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Biomedical subjects

P Rieckmann

Publications and source records attributed to P Rieckmann.

At least 19 recordsLinked to original sources

Symptomatic treatment of multiple sclerosis. Multiple Sclerosis Therapy Consensus Group (MSTCG) of the German Multiple Sclerosis Society.

Besides immunomodulation and immunosuppression, the specific treatment of symptoms is an essential component of the overall management of multiple sclerosis (MS). Symptomatic treatment is aimed at the elimination or reduction of symptoms impairing the functional abilities and quality of life of the affected patients. Moreover, with symptomatic treatment the development of a secondary physical impairment due to an existing one may be avoided. Many therapeutic techniques as well as different drugs are used for the treatment of MS symptoms, but only a few of them have been investigated, especially in MS patients, and are approved by the national health authorities. Despite an overwhelming number of publications, only a few evidence-based studies exist and consensus reports are very rare, too. Therefore, it seemed necessary to develop a consensus statement on symptomatic treatment of MS comprising existing evidence-based literature as well as therapeutic experience of neurologists who have dealt with these problems over a long time. This consensus paper contains proposals for the treatment of the most common MS symptoms: disorders of motor function and coordination, of cranial nerve function, of autonomic, cognitive, and psychological functions as well as MS-related pain syndromes and epileptic seizures.

Humans↗

["Fatigue" in multiple sclerosis. Development and and validation of the "Würzburger Fatigue Inventory for MS"].

BACKGROUND: Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). Several fatigue scales have been developed, but rigorous psychometric methods have not always been applied and validation was mainly based on small numbers of patients. We therefore assembled a new fatigue scale from a set of widely used scales and assessed its psychometric properties in a large sample of MS patients. PATIENTS AND METHODS: Fatigue was assessed in 158 MS patients by four published quantitative scales: the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MS-specific Fatigue Severity Scale (MFSS), and Visual Analogue Scale. From these a new fatigue scale, the Würzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS), was assembled. It contains 17 items with values from 0 to 4. The WEIMuS scale was validated in a subgroup of 67 patients and a control group of 68 patients. RESULTS: The MFIS and FSS but not the MFSS showed high internal consistency and split-half reliability. After applying factor analysis within the scales, fairly reliable and valid items originally found in the MFIS and FSS were selected to construct the final 17-item WEIMuS scale, which showed a high degree of reliability. In the validation study, varimax rotated factor analysis extracted two main factors corresponding to both cognitive and physical fatigue. CONCLUSION: The new, two-dimensional WEIMuS showed good psychometric properties, is easy to use, and may therefore be a useful tool for the assessment of MS-associated fatigue. Multiple sclerosis patients suffer from different types of fatigue which could be attributed to cognitive and physical fatigue. Thus, MS-associated fatigue is different from common tiredness.

Adult↗

Analysis of the C/T(-1) single nucleotide polymorphism in the CD40 gene in multiple sclerosis.

The costimulatory CD40-CD40L pathway plays a critical role in the generation and maintenance of adaptive immune responses. Genetic interference of CD40-CD40L interactions strongly influences the onset and course in many autoimmune disease models including experimental autoimmune encephalomyelitis. We analysed the association of a single nucleotide polymorphism of the CD40 gene (C/T(-1)) in 287 patients with multiple sclerosis (MS) and 184 matched controls. No significant differences were found in the frequency of the C/T(-1) polymorphism between the patients with MS and the controls (53% vs 49%) or among different MS subtypes. Cell surface expression of CD40 did not differ within the different genotypes, but carriers of the T allele showed a trend for a lower stimulatory index compared with individuals with the CC genotype. Although these subtle differences indicate functional consequences in the immune stimulatory capabilities related to the CD40 C/T(-1) polymorphism, our population-based study found no association with disease susceptibility or disease course in MS.

Adolescent↗

Early abnormalities of evoked potentials and future disability in patients with multiple sclerosis.

Evoked potentials (EP) have a role in making the diagnosis of multiple sclerosis (MS) but their implication for predicting the future disease course in MS is under debate. EP data of 94 MS patients examined at first presentation, and after five and ten years were retrospectively analysed. Patients were divided into two groups in relation to the prior duration of disease at the time point of first examination: group 1 patients (n=44) were first examined within two years after disease onset, and group 2 patients (n=50) at later time points. As primary measures sum scores were calculated for abnormalities of single and combined EP (visual (VEP), somatosensory (SEP), magnetic motor evoked potentials (MEP)). In patients examined early after disease onset (group 1), a significant predictive value for abnormal EP was found with MEP and SEP sum scores at first presentation correlating significantly with Expanded Disability Status Scale (EDSS) values after five years, while the VEP sum score was not. The cumulative number of abnormal MEP, SEP and VEP results also indicated higher degrees of disability (EDSS > or = 3.5) after five years. Combined pathological SEP and MEP findings at first presentation best predicted clinical disability (EDSS > or = 3.5) after five years (odds ratio 11.0). EP data and EDSS at first presentation were not significantly linked suggesting that EP abnormalities at least in part represented clinically silent lesions not mirrored by EDSS. For patients in later disease phases (group 2), no significant associations between EP data at first presentation and EDSS at five and ten years were detected. Together with clinical findings and MR imaging, combined EP data may help to identify patients at high risk of long-term clinical deterioration and guide decisions as to immunomodulatory treatment.

Age of Onset↗

Ultrasound derived imaging and quantification of cell adhesion molecules in experimental autoimmune encephalomyelitis (EAE) by Sensitive Particle Acoustic Quantification (SPAQ).

Molecular imaging requires, not only the identification of an appropriate marker, but also its quantitative analysis. We used the Sensitive Particle Acoustic Quantification (SPAQ) technology - a novel ultrasound technique - for detection and quantification of cell adhesion molecules in isolated tissue and in live animals. By conjugating gas-filled microparticles (MPs) with antibodies to intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), we were able to depict and quantify ICAM-1 and VCAM-1 in isolated brain and spinal cord from rats with autoimmune encephalomyelitis (EAE), an established inflammatory disease model of human multiple sclerosis (MS). Depiction and quantification of specific MPs were also feasible in living animals with AT-EAE with similar results. After treatment with methylprednisolone, the measured number of targeted anti-ICAM-1 and VCAM-1-MPs was significantly lower (P<0.01) compared to untreated animals demonstrating the high sensitivity of this imaging technique. Depending on the antibody linked to the surface of the MPs, the technique can be used to quantify the expression of any accessible antigen expressed on the luminal surface of endothelial cells and is therefore a promising tool for the non-invasive and dynamic assessment of disease-related molecules.

Animals↗

[MS registry in Germany--design and first results of the pilot phase].

In the summer of 2001, a nationwide epidemiological multiple sclerosis (MS) register was initiated under the auspices of the German MS Society (DMSG). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. During the 2-year pilot phase, five MS centers with various regional differences and treatment methods participated, leading to a representative selection of patients. In December 2003, standardised data sets of 3,458 MS patients were available for evaluation. After examining the quality of the data, 3,223 sets remained for further analysis. The demographics were similar to those obtained from other epidemiological studies: 72% of the patients were female, mean age was 42.9+/-11.2 years, mean disease duration 12.6+/-8.7 years, and 64% suffered from the relapsing-remitting form of the disease. The median EDSS was 3.0, and 69% of patients had an EDSS </=4.0. The great effect of this disorder was underscored by the fact that one third of the patients had prematurely retired due to MS. After successful completion of the pilot phase, the MS register will provide reliable data and thus serve as an important tool to improve the overall situation of MS patients in Germany.

Adult↗

Impact of the Asp299Gly polymorphism in the toll-like receptor 4 (tlr-4) gene on disease course of multiple sclerosis.

In multiple sclerosis patients, infection is often associated with disease deterioration. Lipopolysaccharide (LPS) from gram-negative bacteria signals via the toll-like receptor 4 (TLR-4) pathway. Therefore, we investigated the role of an Asp299Gly mutation in the TLR-4 receptor in 890 MS patients with multiple sclerosis and 350 healthy controls. No association of different genotypes with MS susceptibility, MS subtypes, or disease severity was found. In vitro LPS stimulation studies showed a significantly lower proliferation of PBMCs from donors heterozygous for the Asp299Gly mutation in comparison to PBMCs from individuals with the wild-type genotype (p=0.01). However, these functional changes seem not to have any impact on the clinical presentation of MS patients with different TLR-4 genotypes.

Adolescent↗

The long-term safety and tolerability of high-dose interferon beta-1a in relapsing-remitting multiple sclerosis: 4-year data from the PRISMS study.

In the prevention of relapses and disability by interferon subcutaneously in multiple sclerosis (PRISMS) study, 560 patients with relapsing-remitting multiple sclerosis were randomized to receive subcutaneous interferon (IFN) beta-1a, 22 or 44 mug three times weekly, or placebo, for 2 years. Patients receiving placebo were then re-randomized to one of the two doses of IFN beta-1a for a further 2 years, whilst patients receiving active treatment continued their original treatment. Safety assessments were performed throughout the study. The most common adverse events for patients originally randomized to active treatment were injection-site inflammation (72% of patients had at least one event), headache (71%) and influenza-like symptoms (69%). These were generally mild in nature and most frequent during the first month of treatment. The 4-year adverse event profiles for the two IFN beta-1a doses were comparable with those observed during the initial phase of the study and, for the most part, with each other. There was no association between IFN beta-1a and depression or suicide/attempted suicide. The most common laboratory abnormalities were asymptomatic lymphopenia and elevated serum liver transaminase levels. These were generally mild and resolved spontaneously. Therapy with subcutaneous IFN beta-1a three times weekly for up to 4 years was well tolerated without dose-limiting safety concerns.

Adjuvants, Immunologic↗

EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.

Relapses, exacerbations or attacks of multiple sclerosis are the dominating feature of relapsing-remitting multiple sclerosis (MS), but are also observed in patients with secondary progressive MS. High-dose methylprednisolone is the routine therapy for relapses at present, but other treatments are also in current use. The objective of the task force was to review the literature on treatment of MS relapses to provide evidence-based treatment recommendations. Review was carried out on the literature with classification of evidence according to the EFNS guidelines for scientific task forces. Short-term, high-dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation). The optimal glucocorticoid treatment regimen, in terms of clinical efficacy and adverse events, remains to be established. A more intense, interdisciplinary rehabilitation programme should be considered as this probably further improves recovery after treatment with methylprednisolone (level B recommendation). Plasma exchange is probably efficacious in a subgroup of patients with severe relapses not responding to methylprednisolone therapy, and should be considered in this patient subgroup (level B recommendation). There is a need for further randomized, controlled trials in order to establish the optimal treatment regimen for relapses of MS.

Evidence-Based Medicine↗

Plasma exchange for severe optic neuritis: treatment of 10 patients.

The authors reviewed a series of 10 consecutive patients treated with plasma exchange (PE) for acute, severe optic neuritis (ON) largely unresponsive to previous high-dose IV glucocorticosteroids. PE was associated with an improvement of visual acuity according to the study criteria in 7 of 10 patients. On follow-up, three of these patients continued to improve, two remained stable, and two had worsened again. PE may be beneficial as an escalating treatment in a subset of patients with severe ON. A controlled trial is warranted.

Adult↗

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↗

Analysis of the monocyte chemoattractant protein 1 -2518 promoter polymorphism in patients with multiple sclerosis.

Cytokines and chemokines like the proinflammatory chemokine, monocytechemoattractant protein 1 (MCP-1) are important for the recruitment of inflammatory cells into multiple sclerosis (MS) lesions. Recently, a nucleotide substitution from adenosine to guanosine (A-->G) at position -2518 of the MCP-1 promoter was shown to be associated with increased MCP-1 expression. We analysed MCP-1 genotypes in 634 MS patients and 405 healthy controls. The allelic frequencies were comparable between both groups. No correlation was found between genotype and disease course, disease severity or age of disease onset. Although statistically no+ significant mRNA expression and MCP-1 secretion were elevated in patients carrying the mutant allele. Thus, our data could not reveal any association between the MCP-1 -2518 polymorphism and susceptibility to or clinical disease course of MS.

Adolescent↗

Frequent detection of Mycoplasma pneumoniae in Bell's palsy.

The cause of Bell's palsy (BP) remains unknown despite various hints to an infectious etiology. Mycoplasma pneumoniae is a common pathogen of the respiratory tract causing pharyngitis, tracheobronchitis or pneumonia. Neurological complications are the most frequent extrapulmonary manifestation. So far, only a few case reports suggested an association between cranial nerve palsy and M. pneumoniae infection. Patients with a BP who were admitted to the Department of Otorhinolaryngology or Neurology of the University of Wuerzburg between 2000 and 2002 were tested serologically for the presence of antibodies against Borrelia burgdorferi, herpes viruses (HSV-1/2, VZV) and M. pneumoniae. The diagnosis of mycoplasmal infection was made when at least one of the following criteria was met: a threefold rise or more in the titer of antibody of M. pneumoniae in paired sample or a microparticle agglutination assay (MAG) of > or =1:40 and the detection of IgA and/or IgM antibodies in the acute phase serum. Ninety-one consecutive patients could be included. Fifteen patients showed a reactivation of a VZV ( n=12) or of a HSV-1 ( n=3) infection. In six cases the immunoblot revealed specific antibody bands for B. burgdorferi. In 24 patients (26.4%) a seroconversion of M. pneumoniae could be detected. Only two patients complained of mild respiratory symptoms. According to our results, M. pneumoniae is frequently associated with Bell's palsy. Thus, a routine screening for this pathogen, even in the absence of respiratory symptoms, is necessary.

Adolescent↗

Painful vascular compression syndrome of the sciatic nerve caused by gluteal varicosities.

The authors report three patients with chronic sciatic pain without focal neurologic deficit. Sitting or lying on the affected side provoked pain, and standing and walking relieved it. MRI revealed varicotic gluteal vessels compressing the sciatic nerve. Decompression of the nerve resulted in complete and permanent pain relief. Sciatic or buttock pain in patients with varicosities and pain provocation in the sitting or lying position suggests this neurovascular compression syndrome.

Aged↗

Modulation of cytokine mRNA expression by brain-derived neurotrophic factor and nerve growth factor in human immune cells.

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) exert various effects on immune cells. Here we studied, whether they influence the cytokine expression pattern in peripheral blood mononuclear cells (PBMCs) or antigen specific T-cells. In PBMCs BDNF and NGF had interindividually variable effects on T helper cell type (Th)1- and Th2-cytokines. However, there was a high correlation between the modulating properties of these neurotrophins (r=0.97) concerning the expression of interleukin (IL) 4, transforming growth factor-beta and tumour necrosis factor-alpha mRNA at a concentration of 100 ng/ml. In myelin basic protein-specific T-cell lines BDNF and NGF increased interferon -gamma mRNA to a moderate extent, but not IL4. No major effects were detected at the cytokine protein level. In conclusion, our results suggest a partial effect of neurotrophins on immune cells, which may be modified by other signals.

Brain-Derived Neurotrophic Factor↗

Combination of serum markers related to several mechanisms in Alzheimer's disease.

Alzheimer's disease (AD) probably involves several pathobiochemical mechanisms and this may be reflected by changes in different serum components. The present study investigated whether the combined analysis of serum molecules related to different mechanisms improves the discrimination of AD patients from healthy controls. Serum of patients with AD was analyzed for a broad spectrum of marker molecules, including 11 inflammatory proteins, 12 sterol intermediates and phytosterols, 2 brain-specific proteins and 4 constituents involved in homocysteine homeostasis. The serum molecule concentrations were combined in a logistic regression model, using a forward stepwise inclusion mode. The results showed that the combination of interleukin-6 (IL-6) receptor, protein alpha1 fraction, cysteine and cholesterol concentrations improved the discrimination between AD patients and healthy controls compared to the single markers. In conclusion, the results of this study have shown that the complex pathology in AD is reflected in a pattern of altered serum concentrations of several marker molecules related to several pathobiochemical mechanisms.

Adult↗