Spinal fluid abnormalities in patients with chronic fatigue syndrome

Abstract:

Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls.

Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having comorbid depression than those with normal fluid.

In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls.

The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.

 

Source: Natelson BH, Weaver SA, Tseng CL, Ottenweller JE. Spinal fluid abnormalities in patients with chronic fatigue syndrome. Clin Diagn Lab Immunol. 2005 Jan;12(1):52-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC540195/ (Full article)

 

Ambulatory monitoring of physical activity and symptoms in fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are associated with substantial physical disability. Determinants of self-reported physical disability are poorly understood. This investigation uses objective ambulatory activity monitoring to compare patients with FM and/or CFS with controls, and examines associations of ambulatory activity levels with both physical function and symptoms during activities of daily life.

METHODS: Patients with FM and/or CFS (n = 38, mean +/- SD age 41.5 +/- 8.2 years, 74% women) completed a 5-day program of ambulatory monitoring of physical activity and symptoms (pain, fatigue, and distress) and results were compared with those in age-matched controls (n = 27, mean +/- SD age 38.0 +/- 8.6 years, 44% women). Activity levels were assessed continuously, ambulatory symptoms were determined using electronically time-stamped recordings at 5 time points during each day, and physical function was measured with the 36-item Short Form health survey at the end of the 5-day monitoring period.

RESULTS: Patients had significantly lower peak activity levels than controls (mean +/- SEM 8,654 +/- 527 versus 12,913 +/- 1,462 units; P = 0.003) and spent less time in high-level activities when compared with controls (P = 0.001). In contrast, patients had similar average activity levels as those of controls (mean +/- SEM 1,525 +/- 63 versus 1,602 +/- 89; P = 0.47). Among patients, low activity levels were associated with worse self-reported physical function over the preceding month. Activity levels were inversely related to concurrent ambulatory pain (P = 0.031) and fatigue (P < 0.001). Pain and fatigue were associated with reduced subsequent ambulatory activity levels, whereas activity levels were not predictive of subsequent symptoms.

CONCLUSION: Patients with FM and/or CFS engaged in less high-intensity physical activities than that recorded for sedentary control subjects. This reduced peak activity was correlated with measures of poor physical function. The observed associations may be relevant to the design of behavioral activation programs, because activity levels appear to be contingent on, rather than predictive of, symptoms.

 

Source: Kop WJ, Lyden A, Berlin AA, Ambrose K, Olsen C, Gracely RH, Williams DA, Clauw DJ. Ambulatory monitoring of physical activity and symptoms in fibromyalgia and chronic fatigue syndrome. Arthritis Rheum. 2005 Jan;52(1):296-303. http://onlinelibrary.wiley.com/doi/10.1002/art.20779/full (Full article)

 

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)

 

Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders?

Abstract:

Autoimmune dysfunction of certain vasoactive neuropeptides may be implicated in a range of disorders associated with fatigue like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome. These substances have neurotrophic, neuroregulatory, and neurotransmission functions, as well as that of immune modulators and hormones. They exert significant control over carbohydrate and lipid metabolism.

The hypothesis is that because these substances have vital and indispensable roles in cellular processes, loss or compromise of these roles would lead to predictable and severe cellular and systemic effects. The important roles of certain VNs make them a vulnerable target for autoimmune dysfunction. They are known to be associated with heat shock proteins for intracellular functioning with which they may form immunostimulating complexes. While peptide-HSP complexes are a relatively new area for research, this paper asserts that attention could be focused on these substances and complexes in an effort to elucidate a number of perplexing fatigue-associated disorders.

 

Source: Staines DR. Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders? Med Hypotheses. 2005;64(3):539-42. http://www.ncbi.nlm.nih.gov/pubmed/15617862

 

Neuropsychiatric sequelae of Nipah virus encephalitis

Abstract:

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome.

Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.

 

Source: Ng BY, Lim CC, Yeoh A, Lee WL. Neuropsychiatric sequelae of Nipah virus encephalitis. J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):500-4. http://www.ncbi.nlm.nih.gov/pubmed/15616178

 

Urinary electrophoretic profiles from chronic fatigue syndrome and chronic fatigue syndrome/fibromyalgia patients: a pilot study for achieving their normalization

Abstract:

Aim of our study was to determine if there were distinct, disease-related patterns of urinary analytes in chronic fatigue syndrome (CFS) and chronic fatigue syndrome/fibromyalgia (CFS/FM) compared to normal controls (NC).

Urine was collected from these subjects for two consecutive 24 h periods and aliquots were submitted to micellar electrokinetic chromatography (MEKC). To compensate for the differences in peak migration times, these were normalized from the 35 min duration of run to a 100-point scale, and each peak was assigned its normalized time measure. Peak heights were also normalized by dividing the mAU by that of the internal standard (creatinine) and multiplying by 100. MEKC with normalization for peak height and migration time generated comparable results within each of the patient groups.

CFS/FM and CFS had significant differences in peaks compared to NC that may be of significance as biomarkers of illnesses.

 

Source: Casado B, Zanone C, Annovazzi L, Iadarola P, Whalen G, Baraniuk JN. Urinary electrophoretic profiles from chronic fatigue syndrome and chronic fatigue syndrome/fibromyalgia patients: a pilot study for achieving their normalization. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jan 5;814(1):43-51. http://www.ncbi.nlm.nih.gov/pubmed/15607706

 

Chronic fatigue syndrome: a review

Abstract:

Chronic fatigue syndrome is a relatively unknown and underdiagnosed entity in Italy where its epidemiology remains uncertain, as well as its etiology, although it causes important disability in those affected. Classification criteria by Fukuda are available to diagnose the syndrome. Its epidemiology indicates that it is probably more frequent in Northern countries and it is described in Gulf War veterans. Etiological hypotheses include infectious diseases, immunology and neurology. Among these hypotheses sickness behavior mimes certain aspects of this syndrome and is characterized by a cytokine imbalance in the central nervous system and in the periphery. There are no valid therapies available at the moment. In the laboratory of Immunogenetics, we are constituting a biological bank of the syndrome to study the immunogenetic aspects of the disease in the hope of elucidating some of the obscure areas of its etiopathogenesis.

 

Source: Carlo-Stella N, Lorusso L, Candura SM, Cuccia M. Chronic fatigue syndrome: a review. Recenti Prog Med. 2004 Nov;95(11):546-52; quiz 560. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/15598093

 

Patients with chronic fatigue syndrome are being ignored

Comment on: What causes chronic fatigue syndrome? [BMJ. 2004]

 

Editor—Earlier this year more than 28, 000 people signed a petition calling for urgent government funded research into the physical causes of myalgic encephalomyelitis and chronic fatigue syndrome. Such is the frustration of people who do not believe that their views are being listened to by the medical establishment.

So White’s editorial reviewing the possible causes of myalgic encephalomyelitis and chronic fatigue syndrome should be welcome news.1 But is it?

Many doctors support the idea of a disease model with predisposing, precipitating, and perpetuating factors. However, White does not offer any innovative suggestions as to how this could be used to better understand an illness that now covers a wide variety of clinical presentations and an equally diverse range of patho-physiological findings. Having created this mess, the medical profession must now accept that this heterogeneous group of patients is unlikely to have the same pathoaetiology and respond to the same form of treatment, be it pharmacological or behavioural.

What is needed is thought provoking research that dispenses with the oversimplistic view that myalgic encephalomyelitis and chronic fatigue syndrome entail little more than a vicious circle of abnormal illness beliefs and behaviour, inactivity, and deconditioning. The World Health Organization now classifies both myalgic encephalomyelitis and chronic fatigue syndrome as neurological disorders in section G93.3 of ICD-10. The time has come to look at the neurology of central fatigue—instead of pouring yet more money into the bottomless pit of psychological research.

You can read the rest of this article here:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535506/

 

Source: Shepherd C. Patients with chronic fatigue syndrome are being ignored. BMJ. 2004 Dec 11;329(7479):1405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535506/ (Full article)

 

Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disease which defined as medically unexplained, disabling fatigue of 6 months or more duration and often accompanied by several of a long list of physical complaints. We aimed to investigate abnormalities of hypothalamic-pituitary-gonadal (HPG) axis hormones and cortisol concentrations in premenopausal women with CFS and find out effects of depression rate on these hormones.

METHODS: We examined follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and cortisol concentrations in 43 premenopausal women (mean age: 32.86 +/- 7.11) with CFS and compared matched 35 healthy controls (mean age: 31.14 +/- 6.19). Patients were divided according to menstrual cycle phases (follicular and luteal) and compared with matched phase controls. Depression rate was assessed by Beck Depression Inventory (BDI), and patients with high BDI scores were compared to patients with low BDI scores.

RESULTS: There were no significant differences in FSH, LH, estradiol and progesterone levels in both of menstrual phases of patients versus controls. Cortisol levels were significantly lower in patients compared to controls. There were no significant differences in all hormone levels in patients with high depression scores versus patients with low depression scores.

CONCLUSION: In spite of high depression rate, low cortisol concentration and normal HPG axis hormones of both menstrual phases are detected in premenopausal women with CFS. There is no differentiation between patients with high and low depression rate in all hormone levels. Depression condition of CFS may be different from classical depression and evaluation of HPG and HPA axis should be performed for understanding of pathophysiology of CFS and planning of treatment.

 

Source: Cevik R, Gur A, Acar S, Nas K, Sarac AJ. Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones. BMC Musculoskelet Disord. 2004 Dec 8;5:47. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539265/ (Full article)

 

Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial

Erratum in: BMJ. 2005 Apr 9;330(7495):820.

 

Abstract:

OBJECTIVE: To evaluate the efficacy of cognitive behaviour therapy for adolescents aged 10-17 years with chronic fatigue syndrome.

DESIGN: Randomised controlled trial.

SETTING: Department of child psychology.

PARTICIPANTS: 71 consecutively referred patients with chronic fatigue syndrome; 36 were randomly assigned to immediate cognitive behaviour therapy and 35 to the waiting list for therapy.

INTERVENTION: 10 sessions of therapy over five months. Treatment protocols depended on the type of activity pattern (relatively active or passive). All participants were assessed again after five months.

MAIN OUTCOME MEASURES: Fatigue severity (checklist individual strength), functional impairment (SF-36 physical functioning), and school attendance.

RESULTS: 62 patients had complete data at five months (29 in the immediate therapy group and 33 on the waiting list). Patients in the therapy group reported significantly greater decrease in fatigue severity (difference in decrease on checklist individual strength was 14.5, 95% confidence interval 7.4 to 21.6) and functional impairment (difference in increase on SF-36 physical functioning was 17.3, 6.2 to 28.4) and their attendance at school increased significantly (difference in increase in percentage school attendance was 18.2, 0.8 to 35.5). They also reported a significant reduction in several accompanying symptoms. Self reported improvement was largest in the therapy group.

CONCLUSION: Cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome in adolescents.

Comment in: Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: data are insufficient and conclusion inappropriate. [BMJ. 2005]

 

Source: Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G. Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ. 2005 Jan 1;330(7481):14. Epub 2004 Dec 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539840/ (Full article)