The connection between chronic fatigue syndrome and neurally mediated hypotension

Abstract:

Research from several groups of investigators indicates that some patients with chronic fatigue syndrome have abnormal vasovagal or vasodepressor responses to upright posture. If confirmed, these findings may explain some of the symptoms of chronic fatigue syndrome. There is also speculation that neurally mediated hypotension may be present in fibromyalgia. This article discusses the original research in this area, the results of follow-up studies, and the current approach to treating patients with chronic fatigue syndrome in whom neurally mediated hypotension is suspected.

 

Source: Wilke WS, Fouad-Tarazi FM, Cash JM, Calabrese LH. The connection between chronic fatigue syndrome and neurally mediated hypotension. Cleve Clin J Med. 1998 May;65(5):261-6. http://www.ncbi.nlm.nih.gov/pubmed/9599909

 

Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome

Abstract:

AIM: To perform a clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS) where patients were told they would receive placebo or active agent at different times during the 6-week trial. We chose selegiline, a specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of lowdose phenelzine, a nonspecific MAO inhibitor, showed a small but significant therapeutic effect.

METHODS: Questionnaires comprised of 19 tests of mood, fatigue, functional status and symptom severity were collected at the start and end of the trial as well as 2 weeks after its start. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg tablet of agent was given twice a day. The plan was to compare the changes in the 19 tests during the placebo phase to those found in the active treatment phase in 19 patients completing the trial.

FINDINGS: Significant improvement in 3 variables-tension/anxiety, vigor and sexual relations-was found. A significant pattern of improvement compared to worsening was found for the 19 self-report vehicles during active treatment as compared with placebo treatment. Evidence for an antidepressant effect of the drug was not found.

CONCLUSIONS: Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect.

 

Source: Natelson BH, Cheu J, Hill N, Bergen M, Korn L, Denny T, Dahl K. Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome. Neuropsychobiology. 1998;37(3):150-4. http://www.ncbi.nlm.nih.gov/pubmed/9597672

 

Alteration of spatial-temporal parameters of gait in Chronic Fatigue Syndrome patients

Abstract:

Chronic Fatigue Syndrome (CFS) has been widely studied and a lot of information is available in the literature regarding the immunological, virological, neuroendocrinal and psychiatric aspects of the disease, but its aetiology is still poorly understood. Great attention has also been paid to the alteration of the muscular function caused by CFS.

The aim of the present work was to study CFS patients’ gait in order to find out objective measures which can better characterize the pathology. Spatial and temporal parameters of gait were collected from a group of 12 CFS informed volunteers by using the typical instrumentation of movement analysis, and raw data were statistically elaborated.

Comparisons with reference data from a population of healthy subjects revealed significant abnormalities in the symmetry indices of the bilateral parameters and in the linear relationships among parameters, and between these parameters and the physical characteristics of the patients.

Interestingly, the abnormalities were present as from the beginning of the gait, which indicates that they are unlikely to be caused by the rapid increasing fatigue. This strengthens the hypothesis of a direct involvement of the central nervous system (CNS) in the onset of the disease.

 

Source: Saggini R, Pizzigallo E, Vecchiet J, Macellari V, Giacomozzi C. Alteration of spatial-temporal parameters of gait in Chronic Fatigue Syndrome patients. J Neurol Sci. 1998 Jan 21;154(1):18-25. http://www.ncbi.nlm.nih.gov/pubmed/9543318

 

The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome

Abstract:

This article reports the results of a within-subject design. Fifty subjects with a physician diagnosis of fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) were interviewed using a structured interview from. Each subject was interviewed initially, and again nine months later (follow-up).

Subjects had, on their own, consumed nutritional supplements including freeze-dried aloe vera gel extract; a combination of freeze-dried aloe vera gel extract and additional plant-derived saccharides; freeze-dried fruits and vegetables in combination with the saccharides; and a formulation of dioscorea complex containing the saccharides and a vitamin/mineral complex.

With medical treatments, approximately 25 percent of FM patients improve, but the beneficial effects of medical treatment rarely persist more than a few months. All subjects in this study had received some form of medical treatment prior to taking the nutritional supplements, but none with enduring success.

Nutritional supplements resulted in a remarkable reduction in initial symptom severity, with continued improvement in the period between initial assessment and the follow-up. Further research is needed to verify these results, specifically crossover designs in well-defined populations.

 

Source: Dykman KD, Tone C, Ford C, Dykman RA. The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome. Integr Physiol Behav Sci. 1998 Jan-Mar;33(1):61-71. http://www.ncbi.nlm.nih.gov/pubmed/9594356

 

Cancer and a fatiguing illness in Northern Nevada–a causal hypothesis

Abstract:

PURPOSE: We investigated the possibility that chronic fatigue syndrome (CFS) predisposes to cancer by comparing the cancer pattern in an area in northern Nevada, where an outbreak of a fatiguing illness, which included cases of CFS, was reported, to an area in southern Nevada, where no such illness was reported.

METHODS: Data from the computerized Nevada Cancer Registry were utilized to compare incidence rates of four malignancies–brain cancer, non-Hodgkin lymphoma (NHL), lung cancer, and breast cancer–in Washoe and Lyon Counties, where an unexplained fatiguing illness was reported during 1984-86, with comparably sized Clark County, where no such illness was reported.

RESULTS: Higher incidences of NHL and primary brain tumors were noted in the two northern Nevada counties (Washoe and Lyon) in 1986 and 1987 respectively, compared to the southern Nevada (Clark) county. Similar patterns were not seen for breast or lung cancer.

CONCLUSIONS: This study provides a model for investigating the possible predisposition of CFS patients to develop cancer using other cohorts, but it is currently premature to accept such a link at this time.

 

Source: Levine PH, Fears TR, Cummings P, Hoover RN. Cancer and a fatiguing illness in Northern Nevada–a causal hypothesis. Ann Epidemiol. 1998 May;8(4):245-9. http://www.ncbi.nlm.nih.gov/pubmed/9590603

 

Post-infection fatigue syndrome following Q fever

Abstract:

In 1989, 147 individuals in the West Midlands, UK, were infected with Q fever. Five years later, following anecdotal reports of fatigue, we used a questionnaire-based case-control study to determine the prevalence of chronic fatigue syndrome symptoms in this group.

Replies from 71 patients were compared with those from 142 age- and sex-matched controls. Increased sweating (52.9% vs. 31.6%, p = 0.006), breathlessness (50.7% vs. 30.6%, p = 0.006), blurred vision (34.3% vs. 17.8%, p = 0.016) and undue tiredness (68.7% vs. 51.5%, p = 0.03) were found in controls compared to cases. These findings were similar to those in Australian abbatoir workers occupationally exposed to Q fever.

CDC criteria for chronic fatigue syndrome were fulfilled by 42.3% of cases and 26% of controls. Using visual analogue scores, symptoms were more severe in cases than in controls. Our findings support the existence of a chronic fatigue state following acute Q fever, in a group of patients exposed just once to the organism, and in circumstances free of such confounding factors as lawsuits over compensation.

 

Source: Ayres JG, Flint N, Smith EG, Tunnicliffe WS, Fletcher TJ, Hammond K, Ward D, Marmion BP. Post-infection fatigue syndrome following Q fever. QJM. 1998 Feb;91(2):105-23. http://qjmed.oxfordjournals.org/content/91/2/105.long

 

Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome, and determine whether the relation is independent of psychiatric factors.

METHODS: The subjects were 53 patients with chronic fatigue syndrome and 32 healthy controls who did not exercise regularly. Subjects were administered a structured psychiatric interview and completed questionnaires focusing on depression and functional disability. They also completed a battery of standardised neuropsychological tasks focusing on the cognitive domains that patients with chronic fatigue syndrome experience as particularly difficult: memory (verbal and visual), and attention/concentration. A test score was defined as failing when it was > or =2 SD below the mean of the healthy controls after controlling for demographic factors.

RESULTS: Those patients with chronic fatigue syndrome with higher numbers of failing neuropsychological test scores reported significantly more days of general inactivity in the past month than those with fewer failing scores. This result remained significant even after partialling out the contribution of the presence of a comorbid axis I psychiatric episode and the overall level of depressive symptomology. Patients with failing verbal memory scores were particularly functionally disabled compared with those with passing scores.

CONCLUSION: A relation was found between cognitive impairment and functional disability which could not be explained entirely on the basis of psychiatric factors.

Comment in: The importance of mental fatigue. [J Neurol Neurosurg Psychiatry. 1998]

 

Source: Christodoulou C, DeLuca J, Lange G, Johnson SK, Sisto SA, Korn L, Natelson BH. Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):431-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170049/

 

The importance of mental fatigue

Comment on: Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. [J Neurol Neurosurg Psychiatry. 1998]

 

The paper by Christodoulou et al in this issue of the Journal (pp 431–4) draws attention to memory deficits in some patients with operationally defined chronic fatigue syndrome, and days of (enforced) physical inactivity. Many studies have assessed cognitive dysfunction in patients with chronic fatigue. The earliest reported superior abilities in such patients against controls or age matched normal subjects, probably reflecting a biased selection of cases from higher socioeconomic groups. Later studies have been the subject of at least two major reviews.1 2

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170046/pdf/v064p00430.pdf

 

Source: Lambert MV, David A. The importance of mental fatigue. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):430. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170046/pdf/v064p00430.pdf (Full article)

 

A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction

Abstract:

Surface and intracellular immunologic and apoptotic markers and functional lymphocyte assays after stimulation with anti-CD3/anti-CD28 antibodies or phytohemagglutinin (PHA) were studied in 44 patients fulfilling the Oxford criteria for chronic fatigue syndrome (CFS). Results were then correlated to scores for the Short Form-36 health questionnaire (SF-36), which assesses eight aspects of patient’s well-being, and for the general health questionnaire (GHQ), which detects current psychiatric disorder.

Patients had significantly increased mean fluorescence intensity readings of HLA-DR in CD4 and CD8 cells (P < 0.05). Expression of the costimulatory receptor CD28 in CD8 cells was significantly reduced, and the apoptosis repressor ratio of bcl-2/bax in both CD4 and CD8 was increased in patients (P < 0.05).

Patients with increased HLA-DR expression had significantly lower SF-36 total scores, worse body pains, and poorer general health perception and physical functioning scores. Increased spontaneous lymphocyte proliferation was associated with poor general health perception. PHA proliferative responses were lower in patients with poor emotional and mental health scores, and the anti-CD3/anti-CD28 response was low in those with low general health perception scores.

Higher spontaneous proliferation and reduced PHA responses correlated with higher GHQ scores. Similarly, GHQ scores were significantly higher, indicating worse mental health, in those with lower total SF-36 scores and worse general and mental health scores in the SF-36 questionnaire.

Finally, higher expression of the costimulatory molecule CD28 correlated with higher total SF-36 scores, general health perception and social functioning scores, and with lower role limitation due to physical health. The increased expression of class II antigens and the reduced expression of the costimulatory receptor CD28, which is a marker of terminally differentiated cells, lend further support to the concept of immunoactivation of T-lymphocytes in CFS and may be consistent with the notion of a viral etiopathogenesis in the illness.

We report, for the first time, increased expression of the apoptosis repressor protein bcl-2, which may contribute to enhanced survival of activated lymphocytes. Using the SF-36 health assessment questionnaire and the GHQ, we demonstrated changes in different immunological parameters, each of which correlated with particular aspects of disease symptomatology.

 

Source: Hassan IS, Bannister BA, Akbar A, Weir W, Bofill M. A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction. Clin Immunol Immunopathol. 1998 Apr;87(1):60-7. http://www.ncbi.nlm.nih.gov/pubmed/9576011

 

Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome

Abstract:

BACKGROUND: Opioidergic pathways have an inhibitory regulatory influence on the hypothalamic-pituitary-adrenal axis (HPA) in man. Previous studies have suggested impairment of pituitary-adrenal activation in chronic fatigue syndrome (CFS). We, therefore, decided to investigate the extent of opioid inhibition of HPA activity in CFS as a possible explanation for the reputed HPA hypofunctioning in patients with CFS.

METHOD: Thirteen patients with CFS, diagnosed according to CDC criteria, were compared with thirteen healthy subjects. Adrenocorticotropin (ACTH) and cortisol (CORT) responses were measured following the administration of the opiate antagonist naloxone.

RESULTS: Baseline ACTH and cortisol levels did not differ between the two groups. The release of ACTH (but not cortisol) was significantly blunted in the CFS subjects compared with controls.

CONCLUSIONS: Naloxone mediated activation of the HPA is attenuated in CFS. Excessive opioid inhibition of the HPA is thus an unlikely explanation for the HPA dysregulation in this disorder.

 

Source: Scott LV, Burnett F, Medbak S, Dinan TG. Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. Psychol Med. 1998 Mar;28(2):285-93. http://www.ncbi.nlm.nih.gov/pubmed/9572086