Genetic Predisposition To Ebv Infection
The diversity of human leukocyte antigen molecules results from selective pressure during co-evolution with pathogens . A characteristic of HLA diversity is the long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species . In humans, there are 13 allelic lineages of DRB1 and, according to the phylogenetic relationship between the different DRB genes of primates described by Bontrop et al, the DRB1*04, *03 and *02 lineages are the oldest, with the DRB1*04 lineage being the most ancestral . Since EBV is the only human-adapted member of the genus Lymphocryptovirus, transferred to a hominid ancestor , it could be hypothesized that immune evasion mechanisms of the EBV have more effectively evolved among older allelic lineages of DRB1. Such an hypothesis could help explaining why individuals with haplotypes DR2-DQ6, DR3-DQ2 or DR4-DQ8 are less resistant to EBV infection and are at greater risk of developing EBV-related disorders .
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Pragmatic Rehabilitation: The Fine Trial
Pragmatic rehabilitation is a programme involving gradually increasing activity designed collaboratively by the patient and the therapist. In response to an earlier successful trial, a larger trial was conducted. In this trial, patients fulfilling 1991 Oxford CFS criteria who were allocated to pragmatic rehabilitation reported a statistically significant though clinically modest improvement in fatigue compared with patients allocated to either supportive listening or treatment as usual, but after 12 months followup the differences were no longer statistically significant nor was there was any significant improvement in physical functioning at any time. About 10% of the trial participants were nonambulatory and about 30% met 1994 London criteria for ME, but separate results for these groups were not published . An accompanying editorial gave some possible reasons for the failure to replicate the earlier success in this trial, and called for further research. The patients in this trial had higher comorbidity and disability than patients in the earlier trial and in most other trials, and received fewer sessions than most successful trials of CBT and GET. The editorial also raised the question of whether generalists are as successful as specialists in offering behavioural interventions .
Depression Stress And Anxiety
Adjusting to a chronic, debilitating illness sometimes leads to other problems, including depression, stress, and anxiety. Many patients with ME/CFS develop depression during their illness. When present, depression or anxiety should be treated. Although treating depression or anxiety can be helpful, it is not a cure for ME/CFS.
Some people with ME/CFS might benefit from antidepressants and anti-anxiety medications. However, doctors should use caution in prescribing these medications. Some drugs used to treat depression have other effects that might worsen other ME/CFS symptoms and cause side effects. When healthcare providers are concerned about patients psychological condition, they may recommend seeing a mental health professional.
Some people with ME/CFS might benefit from trying techniques like deep breathing and muscle relaxation, massage, and movement therapies . These can reduce stress and anxiety, and promote a sense of well-being.
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Aberrant Energy Production Via Increased Glycolysis In The Warburg Effect
Cells from persons with ME/CFS show aberrant energy production, wherein more energy is produced within the cytoplasm via increased glycolysis and fermentation . Oxaloacetate has been shown to reverse this trend in human cancer cells, reducing both glycolysis and the formation of lactate . The Warburg Effect refers to a form of modified cellular metabolism, which tend to use specialized fermentation of pyruvate to lactate in the cytoplasm over the aerobic respiration pathway that burns pyruvate in the mitochondria that is used by most cells in the body under non-pathological conditions. Chronic Fatigue Syndrome patients have been shown to have activated this alternative energy pathway, increasing the amount of energy that is produced by glycolysis in the cytosol that continues after their pathological incident has passed .
Keep Track Of Your Symptoms And Their Onset
Tracking the frequency, timing, and severity of your symptoms might help your doctor better understand what youre experiencing. Tracking your activity level and symptoms can also help you draw connections and learn your limits so that you can reduce flare-ups.
When tracking your symptoms, remember to write down everything ailing you, not just fatigue. People with CFS/ME often also have issues with pain, cognition, such as memory and concentration, and sleep. You might also consider keeping a sleep diary, so your doctor can see how well youre sleeping and determine if sleep might play a role in your symptoms.
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Complementary And Alternative Medicine
CFS/ME patients tend to use more alternative medicine treatments than people without . Patients often leave orthodox medical care because they feel that their condition has been unjustifiably attributed to psychological causes: they are given the message that it is all in the mind. In a twin study, 91% of twins with CFS/ME and 71% without CFS/ME used at least one alternative treatment. A large proportion of the study participants stated that alternative treatments were helpful .
Living With Chronic Fatigue Syndrome
Although experts have not yet found a cure for CFS/ME, many people who have the illness are able to make lifestyle changes and find treatments that allow them to reduce or manage their symptoms. Improvement is possible by living within your limits and working with a doctor to find treatments that help you. There are also many CFS/ME support groups both online and in-person. Meeting with such a group might prove to be helpful.
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Randomized Clinical Trial To Evaluate The Efficacy And Safety Of Valganciclovir In A Subset Of Patients With Chronic Fatigue Syndrome
Abstract:
There is no known treatment for chronic fatigue syndrome . Little is known about its pathogenesis. Human herpesvirus 6 and Epstein-Barr virus have been proposed as infectious triggers.
Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory and Fatigue Severity Scale scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels.
VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore , FSS score , and cognitive function . VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders . In the VGCV arm, monocyte counts decreased , neutrophil counts increased and cytokines were more likely to evolve towards a Th1-profile . Viral IgG antibody titers did not differ between arms.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00478465.
Four Studies Showing That Long Term Antivirals Work
Lerner looked at 106 consecutive cases of CFS/ME and found the presence of Epstein-Barr virus alone in 28% of these cases, in a further 53% of cases there was Epstein-Barr virus combined with cytomegalovirus, or HHV-6, which means that Epstein-Barr virus was involved in a total of 81% of patients with CFS/ME.
Most importantly, he went on to show that the Epstein-Barr virus could be treated effectively with an anti-viral valacyclovir and if there is co-infection with HCMV or HHV-6 then some trials used valganciclovir in addition to the valacyclovir. He reported good responses to treatment. Indeed, he reviewed four studies involving several hundred patients with CFS using this combination of drugs and reported long term patient recovery. This recovery was determined in terms of clinical improvement, improvement in serum EBV titres , EBV viral capsid antigen and immoglobulin-M), together with improvements in 24 hour ECG and improvement in cardiac dynamic studies.
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Ampligen May Work In Chronic Fatigue Syndrome Because
it modulates the activity of a part of the innate immune defense that some studies suggest is disrupted in chronic fatigue syndrome . It does this through its ability to mimic the structure of viral proteins which normally stimulate the bodys immune defenses. Some chronic fatigue syndrome patients have high levels of an unusual type of a molecule which appears to disrupt the innate immune response. Ampligen appears to be able to restabilize the immune response in at least some of these patients.
Hemispherx Biopharma recently reported that Ampligen stimulates the activity of the toll-like receptors on the outer part of the cell that play an important role in the early recognition of pathogens. Some but not all studies suggest that rates of opportunistic infections are increased in chronic fatigue syndrome patients. Ampligens broad anti-pathogenic properties may be able to reduce the activity of these pathogens in some patients.
Post Viral Cfs May Be Due To Low Level Chronic Infection With Epstein
Martin Lerner had been working since 1993 on the idea that many cases of chronic fatigue syndrome result from longstanding infection with herpes viruses. The most important of these is Epstein-Barr virus , but he had also identified two other herpes viruses as a particular problem in CFS/ME sufferers, namely cytomegalovirus and human herpes virus 6 . He demonstrated that in CFS/ME sufferers there is non-permissive replication of virus. By this he meant that there is sufficient viral replication going on in cells to disrupt cellular metabolism and cause cell death, but not sufficient to result in a positive DNA polymerase test, or antigenemia with antibody response. This means that such chronic infection will not be picked up by standard virology tests including antibodies and PCR. This very much echoes the ideas of Dr John Chia, who believes that many patients with chronic fatigue syndrome have ongoing viral infection which he describes as being under the radar, i.e. the immune system does not seem to see it. This is a little bit like HIV infection, where the virus tucks itself away inside cells, again so the immune system cannot see it. See Oxymatrine in the treatment of post viral fatigue
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Concluding Remarks And Future Directions
This review suggests that the beneficial effects of nutritional supplements are not random, but that their action is due to the removal of one of the causes of the CFS/ME. There is evidence that supplements may benefit CFS/ME patients therefore, nutritional supplements should be recommended, at least in CFS/ME patients with a biochemically proven deficiency. Studies investigating nutritional interventions in CFS/ME remain very limited most studies have had small sample sizes, and lacked long term followup . Despite the relative consistency in case definition, the studies differed with regard to inclusion and exclusion criteria and reporting participants sociodemographic characteristics and clinical features . This heterogeneity in study design makes the application of the findings to the clinical setting more difficult. Therefore, longerterm RCTs in homogeneous populations that use more specific case criteria are now warranted.
In agreement with several previous studies, pacing was consistently shown to be the most helpful treatment, CBT was useful for some patients but not all for all graded training may cause the condition to worsen. However, the results must be interpreted with care, as the participants are not a representative sample.
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Case Presentation: Case 2
A previously well white female living in the USA, developed a sudden onset of ill health when 29 years old in 1989. Symptoms included profound fatigue and weakness, flu-like symptoms, postexertional malaise, cognitive impairment, nausea, widespread pain and sleep disturbance. Possible precipitating factors included possible viral infection, early pregnancy and exposure to ticks within 6 weeks of onset. She was diagnosed with chronic fatigue immune dysfunction syndrome by a neurologist after 2 years of ill health and this diagnosis, and/or myalgic encephalomyelitis has been reconfirmed several times since. During subsequent years, she continued with symptoms of postexertional neuroimmune exhaustion ), pain, periodic muscle weakness, flu-like symptoms, orthostatic intolerance and unrefreshing sleep despite seeing many specialists.
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Coenzyme Q10 Plus Nadh And Mitochondrial Dysfunction
Coenzyme Q10 and NADH are common antioxidant supplements that have been used for several decades as dietary supplements for general maintenanceof health. The benefits of their administration have been extensively evaluated in several conditions . However, several studies have shown that there is a mitochondrial dysfunction, which reduces the ATP production, as an immediate effect primary or secondary to symptoms in most CFS/ME patients .
In the UK, Myhill et al. highlighted the power and usefulness of the ATP profile test as a diagnostic tool for differentiating between patients who have CFS/ME and other symptoms as a result of energy wastage due to stress and psychological factors and those who have insufficient energy due to cellular respiration dysfunction. The biochemical tests should be performed in CFS/ME patients before and after appropriate interventions, and possibly in other disabling fatigue conditions as well .
Relatively few pharmacological or other therapies for CFS/ME have been tested in large RCTs. Overall, a report commissioned by the AHRQ based on a systematic review for a US NIH Pathways to Prevention Workshop concluded that no available pharmacotherapy is of proven benefit in CFS/ME. Table 1 summarizes the current drug therapeutic strategies for CFS/ME.
Mitochondrial Damage Is Prevalent In Fatigued Patients
In normal cells, the mitochondria are the powerplants of the cells. Oxaloacetate upregulates PGC-1alpha, which in turn activates mitochondrial biogenesis, leading to increased mitochondrial density . Having more powerplants to burn glucose, and replace defective mitochondria, may be a major factor in reducing fatigue.
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Causes Of Chronic Fatigue Syndrome
Despite considerable research, the cause of chronic fatigue syndrome remains unknown. Controversy exists as to whether there is a single cause or many causes and whether the cause is physical or mental, but either way the symptoms are very real to the person.
Some researchers believe the syndrome ultimately will prove to have several causes, including genetic predisposition and exposure to microbes, toxins, and other physical and emotional factors.
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Cells From Patients With Fatigue Show Significantly Lower Nad+/nadh Ratio Levels
Oxaloacetate increases the NAD+/NADH ratio in animal models which would push this ratio in ME/CFS patients towards normalization. When oxaloacetate enters the cell, it can react to the metabolite malate in the cytoplasm via the action of the ubiquitous enzyme malate dehydrogenase. As part of this reaction, NADH is turned into NAD+, boosting the NAD+/NADH ratio. Krebs measured the change in the NAD+/NADH ratio with supplemental oxaloacetate as a 900% increase within 2 min .
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Popular Medications For Chronic Fatigue Syndrome
Chronic fatigue syndrome can have a devastating effect on a womans life and relationships. Unlike normal tiredness and fatigue, chronic fatigue syndrome is a long-term, incurable form of intense fatigue that does not improve with rest or sleep. While there is no cure for this condition, there are medications for chronic fatigue syndrome that may help manage symptoms. A doctor can help you decide which of these five popular chronic fatigue medications is right for you.
Valganciclovir For Chronic Fatigue Syndrome Patients Who Have Elevated Antibody Titers Against Human Herpes Virus 6 And Epstein
| The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| First Posted : May 24, 2007Last Update Posted : May 27, 2022 |
The purpose of this study determine whether the drug valganciclovir has a significant and real benefit on the central core of symptoms experienced by patients who have high titers to EBV and HHV-6 and are experiencing long-standing fatigue and cognitive impairment .
In addition, to characterize a quantifiable biological marker in these patients that will facilitate the identification of those likely to respond to valganciclovir and will make it possible to assess response to treatment.
Condition or diseaseWe will be executing a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of valganciclovir in patients experiencing chronic fatigue syndrome with elevated antibody titres against Human Herpesvirus-6 and Epstein-Barr Virus
Objectives
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A Reboot For Chronic Fatigue Syndrome Research
Name a remedy, and chances are that Elizabeth Allen has tried it: acupuncture, antibiotics, antivirals, Chinese herbs, cognitive behavioural therapy and at least two dozen more. She hates dabbling in so many treatments, but does so because she longs for the healthy days of her past. The 34-year-old lawyer was a competitive swimmer at an Ivy-league university when she first fell ill with chronic fatigue syndrome, 14 years ago. Her meticulous records demonstrate that this elusive malady is much worse than ordinary exhaustion. Last year, I went to 117 doctor appointments and I paid $18,000 in out-of-pocket expenses, she says.
Mild Pain Relievers And Nsaids
CFS/ME patients may benefit from NSAIDs, which are commonly used to relieve pain and reduce inflammation. In this context, the NSAIDs include ibuprofen and naproxen. They sometimes relieve frequent or severe joint and muscle pain, headaches, and fevers .
Other prescription medicines include anticonvulsants, also called antiseizure medicines. These drugs are sometimes prescribed for pain and sleep problems. They seem to work best when used for nerve pain. Antidepressant medicine is also prescribed to ease depression and anxiety, to enhance the ability to concentrate and to improve sleep quality . For their part, narcotic medicines are sometimes prescribed for pain that is not relieved by overthecounter drugs. Narcotics are generally reserved for the most severe cases because of the risk of addiction, and are used only for a short time .
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