Multiple Sclerosis: Rieckmann P

Anonymous00013, Wiendl H, Toyka KV, Rieckmann P, Gold R, Hartung HP, Hohlfeld R. · Department of Neurology and Clinical Research, Unit for MS and Neuroimmunology, University of Würzburg, Würzburg, Germany. · J Neurol. · Pubmed #19005625 No free full text.

Abstract: This review updates and extends earlier Consensus Reports related to current basic and escalating immunomodulatory treatments in multiple sclerosis (MS). The recent literature has been extracted for new evidence from randomized controlled trials, open treatment studies and reported expert opinion, both in original articles and reviews, and evaluates indications and safety issues based on published data. After data extraction from published full length publications and critically weighing the evidence and potential impact of the data, the review has been drafted and circulated within the National MS Societies and the European MS Platform to reach consensus within a very large group of European experts, combining evidence-based criteria and expert opinion where evidence is still incomplete. The review also outlines a few areas of controversy and delineates the need for future research.

Anonymous00215, Rieckmann P. · No affiliation provided · Nervenarzt. · Pubmed #17136556 No free full text.

Abstract: The updated recommendations presented here reflect new developments in the diagnostic work-up and immunotherapy of multiple sclerosis (MS) as well as optimization of medical care for MS patients. Monoclonal antibodies provide considerable improvement of treatment, but their use in basic therapy is restricted by their side effect profile. Thus, for the time being, natalizumab is only approved for monotherapy after basic treatment has failed or for rapidly progressive relapsing-remitting MS. In contrast, long-term data on recombinant beta-interferons and glatiramer acetate (Copaxone) show that even after several years no unexpected side effects occur and that a prolonged therapeutic effect can be assumed which correlates with the dose or frequency of treatment. Recently IFN-beta1b (Betaferon) was approved for prophylactic treatment after the first attack (clinically isolated syndrome, CIS). During treatment with beta-interferons, neutralizing antibodies can emerge with possible loss of effectivity. In contrast, antibodies play no role in treatment with glatiramer acetate. During or after therapy with mitoxantrone, serious side effects (cardiomyopathy, acute myeloid leukemia) appeared in 0.2-0.4% of cases. Plasmapheresis is limited to individual curative attempts in escalating therapy of a severe attack. According to the revised McDonald criteria, the diagnosis of MS can be made as early as the occurrence of the first attack (CIS). Recommendations for optimized care of MS patients are also new, thus implementing a resolution of the European Parliament.

Rieckmann P, Toyka KV. · Klinische Forschungsgruppe für Multiple Sklerose und Neuroimmunologie, Neurologische Universitätsklinik, Würzburg, Deutschland. · Eur Neurol. · Pubmed #10529535 No free full text.

Abstract: The promising results of several multicenter studies during the last few years have improved the immunomodulatory treatment of multiple sclerosis (MS). The different compounds tested were shown to reduce the number of relapses and to modulate the course of disease to various extents. The transition of the results obtained in therapeutic trials into daily clinical practice is often delayed or even hampered by monetary restrictions or reluctance of the medical community to adjust their approach to new treatments. After an initial inquiry had shown that less than 50% of eligible patients received any active immunomodulating treatment, a consensus group of Austrian, German and Swiss MS societies was formed in order to prepare a report of the current treatment options in MS. The aim of this report is to present the consensus on a new concept of escalating immunotherapy in MS. Future updates of the report are planned on a yearly basis or whenever substantial new evidence becomes available.

Rieckmann P. · Department of Medicine, University of British Columbia, Vancouver, Canada. · J Neurol Sci. · Pubmed #19200866 No free full text.

Abstract: Current treatment options for first-line immunotherapy in relapsing remitting multiple sclerosis are recombinant interferon-beta and glatiramer acetate. However, these therapies are only partially effective and certain patients may fail to respond. For this reason, it is important to elaborate alternative treatment strategies. Induction or escalation strategies have demonstrated their worth in other autoimmune disorders and may also prove to be beneficial in multiple sclerosis. The current concept of escalation therapy involves switching patients who fail first-line therapy to either natalizumab or mitoxantrone, although neither of these agents has been evaluated rigorously in such patient groups. Standardised algorithms are required to monitor treatment outcome, to determine treatment failure and to structure proceeding from one level of therapy to another. In patients with severe disease activity at onset who are at risk for early accumulation of disability, induction therapy with a powerful immunosuppressant followed by maintenance therapy with glatiramer acetate or interferon-beta may be considered. Encouraging findings in this direction have been obtained for immunosuppression with alemtuzumab or mitoxantrone. In all cases, treatment decisions should be tailored to the needs and status of the individual patient and taken pragmatically after informed discussion with the patient.

Sailer M, Fazekas F, Gass A, Kappos L, Radue EW, Rieckmann P, Toyka K, Wiendl H, Bendszus M. · Neurologische Universitätsklinik, Otto-von-Guericke-Universität, Magdeburg. · Rofo. · Pubmed #18937154 No free full text.

Abstract: PURPOSE: Magnetic resonance imaging (MRI) has become a valuable tool for diagnosing and monitoring multiple sclerosis (MS). The high sensitivity for the detection of hyperintense lesions in T 2-weighted scans contributes substantially to diagnosis. The initial lesion number or lesion volume stands for an increased probability of further accumulation of lesion burden, an earlier conversion to clinically definite MS and progression of disability in the next 5 - 15 years. This diagnostic and prognostic information gained from MRI early in the disease course lead in 2001 to a revision of the diagnostic criteria. MATERIALS AND METHODS: For the first time MRI criteria were defined in addition to the clinical and paraclinical criteria using the clinical terms for dissemination with respect to space and time. In particular, the defined MRI criteria are based on lesion number and location, the appearance of new lesions and lesion enhancement using contrast agent. RESULTS: Reliable detection and description of older and new lesions in the disease course by MRI represents subclinical disease activity which can substitute the clinical confirmation of a relapse leading to an earlier diagnosis. This places importance on the assessment of the subclinical disease activity in sequential MR scans requiring a standardized and reproducible approach to minimize variability despite different MR scanners. CONCLUSION: This review provides an updated proposal for the approach and management of cranial and spinal MR scans in patients with MS. We describe the influence of variables which cannot be standardized (scanner, field strength, manufacturer and software) and outline potential pitfalls of clinical MR imaging in MS resulting from a non-standardized approach. This updated proposal for slice positioning, sequences and documentation is a result of a consensus process targeting systematic and standardized use in clinical MR evaluations of MS.

Buttmann M, Rieckmann P. · Julius-Maximilians University, Department of Neurology, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. · Expert Rev Neurother. · Pubmed #18345973 No free full text.

Abstract: Therapeutic monoclonal antibodies (mAbs) are potent new tools for a molecular targeted approach to modify the course of multiple sclerosis (MS). Besides natalizumab, which was approved in 2006, three other mAbs (alemtuzumab, rituximab and daclizumab) were successfully tested in Phase II MS trials. In this review, introductory notes on the development and systematic nomenclature of therapeutic mAbs in general, set the stage for a detailed discussion of the four mAbs mentioned. We summarize non-MS indications, expression and function of target antigens, scientific rationales for MS therapy, putative modes of action and pharmacological aspects. Particularly, we provide a critical discussion of clinical MS trials, including protocols and interim analyses of trials currently underway. The natalizumab section pays special attention to the clinical handling of safety issues and the diagnostic use of neutralizing antibodies. We finally develop a scenario for how each of the four mAbs might evolve into the market of MS therapeutics within the coming years.

Cohen BA, Rieckmann P. · Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. · Int J Clin Pract. · Pubmed #17784852 links to  free full text

Abstract: BACKGROUND: Current disease-modifying drugs (DMDs) have positively affected the treatment of relapsing-remitting multiple sclerosis (RRMS); however, the requirement for long-term injections imposes a burden on patients and may lead to reduced adherence in some cases. Furthermore, not all patients respond adequately to current DMDs, suggesting that certain patients require different therapeutic approaches. Therefore, alternative MS treatments with less invasive routes of administration and new modes of action are needed to expand the current treatment repertoire, increase patient satisfaction and adherence, and thereby improve efficacy. DISCUSSION: This review discusses the current unmet need for an orally administered treatment for RRMS, including potential benefits of this route of administration, and implications for improved treatment outcomes. Oral drugs that are currently in Phase II/III clinical development are discussed.

Buttmann M, Rieckmann P. · Julius-Maximilians University, Department of Neurology, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. · Expert Rev Neurother. · Pubmed #17341170 No free full text.

Abstract: In 1993, interferon (IFN)-beta(1b) for subcutaneous injection became the first US FDA-approved immunomodulatory treatment for multiple sclerosis, a chronic inflammatory disease of the CNS. In this review of IFN-beta(1b), we first present a short introduction to multiple sclerosis and currently available therapeutics. We then summarize current knowledge about the biochemical structure of IFN-beta(1b), as well as pharmacokinetics and pharmacodynamics, including data on putative mechanisms underlying therapeutic as well as adverse effects. Furthermore, a critical review of ongoing and recently published clinical trials investigating IFN-beta(1b) in multiple sclerosis will be provided. Main topics are: trials investigating IFN-beta(1b) after a first clinical event, at higher dosages or in comparison to once-weekly subcutaneous IFN-beta(1a) injections, 16 years of long-term follow-up, IFN-beta(1b) in Japanese patients, the role of neutralizing antibodies, biomarkers for the prediction of therapy response, IFN-beta(1b) and pregnancy, and IFN-beta(1b) treatment of children with multiple sclerosis. Finally, we discuss how novel drugs, especially monoclonal antibodies and orally administered immunosuppressants, might soon challenge the position of this well-established agent on the multiple sclerosis therapeutics market.

Rieckmann P. · Clinical Research Group for Multiple Sclerosis and Neuroimmunology, Dept. of Neurology, University of Wuerzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. · J Neurol. · Pubmed #16998761 No free full text.

Abstract: Neuroimmunological diseases often have a chronic course and a high socio-economic impact, as most of them occur in younger patients and result in progressing disability and loss of work force. Although for many conditions different treatment strategies are available no sufficient data exist to give a reasonable account on the cost effectiveness of individual therapies. Treatment decision should primarily be guided by evidence from high quality clinical studies and-if available-from direct head-to-head trials and cost-effectiveness analysis.

Rieckmann P. · Department of Neurology, University of Würzburg, Josef-Schneider Str. 11, D-97080 Würzburg, Germany. · Neurol Sci. · Pubmed #15883682 No free full text.

This publication has no abstract.

Rieckmann P, Toyka KV, Bassetti C, Beer K, Beer S, Buettner U, Chofflon M, Götschi-Fuchs M, Hess K, Kappos L, Kesselring J, Goebels N, Ludin HP, Mattle H, Schluep M, Vaney C, Baumhackl U, Berger T, Deisenhammer F, Fazekas F, Freimüller M, Kollegger H, Kristoferitsch W, Lassmann H, Markut H, Strasser-Fuchs S, Vass K, Altenkirch H, Bamborschke S, Baum K, Benecke R, Brück W, Dommasch D, Elias WG, Gass A, Gehlen W, Haas J, Haferkamp G, Hanefeld F, Hartung HP, Heesen C, Heidenreich F, Heitmann R, Hemmer B, Hense T, Hohlfeld R, Janzen RW, Japp G, Jung S, Jügelt E, Koehler J, Kölmel W, König N, Lowitzsch K, Manegold U, Melms A, Mertin J, Oschmann P, Petereit HF, Pette M, Pöhlau D, Pohl D, Poser S, Sailer M, Schmidt S, Schock G, Schulz M, Schwarz S, Seidel D, Sommer N, Stangel M, Stark E, Steinbrecher A, Tumani H, Voltz R, Weber F, Weinrich W, Weissert R, Wiendl H, Wiethölter H, Wildemann U, Zettl UK, Zipp F, Zschenderlein R, Izquierdo G, Kirjazovas A, Packauskas L, Miller D, Koncan Vracko B, Millers A, Orologas A, Panellus M, Sindic CJ, Bratic M, Svraka A, Vella NR, Stelmasiak Z, Selmaj K, Bartosik-Psujik H, Mitosek-Szewczyk K, Belniak E, Mochecka A, Bayas A, Chan A, Flachenecker P, Gold R, Kallmann B, Leussink V, Mäurer M, Ruprecht K, Stoll G, Weilbach FX, Anonymous00046. · Dept. of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. · J Neurol. · Pubmed #15592728 No free full text.

Abstract: 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.

Rieckmann P. · Clinical Research Unit for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Julius-Maximilians University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. · J Neurol. · Pubmed #15549359 No free full text.

Abstract: Multiple sclerosis (MS) is a multidimensional, chronic, neurological disease affecting young people that often interferes with their life and career plans. Patient care begins at the time of diagnosis, and particular emphasis should be placed on proper education about the variable disease course and treatment options. Clinical assessment at regular intervals using quantitative measures is recommended in order to obtain important information on the effects of disease-modifying and/or symptomatic treatment. In addition to optimising therapy, it is imperative to develop effective and properly resourced care services for MS patients that will address their complex and lifelong requirements.

Ruprecht K, Klinker E, Dintelmann T, Rieckmann P, Gold R. · Clinical Research Unit for Multiple Sclerosis and Neuroimmunology, Julius-Maximilians University, Josef-Schneider Str. 11, 97080 Würzburg, Germany. · Neurology. · Pubmed #15452303 No free full text.

Abstract: 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.

Flachenecker P, Rieckmann P. · Department of Neurology and Clinical Research Group for Neuroimmunology, Julius Maximilians Universität Würzburg, Würzburg, Germany. · Curr Opin Neurol. · Pubmed #15167058 No free full text.

Abstract: PURPOSE OF REVIEW: Economic considerations are increasingly important in the evaluation of innovative medical technologies. In the past few years, evaluations of cost and cost-effectiveness analysis became a popular topic for multiple sclerosis research. Here, we review cost-of-illness and cost-utility studies in multiple sclerosis published during the past 2 years. RECENT FINDINGS: Despite differences in methodology, several cost-of-illness studies unequivocally demonstrated that indirect costs as a result of sick leave, premature retirement or loss of income made up almost half of the overall costs, and that total costs were higher in the more advanced stages of the disease. Cost-effectiveness studies of recombinant IFN-beta preparations demonstrated a marked variability in the incremental cost per quality-adjusted life-year, with amounts ranging from Euro 28 432 to US$338 738. For glatiramer acetate and mitoxantrone, only limited data are available, but even these few studies differed in their results. SUMMARY: Health outcome studies constitute a new and emerging field of multiple sclerosis research. All studies performed so far underscore the importance of indirect cost in multiple sclerosis. However, the marked differences in cost-effectiveness studies illustrate that the method of economic modeling has considerable impact on the results of these studies, which need standardization in order to evaluate properly the economic consequences of new and expensive therapies in multiple sclerosis.

Flachenecker P, Rieckmann P. · Department of Neurology and Clinical Research Group for Neuroimmunology, Julius-Maximilians University, Würzburg, Germany. · Drugs. · Pubmed #12887260 No free full text.

Abstract: Multiple sclerosis (MS) is thought to be a chronic inflammatory disorder of the CNS. The past decade has seen the introduction of the new immunomodulatory drugs, interferon (IFN)-beta and glatiramer acetate, that have considerably improved the therapeutic options for this often disabling disease. The efficacy of these treatments in terms of reducing relapse rate and slowing progression has been proven in several large, multicentre, randomised, controlled trials. Similarly, early IFNbeta treatment of patients with clinically isolated syndromes suggestive of MS has been shown to lengthen time to conversion into definite MS. Cost-effectiveness has been questioned with the increasing use of these innovative and, therefore, costly therapies; however, modern studies with appropriate economic modelling suggest that treatment with IFNbeta may indeed be cost-effective. Since increasing disability is associated with increasing costs, stabilisation of the disease at low functional grades of disability should aim at not only improving quality of life for the individual patient, but provide for prospective cost-benefit analysis focussing on the socioeconomic aspects of MS.

Martino G, Adorini L, Rieckmann P, Hillert J, Kallmann B, Comi G, Filippi M. · Department of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. · Lancet Neurol. · Pubmed #12849335 No free full text.

Abstract: Inflammation has always been thought of as detrimental in the pathophysiology of multiple sclerosis (MS). However, emerging genetic data, magnetic-resonance-imaging studies, and immunopathological evidence challenge this simplistic view. The evidence leads to the conclusion that inflammation is tightly regulated, and that its net effect may be beneficial in MS, thus explaining some of the results from recent trials of anti-inflammatory agents. We argue that the use of anti-inflammatory drugs to treat MS may not be appropriate in all cases. Precise identification of the inflammatory pathways to be targeted in the different phases of the disease and the timing of such interventions are therefore crucial.

Rieckmann P, Toyka KV, Anonymous00266. · Neurologische Klinik, Julius-Maximilians-Universität, Josef-Schneider-Strasse 11, 97080 Würzburg. · Nervenarzt. · Pubmed #12243005 No free full text.

Abstract: This update of the consensus on escalating immunotherapy in multiple sclerosis includes for the first time also important aspects of diagnosis, documentation, and cost of disease. The application of evidence-based therapeutic recommendations as described in the first two publications of the MSTKG has already improved the treatment situation for MS patients. It appears that the positive attitude towards a more active immunomodulatory therapy also helped to improve MS therapy in general. Due to the increasing use of standardized clinical documentation, individual recommendations for the application of innovative products are now clearer for patients as well as health care providers. The study on the cost of MS performed in several European countries demonstrated that medical treatment constitutes only a small part of the total cost of MS. It was demonstrated that MS-related costs correlate almost exponentially with increasing disability. Therefore, pharmacoeconomic reasons might also speak for early, individually adjusted, and escalating immunotherapy. This would also include a stringent therapy of individual relapses aimed at a complete resolution of clinical symptoms. Recent studies focus on a possible dose-effect relation for recombinant beta-interferons. The available data suggest a possible relation, but they have to be interpreted with caution, as important issues in the design of the studies (e.g., maintenance of blinding) were not adequately addressed. Up to now, there has been no general recommendation for a differential indication of the individual licensed substances, but the different available dose regimes and modes of application allow for an individual adjustment of therapy. In addition to immunomodulatory treatment, vaccinations and their effect on the disease course are important aspects in patient care. According to recent large epidemiological studies, the recommendations have changed as the relevant immunizations with split vaccines (e.g., influenza, tetanus) are now regarded as safe and without increased risk of relapse or disease progression.

Bayas A, Hummel V, Kallmann BA, Karch C, Toyka KV, Rieckmann P. · Clinical Research Unit for Multiple Sclerosis and Neuroimmunology, Department of Neurology, University of Würzburg, Germany. · Cytokine. · Pubmed #12182839 No free full text.

Abstract: Inflammatory stimuli within the central nervous system may not only induce tissue damage but may also convey neuroprotection. It has been shown that brain derived neurotrophic factor (BDNF) is a neuroprotective candidate. Here we show that BDNF is constitutively expressed in cultured human cerebral endothelial cells (HCEC) and can further be upregulated under proinflammatory conditions. TNF-alpha treatment resulted in an increase in BDNF mRNA expression and protein levels were significantly elevated after 72 h (69+/-33%, P<0.01). Using functional assays it was demonstrated that BDNF produced by HCEC is bioactive and supports motoneuron survival. In contrast, BDNF expression was reduced by TNF-alpha in human umbilical vein endothelial cells (HUVEC). We conclude that HCEC likely to contribute to neuronal survival under physiological and inflammatory conditions.

Rieckmann P, Mäurer M. · Clinical Research Unit for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Julius-Maximilians-University, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany. · Curr Opin Neurol. · Pubmed #12045738 No free full text.

Abstract: Axonal injury in multiple sclerosis has attracted considerable interest during the past few years. It has been demonstrated in association with inflammation within active lesions, but it is also present in normal-appearing white matter. Because axonal loss appears to be responsible for persistent neurological deficits in patients with multiple sclerosis, treatment strategies to prevent damage to neurites and restore function are of paramount importance in controlling the disease process. Some of the currently available immunomodulatory therapies may also reduce axonal damage, as demonstrated using improved imaging technologies, but the precise mechanisms that could protect axons during the inflammatory attack are yet to be identified. Factors that are involved in functional impairment of axonal conduction and those elements that are responsible for direct structural damage to the axon are both potential targets for therapeutic interventions.

Rieckmann P, Smith KJ. · Dept of Neurology, Julius-Maximilians University, Würzburg, Germany. · Trends Neurosci. · Pubmed #11488295 No free full text.

This publication has no abstract.

Kiefer G, Rieckmann P. · Klinik und Poliklinik für Augenheilkunde, Julius-Maximilians-Universität Würzburg, Josef-Schneider-Strasse 11, 97080 Würzburg. · Ophthalmologe. · Pubmed #11320823 No free full text.

This publication has no abstract.

Bayas A, Rieckmann P. · Department of Neurology, University of Würzburg, Germany. · Drug Saf. · Pubmed #10672896 No free full text.

Abstract: Interferon-beta is an established therapy in relapsing-remitting multiple sclerosis. Recently, it has also been shown that interferon-beta-1b is effective in secondary progressive multiple sclerosis. However, adverse effects of interferon-beta treatment are common, particularly during the first weeks of treatment, and are a major concern. Flu-like symptoms, injection site reactions and laboratory abnormalities are the most common adverse effects, and may result in reduced compliance or even discontinuation of treatment in a number of patients. Therefore, efforts to minimise these reactions, e.g. appropriate comedication with analgesic/antipyretic drugs, use of correct preparation and injection technique and sometimes modification of the dosage of interferon-beta, are of considerable importance. This article provides an overview of the management of clinically relevant adverse effects related to treatment with interferon-beta, based on a literature review and personal experience. Essential aspects of patient information are also stressed. If these recommendations are followed, adverse effects related to interferon-beta may be substantially reduced in the majority of patients.

Cursiefen S, Flachenecker P, Rieckmann P, Toyka KV. · Neurologische Klinik und Poliklinik, Julius-Maximilians-Universität, Würzburg. · Nervenarzt. · Pubmed #10483572 No free full text.

Abstract: Mitoxantrone is an anthracenedione anti-neoplastic agent that has recently been shown to be effective in ameliorating disease activity in multiple sclerosis (MS) as indicated by clinical and MRI data. However, the role of mitoxantrone in escalating treatment of patients with frequent and severe relapses and with rapid progression of disability is less clear. In this retrospective analysis we report on 15 patients with severe relapsing-remitting (9 patients) and secondary progressive MS with superimposed exacerbations (6 patients) treated open-labeled with mitoxantrone in our Clinical Research Group from July 1994 to October 1998. Eleven of these patients (73%) were treated with azathioprine, interferon-beta-1b or cyclophosphamide before. The patients received mitoxantrone over a period of at least 12 months (19 +/- 6 months) with a single dose of 10 mg/m2 monthly for the first three months. Thereafter, infusions were repeated every 3 months (total dose 141 mg +/- 45 mg). The annual relapse rate could be significantly reduced from 3.0 +/- 1.5 in the year before therapy to 0.5 +/- 0.5 during therapy. Nine patients (60%) were stabilised, while four patients (27%) showed an improvement of disability. The treatment was well tolerated with only minor side effects. These results although retrospectively obtained confirm previous trials showing that mitoxantrone may be useful in MS patients with frequent and severe exacerbations and/or a rapidly progressive course of the disease who have had other immunomodulatory medication.

Henze T, Rieckmann P, Toyka KV, Anonymous00094. · Reha-Zentrum Nittenau, Rehabilitationszentrum fur Neurologie, Nittenau, Germany. · Eur Neurol. · Pubmed #16966832 No free full text.

Abstract: 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.

Sellebjerg F, Barnes D, Filippini G, Midgard R, Montalban X, Rieckmann P, Selmaj K, Visser LH, Sørensen PS, Anonymous00318. · Danish MS Centre, Copenhagen University Hospital, Denmark. · Eur J Neurol. · Pubmed #16324087 No free full text.

Abstract: 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.