Safety and feasibility of intravenous administration of a single dose of allogenic-Muse cells to treat human cervical traumatic spinal cord injury: a clinical trial.

INTRODUCTION: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells. METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip. RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration. CONCLUSION: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI. TRIAL REGISTRATION: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .

Decrease in pelvic incidence after adult spinal deformity surgery is a predictive factor for progression of hip joint osteoarthritis.

BACKGROUND: This study aimed to evaluate the association between spinopelvic alignment parameters and hip osteoarthritis progression after spinal alignment correction surgery for adult spinal deformity, focusing on the preoperative to postoperative change in spinopelvic alignment. METHODS: This retrospective study enrolled 100 adult spinal deformity patients (196 hip joints) who underwent spinal fusion surgery, after excluding four joints with previous total hip arthroplasty. Acetabular roof obliquity (ARO), center edge angle (CE) and Kellgren and Lawrence (KL) grade were measured in the hip joint. Spinopelvic alignment parameters were measured preoperatively and 1-month postoperatively and the changes (Δ) during this period were calculated. Patients were followed-up for ≥ 5 years and factors associated with KL grade progression at 5-years postoperatively were determined by logistic regression analysis. RESULTS: In the analysis with all cases, KL grade progressed in 23 joints. Logistic regression analysis revealed age (OR: 1.098, 95% CI: 1.007-1.198, p = 0.019), ARO (OR: 1.176, 95% CI: 1.01-1.37, p = 0.026), and Δ PI (OR: 0.791, 95% CI: 0.688-0.997, p < 0.001) as parameters significantly associated with KL grade progression. On the other hand, in the analysis limited to 185 cases with 1-month postoperative KL grade of 0, KL grade progressed in 13 joints. Logistic regression analysis revealed PI-LL (OR: 1.058, 95% CI: 1.001-1.117, p = 0.04), ΔPI (OR: 0.785, 95% CI: 0.649-0.951, p < 0.001), and ΔCobb (OR: 1.127, 95% CI: 1.012-1.253, p = 0.009) as parameters significantly associated with progression. CONCLUSIONS: Both the overall and limited analyzes of this study identified preoperative to postoperative change in PI as parameters affecting the hip osteoarthritis progression after spinal fusion surgery. Decrease in PI might represent preexisting sacroiliac joint laxity. Patients with this risk factor should be carefully followed for possible hip osteoarthritis progression.

Histology and chronological magnetic resonance images of congenital spinal deformity: An experimental study in mice model.

BACKGROUND: The natural history of the congenital spinal deformity and its clinical magnitude vary widely in human species. However, we previously reported that the spinal deformities of congenital scoliosis mice did not progress throughout our observational period according to soft X-ray and MRI data. In this study, congenital vertebral and intervertebral malformations in mice were assessed via magnetic resonance (MR) and histological images. METHODS: Congenital spinal anomalies were chronologically assessed via soft X-ray and 7 T MR imaging. MR images were compared to the histological images to validate the findings around the malformations. RESULTS: Soft X-ray images showed the gross alignment of the spine and the contour of the malformed vertebrae, with the growth plate and cortical bone visible as higher density lines, but could not be used to distinguish the existence of intervertebral structures. In contrast, MR images could be used to distinguish each structure, including the cortical bone, growth plate, cartilaginous end plate, and nucleus pulposus, by combining the signal changes on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). The intervertebral structure adjacent to the malformed vertebrae also exhibited various abnormalities, such as growth plate and cartilaginous end plate irregularities, nucleus pulposus defects, and bone marrow formation. In the chronological observation, the thickness and shape of the malformed structures on T1WI did not change. CONCLUSIONS: Spinal malformations in mice were chronologically observed via 7 T MRI and histology. MR images could be used to distinguish the histological structures of normal and malformed mouse spines. Malformed vertebrae were accompanied by adjacent intervertebral structures that corresponded to the fully segmented structures observed in human congenital scoliosis, but the intervertebral conditions varied. This study suggested the importance of MRI and histological examinations of human congenital scoliosis patients with patterns other than nonsegmenting patterns, which may be used to predict the prognosis of patients with spinal deformities associated with malformed vertebrae.

Anterior fusion surgery with overcorrection in the treatment of adolescent idiopathic scoliosis with Lenke 1 AR curve type: how to achieve overcorrection and its effect on postoperative spinal alignment.

BACKGROUND: The efficacy of anterior fusion with overcorrection in the instrumented vertebra for Lenke 1 AR type curves has been reported, but how to achieve overcorrection and how overcorrection affects spinal alignment are unclear. The purpose of this study was to identify the factors that cause overcorrection, and to investigate how overcorrection affects postoperative spinal alignment in the surgical treatment of Lenke 1 AR type curves. METHODS: Patients who had anterior surgery for a Lenke type 1 or 2 and lumbar modifier AR (L4 vertebral tilt to the right) type scoliosis and minimum 2-year follow-up were included. The radiographic data were measured at preoperative, postoperative 1 month, and final follow-up. The UIV-LIV Cobb angle was determined as the Cobb angle between the upper instrumented vertebra (UIV) and the lower instrumented vertebra (LIV), and a negative number for this angle was considered overcorrection. The screw angle was determined to be the sum of the angle formed by the screw axis and the lower and upper endplates in the LIV and UIV, respectively. The change (Δ) in the parameters from postoperative to final follow-up was calculated. The relationships between the UIV-LIV Cobb angle and other radiographic parameters were evaluated by linear regression analyses. RESULTS: Fourteen patients met the inclusion criteria. Their median age was 15.5 years, and the median follow-up period was 53.6 months. The median UIV-LIV Cobb angle was -1.4° at postoperative 1 month. The median screw angle was 4.7°, and overcorrection was achieved in 11 (79%) cases at postoperative 1 month. The screw angle (r2 = 0.42, p = 0.012) and Δ FDUV-CSVL (the deviation of the first distal uninstrumented vertebra from the central sacral vertical line, r2 = 0.53, p = 0.003) were significantly correlated with the UIV-LIV Cobb angle. CONCLUSIONS: Screw placement in the UIV and LIV not parallel to the endplate, but angled, was an effective method to facilitate overcorrection in the instrumented vertebrae. The results of the present study suggest that overcorrection could bring spontaneous improvement of coronal balance below the instrumented segment during the postoperative period.

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.

Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Residual Neuropathic Pain in Postoperative Patients With Cervical Ossification of Posterior Longitudinal Ligament.

STUDY DESIGN: A prospective multi-institutional observational study. OBJECTIVE: To investigate and identify risk factors for residual neuropathic pain after surgery in patients with cervical ossification of posterior longitudinal ligament (c-OPLL). SUMMARY OF BACKGROUND DATA: Patients with c-OPLL often require surgery for numbness and paralysis of the extremities; however, postoperative neuropathic pain can considerably deteriorate their quality of life. METHODS: Out of 479 patients identified from multicenter c-OPLL registries between 2014 and 2017, 292 patients who could be followed up for 2 years postoperatively were reviewed, after excluding patients with nervous system comorbidities. Demographic details; medical history; radiographic factors including the K-line, spinal canal occupancy rate of OPLL, cervical kyphosis angle, and presence of spinal cord myelomalacia; preoperative Japanese Orthopaedic Association (JOA) score; surgical procedure (fusion or decompression surgery); postoperative neurological deterioration; and the visual analogue scale for pain and numbness in the upper extremities (U/E) or trunk/lower extremities (L/E) at baseline and at 2 years postoperatively were assessed. Patients were grouped into residual and non-residual groups based on a postoperative visual analogue scale ≥40 mm. Risk factors for residual neuropathic pain were evaluated by multiple logistic regression analysis. RESULTS: The prevalence of U/E and L/E residual pain in postoperative c-OPLL patients was 51.7% and 40.4%, respectively. The U/E residual group had a poor preoperative JOA score and longer illness duration, and fusion surgery was more common in the residual group than in non-residual group. The L/E residual group was older with a poorer preoperative JOA score. On multivariate analysis, risk factors for U/E residual pain were long illness duration and poor preoperative JOA score, whereas those for L/E residual pain were age and poor preoperative JOA score. CONCLUSIONS: The risk factors for residual spinal neuropathic pain after c-OPLL surgery were age, long duration of illness, and poor preoperative JOA score. LEVEL OF EVIDENCE: IV.

Deep learning-based prediction model for postoperative complications of cervical posterior longitudinal ligament ossification.

PURPOSE: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM. RESULTS: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%). CONCLUSION: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods.

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).

Prospective Investigation of Surgical Outcomes after Anterior Decompression with Fusion and Laminoplasty for the Cervical Ossification of the Posterior Longitudinal Ligament: A Propensity Score Matching Analysis.

The ideal surgical strategy for cervical ossification of the posterior longitudinal ligament (OPLL) remains controversial due to the lack of high-quality evidence. Herein, we prospectively investigated the surgical outcomes of anterior cervical decompression with fusion (ADF) and laminoplasty (LAMP) with cervical OPLL. Three hundred patients were included in this study (ADF: n = 89; LAMP: n = 211 patients), and propensity score matching yielded 67 pairs of patients with ADF and LAMP, in which clinical outcomes were compared. Crude analysis revealed that the ADF group showed greater neurological recovery in cervical Japanese Orthopedic Association scores at two years, compared with that in the LAMP group (53.1% vs. 44.3%, p = 0.037). The ratio of minimum clinically important difference (MCID) success was significantly greater in the ADF group (59.6% vs. 43.6%, p = 0.016). Multivariate analysis showed that the factors affecting MCID success were age, body mass index, duration of symptoms, and choice of ADF. In the 1:1 matched analysis, neurological improvement was more favorable in the ADF group (57.2%) compared to the LAMP group (46.8%) at two years (p = 0.049). However, perioperative complications, such as dysphagia and graft-related complications, were more common in the ADF group.

Clinical Indicators of Surgical Outcomes After Laminoplasty for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multicenter Study.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: This study aims to evaluate patient-reported outcomes using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and clarify clinical factors that affect the therapeutic effects for patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Although previous studies identified factors that affected the surgical outcomes, their assessment was mainly based on the Japanese Orthopedic Association score, which only includes neurological function. Investigating this pathology through multiple functions and quality of life (QOL) is pivotal to understanding the comprehensive clinical pictures of the cervical OPLL and its therapeutic outcomes. MATERIALS AND METHODS: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the patients, 168 received laminoplasties and fully completed questionnaires. Demographic information, imaging findings, and clinical outcomes were collected. Patients were grouped according to effective or ineffective surgical outcomes as defined by the JOACMEQ using logistic regression analyses. RESULTS: Laminoplasty resulted in functional improvement in the cervical spine and upper extremity around 40% of the patients, while QOL showed only 21.4% ( P <0.01). Multivariable analyses revealed that younger age and a postoperative decrease in arm or hand pain were correlated with significantly improved function of the upper extremities. A reduction in lower limb pain favorably affected the postoperative lower extremity function. A postoperative reduction in upper extremity pain enhanced the QOL recovery. CONCLUSIONS: Surgeons should recognize the diversity of surgical outcomes after laminoplasty and understand the necessity of pain management even after the surgery to enhance bodily functions and QOL in patients with cervical OPLL.

Impact of obesity on cervical ossification of the posterior longitudinal ligament: a nationwide prospective study.

Positive association between ossification of the posterior longitudinal ligament of the spine (OPLL) and obesity is widely recognized; however, few studies focused on the effects of obesity on treatment of cervical OPLL. The effects of obesity on surgical treatment of cervical OPLL were investigated by a Japanese nationwide, prospective study. Overall, 478 patients with cervical myelopathy due to OPLL were prospectively enrolled. To clarify the effects of obesity on the surgical treatment for cervical OPLL, patients were stratified into two groups, non-obese (< BMI 30.0 kg/m2) and obese (≥ BMI 30.0 kg/m2) groups. The mean age of the obese group was significantly younger than that of non-obese group. There were no significant differences between the two groups in other demographic information, medical history, and clinical and radiographical findings. Alternatively, the obese group had a significantly higher rate of surgical site infection (SSI) than that of non-obese group. Approach-specific analyses revealed that the SSI was significantly higher in the obese group than in the non-obese group. A logistic regression analysis revealed that age, BMI, and duration of symptoms were significant factors affecting the postoperative minimum clinically important difference success. The result of this study provides useful information for future cervical OPLL treatment.

Thoracic kyphosis in light of lumbosacral alignment in thoracic adolescent idiopathic scoliosis: recognition of thoracic hypokyphosis and therapeutic implications.

BACKGROUND: The uniqueness of spinal sagittal alignment in thoracic adolescent idiopathic scoliosis (AIS), for example, the drastically smaller thoracic kyphosis seen in some patients, has been recognized but not yet fully understood. The purpose of this study was to clarify the characteristics of sagittal alignment of thoracic AIS and to determine the contributing factors. METHODS: Whole spine radiographs of 83 thoracic AIS patients (73 females) were analyzed. The measured radiographic parameters were the Cobb angle of thoracic scoliosis, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (C7 SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Additionally, max-LL, which was defined as the maximum lordosis angle from the S1 endplate, the inflection point between thoracic kyphosis and lumbar lordosis, and the SVA of the inflection point (IP SVA) were measured. The factors significantly related to a decrease in TK were assessed by stepwise logistic regression analysis. In addition, cluster analysis was performed to classify the global sagittal alignment. RESULTS: The significant factors for a decrease in TK were an increase in SS (p = 0.0003, [OR]: 1.16) and a decrease in max-LL (p = 0.0005, [OR]: 0.89). According to the cluster analysis, the global sagittal alignment was categorized into the following three types: Type 1 (low SS, low max-LL, n = 28); Type 2 (high SS, low max-LL, n = 22); and Type 3 (high SS, high max-LL, n = 33). CONCLUSIONS: In thoracic AIS, a decreased TK corresponded to an increased SS or a decreased max-LL. The sagittal alignment of thoracic AIS patients could be classified into three types based on SS and max-LL. One of these three types includes the unique sagittal profile of very small TK.

Is anterior decompression and fusion more beneficial than laminoplasty for K-line (+) cervical ossification of the posterior longitudinal ligament? An analysis using propensity score matching.

OBJECTIVE: It is unclear whether anterior cervical decompression and fusion (ADF) or laminoplasty (LMP) results in better outcomes for patients with K-line-positive (+) cervical ossification of the posterior longitudinal ligament (OPLL). The purpose of the study is to compare surgical outcomes and complications of ADF versus LMP in patients with K-line (+) OPLL. METHODS: The study included 478 patients enrolled in the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament and who underwent surgical treatment for cervical OPLL. The patients who underwent anterior-posterior combined surgery or posterior decompression with instrumented fusion were excluded. The patients with a follow-up period of fewer than 2 years were also excluded, leaving 198 patients with K-line (+) OPLL. Propensity score matching was performed on 198 patients with K-line (+) OPLL who underwent ADF (44 patients) or LMP (154 patients), resulting in 39 pairs of patients based on the following predictors for surgical outcomes: age, preoperative Japanese Orthopaedic Association (JOA) score, C2-7 angle, and the occupying ratio of OPLL. Clinical outcomes were assessed 1 and 2 years after surgery using the recovery rate of the JOA score. Complications and reoperation rates were also investigated. RESULTS: The mean recovery rate of the JOA score 1 year after surgery was 55.3% for patients who underwent ADF and 42.3% (p = 0.06) for patients who underwent LMP. Two years after surgery, the recovery rate was 53.4% for those who underwent ADF and 38.7% for LMP (p = 0.07). Although both surgical procedures yielded good results, the mean recovery rate of JOA scores tended to be higher in the ADF group. The incidence of surgical complications, however, was higher following ADF (33%) than LMP (15%; p = 0.06). The reoperation rate was also higher in the ADF group (15%) than in the LMP group (0%; p = 0.01). CONCLUSIONS: Clinical outcomes were good for both ADF and LMP, indicating that ADF and LMP are appropriate procedures for patients with K-line (+) OPLL. Clinical outcomes of ADF 1 and 2 years after surgery tended to be better than LMP, but the analysis did not detect any significant difference in clinical outcomes between the groups. Conversely, patients who underwent ADF had a higher incidence of surgery-related complications. When considering indications for ADF or LMP, benefits and risks of the surgical procedures should be carefully weighed.

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.

Severity of Myelopathy is Closely Associated With Advanced Age and Signal Intensity Change in Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Nationwide Investigation.

STUDY DESIGN: Prospective, nationwide case series. OBJECTIVE: To identify preoperative factors associated with myelopathy and neurological impairment in patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Various studies have reported clinical outcomes following the surgical treatment of OPLL. However, there has been no large-scale study of preoperative clinical features in patients with cervical OPLL. MATERIALS AND METHODS: Data were prospectively collected from 28 institutions nationwide in Japan. In total, 512 patients with neurological impairment caused by cervical OPLL requiring surgery were enrolled. Basic demographic and clinical data, including age, sex, diabetes status, body mass index, smoking history, and disease duration were collected. C2-7 lordotic angle, canal narrowing ratio, range of motion in flexion-extension at C2-7, and type of OPLL were evaluated on lateral radiographs to identify factors influencing the clinical features of patients with OPLL in whom surgery was planned. RESULTS: Complete documentation was available for 490 patients (362 male, 128 female). In total, 34 patients had the localized type, 181 had the segmental type, 64 had the continuous type, and 211 had the mixed type. Although there were no significant differences in age, body mass index, disease duration, Japanese Orthopedic Association (JOA) score, and lordotic angle at C2-7 according to the type of OPLL, significant differences were observed in a range of motion at C2-7 and the canal narrowing ratio among the 4 types. Multiple regression analysis revealed that the JOA score was significantly associated with age and signal intensity change on magnetic resonance imaging. CONCLUSIONS: This is the first large-scale, prospective, multicenter case series study to investigate factors influencing preoperative neurological status in patients with OPLL. Age and signal intensity change on magnetic resonance images were significantly associated with JOA score in patients requiring surgery. LEVEL OF EVIDENCE: Level II.

Factors Significantly Associated with Postoperative Neck Pain Deterioration after Surgery for Cervical Ossification of the Posterior Longitudinal Ligament: Study of a Cohort Using a Prospective Registry.

Postoperative neck pain has been reported as an unsolved postoperative complication of surgery for cervical ossification of the posterior longitudinal ligament (OPLL). The aim of the present study was to elucidate factors having a significant association with postoperative deterioration of neck pain in cervical OPLL patients. We studied a cohort of patients in a prospective registry of 478 patients who had undergone cervical spine surgery for cervical OPLL. We excluded those without evaluation of preoperative neck pain. Therefore, 438 patients were included in the present study. Neck pain was evaluated with the visual analogue scale (VAS, 0-100 mm). Postoperative neck pain deterioration was defined as a ≥20 mm increase of VAS neck pain. Patient factors, neurological status, imaging factors and surgical factors were assessed. Univariate analyses followed by multivariate analysis using stepwise logistic regression was performed. Six months after surgery, 50 (11.6%) patients showed postoperative neck pain deterioration and 76 (17.4%) patients showed postoperative neck pain deterioration 2 years after surgery. Six months after surgery, the rate of neck pain deterioration was significantly higher in patients who had undergone posterior surgery. Two years after surgery, the number of levels fused was significantly correlated with neck pain deterioration.

Anterior instrumentation surgery for the treatment of Lenke type 1AR curve patterns.

OBJECTIVE: Previous studies have demonstrated that Lenke lumbar modifier A contains 2 distinct types (AR and AL), and the AR curve pattern is likely to develop adding-on (i.e., a progressive increase in the number of vertebrae included within the primary curve distally after posterior surgery). However, the results of anterior surgery are unknown. The purpose of this study was to present the surgical results in a cohort of patients undergoing scoliosis treatment for type 1AR curves and to compare anterior and posterior surgeries to consider the ideal indications and advantages of anterior surgery for type 1AR curves. METHODS: Patients with a Lenke type 1 or 2 and lumbar modifier AR (L4 vertebral tilt to the right) and a minimum 2-year postoperative follow-up were included. The incidence of adding-on and radiographic data were compared between the anterior and posterior surgery groups. The numbers of levels between the end, stable, neutral, and last touching vertebra to the lower instrumented vertebra (LIV) were also evaluated. RESULTS: Forty-four patients with a mean follow-up of 57 months were included. There were 14 patients in the anterior group and 30 patients in the posterior group. The main thoracic Cobb angle was not significantly different between the groups preoperatively and at final follow-up. At final follow-up, the anterior group had significantly less tilting of the LIV than the posterior group (-0.8° ± 4.5° vs 3° ± 4°). Distal adding-on was observed in no patient in the anterior group and in 6 patients in the posterior group at final follow-up (p = 0.025). In the anterior group, no LIV was set below the end vertebra, and all LIVs were set above last touching vertebra. The LIV was significantly more proximal in the anterior group than in the posterior surgery patients without adding-on for all reference vertebrae (p < 0.001). CONCLUSIONS: This is the first study to investigate the surgical results of anterior surgery for Lenke type 1AR curve patterns, and it showed that anterior surgery for the curves could minimize the distal extent of the instrumented fusion without adding-on. This would leave more mobile disc space below the fusion.

Impact of Diabetes Mellitus on Cervical Spine Surgery for Ossification of the Posterior Longitudinal Ligament.

Ossification of the posterior longitudinal ligament (OPLL) is commonly associated with diabetes mellitus (DM); however, the impact of DM on cervical spine surgery for OPLL remains unclear. This study was performed to evaluate the influence of diabetes DM on the outcomes following cervical spine surgery for OPLL. In total, 478 patients with cervical OPLL who underwent surgical treatment were prospectively recruited from April 2015 to July 2017. Functional measurements were conducted at baseline and at 6 months, 1 year, and 2 years after surgery using JOA and JOACMEQ scores. The incidence of postoperative complications was categorized into early (≤30 days) and late (>30 days), depending on the time from surgery. From the initial group of 478 patients, 402 completed the 2-year follow-up and were included in the analysis. Of the 402 patients, 127 (32%) had DM as a comorbid disease. The overall incidence of postoperative complications was significantly higher in patients with DM than in patients without DM in both the early and late postoperative periods. The patients with DM had a significantly lower JOA score and JOACMEQ scores in the domains of lower extremity function and quality of life than those without DM at the 2-year follow-up.

Perioperative Complications in Posterior Surgeries for Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Nationwide Investigation.

STUDY DESIGN: This was a prospective multicenter study. OBJECTIVE: The aim of this study was to investigate the perioperative complications of posterior surgeries for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Surgical treatment for cervical OPLL has a high risk of various complications. Laminoplasty (LAMP) and posterior decompression and instrumented fusion (PDF) are effective for multilevel cervical OPLL; however, few studies have focused on the surgical complications of these 2 procedures. MATERIALS AND METHODS: We prospectively included 380 patients undergoing posterior surgeries for cervical OPLL (LAMP: 270 patients, PDF: 110 patients), and investigated the systemic and local complications, including neurological complications. We further evaluated risk factors related to the neurological complications. RESULTS: Motor palsy was found in 40 patients (10.5%), and motor palsy in the upper extremity was most frequent (8.9%), especially in patients who received PDF (14.5%). Motor palsies involving the lower extremities was found in 6 patients (1.6%). Regarding local complications, dural tears (3.9%) and surgical site infections (2.6%) were common. In the univariate analysis, body mass index, preoperative cervical alignment, fusion surgery, and the number of operated segments were the factors related to motor palsy. Multivariate analysis revealed that fusion surgery and a small preoperative C2-C7 angle were the independent factors related to motor palsy. Motor palsy involving the lower extremities tended to be found at early time points after the surgery, and all the patients fully recovered. Motor palsy in the upper extremities occurred in a delayed manner, and 68.8% of patients with PDF showed good recovery, whereas 81.3% of patients with LAMP showed good recovery. CONCLUSIONS: In posterior surgeries for cervical OPLL, segmental motor palsy in the upper extremity was most frequently observed, especially in patients who received PDF. Fusion and a small preoperative C2-C7 angle were the independent risk factors for motor palsy. LEVEL OF EVIDENCE: Level III.

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use.

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10-40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10-10 ) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10-8 ), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10-4 ). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).