Department of Neurology, University Hospital Clinic, Networked Biomedical Research Centre for Neurodegenerative Diseases, The August Pi i Sunyer Biomedical Research Institute, Spain.
Lancet Neurol. 2010 Nov;9(11):1070-7. doi: 10.1016/S1474-4422(10)70216-7. Epub 2010 Sep 16.
Patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) may develop neurodegenerative conditions associated with substantia nigra dysfunction such as Parkinson's disease. In patients with Parkinson's disease, ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (¹²³I-FP-CIT) SPECT detects striatal dopamine dysfunction resulting from nigral pathology whereas transcranial sonography (TCS) shows increased substantia nigra echogenic size, even before parkinsonism is clinically evident. We postulated that these neuroimaging changes could occur in a proportion of IRBD individuals who might then be at increased risk for development of a neurodegenerative disorder associated with substantia nigra dysfunction.
In our prospective study, we identified patients with IRBD from individuals referred to our sleep disorders centre in Barcelona, Spain. At baseline, we assessed dopamine transporter [corrected] uptake by use of ¹²³I-FP-CIT SPECT, and estimated echogenicity of the substantia nigra by use of TCS. After a follow-up of 2·5 years, participants were clinically assessed to establish whether they had developed neurodegenerative syndromes. Data were compared with those of matched healthy controls.
43 individuals with IRBD agreed to participate in the study. We found reduced ¹²³I-FP-CIT binding in the striatum (p=0·045) in 17 (40%) of 43 participants compared with 18 controls, and substantia nigra hyperechogenicity in 14 (36%) of 39 participants with IRBD, compared with 16 (11%) of 149 controls (p=0·0002). Tracer uptake reduction was more pronounced in the putamen than it was in the caudate nucleus. 27 (63%) participants had reduced ¹²³I-FP-CIT binding or substantia nigra hyperechogenicity at baseline. Eight (30%) of these participants developed a neurodegenerative disorder (five Parkinson's disease, two dementia with Lewy bodies, and one multiple system atrophy). Individuals with normal neuroimaging results remained disease-free. Sensitivity of combined ¹²³I-FP-CIT SPECT and TCS to predict conversion to synucleinopathy after 2·5 years was 100% and specificity was 55%.
In patients with IRBD, ¹²³I-FP-CIT SPECT and TCS can detect subclinical changes much the same as those typically seen in patients with early Parkinson's disease. Decreased striatal ¹²³I-FP-CIT binding and substantia nigra hyperechogenicity might be useful markers to identify individuals at increased risk for development of synucleinopathies.
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特发性快动眼睡眠行为障碍（IRBD）患者可能会出现与黑质功能障碍相关的神经退行性疾病，如帕金森病。在帕金森病患者中，¹²³I-2β- 碳甲氧基-3β-（4-碘苯基）-N-（3-氟丙基）-去甲托烷（¹²³I-FP-CIT）SPECT 可检测到由于黑质病变引起的纹状体多巴胺功能障碍，而经颅超声（TCS）显示黑质回声增加，即使在帕金森病出现临床症状之前也是如此。我们假设这些神经影像学变化可能发生在一部分 IRBD 个体中，这些个体可能会增加与黑质功能障碍相关的神经退行性疾病的发病风险。
在我们的前瞻性研究中，我们从西班牙巴塞罗那的睡眠障碍中心转诊的患者中确定了 IRBD 患者。在基线时，我们使用¹²³I-FP-CIT SPECT 评估多巴胺转运体摄取情况，并使用 TCS 估计黑质的回声强度。经过 2.5 年的随访，对参与者进行临床评估，以确定他们是否患有神经退行性综合征。数据与匹配的健康对照组进行了比较。
43 名 IRBD 患者同意参与研究。与 18 名对照组相比，我们发现 43 名参与者中有 17 名（40%）的纹状体¹²³I-FP-CIT 结合减少（p=0.045），39 名 IRBD 患者中有 14 名（36%）的黑质回声增加，而 149 名对照组中有 16 名（11%）（p=0.0002）。与尾状核相比，壳核的示踪剂摄取减少更为明显。27 名（63%）参与者在基线时出现¹²³I-FP-CIT 结合减少或黑质回声增加。其中 8 名（30%）参与者发展为神经退行性疾病（5 名帕金森病，2 名路易体痴呆，1 名多系统萎缩）。神经影像学结果正常的患者仍未患病。¹²³I-FP-CIT SPECT 和 TCS 联合检测对预测 2.5 年后突触核蛋白病的敏感性为 100%，特异性为 55%。
在 IRBD 患者中，¹²³I-FP-CIT SPECT 和 TCS 可以检测到与早期帕金森病患者中通常观察到的类似的亚临床变化。纹状体¹²³I-FP-CIT 结合减少和黑质回声增加可能是识别突触核蛋白病发病风险增加的有用标志物。
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