MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London SE5 8AF, UK.
Brain. 2012 Mar;135(Pt 3):847-52. doi: 10.1093/brain/awr351. Epub 2012 Jan 23.
Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons, with a median survival of 2-3 years. Although various phenotypic and research diagnostic classification systems exist and several prognostic models have been generated, there is no staging system. Staging criteria for amyotrophic lateral sclerosis would help to provide a universal and objective measure of disease progression with benefits for patient care, resource allocation, research classifications and clinical trial design. We therefore sought to define easily identified clinical milestones that could be shown to occur at specific points in the disease course, reflect disease progression and impact prognosis and treatment. A tertiary referral centre clinical database was analysed, consisting of 1471 patients with amyotrophic lateral sclerosis seen between 1993 and 2007. Milestones were defined as symptom onset (functional involvement by weakness, wasting, spasticity, dysarthria or dysphagia of one central nervous system region defined as bulbar, upper limb, lower limb or diaphragmatic), diagnosis, functional involvement of a second region, functional involvement of a third region, needing gastrostomy and non-invasive ventilation. Milestone timings were standardized as proportions of time elapsed through the disease course using information from patients who had died by dividing time to a milestone by disease duration. Milestones occurred at predictable proportions of the disease course. Diagnosis occurred at 35% through the disease course, involvement of a second region at 38%, a third region at 61%, need for gastrostomy at 77% and need for non-invasive ventilation at 80%. We therefore propose a simple staging system for amyotrophic lateral sclerosis. Stage 1: symptom onset (involvement of first region); Stage 2A: diagnosis; Stage 2B: involvement of second region; Stage 3: involvement of third region; Stage 4A: need for gastrostomy; and Stage 4B: need for non-invasive ventilation. Validation of this staging system will require further studies in other populations, in population registers and in other clinic databases. The standardized times to milestones may well vary between different studies and populations, although the stages themselves and their meanings are likely to remain unchanged.
肌萎缩侧索硬化症是一种神经退行性疾病，其特征是上下运动神经元进行性丧失，中位生存期为 2-3 年。尽管存在各种表型和研究诊断分类系统，并且已经生成了几种预后模型，但尚无分期系统。肌萎缩侧索硬化症的分期标准将有助于提供一种通用和客观的疾病进展衡量标准，有利于患者护理、资源分配、研究分类和临床试验设计。因此，我们试图定义一些易于识别的临床里程碑，这些里程碑可以在疾病过程中的特定点上显示出来，反映疾病进展，并影响预后和治疗。分析了一个三级转诊中心的临床数据库，该数据库包含 1993 年至 2007 年间就诊的 1471 例肌萎缩侧索硬化症患者。里程碑定义为症状发作（一个中枢神经系统区域的无力、消瘦、痉挛、构音障碍或吞咽困难的功能受累，定义为延髓、上肢、下肢或膈肌）、诊断、第二个区域的功能受累、第三个区域的功能受累、需要胃造口术和无创通气。使用已死亡患者的信息将里程碑时间标准化为疾病过程中经过的时间比例，即将到达里程碑的时间除以疾病持续时间。里程碑发生在疾病过程中的可预测比例。诊断发生在疾病过程的 35%，第二个区域的受累发生在 38%，第三个区域的受累发生在 61%，需要胃造口术的发生在 77%，需要无创通气的发生在 80%。因此，我们提出了一种简单的肌萎缩侧索硬化症分期系统。第 1 阶段：症状发作（第一个区域受累）；第 2A 阶段：诊断；第 2B 阶段：第二个区域受累；第 3 阶段：第三个区域受累；第 4A 阶段：需要胃造口术；第 4B 阶段：需要无创通气。需要在其他人群、人群登记处和其他临床数据库中进一步研究来验证该分期系统。在不同的研究和人群中，里程碑的标准化时间可能会有所不同，尽管阶段本身及其含义可能保持不变。
