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ABSTRACT: Cognitive impairment is one of the most frequent symptoms in patients with multiple sclerosis (MS) but its underlying mechanisms are poorly understood. A number of pathogenetic correlates have previously been proposed including psychosocial factors (such as depression and fatigue), inflammation, neurodegeneration, and neuroendocrine dysregulation. However, these different systems have never been studied in parallel and their differential contributions to cognitive impairment in MS are unknown. We studied a well-characterized cohort of cognitively impaired (CI, n=25) and cognitively preserved (CP, n=25) MS patients based on a comprehensive neuropsychological testing battery, a test of hypothalamo-pituitary-adrenal axis functioning (dexamethasone-corticotropin-releasing hormone suppression test, Dex-CRH test) as well as peripheral blood and MRI markers of inflammatory activity. CI patients had significantly higher disability. In addition, CI patients showed higher levels of fatigue and depression. Fatigue was more closely associated with measures of attention while depression showed strongest correlations with memory tests. Furthermore, percentage of IFNγ-positive CD4+ and CD8+ T cells showed modest correlations with processing speed and working memory. MRI markers of inflammation or global atrophy were not associated with neuropsychological function. Compared to previous studies, the number of patients exhibiting HPA axis hyperactivity was very low and no correlations were found with neuropsychological function. We conclude that fatigue and depression are the main correlates of cognitive impairment, which show domain-specific associations with measures of attention and memory.
Brain Behavior and Immunity 10/2010; 24(7):1148-55. · 4.72 Impact Factor
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ABSTRACT: We investigated interrelations between cognitive abilities, behavioural problems, quality of life and disease-related variables of children after LTX.
Our sample consisted of 25 children. They were 8.5/2.8 (M/SD) years old and had received the transplant 5.5/3.1 years previously. For assessment we used well-established instruments.
Liver transplanted children scored below the population mean on the cognitive as well as on the behavioural instrument and showed scores below average in the scales Self-esteem, Friends and Total Score regarding QoL. Behavioural problems were associated with poorer cognitive performance (r=-0.38 to -0.63). QoL regarding physical well-being was correlated with sequential processing (r=0.41). Lower sequential processing scores were associated with lower QoL. Also between behavioural parameters and QoL correlations could be determined. Children with more behavioural problems experienced lower QoL (r=-0.40 to r=-0.76). Age at onset of disease showed correlations with behavioural and QoL parameters (r=-0.49 resp. r=0.44). Cognitive functioning was associated with medical complications (r=-0.44).
High interrelations between cognitive functioning, behavioural deficits and QoL were obtained. Especially noticeable are correlations between sequential processing and internalized behavioural functions as both are associated with left lateralized brain functioning. This relationship could indicate differential effects on brain development during the preoperative phase.
Pediatric Transplantation 06/2010; 14(4):496-503. · 1.48 Impact Factor
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ABSTRACT: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue.
We compared whole blood stimulatory capacity for pro- (TNFalpha, IFNgamma) and anti-inflammatory cytokines (IL-10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS).
Proinflammatory cytokines were significantly higher (TNFalpha: 478.9 v 228.2 pg/ml, p = 0.01; IFNgamma: 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNFalpha values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment.
Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.
Journal of Neurology Neurosurgery & Psychiatry 02/2006; 77(1):34-9. · 4.76 Impact Factor
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ABSTRACT: Epidemiologic studies increasingly have demonstrated a correlation between physical inactivity and certain chronic diseases. Already in the 1970s exercise programs for cardiovascular patients were established, whereas in other severe chronic illnesses such as breast cancer or multiple sclerosis exposure to physical stress seemed to be a contraindication. Today there is a grow ing body of evidence demonstrating positive physical as well as psychic effects of exercise training in patients with these diseases. These studies are summarized and complementary studies of our group are described in more detail. In patients with breast cancer we were able to demonstrate persistent psychosocial effects even 1 year after completion of the training program. In patients with multiple sclerosis we could confirm an induction of neurotrophic factors in trained individuals. Correspondingly, there is accumulating evidence showing positive effects of exercise on cognitive function, especially in the aged. Potential pathophysiological pathways regarding a progression to dementia are presented. Consequently exercise programs could play a pivotal role in the prevention and therapy of the cognitive decline in the aged in an aging society.
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 09/2005; 48(8):906-13. · 0.66 Impact Factor
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ABSTRACT: The need for an early disclosure of the diagnosis of multiple sclerosis (MS) has become more pressing with the publication of two recent randomized trials which have indicated that very early treatment may favourably alter the disease course. We assessed the current status of diagnostic and therapeutic information on MS from the point of view of patients and neurologists.
A standardized questionnaire was sent out through the patients' self-help organization in Hamburg, Germany and to all neurologists.
A total of 434 of 1300 patients and 80 of 250 neurologists replied. Neurologists gave 90% of the diagnoses but only 50% of patients reported them as the major aid helping to understand the disease. Fifty per cent of patients were not informed about any form of therapy at the time of diagnosis regardless of whether their MS diagnosis was disclosed within the last 5 years or earlier. In contrast to physicians, patients voted for information about a possible MS even if the diagnosis may not yet be clear.
From the patients' perspective, information about the diagnosis of MS should be more straightforward, and more information about therapies should be provided.
Acta Neurologica Scandinavica 06/2003; 107(5):363-8. · 2.47 Impact Factor
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Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 01/2002; 45(10):759-760. · 0.66 Impact Factor
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ABSTRACT: There is only scarce information on the quality of life of child recipients of liver transplants and their families. Particularly children with a living related graft and their families never have been compared to children who received a cadaveric graft and their families. We investigated the following issues in our study: How do parents and children from participating families rate their strain, their quality of life and their relationships within their family? Do families with a living - related donor differ from those with a cadaveric donor? What do living donors and their partners think about the donation retrospectively? The study was conducted with 106 participants from 50 families (42 mothers, 40 fathers, and 24 children older than 6 years). In 20 of these families, a living transplantation had been performed. Participants were interviewed and asked to fill out several questionnaires. School-aged children with a liver transplant show good social integration among their peers and in school. The child's disease, however, has a great impact on the family. Family members show a reduction in social contact, and an increase in marital crises, and problematic relations amongst siblings. Families in which a cadaveric graft was performed, are less satisfied with life, and show more symptoms of exhaustion. Every family studied possessed or acquired - a high degree of internal or external coping resources. Living - related donors tried hard to obtain an understanding of the medical context. The partner, rather than the donor himself, feels anxious before the donation. The limited time available for the decision to donate is not perceived by the donors to be critical. Ten percent of living donors feel "a little" that their health is affected. The decision to donate is supported "strongly" or "very strongly" by the partners in 80 % of the cases. A possible strain on the child through the expectation of gratitude by the donor is stated by 20 %. All of the donors agree that if they were to be asked today, they would donate again, only one of the partners raised objections. In summary, as a retrospective pilot study, this study primarily generates hypotheses rather than testing them and helps to develop research tools for the field. Results suggest that a psychological support be made available both prior to and following the operation, not only for the children but also for their families, with particular attention to the partners of the living donors and the siblings of the affected children.
PPmP - Psychotherapie · Psychosomatik · Medizinische Psychologie 01/2002; 51(12):452-64. · 1.02 Impact Factor
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ABSTRACT: Quality of life (QoL) is discussed as an additional outcome measure in multiple sclerosis (MS). However, few questionnaires assessing disease specific QoL in MS have been published. On the basis of the literature and interviews with clinicians and MS patients, we have developed a disease specific QoL instrument and validated it in a broad range of patients with MS. In this study, a heterogeneous sample of n = 237 MS patients completed the newly developed Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS, in German language) and a battery of already validated questionnaires. They further underwent neurological scoring and objective tests. By these means, we investigated its validity, appropriateness, internal consistency, and retest reliability. Internal consistency and retest coefficients were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlations with other health measures. HAQUAMS subscales and its total score distinguished between patient groups of varied disease severity, cognitive impairment, and affective symptomatology. No floor or ceiling effects were found in either of the HAQUAMS subscales. The HAQUAMS is a reliable, valid and appropriate instrument for QoL assessment in multiple sclerosis. Data of responsiveness are currently being obtained.
Multiple Sclerosis 05/2001; 7(2):119-30. · 4.26 Impact Factor
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Transplantation Proceedings 03/2000; 32(1):62-3. · 1.00 Impact Factor
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Transplantation Proceedings 03/2000; 32(1):64-5. · 1.00 Impact Factor
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ABSTRACT: We tested the diagnostic validity of carbohydrate-deficient transferrin (CDT) as an indicator for relapse into elevated alcohol consumption among patients who were examined under follow-up treatment before (n = 147) and after (n = 102) orthotopic liver transplantation (OLT) in the outpatient-department of the University Hospital Department of Surgery in Hamburg-Eppendorf. CDT measurements were performed with two commercial kits in parallel (CDTect-RIA and CDT%-RIA). Short-term parameters of alcohol consumption (ethanol, methanol) indicated relapses into elevated alcohol consumption in 11.4% of the evaluated patients with alcoholic liver disease (ALD) before transplantation. Before OLT, median CDT values were determined to be elevated among patients with alcoholic as well as nonalcoholic end-stage liver diseases (NALD). Among patients with ALD, we found elevated CDT medians even in those who were successfully scheduled for OLT after long-term evidence of abstinence proved by biochemical short-term parameters and psychological tests. Both CDTect and CDT% assays had comparable low specificities in selected patient groups before transplantation. CDT% and CDTect were negatively correlated with the albumin level. Before the study ended, CDT was no longer implemented in the evaluation of whether an OLT should be administered. This was due to inconsistent results of CDT in ALD as well as NALD. After OLT, patients with ALD, as well as NALD, had statistically significant lower CDT medians than before OLT, which ranged within reference levels. We determined, according to CDT, elevated alcohol consumption subsequent to OLT in 4 of 13 patients with ALD who underwent transplantation during the study (median observation period: 10 months). CDT does not appear to be useful in evaluating patients before OLT. With regained specificity and high sensitivity in patients after OLT, CDT could be recommended as a standard instrument for quality control in patients with ALD after liver transplantation.
Alcoholism Clinical and Experimental Research 12/1998; 22(8):1806-12. · 3.34 Impact Factor
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ABSTRACT: Psychoneuroimmunological stress- and intervention studies are summarized and discussed especially with respect to the immunological parameters used. A description is given of the studies on bereavement, on examinations, and on the effects of various psychosocial situations and on experimental manipulations on immunological parameters as well as of intervention studies. Following an analysis of the immunological parameters regarding their susceptibility to psychosocial changes, a model for research in the field of psychoneuroimmunology is presented. This overview reveals that the results of the reviewed studies prove to be inconsistent. Cell counts and mitogen assays are the most frequently used parameters, while NKCA and specific anti-viral antibodies against latent viruses give the clearest results. When interpreting results of psychoneuroimmunological studies it should be considered that for most of the parameters the pathophysiological relevance is not yet established. A model which connects interrelations between psychosocial conditions, immunological parameters and disease outcome can be useful to categorize and evaluate existing and future studies and also can prevent misleading conclusions. Derived from this model recommendations for future research will be discussed.
Psycho-Oncology 06/1992; 1(2):51 - 70. · 3.34 Impact Factor
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ABSTRACT: Cognitive impairment is one of the most frequent symptoms in patients with multiple sclerosis (MS) but its underlying mechanisms are poorly understood. A number of pathogenetic correlates have previously been proposed including psychosocial factors (such as depression and fatigue), inflammation, neurodegeneration, and neuroendocrine dysregulation. However, these different systems have never been studied in parallel and their differential contributions to cognitive impairment in MS are unknown.We studied a well-characterized cohort of cognitively impaired (CI, n = 25) and cognitively preserved (CP, n = 25) MS patients based on a comprehensive neuropsychological testing battery, a test of hypothalamo–pituitary–adrenal axis functioning (dexamethasone-corticotropin-releasing hormone suppression test, Dex-CRH test) as well as peripheral blood and MRI markers of inflammatory activity.CI patients had significantly higher disability. In addition, CI patients showed higher levels of fatigue and depression. Fatigue was more closely associated with measures of attention while depression showed strongest correlations with memory tests. Furthermore, percentage of IFNγ-positive CD4+ and CD8+ T cells showed modest correlations with processing speed and working memory. MRI markers of inflammation or global atrophy were not associated with neuropsychological function. Compared to previous studies, the number of patients exhibiting HPA axis hyperactivity was very low and no correlations were found with neuropsychological function.We conclude that fatigue and depression are the main correlates of cognitive impairment, which show domain-specific associations with measures of attention and memory.
Brain, Behavior, and Immunity.
