Dialysis-related spinal canal stenosis: a clinicopathological study on amyloid deposition and its AGE modification

Three cases operated for spinal canal stenosis induced by dialysis-related amyloidosis (DRA) were investigated clinicopathologically. Cases were all-male, and had undergone hemodialysis around 20 years. In two cases, cervical plain X-rays showed only minor spondylotic changes. However, magnetic resonance imaging (MRI), myelography, and computed tomography (CT) showed extradural thickness with compression on the cervical spinal cord and cauda equina. In one case cervical X-rays showed typical destructive spondyloarthropathy (DSA), and MRI showed compression myelopathy. Surgical treatment on both cervical and lumbar spine in two cases and on cervical spine only in one case successfully reduced the symptoms. Extradural thickened tissue and ligament flavum obtained during surgery were studied histopathologically and immunostained by using anti-CD68, anti-beta2-microglobulin (beta2m), and anti-advanced glycation end product (AGE) antibody. Congo red stain showed diffuse or nodular amyloid deposition, and immunostaining with anti-beta2m and anti-AGE antibodies also demonstrated the same distribution pattern. Thus, beta2m-positive amyloid tissue in the extradural thickness (extradural amyloid deposition) was immunohistochemically demonstrated to be modified with AGE. Inflammatory reaction with histiocytic and giant cell infiltration was also shown around the amyloid tissues. There were CD68-positive cells, and some cells were positive for AGE and beta2m. These findings suggest that beta2m accumulation and inflammatory reaction finally promote destruction of connective tissues. MRI, CT and/or myelography are necessary for diagnosing spinal canal stenosis accompanied by DRA. In conclusion, we propose a more comprehensive concept of dialysis-related spinal canal stenosis, which includes both DSA and myeloradiculopathy induced by extradural thickness.