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解读神经胶质细胞特异性代谢物作为早期颈椎病生物标志物的作用——来自体内磁共振波谱研究的见解

Deciphering the role of glial cell-specific metabolites as biomarkers in early cervical myelopathy-insights from in vivo MRS study.

作者信息

Ramachandran Karthik, Thippeswamy Pushpa Bhari, Shetty Ajoy Prasad, Kanna Rishi Mugesh, Rajasekaran Shanmuganathan

机构信息

Department of Spine Surgery, Ganga Hospital, 313, Mettupalayam Road, Coimbatore, India.

Department of Radiology, Ganga Hospital, 313, Mettupalayam Road, Coimbatore, India.

出版信息

Spine J. 2025 May 24. doi: 10.1016/j.spinee.2025.05.031.


DOI:10.1016/j.spinee.2025.05.031
PMID:40418991
Abstract

BACKGROUND: Early degenerative cervical myelopathy (DCM) presents a diagnostic dilemma due to its variability in presentation, overlap with other clinical conditions, and lack of specific clinical tests. Although magnetic resonance imaging (MRI) is the preferred imaging modality, its ability to detect early cervical myelopathy remains uncertain due to its inability to detect microstructural changes at an early spondylotic stage. Magnetic Resonance Spectroscopy (MRS) is a novel, noninvasive spinal imaging technique that provides metabolic and biochemical information regarding spinal cord function. PURPOSE: This study aims to determine the diagnostic role of MRS and Diffusion Tensor Imaging (DTI) in patients with DCM. Additionally, we intend to explore the role of MRS metabolites/ratio as molecular biomarkers for the early detection of DCM. STUDY DESIGN: Prospective observational study. PATIENT SAMPLE: The study includes a sample size of 89 subjects (20 asymptomatic volunteers and 69 patients with different grades of DCM. OUTCOME MEASURES: Predictability of MRS and DTI in identifying early DCM. The severity of myelopathy was assessed using the modified Japanese Orthopaedic Association (mJOA) score. METHODS: The study populations were classified according to their mJOA scores: Group 1 included asymptomatic volunteers with no clinical features of cervical myelopathy. Group 2 included patients with a mJOA score of 15 to 17 (mild myelopathy) presenting with early symptoms of myelopathy, like arm pain, hand numbness and clumsiness with/ without the symptoms of radiculopathy. Group 3 included patients with mJOA score of 12 to 14 (moderate myelopathy), presenting with symptoms like gait instability and a decrease in hand dexterity. Group 4 included patients with mJOA score of less than or equal to 11 (severe myelopathy), presenting with advanced symptoms like walker/wheelchair-dependence, loss of hand dexterity, and bladder disturbances. We then looked at MR Imaging in these symptomatic patients to evaluate cervical stenosis. Single voxel MRS was placed at the C2 level, and DTI parameters were measured at the site of maximum compression. MRI parameters like the compression level, presence of signal hyperintensity, grading of stenosis, and compression ratio were also analysed in T2W MRI images. RESULTS: Among the 89-study population, 20 asymptomatic volunteers in group 1 and 23 patients each in groups 2, 3 and 4 were included. Among the various parameters, there was a statistically significant difference between the groups for various MRS metabolite ratios, namely NAA/Cr (p=.008), Cho/Cr (p=.025), Cho/NAA (p<.001), Cr/NAA (p<.001) and MIn/NAA (p=.003) as well as DTI parameters namely FA (p=.010) and ADC (p=.011). A significant linear correlation was observed between the severity of myelopathy (mJOA score) and the following parameters: Cho/NAA (R=0.510, p=.000), MIn/NAA (R=0.393, p=.002), Cr/NAA (R=0.354, p=.007), FA (R=-0.331, p=.012), ADC (R=0.321, p=.015), Cho/Cr (R=0.289, p=.029) and NAA (R=-0.288, p=.030). Among the various metabolites, we observed that the glial cell-specific metabolites (Cho, Cr and MIn) with respect to the neuron-specific metabolite, NAA, had good correlation in early identification of DCM patients presenting with mild to moderate disease severity. ROC analysis showed that glial cell-specific metabolites ratio(Cho/NAA, Cr/NAA, MIn/NAA) had good AUC for identifying both mild (0.725, 0.770, 0.765) and moderate (0.825, 0.736, 0.760) myelopathy. CONCLUSION: Our study highlights that MRS-based Glial cell-specific metabolites ratio (Cho/NAA, Cr/NAA, and MIn/NAA) can be reliable molecular biomarkers for identifying early degenerative cervical myelopathy.

摘要

背景:早期退行性颈椎病脊髓病(DCM)由于其临床表现的多样性、与其他临床病症的重叠性以及缺乏特异性临床检查,呈现出诊断难题。尽管磁共振成像(MRI)是首选的成像方式,但由于其在早期脊柱退变阶段无法检测到微观结构变化,其检测早期颈椎病脊髓病的能力仍不确定。磁共振波谱(MRS)是一种新型的无创脊柱成像技术,可提供有关脊髓功能的代谢和生化信息。 目的:本研究旨在确定MRS和弥散张量成像(DTI)在DCM患者中的诊断作用。此外,我们打算探索MRS代谢物/比值作为早期检测DCM的分子生物标志物的作用。 研究设计:前瞻性观察研究。 患者样本:该研究包括89名受试者的样本量(20名无症状志愿者和69名不同程度DCM患者)。 观察指标:MRS和DTI在识别早期DCM中的可预测性。使用改良的日本骨科学会(mJOA)评分评估脊髓病的严重程度。 方法:根据mJOA评分对研究人群进行分类:第1组包括无颈椎病脊髓病临床特征的无症状志愿者。第2组包括mJOA评分为15至17(轻度脊髓病)的患者,表现出脊髓病的早期症状,如手臂疼痛、手部麻木和笨拙,伴有/不伴有神经根病症状。第3组包括mJOA评分为12至14(中度脊髓病)的患者,表现出步态不稳和手部灵活性下降等症状。第4组包括mJOA评分小于或等于11(重度脊髓病)的患者,表现出晚期症状,如依赖步行器/轮椅、手部灵活性丧失和膀胱功能障碍。然后我们观察这些有症状患者的磁共振成像以评估颈椎管狭窄。在C2水平放置单体素MRS,并在最大压迫部位测量DTI参数。还在T2加权MRI图像中分析了诸如压迫水平、信号高信号的存在、狭窄分级和压迫率等MRI参数。 结果:在89名研究人群中,第1组的20名无症状志愿者以及第2、3和4组各23名患者被纳入。在各种参数中,各MRS代谢物比值,即NAA/Cr(p = 0.008)、Cho/Cr(p = 0.025)、Cho/NAA(p < 0.001)、Cr/NAA(p < 0.001)和MIn/NAA(p = 0.003)以及DTI参数,即FA(p = 0.010)和ADC(p = 0.011),在各组之间存在统计学显著差异。观察到脊髓病严重程度(mJOA评分)与以下参数之间存在显著线性相关性:Cho/NAA(R = 0.510,p = 0.000)、MIn/NAA(R = 0.393,p = 0.002)、Cr/NAA(R = 立的分子生物标志物。 0.354,p = 0.007)、FA(R = -0.331,p = 0.012)、ADC(R = 0.321,p = 0.015)、Cho/Cr(R = 0.289,p = 0.029)和NAA(R = -0.288,p = 0.030)。在各种代谢物中,我们观察到相对于神经元特异性代谢物NAA的胶质细胞特异性代谢物(Cho、Cr和MIn)在早期识别疾病严重程度为轻度至中度的DCM患者方面具有良好的相关性。ROC分析表明,胶质细胞特异性代谢物比值(Cho/NAA、Cr/NAA、MIn/NAA)在识别轻度(0.725、0.770、0.765)和中度(0.825、0.736、0.760)脊髓病方面具有良好的曲线下面积(AUC)。 结论:我们的研究强调基于MRS的胶质细胞特异性代谢物比值(Cho/NAA、Cr/NAA和MIn/NAA)可以作为识别早期退行性颈椎病脊髓病的可靠分子生物标志物。

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