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Biomedical subjects

C Heesen

Publications and source records attributed to C Heesen.

At least 19 recordsLinked to original sources

[Effects of a shared decision making model in psychiatric and neurologic practice].

Involving patients in medical decisions is increasingly being advocated in medical fields other than psychiatry and neurology. A model of shared decision making might prove to be an ideal way of bridging the gap between patient-centred and evidence-based medicine. This report provides a survey of this shared decision making model and a discussion of its implications in the fields of mental health and neurology.

Adaptation, Psychological↗

Patient information on cognitive symptoms in multiple sclerosis - acceptability in relation to disease duration.

OBJECTIVE: Recently, regular cognitive screening assessments have been advised in multiple sclerosis (MS). No studies have been carried out yet on the acceptability of information on cognitive deficits among MS patients. MATERIALS AND METHODS: Translation of an information booklet developed by a working group of European MS Rehabilitation Centers. Distribution of the booklet among 133 MS patients of two rehabilitation units and one outpatient clinic together with a one-page questionnaire. RESULTS: The booklet was highly understandable and rated to give moderate new information. Overall, the brochure was perceived as encouraging but significantly less so (P = 0.014) in recently diagnosed patients. Patients with subjectively perceived deficits considered the brochure to be significantly more relevant (P = 0.002). CONCLUSION: Information on cognitive deficits does not increase fears even in recently diagnosed MS patients. Patients with perceived deficits found the information more relevant than others and also less familiar. Thus, it seems appropriate to offer information about cognitive impairments to MS patients.

Adult↗

Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Adrenocorticotropic Hormone↗

[Effects of exercise in chronically ill patients. Examples from oncology and neurology].

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.

Breast Neoplasms↗

Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study.

We investigated electrophysiological correlates of fatigue in patients with multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with fatigue (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to and after the exercise. Prior to the motor task, MS-F patients had less inhibition in the primary motor cortex compared to both other groups. Postexercise, intracortical inhibition was still reduced in the MS-F patients compared to the MS-NF patients. In MS-F patients the postexercise time interval for normalization of the motor threshold was correlated with the fatigue severity. We conclude that MS patients with fatigue have an impairment of inhibitory circuits in their primary motor cortex. The results also indicate that fatigue severity is associated with an exercise-induced reduction of membrane excitability.

Adult↗

[Development and validation of assessment instruments for shared decision making].

The German Ministry for Health and Social Security is funding ten projects to introduce shared decision making into clinical practice. The medical problems the projects are focussing on were chosen from among various diseases (e. g. depression, multiple sclerosis, cancer). The ten projects achieved consensus on a core set of instruments for the measurement of process and outcome of the shared decision making. Instruments developed in German-speaking countries are currently not available. Thus, linguistic and cultural validation had to be performed for the core set instruments. The results of the data analysis as well as patient interviews demonstrate the need for improving these instruments. Therefore, the members of the methodological working group concentrated on the integration of these results in a new instrument. In a first step the construct of "shared decision making" was defined, followed by a definition of the process elements characterising shared decision making. Thereafter, items were developed on the basis of the process elements. The new instrument will now be validated for different diseases.

Decision Making↗

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

Steroid treatment for relapses in multiple sclerosis - the evidence urges shared decision-making.

OBJECTIVES: Therapy of acute relapses in multiple sclerosis with corticosteroids (CC) remains uncertain with respect to route, dosage and effectiveness. This makes the treatment of relapses a clinical field where 'shared decision-making (SDM)' could be of advantage for the patients. A prerequisite for SDM is the provision of evidence-based information for the patients. The British General Medical Council (GMC) has published ethical guidelines on seeking patients' consent for medical interventions, formulating topics of information patients need in order to make an informed treatment decision. METHODS: Medical databases were searched for evidence on the treatment of acute relapses with CC. RESULTS: The available evidence on relapse treatment is ambiguous and weak. It does not provide enough evidence to sufficiently inform patients following the topics formulated by the GMC. CONCLUSION: Good evidence is lacking, supporting the concept of SDM in the therapy of relapses.

Adrenal Cortex Hormones↗

Delivering the diagnosis of MS--results of a survey among patients and neurologists.

OBJECTIVES: 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. METHODS: A standardized questionnaire was sent out through the patients' self-help organization in Hamburg, Germany and to all neurologists. RESULTS: 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. CONCLUSION: From the patients' perspective, information about the diagnosis of MS should be more straightforward, and more information about therapies should be provided.

Adolescent↗

Collateral circulation is an independent radiological predictor of outcome after thrombolysis in acute ischaemic stroke.

We tested the hypothesis that the type of vascular occlusion, recanalisation and collateralisation are predictive of outcome after thrombolytic therapy in acute ischaemic stroke. We carried out angiography and local intra-arterial (97) or systemic (14) thrombolysis within 6 h of the onset in patients with an ischaemic stroke in the territory of the internal carotid artery. Early ischaemic signs (EIS) on pretreatment CT and angiographic findings were classified and analysed in relation to clinical outcome at 3 months. A favourable outcome (Barthel index [BI]>/= 90) was found in 40% of patients with an occlusion of the middle cerebral artery trunk whereas intracranial occlusion of the internal carotid artery ("carotid T occlusion") was followed by death or severe disability (BI<50) in 87%. Significant univariate predictors of favourable outcome were occlusion type ( P<0.01), recanalisation ( P<0.01) and collateralisation ( P<0.01). However, multivariate analysis revealed a significant relationship only between collateralisation and favourable outcome (odds ratio 5.9, 95% confidence interval 1.3-26.7, P=0.02). EIS were not predictive in either case. Occlusion type and recanalisation, are related to outcome only if adequate collateralisation prevents infarction until recanalisation occurs.

Acute Disease↗

Visual recovery in a man with the rare combination of mtDNA 11778 LHON mutation and a MS-like disease after mitoxantrone therapy.

We describe a young man with prognostic unfavourable homoplasmatic mitochondrial DNA(mt DNA) 11778 Leber's hereditary optic neuropathy (LHON) point mutation and confirmed multiple sclerosis (MS). This combination of LHON and MS-like disease is rare in both sexes, and in men has been described in only a few case reports. In a 4-year follow-up during immunosuppressive therapy with mitoxantrone, we found a remarkable time delayed visual recovery 12 months after acute onset of rapid sequential bilateral subtotal visual loss followed by episodes of isolated acute demyelinative optic neuropathy. Visual recovery to such extent after this latency is uncommon in both mtDNA 11778 LHON mutation and optic neuritis (ON) in MS. Relapses in visual deterioration must be considered as extremely rare in LHON. This case might support the hypothesis of an immunological pathogenetic factor in combined LHON and MS, and possibly in LHON alone. We suggest a search for the LHON mutation in MS patients with predominant visual impairment, independent of patients' gender.

Adolescent↗

Failure of ondansetron in treating cerebellar tremor in MS patients--an open-label pilot study.

Cerebellar tremor is a frequent and disabling symptom in multiple sclerosis (MS) patients. Supportive pharmacological treatment with different drugs showed only minor effects in a few studies and in clinical practice. Encouraged by previous studies with ondansetron, a 5HT3-antagonist, we conducted a small open-label, prospective and controlled study with 14 MS patients suffering predominantly from cerebellar tremor of the upper extremities. Principal outcome measure to evaluate a functional improvement of the single intravenous administered ondansetron injection was the subject performance in the 9-hole-peg-test (9HPT) and 3 blind assessed upper extremity writing and copying tasks. We neither found significant improvement in the upper extremity tests nor in the subjective response of the patients. In conclusion we could not confirm a beneficial effect of ondansetron on cerebellar tremor of MS patients.

Adult↗

Disease specific quality of life instruments in multiple sclerosis: validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS).

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.

Adult↗

IL-1ra serum levels in disease stages of MS--a marker for progression?

Interleukin-1 (IL-1) is one of the major proinflammatory cytokines expressed consistently in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1ra) is the only known naturally occurring specific antagonistic cytokine counteracting IL-1. Thus IL-1ra may have a downregulating potential in the disease course of MS. We analysed if circulating IL-1ra could be associated with different disease stages of MS in sera of 84 MS patients and 18 controls. IL-1ra showed considerable variations in MS patients and controls. Nevertheless we found significantly elevated serum levels in active as well as in stable disease stages compared to controls. IL-1ra levels were higher in progressive disease courses compared to relapsing-remitting MS, but not statistically significant (median: 516 versus 434 pg/ml). Further analysis with larger groups of patients and longitudinal studies will clarify if IL-1ra is useful as a prognostic serum marker in MS.

Adult↗

CD95-mediated apoptosis and DNA fragmentation in MS.

OBJECTIVE: To investigate possible associations of soluble CD95 (sCD95) serum levels and DNA defragmentation with different MS disease stages and activities. METHODS: Sera of 114 patients were analysed by an ELISA technique for sCD95. In a subgroup of 18 relapsing-remitting MS patients and controls we studied DNA fragmentation by the TUNEL-method in CSF cytospins. RESULTS: sCD95 was detectable in sera of MS patients, healthy controls and meningitis patients without significant differences. CSF specimens showed modest amounts of apoptotic cells in MS and controls. CONCLUSION: We could not demonstrate an association of MS disease course or activity with the expression of sCD95 in sera. DNA fragmentation in the CSF was not significantly enhanced compared to controls. Thus the analysed markers of programmed cell death appear not suitable to monitor MS disease courses.

Adult↗

Current status of multiple sclerosis therapy in Germany: a national survey.

We conducted a semi-standardized enquiry concerning diagnostic, immunotherapeutic and supportive care strategies for multiple sclerosis (MS). A questionnaire was sent to all German neurological departments in December 1996, with 63% (n = 244) responding before May 1997. As might be expected, MS therapy in Germany is not very standardized. Most clinics use intravenous steroids for treating relapses, although with different dosing regimens. Nevertheless, oral steroids are also used. Interferon-beta and azathioprine are both used for the treatment of relapsing-remitting MS at the same frequency. Only 33% of German neurological departments said that they used an immunomodulating agent for chronic-progressive cases, indicating it in about 50% of cases. Azathioprine is the drug of first choice, followed by methotrexate. Regarding supportive care measures, the technique of intermittent self-catheterization is widely under-represented. Despite the lack of conclusive evidence from prospective studies for the value of azathioprine, it is still one of the most commonly used drugs for the treatment of relapsing-remitting and chronic-progressive MS. There was no evidence of a consensus on treatment standards for chronic-progressive disease courses.

Adjuvants, Immunologic↗