Transthyretin-derived amyloidosis: Probably a common cause of lumbar spinal stenosis

Abstract

Background Senile systemic amyloidosis (SSA) derived from wild-type transthyretin is a fairly common condition of old individuals, particularly men. The main presentation is by cardiac involvement, which can lead to severe restrictive cardiomyopathy. SSA is, however, a systemic disease, and amyloid deposits may appear in many other tissues but are thought to be without clinical symptoms outside the heart. Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and transthyretin has been demonstrated in some deposits. Lumbar spinal stenosis is also a condition of usually elderly individuals in whom narrowing of the lumbar spinal canal leads to compression of nerves to the lower limbs.Results We questioned whether lumbar spinal stenosis sometimes could be a manifestation of undiagnosed SSA. In this first report we have studied the presence of amyloid in material obtained at surgery for spinal stenosis in 26 patients. Amyloid was found in 25 subjects. Transthyretin was demonstrated immunohistochemically in 5 out of 15 studied resected tissues. Four of the positive materials were analyzed with Western blot revealing both full-length transthyretin (TTR) and C-terminal TTR fragments, typically seen in SSA.Conclusion We conclude that lumbar spinal stenosis quite frequently may be a consequence of SSA and that further studies are warranted.

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

“…These features of transthyretin amyloid deposits in the ligamentum flavum were consistent with a few previous reports that evaluated smaller numbers of lumbar spinal canal stenosis patients. 13,14,22 In addition, because we discovered no relationship between the amount of transthyretin amyloid and age, we speculate that aging mainly affects the initiation of transthyretin amyloid formation in the ligamentum flavum. Because we found no symptoms that would indicate cardiac amyloidosis, which is major symptom of senile systemic amyloidosis, an age-related systemic form of amyloidosis, transthyretin-positive amyloid deposition in the ligamentum flavum of lumbar spinal canal stenosis patients may be a localized form of amyloidosis.…”

“…13 Another recent paper suggested that transthyretin amyloid formation may be a common cause of lumbar spinal canal stenosis. 14 We also reported that a senile systemic amyloidosis patient with multifocal spinal transthyretin amyloid deposits developed severe destructive spondylosis and radiculomyelopathy. 15 However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis in which the ligamentum flavum shows degeneration and hypertrophy remains unclear.…”

Transthyretin cardiac amyloidosis: an update on diagnosis and treatment

“…8,9 Recently, ATTRwt-CA is increasingly recognized as a cause of various common diseases. While ATTRwt-CA was identified in 13% of elderly patients (>60 years old) with HFpEF and 16% of patients undergoing transcatheter aortic valve replacement, respectively, 2,4 bilateral carpal tunnel syndrome (CTS) and lumbar spinal stenosis frequently present many years before the development of cardiac symptoms.. 10,11 Hereditary ATTR-CA (ATTRv-CA) is an autosomal-dominant disease in which gene mutations lead to changes in the protein TTR. 12 More than 120 mutations have been reported in the TTR gene with considerable phenotypic and geographical heterogeneity.…”

The quintessential form of diastolic heart failure in older adults: Wild type transthyretin cardiac amyloidosis

“…Lumbar spinal stenosis, the most common indication for back surgery in older adults, may represent yet another potential manifestation of systemic amyloid deposition. In one study of patients who underwent surgery spinal stenosis, 21 of 26 specimens demonstrated amyloid deposition . Of the 15 specimens suitable for immunohistochemical staining, five demonstrated positive TTR immunoreactivity.…”