Non Pandas Daughter has high Cam kimaise

[EAMom]

So, what can this mean??? Can some people have PANDAS with elevated Cam Kinase II and never show full blown symptoms? What other situations cause an elevated Cam Kinase II?

 

If your dd's blood brain barrier stays closed, the high CAM kinase II wouldn't have an effect and she wouldn't have full blown symtpoms.

[EAMom]

Wow...too bad nobody bothered to get an M type on this strep (figure out more about the strain). I definitely believe that certain strains of strep are more likely to trigger pandas (just as there are strains that are more likely to cause RF.)

 

I should say, I think certain strains are more likely to trigger the sentinal episode of PANDAS. However, once the wheels of PANDAS are set in motion, I suspect that many (if not all) strains of strep, as well as other illnesses (eg viruses) can trigger subsequent exacerbations.

[KeithandElizabeth]

EAMom:

 

So what do you mean exactly? Does this mean she just had a strep infection and not necessarily PANDAS? I am still trying to understand this whole disease.

 

elizabeth

[EAMom]

EAMom:

 

So what do you mean exactly? Does this mean she just had a strep infection and not necessarily PANDAS? I am still trying to understand this whole disease.

 

elizabeth

 

Hi Elizabeth,

read this post by Buster: http://www.latitudes.org/forums/index.php?...art=#entry37473

 

If the blood brain barrier is closed, then a high CAM kinase II/high anti-neural antibodies won't get to your dd's brain so there won't be PANDAS symptoms.

 

On the same line of thought, we think this is why some kids have exacerbations following stress (or non-strep illness). The child may already have high CaM kinase II/anti-neural anti-bodies circulating in their bloodstream. However, the blood brain barrier is closed so nothing reaches the brain, so the kid acts fine. With stress (or a viral illness perhaps) the blood brain barrier can open (what Buster calls "the last straw") and the child becomes symptomatic.

 

BTW, you don't need a recent strep infection to have a high CAM kinase II...our dd's CAM kinase was very high even after being on high doses of daily azith. for 1+ year (her ASO was super low..17--undectable). I do think strep exposure (not actually getting the strep, but just being in contact with a carrier, for example) can cause an increase in CAM kinase ll (as that causes an increase in symptoms in our dd). It's a bit like a child with a peanut allergy reacting to peanut dust in the environment. She's not actually eating the peanuts, but there is enough miniscule exposure to trigger a reaction.

[dcmom]

Keith and Elizabeth,

 

I have been watching your posting. I have an older daughter who has show some of the adolescent pandas symptoms since the same time her younger sister had a clear cut pandas episode. I was wondering if you had any response from any of the doctors about your daughter. Please keep me updated, right now I am just watching her closely....

 

thanks,

 

Eileen

[Iowamom]

Keith and Elizabeth,

 

I have been watching your posting. I have an older daughter who has show some of the adolescent pandas symptoms since the same time her younger sister had a clear cut pandas episode. I was wondering if you had any response from any of the doctors about your daughter. Please keep me updated, right now I am just watching her closely....

 

thanks,

 

Eileen

 

 

Hello. I have been watching posts for some time, trying to figure things out right along with everyone else. It is my understanding from an email I rec'd back from Dr. C that the Cam Kinase II is INSIDE the neurons--not coming from other parts of the body. It is in other parts of the body, but she explicitly stated that what we are talking about in PANDAS is inside the cell, not circulating outside of it. It is activated by some antibody (not a strep antibody) and causing the PANDAS symptoms. I would guess that these are what are crossing the BBB, not the Cam. Obviously, CaM Kinase hangs around awhile. Since it causes the release of dopamine, I would think this is why some of these PANDAS symptoms want to persist in so many kids. I'm only trying to figure out the puzzle like everyone else, so I could be all wet. What I am not wet about is the fact that Dr. C stated that the CaM is inside the neuron.

 

Praying for a major breakthrough for our kids!

Dawn

[KeithandElizabeth]

Hi Eileen:

 

I got the rest of our blood work back today and I am simply at a loss with my 10 year old daughter who really shows no signs of PANDAS. Her blood work was so much worse than my 7 year old PANDA son. Although his blood work was drawn 1 week after steroids, which will decrease the numbers.

 

My daughter had 170% CAM KinaseII and then 4 times the Anti-Tubulin at 4000 and then double the the high normal number for everything else.

 

Dr. Leckman and Dr. Kovacevic said, basically, that these numbers are only part of the story and no one is really sure yet on how to interpret them. Dr. Kovacevic said behavior is the biggest diagnostic criteria. Dr. Cunningham said to feel "lucky" that she doesn't show any symptoms and to just watch her. GREAT!!

 

So, my game plan (because I am not good at just watching) is to get the immunological work up on her as well. I also plan to repeat the test in 1 -2 months.

 

My son, on the other hand, had IVIG 1 week ago and he is showing remarkable changes!!

 

Elizabeth

[dcmom]

Elizabeth-

 

Thank you for your response. My dd, 6 has pandas, from a strep throat infection last January. Her sister, age 9, had strep throat around the same time. She also does not show the signs of pandas, however since the strep throat she has had daily stomach aches. The stomach aches cause her alot of anxiety. We have done the GI thing- with no answers. She has also been more emotional, and has had some "friend" issues at school. These things are all unlike her. I attributed it all to the stress of having a sister with pandas... so now I wonder.

 

I guess there is nothing to do at this point anyway. When my pandas daughter has her immunological workup- if anything is amiss, I guess I will have her sister tested as well. PLEASE keep me updated, as this is overwhelming.

 

I am so glad to hear things are going well!

[kim]

Hello. I have been watching posts for some time, trying to figure things out right along with everyone else. It is my understanding from an email I rec'd back from Dr. C that the Cam Kinase II is INSIDE the neurons--not coming from other parts of the body. It is in other parts of the body, but she explicitly stated that what we are talking about in PANDAS is inside the cell, not circulating outside of it. It is activated by some antibody (not a strep antibody) and causing the PANDAS symptoms. I would guess that these are what are crossing the BBB, not the Cam. Obviously, CaM Kinase hangs around awhile. Since it causes the release of dopamine, I would think this is why some of these PANDAS symptoms want to persist in so many kids. I'm only trying to figure out the puzzle like everyone else, so I could be all wet. What I am not wet about is the fact that Dr. C stated that the CaM is inside the neuron.

 

Praying for a major breakthrough for our kids!

Dawn

 

Dawn,

 

I wonder if Cam Kinase II is elevated in other cells as well as neurons? Maybe it doesn't circulate, but nothing saying it isn't elevated in other area's too?

 

When you said "not a strep antibody," I was confused but after reading below, I wonder if she meant not "only strep " but others that may display a protein/glycan chain (GlcNAc) too? It seems the last sentence is worded so as not to exclude other antigens. Just a thought

 

bolding mine

http://www.csus.edu/bios/faculty/Kirvan/Ki...JNI_article.pdf

 

Behavioral and movement disorders may have antibody responses where mimicry and signal transduction may lead to neuropsychiatric abnormalities. In our study, antibodies in pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS) reacted with the neuronal cell surface and caudate–putamen and induced calcium–calmodulin dependent protein (CaM) kinase II activity in neuronal cells. Depletion of serum IgG abrogated CaM kinase II cell signaling and reactivity of CSF was blocked by streptococcal antigen N-acetylbeta-D-glucosamine (GlcNAc). Antibodies against GlcNAc in PANDAS sera were inhibited by lysoganglioside GM1. Results suggest that

antibodies from an infection may signal neuronal cells in some behavioral and movement disorders.

[peglem]

Keith and Elizabeth,

 

I have been watching your posting. I have an older daughter who has show some of the adolescent pandas symptoms since the same time her younger sister had a clear cut pandas episode. I was wondering if you had any response from any of the doctors about your daughter. Please keep me updated, right now I am just watching her closely....

 

thanks,

 

Eileen

 

 

Hello. I have been watching posts for some time, trying to figure things out right along with everyone else. It is my understanding from an email I rec'd back from Dr. C that the Cam Kinase II is INSIDE the neurons--not coming from other parts of the body. It is in other parts of the body, but she explicitly stated that what we are talking about in PANDAS is inside the cell, not circulating outside of it. It is activated by some antibody (not a strep antibody) and causing the PANDAS symptoms. I would guess that these are what are crossing the BBB, not the Cam. Obviously, CaM Kinase hangs around awhile. Since it causes the release of dopamine, I would think this is why some of these PANDAS symptoms want to persist in so many kids. I'm only trying to figure out the puzzle like everyone else, so I could be all wet. What I am not wet about is the fact that Dr. C stated that the CaM is inside the neuron.

 

Praying for a major breakthrough for our kids!

Dawn

But if the CamK is only inside the neurons, how is it being detected in a blood sample? There are neurons in circulating blood? I'm confused.

[kim]

Peg,

 

I don't think it's being detected in the blood. If we went back and read the papers I think you'd see where it's how the neurons act when exposed to a substance (or deprived of one). In the study below, they detected it from an altered mouse and how the heart reacted to exposure to a drug.

 

 

From the Cam KinaseII thread (bolding mine)

 

http://www.latitudes.org/forums/index.php?showtopic=5082

 

In a recent study from Germany, a mouse model that was missing the gene for the pacemaker ion channel surprisingly responded normally to the drug isoproterenol. Similar to adrenaline, isoproterenol can increase heart rate. This response meant that the ion channel, by itself, does not explain the physiological "fight or flight" heart rate response.

 

Based on this observation, Wu and other colleagues in the lab of the paper's senior author, Mark Anderson, M.D., Ph.D., head of the UI Division of Cardiovascular Medicine, developed mice in which the CaM kinase II function was inhibited in heart cells. When these mice were exposed to the adrenaline-like agent isoproterenol, the stimulant's effect did not occur. As a result, the mice without CaM kinase II function had much slower heart rates than mice that had normal CaM kinase II function. The finding underscored that CaM kinase II activation can increase heart rates.

[peglem]

Peg,

 

I don't think it's being detected in the blood. If we went back and read the papers I think you'd see where it's how the neurons act when exposed to a substance (or deprived of one). In the study below, they detected it from an altered mouse and how the heart reacted to exposure to a drug.

 

 

From the Cam KinaseII thread (bolding mine)

 

http://www.latitudes.org/forums/index.php?showtopic=5082

 

In a recent study from Germany, a mouse model that was missing the gene for the pacemaker ion channel surprisingly responded normally to the drug isoproterenol. Similar to adrenaline, isoproterenol can increase heart rate. This response meant that the ion channel, by itself, does not explain the physiological "fight or flight" heart rate response.

 

Based on this observation, Wu and other colleagues in the lab of the paper's senior author, Mark Anderson, M.D., Ph.D., head of the UI Division of Cardiovascular Medicine, developed mice in which the CaM kinase II function was inhibited in heart cells. When these mice were exposed to the adrenaline-like agent isoproterenol, the stimulant's effect did not occur. As a result, the mice without CaM kinase II function had much slower heart rates than mice that had normal CaM kinase II function. The finding underscored that CaM kinase II activation can increase heart rates.

So, the blood samples we send to Cunningham-they're not actually finding the CamK, but an indicator of activation?

[kim]

I'm sorry Peglem, I wasn't thinking in terms of the test results.

 

I'm sure others could explain that in a heartbeat, but I think they add the sera to a human cell line and measure the results. You get different readings with positive and negative sera.

So yes you are getting an actual reading, but not by something that is just measured in the blood.

[kim]

http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf

 

Fig. 2. Induction of calcium/calmodulin-dependent protein (CaM) kinase II

in human neuroblastoma cells by acute and convalescent Pediatric

Autoimmune Neuropsychiatric Disorders Associated with Streptococcal

infection (PANDAS) sera. (a) All acute PANDAS sera (P1–16A) as a group

significantly (P=0.0011) activated CaM kinase II in comparison to all

matched convalescent sera (P1–16C). ( Depletion of IgG from PANDAS

acute sera (P14A) reduced CaM kinase II activation to basal levels in

comparison to undepleted serum. P values determined by Mann–Whitney

 

Buster gives more detailed info here

 

http://www.latitudes.org/forums/index.php?...amp;#entry36261

[peglem]

http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf

 

Fig. 2. Induction of calcium/calmodulin-dependent protein (CaM) kinase II

in human neuroblastoma cells by acute and convalescent Pediatric

Autoimmune Neuropsychiatric Disorders Associated with Streptococcal

infection (PANDAS) sera. (a) All acute PANDAS sera (P1–16A) as a group

significantly (P=0.0011) activated CaM kinase II in comparison to all

matched convalescent sera (P1–16C). ( Depletion of IgG from PANDAS

acute sera (P14A) reduced CaM kinase II activation to basal levels in

comparison to undepleted serum. P values determined by Mann–Whitney

 

Buster gives more detailed info here

 

http://www.latitudes.org/forums/index.php?...amp;#entry36261

Okay that helps....So, what Cunningham's study is measuring is not how much CamK is there, but the extent to which it is activated by the antibodies? Is that right? (Oh, please be right!)

 

But, of course that brings more questions (will I ever understand this?)

So, when Cunningham says the CamK is elevated over the basal levels- like in my child-242%, was the basal determined specifically for my child by depleting her sample of IgG? Or is there a standard basal that everyone is compared to?

 

If depleting IgG lowers CamK activation, then why would IVIG (which administers IgG, right?) be a helpful treatment?

 

Forgive me if I'm asking too many questions, I just feel driven to make sense of this.