Category: Pathogenesis

Multiple chemical sensitivity disorder in patients with neurotoxic illnesses

Abstract:

The data of 466 subjects suffering from neurologic disorders which are suggested to be caused by neurotoxic agents in their environment retrospectively was evaluated and documented. Among these cases there were 151 subjects with symptoms of Multiple Chemical Sensitivity Disorder (MCSD). The relationship between the neurological health impairments and neurotoxic agents in the environment of these patients was characterised using five different categories (probable = A, possible = B, uncertain = C, unclarified = D, not probable = E). From the 466 patients 320 subjects (69%) could be assigned to the categories A and B, respectively.

Within theses 320 cases with chronic neurotoxic health impairments 136 subjects (79 females and 57 males) showed signs of MCSD. Age and gender of cases as well as duration and character of exposure to neurotoxic substances retrospectively were assessed from the explicit files of the patients, which had been made anonymous for this purpose. Frequency of characteristic symptoms of neurotoxicity were analysed. Results are given for patients with neurotoxic health impairments with MCSD (n = 136) and without MCSD (n = 184).

Neurotoxic substances which were used as indoor wood preservatives (mainly Pentachlorophenol and/or Lindane) were found to be the causative agents in 63% of the cases with neurotoxic health impairments and MCSD. Other important neurotoxic substances to which the patients were mainly exposed were organic solvents (25%), formaldehyde (15%), dental materials (15%), pyrethroides (13%), and other biocides (19%) (multiple exposures were possible). The time of exposure was calculated as being > or = 10 years for 55% of the patients with MCSD and for 50% of the group with neurotoxic health impairments but without MCSD.

Out of the 184 cases with neurotoxic health impairments but without MCSD there were 22%, and out of the 136 cases with MCSD there were 39% who showed all symptoms of chronic fatigue syndrome. 53% of the cases with MCSD had an allergic disposition compared to only 20% of the cases without MCSD.

This work is not a controlled epidemiological study but a retrospective documentation and evaluation of data related to environmental medicine. With the present documentation in this purely descriptive manner the proof of a causal relationship was not possible or intended. But because corresponding epidemiological studies are lacking, this documentation can give important information on characteristic features of Multiple Chemical Sensitivity Disorder and chronic neurotoxic health impairments. Such information is essential for planning and carrying out epidemiological studies urgently needed in this field.

Comment in:

Comment on K. Lohmann, Anke Pröhl, E. Schwarz. Multiple chemical sensitivity in patients with neurotoxic illnesses. Gesundheitswesen. 1997 [Article in German]

 

Source: Lohmann K, Pröhl A, Schwarz E. Multiple chemical sensitivity disorder in patients with neurotoxic illnesses. Gesundheitswesen. 1996 Jun;58(6):322-31. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/8766847

 

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome

Abstract:

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group.

PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti.

RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar.

CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Comment in: Etiology of chronic fatigue syndrome. [Am J Med. 1997]

 

Source: MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK. A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med. 1996 May;100(5):548-54. http://www.ncbi.nlm.nih.gov/pubmed/8644768

 

Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a syndrome of uncertain etiopathogenesis characterized by disabling fatigue associated with a variable number of somatic and/or neuropsychologic symptoms. In patients with CFS, several immunologic abnormalities can be detected, including a higher prevalance of allergy.

The aim of this study was to determine whether CFS patients, well studied for their allergy profile, show signs of eosinophil activation, as detectable by the measurement in serum of eosinophil cationic protein (ECP) levels. In 35 consecutive CFS outpatients (diagnosis based on the Centers for Disease Control case definition), ECP was measured in serum by a competitive enzyme immunoassay (ECP-FEIA kit, Kabi Pharmacia Diagnostics, Uppsala, Sweden).

Fourteen disease-free subjects with no history of CFS or allergy were selected as controls. ECP serum levels were significantly higher in CFS patients than in controls (18.0 +/- 11.3 micrograms/l vs 7.3 +/- 2.1 micrograms/l; P < 0.01). In the CFS population, the prevalence of RAST positivity to one or more allergens was 77%, while no control showed positive RAST.

Twelve of the 14 CFS patients with increased ECP serum levels were RAST-positive. However, CFS RAST-positive patients had no significantly higher ECP serum levels than CFS RAST-negative patients (19.3 +/- 12.4 micrograms/l vs 13.6 +/- 3.7 micrograms/l; P = 0.4).

This is the first report of increased serum levels of ECP in CFS. On the basis of the available data, it is discussed whether eosinophil activation has a pathogenetic role in CFS or is linked to the frequently associated allergic condition, or, finally, whether a common immunologic background may exist for both atopy and CFS.

 

Source: Conti F, Magrini L, Priori R, Valesini G, Bonini S. Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome. Allergy. 1996 Feb;51(2):124-7. http://www.ncbi.nlm.nih.gov/pubmed/8738520

 

Chronic fatigue syndrome (myalgic encephalopathy)

Abstract:

Chronic fatigue syndrome is associated with many misconceptions. In this review, we attempt to summarize various pathogenic hypotheses for this disease and discuss new lines of insight into causes and treatments of this baffling and most frustrating condition.

 

Source: Plioplys S, Plioplys AV. Chronic fatigue syndrome (myalgic encephalopathy). South Med J. 1995 Oct;88(10):993-1000. http://www.ncbi.nlm.nih.gov/pubmed/7481975

GPs’ attitudes to a self diagnosis of myalgic encephalomyelitis. Evidence supports presence of encephalitis

Comment on: General practitioners’ attitudes to patients with a self diagnosis of myalgic encephalomyelitis. [BMJ. 1995]

 

EDITOR,-Although the precise pathoaetiology of myalgic encephalomyelitis remains the subject of debate, Shonagh Scott and colleagues are incorrect in asserting that “no evidence exists” of encephalitis. Buchwald et al carried out a large cohort study in which neurological symptoms, results of magnetic resonance imaging, and lymphocyte phenotyping suggested that the patients were experiencing “a chronic, immunologically mediated inflammatory process of the central nervous system.”2 More recently, Schwartz et al, who used single photon emission computed tomography, described abnormalities that were consistent with the hypothesis that “a chronic viral encephalitis” may be present.3 Furthermore, in the only postmortem study to have been published the polymerase chain reaction showed enteroviral sequences (compatible with coxsackie virus B3) in samples from the hypothalamus and brain stem,4 indicating that viral persistence within selective parts of the central nervous system may also play a part.

Given the uncertainties surrounding both the pathoaetiology and the diagnostic criteria for myalgic encephalomyelitis, it is not surprising to learn that self diagnosis produces difficulties in the doctor-patient relationship. The conclusions of and motives behind Scott and colleagues’ study must, however, be questioned in view of the fact that the fictitious patients had a list of vague symptoms that failed to satisfy diagnostic criteria for either a chronic fatigue syndrome (as defined by the International Chronic Fatigue Syndrome Study Group)5 or a postinfectious fatigue syndrome (as defined by current British criteria).6 Neither did the symptoms accord with those that patient support organisations would agree constitute a satisfactory diagnosis of myalgic encephalomyelitis.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2549699/pdf/bmj00593-0058b.pdf

 

Source: Shepherd C. GPs’ attitudes to a self diagnosis of myalgic encephalomyelitis. Evidence supports presence of encephalitis. BMJ. 1995 May 20;310(6990):1330. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2549699/

 

The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia

Abstract:

Syndromes characterized by chronic pain and fatigue have been described in the medical literature for centuries. Fibromyalgia is the term currently used to describe this symptom complex, and considerable research has been performed in the last decade to delineate the epidemiology, pathophysiology, and genesis of this entity. Although fibromyalgia is defined by its musculoskeletal features, it is clear that there are a large number of non-musculoskeletal symptoms, such that we now understand that there is considerable overlap with allied conditions such as the chronic fatigue syndrome, migraine and tension headaches, irritable bowel syndrome, and affective disorders. This article will review our current state of knowledge regarding fibromyalgia and these allied conditions, and present a unifying hypothesis that describes both the pathophysiology of symptoms and the genesis of these disorders.

 

Source: Clauw DJ. The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia. Med Hypotheses. 1995 May;44(5):369-78. http://www.ncbi.nlm.nih.gov/pubmed/8583967

 

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome

Abstract:

A simian cytomegalovirus-related stealth virus, isolated from a patient with the chronic fatigue syndrome, induced an acute neurological illness when inoculated into cats. Histological examination of brain tissue showed foci of cells with cytoplasmic vacuolization and an absence of any inflammatory reaction. Electron microscopy confirmed the presence of herpes-like viral particles and viral-like products in the brain of an inoculated animal. These findings support the role of stealth viruses in the pathogenesis of human neurological diseases and provide an animal model to evaluate potential antiviral therapy.

 

Source: Martin WJ, Glass RT. Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome. Pathobiology. 1995;63(3):115-8. http://www.ncbi.nlm.nih.gov/pubmed/8821627

 

Chronic fatigue syndrome. 1: Etiology and pathogenesis

Abstract:

Chronic fatigue syndrome (CFS) is a disorder of unknown etiology characterized by debilitating fatigue and other somatic and neuropsychiatric symptoms. A range of heterogeneous clinical and laboratory findings have been reported in patients with CFS. Various theories have been proposed to explain the underlying pathophysiologic processes but none has been proved.

Research findings of immunologic dysfunction and neuroendocrine changes suggest the possible dysregulation of interactions between the nervous system and the immune system. Without a clear understanding of its etiopathogenesis, CFS has no definitive treatment.

Management approaches have been necessarily speculative, and they have evolved separately in a number of medical and nonmedical disciplines. The results of several controlled treatment studies have been inconclusive. An accurate case definition identifying homogeneous subtypes of CFS is needed. The integration of medical and psychologic treatment modalities and the use of both biologic and psychologic markers to evaluate treatment response will enhance future treatment strategies.

 

Source: Farrar DJ, Locke SE, Kantrowitz FG. Chronic fatigue syndrome. 1: Etiology and pathogenesis. Behav Med. 1995 Spring;21(1):5-16. http://www.ncbi.nlm.nih.gov/pubmed/7579775

 

Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression

Chronic fatigue syndrome is characterised by debilitating severe fatigue persisting for more than six months. Furthermore, it is associated with physical symptoms, such as mild fever, sore throat, arthralgia, and myalgia, as well as psychological symptoms such as headache, insomnia, depressive state, and neuropsychiatric symptoms. It has often been claimed that the onset of chronic fatigue syndrome follows an infection or infection-like illness; hence a certain microorganism(s) or virus may cause it. Another possible candidate for inducing chronic fatigue syndrome is cellular or humoral immune dysfunction, which has been found in patients with the disease. There is controversy also as to whether or not chronic fatigue syndrome and major depression (mood disorder) represent different entities.

Mild fever, pharyngitis, and lymphadenopathy, which are suggestive of the existence of inflammation, are often associated with chronic fatigue syndrome, but the peripheral leucocyte count, erythrocyte sedimentation rate, and C-reactive protein concentration are usually normal in patients with chronic fatigue syndrome. Hence, it is possible that certain cytokines may produce the symptoms in patients with chronic fatigue syndrome and, possibly, those with major depression. For example, interferon is known to cause fever, fatigue, and psychoneurological abnormalities. We conducted this study to clarify whether or not 2′,5′-oligoadenylate synthetase (2,5-AS), neopterin, adenosine deaminase, endotoxin, or B-glucan participate in the pathogenesis of chronic fatigue syndrome.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073106/pdf/jnnpsyc00038-0135b.pdf

 

Source: Matsuda J, Gohchi K, Gotoh N. Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression. J Neurol Neurosurg Psychiatry. 1994 Aug;57(8):1015-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073106/

 

Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome

Abstract:

Levels of 2′,5′-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15 individuals with chronic fatigue syndrome (CFS) before and during therapy with the biological response modifier poly(I).poly(C12U) and were compared with levels in healthy controls.

Patients differed significantly from controls in having a lower mean basal level of latent 2-5A synthetase (P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean basal level of activated 2-5A synthetase higher than the corresponding control value (P = .009). All seven pretherapy PBMC extracts tested were positive for the replication of human herpesvirus 6 (HHV-6).

Therapy with poly(I).poly(C12U) resulted in a significant decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A synthetase/RNase L pathway in temporal association with clinical and neuropsychological improvement. The upregulated 2-5A pathway in CFS before therapy is consistent with an activated immune state and a role for persistent viral infection in the pathogenesis of CFS. The response to therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this situation.

 

Source: Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Müller WE, Schröder HC, Carter WA, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. http://www.ncbi.nlm.nih.gov/pubmed/8148461