Please Help Me Make Sense Of All This

[Lenna]

Boy, do I need help sorting this out!

When my son was nine years old, he had Kawasaki Disease. That's a really atypical age to have it, but I don't think that's relevant. He was diagnosed and treated in a timely fashion with Intravenous gamma globulin (IVIG). He bounced back quickly and has had all the required follow-up echocardiograms, which have shown no damage to his heart.

Then, when he was 15 years old, he developed POTS.

I spoke to the cardiologist who treated his Kawasaki Disease and to every other doctor who he's seen in the past 2-1/2 years about whether there could be a connection between the Kawasaki Disease and POTS. I mean, how could there not be? How can a kid develop 2 really strange illnesses like that in a 6 year span and not have them be related? But every doctor has said that there is no relationship, or at least none that they know about.

Now I think I found the connection, but before I bring it to his POTS neurologist who already thinks I'm nuts, I'd love some input from any of you who are knowledgeable about things like nitric oxide. Please help me understand if this makes any sense. And please put this in as simple terms as possible, because sometimes I really get lost in all the medical terminology.

So, what I found is that studies have been done that show that after recovery from Kawasaki Disease, there may be long-term endothelial dysfunction. One study from 1996, for example, is looking for a connection to atherogenisis, but the thing that jumped out at me is the mention of endothelial dysfunction causing abnormalities in the L-arginine/nitric oxide pathway which can lead to abnormal control of vascular tone and blood flow. http://circ.ahajournals.org/cgi/content/full/94/9/2103

Could this be a clue or the key to my son's POTS?

Dan has classic symptoms - orthostatic tachycardia, dizziness, fatigue, headache (mild), insomnia, nausea, brain fog. His blood pressure is relatively stable. He drinks 3-litres of water a day but seems to always be hypovolemic. I do NOT think he has pooling in his extremities. Midodrine and Mestinon made him feel worse. Florinef didn't have much of an effect. He recently started on a BB - metropolol - which he's tolerating well but it isn't really helping him so far.

I don't know if I'm making too much of this "link". And I don't know if I should be happy or upset about it. If endothelial dysfunction is his problem, can it be treated? Does this mean he's unlikely to outgrow POTS?

Thanks-

Lenna

[arizona girl]

Lenna, I don't know much about kawasaki or the other stuff, but I do know a bit about how neuropathy can cause pots symptoms. If there is neuropathy of the vessels which your son has had a history of, the vascular nerves are suppose to contract on standing and oppose gravity to get the blood to the brain. If the nerves fail to do this the blood will pool and cause the pots symptoms in attempt to overcome the blood pooling. Some of us have an adrenaline surge on standing, which also causes the vessels to constrict to get blood back up. Those of us that do that tend to get orthostatic hypertension as the adrenaline causes an overcompensation. Some us are only tachy and some of us go hypotensive.

By skin biopsy I was diagnosed with small fiber autonomic neuropathy probably caused by an autoimmunity. Is kawasaki autoimmune? Anyway the small fiber and c nerves are the ones that cause the vessels to contract on standing. Has your son been screened yet for small fiber neuropathy? It could be logical to think that the kawasaki may of damaged those nerves.

The test I had to confirm this were TTT, skin biopsy to look for small fiber damage and supine and standing catecholamines (adrenaline). There are also sweat tests that can look for it.

I don't think you are crazy for looking for a connection, it seems logical to me. If your neuro, though already thinks your nuts, it might be time to have a new neuro put a fresh set of eyes on this. I would look for a neuro who specializes in autoimmune neuropathies and one who knows how to test for and treat small fiber neuropathies. This is a newer field in neurology, so you might have to do some research to find one in your area. The good news is that there are other ways to treat it other then just treating symptoms. None of the treatments your son had were either appropriate for me or worked for me either. I am in that process right now of treating cause. I've had some mild improvements, but it is to soon for me to say this treatment course will in the end work. BTW Ivig is also a treatment for small fiber neuropathy. Good luck with this!

[Lenna]

Hi Arizona Girl,

Thanks for your reply. To answer your questions: Yes, my son has been diagnosed with small fiber neuropathy, based on a quantitative sensory test (QST). He hasn't had any treatment specifically tailored to that. What sort of treatments are you trying? I don't think there's a definitive answer as to whether or not Kawasaki is autoimmune. It's another one of those illnesses - like POTS - where so much is unknown.

Earlier today I emailed his Kawasaki cardiologist and asked her whether the studies indicating endothelial impairment from Kawasaki Disease are valid. Her reply was:

"There is no relationship between POTS and Kawasaki disease. Some research studies have found problems with endothelial function and vascular reactivity that could be relevant to future risk for atherosclerotic disease but this isn?t relevant to POTS."

Am I not getting this? Isn't vascular reactivity completely relevant to POTS??

Lenna

[arizona girl]

And this my friend is the difference of opinion between the research cardiologists and neurologists. Neuropathies cause cardiovascular symptoms, cardiologists if they can't find a cardiovascular cause will simply treat symptoms, which doesn't get at cause outside of cardiology. There are a few cardio's that look broader like Dr. Grubb in toledo, but most don't.

As small fiber neuropathy has already been diagnosed, my guess is that is what is causing the pots symptoms. Perhaps the kawasaki damaged the small fiber nerves leading to it. So there could be a relationship. A cardiologist though may not make that connection because they are not neurologists.

A neurologist treating small fiber neuropathy is who I would see. Of course in my case I didn't make it to a neurologist until I had spent many years testing with all the other specialists out there. Had I seen a neuro sooner maybe I would have been diagnosed sooner.

Both neuro's and cardio's treat pots. Cardio's don't treat neuropathies or autoimmunites. Your cardio is only looking at vessel blockage and is completely ignoring the fact that nerves control how the vessels open and contract. So nerves are involved with vessels and those nerves in the vessels are the small fiber and c nerves. Many other specialists may be involved if you have found another cause for your pots like EDS or Anemia. I think a lot of us get stuck treating with cardio's and never look further into underlying cause.

My treatment course is experimental, but follows same proven treatment plan established for other neuropathies. Those treatments can be symptom based only, IVIG, plasmapheresis, immune dampening meds like cellcept.

[ramakentesh]

While it hasnt been demonstrated that Kawasaki disease is an autoimmune illness its is certainly considered likely that it is. Also I think it was fairly recently speculatively connected to carpet cleaning products - or there was something i read that mentioned this connection.

Whether there is a connection isnt really clear because the cause of either condition is still debated.

if your son has been diagnosed with small fiber neuropathy then that is a fairly common cause of POTS symptoms. Altered endothelial function is another possibility, although this is really only implicated thus far in POTS in relation to either the release of vasoactive inflammatory peptides and alterations of neuronal (noradrenergic and neuronal nitric oxide, parasympathetic) blood flow regulation.

Inflammation alone can explain a model of POTS. Increased C-reactive protein reduces the catabolism of angiotensin II which has a paradoxical effect on blood volume and potentiates the effects of norepinephrine.

[Lenna]

So, Rama, help me understand your reply. Is neuronal nitric oxide different than endothelial nitric oxide? Is one implicated in POTS but not the other?

Can someone be tested for their levels of NO?

Is there treatment for NO deficiencies?

Thanks-

Lenna

[ramakentesh]

yeah they are different. Endothelial nitric oxide is released in the endothelium to vasodilate. Most vasodilators including histamine, substance P, calcitonin gene related peptide, etc all cause the release of nitric oxide in the endothelium. Neuronal nitric oxide controls sympathetic outflow and can regulate vasodilation and vasoconstriction but also seems to regulate how our body responds to a variety of molecules at the neuronal level.

In Low Flow POTS (Stewart and Medows) it was found that bioavailability (the availability) of endo. nitric oxide was normal but neuronal nitric oxide was reduced. Since that time neuronal nitric oxide has been proven to be behind post-exercise malaise in Muscular Distrophy and other conditions.

Neuronal nitric oxide can be regulated by oxidisive stress and perhaps inflammation. Increased angiotensin II levels are associated with increased oxidisive stress and an increase in nitric oxide derived free radicals - more free radicals appears to result in impaired availability of nitric oxide at the neuronal level in the nervous system.

Inflammation can also increase angiotensin II which again has many effects, all which could potentially result in a form of POTS. Increased C-reactive protein results in reduced angiotensin II catabolism, and again reduced neuronal nitric oxide and potentially POTS.

Finally there was research by Emily Garland that suggested that certain genes that regulate endothelial nitric oxide were more likely to predispose someone to developing POTS.

Increased nitric oxide in the endothelial level doesnt automatically suggest that it is the problem - as above, it may be the result of abherant levels of many vasoactivei peptides.

As for there being no connection. Well I went from being prettymuch healthy bar a bit more fatigue than the average person to having POTS and Ankylosing Spondylitis in the space of four months. Im told there is no connection but how many times can someone tell me the sky is purple before I accept what I know isnt true? They just HAVE to be somehow connected - just because it doesnt fit the current medical models of these conditions doesnt mean is isnt true.

[mvdula]

Wow, Rama. You understand all of this so well. I think you will firgure it all out just reading the studies before any of the Drs do! Thanks for your posts - the insight gived me hope that there will be a real cure/effective treatment someday soon!

[ramakentesh]

I cant really accept the praise - my interest is purely for self-interest

i hope that makes sense - its a little confusing when I read it now.

I guess POTS seems to be a label for a lot of different problems - and its hard to say which of those (which are still poorly characterised and understood in all cases) might be related to Kawasaki disease.

Reduced neuronal nitric oxide occurs in things like heart failure as does reduced MIBG uptake and a few other things that are also found in POTS.

[Lenna]

Thank you for your replies! I'll let you know where this leads (if anywhere...)

Lenna