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儿科和成人多发性硬化症:脑脊液中神经免疫反应的年龄相关差异和时间过程。

Paediatric and adult multiple sclerosis: age-related differences and time course of the neuroimmunological response in cerebrospinal fluid.

机构信息

Neurochemistry Laboratory, Department of Neurology, University Göttingen, Germany.

出版信息

Mult Scler. 2009 Dec;15(12):1466-80. doi: 10.1177/1352458509348418. Epub 2009 Dec 7.

Abstract

We investigate common pathophysiology in paediatric and adult multiple sclerosis (MS) by comparison of cerebrospinal fluid (CSF) data. We compared cerebrospinal fluid (CSF) data from eight patient groups with onset of MS at 7 to 29 years (n = 184). A new statistics program allows sensitive detection, quantifies the mean amount of intrathecal Ig synthesis in groups based on the 96% reference range of 4100 non-inflammatory controls, corrects for age-related increase of blood-derived albumin and immunoglobulins in CSF, and presents graphical data interpretation in Reibergrams. Already at onset of MS before puberty (< or =10 years) the frequency of intrathecal IgG synthesis (oligoclonal IgG) was 100% like in adults with 98%, but the amount of intrathecal IgG increases twofold during puberty. Intrathecal IgM synthesis is most frequent before and during puberty (in 57-67% of patients) compared with 41% in adults. The amount of intrathecal IgM synthesis before puberty is only 30% of that in adults. IgG and IgM Index are biased evaluations not suitable for characterizing age-related dynamics. A twofold age-related increase of the albumin quotient, Q(Alb), as a measure of the blood-CSF barrier function, represents normal physiological growth. Cell counts in CSF are low. The pre-puberty gender ratio is about 1:1. Intrathecal antibodies against measles, rubella and/or varicella zoster virus are detected in 73% of patients before puberty compared with 89% of adults. Individual paediatric patients (n = 17), with sequential punctures over 2-5 years, show constant quantities of intrathecal IgM and specific antibodies. In conclusion, paediatric MS already at first clinical manifestation shows the complete, neuroimmunological data pattern in CSF, i.e. inflammatory signs are not gradually evolving. Paediatric and adult MS differ quantitatively but not qualitatively in neuroimmunological patterns which does not allow for discrimination between 'early' and 'late' onset MS. CSF analysis may help to discriminate between acute and mono-symptomatic chronic inflammatory disease already at earliest clinical manifestation.

摘要

我们通过比较脑脊液(CSF)数据来研究儿科和成人多发性硬化症(MS)的共同病理生理学。我们比较了 7 至 29 岁发病的 8 组患者的脑脊液(CSF)数据(n=184)。一个新的统计程序可以敏感地检测到,根据 4100 名非炎症性对照的 96%参考范围,对基于组的鞘内 Ig 合成的平均值进行量化,校正 CSF 中与年龄相关的血液来源白蛋白和免疫球蛋白的增加,并以 Reibergrams 呈现图形数据解释。甚至在青春期前(<或=10 岁)多发性硬化症发作时,鞘内 IgG 合成(寡克隆 IgG)的频率就像 98%的成年人一样为 100%,但在青春期期间,鞘内 IgG 的量增加了两倍。与成年人的 41%相比,在青春期前和青春期期间,鞘内 IgM 合成最为常见(在 57-67%的患者中)。青春期前鞘内 IgM 合成的量仅为成年人的 30%。IgG 和 IgM 指数是有偏差的评估,不适合描述与年龄相关的动态变化。作为血脑屏障功能的衡量标准,白蛋白商(Q(Alb))的两倍与年龄相关的增加是正常的生理生长。CSF 中的细胞计数较低。青春期前的性别比例约为 1:1。与成年人的 89%相比,在青春期前,有 73%的患者检测到针对麻疹、风疹和/或水痘带状疱疹病毒的鞘内抗体。17 名个别儿科患者(n=17),经过 2-5 年的连续穿刺,显示鞘内 IgM 和特异性抗体的数量恒定。总之,儿科多发性硬化症在首次临床表现时已经显示出完整的、神经免疫学数据模式,即炎症迹象不是逐渐演变的。儿科和成人多发性硬化症在神经免疫学模式上存在数量上的差异,但在质量上没有差异,这使得无法区分“早期”和“晚期”多发性硬化症。CSF 分析可能有助于在最早的临床表现时,区分急性和单症状性慢性炎症性疾病。

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