Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue

Abstract:

Chronic fatigue syndrome, which can occur after acute infection and last for years, is characterized by severe and persistent fatigue. Others have reported decreases in mouse running activity following infection and have suggested this may provide an animal model for studying chronic fatigue.

Voluntary running is a highly motivated activity in mice, which will often run 5-7 mi/day in our laboratory. Following 2 weeks of acclimation to running wheels with food and water available ad lib, female BALB/c mice received 0.2-mL tail vein injections of killed Brucella abortus (BA) or saline vehicle. Subsequently the effects on voluntary running and grooming behavior were determined.

Injection of BA caused an immediate large decrease in running and a lack of grooming. Vehicle injections produced no changes in behavior. After the first several days of reduced running behavior, levels of running and grooming slowly returned back to normal over the next 2-4 weeks, with substantial individual differences in the rate of recovery.

The pattern of running during recovery was intriguing in that BA mice first ran at normal levels just after the lights went out, but they stopped after only 1-2 h. As recovery proceeded, they gradually increased the duration of the running bout during the night. Because this model uses voluntary exertion and the ability to run for longer periods of time characterizes recovery, the model may be a good one for studying the biologic underpinnings of chronic fatigue.

 

Source: Ottenweller JE, Natelson BH, Gause WC, Carroll KK, Beldowicz D, Zhou XD, LaManca JJ. Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue. Physiol Behav. 1998 Mar;63(5):795-801. http://www.ncbi.nlm.nih.gov/pubmed/9618001

 

The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue

Abstract:

Past studies have shown that severe fatigue was the presenting symptom in six of seven patients with delayed orthostatic hypotension and that tilt table-induced hypotension was found in 22 of 23 patients with the chronic fatigue syndrome. We have determined the prevalence of fatigue, volunteered in response to a nonspecific pre-examination questionnaire used in 431 patients, each subsequently diagnosed as having one of eight neurological or endocrine disorders.

The results show that fatigue is a very common symptom in patients with delayed orthostatic hypotension (n = 21), as well as both primary (n = 30) and secondary (n = 106) hypocortisolism: 70-83% in all groups. In contrast, fatigue was an uncommon complaint in patients with multiple system atrophy (MSA) (n = 30), pituitary disorders without hypocortisolism (n = 106) or idiopathic hirsutism (n = 96): 7-33% in all groups, and was intermediate in prevalence in patients with acute hyperadrenergic orthostatic hypotension (n = 32): 41%.

It is concluded that fatigue commonly results from delayed orthostatic hypotension and all forms of hypocortisolism but is less common in patients with acute orthostatic hypotension, both idiopathic and due to MSA, which more commonly present with lightheadedness or syncope.

 

Source: Streeten DH, Anderson GH Jr. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res. 1998 Apr;8(2):119-24. http://www.ncbi.nlm.nih.gov/pubmed/9613802

 

Chronic fatigue syndrome: a review for clinicians

Abstract:

Syndromes characterized by persistent fatigue, musculoskeletal pain, sleep disturbance, and subjective cognitive impairment have been common problems in clinical practice for decades. The chronic fatigue syndrome case definition was created to standardize the patient population in research studies and to foster a systematic and comprehensive approach to the attempt to define the etiology and pathophysiology of these syndromes. The pathogenesis of chronic fatigue syndrome remains unknown, though it does appear to be associated with subtle neuroendocrine and immunologic abnormalities. Treatment of chronic fatigue syndrome is empirical. Significant palliation is often possible, though treatment success requires skillful practice of the art of medicine.

 

Source: Goshorn RK. Chronic fatigue syndrome: a review for clinicians. Semin Neurol. 1998;18(2):237-42. http://www.ncbi.nlm.nih.gov/pubmed/9608620

 

Impaired associative learning in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report cognitive difficulties (impaired attention, memory and reasoning). Neuropsychological tests have failed to consistently find cognitive impairments to the degree reported by CFS patients.

We tested patients with CFS and sedentary controls in protocols designed to measure sensory reactivity and acquisition of the classically conditioned eyeblink response. Patients with CFS exhibited normal sensitivity and responsivity to acoustic stimuli.

However, CFS patients displayed impaired acquisition of the eyeblink response using a delayed-type conditioning paradigm. Sensitivity and responsivity to the airpuff stimulus were normal.

In the absence of sensory/motor abnormalities, impaired acquisition of the classically conditioned eyeblink response indicates an associative deficit. These data suggest organic brain dysfunction within a defined neural substrate in CFS patients.

 

Source: Servatius RJ, Tapp WN, Bergen MT, Pollet CA, Drastal SD, Tiersky LA, Desai P, Natelson BH. Impaired associative learning in chronic fatigue syndrome. Neuroreport. 1998 Apr 20;9(6):1153-7. http://www.ncbi.nlm.nih.gov/pubmed/9601685

 

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