Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Brain. 2021 Feb 12;144(1):198-212. doi: 10.1093/brain/awaa347.
Spinal cord involvement is a hallmark feature of multiple sclerosis, neuromyelitis optica with AQP4 antibodies and MOG-antibody disease. In this cross-sectional study we use quantitative spinal cord MRI to better understand these conditions, differentiate them and associate with relevant clinical outcomes. Eighty participants (20 in each disease group and 20 matched healthy volunteers) underwent spinal cord MRI (cervical cord: 3D T1, 3D T2, diffusion tensor imaging and magnetization transfer ratio; thoracic cord: 3D T2), together with disability, pain and fatigue scoring. All participants had documented spinal cord involvement and were at least 6 months post an acute event. MRI scans were analysed using publicly available software. Those with AQP4-antibody disease showed a significant reduction in cervical cord cross-sectional area (P = 0.038), thoracic cord cross-sectional area (P = 0.043), cervical cord grey matter (P = 0.011), magnetization transfer ratio (P ≤ 0.001), fractional anisotropy (P = 0.004) and increased mean diffusivity (P = 0.008). Those with multiple sclerosis showed significantly increased mean diffusivity (P = 0.001) and reduced fractional anisotropy (P = 0.013), grey matter volume (P = 0.002) and magnetization transfer ratio (P = 0.011). In AQP4-antibody disease the damage was localized to areas of the cord involved in the acute attack. In multiple sclerosis this relationship with lesions was absent. MOG-antibody disease did not show significant differences to healthy volunteers in any modality. However, when considering only areas involved at the time of the acute attack, a reduction in grey matter volume was found (P = 0.023). This suggests a predominant central grey matter component to MOG-antibody myelitis, which we hypothesize could be partially responsible for the significant residual sphincter dysfunction. Those with relapsing MOG-antibody disease showed a reduction in cord cross-sectional area compared to those with monophasic disease, even when relapses occurred elsewhere (P = 0.012). This suggests that relapsing MOG-antibody disease is a more severe phenotype. We then applied a principal component analysis, followed by an orthogonal partial least squares analysis. MOG-antibody disease was discriminated from both AQP4-antibody disease and multiple sclerosis with moderate predictive values. Finally, we assessed the clinical relevance of these metrics using a multiple regression model. Cervical cord cross-sectional area associated with disability scores (B = -0.07, P = 0.0440, R2 = 0.20) and cervical cord spinothalamic tract fractional anisotropy associated with pain scores (B = -19.57, P = 0.016, R2 = 0.55). No spinal cord metric captured fatigue. This work contributes to our understanding of myelitis in these conditions and highlights the clinical relevance of quantitative spinal cord MRI.
脊髓受累是多发性硬化症、视神经脊髓炎伴水通道蛋白 4 抗体和髓鞘少突胶质细胞糖蛋白抗体病的标志性特征。在这项横断面研究中,我们使用定量脊髓 MRI 更好地了解这些疾病,对其进行区分,并与相关的临床结果相关联。80 名参与者(每组 20 名患者和 20 名匹配的健康志愿者)接受了脊髓 MRI(颈段:3D T1、3D T2、弥散张量成像和磁化传递率;胸段:3D T2),同时还进行了残疾、疼痛和疲劳评分。所有参与者均有记录的脊髓受累,且至少在急性事件后 6 个月。使用公开可用的软件分析 MRI 扫描。患有水通道蛋白 4 抗体病的患者颈段脊髓横截面积显著减少(P=0.038),胸段脊髓横截面积(P=0.043)、颈段脊髓灰质(P=0.011)、磁化传递率(P≤0.001)、各向异性分数(P=0.004)和平均弥散度增加(P=0.008)。多发性硬化症患者的平均弥散度显著增加(P=0.001),各向异性分数(P=0.013)、灰质体积(P=0.002)和磁化传递率(P=0.011)减少。在水通道蛋白 4 抗体病中,损伤局限于急性发作时受累的脊髓区域。多发性硬化症与病变之间没有这种关系。髓鞘少突胶质细胞糖蛋白抗体病与健康志愿者在任何模态中均无显著差异。然而,当仅考虑急性发作时受累的区域时,发现灰质体积减少(P=0.023)。这表明髓鞘少突胶质细胞糖蛋白抗体性脊髓炎主要涉及中央灰质成分,我们假设这可能部分解释了明显的括约肌功能障碍残留。与单相疾病相比,复发性髓鞘少突胶质细胞糖蛋白抗体病患者的脊髓横截面积减少,即使复发发生在其他部位(P=0.012)。这表明复发性髓鞘少突胶质细胞糖蛋白抗体病是一种更严重的表型。然后,我们进行了主成分分析,然后是正交偏最小二乘分析。髓鞘少突胶质细胞糖蛋白抗体病与水通道蛋白 4 抗体病和多发性硬化症具有中等预测值,可区分开来。最后,我们使用多元回归模型评估这些指标的临床相关性。颈段脊髓横截面积与残疾评分相关(B=-0.07,P=0.0440,R2=0.20),颈段脊髓脊髓丘脑束各向异性分数与疼痛评分相关(B=-19.57,P=0.016,R2=0.55)。没有脊髓指标可以捕获疲劳。这项工作有助于我们了解这些疾病中的脊髓炎,并强调了定量脊髓 MRI 的临床相关性。