JUNIO 2000




Tratamiento de la Esclerosis Múltiple


Neurologia 1999 Dec;14 Suppl 6:1-12 
[Treatment of multiple sclerosis]. 
[Article in Spanish] 
Fernandez Uria D 
Servicio de Neurologia, Hospital San Agustin, Aviles, Asturias. 
In recent years there have been important advances in the treatment of multiple sclerosis (MS), on the demonstration that specific therapies may modify the long term evolution of this disease. There is however still no treatment which definitively stops its evolution and thus there are numerous ongoing studies searching for new therapeutic options. For the acute phase of this disease there is generalized consensus on the use of corticoids. Nonetheless it is not unanimous as to the type, dose or therapeutic schedule of these drugs although the most commonly used drug at present is intravenous methylprednisolone. To prevent the evolution of remittent MS beta interferon is considered as the treatment of choice. However there are questions as to which cases would benefit most and when it should be used in addition to the type of beta interferon, the dose and the route of administration, etc. A possible alternative may be the use of copolimere-1 or azathioprine. The use of interferon beta 1-b has recently been shown to be useful in the secondarily progressive forms of MS. Up to the present the therapies used for primarily progressive MS have been deceiving since no drug has shown clear benefits despite their side effects. In cases of rapid evolution mitozantrone, methotrexate or cyclophosphamide may be considered (with periodic maintenance schedules). Current studies are aimed at: a) combining different treatments which have shown partial effects when used separately, b) searching for immunomodulators which are more specific than indiscriminated immunosuppression, or c) finding therapies promoting remyelinization. The symptomatic, pharmacologic or rehabilitation treatment continue to be fundamental in the quality of life of patients with MS. 
Publication Types: 
· Review 

Neurology 1999 Nov 10;53(8):1622-7 
Multiple sclerosis: side effects of interferon beta therapy and their management. 
Walther EU, Hohlfeld R 
Department of Neurology and Institute for Clinical Neuroimmunology, Munich, Germany. 
Article abstract-Interferon beta (IFNbeta) reduces the relapse rate, disease activity as measured by serial MRI scanning, and disease progression of MS. Therapy with IFNbeta may be associated with a number of adverse reactions. Relatively frequent side effects include flu-like symptoms, transient laboratory abnormalities, menstrual disorders, and increased spasticity. Dermal injection site reactions occur after subcutaneous application of IFNbeta-1b and IFNbeta-1a. Possible side effects of IFNbeta include various autoimmune reactions, capillary leak syndrome, anaphylactic shock, thrombotic-thrombocytopenic purpura, insomnia, headache, alopecia, and depression. We discuss the mechanisms and management of the different side effects of IFNbeta. 
Publication Types: 
· Review 

Curr Opin Neurol 1999 Jun;12(3):279-93 
Treatment of multiple sclerosis: recent trials and future perspectives. 
Noseworthy JH, Gold R, Hartung HP 
Department of Neurology, Mayo Clinic Foundation, Rochester, Minnesota, USA. 
In the past year, further evidence establishing the usefulness of beta interferons and glatiramer in the treatment of relapsing-remitting multiple sclerosis has been advanced. Interferon-beta-1b was also shown to be efficacious in secondary progressive multiple sclerosis. This and other trials of symptomatic treatments are reviewed. Based on an appraisal of recent experimental studies, future promising approaches to intervene in the chain of immunopathogenetic events are discussed.  

Publication Types: 
· Review 

Arch Neurol 1999 Sep;56(9):1079-84 
Disease-modifying drugs for relapsing-remitting multiple sclerosis and future directions for multiple sclerosis therapeutics. 
Rudick RA 
Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology, Cleveland Clinic Foundation, Ohio 44106, USA. 
With the development of effective therapies for multiple sclerosis (MS), therapeutic nihilism, which was so prevalent just 10 years ago, has given way to exuberance and optimism. The current mood is understandable because MS is such a devastating disease. Within 10 years of symptom onset, 50% of patients with MS are unable to carry out household and employment responsibilities; within 15 to 20 years, 50% are unable to walk unassisted; and within 25 years, 50% are unable to walk at all. The average annual cost of MS in the United States has been estimated at greater than $6.8 billion, or $34 103 per person. This review summarizes evidence that disease-modifying drugs can significantly improve the course of patients with relapsing-remitting MS (RRMS) and frames key issues relating to the use of current drugs. Major issues confronting experimental MS therapeutics are discussed. 
Publication Types: 
· Review 

Medicina (B Aires) 1999;59(3):287-92 
[Autotransplantation of hematopoietic progenitor cells in multiple sclerosis]. 
[Article in Spanish] 
Fernandez J, Correale J, Campestri R, Koziner B 
Unidades de Trasplante de Medula Osea, CEMIC (Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno), Buenos Aires. 
Multiple sclerosis (MS) is an autoimmune demyelinating disease exhibiting great clinical variability. For control of its primary and secondary progressive variants, treatment has met with limited success. In recent years, increasing experience has been gained with the administration of high dose chemotherapy supported by the autologous infusion of hematopoietic progenitor cells (HPC), in some instances depleted of T cells. The European and International Registry of Hematopoietic Cell Transplantation for Autoimmune Diseases include 43 MS patients. BEAM was the most frequently used conditioning therapy. Treatment related mortality was 7%. The actuarial disease free survival and the overall projected survival at 38 months were 85% and 90% respectively. The inclusion of an increasing number of MS patients into these treatment programs and the growing submission of cases to the Registries will provide useful information to determine if the initial enthusiasm generated by this approach for the control of primary and secondary progressive forms of MS is justified. 
Publication Types: 
· Review 

Arch Neurol 1999 Mar;56(3):277-80 
Multiple sclerosis: therapeutic update. 
Tselis AC, Lisak RP 
Department of Neurology, Wayne State University School of Medicine, Detroit Medical Center, Mich, USA. 
Therapy for multiple sclerosis (MS) is undergoing rapid changes. We discuss recent developments in the therapy of MS, failures as well as successes, and consider some newer approaches. Multiple sclerosis, a multifocal, initially remitting-relapsing, and in some cases primarily progressive, inflammatory central nervous system immune-mediated demyelinating disease, with some axonal involvement, is currently the most common disabling neurologic disease of young people in North America and Europe. Although much is known about the pathogenesis, there is no cure and the disease must be managed long-term. Recently, there have been a number of advances in the treatment of MS. 
Publication Types: 
· Review 

Arch Neurol 1998 Dec;55(12):1578-80
Interferons in the treatment of multiple sclerosis: do they prevent the progression of the disease? 
Rice G, Ebers G 
Department of Clinical Neurological Sciences, University of Western Ontario, University Hospital, London, Canada. 
Publication Types: 
· Review 
· Review, tutorial 
· Comment in: Arch Neurol 1998 Dec;55(12):1581-3 

Neurology 1998 Dec;51(6 Suppl 5):S25-9 
Intravenous immunoglobulins in multiple sclerosis. 
Lisak RP 
Department of Neurology, Wayne State University School of Medicine, Detroit Medical Center, Michigan, USA. 
The spectrum of diseases being treated with intravenous immunoglobulins (IVIg) appears to be ever broadening, including use in neurologic diseases. After a period of anectodal reports and smaller uncontrolled series, recently there have been several randomized, prospective, double-blind, placebo-controlled studies employing IVIg in patients with relapsing remitting (RR) multiple sclerosis (MS). Reduction in relapse rate and some evidence of decreased MRI activity has been reported, but to date no effect on disability or MRI lesion burden has been noted. Because of differences in methodologic design and patient populations, as well as the relatively small number of patients in some of these studies, a rigorous direct comparison of efficacy with the type I interferons and glatiramer acetate is not possible. Given these data and the high cost of IVIg, routine use of this mode of therapy cannot be recommended, certainly not as a first-line treatment. Larger studies would clearly be helpful. At present there is no evidence to support the use of IVIg in secondary progressive (SP) or primary progressive (PP) MS. 
Publication Types: 
· Review 

Neurology 1998 Sep;51(3):682-9 
Interferon beta in the treatment of multiple sclerosis: mechanisms of action. 
Yong VW, Chabot S, Stuve O, Williams G 
Department of Oncology and Clinical Neurosciences, Faculty of Medicine, University of Calgary, Alberta, Canada. 
Interferon beta (IFN-beta) has been shown in several clinical trials to have efficacy in MS. Its mechanism of action, however, remains unclear. In this review, several biological activities of IFN-beta are highlighted, including its inhibitory effects on proliferation of leukocytes and antigen presentation. Furthermore, IFN-beta may modulate the profile of cytokine production toward that of the anti-inflammatory phenotype, and this appears to occur in the systemic circulation and within the CNS. Finally, IFN-beta can reduce T-cell migration by inhibiting the activity of T-cell matrix metalloproteinases. These activities are likely to act in concert to account for the mechanism of IFN-beta in MS. 
Publication Types: 
· Review 

Neurologia 1998 Apr;13(4):162-5 
New and old treatments for multiple sclerosis. 
Palace J 
Publication Types: 
· Editorial 
· Review 

Neurology 1997 Apr;48(4):832-5 
Clinical safety of serial monthly administrations of gadopentetate dimeglumine in patients with multiple sclerosis: implications for natural history and early-phase treatment trials. 
Tresley RM, Stone LA, Fields N, Maloni H, McFarland H, Frank JA 
National Institutes of Health, Bethesda, MD 20892-1074, USA. 
Serial contrast magnetic resonance imaging (MRI) has played an increasingly important role in understanding natural-history and early-treatment trials of multiple sclerosis patients. The purpose of this study is to determine whether the serial administration of gadopentetate dimeglumine at the conventional dose has any demonstrable effect on routine hematologic or serum chemistries. This study followed 56 patients with multiple sclerosis in a longitudinal natural-history trial using contrast-enhanced MRI scans over a four-year period between 1988 and 1993. Patients received between 3 and 53 doses of gadopentetate dimeglumine at 0.1 mmol/kg intravenously. A retrospective review of regular blood screening tests over this period identified no significant effect either on routine hematologic studies, as defined by complete blood count (hemoglobin, hematocrit, platelet and white blood cell counts, and mean corpuscular volume); standard serum chemistry studies, including electrolytes (sodium, potassium, chloride) and renal and liver function tests; or serum iron profiles. We conclude, therefore, that serial contrast-enhanced MRIs can be used safely as an outcome measure for Phase I/II evaluations of new therapies for multiple sclerosis. 

Rev Neurol 1997 Feb;25(138):267-9 
[Interferons in multiple sclerosis]. 
[Article in Spanish] 
Tintore M 
Unidad de Esclerosis Multiple, Hospital General Universitari Vall d'Hebron, Barcelona, Espana. 
Publication Types: 
· Review 

J Neurol 1996 Aug;243(8):559-65 
Multiple sclerosis: symptomatic treatment. 
Thompson AJ 
Department of Clinical Neurology, National Hospital for Neurology and Neurosurgery, London, UK. 
Reports of new therapeutic agents designed to suppress inflammatory processes in multiple sclerosis have excited much interest but, thus far, have had little influence on symptoms, disability and handicap in patients. The clinical application of recent advances in physical, pharmacological and surgical approaches to management will, at least in the medium-term future, therefore offer significantly greater opportunities for improving the quality of life of patients with multiple sclerosis. Here, symptomatic treatment of the whole range of difficulties encountered by patients with multiple sclerosis is reviewed in the context of the multidisciplinary strategy crucial to an optimal outcome. 
Publication Types: 
· Review 

Rev Neurol 1996 Jun;24(130):708-11 
[New treatments for multiple sclerosis]. 
[Article in Spanish] 
Masdeu JC 
Catedratico de Neurologia New York Medical College, New York, USA. 
Publication Types: 
· Review 

Neurology 1996 Jan;46(1):12-8 
Management of patients receiving interferon beta-1b for multiple sclerosis: report of a consensus conference. 
Lublin FD, Whitaker JN, Eidelman BH, Miller AE, Arnason BG, Burks JS 
Department of Neurology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107-5083, USA. 
Results of a double-blind, placebo-controlled study in ambulatory patients with relapsing-remitting MS showed that interferon beta-1b reduced the rate of exacerbations by one-third compared with placebo and limited new disease activity in the brain as evidenced by MRI. Interferon beta-1b, administered subcutaneously at a dosage of 0.25 mg (8 million IU) every other day is indicated for the treatment of ambulatory patients with relapsing-remitting MS. Interferon beta-1b may help a wider range of patients, but it should be prescribed only for patients with a diagnosis of clinically definite or laboratory-supported definite MS. The decision to treat a patient with interferon beta-1b should be individualized; that is, based on each patient's clinical presentation and course of MS. The most common adverse effects include (1) injection-site reactions and (2) flu-like symptoms, which are generally manageable and usually abate after the first few months of treatment. Spasticity may increase. Patients with severe depression or suicidal ideation should be monitored carefully, and symptomatic treatment should be pursued. Interferon beta-1b is contraindicated in pregnant and nursing women. Interferon beta-1b is effective in reducing the progression of total disease burden as seen on MRI in patients with MS. Its use is relatively straightforward and generally does not require alteration in the symptomatic treatment of MS. Patient education and support remain the mainstays of maintaining compliance through the early phases of therapy. 
Publication Types: 
· Consensus development conference 
· Review 

Rev Neurol 1995 Sep-Oct;23(123):986-90 
[Has it been indicated already to use beta-interferon in patients with multiple sclerosis]? 
[Article in Spanish] 
Fernandez O 
Publication Types: 
· Review 

Neurol Clin 1995 Feb;13(1):173-96 
Published erratum appears in Neurol Clin 1995 May;13(2):following table of contents 
Therapy for multiple sclerosis. 
Weiner HL, Hohol MJ, Khoury SJ, Dawson DM, Hafler DA 
Multiple Sclerosis Unit, Brigham and Women's Hospital, Boston, Massachusetts, USA. 
Multiple sclerosis is hypothesized to be a cell-mediated autoimmune disease directed against central nervous system myelin.Immunotherapy is directed at decreasing the autoimmune response using both specific and nonspecific modulation of the immune system in an attempt to halt accumulation of disability. Symptomatic therapy may also help multiple sclerosis patients. 
Publication Types: 
· Review 

Rev Neurol (Paris) 1993;149(6-7):373-84 
[Immunology of multiple sclerosis. Recent data and therapeutic perspectives]. 
[Article in French] 
Tourbah A, Fontaine B, Lyon-Caen O 
Service de Neurologie et de Neuropsychologie, Hopital de la Salpetriere, Paris. 
Numerous immune abnormalities have been described in multiple sclerosis, including dysfunction of humoral, cellular and non specific immunity. The main abnormality probably concerns suppressive T cell function. The decrease of this function could explain the breakdown of immunological tolerance towards myelin antigens. The primary responsibility of these abnormalities in the triggering of the disease has still to be demonstrated. Moreover, the antigenic target of immune dysfunction has not yet been determined. A better understanding of T cell traffic into the central nervous system and of the mechanisms of interactions
between the T cells and the antigen on one hand, the T cells and the cells presenting antigen on the other hand, offer encouraging therapeutic possibilities. 
Publication Types: 
· Review 

Neurology 1991 Jul;41(7):980-5 
Published erratum appears in Neurology 1992 Jan;42(1):266 
The use of immunosuppressive agents in the treatment of multiple sclerosis: a critical review. 
Goodin DS 
Department of Neurology, University of California, San Francisco 94143. 
Publication Types: 
· Review





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