Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study
Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study
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DOI：
10.1016/s1474-4422(15)00202-1
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发表时间：
2015-11-01
期刊：
影响因子：
48
通讯作者：
Klockgether, Thomas
中科院分区：
文献类型：
--
作者：
Jacobi, Heike;du Montcel, Sophie Tezenas;Klockgether, Thomas
背景脊髓小脑共济失调是一种显性遗传性神经退行性疾病。随着对这些疾病的潜在治疗方法的开发，需要对其自然史的精确了解。我们的目的是研究最常见的脊髓小脑共济失调的长期疾病进展：SCA 1，SCA 2，SCA 3和SCA 6。此外，我们的目的是建立秩序和发生的非共济失调症状，并确定疾病progress.Methods的预测因素在这个纵向队列研究（EUROSCA），我们招募了男性和女性SCA 1，SCA 2，SCA 3，或SCA 6的阳性基因检测和进行性，否则无法解释的共济失调谁是18岁或以上的17个共济失调转诊中心在10个欧洲国家。3年来每年都对患者进行随访，此后不定期随访。主要结局是共济失调评估和评级量表（SARA）和非共济失调体征清单（INAS）。我们使用线性混合模型来分析进展。为了解释辍学，我们应用了模式混合模型。该研究在ClinicalTrials.gov注册，编号NCT 02440763。结果在2005年7月1日至2006年8月31日期间，526例SCA 1、SCA 2、SCA 3或SCA 6患者入组。我们分析了462名至少接受过一次随访的患者的数据。中位观察时间为49个月（IQR 35-72）。SARA进展数据在所有基因型中最适合线性模型。SCA 1患者、SCA 2患者、SCA 3患者和SCA 6患者的年SARA评分增加分别为2.11（SE 0.12）、1.49（0.07）、1.56（0.08）和0.80（0.09）。非共济失调体征数量的增加在SCA 1、SCA 2和SCA 3中达到平台。在SCA 6患者中，非共济失调症状的数量呈线性增加，但比SCA 1、SCA 2和SCA 3患者慢（p
Background Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6. Furthermore, we aimed to establish the order and occurrence of non-ataxia symptoms, and identify predictors of disease progression.Methods In this longitudinal cohort study (EUROSCA), we enrolled men and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplained ataxia who were aged 18 years or older from 17 ataxia referral centres in ten European countries. Patients were seen every year for 3 years, and at irregular intervals thereafter. The primary outcome was the scale for the assessment and rating of ataxia (SARA), and the inventory of non-ataxia signs (INAS). We used linear mixed models to analyse progression. To account for dropouts, we applied a pattern-mixture model. This study is registered with ClinicalTrials.gov, number NCT02440763.Findings Between July 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled. We analysed data for 462 patients with at least one follow-up visit. Median observation time was 49 months (IQR 35-72). SARA progression data were best fitted with a linear model in all genotypes. Annual SARA score increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6. The increase of the number of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3. In patients with SCA6, the number of non-ataxia symptoms increased linearly, but more slowly than in patients with SCA1, SCA2, and SCA3 (p