頸椎脊髓病變患者之大腦白質完整性與感覺和運動功能相關：擴散頻譜影像研究

Abstract

頸痛病人日益增加，有些會發展為退化性脊椎病並導致脊髓神經病變，其臨床表徵包括感覺喪失、異常疼痛、動作失調、平衡及行走功能受限，並影響注意力、情緒及生活品質等，嚴重者須接受手術治療，但手術後有些仍有許多症狀持續，目前確實的致病機轉機制不明。先前的研究表明，脊髓型頸椎病患者在脊髓水平的平均擴散係數(MD)和分數各向異性(FA)均低於正常人。然而，這種局部變化是否會影響大腦中的白質神經束仍不清楚。在這項研究中，我們旨在比較脊髓型頸椎病患者和健康對照組之間大腦白質微觀結構的差異，並期望找出這些變化的神經束與功能指標的相關性。 我們徵召了27位頸椎脊髓神經病變的病人(年齡:56.63±13.05歲，18名男性9名女性)及27位年齡性別配對之健康中老年人(年齡:55.30±13.03歲，18名男性9名女性)，所有受測者皆接受T1權重影像及擴散頻譜造影影像以探討大腦白質的完整性，包括從脊髓到大腦的上行及下行路徑，並以JOA、mJOA、NDI問卷詢問感覺動作功能。我們運用MAP-MRI的組件將擴散頻譜造影的影像計算出4種擴散指標，包括概化部分不等向性(GFA)、軸向擴散係數(AD)、平均擴散係數(MD)及徑向擴散係數(RD)。其後，運用全腦神經束自動化分析(TBAA)來獲得大腦主要76條神經束的四種擴散指標所構成的三維結構腦聯結圖(3D-connectogram)，作為我們探討白質神經纖維束結構的依據。我們使用簇群權重(TFCW)分數來進行組分析，我們計算組間每個步驟的效應量以及估計的加權分數，以找出差異最大的神經束步驟區塊。以線性迴歸分析白質完整性與感覺動作認知功能的相關性，控制年齡的因子後，探討有變化之大腦內神經束與功能之相關性。 我們發現頸椎脊髓神經病變病人之脊髓神經病變造成部分上行及下行路徑的神經束病變，且此部分白質變化與動作感覺能力有相關。此外我們發現大腦內與認知功能相關的白質神經束亦有變化，此變化除了與動作感覺功能有關之外，與疼痛睡眠也有相關。顯示頸部脊髓神經束的受傷，除了對大腦有影響，對認知功能的神經束亦有影響。需再進一步探討病人的認知功能與大腦內白質變化的關係。

Introduction: Cervical myelopathy is a common degenerative condition caused by compression on the spinal cord that is characterized by clumsiness in hands and gait imbalance. Patients demonstrated multiple symptoms and signs, including sensory, motor, control and cognition relate complaints. Severe cases require surgery, but in some cases the symptoms still persist after surgery. Previous studies reported that patients with cervical myelopathy showed higher mean diffusivity (MD) and lower fractional anisotropy (FA) than normal subjects between each spinal level. However, whether this local change would affect white matter tracts in the brain is not clear. In this study, we aimed to compare the differences of cerebral white matter microstructural property between patients with cervical myelopathy and health controls, and we aimed to identify the functional correlation of the change tracts in the brain. Subjects: Two groups of participants were recruited in the study: 27 healthy older adults (age: 56.63 ± 13.05, 18 males and 9 females), 27 patients with cervical myelopathy (age: 55.30 ± 13.03, 18 males and 9 females). Imaging: All participants received T1-weighted imaging and DSI on a 3T Siemens Prisma MRI System (Siemens Medical, Erlangen, Germany) with a 32-channel phased array head coil in National Taiwan University Hospital. The parameters were as follow. T1-weighted imaging used a three-dimensional magnetization-prepared rapid gradient-echo (MPRAGE) sequence, TR/TE = 2000/3 ms, FOV = 352 x 290 x 208 mm3, flip angle = 9o, resolution = 1 x 1 x 1 mm3. Diffusion spectrum imaging (DSI) used an echo planer imaging (EPI) diffusion sequence, TR/TE = 9600/130 ms, matrix size = 80 x 80, FOV = 200 x 200 mm2, resolution = 2.5 mm, 102 diffusion encoding gradients with bmax = 4000 s/mm2. Image Quality Assurance (QA): Only images with signal-to-noise ratio (SNR) higher than 25 were included for subsequent analysis. Analysis: We used whole brain tract-based automatic analysis (TBAA) to obtain a 2D connectogram for each DSI dataset. The connectogram provides generalized fractional anisotropy (GFA), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD) profiles of 76 white matter tract bundles. Each profile contained 100 sampled values at 100 equidistant steps along the tract. We used threshold free cluster weighted (TFCW) scores for group analysis. We calculated the effect size of each step between groups, and estimated weighted scores to select the most different tract steps among the two groups. We did the linear multiple regression to identify the main contributor of the tracts for the specific functional item. Result: A total of 23 segments were found to show top 5% difference in the weighted scores of GFA, AD or RD when comparing patients with cervical myelopathy with normal controls. The values of GFA of the affected segments were uniformly lower in patients. Conclusion: As expected, we found significant reduction in GFA in the sensorimotor tracts, which were supposed to be the primary affected tracts in cervical myelopathy. Moreover, we also found altered tracts that were mostly related to cognitive functions, such as the left fornix, right frontal-striatum to the ventral lateral prefrontal cortex, and the splenium of the corpus callosum. Our results are consistent with previous studies reporting that cognitive dysfunctions may be related to disorders of the cervical spine or spinal cord. We speculate that patients with cervical myelopathy may be subjected to emotion problems due to reduced mobility, which may lead to cognitive decline as reflected by the impairment of cognitive-related tracts. The relationship between cognitive function and white matter changes in the brain needs to be further studied.