Autonomic Medicine Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive MSC-1620, Building 10 Room 8N260, Bethesda, MD, 20892-1620, USA.
Clin Auton Res. 2024 Jun;34(3):329-339. doi: 10.1007/s10286-024-01035-2. Epub 2024 Jun 7.
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 F-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.
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 F-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.
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 F-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.
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.
神经原性直立性低血压（nOH）是由于心脏静脉回流减少时，去甲肾上腺素向心血管受体的反射性传递不足所致。路易体（LB）形式的 nOH 的特征是 F-多巴胺衍生放射性物质低（反映心脏去甲肾上腺素能不足）、宾夕法尼亚大学嗅觉识别测试（UPSIT）嗅觉功能障碍，以及皮肤交感神经去甲肾上腺素能神经中α-突触核蛋白（α-syn）的沉积增加，由α-syn-酪氨酸羟化酶（TH）共定位指数来衡量。这项观察性横断面研究探讨了这些生物标志物的组合是否能特异性地识别 LB 形式的 nOH。
回顾了 2011 年至 2023 年期间在国立卫生研究院因慢性自主神经衰竭而接受评估的患者的临床实验室数据。低心肌 F-多巴胺衍生放射性物质的截断值为 6000 nCi-kg/cc-mCi，嗅觉功能障碍的 UPSIT 评分≤28，以及α-syn-TH 共定位指数增加≥1.57。
共有 44 名患者（31 名 LB、13 名非 LB nOH）有所有三种生物标志物的数据。与非 LB 组相比，LB nOH 组的心肌 F-多巴胺衍生放射性物质低、UPSIT 评分低、α-syn-TH 共定位指数高（p<0.0001 各）。将三种生物标志物结合起来可以完全分离这两组。聚类分析确定了两组不同的群体（p<0.0001），独立于临床诊断，其中一个聚类与 LB nOH 完全吻合。
LB 形式的 nOH 特征为心脏去甲肾上腺素能不足、嗅觉功能障碍和皮肤活检中α-syn-TH 共定位增加。将这些变量的数据结合起来可以有效地将 LB 与非 LB nOH 分开。独立于临床诊断，这种生物标志物三联征可识别出一组具有不同病理生理特征的 nOH 患者。
