Cytokines and the blood brain barrier

[rjayne]

My daughter has a rare neurological/neuropsychiatric autoimmune disease called opsoclonus myoclonus syndrome ( OMS) that is very similar in symptoms and underlying cause as PANDAS. We have done years of steroids, years of monthly ivig, and 7 rounds of chemotherapy in attempt to "deplete and reset" the immune system. Despite treatment, my daughter still suffers from extreme behavioral issues (especially before illness and if there is an infection present) cognitive issues, and intention tremor. In retrospect, the treatments (though they do help many) have been nothing but a band aid. I personally believe that cytokines and chronic inflammation leading to blood brain barrier permeability are responsible for allowing the immune system access to the brain and for the ongoing assault.

My questions to you all are: are cytokines being investigated in PANDAS research? I've done some googling, but haven't found any leads. Is permeability of the bbb considered the big problem as opposed to the defective anti-bodies themselves? Outside of ibuprofen and steroids, have any of you had any luck reducing cytokines activity/ bbb permeability. Do you find your kids suffer from flares when they have an infection or illness outside of strep?

Thank you!

Rebecca

[LaurenK]

My daughter has a rare neurological/neuropsychiatric autoimmune disease called opsoclonus myoclonus syndrome ( OMS) that is very similar in symptoms and underlying cause as PANDAS. We have done years of steroids, years of monthly ivig, and 7 rounds of chemotherapy in attempt to "deplete and reset" the immune system. Despite treatment, my daughter still suffers from extreme behavioral issues (especially before illness and if there is an infection present) cognitive issues, and intention tremor. In retrospect, the treatments (though they do help many) have been nothing but a band aid. I personally believe that cytokines and chronic inflammation leading to blood brain barrier permeability are responsible for allowing the immune system access to the brain and for the ongoing assault.

My questions to you all are: are cytokines being investigated in PANDAS research? I've done some googling, but haven't found any leads. Is permeability of the bbb considered the big problem as opposed to the defective anti-bodies themselves? Outside of ibuprofen and steroids, have any of you had any luck reducing cytokines activity/ bbb permeability. Do you find your kids suffer from flares when they have an infection or illness outside of strep?

Thank you!

Rebecca

 

 

Could you explain a little bit more about the condition? Is the damage from the condition permanent? Did any of the "bandaids" work? Ironically I was just reading a post from you not that long ago about low dose cellcept. Did that become ineffective? I'm curious to know. As far as cytokines, we were told that il17-a might be a problem.

[eljomom]

holy cow---soooo interested in this. I spent most of yesterday going over some of my zillions of scribbled questions and notes about pandas/pans/pitand/cans.....and what you pose is really what I have come up with too. The cytokines (which aren't an abnormal thing in and of themselves, I dont think, but the BBB being opened because of them is the issues. But then what. I fear the ivig, etc are a band-aid too. I am curious who diagnosed your daughters illness? Have you asked them about cytokines, and BBB?

We had a really bad time after dd had a deep skin avulsion at the end of the summer. Within 4 days of it, her tics were through the roof for close to 2 weeks before going downward toward her normal baseline of tics. I know that an injury and immune response/inflammation (from healing) can cause pro-inflammatory cytokines, so to me, this was diagnostic in and of itself.

[rjayne]

Initially, therapy worked incredibly well. First and second rounds of chemotherapy were very effective with behavior. Rituxan only lasts at most 6 months, then b cells begin to regenerate. Treating with rituxan repeatedly can have serious consequences, and the same goes for ivig. The Cellcept did help for a time. We are now discontinuing all immunosupressive therapies to see what happens. Basically by May we should know whether what we are dealing with now is active disease, permanent brain injury due to autoimmune disease, or a combo of the two. My questions to your group may or may not apply to my daughter but answers to them may help children dx'd with OMS and PANDAS in the future. I am really interested in the biological difference between kids who have a mono phasic course of disease and those who are chronic and the ability to potentially identify the difference at onset and treat the root cause.

[eljomom]

LaurenK--I PM'd you

[rjayne]

holy cow---soooo interested in this. I spent most of yesterday going over some of my zillions of scribbled questions and notes about pandas/pans/pitand/cans.....and what you pose is really what I have come up with too. The cytokines (which aren't an abnormal thing in and of themselves, I dont think, but the BBB being opened because of them is the issues. But then what. I fear the ivig, etc are a band-aid too. I am curious who diagnosed your daughters illness? Have you asked them about cytokines, and BBB?

We had a really bad time after dd had a deep skin avulsion at the end of the summer. Within 4 days of it, her tics were through the roof for close to 2 weeks before going downward toward her normal baseline of tics. I know that an injury and immune response/inflammation (from healing) can cause pro-inflammatory cytokines, so to me, this was diagnostic in and of itself.

She was dx'd by a brilliant local neurologist in 2005. She was treated and followed for several years by Dr. Michael Pranzatelli of SIU med in Springfield, IL and was one of the original participants in the clinical trial which established approval for the use of rituxan in OMS. He has done some work with PANDAS, but I have had trouble finding publications. Mainly his work is with movement disorders. He is currently working on finding the cytokines responsible for inflammation with OMS and finding or developing drugs to block them. We haven't seen him in years, he is a research physician and has little interest in treating patients that do not fit into current research.

It is commonly accepted that extreme behavioral/psych issues are caused by OMS and abate with treatment-obviously there are some exceptional cases, my daughter being one of them. It is also not uncommon for other autoimmune diseases (lupus to name one) that can have neuropsychiatric symptoms because there has been a breech in the bbb. It just blows my mind that there is so much question and speculation with PANDAS. I'm sure you all feel the same way.

The root cause of OMS is considered generally to be neuroblastoma, so we don't have a virus (with a few rare exceptions, strep being one) to blame it on and then assume is active when there is a flare. Any immune activity for us = flare, also widely accepted in the OMS world.

[philamom]

I think Dr. T is researching the role of cytokines & BBB permeability.

[rjayne]

I think Dr. T is researching the role of cytokines & BBB permeability.

I've thinking about sending him an email to ask his opinion. Is there a thread or an article in which he discusses this?

[philamom]

I think Dr. T is researching the role of cytokines & BBB permeability.

I've thinking about sending him an email to ask his opinion. Is there a thread or an article in which he discusses this?

Hopefully, others will chime in. I just remember it being addressed here. Maybe fcefxer? I also thinks he talks about in the videos that were just posted...not positive though. I'll bump them up.

Edited January 9, 2012 by philamom

[LNN]

rjayne - I sent you a message with some info. Look in the upper right corner of the screen - your login name appears in a drop-down box. From that box you can access your messages.

 

From my perspective, much research has unfortunately been focused on the "controversy" of proving Pandas existence. The second tier of funding has focused on treatments in the hopes of getting insurance to cover IVIG. This has left little funding for figuring out how to close the BBB to prevent the horse from getting out of the barn. Madeleine Cunningham at Univ of Oklahoma, Mady Hornig at Columbia and Karen Newell Rogers at Texas A&M may be your best hopes for literature on the BBB and cytokines in terms of infection and neuropsych symptoms.

[LaurenK]

I'm lost though, how can your daughters immune system be causing these symptoms if she is on immunosuppressive drugs? Don't they in fact suppress the bad reaction? And taking her off of them in a flare, wouldn't that only cause the symptoms to get worse?

[rjayne]

I'm lost though, how can your daughters immune system be causing these symptoms if she is on immunosuppressive drugs? Don't they in fact suppress the bad reaction? And taking her off of them in a flare, wouldn't that only cause the symptoms to get worse?

There was a time when there was a direct correlation between symptom reduction and treatment. In the past year or so it has become less clear as to whether or not treatment is helping. It could be that a "normal" population of b cells cause problems for my daughter as a result of bbb permeability. B cells begin to regenerate about 3 months after treatment. We can only treat with chemotherapy every 6 months, at the most. Her symptoms at this point may also be caused by permanent brain injury from years of attack. We will not know what is really going on until we end all immunosuppression and see what happens. If she stays the same, then we'll be stuck with brain injury. If she worsens, we'll have to return to some form of immunosuppression. Does that make sense? It's totally confusing I know.

[LaurenK]

I'm lost though, how can your daughters immune system be causing these symptoms if she is on immunosuppressive drugs? Don't they in fact suppress the bad reaction? And taking her off of them in a flare, wouldn't that only cause the symptoms to get worse?

There was a time when there was a direct correlation between symptom reduction and treatment. In the past year or so it has become less clear as to whether or not treatment is helping. It could be that a "normal" population of b cells cause problems for my daughter as a result of bbb permeability. B cells begin to regenerate about 3 months after treatment. We can only treat with chemotherapy every 6 months, at the most. Her symptoms at this point may also be caused by permanent brain injury from years of attack. We will not know what is really going on until we end all immunosuppression and see what happens. If she stays the same, then we'll be stuck with brain injury. If she worsens, we'll have to return to some form of immunosuppression. Does that make sense? It's totally confusing I know.

 

 

even when you "reset" the immune system the b cells come back??

[sptcmom]

My daughter has a rare neurological/neuropsychiatric autoimmune disease called opsoclonus myoclonus syndrome ( OMS) that is very similar in symptoms and underlying cause as PANDAS. We have done years of steroids, years of monthly ivig, and 7 rounds of chemotherapy in attempt to "deplete and reset" the immune system. Despite treatment, my daughter still suffers from extreme behavioral issues (especially before illness and if there is an infection present) cognitive issues, and intention tremor. In retrospect, the treatments (though they do help many) have been nothing but a band aid. I personally believe that cytokines and chronic inflammation leading to blood brain barrier permeability are responsible for allowing the immune system access to the brain and for the ongoing assault.

My questions to you all are: are cytokines being investigated in PANDAS research? I've done some googling, but haven't found any leads. Is permeability of the bbb considered the big problem as opposed to the defective anti-bodies themselves? Outside of ibuprofen and steroids, have any of you had any luck reducing cytokines activity/ bbb permeability. Do you find your kids suffer from flares when they have an infection or illness outside of strep?

Thank you!

Rebecca

 

Rebecca I am an alternative medicine practitioner and have a child with PANDAS and lyme. You should look into GcMAF. www.gcmaf.eu and Stem cell therapy.

Without a good/normal immune response, its extremely hard to find an answer to regulate the BBB. Innate immunity can only be enhanced but adaptive immunity can be gained if the precursor factors are intact. Another imp aspect as many alternative practitioners look at is very often and almost always in my practice leaky gut = leaky brain and its not just the DAN! protocol Im referring to. There are so many critical neurotransmitter biochemical processes happening in the gut.Im pretty sure you must already read and explored the gut connection by now. Weak macrophages keep searching for the antigen and when they find it they can't annihilate so the search continues, molecular mimicry happens and wreaks havoc. GcMAF is helping with all of this and adequate nutritional support will help build the neuronal connections again.

We are currently getting ready to start GcMAF with DS. DS's immune system is currently responsive, awake, alert and producing IgM which is getting converted to IgG at the right time and his body is able to contain new infections. He is getting fevers again and we are very happy with this progress.However the neuropathy in his legs is hard to eradicate and I wish to put an end to the autoimmunity, hence the GcMAF consideration.

We are using a heavy duty integrated protocol to get rid of inflammation (its working), an aggressive approach to put lyme and Co into remission using the Bionic 880 biophoton therapy (its working very well) and repairing the inflammation induced damage with the Bemer 3000 protocols and they all seem to be working great by God's grace.IVIG in 2010 was a band aid but very helpful. No band aids so far with current protocol. Keeping my fingers crossed.

GcMAF seems to be the answer for many children and adults alike and stem cells are becoming the final step after GcMAF.

Thats been my experience.

Edited January 9, 2012 by sptcmom

[T_Mom]

Rjayne--Your post has brought up more questions then answers -- but THANK YOU for posting.

 

The possible connection between OMS and PANS is so interesting.

 

I was fascinated to read that a neuroblastoma tumor is not necessary for this diagnosis--and in fact this AUTOIMMUNE reaction can be caused by a virus.

 

OMS (the virus caused type, with no tumor present) LOOKS like Ps, including:

references to emotional issues

possible explosive rage and personality changes

tremor issues (many Ps children have chorea-like movements, etc.)

learning decline, focus problems

fine motor issues (writing being most evident)

can be repetitively triggered by a virus

may result in the child being mute, immobile, and have eating issues!!!

if you look at the blood work suggested by the leading expert on this childhood illness it looks like a PANDAS/PITAND list.

 

GOOD HEAVENS...and typical treatments include: steroids, IVIG, and at times, plasmapheresis...(WHAT the heck are we dealing with here...)

(I only wonder why the doctors we carried our d to originally didn't suggest a lumbar puncture to check for spinal infections.)

 

Dr. Pranzatelli looks like an absolute genius -- who cares deeply and has obviously devoted his career to help. His website is full of information which is incredibly parallel to PANDAS (or more likely PITAND)

 

www.omsusa.org

Edited January 10, 2012 by T.Mom