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microglial activation


bws
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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?

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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?

rjayne,

We have PM'd before about OMS. This is so interesting, how you explain your view on this. I agree with you, though I know WAY less than you do. Our LLMD explained our child's illness (psych & neuro) in pretty much exactly the way you just did.

I am really interested in the genetic testing. Can you post or PM me on what testing specifically? I have multiple children affected (as lots here do!) and know there must be a genetic link. We have nt had any done yet (barring HLA b27) which actually was done pre-PANDAS for arthritis issues- as we have a family hx of ankylosing spondylitis, crohns & RA (positive for one daughter). the other was checked post-PANDAS onset and was neg .

I think you are talking about other testing. Can you elaborate?

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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.

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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/

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Read the links, very interesting indeed. Just curious ..... how many of us family members of PANDA like children have extended family member with brain tumors? I have 2, one currently with stage IV glioblastoma.

 

 

i don't have the references and it's really just on the edge of my brain. . . but i recall reading something about a link between higher than average incidence of toxoplasma gondii infection in autopsies of patients with glioblastoma.

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