High prevalence of lumbar spinal stenosis in cases of idiopathic normal-pressure hydrocephalus affects improvements in gait disturbance after shunt operation.

Objective: Idiopathic normal-pressure hydrocephalus (iNPH) is characterized by symptoms of dementia, urinary incontinence, and gait disturbance; however, gait disturbance tends to persist after shunt surgery. Gait disturbance and urinary dysfunction are also major symptoms of lumbar spinal stenosis (LSS). Currently, the epidemiology of the complications of LSS in iNPH is unclear. Here, we evaluated the coexistence rate of LSS in iNPH cases. Methods: This was a retrospective case-control study. Between 2011 and 2017, 224 patients with a median age of 78 years, including 119 males, were diagnosed with iNPH and underwent lumboperitoneal shunts or ventriculoperitoneal shunts. LSS was diagnosed with magnetic resonance imaging by two spine surgeons. Age, sex, body mass index (BMI), Timed Up and Go (TUG) test, Mini Mental State Examination (MMSE) score, and urinary dysfunction were examined. We compared the changes in these variables in the group of patients with iNPH without LSS versus those with both iNPH and LSS. Results: Seventy-three iNPH patients (32.6%) with LSS had significantly higher age and BMI. The existence of LSS did not alter the postoperative improvement rates of MMSE and urinary dysfunction; however, TUG improvement was significantly impaired in the LSS-positive group. Conclusions: LSS affects improvements in gait disturbance of iNPH patients after shunt operation. Because our results revealed that one-third of iNPH patients were associated with LSS, gait disturbance observed in iNPH patients should be considered a potential complication of LSS.

CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common pathological condition that causes intractable myelopathy and radiculopathy, mainly the result of an endochondral ossification-like process. Our previous genome-wide association study identified six susceptibility loci for OPLL, including the cell division cycle 5-like (CDC5L) gene region. Here, we found CDC5L to be expressed in type II collagen-producing chondrocyte-like fibroblasts in human OPLL specimens, as well as in differentiating ATDC5 chondrocytes. Cdc5l siRNA transfection in murine chondrocytes decreased the expression of the early chondrogenic genes Sox9 and Col2a1, diminished the cartilage matrix production, and enhanced the expression of parathyroid-hormone-related protein (a resting chondrocyte marker). We also showed that Cdc5l shRNA suppressed the growth of cultured murine embryonal metatarsal cartilage rudiments and that Cdc5l knockdown suppressed the growth of ATDC5 cells. Fluorescence-activated cell sorting analysis revealed that the G2/M cell cycle transition was blocked; our data showed that Cdc5l siRNA transfection enhanced expression of Wee1, an inhibitor of the G2/M transition. Cdc5l siRNA also decreased the pre-mRNA splicing efficiency of Sox9 and Col2a1 genes in both ATDC5 cells and primary chondrocytes; conversely, loss of Cdc5l resulted in enhanced splicing of Wee1 pre-mRNA. Finally, an RNA-binding protein immunoprecipitation assay revealed that Cdc5l bound directly to these target gene transcripts. Overall, we conclude that Cdc5l promotes both early chondrogenesis and cartilage growth and may play a role in the etiology of OPLL, at least in part by fine-tuning the pre-mRNA splicing of chondrogenic genes and Wee1, thus initiating the endochondral ossification process.

Isolated Distal Deep Vein Thrombus Detected before Orthopedic Surgery: Is Preoperative Anticoagulation Preferable?

Objective: We evaluate the efficacy of anticoagulant administration for isolated distal deep vein thrombus (IDDVT), detected before orthopedic surgery. Materials and Methods: The study included 32 patients diagnosed with IDDVT before orthopedic surgery in our hospital between October 2011 and October 2017. They were divided into two groups: the 'pre- and post-operative therapy group,' who were administered anticoagulants both pre- and post-operatively, and the 'post-operative therapy group,' who were administered anticoagulants only after surgery due to risk of bleeding judged by an orthopedic surgeon. We compared the primary efficacy (change in IDDVT size) between the two groups. Results: The proportion of patients with increased post-operative IDDVT sizes was significantly larger in the post-operatively treated group than in the pre- and post-operatively treated group (44.4% vs. 8.7%, p=0.026). No case demonstrated an IDDVT extension proximal to the popliteal vein or presented with symptomatic pulmonary thromboembolism in this study. Conclusion: Based on our findings, we recommend that, in patients with IDDVT detected prior to orthopedic surgery and administered anticoagulant therapy only after the procedure because of a bleeding risk, a lower limb ultrasonography to re-evaluate the existing deep vein thrombus should be conducted before beginning rehabilitation.

Association between Bone Mineral Density of Femoral Neck and Geriatric Nutritional Risk Index in Rheumatoid Arthritis Patients Treated with Biological Disease-Modifying Anti-Rheumatic Drugs.

Treatment of rheumatoid arthritis (RA) with biological disease-modifying anti-rheumatic drugs (bDMARDs) induces rapid remission. However, osteoporosis and its management remains a problem. The Geriatric Nutritional Risk Index (GNRI) evaluates the risk of malnutrition-related complications in elderly patients and has been shown to be a significant predictor of many diseases. We evaluated the correlation between GNRI and RA activity. In addition, risk factors for femoral neck bone loss were evaluated in RA patients treated with bDMARDs. We retrospectively examined the medical records of 146 patients with RA, collecting and recording the patients' demographic and clinical characteristics. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Inverse correlations were observed between GNRI and disease duration, disease activity score-28 joint count serum C-reactive protein (CRP), simple disease activity index, modified health assessment questionnaire score and CRP. GNRI showed correlation with femoral neck BMD and femoral neck BMD ≤ 70% of young adult men (YAM). Multiple regression analysis showed that female sex, increased age and lower GNRI were risk factors for lower BMD of the femoral neck. Multivariate binomial logistic regression analysis showed that female sex (odd ratio: 3.67) and lower GNRI (odd ratio: 0.87) were risk factors for BMD ≤ 70% of YAM. Because the GNRI is a simple method, it might be a simple predictor for RA activity and BMD status in RA patients. Complementary nutritional therapies might improve RA activity and osteoporosis in RA patients who have undergone treatment with bDMARDs.

Risk factors for bone loss in patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs.

OBJECTIVE: Osteoporosis is a complication of rheumatoid arthritis. We examined the risk factors for bone loss in rheumatoid arthritis patients receiving biological disease-modifying anti-rheumatic drugs. Lumbar spine and femoral neck bone mineral density was measured at two time points in 153 patients with rheumatoid arthritis managed with biological disease-modifying anti-rheumatic drugs. We examined patients' variables to identify risk factors for least significant reduction of bone mineral density. RESULTS: Least significant reduction of lumbar spine bone mineral density (≤ - 2.4%) was seen in 13.1% of patients. Least significant reduction of femoral neck bone mineral density (≤ - 1.9%) was seen in 34.0% of patients. Multiple logistic regression analysis showed that a risk factor for least significant reduction of the lumbar spine was high-dose methylprednisolone use. Multiple regression analysis showed that a risk factor for least significant reduction of the femoral neck was short disease duration. Our findings showed that a risk factor for femoral neck bone mineral density reduction was a short disease duration. These findings suggest that rheumatoid arthritis patients receiving treatment with biological disease-modifying anti-rheumatic drugs may benefit from earlier osteoporosis treatments to prevent femoral neck bone loss.

Classification of odontoid destruction in patients with rheumatoid arthritis using reconstructed computed tomography: reference to vertical migration.

OBJECTIVE: To reveal the factors that determine the natural course of subluxation of occipital-cervical lesions in rheumatoid arthritis (RA). The atlanto-axial region is one of the most common locations for lesions in RA. Some cases progress from reducible atlanto-axial subluxation (AAS) to irreducible vertical migration, while others continue to exhibit reducible AAS. No study has revealed the factors that determine the natural course of subluxation. We focus on the odontoid as a key structure of the progression of occipito-cervical lesions and investigated this region in patients with RA using reconstructive computed tomography (CT) images, and analyzed factors in association with CT findings. METHODS: Fifty-eight patients with RA and 40 age-matched controls, all women, were studied. Associated factors, including C-reactive protein, erythrocyte sedimentation rate, steroid usage, and the severity of local osteoporosis, were analyzed as measurements in association with odontoid destruction. RESULTS: The destruction of odontoid and atlanto-odontoid joint were common in patients with RA. The more destruction observed in the odontoid process, the greater is the degree of progression of vertical migration. Local osteoporosis is a significant factor in odontoid destruction, based on a cortico-cancellous index of 42% in cases of grade III odontoid destruction. CONCLUSION: The odontoid process is a key structure in the progression of occipito-cervical lesions in patients with RA.

Magnetic resonance angiography for vertebral artery evaluation in rheumatoid arthritis patients.

OBJECTIVE: To examine the radiological features of vertebral artery (VA) displacement/occlusion associated with rheumatoid arthritis (RA) spine using magnetic resonance angiography. METHODS: Forty-seven RA patients with upper cervical lesions were evaluated for patency or abnormality of the VA by extracranial magnetic resonance angiography, with comparison of findings with those of 46 healthy volunteers. RESULTS: VA occlusion occurred in 4 patients (8.5%) and VA stenosis in 9 patients (19.1%). Anomaly of the VA was also observed in 3 patients (6.4%). No occlusion or anomaly was found in healthy volunteers, but 1 case of stenosis was found. Severity of vertical subluxation was correlated with the presence of VA abnormality in RA patients. CONCLUSION: The incidence of VA abnormality was 34% in RA patients and 2% in healthy volunteers. Magnetic resonance angiography is useful for screening for abnormality of the entire VA.

Evaluation of occipitocervical subluxation in rheumatoid arthritis patients, using coronal-view reconstructive computed tomography.

STUDY DESIGN: Reconstructive computed tomography (CT) study of occipito-atlanto and atlantoaxial joints in RA patients. SUMMARY OF BACKGROUND DATA: The occipitocervical region is one of the most common sites of rheumatoid arthritis (RA). Although lateral radiography has been used for the diagnosis of atlantoaxial subluxation and vertical subluxation, reconstructive CT imaging of the occipito-atlanto and atlantoaxial joints is more sensitive in detecting morphologic changes in this region. We investigated this region in RA patients, using coronal-view reconstructive CT images, and examined the relationship between the morphology and other radiographic parameters. METHODS: The occipitocervical region was examined in 58 female RA patients by reconstructive CT, plain radiography, and MRI. The degree of destructive change on reconstructive CT was compared to that on other radiographic evaluations. RESULTS: Coronal-view reconstructive CT revealed primary destructive changes before detection by lateral radiography, using Redlund-Johnell or Ranawat values. A Redlund-Johnell value less than 34 mm was diagnostic for occipitocervical subluxation in female RA patients. CONCLUSION: Coronal-view reconstructive CT is useful for the diagnosis of occipitocervical joint subluxation in RA.

Occult spinal canal stenosis due to C-1 hypoplasia in children with Down syndrome.

OBJECT: Little has been published about subclinical spinal canal stenosis due to C-1 hypoplasia in patients with Down syndrome. In this paper the authors performed a matched comparison study with cross-sectional survey to investigate occult spinal canal stenosis due to C-1 hypoplasia in children with Down syndrome. METHODS: A total of 102 children with Down syndrome ranging in age from 10 to 15 years were matched according to age and physique with 176 normal children. In all participants, the anteroposterior (AP) diameter of C-1 and the atlas-dens interval (ADI) were measured on plain lateral x-ray images of the cervical spine. The cross-sectional area of the atlas was also measured from a cross-sectional computed tomography image of C-1. RESULTS: Eight children (6.7%) with Down syndrome developed atlantoaxial subluxation associated with myelopathy. The difference in the ADI between the patients and controls was not statistically significant. The average AP diameter of the atlas and the spinal canal area along the cross-section of the atlas were significantly smaller in children with Down syndrome than those in the control group. CONCLUSIONS: Atlantoaxial instability and occult spinal canal stenosis due to C-1 hypoplasia in patients with Down syndrome may significantly increase the risk of myelopathy.

Clinical course of patients with ossification of the posterior longitudinal ligament: a minimum 10-year cohort study.

OBJECT: Ossification of the posterior longitudinal ligament (OPLL) may produce quadriplegia. The course of future neurological deterioration in patients with radiographic evidence of OPLL, however, is not known. The authors conducted a long-term follow-up cohort study of more than 10 years to clarify the clinical course of this disease progression. METHODS: A total of 450 patients, including 304 managed conservatively and 146 treated by surgery, were enrolled in the study. All patients underwent neurological and radiographical follow-up examinations for a mean of 17.6 years. Myelopathy was graded using Nurick classification and the Japanese Orthopaedic Association scale. Fifty-five (17%) of 323 patients without myelopathy evident at the first examination developed myelopathy during the follow-up period. Risk factors associated with the evolution of myelopathy included greater than 60% OPLL-induced stenotic compromise of the cervical canal, and increased range of motion of the cervical spine. Using Kaplan-Meier analysis, the myelopathy-free rate in patients without first-visit myelopathy was 71% after 30 years. A significant difference in final functional outcome was not observed between nonsurgical and surgical cases in which preoperative Nurick grades were 1 or 2. In patients with Nurick Grade 3 or 4 myelopathy, however, only 12% who underwent surgery eventually became wheelchair bound or bedridden compared with 89% of those managed conservatively. Surgery proved ineffective in the management of patients with Grade 5 disease. CONCLUSIONS: Results of this long-term cohort study elucidated the clinical course of OPLL following conservative or surgical management. Surgery proved effective for the management of patients with Nurick Grades 3 and 4 myelopathy.

Prognosis of patients with upper cervical lesions caused by rheumatoid arthritis: comparison of occipitocervical fusion between c1 laminectomy and nonsurgical management.

STUDY DESIGN: A matched controlled comparative study of patients with upper cervical lesions caused by rheumatoid arthritis was performed at two different hospitals to evaluate occipitocervical fusion associated with C1 laminectomy and nonsurgical treatment. OBJECTIVES: To evaluate the long-term results and advantages of occipitocervical fusion associated with C1 laminectomy, and to compare these results with those of nonsurgical management of patients with myelopathy related to rheumatoid arthritis. SUMMARY OF BACKGROUND DATA: Few studies have reported the prognosis of patients with rheumatoid arthritis managed by occipitocervical fusion associated with C1 laminectomy. METHODS: In this study, 40 patients with rheumatoid arthritis and myelopathy caused by irreducible atlantoaxial dislocation with or without upward migration of the odontoid process were studied. Of these 40 patients, 19 were treated by occipitocervical fusion using a rectangular rod associated with C1 laminectomy at one hospital, whereas 21 matched patients were treated conservatively at another hospital. The patients were observed by the same protocol to assess the radiologic and clinical results, including functional recovery and survival rate. All the patients were followed until their death. RESULTS: The atlantodental interval was reduced immediately after surgery, and this result had been well maintained at the final follow-up assessment. Redlund-Johnell values did not vary significantly throughout the course of the study. As for neural assessment with the Ranawat classification system, improvement was found in 13 (68%) of the 19 patients who underwent surgery. The survival rate was 84% 5 years after surgery, and 37% in the first 10 years. In the patients who did not undergo surgical treatment, atlantodental interval and Redlund- Johnell values were aggravated. These patients showed no neural improvement, and aggravation was found in 16 (76%) of the 21 cases during the follow-up period. All the patients were bedridden within 3 years after the onset of myelopathy. The survival rate was 0% in the first 8 years. CONCLUSIONS: The findings lead to the conclusion that occipitocervical fusion associated with C1 laminectomy for patients with rheumatoid arthritis is useful for decreasing nuchal pain, reducing myelopathy, and improving prognosis.