New Paper in Neurology

[Buster]

In the October 20th issue of Neurology, there is a new retrospective study entitled "Streptococcal infection, Tourette syndrome, and OCD: Is there a connection?" http://www.neurology.org/cgi/reprint/73/16/1256

 

The paper is a UK study paralleling the work by Mell in 2005 "Association between streptococcal infection and obsessive-compulsive disorders, Tourette's syndrome, and tic disorder" http://pediatrics.aappublications.org/cgi/reprint/116/1/56

 

The new paper looked at the coding records of 678,862 patients selecting 4784 patients for the study. The subset was selected by looking for OCD/Tourette's diagnosis and then matching for age. It seemed odd that a pediatrician would diagnose OCD (a psychiatric disorder) rather than referring the child to a psychiatrist, but that's what the study found.

 

In any case, they isolating 129 cases of OCD and 126 cases of TS/tics and used 2211 age-matched controls for OCD and 2308 age-matched controls for TS/tics. Curiously the study found only 22 of the OCD cases had onset < 10 yrs old. The majority of cases (71) had onset > 16.

 

This meant that they found the overall incidence of OCD to be 1:5000, and for children < 10 to be 1:33,000.

 

What was also strange was that only 20 of the OCD or tic cases had a preceding strep infection within the last 2 years. 9 of these cases were not treated and 11 were treated with antibiotics.

 

The study concludes that the data does "not support a strong relationship between streptococcal infections and neuropsychiatric syndromes" however, it did note with caution that incidences of OCD were more likely to have had an untreated possible strep infection (i.e., no antibiotics were prescribed).

 

What I found amazing about the whole study was that in looking at 685 cases of likely strep over a 5 year period, there were only 67 throat swabs and only 6 ASO titers. Thus in > 90% of cases, strep throat was being diagnosed by clinical signs. If the sample on this forum is any indiction, there was probably a lot of undiagnosed strep.

 

 

I'm not sure what to make of the study at this point. It did not look at suddenness of onset, did not apparently look for multiple strep infections, did not look at remission of symptoms. It is impossible to tell if the presented cases differ from traditional OCD. If we assume that the <5% of traditional OCD cases are actually PANDAS, then the study is underpowered and no PANDAS children were likely found.

 

Kurlan and Gilbert have commentary about PANDAS and SC in the same issue but don't really help any (particularly as they fail to acknowledge the finding of higher incidence for untreated strep).

 

Buster

[melanie]

In the October 20th issue of Neurology, there is a new retrospective study entitled "Streptococcal infection, Tourette syndrome, and OCD: Is there a connection?" http://www.neurology.org/cgi/reprint/73/16/1256

 

The paper is a UK study paralleling the work by Mell in 2005 "Association between streptococcal infection and obsessive-compulsive disorders, Tourette's syndrome, and tic disorder" http://pediatrics.aappublications.org/cgi/reprint/116/1/56

 

The new paper looked at the coding records of 678,862 patients selecting 4784 patients for the study. The subset was selected by looking for OCD/Tourette's diagnosis and then matching for age. It seemed odd that a pediatrician would diagnose OCD (a psychiatric disorder) rather than referring the child to a psychiatrist, but that's what the study found.

 

In any case, they isolating 129 cases of OCD and 126 cases of TS/tics and used 2211 age-matched controls for OCD and 2308 age-matched controls for TS/tics. Curiously the study found only 22 of the OCD cases had onset < 10 yrs old. The majority of cases (71) had onset > 16.

 

This meant that they found the overall incidence of OCD to be 1:5000, and for children < 10 to be 1:33,000.

 

What was also strange was that only 20 of the OCD or tic cases had a preceding strep infection within the last 2 years. 9 of these cases were not treated and 11 were treated with antibiotics.

 

The study concludes that the data does "not support a strong relationship between streptococcal infections and neuropsychiatric syndromes" however, it did note with caution that incidences of OCD were more likely to have had an untreated possible strep infection (i.e., no antibiotics were prescribed).

 

What I found amazing about the whole study was that in looking at 685 cases of likely strep over a 5 year period, there were only 67 throat swabs and only 6 ASO titers. Thus in > 90% of cases, strep throat was being diagnosed by clinical signs. If the sample on this forum is any indiction, there was probably a lot of undiagnosed strep.

 

 

I'm not sure what to make of the study at this point. It did not look at suddenness of onset, did not apparently look for multiple strep infections, did not look at remission of symptoms. It is impossible to tell if the presented cases differ from traditional OCD. If we assume that the <5% of traditional OCD cases are actually PANDAS, then the study is underpowered and no PANDAS children were likely found.

 

Kurlan and Gilbert have commentary about PANDAS and SC in the same issue but don't really help any (particularly as they fail to acknowledge the finding of higher incidence for untreated strep).

 

Buster

 

HI Buster

 

My md saw this study too. This is why he haulted danny 2nd IVIG!!!But one good thing is he saw a difference from the1st so he knows it works

 

Melanie

[michele]

Gilbert is the one tainting OH Dr's on the PANDAS. He is the naysayer. I have tried to email him and talk to him over the phone and get a perspective on how he would treat my son. He would never say. Ask Vickie. She saw him. He has a research lab in Cinnci that is used for tic studies. Now every neuro in OH takes his opinion on PANDAS. It makes me ill. In the beginning I thought he helped Sweedo's and Murphy's studies. Now it seems he has switched to Kurlan's side on the PANDAS.

 

Michele

In the October 20th issue of Neurology, there is a new retrospective study entitled "Streptococcal infection, Tourette syndrome, and OCD: Is there a connection?" http://www.neurology.org/cgi/reprint/73/16/1256

 

The paper is a UK study paralleling the work by Mell in 2005 "Association between streptococcal infection and obsessive-compulsive disorders, Tourette's syndrome, and tic disorder" http://pediatrics.aappublications.org/cgi/reprint/116/1/56

 

The new paper looked at the coding records of 678,862 patients selecting 4784 patients for the study. The subset was selected by looking for OCD/Tourette's diagnosis and then matching for age. It seemed odd that a pediatrician would diagnose OCD (a psychiatric disorder) rather than referring the child to a psychiatrist, but that's what the study found.

 

In any case, they isolating 129 cases of OCD and 126 cases of TS/tics and used 2211 age-matched controls for OCD and 2308 age-matched controls for TS/tics. Curiously the study found only 22 of the OCD cases had onset < 10 yrs old. The majority of cases (71) had onset > 16.

 

This meant that they found the overall incidence of OCD to be 1:5000, and for children < 10 to be 1:33,000.

 

What was also strange was that only 20 of the OCD or tic cases had a preceding strep infection within the last 2 years. 9 of these cases were not treated and 11 were treated with antibiotics.

 

The study concludes that the data does "not support a strong relationship between streptococcal infections and neuropsychiatric syndromes" however, it did note with caution that incidences of OCD were more likely to have had an untreated possible strep infection (i.e., no antibiotics were prescribed).

 

What I found amazing about the whole study was that in looking at 685 cases of likely strep over a 5 year period, there were only 67 throat swabs and only 6 ASO titers. Thus in > 90% of cases, strep throat was being diagnosed by clinical signs. If the sample on this forum is any indiction, there was probably a lot of undiagnosed strep.

 

 

I'm not sure what to make of the study at this point. It did not look at suddenness of onset, did not apparently look for multiple strep infections, did not look at remission of symptoms. It is impossible to tell if the presented cases differ from traditional OCD. If we assume that the <5% of traditional OCD cases are actually PANDAS, then the study is underpowered and no PANDAS children were likely found.

 

Kurlan and Gilbert have commentary about PANDAS and SC in the same issue but don't really help any (particularly as they fail to acknowledge the finding of higher incidence for untreated strep).

 

Buster

 

HI Buster

 

My md saw this study too. This is why he haulted danny 2nd IVIG!!!But one good thing is he saw a difference from the1st so he knows it works

 

Melanie

[ajcire]

If I am understanding this correct.....Goodness.. it doesn't take a rocket scientist to see that if you are going to use data for a study you better not just go on assumptions... like selecting cases that were not tested for strep but assuming they don't have it...

If every time the dr. looked at my kids and said it doesn't look like strep and left it alone than they would have missed out on the positive cultures that come back 48 hours almost every time. They always tell me that it doesn't look like strep but they swab anyway to humor the mommy and then sure enough it's strep.. that's in my pandas ds and my non pandas dd. Really, if you are going to do a research study you would think you would cross your t's.

 

Of course, if I am not understanding my above rant makes no sense

[Megs_Mom]

Our Therapist at Duke also gave me this study (or one very similar to it) a month ago - thanks largely to this board (BUSTER!!!) I was able to very quickly explain what the study actually looked at and was trying to prove, and why starting with a false premise for a very serious illness missed the point and produces useless info. I made the point that no-one is trying to suggest that all of OCD or TS is caused by Strep. But that a small subset is caused by strep. And that looking at historical data that was not using the right diagnositic criteria for strep is a faulty premise. She had actually not read the study - just the overview.

 

It certainly does not feel fair that we parents need to be so up-to-date on the science in order to protect our kids. Very frustrating. I just hand everyone a copy of the Columbia mouse study - and say that if you do actual research instead of lazy data reviews of incomplete data - you get a very different picture - and one that can save childhoods.

 

Garbage in, garbage out!

[thereishope]

The study cited is from R Gilbert. I couldn't see what what the Cincy Gilbert (D. Gilbert) said in his commentary. D Gilbert still confuses me to this day when I look back at our experience with him.

 

 

Gilbert is the one tainting OH Dr's on the PANDAS. He is the naysayer. I have tried to email him and talk to him over the phone and get a perspective on how he would treat my son. He would never say. Ask Vickie. She saw him. He has a research lab in Cinnci that is used for tic studies. Now every neuro in OH takes his opinion on PANDAS. It makes me ill. In the beginning I thought he helped Sweedo's and Murphy's studies. Now it seems he has switched to Kurlan's side on the PANDAS.

 

Michele

[Buster]

It certainly does not feel fair that we parents need to be so up-to-date on the science in order to protect our kids. Very frustrating. I just hand everyone a copy of the Columbia mouse study - and say that if you do actual research instead of lazy data reviews of incomplete data - you get a very different picture - and one that can save childhoods.

 

Totally agree and wish they'd just repeat Kirvan's and Cunningham's work that explains a plausible pathogenesis that would be diagnostically useful rather than these needles in haystack experiments.

 

The study is fine for what it is, but the reason for my post was to hopefully ensure that folks knew something about the study and in particular the quote that "untreated strep" has a higher correlation with OCD.

 

Given that throat cultures were done in only 10% of the strep diagnosis -- this probably means that lots of strep went undetected (or wasn't coded).

 

Regard,

 

Buster

[kim]

Buster,

 

When I read this excerpt, i have to wonder how many kids in these "disproving studies," are not showing any sign of strep, but autoimmune problems triggered by another illness. Was Kurlan's study strep exclusive, or was he saying that there wasn't anything to indicate that there was immune system activity that would suggest viral or other types of illness?

 

 

http://docs.google.com/gview?a=v&q=cac...Ccyg9fDXQih2SSw

 

 

Epitope Spreading

 

As an autoimmune disease progresses from initial activation to a chronic state there is often an increasein the number of auto antigens targeted by T cells and antibodies (“epitope spreading”)89,90 and, in some cases, a change in participating cells, cytokines, and other inflammatory mediators. Both autoreactiveT cells and B cells contribute to epitope spreading. Activated autoreactive B cells function as antigen-presenting cells; they present novel (cryptic) peptides of autoantigens 91,92 and express costimulatory molecules. They also generate peptides that have not previously been presented to T cells; thus, T cells willnot have become tolerant to such cryptic peptides. Over time, multiple novel peptides within a molecule can activate T cells. Furthermore, if the B cell binds and takes in not a single protein but a complex of multiple proteins, epitopes from each protein in the complex will be processed and presented to naive T cells. The cascade continues, with T cells activating additional autore-active B cells and B cells presenting additional self epitopes, until there is autoreactivity to numerous autoantigens. By then, the identity of the initial antigan can no longer be determined.

 

 

Michelle,

 

I can't help but wonder how much this study has to do with the attitude in Ohio.

 

http://www.journals.uchicago.edu/doi/abs/10.1086/592972

 

Clinical Infectious Diseases 2008;47:1388–1395

 

MAJOR ARTICLE

Emergence of Streptococcus pneumoniae Serotypes 19A, 6C, and 22F and Serogroup 15 in Cleveland, Ohio, in Relation to Introduction of the Protein‐Conjugated Pneumococcal Vaccine

 

Conclusions. This study documents decreases in the incidence of infections involving vaccine serotypes, increases in infections involving other serotypes, and decreases in the activity of macrolides and clindamycin after conjugate vaccine introduction.

[nevergiveup]

What this study is trying to say I am not sure. If SC doesn't show signs for up to 9 months after the strep infection these correlations don't mean much. Since many studies prove children get on an average 2 strp cases per years in elem school years, what are they trying to say here. Without an accurate swab this is just a study of parents opinions. Most docs waive the strep test if child has signs of sinus infect or resp problems because they are going to prescribe abx anyway. Don Gilberts comments were I believe that the study is lacking. He is a statistics guy and knows that this study doesn't measure whether TS has an autoimmune component. He has a problem with parents whom have an opinion any opinion medical. Plus he says right on his web site if you are going down the path of PANDAS try other docs, he doesn't feel there is enough evidence or studies to justify treatment yet. Interesting enough though, he did run tests on my kid to check for autoimmune issues and referred us out of neurology.

[thereishope]

The second I mentioned to Gilbert that my son had a PANDAS reaction to something other than strep, he stopped all communication with me and told me it was time to take him to a psychiatrist.

 

Buster,

 

When I read this excerpt, i have to wonder how many kids in these "disproving studies," are not showing any sign of strep, but autoimmune problems triggered by another illness. Was Kurlan's study strep exclusive, or was he saying that there wasn't anything to indicate that there was immune system activity that would suggest viral or other types of illness?

[thereishope]

nevergiveup,

 

Are you from Cincinnati?

[nevergiveup]

Vicki,

 

From very nearby. Anyway, for a ped Dr. Arar has seen first hand a very young boy suffer a severe pandas attack and is a believer in its existance. If you need a ped I would recommend her. I highly recommend having your sons IGG's and ANA checked. Also Don Gilbert said Dr. Brunner in Rheum has treated sudden onset OCD with IVIG. She's at childrens. Almost impossible to get in to see. Waiting period is months, she sees lupus kids so is normally booked with very sick kids. Does not specialize in PANDAS but has treated. Also gives steriods if she see's undetermined autoimmune markers. Thats whom I know from CVG. None believe in PANDAS rather believe in an autoimmne component of OCD and movement disorders.

[EAMom]

The second I mentioned to Gilbert that my son had a PANDAS reaction to something other than strep, he stopped all communication with me and told me it was time to take him to a psychiatrist.

 

Buster,

 

When I read this excerpt, i have to wonder how many kids in these "disproving studies," are not showing any sign of strep, but autoimmune problems triggered by another illness. Was Kurlan's study strep exclusive, or was he saying that there wasn't anything to indicate that there was immune system activity that would suggest viral or other types of illness?

 

What blockheads!!! This is from Swedo's 1st 50 cases paper:

 

Two clinical notes should be made. First, not all

symptom exacerbations were preceded by GABHS infections;

viral infections or other illnesses could also

trigger symptom exacerbations. This is in keeping with

the known models of immune responsivity—primary

responses are specific (e.g., directed against a particular

epitope on the GABHS), while secondary responses

are more generalized. Thus, the lack of evidence for a

preceding strep infection in a particular episode does

not preclude the diagnosis of PANDAS.

[thereishope]

I know!!!! I've read that except so many times! I'm telling you, I can't pinpoint what is it about him. I think maybe he's confused. Being pulled in different directions? There's more going on behind closed doors than true science, getting down to the root of problems, and helping children.

[Megs_Mom]

I keep wanting a simple summary that I can hand to docs & parents - and then I'll give them the full studies if they want (I find they have the attention span of an ADHD child in general! Maybe most doctors have PANDAS Kidding.) Here are the two pertinent portions that I am pulling - let me know if you think this is accurate to the points we are discussing above.

 

Here is the part that is pertinent to us (from Immune Response to Group A Streptococcal C5a

Peptidase in Children: Implications for Vaccine

Development by Edward L. Kaplan):

 

We also observed that, although 136 (67%) of 202

children showed a significant increase in anti-SCPA, only 109

(54%) showed a significant increase in ASO, 91 (45%) in anti–

DNase B, and 127 (63%) in either ASO and/or anti–DNase B

(figure 6). When the 3 antibodies are compared (ASO, anti–

DNase B, or anti-SCPA), the percentage of children showing

an increase in any of these titers was 69%, which is not appreciably

different from the proportion showing a significant

increase in anti-SCPA alone.

 

If I read it all correctly, all of the children had positive tests for strep. But only 63% show increase in either anti-DNaseB or ASO at 4 weeks. So 37% of kids show no antibody sign of strep. Here is the test requirments for participation:

 

Paired serum samples

previously obtained from 202 children aged 2–12 years

residing in 19 states in the United States were used in the study.

These children had signs and symptoms of acute pharyngitis

and had GAS isolated from their throats at the initial visit.

Acute-phase serum samples were obtained at the acute presentation,

and convalescent-phase serum samples were obtained 4

weeks later.

 

And from the quote above: This is from Swedo's 1st 50 cases paper:

 

Two clinical notes should be made. First, not all

symptom exacerbations were preceded by GABHS infections;

viral infections or other illnesses could also

trigger symptom exacerbations. This is in keeping with

the known models of immune responsivity—primary

responses are specific (e.g., directed against a particular

epitope on the GABHS), while secondary responses

are more generalized. Thus, the lack of evidence for a

preceding strep infection in a particular episode does

not preclude the diagnosis of PANDAS.

 

I think that these two portions of the research studies, taken together, are a clear argument for doctors that they cannot eliminate PANDAS by a strep titer test. Titers can help them rule IN PANDAS, but not be exclusively used to rule OUT. They will need to go further than this and look at the full clinical picture. Failure to understand this was our entire problem for over a year.