Pranzatelli Michael R, Tate Elizabeth D, Travelstead Anna L, Baumgardner Christine A, Gowda Narayana V, Halthore Sri N, Kerstan Peter, Kossak Brian D, Mitchell Wendy G, Taub Jeffrey W
National Pediatric Myoclonus Center and Department of Neurology, SouthernIllinois University School of Medicine, Springfield, Illinois, USA.
J Child Neurol. 2009 Mar;24(3):316-22. doi: 10.1177/0883073808324217.
Opsoclonus-myoclonus syndrome is characterized by abnormal lymphocyte trafficking into brain. The authors hypothesized that mycophenolate mofetil, a lymphocyte proliferation inhibitor, might be therapeutic. The cerebrospinal fluid and blood immunophenotypes of 15 children with predominantly chronic-relapsing opsoclonus-myoclonus syndrome were compared before and after treatment by flow cytometry. Mycophenolate mofetil reduced the cerebrospinal fluid expansion of HLA-DR+ activated T cells (-40%); the frequency of other T-cell or natural killer cell subsets remained unchanged, but cerebrospinal fluid B cells increased significantly. Adrenocorticotropic hormone dose was lowered by 64% over an average of 1.5 years, yet 73% eventually relapsed despite therapeutic drug levels. Prior treatment with rituximab prevented relapse-associated increase in cerebrospinal fluid B cells, without hindering mycophenolate mofetil-induced reduction in T-cell activation. These data demonstrate resistant immunologic problems in chronic-relapsing opsoclonus-myoclonus syndrome. Mycophenolate mofetil did not prevent relapse. The novel effect of mycophenolate mofetil on chronically activated T cells may contribute to its efficacy in T-cell mediated neurological disorders.
眼阵挛-肌阵挛综合征的特征是淋巴细胞异常向脑内迁移。作者推测，淋巴细胞增殖抑制剂霉酚酸酯可能具有治疗作用。通过流式细胞术比较了15例以慢性复发性眼阵挛-肌阵挛综合征为主的儿童在治疗前后的脑脊液和血液免疫表型。霉酚酸酯减少了HLA-DR+活化T细胞在脑脊液中的扩增（-40%）；其他T细胞或自然杀伤细胞亚群的频率保持不变，但脑脊液B细胞显著增加。促肾上腺皮质激素剂量在平均1.5年的时间里降低了64%，然而，尽管药物水平处于治疗范围，仍有73%的患者最终复发。先前使用利妥昔单抗治疗可预防复发相关的脑脊液B细胞增加，且不影响霉酚酸酯诱导的T细胞活化减少。这些数据表明慢性复发性眼阵挛-肌阵挛综合征存在难治性免疫问题。霉酚酸酯不能预防复发。霉酚酸酯对慢性活化T细胞的新作用可能有助于其在T细胞介导的神经系统疾病中的疗效。
