beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome

Abstract:

BACKGROUND: Due to the occurrence of sleep disturbances and fatigue in chronic fatigue syndrome (CFS), an investigation was performed to examine if there is an abnormal excretion of gamma-aminobutyric acid (GABA) and/or its structural analogue beta-alanine in the urine from CFS patients. Both GABA and beta-alanine are inhibitory neurotransmitters in the mammalian central nervous system.

METHODS: The 24 h urine excretion of GABA and beta-alanine was determined by isotope dilution gas chromatography mass spectrometry in 33 CFS patients and 43 healthy controls. The degree of symptoms in both patients and controls was measured by grading of three typical CFS symptoms using a Visual Analogue Scale.

RESULTS: Men had a significantly higher excretion of both beta-alanine and GABA than women. Comparing CFS patients with healthy controls showed no significant difference in excretion of neither beta-alanine nor GABA. No correlation was found between the excretion of beta-alanine or GABA and any of the three characteristic CFS symptoms measured. However, two female and two male CFS patients excreted considerably higher amounts of beta-alanine in their 24 h urine samples than control subjects.

CONCLUSIONS: Increased excretion of beta-alanine was found in a subgroup of CFS patients, indicating that there may be a link between CFS and beta-alanine in some CFS patients.

 

Source: Hannestad U, Theodorsson E, Evengård B. beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome. Clin Chim Acta. 2007 Feb;376(1-2):23-9. Epub 2006 Jul 14. https://www.ncbi.nlm.nih.gov/pubmed/16934791

 

Menopausal transition symptoms in midlife women living with fibromyalgia and chronic fatigue

Abstract:

We aimed to determine how menopausal transition symptoms cluster across 216 midlife women with fibromyalgia, chronic fatigue syndromes (FMS/CFS), or both and subsequently to compare symptom factor severity scores by menopausal status among these women and compare symptom reporting with prior community-based samples of women without obvious illness.

We designed a cross-sectional telephone survey of 216 women aged 35 to 55, diagnosed with FMS/CFS, symptomatic in the prior 6 months, and without hysterectomy. Thirty-six of 61 symptoms loaded on five factors: aroused/anxious mood, depressed mood/withdrawal, musculoskeletal, gastrointestinal (GI), and vasomotor. Peri- and postmenopausal women had higher symptom severity scores for musculoskeletal, GI, and vasomotor factors but not mood factors.

Symptoms for the women we studied who had FMS/CFS clustered similar to those in previous community-based samples of midlife women without major illness; however, the number of women experiencing symptoms was much higher among our sample.

 

Source: Wilbur J, Shaver J, Kogan J, Buntin M, Wang E. Menopausal transition symptoms in midlife women living with fibromyalgia and chronic fatigue. Health Care Women Int. 2006 Aug;27(7):600-14. https://www.ncbi.nlm.nih.gov/pubmed/16844673

 

Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: a systematic review

Abstract:

BACKGROUND: In addition to debilitating fatigue the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain.

AIMS: Conducting a systematic review to critically assess the existing knowledge on chronic pain in CFS. We focussed on the definition, the prevalence and incidence, the aetiology, the relevance and the therapy strategy for chronic musculoskeletal pain and post-exertional pain in CFS.

METHODS: To identify relevant articles, we searched eight medical search engines. The search terms “chronic fatigue syndrome” AND “pain”, “nociception”, “arthralgia” and “myalgia”, were used to identify articles concerning pain in CFS. Included articles were reviewed by two blinded researchers.

RESULTS: Twenty-five articles and two abstract were identified and selected for further appraisal. Only 11 search results focussed on musculoskeletal pain in CFS patients. Regarding the standardized review of the articles, a 96% agreement between the researchers was observed. There is no consensus in defining chronic widespread pain in CFS, and although there is little or no strong proof for the exact prevalence, chronic pain is strongly disabling in CFS. Aetiological theories are proposed (sleep abnormalities, tryptophan, parovirus-B, hormonal and brain abnormalities and central sensitisation) and a reduction of pain threshold after exercise has been shown. Furthermore depression seemed not related to pain in CFS and a staphylococcus toxoid vaccine caused no significant pain reduction.

CONCLUSIONS: The results from the systematic review highlight the clinical importance of chronic pain in CFS, but only few studies addressing the aetiology or treatment of chronic pain in CFS are currently available.

 

Source: Meeus M, Nijs J, Meirleir KD. Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: a systematic review. Eur J Pain. 2007 May;11(4):377-86. Epub 2006 Jul 13. https://www.ncbi.nlm.nih.gov/pubmed/16843021

 

Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications

Abstract:

Patients with chronic fatigue syndrome (CFS) experience chronic musculoskeletal pain which is even more debilitating than fatigue. Scientific research data gathered around the world enables clinicians to understand, at least in part, chronic musculoskeletal pain in CFS patients. Generalized joint hypermobility and benign joint hypermobility syndrome appear to be highly prevalent among CFS sufferers, but they do not seem to be of any clinical importance.

On the other hand, pain catastrophizing accounts for a substantial portion of musculoskeletal pain and is a predictor of exercise performance in CFS patients. The evidence concerning pain catastrophizing is supportive of the indirect evidence of a dysfunctional pain processing system in CFS patients with musculoskeletal pain. CFS sufferers respond to incremental exercise with a lengthened and accentuated oxidative stress response, explaining muscle pain, postexertional malaise, and the decrease in pain threshold following graded exercise in CFS patients.

Applying the scientific evidence to the manual physiotherapy profession, pacing self-management techniques and pain neurophysiology education are indicated for the treatment of musculoskeletal pain in CFS patients. Studies examining the effectiveness of these strategies for CFS patients are warranted.

 

Source: Nijs J, Meeus M, De Meirleir K. Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications. Man Ther. 2006 Aug;11(3):187-91. Epub 2006 Jun 14. https://www.ncbi.nlm.nih.gov/pubmed/16781183

 

How fatigue is related to other somatic symptoms

Abstract:

AIMS: To assess the relation between fatigue and somatic symptoms in healthy adolescents and adolescents with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).

METHODS: Seventy two adolescents with CFS were compared within a cross-sectional study design with 167 healthy controls. Fatigue and somatic complaints were measured using self-report questionnaires, respectively the subscale subjective fatigue of the Checklist Individual Strength (CIS-20) and the Children’s Somatization Inventory.

RESULTS: Healthy adolescents reported the same somatic symptoms as adolescents with CFS/ME, but with a lower score of severity. The top 10 somatic complaints were the same: low energy, headache, heaviness in arms/legs, dizziness, sore muscles, hot/cold spells, weakness in body parts, pain in joints, nausea/upset stomach, back pain. There was a clear positive relation between log somatic symptoms and fatigue (linear regression coefficient: 0.041 points log somatic complaints per score point fatigue, 95% CI 0.033 to 0.049) which did not depend on disease status.

CONCLUSIONS: Results suggest a continuum with a gradual transition from fatigue with associated symptoms in healthy adolescents to the symptom complex of CFS/ME.

 

Source: van de Putte EM, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. How fatigue is related to other somatic symptoms. Arch Dis Child. 2006 Oct;91(10):824-7. Epub 2006 Jun 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2066005/ (Full article)

 

The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome

Abstract:

Evoked or experimental pain is often used as a model for the study of clinical pain, yet there are little data regarding the relationship between the two. In addition, there are few data regarding the types of stimuli and stimulus intensities that are most closely related to clinical pain. In this study, 36 subjects with fibromyalgia (FM), chronic fatigue syndrome (CFS), or both syndromes were administered measures of clinical pain and underwent a dolorimetry evaluation. Subjects also underwent experimental pain testing utilizing heat and pressure stimulation.

Stimulation levels evoking low, moderate and high sensory intensity, and comparable levels of unpleasantness, were determined for both types of stimuli using random staircase methods. Clinical pain was assessed using visual analogue ratings and the short form of the McGill Pain Questionnaire (MPQ). Ratings of heat pain sensation were not significantly associated with clinical pain ratings, with the exception of unpleasantness ratings at high stimulus intensities. Pain threshold and tolerance as assessed by dolorimetry were significantly associated with average measures of clinical pain.

Both intensity and unpleasantness ratings of pressure delivered using random staircase methods were significantly associated with clinical pain at low, moderate and high levels, and the strength of the association was greater at increasingly noxious stimulus intensities. These findings suggest that random pressure stimulation as an experimental pain model in these populations more closely reflects the clinical pain for these conditions. These findings merit consideration when designing experimental studies of clinical pain associated with FM and CFS.

 

Source: Geisser ME, Gracely RH, Giesecke T, Petzke FW, Williams DA, Clauw DJ. The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome. Eur J Pain. 2007 Feb;11(2):202-7. Epub 2006 Mar 20. https://www.ncbi.nlm.nih.gov/pubmed/16546424

 

Sub-typing CFS patients on the basis of ‘minor’ symptoms

Abstract:

The diagnosis of chronic fatigue syndrome (CFS), an illness characterized by medically unexplained fatigue, depends on a clinical case definition representing one or more pathophysiological mechanisms. To prepare for studies of these mechanisms, this study sought to identify subtypes of CFS.

In 161 women meeting 1994 criteria for CFS, principal components analysis of the 10 ‘minor’ symptoms of CFS produced three factors interpreted to indicate musculoskeletal, infectious and neurological subtypes. Extreme scores on one or more of these factors characterized about 2/3 of the sample. Those characterized by the neurological factor were at increased risk of reduced scores on cognitive tests requiring attention, working memory, long-term memory or rapid performance.

In addition, the neurological subtype was associated with reduced levels of function. Those characterized by the musculoskeletal factor were at increased risk for the diagnosis of fibromyalgia (chronic widespread pain and mechanical allodynia) and reduced physical function. Those characterized by the infectious factor were less likely to evidence co-occurring fibromyalgia, and showed lesser risk of functional impairment.

The prevalence of disability was increased in those with the highest scores on any of the subtypes, as well as in those with high scores on multiple factors. Depression and anxiety, while frequently present, were not more prevalent in any particular subtype, and did not increase with the severity of specific symptom reports. Results suggest that subtypes of CFS may be identified from reports of the minor diagnostic symptoms, and that these subtypes demonstrate construct validity.

 

Source: Janal MN, Ciccone DS, Natelson BH. Sub-typing CFS patients on the basis of ‘minor’ symptoms. Biol Psychol. 2006 Aug;73(2):124-31. Epub 2006 Feb 10. https://www.ncbi.nlm.nih.gov/pubmed/16473456

 

Sleep quality and psychological adjustment in chronic fatigue syndrome

Abstract:

Without specific etiology or effective treatment, chronic fatigue syndrome (CFS) remains a contentious diagnosis. Individuals with CFS complain of fatigue and poor sleep–symptoms that are often attributed to psychological disturbance.

To assess the nature and prevalence of sleep disturbance in CFS and to investigate the widely presumed presence of psychological maladjustment we examined sleep quality, sleep disorders, physical health, daytime sleepiness, fatigue, and psychological adjustment in three samples. individuals with CFS; a healthy control group; and individuals with a definite medical diagnosis: narcolepsy. Outcome measures included physiological evaluation (polysomnography), medical diagnosis, structured interview, and self-report measures.

Results indicate that the CFS sample had a very high incidence (58%) of previously undiagnosed primary sleep disorder such as sleep apnea/hypopnea syndrome and restless legs/periodic limb movement disorder. They also had very high rates of self-reported insomnia and nonrestorative sleep.

Narcolepsy and CFS participants were very similar on psychological adjustment: both these groups had more psychological maladjustment than did control group participants. Our data suggest that primary sleep disorders in individuals with CFS are underdiagnosed in primary care settings and that the psychological disturbances seen in CFS may well be the result of living with a chronic illness that is poorly recognized or understood.

 

Source: Fossey M, Libman E, Bailes S, Baltzan M, Schondorf R, Amsel R, Fichten CS. Sleep quality and psychological adjustment in chronic fatigue syndrome. J Behav Med. 2004 Dec;27(6):581-605. http://www.ncbi.nlm.nih.gov/pubmed/15669445

 

Gastric emptying is slow in chronic fatigue syndrome

Abstract:

BACKGROUND: Gastrointestinal symptoms are common in patients with Chronic Fatigue Syndrome (CFS). The objective of this study was to determine the frequency of these symptoms and explore their relationship with objective (radionuclide) studies of upper GI function.

METHODS: Thirty-two (32) patients with CFS and 45 control subjects completed a questionnaire on upper GI symptoms, and the 32 patients underwent oesophageal clearance, and simultaneous liquid and solid gastric emptying studies using radionuclide techniques compared with historical controls.

RESULTS: The questionnaires showed a significant difference in gastric (p > 0.01) symptoms and swallowing difficulty. Nocturnal diarrhoea was a significant symptom not previously reported.5/32 CFS subjects showed slightly delayed oesophageal clearance, but overall there was no significant difference from the control subjects, nor correlation of oesophageal clearance with symptoms. 23/32 patients showed a delay in liquid gastric emptying, and 12/32 a delay in solid gastric emptying with the delay significantly correlated with the mean symptom score (for each p < 0.001).

CONCLUSIONS: GI symptoms in patients with chronic fatigue syndrome are associated with objective changes of upper GI motility.

 

Source: Burnet RB, Chatterton BE. Gastric emptying is slow in chronic fatigue syndrome. BMC Gastroenterol. 2004 Dec 26;4:32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC544348/ (Full article)

 

Neuropathology in rhinosinusitis

Abstract:

Pathophysiologic differences in neural responses to hypertonic saline (HTS) were investigated in subjects with acute sinusitis (n = 25), subjects with chronic fatigue syndrome (CFS) with nonallergic rhinitis (n = 14), subjects with active allergic rhinitis (AR; n = 17), and normal (n = 20) subjects. Increasing strengths of HTS were sprayed into their nostrils at 5-minute intervals. Sensations of nasal pain, blockage, and drip increased with concentration and were significantly elevated above normal. These parallels suggested activation of similar subsets of afferent neurons.

Urea and lysozyme secretion were dose dependent in all groups, suggesting that serous cell exocytosis was one source of urea after neural stimulation. Only AR and normal groups had mucin dose responses and correlations between symptoms and lysozyme secretion (R(2) = 0.12-0.23). The lysozyme dose responses may represent axon responses in these groups. The neurogenic stimulus did not alter albumin (vascular) exudation in any group. Albumin and mucin concentrations were correlated in sinusitis, suggesting that nonneurogenic factors predominated in sinusitis mucous hypersecretion. CFS had neural hypersensitivity (pain) but reduced serous cell secretion. HTS nasal provocations identified significant, unique patterns of neural and mucosal dysregulation in each rhinosinusitis syndrome.

 

Source: Baraniuk JN, Petrie KN, Le U, Tai CF, Park YJ, Yuta A, Ali M, Vandenbussche CJ, Nelson B. Neuropathology in rhinosinusitis. Am J Respir Crit Care Med. 2005 Jan 1;171(1):5-11. Epub 2004 Oct 11. http://www.ncbi.nlm.nih.gov/pubmed/15477496