Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis

Abstract:

OBJECTIVE: To assess cognitive function in patients with chronic fatigue syndrome (CFS) and multiple sclerosis (MS) and to evaluate the role of depressive symptoms in cognitive performance.

DESIGN: Case-control. All subjects were given a neuropsychological battery, self-report measures of depression and fatigue, and a global cognitive impairment rating by a neuropsychologist “blinded” to clinical diagnosis. Patients with MS and CFS were additionally evaluated with a Structured Clinical Interview for DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition) disorders.

SETTING: Institutional and private neurological practices and the community at large.

PATIENTS: Twenty patients with CFS diagnosed in accord with the Centers for Disease Control and Prevention-revised criteria who had cognitive complaints; 20 patients with clinically definite MS who were ambulatory and were matched for fatigue severity, age, and education to CFS subjects; and 20 age- and education-matched healthy controls.

RESULTS: Patients with CFS had significantly elevated depression symptoms compared with patients with MS and healthy controls (P < .001) and had a greater lifetime prevalence of depression and dysthymia compared with MS subjects. Patients with CFS, relative to controls, performed more poorly on the Digit Symbol subtest (P = .023) and showed a trend for poorer performance on logical memory (P = .087). Patients with MS compared with controls had more widespread differences of greater magnitude on the Digit Span (P < .004) and Digit Symbol (P < .001), Trail Making parts A (P = .022) and B (P = .037), and Controlled Oral Word Association (P = .043) tests. Patients with MS also showed a trend of poorer performance on the Booklet Category Test (P = .089). When patients with CFS and MS were directly compared, MS subjects had lower scores on all measures, but the differences reached significance only for the Digit Span measure of attention (P = .035).

CONCLUSIONS: Patients with CFS compared with MS have more depressive symptoms but less cognitive impairment. Relative to controls, a subset of CFS subjects did poorly on tests of visuomotor search and on the logical memory measure of the Wechsler Memory Scale-revised. Poor performance of logical memory in CFS appears to be related to depression, while visuomotor deficits in CFS are unrelated. Cognitive deficits in patients with MS are more widespread compared with those in patients with CFS and are independent of depressive symptoms.

 

Source: Krupp LB, Sliwinski M, Masur DM, Friedberg F, Coyle PK. Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis. Arch Neurol. 1994 Jul;51(7):705-10. http://www.ncbi.nlm.nih.gov/pubmed/8018045

 

Neuropsychiatric status of patients with chronic fatigue syndrome: an overview

Abstract:

Chronic fatigue syndrome (CFS) is an illness that results in debilitating fatigue as well as rheumatological, infectious, and neuropsychiatric symptoms. The present paper is a brief overview of the neuropsychological and psychiatric research on CFS. Studies from our laboratory contrasting CFS with patients with multiple sclerosis, depression, and healthy controls are detailed. Our hypothesis of neuropsychological impairments in CFS is discussed.

 

Source: Deluca J, Johnson SK, Natelson BH. Neuropsychiatric status of patients with chronic fatigue syndrome: an overview. Toxicol Ind Health. 1994 Jul-Oct;10(4-5):513-22. http://www.ncbi.nlm.nih.gov/pubmed/7778111

 

Measuring the functional impact of fatigue: initial validation of the fatigue impact scale

Abstract:

The fatigue impact scale (FIS) was developed to improve our understanding of the effects of fatigue on quality of life. The FIS examines patients’ perceptions of the functional limitations that fatigue has caused over the past month. FIS items reflect perceived impact on cognitive, physical, and psychosocial functioning.

This study compared 145 patients referred for investigation of chronic fatigue (ChF) with 105 patients with multiple sclerosis (MS) and 34 patients with mild hypertension (HT). Internal consistency for the FIS and its three subscales was > .87 for all analyses. Fatigue impact was highest for the ChF group although the MS group’s reported fatigue also exceeded that of the HT group. Discriminant function analysis correctly classified 80.0% of the ChF group and 78.1% of the MS group when these groups were compared.

This initial validation study indicates that the FIS has considerable merit as a measure of patient’s attribution of functional limitations to symptoms of fatigue.

 

Source: Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. http://www.ncbi.nlm.nih.gov/pubmed/8148458

 

Sleep disturbance in chronic fatigue syndrome

Abstract:

Sleep and fatigue characteristics were evaluated in 72 patients who met major criteria for the chronic fatigue syndrome (CFS), 57 multiple sclerosis (MS) patients preselected for fatigue complaints, and 40 healthy controls.

Using previously validated rating scales, CFS patients had significant elevations in fatigue and sleep disturbance compared to the MS and healthy control groups. To confirm these subjective measures, polysomnography was carried out in a subgroup of CFS patients who included sleep disturbance as one of their symptoms on initial clinical interview.

In 10 of 16 (62.5%) polysomnography revealed clinically significant and potentially treatable sleep abnormalities. Their sleep disorders included periodic movement disorder (4), excessive daytime sleepiness (3), apnea (2), and narcolepsy (1).

We conclude that subjective sleep disturbance is common in CFS and some CFS patients may have objective sleep disorders.

 

Source: Krupp LB, Jandorf L, Coyle PK, Mendelson WB. Sleep disturbance in chronic fatigue syndrome. J Psychosom Res. 1993 May;37(4):325-31. http://www.ncbi.nlm.nih.gov/pubmed/8510058

 

Information processing efficiency in chronic fatigue syndrome and multiple sclerosis

Abstract:

OBJECTIVE: To compare the cognitive performance of subjects with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and healthy controls. All subjects were matched for age, education, and verbal intelligence, as previous neuropsychological studies of CFS had not used appropriate control groups.

DESIGN: Case-control design. All subjects were given a neuropsychological battery and the test scores were compared among the groups.

SETTING: Subjects with CFS and subjects with MS were recruited from private and institutional practice and from the community. Healthy subjects were recruited from the community.

PATIENTS/OTHER PARTICIPANTS: Twelve subjects (all female) with CFS participated in the study. Chronic fatigue syndrome was diagnosed in these patients in accordance with the requirements outlined by the Centers for Disease Control as modified subsequently to not exclude patients with concurrent depression and/or anxiety. All subjects with CFS were referred for a neuropsychological examination to assess persistent cognitive complaints. Eleven subjects (10 female, one male) with the diagnosis of clinically stable MS were chosen from clinics and the community because of complaints of mild to moderate cognitive impairment. The subjects with MS and 11 healthy volunteers (10 female, one male) were matched to the group with CFS by age, education, and estimated verbal intelligence (based on the Vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised). The subjects with MS had a mean Kurtzke Expanded Disability Status Scale score of 4.95 (SD, 1.95; range, 2.0 to 7.5). As a result of the matching procedure, there were no differences among the three groups in age (F[2,31] = 0.32), education (F[2,31] = 0.80), and verbal intelligence (F[2,31] = 0.31).

INTERVENTIONS: None.

MAIN OUTCOME MEASURES: These measures included the Beck Depression Inventory (BDI), the Paced Auditory Serial Addition Test (PASAT), Digit Span Test, and the Similarities Test of Verbal Abstract Reasoning.

RESULTS: The mean number of correctly identified responses collapsed across the four PASAT trials was significantly different across groups (F[2,31] = 4.03; P < .05). While the CFS and MS groups did not differ from each other, subjects with CFS (SEM, 124.2 +/- 6.4) and subjects with MS (SEM, 112.9 +/- 10.9) scored significantly below controls (SEM, 146.4 +/- 6.4) (Fisher’s Protected Least Significant Difference test; P < .05). There were significant differences among the three groups on mean Digit Span Test performance (F[2,31] = 5.5; P < .01). While the CFS and MS group did not differ significantly from each other, only the CFS group was significantly lower than control (Fisher’s Protected Least Significant Difference test; P < .05). Mean performance on the Similarities test did not differ among the three groups (F = 0.58). In addition, there were significant differences among the three groups in mean BDI scores (F[2,31] = 7.6; P < .01). The CFS and MS groups did not differ significantly from each other, and both groups showed a statistically significantly elevated mean BDI score relative to the control group (Fisher’s Protected Least Significant Difference test; P < .05). No significant correlations were found between BDI scores and PASAT total scores (CFS, r = -.21; MS, r = .13; control, r = .27), or between BDI and Digit Span Test (CFS, r = -.32; MS, r = -.40; control, r = -.19). Results of the PASAT and Digit Span Test were significantly correlated in the CFS group (r = .71; P < .01), but not in the MS (r = .06) or control groups (r = .49).

CONCLUSIONS: These results indicate that subjects with CSF and subjects with MS show significant impairment on a test of complex concentration when compared with appropriate controls. The data suggest that subjects with CFS and subjects with MS have difficulty on tasks that require the simultaneous processing of complex cognitive information. Selective impairment in information processing efficiency may lie at the root of other cognitive complaints made by patients with CFS.

 

Source: DeLuca J, Johnson SK, Natelson BH. Information Processing Efficiency in Chronic Fatigue Syndrome and Multiple Sclerosis.Arch Neurol. 1993;50(3):301-304. doi:10.1001/archneur.1993.00540030065016. http://archneur.jamanetwork.com/article.aspx?articleid=592247

 

A comparison of neuropsychiatric characteristics in chronic fatigue syndrome, multiple sclerosis, and major depression

Abstract:

Chronic fatigue syndrome (CFS), a controversial clinical entity characterized by severe fatigue and constitutional symptoms, has been associated with a variety of psychiatric disorders. To further understand the psychiatric profile of CFS, the authors compared patients with CFS, multiple sclerosis (MS), and major depression by using diagnostic interviews and self-report measures of Axis I disorders and personality disorders. CFS patients differed from patients with major depression, with significantly less depression and fewer personality disorders. Compared with MS patients, CFS patients did not differ with regard to personality disorders. However, they did have significantly more frequent current depression than MS patients, particularly following onset of their illness.

 

Source: Pepper CM, Krupp LB, Friedberg F, Doscher C, Coyle PK. A comparison of neuropsychiatric characteristics in chronic fatigue syndrome, multiple sclerosis, and major depression. J Neuropsychiatry Clin Neurosci. 1993 Spring;5(2):200-5. http://www.ncbi.nlm.nih.gov/pubmed/8508039

 

Fatigue syndromes: new thoughts and reinterpretation of previous data

Abstract:

Recently, the author has identified 19 patients who have complained of marked fatigue that had abnormal responses to copper test bracelets or necklaces. At this time, 8 have been shown to have at least one enzyme deficiency in the heme pathway. These patients have been diagnosed with multiple sclerosis, chronic fatigue syndrome and other non-specific diagnoses. A lengthy but still limited review of the literature was performed regarding the following conditions: multiple sclerosis (MS), hepatic porphyria (HP), chronic fatigue syndrome (CFS) and paralytic polio (PP). The text will focus on similar epidemiologies, laboratory findings and clinical courses. Copper as a common but not unique etiologic agent will be discussed; as will the heme pathway, a biologic process that may be disordered in all.

 

Source: Downey DC. Fatigue syndromes: new thoughts and reinterpretation of previous data. Med Hypotheses. 1992 Oct;39(2):185-90. http://www.ncbi.nlm.nih.gov/pubmed/1461185

 

Postviral syndrome

Note: This comment appeared in the Journal of the Royal Society of Medicine, Volume 83, October 1990 in reference to The diagnosis of postviral syndrome. [J R Soc Med. 1990]

 

Postviral syndrome Dr D J D Perrins writes (June 1990 JRSM, p 413) of the difficulty in making a definitive diagnosis of postviral syndrome (myalgic encephalomyelitis, ME) echoing the paper by Dr Bowman et aL (December 1988 JRSM, p 712) and goes on to affirm ‘the clinical pattern of ME has much in common with multiple sclerosis (1). No neurologist of experience would agree with this statement. Dr Perrins admits that some of the patients he himself reported upon may in fact have had MS. Seven out of 10 MS patients will tell you the diagnosis if you listen carefully (the late Henry Miller); ‘a blind neurologist is better than a deaf one’ (Mumenthaler, Berne). The clinical course of ME and MS is usually quite different, though occasional ‘difficult’ similarities may be met with.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292897/pdf/jrsocmed00131-0089b.pdf

 

Source:  E. J. Field. Postviral syndrome. J R Soc Med. 1990 Oct;83(10):675-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292897/

 

Epidemic myalgic encephalomyelitis

The letter below, “Epidemic myalgic encephalomyelitis,” was published in the British Medical Journal in 1978. In it, the authors maintain that ME is an organic illness that exists as a distinct clinical entity with recognizable signs and symptoms. The authors propose that the cause may be “a persistent viral infection.

 

Epidemic myalgic encephalomyelitis

Outbreaks of the paralytic disease known as epidemic myalgic encephalomyelitis have puzzled doctors all over the world in the past 30 years. One of the best known of these epidemics was that at the Royal Free Hospital in London in 1955, which affected more than 300 people. (1) Most outbreaks tend to occur in the summer, young adults are predominantly affected, and the incidence is higher in women. The evidence suggests that infection is spread by personal contact, and young hospital personnel seem particularly at risk. The features common to every epidemic include headache, unusual muscular pains (which may be severe), lymphadenopathy-often of the posterior cervical lymph nodes-and low-grade fever.(2, 3) In a minority of cases frank neurological signs can be detected by careful clinical examination: there may be nystagmus, diplopia, myoclonus, bulbar weakness, motor weakness, increased or decreased tendon reflexes, disturbances of the sphincters, and extensor plantar responses.(2-7) Fasciculations, cranial nerve lesions, and extrapyramidal signs have also been reported. Most patients complain of paraesthesiae, and sensory loss is common.”(4) One characteristic feature of the disease is exhaustion, any effort producing generalised fatigue. Often there are psychiatric abnormalities, especially emotional lability and lack of concentration.(1- 3, 4) The clinical outcome may take any of three courses: some patients recover completely, some follow a relapsing course, and some are permanently incapacitated.(3)

At a symposium held recently at the Royal Society of Medicine to discuss the disease and plan research there was clear agreement that myalgic encephalomyelitis is a distinct nosological entity. Other terms that have been used to describe the disease were rejected as unsatisfactory for various reasons: the cardinal clinical features show that the disorder is an encephalomyelitis; “Iceland disease” is not specific enough; and “neuromyasthenia” suggests a relation to myasthenia gravis whereas the muscle fatigability is different, as are the electrophysiological findings.(8) Indeed, the exhaustion and tiredness are similar to that described by patients with multiple sclerosis.(9) From the patient’s point of view the designation benign is also misleading, since the illness may be devastating. Originally the term was used because no deaths had been recorded from myalgic encephalomyelitis. Two patients who had had the disease have now been examined post mortem: one was found to have multiple sclerosis. The adjective epidemic is correct, since most cases occur in an epidemic, but the disease may be endemic, and sporadic cases may occur. (10-12)

Some authors have attempted to dismiss this disease as hysterical, (13) but the evidence now makes such a tenet unacceptable. Some purely psychiatric symptoms may well occur, particularly in patients entering the chronic phase. No doubt, too, in an epidemic some hysterical persons will simulate the symptoms of the disease. Nevertheless, the organic basis is clear-from the finding that the putative agent can be transferred to monkeys(14); the detection of an increased urinary output of creatine2 (15); the persistent finding of abnormal lymphocytes in the peripheral blood of some patients (16); the presence of lymphocytes and an increased protein concentration in the cerebrospinal fluid of occasional patients (3); and the neurological findings. At this symposium more evidence was produced to support the organic nature of the disease. Increased serum concentrations of lactic dehydrogenases and transaminases have been found in several patients examined during the acute attack. In a recent outbreak in London immunological studies showed a high incidence of serum anticomplementary activity and the presence of ill-defined aggregates on electron microscopy of acute-phase sera.(17) A perplexing finding, suggesting the possibility of a persistent virus infection, was the ability of lymphocytes from patients to proliferate and survive in vitro for up to 19 weeks. The results of electroencephalographic studies were also stated to be abnormal, confirming other reports. (10)

We still know nothing about the nature and cause of epidemic myalgic encephalomyelitis, but outbreaks are still occurring. Future epidemics should be studied by a collaborative team of neurologists, epidemiologists, virologists, and immunologists. Its findings would be important not only for the study of epidemic myalgic encephalomyelitis but also for other neurological disorders, including multiple sclerosis.

1 British Medical Journal, 1957, 2, 895.

2 White, D N, and Burtch, R B, Neurology, 1954, 4, 506.

3 Acheson, E D, American Journal of Medicine, 1959, 26, 569.

4 Gilliam, A G, Epidemiological Study of an Epidemic, Public Health Bulletin, No 240. US Public Health Service, Washington, 1938.

5 Acheson, E D, Lancet, 1955, 2, 394.

6 Pellew, R A A, Medical Journal of Australia, 1951, 1, 944.

7 Hill, R C J, South African Medical Journal, 1955, 29, 344.

8 Richardson, A T, Annals of Physical Medicine, 1956, 3, 81.

9 McAlpine, D, Compston, N D, and Lumsden, C E, Multiple Sclerosis, chap 5. Edinburgh and London, Livingstone, 1955. ”

10 Ramsay, A M, and O’Sullivan, E, Lancet, 1956, 1, 761.

11 Jelinek, J E, Lancet, 1956, 2, 494.

12 Ramsay, A M, Lancet, 1957, 2, 1196.

13 McEvedey, C P, and Beard, A W, British Medical Journal, 1970, 1, 7.

14 Pellew, R A A, and Miles, J A R, Medical Journal of Australia, 1955, 2, 480.

15 Albrecht, R M, Oliver, V L, and Poskanzer, D C, Journal of the American Medical Association, 1964, 187, 904.

16 Wallis, A L, MD Thesis, Edinburgh University, 1957.

17 Dillon, M J, et al, British Medical Journal, 1974, 1, 301.

 

Source: BRITISH MEDICAL JOURNAL 3 JUNE 1978 1436-1437

You can read and download a PDF file of the letter at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604957/?page=1