Bob
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I wasn't sure if this should be a personal blog or a general discussion. I'm brain-storming and exploring an idea, or a potential hypothesis.
I've been thinking about the two recent papers that show an increase in glucose in blood/tissue in metabolic studies of ME/CFS. One by Prof Julia Newton et al., and the other by CW Armstrong et al. (BTW, @JaimeS has written a blog re the Armstrong paper, and my thoughts follow along similar lines.)
Both studies found relatively increased levels of glucose: Newton in cultures of tissue biopsies, and Armstrong in blood of ME/CFS patients. This seems to suggest that glucose is being under-utilised or under-metabolised in the energy metabolic pathways. The most obvious metabolic pathway to look at is glycolysis, which is the central glucose energy metabolic pathway that converts glucose to pyruvate and produces ATP in the process.
There's a helpful wiki page on glycolysis, that outlines all of the steps in the process: http://en.m.wikipedia.org/wiki/Glycolysis
If any stage in the glycolysis pathway is inhibited or blocked, for whatever reason, then it would probably mean that glucose would not be fully utilised, as there would be a blockage in the pathway.
Each step of the glycolysis pathway uses a specific enzyme. Last night I couldn't sleep, so i had a look through all the stages of glycolysis and the enzymes used for each stage. (See the glycolysis wiki page, for the list of the enzyme reactions, starting here: http://en.m.wikipedia.org/wiki/Glycolysis#Sequence_of_reactions)
I had a look to see if there were any known disorders involving deficiencies in the enzymes, to see if there were any similarities or overlaps with ME/CFS. There are recorded disorders in relation to deficiencies in most or all of the enzymes, but none of the disorders seem to quite fit the symptoms of ME/CFS. e.g. Most of them involve anaemia, and at least one of them involves brown urine. The nature of the disease for each of them does not look like ME/CFS.
Until I got to the penultimate step in glycolysis, which uses the enzyme enolase. There are a couple of disorders involving enolase that i came across. One is a genetic-related deficiency of enolase and the other is an autoimmune illness called Hashimoto's encephalopathy.
For enolase deficiency, the genetic disorder, the symptoms are listed in wiki as: "Symptoms of enolase deficiency include exercise-induced myalgia and generalized muscle weakness and fatigability, both with onset in adulthood. Symptoms also include muscle pain without cramps, and decreased ability to sustain long term exercise." Similar to ME/CFS? (This is the citation used: http://www.ncbi.nlm.nih.gov/pubmed/11506403)
For the autoimmune illness related to enolase, Hashimoto's encephaolopathy, the clinical features and laboratory/radiological findings are listed in wikipedia. The clinical features are not identical to ME/CFS but there is much overlap including: concentration and memory problems, headaches, sleep abnormalities. And also the following features, which i often see reported by some ME/CFS patients including a good proportion of severely affected ME/CFS patients: transient speech problems, disorientation, lack of coordination, tremors, jerks in muscles, seizures, partial paralysis on the right-side (Vanessa Li had partial paralysis on one side of her body, if my memory serves me well). Familiar? I've seen all of these symptoms discussed on this forum. (But there are other symptoms listed that we do not regularly see in ME/CFS.)
I'm not familiar with laboratory findings in ME/CFS, and other people might like to look to see if there are any familiar patterns there. But what caught my eye, and which seems quite significant to my personal circumstances, and perhaps many of us (and perhaps it's something that @Jonathan Edwards might be interested in?) is an association between this autoimmune disorder and a variety of autoimmune thyroid disorders. Thyroid hormone abnormalities are present in more than 80% of cases. The disorder is associated with raised thyroid stimulating hormone (TSH) levels (which i currently have without other abnormalities) in 55% of cases. There is subclinical hypothyroidism in 35% of cases. Overt hypothyroidism in 20% of cases (which i had transiently for about a year, a few years into having ME) (Is a 20% rate of clinical hypothyroidism a similar rate to ME/CFS patients?) And hyperthyroidism in 5% of cases. (I currently have some severe hyperthyroid symptoms, but no abnormal test results other than raised TSH.) So there is a variety of thyroid autoimmune issues related to this autoimmune disorder. However, perhaps unlike many ME/CFS patients, it says that "Thyroid antibodies - both anti-thyroid peroxidase antibodies (anti-TPO, anti-thyroid microsomal antibodies, anti-M) and antithyroglobulin antibodies (anti-Tg) - in the disease are elevated but their levels do not correlate with the severity." (Or perhaps many of us do have elevated thyroid antibodies? I can't remember the results of the forum survey that Jonathan Edwards carried out.) But it doesn't state what proportion of patients have thyroid antibodies, and it doesn't give a reference for the assertion, so perhaps that doesn't apply to all patients with the disorder.
For treatment of the autoimmune disorder it lists the following:
Anyway, that's as far as I've got in my exploration. It might not be relevant to ME/CFS but perhaps it's food for thought? There do seem to be very similar and specific overlaps between ME/CFS and both of these enolase disorders. I'm not saying that ME/CFS is the same as these specific disorders, but perhaps they are related in some way, directly or indirectly? And I wouldn't be surprised if a minority of us have one of these anolase disorders, but are misdiagnosed.
Note to self - extra wiki reference - there's more about cellular respiration, here:
http://en.m.wikipedia.org/wiki/Cell_energy
I've been thinking about the two recent papers that show an increase in glucose in blood/tissue in metabolic studies of ME/CFS. One by Prof Julia Newton et al., and the other by CW Armstrong et al. (BTW, @JaimeS has written a blog re the Armstrong paper, and my thoughts follow along similar lines.)
Both studies found relatively increased levels of glucose: Newton in cultures of tissue biopsies, and Armstrong in blood of ME/CFS patients. This seems to suggest that glucose is being under-utilised or under-metabolised in the energy metabolic pathways. The most obvious metabolic pathway to look at is glycolysis, which is the central glucose energy metabolic pathway that converts glucose to pyruvate and produces ATP in the process.
There's a helpful wiki page on glycolysis, that outlines all of the steps in the process: http://en.m.wikipedia.org/wiki/Glycolysis
If any stage in the glycolysis pathway is inhibited or blocked, for whatever reason, then it would probably mean that glucose would not be fully utilised, as there would be a blockage in the pathway.
Each step of the glycolysis pathway uses a specific enzyme. Last night I couldn't sleep, so i had a look through all the stages of glycolysis and the enzymes used for each stage. (See the glycolysis wiki page, for the list of the enzyme reactions, starting here: http://en.m.wikipedia.org/wiki/Glycolysis#Sequence_of_reactions)
I had a look to see if there were any known disorders involving deficiencies in the enzymes, to see if there were any similarities or overlaps with ME/CFS. There are recorded disorders in relation to deficiencies in most or all of the enzymes, but none of the disorders seem to quite fit the symptoms of ME/CFS. e.g. Most of them involve anaemia, and at least one of them involves brown urine. The nature of the disease for each of them does not look like ME/CFS.
Until I got to the penultimate step in glycolysis, which uses the enzyme enolase. There are a couple of disorders involving enolase that i came across. One is a genetic-related deficiency of enolase and the other is an autoimmune illness called Hashimoto's encephalopathy.
For enolase deficiency, the genetic disorder, the symptoms are listed in wiki as: "Symptoms of enolase deficiency include exercise-induced myalgia and generalized muscle weakness and fatigability, both with onset in adulthood. Symptoms also include muscle pain without cramps, and decreased ability to sustain long term exercise." Similar to ME/CFS? (This is the citation used: http://www.ncbi.nlm.nih.gov/pubmed/11506403)
For the autoimmune illness related to enolase, Hashimoto's encephaolopathy, the clinical features and laboratory/radiological findings are listed in wikipedia. The clinical features are not identical to ME/CFS but there is much overlap including: concentration and memory problems, headaches, sleep abnormalities. And also the following features, which i often see reported by some ME/CFS patients including a good proportion of severely affected ME/CFS patients: transient speech problems, disorientation, lack of coordination, tremors, jerks in muscles, seizures, partial paralysis on the right-side (Vanessa Li had partial paralysis on one side of her body, if my memory serves me well). Familiar? I've seen all of these symptoms discussed on this forum. (But there are other symptoms listed that we do not regularly see in ME/CFS.)
I'm not familiar with laboratory findings in ME/CFS, and other people might like to look to see if there are any familiar patterns there. But what caught my eye, and which seems quite significant to my personal circumstances, and perhaps many of us (and perhaps it's something that @Jonathan Edwards might be interested in?) is an association between this autoimmune disorder and a variety of autoimmune thyroid disorders. Thyroid hormone abnormalities are present in more than 80% of cases. The disorder is associated with raised thyroid stimulating hormone (TSH) levels (which i currently have without other abnormalities) in 55% of cases. There is subclinical hypothyroidism in 35% of cases. Overt hypothyroidism in 20% of cases (which i had transiently for about a year, a few years into having ME) (Is a 20% rate of clinical hypothyroidism a similar rate to ME/CFS patients?) And hyperthyroidism in 5% of cases. (I currently have some severe hyperthyroid symptoms, but no abnormal test results other than raised TSH.) So there is a variety of thyroid autoimmune issues related to this autoimmune disorder. However, perhaps unlike many ME/CFS patients, it says that "Thyroid antibodies - both anti-thyroid peroxidase antibodies (anti-TPO, anti-thyroid microsomal antibodies, anti-M) and antithyroglobulin antibodies (anti-Tg) - in the disease are elevated but their levels do not correlate with the severity." (Or perhaps many of us do have elevated thyroid antibodies? I can't remember the results of the forum survey that Jonathan Edwards carried out.) But it doesn't state what proportion of patients have thyroid antibodies, and it doesn't give a reference for the assertion, so perhaps that doesn't apply to all patients with the disorder.
For treatment of the autoimmune disorder it lists the following:
Treatment
Because most patients respond to steroids or immunosuppressant treatment, this condition is now also referred to as steroid-responsive encephalopathy.
Initial treatment is usually with oral prednisone (50–150 mg/day) or high dose IV methylprednisolone (1 g/day) for 3–7 days. Thyroid hormone treatment is also included if required.
Failure of some patients to respond to this first line treatment has produced a variety of alternative treatments including azathioprine, cyclophosphamide, chloroquine, methotrexate, periodic intravenous immune globulin and plasma exchange. There have been no controlled trials so the optimal treatment is not known.
Seizures, if present, are controlled with typical antiepileptic agents.
Anyway, that's as far as I've got in my exploration. It might not be relevant to ME/CFS but perhaps it's food for thought? There do seem to be very similar and specific overlaps between ME/CFS and both of these enolase disorders. I'm not saying that ME/CFS is the same as these specific disorders, but perhaps they are related in some way, directly or indirectly? And I wouldn't be surprised if a minority of us have one of these anolase disorders, but are misdiagnosed.
Note to self - extra wiki reference - there's more about cellular respiration, here:
http://en.m.wikipedia.org/wiki/Cell_energy
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