The diagnosis of postviral syndrome

Note: This comment appeared in Journal of the Royal Society of Medicine Volume 83 June 1990. You can view the table referenced in the comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292703/pdf/jrsocmed00135-0083a.pdf

 

The difficulty of making a definitive diagnosis of postviral syndrome (myalgic encephalomyelitis) is emphasized by Dr Bowman and his colleagues (December 1988 JRSM, p 712).

After a patient with this condition reported benefit from hyperbaric oxygen (HBO) (1), 36 other patients requested to be treated at Centres administered by ‘Action and Research for Multiple Sclerosis’ (ARMS). Thirty had been investigated in hospital.

They received 20 daily one hour sessions breathing 100% oxygen under pressure. Thirteen patients reported symptomatic improvement at 1.25 atmospheres absolute (ata), 10 responded at 1.5 ata, three at 1.75 ata and two at 2.0 ata.

The patients were asked to record any changes in their symptoms at the end of the course and their accumulated replies are given in Table 1.

A speculative explanation is that high concentrations of oxygen may limit the excessive intracellular lactic acid in skeletal muscle that has been demonstrated in this disease(2). The clinical pattern of myalgic encephalomyelitis has much in common with multiple sclerosis and it is possible that some of these patients had, in fact, got MS.

However, muscle pains are seldom a feature of MS, while they occurred in all but four of these patients. Seventeen out of the 33 with this symptom reported improvement, a response to HBO which might be elaborated into a therapeutic test.

ARMS treated these patients (with the consent of their doctors) on an empirical basis, and it is not implied that HBO is a definitive treatment for ME. However, these reports of subjective improvement suggest that a formal trial should be initiated.

~D J D PERRINS Adviser on Hyperbaric Medicine to ARMS, 4a Chapel Hill, Stansted, Essex CM24 8AG

 References

1 Newsletter of the M.E. Association No 21, 1986

2 Arnold DL, Bore PJ, Radda GK, et al. Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. Lancet 1984;i:1367-9

 

Source: D J Perrins. The diagnosis of postviral syndrome.  J R Soc Med. 1990 Jun; 83(6): 413. PMCID: PMC1292703  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292703/

 

Immunologic abnormalities in chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS), formerly known as chronic Epstein-Barr virus syndrome, is a clinical state of some complexity and uncertain etiology. In order to characterize in a comprehensive manner the status of laboratory markers associated with cellular immune function in patients with this syndrome, 30 patients with clinically defined CFS were studied.

All of the subjects were found to have multiple abnormalities in these markers. The most consistent immunological abnormality detected among these patients, when compared with normal controls, was low natural killer (NK) cell cytotoxicity. The number of NK cells, as defined by reactivity with monoclonal antibody NKH.1 (CD56), was elevated, but the killing of K562 tumor cells per CD56 cell was significantly diminished.

Lymphoproliferative responses after stimulation with phytohemagglutinin and pokeweed mitogen were decreased in most patients when compared with those in normal controls, as was the production of gamma interferon following mitogen stimulation. Lymphocyte phenotypic marker analysis of peripheral blood lymphocytes showed that there were significant differences between patients with CFS and controls.

There was an increase in the percentage of suppressor-cytotoxic T lymphocytes, CD8, and a proportionally larger increase in the number of CD8 cells expressing the class II activation marker. Most patients had an elevated number of CD2 cells which expressed the activation marker CDw26. The numbers of CD4 cells and the helper subset of CD4+CD29+ cells in patients with CFS were not different from those in controls. There was, however, a significant decrease in the suppressor inducer subset of CD4+ CD45RA+ cells. The number of B cells, CD20 and CD21, were elevated, as were the numbers of a subset of B cells which coexpressed CD20 and CD5.

The patterns of immune marker abnormalities observed was compatible with a chronic viral reactivation syndrome.

 

Source: Klimas NG, Salvato FR, Morgan R, Fletcher MA. Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol. 1990 Jun;28(6):1403-10. http://www.ncbi.nlm.nih.gov/pubmed/2166084

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC267940/

 

Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA

Abstract:

A subgenomic restriction fragment from cDNA prepared from Coxsackie B2 virus (CVB2) RNA was subcloned into a riboprobe vector allowing the production of enteroviral group-specific RNA probes complementary to either the positive (genomic) or negative (template) strand of enteroviral RNA. These riboprobes were used to follow productive infection of cultured cells by CVB2; as expected, positive strand RNA was synthesized in approximately 100-fold excess over negative strand.

RNA was extracted from muscle biopsy samples from patients with chronic fatigue syndrome and probed for the presence of enteroviral RNA. In cases where enteroviral RNA was detected the amounts of positive and negative strands of enteroviral RNA were approximately equal, in contrast to the situation in lytic infection of cultured cells.

This suggests that enterovirus persistence in muscle is due to a defect in control of viral RNA synthesis.

 

Source: Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC. Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. J Gen Virol. 1990 Jun;71 ( Pt 6):1399-402. http://www.ncbi.nlm.nih.gov/pubmed/2161907

 

Depression and myalgic encephalomyelitis

This comment, published in the Journal of the Royal Society of Medicine in May 1990, was written in response to a letter by Dr. Lev. You can read the letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292388/

 

We read the letter from Lev (November 1989 JRSM, p 693) with interest, but see a danger in using assumptions as to aetiology in definition of study groups. Operational definitions not making this assumption will produce replicable findings and progress towards better definitions and understanding of aetiology.

Definitions of depressed control groups are difficult, for example the following need to be controlled:

(1) Demographic variables

(2) Severity of depression symptoms: inappropriate control groups for ME patients would be severely depressed inpatients. Outpatient depressives are not too dissimilar in severity.

(3) Psychotropic medication: this is less likely to be given to ME patients where treatment is not agreed and could modify symptoms to be compared.

(4) Psychiatric history: in possible ME patients a previous significant psychiatric illness prior to fatigue symptoms leads to difficulty in studying this symptom and produces too much overlap with depressed controls.

(5) History of febrile illness: to minimize overlap, one must also control for preceding febrile illness in otherwise typical depressive illness.

Comparison of control groups should be serial, not cross-sectional as physical symptoms and markers may fluctuate, as may fatigue and depression.

Assessment of depressive symptoms is difficult, as Lev points out, due to non-specific ‘biological’ symptoms of depression. However, psychic ones such as pessimism should not overlap and could be assessed.

The concept of fatigue is poorly understood, as is its assessment. The paradigm of pain research has much to offer, where ‘dichotomization’ of physical and psychological components is not thought useful, but assessment emphasizes all components of the experience of pain. Thus, psychometric assessment of fatigue, for example, its severity, frequency, and pattern may be a future research area. Using such a paradigm, our initial findings of differences in fatigue in the two groups are because depressed patients are predominantly anergic, but ‘ME’ patients have more variability and unpredictable onset of fatigue relative to the severity of exercise attempted. Lack of motivation overlaps in both groups, explicable in Lev’s own terms as due to a reaction to a chronic illness.

~SEAN LYNCH Lecturer and Honorary Senior Registrar in Psychiatry

~RAM SETH Senior Registrar in Psychiatry St Charles Hospital, London

 

Source: S Lynch and R Seth. Depression and myalgic encephalomyelitis. J R Soc Med. 1990 May; 83(5): 341. PMCID: PMC1292666. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292666/pdf/jrsocmed00136-0073a.pdf

 

The low yield of physical examinations and laboratory investigations of patients with chronic fatigue

Abstract:

Fatigue is a common symptom but guidelines for its appropriate evaluation are lacking. The authors prospectively studied 100 adults with a chief complaint of fatigue lasting at least 1 month in order to determine the diagnostic contribution of physical examinations and laboratory investigations.

The evaluations were performed in the specialized clinic of a faculty practice. Physical examinations produced diagnostic information in 2% of patients, and laboratory investigations elucidated the cause of fatigue in 5% of patients. Structured follow-up evaluations after an average interval of 10 months failed to reveal any new organic causes for the fatigue symptom. Minor laboratory abnormalities were relatively common but did not contribute to the diagnostic process and did not seem to influence the clinical outcome.

The authors conclude that the traditional medical evaluation of patients complaining of chronic fatigue has a low yield in discovering treatable physical disorders.

 

Source:  Lane TJ, Matthews DA, Manu P. The low yield of physical examinations and laboratory investigations of patients with chronic fatigue. Am J Med Sci. 1990 May;299(5):313-8. http://www.ncbi.nlm.nih.gov/pubmed/2337122

 

The psychiatric status of patients with the chronic fatigue syndrome

Abstract:

The prevalence of psychiatric disorder in 48 patients with chronic fatigue syndrome (CFS) was determined. Twenty-two had had a major depressive (non-endogenous) episode during the course of their illness, while seven had a current major (non-endogenous) depression.

The pre-morbid prevalence of major depression (12.5%) and of total psychiatric disorder (24.5%) was no higher than general community estimates. The pattern of psychiatric symptoms in the CFS patients was significantly different to that of 48 patients with non-endogenous depression, but was comparable with that observed in other medical disorders. Patients with CFS were not excessively hypochondriacal.

We conclude that psychological disturbance is likely to be a consequence of, rather than an antecedent risk factor to the syndrome.

 

Source: Hickie I, Lloyd A, Wakefield D, Parker G. The psychiatric status of patients with the chronic fatigue syndrome. Br J Psychiatry. 1990 Apr;156:534-40. http://www.ncbi.nlm.nih.gov/pubmed/2386862

 

Myalgic encephalomyelitis

Note: This letter appeared in the British Journal of General  Practice in April 1990.

 

Sir, During the past few months the Myalgic Encephalomyelitis Association has initiated a determined effort to find a cure for this devastating disease. A scientific and medical advisory panel has been formed under the chairmanship of Professor James Mowbray of St Mary’s Hospital Medical School, and in order to fund much needed research the Breakthrough Trust has been established and is already attracting money.

The scientific and medical advisory panel is anxious to stimulate new thought on research into the causes of myalgic encephalomyelitis, its possible treatments and, most important of all, research into finding a cure. Because of the complexities of the disease members of the panel would welcome new ideas and requests for grants from a wide variety of disciplines. Any such applications should be sent to me at the Myalgic Encephalomyelitis Association.

STEPHEN POWELL

Myalgic Encephalomyelitis Association

PO Box 8, Stanford le Hope

Essex SS17 8EX

 

Source:  S Powell. Myalgic encephalomyelitis. Br J Gen Pract. 1990 Apr; 40(333): 170. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1371257/

 

Myalgic encephalomyelitis

Note: This letter appeared in the Journal of the Royal Society of Medicine in March 1990.

 

We accept that Martin Lev (November 1989 JRSM, p 693) is correct to point out that the anxiety and depression noted in patients labelled as suffering from ‘ME’ are the consequence of ‘underlying organic processes’. The demonstration of hyperventilation in the overwhelming majority of these patients (Rosen SD, King JC, Nixon PGF, unpublished results), provides a clear metabolic reason for the anxiety (1-3). ‘Depression’ is a predictable reaction to the inability to make and sustain effort due in part to the ease of acidosis of muscle cells depleted of buffer base reserves(4).

We agree with Sargant(5), that the sufferers from the late stages of effort syndrome, who have nothing to gain from their ill health and much to lose, are among the most gifted and energetic of people, and consequently the most upset about the frustration caused by loss of performance.

~S D ROSEN Cardiac Registrar

~J C KING Honorary Head Occupational Therapist (Research)

~P G F NIXON Consultant Cardiologist Charing Cross Hospital London

 

 References

1 Lewis T, et al. Breathlessness in soldiers suffering from irritable heart. Br Med J 14 October 1916:517-19

2 Lum LC. The syndrome of chronic habitual hyperventilation. In: Hill OW, ed. Modern trends in psychosomatic medicine, vol. 3. London: Butterworths, 1976: 196-230

3 Groen JJ. The measurement of emotion and arousal in the clinical physiological laboratory and in medical practice. In: Levi L, ed. The emotions: their parameters and measurement. New York: Raven Press, 1975:727-46

4 Rosen SD, King JC, Nixon PGF. Magnetic resonance muscle studies. J R Soc Med 1988;81:676-7 5 Sargant W. Battle for the mind Aphysiology ofconversion and brain-washing. London: Heinemann 1957

 

Source:  Rosen, SD, King, JC, Nixon, PGF. Myalgic encephalomyelitis. Journal of the Royal Society of Medicine Volume 83 March 1990.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292587/

 

Sensory and cognitive event-related potentials in myalgic encephalomyelitis

Abstract:

Myalgic Encephalomyelitis (ME) is a form of post viral fatigue syndrome resulting in myalgia and fluctuating fatiguability. Symptoms reflecting central nervous system dysfunction are common and include muscle weakness, headache, sensory disturbances, poor short term memory and impairment of concentration.

In view of the fact that sensory and cognitive disturbances are experienced by many patients objective evidence was sought with multi-modality sensory evoked potentials and auditory event-related cognitive potentials in a group of ME patients both with and without the enteroviral antigen, VP1 test positive.

The auditory brainstem, median nerve somatosensory and pattern reversal checkerboard visual potentials were normal for all 37 patients tested. In contrast to the sensory potentials significant differences in the mean latencies of the cognitive potential N2 and P3 were found. Reaction times were also significantly prolonged but the performance in terms of error was not significantly affected. No significant difference emerged in any of the parameters for the VP1 test. P3 was abnormal in latency or amplitude in 36% of the VP1 positive patients for the frequency discrimination task and 48% for the more difficult duration discrimination task.

The abnormalities indicate attentional deficits in some patients and slower speed of information processing in others. The prolonged latencies observed in these patients have not been observed in patients with depression in many other studies.

 

Source: Prasher D, Smith A, Findley L. Sensory and cognitive event-related potentials in myalgic encephalomyelitis. J Neurol Neurosurg Psychiatry. 1990 Mar;53(3):247-53. http://www.ncbi.nlm.nih.gov/pubmed/2324756

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1014138/

 

High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice

Abstract:

We administered a standardized history questionnaire and performed a tender point examination on 27 patients with debilitating fatigue of at least 6 months duration, seen in a primary care practice, as well as on 20 patients with fibromyalgia.

Sixteen of the 27 patients with chronic fatigue met the full criteria for the working case definition of chronic fatigue syndrome (CFS). Eight patients with chronic fatigue denied having any current persistent, diffuse musculoskeletal pain, and their tender point scores were similar to those in 10 normal control subjects. In contrast, 19 patients with chronic fatigue (70%) had persistent, diffuse musculoskeletal pain.

The results of their tender point examinations were similar to those of the patients with fibromyalgia. Thus, the majority of these patients with debilitating chronic fatigue, including those who met criteria for CFS, met the historical and tender point diagnostic criteria for fibromyalgia. The presence of current musculoskeletal pain will identify those CFS patients who have fibromyalgia.

 

Source: Goldenberg DL, Simms RW, Geiger A, Komaroff AL. High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice. Arthritis Rheum. 1990 Mar;33(3):381-7. http://www.ncbi.nlm.nih.gov/pubmed/2317224