ME and CFS

Capita Selecta Quarterly

PHYSIOLOGY AND NEUROPHYSIOLOGY.

Giri, S., Mather, J and Kluger, J. Can clinical history predict neurally mediated hypotension in patients with chronic fatigue syndrome? (Meeting Abstract). Circulation, 1997, 96 (8 Suppl), no. 1217.

Head up tilt testing (HUT) has been used in patients with CFS to diagnose neurally mediated hypotension (NMH); however, whether clinical markers can predict the presence of NMH is unknown. Therefore, 56 consecutive CFS patients referred for HUT (46 females) underwent a detailed interview (symptoms, diet and life-style) and a 2-stage HUT at 70' (stage I: 45 min; stage II: 15 min with 1-2 µg/min of Isuprel). A positive HUT was defined as an abrupt decrease in systolic BP to <70 mmHg with symptoms of syncope.

Forty of the 56 patients (71%) had a positive HUT. These patients were similar in age, sex and CFS characteristics but more often had prior syncope or presyncope 30/40 vs 4/16 p<.001). Similarly, positive patients were more likely to be on a low salt diet (37/40 vs 8/16, p<.001).

The researchers conclude that a dietary and clinical history strongly predict NMH in CFS and that these can be used to identify patients who may benefit from empirical NMH therapy.

Logistic regression model for prediction of positive HUT test in CFS patients.

Jumrussirikul, P., Rowe, PC and Calkins, H. Relationship between severity and duration of symptoms and response to tilt testing in patients with the chronic fatigue syndrome (Meeting Abstract). Circulation, 1997, 96, (8 Suppl), no. 1220.

The researchers previously reported a high prevalence of abnormal responses to upright tilt in a small group of patients with CFS. Here they sought to determine the relationship between the severity and duration of CFS symptoms and the response to tilt in a consecutive series of 224 CFS patients who underwent a 3 stage 70' tilt at Johns Hopkins Hospital (56M, 168F).

Overall, an abnormal haemodynamic response to tilt was observed in 168 of the 224 patients (75%): 136 with neurally mediated hypotension (NMH), 12 with postural orthostatic tachycardia syndrome (POTS: >30 bpm increase in HR within 5 min of tilt), and 20 with both. Among those with NMH, 25 patients demonstrated a vasodepressor response, 7 patients demonstrated a cardioinhibitory response and 124 patients demonstrated a mixed response. Patients with a wellness score <5 (on a scale of 0-10) had a higher prevalence of POTS and a lower prevalence of positive response to tilt typical of NMH as compared to those with a wellness score >5 (15% vs 0%, p=0.02, and 68% vs 86%, p=0.05 respectively). No difference in the prevalence or pattern of an abnormal response to tilt was observed based either on age or duration of CFS.

The researchers conclude that the pattern of abnormal response to tilt CFS vs POTS was related to the severity but not the duration of CFS in this sample. Increased self-reported severity of CFS was associated with a higher prevalence of POTS and a lower prevalence of NMH. "Further studies are needed to determine if the response to therapy is affected more by the pattern of tilt response than by the severity or duration of symptoms".

Yataco A., Talo H., Rowe P., Kass DA., Berger RD and Calkin H. Comparison of heart rate variability in patients with chronic fatigue syndrome and controls. Clinical Autonomic Research, 1997, 7, 293-297.

Recent studies have reported a close association between CFS and neurally mediated hypotension. The researchers hypothesized that this association may result from an abnormality in autonomic function among patients with CFS, which may be detectable using an analysis of heart rate variability. They prospectively studied 19 patients who fulfilled the CDC '88 criteria for CFS and 11 healthy controls. Each subject underwent a two-stage tilt-table test while wearing a Holter monitor. Heart rate variability was assessed in the supine baseline position and during upright tilt using frequency domain parameters.

In the baseline supine position, high frequency (HF) power, low frequency (LF) power, and the ratio of low frequency power to high frequency power (LF/HF ratio) were similar. In both patient groups, upright tilt resulted in a similar decrease in HF power, increase in LF power, and increase in the LF/HF ratio. Seventy-four of the patients responded positively to upright-tilt compared to 0% of the controls (p<.001).

In conclusion, abnormalities of autonomic function, as assessed using an analysis of heart rate variability, are not a likely cause of neurally mediated hypotension. The researchers suggest that the latter may be determined by reduced blood volume, increased venous pooling and other factors.

PATHOLOGY

Vojdani, A., Ghoneum, M., Choppa, PC., Magtoto, L and Lapp, CW. Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein kinase RNA. Journal of Internal Medicine, 1997, 242, 6, 465-478

Evidence of immune dysfunction is present in many patients with CFS. It has recently been shown that apoptosis (programmed cell death) might be mediated by the upregulation of growth inhibitory cytokines and thus be a mechanism for the elimination of cancer cells and virus-infected cells. In this study, the apoptotic cell population, interferon-alpha (IFN-a), and IFN-induced protein kinase RNA (PKR) gene transcripts in the peripheral blood lymphocytes (PBL) and plasma of patients with CFS were evaluated and compared with those of healthy controls.

PBL were obtained from a total of 29 CFS patients (CDC criteria '94) consisting of two groups: three males and six females from a North Carolina clinic and seven males and 13 females from Los Angeles County. All patients complained of fatigue; 80% complained of exhaustion fatigue, sleep disorder, arthralgia/myalgia and sore throat with a duration of symptoms between one and five years. 15 healthy controls seen for routine physical examination came from the Los Angeles area. After the clinical information had been analyzed, it was found that the patients could be placed into a single group. None of the patients' symptoms were present in the controls.

65% and 73% of patients had IFN-a levels above lOpg/mL in plasma and cell [lymphocyte] lysate, respectively, compared with 25% and 8% of controls with similar respective levels. Additionally 44% and 33% of the patients had levels exceeding 100pg/mL, respectively, but none of the controls. The mean value for PKR mRNA in the CFS patients was significantly upregulated as compared with the controls and this was reflected in the raised PKR protein levels in the CFS group. Using flow cytometry with fluorescent staining, the apoptotic cell [lymphocyte] population was measured, revealing a significantly raised level in CFS patients compared with the controls. Analysis of the non-apoptotic cell population in CFS patients indicated an arrest of cells in the late S and G2/M boundaries with a concomitant increase in the cell population in the S and G2/M phases, demonstrating an abnormality of mitotic cell division. Treating the PBL with the PKR inhibitor 2-aminopurine reduced the apoptotic cell population in some of the CFS patients and also those cell populations arrested in the S and G/2M phases.

The authors suggest that the upregulation of PKR levels resulting in disregulated cell metabolism due to inhibition of protein synthesis might be the mechanism responsible for the fatigue observed in CFS patients.

[Ed. note: This study provides further evidence of immune dysfunction in some CFS patients. It would be of interest to study the regulation of apoptosis in other fatigue states.]

ENDOCRINOLOGY

Wood, B., Wessely, S., Papadopoulos, A., Poon, L and Checkley, S. Salivary cortisol profiles in chronic fatigue syndrome. Neuropsychobiology, 1998, 37, 1, 1-4.

This study involved 10 patients with CFS (Oxford and CDC criteria '94, no concurrent depressive disorder) and 10 matched controls. They were interviewed and completed the BDI. Saliva samples were collected hourly from 6.00h to 22.00h to asses (free) cortisol levels.

The mean saliva cortisol concentration was slightly but significantly higher in the patients than in the controls (p<.05). "These findings are at variance with earlier reports that CFS is a hypocortisolaemic state and suggest that in CFS the symptom of fatigue is not caused by hypocortisolaemia".

PSYCHOLOGY, NEUROPSYCHOLOGY AND PSYCHIATRY.

Gaudino, EA., Coyle, PK and Krupp, LB. Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences. Archives of Neurology, 1997, 54, 11, 1372-1376.

Patients with CFS and post-Lyme syndrome (PLS) share many features, including symptoms of severe fatigue and cognitive difficulty. The aim of this study was to examine the neuropsychiatric differences in these disorders and to enhance understanding of how mood, fatigue, and cognitive performance interrelate in chronic illness.

Twenty-five patients with CFS, 38 patients with PLS and 56 healthy controls participated in the study. All patients with CFS met CDC criteria '94 and 52% also met the '88 criteria; only 36% reported a sudden onset. The patients with PLS were seropositive for Lyme disease, had met the CDC 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 (SCI).

Sixteen per cent of the CFS group had a current psychiatric diagnosis compared with 23% of the patients with PLS. Patients with CFS and PLS were similar in several somatic symptoms and in psychiatric profile. Patients with CFS reported more flu-like 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.

"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."

[Ed. note: there was no assessment of the well-being of the patients at the time of testing.]

Lakein, DA., Fantie, BD., Grafman, J., Ross, S., O'Fallon, A., Dale, J and Straus, SE. Patients with chronic fatigue syndrome and accurate feeling-of-knowing judgments. Journal of Clinical Psychology, 1997, 53, 7, 635-645.

Many CFS patients complain of memory impairments which have been difficult to document empirically. Subjective complaints of memory impairment may be due to a deficit in metamemory judgment (i.e. knowledge of one's own memory performance and stored knowledge). Seventeen CFS patients (CDC criteria '88) and matched, healthy controls were tested with a computerized Trivia Information Quiz (TIQ) that required them to rate their confidence about correctly recognizing an answer in a multiple choice format that they had been unable to remember in a fact-recall format.

Even though CFS patients reported significantly greater amounts of fatigue, cognitive and physical symptoms, the accuracy of their confidence levels and recognition responses were similar to those of the controls. This finding suggests that a metamemory deficit is not the cause of the memory problems reported by CFS patients.

There was no relationship between the TIQ scores and the HAD measures for anxiety and depression.

Sharpley, A., Clements, A., Hawton, K and Sharpe, M. Do patients with "pure" chronic fatigue syndrome (neurasthenia) have abnormal sleep? Psychosomatic Medicine, 1997, 59, 6, 592-596.

The sleep characteristics of 20 patients with CFS (CDC criteria '94 plus ICD-10 criteria for neurasthenia*) without depression, anxiety, or sleep disorder were compared with those of 20 healthy subjects matched for age and sex. Measures of sleep included subjective interview reports and sleep diaries plus home-based polysomnography. Subjects also completed the HAD and BDI.

Patients with CFS complained of poor quality unrefreshing sleep. They also napped during the day. Polysomnograph data showed no difference in actual nocturnal sleep time between the two groups although patients with CFS spent significantly longer in bed (p<.01), slept less efficiently (p<.03), and spent longer awake after sleep onset (p<.05). The polysomnographs of seven patients with CFS and one healthy subject were regarded as significantly abnormal. Five patients and one healthy subject had difficulty maintaining sleep. There was no significant correlation between sleep abnormalities and the severity of symptoms.

Patients with "pure" CFS complain of unrefreshing sleep but only a minority have a clearly abnormal polysomnograph. The patients' reports were consistent with the polysomnograph data. Although sleep abnormalities may play a role in the aetiology of CFS, they seem unlikely to be an important cause of daytime fatigue in the majority of patients. However, pharmacological and behavioral methods that improve sleep quality may be an important component of a pragmatically based treatment package for patients who do have abnormal sleep.

EPIDEMIOLOGY

Fitzgibbon, EJ., Murphy, D., O'Shea, K and Kelleher, C. Chronic debilitating fatigue in Irish general practice: a survey of general practitioners' experience. British Journal of General Practice, 1997, 47, 423, 618-622.

The aims of this survey were to estimate the incidence of chronic debilitating fatigue in Irish general practice, to obtain information on management strategy and outcome and to explore the attitudes of practitioners (GPs) towards the concept of a CFS.

A total of 200 names were selected from the database of the Irish College of General Practitioners (ICGP); 164 of these were eligible for the study.

Altogether, 118 questionnaires were returned (72%). Ninety-two (78%) responders identified cases of chronic fatigue, giving an estimated 2.1 cases per practice and an incidence of 1 per 1000 population. All social classes were represented, with a male to female ratio of 1:2. Eleven disparate approaches to treatment were advocated. Many (38%) GPs were dissatisfied with the quality of care delivered and 45% seldom or hardly ever referred cases for specialist opinion. The majority (58%) accepted CFS as a distinct entity, 34% were undecided, and 8% rejected it. Forty-two (35%) GPs volunteered for a prospective study.

The researchers conclude that chronic fatigue is found in Irish general practice among patients of both sexes and all social classes. Doctors differ considerably in their management of patients and are dissatisfied with the quality of care they deliver. A prospective database is required to accurately assess the scale of this public health problem and to develop a protocol of care.

[Ed. note: It is not known whether any of the patients identified with chronic fatigue met the criteria for CFS.]

THERAPEUTICS

King, CP., Jason, LA., Frankenberry, L., Jordan, K and Tryon, W. Think inside the envelope. The CFIDS Chronicle, 1997, 10, 4, 10-14.

This article discusses an alternative treatment programme to graded exercise. By promoting the use of moderation and energy conservation, and more specifically, by monitoring the levels of perceived and expended energy, and keeping the two relatively close, patients remain as active as possible. A case history shows that this approach decreased fatigue and increased levels of perceived energy.

"Our data strongly suggest that patients with CFS need to continuosly monitor and assess their current levels of expended energy, perceived energy and fatigue".

REVIEWS

Dimitrov, M and Grafman, J. Neuropsychological assessment of chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1997, 3, 4, 31-42.

Review article which ignores recent findings relating to subgroups.

Jordan, KM., Landis, DA., Downey, MC., Osterman, SL., Thurm, AE and Jason, LA. Chronic fatigue syndrome in children and adolescents: A review. Journal of Adolescent Health, 1998, 22, 1, 4-18.

Balanced review of the literature on CFS in children and adolescents.

Manu, P. Disability evaluation for chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1997, 3, 4, 9-17.

Editorial summarising some of the issues involved in assessing disability in people suspected as having CFS.

Tiersky, LA., Johnson, SK., Lange, G., Natelson, BH and DeLuca, J. Neuropsychology of chronic fatigue syndrome: A critical review. Journal of Clinical and Experimental Neuropsychology, 1997, 19, 4, 560-586.

This article provides a comprehensive and critical review of the neuropsychological and related literature on CFS and ME. Despite the methodological limitations observed in several studies, some consistent findings are noted. The most consistently documented neuropsychological impairments are in the areas of complex information processing speed and efficiency. General intellectual abilities and higher order cognitive skills are intact. Emotional factors influence subjective report of cognitive difficulty, whereas their effect on objective performance remains uncertain. Although the neuropathological processes underlying cognitive dysfunction in CFS are not yet known, preliminary evidence suggests the involvement of cerebral white matter. The review notes the existence of subgroups and outlines the directions for future research.

MISCELLANEOUS

Ayres, JG., Flint, N., Smith, EG., Tunnicliffe, WS., Fletcher, TJ., Hammond, K., Ward, D and Marmion, BP. Post-infection fatigue syndrome following Q-fever. Quarterly Journal of Medicine, 1998, 91, 105-113.

A follow-up of 71 people who contracted Q fever in 1989 revealed that five years on, 42.3% fulfilled the CDC criteria ('94?) for CFS. The findings support the existence of a post-infection fatigue state following acute Q fever.

Baschetti, R. Lung function test findings in patients with chronic fatigue syndrome (CFS). Australian and New Zealand Journal of Medicine, 1997, 27, 3, 346.

Short letter in response to de Lorenzo et al (ibid, 1996, 26, 563) suggesting that CFS may be related to atypical adrenal insufficiency.

Baschetti, R. Chronic fatigue syndrome. Quarterly Journal of Medicine, 1997, 90, 723.

Letter responding to Joyce et al (QJM 1997, 90, 223). The author notes that a CFS patient's belief that he/she is suffering from a physical illness may be accurate. Poor prognosis associated with physical attributions may reflect the severity of their "atypical adrenal insufficiency".

Baschetti, R. Similarity of symptoms in chronic fatigue syndrome and Addison's disease. European Journal of Clinical Investigation, 1997, 27, 12, 1061. With reply. Dickinson, CJ, p. 1062.

Baschetti discusses the similarity between CFS and Addison's disease. In his reply, Dickenson challenges the notion that most cases are due to atypical Addison's disease, noting the failure of CFS to respond to steroids, and the possibility that low plasma concentrations of cortisol may be primary or secondary to sleep disorder.

Bloom, A. Long-term disability: long-term deception? Journal of Chronic Fatigue Syndrome, 1997, 3, 4, 87-97.

Article on the difficulties which CFS patients experience when trying to obtain disability benefits from insurance companies in America.

See also Anonymous. Negotiating the maze of disability insurance: one patient's perspective (ibid 99-109).

Hall, GH., Hamilton, WT and Round, AP. Increased illness experience preceding chronic fatigue syndrome: a case control study. Journal of the Royal College of Physicians, 1998, 32, 44-48.

Survey of medical records of an insurance company relating to 133 patients with CFS (not defined), 75 people with MS and 162 non-claimant controls.

The patients with CFS had recorded significantly more symptoms at the time of proposal for insurance than the other two groups. Lethargy was the most common problem.

Hedrick, TE. Chronic fatigue syndrome. Quarterly Journal of Medicine, 1997, 90, 723-725.

Detailed analysis of the flaws in the review by Joyce et al (QJM 1997, 90, 223). The author discusses the choice of the literature, the biased interpretations, the failure to discuss plausible alternative explanations, the errors plus the problems relating to the diagnosis of psychiatric morbidity and measurement of improvement.

Lapp, CW and Hyman, HL. Diagnosis of chronic fatigue syndrome. Archives of Internal Medicine, 1997, 157, 2663.

Response to an article by Finestone (ibid, p. 491) which discussed the difficulties of assessing patients with CFS for disability benefits e.g. the heterogeneity of the disorder. Lapp and Hyman challenge the view that CFS is a 'waste-basket' term, and suggest guidelines for medical examiners. With reply by Finestone (p. 2663-4).

Make, B and Jones, JF. Impairment of patients with chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1997, 3, 4, 43-55.

Isokinetic muscle testing of the knee flexors and extensors and elbow flexors and extensors assessed the muscle strength of 13 patients with CFS (CDC criteria '88), 9 patients with depression, 12 patients with allergic rhinitis and 10 healthy controls. Muscle fatigue and recovery (up to 15 minutes post fatigue) were also measured. Exercise capacity was determined using a bicycle ergometer (for 8-10 minutes).

The results revealed normal muscle strength, endurance and recovery measured 10 minutes after exercise in the patients with CFS. However, the maximal exercise capacity was reduced to 76% of predicted workload, a significant decrease compared to the other patient groups and healthy controls. The CFS group had exercised to their maximal capacity and did not terminate the exercise voluntarily. Tests which included a further 6 patients revealed the difficulties in performance of daily activities. This was not the case for the comparison groups.

Manu, P. Long-term disability for chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1997, 3, 4, 19-30.

A survey of the records from 76 patients with CFS evaluated the accuracy of the diagnosis and checked data on psychiatric status, muscle strength and neurological functioning, all regarded as important in the assessment of disability.

The author found that relatively few patients had undergone strength, endurance or neuropsychological evaluation. There were high rates of psychiatric disorder (84%) and 38% did not meet the CDC criteria '94 for CFS.

Plioplys, AV. Antimuscle and anti-CNS circulating antibodies in chronic fatigue syndrome. Neurology, 1997, 48, 6, 1717-1719.

A study of 10 patients with CFS (CDC criteria '88 and '94) and 10 age and gender-matched controls failed to detect pathogenic antibodies (e.g. antineuronal nuclear antibodies type 1 and 2, gastric parietal cell antibodies, smooth muscle antibodies or antimitochondrial antibodies).

Plioplys, AV. Chronic fatigue syndrome should not be diagnosed in children. Pediatrics, 1997, 100, 2, 270-271.

Short paper in which Plioplys discusses the difficulties and dangers of diagnosing CFS in children (uncertain presentation, problems obtaining an accurate history from children and their carers, possibility of misdiagnosis). The author does not state what children with CFS should be told.

Uslan, D. Perspectives on CFS and impairment: proposed guidelines for disability determination. Journal of Chronic Fatigue Syndrome, 1997, 3, 4, 75-85.

Article on the assessment of disability in America.

Vercoulen, JHMM., Bazelmans, E., Swanink, CMA., Fennis, JFM., Galama, JMD., Jongen, PJH., Hommes, O, Van der Meer, JWM and Bleijenberg, G. Physical activity in chronic fatigue syndrome: Assessment and its role in fatigue. Journal of Psychiatric Research, 1997, 31, 6, 661-673.

This study assessed physical activity levels in 51 patients with CFS (Oxford criteria), 50 fatigued but mobile patients with multiple sclerosis (MS) and 53 healthy controls. Activity was measured using a motion-sensing device (Actometer) as well as self-report.

None of the self-report questionnaires correlated strongly with the Actometer readings. The latter showed that the two patient groups had similar activity levels but that these were significantly below those of the healthy controls. Activities which were thought likely to result in higher fatigue levels were less frequently performed. While activity was related to fatigue in the CFS group, this was not the case for the patients with MS. Neither sleep pattern nor depressive symptomatology were related to activity level.

Vollmer-Conna, U., Wakefield, D., Lloyd, A., Hickie, I., Lemon, J., Bird, KD and Westbrook, RF. Cognitive deficits in patients suffering from chronic fatigue syndrome, acute infective illness or depression British Journal of Psychiatry, 1997, 171, 377-381.

The researchers sought to assess the cognitive performance in 21 patients with CFS (criteria equivalent to Oxford guidelines), and compare cognitive performance and subjective workload experience of these patients with that of two disease comparison groups (non-melancholic depression and acute infection, both n=21) and healthy controls (n=21).

A computerised performance battery employed to assess cognitive functioning included tests of continuous attention, response speed, performance accuracy and memory. Severity of mood disturbance and subjective fatigue were assessed by questionnaire (POMS).

All patient groups demonstrated increased errors and slower reaction times, and gave higher workload ratings than healthy controls. Patients with CFS and non-melancholic depression had more severe deficits than patients with acute infection. All patient groups reported more severe mood disturbance and fatigue than healthy controls, but patients with CFS and those with acute infection reported less severe mood disturbance than patients with depression.

The findings in the patient groups suggest a non-specific impairment of attention. Since the deficits in attention and response speed were similar, it is possible that common pathophysiological processes are involved. The results also suggest that the pathophysiological processes in patients with CFS and acute infection are not simply secondary to depressed mood.

[Ed. note: it is not clear how many of the CFS patients were suffering from concurrent depression. The presence of significant mood disorders could have confounded the results (cf. DeLuca et al 1997, Marcel et al 1996). Also of concern is the fact that the fatigue scores in the CFS group were lower than those of the other two patient groups. This suggests an atypical sample. The use of broad criteria and the failure to identify and analyze subgroups separately or to assess the well-being at the time of testing might have further undermined the reliability of the findings above.]

Wesnes, KA., Faleni, RA., Hefting, N., Hoogsteen, G., Houben, JJG., Jonkman, JHJ., Leonard, J., Petrini, O and van Lier, JJ. The cognitive, subjective and physical effects of a combination of panax ginseng and ginkgo biloba in healthy volunteers with neurasthenic complaints. Psychopharmacology Bulletin, 1997, 33, 3, 603.

GincosanR is marketed in Switzerland, The Netherlands, Sweden, Denmark and Hungary. It consists of a combination of extracts of the root of Panax ginseng and of the leafs of Ginkgo biloba. Both Panax ginseng and Ginkgo biloba have been extensively used for various indications in Chinese medicine and are described in the traditional Chinese Pharmacopoeia. Extracts of Ginkgo biloba contain ginkgo-flavone glycosides and terpenoids which are known to have vasoregulating and blood viscosity decreasing properties. Previous experience with the Cognitive Drug Research (CDR) computerized assessment system has identified improvements in cognitive functioning with 3 months dosing of Gingko in elderly volunteers (Wesnes et al. 1987).

The effects of Gincosan were evaluated in this 3-month, double- blind, placebo-controlled, parallel group, tolerability and efficacy study. Sixty-four healthy volunteers (aged 40 to 65) were selected for the study on the basis of fulfilling the ICD-10 F48.0 criteria for neurasthenia. They were randomly assigned to four equal dosing groups, receiving either placebo, Gincosan 80, 160, or 320 mg b.i.d. for 3 months. A range of assessments were performed on the day prior to dosing, and again at Days 1, 30 and 90. Each day the assessments were performed twice, once 60 minutes after the morning dose, and again 5 hours later (60 minutes after the afternoon dose). Three primary outcome variables were defined in the study protocol. The first was the combined accuracy score on a number of computerized memory tests from the CDR computerized system. The second was the number of correct responses on the Vienna Determination Unit, and the third the heart rate at maximum exercise load on a cycle ergometer. Other assessments from these assessment systems were defined as secondary variables, plus a number of others including the Hopkins SCL-90-R, a Global Clinical Impression score, Spirometry and Perceived exertion.

All volunteers completed the study, the treatments being well tolerated, and there were few adverse events. At the pre-defined primary end-point (Day 90 at 1 hour post morning dosing), dose related improvements were seen on the CDR memory tests, 320 mg being highly significantly superior to placebo. However, these effects reversed 5 hours later (60 minutes after the afternoon dose), possibly suggesting that a longer inter-dose interval would be preferable. The 80 mg dose produced a significant benefit on the ergometry assessment of heart rate at maximum load. There were also a number of supporting changes from other assessments, including an advantage of 320 mg over placebo on the global score from the SCL-90-R at Day 90.

"This trial has identified cognitive, physical, and other benefits that occur with Gincosan, and an international multicenter trial is underway to identify the optimal dosing regimen for cognitive function and to measure the time course of improvements over the day."

Wessely, S. Chronic fatigue syndrome: a 20th century illness? Scandinavian Journal of Work Environment & Health, 1997, 23, Suppl. 3, 17-34.

Opinion article discussing the problem of somatization and its relevance to CFS.

[Ed. note: This article contains a number of factual errors (e.g. the D in CFIDS stands for dysfunction, not deficiency; colonic lavage is not a common treatment for ME in the UK etc) and misrepresents the views of the vast majority of patients and patient groups. Moreover, the use of certain statements out of context, the focus on the more unusual ideas and opinions, the lack of balance and the failure to consider alternative explanations may have led the author to exaggerate the influence of somatization as related to CFS. This paper could undermine the understanding of the illness-as-lived and may contribute to the further stigmatisation of the illness.]

Wessely, S., Chalder, T., Hirsch, S., Wallace, P and Wright, D. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: A prospective primary care study. American Journal of Public Health, 1997, 87, 9, 1449-1455.

This study of GP attenders revealed that 11.3% suffered from chronic fatigue for 6 months. Prevalence rates for CFS were lower, ranging from 0.1% (CDC '88 modified, and minus comorbid psychiatric disorders) to 2.6% (CDC '94, with psychiatric disorders).

Being female was associated with chronic fatigue, and functional impairment was associated with psychological morbidity. There were differences between patients with CF and CFS in terms of role performance, social function, health perception and physical limitations.

[Ed. note: details about the modification of the CDC criteria '88 are not entirely clear and make it difficult to compare the results with previous reports. The finding of a lower prevalence figure using the Oxford guidelines (2.2%) compared to the more restrictive CDC criteria '94 (2.6%) is not explained and could reflect a methodological error in the assessment process.]

Various

Chronic fatigue syndrome. Journal of the American Medical Association, 1998, 279, 6, 431-433.

Letters responding to an article by Komaroff (ibid, 1997, 278, 1179).

ARTICLES ON OTHER DISORDERS

Mohr, DC., Goodkin, DE., Likosky, W., Beutler, L., Gatto, N and Langan, MK. Identification of Beck Depression Inventory items related to multiple sclerosis. Journal of Behavioral Medicine, 1997, 20, 4, 407-414.

This study suggests that the Beck Depression Inventory significantly overestimates the level of depression in patients with MS. Three items which are used to diagnose depression but which are confounded by the symptoms of MS are those measuring fatigue, work difficulty and concerns about health.

Copyright EM. Goudsmit 1998. ©
Psychologist/Archivist, London.
All rights reserved. This article may not be reproduced without
permission from the author. See the full copyright notice.

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This issue was compiled by Dr. E.M. Goudsmit, Dr. A. Macintyre and Mrs S. Howes. We gratefully acknowledge the help and support from Dr. C. Shepherd, Dr. J. Dadswell and Mr. D. Axford.