Movement disorders:帕金森氏征,多巴胺代谢和大脑血流代谢有何关系?

2022-06-23 Freeman MedSci原创

在PD和四次重复的tauopathy中,前额叶灌注与同侧黑质多巴胺能功能有关

帕金森病(PD)是一种神经退行性疾病,其特征是黑质多巴胺能神经元逐渐丧失,受影响细胞的胞质中存在路易体。临床特征是运动迟缓、僵硬和静止性震颤,此外还有非运动症状,如自主神经、认知、精神、感觉和睡眠障碍,这些症状可能先于运动功能障碍。多巴胺替代疗法可缓解PD的运动功能障碍,这意味着突触后的多巴胺能系统被相对保留。这种有效性将PD与非典型帕金森综合征(APS)区分开来,包括多系统萎缩(MSA)、进行性核上麻痹(PSP)和皮质基质综合征(CBS)。

 

图1: 论文封面图

由于APS的运动功能障碍通常对多巴胺能治疗无效,与PD相比,APS的疾病进展和预后不佳。因此,早期和准确的诊断是至关重要的。多巴胺转运体(DAT)单光子发射计算机断层扫描(SPECT)使用放射性配体,如123I-N-ω-氟丙基-2β-甲氧羰基-3β-{4-碘苯基}诺托品(123I-FP-CIT),可以使纹状体突触前多巴胺能功能可视化。纹状体DAT结合异常减少是PD的强制性发现,并可能有助于早期诊断,以区别于原发性震颤患者。

尽管如此,APS的特点是纹状体DAT结合率低,使用低纹状体DAT结合率很难区分PD和APS。另一个限制是随着正常老化,黑质体功能减退,使得在不同年龄段的人中量化纹状体DAT结合具有挑战性。最近,为了克服这个问题,在一项大规模的多中心定量研究中,引入了一种方法来规范123I-FP-CIT SPECT中与年龄有关的下降和与扫描仪有关的差异。


脑血流(CBF)和脑葡萄糖代谢图像对帕金森病的鉴别诊断是有效的。值得注意的是,帕金森病患者在额顶联合区的代谢或灌注减少:这被称为帕金森病相关共变模式(PDRP)。

PDRP分数的大小可以通过多巴胺能治疗来调节,尽管多巴胺替代的影响在不同的脑区可能有所不同。


监督机器学习是一种人工智能,最近被应用于从健康参与者中鉴别诊断PD的神经影像学,并可能作为一种新的诊断方法。尽管每种成像模式都可以有效地区分帕金森病,但不同类型的成像模式之间的关系却不太清楚。因此,有监督的机器学习方法可用于评估多模态影像在区分帕金森病的功效。


藉此,日本千叶大学的Yoshikazu Nakano等人,研究帕金森病患者的CBF和DAT SPECT之间的关系,确定每种帕金森病患者的纹状体多巴胺能与CBF的相关性,并比较不同的疾病。

58名PD患者和71名APS患者(24名多系统萎缩,21名进行性核上麻痹,26名皮质基底综合征)接受了123 I-IMP和123 I-FP-CIT单光子发射计算机断层扫描。对每一组进行了CBF和纹状体DAT结合的多元回归分析。通过机器学习和接收器操作特征曲线预测PD概率。

 

图2:论文结果图

他们发现:PD组显示更多的纹状体DAT结合与同侧前额叶灌注呈正相关,与双侧小脑灌注呈负相关。

在皮质基质综合征中,纹状体DAT结合与同侧前额叶灌注呈正相关,与对侧腹前灌注呈负相关。

在Richardson综合征中,纹状体DAT结合与同侧腹前皮层和基底神经节的灌注呈正相关。机器学习显示,CBF和DAT的组合比单独的CBF(0.67)或DAT(0.50)更能区分PD与APS(曲线下面积[AUC]=0.87)。


该研究的重要意义在于发现了:在PD和四次重复的tauopathy中,前额叶灌注与同侧黑质多巴胺能功能有关。这种双tracer的额叶与纹状体的关系可有效地作为划分PD与APS的一种诊断工具。

 

原文出处:
Nakano Y, Hirano S, Kojima K, et al. Dopaminergic Correlates of Regional Cerebral Blood Flow in Parkinsonian Disorders. _Movement Disorders_. Published online March 14, 2022:mds.28981. doi:[10.1002/mds.28981](https://doi.org/10.1002/mds.28981)

 

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    2023-05-18 anminleiryan
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