The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations
The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations
复制标题
DOI：
10.1093/brain/awh303
复制
发表时间：
2004-12-01
期刊：
影响因子：
14.5
通讯作者：
Revesz, T
中科院分区：
文献类型：
--
作者：
Ozawa, T;Paviour, D;Revesz, T
多系统萎缩（MSA）具有不同的临床（MSA-P与MSA-C）和病理[纹状体黑质变性（SND）与橄榄脑桥小脑萎缩（OPCA）]表型。为了研究临床病理相关性，我们对100例具有良好临床表型的MSA病例进行了半定量病理分析。在24个地区，选择从纹状体黑质（StrN）和橄榄脑桥小脑（OPC）地区，神经元细胞丢失和胶质细胞增生的严重程度以及神经胶质细胞（少突胶质细胞）胞质内含物（GCI）和神经元胞质内含物（NCIS）的频率进行了测定。从患者的病历中提取临床信息，并回顾性地对发病第一年和疾病最后阶段的运动迟缓严重程度进行分级。还记录了左旋多巴反应性的程度以及是否存在小脑共济失调和自主神经症状。我们报告说，34%的病例是SND-和17%是OPCA为主，而其余的（49%）有等同的SND和OPCA病理。我们发现GCI的频率和神经元细胞丢失的严重程度之间以及这些病理变化和疾病持续时间之间存在显著相关性。我们的数据还表明，GCI可能有更多的影响OPC比上StrN的病理。此外，我们提出了一种可能性，即一个快速的过程中的神经元细胞的损失，这是独立的GCI的积累，发生在StrN区域MSA。在MSA的SND和OPCA亚型之间，壳核、脑桥核和下橄榄核中的NCI频率没有差异，证实了这种病理异常与疾病的特定亚型无关。在目前的大型尸检系列中，10%的病例有相关的路易体病理学，表明这不是MSA的主要过程。正如预期的那样，在运动迟缓的严重程度和小脑体征的存在方面，病理表型之间存在显著差异：SND表型表现出最严重的运动迟缓，而OPCA表型表现出更频繁的小脑体征，证实了临床表型取决于基底节和小脑内的病理分布。壳胺参与与MSA中左旋多巴反应差相关。我们的研究发现，相对轻度的黑质受累在临床上与明显的帕金森综合征相关，而共济失调需要更先进的小脑病理学，这可能解释了为什么帕金森病表现在MSA中占主导地位。
Multiple system atrophy (MSA) has varying clinical (MSA-P versus MSA-C) and pathological [striatonigral degeneration (SND) versus olivopontocerebellar atrophy (OPCA)] phenotypes. To investigate the spectrum of clinicopathological correlations, we performed a semi-quantitative pathological analysis of 100 MSA cases with well-characterized clinical phenotypes. In 24 areas, chosen from both the striatonigral (StrN) and olivopontocerebellar (OPC) regions, the severity of neuronal cell loss and gliosis as well as the frequency of glial (oligodendroglial) cytoplasmic inclusions (GCIs) and neuronal cytoplasmic inclusions (NCIs) were determined. Clinical information was abstracted from the patients' medical records, and the severity of bradykinesia in the first year of disease onset and in the final stages of disease was graded retrospectively. The degree of levodopa responsiveness and the presence or absence of cerebellar ataxia and autonomic symptoms were also recorded. We report that 34% of the cases were SND- and 17% were OPCA-predominant, while the remainder (49%) had equivalent SND and OPCA pathology. We found a significant correlation between the frequency of GCIs and the severity of neuronal cell loss, and between these pathological changes and disease duration. Our data also suggest that GCIs may have more influence on the OPC than on the StrN pathology. Moreover, we raise the possibility that a rapid process of neuronal cell loss, which is independent of the accumulation of GCIs, occurs in the StrN region in MSA. There was no difference in the frequency of NCIs in the putamen, pontine nucleus and inferior olivary nucleus between the SND and OPCA subtypes of MSA, confirming that this pathological abnormality is not associated with a particular subtype of the disease. In the current large post-mortem series, 10% of the cases had associated Lewy body pathology, suggesting that this is not a primary process in MSA. As might be expected, there was a significant difference in the severity of bradykinesia and the presence of cerebellar signs between the pathological phenotypes: the SND phenotype demonstrates the most severe bradykinesia and the OPCA phenotype the more frequent occurrence of cerebellar signs, confirming that the clinical phenotype is dependent on the distribution of pathology within the basal ganglia and cerebellum. Putaminal involvement correlated with a poor levodopa response in MSA. Our finding that relatively mild involvement of the substantia nigra is associated clinically with manifest parkinsonism, while more advanced cerebellar pathology is required for ataxia, may explain why the parkinsonian presentation is predominant over ataxia in MSA.