodies to bond with the receptors on T-cellsl such that when they pass the laser their pattern of light scattering changes. In this manner you can tell what receptors are on each cell. This is the CD4+/CD8+/... stuff that is talked about in some of the posts. In answer to your actual question, I'm a research scientist and used to build equipment like this for very wacky experiments many years ago... Best regards, Buster That's a toughy. The short answer is that certain strains of GABHS (notably emm-type 6 and 19) can go intracellular -- but that was a relatively recent finding (2004). Intracellular strep appears resistant to amoxicillin -- not because it is, but because the amoxicillin can't get to it. There's anecdotal evidence that kids with intracellular strep have elevated CD4 to CD8 ratios (these are particular receptors on T-cells that determine whether the T-cell is looking for extracellular bacteria or will kill infected cells). Lots of things can cause elevated CD4/CD8 ratio but one is that the immune system is misfiring and activating more Th2 than Th1 cells - i.e., it's looking outside for stuff that is inside. So the short test is trying a macrolide like azithromycin -- the longer test is getting flow cytometry. Hopefully that short explanation helps. Buster What is "flow cymetry"? (and I just have to ask - what is it you do for a living that enables you to understand all this chemistry?!!)

I guess I should add that the 4-6 week item only applied when we had cleared the strep and kept her on prophylactic antibiotics. In situations where we had overlapped illness (i.e., someone else in the house had strep), there was no remission. We plotted symptoms religiously on a daily basis, so after 72 weeks of graph points, you can see the exacerbation points and the sawtooth pattern. Unfortunately, we also saw an increased baseline if there wasn't a sufficient down-time between exacerbations. Buster