Division of Neurology, Grenoble University Hospital Center, Grenoble, France.
Grenoble Alpes University, Grenoble Institute of Neurosciences, Grenoble, France.
Ann Neurol. 2020 Apr;87(4):533-546. doi: 10.1002/ana.25696. Epub 2020 Feb 19.
The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α-synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms.
De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex.
In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level-dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups.
Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533-546.
帕金森病(PD)发病机制的双重打击假说表明,脑干是病理性α-突触核蛋白从外周向大脑传播的汇聚区域。尽管脑干结构可能在疾病早期受到影响,但关于特定脑干区域的详细信息却很缺乏。我们的研究目的是通过脑功能磁共振成像和视觉刺激范式,研究与对照组相比,新诊断的 PD 患者大脑中脑结构顶盖的功能。
招募新诊断的 PD 患者和对照组。在开始 PD 药物治疗之前和之后对 PD 患者进行成像。采用最近开发的功能磁共振成像方案刺激和可视化顶盖以及另外 2 个视觉结构:外侧膝状体核和初级视觉皮层。
在 22 名 PD 患者中,与对照组相比,亮度对比度对顶盖反应没有调节。这意味着对低亮度对比度的超敏反应和对高亮度对比度的异常快速血氧水平依赖信号饱和。与对照组相比,外侧膝状体核仅被 3%至 9%的亮度对比度调制。两组之间在初级视觉皮层中未发现主要差异。
我们的发现表明,新诊断的 PD 患者顶盖的病理性视觉反应在疾病早期就存在。顶盖成像的变化可能作为疾病的临床前生物标志物发挥重要作用。神经病学年鉴 2020;87:533-546。