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.

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.

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

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.

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.

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

We have been doing ivig monthly for opsoclonus myoclonus syndrome (a neurological/neuropsychiatric autoimmune disease with many of the same symptoms as PANDAS) for about 7 years. About two years ago, my daughter began to experience aseptic meningitis about 2-3 days post infusion which would cause extreme migraines, nausea, and vomiting. I began treating prophylactically with ibuprofen (which has since become a part of her daily med routine) right after infusion for 3-4 days and the migraine and nausea went away. We have also used zofran for nausea post chemotherapy ( also used to treat the OMS) and it worked really well. Best of luck!

Steroid psychosis for my daughter mainly consisted of her screaming and raging for most of the time she was awake. Everything and anything made her furious. Giving her a bagel instead of a bowl of cereal, dressing her in the "wrong" clothing.... At the time I found it helpful to google "steroid psychosis". I had found a case study of a few college students admitted to the ER because of steroid induced psychosis and read the descriptions of their behavior. In the end, my daughter's reaction to steroids has been so bad that we avoid it like any drug one would have an allergy to. One thing I forgot to include in one of my entries about treatments is that cellcept is considered a "steroid sparer". Cellcept and other anti-rejection drugs are also used to get people off of steroids if they become intolerable, while still supressing the immune system. Hope this is helpful! Rebecca

I can only speak from experience in dealing with oms, I have no experience in dealing w/ pandas. In oms, immunosuppressants are used to achieve remission and then if all goes well, immunosuppressants are weaned in an attempt to "reset" the immune system. With oms it is thought that if a child can be off of immunosuppressants without any oms symptoms for two years, they are considered "disease free". I believe that this is the methos used for other autoimmune diseases (lupus, RA) as well. There really isn't much info out there about adults still battling oms who became sick as children. We are just now achieving remission after 5 years of trying to get oms under control. Hope this helps.

Oh, where to begin. Side effects. Every drug as I'm sure you all know has it's side effects and risks. My daughter's quality of life has been so severely affected over the past five years that the risks involved in all of the drugs I listed above were outweighed by the potential benefits. Here are the side effects that my daughter experienced.... Steroids: rapid weight gain, her growth was stunted (but she has caught up since steroids were discontinued), precocious puberty, extreme agitation/steroid induced psychosis, and dependency. It took five years to taper off the stuff without inducing relapse. Cytoxan: we did 1 infusion per month for 6 months at a low dose. There were no noticeable side effects (although hair loss and infertility are frequently issues), there was also no noticeable benefit. Rituxan: many positive changes have come with each course of Rituxan. When we do it, we do one infusion 375mg per week for four weeks. The main side effect is death due to anaphylaxis upon the first infusion. This risk decreases with each subsequent infusion. I know, so scary. After rituxan infusions my daughter's oms related behaviors go away. Her motor skills improve. Her cognitive function improves. She is a totally different kid. Ivig: We have been doing IvIG since my daughter was diagnosed in the fall of 2005. Until the fall of this year she had infusions every four weeks at a dose of 1g/kg. Due to relapse this summer, the dose was increased to 2g/kg every three weeks. Side effects have generally been migraine headaches for a couple of days post infusion. As of recently, the IvIG has caused an igA deficiency and we are now switching from Gammunex to Gammaguard. Risks with IvIG are minimal as I understand. Ivig is a blood product so there is always a small chance of contracting a blood born illness. Cellcept: It took close to 6 months for cellcept to reach thereputic levels and start doing it's job. My daughter had two weeks of gi issues while her body adjusted. She gets 2 doses of 600mg 12 hours apart. It's a pain to give because it has to be given one hour before or two hours after eating. But it has been soooooo worth it. Psych meds: My daughter has been on; Prozac, abilify, clonidine, buspar, lexapro, trileptal, and risperdal. All have made her symptoms of opposition, ocd, and extreme anxiety worse. imunosupressants are the only thing that have made a noticeable impact on these behaviors. I hope this answers your questions. Feel free to email me with any more. Best of luck to you all. Rebecca