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eljomom

Are we chasing down the wrong villians?

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I just feel like trying all these abx--none of which seem to be helping, for a case that has been going on for likely a few years, with the really horrible tics starting this summer (not after strep) likely from a virus or staph, not strep....like maybe we're chasing down the wrong villian here in all this??? Maybe it's NOT the bacteria "lurking" anymore, but the autoimmune issue going on. Maybe with pandas, if you've eradicated the bacteria and still aren't improving, it's because the autoantibodies are attacking the basal ganglion (like our 4000 antiD1) that an antibiotic isn't going to touch. How do we get rid of those bad boys---which are across the blood brain barrier, if I understand correctly? I admit, I truly don't know much about autoimmune diseases, especially ones that only zero in on the brain, but I "thought" that they didn't just "right themselves" and go away with eradication of the disease that caused it???? I'm sort of thinking aloud, asking, anything here.

 

Just very very confused, after having a very pandas-literate doc say that it's unlikely pandas if abx arent working. Maybe if it weren't "pandas" but pitand, we could say abx aren't really diagnostic like that.

 

Ugh...sigh.. :(

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Tossing this back over to Buster.

Look at this thread (from the pinned "helpful threads"

http://www.latitudes.org/forums/index.php?showtopic=6265

 

Especially look under the headings Research and Other considerations

 

Under research:

A breach of the blood brain barrier such that the antibody reaches neuronal tissue

 

So, closing the BBB is important to stopping the auto-antibodies from interacting w/ the brain.

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I just feel like trying all these abx--none of which seem to be helping, for a case that has been going on for likely a few years, with the really horrible tics starting this summer (not after strep) likely from a virus or staph, not strep....like maybe we're chasing down the wrong villian here in all this??? Maybe it's NOT the bacteria "lurking" anymore, but the autoimmune issue going on. Maybe with pandas, if you've eradicated the bacteria and still aren't improving, it's because the autoantibodies are attacking the basal ganglion (like our 4000 antiD1) that an antibiotic isn't going to touch. How do we get rid of those bad boys---which are across the blood brain barrier, if I understand correctly? I admit, I truly don't know much about autoimmune diseases, especially ones that only zero in on the brain, but I "thought" that they didn't just "right themselves" and go away with eradication of the disease that caused it???? I'm sort of thinking aloud, asking, anything here.

 

Just very very confused, after having a very pandas-literate doc say that it's unlikely pandas if abx arent working. Maybe if it weren't "pandas" but pitand, we could say abx aren't really diagnostic like that.

 

Ugh...sigh.. :(

 

 

EljoMom - it is so frustrating to try to address this disease with the lack of information available. The immune system is SO complex, and the fact that our children have been suffering for years only complicates matters further.

 

I can only tell you what I cling to when I am trying to make sense out of all of this -

 

When we first went to see Dr. B last year he told us that, in my son's case, we needed to:

 

1. Find and remove any infections (in our case, this was done through blood work and a sinus CT scan)

2. Look at my son's immune status (IGG and IGA levels and s. pneumonaie levels), along with levels of immune complement (C3D). (in our case, this showed some IGG deficiencies and IGA deficiencies, along with very elevated C3D levels)

3. Try a steroid burst to see if there was a reduction in symptoms - indicating an autoimmune response (in our case, we have done this twice. Both times we saw a reduction in PANDAS symptoms. The first time the reduction was temporary because he had a type of cyst in his sinuses and once the cyst was removed he did better; the second time the reduction was longer-lasting and continues to have improvement since the steroid burst ended 3 weeks ago)

4. Test and treat allergies (we are working on this now)

5. Consider IVIG if appropriate (we are planning on doing this once allergies are tested and treated due to low IGG).

 

I don't know if that helps you or not. I am sure every doctor has a different plan of attack and I am sure the plan of attack is different from child to child... but I do not think that changing antibiotics over and over again will help all children. I am sure there are some families on this forum who have been helped greatly by antibiotics alone. We are well-past that point as my son has been battling this for most of his 13 years of life. I think at this point his immune system is so out of whack it does not know when to use antibodies to react to foreign antigens or to his own tissue, when to make an allergy, or when to bundle everything up into an immune complement. It seems that every form of immune response is not working properly for him.

 

I will continue to keep him on antibiotics for a while -the more I can calm down his immune system the better... but I know that antibiotics alone will not do it for us.

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I strongly support kimballot's comments here. Exactly right.

 

There is little disagreement that there is a group of kids who have sudden onset debilitating OCD accompanied with concurrent separation anxiety and regressive behavior. These clincal symptoms are pronounced and distinct.

 

There is considerable debate from certain neurologists at Johns Hopkins (and somewhat at Yale) whether kids with tics must also have sudden onset and debilitating OCD to be considered part of the "syndrome".

 

The real debate is then once you've isolated the symptoms, how do you treat the symptoms. If the sydrome has a different cause then treating it the same as traditional OCD doesn't make sense. It's sort of someone complaining of heart pains and in one case is having a heart attack and in another they have a sword impaled through their chest. You probably want to treat these differently.

 

It took over 100 years for people to recognize that Sydenham Chorea was likely caused by antibodies to an untreated streptococcal infection. It would be practically impossible to "discover" this today because any clincial trial would have to treat any strep infection found (and therefore there would be no untreated strep infection and thus no 1st time event SC).

 

At this point, the best evidence we've got is that PANDAS is caused by 3 things for this specific group of kids with sudden onset OCD:

  1. an untreated GABHS infection that triggers the creation of an anti-host antibody that cross-reacts with neuronal tissue
  2. a failure of the immune system to suppress the anti-host antibody
  3. a breech of the blood brain barrier that allows the antibody to reach neuronal tissue

 

After the first infection, it looks like other infections can trigger the antibody response. It is not clear whether this is just superantigen T-cell recruitment or that the B-cell is easily triggered once activated.

 

The breech of the blood brain barrier seems to be the key item that defines the effectiveness of treatment. The half-life of the antibodies seems to be around 21 days. Rapid relief is typically explained by assuming the BBB is closed. This is a plausible explanation for why IVIG and Pred both have been seen as effective. Antibiotics can affect the antibody creation and can break the cycle of antibody response -- but in and of themselves, the antibiotics don't tend to close the BBB -- this means that it is often 3 weeks before symptoms improve. I realize folks want to see quick responses (like overnight) and frankly that's very unlikely without the BBB closing.

 

Long response, but hope it helps.

 

Buster

 

 

 

 

When we first went to see Dr. B last year he told us that, in my son's case, we needed to:

 

1. Find and remove any infections (in our case, this was done through blood work and a sinus CT scan)

2. Look at my son's immune status (IGG and IGA levels and s. pneumonaie levels), along with levels of immune complement (C3D). (in our case, this showed some IGG deficiencies and IGA deficiencies, along with very elevated C3D levels)

3. Try a steroid burst to see if there was a reduction in symptoms - indicating an autoimmune response (in our case, we have done this twice. Both times we saw a reduction in PANDAS symptoms. The first time the reduction was temporary because he had a type of cyst in his sinuses and once the cyst was removed he did better; the second time the reduction was longer-lasting and continues to have improvement since the steroid burst ended 3 weeks ago)

4. Test and treat allergies (we are working on this now)

5. Consider IVIG if appropriate (we are planning on doing this once allergies are tested and treated due to low IGG).

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Thanks Buster and kimballot for all the insight, and patient explanations. Of course, I now have some more questions:) Hope that's okay....

 

I thought the BBB didn't stay open for long periods of time---just during illness (fevers), extreme stress, etc. but then it closes back up. So if infection has been eradicated, I assume it is now closed again?

 

I wonder if those of us who were clueless about PANDAS and did NOT treat strep over the years -- thus insult after insult--even after strep has cleared (my ped. says strep will clear on it's own, but abx shorten the duration and lessen possibility of RF), there has been cumulative damage? Or that the immune system is just out of whack? But then why would my dd have normal IgG, etc.?

 

Also, my father in lawa had Rheumatic Fever as a child, which damaged his heart in the long term. He had a massive heart attack at 41, was then disabled, and had another, which killed him, at 44. So, I do wonder if, since this pandas is very similar in mechanism to RF (which causes long term damage), maybe we are just looking at irreparable damage to the basal ganglion, rather than the heart????

 

One more ? --- do abx and Motrin cross the BBB? Because isn't the inflammation across the BBB in the basal ganglion? If that's the case, and abx and motrin don't cross BBB, then are they really helping with inflammation in the b.g.????

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Thanks Buster and kimballot for all the insight, and patient explanations. Of course, I now have some more questions:) Hope that's okay....

 

I thought the BBB didn't stay open for long periods of time---just during illness (fevers), extreme stress, etc. but then it closes back up. So if infection has been eradicated, I assume it is now closed again?

 

I wonder if those of us who were clueless about PANDAS and did NOT treat strep over the years -- thus insult after insult--even after strep has cleared (my ped. says strep will clear on it's own, but abx shorten the duration and lessen possibility of RF), there has been cumulative damage? Or that the immune system is just out of whack? But then why would my dd have normal IgG, etc.?

 

Also, my father in lawa had Rheumatic Fever as a child, which damaged his heart in the long term. He had a massive heart attack at 41, was then disabled, and had another, which killed him, at 44. So, I do wonder if, since this pandas is very similar in mechanism to RF (which causes long term damage), maybe we are just looking at irreparable damage to the basal ganglion, rather than the heart????

 

One more ? --- do abx and Motrin cross the BBB? Because isn't the inflammation across the BBB in the basal ganglion? If that's the case, and abx and motrin don't cross BBB, then are they really helping with inflammation in the b.g.????

 

Eljomom - These are such great questions and I hope that someone is able to answer them. I really have the same questions - and will tell you what I have come to "understand" after reading lots of posts.

 

I've asked the question about the breach in the BBB after infection before. My understanding is that there are several immune reactions that can cause inflammation - not just infection. For example, allergy can cause inflammation. Also, immune system complement can result in inflammation... so I think the very simple [infection ->inflammation -> Breach in BBB -> Antibodies affect basal ganglia -> Antibiotics hasten end of infection -> BBB closes -> symptoms end sequence] that we would like to believe exists is just NOT that simple for many children (Imagine that - I just called that whole reaction simple!).

 

 

I think for my son, who has been fighting this for so long, the reactions are very different. I posted a link to some online information on the immune system. You may want to check it out at http://www.niaid.nih.gov/topics/immuneSystem/Documents/theimmunesystem.pdf I just went back to it and put in a "find" for the word "inflammation". There are several different immune system responses that result in inflammation, including the actual autoimmune response itself resulting in inflammation. I think that is why sometimes something more than antibiotics is needed to end the cycle. I know Momto2Pandas has posted questions and information about complement and cytokines in the past. Perhaps she has some ideas about this in addition to Buster or others.

 

Also - remember that antibodies come from B cells, which have "memory". When they see the antigen again they make antibodies again. No one has been able to tell me if B cells can cross the blood brain barrier during inflammation and recognize the basal ganglia cells as an antigen -> thereby producing antibodies even when there is no infection in the body. This might happen, for example, if there were inflammation with allergy. Last time I asked Buster about this he said we didn't have any studies of this yet. Maybe he has new information now.

 

 

Regarding the question of long-term, irreversible basal ganglia problems... that is certainly my greatest fear. My understanding is that the antibodies do not destroy or damage the basal gangila cells - they just alter the chemicals and eventually the neurotransmitters produced by the cells. The neurotransmitters are used to allow one cell to communicate with another across a synpse (gap) between cells. In general, we know that the more times a synapse is used, the stronger the synapse becomes and the more likely we are to use it (that is what makes us learn new things with practice). I wonder if we will find that kids who have had many exacerbations for long periods of time need some "retraining" once the immune system is functional to get different synapses to fire. I think (just my thoughts) that we will find a strong role for CBT / ERP and other types of psychotherapies and physical and occupational therapies once we really understand how to halt the reaction. I think this is several years down the road, though.

Edited by kimballot

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Kimballot said

I wonder if we will find that kids who have had many exacerbations for long periods of time need some "retraining" once the immune system is functional to get different synapses to fire.

 

This is what I think. My daughter has had this a very, very long time- since infancy. We do not see a resolution of OCD and fixations w/ treatment because there is very little else that her brain has practiced or learned to do...those are her pathways and it presents as autism...and this is also why I think PANDAS can cause autism. But, the good news is...w/ time and the proper help, I think we can still bring about some normal development...but just CBT/ERP isn't enough-we have to find a way to stimulate the development of normal relational pathways, since they did not develop.

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Also, my father in lawa had Rheumatic Fever as a child, which damaged his heart in the long term. He had a massive heart attack at 41, was then disabled, and had another, which killed him, at 44. So, I do wonder if, since this pandas is very similar in mechanism to RF (which causes long term damage), maybe we are just looking at irreparable damage to the basal ganglion, rather than the heart????

It is very likely that PANDAS, SC and Acute Rheumatic Fever are all related. My best guess is that there are four or more distinct antibodies that are very similar. One targets heart muscle and produces carditis. One targets joints and produces arthritis, one targets tubulin and affects motor function, one targets D1/D2 receptors and affects neuronal signalling.

 

Maybe it's not that simple. The good news is that MRIs don't seem to indicate any grey or white matter lesions or any demylination (unlike ADEM). I've been trying to find prognosis reports on patients with Sydenham Chorea and look at their long term outlook. Certainly the motor abnormalities go away (with some recurrence during pregnancy). It is unclear about the OCD manifestations.

 

I also see that OCD symptoms sometimes precede motor abnormalities in SC and sometimes follow (by as much as 2 months). In both cases only after untreated GABHS infection. This makes me wonder if the antibodies are distinct between the OCD manifestation and the SC motor abnormality. My guess is this is why Cunningham is checking for multiple cross-reactivities.

 

One more ? --- do abx and Motrin cross the BBB? Because isn't the inflammation across the BBB in the basal ganglion? If that's the case, and abx and motrin don't cross BBB, then are they really helping with inflammation in the b.g.????

 

Well, little is really known here. There was a small study looking at permeability and found that motrin does seem to cross the BBB. The actual mechanism is unknown. http://www.scipharm.at/download.asp?id=452

 

With respect to antibiotics, antibiotics won't do anything to the antibodies (per se). So one of the effects may either be to help control reinfection (i.e., minimize response of inflammatory cytokines by getting rid of the bacteria sooner) or shifting the immune response to a less inflammatory response (i.e., what macrolides are thought to do).

 

 

No one has been able to tell me if B cells can cross the blood brain barrier during inflammation and recognize the basal ganglia cells as an antigen -> thereby producing antibodies even when there is no infection in the body. This might happen, for example, if there were inflammation with allergy. Last time I asked Buster about this he said we didn't have any studies of this yet. Maybe he has new information now.

 

Well, here's the most recent paper I've found: http://www.jneurovirol.com/pdf/5(6)/570-578.pdf

 

It looks like B cells can cross the BBB under certain circumstances. I thought they'd be too big to get across but it does look possible. I asked Cunningham and she thought antibody crossing far more likely than a B cell getting across and running into a APC on the other side. My bias about the B cell was that it might explain the burst of symptoms. Still not sure what to make of the science here, but it does look like B-cells cross.

 

 

Regarding the question of long-term, irreversible basal ganglia problems... that is certainly my greatest fear.

Mine too. What we've observed is that we have to retrain some skills that were lost/not learned during the exacerbation. As far as I can tell from the literature in SC or PANDAS/PITAND cases, the kids recover. I'm ever watchful for the papers here though.

 

I think (just my thoughts) that we will find a strong role for CBT / ERP and other types of psychotherapies and physical and occupational therapies once we really understand how to halt the reaction. I think this is several years down the road, though.

I found CBT extremely helpful for me as a parent because it helped at least me learn coping skills. In an extreme exacerbation, it was useless. In mild ones it was helpful. CBT really requires insight before it can be effective.

 

 

Best regards,

 

Buster

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Thanks again for the info---I'm glad my questions aren't totally "off", and that others have had them too.

 

I am not understanding what "complement" is? Also, as for allergy being autoimmune, would that also go for "sensitivities" (not IgE mediated, but IgG, etc.?)

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There is considerable debate from certain neurologists at Johns Hopkins (and somewhat at Yale) whether kids with tics must also have sudden onset and debilitating OCD to be considered part of the "syndrome". Edited by P.Mom

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Hi P.Mom,

 

I agree with you. Absolutely kids with only tics can have PANDAS or PITAND.

 

If we look through the literature, the kids basically split into five categories:

  1. those with sudden onset OCD and simultaneous separation anxiety/urinary frequency or other symptoms
  2. those with sudden onset OCD and a tic disorder
  3. those with sudden onset separation anxiety/urinary frequency with or without a tic disorder
  4. those with a tic disorder and no other symptoms (who improve on antibiotics or other immuno-modulating therapies)
  5. those with a tic disorder who don't fit the other categories

 

There is significant misunderstanding by doctors about all 5 categories, but if we look at who is stirring up controversy, it is a specific set of neurologists who are studying #5 -- those with a long-term tic disorder. Unfortunately their inability to repeat experiments on patients in #4 or #5 is clouding all the other categories.

 

If we look at the studies done by Kurlan and Singer, they are on patients in #5. The patients were drawn from the Tourette's study group with older children who had consistent tics for > 3 years with no remission > 3 consecutive months. In their 2 year longitudinal study in 2008, none of the greater than 80 subjects had any variance in OCD symptoms.

 

While the sudden onset OCD or OC behavior seems to separate the first 3 categories, I don't think the "controversy" will end until the research community comes to agreement on how to separate category #4 and category #5.

 

Best regards,

 

Buster

 

 

There is considerable debate from certain neurologists at Johns Hopkins (and somewhat at Yale) whether kids with tics must also have sudden onset and debilitating OCD to be considered part of the "syndrome".

 

 

 

As always, thanks Buster for all the information. I would like to respond to this quote because I feel it is necessary for parents to know that the kids do not, in order to be considered PANDAS/PITANDS, need to have OCD, etc. I understand there is much debate with the docs over this. However, there is much debate about the existance of PANDAS and we all know it exists. (regardless of what some docs may say)

 

Edited by Buster

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P.Mom---thank you for validating what we see!! I wish I'd had my daughter tested/treated when it all started (well, wish I'd known about pandas/pitands when it all started!) so maybe we could have seen the benefit from quick treatment. Who is your pandas doc again??

 

 

There is considerable debate from certain neurologists at Johns Hopkins (and somewhat at Yale) whether kids with tics must also have sudden onset and debilitating OCD to be considered part of the "syndrome".

 

 

 

As always, thanks Buster for all the information. I would like to respond to this quote because I feel it is necessary for parents to know that the kids do not, in order to be considered PANDAS/PITANDS, need to have OCD, etc. I understand there is much debate with the docs over this. However, there is much debate about the existance of PANDAS and we all know it exists. (regardless of what some docs may say)

 

As a Mom who witnessed it first hand...yes, you for sure can have a child who only presents with tics be part of the PANDAS/PITANDS syndrome. Both my sons presented after the same, documented strep infection.(both from zero to 10 in a day) Two very different presentations..younger with ocd, tics, anxiety etc....the older with just sudden onset multiple motor tics, no OCD. He was treated rapidly with antibiotics (within 3 days of onset)...and his tics went from 10 to zero (well, lets say 10 to 1) in 48 hrs. There is no doctor on the face of the planet that can tell me my ticcer PANDAS/PITANDS son is not such. I am sure you know...when you witness it first hand...there is no debate.

 

 

Whay can't I work the "quote" thing right? :blink:

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Buster--we are the ocd, hyper, sep. anxiety that---followed by adding a coulple tics, to a sudden explosion of tics....but it's been 6 months since the explosion with no lessening of tics. Does this mean not likely pandas/pitands? because no lessening? or that perhaps whatever started it is still going wacky auto-immune wise? Her CamK was done over 3 months after it started, and it was 168.

 

Hi P.Mom,

 

I agree with you. Absolutely kids with only tics can have PANDAS or PITAND.

 

If we look through the literature, the kids basically split into five categories:

  1. those with sudden onset OCD and simultaneous separation anxiety/urinary frequency or other symptoms
  2. those with sudden onset OCD and a tic disorder
  3. those with sudden onset separation anxiety/urinary frequency with or without a tic disorder
  4. those with a tic disorder and no other symptoms (who improve on antibiotics or other immuno-modulating therapies)
  5. those with a tic disorder who don't fit the other categories

 

There is significant misunderstanding by doctors about all 5 categories, but if we look at who is stirring up controversy, it is a specific set of neurologists who are studying #5 -- those with a long-term tic disorder. Unfortunately their inability to repeat experiments on patients in #4 or #5 is clouding all the other categories.

 

If we look at the studies done by Kurlan and Singer, they are on patients in #5. The patients were drawn from the Tourette's study group with older children who had consistent tics for > 3 years with no remission > 3 consecutive months. In their 2 year longitudinal study in 2008, none of the greater than 80 subjects had any variance in OCD symptoms.

 

While the sudden onset OCD or OC behavior seems to separate the first 3 categories, I don't think the "controversy" will end until the research community comes to agreement on how to separate category #4 and category #5.

 

Best regards,

 

Buster

 

 

There is considerable debate from certain neurologists at Johns Hopkins (and somewhat at Yale) whether kids with tics must also have sudden onset and debilitating OCD to be considered part of the "syndrome".

 

 

 

As always, thanks Buster for all the information. I would like to respond to this quote because I feel it is necessary for parents to know that the kids do not, in order to be considered PANDAS/PITANDS, need to have OCD, etc. I understand there is much debate with the docs over this. However, there is much debate about the existance of PANDAS and we all know it exists. (regardless of what some docs may say)

 

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