A draft of a flow chart on PANDAS

[Buster]

If I'm following this right - I end up at the big red "STOP" box of non-strep trigger, with no where to go but considering the Cam Kinase study. So I have questions about this. What about strep being the original trigger through hindsight, but not the current trigger for exacerbation. Should there be a further path to follow if the Cam Kinase scores end up high? And what about the possibility of intercellular strep that isnt detected by swabs or ASO tests? Should there be a box about this to try 2 weeks of Zith and see if there is positive response?

That's sort of why I put this down. We have to have an argument (for ourselves and for our doctors) for moving from stage to stage. We could say that we think the high-dose azith or augmentin is anti-inflammatory and on subsequent exacerbation we should treat with an anti-inflammatory. I could even see a jump to a trial of pred to see if it is anti-inflammatory -- but if it is a viral or bacterial trigger suppressing the immune response isn't the best thing to do. Hence I chose a check of the CaM Kinase II scores. The problem is that these scores aren't calibrated enough to know exactly what they mean. Perhaps we could separate the two "stops" and have the first one check the CaM Kinase II and if elevated do a trial of azith to see if positive response.

 

Buster

[Buster]

Hi Buster,

Thanks for all this work!

Two comments-

1. would it complicate things too much to have a box suggesting an immuno workup - for IG levels, for lyme, etc - it's certainly a "rule out" thing many have done, but I don't want to lose the message by adding too much.

 

2. Box 7 - a) is it just impetigo that doesn't produce elevated titers? I thought carriage and other individual body reactions could cause a non-rise. b- Should there be a note about doing an ASO 3-6 weeks post-infection, as this is the time when the levels would be highest?

 

Nice job of making sense out of a very confusing journey.

Laura

 

Good point on rule-out. I have to think about where to add that. Perhaps where the other Igg is being tested. I started with a statement in box 7 that ASO won't rise in >46% of cases -- perhaps that is good enough. I also started thinking I'd need to block by time window (i.e, is it within 1 week of exacerbation, 3 weeks, 6 weeks).

 

I also liked the comment about initial versus subsequent. I do see something awfully similar to a hyper-reaction aver a hypo-reaction. Our subsequent exacerbations were more like an allergic reaction (more severe, more immediate) than our initial reaction. I wonder if what is really happening is that the adaptive immune system fails to clear so the humoral system gets involved and now is hyper-responsive.

 

I'll try another revision later today.

 

Buster

[thereishope]

Buster,

 

In between your daughters exacerbations, what was the longest lapse in time? From recovery to another exacerbation?

 

If this is at all like an allergic reaction, I think the longer they go w/o exposing themself to the allergen , the subsequent reaction isn't as bad.

 

Back to the peanut allergy reference. My nephew has a peanut allergy. When they first found out, the dr told them to keep him away from all peanuts at all costs because the longer he goes w/o exposure, the more likely subsequent exposures won't be as bad. They did that and he is improving. Allergy tests show he is still allergic, but if he eats a M and M he won't get hives like he used to.

 

So do you think if you can keep your child away from strep or strep exposure for a long period of time, eventually the viral reactions will become more minute? I'm asking because "knock on wood" that seems like it may be the case with my son. I'm only referring to viral triggers, not strep.

 

Those who have posted here with exacerbations after years after remission, are they mostly strep or mostly viral?

[Buster]

Updated top image to reflect comments

[Buster]

Hi Vickie,

 

In our case, we had 4 months without exacerbation over the '08 summer. Then a series of exacerbations with typically 2 months between episodes. We had 3 month break in '09 summer. Post IVIG (August) we are now 5 months from significant exacerbation.

 

Buster

 

Buster,

 

In between your daughters exacerbations, what was the longest lapse in time? From recovery to another exacerbation?

 

If this is at all like an allergic reaction, I think the longer they go w/o exposing themself to the allergen , the subsequent reaction isn't as bad.

 

Back to the peanut allergy reference. My nephew has a peanut allergy. When they first found out, the dr told them to keep him away from all peanuts at all costs because the longer he goes w/o exposure, the more likely subsequent exposures won't be as bad. They did that and he is improving. Allergy tests show he is still allergic, but if he eats a M and M he won't get hives like he used to.

 

So do you think if you can keep your child away from strep or strep exposure for a long period of time, eventually the viral reactions will become more minute? I'm asking because "knock on wood" that seems like it may be the case with my son. I'm only referring to viral triggers, not strep.

 

Those who have posted here with exacerbations after years after remission, are they mostly strep or mostly viral?

[wornoutmom]

If I'm following this right - I end up at the big red "STOP" box of non-strep trigger, with no where to go but considering the Cam Kinase study. So I have questions about this. What about strep being the original trigger through hindsight, but not the current trigger for exacerbation. Should there be a further path to follow if the Cam Kinase scores end up high? And what about the possibility of intercellular strep that isnt detected by swabs or ASO tests? Should there be a box about this to try 2 weeks of Zith and see if there is positive response?

That's sort of why I put this down. We have to have an argument (for ourselves and for our doctors) for moving from stage to stage. We could say that we think the high-dose azith or augmentin is anti-inflammatory and on subsequent exacerbation we should treat with an anti-inflammatory. I could even see a jump to a trial of pred to see if it is anti-inflammatory -- but if it is a viral or bacterial trigger suppressing the immune response isn't the best thing to do. Hence I chose a check of the CaM Kinase II scores. The problem is that these scores aren't calibrated enough to know exactly what they mean. Perhaps we could separate the two "stops" and have the first one check the CaM Kinase II and if elevated do a trial of azith to see if positive response.

 

Buster

 

 

 

So if the CaM Kinase II scores are not calibrated enough to have meaning, why are so many parents having this done and how would testing this support a PANDAS diagnosis?

[Buster]

So if the CaM Kinase II scores are not calibrated enough to have meaning, why are so many parents having this done and how would testing this support a PANDAS diagnosis?

 

The test is a research trial. This means they are still trying to determine whether the test has diagnostic usefulness. All indications are that it is a reliable source, but the accuracy/repeatability/specificity is not known. So CaM Kinase II is an additional piece of the puzzle of PANDAS.

 

For many, the CaM Kinase II provides enough confirming evidence that helps move along the process -- however, some doctors use preliminary experimental results and others do not. For example, it was only recently that ANA was correlated with Lupus and even then it is more confirming rather than diagnostic. People with Lupus tend to have elevated ANA -- however everyone with elevated ANA doesn't have Lupus.

 

In terms of why parents do this, it's primarily because we're all looking for any clue or additional puzzle pieces that help us determine the underlying cause.

 

Regards,

 

Buster

[T_Mom]

Hi T.Mom,

 

I actually thought about skipping the whole "check for GABHS" and just jump to box 9 on the presumption that a 30 day trial of antibiotics is WAY safer and cheaper than any anti-psychotic/anti-tic medication that would otherwise be prescribed. I thought about just recommending in box 7 to "get the Cam Kinase II results and if > 160 treat as PANDAS". This would catch the 31%+ of kids who don't have elevated ASO or Anti-DNAseB response -- particularly for difficult to culture sinus infections and cover the docs who don't seem to know how to take a simple throat culture -- couldn't believe the high-false negative rate because the nurses cultured throat rather than tonsils. Sigh.

 

Unfortunately, we don't have enough data yet to know if the Cam Kinase II test can become a diagnostic test. It sure seems promising, but we'll have to wait till the research paper comes out.

 

I'm happy to add another box after box 7 that says "suspected GABHS infection coincident with symptom onset" as a vague placeholder... would that work?

 

The reason I didn't collapse all the boxes is that I consistently see doctors pulling rapid and ASO together and making the very false assumption that the ASO is more accurate than the rapid. It's hard to believe that the ASO is about the same as a coin flip.

 

Buster

 

 

Hi Buster-- I really like the idea of "suspected GABHS infection" [/b][/i] I see now BOX 10 addresses the issue, Thanks!

 

Having two daughters with Cam Kinase levels that have been 181 and 160 at the high points...I too wish the test could be a diagnostic tool--wouldn't that break down the doors to help for so many!!

 

Please keep up the good work on behalf of so many Buster, thank you.

[Megs_Mom]

Hi Buster - wow, you always amaze me by your efforts to help kids be diagnosed! Thank you.

 

I may have misread one of the changes already done - but thought I'd post in case others are also confused about how to read. When I follow the path, we end up at the red stop box in step 8. As a reminder, we did not do first onset testing as the exacerbation was in 2005, and she had an ear infection - all signs cleared up after 4 weeks for a complete baseline recovery. At the second onset in 2008, we ran rapid, 72 hour and ASO - all negative. However, our dd's treatment plan has been very succesful after an unbelievably successful steroid burst & then treatment with antibiotics after onset in 2009. I suppose I tend to be on the aggressive side of things, and really want the diagnositic to consider:

8. if negative tests, but sudden onset or extreme exacerbation of OCD or tics - then if reach box 8 move to:

8 a. Trial of prednisone (if OCD or low risk for TS) and abx.

If responsive, this is diagnostic.

 

Running into box 8 feels like what happened to us in the medical community for years. I think this is only the case for those of us who missed testing for the initial onset, or who don't run positive titers for whatever reason. I am also concerned that other parents make the mistake we did of waiting the 4-6 weeks for titers, then finding the Cunningham study & waiting for those results. In retrospect, we held off treatment for far too long, although we already had most of the clinical signs that we needed. Thanks largely to your education and others here, I can look back & see that we already knew she had PANDAS - we just kept doubting it since our tests were not clear cut.

 

I also note that you are suggesting a >160 for the CamK test. Is there another range that parents can also use as a clinical tool? Our score was much less than that(133, I believe) at the end of an exacerbation when we finally tested her, but seemed diagnostic to her Neurologist when combined with high ANA levels, pred response, mild chorea, urinary urgency, severe sudden seperation anxiety and history of sudden onset and severe exacerbations. A burst in late 2009 was over in 8 days with abx treatment. I thought the mean for PANDAS was closer to 140, and for regular OCD, was in the 100/110 range.

 

Thanks - look forward to your thoughts on this! I appreciate your welcoming comment on something that you are clearly working so very hard on. Your spirit of collaboration is impressive.

[Buster]

Hi Meg's Mom,

 

Can you check if you were looking at the latest version -- sorry, I might have been updating based on feedback when you posted.

 

Based on Dr. K's interview yesterday, he says he placed about 5-10% on the culture, ASO/Anti-DNase, sore throat, ..., 60-70% on clinical history and 20-30% on the confirmatory affect of prednisone.

 

As such I tried to make it that even if all cultures/titers are negative, you can decide to progress onto antibiotic trials and pred. The tricky part is that doctors will claim there isn't "good evidence" for the trial and so you have to argue the benefit to risk ratio.

 

On CaM Kinase II, yes, 130 would be supportive. The pilot in the Kirvan Nature article was from the patients in Swedo's study. So it is hard to know what the true mid-point is for a broad population. I think that's the whole reason for the research trial.

 

Regards,

 

Buster

 

 

Hi Buster - wow, you always amaze me by your efforts to help kids be diagnosed! Thank you.

 

I may have misread one of the changes already done - but thought I'd post in case others are also confused about how to read. When I follow the path, we end up at the red stop box in step 8. As a reminder, we did not do first onset testing as the exacerbation was in 2005, and she had an ear infection - all signs cleared up after 4 weeks for a complete baseline recovery. At the second onset in 2008, we ran rapid, 72 hour and ASO - all negative. However, our dd's treatment plan has been very succesful after an unbelievably successful steroid burst & then treatment with antibiotics after onset in 2009. I suppose I tend to be on the aggressive side of things, and really want the diagnositic to consider:

8. if negative tests, but sudden onset or extreme exacerbation of OCD or tics - then if reach box 8 move to:

8 a. Trial of prednisone (if OCD or low risk for TS) and abx.

If responsive, this is diagnostic.

 

Running into box 8 feels like what happened to us in the medical community for years. I think this is only the case for those of us who missed testing for the initial onset, or who don't run positive titers for whatever reason. I am also concerned that other parents make the mistake we did of waiting the 4-6 weeks for titers, then finding the Cunningham study & waiting for those results. In retrospect, we held off treatment for far too long, although we already had most of the clinical signs that we needed. Thanks largely to your education and others here, I can look back & see that we already knew she had PANDAS - we just kept doubting it since our tests were not clear cut.

 

I also note that you are suggesting a >160 for the CamK test. Is there another range that parents can also use as a clinical tool? Our score was much less than that(133, I believe) at the end of an exacerbation when we finally tested her, but seemed diagnostic to her Neurologist when combined with high ANA levels, pred response, mild chorea, urinary urgency, severe sudden seperation anxiety and history of sudden onset and severe exacerbations. A burst in late 2009 was over in 8 days with abx treatment. I thought the mean for PANDAS was closer to 140, and for regular OCD, was in the 100/110 range.

 

Thanks - look forward to your thoughts on this! I appreciate your welcoming comment on something that you are clearly working so very hard on. Your spirit of collaboration is impressive.

[Megs_Mom]

I think you are right - I was clicking on the modified button, but that takes me back to the original. I just clicked on the bottom button, under the diagram image, and that one does take me to a new diagram! Thank you - I couldn't figure out why the revisions you were discussing still seemed not to reflect a common experience. This is great now. I can't print this yet, but when you connect to the modified button, I'll be back to be sure I am reading it all correctly (for some reason the top 2 buttons print great, but the bottom one only prints half. I have a love hate relationship with technology).

 

I wonder if you could submit to someone like Swedo for a "blessing" when you are done - it would be great to be able to distribute this with some sort of university or doctor blessing, so that other docs would take seriously. The work is too good to waste.

 

I enjoyed that interview as well - and that despite all the testing that can be done, that most of the dianosis is still clinical. I was up at 4 am listening - I need to get a life!

 

I thought I'd try to capture the steps folks have been taking in trying to diagnose PANDAS. Please check it over...

 

Probably folks have lots of suggestions to improve, but thought this was a good start

 

EDITED **

Modified : http://pandasdad.home.comcast.net/pandas_diag2.pdf

 

Original : http://pandasdad.home.comcast.net/pandas_diag.pdf

 

Buster

 

P.S. There are obviously other things that should be included like response to advil, ...

 

 

original : http://pandasdad.home.comcast.net/pandas_diag2.gif

[Buster]

I think you are right - I was clicking on the modified button, but that takes me back to the original.

 

Helps if I get the URL right. Try the new page again. Sorry about that.

[Megs_Mom]

I think you are right - I was clicking on the modified button, but that takes me back to the original.

 

Helps if I get the URL right. Try the new page again. Sorry about that.

Ah, now that is really good. Thank you. Only suggestion would be to add Lupus (and possibly Celiac) - both of which have know neurological symptoms similar to PANDAS onset. This is a great chart. Are you leaving it up on this URL? I'd love to share it with other boards if you are done now. Thanks -

[LNN]

One comment about some of the time frames - especially box 16 prednisone. Dr L often goes with a longer course. We've done prednisone twice and both times, it wasn't until the 2nd week that we saw significant improvement. Weeks 2 and 3 saw really big changes. I don't think we'd have gotten the same results with only 5 days. Poison Ivy is often treated with 10 days of prednisone. Since there's difference of opinion between the doctors using this, and no Pandas study to look to, can we change Box 16 to just eliminate the time reference?

 

Similar comment for box 19 - it was 3-4 weeks before we saw big improvements. Wouldn't want to set an expectation that everyone will see improvements in only 2 weeks. And if you've gotten to Box 19, you're most likely dealing with a Pandas doc, so they'd be able to tell what sort of time frame would be reasonable.

 

Finally - can box 13 read "significant symptom remission in 4-6 weeks of good health and can box 21 spell out Immunoglobulin sub-classes - I don't know if Igg1..4 will be clear to everyone who might read this.

 

I think you've covered all the bases I can think of. Nice job!

[Buster]

Thanks for the comments. I get your points, but I'm concerned if we leave the fields without timelines we'll lose the actual benefit of the flow. It was precisely the timelines that I found helpful. Too many people are expecting an immediate change rather than the 2 week effect reported by you and so many others. So, personally, I'd rather keep the time and perhaps add an * that some folks find a longer time.

 

On the 5 day or longer pred burst, I'm basing this more on Dr. K than on Dr. L. I've read the material of Dr. K and he seems to have extremely consistent results here for a large number of cases with a 5 day burst producing results within the 2 week time period. I've tried to track material from Dr. L and been less successful. Perhaps if you are talking with Dr. L you could ask what the average time to impact is. Since pred is not thought to be therapeutic here and has a lot of neg side effects, I'd be very hesitant to just leave it open.

 

With the 10 days vs 5 days -- I'm certainly willing to change it to 5-10 day burst.

 

I like your idea of "healthy" but have to reflect on how it will fit.

 

One of the reasons I did the chart was to see how much rigor can be added to the diagnostic procedure. It's hard to complain about Kurlan or Kaplan's comments on the ambiguity in PANDAS if the diagnostic critieria remains too vague. I realize there are cases like Worried Dad's son and I think a lot about how that could be caught in this cycle. Essentially, I'd like to see how many of the kids already helped on this forum would be caught by such an algorithm.

 

I should stress that the chart is the best that I've found from the material in the literature and controlled trials. I'm sure there are many other tests that folks might run in addition to the ones mentioned.

 

Buster

 

One comment about some of the time frames - especially box 16 prednisone. Dr L often goes with a longer course. We've done prednisone twice and both times, it wasn't until the 2nd week that we saw significant improvement. Weeks 2 and 3 saw really big changes. I don't think we'd have gotten the same results with only 5 days. Poison Ivy is often treated with 10 days of prednisone. Since there's difference of opinion between the doctors using this, and no Pandas study to look to, can we change Box 16 to just eliminate the time reference?

 

Similar comment for box 19 - it was 3-4 weeks before we saw big improvements. Wouldn't want to set an expectation that everyone will see improvements in only 2 weeks. And if you've gotten to Box 19, you're most likely dealing with a Pandas doc, so they'd be able to tell what sort of time frame would be reasonable.

 

Finally - can box 13 read "significant symptom remission in 4-6 weeks of good health and can box 21 spell out Immunoglobulin sub-classes - I don't know if Igg1..4 will be clear to everyone who might read this.

 

I think you've covered all the bases I can think of. Nice job!