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H-P Hartung

Publications and source records attributed to H-P Hartung.

At least 19 recordsLinked to original sources
PubMed2006

[Revision of McDonald's new diagnostic criteria for multiple sclerosis].

In 2001, an international panel suggested new diagnostic criteria for multiple sclerosis (MS). These criteria integrate clinical, imaging (MRI), and paraclinical results in order to facilitate diagnosis. Since then, these so-called McDonald criteria have been broadly accepted and widely propagated. In the meantime a number of publications have dealt with the sensitivity and specificity for MS diagnosis and with implementing these new criteria in clinical practice. Based on these empirical values and newer data on MS, an international expert group recently proposed a revision of the criteria. Substantial changes affect (1) MRI criteria for the dissemination of lesions over time, (2) the role of spinal cord lesions in the MRI and (3) diagnosis of primary progressive MS. In this article we present recent experiences with the McDonald and revised criteria.

Adult↗
PubMed2005

Effect of mitoxantrone on MRI in progressive MS: results of the MIMS trial.

OBJECTIVE: To evaluate the effects of mitoxantrone (Mx) in progressive multiple sclerosis (MS) on MRI. METHODS: A total of 194 patients with worsening relapsing-remitting or secondary progressive MS were treated with Mx 12 mg/m2 (n = 34), Mx 5 mg/m2 (n = 40), or placebo (n = 36) at 3-month intervals IV over a 2-year period. In preselected MRI centers unenhanced and Gd-enhanced MRI scans were performed at month (M) 0, 12, and 24 in a non-randomized subset of 110 patients and non-selected for MRI criteria. The primary MRI outcome measure was the total number of MRI scans with positive Gd enhancement per group. RESULTS: Twelve mg/m2 Mx failed to reach a significant difference from placebo as measured by the primary MRI outcome at month 12 (p = 0.431) and 24 (p = 0.065). Secondary MRI outcome measures: 5 mg/m2 Mx influenced favorably the number of Gd-enhancing lesions only at month 24 (p = 0.004), but not at month 12 (p = 0.095). Twelve mg/m2 Mx reduced the number of T2-weighted lesions at month 24 (p = 0.027) and showed a positive trend at month 12 (p = 0.069), but not 5 mg/m2 Mx. The number of active MR lesions showed a strong trend toward reduction in the 12 mg/m2 Mx group only at month 24 (p = 0.054). All comparisons are vs placebo, and unadjusted for baseline incidence. CONCLUSIONS: In the MIMS trial 12 mg/m2 Mx does not reduce the number of MRI scans with positive Gd enhancement at month 12 and 24 vs placebo. Results of secondary MRI outcome measures are suggestive of a positive impact of 12 and 5 mg/m2 Mx on some of the Gd enhanced and unenhanced MRI measures as expected from other Mx MRI studies in the past.

Adult↗
PubMed2005

[Statins for treatment of CNS diseases. Status report from research and clinical practice].

3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, "statins," are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of L-mevalonate are also involved in posttranslational modifications of specific proteins with cell proliferation and differentiation properties. Thus, statins have important biologic effects beyond their cholesterol-reducing properties. Here we discuss recent experimental and clinical data that may support a potential role for statins in the treatment of three central nervous system (CNS) neurological diseases: Multiple sclerosis (MS), Alzheimer's disease (AD), and ischemic stroke. Despite their considerable pathogenic differences, in animal models of these disorders statins have shown beneficial effects. In both stroke and AD cohort studies suggest a beneficial treatment effect in humans; in MS, results from small open-label studies look encouraging. Multicenter, randomized, placebo-controlled clinical trials are in the planning or recruiting stage to evaluate the therapeutic effects of statins in all three disorders.

Biomedical Research↗
PubMed2005

[Myopathies under therapy with lipid-lowering agents].

Myopathies ranging from myalgia to clinically asymptomatic creatine kinase (CK) elevation and to life-threatening rhabdomyolysis belong to the most important complications of lipid-lowering therapies with fibrates and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, i.e., statins. Rhabdomyolysis is a rare side effect of statin therapy with an estimated incidence of 0.2/1 million prescriptions. Myalgia and muscle cramps were reported by up to 5% of patients, but they were observed with the same percentage in controls receiving placebo. Due to increasing numbers of patients under lipid-lowering therapy, however, more and more patients present in neuromuscular units with the differential diagnosis of a fibrate- or statin-induced myopathy.

Anticholesteremic Agents↗
PubMed2005

[Blocking adhesion molecules with natalizumab in multiple sclerosis].

Natalizumab is a humanized, monoclonal antibody, that inhibits adhesion molecules (alpha(4)-integrins) on the surface of immune cells. These adhesion molecules are important for binding of lymphocytes to endothelial cells of blood vessels and infiltration of inflammatory cells into tissues. Natalizumab is currently being tested in large clinical trials for the treatment of multiple sclerosis (MS) and other autoimmune diseases (inflammatory bowel diseases, rheumatoid arthritis). After demonstrating the safety and potential effectiveness of natalizumab in MS therapy during shorter treatment periods (</=6 months) in clinical phase I and II studies, two ongoing large, double-blinded, placebo-controlled phase III trials (named AFFIRM and SENTINEL) are evaluating its efficacy for patients with relapsing-remitting MS in respect to primary clinical endpoints (relapse rate, disease progression). Based a 1-year interim analysis of these studies, natalizumab was recently authorized by the U.S. Food and Drug Administration for treatment in reducing the frequency of clinical surges in multiple sclerosis, and an application was also made for its use in Europe. After more than 2 years of combined natalizumab (Tysabri) and interferon beta-1a (Avonex) therapy in the so-called Sentinel Study, there was one unexpected death and one appearance of progressive multifocal leukoencephalopathy. As a result, in February 2005 the manufacturers (Biogen/Elan) stopped all running studies of natalizumab and removed the drug from the market. New studies are underway to gain more understanding and especially to determine the risk to patients treated in the Sentinel Study. This article summarizes and updates the results of previous and ongoing natalizumab trials in the context of MS.

Antibodies, Monoclonal↗
PubMed2005

Significance of neutralizing antibodies to interferon beta during treatment of multiple sclerosis: expert opinions based on the Proceedings of an International Consensus Conference.

On August 30, 2002, an international panel of neurologists who specialize in the treatment of multiple sclerosis (MS) was convened in Paris (France) to discuss the issue of neutralizing antibodies (NAb) to interferon beta (IFN-beta) therapy in patients with MS. The goals of this meeting were to: (i) review the most recent clinical information on NAb, (ii) come to a consensus on the clinical relevance of NAb in the management of patients with MS receiving IFN-beta therapy, and (iii) establish a framework for the development of patient management guidelines based on scientific consensus. The meeting was chaired by Hans-Peter Hartung (Heinrich-Heine University, Düsseldorf, Germany) and Huub Schellekens (Utrecht University, Utrecht, the Netherlands). This article summarizes the opinions of the expert panel on a number of key issues raised at the meeting.

Animals↗
PubMed2005

Intravenous immunoglobulins in the treatment of relapsing remitting multiple sclerosis--results of a retrospective multicenter observational study over five years.

Use of intravenous immunoglobulins (IVIG) has been recommended for treatment of RRMS if first line therapy with beta-interferon or glatiramer acetate is not tolerated, or if contraindications exist. This consensus recommendation is based on the demonstration of efficacy and tolerability of IVIG in four randomized controlled trials (RCTs). The impact of non-randomized observational trials on evidence-based recommendations for treatment is still under discussion. In order to evaluate the transferability of study results derived from RCTs into a routine practice setting, we carried out a retrospective data analysis on patients with RRMS who had been treated with IVIG during the last five years. Data sets from 308 out of 1122 screened patients were available for analysis. Treatment with IVIG resulted in a 69% reduction of the mean annual relapse rate (ARR) (calculated over two years) from 1.74+/-1.15 before IVIG treatment to 0.53+/-0.61 after start of IVIG treatment. Mean expanded disability status scale (EDSS) values remained stable throughout the observation period. The results of this observational study were similar to the results of previous RCTs with IVIG.

Adolescent↗
PubMed2004

[Jean-Martin Charcot in German neurology].

Jean-Martin Charcot (1825-1893), well known as the founder of modern neurology, was the most celebrated neurologist in the nineteenth century. His international success stemmed not only from mastery descriptions of various neurological disorders but also from his many contacts with scientists all over the world. The aim of this article is to review Charcot's ambivalent relationship to German neuropsychiatry of the time and to examine the German reception of his personality and work. Wilhelm Erb, Ludwig Hirt, Ernst von Leyden, Max Nonne, Adolph Strümpell, and other German physicians cultivated -to varying degrees - professional contacts with Charcot and, based on the fascination of his personality and significance of his work, were long and intensively influenced by the Salpêtrière school. The extent of their admiration became apparent in 1882 by the award of an honorary doctorate to Charcot by the University of Würzburg. Along with increasingly severe criticism of Charcot's research on hysteria and hypnosis, most German neuropsychiatrists became estranged, without neglecting his importance to the development of neurology in Germany.

France↗
PubMed2004

[Multiple sclerosis: potential therapeutic options and update of ongoing studies].

The therapeutic options for the treatment of multiple sclerosis (MS) have experienced enormous progress over recent years. Despite these encouraging developments, available therapies are only partially effective, and the ultimate goal of curing MS is still far from being attained. The improved understanding of the cellular and molecular mechanisms of MS (immune) pathogenesis together with recent shifts in paradigms led to a variety of new therapeutic targets and approaches. In addition to modulation of the inflammatory process, therapeutic approaches focussing on active neuroprotection, remyelinization, and regeneration have become increasingly important. Based on current concepts of the MS pathogenesis, this article summarizes new therapeutic approaches. Substances and strategies currently tested in clinical trials are reviewed.

Adjuvants, Immunologic↗
PubMed2004

[Neurological aspects of systemic rheumatological disorders].

There are a number of common aspects between rheumatology and neurology. First, many systemic rheumatic diseases also affect the central and peripheral nervous system as well as muscle causing characteristic symptom complexes. Second, there are similarities between neurological and rheumatological autoimmune diseases in terms of underlying pathomechanisms. Here the most important neurological aspects of rheumatological disorders including their diagnosis and therapy are highlighted.

Cerebrovascular Disorders↗
PubMed2004

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↗
PubMed2003

Lack of IL-6 augments inflammatory response but decreases vascular permeability in bacterial meningitis.

Interleukin (IL)-6 is a multifunctional cytokine with diverse actions and has been implicated in the pathophysiology of many neurological and inflammatory disorders. In this study, we investigated the role of IL-6 in pneumococcal meningitis. Cerebral infection in wild-type (WT) mice caused an increase in vascular permeability and intracranial pressure (ICP), which were significantly reduced in IL-6-/- mice. In contrast, meningitis in IL-6-/- mice was associated with a significant increase in CSF white blood cell count compared with infected WT mice, indicating an enhanced inflammatory response. Analysis of mRNA expression in the brain showed an increase in tumour necrosis factor (TNF)-alpha, IL-1beta, and macrophage inflammatory protein 2 (MIP-2) levels, but decreased expression of granulocyte-macrophage colony-stimulating factor in infected IL-6-/- mice compared with infected WT controls. Similar results were obtained when rats challenged with pneumococci were systemically treated with neutralizing anti-IL-6 antibodies, resulting in an increased pleocytosis but at the same time a reduction of vascular permeability, brain oedema formation, and ICP, which was not accompanied by a downregulation of matrix metalloproteinases. Our data indicate that IL-6 plays an important anti-inflammatory role in bacterial meningitis by reducing leukocyte infiltration but contributes to the rise in intracranial pressure by increasing blood-brain barrier (BBB) permeability. These findings suggest that the migration of leukocytes across the BBB and the increase in vascular permeability are two independent processes during bacterial meningitis.

Animals↗