A Review of Chronic Fatigue(ME/NDS)

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A Review of CFS as it stands at this time.  Hopefully news of the XMRV or the new name possibily a human infectious gamma retrovirus – the first one we know of an HGRV….. will be published this week and maybe we will see rapid developments in the field and an expedited time table to finally get to the answers that at least a million people have been waiting for years.

Thanks to the civilian side of the House this is what we know so far, although this is the basics for review purpose. 

What is Chronic Fatigue Syndrome?

We all get tired. Many of us at times have felt depressed. But the mystery known as chronic fatigue syndrome (CFS) is not like the normal ups and downs we experience in everyday life.  The early sign of this illness is a strong and noticeable fatigue that comes on suddenly and often comes and goes or never stops. You feel too tired to do normal activities or are easily exhausted with no apparent reason. Unlike the mind fog of a serious hangover, to which researchers have compared CFS, the profound weakness of CFS does not go away with a few good nights of sleep. Instead, it steals your energy and vigor over months and sometimes years.

DEFINITION:

Just for a sake of clarity, the name of this illness has brought a lot of controversy, and currently they are trying to change it to neuroendocrineimmune dysfunction syndrome, or NDS, which better reflects the symptoms of this illness, is not just fatigue…

Chronic Fatigue Syndrome is an Illness characterized by a permanent fatigue (that it does not improve with the rest), for at least six consecutive months, accompanied of other symptoms as difficulty of concentration, lost of memory, non-refreshing sleep, muscular pains, pains you will articulate (without inflammation), migraines, general discomfort post exercise that extends more than 24 hours and alterations of the sleep.

This Chronic Fatigue Syndrome has also been called Immune Malfunction, epidemic Neuromiastenia and Myalgic Encephalomyelitis.

CAUSES:

There is not known yet the final cause of it, but it is believed that a viral infection is involved in it. Among the viruses responsible for CFS are: Epstein-Barr, HIV, HHV-6, Cytomegalovirus, retrovirus or enterovirus.

The World Health Organization has listed the discrete disease, CFS under neurological disorders specifically excluding it from psychiatric disorders. Doctors treating patients medically diagnosed with CFS describe them as more functionally ill than cancer patients undergoing chemotherapy, patients with HIV, Type 2 diabetes and another neurological disorder MS.

In one study, Ablashi et al. (15) found that 25% of the serum 300 CFS patients, tested for HHV-6 IgG and EBV-VCA IgG antibody, showed elevated antibodies to both HHV-6 and EBV.
Most of us have already been infected with the virus in our first year of life. In most individuals the virus is latent. When HHV-6 is reactivated, or during reinfection, it may contribute to CFS.  Evidence of the involvement of HHV-6 in CFS, compared to that of other human herpes viruses (EBV, CMV, HSV-1 and 2, VZV, HHV-7), is much stronger. The evidence is based on:

1. Elevated IgG antibody;
2. Detection of anti-IgM antibody in equal to or less than 50% of patients, which is a good indication of virus reactivation;
3. Detection of HHV-6 antigen expressing cells in the peripheral blood mononuclear cells of CFS patients by culture techniques;
4. Detection of HHV-6 DNA in lymphocytes of CFS patients by PCR and Southern blot hybridization (22-23,33,35-36).

DIAGNOSTIC AND BIOLOGICAL MARKERS:
A)Diagnostic Valuable Test Although not generally accepted as a diagnostic test, they havebeen claimed by researchers to be useful markers for the disease and tend to be present in most of the patients. Nevertheless the value of these is more for diagnosis than for treatment of the condition.In order of importance: Mitochondrial Profile, H2S in urine, RNASe-L, PKR and Elastase levels, Nitric Oxide in serum and oxidation levels, SPECT andxenon SPECT scans of the brain, MRI scans of the brain, PET scans of the brain, Neuropsychological testing, EEG brain maps and QEEG brain maps, Erythrocyte sedimentation rate (ESR), Insulin levels and glucose tolerance tests, 24-Hour Holter monitor, Tilt table examination, Exercise testing and chemical stress tests, Neurological examination and the Romberg or tandem Romberg test.

B)Aditional abnormalities test found in CFS patients should be checked at least once, and based on the criteria of the physician that is treating you, it might be necessary to repeat them periodically to evaluate the evolution of the protocol followed in your case.

-Tests of the immune system: The Th1-Th2 relationship of the immune system, Low NK activity (as opposed to levels), T-Activated Linfocites Count, % Linfocites, Cellular Inversion at CHMI and/or CHMII level, Elevations of circulating cytokines, Immunoglobulin deficiencies

-Serology Test: IgG for viruses such as Epstein-Barr, CMV, HHV6. Additionally we need to get tested for all possible infections that could have caused a reaction in our hormonal stress, and therefore in the serology we should include: mononucleosis, Hepatitis B & C, LES markers, Toxoplasma, antibodies of candida albicans, Babesia, Erchilia, Bartonella, Borrelia etc…

-Levels of amino acids in blood and urine 24h or spot.

-Liver function

-Candida levels, in order to detect subclinical fungi infections like candida albicans, there are special urine test that measure the metabolites that will help us to rule it out it also can be observed the metabolites through an Organic Acids Test.

According to the results, patients should seek be treated for each one of the abnormalities which show up. There are allopathic treatments (can be problematic for some, as CFS-MEers tend to have also Chemical Sensitivities) or homeopathic treatments (in Germany, they are very commonly used). Diet is also important regarding dealing with chemical sensitivities, amino acid levels, candida levels.

C) Advance testing on CFS: Besides theses regular, although not standard test mentioned above, there are additional test that can be run, and will deliver relevant input for CFS patients. There is a protocol to regulate these different abnormalities, which might be causing part of the symptoms in CFS, as a few of the latest research published postulates.

We will discuss below some of them in here:

-Mitochondrial Profile This is in the latest research the main responsible for CFS. There is a test run in UK by Dr. Myhill. This test measures the enzyme SODase (Superoxide Dismutasa) This enzyme is necessary in the detox process of free radicals of the mitochondria, as well as the CoQ10 levels, Niacinamide and Intracellular Magnesium. And most of all the efficiency of the mitochondria in converting ADP into ATP. It also measures the free ADN which is a nice marker to observe the cellular damage and apoptosis or PKRwhich is the programmed cellular death due to oxidative stress.

-Adrenal Hormones in Saliva: This test is useful to treat the adrenal failure, because there is a treatment for it. The test is run during a whole day (8:00, 12:00, 16:00, 20:00)

Cortisol and DHEA levels are tested. Also is necessary to test for a potential subclinical Thyroids problem (TSH, T3 and T4). Preferably in urine 24h, because subclinical thyroids is not always detectable in serum. Additionally a hair mineral test can be done to observe the unbalance existing in terms of minerals caused by suprarenal malfunction and correct it accordingly.

-HPU Test: This test measures a metabolic disorder, often occuring as a biochemical-enzymatic familiarly during the chemical reaction of formation of the red blood pigment. (Hemosynthesis).
It can be said that Kryptopyrrolurea is not a symptom, but rather the primal cause for different symptoms and disease states, among others hipoglucemia.
In the German-speaking countries, is abbreviated as KPU. In the Netherlands HPU. In England the abbreviation is HPL.

-Hypercoagulation Testing: As a part of Hemex’s research, they have developed a test to determine if a patient has this hypercoagulation disorder. The Immune System Activation of Coagulation (ISAC) tests five substances; abnormal results on any two of the five is considered to be a positive indicator of hypercoagulation. Their results thus far have found 79-92 percent of the CFS and/or FM patients they tested have hypercoagulation. As with many of the more detailed blood tests developed in the past decade, the defects causing hypercoagulation are rarely or not at all detectable by the standard laboratory tests performed at general labs, such as Unilab, Quest Diagnostics, etc. The standard coagulation workup done by these labs assess only the risk of actual clotting, whereas the ISAC panel is 10-20 times more sensitive.

-Metilation Panel (methionine cycle): This blood test is meant to observe the potential blockage of the methylation cycle, and therefore the potential detox treatment and follow up through urine. If after this analysis, you observe a blocked Methylation Cycle, then is wise to do a metal in urine test to have a starting point for the detox treatment. This test will be useful to follow up the metal excretion in the detox protocol or / and adapt the mineral doses intake.

The role of the methylation cycle in the sulfur metabolism is to supply sulfur-containing metabolites to form a variety of important substances, including cysteine, glutathione, taurine and sulfate, via its connection with the transsulfuration pathway.

In autism the methylation cycle was found to be blocked at methionine synthase, which is the step involving methylation of homocysteine to form methionine, resulting in lower plasma levels of cysteine and glutathione and a lowered ratio of reduced to oxidized glutathione. This lowered ratio reflects a state of oxidative stress.

It is known from studies of twins that genetics plays an important predisposing role in autism.The fact that the rate of incidence of autism has increased dramatically in recent years is evidence that there is also an important environmental component in the development of cases of autism, since the population’s genetic inheritance is relatively constant over much longer periods.

Evidence suggests that this same dysfunction is also present in chronic fatigue syndrome:

Low methionine levels in serum and urine, below-normal levels of carnitine, coenzyme Q10 and melatonin. All these substances require methylation for their biosynthesis.

RNase-L remains activated in CFS because of the suppression of the cell-mediated immune response and the consequent failure to defeat the viral infection

There is abundant and compelling evidence that the glutathione depletion methylation cycle block mechanism is an important part of the pathogenesis for at least a substantial subset of chronic fatigue syndrome patients.

-Glutathione and Selenium Test: The best complement to Methylation Panel, would be to check Reduced Glutathione RBC GSH, Oxidated Glutathione (RBC GSSG) and Total Glutathione (RBC).

The important one is RBC GSH, and also the ratio of this one versus RBC GSSG. This is relevant given that the low levels of glutathione due to the blocked methylation cycle, is the main responsible for the symptoms of CFS. In the initial states of oxidative stress in this illness Total Glutathione could be miss leading and be normal or even high, that is why we test for the other two as well. Besides, even if Glutathione comes normal, if Selenium level is low, the enzymes could not work properly.

Depletion of reduced glutathione likewise causes a shift to Th2. Depletion of reduced glutathione is the trigger for the reactivation of latent viral and intracellular bacteria in CFS. In general, intracellular glutathione depletion is associated with the activation of several types of viruses. It is likely that glutathione depletion is responsible for reactivation of Epstein-Barr virus, cytomegalovirus and HHV-6 in CFS. Populations more deficient in selenium would be expected to be more vulnerable to Coxsackie B3 infection.

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