RLS and CFS/ME

For everything and anything else not covered in the other WED/RLS sections.
Frunobulax
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RLS and CFS/ME

Postby Frunobulax » Fri Apr 12, 2019 10:20 am

I have seen little discussion about CFS/ME and thought it would be worth a thread, simply for the fact that I've often read "a lot of us suffer from fatigue" from RLS patients, which got me wondering if the combination of RLS and CFS (that I have, unfortunately) might me more common than we think. Also some characteristics of CFS are very similar to RLS, as there seem to be a lot of causes and no one really understands how it works. In any case it doesn't hurt to know a bit about CFS/ME anyway :-) I thought for many years that my fatigue was a side effect from my severe RLS, but now I know this isn't the case. And I also know that most RLS doctors have never heard of CFS (the ones I know anyway).

DISCLAIMER: I'm not a physician. I'm just a patient suffering from RLS and CFS that has read a lot and talked to many other CFS patients.

Cliff notes:
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* CFS is a disease that causes severe fatigue, sleep problems and often muscle pain for 6 months or more.
* It is not a psychiological or psychosomatic condition, even though it is often misdiagnosed as depression. (The cause is unknown. Some researchers consider it an auto immune disease.)
* Fatigue can be caused by other diseases or treatments (like chemotherapy). CFS is diagnosed only where there are none of these other causes.
* There is no drug based treatment. CFS can be treated by rest, low level activity and vitamin supplements. Patients will get better given correct treatment, but it takes years and they will never reach their previous activity levels.
* CFS patients should avoid physical activity that makes them fatigued. They also should avoid any drugs that are not necessary, in particular antidepressants.
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CFS/ME (chronic fatigue syndrom/myalgicencephalomyelitis) is a severe condition that causes nearly constant fatigue, sleep problems and often muscle pain. (Some recent research led some specialists to consider CFS as an auto immune disease. More on this later.) The cause is unknown, and there is very little research about the condition, even though it affects more people than other, much better known conditions (like multiple sclerosis). Estimates for north America are that about 0.3% of the population suffer from CFS. Extreme cases will die or be in need of care, as they are no longer able to leave the bed. Only ~40% of CFS patients are still able to work at all, only ~5% of CFS patients can work full time.

You may suffer from CFS/ME, if most of the following is true for you:
* Fatigue and sleep issues worsen even after moderate physical and mental activity.
* After unusual physical activities (say a bicycle tour if you don't do sports otherwise) you have long-lasting fatigue (several days or even weeks) and more than usual problems going to sleep.
* Even activities that you enjoy will make you fatigued.
* You don't have treatments or other diseases that may cause fatigue (like chemotherapy).
* You have cognitive defects - memory or the ability to think analytically are impaired.
* You experience muscle pain, joint pain or headaches.
* You tend to experience a lot of side effects from medication.

It is often misdiagnosed as depression, because fatigue and sleep disorders are typical symptoms for depression, and social withdrawal is the inevitable consequence from the fatigue for most CFS patients . CFS is however a somatic disease (and accepted as such for about 30 years, at least in some parts of the world) that shows characteristic bloodwork anomalies and can be checked in physical tests. (Most of these tests are still subject to discussion among scientists.) There is a lot of controversy though, even about the ICD designation G93.3. One problem is that there is a lot of variety in the symptoms, and mild cases may show only few symptoms. Usually only the cases so severe that patients can't lead a normal life (work, social interaction etc.) will be diagnosed correctly, however, some of us had symptoms for many years before that. (I guess if you feel fatigued a lot it's natural to look for reasons in your normal life, and usually plenty of reasons can be found. And if not, most psychiatrist will give you a depression diagnosis without looking too closely.)

Many doctors not familiar with CFS, especially psychiatrists, will stubbornly argue that people with CFS have depression, and try to treat you with antidepressants and activity. (Even Wikipedia is not clear here.) This is a bad, bad idea, because both antidepressants and physical activity will worsen CFS. You are likely to have CFS/ME and no depression if:

* Activity worsens your symptoms (like sports, taking walks, going out and talking to people). Activity usually helps people with depression.
* Antidepressants have no effect or worsen your symptoms.
* You are still enjoying the things that you can do despite your fatigue, even if it is watching your favorite TV series or taking baths.
* You would like to do more, but the fatigue prevents it.

CFS affects the regeneration of "energy reserves" (used here in a non-scientific sense) - CFS patients will get exhausted much more quickly and take a lot longer to regenerate than healthy people. The reason appears to be an impaired function of the mitochondria. (Mitochondia are the little power cells in your body that produce energy.)

However, most doctors agree that it is currently not possible to diagnose CFS through these tests alone, and essential the diagnosis is an issue of ruling out everything else that could cause fatigue.

"Technical" indications for CFS will also separate CFS from depression. They are:
* Low ATP cell levels. Some new research indicates that ATP levels in the cells are significantly lower for CFS patients than for healthy people.
* High levels of nitrosative stress. CFS patients will produce more nitrogen monoxide under physical activity than healthy people (which can be determined by measuring NO in the air exhaled). The nitrogen monoxyde reacts with several other chemicals in your body (subsumed under "nitrosative stress"), some of them are toxic. Some of these substances can be measured in your blood, for example nitrotyrosine. Others act in parts of the body that can't be accessed easily (in the mitochondria or in the brain). Some of these substances will remain in the body for months and years.
* Low levels of most neurotransmitters (Adrenaline, Noradrenaline, Dopamine, Serotonine).
* Physical activity tests. A certain test used in sports medicine will be repeated after exactly 24 hours. CFS sufferers will experience a signific drop in their performance in the second test, while healthy people will show no or little difference in both tests.
* A lot of CFS patients have signs of a previous Epstein-Barr-infection.


Note that RLS and CFS is a pretty bad combination, as CFS patients need to avoid physical activity, while RLS patients need to walk. (I'm lucky enough to say that my RLS is pretty well under control now.)

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Snipp. The rest is about treatment, for those wondering if they might have CFS. Feel free to skip it.
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There is no pharmacological treatment. A few drugs (used to treat autoimmune diseases) appear to help a certain percentile of the patients, but there is nothing that helps the majority of the patients. The therapy that works best appears to be (a) pacing (avoid all activity leading to exhaustion, no sport, limit social interactions), (b) limited low-energy activity like taking short to medium walks (if possible, some really bad cases may need to start with simple excercies of moving arms/legs and flexing muscles), and (c) the supplementation of certain minerals and vitamins in high doses (vitamines B1, B6, B12, folic acid, biotine, C, D, coenzyme Q10, iron, magnesium, calium, zinc, and much much more). Note that the supplementation shouldn't be done blindly, as this can cause further damage. But only after bloodwork checks if they are necessary. But there seem to be trends, for example most CFS patients seem to have deficiencies in vitamin B1 and B12.
Some doctors will suggest (d) a diet reducing carbs (low glycemic index).

What I wrote so far is all scientifically based and can be backed up by research. The rest of this is my highly subjective view.

One very dark side of CFS (besides the psycho-fication) is that it attracts a lot of "alternative medicine". Some of that might actually work, but I've seen things I'd rather not start talking about because I might never stop. I'll just say this: As you know from RLS, people will grasp every straw if they are desperate, and other people will use them for their personal profit. CFS CAN be treated without [energy crystals from the Himalaya] and without [strange herbs plucked at full moon in Tibet], and most certainly without highly expensive devices doing weird things.

There is a natural question I haven't touched yet: "WHAT IS IT?" What caused it? As with RLS, there seem to be a lot of possible causes, and many cases where we can't pinpoint one. I'll give you at least some speculation.

Unfortunately there are a lot of different theories how CFS is caused and how it can be treated. Most CFS specialists will opine that CFS is caused by one specific thing, ignoring other possible causes. I've seen doctors (and patients) being adamant that CFS is ALWAYS the result of [something], but they disagree on the "something":
* autoimmune disease or Epstein-Barr infections
* poisoning from metals (quicksilver and similar substances), pesticides and other substances
* environmental factors like electric smog (which I personally find unlikely)
* long lasting stress and high workload
* side effects from innoculations
* Borreliosis
Be very, very careful if your doctor is certain why you have CFS, as he might be wrong. Most of these doctors can't explain even half of the CFS cases, especially the ones where CFS builds up slowly but basically out of the blue - no poisoning, no Epstein Barr, maybe just intense stress. (The problem here is that some suggested treatments are potentially dangerous - "poisoning" will often be treated by detoxification with substances like DMPS or DMSA, which can be highly problematic because it may reduce levels of desired metals like iron, especially for RLS patients.).

Many of these these causes - except for the environmental factors - are well documented to cause CFS in singular cases. Most researchers seem to favor autoimmune diseases, but I personally know people that were completely healthy before and experienced a sudden onset of CFS after a fume event (2 former commercial pilots) and innoculations as adults (Malaria). I also know CFS patients that had none of these but developed CFS after several months of intense physical and psychiological stress. Also the typical treatments to autoimmune diseases appear to be effective for only 30% to 40% of CFS patients (unpublished research from Charite Berlin, a CFS research center, that was communicated in a speech I heard).

The truth may be close but not exactly this. A german physician (Bodo Kuklinski) explains this by a snowball effect caused by nitrosative stress. I'm not sure if this is correct, but there seems to be a definitive snowball effect caused by something similar. Maybe nitrosative stress is only a part of it or maybe it's completely wrong, but his theory explains a lot of things that other theories do not explain. It goes like this.

* The onset is that the citrate cycle (which is responsible for ATP production in the body) has a reduced efficiency. This can have any number of reasons, including but not limited to the ones I named here.
* The body, who has a huge number of redundancies by evolutionary design, switches to various forms of "backup" energy generation if necessary. (Described in detail in his book, but I won't go into detail here.) Some of these "backup" energy generation mechanisms produce nitrogen monoxyde, which reacts to several substances that are summarized as "nitrosative stress".
* The nitrosative stress will further inhibit the function of the mitochondria, reducing the available energy even further. (I've read from other sources that the peroxynitrite involved will also cause damage on DNA level.)
* As a consequence, the patients will be fatigued more and more, the levels of nitrosative stress will rise continuously, and in the worst case the citrate cycle breaks down and patients become confined to their beds.
* Nitrosative stress can be reduced only over long timespans (up to several years), by avoiding the activities leading to stress and taking high doses of vitamine B12 (along with folic acid and biotine).
* The damages to the mitochondria can be partially repaired over long timespans after the nitrosative stress was reduced sufficiently. This may take years, and patients never reach their previos levels of performance because some damage is permanent.

This theory explains a number of things that most other doctors can't explain, as their theories will not cover all of the typical effects. It explains why the symptoms get worse long term after physical activity, it explains why CFS will appear slowly and progressing over years in most cases (but abruptly in some cases), it explains why it typically takes years to recover partially (and why there is never a full recovery), and it does explain why CFS can be caused by a large number of external influences, as the citrate cycle is complex and may be hampered by a large number of things, including poisoning and events like this. But even simple stress may lead to this snowball effect - if there is enough "load", the citrate cycle will be hampered, nitrosative stress will rise and peroxynitrite will cause lasting damage to mitochondria even if there is no external "event" involved.

For those of you that speak German, the book "Mitochondrien" by Kuklinski is highly recommended. Even though he's also stubborn and assumes that basically EVERY chronic disease is a result of mitochondic malfunction, so take it with a grain of salt. But there are hundreds of pages describing biochemical processes, and symptoms of deficiencies for all the vitamins, minerals and amino acids involved. It can be read by non-physicians, even though I had to read it 3 times to understand most of it.

His treatment plan is basically a 3-step one:
1. Change diet permanently to low-carb/low glycemic index diet. (This will reduce production of nitrosative stress.)
2. Use pacing and high doses of vitamin B12 along with folic acid and biotine to reduce nitrosative stress. Use individual supplements of vitamins to correct deficiencies. (He notes the problem that most CFS patients can't afford expensive blood tests to reveal deficiencies, and some of the tests are expensive. He does have some standard suggestions depending on which symptoms the patient shows though.)
3. After nitrosative stress was reduced sufficiently (which can take a long time), start to rebuild your mitochondria slowly by starting to take walks and doing low-intensity exercies.

I follow Kuklinskis book, and I had some success. After a year of treatment with low glycemic index diet, a lot of supplements and strict pacing I'm finally able to work again, even though only part time. (All that after 8 months where my condition got worse and worse because I was in the questionable care of psychiatrists.) Time to share something :-)

stjohnh
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Re: RLS and CFS/ME

Postby stjohnh » Fri Apr 12, 2019 2:07 pm

Frunobulax wrote:...

There is a natural question I haven't touched yet: "WHAT IS IT?" What caused it? As with RLS, there seem to be a lot of possible causes, and many cases where we can't pinpoint one. I'll give you at least some speculation...

Time to share something :-)


Wow, I think you have given the most cogent discussion of CFS that I have ever read. Congratulations.

One point: The cause of RLS in the last few years is coming into focus. BID (Brain Iron Deficiency) has been confirmed by numerous means (autopsy analysis of RLS brains, neuroimaging studies (contrast MRI/CT, etc.), good (although inconsistent) response to iron therapy, animal models, etc). Low brain iron is almost certainly caused by multiple gene abnormalities and epigenetic factors, accounting for the wide variability in symptom severity and response to therapy that is part of RLS.

BID leads to adenosine abnormalities (accounting for the beneficial effects of dipyridamole, an extracellular adenosine booster), which lead to abnormalities in the dopamine and glutamatergic metabolic pathways (accounting for the urge-to-move symptoms and sleep abnormalities respectively).

There is more research needed, but it seems very unlikely the the central role of iron in RLS will be refuted.
Blessings,
Holland

Frunobulax
Posts: 163
Joined: Mon Jun 02, 2014 7:41 pm

Re: RLS and CFS/ME

Postby Frunobulax » Wed Apr 17, 2019 10:52 am

I certainly hope that we're getting close. (In CFS we also "think" that it's caused by damage to the mitochondria, but we have no clear treatment options.) I'm going back to a clinic for CFS treatment, and hope to convince them to add iron infusions (they do a lot of infusions, vitamin cocktais, gluthation and such). My transferritin levels were always high for RLS patients (200 or higher), but I've also read that transferritin is not always a reliable indicator and I might still have iron deficiency in the brain. Let's see if my doctors go along with that.

I'd certainly like to reduce my opioids, as they are not recommended for CFS patients. But Gabapentin/Lyrica does nothing for me, and I can't take dopamine agonists, so all I can hope is to reduce the opioids, and pray that I don't have to add more drugs to the mix.

In any case, it's interesting that CFS treatment involves extreme doses of vitamins in some cases, and it seems to help. In many cases even when the usual blood markers check out OK. For example, vitamin B12 content in the serum may appear fine but people can still have a B12 intracellular deficiency. An indicator for this is high methylmalonic acid in the blood tests. (I take 1000 micrograms B12 daily, plus daily folic acid and biotine every 3 days.) Maybe the same could be true for RLS, that iron infusions can help patients who have "high" iron levels. From what I read, doctors have rarely tried that because they are afraid of the effects of too much iron.

In any case my RLS got a lot better after taking up the low glycemic index diet recommended for CFS. (I'll create a separate thread on that.)

badnights
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Re: RLS and CFS/ME

Postby badnights » Fri Apr 19, 2019 5:50 am

What a fascinating read! Thank you for sharing your research. Good to hear from you again.

My transferritin levels were always high for RLS patients (200 or higher), but I've also read that transferritin is not always a reliable indicator and I might still have iron deficiency in the brain
Are you referring to your ferritin levels? I don't know much about transferrin, but it is certainly ferritin that is not always a reliable indicator of body iron stores (it gets elevated during infection, for example).
In any case my RLS got a lot better after taking up the low glycemic index diet recommended for CFS. (I'll create a separate thread on that.)
That's particulaly interesting to me because my WED/RLS got much better - over a span of 2 years - after I went on a low-carb diet. I made other changes, too, the relative "importances" of which are mostly impossible to evaluate (eliminate gluten, dairy, added sugar, heavily processed foods, most grains; add vegetables, organ meats, fish). I am becoming convinced, though, that dairy makes my symptoms worse. (I've never been tempted to cheat with the gluten, but 4 times now I've tried to re-introduce cheese :) ). I look forward to your low-glycemic-index diet thread.
Beth - Wishing you a restful sleep tonight
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I am a volunteer moderator. My posts are not medical advice. My posts do not reflect RLS Foundation opinion.

stjohnh
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Re: RLS and CFS/ME

Postby stjohnh » Fri Apr 19, 2019 1:02 pm

Transferrin is the transport protein for iron, ferritin is the intracellular storage protein (some leaks out of cells into the blood). Transferrin level by itself doesn't mean much, but transferrin saturation (IE the % of transferrin molecules that are actually bound to iron) gives additional information about the significance of the ferritin. This is of most help in RLS patients that have a ferritin between 100 and 300 but a low or normal transferrin saturation. This is the pattern that occurs in people with a ferritin over 100 but do not have excessive blood iron. Some RLS experts may give IV iron to a patient with an elevated ferritin if the transferrin saturation is low.

The IRLSSG recommendations for IV iron repeat doses is to consider repeat doses if the ferritin is less than 300 AND the transferrin saturation is less than 45%. This decreases the likelihood of giving IV iron to a patient with excess iron already present, but helps to make IV Iron available to those with a somewhat increased ferritin but without excess blood iron being present (IE, the elderly and those with mild chronic inflammatory states).
Blessings,
Holland

badnights
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Re: RLS and CFS/ME

Postby badnights » Sat Apr 20, 2019 5:27 am

I like your explanation, Holland :)
Beth - Wishing you a restful sleep tonight
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I am a volunteer moderator. My posts are not medical advice. My posts do not reflect RLS Foundation opinion.


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