Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis

Abstract

Background

Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS.

Methods

Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC).

Results

Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (p < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, p = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed.

Conclusions

Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making.

Keywords:

• Early diagnosis
• ligamentum flavum
• lumbar spinal stenosis
• magnetic resonance imaging
• transthyretin amyloid

Author contributions

Adalgisa Condoluci and Bernhard Gerber designed the study, interpreted data and wrote the manuscript. Francesco Marchi performed neurosurgical interventions and biopsies and wrote the manuscript. Chiara Kessler managed sample logistics and biobanking and contributed to manuscript revision. Lodovico Terzi di Bergamo performed bioinformatic analysis, interpreted data and contributed to manuscript preparation. Emanuele Crupi and Fabio Bergamini managed clinical data collection and contributed to manuscript revision. Georg Stussi and Claudio Gobbi provided key scientific insights, contributed to data interpretation, and manuscript revision. Pietro Scarone, Dominique E. Kuhlen and Luca Fumagalli performed neurosurgical interventions and biopsies and contributed to data interpretation and manuscript revision. Christoph Röcken performed pathology studies and contributed to data interpretation and manuscript revision. Daniela Distefano and Emanuele Pravatà performed neuro-radiological assessment, interpreted data results and contributed to manuscript revision.

Disclosure statement

All the authors declare no conflicts of interest.

Data availability statement

Single patient data available upon motivated request by email to the corresponding author.

Additional information

Funding

Unrestricted grant from Pfizer.