1Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden.
2Department of Neurosurgery, Hippokratio General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
J Neurosurg Spine. 2021 Jan 29;34(4):632-641. doi: 10.3171/2020.8.SPINE20965. Print 2021 Apr 1.
Degenerative cervical spondylotic myelopathy (CSM) is a major cause of spinal cord dysfunction with an unpredictable prognosis. Βiomarkers reflecting pathophysiological processes in CSM have been insufficiently investigated. It was hypothesized that preoperative cerebrospinal fluid (CSF) biomarker levels are altered in patients with CSM and correlate with neurological status and outcome.
CSF biomarkers from patients with CSM and controls were analyzed with immunoassays. Spinal cord changes were evaluated with MRI. The American Spinal Cord Injury Association Impairment Scale, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and the EQ-5D questionnaire were applied prior to and 3 months after surgery. A p value < 0.05 was considered statistically significant.
Twenty consecutive CSM patients with a mean age of 67.7 ± 13 years and 63 controls with a mean age of 65.2 ± 14.5 years (p > 0.05) were included in the study. In the CSM subjects, CSF neurofilament light subunit (NF-L) and glial fibrillary acidic protein (GFAP) concentrations were higher (p < 0.05), whereas fatty acid-binding protein 3 (FABP3), soluble amyloid precursor proteins (sAPPα and sAPPβ), and amyloid β (Aβ) peptide (Aβ38, Aβ40, and Aβ42) concentrations were lower than in controls (p < 0.05). Aβ peptide levels correlated positively with symptom duration. Preoperative JOACMEQ lower extremity function and CSF NF-L levels correlated positively, and the JOACMEQ bladder function correlated negatively with sAPPα and sAPPβ (p < 0.05). CSF NF-L and FABP3 levels were higher in patients with improved outcome (EQ-5D visual analog scale difference > 20).
CSF biomarkers of glial and axonal damage, inflammation, and synaptic changes are altered in symptomatic CSM patients, indicating that axonal injury, astroglial activation, and Aβ dysmetabolism may be present in these individuals. These findings reflect CSM pathophysiology and may aid in prognostication. However, future studies including larger patient cohorts, postoperative biomarker data and imaging, and longer follow-up times are required to validate the present findings.
退行性颈椎病(CSM)是一种脊髓功能障碍的主要原因,其预后不可预测。反映 CSM 病理生理过程的生物标志物研究不足。据推测,CSM 患者术前脑脊液(CSF)生物标志物水平发生改变,并与神经状态和预后相关。
采用免疫分析法分析 CSM 患者和对照组的 CSF 生物标志物。通过 MRI 评估脊髓变化。在手术前和手术后 3 个月应用美国脊髓损伤协会损伤量表(AIS)、日本矫形协会颈椎病评估问卷(JOACMEQ)和 EQ-5D 问卷。p 值<0.05 被认为具有统计学意义。
连续纳入 20 例 CSM 患者(平均年龄 67.7±13 岁)和 63 例对照组(平均年龄 65.2±14.5 岁)(p>0.05)。CSM 患者 CSF 神经丝轻链(NF-L)和胶质纤维酸性蛋白(GFAP)浓度较高(p<0.05),而脂肪酸结合蛋白 3(FABP3)、可溶性淀粉样前体蛋白(sAPPα 和 sAPPβ)和淀粉样β肽(Aβ38、Aβ40 和 Aβ42)浓度较低(p<0.05)。Aβ 肽水平与症状持续时间呈正相关。术前 JOACMEQ 下肢功能与 CSF NF-L 水平呈正相关,JOACMEQ 膀胱功能与 sAPPα 和 sAPPβ 呈负相关(p<0.05)。预后改善的患者 CSF NF-L 和 FABP3 水平较高(EQ-5D 视觉模拟评分差值>20)。
有症状 CSM 患者的神经胶质和轴索损伤、炎症和突触变化的 CSF 生物标志物发生改变,表明这些患者可能存在轴索损伤、星形胶质细胞激活和 Aβ 代谢异常。这些发现反映了 CSM 的病理生理学,并可能有助于预测预后。然而,需要包括更大的患者队列、术后生物标志物数据和影像学检查以及更长的随访时间在内的进一步研究来验证目前的发现。