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Study Design Retrospective observational study. Purpose Lumbar spinal stenosis (LSS) has traditionally been evaluated morphologically, there is a paucity of literature on quantitative assessment of LSS. The purpose of this study was to investigate whether intraspinal diffusion tensor imaging (DTI) parameters such as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) are useful for assessing LSS. Overview of Literature Quantitative assessment of LSS is challenging. Methods Study participants comprised five healthy volunteers (mean age, 27.2 years) and 27 patients with LSS (mean age, 58.4 years) who were individually assessed using 3.0 Tesla magnetic resonance imaging. Intraspinal ADC and FA values of 10 intervertebral discs from healthy volunteers and 52 intervertebral discs from LSS patients were measured. Also, intraspinal canal area, Schizas classification (A: normal, B: mild stenosis, C: severe stenosis) and correlations with symptoms were investigated. Clinical symptoms were checked for the presence of low back pain (LBP), intermittent claudication (IMC), and bladder and bowel dysfunction (BBD). Results Compared to healthy individuals, LSS patients had significantly lower ADC (p

Study Design Observational study. Purpose To evaluate healthy volunteers and patients with spinal canal lesions using apparent diffusion coefficient (ADC) maps with diffusion-weighted imaging. Overview of Literature Decompression surgery for lumbar spinal stenosis (LSS) is selected on the basis of subjective assessment and cross-sectional magnetic resonance imaging (MRI). However, there is no objective standard for this procedure. Methods We performed 3T MRI in 10 healthy volunteers and 13 patients with LSS. The ADC values in the spinal canal were evaluated at 46 vertebrae (L4/5 and L5/S1 for each participant), and the reduced and conventional fields of view were compared. Results The ADC values were 2.72±0.12 at L4/5 in healthy volunteers, 2.76±0.19 at L5/S1 in healthy volunteers, 1.77±0.58 at L4/5 in patients with LSS, and 2.35±0.29 at L5/S1 in patients with LSS. The ADC value at L4/5 in patients with LSS was significantly lower than that at L5/S1 in patients with LSS and that at L4/5 and L5/S1 in healthy volunteers (p

Introduction: There are several reports about invasive muscle injury during posterior spinal surgery. However, few reports have evaluated the association between the clinical symptoms and changes in the physical properties of the psoas major after oblique lateral interbody fusion (OLIF). Therefore, the current study aimed to investigate the relationship between the clinical symptoms and changes in the psoas major muscle before and after OLIF. Methods: Twenty-seven patients who underwent single-level OLIF following the diagnosis of degenerative lumbar disease were included in the study. The cross-sectional areas (CSAs) of the psoas major on the approaching and contralateral sides were measured in the axial computed tomography view of the surgical intervertebral space preoperatively and postoperatively at 1 week and 3, 6, and 12 months. The preoperative and postoperative changes in the CSAs were compared. Muscle degeneration was evaluated using axial magnetic resonance images at the same level as that in the CSA evaluation preoperatively and at 12 months postoperatively. Additionally, the relationship between these parameters and postoperative lower limb symptoms was investigated. Results: Significant swelling of the psoas major on the approach side was observed 1 week postoperatively (p < 0.05). No postoperative muscle degeneration was observed. Three cases of paresthesia in the front of the thigh were observed, but no association was found with changes in CSA in any of the cases. Conclusions: The OLIF approach caused swelling of the psoas major 1 week postoperatively with no more muscle degeneration in the mid-term. Although numbness of the lower limbs was found in some cases, no association was found with changes in CSA. Our study findings suggest that the OLIF approach causes temporary injury or swelling of the psoas major, but the long-term damage to the muscle is not significant.

Abstract Background Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. Methods Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. Results The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively (p

Introduction: Limb muscle mass measurement using dual-energy X-ray absorptiometry (DXA) is considered the gold standard for the diagnosis of sarcopenia. Moreover, bioelectrical impedance analysis (BIA) is also recognized as a beneficial tool considering its high correlation with DXA. However, it remains to be elucidated whether DXA and BIA can accurately measure trunk lean mass. The aim of this study was to investigate the correlation between DXA and BIA measurements of trunk muscle mass and the cross-sectional area (CSA) of trunk muscles measured using magnetic resonance imaging (MRI) and to compare measures of trunk muscle mass obtained using DXA and BIA in patients with low back pain (LBP). Methods: In total, 65 patients participated in the study. The correlation between DXA and BIA measurements and the CSA of trunk and paraspinal muscles at the L4-5 level were calculated. In addition, the correlation between DXA and BIA measurements of trunk muscle mass and the differences between these two measurements were determined. Results: The correlation coefficient between DXA and BIA trunk muscle mass measurement and trunk muscle CSA was 0.74 and 0.56 for men and 0.69 and 0.44 for women, respectively. DXA and BIA measurement values showed a significantly moderate correlation with the CSA of the erector spinae (ES) and psoas major (PM). The multifidus (MF) CSA did not correlate with measurements of DXA and BIA in both men and women. Although DXA and BIA measurements were significantly correlated, a significant difference between these two measurements was found. BIA overestimated the trunk muscle mass significantly compared with DXA. Conclusions: Trunk muscle mass measured with DXA and BIA was correlated with the CSA of most trunk muscles. Although the measurement of DXA and BIA showed a high correlation, BIA overestimated trunk muscle mass compared with DXA. Both DXA and BIA are beneficial for measuring trunk muscle mass.

Introduction: Wearable accelerometers can be used to evaluate waking and sleeping movements. Although a correlation between accelerometer data captured at the wrist and waist has been reported, it has not been evaluated in patients with low back pain. Therefore, this study aimed to evaluate correlations between movement measured at the wrist and waist, using wearable accelerometers, in patients with low back pain. Methods: Twenty patients with chronic low back pain and 20 healthy volunteers were enrolled. Two identical accelerometers were simultaneously worn by each participant, one on the nondominant wrist and the other at the waist, for 1 week. We compared the mean number of active movements and mean total amount of movement between the wrist and the waist to evaluate daytime and sleep activities. During sleep, we also evaluated sleep efficiency and time awake after sleep onset. Results: In daytime activity, the mean number of active movements and mean total amount of movement was greater for the wrist than for the waist, and the amount of waist movements relative to wrist movements was significantly lower in patients with low back pain than in healthy volunteers (p < 0.05). Despite these differences, the mean number of active movements and mean total amount of movement at the wrist and waist were strongly correlated in both groups. During sleep, although there was no difference in either measured sleep efficiency at the wrist or waist or time awake after sleep onset, measurements were strongly correlated in both groups. Conclusions: A strong correlation between movement data at the wrist and waist during both daytime activities and sleep was identified in patients with low back pain. Therefore, a wearable accelerometer worn on the wrist can reliably measure the movement of patients with low back pain, simplifying data capture for clinical and research purposes and improving patient comfort.

Introduction: To investigate the risk of epidural hematoma after spinous process-splitting laminectomy (SPSL). Methods: A total of 137 cases (mean age, 72.4 years; 68 men) of SPSL were included. Of these, there were instances (3.7%; mean age, 70.5 years; all male) of postoperative development of new neurologic deficit due to epidural hematoma requiring reoperation. The 133 subjects (72.5 years; 64 men) with normal postoperative course were used as controls, and comparisons were made between both groups using chi-squared and Student's t-tests. Regarding our investigation of risk factors for epidural hematoma, logistic regression was conducted with presence or absence of hematoma as our primary outcome variable, and age, gender, disease duration, number of laminectomies, which levels were decompressed, blood loss, length of case, drain output, coagulopathy, and whether or not there was an intraoperative dural tear were our explanatory variables. Results: All cases of hematoma were single-level laminectomies; there was one case of T9-10 and 3 cases of L2-3. In our direct comparison of both groups (hematoma versus control), the proportion of men was significantly higher in the hematoma group (100% versus 48%, p < 0.05); levels decompressed were also significantly higher (p < 0.05) in the hematoma group, and drain outputs were significantly lower (113 mL versus 234 mL, p < 0.05). From our logistic regression analysis, the levels were significantly higher (χ2 = 15, p = 0.0001) and the drain outputs were smaller (χ2 = 4.6, p = 0.03) in the hematoma group. Conclusions: Single-level decompression higher than the L2-3 level and reduced drain output were risk factors for spinal epidural hematoma. With this method of spinous process suturing and reconstruction there is less decompression compared with more conventional methods; therefore, the effect of hematoma may be more pronounced at higher vertebral levels with reduced canal width, and drain failure may also occur with this limited space.

Abstract Background Giant cell tumor is known to be a benign neoplasm that arises most commonly in the long bones, while cases in the spine are rare. Recently, denosumab, a monoclonal antibody that inhibits receptor activator of nuclear factor-kappa β ligand, has been used to treat patients with giant cell tumor. However, there are few reports of total en bloc spondylectomy being used for paravertebral giant cell tumor lesions following denosumab therapy. Case presentation Our patient was a 20-year-old Japanese woman with a 4-month history of lower back pain. A spinal computed tomography scan and magnetic resonance imaging of her lumbar spine revealed an osteolytic lesion involving the L3 vertebral body, and the tumor extended toward the left side of the paravertebral soft tissue and into the left pedicle. The lesion was diagnosed as a giant cell tumor by needle biopsy. Denosumab treatment calcified the paravertebral giant cell tumor lesion and the tumor vertebral body was removed completely by total en bloc spondylectomy. Conclusion This case report describes a patient with a paravertebral giant cell tumor who was successfully treated by preoperative denosumab injection followed by total en bloc spondylectomy.

Study Design A retrospective observational study was performed. Purpose We investigated the prevalence of sarcopenia in dropped head syndrome (DHS), and the relationship between biochemical markers, including major advanced glycation end products (AGEs), pentosidine, and DHS in older women. Overview of Literature AGEs have been implicated in the pathogenesis of sarcopenia. Methods We studied 13 elderly women with idiopathic DHS (mean age, 77.2 years) and 20 healthy volunteers (mean age, 74.8 years). We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass [kg]/[height (m)]2). Cervical sagittal plane alignment, including C2–C7 sagittal vertical axis (C2–C7SVA), C2–C7 angle, and C2 slope (C2S), was measured. Biochemical markers, such as serum and urinary pentosidine, serum homocysteine, 1, 25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were measured. The level of each variable was compared between DHS and controls. The relationship between biochemical markers and DHS was examined. Results Sarcopenia (SMI

Introduction: Thus far, few reports have described the time series histological variations in injured paravertebral muscle tissues for long durations, considering the type of pain. The purpose of this study is to evaluate histological changes in injured paravertebral muscles and dominant nerves considering the type of pain. Methods: We used 59 eight-week-old male Sprague-Dawley rats. A 115-g weight was dropped from a height of 1 m on the right paravertebral muscle. Fluoro-Gold (FG), a sensory nerve tracer, was injected into this muscle. Hematoxylin and eosin (HE) staining and nerve growth factor (NGF) immunostaining of the muscle were performed for histological evaluation. L2 dorsal root ganglia (DRG) on both sides were resected, and immunohistochemical staining was performed for calcitonin gene-related peptide (CGRP, a pain-related neuropeptide) and for activating transcription factor 3 (ATF3, a neuron injury marker). Each examination was performed at 3 days, 1-3 weeks, and 6 weeks after injury. Results: HE staining of the paravertebral muscle indicated infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side at 3 days and 1 week after the injury. Fibroblasts and adipocytes were present at 2-3 weeks. At 6 weeks, the injured tissue was almost completely repaired. NGF was detected at 2-3 weeks post injury and appeared to colocalize with fibroblasts, but was not observed at 6 weeks post injury. The percentage of cells double-labeled with FG and CGRP in FG-positive cells of the primary muscle was significantly higher in the injured side at 3 days and 1-3 weeks post injury (P < 0.05). However, at 6 weeks, no significant difference was observed. No significant expression of ATF3 was observed. Conclusions: These results suggest that sensitization of the dominant nerve in the DRG, in which NGF may play an important role, can protract pain in injured muscles.

Study Design Cross-sectional observational study. Purpose To compare measurements of appendicular skeletal muscle mass (ASMM) and whole fat mass (WFM) obtained using dualenergy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) among patients with low back pain (LBP). Moreover, the study investigated the correlation between BIA-based ASMM and DXA-based bone mineral density (BMD). Overview of the Literature If reliable, BIA may be a useful alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP. Methods Measurements were performed in 130 patients, including BMD of the lumbar spine and femoral neck. The correlation between DXA and BIA as well as between BIA-ASMM and BMD were evaluated. Results BIA and DXA were highly correlated in both male and female patients (r =0.73–0.90, p

Objective To validate the relationship between residual walking ability and monthly care cost as well as long-term care insurance (LTCI) certification level in elderly patients after surgical treatment for hip fractures in Japan. Methods Elderly patients aged >75 years who underwent surgical treatment for hip fractures in our hospital were included. The preand post-surgical (6-month) walking ability and LTCI certification and the presence or absence of dementia was determined from medical records and questionnaires. Walking ability was classified into 6 levels used in our daily medical practice. Based on these data, we correlated the relationship between walking ability and the LTCI certification level. Further, based on the official statistics pertaining to the average monthly costs per person at each LTCI certification level, we evaluated the relationship between walking ability and monthly care cost. Results A total of 105 cases (mean age, 80.2 years; 16 men; 39 patients with dementia) were included. The correlation between walking ability and average monthly cost per person as well as LTCI certification level at 6 months postoperatively (r=0.58) was demonstrated. The correlation was found in both groups with and without dementia. Conclusion The ability to walk reduced the cost of care in elderly patients who experienced hip fracture, regardless of the presence of dementia.

Introduction: Osteoporosis can produce a persistent state of pain known as osteoporotic pain. One proposed mechanism of this pathology is increased calcitonin gene-related peptide (CGRP; a marker related to inflammatory pain) expression in the dorsal root ganglia (DRG) innervating osteoporotic vertebrae. Alternatively, a previous study revealed that axial loading caused osteoporotic pain in a rodent model of coccygeal vertebrae compression. Because this compression model is associated with trauma, additional mechanistic studies of osteoporotic pain in the absence of trauma are required. The current study aimed to evaluate the expression and relative distribution of transient receptor potential vanilloid 4 (TRPV4), a pain-related mechanoreceptor, in ovariectomized (OVX) osteoporotic rats. Methods: CGRP-immunoreactive (-ir) and TRPV4-ir DRG neurons innervating the L3 vertebrae of Sprague-Dawley rats were labeled with a neurotracer, FluoroGold. Intravertebral pH was also measured during the neurotracer procedure. TRPV4-ir/CGRP-ir FluoroGold-positive DRG neurons were quantified in sham control and OVX rats (n = 10, ea). The threshold for statistical significance was set at P < 0.05. Results: There was no statistical difference in the number of FluoroGold-positive DRG neurons between groups; however, there were significantly more CGRP-ir/TRPV4-ir FluoroGold-positive DRG neurons in the OVX group compared with the sham control group (P < 0.05) as well as the significantly increased molecular production of each peptide. Intravertebral pH was also lower in the OVX group compared with the sham control group (P < 0.05). Conclusion: Sensory neurons innervating osteoporotic vertebrae exhibited increased expression of co-localized CGRP and TRPV4 in OVX osteoporotic rats. Additionally, intravertebral pH was low in the vicinity osteoporotic vertebrae. Considering that TRPV4 is a mechanosensitive nociceptor that is activated in acidic environments, its upregulation may be associated with the pathology of osteoporotic pain derived from microinflammation involved in osteoporosis.

Study Design Retrospective observational study. Purpose We considered the relationship between spinal alignment and skeletal muscle mass on clinical outcomes following a surgery for lumbar spinal stenosis (LSS). Overview of Literature There are no reports of preoperative factors predicting residual low back pain following surgery for LSS. Methods Our target population included 34 women (mean age, 74.4 years) who underwent surgery for LSS. Prior to and 6 months after the surgery, systemic bone mineral density and lean soft tissue mass were measured using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated as the sum of the arm and leg lean mass in kilograms divided by height in meters squared. The spinal alignment was also measured. Clinical outcomes were evaluated using the Japanese Orthopedic Association scoring system, leg and low back pain Visual Analog Scale, and Roland–Morris Disability Questionnaire (RDQ). Additionally, we examined the bone mineral density, skeletal muscle mass, and spinal alignment before and after the surgery. We used the Spearman correlation coefficient to examine the associations among clinical outcomes, preoperative muscle mass, and spinal alignment. Results Sarcopenia (SMI 6.12), RDQ was significantly higher in subjects with sarcopenia (p =0.04). RDQ was significantly negatively correlated with SMI (r =−0.42, p

Introduction: Osteoporosis and sarcopenia are said to be similar disorders. However, few reports have described the effects of anti-osteoporosis drugs on muscle mass in clinical practice. Methods: We selected 150 postmenopausal women with osteoporosis treated by minodronate (osteoporosis medication [OM] group) and 50 postmenopausal women without osteoporosis who did not receive treatment (no osteoporosis [NO] group). The OM group was further divided into two treatment subgroups: a combination of monthly minodronate and daily activated vitamin D vs. monthly minodronate alone. We measured lumbar spine and femoral neck bone mineral density (BMD) with dual-energy X-ray absorptiometry and muscle mass of the upper limbs, lower limbs, and trunk with bioelectrical impedance analysis at baseline and after 6 months. Results: The OM and NO groups contained 130 and 37 patients, respectively (mean age: 73.9 ± 8.3 and 74.1 ± 10.0 years, respectively). In the OM group, lumbar spine BMD significantly increased after 6 months, while lower limb muscle mass significantly decreased. In the NO group, lumbar spine BMD and lower limb muscle mass did not significantly change after 6 months. In the OM group, BMD of the lumbar spine significantly increased but the lower limb muscle mass significantly decreased after 6 months relative to the NO group. In the combination therapy subgroup of the OM group muscle mass decreased significantly less than in the minodronate-alone subgroup. Conclusions: In postmenopausal women with osteoporosis, minodronate can increase BMD but cannot increase muscle mass. However, simultaneous use of activated vitamin D can suppress muscle mass decrease. The combination of activated vitamin D and minodronate may be useful for treating osteoporosis in postmenopausal women.

Introduction: Discogenic back pain remains poorly understood with respect to etiopathogenesis, despite being a considerable burden. We sought to examine the expression of vascular endothelial growth factor in injured intervertebral discs in rat caudal vertebrae. Methods: Forty-eight male Sprague Dawley rats were assigned to 2 groups according to disc puncture injury: puncture (n = 32) or non-puncture (n = 16). Disc puncture was performed percutaneously such that the incision would be in the primary plane of motion for the coccygeal discs 5-6, 6-7, and 7-8. A 26-gauge needle was used to puncture each disc 10 times. Punctured discs were examined histologically by hematoxylin and eosin staining at 1, 7, 14, and 28 days post-injury. Results: Vascular endothelial growth factor was localized immunohistochemically, and determined quantitatively using an enzyme-linked immunosorbent assay. Peak inflammation occurred on the 7th day post-injury, but tissue degeneration continued until day 28. Local expression of vascular endothelial growth factor tended to be highest in the annulus fibrosus on the 7th and 14th days after puncture injury. The level of vascular endothelial growth factor was highest 1-day post-injury, and then gradually decreased thereafter. Furthermore, vascular endothelial growth factor levels in the puncture group were significantly higher than those in the non-puncture control group (p < 0.05). Conclusions: We found increased expression of the inflammatory cytokine vascular endothelial growth factor in injured intervertebral discs, suggesting that vascular endothelial growth factor may be clinically important in discogenic back pain.

Introduction: Failed spinal fusion surgery sometimes requires salvage surgery when symptomatic, especially with postsurgical decrease in intervertebral disc height followed by foraminal stenosis. For such cases, an anterior approach to lumbar lateral interbody fusion (LLIF) provides safe, direct access to the pathological disc space and a potential improvement in the fusion rate. One LLIF approach, oblique lateral interbody fusion (OLIF), targets the oblique lateral window of the intervertebral discs to achieve successful lateral interbody fusion. The current technical note describes spinal revision surgery using the OLIF procedure. Technical Note: The subjects were patients with leg pain and/or lower back pain derived from decreased intervertebral height followed by foraminal stenosis due to failed spinal fusion surgery. These patients underwent additional OLIF surgery and posterior fusion with no additional posterior direct decompression. Their outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scores at baseline and final follow-up. Bony union was also evaluated using computed tomography images at final follow-up. Six subjects were evaluated, with two representative cases described in detail. Four patients had an adjacent segment disorder, and the other two patients had pseudarthrosis due to postoperative infection. The mean JOA score improved from 5.7 ± 5.4 to 21.2 ± 2.3, with a mean recovery rate of 65.0%. All cases showed intervertebral bony union. Conclusions: We introduced a salvage strategy for failed posterior spine fusion surgery cases using the OLIF procedure. Patients effectively achieved recovered intervertebral and foraminal height with no additional posterior direct decompression.

Introduction: Oblique lateral interbody fusion (OLIF) can achieve recovery of lumbar lordosis (LL) in minimally invasive manner. The current study aimed to evaluate the location of lateral intervertebral cages during OLIF in terms of LL correction. Methods: The subjects were patients who underwent OLIF for lumbar degenerative diseases, including lumbar spinal stenosis, spondylolisthesis, and discogenic low back pain. Their clinical outcome was evaluated using visual analogue scale on lower back pain (LBP), leg pain and numbness. The following parameters were retrospectively evaluated on plain radiographic images and computed tomography scans before and at 1 year after OLIF: the intervertebral height, vertebral translation, and sagittal angle. The cage position was defined by equally dividing the caudal endplate into five zones (I to V), and its association with segmental lordosis restoration was analyzed. Subjects were also evaluated for a postoperative endplate injury. Results: Eighty patients (121 fused levels) with lumbar degeneration who underwent OLIF were included. There were no significant specific distribution in preoperative disc pathology such as disc angle, height, and translation. After OLIF, sagittal alignment was improved with an average correction angle of 3.8º at the instrumented segments in a level-independent fashion. All cases showed significant improvement in clinical outcomes, and had improvement in the radiological parameters (P

Study DesignAn experimental animal study.PurposeTo evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model.Overview of LiteratureIncreased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury.MethodsThrough abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP.ResultsCompared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p

Study DesignObservational study.PurposeTo assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD).Overview of LiteratureLow back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial.MethodsUsing the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels.ResultsA gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p=0.002).ConclusionsThese results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.

Study DesignControlled laboratory study.PurposeThis study aimed to evaluate the efficacy of platelet-rich plasma (PRP) stored at room temperature (RT), frozen, or after freeze-drying.Overview of LiteraturePRP enriches tissue repair and regeneration, and is a novel treatment option for musculoskeletal pathologies. However, whether biological activity is preserved during PRP storage remains uncertain.MethodsPRP was prepared from blood of 12 healthy human volunteers (200 mL/person) and stored using three methods: PRP was stored at RT with shaking, PRP was frozen and stored at −80℃, or PRP was freeze-dried and stored at RT. Platelet counts and growth factor content were examined immediately after preparation, as well as 2, 4, and 8 weeks after storage. Platelet activation rate was quantified by flow cytometry.ResultsPlatelet counts were impossible to determine in many RT samples after 2 weeks, but they remained at constant levels in frozen and freeze-dried samples, even after 8 weeks of storage. Flow cytometry showed approximately 80% activation of the platelets regardless of storage conditions. Almost no growth factors were detected in the RT samples after 8 weeks, while low but significant expression was detected in the frozen and freeze-dried PRP. Over time, the mean relative concentrations of various growth factors decreased significantly or disappeared in the RT group. In the frozen group, levels were maintained for 4 weeks, but decreased significantly by 8 weeks (p

Study DesignRetrospective case series.PurposeThe purpose of this study was to determine whether discontinuing teriparatide treatment and replacing it with bisphosphonate treatment maintains the volume of the fusion mass after posterolateral fusion (PLF) in women with postmenopausal osteoporosis.Overview of LiteratureClinical data support the efficacy of parathyroid hormone (PTH) for lumbar PLF. However, the use of PTH is limited to 2 years.MethodsWe treated 19 women diagnosed with osteoporosis and degenerative spondylolisthesis with teriparatide (20 µg daily subcutaneously). All patients underwent one-level instrumented PLF. Teriparatide was used during 2 months prior to surgery and more than 8 months after surgery. After discontinuing teriparatide treatment, all patients used bisphosphonate (17.5 mg risedronate weekly, oral administration). Area of the fusion mass across the transverse processes at one segment was determined on an anteroposterior radiograph at 1, 2, and 3 years after surgery.ResultsWe followed 19 patients for 3 years. The average duration of teriparatide treatment was 11.5 months. The bone union rate was 95%. The average area of the bone fusion mass was not significantly different between the right and left sides at 1, 2, or 3 years after surgery (p>0.05).ConclusionsThis study showed that replacing teriparatide treatment with bisphosphonate maintained the bone fusion mass volume after PLF in women with postmenopausal osteoporosis.

Study DesignRetrospective, observational, single-center study.PurposeTo investigate the long-term outcomes of in situ fusion procedures for treating dysplastic spondylolisthesis.Overview of LiteratureIn situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications.MethodsIn total, 12 of 28 patients who underwent in situ fusion for treating dysplastic spondylolisthesis at Chiba University Hospital from 1974 to 2004 were followed up in August 2013. Surgical complications were evaluated. Low back pain and leg pain were assessed using a visual analog scale (VAS). Vertebral alignment, including the lumbosacral angle and lumbar lordosis angle measurement on radiographic images (profile view in the neutral standing position), was evaluated during preoperative, postoperative, and final examinations.ResultsThe mean follow-up duration, patient age at the final examination, and patient age at operation were 20.0±7.2, 42.3±13.3, and 22.3±11.4 years, respectively. No complications were reported. Mean VAS scores for low back pain and leg pain were significantly lower at the final examination than at the preoperative examination (p

Much progress has been made in neuroimaging with Magnetic Resonance neurography and Diffusion Tensor Imaging (DTI) owing to higher magnetic fields and improvements in pulse sequence technology. Reports on lumbar nerve DTI have also increased considerably. Many studies have shown that the use of DTI in lumbar nerve lesions, such as lumbar foraminal stenosis and lumbar disc herniation, makes it possible to capture images of interruptions of tractography at stenotic sties, enabling the diagnosis of stenosis. DTI can also reveal significant decreases in fractional anisotropy (FA) with significant increases in apparent diffusion coefficient (ADC) values in compression lesions. FA values have higher accuracy than ADC values. Furthermore, strong correlations exist between FA values and indications of neurological severity, including the Japanese Orthopedic Association (JOA) score, the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ) in patients with lumbar disc herniation-induced radiculopathy. Most lumbar DTI has become 3T; 3T MRI has made it possible to take high-resolution DTI measurements in a short period of time. However, increased motion artifacts in the magnetic susceptibility effect lead to signal irregularities and image distortion. In the future, high-resolution DTI with reduced field-of-view may become useful in clinical applications, since visualization of nerve lesions and quantification of DTI parameters could allow more accurate diagnoses of lumbar nerve dysfunctions. Future translational studies will be necessary to successfully bring MR neuroimaging of lumbar nerve into clinical use.

Study DesignAnimal model study.PurposeThe purpose of this study was to evaluate the histological variation in the injured muscle and production of calcitonin gene-related peptide in rats over time.Overview of LiteratureVertebral surgery has been reported to cause atrophy of the back muscles, which may result in pain. However, few reports have described the time series histological variation in the injured muscle and changes in the dominant nerve.MethodsWe used 30 male, 8-week-old Sprague-Dawley rats. The right and left sides of the paravertebral muscle were considered as the injured and uninjured sides, respectively. A 115 g weight was dropped from a height of 1 m on the right paravertebral muscle. Hematoxylin and eosin (H&E) staining of the muscle was performed 1–3 weeks after injury for histological evaluation. Fluoro-Gold (FG) was injected into the paravertebral muscle. The L2 dorsal root ganglia on both sides were resected 1, 2, and 3 weeks after injury, and immunohistochemical staining for calcitonin gene-related peptide was performed.ResultsH&E staining of the paravertebral muscle showed infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side 1 week after injury. Muscle atrophy occurred 3 weeks after injury, but was repaired via spontaneous replacement of muscle cells/fibers. In contrast, compared with the uninjured side, the percentage of cells double-labeled with FG and calcitonin gene-related peptide in FG-positive cells in the dorsal root ganglia of the injured side was significantly increased at each time point throughout the study period.ConclusionsThese results suggest that sensitization of the dominant nerve in the dorsal root ganglia, which may be caused by cicatrix formation, can protract injured muscle pain. This information may be helpful in elucidating the underlying mechanism of persistent pain after back muscle injury.

Purpose: We examined duloxetine's effectiveness in the treatment of neuropathic pain in patients who were intolerant to continuous pregabalin administration. Materials and Methods: The present study is a retrospective study of patients diagnosed with neuropathic pain with neuropathic leg pain as the chief complaint. We analyzed 20 cases in which pregabalin was changed to duloxetine because of adverse effects (16 cases) or treatment failure (4 cases). The incidence of adverse events after duloxetine administration was used as the primary endpoint, with the secondary endpoint being the leg pain level based on a numerical rating scale (NRS). Results: The incidence of adverse events after starting duloxetine was 40%. Average leg pain scores measured on the NRS were 8.4±1.4, 6.4±1.4, and 4.1±2.0 at the time of the patients' first visit, pregabalin discontinuation, and after switching to duloxetine, respectively. A significant difference in NRS scores was found between the first visit and pregabalin discontinuation and also between pregabalin discontinuation and after the switch to duloxetine (p0.05). Conclusion: When patients with neuropathic pain are unable to tolerate pregabalin because of adverse effects, changing the medication to duloxetine may be an option.

Abstract Manganese‐enhanced magnetic resonance imaging (MEMRI) enables tract tracing to follow neural pathways through axonal transport. However, the method is problematic because of the high local concentrations of Mn2+ involved. We developed a tetrananogel containing a dextran‐manganese complex (Dex‐Mn‐Gel) and applied this nanogel to rats. MnCl2 (n = 5), Dex‐Mn‐Gel (n = 5), or saline control (n = 3) was injected into the left knee joint of the rats (n = 13). Inflammation and tissue alterations in the knee joint were also evaluated histologically. T1‐weighted images were obtained on a 7 T MRI system 24 hours after the administration and compared across groups. The sciatic nerve in both legs and the surrounding musculature were used as regions of interest (ROI). No swelling was found in the knee joint infused with Dex‐Mn‐Gel, although prominent swelling of the knee joint was observed with MnCl2. White blood cells inside the knee joint tissue infused with the Dex‐Mn‐Gel were significantly less abundant (45%, P

Study DesignRetrospective case series.PurposeTo examine the efficacy of TachoSil for vessel injury in 6 patients who underwent anterior lumbar fusion surgery (ALF).Overview of LiteratureALF for the lumbar spine has a high rate of success, although intraoperative concerns and iatrogenic complications are known, and injury of a major vessel is sometimes a complication. The efficacy of TachoSil, a fibrin-based hemostat, has been reported for several types of surgery; however, use of TachoSil for ALF surgery has not been described. Here, we report on the efficacy of TachoSil in 6 patients, who underwent ALF after vascular surgeons having difficulty in repairing vessels.MethodsTwo man and 4 women with average age of 50.8±10.9 (mean±standard deviation) were diagnosed with a vertebral tumor (2 patients), L4 degenerative spondylolisthesis (2 patients), and L5 spondylolytic spondylolisthesis (2 patients) and underwent ALF. The blood vessels injured included the common iliac vein in 2 patients and a branch of a segmental artery from the aorta in 4 patients. We consulted a vascular surgeon to suture or repair the vessels during surgery, and although the vascular surgeon attempted to address the injuries, suturing or repair was not possible in these cases. For this reason, we used TachoSil to repair the injury in the vessels walls or to stop the bleeding.Results Time to pressure hemostasis using TachoSil was 34±12 minutes, and total blood loss was 1,488±1,711 mL. Nevertheless, all vessel injuries were controlled by the use of TachoSil.ConclusionsWe recommend the use of TachoSil for vessel injuries that vascular surgeons cannot suture or repair during ALF surgery.

Study DesignRetrospective study.PurposeTo determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain.Overview of LiteratureInadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging.MethodsPatients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed.ResultsNo adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p

Study DesignExperimental animal study.PurposeWe aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF)-α inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury.Overview of LiteratureThe pain-related peptide expression was suppressed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner.MethodsThe neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 µg, 100 µg, or 1,000 µg) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRP-immunoreactive DRG neurons was evaluated in all the groups.ResultsThere were no significant differences between the puncture+saline group and the puncture+10-µg etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double-positive cells in FG-positive cells was observed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner (p

Study DesignRetrospective case series.PurposeTo classify back muscle degeneration using magnetic resonance imaging (MRI) and investigate its relationship with back pain after surgery.Overview of LiteratureBack muscle injury and degeneration often occurs after posterior lumbar surgery, and the degeneration may be a cause of back pain. However, the relationship between back muscle degeneration and back pain remains controversial.MethodsA total of 84 patients (average age, 65.1 years; 38 men, 46 women) with lumbar spinal stenosis underwent posterior decompression surgery alone. MRI (1.5 tesla) was evaluated before and more than a year after surgery in all patients. Muscle on MRI was classified into three categories: low intensity in T1-weighted imaging, high intensity in T2-weighted imaging (type 1), high intensity in both T1- and T2-weighted images (type 2), and low intensity in both T1- and T2-weighted imaging (type 3). The prevalence of the types and their relationship with back pain (determined on a visual analog scale) were evaluated.ResultsMRI revealed muscle degeneration in all patients after surgery (type 1, 6%; type 2, 82%; and type 3, 12%). Type 2 was significantly more frequent compared with types 1 and 3 (p0.05).ConclusionsVarious pathologies of back muscle degeneration after posterior lumbar surgery were revealed. Type 2 (fatty) change was most frequent, and other patients had type 3 (scar) or type 1 (inflammation or water-like) changes. According to the Modic classification of bone marrow changes, Modic type 1 change is associated with inflammation and back pain. However, no particular type of back muscle degeneration was correlated with back pain after surgery.

Study DesignRetrospective observational study.PurposeTo examine fractional anisotropy (FA) values and apparent diffusion coefficient (ADC) values of damaged nerves to discriminate between lumbar intraspinal stenosis (IS) and foraminal stenosis (FS) using diffusion tensor imaging (DTI)Overview of LiteratureIt is important in the selection of surgical procedure to discriminate between lumbar IS and FS, but such discrimination is difficult.MethodsThere were 9 cases of IS, 7 cases of FS, and 5 healthy controls. The regions of interest were established in the lumbar intraspinal zone (Iz), nerve root (N), and extraforaminal zone (Ez). The FA and ADC values were measured on the affected and unaffected sides of the nerves. The FA ratio and the ADC ratio were calculated as the affected side/unaffected side ×100 (%).ResultsIn the Ez, the FA value was significantly lower in FS than in IS (p

Diagnosis of lumbar foraminal stenosis remains difficult. Here, we report on a case in which bilateral lumbar foraminal stenosis was difficult to diagnose, and in which diffusion tensor imaging (DTI) was useful. The patient was a 52-year-old woman with low back pain and pain in both legs that was dominant on the right. Right lumbosacral nerve compression due to a massive uterine myoma was apparent, but the leg pain continued after a myomectomy was performed. No abnormalities were observed during nerve conduction studies. Computed tomography and magnetic resonance imaging indicated bilateral L5 lumbar foraminal stenosis. DTI imaging was done. The extraforaminal values were decreased and tractography was interrupted in the foraminal region. Bilateral L5 vertebral foraminal stenosis was treated by transforaminal lumbar interbody fusion and the pain in both legs disappeared. The case indicates the value of DTI for diagnosing vertebral foraminal stenosis.

Spinal metastasis of differentiated thyroid cancer can have a favorable prognosis if radical surgery is performed. We encountered a case of spinal metastasis involving three anterior vertebral bodies at the posterior element fusion level and successfully achieved adequate stability by radical surgery involving only the anterior elements. A 67-year-old woman who had numbness and muscle weakness in the lower limbs caused by metastatic spinal tumor at the posterior element fusion level of L1–L3 vertebrae was treated with radical surgery of only the anterior element to gain stability. Similar situations may occur in cases involving other malignant tumor metastases or spinal primary tumors. If such a case occurs, this method could be useful in preventing metastasis to the posterior element.