Periodic Paralysis, myotonia, channelopathy and ME

But the only study citing that hypothesis paper which measures stuff in CFS is:

Exercise responsive genes measured in peripheral blood of women with Chronic Fatigue Syndrome and matched control subjects Toni Whistler, James F Jones, Elizabeth R Unger and Suzanne D Vernon*
Background: Chronic fatigue syndrome (CFS) is defined by debilitating fatigue that is exacerbated by physical or mental exertion. To search for markers of CFS-associated post-exertional fatigue, we measured peripheral blood gene expression profiles of women with CFS and matched controls before and after exercise challenge.
Results: Women with CFS and healthy, age-matched, sedentary controls were exercised on a stationary bicycle at 70% of their predicted maximum workload. Blood was obtained before and after the challenge, total RNA was extracted from mononuclear cells, and signal intensity of the labeled cDNA hybridized to a 3800-gene oligonucleotide microarray was measured. We identified differences in gene expression among and between subject groups before and after exercise challenge and evaluated differences in terms of Gene Ontology categories.
Exercise-responsive genes differed between CFS patients and controls. These were in genes classified in chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport, and G protein-coupled receptor ontologies. Differences in ion transport and ion channel activity were evident at baseline and were exaggerated after exercise, as evidenced by greater numbers of differentially expressed genes in these molecular functions.
Conclusion: These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079885/pdf/1472-6793-5-5.pdf

It is evident that ion transport and ion channel activity segregate cases from controls and that exercise seems to intensify these differences. Several other conditions have been reported in which fluctuating fatigue occurs that are known to be caused by abnormal ion channels. These conditions include genetically determined channelopa- thies and acquired conditions such as neuromyotonia, myasthenic syndromes, multiple sclerosis, and polyneu- ropathies
 
Great find, @Jenny TipsforME . I see the authors focused on sodium imbalances in the first study. The second study with Unger and Vernon seems to suggest in the abstract that some ion channelopathy (or at least ion irregularities?) might be inferred?

I wonder why these were not followed up.

@Inara , one specific type of Periodic Paralysis is called Andersen-Tawil Syndrome - ATS.
 
@Jenny TipsforME, would you say Periodic Paralyses and ATS might be found via genome testing? I suppose there are also cases where no gene changes are found but the illness is present?
 
would you say Periodic Paralyses and ATS might be found via genome testing? I suppose there are also cases where no gene changes are found but the illness is present?

Sorry, @Jenny TipsforME , I am on line at the moment, so I hope you don't mind me answering a question directed at you. Yes, @Inara , some forms of PP can be determined through genetic testing, while others cannot. Some of those that cannot be uncovered thru genetic testing can be figured out thru potassium or sodium imbalances.

Some are probably out there with no means of being formally diagnosed yet.
 
If a person with PP would supplement potassium (or sodium in any form), what would happen?

For many there would be a need to first determine if you are hypo vs hyperkalemic. Not everyone can do this, though. My wife cannot, so we do not know which side she should be erring on, ie, supplementing potassium, or avoiding it.

But for many, knowing whether to supplement or avoid becomes a lifelong commitment to scrutinizing your diet.
 
70-80% can be picked up through genetic testing. So can be a false negative.
I understand it this way: a positive genetic test doesn't necessarily mean an illness will break out. But if there are symptoms, the test would ensure the diagnosis. Did I understand you correctly?
 
I don't know how you can avoid potassium...

But still, I don't understand what would happen if potassium is supplemented. Let's assume someone doesn't know he has PP and takes potassium/sodium - what could happen?
 
@Inara it is complicated because there are several types. Hypokalemic and hyperkalemic have opposite responses. Potassium is generally a potentially dangerous thing to mess with even if you don’t have PP.

Re the false negative I meant if you don’t have a currently known mutation that doesn’t necessarily mean you don’t have this. There are other tests too.
 
Thank you, Jenny.

I take ca. 3g potassium-citrate daily (ca. 1g potassium), and for me it helps, I think. (WHO's recommendation is 6-7g daily if I remember correctly, and I don't eat that with my food, I am certain.) I had no problems with it. I know it is said potassium is dangerous - and it can be - but normally (fresh) food contains a lot of potassium (and phosphorous).

I was just wondering...
 
I found this Phoenix Rising paper written in 2012. In that year I was moving house and then having a bedbound relapse so I wasn’t following research debate. It could be there’s some reason people aren’t talking about this anymore? Eg @JaimeS @alicec @Valentijn does anyone remember?

A Neurological Channelopathy in Chronic Fatigue Syndrome (ME/CFS)?
MARCH 4, 2012
(This paper is based on ‘Chronic Fatigue Syndrome is an Acquired Neurological Channelopathy’ by Chaudhuri and Behan)

Background
http://phoenixrising.me/research-2/...annelopathy-in-chronic-fatigue-syndrome-mecfs

This post/essay is good at explaining channelopathy.
Says also

A neurological channelopathy in ME/CFS?
Chaudhuri and Behan set out their case for disrupted ion channel transport in the central nervous system of CFS patients in a 1999 paper (Chaudhuri and Behan 1999). In this paper they first establish that the kind of fatigue found in CFS also commonly occurs in neurological diseases and that CFS patients respond abnormally to the signaling agents – neurotransmitters – that drive nervous system functioning.

Then they show how altered ion channel functioning could disrupt both the response to neurotransmitters and their production of them. Finally they demonstrate some similarities between CFS and neurological ion disorders and suggest potential causes for ion channel dysfunction in CFS.

Myotonia is a similar, overlapping condition to Periodic Paralysis

The myotonias are of special interest in CFS because some people purported to have CFS have turned out to have a myotonia instead (Graves and Hanna 2005). They occur when overly excitable muscle membranes respond to a single nerve impulse with multiple contractions.

Graves and Hanna state myotonias should be considered in anyone who complains of muscle stiffness. Although these diseases are genetically based the symptoms they evoke sometimes do not occur until maturity. In Thomsen’s disease, a chloride channel dysfunction causes constant or intermittent muscle stiffness that is relieved during exercise (the warm up phenomena).

A sodium channel dysfunction in paradoxical myotonia results in muscle stiffness that increases during exercise and can be precipitated by low temperatures. Testing for some of these diseases involves measurements taken in the post- exercise period – obviously a key period in CFS as well (Graves and Hanna 2005).
...
Speculation
Based on the information in the Chaudhuri paper calcium channelopathies appear to be particularly associated with fatigue. Six of the eight neurological diseases associated with fatigue cited by the authors involve calcium channel abnormalities. The authors note a calcium channel blocker, nimodipine, is partially effective in treating myalgia in CFS (Chaudhuri et. al. 2000).

There is some evidence for increased intracellular calcium levels in CFS patients. Decreased serum calcium levels were associated with poor NK cell function and increased RNase L fragmentation in CFS patients. That they did not display the increased serum potassium levels expected in a calcium channelopathy, however, cast doubt on whether the increased calcium levels were due to a channelopathy.
...
Evidence of a Channelopathy in CFS
Some indirect evidence of ion channel disruption is provided by Chaudhuri et al’s finding of increased resting energy expenditure (REE) in CFS patients. Since about 25% of the energy expended during resting goes to maintaining ion gradients in the cell, the authors speculate the increased REE seen in CFS could be due to compensation for faulty ion channel functioning.

CFS patients also appear to be particularly susceptible to some substances (alcohol, anesthesia, some cholesterol lowering drugs) known to effect either membrane integrity (alcohol) and/or ion function (anesthethetics). Indeed fatigue is a common symptom of a new anti-epileptic drug, dezinamide, targeting sodium channels.

Results from a thallium scan of the cardiac muscle in CFS patients suggest a potassium ion channel dysfunction that may be responsible for the cardiomyopathy reported by Lerner and now advocated by Cheney. Chaudhuri and Behan believe a potassium channelopathy is mostly likely to occur in CFS.

Potential causes of channel dysfunction – The natural history of CFS suggests that an early pathogenic or toxic insult often occurs. Several viruses, including HIV and the picornaviruses are able to alter ion channel flow. Herpesviruses have also been linked, interestingly enough given their history in CFS, to altered ion channel functioning.

Ciguatoxin, a neuronal sodium channel disruptor, produces many symptoms, including fatigue, similar to those that occur in CFS. Studies indicate a substantial number of CFS patients have extremely high levels of the ciguatera epitope. (Hokama et al. 2002, 2003a/b). Toxic insults from organophosphates, lead, insecticides, pesticides can also alter ion channel activity.
...
*Update – Since this paper was published in 1999 channelopathies have become a more prominent research topic in CFS.

Ciguatoxin
Greatly increased levels of the ciguatoxin epitope, a marker of altered sodium channel activity, in most CFS patients provide the best evidence yet a (sodium) channelopathy occurs in CFS. Whether these findings reflect a chronic disease process or something more specific to CFS is unclear but research, thankfully, is underway to elucidate the intersection between CFS and ciguatera (Pearn 2001, Hokama et .al. 2002, 2003a/b).

RNase L
The breakup of the RNase L enzyme releases fragments that appear able to interact with the ABC transporters that control the flow of ions in and out of the cell (Englebienne et. al. 2001, Nijs et. al 2004). De Meirleir et. al. did not, however, find strong evidence of systemic channelopathy in CFS (see Patrick Englebienne’s review). Reports from the 2004 AACFS conference indicate, however, that RNase L fragmentation affects the ability of the multi-drug resistant transporter to remove toxins from the cell.

Gene microarray studies
Perhaps most intriguing of all a recent study found that genes involved in ion channel functioning were among those most prominently altered between CFS patients and controls both prior to and after exercise (Whistler et. al. 2005

So what happened to this as a general idea?
 
I found this Phoenix Rising paper written in 2012. In that year I was moving house and then having a bedbound relapse so I wasn’t following research debate. It could be there’s some reason people aren’t talking about this anymore? Eg @JaimeS @alicec @Valentijn does anyone remember?
It's an article, not a paper. I'm not sure which studies you want to discuss ... a lot are cited, but some are just hypotheses (not research), and others are not regarding CFS.
 
@Valentijn it describes itself as a paper ;) I don’t know who wrote it? I’m interested more in the general hypothesis rather than a specific paper. It seemed like it was discussed quite a bit at one point then hasn’t been for a few years. Was this because evidence was found to refute the idea of channelopathy in ME, or was it simply lack of funding?
 
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