Analysis of lumbar spine stenosis specimens for identification of amyloid

Abstract

Background Lumbar spinal stenosis (LSS) is a common reason for spine surgery in which ligamentum flavum is resected. Transthyretin (TTR) amyloid is an often unrecognized and potentially modifiable mechanism for LSS that can also cause TTR cardiac amyloidosis. Accordingly, older adult patients undergoing lumbar spine (LS) surgery were evaluated for amyloid and if present, the precursor protein, as well as comprehensive characterization of the clinical phenotype. Methods A prospective, cohort study in 2 academic medical centers enrolled 47 subjects (age 69 ± 7 years, 53% male) undergoing clinically indicated LS decompression. The presence of amyloid was evaluated by Congo Red staining and in those with amyloid, precursor protein was determined by laser capture microdissection coupled to mass spectrometry (LCM‐MS). The phenotype was assessed by disease‐specific questionnaires (Swiss Spinal Stenosis Questionnaire and Kansas City Cardiomyopathy Questionnaire) and the 36‐question short‐form health survey, as well as biochemical measures (TTR, retinol‐binding protein, and TTR stability). Cardiac testing included technetium‐99m‐pyrophosphate scintigraphy, electrocardiograms, echocardiograms, and cardiac biomarkers as well as measures of functional capacity. Results Amyloid was detected in 16 samples (34% of participants) and was more common in those aged ≥ 75 years of age (66.7%) compared with those <75 years (22.3%, p < 0.05). LCM‐MS demonstrated TTR as the precursor protein in 62.5% of participants with amyloid while 37.5% had an indeterminant type of amyloid. Demographic, clinical, quality‐of‐life measures, electrocardiographic, echocardiographic, and biochemical measures did not differ between those with and without amyloid. Among those with TTR amyloid (n = 10), one subject had cardiac involvement by scintigraphy. Conclusions Amyloid is detected in more than a third of older adults undergoing LSS. Amyloid is more common with advancing age and is particularly common in those >75 years old. No demographic, clinical, biochemical, or cardiac parameter distinguished those with and without amyloid. In more than half of subjects with LS amyloid, the precursor protein was TTR indicating the importance of pathological assessment.

Opportunities for Earlier Diagnosis and Treatment of Cardiac Amyloidosis

“…Unfortunately, of those with amyloid deposition, more than one-third could not be accurately typed. 53 Though sampling and analysis of surgical tissue at the time of surgical procedures may be a low-risk opportunity to identify patients who are at risk for developing ATTR-CM, how to best define the surgical screening cohort for the highest-risk patients, as well as the optimal plan for surveillance of patients with amyloid deposition, merits further investigation.…”

Analysis of lumbar spine stenosis for identification of amyloid

“…In studies looking at patients with ATTRwt, for instance, 46%–49% were found to have CTS 15,16 which in one study manifested on average ~4.4 years before cardiac symptoms 21 . Several studies, the majority retrospective, and single‐center have also confirmed ATTRwt deposition in the ligamentum flavum during lumbar stenosis resections 18–20,22,23 In this issue of the journal, Maurer et al conducted the first prospective pilot study to date involving patients who underwent lumbar spinal surgery to determine whether amyloid was present in the surgically obtained spinal specimens 24 . Of the 742 eligible patients screened from two separate institutions, 47 patients ≥55 years old, were included.…”

“…21 Several studies, the majority retrospective, and single-center have also confirmed ATTRwt deposition in the ligamentum flavum during lumbar stenosis resections [18][19][20]22,23 In this issue of the journal, Maurer et al conducted the first prospective pilot study to date involving patients who underwent lumbar spinal surgery to determine whether amyloid was present in the surgically obtained spinal specimens. 24 Of the 742 eligible patients screened from two separate institutions, 47 patients ≥55 years old, were included. If amyloid was present in the surgical sample, the precursor protein was determined, and further characterization of the cardiac and orthopedic phenotypes was made using an extensive array of testing including biomarkers, electrocardiography, echocardiography, nuclear scintigraphy using technetium pyrophosphate (Tc99m-PYP), TTR stability assays, 6MWT, short physical performance battery and disease-specific questionnaires including Kansas City Cardiomyopathy Questionnaire, Swiss Spinal Stenosis Questionnaire, and ShortF-36.…”

The Future for Patients With Transthyretin Cardiac Amyloidosis Is Looking Brighter

“…Would similar or even better results be obtained for screening programs focused on patients with lumbar spinal stenosis in whom amyloid deposits appear to be more common than among those with carpal tunnel surgery? 16 Can routine pathologic examination of explanted orthopedic tissue with Congo red staining and, if positive, laser dissection with mass spectrometry better identify those who require further evaluation? Or does pathologic assessment add cost without improving the diagnostic yield?…”