Transthyretin amyloid deposits in lumbar spinal stenosis and assessment of signs of systemic amyloidosis

Author:

Eldhagen P.1,Berg S.2ORCID,Lund L.H.1ORCID,Sörensson P.1ORCID,Suhr O.B.3ORCID,Westermark P.4ORCID

Affiliation:

1. From the Department of Medicine Karolinska Institute Karolinska University Hospital Solna Sweden

2. Stockholm Spine Centre Löwenströmska Hospital Upplands Väsby Sweden

3. Department of Public Health and Clinical Medicine Umeå University Umeå Sweden

4. Department of Immunology, Genetics and Pathology Uppsala University Uppsala Sweden

Abstract

AbstractBackgroundWild‐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.

Funder

Pfizer

Publisher

Wiley

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