Hiroto Makino

Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): Inflammation in OPLL

Backgroud Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of ligamentous tissue by ectopic new bone formation. OPLL causes narrowing of the spinal canal, resulting in neurological impairment. However, the pathogenesis of OPLL has not been fully elucidated. We investigated whether inflammation occurs in OPLL or not using high-sensitivity CRP (hs-CRP) in a case-control study. Methods and findings This study included 103 patients with OPLL in the patient group and 95 age- and sex-matched volunteers with degenerative spinal disease in the control group. Of the 103 OPLL patients, 88 patients who were available for more than 2 years follow-up were checked for OPLL progression. A blood sample was obtained and Hs-CRP, and other routine data, including total protein (TP), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glucose (Glu), calcium (Ca), inorganic phosphate (Pi), white blood cell count (WBC), hemoglobin (Hb) and platelet (PLT), were analyzed. The data were compared between the patients with OPLL and the controls. The severity of the ossified lesions in the whole spine were evaluated by the ossification index (OS index) in patients with OPLL. The data were also compared between the patients with OPLL progression (the progression group) and the patients without OPLL progression (the non-progression group). In the results, the mean hs-CRP in the OPLL group was higher than that in the controls. The Pi in the OPLL group was lower than that in the control group. A negative correlation was found between the Pi and the OS index. The mean hs-CRP in the progression group was higher than that in the non-progression group. There was a positive correlation between the average length of the OPLL progression per year and the hs-CRP. Conclusions The results may suggest the occurrence of local inflammation in OPLL and the inflammation might cause OPLL progression. These facts are important for understanding the pathology of OPLL.

Circumferential Spinal Cord Decompression through a Single Posterior Approach with Microendoscopy for Thoracic and Thoracolumbar Ossification of the Posterior Longitudinal Ligament

Thoracic and thoracolumbar ossification of the posterior longitudinal ligament (OPLL) can be difficult to treat due to the anatomical position. The purpose of this study was to report the significance of a novel surgical technique that represented two cases of thoracic or thoracolumbar OPLL. The first patient was a 72-year-old woman who had a beak-type OPLL at the T11/12. The second was a 45-year-old woman who had a beak-type OPLL at the T12/L1. We performed circumferential spinal cord decompression through a single posterior approach with microendoscopy in both cases. The postoperative computed tomography revealed the complete removal of the OPLL, and the magnetic resonance imaging confirmed adequate decompression of the spinal cord. Preoperative symptoms were substantially improved in both patients. To date, we have used this novel technique to treat five patients with thoracic or thoracolumbar OPLL. This new surgical technique is likely to be useful in patients with a beak-type OPLL of the thoracic or thoracolumbar spine.

Lumbar spine surgery in patients with rheumatoid arthritis (RA): what affects the outcomes?

BACKGROUND CONTEXT Although the cervical spine is only occasionally involved in rheumatoid arthritis (RA), involvement of the lumbar spine is even less common. A few reports on lumbar spinal stenosis in patients with RA have appeared. Although disc space narrowing occurs in aging, postoperative adjacent segment disease (ASD) in patients with RA has not been subject to much analysis. PURPOSE The objective of this study was to investigate differences in ASD and clinical outcomes between lumbar spinal decompression with and without fusion in patients with RA. STUDY DESIGN/SETTING This is a retrospective comparative study. PATIENT SAMPLE A total of 52 patients with RA who underwent surgery for lumbar spinal disorders were included. Twenty-seven patients underwent decompression surgery with fusion and 25 underwent decompression surgery alone. OUTCOME MEASURES Intervertebral disc space narrowing and spondylolisthesis of the segment immediately cranial to the surgical site were measured using a three-dimensional volume rendering software. Pre- and postoperative evaluation of RA activity and Japanese Orthopaedic Association (JOA) scores were conducted. MATERIALS AND METHODS All patients had preoperative and annual postoperative lumbar radiographs and were followed up for a mean of 5.1 years (range 3.5-10.9 years). Pre- and postoperative (2 years after surgery) JOA scores were recorded and any postoperative complications were investigated. Degrees of intervertebral disc narrowing and spondylolisthesis at the adjacent levels were evaluated on radiographs and were compared between the two groups. Analysis was performed to look for any correlation between ASD and RA disease activities. RESULTS Postoperative JOA scores were significantly improved in both groups. The rate of revision surgery was significantly higher in the fusion group than that in the non-fusion group. The rate of ASD was significantly greater in the fusion group than that in the non-fusion group at the final follow-up examination. Both matrix metalloproteinase 3 (MMP-3) and the 28-joint disease activity score incorporating C-reactive protein levels (DAS28-CRP) were significantly associated with the incidence and severity of ASD. CONCLUSIONS Adjacent segment disease and the need for revision surgery were significantly higher in the fusion group than those in the non-fusion group. A preoperative high MMP-3 and DAS28-CRP are likely to be associated with postoperative ASD.

A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain

Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

Rod rotation and differential rod contouring followed by direct vertebral rotation for treatment of adolescent idiopathic scoliosis: effect on thoracic and thoracolumbar or lumbar curves assessed with intraoperative computed tomography

BACKGROUND CONTEXT Although direct vertebral rotation (DVR) is now used worldwide for the surgical treatment of adolescent idiopathic scoliosis (AIS), the benefit of DVR in reducing vertebral body rotation in these patients has not been determined. PURPOSE We investigated a possible additive effect of DVR on further reduction of vertebral body rotation in the axial plane following intraoperative rod rotation or differential rod contouring in patients undergoing surgical treatment for AIS. STUDY DESIGN/SETTING The study was a prospective computed tomography (CT) image analysis. PATIENT SAMPLE We analyzed the results of the two intraoperative procedures in 30 consecutive patients undergoing surgery for AIS (Lenke type I or II: 15; Lenke type V: 15). OUTCOME MEASURES The angle of reduction of vertebral body rotation taken by intraoperative CT scan was measured and analyzed. Pre- and postoperative responses to the Scoliosis Research Society 22 Questionnaire (SRS-22) were also analyzed. METHODS To analyze the reduction of vertebral body rotation with rod rotation or DVR, intraoperative cone-beam CT scans of the three apical vertebrae of the major curve of the scoliosis (90 vertebrae) were taken pre-rod rotation (baseline), post-rod rotation with differential rod contouring, and post-DVR in all patients. The angle of vertebral body rotation in these apical vertebrae was measured and analyzed for statistical significance. Additionally, differences between thoracic curve scoliosis (Lenke type I or II; 45 vertebrae) and thoracolumbar or lumbar curve scoliosis (Lenke type V; 45 vertebrae) were analyzed. Pre- and postoperative SRS-22 scores were evaluated in all patients. RESULTS The mean (90 vertebrae) vertebral body rotation angles at baseline, post-rod rotation or differential rod contouring, and post-rod rotation or differential rod contouring or post-DVR were 17.3°, 11.1°, and 6.9°, respectively. The mean reduction in vertebral body rotation with the rod rotation technique was 6.8° for thoracic curves and 5.7° for thoracolumbar or lumbar curves (p<.00005). The mean additional reduction in rotation with the DVR technique was 3.4° for thoracic curves and 4.9° for thoracolumbar or lumbar curves (p<.00005). Direct vertebral rotation displayed a slightly but significantly greater additive effect in reducing rotation following initial reduction with rod rotation or differential rod contouring in thoracolumbar or lumbar than in thoracic curves. In the SRS-22 results, postoperative self-image was significantly better than preoperative image in both groups. CONCLUSIONS Direct vertebral rotation contributed an additional reduction in vertebral body rotation in thoracic and thoracolumbar or lumbar curves. The DVR technique is likely to be more useful in thoracolumbar or lumbar curve scoliosis than in thoracic curve scoliosis.

More Than 20 Years Follow-Up After En Bloc Cervical Laminoplasty.

Study Design. Retrospective study. Objective. The aim of the study was to evaluate clinical outcomes and to clarify the potential risks of cervical laminoplasty by a long-term follow-up of more than 20 years. Summary of Background Data. There is no follow-up report exceeding 20 years after cervical laminoplasty. Methods. Two hundred sixteen patients underwent en bloc cervical laminoplasty for the treatment of cervical compressive myelopathy due to cervical spondylosis or ossification of the posterior longitudinal ligament between 1981 and 1994. Of these, 148 patients with a follow-up of more than 20 years were retrospectively studied (68 survived patients and 80 dead patients). The neurological evaluation was graded using Japanese Orthopaedic Association (JOA) score and the recovery rate. Neurological recovery was defined by the increase in JOA score. Radiological examinations were carried out using pre- and postoperative radiographs. As for the dead patients, the cause and age of death were reviewed. Results. The JOA score and recovery rate increased to 14.2 ± 2.7% and 64.9 ± 28.6%, respectively, at 5 years. The JOA score and recovery rate were maintained at 13.9 ± 3.2% and 61.6 ± 34.6% at 10 years. The JOA score decreased to 11.4 ± 5.1 at the last follow-up. In 32 out of 65 patients (49.2%), the JOA scores worsened mainly due to other spinal lesions. Cervical alignment became kyphotic when comparing preoperatively and at the last follow-up (ossification of the posterior longitudinal ligament: 15.7 ± 12.2° and 6.9 ± 17.8°, cervical spondylosis: 11.0 ± 8.9° and 3.3 ± 9.4°). Range of motion (ROM) decreased and one of the causes of ROM reduction was interlaminar fusion. The mean age at death was 78.2 years. The most frequent cause of death was malignant tumor. Conclusion. Spine surgeons must be aware that patients have a long postoperative lifetime when cervical laminoplasty is performed. A long postoperative follow-up should be carried out after laminoplasty. Level of Evidence: 4

Life Expectancy after Cervical en bloc Laminoplasty: Analysis of Data following more than 20 Years.

Study Design. Case series. Objective. To clarify the following questions How long after cervical laminoplasty did the patients die? What were the causes of the death? Was the severity of the neurological dysfunction related to early death? Summary of Background Data. Life expectancy in patients with cervical myelopathy is unclear. Cervical laminoplasty was performed in 216 patients between 1981 and 1994. It was possible to follow 148 patients for more than 20 years. We used the data of the 68 survivors and the 80 patients had already died. Methods. As for the patients who died by the final follow-up, the survival rate was analyzed by a Kaplan-Meier plot; the results were compared between the patients with cervical spondylosis (CS) and the patients with ossification of the posterior longitudinal ligament (OPLL). The causes of the death were assessed. The neurological evaluation was graded using the score devised by the Japanese Orthopaedic Association (JOA). The pre- and postoperative scores were compared between the patients in the died group (D group) and the surviving patients group (S group). Results. The mean period from surgery to death was 13.4 ± 7.4 years. There was no difference in the survival rate between patients with CS and patients with OPLL. The most frequent cause of death was malignant tumor followed by ischemic heart disease. Preoperative JOA score in the D group was lower than that in the S group. There was no statistical difference in postoperative JOA score between the two groups. Conclusion. The patients who underwent cervical laminoplasty caused by compression myelopathy due to CS and OPLL had a long life expectancy, averaging more than 13 years. Life expectancy did not differ between patients with CS and patients with OPLL. Neurological deficit did not directly affect the life expectancy. Level of Evidence: 4

Increase of the Serum FGF-23 in Ossification of the Posterior Longitudinal Ligament

Study Design: Case-control study. Objectives: To determine the possible pathogenesis of ossification of the posterior longitudinal ligament (OPLL) in regard to the serum concentration of fibroblast growth factor 23 (FGF-23). Methods: The study included 95 patients with OPLL and a control group of 73 age- and sex-matched volunteers. The serum concentrations of FGF-23, creatinine (Cre), alkaline phosphatase, calcium (Ca), inorganic phosphate (Pi), and hypersensitive C-reactive protein (hs-CRP) were analyzed from blood samples, and Cre, Ca, Pi, and tubular reabsorption of phosphate were measured using urine samples. We evaluated the severity of ossified spinal lesions in patients with OPLL according to the ossification index (the OP index and the OS index). Data was compared between the OPLL and control group and between the OPLL progression and no progression group. Results: Serum FGF-23 and hs-CRP were higher, and serum Pi was lower in patients with OPLL than in the controls. There was a positive correlation between FGF-23 and hs-CRP and a negative correlation between serum Pi and the OS index; however, the correlations were very weak. Overall, 31.7% of patients had progression of OPLL during follow-up. FGF-23 and hs-CRP were higher in the progression group than in the no progression group. Conclusions: These results might indicate that FGF-23 and hs-CRP are positive markers for OPLL. Phosphate metabolism via FGF-23 might be a target for future study on the pathogenesis of OPLL.