Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles.

OBJECTIVE: The distribution of folate receptor (FR)-ß+ macrophages and their M1/M2 expression profiles were examined in osteoarthritis (OA) synovial tissues, and compared to those in rheumatoid arthritis (RA) synovial tissues and CD163+ macrophages in both OA and RA synovial tissues. METHOD: The phenotypes and fluorescein isothiocyanate (FITC)-folate uptake of FR-ß+ synovial macrophages were analysed by flow cytometry. The distribution of FR-ß+ macrophages in OA and RA synovial tissues was examined by immunofluorescent microscopy. Tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-10, and transforming growth factor (TGF)-ß expression in FR-ß+ macrophages was detected by double-immunostaining in both OA and RA synovial tissues. RESULTS: FR-ß+ macrophages were predominantly present in the synovial lining layer in OA patients. The proportion of CD163-FR-ß+ cells in synovial mononuclear cells (MNCs) was increased in OA compared to RA synovial tissues. FR-ß(high) macrophages from OA synovial tissues represented the majority of folic acid-binding cells. Although FR-ß+ or CD163+ macrophages in the synovial tissues of OA and RA patients expressed a mixed pattern of M1 and M2 macrophage markers, there were more M2 markers expressing synovial macrophages in OA than in RA patients. CONCLUSIONS: The distribution and M1/M2 expression profiles of FR-ß+ synovial macrophages were different between OA and RA synovial tissues. Thus, the findings underscore that the M1/M2 paradigm using surface markers FR-ß and CD163 is an oversimplification of macrophage subsets. Functional FR-ß present on OA synovial macrophages provides a potential tool for the diagnosis and treatment of OA.

Traumatic spinal-cord herniation associated with pseudomeningocele after lower-thoracic nerve-root avulsion.

BACKGROUND: Traumatic spinal-cord herniation after nerve root avulsion is rare. We report on the first patient with spinal-cord herniation associated with pseudomeningocele in the lower conus medullaris region after nerve avulsion. CASE: This 72-year-old man presented with progressive pain in the left leg and motor weakness after two traumatic accidents. Constructive interference in steady-state (CISS) imaging showed the attachment of the spinal cord to the wall of a herniated pseudomeningocele and associated syringomyelia at the level of T12. At the time of surgery, a herniated pseudomeningocele was observed. The lateral portion of the spinal cord that had herniated into the pseudomeningocele was detached from its wall; this was followed by repair of the dural defect. A redundant nerve root was observed inside the pseudomeningocele, suggesting nerve root avulsion as the primary lesion. To facilitate cerebrospinal fluid drainage from the syringomyelia, we next performed dorsal root entry zone (DREZ)tomy to the pseudomeningocele. Postoperatively, he manifested significant clinical improvement. CONCLUSIONS: This is the first report of spinal cord herniation after nerve root avulsion in the conus medullaris region. CISS imaging is highly useful for the demonstration of spinal cord herniation, syringomyelia and pseudomeningocele. To restore neurological function in patients with progressive symptoms, we recommend surgical treatment.

Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism.

In osteoarthritis (OA), adult articular chondrocytes undergo phenotypic modulation in response to alterations in the environment owing to mechanical injury and inflammation. These processes not only stimulate the production of enzymes that degrade the cartilage matrix but also inhibit repair. With the use of in vitro and in vivo models, new genes, not known previously to act in cartilage, have been identified and their roles in chondrocyte differentiation during development and in dysregulated chondrocyte function in OA have been examined. These new genes include growth arrest and DNA damage (GADD)45beta and the epithelial-specific ETS (ESE)-1 transcription factor, induced by bone morphogenetic protein (BMP)-2 and inflammatory cytokines, respectively. Both genes are induced by NF-kappaB, suppress COL2A1 and upregulate matrix meatalloproteinase-13 (MMP-13) expression. These genes have also been examined in mouse models of OA, in which discoidin domain receptor 2 is associated with MMP-13-mediated remodelling, in order to understand their roles in physiological cartilage homoeostasis and joint disease.

Apoptosis (cell death) induced in mouse bowel by 1,2-dimethylhydrazine, methylazoxymethanol acetate, and gamma-rays.

Apoptosis is a pattern of cell death involving nuclear pyknosis, cytoplasmic condensation, and karyorrhexis. The frequency of apoptosis after treatment with two colon carcinogens and radiation was studied in the crypts of five different portions of mouse bowel. When 1,2-dimethylhydrazine (DMH) was injected s.c., the earliest rise in apoptotic incidence after a high dose (200 mg/kg) was noted at 3 h in small intestine and at 6 h in large bowel. After i.p. administration of methylazoxymethanol (MAM) acetate, apoptotic cells were seen in large bowel after 3 h. When the plateau values attained after high doses of DMH were compared, many apoptotic cells were found in the lower part of the large bowel, whereas few such cells were observed in the small intestine and the upper part of the large bowel. This finding was reversed in the case of radiation-induced apoptosis. In the descending colon, a definite circadian rhythm in the apoptotic incidence was observed 6 h after injection of DMH or MAM acetate. Apoptosis showed a high incidence when these drugs were given between 2400 h and 0900 h, but a low incidence after administration between 1200 h and 2100 h. In the small intestine a rhythm was also noted for MAM acetate, but not significantly for DMH.

Remobilization partially restored the bone mass in a non-growing cancellous bone site following long term immobilization.

There is no report in the rat of the effects of remobilization (RM) in an adult bone site. The aim of this study was to determine whether complete recovery from IM-induced bone loss will occur in a non-growing bone site, the distal tibia. Seventy-five 6-month-old virgin Sprague-Dawley female rats were used in this study. Their hindlimbs were immobilized against the abdomen with bandages for 18 weeks, then remobilized for 2, 10 or 20 weeks. Distal tibial sections were analyzed in the former epiphysis, 0.3 mm proximal from the calcified cartilage, and in trabecular bone of the former metaphysis between 0.3 mm and 1.92 mm proximal to the former epiphysis. A significant bone loss occurred in both former epiphyseal and metaphyseal trabeculae at 18 weeks after IM. The lost bone was partially recovered at 10 weeks of RM, but the bone mass was still lower than in aging controls by the end of the study. The partial recovery was characterized by decreasing former epiphyseal bone porosity and thickening of former metaphyseal trabeculae with no effect on trabecular number. We concluded that both distal tibia regions only partially recovered, during 20 weeks of RM from the long time IM.

Adaptation of non-growing former epiphysis and metaphyseal trabecular bones to aging and immobilization in rat.

No data exit for distal tibia (DT), a bone site with growth plate closure at 3 months of age and with very low trabecular bone turnover rate. The purpose of this study was to characterize the response of DT to aging and immobilization (IM) in 6 to 16.5 month-old female rats. One hundred and forty six 6 month-old Sprague-Dawley rats were divided into aging controls and right hindlimb immobilization (RHLI) groups. The right hindlimb was immobilized against the abdomen with elastic bandages. Rats were sacrificed serially from 6 to 16.5 months old at intervals of 2 to 8 weeks. The histomorphometric study was performed on areas of former epiphyseal and metaphyseal trabecular bone of DT. No changes on bone mass or architecture were found in aging controls throughout the study. There was a decrease in bone mass of the former epiphysis after 3.5 months of IM due to resorption exceeding formation. Then it reverted to the aging control level at 4 months post IM. At the former metaphyseal site, significant bone loss (-19%) was observed as early as two weeks after IM. The peak bone loss (-54%) was reached at 1.5 months after IM and plateaued thereafter. The bone loss was mainly due to the reduction of trabecular thickness although trabecular number decreased significantly after 3.5 months IM. These results suggest that both former epiphysis and metaphyseal trabecular bones in DT can quickly adapt by losing bone to immobilization.

Parathyroid hormone therapy accelerates recovery from immobilization-induced osteopenia.

Previous reports have shown that bone mass and architecture will partially recover by remobilization (RM) in immobilization (IM)-induced osteopenia. The aim of this study was to test whether PTH can accelerate the recovery during RM from the IM-induced osteopenia. Six-month-old Sprague-Dawley female rats were divided into aging and IM groups. The right hindlimb of rats was immobilized against the abdomen by elastic bandages for 18 weeks, then groups of rats were further IM or RM for 2, 10 and 20 weeks and given 30 or 80 micrograms hPTH (1-38)/kg/d s.c. Secondary spongiosa of proximal tibial metaphyses (PTM) were studied. Immobilization reduced the trabecular area, number and thickness at the first 18 weeks post IM, then plateaued. Ten weeks of RM restored 40% trabecular bone from IM controls due to thickening of the trabeculae. However, the trabecular area was still -14% and -13% lower than that of aging controls at 10 and 20 weeks. Two weeks of 30 micrograms PTH/kg/d in IM rats restored the bone to aging control levels, two weeks of 30 micrograms PTH/kg/d in RM rats and of 80 micrograms PTH/kg/d in both RM and IM rats added extra bone. Extending the treatment to 10 and 20 weeks, the same amount of total bone was added to both IM and RM rats. These findings indicate PTH is a powerful agent that can accelerate the recovery and add extra bone to osteopenic cancellous bone in both IM and RM rats.

Co-treatment of PGE2 and risedronate is better than PGE2 alone in the long-term treatment of ovariectomized-induced osteopenic rats.

We studied the effects of prostaglandin (PGE2) and risedronate (Ris) alone or in combination in 3.5-month-old intact and ovx-induced osteopenic rat skeletons to determine whether PGE2 plus Ris was more anabolic than PGE2 alone. Six mg PGE2/kg/d and 5 micrograms Ris/kg/2x/wk alone or in combination were given to sham-ovx and ovx rats for 30 or 90 days beginning 60 days post operation. Secondary spongiosa of proximal tibial metaphyses (PTM) was studied. Ovariectomy (ovx) induced dramatic bone loss. Ris increased bone mass in sham-ovx rats and prevented further bone loss in ovx rats. PGE2 treatment for 30 days added extra bone in sham-ovx rats and no further increase after 90 days treatment. Thirty days of PGE2 alone treatment restored the bone mass in ovx rats to the level of sham-ovx rats, but the restored bone was partially lost by 90 days of treatment. Co-treatment for 30 days produced the same amount of bone mass in both sham-ovx and ovx rats as PGE2 alone did. However, unlike the PGE2 alone treated, co-treatment animals continued to form more bone for 90 days. The difference in tissue-level histomorphometry between co-treatment and PGE2 alone was that the former depressed the bone resorption and turnover. These findings indicated that the long-term administration of PGE2 alone cannot maintain or continue to add bone mass in ovx rats but that co-treatment of a PGE2 with an anti-resorptive or activation agent can resist the influence of the mechanostat induced bone loss as well as continue to add bone.

Effect of corticosteroids on the thymus of the fish Oryzias latipes.

Morphology and development of the thymus in fish Oryzias latipes was studied in response to corticosteroids. Adult fish were subjected to different concentrations of two corticosteroids, deoxycorticosterone acetate (DOCA) and cortisone acetate (CA). Histology of the thymus and thymocyte counts in treated fish were compared to normal ones. There was no change in histology of thymus due to CA treatment even those subjected to 10 mg/l water which is a lethal dose of DOCA. In contrast, the effect of DOCA at low doses (0.01 and 0.1 mg/l water) was examined and resulted in reduction of thymus volume due to depopulation of thymocytes from the entire gland. Thymus subjected to DOCA at a high dose (1 mg/l water) caused destruction of all thymocytes and reticular cells resulting in complete disappearance of the thymus. There was dose dependent mortality associated with DOCA. The maximum lethal dose was 10 mg/l causing death of all treated fish within a few hours. This information is relevant to the use of CS in fish therapy in response to stress.

Cell death (apoptosis) in mouse intestine after continuous irradiation with gamma rays and with beta rays from tritiated water.

Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the calculation of the absorbed dose from HTO, the water content both of the mouse body and of the cells was assumed to be 70%. One megabecquerel of HTO per mouse (i.e., 40 MBq/kg body wt) gave a dose rate of 0.131 mGy/h. The mean lethal doses (D0) were calculated for gamma rays and HTO, and relative biological effectiveness values of HTO relative to gamma rays were obtained. The D0 values for continuous irradiation with gamma rays were 210 mGy for small intestine and 380 mGy for descending colon, and the respective values for HTO were 130 and 280 mGy, indicating the high radiosensitivity of target cells for apoptotic death. The relative biological effectiveness of HTO relative to 137Cs gamma rays for cell killing in both the small intestine and the descending colon in the mouse was 1.4-2.1.

Indomethacin inhibition of ossification induced by direct current stimulation.

In this study, we sought to clarify the mechanism of ossification induced by direct current stimulation by analyzing changes in local blood flow and vascular permeability and by examining the involvement of chemical mediators. Changes in blood flow were studied with laser Doppler flowmetry, and vascular permeability was determined by microquantification. To examine the involvement of chemical mediators, we determined the effect on vascular permeability of histamine H1 and H2-receptor blockers and indomethacin. In addition, direct current stimulation was performed during administration of indomethacin to determine whether indomethacin inhibits electrically induced callus formation. Local blood flow remained unchanged in the control group and in the group receiving 5 microA of stimulation, but it increased in the groups receiving 10 and 50 microA. Vascular permeability increased in the 5 and 10 microA stimulation groups. This increase was not suppressed by histamine-receptor blockers, but it was suppressed by indomethacin. Two weeks of electrical stimulation without concomitant indomethacin treatment resulted in active callus formation around the needle electrode and in the vicinity of the endosteum; however, direct current stimulation during administration of indomethacin inhibited callus formation. The results suggest that these changes serve as microenvironmental factors that play an important role in the promotion of ossification and that a prostaglandin-mediated mechanism is involved in the promotion of ossification by direct current stimulation.

Nonsurgically managed patients with degenerative spondylolisthesis: a 10- to 18-year follow-up study.

OBJECT: Controversy exists concerning the indications for surgery and choice of surgical procedure for patients with degenerative spondylolisthesis. The goals of this study were to determine the clinical course of nonsurgically managed patients with degenerative spondylolisthesis as well as the indications for surgery. METHODS: A total of 145 nonsurgically managed patients with degenerative spondylolisthesis were examined annually for a minimum of 10 years follow-up evaluation. Radiographic changes, changes in clinical symptoms, and functional prognosis were surveyed. Progressive spondylolisthesis was observed in 49 patients (34%). There was no correlation between changes in clinical symptoms and progression of spondylolisthesis. The intervertebral spaces of the slipped segments were decreased significantly in size during follow-up examination in patients in whom no progression was found. Low-back pain improved following a decrease in the total intervertebral space size. A total of 84 (76%) of 110 patients who had no neurological deficits at initial examination remained without neurological deficit after 10 years of follow up. Twenty-nine (83%) of the 35 patients who had neurological symptoms, such as intermittent claudication or vesicorectal disorder, at initial examination and refused surgery experienced neurological deterioration. The final prognosis for these patients was very poor. CONCLUSIONS: Low-back pain was improved by restabilization. Conservative treatment is useful for patients who have low-back pain with or without pain in the lower extremities. Surgical intervention is indicated for patients with neurological symptoms including intermittent claudication or vesicorectal disorder, provided that a good functional outcome can be achieved.

LY309887, antifolate via the folate receptor suppresses murine type II collagen-induced arthritis.

OBJECTIVE: To examine the effect of LY309887, an inhibitor of glycinamide ribonucleotide formyltransferase in de novo purine biosynthesis on murine type collagen-induced arthritis (CIA). METHODS: CIA was induced by immunization with bovine type II collagen in adjuvant. The expression of folate receptors was examined in dissected synovial tissues and bone marrow cells from arthritic and non-arthritic mice by the semi-quantitative reverse transcription-polymerase chain reaction. LY309887 was administered to CIA mice after the onset of arthritis. Mice were monitored for arthritis index for 21 days. Levels of IgG1 and IgG2a antibodies against bovine type II collagen were measured in sera from CIA mice with or without LY309887 treatment by the enzyme-linked immunosorbent assay. Histologic analyse were also performed in synovial tissues from arthritic joints with or without LY309887 treatment. RESULTS: Levels of mRNA of folate receptor beta (FR-beta) were elevated in arthritic joints from CIA mice, compared with those in nonarthritic joints. The expression of mRNA of FR-beta was dominant in bone marrow cells of CIA mice. The administration of LY309887 suppressed the disease progression of CIA mice as defined by the lower arthritis index, and decreased production of serum IgG1 and IgG2a anti-type II collagen antibody, and the damage to cartilage or bone. CONCLUSION: The administration of LY309887 was effective on CIA mice. It was suggested that LY309887 might be useful in the treatment of rheumatoid arthritis.

The effect of pulsing electromagnetic field on bone ingrowth into a porous coated implant.

Electromagnetic stimulation is known to promote bone formation in cases of fracture and pseudoarthrosis. The possibility of using electromagnetic field to promote bone ingrowth into a porous coated implant was investigated in this study using Japanese albino rabbits. A titanium implant coated with beads of 250-300 microns in diameter around a stem of 1.7 mm in diameter was inserted into the humerus cavity of a Japanese albino rabbit. The humerus was stimulated by pulsing electromagnetic fields at 2 Gauss, 10Hz, 25 microseconds for 14 days. The circumference of grown bone into the implant was measured, and calculated in area equivalent for determination of the area of new bone. Bone ingrowth was significantly promoted by consecutive 14 days. The result suggests that electromagnetic stimulation is useful for achieving further bone ingrowth into a porous coated implant.

The circadian rhythm for the number and sensitivity of radiation-induced apoptosis in the crypts of mouse small intestine.

Apoptosis is a mode of cell death involving nuclear pycnosis, cytoplasmic condensation and karyorrhexis. Changes in the number of apoptotic cells at various times (3-12 h) after a single dose of either 0.5 or 9.0 Gy given at 09.00, 21.00 or 03.00 h were studied in histological sections of small intestinal crypts of mice. The incidences of apoptosis were examined 3 or 6 h after irradiation at different times of day with different doses of gamma-rays ranging from 0.15 to 9.0 Gy. Survival curves were constructed from the dose-incidence curves for apoptosis, using the number of apoptotic cells after high doses (NM) as the maximum cell population size. The mean lethal doses (Do) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both Do and NM values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. A possible explanation based on the cell-cycle states of the target cell population for apoptosis (presumably functional stem cells) was drawn. Most of the target cells were assumed to be in an extended G1 phase. Around 21.00 h a transition from G1 to S phase takes place in some of these cells (approximately seven or eight cells per whole crypt). The S phase then lasts till around 06.00 h. They may be at G2 and M around 06.00-09.00 h, and then they re-enter G1. The circadian rhythm for the number and sensitivity of the cells susceptible to apoptosis obtained in the present report agrees well with this pattern of cell-cycle phases of target cells.

Hertwig effect caused by UV-irradiation of sperm of Oryzias latipes (teleost) and its photoreactivation.

When sperm of the fish Oryzias latipes were irradiated with ultraviolet light and allowed to fertilize normal eggs, the so-called "Hertwig effect" was observed, with a dose-dependent decrease in survival rate at low doses (0-27 J . m-2) but a better survival rate at higher dose ranges. Illumination with visible light after fertilization (10-70 min after insemination) showed the existence of photoreactivation (PR), demonstrating that pyrimidine dimers are a lesion in sperm DNA that is mainly responsible for the UV-caused Hertwig effect. Genetic analysis, in which sperm from a wild-type of this fish was used, showed that, after UV-irradiation at the high dose range, male nuclei did not participate in embryonic development (a gynogenetic haploid condition). Embryos having only a maternal set of chromosomes could develop no further than stage 27. Only the visible light during the early part (until around 20-30 min after insemination, at 25 degrees C) of the single-cell stage was effective for PR; illumination thereafter was not.

Results of a longer than 10-year follow-Up of patients with rheumatoid arthritis treated by occipitocervical fusion.

STUDY DESIGN: Evaluation of results a longer than 10-year follow-up of patients with upper cervical lesions due to rheumatoid arthritis who underwent occipitocervical fusion. OBJECTIVE: To determine the final outcome of patients with upper cervical lesions due to rheumatoid arthritis treated by occipitocervical fusion. SUMMARY OF BACKGROUND DATA: There are few studies reporting the final outcome of patients with rheumatoid arthritis treated by occipitocervical fusion and observed for longer than 10 years. METHODS: The subjects were 16 patients with rheumatoid arthritis with myelopathy who underwent occipitocervical fusion with a rectangular rod more than 10 years ago. All 16 patients had irreducible atlantoaxial dislocation, and 11 also had vertical dislocation of the axis. All patients had preoperative nuchal pain, and were classified into Class II (two patients), Class IIIA (nine patients), and class IIIB (five patients) according to Ranawat's preoperative neurologic classification. RESULTS: The atlas-dens interval remained the same as immediately after surgery. Vertical dislocation returned to the preoperative condition, despite successful surgical correction. Preoperative occipital pain disappeared or was reduced in all cases. Myelopathy improved in 12 of the 16 patients (75%) by more than one class in the Ranawat preoperative neurologic classification. Survival rate at 10 years after surgery was 38%; mean age at death was 70.7 years. The postoperative periods during which patients could walk by themselves ranged from 6 months to 13 years (mean, 7.5 years). CONCLUSIONS: Occipitocervical fusion for patients with rheumatoid arthritis is useful for decreasing nuchal pain, reducing myelopathy, and improving prognosis.

Comparison of operative results of lumbar disc herniation in manual laborers and athletes.

The results of various surgical treatments for lumbar disc herniation in laborers and athletes were compared on the basis of the relative success of return to work and athletic activity. The rate of successful return to manual labor was the highest at 89% after spinal fusion, but no difference was observed between simple disc excision and percutaneous discectomy. Return to competitive sports was achieved at rate of 81% after percutaneous discectomy, and the time until return to sports activity was significantly shorter than after other procedures. In individuals whose lumbar region is expected to be subjected to great mechanical stress, it is important to take work needs and the special needs of athletes into consideration when selecting the surgical procedure.

Preoperative and postoperative magnetic resonance image evaluations of the spinal cord in cervical myelopathy.

To evaluate the morphologic changes of the spinal cord in patients with cervical myelopathy due to cervical spondylosis and ossification of the posterior longitudinal ligament, the authors measured the thickness and signal intensity of the cervical cord with magnetic resonance imaging in healthy adults and patients with cervical myelopathy, and compared these findings. In patients with cervical myelopathy, the preoperative and postoperative magnetic resonance imaging findings were compared with the severity of myelopathy and postoperative results. In healthy adults, the anteroposterior diameter of the cervical cord was 7.8 mm at the C3 level and decreased at lower levels. In the patients with cervical myelopathy, the preoperative spinal anteroposterior diameter was significantly reduced at various levels corresponding to the stenosis site within the vertebral canal. In the group with ossification of the posterior longitudinal ligament, the minimal anteroposterior diameter of the cervical cord tended to decrease with increasing severity of myelopathy. However no relationship was observed between the two parameters in the cervical spondylotic myelopathy group. In the group with ossification of the posterior longitudinal ligament, surgical results were good when the postoperative anteroposterior diameter was increased, whereas in the cervical spondylotic myelopathy group there was no relationship between the two parameters. In the patients with myelopathy, a high intensity area was observed in about 40% of all patients before operation and about 30% after operation. However, the presence or absence of a high intensity area did not correlate with the severity of myelopathy or with surgical results in the group with ossification of the posterior longitudinal ligament and the cervical spondylotic myelopathy groups.

Clinical course of conservatively managed rheumatoid arthritis patients with myelopathy.

STUDY DESIGN: The clinical course of rheumatoid arthritis patients with myelopathy who do not undergo surgery was studied. OBJECTIVES: To establish a more accurate prognosis for rheumatoid arthritis patients who do not undergo surgery. SUMMARY OF BACKGROUND DATA: Cervical myelopathy has been reported in two thirds of rheumatoid arthritis patients with atlantoaxial dislocation. Atlantoaxial fusion, or occipitocervical fusion, is widely performed on these patients. However, several researchers reported serious complications from the surgery, including nonunion, worsening myelopathy, and high mortality. The natural course of disease in rheumatoid arthritis patients with myelopathy should be known before definitive treatments can be outlined. MATERIALS AND METHODS: Twenty-one rheumatoid arthritis patients with myelopathy resulting from atlantoaxial dislocation were studied. Fourteen of the 21 cases were associated with upward migration of the odontoid process. All of these patients were recommended for surgery, but they refused. Patients were reviewed by direct examination yearly. Radiographic changes and clinical course, including the survival rate, were observed. RESULTS: Atlantodental interval and Redlund-Johnell measurements deteriorated. The patients showed no neural improvement, and deterioration was found in 16 (76%) cases during follow-up. All patients became bedridden within 3 years of the onset of myelopathy. Seven of the 21 patients died suddenly for unknown reasons, 3 died of pneumonia, and 1 died of multiple organ failure. The three sudden-death cases showed progressive upward migration of the odontoid process. The cumulative probability of survival was 0% in the first 7 years after the onset of myelopathy. CONCLUSIONS: The clinical results for rheumatoid arthritis patients with myelopathy treated without surgery are extremely poor. Surgical treatment is recommended for rheumatoid arthritis patients with myelopathy.