Calcium sensing and signaling are impaired in the lumbar spine of a rat model of congenital kyphosis.

PURPOSE: Kyphosis involves spines curving excessively backward beyond their physiological curvature. Although the normal structure of the spinal vertebrae is extremely important for maintaining posture and the normal function of the thoracic and abdominal organs, our knowledge concerning the pathogenesis of the disease is insufficient. We herein report that the downregulation of the calcium signaling pathway is involved in the pathogenesis of congenital kyphosis. METHODS: The third to fifth lumbar spine segments, the kyphotic region of Ishibashi (IS) rats, which are used as a model of congenital kyphoscoliosis, were collected. A DNA microarray, quantitative PCR, Western blotting, and immunohistochemistry were used to measure the expression of genes and proteins related to intracellular calcium signaling. RESULTS: We found that the expression of calcium-sensing receptor (CaSR) and transient receptor potential vanilloid 1 (Trpv1)-two receptors involved in the calcium signaling-was decreased in the lumbar spine of IS rats. We also observed that the number of CaSR-immunoreactive and Trpv1-immunoreactive cells in the lumbar spine of IS rats was lower than in wild-type rats. Furthermore, the expression of intracellular molecules downstream of these receptors, such as phosphorylated protein kinase C, c-Jun N-terminal kinase, and neural EGFL-like 1, was also reduced. In fact, the calcium content in the lumbar spine of IS rats was significantly lower than that in wild-type rats. CONCLUSION: These results indicate that adequate calcium signaling is extremely important for the regulation of normal bone formation and may also be a key factor for understanding the pathogenesis of congenital kyphosis.

Upregulated miR-224-5p suppresses osteoblast differentiation by increasing the expression of Pai-1 in the lumbar spine of a rat model of congenital kyphoscoliosis.

Congenital scoliosis is defined by the presence of structural anatomical malformations that arise from failures of vertebral formation or segmentation before and after birth. The understanding of genetic background and key genes for congenital scoliosis is still poor. We herein report that the excess expression of plasminogen activator inhibitor-1 (Pai-1) induced by the upregulation of miR-224-5p is involved in the pathogenesis of congenital kyphoscoliosis through impaired osteoblast differentiation. We first investigated the variety and progression of abnormalities of the lumbar spines in Ishibashi (IS) rats, a rat model of congenital kyphoscoliosis. The rats had already shown fusion and division of the primary ossification center at postnatal day 4. Over time, the rats showed various abnormalities of the lumbar spine, including the fusion of the annular epiphyseal nucleus. At postnatal day 42, spinal curvature was clearly observed due to the fusion of the vertebral bodies. Using a microRNA array, we found that the expression of miR-224-5p was increased in the lumbar spine of the rats at postnatal day 4. The expression of Pai-1, which is involved in osteoblast differentiation regulated by miR-224-5p, was also increased, while the levels of type I collagen, a marker of osteoblast differentiation, were decreased in the lumbar spine. These results indicate that the aberrant expression of miRNA-224-5p and its target genes is involved in the impaired osteoblast differentiation and may provide a partial molecular explanation for the pathogenesis of congenital scoliosis.

The retinol-retinoic acid metabolic pathway is impaired in the lumbar spine of a rat model of congenital kyphoscoliosis.

Although congenital scoliosis is defined as a genetic disease characterized by a congenital and abnormal curvature of the spinal vertebrae, our knowledge of the genetic underpinnings of the disease is insufficient. We herein show that the downregulation of the retinol-retinoic acid metabolism pathway is involved in the pathogenesis of congenital scoliosis. By analyzing DNA microarray data, we found that the expression levels of genes associated with the retinol metabolism pathway were decreased in the lumbar spine of Ishibashi rats (IS), a rat model of congenital kyphoscoliosis. The expression of Adh1 and Aldh1a2 (alcohol dehydrogenase), two enzymes that convert retinol to retinoic acid in this pathway, were decreased at both the gene and protein levels. Rarα, a receptor of retinoic acid and bone morphogenetic protein 2, which play a central role in bone formation and are located downstream of this pathway, were also downregulated. Interestingly, the serum retinol levels of IS rats were higher than those of wild-type control rats. These results indicate that the adequate conversion from retinol to retinoic acid is extremely important in the regulation of normal bone formation and it may also be a key factor for understanding the pathogenesis of congenital scoliosis.

The relationship between the degree of displacement of the atlas to axis and the clinical data in atlanto-axial subluxation due to rheumatoid arthritis.

INTRODUCTION: The most common type of anatomical cervical spine involvement is atlanto-axial subluxation (AAS) in rheumatoid arthritis (RA). The purpose of this study was to clarify the relationship between the displacement of the atlas to axis and the clinical data obtained in patients with AAS due to RA. METHODS: Fifty patients with AAS due to RA that were treated by surgery are herein reviewed. Based on the findings of preoperative lateral cervical radiographs in the neutral position, the patients were classified into two groups as follows: a 10 + group with an atlanto-dental interval (ADI) of ≧ 10 mm, and a 10 - group with an ADI < 10 mm. RESULTS: Preoperative lateral cervical radiographs demonstrated 15 cases to belong to the 10 + group, while 35 cases belonged to the 10 - group. In the preoperative MR imaging, an intramedullary high signal intensity was observed in seven cases that belonged to the 10 + group and in four cases belonging to the 10 - group. Regarding the neurological severity, the 10 + group included significantly more cases showing severe neurological deficits before surgery; however, there was no significant difference between the two groups regarding the presence of severe deficits even after surgery. CONCLUSIONS: The severe displacement group included significantly more cases showing an intramedullary high signal intensity in the preoperative MR images. Our results also suggest that a severe displacement before surgery affected the presence of neurological deficits before surgery; however, it did not affect the neurological recovery from such severe neurological deficits.

The clinical outcomes of atlanto-axial arthrodesis in patients with rheumatoid arthritis - Assessment according to the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ).

PURPOSE: The purpose of this study was to evaluate the clinical outcomes of atlanto-axial arthrodesis in rheumatoid arthritis (RA) patients with cervical myelopathy using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). METHODS: Twenty patients who underwent surgery to treat atlanto-axial subluxation (AAS) were reviewed. RESULTS: The rates of success rates for each domain were as follows: cervical spine function, 11 of 18 patients (61.1%); upper extremity function, 3 of 15 patients (20%); lower extremity function, 8 of 18 patients (44.4%); bladder function, 5 of 13 patients (38.5%); and quality of life, 3 of 20 patients (15%). Significant differences of success rate were found between the following domains: cervical spine function and upper extremity function, cervical spine function and the quality of life, and lower-extremity function and quality of life. There were significant differences in the pre- and post-surgery visual analogue scale (VAS) scores for pain or stiffness in the neck or shoulders, and pain or numbness in the arms and hands. CONCLUSION: Atlanto-axial arthrodesis in RA patients provided a better outcome for cervical spine function, with improvement in VAS scores for pain or stiffness in the neck or shoulders. This surgery provided improvement of pain or numbness of the upper extremities but not of upper-extremity function. In contrast, the surgery achieved a relatively good recovery in lower-extremity function but little improvement of pain or numbness of the lower extremities. The success rate with regard to quality of life was found to be significantly lower than the success rates observed for cervical spine function and lower-extremity function.

The Trk family of neurotrophin receptors is downregulated in the lumbar spines of rats with congenital kyphoscoliosis.

Congenital scoliosis is a condition characterized by spinal curvature beyond the physiological norm. The molecular mechanisms underlying the pathogenesis of congenital scoliosis are beginning to be clarified; however, the genes related to congenital scoliosis are still unknown. We herein report the results of a comprehensive analysis of gene expression in the spines from a rat model of congenital kyphoscoliosis obtained using DNA microarrays. The rats (Ishibashi rats, IS) showed decreased expression levels of genes associated with bone formation, such as those associated with retinol metabolism and type I collagen. Interestingly, the flexion sites of the IS rats showed low expression levels of tropomyosin receptor kinases (Trks: TrkA, TrkB, and TrkC), which belong to the neurotrophic receptor tyrosine kinase family. Moreover, this phenomenon was observed only in the flexion sites of the spine, and the expression levels of Trks in other parts of the spine in these rats were normal. The decreased expression levels of Trks were observed at both the mRNA and protein levels. We also observed that the number of Trk-immunopositive cells in the lumbar spine in the IS rats was lower than that in wild-type rats. These findings indicate that the Trks have an important function in regulating normal bone formation, and provide a molecular explanation for the pathogenesis of congenital kyphoscoliosis.

Wrist drop and muscle weakness of the fingers induced by an upper cervical spine anomaly.

PURPOSE: This report presents a case of wrist drop and muscle weakness of the fingers as a false localizing sign induced by stenosis of the upper cervical spine caused by a bony anomaly. METHODS: A 77-year-old male complained of severe muscle weakness of the right hand. Cervical spine MRI showed a severe and sharp compression of the spinal cord from the dorsal side between C2 and C3 with intramedullary intensity changes and mild stenosis at C3/4 and C4/5. RESULTS: The patient underwent laminectomy of C2, cranial side laminotomy of C3, and laminectomy of C4. Decompression of the spinal cord was demonstrated 1 year after surgery. The patient achieved full recovery of the muscle weakness 1 year after undergoing surgery. CONCLUSIONS: The pathophysiology of false localizing signs remains controversial; however, we believe that this unusual compression pattern and level had the possibility to induce atypical myelopathies such as drop hand and finger of the unilateral hand in this case.

Epidemiological study for personal risk factors and quality of life related to Dupuytren's disease in a mountain village of Japan.

BACKGROUND: This study investigated the etiology, personal risk factors, and quality of life related to Dupuytren's disease among residents of a mountain village in Japan. METHODS: Medical examinations were conducted of 401 adult residents (163 men, 238 women; average age of 66.7 years, range 40-92) of a mountain village in Japan. All had completed a self-administered questionnaire including items for gender, weight, height, dominant hand, occupation, history of diabetes mellitus, and frequency of smoking tobacco and drinking alcohol, in addition to EuroQol-5-Dimensions-3-level Japanese version. Blood samples were collected and assessed for biochemical markers related to Dupuytren's disease. The Dupuytren's disease diagnosis was based on clinical signs. Meyerding's classification was used to ascertain the disease severity. After examining background data and physical examination data related to Dupuytren's disease, we evaluated the association of Dupuytren's disease with those factors using univariate and logistic regression analysis. RESULTS: Dupuytren's disease was diagnosed in 28 subjects (7.0%). Univariate analysis revealed associations of age, male gender, occupation, history of diabetes mellitus, and alcohol intake with Dupuytren's disease. Logistic regression analysis after adjustment for age revealed a significant association between Dupuytren's disease and male gender, occupation, and history of alcohol intake. No significant difference was found between Dupuytren's disease patients and participants without this disease in the scoring and visual analog scale of EuroQol. No relation was found in scoring, the visual analog scale of EuroQol, or grading of Meyerding's classification in participants with Dupuytren's disease. CONCLUSION: This cross-sectional study revealed Dupuytren's disease in 7.0% of 401 subjects among the general population of a mountain village in Japan. The prevalence is higher with age and is apparently associated with male gender, occupation and alcohol intake. Risk factors associated with Dupuytren's disease were identified as age, male gender, occupation, and alcohol consumption habits.

Associations between neck and shoulder pain (called katakori in Japanese) and sagittal spinal alignment parameters among the general population.

BACKGROUND: Neck and shoulder pain (NSP), called katakori in Japanese, is one of the most common medical symptoms in the Japanese population; however, the pathogenesis of NSP has not yet been adequately elucidated. The purpose of this study was to investigate the associations between NSP and sagittal spinal alignment among the general population in Japan. MATERIALS AND METHODS: Medical examinations were conducted in the northeast village of Gunma, Japan. A questionnaire regarding NSP was distributed among 329 Japanese subjects (125 men and 204 women). Regarding the prevalence of NSP, the participants were asked to report the occurrence of NSP over the previous two weeks. For each participant, the parameters for sagittal spinal alignment, including thoracic kyphosis angle, lumbar lordosis angle, and spinal inclination relative to a perpendicular line, were measured with a SpinalMouse(®) (Idiag, Vplkerswill, Switzerland), an electronic computer-aided measuring device. We investigated the associations between the prevalence of NSP and the parameters obtained with the SpinalMouse(®). Statistical analyses were performed using Student's t test, Welch's t test, the chi-squared test, and a multivariate logistic regression analysis. A P value of 0.05 was considered to be statistically significant. RESULTS: The prevalence of NSP within the two weeks prior to questioning was 52.0 % (171 of 329 subjects). The subjects in the NSP group were significantly younger than those in the non-NSP group. There was a significant gender difference between the NSP group and the non-NSP group, as significantly more females complained of NSP than males. No significant association between the thoracic kyphosis angle and NSP was observed. However, the lumbar lordosis angles measured in the subjects in the NSP group were significantly larger than those in the non-NSP group, and the inclinations relative to a perpendicular line measured in the subjects in the NSP group were significantly larger than those in the non-NSP group. Furthermore, we performed a logistic regression analysis on each factor that showed a significant difference; age, gender, and the lumbar lordosis angle were each found to be significant. CONCLUSIONS: We investigated the associations between NSP and spinal sagittal alignment using the SpinalMouse(®) system, and demonstrated that some spinal alignment parameters are associated with NSP.

The Association Between the Rotator Cuff Status and the Severity and Recovery of Weakness in the Shoulder Abductor Strength in a Case of Proximal Type Cervical Spondylotic Amyotrophy.

STUDY DESIGN: Case series study. OBJECTIVE: We aimed to clarify the prevalence of rotator cuff tear (RCT), and the association between RCT and the severity and prognosis in patients with proximal type cervical spondylotic amyotrophy (CSA). METHODS: We retrospectively analyzed 35 proximal type CSA patients who were treated conservatively. The following data was collected: age, rotator cuff status on MRI, manual muscle test (MMT) score of shoulder abductor and biceps brachii muscles both at the first visit and final follow-up. We investigated the prevalence of RCT and the association between the rotator cuff status, and the severity and recovery of upper extremity weakness in patients with proximal type CSA. RESULTS: Of the 35 patients, 21 had an RCT on MRI, indicating that the prevalence of RCT in patients with proximal type CSA was 60%. An age-adjusted analysis showed that the presence of RCT was significantly associated with the MMT score of the shoulder abductor muscles both at the first visit and at the final follow-up. The presence of RCT was significantly associated with the recovery of the shoulder abductor muscles. The size of the RCT was negatively correlated with the MMT score of the shoulder abductor muscles at the final follow-up. The size of the RCT was independently correlated with the change of the MMT score of the shoulder abductor muscles. CONCLUSION: RCT was detected in >50% in patients with proximal type CSA, and the presence and severity of RCT can be used as prognostic factors for proximal type CSA patients who are treated conservatively.

Paraplegia due to Thoracic Mobile Schwannoma after Myelography.

INTRODUCTION: Spinal mobile tumors are very rare. We herein report a case of paraplegia caused by migration and incarceration of thoracic mobile schwannoma after myelography. Case Presentation. A 25-year-old man who had weakness and numbness in both his legs also had pain radiating to the back that was induced by back flexion or extension and jumping. Magnetic resonance imaging (MRI) showed an intradural extramedullary lesion at the T10 and T11 levels. Myelography was performed but discontinued due to his back and lower limb pain. Computed tomography after myelography revealed a rostrally migrated intradural mass with a discrepancy in the exact location in comparison to the MRI findings. He underwent a second lumbar puncture and drained the cerebrospinal fluid (CSF) to aid the spinal cord, because the symptoms gradually worsened and led to paraplegia. After the drainage of the CSF, his symptoms were immediately resolved. The day after myelography, he underwent complete resection of the tumor with the diagnosis of schwannoma. One year after the surgery, he had been working despite having hyperreflexia in his lower limbs with no weakness or sensory disturbance. CONCLUSION: Severe neurological deficits associated with spinal cord damage can occur due to migration of mobile tumors.

Unusual Painful Muscle Spasm in a Dialysis-Dependent Patient with Progressive Cervical Kyphosis.

We herein report a case of cervical myelopathy due to destructive spondyloarthropathy (DSA) with an unusual painful muscle spasm. A 51-year-old man presented to our hospital due to numbness in the hands and progressive gait disturbance. The patient underwent laminoplasty for cervical myelopathy. One and a half years after surgery, the patient developed progressive kyphosis of the cervical spine and increasing spastisity. He also started to suffer from intractable pain associated with a muscle spasm. A blood analysis revealed marked CK elevation. The patient underwent 2-stage circumferential decompression and fusion. After the revision procedure, his symptoms improved, and his serum CK level normalized. Physicians should be alert to the possibility of pain associated with an excessive muscle spasm in cervical myelopathy patients.

Risk Factors for Rapidly Progressive Neurological Deterioration in Cervical Spondylotic Myelopathy.

STUDY DESIGN: A retrospective single-center study. OBJECTIVE: This study sought to clarify the risk factors and to evaluate the surgical outcome in patients with rapidly progressive cervical spondylotic myelopathy (rp-CSM). SUMMARY OF BACKGROUND DATA: CSM is a degenerative spine disease presenting a slow development of myelopathy. Some patients, however, show rapidly progressive neurological deterioration (especially gait disturbances) without any trauma. At present, there is little information about this condition. METHODS: We studied 71 consecutive CSM patients (52 men, 19 women) with a mean age of 67.1 years, and the follow-up period was 1 year. Patients were divided into two groups: rp-CSM and chronic-CSM (c-CSM) groups. The Japanese Orthopaedic Association score and various clinical differences, including age, sex, comorbidity, the waiting period from symptomatic onset to surgery, cervical range of motion, and intramedullary MR T2-hyperintensity were analyzed, and independent risk factors were determined using a logistic regression analysis. RESULTS: Eighteen of 71 patients (25.4%) were diagnosed with rp-CSM. There were no significant differences between the two groups with regard to age, sex, or cervical range of motion. In the rp-CSM group, the preoperative upper/lower extremities and bladder functions were worse, and the waiting period for surgery was shorter (rp-CSM 1.2 mo, c-CSM 25.7 mo). Patients with rp-CSM had a history of cardiovascular event (CVE) (rp-CSM 44.4%, c-CSM 15.1%) and presented with MR T2-hyperintensity (rp-CSM 94.4%, c-CSM 58.5%), especially at the C4/5 disc level. Independent risk factors were a history of CVE (odds ratio = 4.7) and MR T2-hyperintensity (odds ratio  = 12.5). The rp-CSM group showed a better neurological recovery after decompression surgery (the Japanese Orthopaedic Association recovery rate: rp-CSM 64.5%, c-CSM 40.7%). CONCLUSION: A history of CVE and MR T2-hyperintensity were risk factors for rp-CSM. Despite rapid neurological deterioration, rp-CSM patients showed a good neurological recovery after surgery, and thus indicating that rp-CSM is a reversible condition. LEVEL OF EVIDENCE: 4.

Assessment of the Relationship between Pelvic Tilt and the Sacro-Femoral-Pubic Angle in Middle-Aged and Elderly Asian Individuals.

STUDY DESIGN: Cross-sectional study. PURPOSE: The purpose of this study was to evaluate the correlation between pelvic tilt (PT) and the sacro-femoral-pubic (SFP) angle, which is easier to identify than PT, in middle-aged and elderly Asian subjects from the general population. OVERVIEW OF LITERATURE: Measuring PT is important in the diagnosis and treatment of adult spinal deformity. However, identifying femoral heads, which are necessary to determine PT, using sagittal radiographs is often difficult. METHODS: Standing coronal and sagittal pelvic radiographs of individuals aged more than 50 years were taken during a local medical examination. The subjects were divided into female, male, and total groups at the time of evaluation. Linear regression analysis was performed to investigate the relationship between PT and the SFP angle, which were obtained from the X-rays. RESULTS: The present study included 291 subjects. There were no statistically significant differences between the left and right SFP angles, and there was gender difference regarding the SFP angle. However, a gender difference was observed regarding PT. The correlation between PT and the SFP angle was substantiated in each group. Pearson's correlation coefficients between PT and the SFP angle in the total, female, and male groups were 0.696, 0.853, and 0.619, respectively. In the linear regression analysis, PT was calculated as follows: PT=60.1-0.77×(SFP angle) in the total group, PT=62.8-0.80×(SFP angle) in the female group, and PT=51.5-0.64×(SFP angle) in the male group. CONCLUSIONS: A significant correlation between PT and the SFP angle was observed in middle-aged and elderly Asian subjects from the general population.

Prevalence of Chronic Nonspecific Low Back Pain and Its Associated Factors among Middle-Aged and Elderly People: An Analysis Based on Data from a Musculoskeletal Examination in Japan.

STUDY DESIGN: A cross-sectional study. PURPOSE: To clarify the prevalence of chronic nonspecific low back pain (CNSLBP) and its associated factors among middle-aged and elderly Japanese individuals using data from a musculoskeletal examination conducted in general Japanese populations. OVERVIEW OF LITERATURE: Most studies evaluating low back pain-associated factors have been conducted in Western countries, but they have not always evaluated CNSLBP. METHODS: We obtained data on 213 subjects aged >50 years who responded to a survey regarding age, gender, body mass index, lifestyle-related diseases (diabetes mellitus, hypertension, and hyperlipidemia), glucocorticoid use, smoking and alcohol-drinking habits, labor intensity, and chronic low back pain (CLBP) and underwent screening for lumbar spinal stenosis, evaluation for quality of life (QOL), and evaluation for specific spinal pathology via thoracolumbar spine X-rays. We investigated the prevalence of CNSLBP and association between CNSLBP and measured variables. RESULTS: The prevalence of CNSLBP and chronic specific low back pain (CSLBP) was 15.4% and 9.3%, respectively. Among the subjects with CLBP, 62.2% had CNSLBP. In age-adjusted logistic models, smoking habits (p=0.049, odds ratio [OR]=2.594), low back pain (p<0.001, OR=0.974), lumbar function (p=0.001, OR=0.967), and social function (p=0.023, OR=0.976) in the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were significantly associated with CNSLBP, whereas EQ-5D utility score (p=0.024, OR=0.068), low back pain (p=0.007, OR=0.981), lumbar function (p=0.001, OR=0.963), walking ability (p=0.001, OR=0.968), and social function (p=0.002, OR=0.966) in JOABPEQ were significantly associated with CSLBP. CONCLUSIONS: CNSLBP among middle-aged and elderly individuals was associated with smoking habits and decreased QOL; however, CSLBP was considered to be more multilaterally associated decreased QOL.