Lysozyme as an amyloid fibril protein together with transthyretin in the ligamentum flavum in association with lumbar spinal stenosis
Background Transthyretin amyloid (ATTR) is frequently found in aging ligaments and may represent an early sign of systemic ATTR amyloidosis, particularly of wild-type origin. Amyloid deposits of other compositions are commonly observed alongside ATTR deposits. Methods Ligamentum flavum samples obtained during surgery for lumbar spinal stenosis, containing distinct ATTR amyloid deposits as well as amyloid of unknown composition, were analyzed using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), electron microscopy, immunohistochemistry, and immunofluorescence confocal microscopy. In vitro fibril formation and potential cross-seeding by the two major proteins, transthyretin and lysozyme, were assessed with the thioflavin-T assay. Results A close topographic association between ATTR deposits and elastic material was evident. Distinct ATTR amyloid was intermingled with non-ATTR amyloid. HPLC-MS/MS identified three major amyloid fibril proteins with high score: transthyretin (TTR), apolipoprotein AI, and lysozyme. Congo red positivity combined with immunoreactivity for TTR and lysozyme demonstrated that ATTR predominated, though distinct lysozyme amyloid deposits were also present. Only minimal apolipoprotein AI-positive amyloid was detected. In vitro, cross-seeding between TTR and lysozyme was not observed; however, lysozyme inhibited TTR fibrillation. Conclusion In lumbar spinal stenosis, ATTR amyloid deposits are predominant but are often intermixed with other amyloid deposits, notably those of lysozyme origin.
- Research Article
72
- 10.1111/joim.13222
- Jan 7, 2021
- Journal of Internal Medicine
BackgroundWild‐type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy.ObjectiveTo study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis.Materials and methodsA total of 250 patients, aged 50–89 (57% women), none with known cardiovascular disease, were included. Ligaments were investigated microscopically for amyloid. ATTR type was determined by immunohistochemistry and fibril type by Western blot. The amount of amyloid was graded 0‐4. All patients with grade 3‐4 ATTR deposits were offered cardiac investigation including ECG, cardiac ultrasound, plasma NT‐proBNP and cardiac magnetic resonance (CMR), including modern tissue characterization.ResultsAmyloid was identified in 221 of the samples (88.4%). ATTR appeared in 93 samples (37%) of whom 42 (17 women and 25 men) were graded 3‐4; all had fibril type A (mixture of full‐length TTR and fragmented TTR). Twenty‐nine of 42 patients with grade 3‐4 ATTR deposits accepted cardiovascular investigations; none of them had definite signs of cardiac amyloidosis, but five men had a history of carpal tunnel syndrome.ConclusionsThe prevalence of ATTR deposits in ligamentum flavum in patients with lumbar spinal stenosis was high but not associated with manifest ATTR cardiac amyloidosis. However, the findings of fibril type A, the prevalence of previous carpal tunnel syndrome and ATTR amyloid in surrounding adipose and vascular tissue indicate that amyloid deposits in ligamentum flavum may be an early manifestation of systemic ATTR disease.
- Research Article
2
- 10.1080/13506129.2025.2481310
- Mar 25, 2025
- Amyloid
Background Wild-type transthyretin (ATTRwt) amyloidosis is underdiagnosed and generally diagnosed with manifest cardiac involvement. Lumbar spinal stenosis (LSS) might be an early sign of systemic transthyretin amyloidosis and a possible screening target for early diagnosis. Objectives To assess the prevalence of cardiac amyloidosis (CA) 6 years post-LSS surgery, among patients with transthyretin amyloid deposits in ligamentum flavum. Methods Twenty-one patients who had surgery for LSS in 2016–2018 and grade 3–4 ATTR amyloid deposits in ligamentum flavum were followed up in 2022–2023, including biomarkers, echocardiography, cardiac magnetic resonance (CMR) and nuclear imaging. Results At follow-up, median age was 79 years, 16% (3/19) displayed cardiac uptake on scintigraphy consistent with ATTR-CA. Forty-eight percent (10/21) had a history of other tenosynovial conditions associated with ATTRwt. We observed a small increase in tissue characteristics using CMR, and a decrease in left ventricular global longitudinal strain and left atrial strain on echocardiography. Conclusions In this prospective cohort study, 16% were diagnosed with ATTRwt cardiomyopathy, six years following surgery for LSS. History of other tenosynovial conditions associated with ATTRwt amyloidosis was common. These findings strengthen the hypothesis that LSS is a possible manifestation of ATTRwt amyloidosis and that in selected patients with LSS, cardiac follow-up is of value.
- Abstract
- 10.1016/j.spinee.2020.05.158
- Sep 1, 2020
- The Spine Journal
55. Early deformity development following decompressive surgery for lumbar spinal stenosis
- Research Article
- 10.1093/eurheartj/ehae666.2096
- Oct 28, 2024
- European Heart Journal
Background Systemic wild type transthyretin (ATTRwt) amyloidosis is underdiagnosed and generally diagnosed in manifest cardiac disease. Lumbar spinal stenosis (LSS) might be an early sign of ATTRwt and a possible screening target for early diagnosis. Aim To characterize patients with transthyretin amyloid deposits in ligamentum flavum six years after surgery for lumbar spinal stenosis, and assess prevalence of undiagnosed cardiac amyloidosis. Materials and methods In this prospective cohort study, 21 patients who had surgery for LSS in 2016-2018 and grade 3-4 ATTR deposits in ligamentum flavum, without manifest cardiac amyloidosis (CA) were followed up in 2022-2023, including biomarkers and multimodality cardiac imaging. Results Median age at follow-up was 79 years and 62% were male; 16% (3/19) of patients had DPD-scintigraphy and were diagnosed with ATTRwt cardiac amyloidosis. 48% (10/21) had a history of other tenosynovial conditions that associate to ATTRwt amyloidosis. on echocardiography. Conclusion In this prospective cohort study, 16% of patients were diagnosed with ATTRwt cardiomyopathy after a median of six years following surgery for lumbar spinal stenosis. These findings strengthen the hypothesis that LSS is a possible manifestation of ATTRwt amyloidosis and that analysis for amyloid in connective tissue and subsequent cardiac follow-up is of value.
- Research Article
- 10.3390/medicina61040628
- Mar 29, 2025
- Medicina (Kaunas, Lithuania)
Background and Objectives: Lumbar spinal stenosis (LSS) is a leading cause of back surgery in elderly individuals. Additionally, LSS can result in buttock pain; abnormal sensations; or even loss of sensation in the thighs, feet, legs, and buttocks, as well as potential loss of bowel and bladder control. As a further consequence, sexual activity is impaired. However, there is limited information on sexual function in patients undergoing LSS surgery, in general, and among male patients, in specific. Accordingly, the aim of this study was to investigate the effect of LSS surgery on sexual function in male patients over 50 years. Materials and Methods: Participants were fifty male patients with LSS aged 50 years and older who underwent LSS surgery at the Imam Reza Hospital in Kermanshah from March 2024 to the end of 2024. To assess sexual performance over time, participants completed the International Index of Erectile Function (IIEF-15) questionnaire both before LSS surgery and six months after LSS surgery. For pre-post comparison, we used paired t-tests. Results: Compared to the pre-surgery stage, six-month post-surgery improvements were erectile function (+21%; Cohen's d: 1.40), orgasmic function (+35.1%; Cohen's d: 1.49), sexual desire (+27.3%; Cohen's d: 1.48), intercourse satisfaction (+14% Cohen's d: 0.77), overall satisfaction (+34.6% Cohen's d: 1.74), and overall sexual function (+25.3%; Cohen's d: 1.48). Conclusions: Among a sample of male patients aged 50 years and older, LSS surgery improved all dimensions of sexual satisfaction, including orgasmic, erectile, and sexual functions; sexual desire; intercourse satisfaction; and overall satisfaction. Medical doctors treating males with LSS might consider informing their patients about the favorable effects of LSS surgery on sexual life and sexual satisfaction.
- Research Article
11
- 10.1080/13506129.2023.2230516
- Jul 10, 2023
- Amyloid
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.
- Research Article
149
- 10.1038/modpathol.2014.102
- Feb 1, 2015
- Modern Pathology
Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis
- Front Matter
- 10.1111/joim.13250
- Feb 20, 2021
- Journal of Internal Medicine
Major recent advances in understanding of systemic transthyretin (ATTR) amyloidosis include the universal recognition that cardiac wild type ATTR amyloidosis is a prevalent cause of fatal heart failure with preserved ejection fraction (HFpEF) and/or fatal arrhythmia in the elderly, predominantly in men. ATTR amyloid cardiomyopathy is strongly associated with carpal tunnel syndrome, caused by wild type ATTR amyloid deposition in the carpal ligaments. The very interesting study by Eldhagen et al in this issue sheds further light on the association between cardiac and ligament ATTR amyloid but tantalisingly leaves several crucial questions unanswered.
- Research Article
72
- 10.1097/01.brs.0000219940.26390.26
- Jun 1, 2006
- Spine
A prospective observational study of patients undergoing surgery for degenerative lumbar spinal stenosis. To determine whether the long-term outcomes differ as a function of age and gender. The long-term results of surgery for lumbar spinal stenosis are not well understood, and the patient characteristics that predispose patients to worse outcomes are unknown. Seventy patients who underwent decompressive laminotomy with or without arthrodesis for degenerative lumbar spinal stenosis were prospectively studied at standard intervals after surgery with respect to symptom severity rated on a visual analog scale (VAS). The VAS scores for younger patients improved steadily for 3 or 6 months, after which the improvement was maintained until 60 months. The VAS scores for older patients showed a similar time course until 36 months, after which the VAS scores were worse compared with those for younger patients. The VAS scores for females were worse than those for males, in three symptoms queried, at one or more of the evaluation time points. In patients undergoing surgery for degenerative lumbar spinal stenosis, older age predicts a greater risk of late recurrence of symptoms, and women have higher VAS scores than men after surgery.
- Research Article
70
- 10.1016/j.wneu.2015.05.055
- Jun 3, 2015
- World Neurosurgery
The Risk of Getting Worse: Predictors of Deterioration After Decompressive Surgery for Lumbar Spinal Stenosis: A Multicenter Observational Study
- Research Article
13
- 10.1097/01.brs.0000261031.10091.f5
- Apr 1, 2007
- Spine
Prospective follow-up and retrospective review of 174 patients surgically treated for degenerative lumbar spinal stenosis. To examine whether the type of leg pain syndrome associated with lumbar spinal stenosis is correlated with outcome. Although classifying patients based on their leg pain syndrome is useful in planning surgical decompression, there is no validated method of classification and its prognostic significance remains unknown. Based on the type of leg pain, the patients were classified into 2 groups: unilateral and bilateral. Improvement in functional status was evaluated using the Quebec Back Pain Disability Scale; the symptoms were rated on a visual analog scale and the change from baseline to 2-year evaluation was noted. Associations between score changes and baseline variables were examined using multivariate analysis. The type of leg pain was independently associated with improvements in function and leg symptom scores but was not associated with improvement in the back pain score. After surgery, patients with unilateral leg pain had significantly greater improvements in function and leg symptoms than patients with bilateral leg pain. In patients undergoing surgery for degenerative lumbar spinal stenosis, the preoperative type of leg pain predicts function and leg symptom outcomes.
- Abstract
2
- 10.1016/j.spinee.2019.05.196
- Aug 22, 2019
- The Spine Journal
179. Predictors of clinical outcome following surgery for lumbar spinal stenosis: a study of postoperative pain and disability trajectories
- Research Article
26
- 10.1016/j.wneu.2022.11.019
- Nov 8, 2022
- World neurosurgery
Complications of Unilateral Biportal Endoscopic Spinal Surgery for Lumbar Spinal Stenosis: A Meta-Analysis and Systematic Review
- Research Article
2
- 10.4103/1793-5482.175623
- Jan 1, 2017
- Asian Journal of Neurosurgery
Background:Poorer postoperative outcome is suggested after repairing surgery in diabetic patients with lumbar spinal stenosis in comparison with nondiabetic patients. The present study aimed to compare the clinical outcome of surgery for lumbar spinal stenosis and diabetic and nondiabetic patients to highlight the effect of diabetes on prognosis of this surgical procedure.Methods:This prospective cohort study is conducted on 25 diabetic patients with lumbar spinal stenosis who were candidate for surgical treatment. A gender, age, and body mass index-matched group including 30 nondiabetic patients with lumbar spinal stenosis was considered as the control. The clinical condition of the patients was assessed based on oswestry disability index (ODI) before and immediately after surgery.Results:There was no difference in baseline ODI index between diabetes and diabetes group (73.68 ± 18.89 vs. 71.20 ± 18.27, P = 0.625), whereas postprocedure ODI was significantly higher in diabetic patients than in nondiabetic group (54.32 ± 19.03 vs. 29.47 ± 18.75, P < 0.001). The multivariable logistic regression analysis could show a difference in postoperative ODI between diabetic and nondiabetic patients with the presence of baseline variables as the confounders (beta = −24.509, P < 0.001).Conclusion:Lower improvement in physical ability is expected in diabetic patients after surgery for lumbar spinal stenosis when compared to nondiabetes patients.
- Research Article
18
- 10.1016/j.arrct.2022.100227
- Dec 1, 2022
- Archives of Rehabilitation Research and Clinical Translation
The Concerns and Experiences of Patients With Lumbar Spinal Stenosis Regarding Prehabilitation and Recovery After Spine Surgery: A Qualitative Study