2002 – Page 2 – American ME and CFS Society

A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function

Abstract:

This study was designed to determine safety and efficacy of a 6-month trial of valacyclovir in single-virus Epstein-Barr virus (EBV) persistent infection. Phase I of this study used four specific criteria to define a subset of patients with chronic fatigue syndrome (CFS). In the second phase, myocardial dynamics were measured by MUGA rest/stress radionuclide ventriculographic (RVG) examinations pre- and posttreatment with valacyclovir.

In phase I, a trial was performed in 19 consecutive CFS patients with the following diagnostic conditions: patients met criteria for diagnosis of CFS; they had had CFS for less than 1 year. They demonstrated repetitively abnormal oscillating T waves (ischemic or flat) at 24-h Holter monitoring; and they had elevated serum IgM antibody titers to EBV viral capsid antigen and/or total diffuse early antigen as measured by the enzyme-linked immunosorbent assay method.

The treatment group comprised 10 CFS patients with no serum antibodies to human cytomegalovirus, but the control group (nine CFS patients) had, additionally, high titers of serum antibodies (IgG) to conformational structural antigens of human cytomegalovirus. Both the parallel treatment and control CFS groups received valacyclovir 1.0-1.5 gm q.6.h. for 6 months.

This valacyclovir dose achieved serum acyclovir C(max) of > 7 microm and high antiviral activity versus EBV (IC(50) of 4.4-13.3 m). In phase II, six additional CFS patients met the same four criteria as the 19 CFS patients in phase I. They had, however, been ill for a mean of 55.8 months. Thus, 25 CFS patients comprise this study.

The studies were carried out at a single outpatient practice in Birmingham, MI, U.S.A. Before initiating valacyclovir, and after 6 months of treatment, clinical and laboratory observations were made. The CFS Energy Index point score (Table I) was used to record each CFS patient’s functional capacity at baseline and after 1, 3 and 6 months of valacyclovir. Energy Index point scores, as well as EBV and human cytomegalovirus serum antibody titers were assessed.

In the second phase, left ventricular dynamics were repeated after 6 months of treatment with valacyclovir. We concluded that the 16 CFS patients (included in both phases of this study) with EBV-persistent infection (EBV single-virus subset) are improved after 6 months of continuous pharmacokinetic dosing with valacyclovir. Nine CFS patients with EBV/human cytomegalovirus co-infection did not benefit from 6 months of similar treatment. Valacyclovir is not an effective anti-human cytomegalovirus antiviral drug. Unimproved CFS patients with co-infections EBV and human cytomegalovirus may require combined treatment with valacyclovir and another drug more active against human cytomegalovirus.

This preliminary trial, with a small number of patients, may be critical to an appropriately designed larger, double-blind, placebo-controlled trial.

Source: Lerner AM, Beqaj SH, Deeter RG, Dworkin HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O’Neill W. A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Drugs Today (Barc). 2002 Aug;38(8):549-61. http://www.ncbi.nlm.nih.gov/pubmed/12582420

Validation of a telephone cognitive assessment test battery for use in chronic fatigue syndrome

Abstract:

We compared a computerized version of the Cognitive Drug Research (CDR) cognitive assessment test battery and a completely automated telephone version of the same battery. These assessed aspects of attention, working memory and long-term memory. Both methods were used to assess the cognitive performance of a cohort of 30 people with confirmed chronic fatigue syndrome (CFS) and a group of 30 healthy controls matched for age and education.

The CFS group had significantly slower reaction times on all four cognitive measures on both the computerized and telephone tests. The mood data followed similar patterns in the computer and telephone assessments. The results from both forms of the test battery confirmed the pattern and severity of cognitive impairment in CFS. Furthermore, the two methods of testing were similarly sensitive in detecting cognitive deficits. The incapacitating nature of CFS may cause problems for researchers if the restrictions to mobility affect the representativeness of the study group. The findings of the present study support the use of a fully automated telephone cognitive testing system for detecting deficits in CFS.

Source: McCue P, Scholey AB, Herman C, Wesnes KA. Validation of a telephone cognitive assessment test battery for use in chronic fatigue syndrome. J Telemed Telecare. 2002;8(6):337-43. http://www.ncbi.nlm.nih.gov/pubmed/12537921

The Mid-Atlantic Twin Registry

Abstract:

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of twin pairs ascertained from birth records and school system records of Virginia, North Carolina, and South Carolina. The MATR was formed in 1997 with the merging of the Virginia and North Carolina Twin Registries, and it expanded to include South Carolina when access to twin birth records in that state was granted in 1998. Registered twins (“participants”) number more than 51,000, with approximately 46,000 of these individuals representing complete pairs. Roughly two-thirds of MATR participants are over age 18, with a mean age of approximately 35 years. These participants have primarily been drawn from the more than 170,000 identical and fraternal twin pairs born in the three states between 1913 and 2000. Twins and their family members have participated in numerous research projects, ranging from general health surveys to studies on specific health topics such as cardiovascular disease; depression and anxiety; seizures; behavioral development; pregnancy complications; conduct disorder; drug use, abuse, and dependence; cleft lip/palate; obesity; and chronic fatigue syndrome. The MATR has established a privacy policy and strict standard operating procedures to protect the confidentiality of participant data. The MATR considers a limited number of qualified requests per year from investigators interested in recruiting MATR participants into their research studies.

Source: Anderson LS, Beverly WT, Corey LA, Murrelle L. The Mid-Atlantic Twin Registry. Twin Res. 2002 Oct;5(5):449-55. http://www.ncbi.nlm.nih.gov/pubmed/12537875

The Swedish Twin Registry in the third millennium

Abstract:

Since the Swedish Twin Registry was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases, it has been expanded and updated on several occasions. The focus has similarly broadened to most common complex diseases. The content of the database is described, ongoing projects based on the registry are summarized, and we review some of the principal findings on aging, cancer and cardiovascular disease that have come from the registry. Ongoing efforts and future plans for the STR are discussed. Among others, we plan blood collection and genotyping to study the genetic bases of complex diseases, a first contact ever with the cohorts born after 1958, and in-depth studies of selected diseases, such as Parkinson’s disease and chronic fatigue syndrome.

Source: Pedersen NL, Lichtenstein P, Svedberg P. The Swedish Twin Registry in the third millennium. Twin Res. 2002 Oct;5(5):427-32. http://www.ncbi.nlm.nih.gov/pubmed/12537870

Possible influence of defenses and negative life events on patients with chronic fatigue syndrome: a pilot study

Abstract:

13 patients with a diagnosis of chronic fatigue syndrome and two contrast groups of conversion disorder patients (n = 19) and healthy controls (n = 13) were assessed using the projective perceptual Defense Mechanism Test to investigate if specific defense patterns are associated with chronic fatigue syndrome. Another objective was to assess the possible influence of perceived negative life events prior the onset of the illness. The overall results showed significant differences in defensive strategies among groups represented by two significant dimensions in a Partial Least Squares analysis. Compared to the contrast groups the patients with chronic fatigue syndrome were distinguished by a defense pattern of different distortions of aggressive affect, induced by an interpersonal anxiety-provoking stimulus picture with short exposures.

Their responses suggested the conversion group was characterized by a nonemotionally adapted pattern and specific constellations of defenses, associated with interior reality orientation compared to the patients with chronic fatigue syndrome and the healthy controls. Rated retrospectively, the group with chronic fatigue syndrome reported significantly more negative life events prior to the onset of their illness than healthy controls. For instance, 5 of the 13 patients reported sexual assault or physical battery as children or teenagers compared to none of the healthy controls. A significant association was found between defense pattern and frequency of reported negative life events. However, these retrospective reports might be confounded to some extent by the experience of the patients’ illness; for example, the reports may be interpreted in terms of present negative affect.

Source: Sundbom E, Henningsson M, Holm U, Söderbergh S, Evengård B. Possible influence of defenses and negative life events on patients with chronic fatigue syndrome: a pilot study. Psychol Rep. 2002 Dec;91(3 Pt 1):963-78. http://www.ncbi.nlm.nih.gov/pubmed/12530752

Chronic fatigue in a population-based study of Gulf War veterans

Abstract:

Fatigue has been associated with illness in veterans of the Gulf War; however, few studies have confirmed self-reported fatigue by using clinical evaluation, and symptomatic veterans have not been evaluated with established criteria for Chronic Fatigue Syndrome (CFS). The authors describe the frequency and clinical characteristics of CFS in a sample of veterans residing in the northwestern United States. The sample was selected randomly from U.S. Department of Defense databases of troops deployed to southwest Asia during the Gulf War. The selected individuals were invited to participate in a clinical case-control study of unexplained illness.

Of 799 survey respondents eligible for clinical evaluation, 178 had fatigue symptoms. Of the 130 veterans who were evaluated clinically, 103 had unexplained fatigue, and 44 veterans met the 1994 U.S. Centers for Disease Control criteria for CFS. In this population, the authors estimated a minimum prevalence of any unexplained fatigue to be 5.1%, and of CFS to be 2.2%. The estimated prevalence was greater among females than among males. Cases were similar to healthy controls, as determined by laboratory tests and physical findings. In comparison to several clinical studies of CFS patients, the authors of this study found a lower proportion of veterans who reported a sudden onset of symptoms (19%) vs. a gradual onset (50%).

Although it has previously been suggested that veterans of the Gulf War suffer from higher rates of chronic fatigue than the general population, the study results described herein–on the basis of clinical examination of a population-based sample of veterans-actually indicate that an increased rate may indeed exist. Gulf War veterans with unexplained fatigue should be encouraged to seek treatment so that the impact of these symptoms on overall quality of life can be reduced.

Source: McCauley LA, Joos SK, Barkhuizen A, Shuell T, Tyree WA, Bourdette DN. Chronic fatigue in a population-based study of Gulf War veterans. Arch Environ Health. 2002 Jul-Aug;57(4):340-8. http://www.ncbi.nlm.nih.gov/pubmed/12530602

Chronic fatigue syndrome/ME

Comment on: Chronic fatigue syndrome/myalgic encephalitis. [Br J Gen Pract. 2002]

In previous correspondence,1 I challenged the trivialisation of chronic fatigue syndrome (CFS), and the generalisation and speculation in an editorial on chronic fatigue.2 The authors dismissed my arguments as, in their opinion, I had not demonstrated that I ‘was prepared and able accurately to read and interpret a scientific article’.3 I consider this remark to be unfair and unjustified.

I shall discuss each of their points in turn. First, they denied that by referring to the illness as ‘fatigue or its synonyms’, they were trivialising ‘the suffering of patients with PUPS (persistent unexplained physical symptoms)’. The authors must be aware of the controversy surrounding the word ‘fatigue’. As one affected surgeon wrote: ‘there is nothing in your experience in medical school, residency, or practice with its gruelling hours and sleep deprivation that even approaches the fatigue you feel with this illness. Fatigue is the most pathetically inadequate term’.4 Other writers on the subject recognise this, which is probably why most tend to describe the main symptom as profound, debilitating or disabling fatigue. But this was not the case here. The authors clearly equated CFS with (normal) tiredness and chronic fatigue. Elsewhere, they referred to ‘commonplace symptoms’ and in their response, again wrote about ‘fatigue and its synonyms’

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314477/pdf/12528593.pdf

Source: Goudsmit E. Chronic fatigue syndrome/ME. Br J Gen Pract. 2002 Dec;52(485):1023-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314477/pdf/12528593.pdf

Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome

Erratum in: Semin Arthritis Rheum. 2003 Apr;32(5):343. Madelain, Fields [corrected to Fields, Madeline]; Hillel, Isseroff [corrected to Isseroff, Hillel].

Abstract:

OBJECTIVE: In studying patients with chronic fatigue syndrome (CFS) we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the ‘hemodynamic instability score’ (HIS). The HIS in CFS patients differed significantly from healthy subjects. The present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope.

METHODS: Patients with CFS (n = 21), non-CFS chronic fatigue (n = 24), syncope of unknown cause (n = 44), and their age and sex-matched healthy controls (n = 21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified ‘clinical outcomes’ (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and ‘HIS endpoint’, i.e. HIS >-0.98.

RESULTS: The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0), healthy = -2.48 (4.07). The odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared with healthy subjects.

CONCLUSION: The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS.

Source: Naschitz JE, Sabo E, Naschitz S, Rosner I, Rozenbaum M, Fields M, Isseroff H, Priselac RM, Gaitini L, Eldar S, Zukerman E, Yeshurun D. Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome. Semin Arthritis Rheum. 2002 Dec;32(3):141-8. http://www.ncbi.nlm.nih.gov/pubmed/12528078

Chronic unexplained fatigue

Comment on: Chronic unexplained fatigue. [Postgrad Med J. 2002]

I found the editorial on chronic fatigue syndrome by White both surprising and disappointing, because he used the title “Chronic unexplained fatigue” and the subtitle “A riddle wrapped in a mystery inside an enigma”, but his editorial, by ignoring very important facts about chronic fatigue syndrome, actually perpetuates that riddle, rather than helping to solve it.

If a puzzling and poorly manageable condition shares more than 40 features, including all of its diagnostic criteria, with a well known and easily treatable disease, this astounding clinical overlap should not be ignored, because reason not only suggests that the mysterious illness may simply be a form of the well known disease, but also hints that it is worthwhile assessing whether the classic therapy for that treatable disease could be effective for the enigmatic condition as well.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757928/pdf/v078p00763a.pdf

Source: Baschetti R. Chronic unexplained fatigue. Postgrad Med J. 2002 Dec;78(926):763; author reply 763. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757928/pdf/v078p00763a.pdf

Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects

Abstract:

BACKGROUND: The association of an infectious agent with chronic fatigue syndrome (CFS) has been difficult and is further complicated by the lack of a known lesion or diseased tissue. Cell-free plasma DNA could serve as a sentinel of infection and disease occurring throughout the body. This type of systemic sample coupled with broad-range amplification of bacterial sequences was used to determine whether a bacterial pathogen was associated with CFS. Plasma DNA from 34 CFS and 55 non-fatigued subjects was assessed to determine plasma DNA concentration and the presence of bacterial 16S ribosomal DNA (rDNA) sequences.

RESULTS: DNA was isolated from 81 (91%) of 89 plasma samples. The 55 non-fatigued subjects had higher plasma DNA concentrations than those with CFS (average 151 versus 91 ng) and more CFS subjects (6/34, 18%) had no detectable plasma DNA than non-fatigued subjects (2/55, 4%), but these differences were not significant. Bacterial sequences were detected in 23 (26%) of 89. Only 4 (14%) CFS subjects had 16S rDNA sequences amplified from plasma compared with 17 (32%) of the non-fatigued (P = 0.03). All but 1 of the 23 16S rDNA amplicon-positive subjects had five or more unique sequences present.

CONCLUSIONS: CFS subjects had slightly lower concentrations or no detectable plasma DNA than non-fatigued subjects. There was a diverse array of 16S rDNA sequences in plasma DNA from both CFS and non-fatigued subjects. There were no unique, previously uncharacterized or predominant 16S rDNA sequences in either CFS or non-fatigued subjects.

Source: Vernon SD, Shukla SK, Conradt J, Unger ER, Reeves WC. Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects. BMC Microbiol. 2002 Dec 23;2:39. Epub 2002 Dec 23. http://www.ncbi.nlm.nih.gov/pubmed/12498618