Dr. Jay Goldstein's Rapid Remission ME/CFS Treatments.

[Hip]

@zzz
Well... thinking about Dr Goldstein's SPECT scan findings you described above, it's possible then that hypoperfusion may be a red herring, and may have little direct causal connection to ME/CFS symptoms; rather the hypoperfusion may arise, like Goldstein suggested, from factors such as increased norepinephrine, which causes vasoconstriction and thus hypoperfusion.

So perhaps my considerations earlier in this thread on the vasodilatation effects of nitroglycerin were wide of the mark, and in fact there might be some other biochemical effects of nitroglycerin which are responsible for bringing about instant remission from ME/CFS in certain patients.

But what?

It could still be nitric oxide-related, perhaps the strong pulse of NO produced by nitroglycerin acting to reset certain NO systems in the brain.

And this study says that nitroglycerin induces induces c-Fos immunoreactivity in brainstem and forebrain structures of the rat. I read that c-Fos immunoreactivity is used as a measure of neuron activation, so nitroglycerin seems to have an activating effect on these brain areas.

@zzz, what are the other main drugs that Dr Goldstein found have instant remission effects, acting within minutes? Did you try any of these other instant remission drugs, by the way?

Do you know if these instant remission drugs always work as per your experience: ie, just a single dose of the drug causes a permanent ME/CFS remission that can last many years, without requiring any further doses? Or do some patients need to take these drugs every day in order to maintain their remission?



It would be interesting to examine viral loads before and after these Goldstein instant remission treatments, for the viruses most commonly associated with ME/CFS, such as enterovirus, Epstein-Barr virus and HHV-6.

For example, a week or two after one of these Goldstein instant remission treatments, would the patient's viral load become greatly reduced? If you look at Dr Chia's work with IV interferon and oxymatrine for enterovirus-associated ME/CFS, the viral loads in his patients' stomach biopsy tissues went down significantly when there were improvements or remissions in their symptoms as a result of these antiviral / immunomodulatory treatments. You can see how effectively oxymatrine reduced stomach tissue viral loads from the images in this post.

It seems that Goldstein did not look at the viral issues of ME/CFS that much; I am curious about how Goldstein's instant remission treatments may have affected the patient, from the viral perspective.

It seems to me that these instant remissions occur too quickly for there to be an antiviral mechanism, at least in the initial stages. For example, you say your remission process began within minutes of taking a single dose of isosorbide dinitrate (and was fully complete in three days). No antiviral response is going operate on a timescale of minutes.

However, if the isosorbide dinitrate normalized your metabolic functioning, it may conceivably have also normalized your immune system too, such that it was then able to better fight off any infections that were playing a role in your ME/CFS. So it would have interesting to have observed your viral loads a few weeks after that single dose of isosorbide dinitrate that caused your full remission.

 

[zzz]

@zzz
Well... thinking about Dr Goldstein's SPECT scan findings you described above, it's possible then that hypoperfusion may be a red herring, and may have little direct causal connection to ME/CFS symptoms; rather the hypoperfusion may arise, like Goldstein suggested, from factors such as increased norepinephrine, which causes vasoconstriction and thus hypoperfusion.

Yet the hypoperfusion only arose when the treatment was immediately successful, and in that case, it always arose. So that doesn't sound like a red herring. It got to the point where Dr. Goldstein could tell exactly what the SPECT scans would look like just by observing the patient's reaction. So he eventually stopped doing these scans, as they were providing no additional information.

It could still be nitric oxide-related, perhaps the strong pulse of NO produced by nitroglycerin acting to reset certain NO systems in the brain.

Except the exact same thing happened with dozens of other drugs.

@zzz, what are the other main drugs that Dr Goldstein found have instant remission effects, acting within minutes? Did you try any of these other instant remission drugs, by the way?

He found that most, if not all, of the drugs in his formulary could have this effect with selected patients. That was a major criterion for including drugs in his formulary. As most of his patients were from out of town, he generally had to get them better in one or two days, which he managed to do with about 75% of his patients. He couldn't wait around weeks for medications to work; people couldn't stay that long, and he had to supervise his protocol directly. Many of these drugs provided instant partial remissions, so he would stack them until he got a satisfactory recovery.

And yes, I've tried quite a few of them so far. As I'm not limited by Dr. Goldstein's time constraints, I tend to give them a while to work. Here are some examples:

My first dose of nimodipine did absolutely nothing. The second day, I took another 30 mg tablet. This time it felt like a veil had been lifted from my brain and body. I felt just like I had before I had gotten sick, and I realized that I had forgotten what that feeling was. I felt like the "old me". My energy was still a little low, so the transformation wasn't complete, but it was very close. My energy was so strong that it was difficult getting to sleep that night.

The next day, I took a quarter tablet with no problem, but it had no real effect. I gradually worked up to a full tablet, and then three tablets a day, but the original experience was never repeated. I am continuing on three tablets per day for now, as a number of people have reported that nimodipine tends to kick in after several months. I had a similar experience with Hydergine - several months with no effect, but then, out of the blue, tremendous energy. Unfortunately, this was accompanied by a mild allergic reaction. I cut back the dose, and am trying to get it to the point where I get a reasonable amount of energy with no allergic reaction.

There's pindolol, a beta blocker. The first time I took it, I got lots of energy, along with a bit of a high feeling. I was able to work very fast without getting tired, and my mind was extraordinarily clear. People really liked the posts I made that day. However, pindolol had some side effects, so I'm holding off it for now.

Finally, there's chlorzoxazone (Parafon Forte). I took three tablets during the day, and then found I had trouble sleeping that night. However, my naps the next day were unusually deep. This was strange. After two more days of this, I figured out what was happening. I was suffering from total sleep reversal at the time, going to bed around 10 a.m. and getting up at 6 p.m. So I was sleeping during the day and my naps were at night. Starting from the first day, the chlorzoxazone made my body want to sleep at night and be awake during the day. When I realized this after three days, I took my sleeping medicines right before my first nap of the "day", at 1 a.m., and slept until 7 a.m. My schedule quickly stabilized, and I was soon getting up at 9 a.m. and going to bed at 1 a.m. Unfortunately, I developed severe tinnitus in reaction to chlorzoxazone, and have had to stop it for now. My sleeping schedule has slipped some, but nowhere near what it used to be. Chlorzoxazone also had the effect of giving me significant energy. As it is a muscle relaxant and muscular pain reliever, it also relieved most of my mild fibromyalgia symptoms.

Why did chlorzoxazone have such a profound and immediate effect on my sleep schedule? Dr. Goldstein reports that circadian rhythms are disrupted by excess glutamate secretion from the prefrontal cortex. Chlorzoxazone works by reducing presynaptic glutamate secretion. It all makes sense.

Do you know if these instant remission drugs always work as per your experience: ie, just a single dose of the drug causes a permanent ME/CFS remission that can last many years, without requiring any further doses? Or do some patients need to take these drugs every day in order to maintain their remission?

In general, patients have to take these drugs on a regular basis to maintain their remission. I was fortunate with the Isordil presumably because ME/CFS is much easier to treat in the initial stages.

It would be interesting to examine viral loads before and after these Goldstein instant remission treatments, for the viruses most commonly associated with ME/CFS, such as enterovirus, Epstein-Barr virus and HHV-6.

For example, a week or two after one of these Goldstein instant remission treatments, would the patient's viral load become greatly reduced?

I would expect so. Immune system problems are endemic among PWME, and dysfunctional immune systems can allow many viruses to thrive. As the hypothalamus exerts a powerful modulating influence on the immune system, and based on Goldstein's case reports, it appears that when remission occurs, immune system activity is normalized, and the viral load drops in response.

It seems that Goldstein did not look at the viral issues of ME/CFS that much; I am curious about how Goldstein's instant remission treatments may have affected the patient, from the viral perspective.

Goldstein viewed this as largely an immune system problem. At the beginning of Betrayal by the Brain, in the Introduction, he lists many conditions that he thought were amenable to his neurosomatic medicine paradigm. Among these are chronic viral infections.

He wasn't saying that all viral infections could be treated by his methods; some clearly require strong antivirals, but that is the domain of the infectious disease expert. He was simply saying that those chronic, low-level viral infections that tended to arise in ME/CFS and other neurosomatic disorders could be cleared up by the general treatment for those disorders.

It seems to me that these instant remissions occur too quickly for there to be an antiviral mechanism, at least in the initial stages. For example, you say your remission process began within minutes of taking a single dose of isosorbide dinitrate (and was fully complete in three days). No antiviral response is going operate on a timescale of minutes.

I agree. These were clearly neurological responses. But they set in motion everything else.

However, if the isosorbide dinitrate normalized your metabolic functioning, it may conceivably have also normalized your immune system too, such that it was then able to better fight off any infections that were playing a role in your ME/CFS.

Exactly.

 

[Hip]

@zzz

Thanks very much for your detailed descriptions about your tests of Dr Jay Goldstein's recommended drugs.

It is infuriating to get a significant remission from ME/CFS symptoms from a drug, only to find that the old ME/CFS symptoms return after a few days or weeks.

I had this experience myself with the drug Wellbutrin (bupropion), an antidepressant and stimulant, which gave me almost full remission from most of my ME/CFS, ADHD and anhedonia symptoms for exactly 2 weeks at a dose of just 60 mg per day, and then mysteriously just stopped working.

In those two weeks, I had so much cognitive power, that I was able to do some computer programming for the first time in many years (I used to work in programming). I actually taught myself two new programming languages (javascript and PHP) within those two weeks, and started using them quite proficiently in a web project. Things were going so well, that I thought I had found my personal cure for ME/CFS, and would soon be back to professional work very soon. But then these extraordinary benefits from Wellbutrin just mysteriously switched off after exactly two weeks, and I was back to square one.

Even taking a two month break from Wellbutrin, to wash out any tolerance I may have developed to it (the drug is a stimulant after all) and then restarting it did not have any effect the second time around. Though if you search online for "Wellbutrin honeymoon", you see that there are a subset of people who take Wellbutrin for depression, and get two fantastic weeks initially, followed by a complete loss of efficacy of this drug. I'd love to know why this happens.



Some Notes on Wellbutrin (Bupropion)

Wellbutrin is a norepinephrine-dopamine reuptake inhibitor (NDRI); though Wellbutrin's dopamine reuptake inhibition is very weak, so it is more of just a norepinephrine reuptake inhibitor (NRI). I read that Wellbutrin is converted into hydroxybupropion relatively quickly, and the dopamine reuptake inhibition is done primarily through Wellbutrin, so once it’s converted into the metabolite it becomes mostly focused around norepinephrine.

Wellbutrin also antagonizes the nicotinic acetylcholine receptor.†

Wellbutrin downregulates beta adrenergic receptors.

Wellbutrin profoundly lowers levels of IL-1beta, TNF-alpha and IFN-gamma, in a mouse LPS-induced inflammation model.†

I think this ability of Wellbutrin to profoundly lower IL-1beta and TNF-alpha could provide an explanation of how this drug abolished most of my ME/CFS fatigue and cognitive symptoms: if you look at it from the perspective of Michael VanElzakker's sickness behavior model of ME/CFS, in which he proposes that the inflammatory cytokines IL-1beta, TNF-alpha and IL-6, arising from a vagus nerve infection, are causing sickness behavior and thereby ME/CFS, then Wellbutrin's action of potently lowering IL-1beta and TNF-alpha could explain how this drug put me into near remission from ME/CFS, albeit for just two weeks.

Dr Paul Goodnick's experience with Wellbutrin in treating ME/CFS is attached below as a pdf file.

Yet the hypoperfusion only arose when the treatment was immediately successful, and in that case, it always arose. So that doesn't sound like a red herring. It got to the point where Dr. Goldstein could tell exactly what the SPECT scans would look like just by observing the patient's reaction. So he eventually stopped doing these scans, as they were providing no additional information.

I meant the idea that hypoperfusion is playing a causal role in ME/CFS could be a red herring, if Goldstein found that hypoperfusion increases as ME/CFS symptoms improve.



I think I am going to add the drugs nitroglycerin, naphazoline and nimodipine to my list of ME/CFS drugs to try out. I actually have lots of drugs I am preparing to try, many sitting on my shelf waiting for a free time slot in my testing schedule. I just started taking lamotrigine (Lamictal) today, at a low initial dose of 12 mg.

Did Dr Goldstein have any perferences over nitroglycerin versus isosorbide dinitrate? I see nitroglycerin 5 mg patches are available here, and isosorbide dinitrate 10 mg tablets are available here.

Naphazoline eye drops of 0.01% concentration are available here. Are these suitable, do you know? I find it hard to imagine that administering eye drops could have such profound effects on some ME/CFS patients.

 

[Adster]

@zzz...... I find it hard to imagine that administering eye drops could have such profound effects on some ME/CFS patients.

Mucous membrane very close to the brain's blood supply?

 

[Helen]

For anyone interested, Dr Goldstein's list of 23 best ME/CFS medications is to be found here.

Thank you all for an interesting thread. And thanks Hip for the link above. I think this great extracts from his book Betrayal by the Brain is a must-read.

I was really impressed by Dr. Goldsteins thourough testing and evaluating drugs that could help PWME. From the presentation:

In this article, Dr. Goldstein provides an in-depth discussion of diagnosis, tests, associated disorders, and neurological findings in CFS/ME patients. From these, Dr. Goldstein draws the conclusion that other than limbic encephalopathy there is no other no other mechanism that could create the constellation symptoms found in CFS/ME.

 

[Hip]

@Helen @zzz
What I would like to do is add these drugs used by Dr Jay Goldstein to the ME/CFS roadmap. The roadmap covers antiviral, antibacterial, and other antimicrobial drugs reasonably well; it details immunomodulators to an extent; and lists drugs for orthostatic symptoms; but the roadmap does not currently have enough info on other types of drug that may be beneficial for ME/CFS.

So I would like to add Dr Goldstein's drugs to the roadmap, along with a brief explanation of how they might work, and what patients they are likely to work for (hopefully in a easy to read, brain fog-friendly format). I will need to read Goldstein's books before this though.

It seems that not enough ME/CFS patients are aware of these drugs which could be very beneficial, and even bring full remission, if they are lucky enough to be a patient who responds well to these drugs.

The idea of the roadmap is to provide a process that any ME/CFS patient can systematic go through in order to find the best treatments for them. So I think the drugs that Goldstein found most frequently led to ME/CFS improvements or even remissions should be in the roadmap.

Look at how isosorbide dinitrate provided @zzz with nearly 8 years of full remission from ME/CFS. Sadly the ME/CFS returned after this time, but nevertheless, 8 years of freedom from this disease would be very desirable for anyone. There may be many patients who are missing the opportunity of a significant improvement or even remission because they are unaware of the full range of drugs that can be effective for ME/CFS, or have not systematically tried all these drugs.

As an aside: if the patients who achieved remission using Dr Goldstein's drugs had, as a precaution, continued to take antivirals, immunomodulators and other drugs known to keep ME/CFS in check, even though they were in remission, would this have prevented their relapse?

I know that if I ever achieve remission, I would be very aware that remission does not equate to cure, so I would try to maintain my use of antiviral etc drugs that are known to keep ME/CFS in check, even if I was in remission.



By the way, in terms of cheaply trying out several of Dr Goldstein's best drugs for treating ME/CFS, United Pharmacies (UK website here) is a very good place to buy these drugs, because in most cases this pharmacy sells drugs in small units of just 10 pills. Often just 10 pills can be enough to work out whether a particular drug has benefits for you or not, or whether it has side effects that make that particular drug unviable for you.

So for just $50 spent at United Pharmacies, you could probably buy small amounts of say 5 different drugs from Goldstein's list to test out.

 

[zzz]

As you might imagine, @Hip, I can really relate to your experiences with Wellbutrin. That's not a drug I could ever take, though.

Yet the hypoperfusion only arose when the treatment was immediately successful, and in that case, it always arose. So that doesn't sound like a red herring. It got to the point where Dr. Goldstein could tell exactly what the SPECT scans would look like just by observing the patient's reaction. So he eventually stopped doing these scans, as they were providing no additional information.

I meant the idea that hypoperfusion is playing a causal role in ME/CFS could be a red herring, if Goldstein found that hypoperfusion increases as ME/CFS symptoms improve.

Ah, I see - I misunderstood. Dr. Goldstein appears to agree with you, though he doesn't say it as explicitly. From page 33:

This result again suggests that symptomatic improvement in CFS/FMS is not dependent upon reversing hypoperfusion, and that post-treatment blood flow changes are epiphenoma.

As for Isordil...

Did Dr Goldstein have any perferences over nitroglycerin versus isosorbide dinitrate?

He never mentioned isosorbide dinitrate. He used sublingual nitroglycerin as a probe, and the patches for maintenance. But as both nitroglycerin and isosorbide dinitrate end up producing nitric oxide (along with a whopping headache), it shouldn't matter which is used.

Naphazoline eye drops of 0.01% concentration are available here. Are these suitable, do you know?

No, they're not. That's the OTC strength; Dr. Goldstein said that those rarely had any effect on his patients at all. You need to use the 0.1% prescription strength, which you can find here.

I find it hard to imagine that administering eye drops could have such profound effects on some ME/CFS patients.

So did the patients. Here are just a couple of the many naphazoline case reports from Tuning the Brain:

A 24-year-old woman, who seemed somewhat bewildered by my hypothesis, became asymptomatic in one second, an uncommon but not rare experience. She got a stunned look on her face, which I'll never forget, like a deer caught in headlights. After incredulously telling me all her symptoms were gone, she got up and ran out of the office. I never heard from her again. I guess some people can't tell the difference between white and black magic.

A 48-year-old woman with bright red hair had been ill for twenty years. All her symptoms resolved after eyedrops. Her gratitude was underwhelming. "My appointment with you was supposed to be two hours. You've made me better in five minutes." (I talked to her first and had reviewed her medical records at length.) She demanded to have the fee for her initial patient visit prorated so that she would pay only 1/24th of it (5 minutes, or $33 instead of $800) thinking that I was somehow ripping her off. I never saw her again either.

And that was all she paid, after 20 years of being sick.

There are many other stories.

As for the eyedrops...

Mucous membrane very close to the brain's blood supply?

No; that route would be too slow. It's the V1 branch of the trigeminal nerve.

What I would like to do is add these drugs used by Dr Jay Goldstein to the ME/CFS roadmap.

That sounds like a fantastic idea to me!

So I would like to add Dr Goldstein's drugs to the roadmap, along with a brief explanation of how they might work, and what patients they are likely to work for (hopefully in a easy to read, brain fog-friendly format). I will need to read Goldstein's books before this though.

Yes, that's the way to go about it. Fortunately, you haven't read Goldstein's books yet. Drugs tend to be referenced in many different places, and not all of those places are in the index. So if you want to do this project really well, I would recommend that while reading the books, whenever you see a drug mentioned, you note the page number and the various salient facts about it. Each drug would occur on this list just once. If you do this, you'll end up with a drug list that's much more usable than what Goldstein currently has.

The idea of the roadmap is to provide a process that any ME/CFS patient can systematic go through in order to find the best treatments for them. So I think the drugs that Goldstein found most frequently led to ME/CFS improvements or even remissions should be in the roadmap.

I agree. There's no reason that Goldstein's high remission rates can't be replicated, especially if people are able to get their doctors involved. For the roadmap to be of most help, it would be really good to put in a basic description of how receptor profiling works. Dr. Goldstein purposely made receptor profiling fairly simple, so that even the majority of doctors who couldn't understand his books could still use his methods successfully to treat patients.

I would personally recommend putting all the drugs that Goldstein used in the roadmap. They are actually divided into four tiers, which is very helpful in deciding what to try. The first tier contains Dr. Goldstein's top 8 treatments, while the second tier contains the next 16; these are both listed at the bottom of page 319 in Tuning the Brain. The third tier consists of the several dozen drugs in the decision tree on page 458, while the fourth tier consists of all the remaining drugs starting on page 459. The third and fourth tiers overlap somewhat both with each other and with the first two tiers.

It would also be important to put a large warning in front of this portion of the roadmap. Although by and large, these are rather benign drugs, and Dr. Goldstein claims never to have had a serious adverse drug reaction among his patients, some of these drugs can have serious and even fatal side effects. Dr. Goldstein could get away with using these drugs because he had the antidotes on hand. But even he recommended against using certain drugs except in very dire circumstances. Yet there are quite a few PWME who find themselves in such dire circumstances, and the benefit may outweigh the risk of such drugs for them, so just as Dr. Goldstein kept these drugs in his books, I would recommend keeping them in the roadmap.

Doing all this should make it possible form many people to get a lot better using Dr. Goldstein's protocol. And hopefully, it will stimulate interest among current researchers to continue the path that Dr. Goldstein started, as it has yielded such fruitful results.

There may be many patients who are missing the opportunity of a significant improvement or even remission because they are unaware of the full range of drugs that can be effective for ME/CFS, or have not systematically tried all these drugs.

I agree. According to Dr. Goldstein's figures, almost all PWME can benefit from these treatments.

As an aside: if the patients who achieved remission using Dr Goldstein's drugs had, as a precaution, continued to take antivirals, immunomodulators and other drugs known to keep ME/CFS in check, even though they were in remission, would this have prevented their relapse?

It's hard to say. What triggered my final relapse was a reactivation of varicella zoster as a result of surgery to remove an old shingles lesion that had turned malignant (basal cell carcinoma). After five years symptom free, I had no idea that I was at any risk at all. If I had started taking a short course of acyclovir starting the day of the operation, would that have prevented my relapse? It certainly seems possible.

By the way, in terms of cheaply trying out several of Dr Goldstein's best drugs for treating ME/CFS, United Pharmacies (UK website here) is a very good place to buy these drugs, because in most cases this pharmacy sells drugs in small units of just 10 pills. Often just 10 pills can be enough to work out whether a particular drug has benefits for you or not, or whether it has side effects that make that particular drug unviable for you.

They're a great pharmacy, and they ship to every state in the U.S. except Oregon - which happens to be where I live. (Their agent is apparently located here.) Three other excellent pharmacies that I've used a lot are Brandmedicines.com, Goldpharma, and Mimaki Family Pharmacy. The last one often has drugs that no one else has, while at the same time it often doesn't carry the more common medications.

 

[Hip]

It's hard to say. What triggered my final relapse was a reactivation of varicella zoster as a result of surgery to remove an old shingles lesion that had turned malignant (basal cell carcinoma). After five years symptom free, I had no idea that I was at any risk at all. If I had started taking a short course of acyclovir starting the day of the operation, would that have prevented my relapse? It certainly seems possible.

Could it have been the anesthetic (which I presume was local) that triggered your relapse into ME/CFS? One trigger of ME/CFS appears to be major surgery, and although nobody knows why surgery can do this, it's possible that the anesthetic used during the surgery is the culprit. Now in your case, although only a local anesthetic was used, could the fact that you already had ME/CFS have made it easier for the anesthetic to trigger ME/CFS?

If you search this forum for anesthetic, you will see a number of threads detailing problems with ME/CFS patients getting anesthesia. Local anesthetics affect sodium channels, and channelopathies have been proposed as a factor in ME/CFS. Given it's a local anesthetic, though, it's effects would presumably be much weaker than a general anesthetic, so I am not sure how much water this holds as an explanation for your relapse.

Yes, that's the way to go about it. Fortunately, you haven't read Goldstein's books yet. Drugs tend to be referenced in many different places, and not all of those places are in the index. So if you want to do this project really well, I would recommend that while reading the books, whenever you see a drug mentioned, you note the page number and the various salient facts about it. Each drug would occur on this list just once. If you do this, you'll end up with a drug list that's much more usable than what Goldstein currently has.

I will definitely do this; thanks for the idea.

No, they're not. That's the OTC strength; Dr. Goldstein said that those rarely had any effect on his patients at all. You need to use the 0.1% prescription strength, which you can find here.

Thanks for that source of 0.1% naphazoline eye drops. I shall be testing naphazoline at some point soon.

It's the V1 branch of the trigeminal nerve.

Might these naphazoline eye drops work through trigeminal nerve stimulation (TNS)? Naphazoline is an alpha adrenergic receptor agonist, so will stimulate the trigeminal nerve when the drops are placed in the eye. Electrical trigeminal nerve stimulation devices are being explored as a treatment for epilepsy, so possibly TNS might have effects in some cases of ME/CFS.

Any idea how long the ME/CFS improvements / remissions induced by naphazoline eye drops lasted? Was this a one-off treatment, or did the ME/CFS patients require regular use of naphazoline eye drops to maintain their improvements in ME/CFS symptoms?

 

[zzz]

Could it have been the anesthetic (which I presume was local) that triggered your relapse into ME/CFS? One trigger of ME/CFS appears to be major surgery, and although nobody knows why surgery can do this, it's possible that the anesthetic used during the surgery is the culprit. Now in your case, although only a local anesthetic was used, could the fact that you already had ME/CFS have made it easier for the anesthetic to trigger ME/CFS?

I'm fairly certain it wasn't the anesthetic. It was a very small lesion, and I believe they just used lidocaine, which is actually one of Dr. Goldstein's best treatments for ME/CFS. But the lesion was at the end of a nerve that went straight into the spine where the varicella zoster were presumably hiding out ever since my shingles episode.

I also had a mild shingles outbreak about five days after the surgery as my ME/CFS was getting worse, indicating a reactivation of the varicella zoster.

Might these naphazoline eye drops work through trigeminal nerve stimulation (TNS)? Naphazoline is an alpha adrenergic receptor agonist, so will stimulate the trigeminal nerve when the drops are placed in the eye.

That's basically what Dr. Goldstein was saying; he goes into a fair amount of detail about this on pages 28-29.

Any idea how long the ME/CFS improvements / remissions induced by naphazoline eye drops lasted? Was this a one-off treatment, or did the ME/CFS patients require regular use of naphazoline eye drops to maintain their improvements in ME/CFS symptoms?

All the cases I can recall required regular use of the eyedrops - one drop in each eye three times per day.

 

[knackers323]

This is an extremely interesting thread.

However it does seem that because these medications only work for a limited time in many (most?) cases and that relapses occur it is not actually getting to the root of the problem, but rather providing a temporary circumvent to the real issue.?

Is this idea that a trigger like an infection or trauma can start a chain of events that the body gets locked in to, known in any other illness?

I know it is similar to the thoughts of dr Lloyd in oz but I think his idea is more that the brain/nervous system is damaged by the trigger, which i guess is somewhat similar to dr Goldsteins theory.

Anyone else have any theory's why things stop working after a while, sometimes they work only once as in the case of pindolol for @zzz. This has happened to me with other substances too.

Again it seems that an hidden ongoing infection is involved.

Or an immune system that is acting like there is one.

The other thing that seems odd with this theory is, why does it seem cfs has only seem to have only come about recently, is something about modern life changing genes or epigenetics?

Also how does this theory explain the cfs breakouts that have occurred?

More and more questions that need to be answered.

At this point I would definitely welcome an eight year remission though.

@Hip or anyone know whet to buy kuvan with no prescription on the net?

 

[zzz]

However it does seem that because these medications only work for a limited time in many (most?) cases...

It was definitely a minority of the cases where they worked only for a limited time, and where it occurred, Dr. Goldstein could almost always come up with replacement treatments that worked. The replacement treatments tended to be more permanent.

it is not actually getting to the root of the problem, but rather providing a temporary circumvent to the real issue.?

I don't think that's the case. It's not at all clear that ME/CFS can be "cured", especially in long term cases. One reasonable explanation would be that a precipitating event causes damage to certain parts of the brain, and this damage can be corrected via medication. There are certainly plenty of examples of this for other illnesses. But the underlying damage cannot be reversed, at least with what we know now about the brain.

I should also mention in this context that four months after the completion of my initial recovery, when I was in seemingly perfect health (and felt that way), I was on a business trip when I came down with shingles. The notable point here is that I was 38 at the time, and shingles does not usually occur before age 50. As shingles happens when the immune system is weak, my doctor thought that I should be checked for HIV, just in case. My test came back indeterminate; the ELISA was positive, along with two of the five Western blot tests, including P24, which tests for the core HIV virus. A repeat test six weeks later showed negatives on all tests. Over the years, even when I was symptom free for ME/CFS, the indeterminate results would come and go, until eventually they stopped.

Indeterminate results can generally arise for one of three reasons: 1) Pregnancy (I have never been pregnant); 2) infection with a similar virus (I tested negative for the HTLV viruses); and 3) infection with an autoimmune illness. Hmm... So it appears that during my long remission, ME/CFS was still there in the background, showing up occasionally on these tests, and in the weakened immune system that allowed the shingles to occur. This is important because it indicates that my final relapse was indeed a relapse, and not a new occurrence of the illness.

Is this idea that a trigger like an infection or trauma can start a chain of events that the body gets locked in to, known in any other illness?

Quite a few people with fibromyalgia can trace the onset of their illness to a car accident or a similar traumatic event. Complex regional pain syndrome is another example of this. There are various other examples.

Anyone else have any theory's why things stop working after a while, sometimes they work only once as in the case of pindolol for @zzz. This has happened to me with other substances too.

This is a well-known phenomenon; Dr. Goldstein has a chapter in Betrayal by the Brain devoted to explaining it.

Again it seems that an hidden ongoing infection is involved.

I don't see why. Dr. Goldstein managed to explain what was going on in a very reasonable way without having to invoke any hypotheses involving hidden infections.

Or an immune system that is acting like there is one.

This is a different story, though. As the immune system is modulated by the brain, then brain dysfunction can certainly result in immune system dysfunction. This is undoubtedly why Dr. Goldstein listed "chronic viral infections" as something that was a candidate to be treated by his methods.

The other thing that seems odd with this theory is, why does it seem cfs has only seem to have only come about recently, is something about modern life changing genes or epigenetics?

There are many, many possible answers to that question. For example, the amount of environmental pollutants has been rising steadily for some time.

Also how does this theory explain the cfs breakouts that have occurred?

Dr. Goldstein acknowledges the many possible triggers that can set off ME/CFS in susceptible individuals. Some of these triggers are very powerful. and if many people are exposed to them at once, an outbreak among susceptible individuals may occur.

Note that most people in the area of an outbreak do not come down with ME/CFS. For example, in the Incline Village outbreak, approximately 10% of the population was affected. However, that was hundreds of people, so that was quite significant.

 

[nandixon]

Folic Acid Prevents Nitroglycerin-Induced Nitric Oxide Synthase Dysfunction

This study found that folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction; the authors hypothesis that tetrahydrobiopterin (BH4) is involved. And this study demonstrates that folic acid reverses the endothelial dysfunction induced by BH4 depletion.

So folic acid and BH4 supplementation may help nitroglycerin regain its vasodilating effect. You can buy BH4 in 2.5 mg capsules at these places: 1, 2, 3, 4. But 2.5 mg is quite low compared to the 100 mg found in the prescription BH4 medication called Kuvan. This paper says sauna may help raise BH4. I understand that BH4 is sensitive to degradation by free radicals, so you would be advised to take antioxidants when you take BH4.

More info on BH4 as an essential cofactor for the activation of nitric oxide synthase is found in this article. It mentions that methylfolate (L-5-MTHF) may help substitute for BH4 when BH4 is deficient.

Just to update this section, we now know (since 2006) that with respect to eNOS that methylfolate acts as a peroxynitrite scavenger and this is apparently how "folic acid" helps maintain BH4 levels (and prevents decoupling of NOS). See this post:
http://forums.phoenixrising.me/index.php?threads/a-few-questions-about-bh4.27273/page-2#post-535258

And, relatedly, with respect to iNOS production of nitric oxide and inhibition of EBV, see this post:
http://forums.phoenixrising.me/index.php?threads/nos2-snps-up-or-down.34511/#post-537372

 

[Helen]

Could it have been the anesthetic (which I presume was local) that triggered your relapse into ME/CFS? One trigger of ME/CFS appears to be major surgery, and although nobody knows why surgery can do this, it's possible that the anesthetic used during the surgery is the culprit. Now in your case, although only a local anesthetic was used, could the fact that you already had ME/CFS have made it easier for the anesthetic to trigger ME/CFS?

Maybe this has already been mentioned, but anesthetic containing nitrous oxide might decrease the storage of vitamin B12. This could support the hypothesis of Richvank that a blocked methylation, due to low B12, is connected to the onset of ME/CFS.
http://www.ncbi.nlm.nih.gov/pubmed/23731042

 

[Hip]

@knackers323

Regarding the infectious associations of ME/CFS, and Goldstein's treatments: the fact that Goldstein's treatments might work on a patient does not contradict the possibility that the patient's ME/CFS may be underpinned by an ongoing low level infection.

There are two things here: first there is the ongoing infection, and second there is the mechanism by which this infection induces ME/CFS symptoms. So to treat infection-induced ME/CFS, you could either treat the underlying infection (which is not easy, given the lack of good antivirals in the medical armory); or you could take drugs that target the mechanism by which the infection induces ME/CFS symptoms, thereby ameliorating ME/CFS by that approach (this second approach might be the only recourse if you cannot do much to treat the infection). Or you can employ both approaches, which would be sensible.



Note also that it is also possible many of Goldstein's treatments may have an unusual antiviral or immunomodulatory effect, as well as having the ability to target and remediate the mechanism by which the infection induces ME/CFS symptoms.



I speculated in this post (in another thread) that @zzz's isosorbide dinitrate-induced eight year full remission from ME/CFS may have involved the antiviral action of isosorbide dinitrate on coxsackievirus B. The nitric oxide donor isosorbide dinitrate is known to inhibit a crucial protein that coxsackievirus B makes, called 3C protease. 3C protease blocks the immune system's ability to mount an antiviral attack on a coxsackievirus B infection inside cells. But as isosorbide dinitrate inhibits 3C protease, it may allow the immune system to then clear the viral infection from the cell.

However, I also speculated in this post above that ME/CFS, at least in some cases, may be due to the brain getting locked into a disease state that is a self-perpetuating (ie, a vicious circle), and that isosorbide dinitrate may have knocked the brain out of this particular self-perpetuating vicious circle, thereby resetting the brain, and allowing brain to settle back into its normal healthy state. Once the brain is back to operating normally, perhaps it may also be in a better state to fight off viral infections in the brain.

So both an antiviral effect, and/or a brain resetting effect may have contributed to @zzz's remission.

 

[adreno]

So this suggests that HDAC inhibitor sodium butyrate, which is available as a supplement, might help make epigenetic changes that then stops the repression of eNOS expression, allowing eNOS to do its job of dilating blood vessels; and in addition, it's conceivable that sodium butyrate will help nitroglycerin to regain its effect.

Butyrate is produced by bacteria in the gut; this might be an indication of gut dysbiosis in ME/CFS. Prebiotics can dramatically increase the bacteria that produce SCFAs, including butyrate.

 

[knackers323]

It was definitely a minority of the cases where they worked only for a limited time, and where it occurred, Dr. Goldstein could almost always come up with replacement treatments that worked. The replacement treatments tended to be more permanent.

My reply-

Hi@zzz thanks for your reply and I definately hope your right about these people being in the minority.

Where the hell are all these people? You would think after suffering this illness and then finding someone or something that helps significantly you would get the word out and it would spread.

I don't think that's the case. It's not at all clear that ME/CFS can be "cured", especially in long term cases. One reasonable explanation would be that a precipitating event causes damage to certain parts of the brain, and this damage can be corrected via medication. There are certainly plenty of examples of this for other illnesses. But the underlying damage cannot be reversed, at least with what we know now about the brain.

My reply-

Could you tell me what other illnesses can be caused by infections, accidents and stress.

What determines one person to get cfs from these events and many other people don't?

I should also mention in this context that four months after the completion of my initial recovery, when I was in seemingly perfect health (and felt that way), I was on a business trip when I came down with shingles. The notable point here is that I was 38 at the time, and shingles does not usually occur before age 50. As shingles happens when the immune system is weak, my doctor thought that I should be checked for HIV, just in case. My test came back indeterminate; the ELISA was positive, along with two of the five Western blot tests, including P24, which tests for the core HIV virus. A repeat test six weeks later showed negatives on all tests. Over the years, even when I was symptom free for ME/CFS, the indeterminate results would come and go, until eventually they stopped.

Indeterminate results can generally arise for one of three reasons: 1) Pregnancy (I have never been pregnant); 2) infection with a similar virus (I tested negative for the HTLV viruses); and 3) infection with an autoimmune illness. Hmm... So it appears that during my long remission, ME/CFS was still there in the background, showing up occasionally on these tests, and in the weakened immune system that allowed the shingles to occur. This is important because it indicates that my final relapse was indeed a relapse, and not a new occurrence of the illness.

My reply-

That's what I mean, the core issue was not resolved, only a way around it was found. Why was your immune system still low.

Quite a few people with fibromyalgia can trace the onset of their illness to a car accident or a similar traumatic event. Complex regional pain syndrome is another example of this. There are various other examples.

My reply-

Are there any examples in conditions that are better understood?

This is a well-known phenomenon; Dr. Goldstein has a chapter in Betrayal by the Brain devoted to explaining it.

My reply-

Could you give us a brief explanation of what he says please.

I don't see why. Dr. Goldstein managed to explain what was going on in a very reasonable way without having to invoke any hypotheses involving hidden infections.

My reply-

What is dr Goldsteins explanation?

Again though, why do these triggers only seem to be causing such results until recently.

As I said, is there any other known examples of this kind of thing happening anywhere else?

This is a different story, though. As the immune system is modulated by the brain, then brain dysfunction can certainly result in immune system dysfunction. This is undoubtedly why Dr. Goldstein listed "chronic viral infections" as something that was a candidate to be treated by his methods.


There are many, many possible answers to that question. For example, the amount of environmental pollutants has been rising steadily for some time.

My reply-

Yes this could very well be a factor.


Dr. Goldstein acknowledges the many possible triggers that can set off ME/CFS in susceptible individuals. Some of these triggers are very powerful. and if many people are exposed to them at once, an outbreak among susceptible individuals may occur.

It seems unlikely that all these suseptable people would be in the one spot at the same time, while at other times there are big out breakers of the same triggers and no one or few people get cfs.

Note that most people in the area of an outbreak do not come down with ME/CFS. For example, in the Incline Village outbreak, approximately 10% of the population was affected. However, that was hundreds of people, so that was quite significant.

I have replied above. Don't get me wrong, I am not trying to refute the hypothesis I'm happy for cures or treatments to be found no matter what the explanation is, I just feel that these are some questions that we need to answer.

 

[Gingergrrl]

@zzz and @Hip Thank you for starting this thread and I wish I had time to comment and add to the discussion here. I bought "Betrayal of the Brain" and the companion volume by Katie Courmel a while ago and you can get very cheap used copies on Amazon. I read the companion volume but not yet the main book (only b/c of lack of time but am planning to read it soon.) I am also going to be asking my own CFS dr about the book and concept of receptor profiling. I don't have the science background to contribute much to it but am glad this thread is here and am enjoying the discussion.

 

[knackers323]

@knackers323

Regarding the infectious associations of ME/CFS, and Goldstein's treatments: the fact that Goldstein's treatments might work on a patient does not contradict the possibility that the patient's ME/CFS may be underpinned by an ongoing low level infection.

There are two things here: first there is the ongoing infection, and second there is the mechanism by which this infection induces ME/CFS symptoms. So to treat infection-induced ME/CFS, you could either treat the underlying infection (which is not easy, given the lack of good antivirals in the medical armory); or you could take drugs that target the mechanism by which the infection induces ME/CFS symptoms, thereby ameliorating ME/CFS by that approach (this second approach might be the only recourse if you cannot do much to treat the infection). Or you can employ both approaches, which would be sensible.



Note also that it is also possible many of Goldstein's treatments may have an unusual antiviral or immunomodulatory effect, as well as having the ability to target and remediate the mechanism by which the infection induces ME/CFS symptoms.



I speculated in this post (in another thread) that @zzz's isosorbide dinitrate-induced eight year full remission from ME/CFS may have involved the antiviral action of isosorbide dinitrate on coxsackievirus B. The nitric oxide donor isosorbide dinitrate is known to inhibit a crucial protein that coxsackievirus B makes, called 3C protease. 3C protease blocks the immune system's ability to mount an antiviral attack on a coxsackievirus B infection inside cells. But as isosorbide dinitrate inhibits 3C protease, it may allow the immune system to then clear the viral infection from the cell.

However, I also speculated in this post above that ME/CFS, at least in some cases, may be due to the brain getting locked into a disease state that is a self-perpetuating (ie, a vicious circle), and that isosorbide dinitrate may have knocked the brain out of this particular self-perpetuating vicious circle, thereby resetting the brain, and allowing brain to settle back into its normal healthy state. Once the brain is back to operating normally, perhaps it may also be in a better state to fight off viral infections in the brain.

So both an antiviral effect, and/or a brain resetting effect may have contributed to @zzz's remission.

Yes I agree but if the remissions are not lasting, then if possible the best treatment would be to treat the causal factor, the infection, if it does actually exist and go for the full cure.

I wish more people were looking for infections in more places than just the blood.

Also since my earlier post I have been thinking that there are some similarities with the Brain injury theory and acquired brain injury, which can also happen through infection, trauma etc, (in which sufferers commonly have increased fatigue and sensory changes) and regional pain syndrome.
Which females are also apparently more susceptible to.

I how Goldsteins treatments would fair in these illnesses.

Also anyone know if someone has looked into gene mutation, which can be caused by infections, chemicals and presumably mould.

 

[Hip]

Yes I agree but if the remissions are not lasting, then if possible the best treatment would be to treat the causal factor, the infection, if it does actually exist and go for the full cure.

The infection may not be the only causal factor: other people get the same infections, but don't develop ME/CFS; so this indicates that more than one causal factor is at play in the development of ME/CFS.

And even if some of Goldstein's treatments were not long lasting, the fact they worked at all should make people want to investigate the possible biochemical mechanisms behind these treatments, as this may help throw light on the pathophysiology of ME/CFS. So it's not just the therapeutic value of Goldstein's treatments which is interesting; it is also their value in possibly illuminating ME/CFS pathophysiology.

And note that you sometimes get the same problem with treatments that target pathogens: for example the immunomodulators Imunovir or inosine are reported to lose their effect a year or two down the line. Likewise, Dr Chia found that when patients got better on the immunomodulator oxymatrine, if the patient stopped taking oxymatrine they would relapse, and when they started taking oxymatrine again, it would not work as well, or at all, the second time around.

 

[knackers323]

Yes absolutely. It is worth looking in to. I will definitely be trying these treatments