Abstract：
OBJECTIVE: Neurogenic orthostatic hypotension (nOH) results from deficient reflexive delivery of norepinephrine to cardiovascular receptors in response to decreased cardiac venous return. Lewy body (LB) forms of nOH are characterized by low 18F-dopamine-derived radioactivity (a measure of cardiac noradrenergic deficiency), olfactory dysfunction by the University of Pennsylvania Smell Identification Test (UPSIT), and increased deposition of alpha-synuclein (α-syn) in dermal sympathetic noradrenergic nerves by the α-syn-tyrosine hydroxylase (TH) colocalization index. This observational, cross-sectional study explored whether combinations of these biomarkers specifically identify LB forms of nOH.
METHODS: Clinical laboratory data were reviewed from patients referred for evaluation at the National Institutes of Health for chronic autonomic failure between 2011 and 2023. The cutoff value for low myocardial 18F-dopamine-derived radioactivity was 6000 nCi-kg/cc-mCi, for olfactory dysfunction an UPSIT score ≤ 28, and for an increased α-syn-TH colocalization index ≥ 1.57.
RESULTS: A total of 44 patients (31 LB, 13 non-LB nOH) had data for all three biomarkers. Compared to the non-LB group, the LB nOH group had low myocardial 18F-dopamine-derived radioactivity, low UPSIT scores, and high α-syn-TH colocalization indexes (p < 0.0001 each). Combining the three biomarkers completely separated the groups. Cluster analysis identified two distinct groups (p < 0.0001) independently of the clinical diagnosis, with one cluster corresponding exactly to LB nOH.
CONCLUSIONS: LB forms of nOH feature cardiac noradrenergic deficiency, olfactory dysfunction, and increased α-syn-TH colocalization in skin biopsies. Combining the data for these variables efficiently separates LB from non-LB nOH. Independently of the clinical diagnosis, this biomarker triad identifies a pathophysiologically distinct cluster of nOH patients.
METHODS: Clinical laboratory data were reviewed from patients referred for evaluation at the National Institutes of Health for chronic autonomic failure between 2011 and 2023. The cutoff value for low myocardial 18F-dopamine-derived radioactivity was 6000 nCi-kg/cc-mCi, for olfactory dysfunction an UPSIT score ≤ 28, and for an increased α-syn-TH colocalization index ≥ 1.57.
RESULTS: A total of 44 patients (31 LB, 13 non-LB nOH) had data for all three biomarkers. Compared to the non-LB group, the LB nOH group had low myocardial 18F-dopamine-derived radioactivity, low UPSIT scores, and high α-syn-TH colocalization indexes (p < 0.0001 each). Combining the three biomarkers completely separated the groups. Cluster analysis identified two distinct groups (p < 0.0001) independently of the clinical diagnosis, with one cluster corresponding exactly to LB nOH.
CONCLUSIONS: LB forms of nOH feature cardiac noradrenergic deficiency, olfactory dysfunction, and increased α-syn-TH colocalization in skin biopsies. Combining the data for these variables efficiently separates LB from non-LB nOH. Independently of the clinical diagnosis, this biomarker triad identifies a pathophysiologically distinct cluster of nOH patients.
摘要：
目的：神经源性直立性低血压（nOH）是由于心脏静脉回流减少导致去甲肾上腺素向心血管受体的反射传递不足。nOH的路易体（LB）形式的特征在于低18F-多巴胺衍生的放射性（心脏去甲肾上腺素能缺乏症的一种量度），宾夕法尼亚大学嗅觉识别测试（UPSIT），并通过α-syn-酪氨酸羟化酶（TH）共定位指数增加了真皮交感神经中α-突触核蛋白（α-syn）的沉积。这个观测,横断面研究探讨了这些生物标志物的组合是否特异性鉴定了nOH的LB形式。
方法：回顾了2011年至2023年在美国国立卫生研究院接受慢性自主神经功能衰竭评估的患者的临床实验室数据。低心肌18F-多巴胺衍生放射性的临界值为6000nCi-kg/cc-mCi，对于嗅觉功能障碍，UPSIT评分≤28，并且对于增加的α-syn-TH共定位指数≥1.57。
结果：共有44例患者（31LB，13non-LBnOH）具有所有三种生物标志物的数据。与非LB组相比，LBnOH组有较低的心肌18F-多巴胺来源的放射性，UPSIT得分低，和较高的α-syn-TH共定位指数(各p<0.0001)。将三种生物标志物组合完全分离各组。聚类分析确定了两个不同的组（p<0.0001），与临床诊断无关，一个簇精确对应于LBnOH。
结论：LB形式的nOH以心脏去甲肾上腺素能缺乏症为特征，嗅觉功能障碍,并增加了皮肤活检中的α-syn-TH共定位。组合这些变量的数据有效地将LB与非LBnOH分离。独立于临床诊断，该生物标志物三联征确定了一组病理生理上不同的nOH患者。
方法：回顾了2011年至2023年在美国国立卫生研究院接受慢性自主神经功能衰竭评估的患者的临床实验室数据。低心肌18F-多巴胺衍生放射性的临界值为6000nCi-kg/cc-mCi，对于嗅觉功能障碍，UPSIT评分≤28，并且对于增加的α-syn-TH共定位指数≥1.57。
结果：共有44例患者（31LB，13non-LBnOH）具有所有三种生物标志物的数据。与非LB组相比，LBnOH组有较低的心肌18F-多巴胺来源的放射性，UPSIT得分低，和较高的α-syn-TH共定位指数(各p<0.0001)。将三种生物标志物组合完全分离各组。聚类分析确定了两个不同的组（p<0.0001），与临床诊断无关，一个簇精确对应于LBnOH。
结论：LB形式的nOH以心脏去甲肾上腺素能缺乏症为特征，嗅觉功能障碍,并增加了皮肤活检中的α-syn-TH共定位。组合这些变量的数据有效地将LB与非LBnOH分离。独立于临床诊断，该生物标志物三联征确定了一组病理生理上不同的nOH患者。
