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Spinal stenosis is one of the most common neurosurgical diseases and a leading cause of pain and disability. Wild-type transthyretin amyloid (ATTRwt) has been found in the ligamentum flavum (LF) of a significant subset of patients with spinal stenosis who undergo decompression surgery. Histologic and biochemical analyses of LF specimens from spinal stenosis patients, normally discarded as waste, have the potential to help elucidate the underlying pathophysiology of spinal stenosis and possibly allow for medical treatment of stenosis and screening for other systemic diseases. In the present review, we discuss the utility of analyzing LF specimens after spinal stenosis surgery for ATTRwt deposits. Screening for ATTRwt amyloidosis cardiomyopathy through LF specimens has led to the early diagnosis and treatment of cardiac amyloidosis in several patients, with more expected to benefit from this process. Emerging evidence in the literature also point to ATTRwt as a contributor to a previously unrecognized subtype of spinal stenosis in patients who might, in the future, benefit from medical therapy. In the present report, we review the current literature regarding the early detection of ATTRwt cardiomyopathy via LF screening and the possible contribution of ATTRwt deposits in the LF to spinal stenosis development., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: One key contributor to lumbar stenosis is thickening of the ligamentum flavum (LF), a process still poorly understood. Wild-type transthyretin amyloid (ATTRwt) has been found in the LF of patients undergoing decompression surgery, suggesting that amyloid may play a role. However, it is unclear whether within patients harboring ATTRwt, the amount of amyloid is associated with LF thickness., Methods: From an initial cohort of 324 consecutive lumbar stenosis patients whose LF specimens from decompression surgery were sent for analysis (2018-2019), 33 patients met the following criteria: 1) Congo red-positive amyloid in the LF, 2) ATTRwt by mass spectrometry-based proteomics, and 3) an available preoperative magnetic resonance imaging. Histological specimens were digitized, and amyloid load was quantified through Trainable Weka Segmentation machine learning. LF thicknesses were manually measured on axial T2-weighted preoperative magnetic resonance imaging scans at each lumbar level, L1-S1. The sum of thicknesses at every lumbar LF level (L1-S1) equals "lumbar LF burden"., Results: Patients had a mean age of 72.7 years (range = 59-87), were mostly male (61%) and white (82%), and predominantly had surgery at L4-L5 levels (73%). Amyloid load was positively correlated with LF thickness (R = 0.345, P = 0.0492) at the levels of surgical decompression. Furthermore, amyloid load was positively correlated with lumbar LF burden (R = 0.383, P = 0.0279)., Conclusions: Amyloid load is positively correlated with LF thickness and lumbar LF burden across all lumbar levels, in a dose-dependent manner. Further studies are needed to validate these findings, uncover the underlying pathophysiology, and pave the way toward using therapies that slow LF thickening., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Transthyretin wild-type (ATTRwt) amyloidosis is a systemic process resulting in deposition of misfolded transthyretin protein in several different tissues throughout the body. It is known to be a cause of progressive, life-threatening cardiomyopathy and lumbar spinal stenosis and carpal tunnel syndrome., Case Description: Here we present the case of a 71-year-old man who has clinical manifestations of all 3 entities over several years, providing a picture of the natural history of ATTRwt amyloidosis. This patient eventually underwent a heart transplant because of progressive cardiac amyloidosis (CA) resulting in end-stage heart failure. However, symptoms in carpal tunnel and lumbar spine manifested years before the symptoms of heart failure. ATTRwt amyloidosis may present as a clinical triad of lumbar stenosis, carpal tunnel syndrome, and heart failure. Recently developed medications have shown efficacy in slowing the progress of systemic and cardiac amyloidosis., Conclusions: Knowing that extracardiac symptoms may occur first, we propose that sending ligamentum flavum and flexor tenosynovium for pathologic evaluation may be a unique opportunity to screen and treat a population of patients at risk for developing CA and heart failure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Intracranial metastasis is a common complication of systemic malignancy. A rare subset of intracranial masses constitutes tumor-to-tumor metastasis, in which an extracranial neoplasm hematogenously spreads to an existing intracranial lesion., Case Description: Here we present the unique case of a 59-year-old man with known hepatocellular carcinoma who presented with acute headaches, double vision, vertigo, and gait instability in the context of 2 years of right-sided hearing loss. Head imaging showed a heterogeneous right cerebellopontine angle mass extending into the porus acousticus with adjacent cerebellar edema. Histopathologic analysis after resection found coexisting hepatocellular carcinoma within a vestibular schwannoma., Conclusions: Tumor-to-tumor metastasis is an important consideration in the diagnostic work-up and treatment of patients with known systemic malignancy who present with a new intracranial lesion. This pathologic entity could be missed if this patient were treated with single-fraction radiosurgery such as Gamma Knife., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inhibitory killer immunoglobulin (Ig)-like receptors (KIRs) recognize HLA-C and -B epitopes on target cells, thereby regulating natural killer (NK) cell activity. In 178 patients receiving T-cell-depleted HLA-identical sibling transplants for acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS), analysis of donor KIR genotype with HLA genotype demonstrated that 62.9% of the patients lacked an HLA ligand for donor-inhibitory KIR. Lack of HLA ligand for donor-inhibitory KIR (missing KIR ligand) had no effect on disease-free survival (DFS), overall survival (OS), or relapse in patients receiving transplants for CML and ALL. In patients with AML and MDS, however, there was a significant missing KIR ligand effect on DFS (P = .014; hazard ratio [HR], 0.53; 95% confidence interval [95% CI], 0.28-0.88) and OS (P = .03; HR, 0.53; 95% CI, 0.3-0.93). Incidence of relapse was also lower in patients with AML and MDS who lacked the HLA ligand for donor-inhibitory KIR (P = .04; HR, 0.41; 95% CI, 0.18-0.97). AML and MDS patients lacking 2 HLA ligands for donor-inhibitory KIR had the highest DFS (P = .002) and OS (P = .003). There was no significant contribution of donor-activating KIR to transplantation outcome in these patients. These data indicate that the absence of class I ligand in the recipient for donor-inhibitory KIR can be a prognostic factor for transplantation outcome in HLA-identical sibling transplantation and that the lack of HLA-C or -B ligands for donor-inhibitory KIR can contribute to improved outcomes for patients with AML and MDS.