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.
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. 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: 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 (latitudes.org).
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
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)
Q: 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.
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. Group A Beta-Hemolytic Strep can colonize on the skin or the sinuses (plus ear infections, meningitis, pneumonia, GI infection, peri-anal/vaginal infections). A throat culture can confirm GABHS colonization but not rule out 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: About 5% of children carry strep without any other symptoms. This is thought to be caused by some interaction with other flora in the throat or some defect in the immune system that prevents it from removing the offending bacteria. There is mounting evidence that carriage is not as benign as once thought. Most doctors only treat asymptomatic carriers if someone else in the family is immuno-compromised. Carriage is typically broken by stronger antibiotics like azithromycin or clindimycin.
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 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 4 and 5 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: Kirvan and Cunningham have been studying specific antibodies to GABHS. Cunningham has an open trial where she is recruiting patients to investigate the relationship between these antibodies and PANDAS symptoms. Many parents on this forum have participated in the study. These studies are still research studies and are not yet diagnostic for PANDAS -- but we're all hopeful they might be soon.
Q: What are CaM Kinase II tests?
A: These tests are also known as Cunningham tests on this forum (see above). In 2006, 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 causing a form of dystonia. It is important, however, to highlight that this is a research trial and the accuracy, specificity and repeatability of the test is not yet known.
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: 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: 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 at 10-12 days 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.
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: 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: 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 the prophylactic antibiotics is critical as many have had a recurrence when their child has been re-exposed to GABHS.
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 (this latitudes.org discussion).
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.
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 (this study). 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.
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 new disease (< 12 years old) and there's a lot not known about the disease. The primary controversy is really from researchers who think GABHS is too common an infection to treat as causal for PANDAS. They think it is likely coincidence. In reading studies, most of the criticism come from researchers studying children with Tourette's Syndrome. Unfortunately, by the time a child has had Tourette's Syndrome, they typically have had motor and vocal tics for more than 1 year with no remission for > 3 months. This means that most researchers pulling subjects who have Tourette's are not studying the rapid onset of symptoms (i.e., what most parents coming here are struggling with). Most of the controversy surrounding PANDAS comes from a particular group of researchers who have not been able to replicate other researcher experiments. We hope they all get together soon and compare notes and methods.
A second source of controversy comes from researchers who think that antibiotics, IVIG and PEX all have powerful placebo effect and studies in Russia and in US on efficacy should not be trusted. It's hard to know how to respond to these researchers except to think they've never had a PANDAS child in their test group. This board has lots of samples of children who are dramatically improved after antibiotics and in severe cases with IVIG and PEX.
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 recieving vaccinations. This is a very controversial area and talking with an immunologist with experience with Multiple Schlerosis, Acute Rheurmatic 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.