Histopathology of the cerebellar cortex in essential tremor and other neurodegenerative motor disorders: comparative analysis of 320 brains.
Histopathology of the cerebellar cortex in essential tremor and other neurodegenerative motor disorders: comparative analysis of 320 brains.
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DOI：
10.1007/s00401-022-02535-z
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发表时间：
2023-03
影响因子：
12.7
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中科院分区：
文献类型：
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近年来，在特发性震颤（ET）小脑皮质中发现了许多形态学变化，将ET与对照脑区分开来。这些发现尚未在更广泛的退行性疾病谱中得到充分考虑，因此限制了其可解释性。在我们先前研究的基础上，现在将样本量增加一倍，我们对320例脑的尸检系列进行了比较分析，分析了ET（n = 100）、小脑其他神经退行性疾病[脊髓小脑共济失调]（SCA，n = 47，包括13例SCA 3和34例SCA 1、2、6、7、8、14）; Friedreich共济失调（FA，n = 13）;多系统萎缩（MSA），n = 29]，以及其他可能涉及小脑的疾病[帕金森病（PD），n = 62;肌张力障碍，n = 19]与对照组（n = 50）。我们生成了37个定量形态学指标的数据，分为8大类：浦肯野细胞（PC）损失，异位PC，PC树突状细胞的变化，PC轴突的变化（鱼雷），PC轴突的变化（鱼雷以外），PC轴突的变化（鱼雷相关），篮状细胞轴突肥大，爬纤维PC突触的变化。所有诊断（11，651个数据项）的z评分原始数据的主成分分析显示，诊断组在病理学方面并不一致。肌张力障碍和PD分别仅在4/37和5/37的指标上与对照组不同，而ET在21中不同，FA在10中不同，SCA 3在10中不同，MSA在21中不同，SCA 1/2/6/7/8/14在27中不同。病理变化通常在ET、FA和SCA 3中处于退行性疾病谱的较轻端，在SCA 1/2/6/7/8/14中处于该疾病谱的较重端。不同形态学类别的比较分析表明，相对表达的差异，在这些群体中定义了独特的变化模式。总之，我们提出了一个强大的和可重复的方法，确定一些不同的签名小脑皮质的退行性变化，标志着每一个这些疾病。
In recent years, numerous morphologic changes have been identified in the essential tremor (ET) cerebellar cortex, distinguishing ET from control brains. These findings have not been fully contextualized within a broader degenerative disease spectrum, thus limiting their interpretability. Building off our prior study and now doubling the sample size, we conducted comparative analyses in a postmortem series of 320 brains on the severity and patterning of cerebellar cortex degenerative changes in ET (n = 100), other neurodegenerative disorders of the cerebellum [spinocerebellar ataxias (SCAs, n = 47, including 13 SCA3 and 34 SCA1, 2, 6, 7, 8, 14); Friedreich’s ataxia (FA, n = 13); multiple system atrophy (MSA), n = 29], and other disorders that may involve the cerebellum [Parkinson’s disease (PD), n = 62; dystonia, n = 19] versus controls (n = 50). We generated data on 37 quantitative morphologic metrics, grouped into 8 broad categories: Purkinje cell (PC) loss, heterotopic PCs, PC dendritic changes, PC axonal changes (torpedoes), PC axonal changes (other than torpedoes), PC axonal changes (torpedo-associated), basket cell axonal hypertrophy, and climbing fiber-PC synaptic changes. Principal component analysis of z scored raw data across all diagnoses (11,651 data items) revealed that diagnostic groups were not uniform with respect to pathology. Dystonia and PD each differed from controls in only 4/37 and 5/37 metrics, respectively, whereas ET differed in 21, FA in 10, SCA3 in 10, MSA in 21, and SCA1/2/6/7/8/14 in 27. Pathological changes were generally on the milder end of the degenerative spectrum in ET, FA and SCA3, and on the more severe end of that spectrum in SCA1/2/6/7/8/14. Comparative analyses across morphologic categories demonstrated differences in relative expression, defining distinctive patterns of changes in these groups. In summary, we present a robust and reproducible method that identifies somewhat distinctive signatures of degenerative changes in the cerebellar cortex that mark each of these disorders.
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影响因子：
14.5
作者：
Louis, Elan D.;Lee, Michelle;Faust, Phyllis L.
通讯作者：
Faust, Phyllis L.
影响因子：
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作者：
HIRANO, A;LLENA, JF;GHATAK, NR
通讯作者：
GHATAK, NR
影响因子：
8.6
作者：
Louis, Elan D.;Babij, Rachel;Faust, Phyllis L.
通讯作者：
Faust, Phyllis L.
影响因子：
12.7
作者：
Kuo, Sheng-Han;Lin, Chi-Ying;Faust, Phyllis L.
通讯作者：
Faust, Phyllis L.
影响因子：
14.5
作者：
Babij, Rachel;Lee, Michelle;Louis, Elan D.
通讯作者：
Louis, Elan D.