Goldstein David S, Sewell LaToya
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA.
Parkinsonism Relat Disord. 2009 Aug;15(7):516-20. doi: 10.1016/j.parkreldis.2008.12.009. Epub 2009 Feb 7.
Pure autonomic failure (PAF) and Parkinson disease (PD) both are Lewy body diseases, and both entail substantia nigra dopaminergic, locus ceruleus noradrenergic, and cardiac sympathetic denervation. Multiple system atrophy (MSA) is a non-Lewy body disease in which alpha-synuclein accumulates in glial cells, with central catecholamine deficiency but preserved cardiac sympathetic innervation in most patients. PD is associated with more severe and consistent olfactory dysfunction than in MSA; whether PAF entails olfactory dysfunction has been unknown. In this study we assessed olfactory function in PAF in comparison with the two other synucleinopathies and whether olfactory dysfunction correlates with neuroimaging evidence of cardiac noradrenergic or nigrostriatal dopaminergic denervation.
The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 8 patients with PAF, 23 with PD, and 20 with MSA. 6-[(18)F]Fluorodopamine positron emission tomographic (PET) scanning was used to indicate cardiac noradrenergic innervation and the putamen:occipital cortex (PUT:OCC) and substantia nigra (SN):OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity to indicate nigrostriatal dopaminergic innervation.
The PAF group had a low mean UPSIT score (22+/-3), similar to that in PD (20+/-2) and lower than in MSA (31+/-2, p=0.004). Individual UPSIT scores correlated positively with cardiac 6-[(18)F]fluorodopamine-derived radioactivity (r=0.63 in the septum, p<0.0001; r=0.64 in the free wall, p<0.0001) but not with PUT:OCC or SN:OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity.
In synucleinopathies, olfactory dysfunction is related to Lewy body pathology and cardiac sympathetic denervation, independently of parkinsonism or striatal dopamine deficiency.
纯自主神经功能衰竭（PAF）和帕金森病（PD）均为路易体病，二者均伴有黑质多巴胺能、蓝斑去甲肾上腺素能及心脏交感神经去神经支配。多系统萎缩（MSA）是一种非路易体病，其中α-突触核蛋白在胶质细胞中积聚，存在中枢儿茶酚胺缺乏，但大多数患者的心脏交感神经支配保留。与MSA相比，PD与更严重且一致的嗅觉功能障碍相关；PAF是否伴有嗅觉功能障碍尚不清楚。在本研究中，我们评估了PAF患者的嗅觉功能，并与另外两种突触核蛋白病进行比较，以及嗅觉功能障碍是否与心脏去甲肾上腺素能或黑质纹状体多巴胺能去神经支配的神经影像学证据相关。
对8例PAF患者、23例PD患者和20例MSA患者进行了宾夕法尼亚大学嗅觉识别测试（UPSIT）。使用6-[(18)F]氟多巴胺正电子发射断层扫描（PET）来显示心脏去甲肾上腺素能神经支配，以及6-[(18)F]氟多巴衍生放射性的壳核：枕叶皮质（PUT:OCC）和黑质（SN）：OCC比值来显示黑质纹状体多巴胺能神经支配。
PAF组的UPSIT平均得分较低（22±3），与PD组（20±2）相似，低于MSA组（31±2，p = 0.004）。个体UPSIT得分与心脏6-[(18)F]氟多巴胺衍生放射性呈正相关（在间隔中r = 0.63，p < 0.0001；在游离壁中r = 0.64，p < 0.0001），但与6-[(18)F]氟多巴衍生放射性的PUT:OCC或SN:OCC比值无关。
在突触核蛋白病中，嗅觉功能障碍与路易体病理和心脏交感神经去神经支配有关，与帕金森症或纹状体多巴胺缺乏无关。
