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Deep tendon reflexes are one of the main components of the clinical nervous system examinations. These assessments are inexpensive and quick. However, evaluation can be subjective and qualitative. This study aimed to objectively evaluate hyperreflexia of the patellar tendon reflex using portable mechanomyography (MMG) and electromyography (EMG) devices. This study included 10 preoperative patients (20 legs) who had a pathology that could cause bilateral patellar tendon hyperreflexia and 12 healthy volunteers (24 legs) with no prior history of neurological disorders. We attached MMG/EMG sensors onto the quadriceps and tapped the patellar tendon with maximal and constant force. Our results showed a significantly high amplitude of the root mean square (RMS) and low frequency of the mean power frequency (MPF) in the rectus femoris, vastus medialis, and vastus lateralis muscles in both EMG and MMG with both maximal and constant force. Especially in the patients with cervical and thoracic myelopathy, the receiver operating characteristic (ROC) curve for diagnosing hyperreflexia of the patellar tendon showed a moderate to very high area under the curve for all EMG–RMS, EMG–MPF, MMG–RMS, and MMG–MPF values. The use of EMG and MMG for objectively quantifying the patellar tendon reflex is simple and desirable for future clinical applications and could help diagnose neurological disorders.

Unstable pelvic fractures, especially vertical shear fractures, require surgery for correct reduction, rigid fixation, and improved postoperative outcomes. Herein, we assess the effectiveness of our minimally invasive procedure for the management of unstable pelvic fractures.We hypothesized that this procedure would be useful for the management of unstable pelvic fractures.This study included 28 patients with unstable pelvic fractures (vertical shear injuries; AO types C1-3) treated using minimally invasive surgery for spinopelvic fixation (MIS-SP) between 2014 and 2020 (mean follow-up time, 15 months). The MIS-SP requires four percutaneous pedicle screws and four iliac screw insertions. Subsequently, reduction and fixation are performed.The mean preoperative displacement of the posterior pelvic elements in craniocaudal correction was 17.6 (range, 9.0-32.2) mm. The mean length of the craniocaudal reduction was 16.5 (8.1-30.1) mm, with a mean reduction rate of 93.5% (78%-100%). The mean length of the mediolateral reduction was 11.3 (3.9-19.6) mm, with a mean reduction rate of 87.3% (76%-100%).Our novel reduction and fixation procedure is a powerful, minimally invasive option for the treatment of unstable pelvic ring fractures.III.

Background: To compare the clinical, surgical and radiographic outcomes of O-arm navigated C-arm free, simultaneous single-position oblique lumbar interbody fusion (OLIF) and percutaneous pedicle screw (PPS) fixation with minimally invasive posterior/ transforaminal lumbar interbody fusion (MI-PLIF/TLIF).Methods: This is retrospective comparative study. The study included 98 patients, 63 in single position OLIF (group SO) and 35 in MI-PLIF/TLIF (group P/T). Surgical time, blood loss, mobilization time after surgery and complications were analyzed for all patients. Clinical evaluation included visual analog scale (VAS) for back pain, oswestry disability index (ODI). Radiological parameters included cage height (CH), cage to disc ratio (CDR), DH change, pre and postoperative disc height (DH), foraminal height (FH), foraminal area (FA), segmental lordosis (SL). Results: In group SO (vs group P/T), surgical time, blood loss and mobilization time were 117.7± 34.1 minutes (171.8 ± 40.6 minutes, pppConclusions: Simultaneous single position O-arm navigated C-arm free OLIF reduces the surgical time, blood loss, mobilization time after operation without the risk of an adverse event of intraoperative radiation to operating staff. Good indirect decompression can be achieved with this method. Clinical results were similar in both groups.

Minimally invasive posterior or transforaminal lumbar interbody fusion (MI-PLIF/TLIF) are widely accepted procedures for lumbar instability due to degenerative or traumatic diseases. Oblique lateral interbody fusion (OLIF) is currently receiving considerable attention because of the reductions in damage to the back muscles and neural tissue. The aim of this study was to compare clinical and radiographic outcomes of simultaneous single-position OLIF and percutaneous pedicle screw (PPS) fixation with MI-PLIF/TLIF. This retrospective comparative study included 98 patients, comprising 63 patients with single-position OLIF (Group SO) and 35 patients with MI-PLIF/TLIF (Group P/T). Cases with more than 1 year of follow-up were included in this study. Mean follow-up was 32.9 ± 7.0 months for Group SO and 33.7 ± 7.5 months for Group P/T. Clinical and radiological evaluations were performed. Comparing Group SO to Group P/T, surgical time and blood loss were 118 versus 172 min (p &lt, 0.01) and 139 versus 374 mL (p &lt, 0.01), respectively. Cage height, change in disk height, and postoperative foraminal height were significantly higher in Group SO than in Group P/T. The fusion rate was 96.8% in Group SO, similar to the 94.2% in Group P/T (p = 0.985). The complication rate was 6.3% in Group SO and 14.1% in Group P/T (p = 0.191). Simultaneous single position O-arm-navigated OLIF reduces the surgical time, blood loss, and time to ambulation after surgery. Good indirect decompression can be achieved with this method.

Study Design: This is a virtual three-dimensional (3D) imaging study examining computed tomography (CT) data to investigate instrumentation placement.Purpose: In this study, we aim to clarify the ideal entry point and trajectory of the sacral alar iliac (SAI) screw in relationship to the dorsal foramen at S1 and the respective nerve root.Overview of Literature: To the best of our knowledge, there is yet no detailed 3D imaging study on the ideal entry point of the SAI screw. Despite the evidence suggesting that the dorsal foramen at S1 is a landmark on the sacrum, the S1 nerve root disruption is a general concern during the insertion of SAI screws. No other study has been published examining the nerve root location at the S1and SAI screw insertions.Methods: Preoperative CT data from 26 patients pertaining to adult spinal deformities were investigated in this study. We applied a 3D image processing method for a detailed investigation. Virtual cylinders were used to mimic SAI screws. These were placed to penetrate the sacral iliac joint without violating the other cortex. We then assessed the trajectory of the longest SAI screw and the ideal entry point of SAI using a color mapping method on the surface of the sacrum. We measured the location of the nerve root at S1 in relation to the foramen at S1 and the sacral surface.Results: As per the results of our color mapping, it was determined that areas that received high scores are located medially and caudally to the dorsal foramen of S1. The mean angle between a horizontal line and a line connecting the medial edge of the foramen and nerve root at S1 was 93.5°. The mean distances from the dorsal medial edge of the foramen and sacral surface to S1 nerve root were 21.8 mm and 13.9 mm, respectively.Conclusions: The ideal entry point of the SAI screw is located medially and caudally to the S1 dorsal foramen based on 3D digital mapping. It is also shown that this entry point spares the S1 nerve root from possible iatrogenic injuries.

Spinopelvic fixation provides a strong fixation for unstable pelvic ring fractures. However, the technique is usually performed with the patient in the prone position, with the applied weight on the anterior superior iliac crests aggravating fracture displacement. We developed a novel approach for minimally invasive percutaneous spinopelvic fixation that is performed with the patient in a lateral (side lying) position. We describe the application of our technique for the treatment of a bilateral pelvic ring and acetabulum fracture in a 79-year-old woman injured in a traffic accident. Initial posterior fixation was performed with the patient in the left-side lying position, using bilateral pedicle screws at L3 and L4 and a left sacral-alar iliac screw and 2 right iliac screws inserted under navigation. The lateral and cranial displacement of the right pelvic ring was reduced percutaneously. One week after this initial surgery, we proceeded with an open anterior reduction and internal fixation of the left pelvic ring and acetabulum fracture. The postoperative course was uneventful and clinical outcomes were satisfactory. Reduction of a pelvic ring fracture in a lateral position, with subsequent spinopelvic fixation, is a reasonable option for the treatment of an unstable pelvic ring fracture.

A 24-year-old man presented with a dumbbell-shaped right posterior mediastinal mass. The patient was placed in the prone position following general anaesthesia and intubation. After laminectomy and dissection of the dorsal part of the tumour using a posterior approach were performed, the tumour was completely resected using a robotic approach in the thoracic cavity without repositioning. This is the first report of robotic resection for posterior mediastinal tumour in the prone position as well as a novel combined posterior approach and robotic resection for dumbbell tumours.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population., Koda et al. present the results of a randomized phase 3 trial comparing granulocyte colony-stimulating factor versus placebo in patients with acute spinal cord injury. While the primary endpoint was not met, a sub-analysis revealed a trend towards superior efficacy of G-CSF versus placebo in an elderly population.

Background Mirogabalin, which is approved for the treatment of peripheral neuropathic pain in Japan, is a ligand for the α2δ subunit of voltage-gated calcium channels. Both pregabalin and mirogabalin act as nonselective ligands at the α2δ-1 and α2δ-2 subunits. Mirogabalin has a unique binding profile and long duration of action. Pregabalin has been reported to produce intolerable adverse effects in some patients. This study investigated outcomes associated with mirogabalin administration in patients with peripheral neuropathic pain who ceased treatment with pregabalin. Methods We retrospectively assessed peripheral neuropathic pain using the neuropathic pain screening questionnaire (NeP score) in 187 patients (58 men, 129 women) who were treated with mirogabalin. All patients had switched from pregabalin to mirogabalin due to lack of efficacy or adverse events. Differences in the treatment course (i.e., numeric rating scale (NRS) scores) were compared using one-way analysis of variance with Bonferroni post hoc tests. Results The mean age of the patients was 72.3 years (range, 30–94 years), and the mean duration of disease was 37 months (range, 3–252 months). After treatment with mirogabalin for 1 week, NRS scores significantly decreased compared with baseline and continued to decrease over time. After 8 weeks, NRS scores improved by ≥ 30% from baseline in 113 patients (69.3%). Twenty-four patients (12.8%) stopped mirogabalin treatment due to adverse events. Somnolence (26.7%), dizziness (12.3%), edema (5.9%), and weight gain (0.5%) were noted as adverse events of mirogabalin. Conclusions The results of this investigation indicate that mirogabalin is safe and effective for reducing peripheral neuropathic pain.

Study DesignCross sectional study.PurposeTo clarify the difference in position of the psoas muscle between adult spinal deformity (ASD) and lumbar spinal stenosis (LSS).Overview of LiteratureAlthough it is known that the psoas major muscle deviates in ASD patients, no report is available regarding the difference in comparison with LSS patients.MethodsThis study investigates 39 patients. For evaluating spinal alignment, pelvic tilt (PT), pelvic incidence (PI), sacral slope, lumbar lordosis (LL), PI–LL, Cobb angle, and the convex side, the lumbar curves were measured. For measuring the position of the psoas major at the L4/5 disk level, magnetic resonance imaging was used. The displacements of psoas major muscle were measured separately in the anterior–posterior and lateral directions. We examined the relationship between the radiographic parameters and anterior displacement (AD) and lateral displacement (LD) of the psoas major muscle.ResultsAD was demonstrated in 15 cases with ASD and nine cases with LSS (p>0.05). LD was observed in 13 cases with ASD and no cases with LSS (pp=0.04). PT, LL, PI–LL, and Cobb angle were significantly greater in cases with LD (ppConclusionsDespite AD being observed in LSS as well, LD was observed only in the ASD group. Radiographic parameters were worse when LD was seen, rather than AD.

Study DesignRetrospective analysis using magnetic resonance imaging (MRI).PurposeTo identify MRI features that could discriminate benign from malignant vertebral fractures.Overview of LiteratureDiscrimination between benign and malignant vertebral fractures remains challenging, particularly in patients with osteoporosis and cancer. Presently, the most sensitive means of detecting and assessing fracture etiology is MRI. However, published reports have focused on only one or a few discriminators.MethodsTotally, 106 patients were assessed by MRI within six weeks of sustaining 114 thoracic and/or lumbar vertebral fractures (benign, n=65; malignant, n=49). The fractures were pathologically confirmed if malignant or clinically diagnosed if benign and were followed up for a minimum of six months. Seventeen features were analyzed in all fractures' magnetic resonance images. Single parameters were analyzed using the chi-square test; a logit model was established using multivariate logistic regression analysis.ResultsThe chi-square test revealed 11 malignant and 4 benign parameters. Multivariate logistic regression analysis selected (i) posterior wall diffuse protrusion (odds ratio [OR], 48; 95% confidence interval [CI], 4.2–548; p=0.002), (ii) pedicle involvement (OR, 21; 95% CI, 2.0–229; p=0.01), (iii) posterior involvement (OR, 21; 95% CI, 1.5–21; p=0.02), and (iv) band pattern (OR, 0.047; 95% CI, 0.0005–4.7; p=0.19). The logit model was expressed as P=1/[1+exp (x)], x=−3.88×(i)−3.05×(ii)−3.02×(iii)+3.05×(iv)+5.00, where P is the probability of malignancy. The total predictive value was 97.3%. The only exception was multiple myeloma with features of a benign fracture.ConclusionsAlthough each MRI feature had a different meaning with a variable differentiation power, combining them led to an accurate diagnosis. This study identified the most relevant MRI features that would be helpful in discriminating benign from malignant vertebral fractures.

Background Although a multidisciplinary approach is often recommended to treat intractable pain, this approach does not completely prevent uncontrolled pain in some patients. The aim of this retrospective study was to investigate the exacerbating factors of prolonged, intractable pain among patients being treated at a pain liaison clinic. Methods The participants of this study were 94 outpatients (32 men, 62 women) with chronic intractable pain who visited our hospital between April 2013 and February 2015. Demographic and clinical information was obtained from all patients at baseline. Experts in various fields, including anesthesia, orthopedic surgery, psychiatry, physical therapy, and nursing, were involved in the treatment procedures. All patients were assessed before and after a 6-month treatment period using the following measures: the Numeric Rating Scale (NRS); the Pain Catastrophizing Scale (PCS); the Hospital Anxiety and Depression Scale (HADS); the Pain Disability Assessment Scale (PDAS); and the Oswestry Disability Index (ODI). All participants were then divided into two groups based on their self-reported pain after treatment: a pain relief group ( n = 70) and a prolonged pain group ( n = 24). The exacerbating factors of prolonged pain after treatment in the pain liaison outpatient clinic were analyzed using univariate and multiple logistic regression analysis. Results A significant improvement in NRS scores was observed after the 6-month follow-up period. After treatment, 24 (25.5%) of the 94 patients reported having prolonged pain. Significant improvements were seen in the PCS, PDAS, and ODI scores in the pain relief group, and in the HADS depression scores in the prolonged pain group. On univariate and multiple regression analysis, HADS depression scores were identified as a factor related to prolonged pain after treatment. Conclusions The results of the present study suggest that severe depression at the initial visit to the liaison outpatient clinic was an exacerbating factor for prolonged pain after treatment.

Introduction Denosumab specifically inhibits the receptor activator for nuclear factor-kappa B ligand (RANKL), and prevents osteoporotic fractures. Several reports have analyzed the effects of denosumab and alendronate alone on bone mineral density (BMD) or reduction of fracture risk. The objective of this study was to analyze the effects of antiresorptive osteoporosis pharmacotherapy on pain relief in patients with fresh vertebral fracture. Methods This retrospective, single-center study included 80 patients (10 males, 70 females) with fresh osteoporotic vertebral fractures treated using denosumab at a dose of 60 mg subcutaneously every 6 months (40 patients) or alendronate at a dose of 35 mg orally every week (40 patients) for 6 months in our hospital. The mean age of subjects was 77 years (range, 55–92 years). The primary outcome was duration of back pain. Secondary outcomes included changes in BMD, serum type 1 collagen cross-linked N-telopeptide (NTX), and serum N-terminal propeptide of type 1 collagen (P1NP) from baseline to 6 months. Pain catastrophizing due to back pain was assessed using the Pain Catastrophizing Scale (PCS). The incidences of further vertebral fracture and adverse events were also assessed. Results Pain relief was obtained at a mean of 3.3 weeks with denosumab and 5.4 weeks with alendronate. Pain relief was achieved significantly earlier with denosumab than with alendronate. At 6 months, change in BMD was higher with denosumab (6.1%) than with alendronate (0.8%). No significant differences in changes in NTX and P1NP were observed between groups. Scores for PCS were significantly lower for denosumab than for alendronate. The incidence of further vertebral fractures was 5% with denosumab and 10% with alendronate. Adverse event rates were similar between groups. Conclusions Denosumab enabled earlier pain relief than alendronate and avoided catastrophizing in patients with osteoporotic vertebral fractures after 6 months of treatment.

Vertical sacral fracture is one of the most difficult fractures to treat. Posterior fixation using spinal dual rods is a novel method for treating this fracture, but its biomechanical strength has not yet been reported. The aim of this study was to evaluate the biomechanical strength produced by posterior fixation using spinal instrumentation. Sacral fractures were created in eight pelvic bone models and classifi ed into a posterior plate fixation group [P group, n＝4] and a spinal instrumentation group [R group, n＝4]. The biomechanical strength was tested by pushing down on the S1 vertebra from the top. The mean maximum loads were 1,057.4 N and 1,489.4 N in the P and R groups, respectively (p＝ 0.014). The loads applied to the construct at displacements of 5mm and 7.5mm from the start of the universal testing machine loading were also significantly higher in the R group. The mean stiffness levels in the P and R groups were 88.3N/mm and 119.6N/mm, respectively (p＝0.014). Posterior fixation using spinal instrumentation is biomechanically stronger than conventional posterior plate fixation. This procedure may be the optimal method for treating unstable sacral fracture fixation.

Study design Retrospective case series of one institute database. Objective To investigate the differences in the metallic strength of rods used for implant failure in the dual growing rod technique and evaluate clinical outcomes. Summary of background data The dual growing rod technique in which implanted rods extend with the growth of the spine is a useful treatment for early onset scoliosis. However, many complications, particularly those associated with rods, exist. Especially, the implant failure of growing rod focused on metallic strength is unknown. Methods Thirteen patients (42 lengthening surgeries) who underwent surgery by this technique at our hospital from 2007 were divided into a titanium rod plus titanium connector group (T group, n = 4, 26 lengthening surgeries) and cobalt-chromium rod plus titanium connection group (C group, n = 9, 16 lengthening surgeries). The incidence of implant failure and the site of fracture were retrospectively investigated. Results Implant failure occurred in three patients in the T group, because of rod fracture in two patients and connector fracture in one. In the C group, implant failure occurred in six patients, because of rod fracture in one patient and connector fracture in seven. Fracture occurred twice in two patients. The rod fracture rate decreased with the use of cobalt-chromium rods but the rate of connector fracture increased. We performed a stress distribution analysis using the finite element method to clarify the mechanisms underlying implant failure in both groups. Regardless of the rod type, the greater load was placed on the distal rod. However, differences in the metallic strength caused the rod to fracture when titanium rods were used and connectors (weak metallic strength) to fracture when cobalt-chromium rods were used. Conclusion Rod fractures occurred more commonly with titanium rods and connector fractures with cobalt-chromium rods.

Computer-assisted spinal surgery is becoming more common; however, this is the first technical report to describe the technique of minimally invasive spinal posterior lumbar interbody fusion (MIS-PLIF) without using C-arm fluoroscopy. The authors report 2 years of follow-up of a 49-year-old female patient with L4 degenerative spondylolisthesis. The patient suffered from low back pain and intermittent claudication for more than 6 years. The authors performed computer-assisted MIS-PLIF without C-arm fluoroscopy. Instead, O-arm® navigation, the use of which reduces radiation exposure to patients as well as others in the operating room, was employed. Surgery was successful, and correct lumbar alignment was maintained. She had neither neurological deficits nor low back pain at her 12-month final follow-up. In conclusion, computer-assisted MIS-PLIF without C-arm fluoroscopy is a useful technique that reduces radiation exposure to the surgeon and operating room staff.

The presence of preoperative kyphosis has been identified as a risk factor for laminar closure (LC). We have been performing modified open-door laminoplasty with reattachment of the spinous processes and extensor musculature for patients with reduced cervical lordosis because this procedure can prevent progression of cervical kyphosis. This procedure may also prevent LC. The purpose of this study was to evaluate the rate of LC after the modified open-door laminoplasty. A total of 104 patients who underwent open-door laminoplasty were retrospectively reviewed. Of these patients, 18 underwent modified open-door laminoplasty (group M), whereas the other 86 underwent Hirabayashi open-door laminoplasty (group H). Group H was divided into two classes according to the preoperative cervical lordosis angle (group H1 ≤ 10° vs. group H2 ≥ 11°). All 18 patients in group M had a preoperative lordosis angle ≤10°. The outcomes were assessed using the rate of LC, the cross-sectional area (CSA) of the erector muscle on magnetic resonance imaging, and the Japanese Orthopaedic Association score (JOA score). The rate of laminar closure was significantly lower in group M (39 %) than in group H1 (76 %) (P

Background Intraoperative neuromonitoring using motor evoked potentials (MEP) satisfactorily detects motor tract integrity changes during spinal surgery. However, monitoring is affected by “anesthetic fade,” in which the stimulation threshold increases because the waveform amplitude decreases with the accumulation of propofol. Therefore, the purpose of this study was to clarify the effect of anesthetic fade on transcranial MEPs by investigating the time-dependent changes of amplitude during spinal deformity surgeries. Methods We retrospectively reviewed medical records of 142 spinal deformity patients (66 patients with idiopathic scoliosis, 28 with adult spinal deformities, 19 with neuromuscular scoliosis, 17 with syndromic scoliosis, and 12 with congenital scoliosis). The average age was 28 years (range, 5 to 81 years). MEPs were recorded bilaterally from the abductor digiti minimi (ADM) and abductor hallucis (AH) muscles during spinal deformity surgeries. The Wilcoxon signed-rank test was used to investigate the time-dependent changes of amplitude after propofol infusion to evaluate anesthetic fade effects. Results The average time to baseline from initial propofol infusion was 113 min (range, 45 to 182 min). In the ADM, the amplitude was 52% at 1 h after initial propofol infusion, 102% at 2 h, 105% at 3 h, 101% at 4 h, 86% at 5 h, and 81% at 6 h. Compared to the 2-h time point, MEP decreased significantly by 16% at 5 h (P

Spinal cord injury (SCI) results in neural tissue loss and so far untreatable functional impairment. In addition, at the initial injury site, inflammation induces secondary damage, and glial scar formation occurs to limit inflammation-mediated tissue damage. Consequently, it obstructs neural regeneration. Many studies have been conducted in the field of SCI; however, no satisfactory treatment has been established to date. Hepatocyte growth factor (HGF) is one of the neurotrophic growth factors and has been listed as a candidate medicine for SCI treatment. The highlighted effects of HGF on neural regeneration are associated with its anti-inflammatory and anti-fibrotic activities. Moreover, HGF exerts positive effects on transplanted stem cell differentiation into neurons. This paper reviews the mechanisms underlying the therapeutic effects of HGF in SCI recovery, and introduces recent advances in the clinical applications of HGF therapy.

Background To evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression. Methods The participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). Results The rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021). Conclusions Under BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae.

Recent studies have recognized the involvement of microRNAs (miRNAs) in the development of osteoporosis, which regulate the balance between osteogenesis and osteoclasis. In this study, we investigated the regulation by miRNA-133a-5p on the osteoblast differentiation-associated markers in the mouse osteoblast-like MC3T3-E1 cells by RUNX2. First, we manipulated the miRNA-133a level in the MC3T3-E1 cells with 20 or 40 nM miR-133a-5p mimics, miR-133a-5p inhibitor, or scramble miRNA. Then, we quantified with real-time polymerase chain reaction (qRT-PCR) the expression of Collagen I, osteocalcin (OCN), and osteopontin (OPN) in the miR-133a-5p-manipulated MC3T3-E1 cells. And the confocal microscopy was also utilized to confirm the regulation by miR-133a-5p on the expression of the three molecules. We also investigated the extracellular matrix (ECM) mineralization and the alkaline phosphatase (ALP) activity in the miR-133a-5p-manipulated MC3T3-E1 cells. In addition, we explored the possible targeting by miR-133a-5p on RUNX2, which was a well-recognized promoter to osteoblast differentiation, with luciferase reporter, qRT-PCR, and Western blotting assay. Results demonstrated that the miRNA-133a-5p mimics markedly reduced, whereas the miRNA-133a-5p inhibitor significantly promoted the expression of Collagen I, OCN, and OPN, the ECM mineralization, and the ALP activity in MC3T3-E1 cells. The alignment analysis demonstrated a high homology between miRNA-133a-5p and the 3' UTR of RUNX2. Moreover, the luciferase reporter assay demonstrated that miRNA-133a-5p targeted the 3' UTR of RUNX2, and inhibited the expression of RUNX2 in both mRNA and protein levels. In conclusion, we identified the inhibition by miRNA-133a-5p to the expression of osteoblast differentiation markers, to the ECM mineralization, and to the ALP activity in MC3T3-E1 cells, by targeting the 3' UTR of RUNX2. Our study suggests that miRNA-133a-5p might be an important target to inhibit osteoblast differentiation in osteoporosis.

Radiation therapy (RT) is the common treatment for painful vertebral bone metastases without paralysis by malignant spinal cord compression. However, no studies have focused on the time course of pain after RT. Then, we investigated the change of pain after RT for painful vertebral bone metastases without paralysis.Participants included 101 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. All patients received RT and pain response was evaluated by Numeric Rating Scale (NRS). Follow-up assessments were performed just before the start of RT and every month for six months after RT. Pain response was classified as complete response (CR), partial response (PR), pain progression (PP), and indeterminate response (IR) based on the response criteria of International Bone Metastases Consensus Working Party. Responders were classified as either CR or PR, and non-responders as either PP or IR.Median NRS scores for pain were 5 before RT, decreasing to 0 by one month after RT and remaining zero until last follow-up, representing a significant decrease over time (P 0.001). The rate of responders at each month from one to six months was 93, 96, 95, 100, 98, and 96%, respectively. Multivariate analysis revealed that Spinal Instability Neoplastic Score (SINS) was the only risk factor for response to RT at one month. At one month pain disappeared in 88% of the patients with spinal stability (SINS 7), although pain disappeared 58% of the patients with spinal instability (SINS ≥ 7), which was significant (P = 0.002).Pain decreased significantly over time and 93% of patients were classified as responders as early as one month after RT in patients with painful vertebral bone metastases without paralysis. Pretreatment SINS could be a predictor of pain response to RT.

Although a C2 pedicle screw and a C1–2 transarticular screw are the most rigid anchors, these screws cannot be used in cases with bilateral high-riding vertebral arteries. The authors describe their recent experience using a novel method of C2–3 transuncovertebral joint screw placement for occipitocervical fixation. A 67-year-old patient suffered myelopathy due to instability at C1–2. The patient had bilateral high-riding vertebral arteries that precluded the use of a C2 pedicle screw or a C1–2 transarticular screw. A C2–3 transuncovertebral joint screw was applied bilaterally under 3D navigation guidance. The patient’s postoperative course was uneventful, and his neurological status improved after the surgery. Bony fusion was achieved after the surgery. This is the first report to describe the technique of transuncovertebral joint screw. Using a C2–3 transuncovertebral joint screw, a long screw could be used, and it provided an anchor at C3 and C2 from a posterior approach.

Cervical orthosis is used to immobilize the neck in various disorders such as trauma and post-operation. However, it is still uncertain how cervical orthosis restricts the degree of movement of the cervical spine during swallowing and how they affect swallowing physiology. The purpose of this study was to evaluate these issues using the Philadelphia(®) Collar. We conducted videofluorography of swallowing in 39 healthy subjects (23 men, 16 women; mean age of 34.3 years) with and without cervical orthosis. To compare the two conditions regarding the cervical spine motion, we determined the angular and positional changes of the occipital bone (C0) and each cervical vertebra (C1-C7) from the oral phase to the pharyngeal phase. Similarly, to compare swallowing physiology, we assessed the start and end times and the durations of soft palate elevation, rapid hyoid anterosuperior movement, epiglottis inversion, closure of the laryngeal vestibule, and pharyngoesophageal segment (PES) opening. Finally, we compared the transit times of contrast agent in the two conditions. The respective extensions of C1, C2, and C3 were 0.31°, 0.07°, and 0.05° (mean) with cervical orthosis, and the respective flexions of C1, C2, and C3 were 0.98°, 1.42°, and 0.85° (mean) without. These results suggested that cervical orthosis restricted the flexion of C1-C3. Analysis of swallowing physiology revealed that the average durations of hyoid anterosuperior elevation, epiglottic inversion, and PES opening were prolonged by 0.09, 0.19, and 0.05 s, respectively. In conclusion, the cervical orthosis restricted the movement of the cervical spine during swallowing and changed swallowing physiology.

Primary spinal osteosarcoma is quite rare, and the 5-year survival rate is very low. Because of its rarity, successful treatment experience with spinal osteosarcoma is limited. The purpose of this study is to report the effect of therapy of primary osteosarcoma of spine by carbon-ion radiotherapy (CIRT) and long-term follow. A 70-year-old with primary spinal osteosarcoma who received CIRT underwent combined anterior artificial vertebral body replacement and posterior lumbar fusion (L1–L5) 3 years later. According to the surgical resection of tumoral lesion, pathological results showed that the intertrabecular space previously filled with tumor cells on the initial biopsy sample now contained necrotic tissue without tumor cells. This means that primary osteosarcoma of the spine was completely eliminated and achieved local control with CIRT, with a 7-year follow-up after the initial treatment. Carbon ion beam treatment is an effective local treatment for patients with spinal osteosarcoma for whom surgical resection is not a feasible option, especially for elderly patients. However, more patients need to be evaluated over a longer term to assess the curative effect of CIRT.

In our previous study, we focused on the motion of cervical spines in video-fluorography (VF), and we revealed that the physiological lordosises were reduced during normal swallowing. In the study, cervical spines were required to be manually extracted in all the frames of VF. Therefore the study had a difficulty in performing the statistical analysis based on a large amount of patient data. The present study proposes an automatic tracking method of cervical spines in VF by use of the two-dimensional template matching technique. In the method, cervical spines can be extracted automatically, though templates should be set manually only in the first frame of VF. The automatic tracking method was applied to cervical spines, from C1 to C6, in actual VF of ten cases who were planned to undergo posterior cervical spinal fusion. The cervical spines were able to be tracked at the accuracy of more than 77% in the Jaccard index. The experimental results demonstrated that the proposed method was able to analyze the motion of cervical spines in VF during swallowing.

The anti-seizure drug pregabalin is currently used for peripheral neuropathic pain, including degenerative lumbar disease with a neuropathic component. Although there are many reports associated with pregabalin, treatment outcome in low back pain (LBP) patients with depression remains uncertain. This study investigated the outcomes of pregabalin in LBP patients with depression.We assessed 64 patients (29 men and 35 women) using a Visual Analogue Scale, a Self-Rating Depression Scale (SDS) and the Oswestry Disability Index (ODI). Mean age was 63.3 years (range 20-81), and mean duration of disease was 69.8 months (range 3-576). The patients were divided into two groups according to SDS: normal (n = 37) and depressed group (n = 27).Pregabalin significantly reduced both SDS and ODI in the depressed group (p0.05). Effect size was larger for both SDS and ODI in the depressed group than in the normal group. Pain was significantly relieved, even in the depressed group (p0.01). Pain reduction was achieved by the direct effect of pregabalin, as well as indirect effects attributed to change in depressive symptoms. Although both somnolence and dizziness were detected, the use of hypnotic agents was decreased in half of cases. Somnolence did not influence the analgesic effects of the drug or psychotic state.This investigation indicated that pregabalin is safe and effective for reducing both LBP and mood disturbance in patients with depression.

The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous forAdamts4orAdamts5null alleles after spinal cord injury (SCI). ADAMTS-derived 50–60 kDa aggrecan and 50 kDa brevican fragments were observed inAdamts4−/−,Adamts5−/−, andwtmice but not in the sham-operated group. By contrastAdamts4−/−andAdamts5−/−mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot inAdamts4−/−mice’ spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated inAdamts4−/−orAdamts5−/−mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.

Craniometaphyseal dysplasia is a rare genetic condition characterized by progressive thickening of bones in the skull and metaphyseal abnormalities in the long bones. This disorder often causes progressively symptomatic cranial nerve compression, but in rare cases foramen magnum stenosis may lead to quadriplegia. Chiari I malformation with craniometaphyseal dysplasia is extremely rare. The authors report on a 25-year-old woman with myelopathy due to Chiari I malformation along with craniometaphyseal dysplasia. There are only four previous case reports of this condition. The authors present here the fifth case report of this rare condition and summarize its characteristics.

There have been several studies regarding the relationship between deglutition and the cervical spine; however, the movement of the cervical spine during deglutition has not been specifically studied. The purpose of the present study was to clarify how the cervical spine moves during normal deglutition.We conducted videofluorography in 39 healthy individuals (23 men; 16 women; mean age, 34.3 years) with no evidence of cervical spine disease and analyzed images of the oral and pharyngeal phases of swallowing using an image analysis technique. Analyzed sections included the occiput (C0) and the first to seventh cervical vertebrae (C1-C7). The degrees of change in angle and position were quantified in the oral and pharyngeal phases.In the pharyngeal phase, C1, C2, and C3 were flexed (the angle change in C2 was the most significant with a mean flexion angle of 1.42°), while C5 and C6 were extended (the angle change in C5 was the most significant with a mean extension angle of 0.74°) in reference to the oral phase. Angle changes in C0, C4, and C7 were not statistically significant. C3, C4, C5, and C6 moved posteriorly (the movement in C4 was the most significant, mean = 1.04 mm). C1, C2, and C3 moved superiorly (the movement in C2 was the largest, mean = 0.55 mm), and C5 and C6 moved inferiorly. Movements in C0 and C7 were not statistically significant.These findings suggest that the cervical spine moves to reduce physiological lordosis during deglutition.

Depression can exacerbate symptoms of chronic pain and worsen disability. The symptoms of lumbar disease may be particularly sensitive to psychological state, but statistical associations between low back pain (LBP) severity and mental health status have not been established.Of the 151 patients with LBP, 122 completed questionnaires probing depressive symptoms, LBP severity, and degree of disability. In addition to completing self-report questionnaires, patients provided demographic and clinical information. A self-rating depression scale (SDS) was used to screen for depression. Pain and disability were assessed by the visual analog scale (VAS) and the Roland-Morris disability questionnaire (RDQ), respectively. Overall clinical severity was assessed using the Japanese Orthopaedic Association (JOA) score. Kendall's tau correlation coefficients were calculated to examine the relationships among these variables.Ninety-four patients (77 %) were in a depressive state as indicated by SDS score ≥40, including mild depression group (47 patients, SDS score from 40 to 49) and depression group (47 patients, SDS score ≥50). There were only 28 patients in the no depression group (SDS score ≤39). There was no significant difference in both age and pain duration among the three groups. The mean VAS score in the depression group (70 ± 19 mm) was higher than both no depression (41 ± 24 mm) and mild depression groups (52 ± 21 mm). The mean JOA score in the no depression group (14 ± 5.0 points) was higher than both mild depression (12 ± 4.0 points) and depression groups (10 ± 6.0 points). The mean RDQ in the depression group (15.1 ± 6.0 points) was higher than both no depression (6.4 ± 5.0 points) and mild depression groups (10.9 ± 5.4 points). Factors significantly correlated with SDS score included VAS, JOA score, and RDQ score. In contrast, SDS did not correlate with patient age or pain duration.The majority of chronic LBP patients examined were in a depressed state and the severity of depression correlated with pain severity, degree of self-rated disability, and clinical severity.

Spinal deformity is an important clinical manifestation after surgery for spinal cord tumors. One-third of patients who receive laminectomies and irradiation of the spinal column develop scoliosis, kyphosis, or kyphoscoliosis. Recent reports indicate good results after scoliosis surgery using segmental pedicle screws and a navigation system, but these reported studies have not included surgery for post-laminectomy kyphosis. Hooks and wires are ineffective in such patients who undergo laminectomy, and there are also high perioperative risks with insertion of pedicle screws because landmarks have been lost. Here, we report on the 5-year follow-up of a 13-year-old male patient with post-laminectomy and post-irradiation thoracic kyphoscoliosis after surgical treatment of spinal astrocytoma. Posterior segmental pedicle screw fixation was performed safely using a computer-assisted technique. The authors present the first case report for treatment of this condition using a navigation system.

Study design In vitro human cadaveric biomechanical study. Objective The objective was to evaluate and compare the construct stability of occiput-C1-C2 fixation provided by C0-C1 transarticular screws or occipital condyle screws. Summary of background data The placement of an occipital plate is commonly recommended in occipitocervical fixation surgery. However, there are unique clinical situations in which the placement of the occipital plate may not be possible or may have already failed. For these situations, 2 novel techniques that use the occipital condyle have been recently introduced: (1) C0-C1 transarticular screws fixation and (2) direct occipital condyle screws and C1 lateral mass screws fixation. However, there is a lack of thorough biomechanics studies of these techniques. Methods Nondestructive kinematic tests and destructive tests were conducted in 16 fresh frozen cadaveric spines. As a nondestructive kinematic test, a pure moment of up to 2.0 N·m was applied in smooth continuous flexion/extension, lateral bending, and axial rotation motions. In addition to an intact-state case, a total of 5 different constructs (standard occipital plate, C0-C1 transarticular screws with/without occipital plate, and occipital condyle screws with/without occipital plate) were tested after destabilization of C0-C1 and C1-C2. All constructs had C2 pedicle screws fixation, and occipital condyle screws were incorporated with C1 lateral screws. Results All fixation techniques significantly reduced ranges of motion compared with the intact state. In comparison with the standard occipital plate construct, the 2 novel techniques showed higher stability in axial rotation and lower stability in lateral bending. In both nondestructive and destructive tests, there were no statistical differences between C0-C1 transarticular screw construct and occipital condyle screw construct. Conclusion The C0-C1 transarticular screw technique and direct occipital condyle screw with C1 lateral mass screw technique can be salvage fixation methods when occipital plate fixation is not feasible.