弗里德里希共济失调中的进行性脊髓变性：来自 ENIGMA-Ataxia 的结果。
Progressive Spinal Cord Degeneration in Friedreich's Ataxia: Results from ENIGMA-Ataxia.
机构信息
Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
出版信息
Mov Disord. 2023 Jan;38(1):45-56. doi: 10.1002/mds.29261. Epub 2022 Oct 29.
BACKGROUND
Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear.
OBJECTIVE
The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort.
METHODS
We performed a cross-sectional analysis of cervical spinal cord (C1-C4) cross-sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age.
RESULTS
Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d > 2.1) and significant correlations with disease severity (r < -0.4). Similarly, we found significantly increased eccentricity (d > 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time.
CONCLUSIONS
Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
背景
脊髓损伤是弗里德里希共济失调症（FRDA）的标志，但该病的进展及其临床相关性尚不清楚。
目的
本研究旨在对 FRDA 大型多中心队列中的颈脊髓结构损伤进行特征描述。
方法
我们对 ENIGMA-Ataxia 倡议的 8 个中心的磁共振成像数据进行了颈脊髓（C1-C4）横截面积（CSA）和偏心度的横断面分析，共纳入 256 例 FRDA 患者和 223 名年龄和性别匹配的对照者。在 FRDA 队列中，根据疾病持续时间、共济失调严重程度和发病年龄进行相关性和亚组分析。
结果
与对照组相比，FRDA 患者所有检查水平的 CSA 均显著降低，效应量较大（d＞2.1），与疾病严重程度呈显著负相关（r＜-0.4）。同样，我们发现 CSA 显著增加（d＞1.2），但与临床无显著相关性。亚组分析表明，在所有疾病阶段 CSA 和偏心度均异常。然而，虽然 CSA 似乎逐渐降低，但偏心度随时间保持稳定。
结论
既往研究表明，偏心度增加反映了背柱（DC）损伤，而 CSA 降低则反映了 DC 或皮质脊髓束（CST）损伤，或两者兼而有之。因此，我们的数据支持这样一种假设，即 DC 和 CST 的损伤在 FRDA 中遵循不同的过程：发育异常可能定义了 DC，而 CST 的改变可能既有发育性的，也有退行性的。这些结果为 FRDA 的发病机制提供了新的见解，并表明颈脊髓 CSA 应作为疾病进展的潜在生物标志物进一步研究。
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