Different standing postures are the influencing factors for the efficacy of laminoplasty in the treatment of K-Line (-) patients with ossification of the posterior longitudinal ligament.

OBJECTIVE: To investigate the relationship between different standing postures and surgical outcomes of K-Line (-) ossification of the posterior longitudinal ligament (OPLL) patients after laminoplasty with a titanium basket. There is a lack of data evaluating the relationship between the postoperative satisfaction of K-Line (-) patients and their standing postures. METHODS: OPLL patients enrolled in the study were divided into a K-Line (+) group (Group A) and a K-Line (- group (Group B) in natural and relaxed standing positions. We compared the postoperative outcomes after cervical laminoplasty with titanium basket surgery using the Japanese Orthopaedic Association score (JOA), recovery rate and the degree of improvement in the six JOA score items. The degree of satisfaction with the outcome was assessed at the 1-year follow-up using a 7-point numerical rating scale. RESULTS: A total of 34 K-Line (+) patients with OPLL (age 61.9 ± 2.9 years) in Group A and 40 K-Line (-)patients with OPLL (age 60.4 ± 3.5 years) in Group B in natural and relaxed standing positions were recruited. In Group A, the mean preoperative and postoperative JOA scores were 10.1 ± 1.4 and 13.1 ± 0.8 points, respectively, and in Group B, the mean preoperative and postoperative JOA scores were 9.7 ± 1.3 and 11.1 ± 0.9 points, respectively. A significant improvement in the JOA score was seen in both groups postoperatively, but the recovery rate of the patients' JOA scores was significantly lower in Group B. In Group A, significant improvements were seen in all JOA score items, but in Group B, improvements were seen only in upper- and lower-extremity sensory functions. CONCLUSION: Different standing postures are risk factors in the treatment of K-Line (-) patients, and therefore, natural and relaxed standing positions should be given more attention before devising the surgical plan.

Posterolateral Floating Technique for the Thoracic Ossification of the Posterior Longitudinal Ligament with Navigation: A Technical Note.

We describe a floating technique via a posterolateral approach with intraoperative O-arm navigation to facilitate decompression of the spinal cord in thoracic myelopathy due to severe ossification of the posterior longitudinal ligament (OPLL). A 62-year-old man with myelopathy due to thoracic OPLL had left-leg muscle weakness, urinary disturbance, and spastic gait. Bilateral leg pain and gait disturbance had persisted for 2 years. He was successfully treated by the posterolateral OPLL floating procedure and posterior pedicle fixation under O-arm navigation. At a 2-year follow-up, manual muscle testing results and sensory function of the left leg had recovered fully. His cervical Japanese Orthopedic Association score had improved from 5/12 to 11/12. The novel intraoperative O-arm navigation-guided posterolateral floating procedure for thoracic OPLL is effective for achieving precise decompression and strong fixation with a posterior approach only and can provide an excellent result for severe thoracic OPLL without the risk of adverse events from intraoperative radiation.

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells.

Ossification of the posterior longitudinal ligament (OPLL) is a spinal disorder characterized by progressive ectopic bone formation in the PLL of the spine. Dickkopf-1 (Dkk1) is a secreted inhibitor of the Wnt pathway that negatively regulates bone formation during skeletal development. However, whether Dkk1 impacts the pathogenesis of OPLL has not been reported. This study is to investigate the role of Dkk1 in the development of OPLL. Our results show that the serum levels of Dkk1 are decreased in OPLL patients compared with non-OPLL controls. The expression of Dkk1 is also reduced in OPLL ligament cells. Downregulation of Dkk1 in ligament cells is associated with activation of the Wnt/ß-catenin signaling, as indicated by stabilized ß-catenin and increased T-cell factor-dependent transcriptional activity. Functionally, Dkk1 exerts a growth-inhibitory effect by repressing proliferation but promoting apoptosis of ligament cells. Dkk1 also suppresses bone morphogenetic protein 2-induced entire osteogenic differentiation of ligament cells, and this suppression is mediated via its inhibition of the Wnt pathway. Our results demonstrate for the first time that Dkk1 acts as an important negative regulator in the ossification of the PLL. Targeting the Wnt pathway using Dkk1 may represent a potential therapeutic strategy for the treatment of OPLL.

Concomitant Fahr's syndrome and thoracic ossification of the posterior longitudinal ligament caused by idiopathic hypoparathyroidism - case report.

BACKGROUND: Fahr's syndrome presenting multiple and symmetric calcification of basal ganglia and cerebral cortex is rare, and idiopathic hypoparatyroidism is known as one of the causes. The relationship between ossification of posterior longitudinal ligament (OPLL) and idiopathic hypoparatyroidism is also reported in a few cases. Here, we report a patient presenting concomitant Fahr's syndrome and thoracic OPLL developed by idiopathic hypoparatyroidism. CASE PRESENTATION: 53-year-old female patient presented myelopathic sign including gait disturbance and both leg weakness (Grade 3) for 4 months after slip down, and has the history of anti-epileptic medication for several years. Magnetic resonance imaging revealed cord compression by the mixed-type OPLL from T5 to T9, and decompressive surgery was planned. Sudden onset generalized tonic-clonic seizure attack developed before the surgery. Hypocalcemia (3.7 mg/dL) with QT prolongation on electrocardiogram, hypomagnesemia (1.4 mg/dL), hyperphosphatemia (7.7 mg/dL), hypoparathyroidism, and normal range of vitamin D was noted. Brain study showed Fahr's syndrome with multiple and symmetric calcification of basal ganglia, cerebral cortex, and cerebellum. Decompressive laminectomy was performed after transient correction of hypocalcemia. The myelopathic symptoms improved to normal walking by the 14-month follow-up. The cause of hypoparathyroidism was concluded to be idiopathic. CONCLUSION: Concomitant expression of Fahr's syndrome and OPLL related with idiopathic hypoparatyroidism is very rare. However, we recommend considering the possibility of hypoparathyroidism and Fahr's syndrome when we evaluate the patients with OPLL to avoid the risks of sudden onset seizure and cardiac arrhythmia due to cerebral lesions and hypocalcemia.

Risk Factors of Cage Subsidence in Patients with Ossification of Posterior Longitudinal Ligament (OPLL) After Anterior Cervical Discectomy and Fusion.

BACKGROUND There are numerous reports on cage subsidence after ACDF; however, few studies have identified its risk factors. The current study aimed to identify risk factors for cage subsidence after ACDF using the PEEK cage packed with local autobone implant with plate and provides evidence for surgical decision-making. MATERIAL AND METHODS We retrospectively reviewed 77 patients with OPLL who underwent 1/2-level ACDF using the PEEK cage packed with local autobone implant with plate from March 2013 to December 2015. Implant subsidence was defined as the decrease in interbody height at the final follow-up compared to that measured on the first postoperative day ≥2 mm. Intervertebral fusion was evaluated on the basis of no motion across the fusion site and the presence of trabeculae between bone and implant in the X-rays. Multivariate logistic regression analysis was used to identify the risk factors for cage subsidence. RESULTS In comparing the end-plate removal group with the end-plate preservation group, we found that the fusion rate (removal group, 35.90%; preservation group, 10.50%) and the change of IH (P=0.011) were significantly different during the first 6 weeks after surgery. Advanced age (OR=1.34, 95% CI=1.04-1.24, P=0.004), end-plate removal (OR=11.84, 95% CI=2.91-48.28, P=0.001), and nonunion within 6 weeks after surgery (OR=22.67, 95% CI=2.36-217.67, P=0.007) played an important role in predicting cage subsidence. CONCLUSIONS These findings suggest that advanced age, end-plate removal, and nonunion within 6 weeks after surgery are risk factors for the cage subsidence after ACDF using the PEEK cage packed with local autobone implant with plate in patients with OPLL.

Combined use of leptin and mechanical stress has osteogenic effects on ossification of the posterior longitudinal ligament.

PURPOSE: To evaluate the effects of leptin/leptin receptor (LepR) combined with mechanical stress on the development of ossification of the posterior longitudinal ligament (OPLL), which is a disease characterized by ectopic bone formation of the posterior longitudinal ligament (PLL) and can lead to radiculopathy and myelopathy. METHODS: Six human samples of the PLL were analyzed for the expression of leptin and LepR by RT-PCR and western blotting. PLL cells were stimulated with leptin and mechanical stress delivered via a Flexcell tension system, and osteogenic differentiation was evaluated by RT-PCR and western blotting analysis of osteogenic marker expression as well as by alkaline phosphatase (ALP) staining and alizarin red S staining. Activation of mitogen-activated protein kinase (MAPK), Janus kinase (JAK) 2-signal transducer, activator of transcription (STAT) 3 and phosphatidylinositol 3-kinase (PI3K)-Akt was evaluated by western blotting. RESULTS: Samples from the OPLL group had higher LepR mRNA and protein levels and lower leptin levels than those from healthy controls. Exposure to leptin and Flexcell increased the number of ALP-positive cells and calcium nodules in a dose-dependent manner; this effect was accompanied by upregulation of the osteogenic markers osteocalcin, runt-related transcription factor 2 (RUNX2) and osteopontin. Extracellular signal-regulated kinase, P38 MAPK, JAK2, STAT3, PI3K and Akt signaling, was also activated by the combined effects of leptin and mechanical stress. CONCLUSIONS: Leptin and LepR are differentially expressed in OPLL tissues, and the combined use of leptin/LepR and mechanical stress promotes osteogenic differentiation of PLL cells via MAPK, JAK2-STAT3 and PI3K/Akt signaling. These slides can be retrieved under Electronic Supplementary Material.

Multiplex analysis of serum hormone and cytokine in patients with cervical cOPLL: towards understanding the potential pathogenic mechanisms.

Cervical ossification of the posterior longitudinal ligament (cOPLL) is one of the major causes of myelopathy. However, the mechanism underlying remains elusive. In the present study, using MILLIPLEX magnetic bead panel, we investigated four serum hormones and six serum cytokines in cOPLL patients and healthy subjects. The results showed that tumor necrosis factore-α (TNF-α) were significantly increased, and DDK-1 was significantly decreased in the serum from male and female cOPLL patients compared with those from healthy controls, respectively. Osteopontin (OPN) and fibroblast growth factor-23 (FGF-23) were significantly increased in male cOPLL patients compared with that in healthy male controls. Further analysis showed that FGF-23 and OPN significantly increased, dickkopf-1 (DKK-1) decreased in the extensive cOPLL group. In addition, a significant positive correlation between the OPN and FGF-23 was observed in male cOPLL patients. The results are useful for understanding the mechanism underlying cOPLL.

[Ossification of posterior longitudinal ligament].

Ossification of posterior longitudinal ligament (OPLL) is a hyperostotic disease of the spine associated with myelopathy which is occurred by an anterior compression to the spinal cord. OPLL was first reported by Key GA in 1838, and was previously considered specific to east Asian people, especially Japanese. However, now OPLL is recognized as a subtype of diffuse idiopathic skeletal hyperosteosis, which is detected in Europe and the United States. We discuss the etiology and natural history of OPLL in this review.

Association of VKORC1-1639G>A polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine: a Korean study.

BACKGROUND: Abnormalities of bone metabolism may be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) of the spine. Besides its hemostatic effect, vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a pivotal role in bone mineralization. The aim of this study is to investigate whether single nucleotide polymorphisms (SNPs) of the VKORC1 gene are associated with the occurrence of OPLL in a Korean population. METHOD: A total of 98 patients with OPLL and 200 controls were genotyped for the VKORC1-1639G>A SNP (rs9923231) by polymerase chain reaction and restriction fragment length polymorphism analysis. All the patients (n = 98) in this study underwent surgery (60, posterior-only approach; 36, anterior-only approach; 2, combined anterior and posterior approach) during their admission. We analyzed this association separately according to the gender and OPLL subgroup: OPLL continuous group (continuous type plus mixed type) and OPLL segmental group (segmental and localized type). RESULTS: We found that the genotype VKORC1-1639G>A frequency was significantly associated with the occurrence of the OPLL in the female group (adjusted odds ratio = 5.22, 95 % confidence interval: 1.675 to 16.269, p = 0.004). However, there was no overall association between the OPLL susceptibility and VKORC1-1639G>A polymorphism. A subgroup analysis did not show any significant correlation between VKORC1-1639G>A polymorphism and subgroup of OPLL either. CONCLUSION: Our results suggest that the VKORC1-1639G>A SNP may increase susceptibility to OPLL in women. However, there was only a statistical association in the female group despite a number of stratified analyses. Therefore, the findings should be interpreted with caution, and further genetic study is needed to improve our understanding of the role of VKORC1 polymorphisms in determining the risk of OPLL occurrence.

A case of psoriasis vulgaris with diffuse idiopathic skeletal hyperostosis involved with ossifications of posterior and anterior longitudinal ligament.

Diffuse idiopathic skeletal hyperostosis (DISH) is difficult to distinguish from various forms of inflammatory arthritis, including psoriatic arthritis (PsA), rheumatoid arthritis, and ankylosing spondylitis. A 67-year-old Japanese male had been treated for psoriasis vulgaris for 13 years. Numbness of his right arm and lower limbs and spinal stiffening had developed 7 years prior to his initial evaluation at our facility. He noticed pain mainly while exercising. There were symmetrical marginal syndesmophytes in the spine, from the thoracic vertebrae to the upper lumbar vertebrae, on radiological examinations. We therefore suspected DISH. Furthermore, ossifications of the posterior and anterior longitudinal ligaments were noted in the cervical spine. Laboratory examinations revealed a normal peripheral white blood cell count, serum C-reactive protein, and erythrocyte sedimentation rate, and he was negative for rheumatoid factor. We detected human leukocyte antigen B39 but not B27. All distal interphalangeal joints were swollen but without pain. X-ray imaging showed narrowing of the joint space, and the consolidation of the joint was recognized, but there was no new juxta-articular bone formation. Based on clinical and radiological findings, we concluded that he had DISH and not PsA. DISH was indicated by marked radiological features of the axial skeleton, particularly the thoracic spine, but may also have involved the peripheral joints. DISH is one of the entheseal disorders, and 10% of Japanese middle-aged and elderly men have DISH. Therefore, the differentiation of DISH from PsA is necessary in psoriasis patients with spinal involvement.

Thoracic myelopathy caused by ossification of the yellow ligament in patients with posterior instrumented lumbar fusion.

PURPOSE: The objective of this study was to investigate thoracic myelopathy caused by ossification of the yellow ligament (OYL) in patients with posterior instrumented lumbar fusion. METHODS: Seven patients, who had undergone posterior instrumented lumbar fusion, presented with thoracic myelopathy caused by OYL. No patient had a history of thoracic myelopathy at previous surgery. Instrumented fusions were performed from L1-5 in two patients, L2-5 in three patients and L1-S1 and L2-S1 in one patient each, respectively. MRI and CT scans were performed to confirm cord compression by OYL. Of the seven patients, six patients underwent decompressive laminectomy and OYL removal while one was treated conservatively. RESULTS: The average time to presentation after first surgery was 63.4 months. OYL was located at T9-10 in two patients, T11-12 in three patients, and T10-11 and T9-11 in one patient each, respectively. All patients had a myelopathic gait and the average Japanese Orthopaedic Association (JOA) score was 3.9, preoperatively. The average JOA score improved from 3.7 to 8 and the average recovery rate was 58.9 % in the six patients who underwent surgical intervention. However, the JOA score fell from 5 to 4 in the one patient who was treated conservatively. CONCLUSIONS: We report seven patients who suffered from thoracic myelopathy after instrumented lumbar fusion. Surgeons must be aware of the possibility of thoracic myelopathy caused by OYL at the thoracolumbar junction, especially in patients with a complaint of gait disturbance after long instrumented lumbar fusion.

Comparative Effectiveness and Functional Outcome of C2 Dome-like Expansive Versus C2 Expansive Open-door Laminoplasty for Upper Cervical Ossification of the Posterior Longitudinal Ligament: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: This study compared the function and radiographical outcomes of the patients who underwent C2 dome-like expansive laminoplasty to those C2 expansive open-door laminoplasty for the treatment of OPLL with C2 involved. SUMMARY OF BACKGROUND DATA: There are few comparative studies of these two surgical methods. C2 dome-like and C2 expansive open-door laminoplasty are posterior approaches for posterior longitudinal ligament ossification with C2 level and above. METHODS: This study performed a retrospective cohort analysis of 59 patients with OPLL up to C2 which cause compression symptoms. 31 patients underwent C2 dome-like expansive laminoplasty with C3-7 expansive open-door laminoplasty (Group Dom) and 28 underwent C2-7 expansive open-door laminoplasty (Group Exp). The preoperative and postoperative space available for cord (SAC) of C2 segment, cervical curvature index of C2-7, C2-7 range of motion, Japanese orthopedic association (JOA) score, visual analog scale (VAS) score, and neck disability index (NDI) were used to assess clinical out-comes and statistically analyzed. RESULTS: The cervical curvature index, JOA score, and NDI significantly changed at the final follow-up in two groups with no significant intergroup differences. There were no significant differences in preoperative SAC and VAS between the two groups. At the final follow-up, the SAC of C2/3 in Group Exp was significantly larger than Group Dom, while the VAS and range of motion of Group Dom became significantly better than Group Exp. CONCLUSION: The C2 dome-like expansive laminoplasty can reduce postoperative neck pain more obviously and achieve better cervical curvature. C2 expansive open-door laminoplasty can get more adequate decompression in the spinal canal, which may be recommend to the patients with OPLL occupying more than 50% of the vertebral canal at C2/3, or with developmental spinal stenosis. LEVEL OF EVIDENCE: 3.

Transcranial Motor-evoked Potential Alert After Supine-to-Prone Position Change During Thoracic Ossification in Posterior Longitudinal Ligament Surgery: A Prospective Multicenter Study of the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research.

STUDY DESIGN: A prospective, multicenter study. OBJECTIVE: To evaluate the usefulness of transcranial motor-evoked potentials (Tc-MEPs) during supine-to-prone position change for thoracic ossification of the posterior longitudinal ligament (T-OPLL). SUMMARY OF BACKGROUND DATA: Supine-to-prone position change might be a risk of spinal cord injury in posterior decompression and fusion surgeries for T-OPLL. METHODS: The subjects were 145 patients with T-OPLL surgically treated with posterior decompression and fusion using Tc-MEPs in 14 institutes. Tc-MEPs were monitored before surgery from supine-to-prone position and intraoperatively in seven institutes and only intraoperatively in the other seven institutes because of disapproval of the anesthesia department. In cases of Tc-MEP alert after position change, we adjusted the cervicothoracic posture. When the MEP did not recover, we reverted the position to supine and monitored the Tc-MEPs in supine position. RESULTS: There were 83 and 62 patients with/without Tc-MEP before position change to prone (group A and B). The true-positive rate was lower in group A than group B, but without statistical significance (8.4% vs. 16.1%, P = 0.12). In group A, five patients who had Tc-MEP alert during supine-to-prone position change were all female and had larger body mass index values and upper thoracic lesions. Among the patients, three underwent surgeries after cervicothoracic alignment adjustment, and two had postponed operations to 1 week later with halo-vest fixation because of repeated Tc-MEP alerts during position change to prone. The Tc-MEP alert at exposure was statistically more frequent in group B than in group A ( P = 0.033). CONCLUSION: Tc-MEP alert during position change is an important sign of spinal cord injury due to alignment change at the upper thoracic spine. Tc-MEP monitoring before supine-to-prone position change was necessary to prevent spinal cord injury in surgeries for T-OPLL.

Ossification of the posterior longitudinal ligament: pathogenesis, management, and current surgical approaches. A review.

Ossification of the posterior longitudinal ligament (OPLL) is an important cause of cervical myelopathy that results from bony ossification of the cervical or thoracic posterior longitudinal ligament (PLL). It has been estimated that nearly 25% of patients with cervical myelopathy will have features of OPLL. Patients commonly present in their mid-40s or 50s with clinical evidence of myelopathy. On MR and CT imaging, this can be seen as areas of ossification that commonly coalesce behind the cervical vertebral bodies, leading to direct ventral compression of the cord. While MR imaging will commonly demonstrate associated changes in the soft tissue, CT scanning will better define areas of ossification. This can also provide the clinician with evidence of possible dural ossification. The surgical management of OPLL remains a challenge to spine surgeons. Surgical alternatives include anterior, posterior, or circumferential decompression and/or stabilization. Anterior cervical stabilization options include cervical corpectomy or multilevel anterior cervical corpectomy and fusion, while posterior stabilization approaches include instrumented or noninstrumented fusion or laminoplasty. Each of these approaches has distinct advantages and disadvantages. While anterior approaches may provide more direct decompression and best improve myelopathy scores, there is soft-tissue morbidity associated with the anterior approach. Posterior approaches, including laminectomy and fusion and laminoplasty, may be well tolerated in older patients. However, there often is associated axial neck pain and less improvement in myelopathy scores. In this review, the authors discuss the epidemiology, imaging findings, and clinical presentation of OPLL. The authors additionally discuss the merits of the different surgical techniques in the management of this challenging disease.

Surgical management of cervical ossification of the posterior longitudinal ligament: natural history and the role of surgical decompression and stabilization.

OBJECT: Ossification of the posterior longitudinal ligament (OPLL) is a complex multifactorial disease process combining both metabolic and biomechanical factors. The role for surgical intervention and choice of anterior or posterior approach is controversial. The object of this study was to review the literature and present a single-institution experience with surgical intervention for OPLL. METHODS: The authors performed a retrospective review of their institutional experience with surgical intervention for cervical OPLL. They also reviewed the English-language literature regarding the epidemiology, pathophysiology, natural history, and surgical intervention for OPLL. RESULTS: Review of the literature suggests an improved benefit for anterior decompression and stabilization or posterior decompression and stabilization compared with posterior decompression via laminectomy or laminoplasty. Both anterior and posterior approaches are safe and effective means of decompression of cervical stenosis in the setting of OPLL. CONCLUSIONS: Anterior cervical decompression and reconstruction is a safe and appropriate treatment for cervical spondylitic myelopathy in the setting of OPLL. For patients with maintained cervical lordosis, posterior cervical decompression and stabilization is advocated. The use of laminectomy or laminoplasty is indicated in patients with preserved cervical lordosis and less than 60% of the spinal canal occupied by calcified ligament in a "hill-shaped" contour.

Relationship between Scheuermann disease and symptomatic thoracic spinal stenosis: A retrospective study.

OBJECTIVE: This study aimed to investigate the possible relationship between Scheuermann disease (SD) and the pathophysiological factors of thoracic spinal stenosis (TSS), including ossification of the ligamentum flavum (OLF), ossification of the posterior longitudinal ligament (OPLL), and thoracic disc herniation (TDH) in patients with symptomatic TSS. METHODS: Demographic and radiological data from 66 consecutive patients diagnosed with symptomatic TSS from 2013 to 2018 were retrospectively collected and divided into 3 groups depending on the underlying pathomechanism of TSS: TDH group (18 patients; 6 women; mean age ± standard deviation [Sd] = 59.89 ± 11.34), OPLL group (12 patients; 8 women; mean age ± Sd = 56.08 ± 14.74), and OLF group (36 patients; 20 women; mean age ± Sd = 58.69 ± 9.77). A total of 41 age-matched healthy individuals (19 women; mean age ± Sd = 54.88 ± 13.63) were designated as the control group. In each group, both typical and atypical SD criteria were radiologically examined. The demographic data and presence of SD between the control group and 3 subgroups of TSS pathomechanisms were evaluated. RESULTS: SD characteristics were identified in 83.33% (15/18) of patients in the TDH group, 44.44% (16/36) in the OLF group, 25% (3/12) in the OPLL group, and 17.07% (7/41) of the control individuals. When analyzed by the chi-squared test and logistic regression analysis, the presence of SD was significantly associated with TDH (P < 0.01) and OLF (P < 0.05) but not OPLL (P > 0.05). Patients with TDH and OLF showed peak involvement of T10/11, and patients with OPLL did not. Furthermore, we determined that age, sex, body-mass index, and smoking status were not the risk factors for TDH, OPLL, and OLF (P > 0.05). SD was found to be a risk factor for TDH (P < 0.01) and OLF (P < 0.05) but not for OPLL (P > 0.05). CONCLUSION: Evidence from this study indicated that SD might be a risk factor for OLF and TDH but not for OPLL.

The "moustache" sign: localized intervertebral disc fibrosis and panligamentous ossification in ankylosing spondylitis with kyphosis.

Localized intervertebral disc and ligamentous ossification may precipitate neurological deficits at any time during the natural course of ankylosing spondylitis (AS). We report 2 patients with AS with "moustache' sign (localized intervertebral disc fibrosis and panligamentous ossification) and neurological deficits. One patient had syndesmophytosis (with paraparesis secondary to thoracic spinal canal stenosis), and the other had "bamboo spine" above and below the involved level. A laminectomy in the former relieved paraparesis, and posterior element excision in both the patients relieved focal tenderness and pain; and both of them could lie supine following surgery.

Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament.

BACKGROUND: The molecular mechanisms of ossification of the posterior longitudinal ligament (OPLL) remain to be elucidated. The aim of the present study was to investigate the autophagy of spinal ligament fibroblasts derived from patients with OPLL and to examine whether autophagy-associated gene expression was correlated with the expression of osteogenic differentiation genes. METHODS: Expression of autophagy-associated genes was detected in 37 samples from 21 OPLL patients and 16 non-OPLL patients. The correlation of autophagy-associated gene expression and the expression of osteogenic differentiation genes was analyzed by Pearson's correlation. The expression of autophagy-associated genes of ligament fibroblasts was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunofluorescence. The incidence of autophagy was assessed by flow cytometry. After knockdown using small interfering RNA targeting Beclin1, the expression of osteogenic differentiation genes were compared in spinal ligament fibroblasts. RESULTS: In clinical specimens, mRNA expression levels of microtubule-associated protein 1 light chain 3 and Beclin1 were higher in the OPLL group compared with the non-OPLL group. Pearson correlation analysis demonstrated that Beclin1 expression was positively correlated with expression of osteocalcin (OCN) (r = 0.8233, P < 0.001), alkaline phosphatase, biomineralization associated (ALP) (r = 0.7821, P < 0.001), and collagen type 1 (COL 1) (r = 0.6078, P = 0.001). Consistently, the upregulation of autophagy-associated genes in ligament fibroblasts from patients with OPLL were further confirmed by western blotting and immunofluorescence. The incidence of autophagy was also increased in ligament fibroblasts from patients with OPLL. Furthermore, knockdown of Beclin1 led to a decrease in the expression of OCN, ALP, and COL 1 by 63.2% (P < 0.01), 52% (P < 0.01), and 53.2% (P < 0.01) in ligament fibroblasts from patients with OPLL, respectively. CONCLUSIONS: Beclin1-mediated autophagy was involved in the osteogenic differentiation of ligament fibroblasts and promoted the development of OPLL.