rjayne

Thanks! Any ideas on where Cunningham or Swedo stand on the genetic thing?

I read on this forum a few months ago that there were some genetic mutations that have been identified in PANS patients. I think I also remember reading that the exact mutations haven't been made public, because the research hasn't been published yet. I'm looking for the physician that made these discoveries. I have a child who has opsoclonus myoclonus syndrome. OMS and PANDAS are shockingly similar in onset and symptoms, but OMS is significantly more severe in terms of physical, motor symptoms, and has the presence of neuroblastoma in the mix. We're in the process of having my daughter's genome sequenced and I'm interested in comparing any abnormalities that she has to those of children with PANDAS. Thanks in advance for your help. I know I could have scoured the site for this info, but I'm having trouble searching the forum. Best, Rebecca

In terms of family history, it's important to look at history of mental illness and history of inflammatory autoimmune disease. MS, Parkinson's Alzheimer's, rheumatoid arthritis, lupus, etc. The cancer aspect is specific in oms, because of the movement disorder that ensues after neuroinflmmation begins and the BBB becomes permeable flooding the CNS with anti-bodies to neuroblastoma. Neuroblastoma is a tumor of neural crest cells in origin, but becomes a tumor when in fetal developement, the cells migrate somewhere else in the body and grow. Most neuroblastoma are found in the abdomen or trunk. Cancer is most likely not an issue in PANDAS. My dd's family history is rampant with mental illness (bi-polar, anxiety, depression) and inflammatory autoimmune disease (behcet's, lupus, RA, Alzheimer's). I read a fantastic chart of these specific issues in families of children with PANDAS somewhere on the interwebs. I'm sure you guys have seen it, showing a very high incidence of mental illness, childhood illness, and autoimmune disease. Here's the link to the chart. http://pandasnetwork.org/family-history-table/

PowPow, I wish I could elaborate. Genetics is totally new to me, I've spent the last several years focussing on the acquired immune system and only recently began to learn about the innate immune system. Dr. Maris at CHOP seems to think that in OMS, there is a problem with the ALK gene. He spoke at the international OMS workshop in London a few weeks ago and I was only able to get choppy notes from a friend explaining his theory. As I know more, I will post. I have been following the group Stop Calling it Autism and their clinical trial using ibuprofen, ivig, probiotics, anti-virals, anti-fungals, and modified diet to decrease/inhibit microglial activation in children with regressive autism. They just won first prize for research funding from Autism Speaks and while I'm not sure how their protocol induces permanent change in microglial activation, I think what they are doing is pretty interesting. May be worth a look, as I know ibuprofen alone has been really helpful for us and I've read here that it helps children with PANDAS as well.

So glad to see you posted this. My opinion may be controversial, but here goes: Microglial activation is the root cause of chronic neuroinflammation. It is my understanding that it is the result of a genetic defect activated by an environmental trigger ( virus, toxin, bacteria, etc). Neuroinflammation is thought to be the cause of many neurological autoimmune diseases ( ms, Parkinson's, Alzheimer's, etc) as well as schizophrenia, autism, and other mental illnesses. Not only can neuroinflammation cause OCD, anxiety, problems with movement, cognitive dysfunction, but it can also cause permeability of the blood brain barrier allowing lymphocytes into the brain which as we know, causes serious issues. My daughter was diagnosed with opsoclonus myoclonus syndrome in 2005. The behavioral/psych aspects of the disease mirror PANDAS, the dx is made based on the presence of specific eye movements, ataxia, and full-body jerking and tremor. Until very recently, it was thought that the disease was all about lymphocytes in the CSF, and if those were eliminated with immunsupression (steroids, chemotherapy, and ivig) and the tumor was removed (OMS is paraneoplastic), then the child would be cured. In a very small number of kids this is true. Most children, suffer from ongoing severe behavioral, cognitive, and fine and gross motor issues that were once considered to be "permanent brain damage". Here's the problem, the chronic symptoms wax and wane with heat, stress, and infection - they are not static. And they occur despite the fact that lymphocytes are no longer detectable in the CSF. My daughter and another patient with OMS (they both see the same neuro) both just had PET scans of their brains to look for damage as well as lumbar punctures looking for lymphocytes to explain both girls' issues. The PET scans came back perfectly normal in function and structure, and the LP's showed no lymphocytes in the CSF (both girls had high b cell counts in the CSF at onset before treatment w/ chemotherapy). The neurologist's answer: chronic neuroinflammation. There is an oncologist at CHOP, Dr. John Maris, who thinks that OMS is caused by a "perfect storm" of three things: genetic defect activated by a virus plus neuroblastoma. So, if the child doesn't have a tumor, do they get PANDAS instead of OMS? Could it be that whether or not the inflammation is caused by the activation of a genetic defect or just a virus or head injury determines whether a child will have only one acute episode or a chronic course? We are in the process of beginning genetic testing to see if in fact my daughter has a genetic abnormality that when activated would cause her chronic neuroinflammation. Has there been any genetic testing of children with chronic PANDAS to determine if there is a common genetic defect?

My daughter did have neuroblastoma but was it missed for a few years, so the diagnosis was made w/o the cancer finding. The diagnosis is based on symptoms alone, the presence of ataxia, myoclonus, and opsoclonus. She also had high b cell and slightly elevated t cell population in her CSF. Also, she went from perfectly normal to jerking, non-verbal, not walking, not sitting, eyes darting and screaming all the time in about three days-very acute onset. Is your child exhibiting ataxia, myoclonus, or opsoclonus?

I have discussed in a few posts on this forum the paraneoplastic neurological disease that my daughter has. It's called opsoclonus myoclonus syndrome and the behavioral symptoms of the disease are nearly identical to what I have read parents here describing. Interestingly enough, not all cases of OMS are caused by neuroblastoma, there are cases that have been caused by gluten intolerance, swine flu, and strep to name a few. Rebecca

I couldn't agree more. My daughter's neuropsychiatric disease/movement disorder, OMS is caused by antibodies to neuroblastoma, the most common childhood cancer. But only 2% of children with neuroblastoma will get OMS, they have the same anti-bodies, but only in the children with OMS, do the anti-bodies make it into the brain. A very small percentage of kids with OMS either spontaneously recover, or get better with treatment of steroids alone or with ivig. The others require chemotherapy and other major immunosuppressants. Of those who chronically relapse, chemo will help until it wears off and the b or t cell population regenerates and goes right back battling the brain. In chronic relapsers, any infection or virus will cause an increase of symptoms or relapse. "Resetting" acquired immunity doesn't happen, unless you eliminate it and introduce a new one with stem cell or bone marrow transplant. I believe the difference in severity and course of oms is directly linked to permeability of the bbb. I also think that factors contributing to permeability are possibly genetic but require a virus or exposure to something environmental to "flip the switch" and lead to an endless cycle of Neuroinflammation. Stress can absolutely cause flares in children with OMS, I have often sent the article posted above to parents whose children came out of "remission" after a seriously stressful event. Here's a link to an article published recently about a newly found protein thought to be a protective mechanism in ms. http://m.facebook.com/l.php?u=http%3A%2F%2Fwww.doctortipster.com%2F7071-scientists-discovered-new-multiple-sclerosis-protective-mechanism.html&h=eAQH0UWJJ Hope this all makes sense, I have flu brain. Thanks for letting me lurk and participate. Rebecca

Is he on any anti-psychotics? High dose Abilify made my dd's WBC low while she was on it. Just a thought.

We're going to do a PET scan of the brain in about two weeks to determine the extent of brain injury. If you'd like I can share the results.

I discussed at length using full dose Cellcept as part of my daughter's treatment for opsoclonus myoclonus. If you search Cellcept, you'll find it. At first it seemed beneficial as it suppresses both b and t cells and we were using it with rituxan which eliminates b cells only. The OMS related behaviors and rages eventually returned and we discontinued after a year. Some parents have had success with it. There has also been success with cytoxan and 6 mp as far as chemotherapy drugs go. Lately Dr's have been prescribing pulse dexamethasone in place of ACTH or daily prednisone and some of those kids are finally approaching remission when other steroids failed. Hope this is helpful.

Thank you all for your input. We're considering lamictal as well because I've read many of you have had success with it. I think we are going to give the Lyrica a shot and later add namenda for the cognitive and memory issues. If the Lyrica is a flop, we'll try the lamictal. Both in very small amounts. This forum has been so helpful in terms of behaviors, meds, and treatment. Thank you all again!

My 9 year old daughter suffers from opsoclonus myoclonus syndrome which in many, many ways is very similar to PANDAS. I believe the root cause, inflammation and bbb permeability to be the same for both. The most severe symptoms of her disease are cognitive/memory issues and crazy, violent, explosive rage attacks which she does not remember. These symptoms wax and wane depending on immune activity. We have tried so many psych meds with very little success. Most meds have made her rage/situational OCD so much worse and she has been hospitalized on several occasions. We have tried: Prozac,lexapro, bus par, trileptal, topamax, depakote, clonidine, proplanolol, Ativan, trazodone, gabapentin, and Klonipin. She is currently on a tiny bit (1mg) of abilify and seroquel, she's better, but I fear for what will happen when she gets the next cold/infection. I spoke with our neurologist today, and he recommended Lyrica and Namenda. He said he had a few kids with neurodegenerative disease and brain injury whose terrible rage greatly improved with Lyrica. He also agreed to try the namenda for her cognitive and memory issues. My questions for you guys: have any of you tried Lyrica with your children for rage/anxiety? Was it helpful? And of those of you who have used Namenda, did you find it affected behavior in any way, positive or negative? Oh, and these meds are being given in addition to ivig, and immune suppressing chemotherapy ( which will be ending soon after 7 years). Thanks!

LLM- of every parent review I read, not one said they were adhering to a lower carb diet. I will certainly keep you updated :-) I had a nice talk with the "inventor" of lutimax and forked out the cash desperately hoping it would help with my daughter who has Opsoclonus myoclonus. The first day, the results were remarkable. She was doing things she had never done before (cleaning her room, helping around the house) cognitive fog lifted and she was using words I'd never heard her use, etc. Things took a drastic turn for the worse two days later. She became manic, couldn't stop talking and the tantrums were much worse than before the lutimax. Such a disappointment, as the published research showed so much promise.

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?? B and t cells will re-generate within a certain amount of time post-treatment. Many children with OMS achieve remission with rituxan leading us to believe either their b cells were "reset" OR the inflammation which caused bbb permeability has subsided and b cells potentially carrying the same defective message can't make it in. We've had six rounds of the stuff and it doesn't appear that rituxan has "reset" the B's.