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The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1β (IL-1β). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1β is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1β-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1β-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1β-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1β-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression.

Vertebral fractures (VFs) cause serious problems, such as substantial functional loss and a high mortality rate, and a delayed diagnosis may further worsen the prognosis. Plain thoracolumbar radiography (PTLR) is an essential method for the evaluation of VFs. Therefore, minimizing the diagnostic errors of VFs on PTLR is crucial. Image identification based on a deep convolutional neural network (DCNN) has been recognized to be potentially effective as a diagnostic strategy; however, the accuracy for detecting VFs has not been fully investigated. A DCNN was trained with PTLR images of 300 patients (150 patients with and 150 without VFs). The accuracy, sensitivity, and specificity of diagnosis of the model were calculated and compared with those of orthopedic residents, orthopedic surgeons, and spine surgeons. The DCNN achieved accuracy, sensitivity, and specificity rates of 86.0% [95% confidence interval (CI) 82.0–90.0%], 84.7% (95% CI 78.8–90.5%), and 87.3% (95% CI 81.9–92.7%), respectively. Both the accuracy and sensitivity of the model were suggested to be noninferior to those of orthopedic surgeons. The DCNN can assist clinicians in the early identification of VFs and in managing patients, to prevent further invasive interventions and a decreased quality of life.

Study design Retrospective study of prospectively collected outcome data. Objective The aim of this study was to investigate reoperation cases and determine whether or not the experience period of a single surgeon was associated with the causes of reoperations following lumbar microendoscopic discectomy for disc herniation (MEDH) and microendoscopic decompression for spinal stenosis (MEDS). Summary of background data There have been few studies that investigated reoperation cases following MEDH and MEDS. Methods Between June 2005 (first experience of MEDH) and September 2013, the same surgeon had been using MEDH and/or MEDS on 441 consecutive patients. The follow-up rate was 89.3%. The causes and rates of reoperations (RORs) were determined at 5 years after the initial operations. We also investigated the experience period of a single surgeon (EPS, interval between June 2005 and initial operation: median, 37 months). Results The 5-year reoperation rate for all patients combined was 12.4% (49/394). The main causes for reoperations were recurrence of disc herniation (ROR, 7.01%) and increase of postoperative spondylolisthesis and/or instability (ROR, 9/394 = 2.28%); two of the nine cases were caused by excessive decompression, and the EPSs were 11 and 16 months. The other causes for reoperations were postoperative epidural hematoma (ROR, 0.76%; median EPS, 20 months), insufficient decompression (ROR, 0.25%; EPS, 17 months), and residual segmental scoliosis (ROR, 7.69%); two segmental scoliosis cases did not provide relief from sciatica, and therefore L4/5 transforaminal interbody fusions were performed. Conclusion Postoperative epidural hematoma and excessive or insufficient decompression were often observed in the initial series of patients as the causes for reoperations. We think that it is important to be aware of and prevent such potential problems in any initial series of patients, as there are limitations to any surgical indications for the use of microendoscopic decompression for degenerative segmental scoliosis because of original traction and/or kinking of nerve roots. Level of evidence 4.

Background To date, the histopathologic characteristics of dropped head syndrome (DHS) have not been reported sufficiently. The present study investigates the histopathology of biopsy specimens from the cervical paravertebral region in patients with DHS. Methods Histopathological parameters were evaluated in biopsy specimens of the cervical paravertebral soft tissue from 15 patients with DHS. Results Among the 15 cases of DHS examined, skeletal muscle was identified in 7 cases, all of which showed necrosis, microvessel proliferation and atrophy. The ligament was identified in 12 cases, 8 of which showed degeneration. The lag time between the onset of symptoms and the performance of a biopsy in all 8 cases, which showed degeneration was over 3 months. Microvessel proliferation in the ligament was observed in 1 of the 4 cases, in which the lag time between the onset of symptoms and the performance of a biopsy was less than 3 months (acute or subacute phase), and in 7 of the 8 cases, in which the lag time between the symptoms and the performance of a biopsy was over 3 months (chronic phase). Chronic inflammation in the ligament was identified in 1 of the 12 cases. Conclusions The identification of necrosis, microvessel proliferation, and atrophy in the skeletal muscle of patients with DHS and the presence of ligament degeneration and microvessel proliferation in the chronic but not acute or subacute phases may suggest that persistent skeletal muscle damage of the cervical paravertebral region causes subsequent ligament damage in patients with DHS.

To investigate the 10-year rates and causes of reoperations following lumbar microendoscopic discectomy for disc herniation (MEDH) and microendoscopic decompression for spinal stenosis (MEDS), as well as to define the reoperations at index and different lumbar levels.Between June 2005 and May 2011, the same surgeon had been using MEDH and/or MEDS on 355 consecutive patients. The follow-up rate was 88.3%. The causes and rates of reoperations (RORs) were determined at 10 years after the initial operations.The 10-year reoperation rate for all patients combined was 22.1% (67/303). The 10-year reoperation rate for all cases that underwent repeat operations in the same segment was 16.5% (50/303); the most frequent reason for reoperation (FRR) was recurrence of disc herniation (ROR, 25/251 = 9.96%), the second FRR was an increase of postoperative spondylolisthesis and/or instability (ROR, 8/303 = 2.64%), and the third FRR was surgical site infection (ROR, 5/303 = 1.65%). Ten-year reoperation rate for all cases that underwent repeat operation at different lumbar levels was 5.61% (17/303); the most FRR was new disc herniation at another lumbar level (ROR, 10/303 = 3.30%), the second FRR was residual segmental stenosis (ROR, 4/303 = 1.32%), and the third FRR was new segmental stenosis at other lumbar levels (ROR, 2/303 = 0.66%).Three-fourths of all repeat operations were conducted in the same segment and one-fourth were performed at different lumbar levels. We believe that it is important to understand and prevent related problems.

Sagittal spinal alignment has mainly analyzed in the standing position. According to previous studies, there are significant differences in lumbopelvic alignment between the standing and sitting positions and cervical alignment is affected by lumbopelvic alignment. In this study, therefore, we hypothesized that cervical sagittal alignments are different between the standing and sitting positions.A total of 108 patients with spinal degenerative diseases underwent whole spine radiography. Cervical lordosis (CL), C2-7 SVA, T1S, C7-S1 SVA, TK, LL, SS, PT, and PI were measured in the standing and sitting positions. Patients were classified into 3 groups according to the changes in CL (ΔCL, CL in the sitting position - CL in the standing position); ΔCL -3° (Decreased group: DG; 28.7%), -3° ≤ ΔCL ≤ 3° (Unchanged group: UG; 41.7%), and ΔCL 3° (Increased group: IG; 29.6%).The parameters of the UG in the standing position were closer to the ideal alignment (SRS-Schwab classification). In the DG, CL, T1S, and C7-S1 SVA in the standing position were significantly higher than in the UG. In the IG, PI-LL in the standing position was significantly higher than in the UG. In the sitting position, pelvis was rotated posteriorly (decrease in SS and increase in PT) and lumbar lordosis was flattened (decrease in LL) in all groups, and C2-7 SVA was significantly higher in the DG than in the UG.CL was different between the standing and sitting positions in 58.3% of individuals. However, patients with good spinal sagittal alignment appeared to not undergo any changes in cervical alignment. Our results suggest the possibility that patients who had a positive imbalance and large PI-LL mismatch in the standing position had decreased CL and increased CL, respectively, when in the sitting position.

Background: Dropped head syndrome (DHS) can be divided into two types, the positive sagittal vertical axis (SVA) type and the negative SVA type. However, the cervical sagittal alignment of DHS including global sagittal spinal alignment and the typical cervical alignment of the types of DHS is still unclear. The purpose of this study was to clarify the character of cervical sagittal alignment of DHS and analyze the relationship between cervical sagittal alignment and global sagittal spinal alignment. Methods: The subjects were 35 DHS patients (10 men, 25 women, mean 71.1 years old). They were divided into two groups: negative DHS (N-DHS group, SVA < 0 mm) and positive DHS group (P-DHS group, SVA ≥ 0 mm). As control, 28 age-matched cervical spondylosis patients (CS, 21 men, 7 women, mean 67.4 years old) were analyzed. The following parameters were measured on lateral global-spine standing radiographs: cervical SVA (C2-C7SVA), O-C2A (O-C2 angle), C2 slope (C2S), C2-7A (C2-7 angle), T1 slope (T1S) and C7SVA. Results: The results of measurements of each of the averaged sagittal alignment parameters were (CS, P-DHS, N-DHS): C2-7SVA(26.2 mm, 47.3 mm, 44.5 mm), O-C2 angle (35.0°, 37.1°, 39.3°), C2S (16.5°, 31.4°, 33.8°), C2-7A (9.3°, 9.9°, −16.6°), T1S (22.9°, 39.7°, 25.7°), C7SVA (35.3 mm, 51.0 mm, −43.1 mm). C2-C7SVA and C2S were significantly larger in both types of DHS compared to CS. Comparing P-DHS with N-DHS, C2-C7A and T1S were significantly smaller in N-DHS. Conclusions: O-C2A did not differ significantly among CS, P-DHS and N-DHS. In DHS patients, C2-7SVA and C2S were significantly larger than those of CS regardless of the type of DHS. The typical cervical sagittal alignment of DHS was different between P-DHS and N-DHS. In P-DHS, C2-7A and T1S were larger than those in N-DHS and the imbalance of thoraco-lumbar alignment should be noted.

Ossification of the posterior longitudinal ligament (OPLL) causes serious problems, such as myelopathy and acute spinal cord injury. The early and accurate diagnosis of OPLL would hence prevent the miserable prognoses. Plain lateral radiography is an essential method for the evaluation of OPLL. Therefore, minimizing the diagnostic errors of OPLL on radiography is crucial. Image identification based on a residual neural network (RNN) has been recognized to be potentially effective as a diagnostic strategy for orthopedic diseases; however, the accuracy of detecting OPLL using RNN has remained unclear. An RNN was trained with plain lateral cervical radiography images of 2,318 images from 672 patients (535 images from 304 patients with OPLL and 1,773 images from 368 patients of Negative). The accuracy, sensitivity, specificity, false positive rate, and false negative rate of diagnosis of the RNN were calculated. The mean accuracy, sensitivity, specificity, false positive rate, and false negative rate of the model were 98.9%, 97.0%, 99.4%, 2.2%, and 1.0%, respectively. The model achieved an overall area under the curve of 0.99 (95% confidence interval, 0.97-1.00) in which AUC in each fold estimated was 0.99, 0.99, 0.98, 0.98, and 0.99, respectively. An algorithm trained by an RNN could make binary classification of OPLL on cervical lateral X-ray images. RNN may hence be useful as a screening tool to assist physicians in identifying patients with OPLL in future setting. To achieve accurate identification of OPLL patients clinically, RNN has to be trained with other cause of myelopathy.

Introduction: Cervical ossification of the anterior longitudinal ligament (OALL) occasionally leads to dysphagia by the anterior osteophyte. A recent report explained that the dysphagia after an occipito-cervical fusion is caused by the narrowing of pharyngeal space due to the cranio-cervical malalignment. The purpose of this study was to evaluate the cranio-cervical alignment in patients with OALL complaining of the dysphagia. Subjects and methods: The subjects were 11 cases with complaining of dysphagia due to cervical OALL who underwent anterior cervical OALL resection and as control, age-matched 12 cases without dysphagia who have diffuse idiopathic skeletal hyperostosis in cervical spine. All subjects were male, and the mean age was 59.5 ± 9.1 years. The subjects were divided into two groups according to the symptoms of dysphagia (dysphagia, group A; control, group B). The O–C2 angle, C2–C7 angle, and the maximum thickness of OALL and the cranio-cervical alignment (pharyngeal inlet angle; PIA) and swallowing line (S-line) were measured before and after the operation on the lateral cervical radiogram at the sitting position. Results: Group A showed significantly large maximum thickness of OALL, small cervical range of motion, small O–C2 angle, large C2–C7 angle, and small PIA. The S-line crossed the anterior apex of cervical osteophyte in group A. After OALL resection, dysphagia had improved, PIA had increased, and the S-line uncrossed the apex of cervical vertebrae in all cases. Conclusion: The prevalence of dysphagia in patients with cervical OALL was influenced by the thickness of osteophyte, cervical mobility, and cranio-cervical alignment.

Objective To determine whether preoperative presence of degenerative lumbar spondylolisthesis (DS) worsens the minimum 10-year outcome of patients undergoing microendoscopic decompression (MED) for lumbar spinal stenosis (SS). Methods Eighty patients undergoing MED were classified into 2 groups: DS group (34 SS with DS patients) and SS group (46 SS without DS patients). The degrees of improvement (DOIs) by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and intensities of improvement (IOIs) by Visual Analog Scale (VAS) at 120–159 (mean, 138.4) months after MED of the DS and SS groups were statistically compared. Patients with DS were classified into 2 groups based on the effectiveness by VAS or JOABPEQ: effective group (E group: IOI or DOI ≥20) and ineffective group (I group). All preoperative radiologic measurements were statistically compared between the E and I groups. Results Significant decreases in low back pain, leg pain, and numbness, as measured by VAS, were noted at follow-up in the DS and SS groups. The effectiveness rates of pain-related disorders, lumbar spine dysfunction, and gait disturbance by JOABPEQ were almost equally high in the DS and SS groups. Statistical comparisons of the DOIs in all 5 functional scores and IOIs in low back pain, leg pain, and numbness showed no significant differences between the DS and SS groups. No significant differences were confirmed between the E and I groups concerning preoperative spondylolisthesis and instability. Conclusions Our study indicated that preoperative DS did not worsen the outcome of patients with SS undergoing MED.

Purpose: Dropped head syndrome (DHS) is characterized by the passively correctable chin-on-chest deformity. The characteristic feature is emphasized in the cervical flexion position. The purpose of this study was to analyze the influence of cervical flexion on sagittal spinal alignment in patients with DHS. Methods: The study included 15 DHS subjects and 55 cervical spondylosis (CS) subjects as the control group. The following parameters were analyzed: cervical sagittal vertical axis (C-SVA), occipitoaxial angle (O–C2A), C2 slope (C2S), C2–C7 angle (C2–C7A), T1 slope (T1S), sagittal vertical axis, T1–T4 angle (T1–T4A), T5–T8 angle (T5–T8A), T9–T12 angle, lumbar lordosis, sacral slope, and pelvic tilt, in cervical flexion and neutral positions. Results: The values of C-SVA, O–C2A, C2S, and T1S were significantly different between CS and DHS at cervical neutral and flexion positions. C2–C7A showed significant difference in cervical neutral position, but the difference disappeared in flexion position. T1–T4A did not present a significant difference, but T5–T8A showed a difference in neutral and flexion positions. Conclusions: Malalignment of DHS extended not only to cervical spine but also to cranio-cervical junction and thoracic spine, except T1–T4. It is known that global sagittal spinal alignment is correlated with adjacent parameters, although in DHS the reciprocal change was lost from cranio-cervical junction to the middle part of thoracic spine at cervical flexion.

Background:Malignant solitary fibrous tumor (MSFT) arising from the spinal cord is extremely rare and poorly understood mesenchymal neoplasms: only a few MSFT in the spinal canal has been described. We describe the clinical course of the patient with MSFT arising from the thoracic spinal cord.Case report:We describe the clinical course of the patient and the radiological and pathological findings of the tumor. The tumor had been resected by microscopic posterior approach and video-assisted thoracic surgery, but local recurrence was observed by MRI at 1-year follow-up period. No metastatic lesion was confirmed. Then, carbon ion radiotherapy (CIRT) was administered to the recurrent lesion. Local suppression has been observed for 40 months after irradiation.Conclusion:Dumbbell-shaped MSFT arising from thoracic spinal cord is a highly unusual presentation. CIRT might be effective for treatment of recurrent tumors.

This is a retrospective radiographic study of a consecutive case series of dropped head syndrome (DHS) at a single tertiary referral center.The aim was to clarify the spinal sagittal alignment of DHS.DHS is characterized by chin-on-chest deformity and devastatingly impedes activities of daily living in affected individuals. Among various forms of DHS, isolated neck extensor myopathy (INEM) is considered to cause the chin-on-chest symptom in the absence of specific abnormality. There is a paucity of literature about spinal sagittal alignment, of this condition however.Thirty-seven patients diagnosed with INEM DHS were enrolled. Radiographic measurements were made, including the following parameters: C2 slope (C2S), C2-C7 A, C2-C7 sagittal vertical axis (SVA), T1 slope (T1S), C7-S1 SVA, T1-T4 thoracic kyphosis (TK), T4-T12 TK, lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). Sixty-one patients with cervical spondylosis were enrolled as a control group.C2-C7 SVA was greater in INEM DHS (52.0 ± 2.9 vs. 18.6 ± 1.9 mm). C2S and T1S were larger to the control (C2S: 52.6° ± 2.0° vs. 13.0° ± 1.4°, T1S: 37.3° ± 2.2° vs. 22.7° ± 1.4°). C2-C7 A was smaller in INEM DHS (-7.8° ± 2.6° vs. 15.2° ± 2.7°). Among sagittal parameters, C2S, T1S, and T1-T4 TK positively correlated with C2-C7 SVA (r = 0.63, r = 0.54, and r = 0.58). For these correlations with C2-C7 SVA, both logistic and linear regression models predicted threshold of 40° for C2S, 40° for T1S, and 15° for T1-T4 TK responsible for C2-C7 SVA40 mm, respectively.Increased offset of the gravity axis of the head represented by C2-C7 SVA was observed in INEM DHS. Magnified offset of the gravity axis of the head was affected by enlarged C2S, T1S, and T1-T4 TK for the strong correlation with C2-C7 SVA, respectively. Cervical kyphosis was considered as some of the anthropometric characteristics due to regressive changes in affected individuals; a correlation between C2-C7 A and C2-C7 SVA was exhibited.4.

Study Design Retrospective study of prospectively collected outcome data. Background No studies have evaluated the long-term outcomes following microendoscopic diskectomy for lumbar disk herniation (MEDH) and microendoscopic decompression for lumbar spinal stenosis (MEDS) using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Objective To assess the minimum 10-year outcomes following MEDH and MEDS. Patients and Methods Seventy-six patients were classified into three groups: disk herniation (DH) group (33 patients underwent MEDH); spinal stenosis (SS) group (23 patients underwent MEDS); and degenerative spondylolisthesis (DS) group (20 DS patients underwent MEDS). The follow-up rate was 50.3% (76/151). The results were statistically compared using Scheffé's F test for differences among the DH, SS, and DS groups. The paired t test was used to compare the preoperative and postoperative visual analog scale (VAS) scores. The degrees of improvement (DOIs) on JOABPEQ and the intensities of improvement (IOIs) on VAS at the first follow-up evaluation (FFE) (mean: 12 months after the operation) and at the most recent follow-up evaluation (MRFE) (mean: 126 months) of the DH group were statistically compared by the paired t test. DOIs and IOIs at MRFE of the SS group (mean: 126 months) and DS group (mean: 125 months) were statistically compared by the unpaired t test. A p value Results Statistical comparisons of the DOIs in all five functional scores and IOIs in low back pain (LBP), leg pain, and leg numbness showed no significant differences among the DH, SS, and DS groups. The effectiveness rates of pain-related disorders, gait disturbance, and social life disturbance in JOABPEQ were almost equally high in all three groups. Significant decreases in LBP, leg pain, and numbness, as measured with VAS, were noted at MRFE in all three groups. No significant differences were observed between FFE and MRFE concerning the DOIs and IOIs of the DH group, and between the SS and DS groups concerning the DOIs and IOIs at MRFE. Conclusion Clinical 1-year outcomes of MEDH were thought to be maintained for > 10 years, and MEDS leads to the same clinical long-term outcomes with DS as without DS. Moreover, MEDH and MEDS were almost equally effective for > 10 years not only in improving LBP, leg pain, and numbness but also especially in improving pain-related disorders, gait disturbance, and social life disturbance by detailed quality-of-life assessment using JOABPEQ.

Background Dropped head syndrome (DHS) is a low prevalence and the clinical features remain unclear. The purpose of the present study was to clarify the general overview of DHS. Methods The subjects were 67 consecutive DHS patients (17 men and 50 women; average age 72.9 ± 10.2 years) presenting difficulty of horizontal gaze in up-right position. The patients' background, global spinal alignment, clinical findings and treatment were analyzed. Results The peak population of DHS was 75–79-year-old females. The comorbidities included Parkinson's disease in 9 cases, minor trauma in 9 cases, post-cervical operation in 3 cases, mental depression in 3 cases, malignant tumor in 3 cases, diabetes mellitus in 2 cases and rheumatoid arthritis in 2 cases. The C2–C7 cervical coronal vertical axis was distributed more to the right side (2.6 ± 12.8 mm). Regarding sagittal alignment, 24 cases (35.8%) showed negative balanced DHS (N-DHS) and 43 cases (64.2%) showed positive balanced DHS (P-DHS). There were significant differences in C2–C7 angle, T1S, LL and PI-LL between the two groups. Cervical or back pain was present in 62 cases (92.5%), and average numerical rating scale was 3.0 ± 2.6. Fourteen cases (20.9%) recovered (average 11.3 months), but 29 cases (43.3%) did not recover without surgery. Twenty-four cases (35.8%) underwent surgery, 20 for cervical spine and 4 for thoraco-lumbar spine, and horizontal gaze difficulty was improved in all patients post-surgery. Conclusion DHS was mainly observed in elderly women. About 20% of DHS patients recovered without surgical treatment. DHS was accompanied by scoliosis in 37.3% of the cases.

Osteoporotic vertebral fracture (OVF) with nonunion or neurological deficit may be a candidate for surgical treatment. However, some patients do not show improvement as expected. Therefore, we conducted a nationwide multicenter study to determine the predictors for postoperative poor activity of daily living (ADL) in patients with OVF. We retrospectively reviewed the case histories of 309 patients with OVF who underwent surgery. To determine the factors predicting postoperative poor ADL, uni- and multivariate statistical analyses were performed. The frequency of poor ADL at final follow-up period was 9.1%. In univariate analysis, preoperative neurological deficit (OR, 4.1; 95% CI, 1.8–10.3; P

Background Nerve growth factor (NGF) is associated with arthritic pain and metalloproteinases are implicated in collagen and aggrecan degradation. Although selective COX-2 inhibitors are recommended for the treatment of arthritic diseases, their effects on NGF and metalloproteinases remain unclear. This study investigated the regulations of NGF and metalloproteinases by selective COX-2 inhibitors in isolated human synovial cells. Methods The isolated human synovial cells were stimulated with IL-1β in the presence of selective COX-2 inhibitors (NS-398 or celecoxib) with or without exogenous PGE 2 or its receptor (EP1-4) agonists. The expressions of NGF, MMP-1, -3, -13, ADAMTS-4, and -5 were quantified by real-time PCR and their proteins were determined by Western blotting. The amount of PGE 2 released was measured by enzyme-linked immunosorbent assay (ELISA). Results The IL-1β inductions of NGF and MMP-1 and MMP-13 were augmented by the COX-2 inhibitors, whereas the inductions of ADAMTS-4 and ADAMTS-5 were inhibited. These actions were reversed by supplementing PGE 2 or the EP4 agonist exogenously. Conclusion Our comprehensive analysis revealed that COX-2 inhibitors may be beneficial for suppressing aggrecan degradation and for reducing inflammatory pain by inhibiting PGE 2 release, although they may have limited efficacy in suppressing collagen degradation and nerve growth. This study suggests the feedback roles of PGE 2 in the negative regulation of NGF and MMP-1 and MMP-13 and the positive regulation of ADAMTS-4 and ADAMTS-5.

Purpose: The initial treatment of dropped head syndrome (DHS) is basically nonsurgical, but the mode of onset of DHS and efficacy of conservative treatment have not been fully clarified. Methods: The subjects were 38 DHS patients without neuromuscular disease (11 men and 27 women, average age 74.5 years). Cervical collar, physical therapy, and temporary medication for cervical pain were provided for all DHS patients. The following parameters were measured on lateral global spine standing radiographs: sagittal vertical axis (SVA), cervical sagittal vertical axis, C2–C7 angle, first thoracic slope, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence. According to the mode of onset of DHS, the subjects were classified into acute-onset group (Results: Acute- and chronic-onset DHS were observed in 20 and 18 patients, respectively. A history of cervical trauma was involved in nine and two cases of acute- and chronic-onset DHS, respectively. Acute-onset DHS included more balanced-SVA (B-SVA: −30 mm Conclusions: Acute-onset DHS includes more balanced SVA and a history of cervical trauma, while acute-onset DHS without a history of cervical trauma has better prognosis by conservative treatment. Surgical indications for DHS should be carefully determined, and sufficient conservative treatment is essential.

Pulsed electromagnetic fields (PEMFs) have been shown to be a noninvasive physical stimulant for bone fracture healing. However, PEMF stimulation requires a relatively long period of time and its mechanism of action has not yet been fully clarified. Recently, the mammalian target of rapamycin (mTOR) pathway has been shown to be involved in bone formation. This study aimed to investigate the effects of PEMFs on osteoblastic MC3T3-E1 cells by examining various cellular responses including changes in the mTOR pathway. Continuous PEMF stimulation induced a transient phosphorylation of the mTOR pathway, whereas intermittent PEMF stimulation (1 cycle of 10 min stimulation followed by 20 min of stimulation pause) revitalized the reduced phosphorylation. Moreover, PEMF stimulation stimulated cell proliferation (bromodeoxyuridine incorporation) rather than differentiation (alkaline phosphatase activity), with a more notable effect in the intermittently stimulated cells. These results suggest that intermittent PEMF stimulation may be effective in promoting bone fracture healing by accelerating cell proliferation, and in shortening stimulation time. Bioelectromagnetics. 2019;40:412-421. © 2019 Bioelectromagnetics Society.

OBJECTIVEPreoperative positive cervical sagittal imbalance and global sagittal imbalance are risk factors for postoperative cervical kyphosis after expansive open-door cervical laminoplasty (ELAP). The purpose of this study was to investigate the relationship between the incidence of postoperative cervical kyphosis after ELAP and the preoperative global sagittal spinal alignment in patients with cervical spondylotic myelopathy (CSM) without spinal sagittal imbalance.METHODSAmong 84 consecutive patients who underwent ELAP for CSM at the authors’ hospital, 43 patients without preoperative cervical kyphosis (C2–7 angle ≥ 0°) and spinal sagittal imbalance (C2–7 sagittal vertical axis [SVA] ≤ 80 mm and C-7 SVA ≤ 95 mm) were included in the study. The global spinal sagittal parameters were measured on lateral whole-spine standing radiographs preoperatively and at 1 year postoperatively. The difference in preoperative global sagittal spinal alignment between the postoperative cervical lordosis group and the cervical kyphosis group was analyzed.RESULTSThe incidence of postoperative cervical kyphosis after ELAP was 25.6% (11 of 43 cases). Thirty-two patients (16 men and 16 women; mean age 67.7 ± 12.0 years) had lordosis, and 11 (7 men and 4 women; mean age 67.2 ± 9.6 years) had kyphosis. The preoperative C-7 SVA and pelvic incidence minus lumbar lordosis (PI−LL) in the kyphosis group were significantly smaller than those in the lordosis group (p < 0.05). The smaller C-7 SVA accompanied by a small PI−LL, the “truncal negative offset,” led to postoperative cervical kyphosis due to posterior structural weakening by ELAP.CONCLUSIONSIn patients with CSM without preoperative cervical and global spinal sagittal imbalance, a small SVA accompanied by lumbar hyperlordosis is the characteristic alignment leading to postoperative cervical kyphosis after ELAP.

Lumbo-pelvic sagittal alignment is affected by pelvic incidence (PI), and the PI represents the compensatory capacity of lumbo-pelvic sagittal alignment. The purpose of this study was to analyze changes in lumbo-pelvic sagittal alignment between the standing and sitting positions and to analyze its association with PI. This study included 253 subjects (160 men and 93 women; age 53.6 ± 7.4 years). The subjects were divided into three groups (younger age group (YG), from 20 to 49 years; middle age group, from 50 to 69 years, and older age group (OG), of 70 years and above). Lumbar lordotic angle (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and the associations between the changes in LL (∆LL), SS (∆SS), PT (∆PT), and PI were analyzed. In the YG, the amount of change in LL, SS, and PT was larger than in the OG. These parameters correlated with age in the standing position but not in the sitting position. On the other hand, in all groups, there were positive correlations between PI and changes between the standing and sitting positions. Multiple logistic regression analysis demonstrated that ∆LL = 3.81 − 0.72 × PT + 0.52 × PI, ∆SS = − 4.50 − 5.3 × PT + 0.34 × PI, and ∆PT = − 9.1 + 3.5 × PT − 0.21 × PI. Change in lumbo-pelvic parameters between the sitting and standing positions correlated with PI. These slides can be retrieved under Electronic Supplementary Material.

Purpose: Global sagittal spinal alignment undergoes changes on the basis of sagittal malalignment (trunk inclined forward) in natural degenerative progression. We hypothesized that this change would associate with the disease state of the degenerative lumbar spondylolisthesis (DS). This study aimed to evaluate the global sagittal spinal alignment of low-grade DS by classifying in accordance with sagittal vertical axis (SVA). Methods: The DS group was classified into three types according to the adult spinal deformity classification: type 1, SVA < 40 mm; type 2, 40 mm ≤ SVA < 95 mm; and type 3, 95 mm ≤ SVA. Age and sagittal spinal parameters (thoracic kyphosis, lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI)) were compared among three types. Results: There were statistically significant differences in age, LL, PI, and PT among the three types. In comparison between two types, there was a statistically significant difference between type 1 and type 2 and between type 1 and type 3, but not between type 2 and type 3 in these parameters. PI tended to increase as the type increases. Furthermore, there was significant difference between types 1 and 3. Conclusion: We evaluated the features of the DS types classified by sagittal alignment. Large PI is one of the risk factors for SVA deterioration of DS. PI may be involved in the onset and progression of DS.

Study design Regulation of nerve growth factor (NGF) by 2 different anti-inflammatory drugs was investigated in vitro using isolated human intervertebral disc (IVD) cells stimulated with the proinflammatory cytokine interleukin-1 (IL-1). Objective To investigate the regulation of NGF by a synthetic steroid and a selective cyclooxygenase-2 (COX-2) inhibitor and to clarify the biological role of prostaglandin E2 (PGE2) in this process. Summary of background data NGF is known to play an important role in pain, including low back pain, and to be induced by proinflammatory cytokines in IVD cells. However, the effect of clinically used drugs for managing low back pain on the regulation of NGF is unclear. Methods Isolated human IVD cells were stimulated with interleukin-1 (IL-1) in the presence or absence of dexamethasone or a selective COX-2 inhibitor (NS-398). NGF expression and release were determined by real-time polymerase chain reaction and enzyme-linked immuno sorbent assay, respectively. Inhibition of PGE2 release was determined by enzyme-linked immuno sorbent assay. The effects of exogenous PGE2 and its receptor (E-series prostanoid receptors [EPs] 1-4) agonists were also tested for NGF regulation. Results IL-1 transiently induced, in a dose-dependent manner, the induction of NGF in human IVD cells. Pretreatment with dexamethasone strongly inhibited the NGF expression, whereas NS-398 significantly enhanced it at the concentration at which PGE2 release was substantially inhibited. Exogenous PGE2 inhibited IL-1 induction of NGF and this effect was mimicked when EP2 and EP4, but not EP1 and EP3, agonists were supplemented to the culture. Conclusion Although selective COX-2 inhibitors have been shown to be effective for acute low back pain by inhibiting PGE2 release, our findings suggest that it may have a limited efficacy because it exaggerated NGF expression, whereas dexamethasone inhibited it. On the other hand, PGE2 had an inhibitory function for NGF induction by mediating EP2/4 in human IVD cells. Further studies are needed to clarify whether these observations could take place in vivo. Level of evidence N/A.

Purpose.To evaluate the association between cervical sagittal alignment and thoracic/lumbopelvic sagittal alignment in healthy Japanese adults.Methods.30 male and 22 female healthy adults aged 22 to 50 years were recruited. Spinal parameters were measured on radiographs, including the cervical sagittal vertical axis, sagittal vertical axis, C7 tilt angle, Ishihara index for cervical lordosis, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence.Results.The C7 tilt angle positively correlated with the Ishihara index ( r=0.52, pConclusion.In healthy Japanese adults, cervical sagittal alignment is associated with thoracic sagittal alignment but not with lumbopelvic alignment.

STUDY DESIGN In vitro study using isolated human intervertebral disc (IVD) cells. OBJECTIVE To investigate the effects of prostaglandin (PG)E1 and its orally available derivative limaprost on the regulation of nerve growth factor (NGF) expression and to compare their actions with other prostanoids using interleukin (IL)-1-stimulated human IVD cells. SUMMARY OF BACKGROUND DATA We previously reported that a selective COX-2 inhibitor enhanced, whereas PGE2 suppressed the induction of NGF by IL-1 in human IVD cells, and proposed that PGE2 can suppress NGF expression by a negative feedback mechanism. METHODS Isolated human IVD cells were stimulated with IL-1 in the presence or absence of increasing concentrations of PGE2, PGE1, limaprost, PGI2, PGD2, or PGF2α (10-10,000 nM). For some experiments, an E-series prostanoid receptor (EP)4 antagonist (L-161,982) was added prior to the stimulation. NGF expression was determined by real-time polymerase chain reaction and its protein level was quantified by enzyme-linked immunosorbent assay. RESULTS PGE2, PGE1, and limaprost inhibited the IL-1-mediated induction of NGF in a concentration-dependent manner, with IC50 values of 9.9, 10.6, and 70.9 nM, respectively. PGI2 also suppressed NGF expression but to a much less extent. PGD2, on the other hand, significantly enhanced NGF expression, whereas PGF2α had no effect. Protein expression levels of NGF mirrored its mRNA levels. The suppression of NGF expression by PGE2 and PGE1 was partly reversed by L-161,982. CONCLUSION PGE1 and limaprost exhibited a novel pharmacological action that suppresses NGF expression in human IVD cells, and other prostanoids differentially regulated NGF expression. Limaprost has been used to treat patients with lumbar spinal stenosis in Japan and was proved to be effective in relieving symptoms. Our in vitro results may explain, in part, the mechanism of action of limaprost for low back pain. LEVEL OF EVIDENCE N/A.

Expression of membrane type-1 matrix metalloproteinase (MT1-MMP) is closely correlated with tumor invasiveness. We investigated the effect of hyperthermia on the production of MT1-MMP in human fibrosarcoma HT-1080 cells. Heat shock at 42 degrees C suppressed the production and gene expression of MT1-MMP in HT-1080 cells. Heat shock-induced suppression of MT1-MMP production resulted in the inhibition of progelatinase A (proMMP-2) activation and the increased release of tissue inhibitor of metalloproteinases 2 from cell surface. In addition, in vitro tumor invasion assay in a Matrigel model indicated that heat shock inhibited the invasive activity of HT-1080 cells. These results suggest that heat shock preferentially suppresses the production of MT1-MMP and thereby inhibits proMMP-2 activation, events which subsequently inhibit tumor invasion. Therefore, heat shock shows an anti-invasive effect along with the known mechanism of inhibiting tumor growth.