Lumbar stenosis due to wild-type transthyretin amyloid-induced thickening of the ligamentum flavum: a separate etiology from degeneration of intervertebral discs?

Abstract

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.