The American M.E. Review

COMPILED BY THE M.E. SOCIETY OF AMERICA, P.O. BOX 44402, SHREVEPORT, LA 71134

MARYANN SPURGIN, Ph.D., EDITOR

THOMAS EDLEMAN, RESEARCH/EDITORIAL ASSISTANT

VOLUME 1, NUMBER 1                                                           30 JUNE 2002

© Copyright M.E. Society of America 2002

The American M.E. Review publishes articles, advocacy alerts, and research reviews when useful information arises and not on a set schedule. We frequently update our website with new research.

RESEARCH REVIEWS

ORTHOSTATIC INTOLERANCE

Farquhar WB, Hunt BE, Taylor JA, Darling SE, Freeman R. "Blood volume and its relation to peak O(2) consumption and physical activity in patients with chronic fatigue syndrome." Am J Physiol Heart Circ Physiol 282.1 (2002):H66-71.  ABSTRACT: The authors hypothesize that hypovolemia, through its interaction with central hemodynamics, would contribute to the exercise intolerance associated with CFS. They examined blood volume, peak aerobic power, habitual physical activity, fatigue level, and their interrelations to understand the physiological basis of the disorder. Seventeen patients who met the CDC criteria for CFS and 17 age-matched controls participated. Blood volume was assessed using a single Bolus injection of Evans blue dye. Peak oxygen consumption was measured during exercise on an upright cycle ergometer. Supine cardiac output and stroke volumes were measured using CO(2) rebreathing. Questionnaires were used to assess habitual physical activity and fatigue. Patients displayed a trend for a 9% lower blood volume and had a 35% peak oxygen consumption. These two variables were highly related within the patients and the controls. Peak ventilation and habitual physical activity were significantly lower in the patients. Fatigue level was not related to any of the measured physiological parameters within the CFS group. Individuals with CFS have a significantly lower peak oxygen consumption and an insignificant trend toward lower blood volume compared with controls. These variables were highly related in both subject groups, indicating that blood volume is a strong physiological correlate of peak oxygen consumption in patients with CFS. [Editor's note: We hypothesize that the Streeten/Bell findings showed lower blood volumes because the patients they selected were more severely affected, were unable to exercise at all, and were unable to remain upright for any reasonable period of time.  We argue that researchers need to introduce "degree of illness" subsets into their research to achieve more consistency of results in the research data.]

Tanaka H, Matsushima R, Tamai H, Kajimoto Y. "Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance." J Pediatr 140.4 (2002):412-17. ABSTRACT: The purpose of this study was to measure postural changes in cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance. "We studied 28 patients (age, 10 to 22 years) and 20 healthy control subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and deoxygenated Hb were noninvasively and continuously measured with near infrared spectroscopy during active standing . Beat-to-beat arterial pressure was monitored by Finapres. Orthostatic intolerance determined by cardiovascular responses was observed in 16 of 28 patients, instantaneous orthostatic hypotension in 8,delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing. CONCLUSIONS: Impaired cerebral hemodynamics in patients with chronic fatigue syndrome and postural orthostatic tachycardia suggest a link between impaired cerebral oxygenation and chronic fatigue. However, this cannot explain the symptoms in patients meeting the criteria for chronic fatigue without orthostatic intolerance." [Editor's note: “Chronic fatigue” is a poorly defined concept.  We wonder why "chronic fatigue" was used in the title of this article.]

Rowe PC. "Orthostatic intolerance and chronic fatigue syndrome: new light on an old problem." J Pediatr 140.4 (2002):387-9. Chronic fatigue is a prominent symptom in a variety of overlapping syndromes of circulatory dysfunction, the most notable examples of which are neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS). An early suggestion that such abnormalities were treatable causes of symptoms in what we now call chronic fatigue syndrome (CFS) was made in 1940 by Alexander MacLean and Edgar Allen.  They described a group of patients who experienced excessive acceleration of the heart and hypotension after moving from the recumbent to the erect posture, usually associated with symptoms of orthostatic exhaustion, blurring of vision, weakness on exercise, and syncopal episodes. McLean and Allen attributed the tachycardia to a reduced venous return to the heart, in part because symptoms and hemodynamic changes could be provoked within 10 seconds by
Flack's test, which involved forced expiration into a tube to maintain a mercury column at 40 mm, thereby reducing blood flow into the thorax.1,2 They concluded that this orthostatic tachycardia syndrome seemed similar to "effort syndrome, irritable heart, or neurocirculatory asthenia" the synonyms of the day for what we now call CFS. McLean and Allen reported that patients improved by increasing their intake of fluids and sodium, and by sleeping with the head of the bed elevated. The head-up bed may have helped to conserve intravascular volume by reducing blood flow to the kidney at night. It is a medical curiosity that these detailed observations were largely ignored for several decades.

Naschitz JE, Rozenbaum M, Rosner I, Sabo E, Priselac RM, Shaviv N, Ahdoot A, Ahdoot M, Gaitini L, Eldar S, Yeshurun D. "Cardiovascular response to upright tilt in fibromyalgia differs from that in chronic fatigue syndrome." J Rheumatol 28.6(2001):1356-60. OBJECTIVE: To compare the cardiovascular response during postural challenge of patients with fibromyalgia (FM) to those with chronic fatigue syndrome (CFS). METHODS: Age and sex matched patients were studied, 38 with FM, 30 with CFS, and 37 healthy subjects. Blood pressure (BP) and heart rate (HR) were recorded during 10 min of recumbence and 30 min of head-up tilt. Differences between successive BP values and the last recumbent BP, their average, and standard deviation (SD) were calculated. Time curves of BP differences were analyzed by computer and their outline ratios (OR) and fractal dimensions (FD) were measured. HR differences were determined similarly. Based on the latter measurements, each subject's discriminant score (DS) was computed. RESULTS: For patients and controls average DS values were: FM: -3.68 (SD 2.7), CFS: 3.72 (SD 5.02), and healthy controls: -4.62 (SD 2.24). DS values differed significantly between FM and CFS (p < 0.0001). Subgroups of FM patients with and without fatigue had comparable DS values. CONCLUSION: The DS confers numerical expression to the cardiovascular response during postural challenge. DS values in FM were significantly different from DS in CFS, suggesting that homeostatic responses in FM and CFS are dissimilar. This observation challenges the hypothesis that FM and CFS share a common derangement of the stress-response system.  [Editor’s note: FM and M.E. are clinically distinct entities, and we applaud these researchers for doing comparison studies.]

Streeten DH. "Role of impaired lower-limb venous innervation in the pathogenesis of the chronic fatigue syndrome." Am J Med Sci 321.3(2001):163-67. BACKGROUND: In patients with acute orthostatic hypotension, there is excessive pooling of blood in the legs, which may result from the strikingly subnormal compliance that is demonstrable in the pedal veins during norepinephrine infusion. The common occurrence of delayed orthostatic hypotension and/or tachycardia in the chronic fatigue syndrome (CFS) led to the present studies of foot vein compliance in CFS patients with a linear variable differential transformer. METHODS: Seven patients with CFS were compared with 7 age- and gender matched healthy control subjects in their blood pressure, heart-rate, and plasma norepinephrine responses to prolonged standing and in measurements of their foot vein contractile responses to intravenous norepinephrine infusions with the linear variable differential transformer. RESULTS: Excessive, delayed (usually after 10 min) orthostatic reductions in systolic and diastolic blood pressure (P < 0.01) and inconsistently excessive increases in heart rate were found in the CFS patients, in whom venous compliance in response to infused norepinephrine was significantly reduced (P < 0.05). CONCLUSIONS: In these patients with CFS, delayed orthostatic hypotension was clearly demonstrable, and, as in previously reported patients with orthostatic hypotension of acute onset, this was associated with reduced pedal vein compliance during norepinephrine infusion, implying impaired sympathetic innervation of foot veins. The rapid symptomatic improvement demonstrated in previous studies of CFS patients during correction of orthostatic venous pooling by inflation of military antishock trousers (MAST) to 35 mm Hg may suggest that excessive lower body venous pooling, perhaps by reducing cerebral perfusion, is involved in the orthostatic component of fatigue in these patients.

Streeten DH, Thomas D, Bell DS. The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome. Am J Med Sci 320.1(2000): 1-8.  Abstract: BACKGROUND: Orthostatic hypotension during upright tilt is an important physical disorder in patients with chronic fatigue syndrome. We have tested its occurrence during prolonged standing, whether it is correctable, and whether reduced circulating erythrocyte volume is present. METHODS: Fifteen patients were randomly selected from a large population of patients with chronic fatigue syndrome, studied, and observed for several years (by DSB). Blood pressure (BP) and heart rate (HR) measured with Dinamap every minute for 30 minutes supine and 60 minutes standing were compared with these findings in 15 healthy age- and gender-matched control subjects and later during lower body compression with military antishock trousers (MAST). Plasma catecholamines and circulating erythrocyte and plasma volumes were also measured by isotopic dilution methods. RESULTS: Abnormal findings in the patients included excessive orthostatic reductions in systolic (P < 0.001) and diastolic BP (P < 0.001) and excessive orthostatic tachycardia (P < 0.01), together with presyncopal symptoms in 11 of the 15 patients and in none of the control subjects after standing for 60 min. Lower body compression with the MAST restored all orthostatic measurements to normal and overcame presyncopal symptoms within 10 min. Circulating erythrocyte but not plasma volumes were subnormal in the 12 women (P < 0.01) and plasma norepinephrine concentration rose excessively after standing for 10 min. CONCLUSION: Delayed orthostatic hypotension and/or tachycardia caused by excessive gravitational venous pooling, which is correctable with external lower-body compression, together with subnormal circulating erythrocyte volume, are very frequent, although not invariably demonstrable, findings in moderate to severe chronic fatigue syndrome. When present, they may be involved in its pathogenesis.

NEUROLOGY, ENDOCRINOLOGY, AND/OR IMMUNOLOGY

Quan N, Herkenham M. "Connecting cytokines and brain: a review of current issues." Histol Histopathol 17.1 (2002):273-88. The authors review over 15,000 articles published concerning the relationship between cytokines and the central nervous system (CNS), most of which were published in the past five years. From these articles, the authors point to two major topics which have emerged as central issues: (1) how do cytokines modulate the functions of the CNS? and (2) what is the role of cytokines in the pathogenesis of neurological diseases? The authors state, "Thus far, it has been clearly established that cytokines can alter the functions of the CNS in specific manners, invoking CNS-controlled autonomic, neuroendocrine, and behavioral responses. Induced expression of cytokines has also been found in the CNS during brain injury and infection, contributing to the immunological processes at this 'immunologically priviledged' site. Furthermore, increasing evidence points to the potential involvement of cytokines in the induction and modulation of an array of neurological diseases ranging from Alzheimer's disease to chronic fatigue syndrome. Despite such progress, however, substantial obstacles remain for both the basic understanding and the potential clinical exploitation of how cytokines interact with CNS." [Editor's note: We hypothesize that respiratory chain dysfunction plays a role in neurological disease. We urge researchers to investigate the mitochondrial connection.  See quote by Dr. Bruce Cohen in the abstract on nitric oxide below.]

Pall ML, Satterle JD. Elevated nitric oxide /peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder. Annals NY Acad Sci 933 (Mar. 2001):323-9. The authors note that nitric oxide and an oxidant, possibly peroxynitrite, are implicated in multiple chemical sensitivity (MCS) and chemical intolerance (CI). The authors add: "The positive feedback loops proposed earlier for CFS may explain the chronic nature of MCS (CI) as well as several other of its reported properties. These observations raise the possibility that this proposed elevated nitric oxide/peroxynitrite mechanism may be the mechanism of a new disease paradigm." [Editor's note: This finding fits into our mitochondrial hypothesis regarding M.E. The following quote is from the Spring 1998, Vol. 3, No. 1, p. 7, issue of Mitochondrial News in an article titled "Anasthesia and Mitochondrial Cytopathies" by Bruce  Cohen, M.D. (one of the country's leading mitochondrial experts), John Shoffner, M.D., and Glenn DeBoer, M.D.: "During infections, the body responds by making chemicals known as cytokines...[which] help the body fight infections...[but] are also responsible for the fever, aches, chills, and overall 'rotten' feeling we get when we are ill. Cytokines induce formation of nitric oxide (NO)...which inhibits cisacotinase (a citric acid cycle enzyme) and the iron-containing cytochromes of the respiratory chain. Therefore, NO...may decrease energy production [and] can also interact with other chemicals in the body that result in damage to the mitochondrial DNA and mitochondrial structure itself. TNF is...known to be a potent inhibitor of complex III [of the respiratory chain.]" Since elevated TNF and NO are frequently reported in the disease, we continue to hypothesize that destruction of the respiratory chain is part of the pathophysiology of M.E.]

Pall ML. "Common etiology of post traumatic stress disorder, fibromyalgia, chronic fatigue syndrome, and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite." Med Hypotheses 57.2 (2001):139-45. ABSTRACT: Three types of overlap occur among the disease states CFS, FM, MCS, and PTSD. They share common symptoms. Many patients meet the criteria for diagnosis for two or more of these disorders and each disorder appears to be often induced by a relatively short-term stress which is followed by a chronic pathology, suggesting that the stress may act by inducing a self-perpetuating vicious cycle. Such a vicious cycle mechanism has been proposed to explain the etiology of CFS and MCS, based on elevated levels of nitric oxide and its potent oxidant product, peroxynitrite. Six positive feedback loops were proposed to act such that when peroxynitrite levels are elevated, they may remain elevated. The biochemistry involved is not highly tissue-specific, so that variation in symptoms may be explained by a variation in nitric oxide/peroxynitrite tissue distribution. The evidence for the same biochemical mechanism in the etiology of PTSD and FM is discussed, and while less extensive than in the case of CFS and MCS, it is nevertheless suggestive. Evidence supporting the role of elevated nitric oxide/ peroxynitrite in these four disease states is summarized, including induction of nitric oxide by common apparent inducers of these disease states, markers of elevated nitric oxide/peroxynitrite in patients and evidence for an inductive role of elevated nitric oxide in animal models. This theory appears to be the first to provide a mechanistic explanation for the multiple overlaps of these disease states and it also explains the origin of many of their common symptoms and similarity to both GWI and chronic sequelae of carbon monoxide toxicity. This theory suggests multiple studies that should be performed to further test this proposed  mechanism. If this mechanism proves central to the etiology of these four conditions, it may also be involved in other conditions of currently obscure etiology and criteria are suggested for identifying such conditions. [Editor's note: See note in previous reference.]

Manuel y Keenoy B, Moorkens G, Vertommen J, DeLeeuw I. "Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome." Life Sci 68.17(2001):2037-49. The aetiology and pathogenesis of the Chronic Fatigue Syndrome (CFS) are still largely unresolved. Accompanying metabolic disorders such as selective n-6 fatty acid depletion suggest that oxidative stress and more specifically lipid peroxidation might play a role in its pathogenesis. In order to investigate this hypothesis, oxidant-antioxidant status and its impact on lipoprotein peroxidation in vitro was examined in 61 patients with unexplained fatigue lasting more than 1 month. They were subdivided into 2 groups: group CFS+ (33 subjects) fulfilled the 1988 Center of Disease Control criteria for CFS and group CFS- did not but was similar as regards age, sex distribution and clinical characteristics. Antioxidant status was similar in the 2 groups except for lower serum transferrin in the CFS + (mean ! (95 % CI) 2.41 (2.28-2.54) versus 2.73 (2.54-2.92) g/L in the CFS-, p = 0.009) and higher lipoprotein peroxidation in vitro: 6630 (5949-7312) versus 5581 (4852-6310) nmol MDA/mg LDL and VLDL cholesterol x minutes, p = 0.035). CFS intensified the influence of LDL cholesterol (p = 0.012) and of transferrin (p = 0.045) on peroxidation in vitro, suggesting additional pro-oxidant effects. These results indicate that patients with CFS have increased susceptibility of LDL and VLDL to copper-induced peroxidation and that this is related both to their lower levels of serum transferrin and to other unidentified pro-oxidising effects of CFS.

Ogawa M, Nishiura T, et al. "Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome." Eur J Clin Invest 28.11(1998):937-43. Natural killer cell activity was evaluated in 20 patients with CFS and compared with 21 healthy controls. RESULTS: In healthy control subjects, NK activity was significantly increased after treatment with L-Arginine (L-Arg), an NK function enhancer, for 24 hours whereas the same treatment failed to enhance NK activity in the CFS patients. The authors then "...focused on L-Arg metabolism, which involves nitric oxide(NO) production through NO synthase (NOS). The expression of inducible NO synthase (iNOS) transcripts in peripheral blood mononuclear cells was not significantly different between healthy control subjects and CFS patients. The L-Arg-mediated NK cell activation was abolished by addition of NG-monomethyl- L-arginine, an inhibitor for iNOS. Furthermore, incubation with S-nitroso-N-acetyl-penicillimine, an NO donor, stimulated NK activity in healthy control subjects but not in CFS patients. These results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK cell activation in CFS patients."

Gow JW, Simpson K, Behan PO, Chaudhuri A, McKay IC, Behan WM. "Antiviral pathway activation in patients with chronic fatigue syndrome and acute infection." Clin Infect Dis 33.12 (2001):2080-81. Gene expression of key enzymes in two antiviral pathways (RNase L and RNA-regulated protein kinase [PKR]) was compared in 22 patients with chronic fatigue syndrome, 10 patients with acute gastroenteritis, and 21 healthy volunteers. Pathway activation in the group of patients with infections differed significantly from that of the other two groups, in whom there was no upregulation. [Editor's note: We hope that researchers will investigate the connection between antiviral pathway activation and impairment of the respiratory chain.]

Buskila D, Press J. "Neuroendocrine mechanisms in fibromyalgia-chronic fatigue." Best Pract Res Clin Rheumatol 15.5 (2001):747-48. FMS and CFS are poorly understood disorders that share similar demographic and clinical characteristics. Because of the clinical similarities it has been suggested that they share a similar pathophysiological mechanism, namely central nervous system dysfunction. This chapter presents data demonstrating neurohormonal abnormalities, abnormal pain processing, and autonomic nervous system dysfunction in FMS and CFS. The possible contribution of the CNS dysfunction to the development and symptomatology of these conditions is discussed. The chapter concludes by reviewing the effect of current treatments and emerging therapeutic modalities. [Editor's note: This research overemphasizes the connection between fibromyalgia and M.E., which are clinically dissimilar. Fibromyalgia generally involves muscle trigger point pain, while M.E. involves more neurological (i.e., neuropathy pain, cognitive dysfunction, etc.), orthostatic, and exercise intolerance problems. Other studies have found marked differences between the two syndromes. Linking groups by “fatigue” is unproductive.  See abstract 4 above.  While some patients may suffer from both M.E. and FM, we hold that the two syndromes are clinically distinct.]

Palaniappan R, Sirimanna T. "Peripheral vestibular dysfunction in chronic fatigue syndrome." Int J Pediatr Otorhinolaringol 64.1(2002): 69-72. ABSTRACT: The objective of this study was to report left-sided peripheral vestibular failure as the cause of dizziness in a 12-year-old boy diagnosed as having chronic fatigue syndrome. The authors conclude: "We recommend proper vestibular assessment for CFS patients presenting with dizziness, as effective treatment for peripheral vestibular disorder exists in the form of balance rehabilitation exercises."

Robinson GL, McGregor NR, Roberts TK, Dunstan RH, Butt H. "A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction." Percept Mot Skills 93.2(2001):486-504. This study investigated the biological basis of visual processing disabilities in adults with chronic fatigue syndrome. The study involved 61 adults with symptoms of CFS who were screened for visual processing problems (Irlen Syndrome) and divided into two groups according to the severity of symptoms of Irlen Syndrome. Significant variations were identified in blood lipids and urine amino and organic acids of the two groups which may be indicative of activation of the immune system due to some infective agent. It was suggested that metabolic profiling may help the development of more valid diagnostic categories and allow more investigation of immune system dysfunction as a possible causal factor in a range of learning and behaviour disorders. [Editor's note: Visual and neurological disturbances are symptoms of M.E. We urge researchers to use more strict selection criteria when studying patients.]

Michiels V, Cluydts R. "Neuropsychological functioning in chronic fatigue syndrome: a review." Acta Psychiatr Scand 103.2 (2001):84-93. Abstract: OBJECTIVE: In this paper we review critically the current status of neurocognitive studies in patients with chronic fatigue syndrome (CFS). METHOD: CFS literature was monitored as part of a large research project which involved several neuropsychological and psychopathological studies. The literature survey was the result of several consecutive searches on Medline and PsycInfo databases. RESULTS: The neurocognitive studies are reviewed in terms of scientificaly accepted aspects of attention and memory. In addition, we review possible explanations for cognitive dysfunction in CFS. This is preceded with a discussion of the methodological limitations that are considered to explain inconcistencies across neuropsychological studies in CFS. CONCLUSION: The current research shows that slowed processing speed, impaired working memory and poor learning of information are the most prominent features of cognitive dysfunctioning in patients with CFS. Furthermore, to this date no specific pattern of cerebral abnormalities has been found that uniquely characterizes CFS patients. There is no overwhelming evidence that fatigue is related to cognitive performance in CFS, and researchers agree that their performance on neuropsychological tasks is unlikely to be accounted solely by the severity of the depression and anxiety.

Binder LM, Storzbach D, Campbell KA, Rohlman DS, Anger WK. "Neurobehavioral deficits associated with chronic fatigue syndrome in veterans with Gulf War unexplained illness." J Int Neuropsychol Soc 7.7 (Nov. 2001):835-9. The researchers tested the hypothesis that in a sample of Gulf War veterans CFS was associated with cognitive deficits on computerized cognitive testing after controlling for the effects of premorbid cognitive differences. They obtained the Armed Forces Qualification Test (AFQT) data required around the date of induction in the military of 94 veterans of the Gulf War, 32 with CFS and 62 healthy controls. Controls performed better than participants diagnosed with CFS on 3 of 8 variables after the effect of premormid AFQT scores was removed with ANCOVA.

Brunet JL, Fatoohi F, Liaudet AP, Cozon GJ. "Role of pathological delayed-type hypersensitivity in chronic fatigue syndrome: importance of the evaluation of lymphocyte activation by flow cytometry and the measurement of urinary neopterin." Allerg Immunol (Paris) 34.2(2002):38-44. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost 50% of patients with chronic fatigue syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans, and then monitoring for a systemic reaction over the following 6-48 hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans antigens by three-color flow cytometry based on CD3, CD4, and either CD69 or CD25. Another useful parameter is the kinetics of neopterin excretion in urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other.

Shetzline SE, Martinand-Mari C, Reichenbach NL, Buletic Z, Lebleu B, Pfleiderer W. Charubala R, DeMeirleir K, DeBecker P, Peterson DL, Herst CV, Englebeinne P, Suhadolnik RJ. "Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome." J Interferon Cytokine Res 22.4(2002): 443-56. In the current study, analytic gel permeation FPLC, azido photoaffility labeling, two-dimensional gel electro- phoresis, and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) have been used to examine the biochemical relationship between the 80-kDa RNase L in healthy control PBMC and the 37-kDa RNase L in PBMC in individuals with CFS. Like the 80-kDa RNase L, the 37-kDa RNase L is present as a catalytically inactive heterodimer complex with the RNase L inhibitor (RLI). Formation of the 37-kDa RNase L-RLI complex indicates that the 37 kDa RNase L is structurally similar to the 80-kDa RNase L at the N-terminus, whic! h contains the 2-5A binding domain. The enzomatically active monomer form of 37-kDa RNase L resolved by 2-D electrophoresis has a pI of 6.1. RT-PCR and Southern blot analysis demonstrated that the 37-kDa RNase L is not formed by alternative splicing. In-gel tryptic digestion of the 37-kDa RNase L that was excised from the 2-D gels and subsequent MALDI-MS analysis identified three peptide masses that are identical to three predicted peptide masses in the 80-kDa RNase L. The electrophoretic mobility of the 2-5A azido photolabeled/immunoprecipitated 37-kDa RNase L in PBMC shares structural and functional features with the 80- kDa RNase L, in particular in the 2-5A binding and catalytic domains.

Cook DB, Lange G, DeLuca J, Natelson B. "Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome." Int J Neurosci 107.1-2(2001):1-6. Chronic Fatigue Syndrome (CFS) is an unexplained illness that is characterized by severe fatigue. Some have suggested that CFS is a "functional somatic syndrome" in which symptoms of fatigue are inappropriately attributed to a serious illness. However, brain magnetic resonance imaging (MRI) data suggest that there may be an organic abnormality associated with CFS. To understand further the significance of brain MRI abnormalities, we examined the relationship between MRI identified brain abnormalities and self-reported physical functional status in 48 subjects with CFS who underwent brain MR imaging and completed the Medical Outcomes Study SF-36. Brain MR images were examined for the presence of abnormalities based on 5 general categories previously shown to be sensitive to differentiating CFS patients from healthy controls. There were significant negative relationships between the presence of brain abnormalities and both the physical functioning (PF) (rho=-.31, p=.03), and physical component summary PCS (rho=-.32, p=.03) subscales of the SF-36. CFS patients with MRI identified brain abnormalities scored significantly lower on both PF (t(1,46) =2.3, p=.026) and the PCS (t(1,41) =2.4, p=.02) than CFS subjects without an identified brain abnormality. When adjusted for age differences only the PF analysis remained significant. However, the effect sizes for both analyses were large indicating meaningful differences in perceived functional status between the groups. These results demonstrate that the presence of brain abnormalities in CFS are significantly related to subjective reports of physical function and that CFS subjects with MRI brain abnormalities report being more physically impaired than those patients without brain abnormalities. [Editor’s note: Brain SPECT abnormalities are also common in the disease.  We applaud these researchers for investigating a biological basis but ask them not to focus on “fatigue.”  Further, although no single etiology has been found, “unexplained illness” may not be an accurate characterization given the many research articles on the disease.  This is a disease, which, like lupus, has no single marker, but medical explanations have been offered for many aspects of the pathophysiology of the disease, even though we do not yet have a final theory.]

Dale E, Komaroff AL, Bloomingdale K, Wilson S, Albert MS. "Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression." Appl Neuropsychol 8.1(2001):12-22. Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls. After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.

Nishikai M, Tomamatsu S, Hankins RW, Takagi S, Miyachi K, Kosaka S, Akiya K.  “Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders.” Rheumatol (Oxford) 40.7(2001):806-10. OBJECTIVE: To identify antinuclear antibodies (ANA) specific for chronic fatigue syndrome (CFS), and in related conditions such as fibromyalgia (FM) or psychiatric disorders. METHODS: One hundred and fourteen CFS patients and 125 primary and secondary FM patients were selected based on criteria advocated by the Centers for Disease Control and Prevention and by the American College of  Rheumatology, respectively. As controls, healthy subjects and patients with either various psychiatric  disorders or diffuse connective tissue diseases were included. Autoantibodies were examined by immunoblot utilizing HeLa cell extracts as the antigen. RESULTS: Autoantibodies to a 68/48 kDa protein were present in 13.2 and 15.6% of patients with CFS and primary FM, respectively. In addition, autoantibodies to a 45 kDa protein were found in 37.1 and 21.6% of the patients with secondary FM and psychiatric disorders, respectively. Meanwhile, these two autoantibodies were not found at all in connective tissue disease patients without FM, nor in healthy subjects (P<0.05). As a group, the anti-68/48 kDa-positive CFS patients presented more frequently with hypersomnia (P<0.005), short-term amnesia  (P<0.07) or difficulty in concentration (P<0.05) than those CFS patients without the antibodies.  CONCLUSIONS: The presence of the anti-68/48 kDa protein antibodies in a portion of both CFS and primary FM patients suggests the existence of a common immunological background. These antibodies may find utility as possible markers for a clinicoserological subset of CFS/FM patients with hypersomnia and  cognitive complaints.

INFECTIONS

Krueger GR, Koch B, Hoffmann A, Rojo J, Brandt ME, Wang G, Buja LM.  “Dynamics of chronic active herpesvirus-6 infection in patients with chronic fatigue syndrome: data acquisition for computer modeling.” In Vivo 15.6(2001):461-65. Ten adult patients with persistent active HHV-6 variant A infection and clinical chronic fatigue syndrome (CFS) were studied over a period of 24 months after initial clinical diagnosis. CFS was diagnosed according to IIIP-revised CDC-criteria as defined by the CFS Expert Advisory Group to the German Federal Ministry of Health in 1994. Changes in HHV-6 antibody titer, viral DNA load, peripheral blood T lymphocytes and subpopulations, as well as CD4/CD8 cell ratio and cell death (apoptosis) were monitored. Data were collected for comparison with respective changes in acute HHV-6 infection and as a basis for future computer simulation studies. The results showed variable but slightly elevated numbers of HHV-6 DNA copies in the blood of patients with CFS, while PBL (peripheral blood lymphocyte) apoptosis rates were clearly increased. CD4/CD8 cell ratios varied from below 1 up to values as seen in autoimmune disorders.  Contrary to acute HHV-6 infection, T lymphocytes do not exhibit the usual response to HHV-6, that is elevation of mature and immature populations suggesting a certain degree of unresponsiveness. The data suggest that persistent low-dose stimulation by HHV-6 may favor imbalanced immune response rather the overt immune deficiency. This hypothesis requires confirmation through additional functional studies.

PROGNOSIS

Bell DS, Jordan K, Robinson M. "Thirteen-year follow-up of children and adolescents with chronic fatigue syndrome." Pediatr 107.5 (2001):994-98. This study focused on the educational, social, and symptomatic outcome of children and adolescents with chronic fatigue syndrome 13 years after onset of illness. ABSTRACT: "Of the 35 participants, 24 were female (68.6%) and 11 were male (31.4%). Average age at illness onset was 12.1 years. Eight participants had an acute onset of symptoms, 27 had a gradual onset. No participant received an alternative medical diagnosis that could have explained the symptom complex between illness onset and follow-up. Thirteen participants considered themselves resolved of illness at follow-up; 15 participants considered themselves well but not resolved; 4 considered themselves chronically ill; and 3 considered themselves more ill than during the early years of illness. . . . These data demonstrate the presence of an illness consistent with the current definition of chronic fatigue syndrome. Eighty percent of children and adolescents affected had a satisfactory outcome from their fatiguing illness, although the majority of these patients had mild to moderate persisting symptoms. Twenty percent of participants remain ill with significant symptoms and activity limitation 13 years after illness."

TREATMENT

Goudsmit EM. "Measuring the quality of trials of treatments of chronic fatigue syndrome." [letter] JAMA 286.24 (2001): 3078-9.  [Editor’s note: We urge readers to access the JAMA website to read this letter.]

CASE DEFINITION/DIAGNOSIS

Tan EM, Sugiura K, Gupta S. "The case definition of chronic fatigue syndrome." J Clin Immunol 22.1 (2002): 8-12. ABSTRACT: The 1994 definition of CFS was widely used not only for diagnosis but also for clinical and laboratory- based observations of this clinical entity. The criteria for the 1994 case definition are based on symptoms and not on physical signs or chemical or immunological tests. This situation has resulted in conflicting clinical and laboratory observations "...that in all likelihood is due to different populations of patients being studied in different centers." Based on some of the recent publications, the authors state, there "appears to be an emerging picture of this disease entity that we propose could be used to subgroup chronic fatigue syndrome into four subclasses." These include: (1) chronic fatigue with primarily nervous system disorders such as impaired memory or concentration and headache, (2) chronic fatigue with primarily endocrine system disorders such as unrefreshing sleep and post-exertional malaise, (3) chronic fatigue with musculoskeletal system disorders such as muscle pain and joint pain, and (4) chronic fatigue with immune system/infectious disorders such as sore throat and tender lymph nodes. The researchers suggest that "...if clinical and laboratory-based studies on CFS were conducted on more homogenious subgroups of patients, the data from one center to the other might not be as conflicting and more insights can be shed on the nature of this clinical condition." [Editor's note: This is an excellent suggestion. We highly approve of the concept of subsets to improve the quality of research. However, we disagree with use of the word "fatigue" or "chronic fatigue" and believe that this word does not represent patient symptomatology. We urge researchers to eliminate the unscientific concept of "fatigue" from their discussion and to use more specific language. We also urge selection of patients using a Ramsay framework.]

DeBecker P, McGregor N, DeMeirleir K. "A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome." J Int Med 250.3(Sept. 2001):234. This study was conducted to answer the need to assess the homogeneity of a large CFS population in relationship to the Fukuda or Holmes definitions and to assess the importance of a symptom severity scale. Multivariate analyses were performed to assess the symptom presentation in a fatigued population. the difference between the Fukuda and Holmes definitions compared with an excluded chronic fatigued group in a large group of fatigued patients. The main outcome measures were prevalence and severity of symptoms and signs in a CFS population and in a chronic fatigued population. A total of 2,073 consecutive patients with major complaints for prolonged fatigue participated in this study. Multivariate analyses were performed to assess the symptom presentation and severity and the differences between the Fukuda and Holmes definitions. Of the 2,073 patients complaining of chronic fatigue (cf), 1,578 CFS patients fulfilled the Fukuda criteria (100% of the CFS group) and 951 (60.3% of the CFS group) fulfilled the Holmes criteria. Discriminant dysfunction analysis revealed that the Fukuda and Holmes definitions can be differentiated by symptom severity and prevalence. The Holmes definition was more strongly associated than the Fukuda definition with the symptoms that differentiated CFS patients from the patients that did not comply with the CFS definitions. The inclusion of 10 additional symptoms was found to improve the sensitivity/specificity and accuracy for selection of CFS patients. The authors conclude that "the CFS patients fulfilling the Holmes criteria have an increased symptom prevalence and severity of many symptoms. Patients fulfilling the Fukuda criteria were less severely affected patients which leads to an increase in clinical heterogeneity." [Editor's note: This is an excellent article, and we hope that researchers will also do similar studies using a Ramsay definitional framework.]

Hanson SJ, Gause W, Natelson B. "Detection of immunologically significant factors for chronic fatigue syndrome using neural-network classifiers." Clin Diagn Lab Immunol 8.3(2001):658-62. Abstract: Neural-network classifiers were used to detect immunological differences in groups of chronic fatigue syndrome (CFS) patients that heretofore had not shown significant differences from controls. In the past linear methods were unable to detect differences between CFS groups and non-CFS control groups in the nonveteran population. An examination of the cluster structure for 29 immunological factors revealed a complex, nonlinear decision surface. Multilayer neural networks showed an over 16% improvement in an n-fold resampling generalization test on unseen data. A sensitivity analysis of the network found differences between groups that are consistent with the hypothesis that CFS symptoms are a consequence of immune system dysregulation. Corresponding decreases in the CD19(+) B-cell compartment and the CD34(+) hematopoietic progenitor subpopulation were also detected by the neural network, consistent with the T-cell expansion. Of significant interest was the fact that, of all the cytokines evaluated, the only one to be in the final model was interleukin-4 (IL-4). Seeing an increase in IL-4 suggests a shift to a type 2 cytokine pattern. Such a shift has been hypothesized, but until now convincing evidence to support that hypothesis has been lacking.  [Editor’s note: We applaud these researchers for uncovering evidence of this long-hypothesized type 2 cytokine pattern.]

Linder R, Dinser R, Wagner M, Krueger GR, Hoffman A. "Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set." In Vivo 16.1 (2002):37-43.   Artificial neural networks (ANN) are computer-based models that can help to evaluate complex correlations. This study examines the utility of ANN and other conventional methods in generating classification criteria for CFS compared to other diseases with prominent fatigue, SLE, and FMS. Ninety-nine case patients with CFS, 41 patients with SLE, and and 58 with FMA were recruited from a generalist outpatient population . Clinical symptoms were documented with help from a predefined questionnaire. Patients were randomly divided into two groups: one group (N=158) served to derive classification criteria sets by two-fold cross-validation using unweighted application of criteria, regression coefficients, regression tree analysis, and artificial neural networks in parallel. These criteria were validated with the second group (N=40). Results: Classification criteria developed by ANN were found to have a sensitivity of 95% and a specificity of 85%. ANN achieved a higher accuracy than any of the other methods. The authors conclude: "We present validated criteria for the classification of CFS versus SLE and FMA, comparing different classification approaches. The most accurate criteria were derived with the help of ANN. We therefore recommend the use of ANN for the classification of syndromes with complex interrelated symptoms like CFS."

Naschitz JE, Sabo E, et al. "Hemodynamic instability in chronic fatigue syndrome: indices and diagnostic significance." Semin Arthritis Rheum 31.3 (2001): 199-208. Patients with CFS (N=25) and their age- and gender-matched healthy controls (N=37), patients with FMS (N=30), generalized anxiety disorder (N=15), and essential hypertension (N= 20) were evaluated with the aid of a standardized tilt test. On multivariate analysis, the independent predictors of CFS patients versus healthy controls were the fractal dimension of absolute values of the systolic BP changes (SYST-FD-abs), the standard deviation of the current values of the systolic BP changes SYST-SD.cur), and the standard deviation of the current values of the heart rate changes (HR-SD.cur). The following equation was deduced to calculate the hemodynamic instability score (HIS) in the individual patient: HIS=64.3303 + (SYST-FD.abs x -68.0135) = (SYST-SC.cur x 111.3726) + (HR-SD.cur x 60.4164). The best cutoff differentiating CFS from the healthy controls was -0.98. HIS values > 0.98 were associated with CFS (sensitivity 97%, specificity 97%). The HIS differed significantly between CFS and other groups (P < .0001) except for generalized anxiety disorder. The authors conclude: "The HIS adds objective criteria confirming the diagnosis of CFS."

Gray GC, Reed RJ, Kaiser KS, Smith TC, Gastanaga VM. "Self-reported symptoms and medical conditions among 11,868 Gulf War-era veterans." Am J Epidemiol 155.11 (2002):1033-44. ABSTRACT: In this survey of 11,868 Gulf War-era veterans, Gulf War Seabees reported poorer general health, a higher prevalence of all 33 medical problems assessed, more cognition difficulties, and a higher prevalence of four physician-diagnosed multisymptom conditions: chronic fatigue syndrome, post traumatic stress disorder, multiple chemical sensitivity, and irritable bowel symdrome. Because these four conditions were highly associated with each other, the authors aggregated them into a working case definition of Gulf War Syndrome. Among the 3,831 (22% cases) of Gulf War Seabee participants, multivariable modeling revealed that female, reserve, and enlisted personnel and participants belonging to either of two particular Seabee units were most likely to meet the case definition. Twelve o! f 34 self-reported Gulf War exposures were mildly associated with meeting the definition of Gulf War syndrome, with exposure to fumes from munitions having the highest odds ratio (odds ratio = 1.9, 95% confidence interval: 1.5, 2.4). While these data do not implicate a specific etiologic exposure, they demonstrate a strong association and a high prevalence of self-reported multisymptom conditions in a large group of symptomatic Gulf War veterans.

Jason LA, Torres-Harding SR, Carrico AW, Taylor RR. "Symptom occurrence in persons with chronic fatigue syndrome." Biol Psychol 59.1(2002):15-27. ABSTRACT: This investigation compared differences in the occurrence of symptoms in participants with CFS, melancholic depression, and no fatigue (controls). The following Fukuda et al. criteria symptoms differentiated the CFS group from controls: headaches, lymph node pain, sore throat, joint pain, and muscle pain. In addition, participants with CFS uniquely differed from controls in the occurrence of muscle weakness at multiple sites as well as the occurrence of various cardiopulmonary, neurological, and other symptoms not currently included in the current case definition. [Editor's note: We urge researchers working on neurological and cardiocirculatory symptoms and muscle weakness no longer to use the Fukuda criteria for selecting patients or the name "CFS." We urge use of a Ramsay framework. The patients in this study fit our M.E. definitional framework.]

Colby J. "Chronic fatigue syndrome and myalgic encephalomyelitis." [letter] Lancet 359 (11 May 2002):1698.  [Editor’s note: This is an excellent letter and we urge readers to access the Lancet website.]

CASE DEFINITION/TREATMENT

Richardson A. "The symptoms and management of myalgic encephalomyelitis." Nurs Times 98.19 (2002): 32-5. M.E. is a chronic, debilitating illness with varying symptoms and patterns of progression. Research has yet to establish its aetiology and pathogenesis, and there is no cure. A number of management strategies have proved effective, but these should always be tailored to the individual patient. Although no drug treatment has been developed specifically for M.E., therapies used to manage the same symptoms in other conditions can provide some relief. Treatment and management should be planned in partnership with the patient.

ETIOLOGY

Buchwald D, Herrell R, Ashton S, Belcourt M, Schmaling K, Sullivan P, Neale M, Goldberg J. "A twin study of chronic fatigue." Psychosom Med 63.6 (2001):936-43. The purpose of this study was to investigate genetic factors in the development of unexplained chronic fatigue. Fatigue lasting greater than 6 months, fatigue not explained by exclusionary medical conditions, and idiopathic chronic fatigue not explained by medical or psychiatric exclusionary criteria for CFS were studied by collating the data resulting from a questionnaire given to 146 female- female twin pairs. RESULTS: Concordance rates in monozygotic and dizygotic twins were calculated for each fatigue definition along with estimates of the relative magnitude of genetic and environmental influences on chronic fatigue. The concordance rate was higher in monozygotic than dizygotic twins for each definition of chronic fatigue. For idiopathic cf, the concordance rates were 55% in monozygotic and 19% in dizygotic twins. The estimated heritability in liability was 19% for chronic fatigue > or = to 6 months, 30% for cf not explained by medical conditions, and 51% for idiopathic cf. The authors conclude: "These results provide evidence supporting the familial aggregation of fatigue that suggest that genes play a role in the etiology of chronic fatigue syndrome." [Editor's note: While genetic factors may play a role in the etiology of M.E., and we encourage researchers to investigate genetic (including mitochondrial) factors, we believe that M.E. should be an exclusionary medical condition, like MS or lupus, not to be studied in the same category as "fatigue" states. Fatigue is a poorly defined symptom present in many diseases and is not a scientific concept. No progress will be made in understanding this complex of diseases when researchers focus on "fatigue" or "familial aggregation of fatigue." Researchers should focus on uncovering the disease process. Lumping patients according to their proposed fatigue confuses the issue. However, we do believe that there may be genetic links to many diseases and we applaud these researchers for encouraging research into genetic factors.]

Sabath DE, Barcy S, Koelle DM, Zeh J, Ashton S, Buchwald D. "Cellular immunity in monozygotic twins discordant for chronic fatigue syndrome." J Infect Dis 185.6 (2002):828-32. Abstract: The objective of this study was to assess the nature and extent of abnormalities in lymphocyte cell surface markers and NK cell activity in patients with CFS while controlling for genetic factors. A co-twin control study of immune system parameters was conducted for 22 pairs of twins discordant for CFS and 9 healthy pairs of twins. The CFS twins had greater numbers of CD62L(+) T cells in several T cell subsets, although these differences did not achieve statistical significance. Significantly greater variability was noted in twins discordant with CFS than in the concordant healthy twins for 20 of 48 variables examined. The monozygotic co-twin control design is of unique value because of its ability to control for genetic influences on CFS; however, additional studies will be required to assess immune dysregulation in this illness.

ADVOCACY/NAME CHANGE

Jason LA, Eisele H, Taylor RR. "Assessing attitudes toward new names for chronic fatigue syndrome." Eval Health Prof 24.4 (2001):424-35. Abstract: A questionnaire was distributed at the American Association of Chronic Fatigue Syndrome's biannual convention in Washington in January 2001 as well as through various Internet Web sites and listserves during early February and March of 2001. The sample consisted of 432 respondents. Most respondents (86%) indicated they wanted a name change, although more patients than scientists were in favor of this change. It was also apparent that the patients and physicians were clearly split between adopting a name such as myalgic encephalopathy versus one such as neuro-endocrine immune disorder. Also, among those respondents who selected either of these two choices for a new name, less than 30% of them supported the other name. Although the majority of respondents feel the name should be changed at this time, this survey suggests there are different stakeholders involved in the name-change process, each with strong and sometimes disparate feelings about changing the name.

Jason LA, Taylor RR, Plioplys S, Stepanek Z, Shlaes J. "Evaluating attributions for an illness based upon the name: chronic fatigue syndrome, myalgic encephalopathy, and Florence Nightingale disease." Am J Community Psychol 30.1 (2002):133-48. Considerable discussion has occurred about stigma surrounding the name given to an illness currently known as CFS. Although patients and medical personnel have expressed varying opinions on this issue, no studies have evaluated how beliefs about the illness change based upon the type of name used for diagnostic purposes. In this study, attributions about CFS were measured in three groups of medical trainees. All groups read the same case study of a person with classic symptoms of CFS, with the only difference being the type of name given. Trainees were then asked to provide attributions about certain aspects of the illness, including its cause, severity, and prognosis. Results suggested that, across name conditions, most trainees appeared to consider the symptom complex of CFS a serious illness resulting in poor quality of life. In addition, findings indicated that the name CFS may be regarded less seriously than the M.E. name with respect to some important aspects of the illness. In this study, specialty of the medical trainee also played a role in how the illness was perceived.

Jason LA, Taylor RR, Richman JA. "The role of science and advocacy regarding a chronic health condition: the case of chronic fatigue syndrome." In Social Psychological Applications to Social Issues: The Social Psychology of Politics. Ed. Vottati, RS, Tinsdale, et al. NY: Kluwer Academic Publishers (2002):157-172.   This paper explores an illness, chronic fatigue syndrome, that is ambiguous in nature and has engendered problematic, stigmatizing societal responses. It offers research strategy to prevent the stigmatization caused by biases and unexamined assumptions about the nature and the likely etiology of the disorder. In the area of CFS, key decisions regarding the name, case definition, epidemiolgy and treatment were made many years ago within a sociopolitical context to which CFS was assumed to be a psychologically based problem. The focus of this paper is on how those in decision-making positions regarding health issues (e.g., medical personnel, CDC officials, and grant funders) have impacted the name of the syndrome (and its implications), its definition, funding, research, and treatment.

OTHER DISEASES

Donaldson CC, Snelling LS, MacInnis AL, Sella GE, Mueller HH. "Diffuse muscular coactivation (DMC) as a potential source of pain in fibromyalgia." NeuroRehabilitation 17.1 (2002):33-9; 41-8 Abstract 1: Fibromyalgia is characterized by diffuse pain, the origin of which remains obscure. This study explored a phenomenon labeled Diffuse Muscle Coactivation (DMC) as a possible source of pain in fibromyalgia. DMC is defined as an increase from resting levels (tonus) in the electrical activity of any muscle during a movement which does not involve that muscle and is not part of the agonist-antagonist unit. When compared to controls this activity in persons with fibromyalgia was 1.75 times more prevalent and demonstrated significantly higher peak amplitudes. Possible neurological mechanisms are discussed. Abstract 2: This study examined the electrical characteristics (Root Mean Square -- RMS and median frequency) of Diffuse Muscular Coactivation (DMC) associated with the tender points of fibromyalgia. DMC is defined as an increase from resting levels (tonus) in the electrical activity of any muscle during a movement which does not involve that muscle and is not part of the agonist -- antagonist unit. The results show an increase in RMS in fibromyalgia sufferers as compared to controls. Coactivation was stronger proximal to the neck and decreased in intensity as the area recorded moved distally. Median frequency changed over time but not significantly between groups. Possible neurological mechanisms are discussed. [Editor’s note: We decided to publicize a few research articles on FM to help some patients even though we hold that FM and M.E. are distinct entities.]

Gursel Y, Ergin S, Ulus Y, Erdogan MF, Yalcin P, Evcik D. "Hormonal responses to exercise stress test in patients with fibromyalgia syndrome." Clin Rheumatol 20.6(2001):401-5. Abstract: Twenty patients with fibromyalgia syndrome (FMS) and 20 matched healthy controls were subjected to an exercise stress test above their anaerobic threshold. Serum samples for the measurement of growth hormone (GH), insulin-like growth factor-1 (IGF-1), prolactin (PRL), adrenocorticotrophic hormone (ACTH) and cortisol were taken prior to and after the test at 30-min intervals. Compared to the controls, the patients with FMS displayed significantly lower basal GH levels and slightly, though significantly, higher prolactin levels. Following the exercise test there was a significant increase in the mean GH level in the patient group (P = 0.0474) and a significant decrease in the control group (P = 0.0286) 1 hour after the exercise. A slight decrease in ACTH levels in the control group was observed (P= 0.0002), but there was no significant change in FMS patients. Cortisol levels were significantly lower in both groups after the exercise (P = 0.0001). These results suggest the possibility of a perturbation in hormonal response to exercise in patients with FMS.

DISCLAIMER: Our materials may be reproduced by not-for-profit publications as long as nothing is cut or altered, copyright notices are included and items are attributed to the M.E. Society of America. They may be photocopied, distributed, and e-mailed, but not put on Web sites without permission. Anyone may freely link to our materials on our Web site, however. We give permission to support groups and support group leaders to photocopy and distribute our materials to physicians and patients to facilitate access to research for those not on e-mail.  The M.E. Society of America does not dispense medical advice or recommend treatment, and assumes no responsibility for treatments undertaken by readers of the American M.E. Review. We are a research-information and advocacy group only.