My views on the Cunningham test

[Dr_Rosario_Trifiletti]

anti-CaMK2 must be marking a common final pathway NEUROimmune reaction - after all these are mostly brain symptoms that we are talking about here.

 

It is very likely NOT infectious etiology specific

 

A positive Cunningham test likely means a neuroimmune etiology, need not be bacterial, need not even be infectious (for example lupus-like illnesses).

 

This is what I find it most useful for:

 

1. Distinguishing non-immunological TS and/or OCD from PANDAS-like illnesses. If this can be verified, we may be able to answer questions like "How many kids with tics and/or OCD really have PANDAS-like illness" - just sample 1000 kids with tics or OCD (all comers) and find out what percentage have positive Cunningham tests. (it can't be that easy ....).

 

2. Get a sense (along with response to steroid burst) if costly immunological interventions like IVIG and/or PEX are likely to work

 

3. Distinguish between PANDAS and SC when there is clinical confusion. I realize there are kids out there (I know of three) that have anti-CaMK2 in the SC range (200's) but do not appear to have SC. I don't routinely do echocardiograms on patients with clear-cut PANDAS any more; but I think if anti-CaMK2 >200 maybe it should be done, as it can be missed. THIS DISTINCTION IS IMPORTANT AS IT CHANGES LONG TERM MANAGEMENT.

 

4. Separate out non-immunological TS and/or OCD from "pure OCD" and "pure TS group" and focus genetic studies on large pedigree "pure OCD" and "pure TS groups". Essentially, try to filter out a major epigenetic factor which confounds linkage analysis. This may be the way to looking at underlying genetics of these disorders, which leads to proteins, which leads to disease pathways, which leads to rational treatment.

 

At the end of the day, in PANDAS patients, there is still the trigger. It is very very important to try to find the trigger(s) as early as possible and try to treat them. Immune treatments will put the disease into remission, but root cause treatments are the only way to a cure.

 

Dr. T

[momaine]

At the end of the day, in PANDAS patients, there is still the trigger. It is very very important to try to find the trigger(s) as early as possible and try to treat them. Immune treatments will put the disease into remission, but root cause treatments are the only way to a cure.

 

Dr. T

 

And do you think that if we find the cause (for instance M.P.) and treat it with the correct antibiotics, that these kids will be cured? Or do you think they need IVIG to reset their immune systems? (Not sure if I've said that correctly, but I've read that Dr. K believes there is no cure except IVIG, just remission)

 

Angela

[peglem]

I get that high CamK2 activity could be caused by many things, but I'm wondering if you find the anti-neuronal antibodies from the Cunningham test significant in any way. My daughter's CamK2 was at 242%- solidly in the SC range. But, it seems to me the fact that she had very high anti-D2 seems more important to me. I mean, you can say that we're not sure why the CamK2 activity is high, but an anti-neuronal antibody just should not be there and whether its still being studied or not....there definitely is a high level of an anti-neuronal antibody. Am I understanding this correctly?

[Dr_Rosario_Trifiletti]

I get that high CamK2 activity could be caused by many things, but I'm wondering if you find the anti-neuronal antibodies from the Cunningham test significant in any way. My daughter's CamK2 was at 242%- solidly in the SC range. But, it seems to me the fact that she had very high anti-D2 seems more important to me. I mean, you can say that we're not sure why the CamK2 activity is high, but an anti-neuronal antibody just should not be there and whether its still being studied or not....there definitely is a high level of an anti-neuronal antibody. Am I understanding this correctly?

 

I think it's a complex neuroimmune response. I just mention CaMK2 only because there seems to be the most known about this. Obviously Dr. Cunningham would like to try to try to correlate the 4 antibodies she measures to clinical phenotype. All 4 (and I'll bet quite a few more) are important, but we're just having difficulty making sense of the anti-CaMk2 info. I think this will end up being like the chicken soup of autoantibodies that rheumatologists that treat patients with lupus-like illnesses think about all the time.

 

Dr. T

[PacificMama]

Glad to see this being raised. I obviously have no detailed information on the Cunningham study, but had wondered if people were under the impression that somehow the findings were unique to strep -- and what you are saying is "no". I'm sure people will want to get opinion or comment from Dr. C for further thought.

[Megs_Mom]

we had another doc tell us something similar - very helpful in diagnosing PANDAS or other infection triggered/inflamation based neuropsychiatric illness. But not specific to strep. Combined with high ANA & Peptic Ulcers (additional sign of inflamation) - as well as response to Predn - gave us the diagnosis we needed to get help. It's still such a clinical diagnosis, and not an easy one either.

[thereishope]

I don't think it was ever said that her findings were unique to strep. I believe what she has studied over the last years focused on strep. Am I right with this? Also, because this is PANDAS forum and for a long time dealt with strep was the main trigger perhaps some inferred it was strep only? But I don't think that was actually ever said.

[PANDAS_Denmark]

"At the end of the day, in PANDAS patients, there is still the trigger. It is very very important to try to find the trigger(s) as early as possible and try to treat them. Immune treatments will put the disease into remission, but root cause treatments are the only way to a cure.

 

Dr. T"

 

I couldn´t agree more !

However I have to ask : How do you define "root cause treatments" : IVIG, PEX ... or ?

[justinekno]

There is a good explanation about her study on the University of Oklahoma's website. I googled her name and it brought me directly to her page on their website. I printed out the info and gave it to our dr for him to review.

 

I don't think it was ever said that her findings were unique to strep. I believe what she has studied over the last years focused on strep. Am I right with this? Also, because this is PANDAS forum and for a long time dealt with strep was the main trigger perhaps some inferred it was strep only? But I don't think that was actually ever said.

[kimballot]

I don't think it was ever said that her findings were unique to strep. I believe what she has studied over the last years focused on strep. Am I right with this? Also, because this is PANDAS forum and for a long time dealt with strep was the main trigger perhaps some inferred it was strep only? But I don't think that was actually ever said.

 

Perhaps she has not focused on strep, but the acronym PANDAS really focuse on strep, and that is what most people hear. I think this is making it difficult for general docs to think of the PANDAS/PITAND coninuum. Why do we not include PITAND when we talk about PANDAS?

[trggirl]

I suspect in my daughter's case with a CamKinase of 237, it was triggered earlier (age 3), but the tics came on specifically after strep last year and this year at age 7.

 

Of course way back at age 3, my daughter had strep as well as some other infections that caused hospitalization. I'm not sure how one would ever figure out the trigger.

[momto2pandas]

Your last part here is where I'm trying to figure out chicken and egg, though. My kids, I now know, have immunodeficiencies, and they can't seem to kick these infections permanently no matter how many courses of different antibiotics we try. So how do we get at the "root cause"? Just higher, longer courses of the right drugs, or do we have to "fix" the immune system with e.g IVIG first before we can expect any of those drugs to provide a lasting fix? I.e., is the immunodeficiency the "root cause" and the infections actually a symptom of that (and subsequently the root cause of PANDAS)? Or is the infection the root cause and the immunodeficiency something that wouldn't really matter much had we not gotten stuck with that particular infection?

 

Hopefully their immuno can sort it out.

 

 

anti-CaMK2 must be marking a common final pathway NEUROimmune reaction - after all these are mostly brain symptoms that we are talking about here.

 

It is very likely NOT infectious etiology specific

 

A positive Cunningham test likely means a neuroimmune etiology, need not be bacterial, need not even be infectious (for example lupus-like illnesses).

 

This is what I find it most useful for:

 

1. Distinguishing non-immunological TS and/or OCD from PANDAS-like illnesses. If this can be verified, we may be able to answer questions like "How many kids with tics and/or OCD really have PANDAS-like illness" - just sample 1000 kids with tics or OCD (all comers) and find out what percentage have positive Cunningham tests. (it can't be that easy ....).

 

2. Get a sense (along with response to steroid burst) if costly immunological interventions like IVIG and/or PEX are likely to work

 

3. Distinguish between PANDAS and SC when there is clinical confusion. I realize there are kids out there (I know of three) that have anti-CaMK2 in the SC range (200's) but do not appear to have SC. I don't routinely do echocardiograms on patients with clear-cut PANDAS any more; but I think if anti-CaMK2 >200 maybe it should be done, as it can be missed. THIS DISTINCTION IS IMPORTANT AS IT CHANGES LONG TERM MANAGEMENT.

 

4. Separate out non-immunological TS and/or OCD from "pure OCD" and "pure TS group" and focus genetic studies on large pedigree "pure OCD" and "pure TS groups". Essentially, try to filter out a major epigenetic factor which confounds linkage analysis. This may be the way to looking at underlying genetics of these disorders, which leads to proteins, which leads to disease pathways, which leads to rational treatment.

 

At the end of the day, in PANDAS patients, there is still the trigger. It is very very important to try to find the trigger(s) as early as possible and try to treat them. Immune treatments will put the disease into remission, but root cause treatments are the only way to a cure.

 

Dr. T

[kimballot]

I think it's a complex neuroimmune response. I just mention CaMK2 only because there seems to be the most known about this. Obviously Dr. Cunningham would like to try to try to correlate the 4 antibodies she measures to clinical phenotype. All 4 (and I'll bet quite a few more) are important, but we're just having difficulty making sense of the anti-CaMk2 info. I think this will end up being like the chicken soup of autoantibodies that rheumatologists that treat patients with lupus-like illnesses think about all the time.

 

Dr. T

 

It makes sense that we would begin with something that is not infection specific. If we can just show an autoimmune response that was significantly different from the general population or from kids with non-inflammatory tourette/ OCD/ADH (did I just create that term?) then we could show that PANDAS/ PITAND is a distinct "syndrome". Once that is done, we may be able to get insurance coverage for the test - and then future research would be funded.

 

I am wondering if - currently - there is good normative information for the CaMK2. Do we have large enough normative samples to know what typical - "non inflammatory" reactions look like?

[thereishope]

I need reread her bio. I believe she has had an interest in strep, not necessarily always focusing on PANDAS but also SC. But I'm not saying all her results would only pertain to strep.

 

As for PANDAS vs PITAND, I think right now they are being used almost interchangeably. I would think PANDAS is a subgroup of PITANDS, but PANDAS got more known now due to Swedo concentrating on that. Again, I can look up the history Buster posted in the pinned thread. There is the whole debate if the whole thing should just get renamed to PAND, but who knows what will happen.

 

 

I don't think it was ever said that her findings were unique to strep. I believe what she has studied over the last years focused on strep. Am I right with this? Also, because this is PANDAS forum and for a long time dealt with strep was the main trigger perhaps some inferred it was strep only? But I don't think that was actually ever said.

 

Perhaps she has not focused on strep, but the acronym PANDAS really focuse on strep, and that is what most people hear. I think this is making it difficult for general docs to think of the PANDAS/PITAND coninuum. Why do we not include PITAND when we talk about PANDAS?

[thereishope]

I was thinking...for those who have done the Cunningham test then found out later that Mycroplasma was involved, are you contacting her with follow up info? I know in the past she has requested that those who did her test to follow up how they are doing.