Clonidine, an angioplasty alternative?

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Clonidine, an angioplasty alternative?

Postby Anonymoose » Sun Jan 06, 2013 11:55 am

http://www.nature.com/hr/journal/v33/n6 ... 1041a.html
Efficacy of clonidine in patients with essential hypertension with neurovascular contact of the rostral ventrolateral medulla

Takao Sakuma, Satoshi Morimoto, Yasuko Aota, Nobuyuki Takahashi, Nagaoki Toyoda, Atsushi Kosaki, Minoru Maehara, Noboru Tanigawa, Koshi Ikeda, Satoshi Sawada and Toshiji Iwasaka

Abstract
The rostral ventrolateral medulla (RVLM) is an important center for regulation of sympathetic nerve activity. Several clinical studies have suggested an association between neurovascular contact (NVC) of RVLM and essential hypertension. Microvascular decompression (MVD) of RVLM decreases blood pressure (BP) in hypertensive patients with NVC of this region. Therefore, MVD could be a useful therapeutic strategy to reduce BP in these patients. However, as MVD is an invasive procedure, it is worthy to seek useful antihypertensive agents for hypertensive patients with NVC. It is reported that sympathetic nerve activity is elevated in patients with hypertension accompanied by NVC of RVLM. It is anticipated that sympatholytic agents could be effective in lowering BP in these patients. In this study, we investigated the efficacy of clonidine, an α2 adrenergic agonist, in essential hypertensives with NVC of RVLM. Thirty consecutive essential hypertensive patients with NVC and 30 consecutive essential hypertensive patients without contact were treated with clonidine for 4 weeks, and decreases in BP and plasma norepinephrine levels were compared between the two groups. Decreases in BP and plasma norepinephrine levels were significantly greater in patients with NVC than in those without contact. These results suggest that clonidine exhibits significantly greater reductions of BP and sympathetic nerve activity in essential hypertensive patients with NVC compared with those without contact of the rostral ventrolateral medulla.
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Mon Jan 07, 2013 1:15 pm

This sounds eerily like the random CCSVI angioplasty results. Works in some...doesn't in others. The warm finger effect was kind of exciting. :)

http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract
In the MS patients after clonidine, the haemodynamic responses varied. In five out of ten MS patients, as in the controls, there was a fall in blood pressure and superior mesenteric vascular resistance, while finger temperature rose. There was no haemodynamic response to clonidine in the other five MS patients. In eight out of ten MS patients there was no rise in plasma growth hormone levels after clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction with the previous physiological studies, suggest involvement of central sympathetic interconnections in five of the MS patients, probably as part of the demyelinating process.
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Re: Clonidine, an angioplasty alternative?

Postby Cece » Mon Jan 07, 2013 2:00 pm

Anonymoose wrote:This sounds eerily like the random CCSVI angioplasty results. Works in some...doesn't in others.

It's not clear if "it works in some, doesn't in others" is true for CCSVI. First step is to make sure we are evaluating if the venoplasty works or not based on CCSVI symptoms. Not on MS symptoms. Second is to be sure that all CCSVI is diagnosed and treated successfully and that the veins don't close up.
The warm finger effect was kind of exciting. :)

http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract
In the MS patients after clonidine, the haemodynamic responses varied. In five out of ten MS patients, as in the controls, there was a fall in blood pressure and superior mesenteric vascular resistance, while finger temperature rose. There was no haemodynamic response to clonidine in the other five MS patients. In eight out of ten MS patients there was no rise in plasma growth hormone levels after clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction with the previous physiological studies, suggest involvement of central sympathetic interconnections in five of the MS patients, probably as part of the demyelinating process.

Abnormalities of the autonomic nervous system seen in the MS patients.
I wonder why I didn't hear more about this as part of MS, prior to experiencing the autonomic improvements after CCSVI treatment. I suppose the assumption in MS is that it is due to demyelination and there's nothing you can do about it? Because they should have been trying to do something about it. Being able to sweat is fundamental and useful and my life is better now: exercising, being outside in the summer, outlasting a fever.

Here's the wikipedia entry on clonidine. http://en.wikipedia.org/wiki/Clonidine
It's an antihypertensive?

Clonidine treats high blood pressure by stimulating α2 receptors in the brain, which decreases cardiac output and peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic tone.[20]
It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1-receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Mon Jan 07, 2013 2:42 pm

IF (that's a big if) the ccsvi angioplasties reduce the NVC between RVLM and adjacent vessels by eliminating pressure build-up in the vessels, then we may have an explanation as to why angioplasty works in some patients...why it only works to alleviate some of the MS symptoms...and why it doesn't work in some as other factors are contributing to their autonomic dysregulation. If IRs had a looky-looky at the RVLM and adjacent vessels before, during, and after angioplasty, we'd have a better idea if this plays a part. Seems easy enough. lol

I don't know why our doctors aren't more proactive in the care of our autonomic and hpa-axis issues. I had no idea they played a part in MS until I clumsily worked my way backwards with my aldosterone obsession. These issues CAN likely be controlled, decreasing the negative impact of MS.
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Mon Mar 04, 2013 7:07 pm

http://www.inrs-nrr.org/category/uncategorized/page/3/
Clonidine improves cognitive deficits by regulating synaptic strength in chronic cerebral hypoperfused rats
Uncategorized11/08/2012 17:12:460 Comments
Changjun Li, Yun Lu, Qing Lv, Xulin Xu, Lianjun Guo

Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China

Corresponding author: Lianjun Guo, gljyl@yahoo.com.cn.

Abstract
Permanent bilateral occlusion of the common carotid arteries in rats is an established experimental model to investigate chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Three weeks after surgery, intraperitoneal injection of clonidine (0.05 mg/kg) was administered once a day. After 1 week of treatment, the Morris water maze was utilized to evaluate the effect of clonidine on spatial learning and memory performance. Electrophysiological recordings were performed in vivo. A concentric bipolar stimulating electrode was placed in the ipsilateral Schaffer collaterals of the right hemisphere. Recording electrode was positioned in the CA1 stratum radiatum. LTP was induced with four trains of 100 Hz, 1s stimulation separated by 5 minutes. Immunofluorescence staining was used to investigate the influence of clonidine on pyramidal neuron numbers and expression of HCN1 and HCN2 in hippocampus CA1. Latency to find the platform of chronic hypoperfusion treated rats was longer than sham-operated group (P < 0.01). Escape latency of clonidine group was significantly shorter compared with the ischemic group (P < 0.05). Induction of LTP in hippocampal CA1 region was significantly enhanced in ischemic group compared with sham-operated rats (P < 0.01) and this pathological enhancement was attenuated by clonidine (P < 0.05). In hippocampal CA1 subdivisions, pyramidal neuron numbers were significantly lower in the ischemic group, which could be reduced by Clonidine. In the ischemic group, the fluorescence intensity of HCN1 and HCN2 was significantly lower than sham-operated group, and clonidine could improve the expression of HCN1 and HCN2 in CA1 region of ischemic rats. Thus, clonidine improves cognitive deficit possibly by inhibiting decreased expression of HCN1 and HCN2 channels to alleviate the over-excited synapse, caused by chronic cerebral ischemia.
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Re: Clonidine, an angioplasty alternative?

Postby Cece » Mon Mar 04, 2013 7:35 pm

Really interesting, as usual, Anonymoose.
Thus, clonidine improves cognitive deficit possibly by inhibiting decreased expression of HCN1 and HCN2 channels to alleviate the over-excited synapse, caused by chronic cerebral ischemia.
How does chronic cerebral ischemia cause the synapse to be over-excited? Do you know? And then clonidine increases the expression of HCN1 and HCN2 channels? I'm not sure what those are or if I'm following this correctly.
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Mon Mar 04, 2013 7:58 pm

Hehe. I have no idea. I ran into that study while looking for something else and had to "file" it before I lost it. That paper will take significant research (for me) to understand...a lot of new terminology. So for now it just sounds like a good thing to me. :P
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Mon Mar 04, 2013 8:58 pm

Whoa. I'm still trying to figure this all out but something just hit me.
In hippocampal CA1 subdivisions, pyramidal neuron numbers were significantly lower in the ischemic group, which could be reduced by Clonidine.

That means hypo perfusion/ischemia could cause hpa axis dysregulation. Which means successful and complete ccsvi PTA might fix the Aldosterone issue...especially if done early before all of the vascular damage occurs.
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Please do not use Clonidine as angioplasty alternative

Postby MarkW » Tue Mar 05, 2013 2:30 am

Hello Anonymoose and anyone considering Clonidine,
Please do not use Clonidine as an angioplasty alternative. Get the venoplasty done by a leading practitioner (diagnosis with CV +IVUS) before considering Clonidine and then under medical supervision. I was an industrial pharmacist and my industry loves long term use of medicine. But CCSVI syndrome produces a physical problem (stenoses) and needs a physical treatment first.
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Please do not use Clonidine as angioplasty alternative

Postby Anonymoose » Tue Mar 05, 2013 8:44 am

MarkW wrote:Hello Anonymoose and anyone considering Clonidine,
Please do not use Clonidine as an angioplasty alternative. Get the venoplasty done by a leading practitioner (diagnosis with CV +IVUS) before considering Clonidine and then under medical supervision. I was an industrial pharmacist and my industry loves long term use of medicine. But CCSVI syndrome produces a physical problem (stenoses) and needs a physical treatment first.
Kind regards,
MarkW

MarkW,
I do believe you are correct. :) Given that reduced perfusion can cause hpa-axis dysregulation, I now believe that CCSVI *can* cause MS, the whole shaboodle. I'm no longer worried about Cece and those who have found near complete recovery through PTA. I think they are cured (so long as veins stay open). Yay!

I'm pretty sure I don't have CCSVI. I don't have any of the trademark symptoms and I've had a lifetime of high stress levels to botch my hpa-axis w/o any other contributing factors. Clonidine is doing wonders for me and I'm starting to suspect my hippocampus is recovering from it's insensitivity to cortisol. The clonidine is starting to make me feel a bit sleepy, which to me indicates that my hpa-axis might be becoming less active, warranting less suppression. So, maybe taking clonidine isn't a forever thing for those w/o ccsvi.

For those who haven't found success through PTA (or chiro/dental options, I keep forgetting about those), CCSVI or not, I think clonidine is a great and relatively safe option. It's ability to tame MS symptoms and make life more comfortable and normal alone should make it worth a try. Of course, thus far, it's a study of one. I can only hope it would have the same results for others. Luckily, just like there are IRs willing to perform PTA, there are doctors willing to prescribe Clonidine off label. If you (a general "you") think this makes sense, you don't have to wait for the MS doctors to come to this conclusion. Just try it. <shrug>

Btw, that study about hypoperfusion and CA1 pyramidal neuron activity in the hippocampus...that's the CCSVI tie-in to MS. It's (almost) proof that CCSVI can cause the MS cascade...well, once they realize that hpa-axis dysregulation is a key factor in the development and progression of MS. Oh boy. This could take a while. :roll:
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Re: Clonidine, an angioplasty alternative?

Postby Music » Tue Mar 05, 2013 9:23 am

Anonymoose,
I am very happy for you that clonidine is doing great things for you. Unfortunately it was not so for me. In the middle of my two year stint with baclofen in the late ‘90’s, my neuro had me take clonidine as well. WHOA! Mentally and emotionally I felt like I was going to fall off the edge of the earth. Only took it for a month. Quit the baclofen also as I had gotten EXTREME insomnia from it. Was it the mixing of the two, I don’t know. Neuro said one thing, head nurse said another. As all of us will react differently to different treatments, I guess I’m not a good candidate for meds. I am glad you are having good luck.

P.S. LDN didn’t help me also. Haven’t been on anything since.
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Tue Mar 05, 2013 9:52 am

Music wrote:Anonymoose,
I am very happy for you that clonidine is doing great things for you. Unfortunately it was not so for me. In the middle of my two year stint with baclofen in the late ‘90’s, my neuro had me take clonidine as well. WHOA! Mentally and emotionally I felt like I was going to fall off the edge of the earth. Only took it for a month. Quit the baclofen also as I had gotten EXTREME insomnia from it. Was it the mixing of the two, I don’t know. Neuro said one thing, head nurse said another. As all of us will react differently to different treatments, I guess I’m not a good candidate for meds. I am glad you are having good luck.

P.S. LDN didn’t help me also. Haven’t been on anything since.

Thanks, Music. That's good to know. Was it an intrathecal combination or oral/transdermal? The two drugs are sometimes combined intrathecally to reduce spasticity but I'm not sure they would work the same administered via different avenues. Also, the two apparently have some pretty strange interactions. Baclofen can make you feel spacey and clonidine can increase the effect of baclofen. Maybe that's why you fell off the edge of the earth? http://www.ncbi.nlm.nih.gov/pubmed/2873522

At any rate, it really is useful to know the two drugs sometimes don't play well together. Thank you!
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Re: Please do not use Clonidine as angioplasty alternative

Postby Cece » Tue Mar 05, 2013 12:53 pm

Anonymoose wrote:I'm pretty sure I don't have CCSVI. I don't have any of the trademark symptoms and I've had a lifetime of high stress levels to botch my hpa-axis w/o any other contributing factors.

This is really interesting too. Awhile back, I speculated that we might be self-selecting: that those of us who went in to get checked for CCSVI were more likely to have CCSVI because we recognized the symptoms and we had them. So you have self-selected yourself not to get checked because you do not recognize the symptoms in yourself.

If CCSVI is present in nearly 100% of pwMS, then we all are almost guaranteed to have CCSVI and self-selecting isn't a big issue.
Otherwise self-selecting could explain why the very high percentages of CCSVI in MS that are being seen clinically are not being seen in the ultrasound studies.

I also remember a conversation with a fellow patient back in 2011, right before she had angioplasty done, and afterwards she said that she was having improvements in a lot of the usual symptoms that she hadn't even been aware that she had until they improved.

(And I hope you are right about those of us who've had big improvements no longer needing to worry. I still worry.)
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Tue Mar 05, 2013 2:43 pm

Cece wrote:This is really interesting too. Awhile back, I speculated that we might be self-selecting: that those of us who went in to get checked for CCSVI were more likely to have CCSVI because we recognized the symptoms and we had them. So you have self-selected yourself not to get checked because you do not recognize the symptoms in yourself.

If CCSVI is present in nearly 100% of pwMS, then we all are almost guaranteed to have CCSVI and self-selecting isn't a big issue.
Otherwise self-selecting could explain why the very high percentages of CCSVI in MS that are being seen clinically are not being seen in the ultrasound studies.

I also remember a conversation with a fellow patient back in 2011, right before she had angioplasty done, and afterwards she said that she was having improvements in a lot of the usual symptoms that she hadn't even been aware that she had until they improved.

(And I hope you are right about those of us who've had big improvements no longer needing to worry. I still worry.)

I think you might be on to something with the self-selecting theory. At this point, I wouldn't pursue PTA. I have wussy MS (so far) and the thought of having my veins roto rooted skeeves me out much more than my mild symptoms bother me. I would be interested in helping out in a study though. I'm sure there are a lot of other wussy MSers out there feeling the same way, if they are even aware of CCSVI. No wonder the numbers are all messed up. I propose they throw them out!

Do you recall which symptoms your fellow PTA patient wasn't aware of? I feel like I'm pretty aware of the changes I've experienced since the onset of my MS. But if one person can be oblivious, I certainly could be too.

I hope I'm right too. :)
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Re: Clonidine, an angioplasty alternative?

Postby Anonymoose » Thu Mar 07, 2013 9:05 am

http://www.nationalmssociety.org/news/n ... x?nid=7446

As we constantly secrete aldosterone, our bodies retain far more salt than is healthy. According to info in link, this will stimulate MS related Th17 activity. Clonidine, and other drugs suppressing or blocking aldosterone, will return our sodium levels to normal.

I felt I needed to post this here because not everyone reads the general forums.

On a sidenote: After less than two months on Clonidine, I have become more responsive to the drug (the opposite of what usually happens) and I am having to cut down on my dosage or maybe the doctor will say to just stop taking it when I call him today. I believe my hippocampus has regained sensitivity to cortisol and my negative feedback loop is once again working...hpa-axis is correcting on short term therapy. This time-frame is consistent with studies performed on cortisol suppression and hippocampus re-sensitization. I don't think it will happen this way in people with untreated CCSVI because the hypoperfusion will continue to be an issue with hippocampus function. However, the clonidine should still work to address hpa-axis activation so long as one takes it.
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