No treatment works for me

[Castorp]

During the last two years I have been experiencing various debilitating symptoms, including tachycardia when standing, problems of temperature regulation (chills and hot flashes, although the temperature is usually below 98.6), unrefreshing sleep and chest pain. However, the worst symptom I have is a non-stop crushing fatigue-malaise 24/7. I have been suffering this unrelenting fatigue-malaise every time since the beginning of my illness, even while resting and my heart rate and blood pressure are okay. This horrible feeling is really incapacitating and never goes away.

After ruling out other conditions, my doctors thought that I may have CFS/ME. However, this diagnosis was dismissed because I have no post-exertional malaise (PEM), which appears to be the cardinal symptom in this condition. Finally,   my doctors diagnosed me with POTS from the results of a Tilt test. My POTS seems to be apparently autoimmune, as I  am positive for various adrenergic receptor antibodies. Since then, I have attempted numerous treatments:

-Treatments to address the (apparently) autoimmune cause of POTS: Steroids, IVIG, plasmapheresis and CellCept.

-Meds to treat the symptoms: beta-blockers (bisoprolol, propanolol), ivabradine, mestinon, LDN, antidepressants (mirtazapine, duloxetine), amantadine, gabapentin and anti-inflamatory drugs.

-Supplements: vitamin B12, vitamin D, magnesium, acetyl-L-carnitine, coenzime Q10, inosine, tyrosine and fatty acids.

Unfortunately, none of this treatments have worked for me. Indeed, they have had absolutely no effect on my symptoms, which means I continue to suffer every time. I am really desperate and my doctors seem not to know what to do. Are there other treatments that I could try to improve my situation? I would be very grateful if you could share your experiences.

Thank you so much for your help.

[RecipeForDisaster]

I would love to follow you because you sound similar to me, and I’m so let down that these things didn’t help you. I haven’t gotten to try the autoimmune parts of your trial, because I am waiting on a biopsy to try to qualify for IVIG and I don’t have any of my 17 doctors working on the immune end very well. I thought steroids could help, but I may have too much cortisol already, because my eosinophils are persistently 0.

I have very low BP and no POTS.

I’ve read about things like Ubrelvy being used for CFS, and one doctor mentioned this to me (but I guess he lost interest in me when I couldn’t do the invasive CPET). You could also try different beta blockers - I don’t think I’d get ANY sleep if not for mine. DDAVP is somewhat helpful. IV fluids are the only thing that is super helpful for me. Adderall is good, but it’s a pain to get. It doesn’t help me sleep, and I badly need to do that… good luck and keep us posted!

[CallieAndToby]

I'm going to follow this thread too, I'm a very complex mystery case and I can't really tolerate the autonomic medications and they don't help in me being upright. 

So I was diagnosed with ME (myalgic encephalomyelitis) by 3 different physicians and it does usually involve post exertional malaise which is basically crashing and getting very very sick (or at least more fatigued) after any physical or mental activity. Though to receive a diagnosis there is a huge packet your physician has to go through and there is a lot of testing involved. I.E. they look at natural killer cell count and function, B cells, T cells, cytokine levels, potential chronic infections which is also hallmark of ME but some people don't respond to the treatment but over a decade ago I tested positive for Parvo and different strains of coxsackie. I am extremely fatigued too, it's just insane.

IVIG did help me in the past, saline infusions as well, and I was just diagnosed with small fiber neuropathy but no word from the physician who ordered the biopsies. There isn't really a concrete treatment for ME and it's so complicated, there's just no funding over here for this disabling disease but many patients get help from different things sounds like you've tried some with the LDN, anti-inflammatory medications, etc. 

Some ME patients have found through geneticists (genetic testing) that they have Mitochondrial disease. I don't really know the treatment for this but causes bad fatigue starting at a cellular level. 

 

[supertired]

I'm in this boat too, but not down the road as far... I've been doing IVIG for a long time now... gave it a shot well past the year mark. I'd be interested in your treatments re the autoimmune cause, if you'd care to share? IVIG is torture for me, so I'm wondering if I should even bother to try something else... like if it's really autoimmune, wouldn't IVIG work? Why try the others?

I get a tiny touch of help from the mestinon, maybe like 5 percent. 

I had to laugh (cry)... I have all those vitamins and supplements in my cabinet too... was getting ready to try some of the acetyl-L-carnitine and coenzime Q10 ones... they are supposed to help your body use oxygen better, right?

[RecipeForDisaster]

Mestinon helps me about 15%. It’s worth taking it but not by a lot. 
 

At least acetyl L carnitine and alpha lipoic acid help my neuropathy. My neurologist confirmed yesterday that he is interested in trying IVIG if my biopsy comes out with eligible results. I did dread IVIG, but I dreaded iron infusions and did fine with them. Hopefully this would also go well.

[Castorp]

Thank you so much for your replies.

@supertired, in my opinion IVIG is clearly worth trying if there are signs of autoinmunity (e.g. positive antibodies,...).  In fact, IVIG  has been used increasingly with significant efficacy in the treatment of autoimmune forms of dysautonomia and small fiber neuropathy. As an example,

https://www.karger.com/Article/Fulltext/498858

Unfortunately, there is not one-size-fits-all solution in these diseases, and not all patients improve with IVIG. Nevertheless, theoretically failure to respond to IVIG does not preclude a  positive response to other immune-modulatory therapies such as plasmapheresis, rituximab ororal immunosupressant drugs (e.g. Cellcept). However, taking into account the potentially serious side effects of these other treatments, I think that it is a good idea to start with IVIG.

I have used acetyl-l-carnitine and coenzime q10 because their ability to enhance cellular energy production. Nevertheless, as with all the treatments I have attempted during these two years, these supplements did not have any effect on my crushing fatigue.

In view that currently I have no treatment,  I am thinking about attempting mestinon again.@RecipeForDisaster@supertired, what dose of this medication do you take? How long did you have to wait before see the effect its effect?

Thanks again for your help.

 

[RecipeForDisaster]

2 hours ago, Castorp said:

Thank you so much for your replies.

@supertired, in my opinion IVIG is clearly worth trying if there are signs of autoinmunity (e.g. positive antibodies,...).  In fact, IVIG  has been used increasingly with significant efficacy in the treatment of autoimmune forms of dysautonomia and small fiber neuropathy. As an example,

https://www.karger.com/Article/Fulltext/498858

Unfortunately, there is not one-size-fits-all solution in these diseases, and not all patients improve with IVIG. Nevertheless, theoretically failure to respond to IVIG does not preclude a  positive response to other immune-modulatory therapies such as plasmapheresis, rituximab ororal immunosupressant drugs (e.g. Cellcept). However, taking into account the potentially serious side effects of these other treatments, I think that it is a good idea to start with IVIG.

I have used acetyl-l-carnitine and coenzime q10 because their ability to enhance cellular energy production. Nevertheless, as with all the treatments I have attempted during these two years, these supplements did not have any effect on my crushing fatigue.

In view that currently I have no treatment,  I am thinking about attempting mestinon again.@RecipeForDisaster@supertired, what dose of this medication do you take? How long did you have to wait before see the effect its effect?

Thanks again for your help.

 

I just saw my neurologist yesterday and he confirmed he is interested in IVIG - BUT I a have to have the right findings on my biopsy, even though I have an insanely high (and increasing) IGG abs FGFR3. 
 

I take 2-3 180mg extended release pyridostigmine tabs daily. I’ve never had side effects, and it didn’t take long to see mild effects from even 60mg 3 times daily. 

[Castorp]

39 minutes ago, RecipeForDisaster said:

I just saw my neurologist yesterday and he confirmed he is interested in IVIG - BUT I a have to have the right findings on my biopsy, even though I have an insanely high (and increasing) IGG abs FGFR3.

Curiously I also have a high level of FGFR3 antibodies, although this finding is not particularly relevant for my doctors. However, as far as I am aware, FGFR3 antibodies are positively associated with small fiber neuropathy. I hope that the findings of your biopsy allow you to attempt IVIG, which is an  useful treatment for many people.

[CallieAndToby]

8 hours ago, Castorp said:

Thank you so much for your replies.

@supertired, in my opinion IVIG is clearly worth trying if there are signs of autoinmunity (e.g. positive antibodies,...).  In fact, IVIG  has been used increasingly with significant efficacy in the treatment of autoimmune forms of dysautonomia and small fiber neuropathy. As an example,

https://www.karger.com/Article/Fulltext/498858

Unfortunately, there is not one-size-fits-all solution in these diseases, and not all patients improve with IVIG. Nevertheless, theoretically failure to respond to IVIG does not preclude a  positive response to other immune-modulatory therapies such as plasmapheresis, rituximab ororal immunosupressant drugs (e.g. Cellcept). However, taking into account the potentially serious side effects of these other treatments, I think that it is a good idea to start with IVIG.

I have used acetyl-l-carnitine and coenzime q10 because their ability to enhance cellular energy production. Nevertheless, as with all the treatments I have attempted during these two years, these supplements did not have any effect on my crushing fatigue.

In view that currently I have no treatment,  I am thinking about attempting mestinon again.@RecipeForDisaster@supertired, what dose of this medication do you take? How long did you have to wait before see the effect its effect?

Thanks again for your help.

 

What kind of antibody testing are y'all getting? Even after the positive small fiber neuropathy biopsy results, nobody has done any further digging or antibody testing and IVIG helped me in the past with dysautonomia but I only got approved for 6 months for autoimmune encephalitis. It's too expensive as well and the insurance companies don't want to pay for it, a close family member has an FDA approved condition of primary immunodeficiency and she can't get it either but has constant infections. I personally can't tolerate any immunosuppressive medications (steroids, rituximab). 

[Pistol]

@CallieAndToby - I know od someone who recently had extensive genetic testing done for dysautonomia at Mayo. I assume Vandi will do it too, but I know you were not able to tolerate the trip when you had your appointment. 

[Castorp]

9 hours ago, CallieAndToby said:

What kind of antibody testing are y'all getting? Even after the positive small fiber neuropathy biopsy results, nobody has done any further digging or antibody testing and IVIG helped me in the past with dysautonomia but I only got approved for 6 months for autoimmune encephalitis. It's too expensive as well and the insurance companies don't want to pay for it, a close family member has an FDA approved condition of primary immunodeficiency and she can't get it either but has constant infections. I personally can't tolerate any immunosuppressive medications (steroids, rituximab). 

I live in Spain and here the employment of IVIG for dysautonomia mainly depends on the criterium of your doctor. In my case my doctor considered that the presence of positive adrenergic receptor antibodies was enough to justify the use of IVIG. Nevertheless, in view of the null response and probably for economic reasons, I only  received two cycles of IVIG.

[supertired]

@Castorp @RecipeForDisaster - for the Mestinon, I have a script for 60mg 3X a day - I can't really tolerate that though, as I get tremor with it... so I take it "as needed"... like, if I *have* to get up and out the door for an appointment, taking one can make the difference between being able to get out the door and not. For me, I feel the effects of one pill within 10-15 min or so, and it lasts for about ~4 hours. So if I'm having a weak day and need a little extra strength, it can help a bit. It does mask the signs I'm going to pass out though, so I have to be more careful if I take it. And like I said, the tremor it induces is small, but annoying. (and seemed to cause some weird interaction with some nasal sprays I was prescribed and made the tremors really, really bad.) but this seems very unusual.

FWIW - for the IVIG, justified by biopsy - you can remind your doctors that if your SFN biopsy comes close to the cutoff - that the cutoff is pretty arbitrary - and that really understanding your results depends on your "starting point". so if there is clinical evidence/opinion that justifies a dx of SFN, that can help not being tied so closely to the exact SFN biopsy percentile. but, obvs, approval depends a lot on your insurance and how much your doc thinks it's justified.

i have a really hard time with IVIG... i'm one of those cases that has to have insanely slow rates, and infusions spaced weekly apart. been on it a long time now - i think i'm probably going to be one of the "non-responders", but i want to give it it's due just in case - i've come this far, lolz - would hate to have to start over with the "it may take a year or more to start working" 😕

interesting that the supplements may help neuropathy... i'm excited to start trying that... 

[RecipeForDisaster]

4 hours ago, supertired said:

@Castorp @RecipeForDisaster - for the Mestinon, I have a script for 60mg 3X a day - I can't really tolerate that though, as I get tremor with it... so I take it "as needed"... like, if I *have* to get up and out the door for an appointment, taking one can make the difference between being able to get out the door and not. For me, I feel the effects of one pill within 10-15 min or so, and it lasts for about ~4 hours. So if I'm having a weak day and need a little extra strength, it can help a bit. It does mask the signs I'm going to pass out though, so I have to be more careful if I take it. And like I said, the tremor it induces is small, but annoying. (and seemed to cause some weird interaction with some nasal sprays I was prescribed and made the tremors really, really bad.) but this seems very unusual.

FWIW - for the IVIG, justified by biopsy - you can remind your doctors that if your SFN biopsy comes close to the cutoff - that the cutoff is pretty arbitrary - and that really understanding your results depends on your "starting point". so if there is clinical evidence/opinion that justifies a dx of SFN, that can help not being tied so closely to the exact SFN biopsy percentile. but, obvs, approval depends a lot on your insurance and how much your doc thinks it's justified.

i have a really hard time with IVIG... i'm one of those cases that has to have insanely slow rates, and infusions spaced weekly apart. been on it a long time now - i think i'm probably going to be one of the "non-responders", but i want to give it it's due just in case - i've come this far, lolz - would hate to have to start over with the "it may take a year or more to start working" 😕

interesting that the supplements may help neuropathy... i'm excited to start trying that... 

I have very good insurance that doesn’t give me a hard time about much. I doubt I even need the biopsy for them! I have every sign of neuropathy as well as autonomic problems… I feel like my feet are buzzing all the time, I get the burning numbness, pins and needles, etc. My nurse case manager sounded like she could get IVIG approved for me just because, but I think the neurologist treats me like any other patient with average insurance. I don’t blame him.

 

I dread having that sort of relationship with IVIG, but I figure I can get a lot of hydration with it and be a step ahead. I have orders for that already.

[Sarah Tee]

@Castorp, I know this is an old post, but, as you asked for suggestions of anything else to try, I thought I would mention IV albumin. This helped me when IV fluids didn’t. I also have crushing fatigue.

Halfway through a 500mL infusion of 4% albumin, I fely my fatigue lift. I did not feel normal while moving around, but certainly a lot better. While sitting quietly, I felt close to normal. Unfortunately this improvement only lasted a day or two. However, I have read that some people with POTS have a better result, with the improvement in symptoms lasting closer to a week.

Here’s a thread that documents my experience with links to the very small amount of information published on this topic:

https://www.dinet.org/forums/topic/32832-albumin-infusions/

It seems to have been pioneered as a POTS treatment in Canada. I think it works because of the oncotic pressure of albumin, meaning it “holds onto” the fluid it comes in. (The albumin is delivered in a bottle of fluid, so you get fluid as well.) I had two 500mL bottles, the  switched to one because that seemed sufficient. It’s also possible the benefits come from albumin’s immune-modulating properties.

 

Also, a question: have you had your blood volume checked or had a transcranial Doppler test? Blood volume testing is poised to become much more available (new machine coming on to market) and transcranial Doppler is offered now by a few autonomic specialists in the US and Canada. It is also becoming available for use in stroke and PFO in many countries, and a persuasive autonomic specialist may be able to parlay that into having it in a “lie, sit, stand” scenario, or even during a TTT.

Edit: Did I read right that younlive in Spain? The new device for measuring blood volume is made in Denmark and has recently been approved for use in Europe. If you have a specialist with an interest in dysautonomia, you could let them know that the company that makes the machines has a scheme to lend them out at no cost for two months.

https://detalo-health.com/demonstration-program/

The machine would need to be set up in a hospital or clinic with access to a phlebotomist and pathology service because the testing requires blood to be taken and analysed.

[Asmaa]

@Sarah Tee why is Blood Volume Testing and Transcranial Dopple2t Tests important?

[Sarah Tee]

@Asmaa, that is a good question. I will try to answer!

The person I was replying to, who started this thread, has already tried many treatments with no success, and was asking for any other suggestions of things to try.

These two tests are hard to get in Australia. Castorp lives in Spain and I don’t know whether those tests are available there. But given that Castorp had IVIg, which is an “advanced” treatment that is hard to get and is only given as a last resort or to very sick patients, I thought maybe Castorp’s specialists might want to try to get these tests too.

For someone who is just starting out in their diagnosis journey, these tests would be nice to have, but they are hard to access, and not necessary for diagnosis in most cases.

I myself am trying to get these two tests, but I have been diagnosed and trying various treatments for two years. Things have gotten complicated and these tests might help my doctors now. I might also need the results to prove disability if I want to apply to the NDIS.

(For non-Aussies, NDIS stands for National Disability Insurance Scheme. It funds assistance for disabled people and is somewhat notorious for demanding evidence.)

I might also try to get a SPECT scan of the brain, which shows blood perfusion and might prove that my brain isn’t getting enough blood.

The reason I might need this evidence is that even though I have been diagnosed with chronic orthostatic intolerance caused by dysautonomia, in my case it is hard to measure because I have normal blood pressure and heart rate and don’t faint.

Sorry for the long answer, but, in a nutshell, you don’t need to worry about these tests now, and you may never need to 🙂

[Castorp]

@Sarah Tee Thank you very much for your suggestions, I find them very interesting.My neurologist has never mentioned them to me, and I suspect it must be difficult to obtain them in Spain, but I would like to discuss it with them on my next visit. Do you know any literature on this?

[Sarah Tee]

@Castorp, here’s a few links.

1. IV albumin

https://www.dinet.org/forums/topic/32832-albumin-infusions/

This is a thread I wrote about my experience with IV albumin. I also put links in to the information I found on it. There’s not much published, but a couple of doctors in Canada have been using it for about ten years for a small number of patients with POTS. One is Dr Zaeem Siddiqi, a neurologist. Maybe your neurologist could contact him.

 

2. Blood volume measurement

This used to be done as a nuclear medicine test for people with heart and kidney failure and some blood disorders. Since the 1980s, it’s not used as much and many machines were retired and not replaced. Some hospitals still have them to test people with polycythemia vera. If your neurologist can find a hospital that has this machine still, and persuade them, then maybe you can get your blood volume checked. Given all the treatments you have been theough, it might be useful to know whether or mot you have low blood volume.

There is a new, cheaper, simpler way of measuring blood volume coming onto the market:

https://detalo-health.com

I am sure it will eventually get to Spain. Maybe about the same time it gets to Australia!

For general information on blood volume in dysautonomia, this video lecture is good:

https://vimeo.com/540671549

You can find the research papers on PubMed by searching for hypovolemia + postural orthostatic tachycardia syndrome. Sorry I don’t have time to search them up for you.

 

3. Transcranial Doppler to measure cerebral blood flow volume

The person who has used this most recently in POTS and similar disorders is Dr Peter Novak. Again you can find his research papers on PubMed. He also has a textbook called “Autonomic Testing”, which explains how to do this and other testing, then illustrates testing in case studies. Your neurologist may be able to access this through their university library.

https://academic.oup.com/book/24760

The TCD device is fairly new for hospitals, but a few places have it to test blood flow in stroke patients. If your neurologist can find one at a hospital, maybe it can be used to check your blood flow. Ideally this would be done during a tilt table test, but if that isn’t possible, a “lie, sit, stand” test could work.

Here is a link to a hospital in my capital city:

It says:

“Outpatient Doppler ultrasound services are provided for investigation of cerebrovascular disturbances, including stroke, with the use of a non-invasive procedure.”

https://www.austin.org.au/diagnosing-brain-spinal-cord-nerve-muscle-disorders/for-health-professionals/

“A Transcranial Doppler (TCD) ultrasound looks at the blood flow of the arteries in the brain. This is done by placing an ultrasound probe on the side and back of the head. This procedure is safe and takes around 30 minutes to complete. This test is not available elsewhere.”

https://www.austin.org.au/diagnosing-brain-spinal-cord-nerve-muscle-disorders/for-patients/

When it says “This test is not available elsewhere”, I think it means no other hospitals in Melbourne have it yet. But it is starting to catch on. Some private cardiologists have it in other cities in Australia to diagnose PFO, a heart condition. I think many larger hospitals with stroke and heart units will have it soon. It’s not very expensive (for a medical device).

[Sarah Tee]

@Castorp, I just thought of one more test that is easier to access and that you may not have had: supine and standing catecholamines. It is a blood test with one vial collected after you have been lying down and another after you stand up.

I’m sorry but I can’t find a link to description of it right now. Sometimes they measure norepinephrine, one of the catecholamines. Dr Satish Raj mentions this test in some of his research and lectures.

Maybe this one: https://vimeo.com/244851345

 

On a different tack, I recently found that a calcium-channel blocker (CCB) helps the blood flow to my brain. (This is what would be measured in the transcranial Doppler test if I could get one.) I am still low on energy compared to normal, but I felt the crushing fatigue lift. Maybe you could try this if your doctors think it is okay for you.

(I have slightly high blood pressure, and CCBs are used to lower BP, so it was fine for me to try for a potential dual purpose.)

[Castorp]

@Sarah Tee thanks again. I have a (supine-standing) catecholamines test done to rule out hyperadrenergic POTS. 

I did not know that a CCB can be used to increase blood flow to the brain, but I think it may be worth a try in my case (I also had a slightly high BP).

[Sarah Tee]

@Castorp, I do hope you can try it. Calcium-channel blockers can cause a few side effects, such as swollen ankles, insomnia, and muscle aches, so do start “low and slow”.

I have just watched a lecture by Dr Peter Novak, and he mentions that some patients with low blood flow to the head respond to calcium channel blockers or ACE inhibitors. I hadn’t heard about the ACE inhibitors potentially helping before. So that is two classes of multiple drugs to try.

I am afraid the sound in the video lecture is terrible, so I won’t link it. Dr Novak also has a textbook (the one I linked to in a previous comment). This book may explain about CCBs and ACE inhibitors in more detail. Maybe your doctor can access it.

I have just tried amlodipine (CCB). It worked well on my OI symptoms but my ankles and feet swelled a fair bit. I am going to go back to my doctor to discuss further. I found a few mentions of some CCBs being less likely to cause swelling, so hopefully my doctor can work on finding me one that I can tolerate, or adjusting the dose.

Good luck!

[Castorp]

@Sarah Tee, many thanks once again. I had reached a point where I didn't know what else to try. That's why I appreciate your suggestions so much.

[Sarah Tee]

@Castorp, no worries, as we say here in Australia. I have been at that point a few times and have always found good suggestions here. I would not be diagnosed without this board. The forum discussions new and old and the info pages have so much to give. The Dysautonomia International lectures are my other best resource.

I do hope you can make some progress.

[Macho319]

@Sarah TeeI remember when I heard "No worries" for the first time. I was in Perth Australia in December 2002. 😊

[Sarah Tee]

@Macho319, so you’ve been “Down Under”! My dad used to live in Fremantle, near Perth, when I was younger so I visited Western Australia a few times. Everyone went to the beach later in the day to get the afternoon breeze and stayed till dusk, which was a huge novelty for me.