Grading of neuropathology in multiple system atrophy: Proposal for a novel scale
Grading of neuropathology in multiple system atrophy: Proposal for a novel scale
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DOI：
10.1002/mds.20537
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发表时间：
2005-08-01
影响因子：
8.6
通讯作者：
Wenning, GK
中科院分区：
文献类型：
--
作者：
Jellinger, KA;Seppi, K;Wenning, GK
多系统萎缩（MSA）是一种老年散发性进行性突触核病，临床病理分为两种亚型：以帕金森病为主要特征的MSA- p（纹状核变性[SND]）和以小脑共济失调为主要特征的MSA- c （olivopontocerebellar atrophy [OPCA]）。我们提出了一种新的形态学分级系统，用于比较两种亚型的病变强度及其可能的临床有效性。根据纹状体、白球、黑质、脑桥基底、小脑和下橄榄的神经元丢失、星形胶质增生和a-突触核蛋白阳性胶质细胞质包裹体（GCI）的半定量评估，将42例MSA尸检病例分为4个等级（SND 0-III和OPCA 0-III）。尽管最近的分级系统仅限于SND，反映了疾病进展和多巴反应性，但SND和OPCA之间的形态学组合存在相当大的差异，只有大约一半的OPCA II（中度）和III（严重）的病例显示两种类型的级别相当，而OPCA 0和I（没有或很少退变）合并了所有级别的SND。22例显示OPCA 0 + SND II (n = 3), OPCA I + SND I-II (n = 11), OPCA I + SND III （n = 8）被归类为纯粹或显性SND，与MSA-P一致。20例出现OPCA II + SND II/III （n = 7）和OPCA III + SND III （n = 13）为显性OPCA，与MSA-C一致。MSA-P的平均发病年龄高于MSA-C（55.1岁比50.5岁），但MSA-P的平均病程较短（5.3年比6.7年）。MSA-P组主要表现为帕金森病，而MSA-C组主要表现为步态障碍（14比1，P < 0.001）。在临床关键症状中，帕金森症状多于小脑体征；MSA-C则相反（P < 0.01），而其他症状（自主神经/尿功能衰竭）无差异。即使OPCA与SND相关，MSA-C中帕金森病也不常见，提示小脑系统受累的掩蔽效应。高终末Hoehn和Yahr期在MSA-P组多见（P < 0.01），部分患者有良好至中度的左旋多巴初始反应。虽然MSA- p和-C的形态学分级与两种类型的初始症状和临床关键特征有很好的相关性，但需要进一步的前瞻性研究来验证MSA分级量表在未来干预研究中的临床实用性。(c) 2005年运动障碍协会。
Multiple system atrophy (MSA), a sporadic progressive synucleinopathy of advanced age, is separated into two clinic opathological subtypes: MSA-P (striatonigral degeneration [SND]) with predominant parkinsonian features and MSA-C (olivopontocerebellar atrophy [OPCA]) with predominant cerebellar ataxia. We propose a novel morphological grading system for both subtypes to compare lesion intensities and their possible clinical validity. Forty-two autopsy cases of MSA were separated into four grades (SND 0-III and OPCA 0-III) based on semiquantitative assessment of neuronal loss, astrogliosis, and presence of a-synuclein-positive glial cytoplasmic inclusions (GCI) in striaturn, globus pallidus, substantia nigra, pontine basis, cerebellum, and inferior olives. Whereas a recent grading system restricted to SND reflected disease progression and dopa-responsiveness, there was considerable variation in the morphological combination between SND and OPCA, with only around half the cases with OPCA II (moderate) and III (severe) showing comparable grades of both types, whereas OPCA 0 and I (no or little degeneration) was combined with all grades of SND. Twenty-two cases showing OPCA 0 + SND II (n = 3), OPCA I + SND I-II (n = 11), and OPCA I + SND III (n 8) were classified as pure or predominant SND, consistent with MSA-P. Twenty cases showing OPCA II + SND II/III (n = 7) and OPCA III + SND III (n = 13) were classified as predominant OPCA, consistent with MSA-C. In MSA-P, the mean age of onset was higher than it was in MSA-C (55.1 vs. 50.5 years), but the mean duration of illness was shorter in MSA-P (5.3 vs. 6.7 years). Presenting symptoms in MSA-P were mainly parkinsonism, whereas in MSA-C they were mainly gait disorders (14 vs. 1; P < 0.001). Among clinical key symptoms, parkinsonism was more frequent than were cerebellar signs in MSA-P; in MSA-C it was the reverse (P < 0.01), whereas other symptoms (autonomic/ urinary failure) showed no differences. Parkinsonism was infrequent in MSA-C even when OPCA was associated with SND, suggesting a masking effect by cerebellar system involvement. High terminal Hoehn and Yahr stages were more frequent in MSA-P (P < 0.01), some with good-to-moderate initial levodopa (L-dopa) response. Although the proposed morphological grading of both MSA-P and -C correlates well with initial symptoms and clinical key features of both types, further prospective studies are required to validate the clinical utility of the proposed MSA grading scales for future intervention studies. (c) 2005 Movement Disorder Society.