Are symptoms from inflam. or autoantibodies....why some "remit&#34

[eljomom]

I am sure many of you are tiring of me and my repeated questions....thinking it part of perimenopause but one minute I grasp it, and then I don't....

 

So, in thinking about symptoms of pandas/pitand--how some kids have distinct "exacerbations" and then remissions to baseline or almost, but there's a definite beginning and ending....and why some (or at least us) may have had that MILDLY so it wasn't even noticed as a pattern (or maybe having 4 kids in 6 years kept me too busy to notice). My question is: WHAT EXACTLY IS CAUSING THE SYMPTOMS? I mean, I get that it's autoimmune...I think. That body is attacking its own basal ganglia in some way (but NOT causing damage???) and causing signaling issues with dopamine. But what makes it "wax" or remit or lesson in some kids, and in others, not? I know some will say "underlying infection." Okay....that is a possibility....BUT, let's look at those kids who have tried every abx under the sun, tested for every infection under the sun, and everything is negative, and the kids still have continuous tics, etc.....WHAT IS THE ISSUE? Is it inflammation in the brain? If so, from WHAT? (if no infection)? If Cam K is high, then there are inflammatory cytokines running around, right? Which can be a normal response in a healthy person, correct? But also, if anti-dopamine antibodies are high, then antibodies are running around, right? With no infection? So they are just running around in blood, on a mission to attack basal ganglia?

Sigh...breath...sigh... Thoughts???

[kimballot]

EljoMom - you always have such good questions. I think the problem is that these are the same questions the researchers have and we don't have answers yet.

 

I know we have talked before about the blood-brain-barrer (BBB) and about antibodies crossing over to interfere with Basal Ganglia function and elevate cam Kinase and dopamine. It does seem that the BBB is breached more easily in some kids than in others and that it is breached more easily when there is infection or inflammation in the body. So... one answer is that in some kids the BBB closes up more quickly than in others - probably depending on the child's individual body makeup.

 

Now.. here is my other thought. Antibodies are formed from B cells that float through the blood. Some of these B cells are memory B cells - these are the cells that remember previous infections and make the right antibodies really quickly when they see the infection again. I've been asking for a while if the B cells can cross the BBB (B cells are pretty big, so it is not real likely), or if only the antibodies cross. If the B cells can cross, then anytime there is a breach in the BBB, the memory B cells could see the basal ganglia neurons, think it is strep or some other nasty antigen, and make lots of antibodies to fight it. In that case, even when the real infection is gone, the child will still have PANDAS symptoms - until the BBB is closed and the B-cells and antibodies all die off.

 

I thought I was the only person wondering about his until I looked at the Moretti article again recently. Here is what Moretti says:

 

The presence of systemic anti-basal ganglia autoantibodies has been proposed as possible evidence for an immunological pathogenesis of a subset of OCD. The modulation of intracellular signalling pathways by autoantibodies has been described in myasthenia gravis [58] (autoantibodies to the acetylcholine receptor blocking neuromuscular transmission) and Graves disease [59] (autoantibodies against thyroid-stimulating hormone). Nonetheless basal ganglia, like most CNS structures, are relatively inaccessible to circulating antibodies owing to the presence of the blood-brain barrier (BBB). Although the mechanism by which circulating antibodies or cytokines might gain access to the CNS is unknown, with the exception of the circumventricular/lamina terminalis region, where the BBB is absent [60], a variety of hypothetic mechanisms exist. For example, circulating antibodies could reach the CNS if an inflammation of the meninges causes a local BBB breakdown. Cytokines, probably crossing the BBB at circumventricular organs, can trigger an immune activation on the CNS side of the BBB. Moreover, peripheral B cells that are cross-reactive to a CNS epitope may cause intrathecal production of antibodies [61].

 

Intrathecal production means production of antibodies on the brain side of the BBB. According to reference 61 in this article, this is something that has been found in rats.

 

I think it is extremely important that Dr. Cunningham hired a B-cell immunologist (in - part with the Pepsi refresh grant). I really think this will help to further the PANDAS theory and our treatments and will help us to understand more about why some children do well with antibiotics or steroids or IVIG and some do not.

[butterflymom]

=

Edited October 5, 2015 by tampicc

[JAG10]

Many questions, not as many answers...

 

Is one of your main questions why do some kiddos explode with symptoms then go back to normal or nearly normal while others are in more of a chronic state of bad and sometimes even worse?

 

I think most kids start out with the dramatic wax and wane pattern (even though for some under age 5 that might be difficult to tease apart from some typical periods of equilibrium and disequilibrium.) If PANDAS goes untreated, misdiagnosed, ect. the shifting farther and father from baseline can eventually "go chronic" in that the bad anti-neuronal antibody faucet is broken in the turned-on state and Big Guns are needed to try and turn it off. THe symptoms no longer wax and wane bcs the BBB never "closes" and the inflammation persists. One PANDAS doc explained it as a sprain that you keep walking on and never allow to heal; it's not "broken", there is no lesion like in a stroke, just swelling like in a sprain, thus no permenent damage if it could just have a chance to heal.

 

It seems some kids have their initial onset and are chronic immediately, at least that is the way Sammy's story seemed to play out.

 

I'm sorry, I probably didn't answer one question you asked!

[EAMom]

re the BBB (from FAQ)...IVIG can help close the BBB, halting the feedback loop of the immune system (b-cells or whatever) reaching the basal ganglia and seeing/attacking it as "foreign".

 

Q: Why does IVIG or Plasmapheresis work?

A: PANDAS is thought to be caused by three events:

1.the creation of an antibody to Group A Beta-Hemolytic Streptococcus that can react with neuronal tissue

 

2.the failure of the immune system to suppress the antibody

 

3.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.

[coachadamb]

Just some thoughts to ponder, As was stated in an earlier reply, we are really on the forefront of something much larger than any of us really know. Myself, I have an 18 year old who is being treated in Detroit by Dr. Chugani. I know that through Nathans PET scan his right frontal lobe and the complete right side of the Basal Ganglia are inflammed extensivly. It is my opnion that had Nathan been diagnossed at a much younger age perhaps the symptoms would not be so life altering. As with any inflammation, left untreated especially in the brain, there will come a time when it begins to cause damage probably within the inflammation itself. Parkensons Diesease is caused by degeneration of the Basal Ganglia. Could our kids PANDAS be a precurser to this diesease if the Pandas is left untreated??? The brain will heal by removing the bacteria, its just a matter of time and without further exposure to the bacteria during the healing process. My appologies for the spelling!!! The inflammation is so bad that my son has developed tics and tremors

simular to parkensons. He will have IVIG treatments next week...a hope and a lot of prayer.

 

This brings me to my second point. The wide range in the ages of kids that have symptoms. Time will tell as studies are released but there seems to be a direct corolation between symptoms, or what seem to be stages of symptoms, and the ages of children. PANDAS caught early perhaps treatments seem to be not so invasive? easier to maintain? Where as our kids that have lived with it longer say late teens early adulthood, without treatment are having a diffucult time with treatments and or maintaining. One thing we have to remember is that the frontal lobe and the Basal ganglia share the same protein as the strep bacteria. Thus a safe and easy place to hide once its in the blood stream. So when the body releasses antibodies to fight the bacteria one of two things are going to happen. one, its going to attack the bacteria and the part of the brain its attached to or, it not going to attack anything because it recognizes it as the brain.

 

Eljomom, you are not wacko, Its questions like yours that keep researchers busy getting answers, and answers are comming. So keep asking and insisting on answers.

 

Adam

 

I am sure many of you are tiring of me and my repeated questions....thinking it part of perimenopause but one minute I grasp it, and then I don't....

 

So, in thinking about symptoms of pandas/pitand--how some kids have distinct "exacerbations" and then remissions to baseline or almost, but there's a definite beginning and ending....and why some (or at least us) may have had that MILDLY so it wasn't even noticed as a pattern (or maybe having 4 kids in 6 years kept me too busy to notice). My question is: WHAT EXACTLY IS CAUSING THE SYMPTOMS? I mean, I get that it's autoimmune...I think. That body is attacking its own basal ganglia in some way (but NOT causing damage???) and causing signaling issues with dopamine. But what makes it "wax" or remit or lesson in some kids, and in others, not? I know some will say "underlying infection." Okay....that is a possibility....BUT, let's look at those kids who have tried every abx under the sun, tested for every infection under the sun, and everything is negative, and the kids still have continuous tics, etc.....WHAT IS THE ISSUE? Is it inflammation in the brain? If so, from WHAT? (if no infection)? If Cam K is high, then there are inflammatory cytokines running around, right? Which can be a normal response in a healthy person, correct? But also, if anti-dopamine antibodies are high, then antibodies are running around, right? With no infection? So they are just running around in blood, on a mission to attack basal ganglia?

Sigh...breath...sigh... Thoughts???

[JAG10]

Adam,

 

Your post is very confusing to me. Your doctor told you the strep A bacteria is in the brain? Not my understanding. The Basal Ganglia is inflamed from anti-neuronal antibodies attacking it ( these menacing antibodies think they are attacking strep because of molecular mimicry.) The auto-immune process can be in full swing even after the infection has been eliminated; those bad, anti-neuronal antibodies can be cranked out in a chronic fashion and that is what is causing the inflammation of the basal ganglia via breach of the BBB.

 

I would also ask this doctor where he is getting his info regarding permanent brain damage. Again, not my understanding after seeing 4 PANDAS experts and reading this board over a year; quite the opposite. You can also search the forum or tagged literature that refers to a significant percentage (>40%) of children who "outgrow" PANDAS (post) puberty with no residual symptoms (or damage.) I don't think anyone can say there is NEVER a possibility of damage, but all the brain damage chatter is speculation.

 

I'm not one fluent in quoting the research as many on here are..... There is a FAQs page pinned at the top that can better articulate these points. I would agree with you on the importance of early intervention to minimize the impact of PANDAS symptoms that sour or devastate childhood. Dr. K used to claim that treatment was most effective if it began before the onset of puberty, but more recently he has treated some older patients as well.

 

Best wishes that Nathan experiences some symptom relief from treatment.

 

Jill

[Bill]

I am sure many of you are tiring of me and my repeated questions....thinking it part of perimenopause but one minute I grasp it, and then I don't....

 

So, in thinking about symptoms of pandas/pitand--how some kids have distinct "exacerbations" and then remissions to baseline or almost, but there's a definite beginning and ending....and why some (or at least us) may have had that MILDLY so it wasn't even noticed as a pattern (or maybe having 4 kids in 6 years kept me too busy to notice). My question is: WHAT EXACTLY IS CAUSING THE SYMPTOMS? I mean, I get that it's autoimmune...I think. That body is attacking its own basal ganglia in some way (but NOT causing damage???) and causing signaling issues with dopamine. But what makes it "wax" or remit or lesson in some kids, and in others, not? I know some will say "underlying infection." Okay....that is a possibility....BUT, let's look at those kids who have tried every abx under the sun, tested for every infection under the sun, and everything is negative, and the kids still have continuous tics, etc.....WHAT IS THE ISSUE? Is it inflammation in the brain? If so, from WHAT? (if no infection)? If Cam K is high, then there are inflammatory cytokines running around, right? Which can be a normal response in a healthy person, correct? But also, if anti-dopamine antibodies are high, then antibodies are running around, right? With no infection? So they are just running around in blood, on a mission to attack basal ganglia?

Sigh...breath...sigh... Thoughts???

 

 

I have no idea! But, I wonder if the variances might be due to the exact bugs causing the disorders and in what order they enter the picture. Sudden onset of OCD brought us to a PANDAS doctor after years of behavioral changes and dystonia. He has since been diagnosed with Lyme & co-infections as well. If our current doctor is right, Lyme - or at least bartonella - was part of the picture as long as 9 years ago (he tested positive for bartonella). So, my current thinking is that Lyme and co-infections were probably doing their number on my son before strep really got involved. Or - they all hit at about the same time at a very young age (lots of strep in his history as well). Each child or person is different, they catch stuff at different ages and phases of development, their immune systems alternately mount defenses or not...I concur with others - no one really knows. Too many variables.

 

We never had strong waxing/waning either. More like he periodically got worse over time, would remain steady, and then get worse again 2-3 years later. Now that he is on heavy ABX, I can say that we are seeing some (minor) improvements and he never really had those moments before.

 

Oh and probably not everyone's symptoms are the result of an immune system disorder either. We're all just a group of folks searching for answers. Some of us will stay here and others may have to keep searching.

[Fixit]

this is just in response to someones question on remittance....

 

ds 11 used to remit in full with standard course of abx.(10 days)..no one would listen to me about pandas..but luckily there was a strep or other infection to treat and he would return to 100% the 15 or so times of episodes...

till this one..which started 2 years ago april....

 

ds 8 has had many ear infections..i thought non pandas ...got strep 11/11/10 still no pandas..another illness hit 12/16 and on 12/21 he had his first tic...since then while on abx.he has gotten an ear infection, mono, and some other throat infection....he just went 100% week..98-99% last week..

 

ds 3 had first episode in july 2010..i thought it was from a vaccine a few weeks earlier...or maybe the final trigger...a couple weeks later docs found ear infection..he got better...i take in 2 weeks after that still infected..and then he remits....so that has been since august 2010 sometime...

i found notes in ds11 notebook...ds3 had pink eye a month before tic started....

but he did have myco p a year earlier..which i think was ds11 final trigger....

 

so 2 at 100% and ds11 is not doing well since starting lymes treatment one month ago...we were not at 100% but a solid 80-85..maybe better..depending...

 

why are the other 2 in remittance??? age???? quick action and panda accepting doctors..finally????

why is ds not remitted in almost 2 years???? age??? number of onsets???? no one would treat with abx till 10 months later??????? lymes?????

 

ok..as i'm typing...spoke with grandmother of ds(dh's mom)..the side where this genetic pan/pit cr*&^ comes from....

she told me..that her parents who are still alive and in their 90's , and her sister and herself cannot take...

biaxin, augmentin, any pencillian and perhaps a sulfer based abx...

can someone throw me a bone!!!!!!???????? they know i have him on different abx?!?!?!...they know all the docs i see??

did not do biaxin recently..but did do aug and pen..i don't even have words.....

a year ago..almost to the date...the sh)(** hit the fan within 48-72 hours of starting biaxin(so i knew not to do again) and a steriod(though 21 days later we had 4 days of 95% remission...so was not afraid of steroid (and the taper in july was more awesome 98% and lasted a while longer...no rebound, but stuff crept back in, not to worst point)

[PhillyPA]

Adam I have heard amazing things about Dr. Chugani. I was recently discussing this doctor with Diana P and he is one of the only people able to scan the brain/basil ganglia the way he does. It is a lot of radiation so I hesitate to get involved in his research. His research will be so valuable to PANDAS. I know that in theory pandas does not cause permanent brain damage but I guess we will all see if that is true in the years to come.

 

I am curious - what does Dr. Chugani believe that outcome will be for your child? How long has your child had pandas?

[airial95]

I think that some of the issue is also how sensitive your child is to exposure. We had a seemingly endless road last year to just get back to 85% on consistent abx because strep was RAMPANT in our day care last year. My son (on abx) caught it twice, and my daughter had several different variants of strep related rashes last year, not to mention we were notified by the school at least 2x per month about an active case somewhere in the school (usually in my son or daughter's class). Using our tracking spreadsheets, we noticed how crazy sensitive my son was to just being exposed. We took him off the abx in December - about the time that the notifications slowed down as well (although it was coincidence), and he held steady at 85% for some time, until his food OCD started to slowly creep back up over the last few weeks. On a hunch, we got him swabbed a week or so ago and true to form - strep. Took my daughter (and the rest of the family for that matter) to get cultured and she had it as well - but was pretty asymptomatic. (she had been not feeling well for some time, but previous swabs came back negative - but no other signs of strep, signs of other viral illnesses didn't cause us to press the issue - we think now that a culture may have shown us sooner it was strep.)

 

So I think that how sensitive a child's immune system is simply to exposure has a lot to do with it. Our episodes at each exposure last 3-4 days, and he's back to "baseline". If your school or other activities your child is involved with aren't as proactive at notifying you of stre, it's almost impossible to know how often they're being exposed.

[dut]

Hi - I can only speak for my 2 kids...and what I 'think' is going on.

 

Ds is really too nebulous to get a hold on what is going on but dd is/was clearer.

 

Dd7 had her 1st recognised episode at 4. In 3 years she's had 2 major episodes, 2 that were going bad but steroids stopped them in their tracks, totally for one and mainly for another. She has also had some microflares (as I believe Dr Murphy calls them) that last anywhere form a few days to a couple of weeks.

 

Historically, she has always totally remitted between episodes. Last summer she had 3 back to back episodes. After the third, steroids got rid of 80%+ of symptoms but we have been left with some stragglers.

 

We have never found Group A, only beta hemalytic NOT group A, once! Rest of the time it seems as though she has virtually no exposure to bugs according to tests and we've done a few :-) She has flared in response to various illnesses including an acute food allergic reaction.

 

She was in high middle PANDAS range in the Cunningham test and has some elevated liver/low thyroid/adrenal issues etc but fine for all immuno testing (low for 13 out of 14 pnuemococcal but she never had prevnar vac).

 

We can't find mycoplasma pneumoniae either by IgG or IgM but I am positive for IgG. She has often presented with myco. p. type symptoms with long lingering cough at times of major episodes. We now think/feel that myco. p. is her underlying trigger and maybe the fact that she previously remitted was her managing to keep a lid on the myco. Perhaps as these children have these underlying infections longer it does more damage to their innate immune system.

 

Mycoplasmas are very difficult to test for like Lyme, as they too are stealth pathogens that can switch off your innate system and are implicated in up to 25% of PANDAS cases (according to Dr Garth Nicholson). Our ped explained it like this - mycos swith off the innate system forcing your body to use the next level down which is antibodies and inflammation to protect itself, leading to increased risk of autoimmunity and increased inflammation.

 

It does seem to be a pattern that children often go from being able to remit between episodes to their baseline changing and full remission not being attainable. Could also be why some kids need longterm abx to treat and cure despite tests coming back showing no infection. Mycoplasmas, and presumably there are others (Lyme, viruses etc), are notortiously difficult to treat and can take many abx courses over months/years to eradicate.

 

We are looking into PCR tests on blood via a specialty lab to see if we can find myco in the kids. I'll post what we find out...

 

Sorry to rant - this is one of those rare moments these days where I feel as though I'm not lost in the woods with this disorder but actually have something to run with for a change. I suspect I'll be back in the woods if those PCR tests come back negative....

Edited March 1, 2011 by dut

[Guest pandas16]

.

Edited May 3, 2011 by pandas16

[MomWithOCDSon]

I thought that pro inflammatory cytokines and macrophages weaken the blood brain barrier and allow auto antibodies to interfere with neuronal signaling--- most notable glutamate which explains the swelling of the caudate nucleus. I don't think it's known why some kids explode with symptoms and others go completely back to normal, but it makes sense that the longer the inflammation and the younger the age the problem starts the more problems you will have.

 

Well, the glutamate thing is of a lot of interest to me. You say "notable glutamate which explains the swelling of the caudate nucleus." Is this a conclusion you've drawn yourself from some research, or is this a conclusion provided by a doctor or researcher? I've always wondered which came first, the chicken or the egg? Is the caudate swollen because glutamate is collecting there? Or is the glutamate collecting there because inflammation in the area makes the space available for the glutamate to collect? And the answer matters, doesn't it? Because if it's the former, if we control the glutamate, then we might control the inflammation of the caudate. But if it's the latter, we need to control the inflammation first and foremost and that alone may, in turn, limit the collection of the glutamate.

 

[eljomom]

wow, dd7 was negative for myco p. IgG and IgM, despite having had pneumonia 3 times, and walking pneumonia (?) 7 months prior to test. Was told it was negative.....is this another thing like Lyme has become...it's positive even when it's negative?? Sigh.

 

Also, the Group B strep is interesting. Our pandas doc AND the I.D. doc have not tested our family yet, but my mom's doctor happily did a throat culture on her. She was positive for Group B strep. She is around my kids a lot (and always sharing food with them, etc...). Her doc told her Group B strep you don't treat, and it's not the one implicated in Pandas (he called someone about it...he's an Internist). Curious now though.

 

 

Hi - I can only speak for my 2 kids...and what I 'think' is going on.

 

Ds is really too nebulous to get a hold on what is going on but dd is/was clearer.

 

Dd7 had her 1st recognised episode at 4. In 3 years she's had 2 major episodes, 2 that were going bad but steroids stopped them in their tracks, totally for one and mainly for another. She has also had some microflares (as I believe Dr Murphy calls them) that last anywhere form a few days to a couple of weeks.

 

Historically, she has always totally remitted between episodes. Last summer she had 3 back to back episodes. After the third, steroids got rid of 80%+ of symptoms but we have been left with some stragglers.

 

We have never found Group A, only beta hemalytic NOT group A, once! Rest of the time it seems as though she has virtually no exposure to bugs according to tests and we've done a few :-) She has flared in response to various illnesses including an acute food allergic reaction.

 

She was in high middle PANDAS range in the Cunningham test and has some elevated liver/low thyroid/adrenal issues etc but fine for all immuno testing (low for 13 out of 14 pnuemococcal but she never had prevnar vac).

 

We can't find mycoplasma pneumoniae either by IgG or IgM but I am positive for IgG. She has often presented with myco. p. type symptoms with long lingering cough at times of major episodes. We now think/feel that myco. p. is her underlying trigger and maybe the fact that she previously remitted was her managing to keep a lid on the myco. Perhaps as these children have these underlying infections longer it does more damage to their innate immune system.

 

Mycoplasmas are very difficult to test for like Lyme, as they too are stealth pathogens that can switch off your innate system and are implicated in up to 25% of PANDAS cases (according to Dr Garth Nicholson). Our ped explained it like this - mycos swith off the innate system forcing your body to use the next level down which is antibodies and inflammation to protect itself, leading to increased risk of autoimmunity and increased inflammation.

 

It does seem to be a pattern that children often go from being able to remit between episodes to their baseline changing and full remission not being attainable. Could also be why some kids need longterm abx to treat and cure despite tests coming back showing no infection. Mycoplasmas, and presumably there are others (Lyme, viruses etc), are notortiously difficult to treat and can take many abx courses over months/years to eradicate.

 

We are looking into PCR tests on blood via a specialty lab to see if we can find myco in the kids. I'll post what we find out...

 

Sorry to rant - this is one of those rare moments these days where I feel as though I'm not lost in the woods with this disorder but actually have something to run with for a change. I suspect I'll be back in the woods if those PCR tests come back negative....