Tag: Salit

Precipitating factors for the chronic fatigue syndrome

Abstract:

The etiology of the Chronic Fatigue Syndrome (CFS) is unknown but it is usually considered to be postinfectious or postviral. Many infecting agents have been suspected as causative but none has been proven.

We investigated precipitating factors in 134 CFS patients through the use of a questionnaire, interview, clinical examination and serology for infecting agents; 35 healthy controls completed a similar questionnaire. CFS started with an apparently infectious illness in 96 (72%) but a definite infection was only found in seven of these 96 (7%). Thirty-eight (28%) had no apparent infectious onset: 15/38 (40%) had noninfectious precipitants (trauma, allergy, surgery).

There was no apparent precipitating event in 23/38 (61%). Immunization was not a significant precipitant. Stressful events were very common in the year preceding the onset of CFS (114/134, 85%) but these occurred in only 2/35 (6%) of the controls (p < .0001). The onset of CFS may be associated with preceding stressful events and multiple other precipitants. An infectious illness is not uniformly present at the onset and no single infectious agent has been found; CFS is most likely multifactorial in origin.

 

Source: Salit IE. Precipitating factors for the chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):59-65. http://www.ncbi.nlm.nih.gov/pubmed/9201648

 

Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a severely disabling illness of uncertain aetiology. It is characterized by a chronic, sustained or fluctuating sense of debilitating fatigue without any other known underlying medical conditions. It is also associated with both somatic and neuropsychological symptoms. Both physical and laboratory findings are usually unremarkable.

Regional cerebral blood flow (rCBF) was assessed in 60 clinically defined CFS patients and 14 normal control (NC) subjects using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomography (SPECT). Compared with the NC group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values.

The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced. 99Tcm-HMPAO brain SPECT provided objective evidence for functional impairment of the brain in the majority of the CFS subjects. The findings may not be diagnostic of CFS but 99Tcm-HMPAO SPECT may play an important role in clarifying the pathoaetiology of CFS. Further studies are warranted.

 

Source: Ichise M, Salit IE, Abbey SE, Chung DG, Gray B, Kirsh JC, Freedman M. Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun. 1992 Oct;13(10):767-72. http://www.ncbi.nlm.nih.gov/pubmed/1491843

 

The neuropsychological dimensions of postinfectious neuromyasthenia (chronic fatigue syndrome): a preliminary report

Abstract:

Postinfectious neuromyasthenia (PIN) is a clinical syndrome of protracted and incomplete recovery after an apparent viral-like illness. Medical investigation yields few abnormalities which might account for the symptomatology. A substantial number of PIN patients complain of cognitive changes.

Specific complaints include impaired attention, concentration and abstraction skills. This study was designed to systematically investigate whether the aforementioned subjective complaints could be quantified objectively using standard neuropsychological instruments. Results indicated that on all tests but one, the subjects’ performances were significantly higher than those of their age matched groups in the normative data.

Specifically, PIN patients scored significantly better than their age matched norms on tests of concentration, attention and abstraction. What is most striking is the discrepancy between the subjective complaints of cognitive impairment and the objective results of the subjects’ performances on all tests.

These findings suggest that psychological factors may play an important role in the cognitive functioning of individuals diagnosed with postinfectious neuromyasthenia.

 

Source: Altay HT, Toner BB, Brooker H, Abbey SE, Salit IE, Garfinkel PE. The neuropsychological dimensions of postinfectious neuromyasthenia (chronic fatigue syndrome): a preliminary report. http://www.ncbi.nlm.nih.gov/pubmed/2394541

 

Chronic fatigue syndrome

Note: This letter appeared in the February 15, 1989 edition of the Canadian Medical Association Journal in response to Dr. Ray Holland’s letter of August 1, 1988 . You can read Dr. Holland’s letter as well as Dr. Salit’s response here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1268060/?page=1 and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1268061/

 

A useful supplement to the letters about chronic fatigue syndrome from Drs. Ray G.L. Holland (Can Med Assoc J 1988; 139: 198-199) and Irving E. Salit (ibid: 199) might be the working case definition of this syndrome proposed by Holmes and colleagues,(1) of the US Centers for Disease Control.

Holmes and colleagues have suggested that a case of chronic fatigue syndrome must fulfill two major criteria: that it consist of persistent or relapsing debilitating fatigue of new onset that has reduced the patient’s activity level to below 50% of normal for at least 6 months and that other clinical conditions that may produce similar symptoms have been excluded by thorough evaluation.

In addition, there must be 6 or more of 11 minor features (mild fever, sore throat, painful neck or axillary lymph nodes, generalized muscle weakness, myalgia, easy fatigability, headaches, migratory arthralgia, neuropsychologic complaints, sleep disturbances and rapid onset of the main symptom complex), along with 2 or more of 3 physical findings (low-grade fever, nonexudative pharyngitis, and palpable or tender neck or axillary lymph nodes).

We have found that many people with this clinical picture have concomitant food and chemical sensitivities and may have an intracellular magnesium deficiency in spite of normal serum levels.(2) This is probably the result of the inordinate amount of this essential mineral that they spill in their urine. The generalized aching and muscle tightness these patients experience can frequently be eased by appropriate magnesium (and calcium) supplementation, presumably because of the reduction of neuromuscular irritability.

We were therefore greatly surprised to learn in a later letter from Dr. Holland (ibid: 706) that “it would be nontherapeutic to offer such a patient empathy” and that we must not condone a belief in a “nonexistent disease”.

These statements are difficult to reconcile with the immunologic abnormalities,(3,5) disorders of muscle metabolism (5) and abnormal results of muscle biopsy (5) found in such patients. Specific flow cytometric measurements of lymphocyte dysfunction may prove to be a means of characterizing and diagnosing this syndrome.(6)

Holland, who reminds us of the dictum “Primum non nocere”, should take his own advice to heart. We are only beginning to unravel the secrets of this debilitating condition, which is very likely caused by a combination of triggering factors, including infective and environmental influences.

This condition, called myalgic encephalomyelitis in Britain, is most certainly not psychosomatic, in spite of the frequently associated emotional turmoil.

Most normal healthy people will react “emotionally” when their finances, lifestyle and health are shattered by a debilitating condition, and they may well respond to a sympathetic approach to their total well-being.

~Gerald H. Ross, MD, CCFP, Fellow in environmental medicine

~Jean A. Monro, MB, BS, LRCP, MRCS, Medical director Breakspear Hospital for Allergy and Environmental Medicine Abbots Langley, England

 

References

  1. Holmes GP, Kaplan JE, Gantz NM et al: Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387-389
  2. Rea WJ, Johnson AR, Smiley RE et al: Magnesium deficiency in patients with chemical sensitivity. Clin Ecol 1986; 4:17-20
  3. Tosato G, Straus SE, Werner H et al: Characteristic T cell dysfunction in patients with chronic active EpsteinBarr virus infection (chronic infectious mononucleosis). J Immunol 1985; 134:3082-3088
  4. Kuis W, Roord JJ, Zegers BJM et al: Heterogeneity of immune defects in three children with a chronic active Epstein-Barr virus infection. J Clin Immunol 1985; 5: 377-385
  5. Behan PO, Behan WMH, Bell EJ: The postviral fatigue syndrome – an analysis of the findings in 50 cases. J Infect 1985; 10: 211-222
  6. Johnson TS, Gratzner HG, Steinbach T et al: Flow cytometric measurement of lymphocyte immune function in chronic fatigue syndrome patients. Presented at 22nd scientific session, American Academy of Environmental Medicine, Lake Tahoe, Nev, Oct 22-25, 1988

Source: Gerald H. Ross and Jean A. Monro. Chronic fatigue syndrome. CMAJ. 1989 Feb 15; 140(4): 361. PMCID: PMC1268650 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1268650/?page=1

 

“Virus of the year”?

Note: This letter by Dr. Ray Holland, published in the Canadian Medical Association Journal on August 1, 1988, generated several responses. Dr. Salit’s response appears below. 

 

There appears to be a scarcity of information in medical and psychiatric journals (although not in the lay press) on what was initially termed the Epstein-Barr syndrome but was later renamed chronic fatigue syndrome because it can be caused by infective agents other than the Epstein-Barr virus (EBV). For example, the last article on the subject in CMAJ appeared in 1985.(1) There the syndrome, consisting of fatigue, depression, myalgia, muscle weakness, headaches and paresthesia, was named sporadic postinfectious neuromyasthenia (PIN), a term preferable to chronic fatigue syndrome because it is not ambiguous and because the condition can be of both infectious and psychologic origin.

Presumably the condition was named chronic fatigue syndrome because fatigue is the main presenting symptom, but in psychologic depression fatigue can also be the main manifestation. It is unfortunate, therefore, that the American Medical Association appears to have adopted such an ambiguous term while lamenting that the lack of a definitive diagnosis leaves both patients and health care providers frustrated.(2)

To confuse matters further, the media have labelled the condition chronic fatigue in overachievers or Yuppie flu. In fact, traditional psychiatrists have for some timed called chronic fatigue in overachievers anhedonia (inability to experience pleasure), which, if untreated, may lead to fatigue, depression and the other symptoms mentioned.

While the clinical picture may be ambiguous, the serologic findings may be more so, even when interpreted along with the clinical findings, because those exposed to EBV may have positive serologic results but no chronic sequelae, in much the same way as most people exposed to tuberculosis have subclinical infection. How high does the antibody titre have to be for a definite diagnosis of chronic fatigue syndrome in those who were apparently well before the acute viral attack, even if one excludes those with a previous psychiatric history, as Salit did? One must suspect that a high antibody titre that does not correlate with the clinical findings implies a psychologic origin, as does a low antibody titre. However, it appears that many patients who are told that they have positive but inconclusive serologic results of testing for EBV are choosing to believe that they have the disease. The local medical laboratory has informed me that there is not even a range of titres for EBV but that patients must find their own range by correlating values with how they feel! The media seem to infer that cases with negative results of EBV testing either have not been diagnosed because of lack of the necessary technology or have been misdiagnosed, because there is no mention that the cause may be psychologic.

Such a state of affairs is only too likely in today’s society, in which people are actually healthier than ever before but are more disease conscious and in which the media have a lively interest in medical matters. Rather than an epidemic of the disease, there appears to be an epidemic of the diagnosis, such that EBV should be named “virus of the year”.

May primum non nocere prevail as high-tech medicine continues to advance, at an alarming rate.

~Ray G.L. Holland, MD, FRCPC Box 458 Port Colbome, Ont.

References

  1. Salit IE: Sporadic postinfectious neuromyasthenia. Can Med Assoc J 1985; 133: 659-663
  2. Straus SE: EB or not EB – that is the question [E]. JAMA 1987; 257: 2335- 2336

 

[Dr. Salit responds:]

I too believe that the lack of information in medical journals on PIN [postinfectious neuromyasthenia] is a problem. There appears to be confusion about the condition among physicians, granting agencies and medical journals; they are unable to neatly classify the ailment into a nosologic category. The comment has been that the illness is “too vague” or “ill-defined”. This translates into an inability to have studies related to this subject published. Indeed, last year CMAJ rejected my article on immunologic aberrations in PIN, citing similar reasons.

The term chronic fatigue syndrome (1) was probably chosen by US investigators because it is a generic term. In 1985 these investigators thought that the illness was due to EBV; hence the common designation chronic EBV infection.(2) At that time I felt that the illness was induced by many etiologic agents, so I used the term PIN.(3) Most investigators in this area have come around to this way of thinking but have chosen not to use the term PIN.

Dr. Holland indicates that this disease has been acknowledged by psychiatrists in the past under other designations. Indeed, very similar illnesses have been known to different specialists by different names for decades. I have suggested a unifying hypothesis concerning a common pathophysiologic mechanism.(4)

EBV serologic findings have been the most confusing diagnostic aspect of this illness. Some patients after typical acute infectious mononucleosis have a form of chronic mononucleosis that symptomatically resembles PIN.(5) The serologic findings strongly suggest chronic active EBV infection. However, in most cases of PIN the illness probably did not start with acute infectious mononucleosis, and the patients probably do not have continuing active EBV infection. Using a sensitive DNA probe we found that PIN patients were not excreting EBV.(6) Furthermore, there is such extensive overlap between PIN patients and healthy controls that EBV serologic findings cannot be used to make the diagnosis.(7) It is also likely that such patients have moderately elevated titres of antibodies to a variety of other antigens. Most adults in Canada have EBV antibodies from a prior infection. Too often a diagnosis of chronic EBV infection is made on the basis of certain symptoms and the findings of any EBV antibody. This is inappropriate.

Holland says that “there appears to be an epidemic of the diagnosis”. What has become very apparent to me is that there are a large number of people in the community with illnesses that might be included under the rubric PIN. Physicians argue about the existence of this disease, but it is clear to me that PIN patients have an illness (or a deviation from a normal state of health). Despite the fact that we do not understand the disease process that results in this illness, the patients still require appropriate medical care, consisting of empathy, an acknowledgement that they are ill, reassurance that there is an absence of a more severe disease and, finally, guidelines on how best to manage the condition.(4’8’9)

I do not think that primum non nocere should prevail, although I can accept secundum non nocere. First we should show some understanding and compassion.

~ Irving E. Salit, MD, FRCPC Division of Infectious Diseases Toronto General Hospital Toronto, Ont.

References

  1. Holmes GP, Kaplan JE, Gantz NM et al: Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387-389
  2. Jones JF, Ray CG, Minnich LL et al: Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated antiearly antigen antibodies. Ann Intern Med 1985; 102: 1-7 3. Salit IE: Sporadic postinfectious neuromyasthenia. Can Med Assoc J 1985; 133: 659-663
  3. Idem: Chronic EBV infections (postinfectious neuromyasthenia). Med North Am 1987; 10: 1944-1950
  4. Straus SE: The chronic mononucleosis syndrome. J Infect Dis 1988; 157: 405- 412
  5. Salit IE, Diaz-Mitoma F, Walmsley S et al: Absence of Epstein-Barr virus excretion in post-infectious neuromyopathies. Presented at the American Society for Microbiology annual meeting, Miami Beach, May 9, 1988
  6. Buchwald D, Sullivan JL, Komaroff AL: Frequency of “chronic active Epstein-Barr virus infection” in a general medical practice. JAMA 1987; 257: 2303-2307
  7. Salit IE: Post-infectious fatigue. Can Fam Physician 1987; 133: 1217-1219 9. Taerk GS, Toner B, Salit IE et al: Depression in patients with neuromyasthemia. Int J Psychiatry Med 1987; 17: 49-56

 

Source: R G Holland. “Virus of the year”? CMAJ. 1988 Aug 1; 139(3): 198–199. PMCID: PMC1268060 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1268060/?page=1 and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1268061/