Lumbar ligamentum flavum burden: Evaluating the role of ATTRwt amyloid deposition in ligamentum flavum thickness at all lumbar levels

Keith M George; Nicholas S Hernandez; Jeffrey Breton; Baillee Cooper; Richard S Dowd; Jayde Nail; Anthony Yu; Michael Mastroianni; Andy Wang; Amandeep Godara; Diana Zhang; Knarik Arkun; Ayan R Patel; Cindy Varga; Oscar Soto; James Kryzanski; Raymond Comenzo; Ron Riesenburger

doi:10.1016/j.clineuro.2021.106708

Lumbar ligamentum flavum burden: Evaluating the role of ATTRwt amyloid deposition in ligamentum flavum thickness at all lumbar levels

Clin Neurol Neurosurg. 2021 Jul:206:106708. doi: 10.1016/j.clineuro.2021.106708. Epub 2021 May 25.

Authors

Keith M George¹, Nicholas S Hernandez¹, Jeffrey Breton¹, Baillee Cooper¹, Richard S Dowd², Jayde Nail², Anthony Yu¹, Michael Mastroianni¹, Andy Wang¹, Amandeep Godara³, Diana Zhang⁴, Knarik Arkun⁵, Ayan R Patel⁶, Cindy Varga⁷, Oscar Soto⁸, James Kryzanski², Raymond Comenzo⁷, Ron Riesenburger⁹

Affiliations

¹ Tufts University School of Medicine, 145 Harrison Ave., Boston, MA 02111, USA; Tufts Department of Neurosurgery, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
² Tufts Department of Neurosurgery, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
³ University of Utah Health Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
⁴ Tufts Department of Internal Medicine, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
⁵ Tufts Department of Pathology, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
⁶ Tufts Department of CardioVascular Center, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
⁷ Tufts Department of Hematology and Oncology, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
⁸ Tufts Department of Neurology, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
⁹ Tufts Department of Neurosurgery, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA. Electronic address: RRiesenburger@TuftsMedicalCenter.org.

PMID: 34053807
DOI: 10.1016/j.clineuro.2021.106708

Abstract

Background: Wild-type transthyretin (ATTRwt) amyloid deposition has been found in the ligamentum flavum (LF) of patients undergoing spinal stenosis surgery. Our group previously reported that ATTRwt amyloid is associated with an increased lumbar ligamentum flavum thickness at symptomatic levels that required surgery. A comprehensive evaluation of LF thickness at asymptomatic levels in addition to symptomatic, treated levels has never been performed in ATTRwt patients. In this study, we compare the total LF thickness of all lumbar levels (lumbar LF burden) in ATTRwt and non-ATTRwt patients.

Methods: We retrospectively identified 177 patients who underwent lumbar spine surgery. Ligamentum flavum thickness of 885 lumbar levels was measured on T2-weighted axial MRI. Amyloid presence was confirmed through Congo red staining of specimens, and subtype of ATTRwt was confirmed using mass-spectrometry and gene sequencing.

Results: Of the 177 patients, 30 (16.9%) were found to have ATTRwt in the ligamentum flavum. One hundred and fifty ATTRwt levels and 735 non-ATTRwt levels were measured by four different reviewers, with an intraclass coefficient (ICC) of 0.79. Mean ligamentum flavum thickness was 4.64 (±1.31) mm in the ATTRwt group and 3.99 (±1.45) mm in the non-ATTRwt group (p < 0.001). The lumbar LF burden (sum of ligamentum flavum thickness at all lumbar levels) for ATTRwt patients was 23.22 (±4.48) mm, and for non-ATTRwt patients was 19.96 (±5.49) mm (p = 0.003) CONCLUSION: The lumbar LF burden is greater in patients with ATTRwt amyloid compared to non-ATTRwt patients. This supports prior evidence that ATTRwt amyloid deposition might be associated with increased LF thickness and lumbar stenosis. This potential association requires more research and could be an important finding, as medications have recently become available that can treat patients with ATTRwt amyloid deposition.

Keywords: ATTRwt amyloid; Amyloid; Ligamentum flavum; Lumbar ligamentum flavum burden; Spinal stenosis.

MeSH terms

Adult
Aged
Amyloid Neuropathies, Familial / pathology*
Female
Humans
Ligamentum Flavum / pathology*
Lumbosacral Region
Male
Middle Aged
Prealbumin
Retrospective Studies

Substances

Prealbumin
TTR protein, human

Supplementary concepts

Amyloidosis, Hereditary, Transthyretin-Related