Development of Screening Criteria to Detect Transthyretin Amyloid in the Ligamentum Flavum: Early Detection of Amyloidosis.

Abstract

Study design: Prospective cross-sectional study.

Objective: To develop and apply screening criteria for patients at risk of systemic amyloidosis undergoing routine lumbar decompression, using histopathological evaluation of ligamentum flavum (LF) tissue.

Summary of background data: Amyloidosis is the extracellular deposition of insoluble, misfolded proteins, leading to progressive multiorgan dysfunction. Although recent therapies can slow disease progression, they do not reverse existing organ damage, underscoring the importance of early detection. Musculoskeletal manifestations of amyloidosis, such as lumbar stenosis (LS), can precede cardiac symptoms, providing an opportunity for early detection and treatment. Amyloid deposition within the LF has been identified as a contributing factor to LF hypertrophy and spinal stenosis, yet no standardized guidelines exist for determining which patients should undergo LF tissue sampling during lumbar decompression surgery.

Methods: Patients with conditions linked to amyloidosis and axial T2 magnetic resonance imaging (MRI) LF thickness >4.9 mm were prospectively enrolled. LF tissue samples were stained with Congo red (CR), and positive cases were subtyped. Patients with confirmed amyloid were referred for cardiac evaluation.

Results: Fifty patients were enrolled in the study; 14 (28%) had positive CR staining, and 10 (20%) were determined to have transthyretin amyloidosis (ATTR) (95% CI, 17.5-41.7% and 11.2-33.0%, respectively). LF was thicker in the positive cohort (6.3±0.6 vs. 5.6±0.8; P≤.001). There was no difference in age or number of levels decompressed. Six of the 14 patients elected to undergo further cardiac evaluation, including a 99mTc-PYP scan; all results were negative.

Conclusion: The screening criteria identified patients at risk for amyloidosis. 20% of patients were found to have ATTR, and those who completed cardiac evaluation had no evidence of cardiac involvement at the time of evaluation. While larger studies are needed, LF analysis during routine decompression may provide a practical method for early detection.