Hao1 Is Not a Pathogenic Factor for Ectopic Ossifications but Functions to Regulate the TCA Cycle In Vivo

Ossification of the posterior longitudinal ligament (OPLL), a disease characterized by the ectopic ossification of a spinal ligament, promotes neurological disorders associated with spinal canal stenosis. While blocking ectopic ossification is mandatory to prevent OPLL development and progression, the mechanisms underlying the condition remain unknown. Here we show that expression of hydroxyacid oxidase 1 (Hao1), a gene identified in a previous genome-wide association study (GWAS) as an OPLL-associated candidate gene, specifically and significantly decreased in fibroblasts during osteoblast differentiation. We then newly established Hao1-deficient mice by generating Hao1-flox mice and crossing them with CAG-Cre mice to yield global Hao1-knockout (CAG-Cre/Hao1flox/flox; Hao1 KO) animals. Hao1 KO mice were born normally and exhibited no obvious phenotypes, including growth retardation. Moreover, Hao1 KO mice did not exhibit ectopic ossification or calcification. However, urinary levels of some metabolites of the tricarboxylic acid (TCA) cycle were significantly lower in Hao1 KO compared to control mice based on comprehensive metabolomic analysis. Our data indicate that Hao1 loss does not promote ectopic ossification, but rather that Hao1 functions to regulate the TCA cycle in vivo.

Combined Anterior and Posterior Decompression With Fusion for Cervical Ossification of the Posterior Longitudinal Ligament

Objective:Cervical myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) is not uncommon among Asian ethnic groups. Despite reports comparing the pros and cons of anterior- and posterior-only approaches, the optimal management remains debatable. This study aimed to evaluate the outcomes of patients who underwent a combined anterior and posterior approach, simultaneous circumferential decompression and fixation, for cervical OPLL.Method:The study retrospectively reviewed patients with OPLL and who underwent circumferential decompression and fixation, combined anterior corpectomy and posterior laminectomy. The clinical outcomes were evaluated by the Visual Analog Scale of neck and arm pain, the Japanese Orthopedic Association scores, Neck Disability Index, and Nurick scores at each time-point of evaluation. Radiological evaluations included plain and dynamic radiographs and computed tomography for every patient within 2 years post-operation. Subgroup analyses were further performed between the groups, with and without intra-operative cerebrospinal fluid (CSF) leakage.Results:A total of 41 patients completed the follow-up for more than 2 years (mean = 39.8 months) and were analyzed. Continuous-type OPLL was the most common (44%), followed by segmental (27%), mixed (22%), and localized types (7%) in the cohort. Myelopathy and all other functional outcomes improved significantly at 2 years post-operation (all p < 0.05). There were 13 (32%) patients who had intra-operative CSF leakage. At 2 years post-operation, there were no differences in the demographics, functional outcomes, and complication rates between the CSF-leakage and no-leakage groups. The CSF-leakage group had more patients with continuous-type OPLL than the no-leakage group (77 vs. 29%, p = 0.004 < 0.05). During the follow-up, there was no secondary or revision surgery for pseudomeningocele, pseudarthrosis, or other surgery-related complications.Conclusions:Simultaneous circumferential decompression and fixation combine the surgical benefits of sufficient decompression by the posterior approach and direct decompression of OPLL by the anterior approach. It is an effective surgical option for patients with cervical myelopathy caused by OPLL, given that myelopathy unanimously improved without neurological complications in this study. The fusion rates were high, and reoperation rates were low. Despite higher rates of CSF leakage, there were no related long-term sequelae, and minimal wound complications.

Comparison of laminoplasty and posterior fusion surgery for cervical ossification of posterior longitudinal ligament

This prospective multicenter study, established by the Japanese Ministry of Health, Labour and Welfare and involving 27 institutions, aimed to compare postoperative outcomes between laminoplasty (LM) and posterior fusion (PF) for cervical ossification of the posterior longitudinal ligament (OPLL), in order to address the controversy surrounding the role of instrumented fusion in cases of posterior surgical decompression for OPLL. 478 patients were considered for participation in the study; from among them, 189 (137 and 52 patients with LM and PF, respectively) were included and evaluated using the Japanese Orthopaedic Association (JOA) scores, the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiographical measurements. Basic demographic and radiographical data were reviewed, and the propensity to choose a surgical procedure was calculated. Preoperatively, there were no significant differences among the participants in terms of patient backgrounds, radiographical measurements (K-line or cervical alignment on X-ray, OPLL occupation ratio on computed tomography, increased signal intensity change on magnetic resonance imaging), or clinical status (JOA score and JOACMEQ) after adjustments. The overall risk of perioperative complications was found to be lower with LM (odds ratio [OR] 0.40, p = 0.006), and the rate of C5 palsy occurrence was significantly lower with LM (OR 0.11, p = 0.0002) than with PF. The range of motion (20.91° ± 1.05° and 9.38° ± 1.24°, p < 0.0001) in patients who had PF was significantly smaller than in those who had LM. However, multivariable logistic regression analysis showed no significant difference among the participants in JOA score, JOA recovery rate, or JOACMEQ improvement at two years. In contrast, OPLL progression was greater in the LM group than in the PF group (OR 2.73, p = 0.0002). Both LM and PF for cervical myelopathy due to OPLL had resulted in comparable postoperative outcomes at 2 years after surgery.

Recurrent ossification of the posterior longitudinal ligament in the upper thoracic region 10 years after initial decompression

Background: Posterior decompression surgery consisting of laminoplasty is generally considered be the treatment of choice for upper thoracic OPLL. Here, we describe a patient who, 10 years following a C3–T4 level laminectomy, developed recurrent OPLL at the T2–3 level with kyphosis requiring a posterior fusion. Case Description: A 64-year-old male with CT documented OPLL at the C3–4, C6–7, and T1–4 levels, originally underwent a cervicothoracic laminectomy with good results. However, 10 years later, when T2–3 OPLL recurred along with kyphosis, he warranted an additional posterior fusion. Conclusion: Due to the long-term risks of developing kyphotic deformity/instability, more patients undergoing initial decompressive surgery alone for upper thoracic OPLL should be considered for primary fusions.

Surgical management of continuous and mixed type of OPLL in cervical spine: Experience in tertiary level hospital.

Background: Ossification of the posterior longitudinal ligament (OPLL) is a chronically progressive disease of ectopic enchondral and membranous ossification of posterior longitudinal ligament (PLL). Controversy still persists over the superiority of various surgical approaches for cervical OPLL management. Purpose: To see the efficacy of expansive laminoplasty for the management of continuous and mixed type of cervical OPLL retrospectively. Methods: Records of 20 male and 8 female aged 36-72 years (mean, 56.64 years), who underwent surgical treatment posteriorly for continuous and mixed type OPLL by laminoplasty were obtained from the year 2004 - 2020. Clinical features along with imaging studies, which included X -ray/CT /MRI, were done for the diagnosis of OPLL. Multiple variables were studied, including demographics, surgical parameters, complications and functional outcomes. Results: They were followed on an average of 59.86 ± 20.95 months (range, 24 -108 months). The average operative duration was 95 ± 15.52 min (range: 70 - 140), and the intraoperative blood loss was 199.29 ± 33.55 ml. The cervical curvature index reduced to 8.81 ± 1.96 from 11.00 ± 2.49 and the VAS score decreased from 4.25 ± 0.75 to 2.43 ± 1.40. mJOA score improved from 8.64 ± 1.03 to 13.96 ± 1.26 on the last follow-up after surgery (p < 0.01), with average recovery rate of 65.5 %. Conclusions: The management for cervical myelopathy with multilevel stenosis due to continuous and mixed type of OPLL by Laminoplasty is safe and effective.

New anterior controllable antedisplacement and fusion surgery for cervical ossification of the posterior longitudinal ligament: a biomechanical study

OBJECTIVE The traditional anterior approach for multilevel severe cervical ossification of the posterior longitudinal ligament (OPLL) is demanding and risky. Recently, a novel surgical procedure—anterior controllable antedisplacement and fusion (ACAF)—was introduced by the authors to deal with these problems and achieve better clinical outcomes. However, to the authors’ knowledge, the immediate and long-term biomechanical stability obtained after this procedure has never been evaluated. Therefore, the authors compared the postoperative biomechanical stability of ACAF with those of more traditional approaches: anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF). METHODS To determine and assess pre- and postsurgical range of motion (ROM) (2 Nm torque) in flexion-extension, lateral bending, and axial rotation in the cervical spine, the authors collected cervical areas (C1–T1) from 18 cadaveric spines. The cyclic fatigue loading test was set up with a 3-Nm cycled load (2 Hz, 3000 cycles). All samples used in this study were randomly divided into three groups according to surgical procedures: ACDF, ACAF, and ACCF. The spines were tested under the following conditions: 1) intact state flexibility test; 2) postoperative model (ACDF, ACAF, ACCF) flexibility test; 3) cyclic loading (n = 3000); and 4) fatigue model flexibility test. RESULTS After operations were performed on the cadaveric spines, the segmental and total postoperative ROM values in all directions showed significant reductions for all groups. Then, the ROMs tended to increase during the fatigue test. No significant crossover effect was detected between evaluation time and operation method. Therefore, segmental and total ROM change trends were parallel among the three groups. However, the postoperative and fatigue ROMs in the ACCF group tended to be larger in all directions. No significant differences between these ROMs were detected in the ACDF and ACAF groups. CONCLUSIONS This in vitro biomechanical study demonstrated that the biomechanical stability levels for ACAF and ACDF were similar and were both significantly greater than that of ACCF. The clinical superiority of ACAF combined with our current results showed that this procedure is likely to be an acceptable alternative method for multilevel cervical OPLL treatment.

Double Dome Laminoplasty: A Novel Technique for C2 Decompression

Objective: To introduce a new surgical technique - double dome laminoplasty for decompression of the entire C2 lamina and preservation of an extensor muscle insertion.Methods: Eleven consecutive cervical myelopathy patients due to ossification of the posterior longitudinal ligament involving the Axis (C2) area were contained at this study. Direct decompression was evaluated as an increasing rate in space available cord (%) and posterior cord shift (mm) at C2 level. The Japanese Orthopaedic Association (JOA) score, visual analogue scale, and C2–7 Cobb angle in a neutral lateral x-ray were analyzed.Results: The mean increase in space available for spinal cord at the C2 level, average posterior cord shift, and JOA recovery rate were 69.7%, 5.3 ± 0.15 mm, and 58.0%, respectively. Cervical lordotic angle was maintained in all patients. One patient reported neck pain (visual analogue scale 6) postoperatively. No specific complications such as C2 laminar fracture or insufficient decompression were observed.Conclusion: We recommend double dome laminoplasty for treating patients with cervical myelopathy involving the C2 area to avoid C2 laminectomy, reduce postoperative neck pain, and maintain lordotic cervical spine alignment.