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

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.

Increased thickness of lumbar spine ligamentum flavum in wild-type transthyretin amyloidosis.

BACKGROUND: Wild-type transthyretin (ATTRwt) amyloid deposits have been found in the ligamentum flavum of patients undergoing surgery for spinal stenosis. The relationship between ATTRwt and ligamentum flavum thickness is unclear. We used pre-operative magnetic resonance imaging (MRI) to analyze ligamentum flavum thickness in lumbar spinal stenosis patients with and without ATTRwt amyloid. METHODS: We retrospectively identified 178 patients who underwent lumbar spine surgery. Ligamentum flavum thickness of 253 specimens was measured on T2-weighted axial MRI. Amyloid presence was confirmed through Congo red staining of specimens, and ATTRwt was confirmed using mass-spectrometry and gene sequencing. RESULTS: Twenty four of the 178 patients (13.5%) were found to have ATTRwt in the ligamentum flavum. Forty ATTRwt specimens and 213 non-ATTRwt specimens were measured. Mean ligamentum flavum thickness was 4.92 (±1.27) mm in the ATTRwt group and 4.00 (±1.21) mm in the non-ATTRwt group (p < 0.01). The ligamentum flavum was thickest at L4-L5, with a thickness of 5.15 (±1.27) mm and 4.23 (±1.29) mm in the ATTRwt and non-ATTRwt group, respectively (p = 0.007). There was a significant difference in ligamentum flavum thickness between ATTRwt and non-ATTRwt case for both patients younger than 70 years (p = 0.016) and those older than 70 years (p = 0.004). ATTRwt patients had greater ligamentum flavum thickness by 0.83 mm (95% confidence interval (CI): 0.41-1.25 mm, p < 0.001) when controlled for age and lumbar level. CONCLUSION: Patients with ATTRwt had thicker ligamentum flavum compared to patients without ATTRwt. Further studies are needed to investigate the pathophysiology of ATTRwt in ligamentum flavum thickening.

Wild-Type Transthyretin Amyloidosis Occurring in the Ligamentum Flavum of the Cervicothoracic Spine.

BACKGROUND: Wild-type transthyretin amyloid (ATTRwt) has been noted to deposit in the ligamentum flavum of the spine. Prior studies have focused on ATTRwt in the lumbar region, but studies discussing its presence in other levels of the spine are lacking. We report on the presentation of patients with confirmed amyloid in the cervicothoracic regions and discuss the literature to date. METHODS: We retrospectively identified patients at a single institution who underwent surgery for spinal stenosis and had pathologic specimens sent for amyloidosis testing with Congo red staining. ATTRwt was confirmed by the presence of transthyretin amyloid by typing and the absence of mutations in the TTR gene sequence. A final study group of patients with ATTRwt and spinal involvement was established (n = 27). RESULTS: Of 27 patients with amyloid in the spine, 24 (89%) had amyloid present in the lumbar region, 2 (7%) had amyloid in the cervical region, and 1 (4%) had amyloid in the thoracic region. The median age at which patients in the study underwent surgery was 71 years (interquartile range: 9). Spinal stenosis was the indication for surgery in 26 of 27 (96%) patients. Surgery involved 1 or 2 spinal levels in 24 of 27 (89%) patients. CONCLUSIONS: ATTRwt amyloid predominantly deposits in the lumbar region, but it can also be present in the cervical and thoracic regions. While the lumbar regions should remain a focus for evaluation of ATTRwt amyloidosis, the cervicothoracic region should not be ignored.