https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673604157942.pdf

Fatigue in neurological disorders

Background: Chronic fatigue syndrome (CFS) is a multisystem disease, the pathogenesis of which remains undetermined. Aims: To test the hypothesis that there are reproducible abnormalities of gene expression in patients with CFS compared with normal healthy persons. Methods: To gain further insight into the pathogenesis of this disease, gene expression was analysed in peripheral blood mononuclear cells from 25 patients with CFS diagnosed according to the Centers for Disease Control criteria and 25 normal blood donors matched for age, sex, and geographical location, using a single colour microarray representing 9522 human genes. After normalisation, average difference values for each gene were compared between test and control groups using a cutoff fold difference of expression > 1.5 and a p value of 0.001. Genes showing differential expression were further analysed using Taqman real time polymerase chain reaction (PCR) in fresh samples. Results: Analysis of microarray data revealed differential expression of 35 genes. Real time PCR confirmed differential expression in the same direction as array results for 16 of these genes, 15 of which were upregulated (ABCD4, PRKCL1, MRPL23, CD2BP2, GSN, NTE, POLR2G, PEX16, EIF2B4, EIF4G1, ANAPC11, PDCD2, KHSRP, BRMS1, and GABARAPL1) and one of which was downregulated (IL-10RA). This profile suggests T cell activation and perturbation of neuronal and mitochondrial function. Upregulation of neuropathy target esterase and eukaryotic translation initiation factor 4G1 may suggest links with organophosphate exposure and virus infection, respectively. Conclusion: These results suggest that patients with CFS have reproducible alterations in gene regulation.

https://jcp.bmj.com/content/jclinpath/58/8/826.full.pdf

Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome

In this article we offer an approach to management of functional symptoms based on our own experience and on the evidence from other specialities (because the evidence from neurology is so slim). We also tackle some of the most difficult questions in this area. What causes functional symptoms? Does treatment really work? What about malingering?

We give two example cases adapted from real patients to illustrate our approach.

Table 1 is not comprehensive but it summarises a large literature on the suggested causes of functional symptoms. This is a question that has been approached from many angles—biological, cognitive, psychoanalytic, psychological, social, and historical. The factors shown have been found to be more common in patients with functional symptoms than in patients with similar symptoms clearly associated with disease pathology. Tables like this can help you to make a formulation of the aetiology of the patient’s symptoms rather than just a diagnosis. An important feature of the table is the recognition of biological as well as psychological and social factors in the production and persistence of functional symptoms.

View this table:

 Table 1 
 A scheme for thinking about the aetiology of functional symptoms in neurology



Most of the factors in table 1 have also been associated with other types of functional somatic symptoms such as irritable bowel syndrome and chronic pain as well as with depression or anxiety. Consequently they should be regarded more as vulnerability factors for developing symptoms, than as specific explanations for why some patients develop certain symptoms such as unilateral paralysis and others have attacks that look like epilepsy. Recent functional imaging studies of patients with functional motor and sensory symptoms1 are beginning to offer biological clues (fig 1); they also challenge the idea that that such symptoms are “all in the mind”—they are in the brain too.2



 Figure 1 
 A composite …

https://jnnp.bmj.com/content/jnnp/76/suppl_1/i13.full.pdf

Functional symptoms in neurology: management

Background: Persistent fatigue among employees, burnout, and chronic fatigue syndrome (CFS) are three fatigue conditions that share some characteristics in theory. However, these conditions have not been compared in empirical research, despite conceptual similarities. Methods: This cross sectional study aimed to investigate relations between persistent fatigue, burnout, and CFS by describing the clinical features of a sample of 151 fatigued employees on sick leave. Using validated instruments, subgroups based on research criteria for CFS and burnout within the sample of fatigued employees and a reference group of 97 diagnosed CFS patients were compared. Analyses of covariance were performed. Results: A total of 66 (43.7%) fatigued employees met research criteria for CFS (except symptom criteria) and 76 (50.3%) met research criteria for burnout. “CFS-like employees” (fatigued employees who met CFS criteria) reported stronger somatic attributions than “non-CFS-like employees”. Burnt out CFSlike employees were more depressed and distressed than CFS-like employees who were not burnt out. Burnout cases among the non-CFS-like employees had stronger psychological attributions than fatigued employees who were not burnt out. Compared to diagnosed CFS patients, CFS-like employees merely had a shorter duration of fatigue complaints. Burnt out CFS-like employees had stronger psychological attributions and were more distressed than CFS patients. Conclusions: Fatigued employees shared many important characteristics with CFS patients, regardless of burnout status, and many fatigued employees met CFS criteria and/or burnout criteria. Differences however concerned the causal attributions that were made. This raises questions about the role of causal attributions: are they modified by fatigue complaints or do they determine illness outcome?

https://oem.bmj.com/content/oemed/60/suppl_1/i26.full.pdf

Fatigue, burnout, and chronic fatigue syndrome among employees on sick leave: do attributions make the difference?

Background: Patients with chronic fatigue syndrome (CFS) and post-Lyme syndrome (PLS) share many features, including symptoms of severe fatigue and cognitive difficulty. Objective: To examine the neuropsychiatric differences in these disorders to enhance understanding of how mood, fatigue, and cognitive performance interrelate in chronic illness. Methods: Twenty-five patients with CFS, 38 patients with PLS, and 56 healthy controls participated in the study. Patients with CFS met 1994 criteria for CFS and lacked histories suggestive of Lyme disease. Patients with PLS were seropositive for Lyme disease, had met the Centers for Disease Control and Prevention criteria, or had histories strongly suggestive of Lyme disease and were experiencing severe fatigue that continued 6 months or more following completion of antibiotic treatment for Lyme disease. All subjects completed self-report measures of somatic symptoms and mood disturbance and underwent neuropsychological testing. All patients also underwent a structured psychiatric interview. Results: Patients with CFS and PLS were similar in several somatic symptoms and in psychiatric profile. Patients with CFS reported more flulike symptoms than patients with PLS. Patients with PLS but not patients with CFS performed significantly worse than controls on tests of attention, verbal memory, verbal fluency, and motor speed. Patients with PLS without a premorbid history of psychiatric illness did relatively worse on cognitive tests than patients with PLS with premorbid psychiatric illness compared with healthy controls. Conclusions: Despite symptom overlap, patients with PLS show greater cognitive deficits than patients with CFS compared with healthy controls. This is particularly apparent among patients with PLS who lack premorbid psychiatric illness.

Stephen E. Strauss

Papers

The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study