Iranzo Alex, Fernández-Arcos Ana, Tolosa Eduard, Serradell Mónica, Molinuevo José Luis, Valldeoriola Francesc, Gelpi Ellen, Vilaseca Isabel, Sánchez-Valle Raquel, Lladó Albert, Gaig Carles, Santamaría Joan
Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain ; CIBERNED, Barcelona, Spain.
Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
PLoS One. 2014 Feb 26;9(2):e89741. doi: 10.1371/journal.pone.0089741. eCollection 2014.
To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up.
Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013.
The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case.
In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.
在一大群接受长期随访的特发性快速眼动睡眠行为障碍（IRBD）患者中，评估发生特定神经退行性综合征的风险。
采用Kaplan-Meier法，我们估算了1991年11月至2013年7月期间在我们三级转诊睡眠中心确诊并随访的所有连续性IRBD患者中，未发生特定神经退行性综合征的生存率。
该队列包括174例患者，IRBD诊断时的中位年龄为69岁，中位随访时间为4年。从IRBD诊断时起，发生特定神经退行性综合征的风险在5年时为33.1%，10年时为75.7%，14年时为90.9%。中位转化时间为7.5年。新出现的诊断（37.4%）包括29例路易体痴呆（DLB）、22例帕金森病（PD）、2例多系统萎缩（MSA）和12例轻度认知障碍（MCI）。在6例进行了尸检的病例中，神经病理学检查显示每例患者大脑中均有神经元丢失和广泛的路易体样病理改变。
在三级转诊睡眠中心诊断的一大群IRBD患者中，延长随访表明大多数患者最终被诊断为突触核蛋白病PD、DLB，较少见的是MSA。IRBD代表了这些疾病的前驱期。我们在IRBD中的发现对临床实践、突触核蛋白病早期病理事件的研究以及潜在疾病修饰剂干预措施的设计具有重要意义。
