Gulf War illnesses: complex medical, scientific and political paradox

Abstract:

Gulf War illnesses are a collection of disorders that for the most part can be diagnosed and treated, if effective programmes exist to assist veterans, and in some cases their immediate family members.

Although these illnesses are complex and have multi-organ signs and symptoms, a proportion of these patients can be identified as having Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and/or Fibromyalgia Syndrome (FMS).

Although there are many possible causes of CSF/ME/FMS, chronic infections can explain, at least in a subset of patients, the apparent transmission of these illnesses to family members and the appearance of chronic, multi-organ and auto-immune signs and symptoms. Unfortunately, many veterans who have been diagnosed with chronic infections, such as mycoplasmal infections, cannot obtain adequate treatment for their condition, resulting in their reliance on private physicians and clinics for assistance. This lack of response may ultimately be responsible for the transmission of the illness to non-veterans.

 

Source: Nicolson GL, Nicolson NL. Gulf War illnesses: complex medical, scientific and political paradox. Med Confl Surviv. 1998 Apr-Jun;14(2):156-65. http://www.ncbi.nlm.nih.gov/pubmed/9633269

 

Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle

Abstract:

It has been shown previously that some patients with chronic fatigue syndrome show an abnormal increase in plasma lactate following a short period of moderate exercise, in the sub-anaerobic threshold exercise test (SATET).

This cannot be explained satisfactorily by the effects of ‘inactivity’ or ‘deconditioning’, and patients with abnormal lactate responses to exercise (SATET +ve) have been found to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary volunteers.

There were no differences in resting spectra between these groups but at the end of exercise, intracellular pH in the SATET +ve patients was significantly lower than in both the SATET -ve cases and controls (P < 0.03), and the SATET +ve patients also showed a significantly lower ATP synthesis rate during recovery (P < 0.01), indicating impaired mitochondrial oxidative phosphorylation.

These observations support other evidence which indicates that chronic fatigue syndrome is a heterogeneous disorder, and confirms the view that some chronic fatigue syndrome patients have a peripheral component to their fatigue.

 

Source: Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R. Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul Disord. 1998 May;8(3-4):204-9. http://www.ncbi.nlm.nih.gov/pubmed/9631403

 

Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array of diffuse somatic symptoms.

Our group has established that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. The relevance of this finding to the pathophysiology of CFS is supported by the observation that the onset and course of this illness is excerbated by physical and emotional stressors. It is also notable that this HPA dysregulation differs from that seen in melancholic depression, but shares features with other clinical syndromes (e.g., fibromyalgia).

How the HPA axis dysfunction develops is unclear, though recent work suggests disturbances in serotonergic neurotransmission and alterations in the activity of AVP, an important co-secretagogue that, along with CRH, influences HPA axis function.

In order to provide a more refined view of the nature of the HPA disturbance in patients with CFS, we have studied the detailed, pulsatile characteristics of the HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS. Results of that work are consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive. These observations provide an important clue to the development of more effective treatment to this disabling condition.

 

Source: Demitrack MA, Crofford LJ. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann N Y Acad Sci. 1998 May 1;840:684-97. http://www.ncbi.nlm.nih.gov/pubmed/9629295

 

Depression and short REM latency in subjects with chronic fatigue syndrome

Abstract:

OBJECTIVE: The hypothesized polysomnographic marker for depression, Rapid Eye Movement Latency (REML), was used to investigate two groups of subjects; Chronic Fatigue Syndrome (CFS)-not depressed and CFS-depressed.

METHOD: CFS subjects were classified into depressed and not depressed groups, using the Diagnostic Interview Schedule (DIS), and subsequently were studied in a sleep laboratory to ascertain REML.

RESULTS: Short REML showed a statistically significant correlation with the depressed state in CFS subjects.

CONCLUSION: Short REM latency is associated with depression in the CFS population.

 

Source: Morehouse RL, Flanigan M, MacDonald DD, Braha D, Shapiro C. Depression and short REM latency in subjects with chronic fatigue syndrome. Psychosom Med. 1998 May-Jun;60(3):347-51. http://www.ncbi.nlm.nih.gov/pubmed/9625223

 

No strong evidence of disturbed regulation of blood pressure in chronic fatigue syndrome

Abstract:

Recent medical publications postulate a connection between the Chronic Fatigue Syndrome (CFS) and disturbed regulation of the circulation, manifesting itself during orthostatic stress testing.

Four studies were published on the circulatory response on prolonged head up tilt testing. Numerous CFS patients displayed postural tachycardia or syncope during the test. However, many CFS patients examined had had orthostatic symptoms prior to the examination.

It is not certain that cardiovascular dysregulation is present in CFS patients without orthostatic symptoms. It is also not clear whether such a dysregulation would be the effect of physical inactivity or a manifestation of a subtle form of autonomic neuropathy.

 

Source: Smit AA, Bolweg NM, Lenders JW, Wieling W. No strong evidence of disturbed regulation of blood pressure in chronic fatigue syndrome. Ned Tijdschr Geneeskd. 1998 Mar 21;142(12):625-8.[Article in Dutch] http://www.ncbi.nlm.nih.gov/pubmed/9623125

 

Predictors of a medical-offset effect among patients receiving antidepressant therapy

Abstract:

OBJECTIVE: Characteristics of patients receiving antidepressant therapy were examined to identify factors that may be associated with a medical-offset effect.

METHOD: In a retrospective study, the authors analyzed claims data from a large health insurer in New England. The study subjects included 1,661 persons initiating treatment for depression with selective serotonin reuptake inhibitors or tricyclic antidepressants between July 1991 and June 1993.

RESULTS: Patients with anxiety disorders, coronary heart disease, cancer, and chronic fatigue syndrome and those remaining on their initial regimens of antidepressant therapy for at least 6 months were more likely to experience significant reductions in the costs of medical care services. The number of visits to mental health providers had no effect on the costs of medical services.

CONCLUSIONS: Specific comorbid conditions and sustained use of antidepressant drugs may be associated with a medical-offset effect for patients receiving treatment for depression.

 

Source: Thompson D, Hylan TR, McMullen W, Romeis ME, Buesching D, Oster G. Predictors of a medical-offset effect among patients receiving antidepressant therapy. Am J Psychiatry. 1998 Jun;155(6):824-7. http://www.ncbi.nlm.nih.gov/pubmed/9619157

 

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