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With improvements in daily living and therefore could not be considered clinically significant changes. Furthermore fluctuations in the ataxia symptoms and signs can be influenced by other factors such as stress, fatigue etc. There is therefore a need to estimate the efficacy of immunotherapy by assessing improvement in daily living. The aim of this paper was to propose guidelines for management of patients with IMCAs. Specifically, (1) we collected IMCAs cases described in published case reports and retrospective studies, and (2) we assessed the efficacy of various immunotherapies in terms of improvement of daily activity. Our study focused on GA, PCD, and GAD Abs-CA. First, we analyzed immunotherapies for GA and PCD, in both of which autoimmunity is triggered by known antigenic determinant (gluten and neoplasm,respectively). We also analyzed immunotherapies for GAD Abs-CA, in which there is no underlying condition that triggers autoimmunity. The main goals were to define the response of each subtype of IMCA to provide a rational therapeutic strategy for each subtype that could be tested.Gluten ataxia What is the first line immunotherapy?Whilst the benefits of a gluten-free diet in patients with coeliac disease and dermatitis herpetiformis have long been established [12], there are only a few studies on the effects of gluten-free diet on neurological manifestations. Most are case reports primarily concerning patients with established coeliac disease who then developed clinical neurological symptoms. Such studies described variable but overall favorable response to gluten-free diet [12]. In their systematic study on the effect of gluten-free diet in patients with GA, with or without enteropathy, Hadjivassiliou et al.Mitoma et al. Cerebellum Ataxias (2015) 2:Page 3 of[12] concluded that gluten-free diet is clinically useful in patients with GA [12]. Their study included 43 patients with GA, and 26 who adhered to the gluten-free diet showed serological evidence of elimination of antibodies (treatment group, versus 14 patients of the control group who refused the diet). In their study [12], patients of the two groups were matched at baseline for various variables (e.g., age, duration of CAs, severity of CAs). There were no significant differences in baseline performance in each ataxia test between the two groups. However, significant improvement was observed in the performance test scores (computerized finger-nose latency, hand or Nelfinavir (Mesylate) foot taping, Peg and quantitative Romberg's test) and in the subjective global clinical impression scale in the treatment group compared with the control group. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 The improvement was apparent even after excluding patients with enteropathy. The study also provided serological evidence of elimination of anti-gliadin Abs as a confirmation of strict adherence to the diet. The long-term effects of strict gluten-free diet were retrospectively examined in 371 patients with GA. Seventy four percent of these patients had mild ataxia (patient able to walk unaided), 16 had moderate ataxia (patient needs walking aid/support to walk) and 10 had severe ataxia (wheelchair bound). Strict gluten-free diet for one year (with evidence of elimination of all serological tests for gluten sensitivity) resulted in improvement of gait or stabilization in all. Improvement was most marked in the mild ataxia group. In the moderate and severe groups stabilization was the norm despite MR spectroscopic evidence of improvement of NAA/Cr of.