wisdom_seeker

Faith:
 
I think about the question you pose every single day. Why did the "Saving Sammy" dose of 2000 mg. of Augmentin help Sammy. Was it a deep rooted or intracellular strep that needed the high dose antibiotics the issue or was it the anti-inflammatory properties of the antibiotics that helped his possible auto-immune disease?
 
And the answer may be different for every child. Sammy did have elevated strep and I believe so does Worried Dad's son. So, maybe that is why they needed the high dose antibiotics.
 
In our case, strep was the initial trigger, but any virus, lack of sleep or too much sugar can create a little exacerbation. Basically, anything that can tax the immune system can produce a little flare of symptoms. And our son's ASO levels did not always match his symptoms.
 
Just thinking out loud.
 
Elizabeth

There are multiple things here:
 
1) For SC or RF, prophylatic antibiotics are used to prevent re-infection after the intial illness. Subsequent attacks are usually much more severe so the attempt is made to prevent or reduce the severity of re-occurance through long-term antibiotics.
 
2) In 1976, Husby http://www.ncbi.nlm.nih.gov/pmc/articles/P.../je14441094.pdf showed that emm-type 6, 11, and 12 were implicated in RF and SC. Subsequent studies by Wannemaker and Kaplan have implicated other strains (such as those exhibiting M1 and M18).
 
3) While penicillin is still effective invitro against GABHS, in early 2003 it was shown that strep can go intracellular (like a virus) http://www.journals.uchicago.edu/doi/pdf/10.1086/508773 . Penicillin is less effective at clearing for patients who have this strain (even in immune competent individuals)
 
4) The treatment dose and duration for antibiotics is based on studies of children who are not immuno-compromised. The objective of most of the studies investigating efficacy is to clear the disease in > 80% of children within a prescribe time window (typically 14 days). However in greater than 10% of cases, GABHS is not cleared.
 
Now we get to PANDAS. Antibiotics do not in and of themselves kill GABHS, you need a competent immune system to do so. Some of the kids have low IgG levels and it is thought that they do not mount a sufficient response. While carriage may explain positive throat cultures in some children (with low ASO and antiDNAseB) it is not actually known whether carriage is benign or whether it is rather a lingering long term infection.
 
Thus, the prophylaxis is intended to keep an infection from occuring (or if it does occur that it will be quickly curtailed). The high dose prophylaxis is (in my opinion) to clear intracellular strep or help an immunocompromized child fight an infection. There are also some anti-inflammatory and immuno-moculating properties of macrolides that help all of these items.
 
The exact dosage needed to maintain prophylaxis in children is not really known and seems to vary by weight, immune response and GABHS strain.
 
Long answer, but I hope it helps with your question.
 
Buster

I don't know that this is an unusually high number of mutations. I've seen more than this for a number of kids and even I have more than this. Your son does have a few that will make heart disease a potential problem (ACE, NOS & SOD), especially since high ammonia is an issue.
 
But the good news is I don't see a ton of mutations on the genes that have bigger impact on mood - other than COMT. His MTHFR, CBS and VDR Taq are normal, and these are biggies for mood. COMT is the warrior/worrier gene and being homozygous, along with +/+ for MAO-B, means he will stay ramped up on epinephrine and dopamine longer that others around him - making him more prone to anxiety and anger. But MAO-B has lesser impact than MAO-A. It looks like he's more likely an over-methylator rather than an undermethylator, so you might see benefit from adding Vitamin B3 to soak up some extra methyl donors. B3 comes in several forms. If you use niacin, you'll periodically see a "niacin flush" - a hot flash where the capillaries dialate rapidly. It's harmless but uncomfortable for about 20 min. The flush also releases histamine, causing an itchiness. Niacinamide is a form that won't cause a flush, so it's the form I'd recommend. My son is an over-methylator and niacin makes him much more even tempered (he takes 100mg niacinamide in addition to what's in his B Complex vitamin).
 
I believe SOD plays a role in sulfur and ammonia, but you'll need to double check me. It's been awhile since I've looked at this. Also look into GAD and FUT, as I recall some link with gut health.
 
In terms of high ammonia, I can't speculate on what's causing it to be high. But a supplement that can help is l-ornithine, an amino acid. There are three amino acids involved in the urea cycle - arginine, ornithine and citrulline. All three recycle into each other but ornithine is the rate-limiting factor in the cycle. Ornithine uses ammonia to do it's thing, so adding ornithine helps the body soak up more ammonia. It's used in ERs for cases of hyperammonium. You can buy l-ornithine alone or in combo with one or both of the other two aminos listed above. It's a popular supplement in body building because breaking down muscle increases ammonia. We used a combo supplement that had 250mg of ornithine. We started with 3x/day because my daughter had an adverse reaction to cipro and she stopped peeing. She was so weak and toxic. But once she started feeling better, we tapered down to once a day until she no longer needed it.
 
Yucca root is also great for reducing ammonia, but it's slightly estrogenic, so it shouldn't be taken for more than 3 months at a time. Hibiscus Sabdarifa (aka Roselle) is also a good herb for reducing ammonia and lowering blood pressure. You can find research on all three (ornithine, yucca, roselle) on Pubmed. Here are some links on general methylation issues
 
http://autismnti.com/images/Website-_Yasko_Education.pdf
 
You can go to Youtube and search for videos by Amy Yasko, Kendall Stewart and ? Rawlins (can't recall his first name).

Actually, I want to clarify what I wrote: your daughter has PANDAS, since she did have strep-associated OCD in the past, and she is having a PANS flare. The only question is whether this is a strep-associated flare.... or from another bacterial infection.
 
Now why might she have had a negative culture? And which test is the more accurate?
 
The rapid test. (You need the culture to do susceptibility testing, or if the rapid test is negative, but if the rapid test is positive, I claim that's definitive). Here's the expanded argument:
 
According to a large literature review of rapid strep test accuracy, the rapid strep test is highly specific -- in the quote below, according to a large meta-analysis:
96% of kids who test positive on rapid strep do test positive on culture [meaning on a well-done follow up culture or blood agar]. That's why guidelines in the US and Europe say that you can rely on the rapid test alone.
 
Sensitivity = % of finding a positive if it is truly infected
specificity = likelihood of a positive being a true positive.
 
 
So in the above review of studies, the rapid test missed 11-16% of the true strep cases, (false negatives) however a positive rapid test would be a true positive in 95-97% of the time (3-5% false positive).
 
 
Meaning that when using these current rapid GAS test technologies, 99% of the time a positive rapid test is a correct reflection of a strep infection.
 
So why might your daughter test negative on a culture? Here are some ideas:
If it had been a while since her infection, her body might have cleared most of the infection, leaving few live cocci. Perhaps only left over on one part of one tonsil, or maybe even just in one sinus, with post-nasal drip infected on one side, but not the tonsils.

(Analogy: I get frequent sinusitis and I have asthma. Because I sleep on my left, if I have only a smoldering infection it's on the left. In addition to left cheek pain, I typically have left-sided sore throat, swollen neck nodes on the left, both from the left-sided post-nasal drip, and left-sided chest tightness, so I know it can get lateralized this way).
If she gagged enough on the rapid test swab that she gagged almost instantly on the culture swab, it's quite possible the RN/MD wasn't able to get an adequate throat culture swab. (Adequate requires both tonsils and the back of the throat. ... for the reason in #1. W/o that you can get a false negative.)
If the culture was read after 24 hrs and discarded, rather than cultured for 72 hrs, rare strep might not have had time to grow enough and would have been falsely read as negative.
Or, if the strep cells are mostly dead, then their DNA will still be identified on the rapid strep test, (DNA/protein based), but dead cells will not grow on a culture.
Finally, apparently occasionally strep grows w/in epithelial cells, and would require a scrape/punch to get live strep organisms and a longer(?) anaerobic culture. The rapid strep test does not care whether the strep DNA found is aerobic or anaerobic the test simply looks for DNA or cell fragments. (DNA probe, PCR, etc). Sources -- I can come up with more, but it's late.
Medscape: "Rapid Strep test accurate" 9/8/14
http://www.medscape.com/viewarticle/831298 (free registration)
http://latitudes.org/forums/index.php?showtopic=13068
(others who have your situation, trying to figure out why)
For #4, read Stephanie's recollection
"....Our ped later explained why [positive rapid, neg culture].... Something about [her] strep being "dead cells" meaning that since he had been exposed to azith that week (his usual prophylactic dose), whatever grew back from that was only able to show up on the rapid."

My daughter (10) struggled/struggles with MARCONS. I don't think you'll find much literature aside from Shoemaker because I think this is his name for the condition. But if you search for "chronic sinusitis" or "resistant staph sinus infection" you'll find more research. You'll also find a lot searching for chronic fungal infections. It's real and it's recognized as the nemesis of people who suffer from chronic sinus issues but it isn't called MARCONS in the literature. Yet MRSA is unquestioned as a resistant staph infection of the skin, so it seems reasonable that a chronic infection of sinus tissue could also cause a subset of people some serious problems.
 
I get where Buhner is coming from and I respect his knowledge as an herbalist. There can be a lot of "the sky is falling" panic among people who have chronic diseases like lyme. But I lived through Pandas and Lyme with my son and in my experience, when people stay sick, you need to keep digging beyond the obvious infections because something else is keeping you from getting well. For both my son and daughter, mold was one of those roadblocks and I think Shoemaker correctly sheds light on mold and MARCONS as things that, when treated, can help people get on the road to recovery. You can fault Shoemaker for being a bit too zealous, for being too quick to blame mold for everything. Buhner's probably right in that for some people, staph is no big deal. But for a group of people, Shoemaker's dead on and has solid research to substantiate his views. The question becomes - is your child part of Buhner's group or Shoemaker's group?
 
My daughter is part of Shoemaker's group. She struggled with serious health problems due to mold in her school and developed MARCONs and a chronic fungal sinus infection. So the bad stuff in school eventually lived inside her, making her sick no matter where she was physically located. She didn't recover her health until we finally eradicated both the fungal and staph infections. BEG spray didn't work for her. She needed a nebulized concoction of itraconozole and clindamycin for several months. But it did slowly work.
 
I have to disagree with Buhner on one other often quoted statement he's made regarding the use of certain herbs. He recommends a blend of cryptolepis, sida acuta and alchornea. He says that he knows of no ill effects even tho cryptolepis and sida have the same mechanism of action as fluoroquinolones like cipro. Cipro caused serious side effects in my daughter and I think he's sometimes too dismissive of the potential side effects of cyrptolepis and sida. I have both of his books on antibiotic and antiviral herbs and while he does a great job explaining how they work and their benefits, the books are light on things to look out for, potential side effects, warnings about overuse. etc. I'd feel better if his message were a little more balanced. So I think you need to take statements from both men and evaluate them in terms of what seems to ring true for your family and your experiences.
 
One final thought - the research paper that came out a few weeks ago showed that Pandas occurs when antibodies against an infection travel up the sinus passages into the olfactory bulb and breaches the BBB via the cribiform plate at the top of the olfactory bulb. The paper then goes on to say that chronic sinus infections then seem to prime the immune system to (over)react to other infections beyond strep and specifically names staph and mycoplasma as triggers. So if your child has Pandas already and now has a resistant staph infection in his sinuses, then it seems like the stage would be set for a Pans flare if the MARCONS goes untreated. This was true for my daughter, who for years has been borderline Pandas but always quickly recovered if we got her on antibiotics quickly. Now, after the mold and MARCONS issues, she seems to be full blown Pans and after a second MARCONS infection in October, is taking a very long time to recover.
 
Only you know what's best for your child, especially since he's a teen. Neti pots can be tough and treatments can be hard for a teen who just wants to be like everyone else and who wants to assert his independence. But he might be playing roulette in this case. I don't know that irrigation is your only option. As I said, a nebulizer helped my daughter and she's recently had success with a spray that's similar to BEG but uses clindamycin not gentamicin and also includes an anti-fungal. BEG spray stings. Her concoction doesn't. So I don't know that you need to follow Shoemaker's protocol to the T (tho he'd disagree of course). You have options. But some sort of treatment that your son can get on board with might be worth pursuing.

Here's the link to the paper https://www.jci.org/articles/view/80792/version/1/pdf/render
and a summary
 
Researchers have discovered how immune cells triggered by recurrent Strep A infections enter the brain, cause inflammation, and may lead to autoimmune neuropsychiatric disorders in children, including PANDAS. Children with PANDAS exhibit high levels of anxiety, motor and vocal tics, obsessive-compulsive behaviors and a host of other symptoms that often appear “out of the blue” or increase dramatically, seemingly overnight.Their study found that immune cells reach the brain by traveling along neurons that originate from the nasal cavity.
 
This study explains, for the first time, exactly how upper respiratory infections can trigger both physical and neuropsychiatric symptoms.
 
According to the study’s co-leader, Dritan Agalliu, PhD, at Columbia University Medical Center, the Strep A bacterial cell wall contains molecules similar to those found in human heart, kidney, or brain tissue. These “mimicking” molecules are recognized by the immune system, which responds by producing protective antibodies. But because of this molecular mimicry, the antibodies react not only to the bacteria but also to the body’s own tissues. The molecular mimicry process has been well researched by others. But previously, scientists didn’t understand how these autoantibodies would gain access to the brain, because brain vessels form an extremely tight blood-brain barrier. This study answers that question.
 
Researches have known that recurrent Strep A infections trigger the production of immune cells known as Th17 cells, a type of helper T cell, in the nasal cavity. But it was unclear how these Th17 cells lead to brain inflammation and symptoms such as those seen in children with PANDAS. Through this study, Drs. Agalliu and colleagues found that bacterial-specific Th17 cells move along the surface of olfactory, or odor-sensing, axons that extend from the nasal cavity through the cribriform plate, a sieve-like bone that separates the nasal cavity from the brain. From there, the cells reach the olfactory bulb in the brain, which processes information about odors. The Th17 cells break down the blood-brain barrier and enter the brain,, allowing autoantibodies and additional Th17 cells to enter the brain, causing neuroinflammation.

In addition to illustrating how PANDAS occurs, the study also validated some of the experiences many parents have had regarding their PANDAS children:
Strep A is not the only trigger – Parents have often reported that infections other than Strep A seem to trigger PANDAS symptoms. This feedback was so abundant that researchers proposed making PANDAS a sub-set of a new, larger category called PANS – Pediatric Acute Onset Neuropsychiatric Syndrome. Unlike PANDAS, PANS does not associate the onset of symptoms specifically to a Strep A infection. Dr. Agalliu’s study shows that Th17 cells persist in the brain for at least 56 days after initial infection, even when nasal tissues no longer show signs of an active infection. “Several other bacterial and viral pathogens, including influenza virus, mycoplasma and Staphylococcus aureus (nasal staph infections) induce robust Th17 responses and could also play a role in an exacerbation of behavioral symptoms in children with PANDAS if autoantibody levels are primed by previous (Strep A) infections.” (pg 11 of article).

I don't have the MARCONS lab report in front of me and don't remember if it lists the exact type of staph - I want to say it doesn't. But it does give you a list of antibiotics and lists whether the staph is Resistant, Sensitive or I (which I can't recall the wording but means somewhat sensitive but not completely). I don't know if a regular lab culture would reveal the same infection - I know it's always taken a minimum of 2 weeks to get results. The fungal report takes even longer. If your sinus guts are open minded, they may be willing to do a slow growing culture. I'd certainly also ask for fungal culture.
 
You mention a nebulized formula that uses cipro - cipro causes horrible side effects for my daughter and she too is allergic to a number of abx (penicillins and cephalosporins in her case). In Nov. the FDA voted to change it's position on cipro and related abx and now urges extreme caution and suggests using alternative abx for most situations. Gentamycin also has a serious risk profile and can cause hearing loss. So just be very careful. Although literature suggests that abx delivered in a nebulizer aren't systemic, that they stay localized in the sinuses, that doesn't seem to be my daughter's experience. Have a detailed conversation with the prescribing doctor and make sure you know the risks of any medication before you start using it. Cipro and gentamycin side effects can be permanent.
 
We've used two different approaches. We've used a compounded powder that we mixed with saline and then neublized it, and we've used a liquid spray. The nebulizer seems to penetrate the upper sinuses much better but it can take 20 min, twice a day and after months, can become hard for a kid - makes them start to think of themselves as "always sick". The spray only takes a few seconds and is easier on the psyche, but seems better for less invasive or less chronic infections.
 
As for how we found the mold, my daughter would go to school on a Monday feeling great and by Wednesday would be sick as a dog, unable to go to school. During school breaks, her health would return. The school was initially cooperative but then became difficult. My daughter recovered her health over the summer but then missed 9 of the first 13 days of school in Sept. so we decided to home school this year. We've also done a great deal in our home to make sure there's no problem here ( replacing carpet with hardwood, getting rid of house plants, no mold-friendly material in the basement like cardboard boxes or fabrics, de-humidifiers and testing). Your best bet would be to put absences or flares onto a calendar to look for a pattern.
 
In your other post, it sounds like lyme might also be a possibility. It's hard to tease out mold vs. lyme vs. marcons vs Pandas. Between my two kids, we've dealt with all of it but it was a process of whittling it away. See if Amy will order C4a and C3a blood tests. Shoemaker feels that C4a is indicative of mold and C3a is indicative of lyme. Also talk to her about doing an Igenex lyme test. Sometimes, it's more than one hurdle in your way.

Thank you all for your words of support. And also the advice to just move on.
 
With your support, I don't feel so alone, and I think I have moved on.
 
It also helps that one of our MDs said that he wouldn't have had any expectations for this particular neurologist -- that he's OK for textbook cases, but not for anything complex, anything that requires 'out of the box' thinking, the sort that both my sons seem to need.
 
I've now gotten a referral to one of the child neurologists who work at the PANS/PANDAS clinic, and hope for a better outcome. I am a bit apprehensive, because he just isn't a textbook case.
 
Now (after 3 weeks of abx and 2 weeks of prednisone) he doesn't have the choreiform movements any more, the sensory defensiveness is a bit better, though rubber and water are still his enemies. But mostly, his symptom where his brain thinks that his other hand must be the actor if someone touches his arm is so weird (e.g. L hand if touched on R arm). Especially the part where the supposed "actor" hand then disappears (and then fades in and out) of his brain's body map. The shrink still thinks it's part of the ganglia driven sensorimotor dysfunction, but I still worry it will make him labeled a crockpot.
 
So I hope that the neurologist can still see some signs that say "he's telling the truth". And that she will order the set of tests to confirm the Dx and to figure out what the trigger(s) might be.

I would think a neurologist visit will rule other things out, and an MRI may identify areas of the brain that are suffering from inflammation, as well. There's another neurological diagnostic tool -- a PET scan -- that some doctors at Detroit Children's Hospital/Wayne State have used with respect to PANDAS and OCD in kids.
 
http://pandasnetwork.org/petscanresearchfindings/