Department of Neurosciences, KU Leuven, Leuven, Belgium.
Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
Mov Disord. 2023 Aug;38(8):1515-1526. doi: 10.1002/mds.29501. Epub 2023 Jun 29.
Development of disease-modifying treatments for Huntington's disease (HD) could be aided by the use of imaging biomarkers of disease progression. Positron emission tomography (PET) with C-UCB-J, a radioligand for the brain-wide presynaptic marker synaptic vesicle protein 2A (SV2A), detects more widespread brain changes in early HD than volumetric magnetic resonance imaging (MRI) and F-fludeoxyglucose ( F-FDG) PET, but longitudinal C-UCB-J PET data have not been reported. The aim of this study was to compare the sensitivity of C-UCB-J PET, F-FDG PET, and volumetric MRI for detection of longitudinal changes in early HD.
Seventeen HD mutation carriers (six premanifest and 11 early manifest) and 13 healthy controls underwent C-UCB-J PET, F-FDG PET, and volumetric MRI at baseline (BL) and after 21.4 ± 2.7 months (Y2). Within-group and between-group longitudinal clinical and imaging changes were assessed.
The HD group showed significant 2-year worsening of Unified Huntington's Disease Rating Scale motor scores. There was significant longitudinal volume loss within the HD group in caudate (-4.5% ± 3.8%), putamen (-3.6% ± 3.5%), pallidum (-3.0% ± 2.7%), and frontal cortex (-2.0% ± 2.1%) (all P < 0.001). Within the HD group there was longitudinal loss of putaminal SV2A binding (6.4% ± 8.8%, P = 0.01) and putaminal glucose metabolism (-2.8% ± 4.4%, P = 0.008), but these changes were not significant after correction for multiple comparisons. Premanifest subjects at BL only had significantly lower SV2A binding than controls in basal ganglia structures, but at Y2 additionally had significant SV2A loss in frontal and parietal cortex, indicating spread of SV2A loss from subcortical to cortical regions.
Volumetric MRI may be more sensitive than C-UCB-J PET and F-FDG PET for detection of 2-year brain changes in early HD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
开发亨廷顿病（HD）的疾病修饰治疗方法，可以通过使用疾病进展的成像生物标志物来辅助。正电子发射断层扫描（PET）使用 C-UCB-J，一种用于全脑突触前标志物突触小泡蛋白 2A（SV2A）的放射性配体，比容积磁共振成像（MRI）和 F-氟脱氧葡萄糖（ F-FDG）PET 更早地检测到早期 HD 中更广泛的脑变化，但尚未报告纵向 C-UCB-J PET 数据。本研究的目的是比较 C-UCB-J PET、 F-FDG PET 和容积 MRI 对早期 HD 纵向变化的检测灵敏度。
17 名亨廷顿病基因突变携带者（6 名前驱期和 11 名早期）和 13 名健康对照者在基线（BL）和 21.4±2.7 个月（Y2）时接受 C-UCB-J PET、 F-FDG PET 和容积 MRI。评估了组内和组间的纵向临床和影像学变化。
HD 组在 2 年内出现明显的统一亨廷顿病评定量表运动评分恶化。HD 组的尾状核（-4.5%±3.8%）、壳核（-3.6%±3.5%）、苍白球（-3.0%±2.7%）和额皮质（-2.0%±2.1%）均有明显的纵向体积损失（均 P<0.001）。HD 组的壳核 SV2A 结合纵向丢失（6.4%±8.8%，P=0.01）和壳核葡萄糖代谢（-2.8%±4.4%，P=0.008），但在进行多次比较校正后，这些变化并不显著。BL 时的前驱期患者仅在基底节结构中的 SV2A 结合明显低于对照组，但在 Y2 时还出现了额皮质和顶叶皮质的 SV2A 丢失，表明 SV2A 从皮质下区域向皮质区域的丢失扩散。
容积 MRI 可能比 C-UCB-J PET 和 F-FDG PET 更敏感，可检测早期 HD 中 2 年的脑变化。 © 2023 作者。运动障碍由 Wiley Periodicals LLC 代表国际帕金森病和运动障碍协会出版。
