Tag: 2003

Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports

Abstract:

Chronic fatigue syndrome (CFS) is characterized by persistent mental and physical fatigue for at least 6 months. Its pathophysiology is unknown and there is no proven effective treatment. We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition.

Case 1: 18-year-old female with a 3-year history of CFS. Response of compound-muscle-action potential, recorded using surface recording electrode, over left abductor pollicis brevis muscle, to repetitive nerve stimulation (RNS) at a rate of 10 Hz showed a 42% incremental response. Composite autonomic scoring system (CASS) showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2). Serological tests for Epstein-Barr virus (EBV) revealed positive antiviral capsid antigens (anti-VCA) immunoglobulins G (IgG). Oral pyridostigmine therapy (30 mg) resulted in marked improvement in symptoms.

Case 2: 28-year-old female with 10-year history of CFS. RNS, using identical protocol, showed a 60% incremental response over the same muscle. CASS showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2) and this patient was also positive for EBV. This patient responded dramatically to 10-mg pyridostigmine.

Case 3: 29-year-old female with a history of CFS for longer than 15 years. Repetitive stimulation, using identical paradigm to left abductor pollicis brevis muscle, showed a 42% incremental response. CASS showed mildly cholinergic impairment (cardiovagal score: 2; sudomotor score: 1). EBV antibody titers were positive. Patient responded to 30-mg pyridostigmine with an improvement in her fatigue.

These three cases generate the hypothesis that the fatigue in some patients with clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia. Support for this thesis derives from the improvement with cholinesterase inhibition.

 

Source: Kawamura Y, Kihara M, Nishimoto K, Taki M. Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports. Pathophysiology. 2003 May;9(3):189-194. http://www.ncbi.nlm.nih.gov/pubmed/14567934

 

Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects

Abstract:

Enterovirus RNA has been found previously in specimens of muscle biopsy from patients with idiopathic dilated cardiomyopathy, chronic inflammatory muscle diseases, and fibromyalgia or chronic fatigue syndrome (fibromyalgia/chronic fatigue syndrome). These results suggest that skeletal muscle may host enteroviral persistent infection.

To test this hypothesis, we investigated by reverse transcription-polymerase chain reaction (RT-PCR) assay the presence of enterovirus in skeletal muscle of patients with chronic inflammatory muscle diseases or fibromyalgia/chronic fatigue syndrome, and also of healthy subjects.

Three of 15 (20%) patients with chronic inflammatory muscle diseases, 4 of 30 (13%) patients with fibromyalgia/chronic fatigue syndrome, and none of 29 healthy subjects was found positive. The presence of VP-1 enteroviral capsid protein was assessed by an immunostaining technique using the 5-D8/1 monoclonal antibody; no biopsy muscle from any patient or healthy subject was found positive.

The presence of viral RNA in some muscle biopsies from patients exhibiting muscle disease, together with the absence of VP-1 protein, is in favor of a persistent infection involving defective viral replication.

Copyright 2003 Wiley-Liss, Inc.

 

Source: Douche-Aourik F, Berlier W, Féasson L, Bourlet T, Harrath R, Omar S, Grattard F, Denis C, Pozzetto B. Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects. J Med Virol. 2003 Dec;71(4):540-7. http://www.ncbi.nlm.nih.gov/pubmed/14556267

 

Diagnostic evaluation of 2′, 5′-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan

Abstract:

To investigate the association of viral infections with chronic fatigue syndrome (CFS), we assayed 2′, 5′-oligoadenylate synthetase (2-5AS) activities in peripheral blood mononuclear cells from CFS patients in Japan. These patients were diagnosed in two hospitals, H1 and H2, located in different areas of the country.

The activities were detected in 19 (86%) and 7 (32%) of each of the 22 patients in H1 and H2, respectively, while they were detected in only four (11%) out of the 38 healthy controls. IFN-alpha was similarly detected in a few CFS patients and healthy controls.

We also assayed the antibody titers against Epstein-Barr virus (EBV) and Coxiella burnetii in these patients. The EBV anti-EA-IgG antibodies were detected in two (9%) and seven (32%) of each of the 22 patients in H1 and H2, respectively. Anti-C. burnetii IgG antibodies were detected in six (27%) out of 22 patients in H1 but not in 22 patients in H2, while they were detected in one (11%) of the nine healthy controls.

Some CFS patients may be associated with EBV or C. burnetii infection. There were some statistical correlations between the 2-5AS activities and antibody titers of EA-IgG (P < 0.05, Student’s t-test) but not to the antibody titers of C. burnetii. The up-regulation of 2-5AS activities suggests immunological dysfunctions with some virus infections in the CFS patients. Our results indicate that 2-5AS activities are useful for a diagnostic marker of CFS and for exploring the complicated pathogenesis of CFS.

 

Source: Ikuta K, Yamada T, Shimomura T, Kuratsune H, Kawahara R, Ikawa S, Ohnishi E, Sokawa Y, Fukushi H, Hirai K, Watanabe Y, Kurata T, Kitani T, Sairenji T. Diagnostic evaluation of 2′, 5′-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan. Microbes Infect. 2003 Oct;5(12):1096-102. http://www.ncbi.nlm.nih.gov/pubmed/14554250

 

Aerobic capacity of Gulf War veterans with chronic fatigue syndrome

Abstract:

A large overlap exists between the diagnosis of chronic fatigue syndrome (CFS) and the unexplained symptoms reported by many Gulf War veterans (GV). Previous investigations have reported reduced aerobic capacity in civilians with CFS. The present investigation examined metabolic responses to maximal exercise in GVs with CFS compared with healthy GVs.

Cardiorespiratory and metabolic responses were recorded during a maximal exercise test on a cycle ergometer. The groups were not different in any demographic category (p > 0.05) or self-reported physical activity (p > 0.05). No differences were observed between groups for maximal oxygen uptake (28.9 +/- 6.7 mL/kg/min for CFS vs. 30.8 +/- 7.1 mL/kg/min for controls; p = 0.39), heart rate (155.8 +/- 16.1 bpm for CFS vs. 163.3 +/- 14.9 bpm for controls; p = 0.17), exercise time (9.6 +/- 1.5 minutes for CFS vs. 10.2 +/- 1.4 minutes for controls; p = 0.26), or workload achieved (208 +/- 36.7 W for CFS vs. 224 +/- 42.9 W for controls; p = 0.25). Likewise, no differences were observed at submaximal intensities (p > 0.05).

Compared with healthy controls, GVs who report multiple medically unexplained symptoms and meet criteria for CFS do not show a decreased exercise capacity. Thus, it does not appear that the pathology of the GVs with CFS includes a deficiency with mobilizing the cardiopulmonary system for strenuous physical effort.

 

Source: Nagelkirk PR, Cook DB, Peckerman A, Kesil W, Sakowski T, Natelson BH, LaManca JJ. Aerobic capacity of Gulf War veterans with chronic fatigue syndrome. Mil Med. 2003 Sep;168(9):750-5. http://www.ncbi.nlm.nih.gov/pubmed/14529252

 

Rupture of silicone gel breast implants and symptoms of pain and fatigue

Abstract:

OBJECTIVE: To compare symptoms of women with silicone gel breast implants and women with chronic fatigue syndrome (CFS), and to study the effect of rupture of the silicone implant.

METHODS: Five hundred readers of the Dutch silicone breast implant support group magazine were asked to respond if they had been informed by the surgeon about the silicone implant status at operation, and to answer questions about symptoms of CFS. Their complaints were compared with those of 100 female patients with CFS and 40 female controls.

RESULTS: The questionnaires were returned by 319 women. Of these, 227 had symptoms of debilitating chronic fatigue. The patterns of symptoms differed from those in patients with CFS. An analysis of the relation between integrity of the implants and the symptoms could be carried out in 176 women, and 74% of these latter women reported ruptured implants. Significantly more women with ruptured implants than those with intact implants had debilitating chronic fatigue (75% vs 51%), postexertional malaise > 24 h (77% vs 51%), impaired short term memory (58% vs 38%), and multi-joint pain (77% vs 60%).

CONCLUSION: Women with silicone breast implants often report severe pain and chronic fatigue. Rupture of the implant is associated with an increase in symptoms of pain and chronic fatigue.

Comment in:

Where there’s smoke there’s fire: the silicone breast implant controversy continues to flicker: a new disease that needs to be defined. [J Rheumatol. 2003]

Breast implant related disease. [J Rheumatol. 2004]

 

Source: Vermeulen RC, Scholte HR. Rupture of silicone gel breast implants and symptoms of pain and fatigue. J Rheumatol. 2003 Oct;30(10):2263-7. http://www.ncbi.nlm.nih.gov/pubmed/14528527

 

First-night effect in the chronic fatigue syndrome

Abstract:

Since the magnitude of the first-night effect has been shown to be a function of medical conditions and of settings in which polysomnographies are performed, it is essential to evaluate the habituation phenomenon in each case in order to determine the optimal recording methodology. A first-night effect was evidenced in certain cases of chronic fatigue syndrome, but not in others.

To clarify this issue, a large group of patients with chronic fatigue syndrome who had no primary sleep disorders were selected and recorded for two consecutive nights in a hospital sleep unit. Several parameters, frequently associated with the first-night effect, were found to be influenced by the recording methodology: Total Sleep Time, Sleep Efficiency, Sleep Efficiency minus Sleep Onset, Sleep Onset Latency, Wake Time, Slow Wave Sleep, Rapid Eye Movement Sleep, Rapid Eye Movement Sleep Latency and Number of Sleep Cycles. Bland and Altman plots determined that the difference scores between the nights included a systematic bias linked to the order of recordings (first-night effect). Factorial analysis grouped the difference scores into three factors.

No significant difference was observed between patients with generalized anxiety comorbidity and those with no psychiatric comorbidity, or between those with and without psychiatric comorbidity. Chronic fatigue syndrome must thus be added on the list of conditions where a clinically significant habituation effect takes place.

 

Source: Le Bon O, Minner P, Van Moorsel C, Hoffmann G, Gallego S, Lambrecht L, Pelc I, Linkowski P. First-night effect in the chronic fatigue syndrome. Psychiatry Res. 2003 Sep 30;120(2):191-9. http://www.ncbi.nlm.nih.gov/pubmed/14527650

 

Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of persistent fatigue. Recent studies have shown that patients with CFS have an increased prevalence of nonallergic rhinitis. Inflammation of the nasal passages due to allergic rhinitis can cause nasal congestion resulting in an increased number of sleep disturbances and daytime fatigue. While topical nasal corticosteroids have been shown to alleviate nasal obstruction effectively in patients with rhinitis who do not have CFS, it is unknown whether topical nasal corticosteroids will reduce CFS symptoms.

STUDY OBJECTIVE: The purpose of this study is to determine whether topical nasal corticosteroids will reduce daytime sleepiness in patients with CFS and rhinitis.

METHODS: Twenty-eight of 31 subjects with rhinitis and a diagnosis of CFS completed the double-blind, randomized, placebo-controlled trial. Two subjects failed screening, and 3 subjects withdrew from the study prior to its completion. Subjects were randomized according to Balaam’s crossover design, and one of the following interventions was used for each group in the study: 8-week treatment with a topical nasal corticosteroid, 8-week treatment with a placebo saline spray, 4-week treatment with a topical nasal corticosteroid followed by a 4-week treatment with a placebo saline spray, or a 4-week treatment with a placebo saline spray followed by a 4-week treatment with a topical nasal corticosteroid. Data focusing on rhinitis symptoms, severity of chronic fatigue symptoms, and quality of life were gathered at biweekly office visits and with daily diaries.

RESULTS: The results indicated that daytime sleepiness was reduced when patients with rhinitis and CFS were treated with topical nasal corticosteroids. The severity of associated CFS symptoms, specifically fatigue, muscle pain, postexertional fatigue, and daily activity, did not improve with treatment.

CONCLUSION: Treating the symptoms of rhinitis in patients with CFS does not appear to alleviate daytime fatigue or associated nasal, musculoskeletal, or cognitive complaints. Therefore, it is unlikely that aggressive treatment of such symptoms with topical nasal corticosteroids will provide significant benefit to patients with CFS who do not have allergic rhinitis. These results indicate that the nonallergic rhinitis seen in patients with CFS may arise from a mechanism other than chronic inflammation.

 

Source: Kakumanu SS, Mende CN, Lehman EB, Hughes K, Craig TJ. Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis. J Am Osteopath Assoc. 2003 Sep;103(9):423-7. http://www.ncbi.nlm.nih.gov/pubmed/14527077

 

Identification of novel expressed sequences, up-regulated in the leucocytes of chronic fatigue syndrome patients

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is an increasing medical phenomenon of unknown aetiology leading to high levels of chronic morbidity. Of the many hypotheses that purport to explain this disease, immune system activation, as a central feature, has remained prominent but unsubstantiated. Supporting this, a number of important cytokines have previously been shown to be over-expressed in disease subjects. The diagnosis of CFS is highly problematic since no biological markers specific to this disease have been identified. The discovery of genes relating to this condition is an important goal in seeking to correctly categorize and understand this complex syndrome.

OBJECTIVE: The aim of this study was to screen for changes in gene expression in the lymphocytes of CFS patients.

METHODS: ‘Differential Display’ is a method for comparing mRNA populations for the induction or suppression of genes. In this technique, mRNA populations from control and test subjects can be ‘displayed’ by gel electrophoresis and screened for differing banding patterns. These differences are indicative of altered gene expression between samples, and the genes that correspond to these bands can be cloned and identified. Differential display has been used to compare expression levels between four control subjects and seven CFS patients.

RESULTS: Twelve short expressed sequence tags have been identified that were over-expressed in lymphocytes from CFS patients. Two of these correspond to cathepsin C and MAIL1 – genes known to be upregulated in activated lymphocytes. The expression level of seven of the differentially displayed sequences have been verified by quantifying relative level of these transcripts using TAQman quantitative PCR.

CONCLUSION: Taken as a whole, the identification of novel gene tags up-regulated in CFS patients adds weight to the idea that CFS is a disease characterized by subtle changes in the immune system.

 

Source: Powell R, Ren J, Lewith G, Barclay W, Holgate S, Almond J. Identification of novel expressed sequences, up-regulated in the leucocytes of chronic fatigue syndrome patients. Clin Exp Allergy. 2003 Oct;33(10):1450-6. http://www.ncbi.nlm.nih.gov/pubmed/14519154

 

Baroreceptor reflex and integrative stress responses in chronic fatigue syndrome

Abstract:

OBJECTIVE: Altered cardiovascular responses to mental and postural stressors have been reported in chronic fatigue syndrome (CFS). This study examined whether those findings may involve changes in baroreceptor reflex functioning.

METHODS: Chronotropic baroreceptor reflex (by sequential analysis) and cardiovascular stress responses were recorded during postural (5-minute of active standing) and cognitive (speech task) stress testing in patients with CFS grouped into cases with severe (N = 21) or less severe (N = 22) illness, and in 29 matched control subjects.

RESULTS: Patients with CFS had a greater decline in baroreceptor reflex sensitivity (BRS) during standing, although only those with severe CFS were significantly different from the controls. Systolic blood pressure declined during standing in the control group but was maintained in the CFS patients. In contrast, the patients with less severe CFS had blunted increases in blood pressure during the speech task, which could not, however, be explained by inadequate inhibition of the baroreceptor reflex, with all groups showing an appropriate reduction in BRS during the task.

CONCLUSIONS: These results indicate that in CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex. This study also suggests that classifying patients with CFS on illness severity may discriminate between patients with abnormalities in peripheral vs. central mechanisms of cardiovascular stress responses.

 

Source: Peckerman A, LaManca JJ, Qureishi B, Dahl KA, Golfetti R, Yamamoto Y, Natelson BH. Baroreceptor reflex and integrative stress responses in chronic fatigue syndrome. Psychosom Med. 2003 Sep-Oct;65(5):889-95. http://www.ncbi.nlm.nih.gov/pubmed/14508037

 

Illness perceptions and levels of disability in patients with chronic fatigue syndrome and rheumatoid arthritis

Abstract:

OBJECTIVE: To investigate the strength of chronic fatigue syndrome (CFS) patients’ negative illness perceptions by comparing illness perceptions and self-reported disability in patients with CFS and rheumatoid arthritis (RA).

METHODS: Seventy-four RA patients and 49 CFS patients completed the Illness Perception Questionnaire-Revised and the 36-item Short-Form Health Survey.

RESULTS: When compared to the RA group, the CFS group attributed a wider range of everyday somatic symptoms to their illness, perceived the consequences of their illness to be more profound and were more likely to attribute their illness to a virus or immune system dysfunction. Both groups reported equivalent levels of physical disability but the CFS group reported significantly higher levels of role and social disability.

CONCLUSION: Although the symptoms of CFS are largely medically unexplained, CFS patients have more negative views about their symptoms and the impact that these have had on their lives than do patients with a clearly defined and potentially disabling medical condition. The data support the cognitive behavioural models of CFS that emphasise the importance of patients’ illness perceptions in perpetuating this disorder.

 

Source: Moss-Morris R, Chalder T. Illness perceptions and levels of disability in patients with chronic fatigue syndrome and rheumatoid arthritis. J Psychosom Res. 2003 Oct;55(4):305-8. http://www.ncbi.nlm.nih.gov/pubmed/14507540