Behavioural problems associated with the chronic fatigue syndrome

Abstract:

Disturbances of memory, concentration and motor function are often reported by patients with the chronic fatigue syndrome (CFS). The present study objectively evaluated these behavioural problems using a computerized test battery measuring memory, attention and motor skills.

Fifty-seven CFS patients were compared with 19 matched controls and all subjects completed the performance test battery and filled in questionnaires measuring psychopathology and mood. The patients reported significantly higher levels of depression, anxiety, physical symptoms and cognitive failures than the controls. Similarly, they reported more negative affect at the time of testing.

The patients were slower on psychomotor tasks, showed increased visual sensitivity and impaired attention. Digit span and free recall were not impaired but retrieval from semantic memory and logical reasoning were slower. None of the performance differences between patients and controls could be attributed to differences in psychopathology. These results agree with recent findings from other laboratories, and it is now time to consider the nature of the neurological dysfunction underlying these effects.

 

Source: Smith AP, Behan PO, Bell W, Millar K, Bakheit M. Behavioural problems associated with the chronic fatigue syndrome. Br J Psychol. 1993 Aug;84 ( Pt 3):411-23. http://www.ncbi.nlm.nih.gov/pubmed/8401992

 

Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome

Abstract:

Water metabolism and the responses of the neurohypophysis to changes in plasma osmolality during the water loading and water deprivation tests were studied in nine patients with postviral fatigue syndrome (PVFS) and eight age and six-matched healthy control subjects. Secretion of arginine-vasopressin (AVP) was erratic in these patients as shown by lack of correlation between serum and urine osmolality and the corresponding plasma AVP levels. Patients with PVFS had significantly low baseline arginine-vasopressin levels when compared with healthy subjects. Patients with PVFS as a group also showed evidence of increased total body water content. These results may be indicative of hypothalamic dysfunction in patients with PVFS.

 

Source: Bakheit AM, Behan PO, Watson WS, Morton JJ. Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome. Acta Neurol Scand. 1993 Mar;87(3):234-8. http://www.ncbi.nlm.nih.gov/pubmed/8475696

 

Enteroviruses and postviral fatigue syndrome

Abstract:

Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them.

The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome.

We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy.

An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism.

A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS.

 

Source: Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S. Ciba Found Symp. 1993;173:146-54; discussion 154-9. http://www.ncbi.nlm.nih.gov/pubmed/8387908

 

Search for retrovirus in the chronic fatigue syndrome

Abstract:

AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus.

METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques.

RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus.

CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.

 

Source: Gow JW, Simpson K, Schliephake A, Behan WM, Morrison LJ, Cavanagh H, Rethwilm A, Behan PO. Search for retrovirus in the chronic fatigue syndrome. J Clin Pathol. 1992 Dec;45(12):1058-61. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494996/ (Full article)

 

Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome

Abstract:

OBJECTIVE: To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.

DESIGN: Prospective comparison of patients with postviral fatigue syndrome with two control groups.

SETTING: Department of neurology, University of Glasgow, Southern General Hospital; department of psychiatry, St James’s Hospital, Dublin.

SUBJECTS: 15 patients with postviral fatigue syndrome, 13 age and sex matched healthy subjects, and 13 patients with primary depression.

MAIN OUTCOME MEASURES: Serum prolactin concentrations before and one, two, and three hours after administration of buspirone.

RESULTS: Because of the effects of sex hormones on prolactin secretion data for men and women were analysed separately. There was no significant difference in baseline prolactin concentrations between patients with postviral fatigue syndrome and healthy subjects or those with primary depression. However, the percentage difference between peak and baseline values was significantly higher in patients with postviral fatigue syndrome than the control groups (one way analysis of variance: women, p = 0.003; men, p = 0.004).

CONCLUSIONS: The results suggest upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression. The buspirone challenge test may therefore be useful in distinguishing these two conditions. Larger studies are required to explore the potential value of drugs acting on central 5-hydroxytryptamine receptors in the treatment of patients with the postviral fatigue syndrome.

Comment in:

Postviral fatigue syndrome. [BMJ. 1992]

Postviral fatigue syndrome. [BMJ. 1992]

Postviral fatigue syndrome. [BMJ. 1992]

Postviral fatigue syndrome. [BMJ. 1992]

 

Source: Bakheit AM, Behan PO, Dinan TG, Gray CE, O’Keane V. Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.BMJ. 1992 Apr 18;304(6833):1010-2. http://www.ncbi.nlm.nih.gov/pubmed/1586780

Note: You can read the full article herehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1881733/

 

Clinical spectrum of postviral fatigue syndrome

Abstract:

Many different neurological and psychiatric syndromes follow viral infections, but their clinical pictures and pathogeneses are poorly understood. The syndromes include acute disseminated encephalomyelitis (post-infectious encephalomyelitis), the Guillain-Barre syndrome (post-infectious neuritis) and Reye’s syndrome.

Recently, attention has been focused on another common postviral neurological syndrome, i.e. the postviral fatigue syndrome (PVFS)–termed myalgic encephalomyelitis (ME) and a host of other designations. PVFS occurs both sporadically and in epidemics, with cases being reported from all over Europe, the United States, Australasia and South Africa.

It is difficult to make the diagnosis and this has meant, in the past, that it is not until an epidemic has occurred that random cases which presented in the preceding years are realised to represent the same condition. With renewed interest in the syndrome and greater attention from physicians, however, diagnosis of sporadic cases is now becoming more common.

 

Source: Behan PO, Bakheit AM. Clinical spectrum of postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):793-808. http://www.ncbi.nlm.nih.gov/pubmed/1794085

 

Amplification and identification of enteroviral sequences in the postviral fatigue syndrome

Abstract:

Evidence from several sources has long suggested that enteroviruses might play a role in the postviral fatigue syndrome (PVFS).

We used the most sensitive molecular virological method available at present, the polymerase chain reaction (PCR) amplification technique, to look for enteroviral copies in peripheral blood leucocytes and muscle from a well-defined group of patients. We demonstrated that our PCR method amplified a sequence common to a wide range of enteroviral serotypes. A highly significant number of the muscle biopsies (53%: P = less than 0.001) from the patients were positive for enteroviral sequences. With regard to the leucocyte samples, 16% in both patient and control were positive.

The PCR results on the peripheral blood leucocytes were in keeping with serological findings, in showing that the level of exposure to enteroviruses seemed to be the same in patients and controls: it was therefore of the greatest interest that patients were 6.7 times more likely to have enteroviral genome in their muscle.

We conclude that persistent enteroviral infection plays a role in the pathogenesis of PVFS, also providing preliminary evidence that severe mitochondrial injury is one of the mechanisms involved.

 

Source: Gow JW, Behan WM. Amplification and identification of enteroviral sequences in the postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):872-85. http://www.ncbi.nlm.nih.gov/pubmed/1665380

 

Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome

Abstract:

OBJECTIVE: To determine the presence of enteroviral sequences in muscle of patients with the postviral fatigue syndrome.

DESIGN: Detection of sequences with the polymerase chain reaction in a well defined group of patients with the syndrome and controls over the same period.

SETTING: Institute of Neurological Sciences, Glasgow.

SUBJECTS: 60 consecutive patients admitted to the institute with the postviral fatigue syndrome who had undergone extensive investigation to exclude other conditions. 41 controls from the same catchment area without evidence of fatigue, all undergoing routine surgery.

MAIN OUTCOME MEASURES: Routine investigations, serological screen for antibodies to a range of viruses, and presence of enteroviral RNA sequences in muscle biopsy specimens.

RESULTS: 15 (25%) patients and 10 (24.4%) controls had important serological findings. 12 patients had neutralising antibody titres of greater than or equal to 256 to coxsackieviruses B1-5 (six positive for enteroviral RNA sequences, six negative); three were positive for Epstein-Barr virus specific IgM (two positive, one negative). Six controls had similar neutralising antibody titres to coxsackieviruses (all negative); one was positive for Epstein-Barr virus specific IgM (negative); and three had titres of complement fixing antibody greater than or equal to 256 to cytomegalovirus (all negative). Overall, significantly more patients than controls had enteroviral RNA sequences in muscle (32/60, 53% v 6/41, 15%; odds ratio 6.7, 95% confidence interval 2.4 to 18.2). This was not correlated with duration of disease, patient and age, or to raised titres of antibodies to coxsackieviruses B1-5.

CONCLUSIONS: Persistent enteroviral infection of muscle may occur in some patients with postviral fatigue syndrome and may have an aetiological role.

Comment in: Postviral fatigue syndrome. [BMJ. 1991]

 

Source: Gow JW, Behan WM, Clements GB, Woodall C, Riding M, Behan PO. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome. BMJ. 1991 Mar 23;302(6778):692-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1669122/ (Full article)

 

Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome

Abstract:

We analysed peripheral blood CD56+ natural killer (NK) cell subsets in 23 carefully characterized patients with post-viral fatigue syndrome (PFS), compared with 19 healthy controls, using fluorochrome-conjugated, specific monoclonal antibodies and the FACScan.

We found significantly increased percentages of CD56+, and especially CD56bright+ NK cells in PFS patients. We also found significantly increased percentages of CD56+ high affinity interleukin-2 (IL-2) receptor (CD25)+ and CD56+ transferrin receptor (CD71+) subsets of cells, most of which also stained brightly for CD56.

Also, we found an increased percentage of CD56+ CD3+ cells, many of which stained brightly for CD56, although there was no increase in the percentage of CD56- CD3+ T cells in these patients. These observations, in conjunction with very low percentage of CD56- CD25+ cells, suggest that there is a preferential involvement of this minor subset of CD56+ CD3+ T cells in PFS.

Finally, a decreased percentage of CD56+ Fc gamma receptor (CD16)+ NK cells was identified, which suggests a reduced capacity of antibody-dependent cellular cytotoxicity in PFS patients. Subsets of CD56+ NK cells co-expressing CD2, CD4 or CD8 did not show any significant difference between PFS patients and healthy controls.

These phenotypic changes provide laboratory evidence of immunological abnormalities in this syndrome, and, we suggest, may be consistent with persistent viral infection.

 

Source: Morrison LJ, Behan WH, Behan PO. Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome. Clin Exp Immunol. 1991 Mar;83(3):441-6. http://www.ncbi.nlm.nih.gov/pubmed/1706238

You can read the full article herehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535328/

 

A report–chronic fatigue syndrome: guidelines for research

Introduction:

Patients who present with a principal complaint of disabling fatigue of uncertain cause have received much attention in recent years. Correspondingly there has been an increasing amount of research into this problem. The findings have however often been contradictory. Resolution of these contradictions depends on the ability to compare research studies, but such constructive comparison has rarely been possible. This is largely because research has been carried out by investigators trained in different disciplines, using different criteria to define the condition. Whilst such an eclectic approach is to be welcomed, agreement on case definition, and assessment methods is necessary if progress is to be made.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/pdf/jrsocmed00127-0072.pdf

 

Source: Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al. A report–chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb;84(2):118-21. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/