Wang Andy Y, Kanter Matthew, Olmos Michelle, McPhail Ellen D, Safain Mina G, Kryzanski James, Arkun Knarik, Riesenburger Ron I
1Department of Neurosurgery, Tufts Medical Center, Boston, Massachusetts.
2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; and.
J Neurosurg Spine. 2022 Jun 24;37(5):687-693. doi: 10.3171/2022.5.SPINE22362. Print 2022 Nov 1.
Wild-type transthyretin amyloid (ATTRwt) is deposited in the ligamentum flavum (LF) of a subset of patients with spinal stenosis who undergo decompressive surgery, although its role in the pathophysiology of spinal stenosis is unknown. It has been theorized that degeneration of intervertebral discs causes increased mechanical stress and inflammatory/degenerative cascades and ultimately leads to LF fibrosis. If ATTRwt deposits contribute to LF thickening and spinal stenosis through a different pathway, then patients with ATTRwt may have less severe disc degeneration than those without it. In this study, the authors compared the severity of disc degeneration between patients with lumbar stenosis with and without amyloid in their LF to test whether ATTRwt is a unique contributor to LF thickening and spinal stenosis.
Of 324 consecutive patients between 2018 and 2019 who underwent decompression surgery for spinal stenosis and had LF samples sent for pathological analysis, 31 harboring ATTRwt were compared with 88 controls. Patient medical records were retrospectively reviewed for demographic and surgical information. Disc degeneration was assessed on preoperative T2-weighted MR images with the modified Pfirrmann grading system at every lumbar disc level.
Baseline characteristics were similar between the groups, except for a statistically significant increase in age in the ATTRwt group. The crude unadjusted comparisons between the groups trended toward a less severe disc degeneration in the ATTRwt group, although this difference was not statistically significant. A multivariable linear mixed-effects model was created to adjust for the effects of age and to isolate the influence of ATTRwt, the presence of an operation at the level, and the specific disc level (between L1 and S1). This model revealed that ATTRwt, the presence of an operation, and the specific level each had significant effects on modified Pfirrmann scores.
Less severe disc degeneration was noted in patients with degenerative spinal stenosis harboring ATTRwt compared with those without amyloid. This finding suggests that ATTRwt deposition may play a separate role in LF thickening from that played by disc degeneration. Future studies should aim to elucidate this potentially novel pathophysiological pathway, which may uncover an exciting potential for the development of amyloid-targeted therapies that may help slow the development of spinal stenosis.
野生型转甲状腺素蛋白淀粉样变（ATTRwt）沉积于接受减压手术的脊柱狭窄患者亚组的黄韧带（LF）中，但其在脊柱狭窄病理生理学中的作用尚不清楚。理论上，椎间盘退变会导致机械应力增加以及炎症/退变级联反应，最终导致LF纤维化。如果ATTRwt沉积通过不同途径导致LF增厚和脊柱狭窄，那么ATTRwt患者的椎间盘退变可能比无ATTRwt患者轻。在本研究中，作者比较了LF中有和没有淀粉样变的腰椎管狭窄症患者之间的椎间盘退变严重程度，以检验ATTRwt是否是LF增厚和脊柱狭窄的独特促成因素。
在2018年至2019年间连续324例接受脊柱狭窄减压手术并送检LF样本进行病理分析的患者中，将31例有ATTRwt的患者与88例对照进行比较。回顾性查阅患者病历以获取人口统计学和手术信息。在术前T2加权磁共振成像上，使用改良的Pfirrmann分级系统对每个腰椎间盘水平的椎间盘退变进行评估。
两组的基线特征相似，但ATTRwt组的年龄有统计学意义的显著增加。两组之间未经调整的粗略比较显示，ATTRwt组的椎间盘退变有较轻的趋势，尽管这种差异无统计学意义。建立了一个多变量线性混合效应模型，以调整年龄的影响并分离ATTRwt、该水平手术的存在以及特定椎间盘水平（L1至S1之间）的影响。该模型显示，ATTRwt、手术的存在以及特定水平对改良的Pfirrmann评分均有显著影响。
与无淀粉样变的患者相比，有ATTRwt的退行性脊柱狭窄患者的椎间盘退变较轻。这一发现表明，ATTRwt沉积在LF增厚中可能起与椎间盘退变不同的作用。未来的研究应旨在阐明这一潜在的新病理生理途径，这可能为开发针对淀粉样变的疗法揭示令人兴奋的潜力，这些疗法可能有助于减缓脊柱狭窄的发展。
