Multifocal motor neuropathy: A retrospective study of the response to high-dose intravenous immunoglobulin (IVIg) and current perspectives for diagnosis and treatment
Centre de Référence Maladies Neuromusculaires rares Paris Est Bâtiment Babinski, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital, 75651 Paris cedex 13. Bulletin de l'Académie nationale de médecine
(Impact Factor: 0.22).
11/2007; 191(7):1395-407; discussion 1407-9.
Multifocal motor neuropathy (MMN) was first distinguished from other motor neuropathies in 1986. It is characterised by slowly progressive predominantly distal and asymmetric limb weakness and wasting that predominates in the arms, with muscle cramps and fasciculations, within an anatomical distribution of individual motor nerves. Sensory involvement is minimal or absent. The electrodiagnostic hallmark is focal motor conduction block (CB), persisting for years at atypical sites. The most typical laboratory finding is increased serum IgM autoantibody titers to the ganglioside GM1. High-dose intravenous immunoglobulin (IVIg) is currently the gold-standard treatment for MMN. To document short-term and long-term responses to IVIg, we conducted a retrospective study of 40 patients with MMN defined using ENMC Workshop criteria and treated with periodic IVIg infusions (Tégéline) between 1995 and 2003. For the short-term analysis we compared the 22 patients who had never previously received IVIg with the 18 IVIg-experienced patients. For the long-term evaluation (> 6 months), the patients were classified into four groups according to their dependence on periodic IVIg. The MRC score improved significantly in 14 (70% ; 95% CI 0.46 to 0.88) of the 20 assessable treatment-naive patients (data were missing for two patients). This rate was significantly higher than at six months in a historical group of placebo-treated patients (20%; p < 0.0001). No criteria predictive of the response were identified. At the end of follow-up (mean 2.2 +/- 2.0 years) only 8 patients (22%) in the cohort remained in remission after a good initial response to IVIg, while 25 patients (68%) were dependent on periodic IVIg infusions. This study confirms the good short-term response of MMN to IVIg but indicates that the longer-term results are variable. New therapeutic strategies are required to increase the short-term and long-term efficacy of IVIg, and to reduce reliance on this treatment.
Available from: Benoit Ben Said
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ABSTRACT: This review presents the current knowledge of the role of T cells in drug allergy manifesting as exanthematous, pustular and bullous skin diseases, collectively referred to as nonimmediate allergic drug reactions.
Both CD4+ and CD8+ T cells producing type 1 and type 2 cytokines and endowed with cytotoxic properties are involved in nonimmediate allergic drug reactions. Recent studies have confirmed that CD8+ T cells play a major role in the pathophysiology of nonimmediate allergic drug reactions, and have characterized new cytotoxic molecular pathways responsible for the severity of the bullous forms of nonimmediate allergic drug reactions.
Nonimmediate allergic drug reactions are mediated by T cells and mostly affect the skin. Nonimmediate allergic drug reactions comprise several diseases ranging from the frequent and benign maculo-papular exanthema to the severe and rare toxic epidermal necrolysis. Progress in the knowledge of the pathophysiology of nonimmediate allergic drug reactions comes from a better understanding of the mechanisms of drug recognition by T cells and from a careful analysis of the phenotype and functions of CD4+ and CD8+ T cells infiltrating the skin lesions. Recent studies have confirmed that the different clinical forms of nonimmediate allergic drug reactions are associated with distinct types of T cell-mediated skin inflammation. However, CD8+ T cells appear as major effector T cells in most of the nonimmediate allergic drug reactions. Future studies to analyze the early cellular and molecular events leading to the development of the allergic skin reaction will be helpful in order to define diagnostic and therapeutic targets.
Available from: Chafic Karam
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