2012 – American ME and CFS Society

Chronic fatigue syndrome: System under stress

Australian researchers have discovered for the first time that reduced heart rate variability — or changes in heart beat timing — best predicts cognitive disturbances, such as concentration difficulties commonly reported by people with chronic fatigue syndrome (CFS). This adds to the growing body of evidence linking autonomic nervous system imbalance to symptoms of this poorly understood disorder.

The findings are reported in the journal PLOS ONE.

Chronic fatigue syndrome is characterised by medically unexplained, disabling fatigue and neuropsychiatric symptoms of at least six months’ duration. The disturbance underlying the symptoms in CFS is still poorly understood.

“We have studied autonomic function in CFS for some time and our findings clearly indicate a loss of integrity in stress-responsive neural and physiological systems in CFS. Patients with this condition are hyper-responsive to challenges arising both from within the body and from the environment,” says lead researcher, Associate Professor Ute Vollmer-Conna of the University of New South Wales in Sydney, Australia.

“Even when they sleep, their stress-responsive neural systems are on high alert, signalling that it is not safe to relax. I think this condition may be understood by analogy to post-traumatic stress disorder, just that in CFS the original trauma is most likely a physiological, internal one, such as a severe infection.”

In a study of 30 patients with CFS and 40 healthy individuals, UNSW researchers recorded the heart beats of participants (via ECG) and analysed cardiac responses to cognitive challenges, and associations with mental performance outcomes.

The patients with CFS performed with similar accuracy, but they took significantly longer to complete the tests than people without the condition. They also had greater heart rate reactivity; low and unresponsive heart rate variability; and prolonged heart rate-recovery after the cognitive challenge.

Resting heart rate variability (an index of vagus nerve activity) was identified as the only significant predictor of cognitive outcomes, while current levels of fatigue and other symptoms did not relate to cognitive performance.

“This is the first demonstration of an association between reduced cardiac vagal tone and cognitive impairment in CFS. Our findings confirm previous reports of a significant loss of vagal modulation, which becomes particularly apparent when dealing with challenging tasks. The current results are consistent with the notion that CFS represents a ‘system under stress’,” Associate Professor Vollmer-Conna says.

The findings could lead to new ways to improve cognitive difficulties in people with CFS, including biofeedback assisted retraining of autonomic functioning, the researchers say.

Journal Reference: Alison Beaumont, Alexander R. Burton, Jim Lemon, Barbara K. Bennett, Andrew Lloyd, Uté Vollmer-Conna. Reduced Cardiac Vagal Modulation Impacts on Cognitive Performance in Chronic Fatigue Syndrome. PLoS ONE, 2012; 7 (11): e49518 DOI: 10.1371/journal.pone.0049518

Source: University of New South Wales. “Chronic fatigue syndrome: System under stress.” ScienceDaily. ScienceDaily, 15 November 2012. https://www.sciencedaily.com/releases/2012/11/121115133806.htm

Discovery could lead to faster diagnosis for some chronic fatigue syndrome cases

For the first time, researchers have landed on a potential diagnostic method to identify at least a subset of patients with chronic fatigue syndrome (CFS), a complex disorder with no known definitive cause or cure.

In a pilot study of six patients, scientists detected specific antibodies linked to latent Epstein-Barr virus reactivation in blood samples from people who had experienced classic CFS symptoms and responded to antiviral treatment. Control blood samples from 20 healthy people showed no such antibodies.

The research team, led by scientists from Ohio State University and Oakland University William Beaumont School of Medicine, acknowledges that the number of patients is small. But the researchers say the study’s power rests in their access to 16 months of blood samples for each patient — a collection allowing for an unprecedented longitudinal look at CFS.

The researchers plan to move forward with development of a clinical laboratory test that can detect these antibodies in blood samples.

The study is published in the Nov. 14 issue of the journal PLOS ONE.

The Epstein-Barr virus is a human herpes virus that causes infectious mononucleosis and several different types of tumors. An estimated 95 percent of Americans have been infected with the virus by adulthood, according to the Centers for Disease Control and Prevention (CDC), but fewer than half have experienced an active illness. Once a person is infected, the virus remains dormant in the body, and can be reactivated without causing symptoms of illness.

In these six patients, the study suggests that a latent Epstein-Barr virus had begun to reactivate, but that the newly awakened virus never reached its full potential to take over its host cells. That partial reactivation advanced enough to generate at least two viral proteins, DNA polymerase and dUTPase, and these patients produced antibodies specifically designed to identify and neutralize those proteins for more than a year.

The scientists theorize that even in the absence of a complete active infection, these viral proteins’ ability to induce inflammatory chemical signals causes enough immune system chaos to lead to CFS. The disorder’s main symptom is profound fatigue for at least six months that does not improve with rest, and is accompanied by problems that can include weakness, muscle pain, impaired memory and depression. Because the illness mimics many other disorders, diagnosis is difficult. An estimated 1 million Americans have CFS, but experts believe only 20 percent are diagnosed.

The study’s senior researchers agree that the work should be repeated in more patients “to confirm that these observations are real,” said virologist Ron Glaser, director of the Institute for Behavioral Medicine Research at Ohio State and a co-author of the study. “But finally, after more than 20 years, this is at least something to go on.”

Glaser’s primary collaborators on this work are Marshall Williams, professor of molecular virology, immunology and medical genetics at Ohio State, and A. Martin Lerner, a professor of internal medicine at Oakland University William Beaumont School of Medicine.

Ohio State and Lerner’s private practice, CFS LLC, have applied for a patent for the diagnostic method.

Glaser and Williams first published a paper in 1988 suggesting that these two viral proteins associated with partially reactivated Epstein-Barr virus could function as biomarkers for certain illnesses, including CFS. Meanwhile, Lerner became severely ill in 1986 and struggled for 10 years with CFS symptoms before treatment with antivirals dramatically improved his health.

Lerner, an infectious diseases specialist, runs his private CFS practice in Michigan, and his long-term tracking of patients’ characteristics and response to treatment made this longitudinal research possible.

The fact that CFS patients experience different symptoms and multiple types of viral and bacterial infections has led researchers to believe CFS potentially has numerous causes. That lack of uniformity also complicates the diagnostic process and development of treatments.

“Part of the problem in trying to identify an agent or biomarkers for chronic fatigue syndrome is the extreme variability among people who say they have CFS. How to sort that out has held the field back a lot of years,” said Glaser, who has studied the Epstein-Barr virus (EBV) for decades.

Lerner had long ago separated 142 of his patients into two groups: those who had tested positive for various antibodies against three types of herpes viruses and responded to months-long treatment with one of two types of antivirals, and a smaller group that had viral infections and a variety of co-infections who showed minimal response to antiviral treatment. As part of this tracking, he collected multiple blood serum samples for more than a year from each patient.

From those patients, he selected blood samples from six for this study. Five had been identified as an Epstein-Barr virus subset, and the sixth had Epstein-Barr virus and a bacterial co-infection. For comparison, researchers collected samples from 20 healthy people matched to the six CFS patients for age and sex.

Lerner, too, had independently hypothesized that CFS patients might be experiencing partial virus reactivation. Patients might test negative for the most active antibodies required to fight a virus, but could still recover from CFS after long-term antiviral treatment. One antiviral he uses is known to inhibit DNA polymerase, which would halt Epstein-Barr virus reactivation in its tracks.

With the CFS patients’ and control blood samples in hand, Williams used a highly sensitive laboratory method to detect whether they contained antibodies to the two target Epstein-Barr viral proteins, DNA polymerase and dUTPase, that are produced early in the process of viral reactivation.

Overall, 78.8 percent of the serum samples from the six CFS patients were positive for antibodies against DNA polymerase and 44.2 percent were positive for antibodies against dUTPase. No antibodies to these two proteins were detected in the 20 control samples.

“Every one of the six had antibodies to DNA polymerase or EBV dUTPase and those antibodies persisted over some 408 days,” Lerner said. “And the antibody levels were extraordinarily high.” High levels of antibodies circulating in the blood suggest long-term immune activation against those proteins.

Williams noted that the levels might be less significant than the antibodies being present in the first place.

“If you look at most healthy individuals, they wouldn’t have any reason to have an antibody against either of these proteins,” he said. “The antibodies alone are a good differentiator.”

This work was partially supported by the National Institutes of Health.

Additional co-authors include Maria Ariza of the Department of Molecular Virology, Immunology and Medical Genetics and Stanley Lemeshow, dean of the College of Public Health, both at Ohio State; Leonard Jason of DePaul University; Safedin Beqaj of Pathology Inc., in Torrance, Calif.; and James Fitzgerald of the University of Michigan School of Medicine.

Journal Reference: A. Martin Lerner, Maria E. Ariza, Marshall Williams, Leonard Jason, Safedin Beqaj, James T. Fitzgerald, Stanley Lemeshow, Ronald Glaser. Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset. PLoS ONE, 2012; 7 (11): e47891 DOI: 10.1371/journal.pone.0047891

Source: Ohio State University. “Discovery could lead to faster diagnosis for some chronic fatigue syndrome cases.” ScienceDaily. ScienceDaily, 14 November 2012. https://www.sciencedaily.com/releases/2012/11/121114171708.htm

Chronic fatigue syndrome patients had reduced activity in brain’s ‘reward center’

Chronic fatigue syndrome, a medical disorder characterized by extreme and ongoing fatigue with no other diagnosed cause, remains poorly understood despite decades of scientific study. Although researchers estimate that more than 1 million Americans are affected by this condition, the cause for chronic fatigue syndrome, a definitive way to diagnose it, and even its very existence remain in question. In a new study, researchers have found differing brain responses in people with this condition compared to healthy controls, suggesting an association between a biologic functional response and chronic fatigue syndrome.

The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward. Additionally, the extent of this lowered activation was associated with each patient’s measured level of fatigue. The basal ganglia are at the base of the brain and are associated with a variety of functions, including motor activity and motivation. Diseases affecting basal ganglia are often associated with fatigue. These results shed more light on this mysterious condition, information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.

The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC), Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia. An abstract of their study entitled, “Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue,” will be discussed at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

More Fatigue, Less Activation

Dr. Unger says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue. Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy. Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

The researchers recruited 18 patients with chronic fatigue syndrome, as well as 41 healthy volunteers with no symptoms of CFS. Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward. The participants were each told that they’d win a small amount of money if they correctly guessed whether a preselected card was red or black. After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient’s fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change.

Results Suggest Role of Inflammation

Unger notes that the findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome. “Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness,” she says. “They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.”

The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future, she adds. Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. Similarly, the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.

Estimates from the CDC suggest that annual medical costs associated with chronic fatigue syndrome total about $14 billion in the United States. Annual losses to productivity because of lost work time range between $9 and $37 billion, with costs to individual households ranging between $8,000 and $20,000 per year.

Source: Federation of American Societies for Experimental Biology (FASEB). (2012, April 24). Chronic fatigue syndrome patients had reduced activity in brain’s ‘reward center’. ScienceDaily. Retrieved March 4, 2017 from https://www.sciencedaily.com/releases/2012/04/120424142109.htm

Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial

Abstract:

BACKGROUND: Although enhanced temporal summation (TS) and conditioned pain modulation (CPM), as characteristic for central sensitization, has been proved to be impaired in different chronic pain populations, the exact nature is still unknown.

OBJECTIVES: We examined differences in TS and CPM in 2 chronic pain populations, patients with both chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) and patients with rheumatoid arthritis (RA), and in sedentary, healthy controls, and evaluated whether activation of serotonergic descending pathways by acetaminophen improves central pain processing.

STUDY DESIGN: Double-blind randomized controlled trial with cross-over design.

METHODS: Fifty-three women (19 CFS/FM patients, 16 RA patients, and 18 healthy women) were randomly allocated to the experimental group (1 g acetaminophen) or the placebo group (1 g dextrose). Participants underwent an assessment of endogenous pain inhibition, consisting of an evaluation of temporal summation with and without conditioned pain modulation (CPM). Seven days later groups were crossed-over. Patients and assessors were blinded for the allocation.

RESULTS: After intake of acetaminophen, pain thresholds increased slightly in CFS/FM patients, and decreased in the RA and the control group. Temporal summation was reduced in the 3 groups and CPM at the shoulder was better overall, however only statistically significant for the RA group. Healthy controls showed improved CPM for both finger and shoulder after acetaminophen, although not significant.

LIMITATIONS: The influence of acetaminophen on pain processing is inconsistent, especially in the patient groups examined.

CONCLUSION: This is the first study comparing the influence of acetaminophen on central pain processing in healthy controls and patients with CFS/FM and RA. It seems that CFS/FM patients present more central pain processing abnormalities than RA patients, and that acetaminophen may have a limited positive effect on central pain inhibition, but other contributors have to be identified and evaluated.

Source: Meeus M, Ickmans K, Struyf F, Hermans L, Van Noesel K, Oderkerk J, Declerck LS, Moorkens G, Hans G, Grosemans S, Nijs J. Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial. Pain Physician. 2013 Mar-Apr;16(2):E61-70. http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=16&page=E61 (Full article available as PDF file)

Energy Conservation/Envelope Theory Interventions to Help Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

OBJECTIVES: Treatment approaches for patients with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been controversial. This paper provides the theoretical and conceptual background for the Energy Envelope Theory to assist patients with ME/CFS and reviews evidence of its treatment efficacy.

METHODS: Over a 15-year period, efforts were directed to develop a non-pharmacologic intervention that endeavored to help patients with ME/CFS self-monitor and self-regulate energy expenditures and learn to pace activities and stay within their energy envelope.

CONCLUSIONS: Studies show that the energy envelope approach, which involves rehabilitation methods, helps patients with ME/CFS pace activities and manage symptoms and can significantly improve their quality of life.

Source: Jason LA, Brown M, Brown A, Evans M, Flores S, Grant-Holler E, Sunnquist M. Energy Conservation/Envelope Theory Interventions to Help Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fatigue. 2013 Jan 14;1(1-2):27-42. Epub 2012 Aug 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596172/ (Full article)

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements.

Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea.

In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness.

In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

Source: Ravindran M, Adewuyi O, Zheng Y, Rayhan RU, Le U, Timbol C, Merck S, Esteitie R, Read C, Cooney M, Baraniuk J. Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies. Glob J Health Sci. 2012 Dec 12;5(2):94-110. doi: 10.5539/gjhs.v5n2p94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209305/ (Full article)

Association of monoamine-synthesizing genes with the depression tendency and personality in chronic fatigue syndrome patients

Abstract:

AIMS: Tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GCH) are the rate-limiting enzymes for the biosynthesis of catecholamines and tetrahydrobiopterin (BH4), respectively. Since catecholamines and BH4 are thought to be involved in the pathophysiology of CFS, we explored the genetic factors that influence CFS development and examined the possible association between the SNPs of the TH and GCH genes and the various characteristics of CFS patients.

MAIN METHODS: After drawing venous blood from CFS patients and controls, genomic DNA was then extracted from whole blood in accordance with standard procedures. Digestion patterns of the PCR products were used for genotyping the SNPs of GCH (rs841; C+243T) and TH (rs10770141; C-824T). We also performed questionnaires consisting of fatigue-scale and temperament and character inventory scale (TCI) to CFS patients.

KEY FINDINGS: Our results demonstrated that the allele differences for the GCH and TH SNPs were not associated with CFS patients. We did find that the GCH gene with the C+243T polymorphism affected harm avoidance, while the TH gene with the C-824T polymorphism affected persistence in the CFS patients. The concept of persistence has been linked to specific personality, such as perfectionism, in CFS.

SIGNIFICANCE: Our results suggest that the biosynthetic pathways of the monoamine neurotransmitters that are mediated by TH and GCH might be associated with the CFS clinical findings, because persistence is one of the typical personality traits observed in CFS and patients with major depressive disorder exhibit a higher harm avoidance score.

Source: Fukuda S, Horiguchi M, Yamaguti K, Nakatomi Y, Kuratsune H, Ichinose H, Watanabe Y. Association of monoamine-synthesizing genes with the depression tendency and personality in chronic fatigue syndrome patients. Life Sci. 2013 Feb 27;92(3):183-6. doi: 10.1016/j.lfs.2012.11.016. Epub 2012 Dec 13. https://www.ncbi.nlm.nih.gov/pubmed/23246742

Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a clinical condition characterized by severe and disabling fatigue that is medically unexplained and lasts longer than 6 months. Although it is possible to effectively treat CFS, the nature of the underlying physiology remains unclear. Various studies have sought evidence for an underlying disturbance in immunity. The aim of this study was to compare the humoral and cellular immune responses upon influenza vaccination in CFS patients and healthy controls.

RESULTS: Identical antibody titers were observed in CFS patients and healthy controls. Patients and controls demonstrated similar seroprotection rates against all three virus-strains of the influenza vaccine, both pre- and post-vaccination. Functional T cell reactivity was observed in both CFS patients and healthy controls. CFS patients showed a non-significant, numerically lower cellular proliferation at baseline compared to controls. Vaccination induced a significant increase in cellular proliferation in CFS patients, but not in healthy controls. Cytokine production and the number of regulatory T cells were comparable in patients and controls.

CONCLUSIONS: The humoral and cellular immune responses upon influenza vaccination were comparable in CFS patients and healthy controls. Putative aberrations in immune responses in CFS patients were not evident for immunity towards influenza. Standard seasonal influenza vaccination is thus justified and, when indicated, should be recommended for patients suffering from CFS.

Source: Prinsen H, de Vries IJ, Torensma R, Pots JM, Mulder SF, van Herpen CM, Elving LD, Bleijenberg G, Stelma FF, van Laarhoven HW. Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome. BMC Immunol. 2012 Dec 17;13:71. doi: 10.1186/1471-2172-13-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534525/ (Full article)

Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a chronic, disabling illness that affects approximately 0.2% of the population. Non-restorative sleep despite sufficient or extended total sleep time is one of the major clinical diagnostic criteria; however, the underlying cause of this symptom is unknown.

This review aims to provide a comprehensive overview of the literature examining sleep in CFS/ME and the issues surrounding the current research findings. Polysomnographic and other objective measures of sleep have observed few differences in sleep parameters between CFS/ME patients and healthy controls, although some discrepancies do exist. This lack of significant objective differences contrasts with the common subjective complaints of disturbed and unrefreshed sleep by CFS/ME patients.

The emergence of new, more sensitive techniques that examine the microstructure of sleep are showing promise for detecting differences in sleep between patients and healthy individuals. There is preliminary evidence that alterations in sleep stage transitions and sleep instability, and other physiological mechanisms, such as heart rate variability and altered cortisol profiles, may be evident. Future research investigating the etiology of non-restorative sleep in CFS/ME may also help us to undercover the causes of non-restorative sleep and fatigue in other medical conditions.

Source: Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review. J Clin Sleep Med. 2012 Dec 15;8(6):719-28. doi: 10.5664/jcsm.2276. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501671/ (Full article)

Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor

Abstract:

BACKGROUND: Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(-)] autoantibodies.

METHODOLOGY: Five CFS(+) and six CFS(-) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[(11)C]methyl-3-piperidyl benzilate [(11)C](+)3-MPB for the mAChR binding and N-[(11)C]methyl-4-piperidyl acetate [(11)C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [(11)C](+)3-MPB binding in CFS(-) patients did not differ from normal controls, CFS(+) patients showed significantly lower [(11)C](+)3-MPB binding than CFS(-) patients and normal controls. In contrast, the [(11)C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups.

CONCLUSION: The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients.

Source: Yamamoto S, Ouchi Y, Nakatsuka D, Tahara T, Mizuno K, Tajima S, Onoe H, Yoshikawa E, Tsukada H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor. PLoS One. 2012;7(12):e51515. doi: 10.1371/journal.pone.0051515. Epub 2012 Dec 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519853/ (Full article)