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Posted to Co-Cure Tue, 5 Jun 2001 23:35:34 -0400 by Fred Springfield

Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in CFS

Full Title: Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome.

Journal: Appl Neuropsychol 2001;8(1):41-50

Authors: Tiersky LA, DeLuca J, Hill N, Dhar SK, Johnson SK, Lange G, Rappolt G, Natelson BH.

Affiliation: School of Psychology, Fairleigh Dickinson University, 1000 River Road, Mail Stop T-WH1-01, Teaneck, NJ 07666, USA.

NLM Citation: PMID: 11388123

The longitudinal course of subjective and objective neuropsychological functioning, psychological functioning, disability level, and employment status in chronic fatigue syndrome (CFS) was examined. The relations among several key outcomes at follow-up, as well as the baseline characteristics that predict change (e.g., improvement), were also evaluated.

The study sample consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Centers for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM = 1.7) months following their initial visit (range = 24-63 months).

Results indicated that objective and subjective attention abilities, mood, level of fatigue, and disability improve over time in individuals with CFS. Moreover, improvements in these areas were found to be interrelated at follow-up. Finally, psychiatric status, age, and between-test duration were significant predictors of outcome.

Overall, the prognosis for CFS appears to be poor, as the majority of participants remained functionally impaired over time and were unemployed at follow-up, despite the noted improvements.

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Posted to Co-Cure Tue, 5 Jun 2001 23:35:34 -0400 by Fred Springfield

Cytokine and other immunologic markers in CFS and their relation to neuropsychological factors

Full Title: Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors.

Journal: Appl Neuropsychol 2001;8(1):51-64

Authors: Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG.

Affiliation: E. M. Papper Laboratory of Clinical Immunology, Center for Behavioral Medicine Research, Miami Veterans Administration Medical Center, University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101, USA. NLM Citation: PMID: 11388124

The literature is reviewed and data are presented that relate to a model we have developed to account for the perpetuation of the perplexing disorder currently termed chronic fatigue syndrome (CFS).

In patients with CFS there is chronic lymphocyte overactivation with cytokine abnormalities that include perturbations in plasma levels of proinflammatory cytokines and decrease in the ratio of Type 1 to Type 2 cytokines produced by lymphocytes in vitro following mitogen stimulation.

The initiation of the syndrome is frequently sudden and often follows an acute viral illness. Our model for the subsequent chronicity of this disorder holds that the interaction of psychological factors (distress associated with either CFS-related symptoms or other stressful life events) and the immunologic dysfunction contribute to (a) CFS-related physical symptoms (e.g., perception of fatigue and cognitive difficulties, fever, muscle and joint pain) and increases in illness burden and (b) impaired immune surveillance associated with cytotoxic lymphocytes with resulting activation of latent herpes viruses.

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Posted to Co-Cure Tue, 5 Jun 2001 23:23:08 -0400 by Fred Springfield

Cognitive compromise following exercise in monozygotic twins discordant for CFS...

Full Title: Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact?

Journal: Appl Neuropsychol 2001;8(1):31-40

Authors: Claypoole K, Mahurin R, Fischer ME, Goldberg J, Schmaling KB, Schoene RB, Ashton S, Buchwald D.

Affiliations: Departments of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.

NLM Citation: PMID: 11388121

This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function.

Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise.

The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.

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Posted to Co-Cure Tue, 5 Jun 2001 23:19:57 -0400 by Fred Springfield

Quantitative assessment of cerebral ventricular volumes in CFS

Full title: Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome.

Journal: Appl Neuropsychol 2001;8(1):23-30

Authors: Lange G, Holodny AI, DeLuca J, Lee HJ, Yan XH, Steffener J, Natelson BH.

Affiliations: Departments of Psychiatry and Radiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 30 Bergen Street, Newark, NJ 07107, USA.

NLM Citation: PMID: 11388120

Previous qualitative volumetric assessment of lateral ventricular enlargement in chronic fatigue syndrome (CFS) has provided evidence for subtle structural changes in the brains of some individuals with CFS.

The aim of this pilot study was to determine whether a more sensitive quantitative assessment of the lateral ventricular system would support the previous qualitative findings.

In this study, we compared the total lateral ventricular volume, as well as the right and left hemisphere subcomponents in 28 participants with CFS and 15 controls. Ventricular volumes in the CFS group were larger than in control groups, a difference that approached statistical significance.

Group differences in ventricular asymmetry were not observed. The results of this study provide further evidence of subtle pathophysiological changes in the brains of participants with CFS.

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Posted to Co-Cure Fri, 8 Jun 2001 14:54:13 -0400 by Kimberly Hare

A practical approach to fibromyalgia

Full title: A practical approach to fibromyalgia.

Journal: J Am Osteopath Assoc 2001 Apr;101(4 Suppl Pt 2):S12-7

Authors: Brecher LS, Cymet TC.

Affiliation: University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine, Stratford, NJ, USA.

NLM Citation: PMID: 11392205

The term fibromyalgia refers to a collection of symptoms with no clear physiologic cause, but the symptoms together constitute a clearly recognizable and distinct pathologic entity. The diagnosis is made through the examiner's clinical observations. The differential diagnosis must include other somatic syndromes as well as disease entities, including hepatitis, hypothyroidism, diabetes mellitus, electrolyte imbalance, multiple sclerosis, and cancer. Diagnostic criteria serve as guidelines for diagnosis, not as absolute requirements.

Treatment of fibromyalgia, which is an ongoing process, remains individualized, relying on a good physician-patient relationship. It is goal-oriented, directed at helping patients get restorative sleep, alleviating the somatic pains, keeping patients productive, and regulating schedules.

It can be achieved through a goal-oriented agreement between patient and provider. Because fibromyalgia is chronic and may affect all areas of an individual's functioning, the physician needs to also evaluate the social support systems of patients with fibromyalgia.

The approach to treatment should integrate patient education as well as non-pharmacologic and pharmacologic modalities. To keep patients well educated and involved in their healthcare, physicians should provide patients with adequate sources for reliable information.

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Posted to Co-Cure Tue, 5 Jun 2001 23:26:18 -0400 by Fred Springfield

Divided attention deficits in patients with chronic fatigue syndrome

Full Title: Divided attention deficits in patients with chronic fatigue syndrome.

Journal: Appl Neuropsychol 2001;8(1):4-11

Authors: Ross S, Fantie B, Straus SF, Grafman J.

Affiliation: Department of Psychology, American University, Washington, DC, USA.

NLM Citation: PMID: 11388122

Chronic fatigue syndrome (CFS) patients and controls were compared on a variety of mood state, personality, and neuropsychological measures, including memory, word finding, and attentional tasks that required participants to focus, sustain, or divide their attention, or to perform a combination of these functions.

CFS patients demonstrated a selective deficit on 3 measures of divided attention. Their performance on the other neuropsychological tests of intelligence, fluency, and memory was no different than that of normal controls despite their reports of generally diminished cognitive capacity.

There was an inverse relation between CFS patient fatigue severity and performance on 1 of the divided attention measures.

Given these findings, it is probable that CFS patients will report more cognitive difficulties in real-life situations that cause them to divide their effort or rapidly reallocate cognitive resources between 2 response channels (vision and audition).

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Posted to Co-Cure Mon, 4 Jun 2001 17:41:52 -0400 by Fred Springfield

CFS and Abnormal Biological Rhythms in School Children

Full Title: Chronic Fatigue Syndrome and Abnormal Biological Rhythms in School Children

Journal: Journal of Chronic Fatigue Syndrome, Vol. 8 (2) 2001, pp. 29-37

Authors: Akemi Tomoda, MD; Takako Jhodoi, MD; Teruhisa Miike, MD

Affiliation: Department of Child Development, Kumamoto University School of Medicine, Japan.
Address correspondence to: Dr. Akemi Tomoda, Department of Child Develop­ment, Kumamoto University School of Medicine, 1 - 1 - 1 Honjo, Kumamoto 860-0811, Japan (E-mail:

ABSTRACT. Chronic fatigue syndrome occurring in previously healthy children and adolescents is one of the most vexing problems encountered by pediatric practitioners. To investigate the biological rhythms in the pediatric patients with CFS, we examined sleep pattern, circadian rhythm of core body temperature (CBT), and plasma cortisol in 41 patients, aged between 10 and 19 years, who did not have any physical or psychiatric disorders, but had non-specific complaints, and were suspected to have a circadian rhythm disturbance. They were diagnosed as having CFS on the basis of published criteria.

Circadian variation of CBT in the CFS patients did not present a clear rhythm, and appearance time of their lowest CBT was significantly de­layed compared to healthy subjects. Amplitude of circadian CBT changes, fitted to a cosinor curve by the least square method, was significantly smaller in the patients than in healthy subjects. Moreover, circadian rhythm of plasma cortisol in the patients appeared to be quite different, compared to healthy subjects. These findings suggest that their clinical psychosomatic symptoms (e.g., fatigue and sleep disturbance) might be closely related to the desynchronization of their biorhythms, particularly the circadian rhythm of body temperature and cortisol rhythm.

KEYWORDS. Chronic fatigue syndrome (CFS), core body temperature (CBT), cortisol circadian rhythm, biological disturbance


Chronic fatigue syndrome (CFS) is a condition in which a subject complains of persistent fatigue associated with fever, myalgia, pharyn­gitis, headache, adenopathy, gastrointestinal symptoms, and other neu­rological problems (1-3). Almost all CFS cases have central nervous system symptoms, such as moderate or severe depression, memory disturbance, confusion and poor concentration, according to the diagnostic criteria for CFS (I ,2,4,5). These symptoms in child and adolescent cases significantly interfere with normal school functioning (3-8). We have encountered many such patients usually with associated indefinite or definite complaints, their major symptoms being general fatigue, fever, headache (not migraine), and/or sleep disturbance (4,5). In our clin­ical practices, we recognized that the majority of our patients have a circadian rhythm disorder even though they usually do not mention or recognize this problem at the first interview. We hypothesized that there could be certain relationships between biological rhythm disorders in these patients and the definite symptoms. This study examined sleep patterns and circadian rhythms of core body temperature (CBT) and of plasma cortisol level in CFS children and adolescents.

[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: Web site:]

© 2001 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Sun, 3 Jun 2001 12:04:33 -0400 by Fred Springfield

Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia...

Full Title: Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia - A Randomized, Double-Blind, Placebo-Controlled, Intent-To-Treat Study

Journal: Journal of Chronic Fatigue Syndrome, Vol.8 (2) 2001, pp. 3-28

Authors: Jacob E. Teitelbaum, MD; Barbara Bird, MT, CLS; Robert M. Greenfield, MD; Alan Weiss, MD; Larry Muenz, PhD; Laurie Gould, BS

Affiliations: Jacob E. Teitelbaum is affiliated with the Annapolis Research Center for Effective FMS/CFIDS Therapies and the Anne Arundel Medical Center, Annapolis, MD.
Barbara Bird is affiliated with the Annapolis Research Center for Effective FMS/CFIDS Therapies, Annapolis, MD.
Robert M. Greenfield is affiliated with the Anne Arundel Medical Center, Annapolis, MD.
Alan Weiss is affiliated with the Anne Arundel Medical Center, Annapolis, MD.
Larry Muenz resides in Gaithersburg, MD.
Laurie Gould is affiliated with the Annapolis Research Center for Effective FMS/CFiDS Therapies, Annapolis MD, and also the USDA, Beltsville, MD.

Address correspondence to: Jacob E. Teitelbaum, MD, Director, Annapolis Re­search Center for Effective FMS/CFIDS Therapies, 466 Forelands Road, Annapolis, MD 21401 (E-mail:

No outside funding. Funding was provided by Dr. Teitelbaum and time was donated by the authors. Many of the treatments were supplied by the companies making the medications.

Background: Hypothalamic dysfunction has been sug­gested in fibromyalgia (FMS) and chronic fatigue syndrome (CFS). This dysfunction may result in disordered sleep, subclinical hormonal defi­ciencies, and immunologic changes. Our previously published open trial showed that patients usually improve by using a protocol which treats all the above processes simultaneously. The current study examines this protocol using a randomized, double-blind design with an intent-to-treat analysis.

Methods: Seventy-two FMS patients (38 active:34 placebo; 69 also met CFS criteria) received all active or all placebo therapies as a unified intervention. Patients were treated, as indicated by symptoms and/or lab testing, for: (1) subclinical thyroid, gonadal, and/or adrenal insufficiency, (2) disordered sleep, (3) suspected neurally mediated hypotension (NMH), (4) opportunistic infections, and (5) suspected nutritional deficiencies.

Results: At the final visit, 16 active patients were "much better," 14 "better," 2 "same," 0 "worse," and 1 "much worse" vs. 3, 9, 11, 6, and 4 in the placebo group (p <.0001, Cochran-Mantel-Haenszel trend test). Significant improvement in the FMS Impact Questionnaire (FIQ) scores (decreasing from 54.8 to 33.2 vs. 51.4 to 47.7) and Analog scores (im­proving from 176.1 to 310.3 vs. 177.1 to 211.9) (both with p <.0001 by random effects regression), and Tender Point Index (TPI) (31.7 to 15.5 vs. 35.0 to 32.3, p <.0001 by baseline adjusted linear model) were seen. Long term follow-up (mean 1.9 years) of the active group showed con­tinuing and increasing improvement over time, despite patients being able to discontinue most treatments.

Conclusions: Significantly greater benefits were seen in the active group than in the placebo group for all primary outcomes. An integrated treatment approach appears effective in the treatment of FMS/CFS.

KEYWORDS. Fibromyalgia, chronic fatigue syndrome, adrenal insuf­ficiency, fatigue, therapy


Fibromyalgia (FMS), which currently affects an estimated 3 to 6 mil­lion Americans (1,2), and chronic fatigue syndrome (CFS) are two ill­nesses which often coexist. Severe persistent fatigue, diffuse migratory pain, cognitive dysfunction, and disordered sleep are common symp­toms that patients often report in these overlapping syndromes. Current research suggests that many triggers can initiate a cascade of events, causing hypothalamic-target gland axis dysfunction (3,4) and associ­ated loss of normal circadian cycling of cortisol secretion (5). Hypotha­lamic dysfunction may result in some of the changes reported in FMS and/or CFS. These include:

1. Disordered sleep (6,7) with associated pain (8). Disordered sleep (as well as hormonal and other changes) may cause immune dys­function, e.g., natural killer cell dysfunction (9), decreased pro­liferative responses (10) and opportunistic infections (6,11),

2. Hormonal deficiencies and hypothalamic-pituitary-target gland axis dysfunction (3,4,6,12). These can also contribute to the neu­rotransmitter changes seen in FMS (13), and

3. Autonomic dysfunction-including neurally mediated hypotension (NMH) (14,15).

Macro- and micro-nutrient deficiencies have also been shown by some authors (16- 19). In our initial pilot study (20), we explored the side effects, dosing and effectiveness of simultaneously treating the above problems. We found that simultaneously treating these resulted in significant clinical improvement. Which mix of treatments were needed, however, varied from patient to patient.

Although a concept that is sometimes uncomfortable and foreign to traditional styles of thinking, the need for multiple interventions can occur when an illness affects a critical control center (such as the hypothalamus) which impacts the multiple systems noted above. Unfortunately, we have not yet found a single treatment that reverses hypothalamic dysfunction directly. Thus, this situation is different from illnesses that affect a single target organ and which can be treated with a single intervention. For example, pituitary dysfunction itself often requires treat­ment with several hormones. This effect is multiplied in hypothalamic dysfunction, which affects several critical systems in addition to the pi­tuitary gland. We therefore hypothesized that an integrated treatment approach based on simultaneously treating the above problems (even if a modest degree of suspicion that would usually not be treated is present) will be clinically beneficial in CFS and FMS. Subgroup analysis was done to assess the effect of antidepressant therapy. Our current study tests the efficacy of this therapeutic approach and the above hy­pothesis using a randomized, double-blind, placebo-controlled protocol with an intent-to-treat analysis in an outpatient setting.

[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: Web site:]

© 2001 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Fri, 1 Jun 2001 16:25:33 -0400 by Fred Springfield

Monozygotic Twins Discordant for CFS: Regional Cerebral Blood Flow SPECT

Full Title: Monozygotic Twins Discordant for Chronic Fatigue Syndrome: Regional Cerebral Blood Flow SPECT

Journal: Radiology 2001 Jun;219(3):766-73

Authors: David H. Lewis, MD, Helen S. Mayberg, MD, Mary E. Fischer, MS, Jack Goldberg, PhD, Suzanne Ashton, BS, Michael M. Graham, MD, PhD and Dedra Buchwald, MD

Received June 29, 2000; revision requested August 10; final revision received November 30; accepted December 4.

D.B. supported by National Institutes of Health grant U19 AI38429. Address correspondence to D.B., Harborview Medical Center, 325 Ninth Ave, Box 359780, Seattle, WA 98104.

NLM Citation: PMID: 11376266

PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS.

MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m–hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors.

RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging.

CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.

Index terms: Brain, abnormalities, 13.899 • Brain, perfusion • Brain, SPECT, 13.12162 • Nervous system, abnormalities, 13.899 • Twins

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