Zhang Chengyi, Yao Yajun, Sun Jiali, Xu Yun, Wang Huabing, Zhuo Zhi-Zheng, Duan Yunyun, Zhang Xinghu, Liu Yaou, Ding Wencai, Tian De-Cai
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100013, China.
Brain Commun. 2025 Jun 27;7(4):fcaf257. doi: 10.1093/braincomms/fcaf257. eCollection 2025.
Widespread white matter changes, including those in the corticospinal tract (CST), have been observed in patients with neuromyelitis optica spectrum disorder (NMOSD). However, whether these alterations originate within the brain or result from spinal cord damage remains unclear. To investigate the CST alteration in AQP4-IgG positive NMOSD with longitudinally extensive transverse myelitis (LETM), and evaluate its relevance to LETM via fixel-based analysis. AQP4+ LETM patients and healthy controls were from ongoing clinical and imaging patterns of neuroinflammation diseases in China cohort between December 2018 and September 2023. Fibre density, fibre cross-section, and the combined measure of fibre density and fibre cross-section were calculated in CST. Serum neurofilament light chain and glial fibrillary acidic protein levels were determined using single-molecule arrays. Multivariate linear model was used to assess associations in AQP4+ LETM between fixel parameters and clinical variables. 44 AQP4+ LETM and 48 healthy controls were included in the study. Among AQP4+ LETM, CST exhibited a decreased mean fibre cross-section ( = 0.001) and the combined measure of fibre density and cross-section ( = 0.004) compared to controls, particularly pronounced in the inferior segments. Negative associations were revealed: pyramidal function score with fibre density ( = -0.335, = 0.037); LETM segments with fibre density ( = -0.429, = 0.006); and the combined measure of fibre density and cross-section with duration of pyramidal tract impairment ( = -0.349, = 0.032) and LETM segment ( = -0.384, = 0.014). Serum neurofilament light chain and glial fibrillary acidic protein were elevated in AQP4+ LETM than healthy controls ( < 0.0001). Serum neurofilament light chain was negatively related to the combined measure of fibre density and cross-section ( = -0.428, = 0.01) and fibre cross-section ( = -0.379, = 0.025). Distinct reduction of fibre cross-section and the combined measure of fibre density and cross-section in brain CST were observed in AQP4+ LETM. The fixel parameters of CST in AQP4+ LETM were negatively correlated with the severity and duration of LETM impairment.
视神经脊髓炎谱系障碍（NMOSD）患者中已观察到广泛的白质变化，包括皮质脊髓束（CST）中的变化。然而，这些改变是源于脑内还是由脊髓损伤引起仍不清楚。为了研究伴有纵向广泛横贯性脊髓炎（LETM）的水通道蛋白4-IgG阳性NMOSD患者的CST改变，并通过基于固定点的分析评估其与LETM的相关性。水通道蛋白4阳性LETM患者和健康对照来自2018年12月至2023年9月中国队列中正在进行的神经炎症性疾病临床和影像学研究。计算CST中的纤维密度、纤维横截面积以及纤维密度和纤维横截面积的综合测量值。使用单分子阵列测定血清神经丝轻链和胶质纤维酸性蛋白水平。采用多变量线性模型评估水通道蛋白4阳性LETM患者中固定点参数与临床变量之间的关联。该研究纳入了44例水通道蛋白4阳性LETM患者和48例健康对照。在水通道蛋白4阳性LETM患者中，与对照组相比，CST的平均纤维横截面积降低（P = 0.001），纤维密度和横截面积的综合测量值降低（P = 0.004），在下段尤为明显。发现了负相关关系：锥体功能评分与纤维密度（r = -0.335，P = 0.037）；LETM节段数与纤维密度（r = -0.429，P = 0.006）；纤维密度和横截面积的综合测量值与锥体束损伤持续时间（r = -0.349，P = 0.032）和LETM节段数（r = -0.384，P = 0.014）。水通道蛋白4阳性LETM患者的血清神经丝轻链和胶质纤维酸性蛋白水平高于健康对照（P < 0.0001）。血清神经丝轻链与纤维密度和横截面积的综合测量值（r = -0.428，P = 0.01）以及纤维横截面积（r = -0.379，P = 0.025）呈负相关。在水通道蛋白4阳性LETM患者中观察到脑CST的纤维横截面积以及纤维密度和横截面积的综合测量值明显降低。水通道蛋白4阳性LETM患者CST的固定点参数与LETM损伤的严重程度和持续时间呈负相关。
