Amyloidosis is a protein conformational disorder with the distinctive feature of extracellular accumulation of amyloid fibrils that come from different proteins. In the ligamentum flavum of the lumbar spine, amyloid deposits were frequently found in elderly patients with lumbar spinal canal stenosis and were at least partially formed by wild-type transthyretin. However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis has remained unclear. In this study, we analyzed clinical, pathologic, and radiologic findings of patients with lumbar spinal canal stenosis who had amyloid deposits in the ligamentum flavum. We studied 95 ligamentum flavum specimens obtained from 56 patients with lumbar spinal canal stenosis and 21 ligamentum flavum specimens obtained from 19 patients with lumbar disk herniation. We evaluated histopathologic findings and clinicoradiologic manifestations, such as thickness of the ligamentum flavum and lumbar spinal segmental instability. We found that all 95 ligamentum flavum specimens resected from patients with lumbar spinal canal stenosis had amyloid deposits, which we classified into two types, transthyretin-positive and transthyretinnegative, and that transthyretin amyloid formation in the ligamentum flavum of patients with lumbar spinal canal stenosis was an age-associated phenomenon. The amount of amyloid in the ligamentum flavum was related to clinical manifestations of lumbar spinal canal stenosis, such as thickness of the ligamentum flavum and lumbar spinal segmental instability, in the patients with lumbar spinal canal stenosis with transthyretin-positive amyloid deposits. To our knowledge, this report is the first to show clinicopathologic correlations in transthyretin amyloid deposits of the ligamentum flavum. In conclusion, transthyretin amyloid deposits in the ligamentum flavum may be related to the pathogenesis of lumbar spinal canal stenosis in elderly patients.

Radiation therapy (RT) is pivotal in the treatment of many central nervous system (CNS) pathologies; however, exposure to RT in children is associated with a higher risk of secondary CNS tumors. Although recent research interest has focused on the reparative and therapeutic role of microglia, their recruitment following RT has not been elucidated, especially in the developing CNS. Here, we investigated the spatiotemporal dynamics of microglia during tissue repair in the irradiated embryonic medaka brain by whole-mount in situ hybridization using a probe for Apolipoprotein E (ApoE), a marker for activated microglia in teleosts. Three-dimensional imaging of the distribution of ApoE-expressing microglia in the irradiated embryonic brain clearly showed that ApoE-expressing microglia were abundant only in the late phase of phagocytosis during tissue repair induced by irradiation, while few microglia expressed ApoE in the initial phase of phagocytosis. This strongly suggests that ApoE has a significant function in the late phase of phagocytosis by microglia in the medaka brain. In addition, the distribution of microglia in p53-deficient embryos at the late phase of phagocytosis was almost the same as in wild-type embryos, despite the low numbers of irradiation-induced apoptotic neurons, suggesting that constant numbers of activated microglia were recruited at the late phase of phagocytosis irrespective of the extent of neuronal injury. This medaka model of microglia demonstrated specific recruitment after irradiation in the developing CNS and could provide a useful potential therapeutic strategy to counteract the detrimental effects of RT.

Dystrophic calcinosis in soft tissue occurs in damaged or devitalized tissues in the presence of normal calcium and phosphorous metabolism. It is often noted in subcutaneous tissues in patients with collagen vascular diseases and may involve a relatively localized area or be widespread. A 74-year-old Japanese woman with an overlap of rheumatoid arthritis, Sjögren's syndrome, and systemic sclerosis developed a huge tumor-like mass at the atlanto-axial vertebral joint region that caused severe cervical pain and difficulty in activities of daily living. She also had subcutaneous dystrophic calcification in the soft tissue of the chest wall. Calcinosis associated with systemic sclerosis is a well-recognized phenomenon, but a destructive paraspinal tumor in the cervical spine associated with overlap syndrome is extremely unique. Because calcinosis in spinal locations can be complicated by neurological involvement, patients with progressive symptoms may require surgical intervention. Surgical resection and biological therapy improved this patient's life and activities of daily living. Calcinosis is common in the conditions reviewed here, and different agents have been used for treatment. However, calcinosis management is poorly organized and lacks an accepted classification, systematic studies, and clinical therapeutic trials. The association of calcinosis and collagen vascular diseases is clinically and etiologically important. Although a combination of calcinosis and rheumatoid overlap syndrome is rare, various collagen vascular diseases may occur simultaneously. A perceptive diagnostic approach toward these diseases is critical, and early diagnosis and treatment are needed to prevent dystrophic calcinosis.

Hypertrophic pachymeningitis (HP) is extremely rare and an inflammatory process that thickens the dura mater. A 59-year-old Japanese woman developed backache, became paraplegic, and magnetic resonance imaging revealed diffuse thickening of the thoracic dura mater encompassing the spinal cord. Although a test for myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) was shown to be positive, vasculitis was not found and CD8(+) T lymphocytes that predominated in the inflammatory foci. Both interleukin (IL)-2 and IL-6 were markedly elevated in not only sera but also cerebrospinal fluids, very much higher in the latter. Human leukocyte antigen (HLA) typing revealed A24 positivity, suggesting this molecule was interacting with CD8(+) T lymphocytes. It was suggested that immunological disharmony and autoimmunity would play a pivotal role in the development of HP under genetic background of HLA-A24, and HP would be one feature of multiple organ involvement in ANCA-associated diseases.

Hypertrophic pachymeningitis (HP) is extremely rare and an inflammatory process that thickens the dura mater. A 59-year-old Japanese woman developed backache, became paraplegic, and magnetic resonance imaging revealed diffuse thickening of the thoracic dura mater encompassing the spinal cord. Although a test for myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) was shown to be positive, vasculitis was not found and CD8(+) T lymphocytes that predominated in the inflammatory foci. Both interleukin (IL)-2 and IL-6 were markedly elevated in not only sera but also cerebrospinal fluids, very much higher in the latter. Human leukocyte antigen (HLA) typing revealed A24 positivity, suggesting this molecule was interacting with CD8(+) T lymphocytes. It was suggested that immunological disharmony and autoimmunity would play a pivotal role in the development of HP under genetic background of HLA-A24, and HP would be one feature of multiple organ involvement in ANCA-associated diseases.

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