On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics

Abstract:

Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic.

The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors.

An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia.

Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms.

As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

Comment in: Hypotheses concerning rickettsial microorganisms, autoimmune diseases and new treatment strategies. [Med Hypotheses. 2010]

 

Source: Frykholm BO. On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics. Med Hypotheses. 2009 Jun;72(6):736-9. doi: 10.1016/j.mehy.2008.11.045. Epub 2009 Mar 6. https://www.ncbi.nlm.nih.gov/pubmed/19269110

 

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects.

No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also had significantly more CD20(+)/CD5(+) B cells, a subset associated with the production of autoantibodies.

Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s).

 

Source: Robertson MJ, Schacterle RS, Mackin GA, Wilson SN, Bloomingdale KL, Ritz J, Komaroff AL. Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression. Clin Exp Immunol. 2005 Aug;141(2):326-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809442/ (Full article)

 

Correlates of illness worry in chronic fatigue syndrome

Abstract:

BACKGROUND: Anxiety about illness leading to restriction of activity and physical deconditioning has been hypothesized to contribute to the chronicity of fatigue. Pathological symptom attributions, personality traits, and depression have all been hypothesized to contribute to illness worry.

METHODS: We compared 45 chronic fatigue syndrome (CFS) and 40 multiple sclerosis (MS) outpatients using a battery of psychometric instruments comprising the 12-item Illness Worry scale, the Symptom Interpretation Questionnaire (SIQ), the NEO Five-Factor Inventory (NEO-FFI), and a modified version of the SCL-90R Depression scale.

RESULTS: There was no difference between the two diagnostic groups on neuroticism, depressive symptoms, as well as the three scales of the SIQ. On the illness worry index, the CFS group had significantly higher scores than the MS group. This difference was due to items tapping vulnerability to illness and the perception that others are not taking their illness seriously. Somatic attributional style, neuroticism, depressive symptoms, and age were all significant predictors of illness worry in both CFS and MS patients.

CONCLUSIONS: Somatic attributions, neuroticism, and depression all contribute to illness worry in chronic illness. However, these factors do not account for the higher levels of illness worry in CFS as opposed to MS, which may be due to other specific cognitive and social interactional processes.

 

Source: Taillefer SS, Kirmayer LJ, Robbins JM, Lasry JC. Correlates of illness worry in chronic fatigue syndrome.  J Psychosom Res. 2003 Apr;54(4):331-7. http://www.ncbi.nlm.nih.gov/pubmed/12670610

 

Psychological correlates of functional status in chronic fatigue syndrome

Abstract:

BACKGROUND: The present study was designed to test a cognitive model of impairment in chronic fatigue syndrome (CFS) in which disability is a function of severity of fatigue and depressive symptoms, generalized somatic symptom attributions and generalized illness worry.

METHODS: We compared 45 CFS and 40 multiple sclerosis (MS) outpatients on measures of functional ability, fatigue severity, depressive symptoms, somatic symptom attribution and illness worry.

RESULTS: The results confirmed previous findings of lower levels of functional status and greater fatigue among CFS patients compared to a group of patients with MS. Fatigue severity was found to be a significant predictor of physical functioning but not of psychosocial functioning in both groups. In CFS, when level of fatigue was controlled, making more somatic attributions was associated with worse physical functioning, and both illness worry and depressive symptoms were associated with worse psychosocial functioning.

CONCLUSIONS: Our findings support the role of depression and illness cognitions in disability in CFS sufferers. Different cognitive factors account for physical and psychosocial disability in CFS and MS. The SF-36 may be sensitive to symptom attributions, suggesting caution in its interpretation when used with patients with ill-defined medical conditions.

 

Source: Taillefer SS, Kirmayer LJ, Robbins JM, Lasry JC. Psychological correlates of functional status in chronic fatigue syndrome. J Psychosom Res. 2002 Dec;53(6):1097-106. http://www.ncbi.nlm.nih.gov/pubmed/12479992

 

Interpretation of symptoms in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterised by fatigue and other symptoms. Both psychological and biological aetiological factors have been proposed, but the disorder is of uncertain origin. The aetiology of the symptoms is therefore ambiguous. It has been suggested (a) that patients with CFS tend to interpret their symptoms as indicating physical illness and (b) they tend not to interpret these symptoms in terms of negative emotion.

In order to test these hypotheses we developed a self-report questionnaire to assess the interpretation of symptoms in patients with CFS. It was administered to patients with CFS, patients with depression, patients with multiple sclerosis (MS), and normal controls. Preliminary results suggest that the measure has acceptable psychometric properties.

Patients with CFS were more likely than either depressed patients or normal controls to interpret symptoms (characteristic of CFS) in terms of physical illness, but did not differ in this from the MS patients. When compared with all three other groups (including the MS patients), the patients with CFS were least likely to interpret symptoms in terms of negative emotional states. The theoretical and clinical implications of the findings are discussed.

 

Source: Dendy C, Cooper M, Sharpe M. Interpretation of symptoms in chronic fatigue syndrome. Behav Res Ther. 2001 Nov;39(11):1369-80. http://www.ncbi.nlm.nih.gov/pubmed/11686271

 

Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression

Abstract:

Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability.

A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls.

After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.

 

Source: Daly E, Komaroff AL, Bloomingdale K, Wilson S, Albert MS. Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol. 2001;8(1):12-22. http://www.ncbi.nlm.nih.gov/pubmed/11388119

 

Feminist perspectives on the social construction of chronic fatigue syndrome

Abstract:

We contrast Western medical views of chronic fatigue syndrome (CFS) etiology, diagnosis, and treatment with views maintained by a predominantly female CFS population. We argue that the failure of Western medicine to demonstrate a viral etiology for CFS led to a paradigmatic shift in research perspectives, which then embraced psychiatric and sociocultural explanations for CFS. As a result, CFS was delegitimized as a biomedical phenomenon within medical, academic, governmental, and public arenas.

We compare alternative social constructions of CFS with issues pertaining to multiple sclerosis (MS), an illness that similarly predominates among women. Patient perspectives suggest that the history of medical attitudes toward CFS may eventually parallel the transformations that occurred in relation to MS. In particular, the discovery of biological markers for CFS may lay to rest the categorization of CFS as largely within the psychiatric realm.

 

Source: Richman JA, Jason LA, Taylor RR, Jahn SC. Feminist perspectives on the social construction of chronic fatigue syndrome. Health Care Women Int. 2000 Apr-May;21(3):173-85. http://www.ncbi.nlm.nih.gov/pubmed/11111464

 

Controversies in neurological infectious diseases

Abstract:

The past several years have seen major advances in our understanding of neurological infectious diseases, their diagnosis, and their treatment. Along with these advances, however, new information about infectious agents and new therapeutic options have also introduced both uncertainty and controversy in the approach and management of patients with diseases of the central nervous system. Here, we discuss six such areas: the long-term efficacy of HAART therapy in treatment of HIV infection; the role of viral infection in chronic fatigue syndrome; Rasmussen’s encephalitis as an infectious or autoimmune disease; the spectrum of neurological diseases caused by rickettsial infection; the role of Mycoplasma pneumoniae in human central nervous system disease; and the possible association of Chlamydia pneumoniae and human herpesvirus 6 with multiple sclerosis.

 

Source: Greenlee JE, Rose JW. Controversies in neurological infectious diseases. Semin Neurol. 2000;20(3):375-86. http://www.ncbi.nlm.nih.gov/pubmed/11051301

 

Abnormal neuropsychological findings are not necessarily a sign of cerebral impairment: a matched comparison between chronic fatigue syndrome and multiple sclerosis

Abstract:

OBJECTIVE: The aim of this study was to assess the potential impact of effort in comparative studies assessing neurocognitive dysfunction in patients with and without a neurologic diagnosis.

BACKGROUND: It was hypothesized that a subgroup within a group of patients with prominent neurocognitive complaints but without a neurologic diagnosis would have impaired performance on a task originally designed to detect malingering.

METHOD: We compared the neuropsychological performance of a group of 40 patients with a definite diagnosis of multiple sclerosis (MS) with that of 67 patients with chronic fatigue syndrome (CFS). The Amsterdam Short-Term Memory Test, a forced-choice memory task, served as measure to detect submaximal effort. In addition, we administered a regular neuropsychological task generally considered to be sensitive for cognitive deterioration.

RESULTS: Compared with the MS group (13%), a larger proportion of the matched CFS group (30%) obtained scores indicative of reduced effort. In contrast, the proportions of patients scoring below the cutoff value on a conventional neuropsychological test did not differ significantly (17% of MS patients and 16% of CFS patients).

CONCLUSIONS: The results obtained raise the question of to what extent abnormal test findings in the absence of documented neurologic impairment should be interpreted as a sign of cerebral impairment. The suggestion has been made to screen more often for biased results in comparative research studies so as to enhance valid interpretation of neuropsychological findings.

 

Source: van der Werf SP, Prins JB, Jongen PJ, van der Meer JW, Bleijenberg G. Abnormal neuropsychological findings are not necessarily a sign of cerebral impairment: a matched comparison between chronic fatigue syndrome and multiple sclerosis. Neuropsychiatry Neuropsychol Behav Neurol. 2000 Jul;13(3):199-203. http://www.ncbi.nlm.nih.gov/pubmed/10910092

 

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients

Abstract:

BACKGROUND: HHV-6 is a ubiquitous virus and its infection usually occurs in childhood and then becomes a latent infection. HHV-6 reactivation has been shown to play a role in the pathogenesis of AIDS and several other diseases.

OBJECTIVES: To determine what role HHV-6 infection or reactivation plays in the pathogenesis of multiple sclerosis (MS) and chronic fatigue syndrome (CFS).

RESULTS: Twenty-one MS and 35 CFS patients were studied and followed clinically. In these patients, we measured HHV-6 IgG and IgM antibody levels and also analyzed their peripheral blood mononuclear cells (PBMCs) for the presence of HHV-6, using a short term culture assay. In both MS and CFS patients, we found higher levels of HHV-6 IgM antibody and elevated levels of IgG antibody when compared to healthy controls. Seventy percent of the MS patients studied contained IgM antibodies for HHV-6 late antigens (capsid), while only 15% of the healthy donors (HD) and 20% of the patients with other neurological disorders (OND) had HHV-6 IgM antibodies. Higher frequency of IgM antibody was also detected in CFS patients (57.1%) compared to HD (16%). Moreover, 54% of CFS patients exhibited antibody to HHV-6 early protein (p41/38) compared to only 8.0% of the HD. Elevated IgG antibody titers were detected in both the MS and the CFS patients. PBMCs from MS, CFS and HD were analyzed in a short term culture assay in order to detect HHV-6 antigen expressing cells and to characterize the viral isolates obtained as either Variant A or B. Fifty-four percent of MS patients contained HHV-6 early and late antigen producing cells and 87% of HHV-6 isolates were Variant B. Isolates from CFS, patients were predominately Variant A (70%) and isolates from HD were predominately Variant B (67%). Moreover, one isolate from OND was also Variant B. Persistent HHV-6 infection was found in two CFS patients over a period of 2.5 years and HHV-6 specific cellular immune responses were detected in PBMCs from ten CFS patients.

CONCLUSION: In both MS and CFS patients, we found increased levels of HHV-6 antibody and HHV-6 DNA. A decrease in cellular immune responses was also detected in CFS patients. These data suggest that HHV-6 reactivation plays a role in the pathogenesis of these disorders.

 

Source: Ablashi DV, Eastman HB, Owen CB, Roman MM, Friedman J, Zabriskie JB, Peterson DL, Pearson GR, Whitman JE. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. J Clin Virol. 2000 May;16(3):179-91. http://www.ncbi.nlm.nih.gov/pubmed/10738137