Calcium pyrophosphate dehydrate crystal deposition in the ligamentum flavum of the cervical spine: histopathological and immunohistochemical findings.

OBJECTIVE: To investigate the histopathological and immunohistochemical properties of degenerative changes in the ligamentum flavum of the cervical spine with calcium crystal deposition. METHODS: Sections of the calcified ligamentum flavum harvested from 26 patients who required cervical decompression were examined by scanning electron microscopy (SEM), energy dispersive X-ray microanalysis, immunohistochemical staining [for transforming growth factor (TGF)-Beta, vascular endothelial growth factor (VEGF), Sox9, and Msx2] and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) method (for cell apoptosis). RESULTS: Energy dispersive x-ray microanalysis and SEM confirmed the deposited calcium to be calcium pyrophosphate dihydrate (CPPD) crystals. The calcified ligamentum flavum showed disorganisation of the elastic fibre bundles together with increased collagen fibrils in the matrix. Abundant hypertrophic chondrocytes were noted around the calcified lesions, which were strongly immunoreactive to TGF-Beta and VEGF. Staining for Sox9 was positive in metaplastic chondrocytes but negative in hypertrophic chondrocytes. Both chondrocytes and mesenchymal cells were positive for Msx2. TUNEL-positive hypertrophic chondrocytes were significantly more noticeable in nodular than diffusely scattered type of CPPD deposition. CONCLUSIONS: Calcium crystal deposition in the cervical ligamentum flavum seems to progress with reduction in elastic fibres, increase in collagen fibrils in the matrix, and migration of metaplastic hypertrophic chondrocytes, whose differentiation is controlled by cytokines and transcriptional factors, and potentially regulate crystal formation. The presence of abundant TUNEL-positive hypertrophic chondrocytes around CPPD deposition suggests that materials from apoptotic cells play some role in crystal deposition.

Microsurgical excision of multiple clear cell meningiomas of the cauda equina: a case report.

We report the case of a 21-year-old woman who presented with a 2-year history of worsening radicular pain on the right leg. The Valsalva manoeuvre provoked radicular pain and radiography showed right-convex 36 degrees scoliosis. Examination showed slight hypoesthesia on the right L3-S1 dermatomes but abnormal muscle power and reflexes. Magnetic resonance imaging identified cauda equina tumours at the L2-3 and L4 levels. The tumours showed heterogeneously isointense signals on T(1)-weighted image, hypointense signals on T(2)-weighted image, and hyperintense signal on gadolinium-enhanced T(1)-weighted sequences. The tumour was microsurgically extirpated from the cauda equina and resected through multiple small laminotomies. Macroscopically, the tumours were poorly encapsulated, hard in consistency, adherent to the adjacent cauda equinas, irregularly shaped like a "horseradish", and yellowish-grey in colour. Histopathological diagnosis was clear cell meningioma.

Microsurgical intraneural extracapsular resection of neurinoma around the cervical neuroforamen: a technical note.

Dumb-bell tumours often require extended resection of osseous structures of the spine and subsequent anterior and/or posterior stabilization. Minimally addressed microsurgical intraneural extracapsular resection of a neurinoma originating from around the neuroforamen often provides immediate benefits. We describe our experience with microsurgical intraneural extracapsular resection of four cervical dumb-bell neurinomas in four patients. After a 4- to 7-cm skin incision, a small resection of the laminae and neuroforamen allowed visualisation of the tumour. The procedure was followed by microsurgical intraneural extracapsular complete "enucleation" resection of the tumour, without sacrificing motor funiculi or causing damage to surrounding arteries and radicular veins. One patient had a giant neurinoma at the C5-C6 and C6-C7 foraminal levels that required simultaneous anterior fusion at C5-C6 level only. The average blood loss during surgery was 35 mL (range: 11-59) and all showed neurological improvement immediately after surgery. Minimally addressed microsurgical intraneural extracapsular "enucleating" resection of tumours around the neuroforamen may be beneficial for patients, is not associated with vascular morbidity, and avoids the subsequent need for extensive spinal instrumentation.

Insidious progression of paraparesis secondary to type III spinal meningeal cyst: a study of six difficult cases.

STUDY DESIGN: Case report. SETTING: Neuro-orthopaedic Unit, Fukui University Hospital, Japan. CASE REPORT: We studied six patients with insidious progression of paraparesis caused by thoracic and thoracolumbar spine type III spinal meningeal cyst and intradural arachnoid cyst, who underwent microsurgical decompression. Histologically, some samples showed oedematous and hypertrophic changes of the arachnoidal tissue together with occasional tophaceous deposits and calcification. Surgical treatment was complete excision of the cyst, or wide fenestration of these membrane, and close a communicating fistula, if detectable. All patients improved neurologically after microscopic surgery. CONCLUSION: We stress the significance of neuroimaging and neurological assessment in patients with gradual progression of paraparesis caused by intradural arachnoid cyst, but surgical procedure and timing of operative intervention require further considerations.

Posterior 360-degree stabilisation of the upper thoracic spine: a technical note.

PURPOSE: To describe a technique involving posterior 360-degree stabilisation of the upper thoracic spine: spinal cord decompression, posterior vertebral body replacement, and then posterior instrumentation and intercostal posterolateral vertebral stabilisation. METHODS: Three men and 4 women aged 41 to 77 (mean, 58) years underwent posterior 360-degree stabilisation of the upper thoracic spine. Their indications for surgery were bone metastasis (n=5), burst fracture (n=1), and osteoporotic collapse with cord compression (n=1). Their clinical and radiological findings and treatment outcomes were retrospectively reviewed. RESULTS: Pain status of all patients improved after surgery: 4 had severe and 3 had mild pain preoperatively; in 3 pain became minimal and 4 had none postoperatively. All patients except one had Frankel/American Spinal Injury Association scores of E after surgery indicating complete recovery of sensory and motor function. There were no complications related to surgery or instrumentation construct. At the time of review, one patient had died of old age 8.6 years after surgery and another from local recurrence and lung metastasis 5.7 years after surgery. All other patients were living. CONCLUSION: One-stage posterior 360-degree stabilisation and vertebral body replacement is a useful technique for upper thoracic spine surgery.

A schwannoma of the S1 dural sleeve was resected while the intact nerve fibers were preserved using a microscope. Report of a case with early MRI findings.

In this report, we describe a small schwannoma of the dural sleeve and mention that it is often difficult to differentiate this tumor from lumbar disc herniation, especially a sequestered hernia, or a discal cyst. Gadolinium-enhanced MR images were a useful preoperative examination modality for differentiating this lesion from other diseases. Microscopically, the intradural tumor was successfully removed. The dura mater of the S1 nerve root was opened microsurgically, allowing the nerve fibers involved in the tumor to be identified. The involved fibers were cut around the tumor, and the lesion was resected while the intact nerve fibers were preserved. Based on histological examination of the resected specimen, the tumor was diagnosed as a schwannoma with multilocular cystic degeneration. Microsurgery allowed the tumor to be removed with minimal impairment from cutting of nerve fibers in the nerve root.

Cruciate paralysis and hemiplegia cruciata: report of three cases.

STUDY DESIGN: Report of three cases of cruciate paralysis and hemiplegia cruciata. OBJECTIVE: To stress the importance of upper cervical spine lesions causing neurological symptoms and signs. SETTING: Neuro-orthopedic service, Fukui University Hospital, Japan. RESULTS: Three patients (all females; one with congenital anomaly at the occiput-atlas level, one with assimilation of the atlas, and one with rheumatoid arthritis-related proliferative synovium) had clinical features of cruciate paralysis and hemiplegia cruciata. All three cases underwent decompressive surgeries. CONCLUSION: Neurological symptoms and signs of cruciate paralysis and hemiplegia cruciata should be carefully assessed, and surgical therapy should be based on the pathological condition.

Cervical angina: a seemingly still neglected symptom of cervical spine disorder?

STUDY DESIGN: Retrospective, case series. DESIGN: A review of 10 surgical cases with symptoms of cervical angina. OBJECTIVE: To stress the importance of symptoms of cervical angina in patients with cervical spine disorders. SETTING: Fukui University Hospital, Japan. RESULTS: A total of 10 patients complaining of symptoms of cervical angina were admitted with a tentative diagnosis of coronary artery disease. Pain relief was achieved by anterior surgical decompression in all patients. CONCLUSION: We stress that physicians should be aware of the symptoms of cervical angina and that surgical intervention often leads to complete relief of symptoms.

Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis.

OBJECTIVE: To investigate the histological and immunohistochemical properties of degenerative changes and calcium crystal deposition in the lumbar ligamentum favum. METHODS: We examined the ligamentum flavum harvested from 119 surgical cases with symptomatic lumbar spinal stenosis. Sections of the ligament were examined by scanning electron microscopy (SEM), energy dispersive X-ray micro-analysis, and were immunostained for S-100 protein, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and CD34. The results were compared with those of ligament tissue harvested from 10 cases of lumbar disc herniation. RESULT: The elastic fibres of the ligamentum favum showed regular, or sometimes irregular, and fragmented fibre bundles. Large areas of fibrosis with reduced elastic component and increased collagenous tissue were frequently seen in the degenerated ligaments. Calcium crystal deposits were observed in these fibrous ligaments, associated with many hypertrophic chondrocytes, and with small blood vessel formation. These chondrocytes stained positively for S-100 protein, VEGF and bFGF Calcium pyrophosphate dihydrate crystals were identified in the calcium deposit area. CONCLUSION: We believe that rupture of elastic fibre bundles is the first change to occur in degeneration of the ligamentum favum. Calcium crystal deposition was seen within these fibrous and chondrometaplastic areas. Hypertrophic chondrocytes regulate crystal formation and tissue reconstruction by secreting cytokines.

Primary osteosarcoma of the thoracic spine: report of an unusual elderly patient with autopsy findings.

STUDY DESIGN: A case report of primary osteosarcoma of the spine in an elderly patient. OBJECTIVE: The histopathological features of osteosarcoma vary widely, often leading to diagnostic difficulties particularly when there is little evidence of osteoid formation. The report describes the difficulty in the diagnosis of osteosarcoma of the thoracic vertebra. SETTING: Department of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medicine, Fukui, Japan. METHOD: A 78-year-old man presented with paraparesis and underwent urgent anterior excision of a primary spinal tumor emanating from the T10 vertebra followed by artificial vertebral replacement. The patient eventually died of disseminated disease of vertebral osteosarcoma. RESULTS: Samples from the T10 vertebral tumor showed neoplastic growth of atypical spindle-shaped cells, with foci of storiform-like proliferation. The tissue also demonstrated positive immunohistochemical staining for vimentin and alpha-smooth muscle actin and a tentative diagnosis of leiomyosarcoma was made. However, a metastatic nodule of the chest wall at autopsy showed focal osteoid formation, a finding not seen in the primary tumor. CONCLUSION: Early detection and accurate diagnosis is important for improving not only patient prognosis but also the quality of life. We should always consider this rare entity, particularly in elderly patients who present with back pain and vertebral collapse.

[A clinical case of ABO-incompatible living renal transplantation].

We successfully made ABO-incompatible renal transplantation, of which report is methodologically the first in Japan and probably the second in the world to our knowledge. Sixty year-old-female (mother) with B-blood type donated her right kidney to 36 years-old male (son) with O-blood type. Pretransplant removal of plasma isoagglutinin of the recipient through plasma exchange with albumin solution followed by hemodialysis with administration of fresh frozen B-type plasma effectively reduced the anti-BIgM-antibody titre of x256 to x8 and the anti-IgG-antibody titre of x512 to x16. Splenectomy was performed at the time of transplantation. On the 10th POD, the anti-B antibody titres were more decreased to IgM antibody x2 and IgG antibody x8. Patient is doing well without any sign of rejection as of 4 months postoperatively.

[The alternation of CD8+ cells and its subpopulations by serial monitoring of peripheral blood lymphocytes of renal allograft recipients].

To catch and treat the initial alternation of a rejection and infection, we have introduced the serial analysis of lymphocyte surface antigens of peripheral blood lymphocytes by flow cytometry for 9 cases of renal allo-graft recipients since September 30 in 1988. In three recipients without rejection and infection, we found that T8+(CD8+), T8+Mo1+(CD11b+), T8+Mo1-(CD11b-), and T8+IL-2R+(CD25+) subsets were variable for first 20 days and then they were stable. However, another activated CD8+ T-cell subset such as T8+I2+(HLA-DR+) subset gradually increased after first 20 days, so that we investigated the different processes between these two activated subsets. On primary rejection of 5 cases, T8+I2+ and T8+IL-2R+ subsets showed peak formations within 2 days before the rejection. Two of these 5 cases resisted to a primary rejection therapy and showed rebounding arise of these subsets. We could easily convert to OKT-3 rescue therapy and treat them successfully. In order to catch the initial alternation of the primary rejection and treat the rebounding reaction successfully, we should monitor the T8+I2+ and T8+IL-2R+ subsets daily for first 2 weeks and after then 3 times a week.

[The alternation of CD4+ cells and its subpopulations by serial monitoring of peripheral blood lymphocytes of renal allograft recipients].

Immunologic monitoring for renal allograft recipients should be carried out serially and as conveniently as possible so that we can catch and treat the initial alternation of the rejection and infection. We have introduced the serial analysis of lymphocyte surface antigens of peripheral blood lymphocytes by flow cytometry for 9 cases of renal allograft recipients (3 cases of living related, 2 cases of living non-related, and 4 cases cadaver donors). In three recipients without rejection and infection, T4+(CD4+), T4+4B4+(CDw29+), T4+2H4+(CD45R+), T4+I2+(HLA-DR+), and T4+IL-2R+(CD25+) subsets showed variable processes for first 10 days and then stable processes. On primary rejection of 5 cases, activated T cell subsets such as T4+I2+ and T4+IL-2R+ subsets showed peak formations within 2 days before the rejection. Two of these 5 cases resisted a primary rejection therapy and showed a rebounding rise of these subsets. We could easily convert to OKT-3 rescue therapy and treat them successfully. We could not find out the specific alternation in the secondary rejection of 2 cases and all the infection cases. On the basis of these findings, we should serially monitor the T4+I2+ and T4+IL-2R+ subsets daily for first 2 weeks and after then 3 times a week, in order to catch the initial alternation of the primary rejection and treat its rebound successfully.

In vitro primary induction of T cells mediating delayed footpad reaction and acquired cellular resistance to Listeria monocytogenes.

We established an in vitro system generating L. monocytogenes-specific T cells primarily from unprimed spleen cells of mice. Normal spleen cells were cultured for 5 days in the presence of L. monocytogenes in vitro. Viable cells were harvested and assessed for their capacity to confer acquired cellular resistance (ACR) and delayed footpad reaction (DFR) upon local passive transfer to naive syngeneic recipient mice. When normal spleen cells were stimulated with viable L. monocytogenes, the viable cells that were recovered after 5 days of culture conferred a high level of ACR and DFR. Negative selection revealed that the effector cells obtained in primary in vitro culture were Thy 1+, L3T4+, Lyt2- cells. T cells mediating ACR could not be generated in the culture of normal spleen cells with heat-killed bacteria; however, cells mediating only DFR were generated in the presence of a large number of killed L. monocytogenes. The expression of DFR and ACR by T cells generated in this primary culture system was Listeria-specific; reactions were not observed against unrelated bacterial antigens including S. typhimurium, S. aureus, E. coli and PPD. FACS analysis of the cells in culture showed that L3T4+ and Lyt2- T cells were being enriched during culture. The primary generation of antigen-specific T cells in vitro was also possible with spleen cells from NTx mice but not with cells from nude mice, suggesting the presence of Listeria-specific precursors in NTx mice.

Induction by killed Listeria monocytogenes of effector T cells mediating delayed-type hypersensitivity but not protection in mice.

Using a local passive transfer system, we found that effector T cells mediating delayed-type hypersensitivity (DTH) but not acquired cellular resistance (ACR) to Listeria monocytogenes (strain EGD) were generated in mice immunized with killed Listeria, although immunized mice did not express DTH or ACR. When non-adherent cells of peritoneal, lymph node, or spleen cells from mice immunized with killed Listeria were transferred into the footpad of naive recipient mice along with eliciting antigen, positive delayed footpad reaction (DFR) was elicited. However, there was no evident protection against challenge at the site of the local transfer. Cells from mice immunized with viable Listeria conferred significant degrees of DFR and ACR on the recipients. DFR transferred by cells immunized with killed Listeria was mediated by L3T4+ T cells in an antigen-specific manner. The antigen-specific proliferative response of T cells from mice immunized with killed Listeria was much lower than that of T cells from mice immunized with viable Listeria. The production of macrophage chemotactic factor (MCF) by cells from killed Listeria-immune mice was much the same as that by cells from viable Listeria-immune mice. In contrast, the production of interleukin-2 (IL-2) and macrophage activating factor (MAF) was much lower in cells from killed Listeria-immune mice. The elimination of L. monocytogenes (strain L461), a strain of low virulence, was enhanced at the site of DFR transferred with cells from killed Listeria-immune mice. These results suggest that stimulation with killed bacteria is effective for the generation of DTH-mediating effector T cells, and that different effector T cells mediating DTH or ACR are involved in cell-mediated immunity to L. monocytogenes.

Intravenous cimetidine as an effective treatment for systemic anaphylaxis and acute allergic skin reactions.

Intravenous cimetidine treatment was prescribed for patients suffering from anaphylaxis, urticaria, pruritus, and contact dermatitis. Most of these patients recovered promptly from shock status, itching, and/or flushing after the administration of cimetidine. Intravenous cimetidine therefore may be an effective treatment for those allergic reactions.