Buster

The editorial is quite short 1 1/2 pages . The substance of the editorial is that symptoms of sydenham chorea are clearly different from other conditions. Their argument is that SC is separable from the "herd of those with Tourette syndrome" whereas PANDAS is not well separated. They complain that the clinical presentation of dramatic waxing/waning in PANDAS is not a bright stripe -- since "regular tics and OCD often dramatically wax, [and] streptococcal infections and symptoms are ubiquitous." Then they go on to say that even if PANDAS were a common horse and didn't stand out from the herd of other OCD/tic illnesses by symptoms, then one should be able to see a relationship between an antcedent streptococcal infection and the occurence of tic or OCD diagnoses. They then reference their own prior longitudinal study of checking older children with Tourette Syndrome (i.e., not clear they had a PANDAS kid in the mix) where they did not find any OCD variance and found no correlation of tic symptoms with GABHS. So rather than realize that they selected the wrong group of horses (i.e., took no OCD-only children and chose those with long term tics and checked kids who were treated for GABHS infection (meaning that they did not study untreated GABHS but only treated GABHS)... sigh, so many things wrong with their study.) They finally conclude, "Current evidence indicates that ... GABHS infection does not seem to be an important etiologic factor and therefore not an appropriate target for assessment or therapy" and "if you hear hooves, we can safely act like they are horses" (by which they mean that if you see tics or OCD treat as you would any other tics/OCD). I hate these types of editorials -- they are clever -- so they'll get repeated, and wrong, because the conclusion is not justified by the proported evidence. Those writing these editorials do not know of the pathogenesis of "horses" and weren't part of the separation of "zebras". They don't know what causes the symptoms they are seeing. There is just not sufficient evidence to conclude "if we hear hooves, we can safely act like there are horses." They could conclude that if we hear hooves with no OCD symptoms, then the likelihood is they are horses. If there is a separate pathogenesis PANDAS, then you can't conclude you should "act like they are horses" -- this would be like treating all chest pain the same way. Chest pain is a symptom not a cause. It could be a heart attack, indigestion, or the knife stuck in there.... I hate retrospective studies -- especially one where there were almost no throat cultures. Grrrr... Buster

Based on my interaction, a short write up is helpful. Primarily she's looking for information about whether your child has OCD or tics. If tics, whether vocal or motor. Was your child in an exacerbation at the time of the draw. Was the exacerbation correlated with a streptococcal infection (via throat culture or other mechanism). How long has your child had the condition? Is it mostly constant or does it wax/wane? Has it gone in remission for > 3 months? If OCD, what are the symptoms/diagnosis? that sort of stuff.... more like a parent history. Buster

I posted about the study here: http://www.latitudes.org/forums/index.php?...&hl=gilbert Let me know if you'd like the actual paper. Buster

Yes, in our dd's case we had 2 weeks of significant exacerbations post IVIG -- we saw a lot of old behavior briefly. It was like watching the last year on fast reverse. On day 3 she ran a low-grade fever (99.5-100). This passed in 2 days. Buster

I think that is what every researcher wonders... In 2009, $20B was spent by the National Institute of Health. Of that $2B was invested in research on mental health for 7338 grants for an average grant size of $217K. 175 grants were > $1M 795 grants were between 500K and $1M 4419 grants were between 100K and 500K and the remainder < $100K Dr. Swedo had a 2009 grant of $200K. Of this only a small portion was available for funding researchers at Univ of Oklahoma. You'll see in the research grant summary below that the majority of the study is around the recruitment and testing of PANDAS children with riluzole. It is likely with so many requests for funding last year (and this year) and the relatively low diagnosis of PANDAS that they decided to only fund one study. Hard to say though. The inner workings of NIH and NIMH remain an enigma ... Buster

We posted here about donations: http://www.latitudes.org/forums/index.php?...art=#entry40296 Buster

Hi folks, Some of us had gotten together and provided funds to offset the cost of the tests for parents last year and that's what you were seeing. Those funds were meant to help carry over experiments/trial in hopes that research funding would come in for this year from NIMH. The new funds didn't come in and the bridging funds are largely exhausted. We really need NIMH to fund research here. Buster

Updated FAQ

This is a little tricky to answer, so perhaps other parents could help here on what would be useful for the FAQ. It's hard to balance accuracy with understandability. See if this makes sense. Within the scope of PANDAS, CaM Kinase II test is a measure of whether antibodies in the blood would cause signaling of neuronal tissue if the blood brain barrier were open. In many patients, the blood-brain barrier will be closed and so the test only indicates that there is a potential for neuronal signalling as opposed to any being actually caused by antibodies. CaM Kinase II activation of neuronal cells has been shown to be elevated in children with Sydenham Chorea and in children with PANDAS. Cam Kinase II acts to convert the amino acid tyrosine into L-dopa that later becomes dopamine. The antibody seems to interfere with the regulation of dopamine and creates symptoms similar to tyrosine hydroxylase deficiency (THD). How about where can you get these tests done how do you ask your md to do this? Unfortunately there aren't any commercially available tests for CaM Kinase II on neuroblastoma cells. As far as I know the only location is the research trial being conducted through Oklahoma (referred on this forum as Cunningham tests). We could provide contact info -- but it isn't clear how long the trial will remain open -- especially as funding for the continued brain research wasn't approved. The problem with the research trial is we all want the numbers to mean something, but it's still too early to know. Probably we'd need a caveat/disclaimer that the accuracy, specificity and repeatability of the test is not yet known as this is a research trial. With respect to getting an MD to do it, you ask your MD to help you participate in a research trial -- some doctors will and some won't. Essentially the doctor has to approve a blood draw and spin down of the blood to serum for shipment to the lab in Oklahoma. Anyone want to take a crack at how to phrase a response here for the FAQ? My slight bias is that the FAQ is already gettingpretty large and this level of detail might be better for a thread... thoughts? The tests are now commercially available for most states through www.moleculera.com. Buster

This is a little tricky to answer, so perhaps other parents could help here on what would be useful for the FAQ. It's hard to balance accuracy with understandability. See if this makes sense. Within the scope of PANDAS, CaM Kinase II test is a measure of whether antibodies in the blood would cause signaling of neuronal tissue if the blood brain barrier were open. In many patients, the blood-brain barrier will be closed and so the test only indicates that there is a potential for neuronal signalling as opposed to any being actually caused by antibodies. CaM Kinase II activation of neuronal cells has been shown to be elevated in children with Sydenham Chorea and in children with PANDAS. Cam Kinase II acts to convert the amino acid tyrosine into L-dopa that later becomes dopamine. The antibody seems to interfere with the regulation of dopamine and creates symptoms similar to tyrosine hydroxylase deficiency (THD).

Streptolycin O is an toxin produced by streptococcal bacteria. Anti-Streptolycin O (ASO) is an antibody produced by the immune system to this toxin. Streptolycin O can be produced by Strep A, Strep C and Strep G. The antibodies of Streptolycin O rise 1-4 weeks after a strep infection but can remain elevated for a considerable amount of time. Direction of titer is much more important than level as many school age children can have chronically elevated ASO levels. Most children do not have two measurements (i.e., to look for a rise) so a laboratory uses statistics to compute something known as the upper limit of normal -- this is typically age and geography dependent. If your child's ASO is higher than 30% above the upper limit of normal it is considered elevated -- however, technically you need two measurements to know if the titer is rising (indicating a strep infection in the prior 1-4 weeks) or falling. Only the rise is meaningful. While most folks think blood tests are "more accurate" this is not really true in the case of ASO. In a study by Shet in 2003 http://www.journals.uchicago.edu/doi/pdf/10.1086/377700 ASO reported a false negative in 46% of cases despite colonized strep in subjects and perfect timing of the measurement. Anti-DNAse B actually isn't better. It has a false negative response of 55% (with perfect timing). What is interesting is if you combine the two measurements one of the two measurements will rise in 69% of cases. However, this still leaves 31% of the cases where it won't rise (despite a positive culture). The bottom line is that the throat culture (rapid or 72 hour) is still the most accurate for onset -- you just have to get it within a week of colonization/infection. ASO and AntiDNAse B should be used if you don't get a positive culture (but still suspect GABHS). You really need two blood draws to check ASO and AntiDNAse B and an idea of when your child would have been exposed to strep. The draw is typically done for both at 3 weeks (post infection) and then again at 5 weeks. A rising titer in either can confirm a prior strep infection but cannot rule out a prior strep infection (due to the high false negatives). Best regards, Buster P.S. A bit more on ASO can be found at: http://www.latitudes.org/forums/index.php?showtopic=3756 There's also some information in a PANDAS FAQ at: http://www.latitudes.org/forums/index.php?showtopic=6266

Okay, I'll try a translation -- please jump in... In 2001, Collin showed in http://iai.asm.org/cgi/reprint/69/11/7187.pdf that GABHS produced two enzymes (SpeB and EndoS) that acted in different ways to neutralize Immunoglobulins. In 2009, Egesten and Collin found that SpeB actually disables most of the antibacterial chemokines (inflammatory chemicals) and degrades/destroys the ability of epithelial cells to advertise bacterial infections. http://www.plosone.org/article/info:doi%2F...al.pone.0004769 Also in 2009, Allhorn and Collin http://www3.interscience.wiley.com/cgi-bin...582871/PDFSTART found that EndoS is specific for IgG 1-4 whereas SpeB seems to go after IgM, IgA, IgG, IgD, ... When EndoS bound to IgG antibodies, the antibodies did not "signal" phagocytes to "kill bacteria" -- essentially EndoS disables the IgG's ability to signal bacteria (and cells) for phagocytosis. What was actually the most fascinating part of the article is that for auto-immune diseases, EndoS might be therapeutic by inhibiting the binding/activation of IgG antibodies that are oriented towards the host. This is very very preliminary work, but they showed that adding EndoS could cause IgG to stop attacking host cell -- and put mice in remission who had EAE or rheumatoid arthritis. Again, this is WAY too early here to know the real effects. Hope that helps. That's my brief interpretation of the papers. Buster

I recommend starting here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100124/ Buster

Thank you Chemar. The link is excellent and almost all of it applies. We were able to get an OHI under IEP since she also has speech issues. When the speech issue completes we may switch to a 504. Best regards, Buster

Freezing this thread Reposting cleaned up version at http://www.latitudes.org/forums/index.php?showtopic=6265

Closing this thread after incorporating above feedback. Please don't add more on this thread. Please add comments on the new thread at http://www.latitudes.org/forums/index.php?showtopic=6266

This post collects the most frequently asked questions over the years. We're not doctors so nothing here should be taken as medical advice. We're parents struggling to understand this disease and these comments are based on our understanding. If your question isn't here, start a new thread on your question or join a thread near the topic. There's likely another person on the forum who has a similar question and maybe an answer. < Updated May 25, 2013 - updated based on reviews/comments, added update on Moleculera Labs> ----------------------------------------------------------------------------------------------------------------------------------------- Signs and Symptoms Q: How do I know if my child has PANDAS? A: That's actually the hardest question to answer. We don't know. Most parents have gotten to this forum because something has already gone really wrong with their child and they are searching for an explanation. Your child is likely suffering from or been diagnosed with either an obsessive compulsive disorder or a tic disorder. The key signs of PANDAS are typically the sudden onset and unusual pre-cursor symptoms like daytime urinary frequency. Other symptoms can be found here: http://www.latitudes.org/forums/index.php?showtopic=6265. A positive throat culture for group A Beta-Hemolytic streptococcus at time of exacerbation and remission of symptoms after treatment of GABHS is a strong indication of PANDAS. Q: How can I distinguish PANDAS from childhood onset OCD or tics? A: This has essentially been the debate for the past decade. Dr. Murphy (see Journal of Pediatrics Aug 2011 notes that children in the PANDAS group had: 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. when compared with age-matched OCD and tic controls. Q: Is PANDAS just misdiagnosed Sydenham Chorea? A: We don't know. But it appears from studies by Kirvan and others that PANDAS has a lot of similarities to Sydenham Chorea. About 70% of Sydenham Chorea cases have OCD symptoms. This number also seems to be true for PANDAS cases. In the original definition of PANDAS, Dr. Swedo excluded those cases that had a history of Acute Rheumatic Fever or were exhibiting the explicit Sydenham Chorea (also known as St. Vitus Dance). Q: Is it possible that my PANDAS child reacts when others have strep? A: Yes. There is good anecdotal evidence from parents on this forum that exacerbations in the PANDAS child are correlated with family members contracting GABHS. One parent relayed the experience as being similar to a peanut allergy -- instead of the throat closing the basal-ganglia gets affected. Q: Is it possible for a child to have strep without a sore throat? A: Yes. Strep can colonize on many parts of the body (most notably around the genitals or a recent cut). In addition, some children do not exhibit "classic strep throat symptoms" although they may be positive for GABHS. Q: What does OCD look like in a child? A: There's a great thread regarding this at http://www.latitudes.org/forums/index.php?...ic=6153&hl= A short summary of things from that thread are: obsessive handwashing, due to fear of germs or stickiness or chemicals obsessive need to pee obsessively sure that all pee or poop is not out, or that they are not clean - often leading to a compulsion of obsessive wiping need to confess "bad things" such as unkind behavior to another child feeling that they have cheated on tests or in school constantly asking for reassurance on the same/similar topic (ex: am I sick, will I get sick, did I do that) inability to make a previously simple decision for fear of consequences (sometimes logical, sometimes just a fear of it being a wrong decision). worry of choking on food - asking for food to be cut into small pieces ... ----------------------------------------------------------------------------------------------------------------------------------------- Pathogenesis (cause) Q: Is PANDAS caused by Strep? A: Not exactly. PANDAS is currently thought to be caused by the immune system creating an antibody to Group A Beta-Hemolytic Streptococcus and a breach in the blood-brain-barrier due to inflammation from the immune systems reaction. It seems to be the combination of the two -- the antibody and the breach. Some researchers have reported that there is inflammation of the basal ganglia (leading to symptoms), while others report that the antibody interferes with neuronal signalling. The combination of the antibody, inflammation and the breach of the blood-brain-barrier appear to cause the neuropsychiatric symptoms of OCD and tics. Q: How do antibodies get across the BBB? A: We don't exactly know. One recent paper indicates that T-cells are attracted to weaknesses in the blood-brain barrier and are able to cross the barrier. Once across the T-cells bind with macrophages and cause inflammation. The inflammation brings other T-cells and eventually a breach in the BBB occurs. It appears that either antibodies or B-cells are now able to cross causing the interaction with the neuronal tissue. ----------------------------------------------------------------------------------------------------------------------------------------- Tests: Strep Culture (rapid and 72 hr agar plate) My child's PANDAS symptoms are surfacing and the strep test was negative, what's going on? A: This is an area of active research debate. There are really two questions here. How accurate is a strep test for detecting strep and is GABHS the only trigger for PANDAS symptoms? PANDAS researchers have only looked at symptom exacerbations associated with strep throat; however, GABHS can colonize elsewhere on the skin, sinuses, eye, ear, gastrointenstinal area or peri-anal/vaginal areas. The accuracy of the throat culture is highly dependent on the sample. As anyone will tell you, getting a culture from a squiggling 5 year old is tough. Finally and most importantly, the exacerbations are thought to be from an antibody to GABHS getting across to neuronal tissue (i.e., crossing the blood brain barrier). These antibodies can exist for 4-6 weeks and thus if some other virus or bacteria causes inflammation of the blood-brain-barrier the antibody could then cross. Once the antibodies find neuronal tissue there can be a feedback loop continuing the production of antibodies. This is a long way of saying that we don't know, but many on this forum will tell you this is exactly what happens for their child. Q: We had a negative throat culture, does that rule out PANDAS? A: No. A throat culture can confirm GABHS colonization but not rule out PANDAS. It is important to know that PANDAS is not "due to GABHS" but rather thought to be due to auto-antibodies in the blood stream that were triggered by an initial GABHS infection. In Swedo's original 50 cases paper, she notes that "Not all symptom exacerbations were preceded by GABHS infections; viral infections or other illnesses could also trigger symptom exacerbations. This is in keeping with the known models of immune responsivity -- primary responses are specific...while secondary responses are more generalized. Thus, the lack of evidence for a preceding strep infection in a particular episode does not preclude the diagnosis of PANDAS." Q: My doctor has said that my daughter is a strep carrier and that the positive strep culture is meaningless. Is this true? A: No. Clinically, if you are having symptoms with GABHS carriage then this is by definition not asymptomatic carriage. Immunologically, it is not asymptomatic if there is an immune response to GABHS (rise or elevated ASO, AntiDNAse B, anti-lysoganglioside, anti-dopamine D1, anti-dopamine D2, anti-tubulin or CaM Kinase activation). As there are other severe side effects of not treating known GABHS infections (such as Acute Rheumatic Fever and Sydenham Chorea), current guidelines recommend treatment of positive throat culture. The guidelines do not recommend checking for clearance to try to avoid continual treatment of a child with asymptomatic GABHS carriage. It is estimated that only about 5% of children are thought to truly have asymptomatic chronic carriage. Q: Can you get strep somewhere other than the throat? A: Yes. PANDAS is associated with Group A Beta-Hemolytic Strep and this form of strep can exist on skin. There are many diseases (such as Kawasaki's disease and Impetigo) that are caused by Group A Beta-Hemolytic Strep. Skin GABHS infections often do not show a rise in ASO titers. Q:If my child has PANDAS should I have strep tests done on siblings? A: Yes. Many on this forum will say that when their PANDAS child was in an exacerbation, a sibling was culture positive for strep. Some call their PANDAS child a strep detector. ----------------------------------------------------------------------------------------------------------------------------------------- Tests: Streptococcal Exotoxin antibody tests (ASO and AntiDNAseB) Q: My child has a positive throat culture. Should I also have tests for ASO or Anti-DNAseB? A: We'd recommend against it. The unfortunate reason is that some doctors think that if your ASO comes back negative you can't have PANDAS. That is not true. ASO has a 46% false-negative rate. That's almost the same as a coin flip. If you have a positive throat culture, treat it. If it is associated with significant exacerbation, PANDAS is probable. Q: My child was negative for a strep culture. Should I have get ASO or AntiDNAse B tests? A: Yes, ASO and Anti-DNAse together are better than either test individually; however, you still need to determine when you likely were exposed to strep. ASO rises approximately 1-4 weeks from colonization and Anti-DNAseB rises between 6-8 weeks from colonization. Even then ASO and Anti-DNAse B together fail to show a rise in 31% of children with strep colonization. Q: Is a single measurement of ASO or Anti-DNAse B enough? A: Actually no. titers have to be measured at two points (typically a week apart). ASO is typically measured at 3 and 4 weeks from the date of suspected infection and Anti-DNAseB measured at 6 weeks and 8 weeks from the suspected event. The two data points are needed to look for a rise. Absolute values are not as important as the rise/fall of the titer. For this reason it is important that both samples are done by the same lab. In the absence of having two titers, many labs use a measure known as the "upper-limit-of-normal". This value is helpful if the measured value is significantly higher than the upper limit. If it is lower than the ULN, then typically two samples are needed to look at the slope/trend. Q: We had low ASO titers, does that rule out PANDAS? A: No. Anti-Streptolycin O is a measure of an exotoxin of Group A Beta-Hemolytic streptococcus. Although most strains of GABHS do produce Streptolycin-O, cholesterol (particularly in the skin) can absorb this exotoxin. In one study, ASO did not rise in 46% of patients despite positive throat cultures and perfect timing for taking the ASO titer. So ASO can confirm a previous strep infection but cannot rule out strep or PANDAS. Q: We had low Anti-DNAseB and ASO titers, does that rule out PANDAS? A: Unfortunately, No. First, the tests have to be taken during the rising titer period. ASO tends to rise 1-4 weeks post infection and Anti-DNAseB tends to reach a peak at around 6-8 weeks. Even with perfect timing of titer draws, 31% of children with confirmed colonized strep did not have a rise in either ASO or Anti-DNAse B. So anti-DNaseB and ASO can confirm a previous strep infection, but cannot rule one out. ----------------------------------------------------------------------------------------------------------------------------------------- Tests: Antineuronal Antibodies Tests Q: What are Cunningham tests? A: In 2006, Kirvan and Cunningham published findings that patients with the symptoms of Sydenham Chorea and PANDAS could be distinguished from patients with classic OCD and Tourette’s Syndrome based on the amount of four autoantibodies found in blood serum. In 2013, Dr. Cunningham opened a commercial lab (see www.moleculera.com) where these tests could be ordered by physicians to increase confidence of a PANDAS diagnosis. Q: What are CaM Kinase II tests? A: These tests are also known as Cunningham tests on this forum (see above). Kirvan and Cunningham found that specific antibodies to GABHS in the blood serum of PANDAS and Sydenham Chorea patients interacted with neuronal tissue causing a reaction known as CaM Kinase II activation. CaM Kinase II is part of a series of reactions that lead to dopamine release by neuronal cells. The activation of CaM Kinase II by an antibody indicates that if the antibody can cross the blood-brain barrier, it could interfere with dopamine regulation potentially creating motor abnormalities or affecting memory. It is important, however, to highlight that the results are still in a research stage and the accuracy, specificity and repeatability of the test is not yet known. Q: Can we still get the Cunningham Tests? A: Yes. Moleculera Labs, LLC (www.moleculera.com) has commercialized the tests and is making these tests available to physicians. The lab is accredited by COLA www.cola.org/about as meeting the federal CLIA laboratory standards. Please check the moleculera web site to see if moleculera is accredited for your state. The tests are being used in the clinical trial being conducted by the National Institute of Health (see http://www.clinicaltrial.gov/ct2/show/NCT01281969). ----------------------------------------------------------------------------------------------------------------------------------------- Tests: Predinsone Burst Test Q: What is the purpose of a prednisone burst and why does it work? A: The prednisone burst is used to temporarily slow down the immune system response by reducing inflammation (from T-cells) and reducing antibody production by B-cells. It is thought that prednisone helps close the blood-brain barrier temporarily. Essentially, abatement of symptoms in a prednisone burst helps indicate that the issue is auto-immune. It is important to know that the prednisone burst is a short term treatment (typically 5 days) and is not intended as a long term treatment. Prednisone does have significant side effects particularly for any long term use. Prednisone has no known positive effect on non-PANDAS OCD or non-PANDAS tics. Q: I've heard that some doctors use a 5 day burst and others a 30 day tapered burst. Why the different protocols? A: The 5 day burst is used by some doctors as a diagnostic technique to confirm that the symptoms are auto-immune in nature. The longer tapered burst theoretically can help break a cycle of inflammation by suppressing the creation of new antibodies while the existing ones get used up. A longer sustained suppression of symptoms does help remove placebo effect, but also has more risks due to the impact of prednisone on the rest of the immune system. Q: How long after starting a prednisone burst should I expect a response? A: Similar to antibiotics, most parents have reported significant immediate improvement during severe exacerbation and temporary remission of symptoms within 2 weeks post initiation of prednisone. This test seems to vary with age, symptoms and gender. Caution should be noted here that parents of children with diagnosed Tourette's Syndrome have noted that symptoms actually got much worse during a prednisone burst. As such, there should be good clinical reasons for a PANDAS diagnosis before using a prednisone burst. ----------------------------------------------------------------------------------------------------------------------------------------- Treatment: Antibiotics Q: If PANDAS is caused by an antibody, why do so many parents have their kids on prophylactic antibiotics? A: The antibody is an immune response to Group A Beta-Hemolytic Streptococcus. Many of the parents on this board have seen that subsequent exacerbations are much more severe (similar to the case for other auto-immune disorders to GABHS such as Sydenham Chorea). The prophylaxis is to minimize colonization and infection by GABHS. Q: Can Amoxicillin and Augmentin be given only once a day for prophylaxis? A: Apparently not. Amoxicillin and Augmentin both have extremely short half-lives (1-1.5 hours). This means that most of Amoxicillin/Augmentin is removed from the body in ~10hours. If a dose is skipped, the child is actually unprotected for 1-2 days. Azithromycin has a longer half-life (~1.5 days), can be taken once per day and is easier on the GI tract, but there are reports of macrolide resistant strains of GABHS. Q: Do antibiotics kill Group A Beta-Hemolytic Streptococcus? A: Not exactly. Antibiotics such as Amoxicillin, Azithromycin and Augmentin slow down the progression of the bacteria and prevent it from rapidly growing. This gives the child's immune system a chance to respond to the infection and kill the bacteria. Antibiotics alone aren't sufficient to eradicate strep, the body's immune system must complete the job. Q: Which is better amoxicillin, augmentin or azithromycin? A: This is a matter of considerable debate. Both Augmentin and Azithromycin are more clinically effective in clearing GABHS than Amoxicillin. Some strains of strep can go intracellular (where azithromycin is more effective) and some strains are macrolide tolerant (where augmentin is more effective). Often a parent will try 2 different antibiotics over a period of 2 months to find one that seems to work. Q: How long after starting antibiotics should I expect a response? A: In severe exacerbations, some parents have reported a response within 24 hours. However, more parents have reported significant improvement 10-12 days post initiation of antibiotics. Anecdotal evidence indicates that exacerbations can last for many weeks (often 4-6 weeks). Parents with children on prophylactic antibiotics seem to report that subsequent exacerbations do occur but are less severe than without antibiotics. Q: My child doesn't seem any better after 10 days of amoxicillin. Does this mean he doesn't have PANDAS? A: No. Many children actually need a stronger antibiotic than the standard treatment of amoxicillin. The standard dosage of antibiotics is based on clearing 80% of children who have a healthy immune system. For others who fall outside the standard dosing parameters, typically either augmentin or azithromycin are used. Anecdotally, parents on the forum have found that a month is needed to really evaluate whether a particular antibiotic is working. In addition, some strains of GABHS are more sensitive to one antibiotic versus another. Azithromycin is helpful if the strain is one that goes intracellular, Augmentin is helpful inhibiting extracellular strains. Q: "Saving Sammy" said they used high dose Augmentin/XR. Why is that thought to work? A: This isn't exactly known. At very high dosage, Augmentin is bacteriacidal (meaning it actually does kill strep). One theory is that there is a strep infection hidden (perhaps inside cells) and once the cell dies it releases strep into the blood stream. In this case, Augmentin could stop the GABHS before an immune response. There is some good anecdotal evidence for this, but this has not been clinically studied. Some researchers have indicated to parents that Augmentin may be anti-inflammatory at high dose, but there is no clinical studies to support this hypothesis. Q: Why use prophylactic abs in PANDAS children...why not just wait until my child gets a strep infection and treat it then? A: There is mounting evidence that each exacerbation has increased symptoms and thus prophylaxis prevents significant psychological and neurological symptoms. Gratefully, there does not appear to be any long-term damage from PANDAS; however, this is still a matter of research. Q:Should I check for clearing of my non-PANDAS children if treated for strep A: Yes. About 3 weeks after completing treatment for strep you can check for clearance by getting a negative culture. The dosing levels on antibiotics are designed so that about 80% of children with normal immune systems are cleared with a "standard" dosing of antibiotics. Some strains of strep are harder to eradicate and either longer treatments or use of antibiotics like azithromycin and augmentin seem to be effective on these strains. Q:Why are doctors so hesitant to prescribe antibiotics or check for GABHS in asymptomatic children A: The concern is primarily around creating a treatment resisitant form of GABHS. By overprescribing antibiotics, doctors worry that some of the bacteria that is resistant to that form of antibiotic will survive and replicate. Antibiotics slow down the growth of the target (e.g., GABHS) and also helpful bacteria. This means that an antibiotic resistant strain could grow uncontrolled while the normal competing non-dangerous bacteria is held back. It's all a matter of balance and antibiotics do upset that balance. In terms of checking for GABHS in asymptomatic children, this is a matter of considerable debate. The exact reason why some children don't exhibit classic "sore throat" signs or why their colonization doesn't seem to turn into full infections is just not known. There is mounting evidence that asymptomatic carriage is not as benign as once thought, but most doctors have not read these research reports. ----------------------------------------------------------------------------------------------------------------------------------------- Treatment: IVIG, Plasmapherisis, and Plasma Exchange Q: What is IVIG and PEX? IVIG stands for Intravenous Immunoglobulin. Immunoglobulin antibodies, type G, are extracted from donated blood. These antibodies are transferred to the recipient through an intravenous line. IVIG is used in many auto-immune diseases but the exact nature of how it works is not known. IVIG is highly anti-inflammatory and may help T-regulatory cells become re-activated to help remove anti-host antibodies. In addition, some of the infused antibodies may help recognize infected cells or bacteria that was missed by the recipient's own antibodies. PEX technically stands for Plasma Exchange. It is sometimes used interchangeably (especially on this forum) with plasmapheresis. Plasmapheresis is a process of removing antibodies from the blood stream through filtration. In Plasma Exchange (PEX), another donor's plasma is added on the return so that new antibodies are added (similar to IVIG). Plasmapheresis is used in severe auto-immune diseases because it can address acute antibody levels. Q: Why does IVIG or Plasmapheresis work? A: PANDAS is thought to be caused by three events: the creation of an antibody to Group A Beta-Hemolytic Streptococcus that can react with neuronal tissue the failure of the immune system to suppress the antibody a breach of the blood-brain barrier so that a B-cell or the antibody can reach the neuronal tissue IVIG is highly anti-inflammatory and can close #3. There are also reports that IVIG resets the T-regulatory cells addressing #2. Plasmapherisis works by removing the antibodies in #1. Antibiotics also help with #1 by slowing an infection so the immune system can kill the bacteria. Once the antigen (the bacteria) is removed, the antibodies generally disappear in ~4-6 weeks. Q: What is low-dose IVIG and high-dose IVIG? A: Low dose IVIG is typically 100-500mg/kg and used for treating primary immune dysfunction. This dosage provides basic antibodies to help a child fight off common infections. High dose IVIG is typically in the range of 1.5-2gm/kg and is used in neurologic and auto-immune diseases (such as PANDAS). The NIMH clinical trial is using 2 gm/kg distributed over 2 days (1 gm/kg/day). There are several theories as to how high-dose IVIG affects the immune system (see http://www.latitudes.org/forums/index.php?showtopic=7855). The general theory is that high-dose IVIG triggers a suppression mechanism in the immune system (perhaps by using up all the antigen presenting cells) that limits the feedback cycle that manufactures the PANDAS antibodies. In addition, the highly anti-inflammatory effect of high-dose IVIG is thought to help close the blood brain barrier. The exact mechanism by which high-dose IVIG works is not known. Q: Do I need IVIG or PEX to cure PANDAS? A: Most of the studies and certainly parents on this forum report that IVIG and PEX are helpful in putting PANDAS in remission, but don't "cure" PANDAS. There are many reports of PANDAS symptoms returning after re-exposure to GABHS. This is why many parents use long term prophylactic antibiotics. It is also important to mention that some parents report that antibiotics used aggressively at initial onset of symptoms seem to put PANDAS in remission. Q: Is this a chronic condition or will IVIG and PEX fix what's wrong? A: We don't know. There is good anecdotal evidence that IVIG and PEX have both been effective at removing 50+% of symptoms and that these treatments with prophylactic followup antibiotics have kept patients in remission for > 1 year. It does appear, however, that prophylactic antibiotics is critical as many have had a recurrence when their child has been re-exposed to GABHS. ----------------------------------------------------------------------------------------------------------------------------------------- Treatment : Other Q:I've read a lot about Ibuprofen, what can it do for my child? A: Many parents report anecdotally that Ibuprofen (e.g., Advil, Motrin) seems to lessen symptoms. The exact reason is not known. Several recent papers indicate that this could be caused by reduced inflammation of the blood-brain barrier and thereby preventing the anti-neuronal antibodies from reaching neuronal tissue. For those interested in how T-cells cross the blood brain barrier and the effect of ibuprofen on ICAM-1 adhesion modules see http://www.latitudes.org/forums/index.php?...art=#entry46222 Q:Where can I find a list of doctors in my area? A: You can ask on this forum. We've collected some of the names of doctors others have seen here: http://www.latitudes.org/forums/index.php?showtopic=5023 Q:Why shouldn't PANDAS be treated "like any other case of OCD or tics" like the NIMH website recommends? A:PANDAS is thought to have a different cause than non-PANDAS OCD and tics. Research studies thus far indicate that children with PANDAS had higher behavioral activation rates on SSRIs see http://mbldownloads.com/0806PP_Murphy.pdf. Anti-psychotics have many serious side effects and there are not controlled studies on the use of these medications on children in the PANDAS subgroup. There has been studies of Cognitive Behavioral Therapy that has shown some efficacy with older PANDAS children; however, the main benefit raised in the report was that parents learned techniques for managing exacerbations. There are not controlled clinical studies on Exposure Response Prevention, but some parents on this forum have tried this technique. Anecdotal reports are mixed on the effectiveness for PANDAS children. Q: What else should I do to keep my PANDAS child strep-free? A: It is very important to test everyone in the household for GABHS. Many families have found that there is a someone else in the family (children and parents) with strep during an exacerbation. The positive individual often is asymptomatic and parents and doctors are often surprised when they come back positive. This individual needs to be treated to prevent reinfection of others. Antibiotics don't prevent colonization or infection, antibiotics slow down the infection but the immune system still responds. Be sure to check 2 weeks later to ensure the positive individual cleared. ----------------------------------------------------------------------------------------------------------------------------------------- Research questions Q: When some research says they didn't find a correlation does that disprove PANDAS? A: No. In science, a negative finding is that the evidence in an experiment doesn’t significantly support a hypothesis. When there is a negative finding, researchers compare results and look for methodological differences. In the case of Kurlan’s papers, it appears there were differences in how “episodic course and sudden onset” were treated. In addition, Kurlan used children with long term Tourette’s Syndrome who did not have the other telltale neuropsychiatric conditions of separation anxiety, enurisis, and behavioral regression. Q: What is PANS and how is it related to PANDAS? PANS stands for Pediatric Acute-Onset Neuropsychiatric Syndrome. PANS is a clincial diagnosis that was negotiated in 2011 when debate could not be settled on distinguishing PANDAS patients from children with Tourette’s Syndrome or other conditions. As long as debate continued on identifying patients, it was not possible to compare results between studies trying to look for correlations. The PANS definition is both broader and more narrow than PANDAS. PANS requires sudden onset OCD and then two or more coexisting neuropsychiatric conditions (e.g. separation anxiety, emotional lability, depression, oppositional behavior, behavioral regression, motor abnormalities such as dysgraphia, sensory issues, sleep disturbances and urinary frequency). The original PANDAS definition remains but in an attempt to compare tests, researchers will generally look for patients who intersect both the PANDAS definition and the PANS definition (i.e., have the coexisting conditions). Q: What is intracellular strep? A: Several strains of GABHS are able to penetrate into cells and act like viruses. This has the property of enabling the GABHS to evade the typical discovery mechanism of the immune system by hiding in cells. When the cell eventually dies, the GABHS is released into the blood stream and can grow/reinfect other cells. Q: Why is PANDAS controversial? A: PANDAS is a relatively new disease (< 20 years old) and there's a lot not known. The controversy in PANDAS is not whether the children have the symptoms, the controversy is whether GABHS is the cause of the symptoms. Some researchers think GABHS is too common an infection to treat as the cause of PANDAS and any correlation is likely coincidence. Others find that non-GABHS infections trigger exacerbations (as stated in Swedo’s original paper) and therefore question the causal effect of GABHS. Finally others are concerned that children with Tourette’s Syndrome might be misdiagnosed with PANDAS and treated with anitbiotics, IVIG or plasmapherisis when there is little evidence that Tourette’s Syndrome is responsive to these treatments. An additional source of controversy comes from researchers who think that antibiotics, IVIG and PEX all have powerful placebo effect and studies have not properly controlled for that effect. Probably the biggest issue for PANDAS research has been ensuring that the patients selected for a study actually have PANDAS. This has not been easy as different researchers have interpreted the “sudden onset and episodic course” differently and then stated conclusions based on having purported PANDAS subjects. This difference in selection criteria likely is a key driver of different experimental outcomes and created considerable confusion. (see http://www.latitudes.org/forums/index.php?showtopic=8027 ). The Boston Globe had a nice article on this in 2012: http://www.bostonglobe.com/magazine/2012/10/27/the-pandas-puzzle-can-common-infection-cause-ocd-kids/z87df6Vympu7bvPtapETLJ/story.html Q: I'm concerned about vaccinations and whether they cause of PANDAS A: The research at this point indicates that the disease is an incorrect response by the immune system to Group A Beta-Hemolytic Streptococcus and not a result of vaccines. Q: Will a vaccine trigger an exacerbation? A. Possibly. There are several parent reports of onset or worsening of symptoms within a short period of time after receiving vaccinations. This is a very controversial area and talking with an immunologist with experience with Multiple Sclerosis, Acute Rheumatic Fever or Sydenham Chorea is probably the best recommendation here. Q: Does PANDAS cause permanent brain injury? A: At present, it looks like exacerbations in PANDAS do not cause permanent harm to the brain. MRIs reveal no demyelization and while there are reports of enlargement of the basal ganglia (a part of the brain controlling fear, hunger, and motor skills), this seems to remit after treatment. We all certainly hope this is the case.

What is PANDAS? PANDAS is a pediatric autoimmune disorder characterized by the dramatic onset of neuropsychiatric symptoms such as obsessions, compulsions, motor or vocal tics [swedo1997]. PANDAS is thought to be similar to Sydenham Chorea where there is dramatic symptom exacerbation following a strep infection[Kirvan2006]. Signs and Symptoms: Children with PANDAS must be initially diagnosed with Obsessive Compulsive disorder or a tic disorder [swedo2004]. These children may have some of the following symptoms that accompany the OCD or tic disorder [swedo1998][Moretti2006]: 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) PANDAS/OCD is a clinical diagnosis, often marked by the sudden onset and extreme symptom exacerbations (such as an increase of +18 points on the OCD CY-BOCS score during an exacerbation [Murphy2004]). The abrupt onset and remission after eradication of streptococcal infection separates the child from non-PANDAS OCD[swedo2004]. Many parents can pinpoint a day or a week when behaviors changed [Çengel-Kültür2009] When a child has primarily vocal and motor tics, the symptoms may appear to overlap with symptoms of Tourettes Syndrome; however, the children can be differentiated by observing symptom exacerbations over time [Pavone2006]. In PANDAS children, a streptococcal infection precedes symptom exacerbation and once treated, initial exacerbations generally remit. The rapid onset with significant remission is characteristic of PANDAS. Researchers have described chronic PANDAS [Pavone2006] where the tics and/or obsessive-compulsive disorder have a much more gradual course. These cases are difficult to separate from non-PANDAS tics or OCD. Some researchers have found other immunologic markers (anti-neuronal and anti-basal-ganglia antibodies) that help separate PANDAS and non-PANDAS children[Kirvan2006]. Diagnostic tests: At this time, there are no commerically available tests for diagnosing PANDAS. There are ongoing research trials that indicate there are differences in specific antibodies that can be tested in blood serum. [Kirvan2006] [Church2006][Martono2007]. These are recent findings and the accuracy, repeatability and specificity of the results are not known. Additional research funding is needed to repeat the experiments at independent laboratories and confirm the diagnostic effectiveness. A throat culture for Group A Beta-Hemolytic streptococcus (GABHS) at time of exacerbation onset is recommended to diagnose a pharyngeal streptococcal infection [swedo2004]. If the culture is negative, a blood test may be able to test for streptococcal exotoxins. A common blood test is Anti-Streptolycin O. While this test can confirm a previous strep infection, it cannot exclude a prior infection or a diagnosis of PANDAS. This test is affected by many factors and in one study over 46% of children did not have a rising ASO titer despite having colonized strep [shet2003]. For children affected by PANDAS, a GABHS infection is considered to be the triggering event that causes an initial episode. However, as is the case with Sydenham's Chorea, subsequent PANDAS exacerbations may be triggered by recurrent GABHS, or by other bacterial or viral infections (ear infections, sinusitis, pneumonia, meningitis, impetigo) further complicating diagnosis [swedo1998]. Treatment: Streptococcal infections are treated with antibiotics. Cognitive Behavioral Therapy (CBT) has been shown to be effective in some children with PANDAS and to provide families with coping strategies during a PANDAS flare [storch2006]. Caution is recommended for using SSRI's with PANDAS/OCD as there are reports of higher activation rates in such cases [Murphy2006]. In addition, there is a lack of controlled studies showing safety and efficacy of anti-tic or anti-OCD medications (e.g., SSRI and anti-psychotics) for children in the PANDAS subgroup. Several reports have shown effectiveness of immunomodulating therapy (IVIG and PEX) in combination with longer term prophylactic antibiotics[Perlmutter1999]. In addition, several studies have shown efficacy of longer term prophylactic antibiotics alone [snider2005]. These treatments are still considered experimental and have several risks. Some physicians will use a prednisone steroid burst for a short period of time to assist in diagnosis of an auto-immune disorder. Immunomodulating therapies are not effective for Tourettes Syndrome or other non-PANDAS OCD cases, again separating the child with PANDAS [Nicolson2000]. Getting Help: PANDAS was only identified in 1998 and as such is a recent disease [swedo1998]. Additional research is needed to identify the most effective treatment protocols. Taking copies of recent studies to your doctor may help them diagnose and treat your child. You may need to interview pediatricians, neurologists and immunologists. For referrals to local doctors with experience, one source is a parent's support group at http://www.latitudes.org/forums/index.php?showtopic=3928. Research: PANDAS is thought to be caused by the following sequence of events in this order: The production by the immune system of an antibody that can interact with neuronal tissue [Kirvan2006][Kirvan2003] A failure of the immune system to suppress this antibody [Kawikova2007] A breach of the blood brain barrier such that the antibody reaches neuronal tissue [Yaddanapudi2009] All three areas have active research results and require duplication of experiments to help reach consensus in the research community. For those interested in a brief history of PANDAS research, please see http://www.latitudes.org/forums/index.php?...amp;#entry36300 Other considerations: Other autoimmune illnesses that may cause sudden onset OCD and other neuropsychiatric disorders include: Lyme Disease, Thyroid Disease, Celiac Disease, Lupus, Sydenham Chorea, Kawasaki's disease, and acute Rheumatic Fever [schneider2002]. Some children have been found to have Immunology challenges such as IgG subclass deficiencies [Kawikova2009]. Children will need to be evaluated for this issue by an immunologist. In addition, while there is good evidence of anti-neuronal antibodies in PANDAS, the diagnosis remains controversial primarily due to the observations by Johns Hopkins researchers who have not been able to detect such antibodies in their research subjects [Martono2007]. References [swedo1997] S Swedo et al, "Identification of Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections by a Marker Associated With Rheumatic Fever", Am J Psychiatry 154:1, January 1997 http://ajp.psychiatryonline.org/cgi/reprint/154/1/110.pdf [Kirvan2003] Kirvan CA, Swedo SE, Heuser JS, Cunningham MW, "Mimicry and Auto-antibody mediated neuronal Signaling Cells in Sydenham Chorea", Nature Medicine 9, 914 - 920 (2003) http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf [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 [swedo2004] Swedo SE, Leonard HL, Rapoport JL." The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction", Pediatrics. 2004 Apr;113(4):907-11. http://pediatrics.aappublications.org/cgi/reprint/113/4/907 [Moretti2008] Moretti G, Pasquini M, Mandarelli G, Tarsitani L, Biondi M (2008). "What every psychiatrist should know about PANDAS: a review". Clin Pract Epidemol Ment Health 4: 13. http://www.ncbi.nlm.nih.gov/pmc/articles/P...5-0179-4-13.pdf [swedo1998] Swedo SE et al., "Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases", Am J Psychiatry 155:2, February 1998. http://ajp.psychiatryonline.org/cgi/reprint/155/2/264 [Çengel-Kültür2009]Çengel-Kültür2009, et al. "The relationship between group A beta hemolytic streptococcal infection and psychiatric symptoms: a pilot study", The Turkish Journal of Pediatrics 2009; 51: 317-324, http://www.turkishjournalpediatrics.org/pe...pdf_TJP_674.pdf [Murphy2004] Murphy TK, Muhammad S, Soto O, et al. "Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics", Biological Psychiatry, Volume 55, Issue 1, Pages 61-68, January 2004 http://www.journals.elsevierhealth.com/per...0704-2/abstract [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 [shet2003]Shet A, Kaplan EL, Johnson DR, Cleary PP, "Immune response to group A streptococcal C5a peptidase in children: implications for vaccine development", J Infect Dis. 2003 Sep 15;188(6):809-17. http://www.journals.uchicago.edu/doi/pdf/10.1086/377700 [storch2006]Storch EA, Murphy TK, Geffken, G et al, "Cognitive-Behavioral Therapy for PANDAS-Related Obsessive-Compulsive Disorder: Findings From a Preliminary Waitlist Controlled Open Trial", Journal of the American Academy of Child & Adolescent Psychiatry: October 2006 - Volume 45 - Issue 10 - pp 1171-1178 http://www.ncbi.nlm.nih.gov/pubmed/17003662 [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 [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 [snider2005]Snider L, Lougee L, Slattery M, Grant P, Swedo S. "Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders". Biol Psychiatry 57 (7): 788–92. 2005 http://intramural.nimh.nih.gov/pdn/pubs/pub-9.pdf [Nicolson2000]Nicolson et al, "An Open Trial of Plasma Exchange in Childhood Onset Obsessive-compulsive Disorder Without Poststreptococcal Exacerbations. " J Am Acad Child Adolesc Psychiatry 2000, 39[10]: 1313-1315 http://www.ncbi.nlm.nih.gov/pubmed/11026187 [Yaddanapudi2009] K Yaddanapudi, M Hornig, R Serge, J De Miranda, A Baghban, G Villar, W I Lipkin Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Molecular Psychiatry August 11, 2009 doi:10.1038/mp.2009.77 http://www.nature.com/mp/journal/vaop/ncur.../mp200977a.html [schneider2002]Schneider R., Robinson M., Levenson J., "Psychiatric presentations of non-HIV infectious diseases: Neurocysticercosis, lyme disease, and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection", Psychiatric Clinics of North America, Volume 25, Issue 1, Pages 1-16 http://www.ncbi.nlm.nih.gov/pubmed/11912935 [Martono2007]Martono D, Church A, Giovannoni G, "Are antibasal ganglia antibodies important and clinically useful?", Practical Neurology, 2007; 7: 32-41 http://pn.bmj.com/content/7/1/32.extract [Kawikova2007]Kawikova I, Leckman J, Kronig H, et al. "Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study", Biol Psychiatry. 2007 Feb 1;61(3):273-8. http://www.journals.elsevierhealth.com/per...0804-3/abstract [Kawikova2009]Kawikova I, Grady BP, Tobiasova Z, et al., "Children with Tourette's Syndrome May Suffer Immunoglobulin A Dysgammaglobulinemia: Preliminary Report", Biological Psychiatry, Sept 2009. http://www.ncbi.nlm.nih.gov/pubmed/20006327

Yes, she's had the "stealth dyslexia"/orthographic memory issues since 1st grade and we had extensive neuropsych consults (as well as the school running tests) all confirming what we already knew -- that there was a 2-3 year distance between her knowledge and her production. Her vocabulary is off the charts, but her spelling is worse than a 1st grader. Her reading comprehension is off the charts, but her punctuation is less than a 2nd grader. She has a great understanding of algebra but can't tell you 2x3 without calculating it. All individual tests came out fine, but problems showed up when combining individual tests (i.e., copying rather than reading) -- where fine motor, visual memory, and ordering all have to come together. When tests were combined she dropped like a stone to the 4th percentile. Again all of this may be PANDAS still. We do see enormous improvement in her handwriting, margins and memorization since IVIG. I thoroughly agree. She's actually a hard worker and really does want to get all the homework done, but would rather do her math schoolwork at home where no one judges her. The teacher is treating this as her not trying. Totally agree and my biggest fear. I read so many stories of dyslexics who fall off the curve in 3rd grade -- and are never caught. Her dyslexia (spelling/writing) may be an underlying condition or attributable to PANDAS. We really just want her comfortable in school. Mine too... especially since we already got the IEP, already talked about these issues and then we get the "she's not trying in class" bizarre comment on her report card -- and then a refusal from the teacher to meet to discuss without waiting 1 month for an IEP meeting. I really don't get why the teacher can't tell us what he means without waiting a month for a formal IEP meeting. Buster

Two years ago, we got an IEP for my daughter for speech and then extended the IEP under OHI for PANDAS when all #$@$@# broke loose in Feb 2008. We're now back to the underlying conditions that my daughter has always had: * mild dysgraphia -- poor penmanship, fine motor tremor (on long assignments) * orthographic memory issues -- can't spell, can't recall math facts (must recompute them) * social anxiety -- very pronounced and doesn't want to be different from others This last one is a pain because it means she doesn't want to use accomodations (such as using an AlphaSmart to type) if others in the class aren't doing it too. Another weird thing about her condition is that she can recognize misspelled words, but can't spell them (and often can't copy them). She writes phonetically, but reads by sight. It's like the two parts of her brain never quite got together. We've gotten some accomodations through the school, but her teacher is now thinking she's just not putting in enough effort. He actually wrote in her report card that "she needs to put more time and energy into studying for tests." While that may seem an innocent comment, we see her each night struggling to do her homework and often in tears as she tries to produce written work. The physical writing is the struggle -- trying to get her thoughts, orientation of letters and the fine motor all to cooperate. Bottom line, it's not for a lack of trying. In reading essays they have to write, you can literally see the degradation of her handwriting after 4 sentences. She comes home exhausted from this. We've tried to get the IEP to give her "multiple choice" or "fill in blank" or to reduce copying (like have the teacher hand her stuff that is typically copied from the board), but this has not been followed through although documented. The teacher wants her to go to the resource room to learn stuff she should have learned in 2nd and 3rd grade. This would make sense but her social anxiety is so severe that she literally breaks down in tears when pulled from the class. I'm now in the "enough stress" moments and while this is soooo small an issue compared to last year and what other parents have been through, I'm hoping you might all have suggestions of what to do here. The key issue is producing material (i.e., the physical act of writing). She totally understands the concepts but seems to get confused about how things look. Any suggestions? Buster

So here's what I got: Your ds has had tics since he was 2.5 2.5-5 he had a blick tic 5-9 he had shoulder shrug 9 - jump, kicking self, jaw juts - now head twist, shakes He also has significant allergies Throughout the last few years he's been on antibiotics 3-4 x/yr due to symptoms (although no positive cultures). His tics in the past have gone into full remission following treatment with antibiotics. In his current exacerbations your ds had significant inflammation of his neck lymph nodes indicating he had some infection. ---- Given that you've been seeing his exacerbations correlated with infections, you are wondering if the "normal" CaM Kinase II results indicate that he doesn't have PANDAS? The short answer is we don't know. On the forum, we've seen that CaM Kinase II scores seem to be elevated when someone is in an exacerbation. Many of us have had a couple sample, and the numbers do seem to be higher in an exacerbation and "normal" when not in an exacerbation. So, was your son having a significant tic exacerbation when you drew serum? On the paper about passive transfer. That is a good paper, but its also really early and it is basically showing that antibodies do cross the blood-brain barrier (at least in mice) and cause behavioral changes. The key of the paper is that they were showing that a weakened blood brain barrier is one of the necessary conditions. I'm not sure what to say except if his symptoms seem to remit with antibiotics terrific, stick with your program. Your case might end up being the one that helps find yet another antibody that wasn't known before. Buster

Hi Dcmom, It sure does sound like OCD with physical manifestation. Have you tried the over-the-counter stuff like Pepcid or Tums? It's unlikely these will change things, but who knows. They're definitely worth a short trial. Do you think the food item is more an excuse to not eat (i.e., do you think she's having anorexia)? Is she able to express what she's worried about ... also how old is Caroline? Buster

I've had several conversations regarding strep titers with specialists at the World Health Organization and they consistently say that there are no studies on the rate of titer drops. ASO is an antibody to an exotoxin of streptococcus and the half-life of the antibody is supposed to be 4-6 weeks. However, they noted that in one study, the ASO remained elevated (but falling) for over 18 months. So direction is more important than level. Best regards, Buster

If your friend is scared, get help! Seriously, while vocalization is different from action you have to take every threat seriously. When someone is vocalizing self harm it is a declaration of the degree of suffering they are going through, the height of the emotional hurt. It absolutely must be acknowleged and addressed. Here's one site to look through that has some help http://www.brandonrha.mb.ca/en/Mental_Heal...and_Others.html But please, please refer your friend to a psychiatrist or pschologist -- suicidal vocalizations must be addressed. Our dd9 was literally in the middle of the pediatrician's office screaming at the top of her lungs "I need to die" "I need to be killed" -- the doctor came in and said "we have other patients, you will need to come back"... I've never been so mad in my life -- I'm like "here's your patient -- this is not normal!!!" Gratefully it wasn't more than that, but we were scared. Bottom line -- seek help. Buster

I just watched it. I would have liked to have more Trifiletti and have more credibility given to him (i.e., number of kids he's seen, differential to other OCD or tic disorders, time spent researching this topic)... but it came across fine. Hoping that the family gets some downtime -- I can't even imagine how tiring this must be -- Buster