Rooney James, Murray Deirdre, Campion Anna, Moloney Hannah, Tattersall Rachel, Doherty Mark, Hammond Michaela, Heverin Mark, McLaughlin Russell, Hardiman Orla
Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Beaumont Hospital, Dublin, Ireland.
HRB Open Res. 2019 Sep 26;2:23. doi: 10.12688/hrbopenres.12940.1. eCollection 2019.
: The hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese patients. : Cases presenting to the Irish ALS clinic with both longitudinal occluded sniff nasal inspiratory pressure (SNIP) and testing were including in the study. Clinical variables and survival characteristics of these patients were collected. Joint longitudinal and time to event models were constructed to explore the longitudinal characteristics of the cohort by status. : In total, 630 cases were included, of which 58 (9.2%) carried the repeat expansion. Plots of the longitudinal trend after joint modelling revealed that those carrying the expansion had worse respiratory function throughout the course of their disease than those without. The ALS Functional Rating Scale-revised (ALSFRS-R) respiratory sub-score did not distinguish normal from expanded cases. Furthermore, modelling by site of onset and gender sub-groups revealed that this difference was greatest in male spinal onset cases. Joint models further indicated that occluded SNIP values were of prognostic importance. : Our results confirm findings from Portugal that the repeat expansion is associated with accelerated respiratory function decline. Analysis via joint models indicate that respiratory function is of prognostic importance and may explain previous observations of poorer prognosis in male spinal onset patients carrying the expansion.
六核苷酸重复序列扩增是肌萎缩侧索硬化症（ALS）的病因，且对预后有负面影响。在一组372名葡萄牙患者中，该重复序列扩增与呼吸功能加速恶化及生存率降低有关。
纳入研究的病例为就诊于爱尔兰ALS诊所且同时进行了纵向闭塞嗅吸鼻吸气压力（SNIP）检测的患者。收集了这些患者的临床变量和生存特征。构建了联合纵向和事件发生时间模型，以按状态探索该队列的纵向特征。
总共纳入了630例病例，其中58例（9.2%）携带该重复序列扩增。联合建模后的纵向趋势图显示，携带该扩增的患者在整个病程中的呼吸功能比未携带的患者更差。ALS功能评定量表修订版（ALSFRS-R）的呼吸亚评分无法区分正常病例和扩增病例。此外，按发病部位和性别亚组进行建模显示，这种差异在男性脊髓发病病例中最为明显。联合模型进一步表明，闭塞SNIP值具有预后重要性。
我们的结果证实了葡萄牙的研究结果，即该重复序列扩增与呼吸功能加速下降有关。通过联合模型分析表明，呼吸功能具有预后重要性，这可能解释了之前观察到的携带该扩增的男性脊髓发病患者预后较差的现象。
