Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

Combined effect of DBM, PRP, and bone marrow fluid on bone union in a rat posterolateral fusion model.

Platelet-rich plasma (PRP) promotes bone union through osteoinduction. We investigated whether adding demineralized bone matrix (DBM), derived naturally from biomaterial and with various growth factors, for osteoconductivity and bone marrow fluid for osteogenesis results in different bone unions. Eight-week-old male Sprague-Dawley rats were divided into four groups of five based on transplantation material: sham control (C group); DBM alone (D group); DBM + PRP (DP group); and DBM + PRP + bone marrow fluid (DPB group). After posterolateral fusion at L3-5, postoperative weekly CT imaging determined average number of bone union in facet joints (4 joints × 5 animals = 20 joints) and bone formation. Pathological evaluation and bone strength were assessed using 3-point bending two weeks postoperatively. Facet joint bone union at four weeks postoperatively was 4/20 (20%, DP group) and 8/20 (40%, DPB group) joints. Six weeks postoperatively, it was 7/20 (35%, D group), 12/20 (60%, DP group), and 16/20 (80%, DPB group). Eight weeks postoperatively, it was 13/20 (65%, D group), 17/20 (85%, DP group), and 20/20 (100%, DPB group), suggesting that DPB > DP > D > C. Bone formation and bone strength showed a similar DPB > DP > D > C group trend. Adding PRP and bone marrow fluid to DBM promotes bone union and strength.

Analgesic effects and arthritic changes following intra-articular injection of diclofenac etalhyaluronate in a rat knee osteoarthritis model.

BACKGROUND: Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). METHODS: We injected MIA into the right knees of eight 6-weeks-old male Sprague-Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. RESULTS: Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. CONCLUSION: DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.

Cross-cultural Adaptation and Validation of the Japanese Version of the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS).

Background: The Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) is a specifically designed scoring system for children and has been translated into several languages. However, to date, no validated Japanese version of this scoring system is available. Purpose: To translate the HSS Pedi-FABS into Japanese and assess its reliability and validity. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The HSS Pedi-FABS was translated into Japanese and back-translated into English to confirm the appropriateness of the translation. A total of 764 children aged 9 to 15 years participated in the validation study. The participants answered the Japanese version of the HSS Pedi-FABS along with 2 other questionnaires in Japanese (the Physical Activity Questionnaire for Older Children [PAQ-C] and the physical activity questionnaire of the World Health Organization's Health Behavior in School-aged Children [HBSC PAQ]). At 1 month after the first assessment, the children answered the Japanese version of the HSS Pedi-FABS again. We evaluated reliability using the Cronbach alpha and the intraclass correlation coefficient. Validity was evaluated by quantifying floor and ceiling effects, correlations between the HSS Pedi-FABS and the PAQ-C, the HSS Pedi-FABS discrepancy between active and inactive groups divided by the HBSC PAQ, and correlation between the HSS Pedi-FABS and body mass index. Results: HSS Pedi-FABS scores were slightly but significantly higher in male participants (mean = 16.7) than in female participants (mean = 13.2). The Cronbach alpha coefficient was .90, and the intraclass correlation coefficient value was 0.90, indicating excellent internal consistency and test-retest reliability, respectively. No floor (2.6%) or ceiling effect (1.0%) was observed. The HSS Pedi-FABS was significantly correlated with the PAQ-C (r = 0.70). The active group demonstrated a significantly higher score on the HSS Pedi-FABS (mean = 18.9) than did the inactive group (mean = 11.2). In terms of discriminative validity, the HSS Pedi-FABS was not correlated with body mass index (r = -0.15). Conclusion: The Japanese version of the HSS Pedi-FABS demonstrated appropriate reliability and validity, indicating that it is a useful tool to assess physical activity levels in Japanese children.

Risk Factors for Lateral Translation in Residual Adolescent Idiopathic Scoliosis with a Thoracolumbar/Lumbar Curve.

Introduction: Although lateral vertebral translation is associated with inducing curve progression and pain, no study has analyzed risk factors for lateral slip in patients with residual adolescent idiopathic scoliosis (AIS). This study aimed to investigate risk factors for lateral slip in patients with residual AIS. Methods: We included 42 preoperative patients with residual AIS with a thoracolumbar/lumbar (TL/L) curve (3 male, 39 female; age 41.9±18.2 years, TL/L Cobb angle 55.5±10.0°). All patients were >20 years and had been diagnosed with AIS during their adolescence. Lateral slip was defined as more than a 6-mm slip on coronal CT images. Results: Patients were divided into slip (n=22) and nonslip (n=20) groups. Significant differences were observed in age, TL/L Cobb angle, TL/L curve flexibility, lumbar lordosis, thoracolumbar kyphosis, apical vertebral rotation, apical vertebral translation, and L3 and L4 tilt between the groups. Multivariate analyses and receiver operating characteristic curves found that only older age was a significant risk factor for lateral slip (odds ratio: 1.214; 95% confidence interval: 1.047-1.407; P=0.010), with a cutoff value of 37 years old. Conclusions: Older age, especially >37 years, is a risk factor for lateral slip in patients with residual AIS. These findings suggest that surgery for residual AIS should be considered before patients are in their mid-30s to avoid lateral translation.

Bone union-promoting effect of romosozumab in a rat posterolateral lumbar fusion model.

This study investigated the effect of romosozumab on bone union in a rat posterolateral lumbar fixation model. Posterolateral lumbar fixation was performed on 8-week-old male Sprague Dawley rats (n = 20). For bone grafting, autogenous bone (40 mg) was harvested from the spinous processes of the 10th thoracic vertebra until the 2nd lumbar vertebra and implanted between the intervertebral joints and transverse processes of the 4th and 5th lumbar vertebrae on both sides. Rats were matched by body weight and equally divided into two groups: R group (Evenity®, 25 mg/kg) and control (C) group (saline). Subcutaneous injections were administered twice a week until 8 weeks after surgery. Computed tomography was performed at surgery and week 8 after surgery. The area and percentage of bone trabeculae in the total area of bone fusion were calculated. Statistical analysis was performed using an unpaired t test (p < 0.05). We found that the R group rats had significantly higher mean bone union rate and volume than did the C group rats at all time courses starting week 4 after surgery. The R group had significantly higher increase rates than did the C group at weeks 4 and 6 after surgery. The percentage of bone trabeculae area in the R group was approximately 1.7 times larger than that in the C group. Thus, we demonstrated that romosozumab administration has stimulatory effects on bony outgrowth at bone graft sites. We attribute this to the modeling effect of romosozumab.

Usefulness of Simultaneous Magnetic Resonance Neurography and Apparent T2 Mapping for the Diagnosis of Cervical Radiculopathy.

STUDY DESIGN: Retrospective observational study. PURPOSE: We investigated the correlation between T2 relaxation times and clinical symptoms in patients with cervical radiculopathy caused by cervical disk herniation. OVERVIEW OF LITERATURE: There are currently no imaging modalities that can assess the affected cervical nerve roots quantitatively. METHODS: A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side. RESULTS: When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio. CONCLUSIONS: In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.

Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody.

STUDY DESIGN: Prospective cohort study (open-label, single-arm, and non-blinded). PURPOSE: This study aims to determine the effects of systemic administration of tocilizumab, an anti-interleukin-6 (IL-6) receptor antibody on refractory low back pain and leg symptoms. OVERVIEW OF LITERATURE: IL-6 overexpression is associated with neuropathic pain pathogenesis, which is potentially followed by chronic low back pain, including leg pain and numbness. This finding suggest that inhibition of IL-6 at the site of pain or in the transmission pathway could provide novel therapeutic targets for chronic low back pain. METHODS: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months' chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. RESULTS: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. CONCLUSIONS: Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1-4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Early mobilization reduces the medical care cost and the risk of disuse syndrome in patients with acute osteoporotic vertebral fractures.

STUDY DESIGN: A retrospective observational study. PURPOSE: To compare two conservative treatments for acute osteoporotic vertebral fractures (OVFs). OVERVIEW OF LITERATURE: Several studies have reported conservative treatments for OVFs in terms of using a brace, rehabilitation, and bed rest. However, there is no consensus about the conservative treatment for OVFs. METHODS: We evaluated 68 patients with acute OVF treated in our hospital from 2007 to 2011. Thirty-four patients treated in prolonged bed rest (PBR) regimen underwent rehabilitation wearing a Jewett's brace after three weeks of bed rest. In contrast, the other 34 patients underwent rehabilitation wearing a Jewett's brace as soon as possible, which we called a stir-up (SU) regimen. We compared two treatment groups for medical costs, hospital length of stay (LOS), pain according to the numeric rating scale (NRS), the activities of daily living (ADL), and imaging studies. RESULTS: The average hospital LOS was significantly shorter in patients treated by the SU regimen, which resulted in the medical costs reduction. There was no significant difference in the NRS through 6 months between the two groups. Although many patients in both groups experienced at least one level reduction in ADL at 6 months after the injury, patients in the SU group tended to maintain their pre-injury ADL, which almost agrees with past reports. In terms of imaging studies, patients in the PBR group showed milder vertebral compression rate over time. Pseudoarthrosis occurred in 2 patients in the SU group, who presented with mild pain, which had little influence on their daily lives. CONCLUSION: We compared two conservative treatments for OVFs. Early rehabilitation was useful treatment for OVFs to minimize the risk for disuse syndrome, maintain pre-injury ADL status, and reduce the medical costs.

Comparison between intervertebral oblique lumbar interbody fusion and transforaminal lumbar interbody fusion: a multicenter study.

This study aimed to perform a comparative analysis of postoperative results between lumbar degenerative spondylolisthesis (LDS) treated with oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) from the Chiba spine surgery registry database. Sixty-five patients who underwent single-level OLIF (O group) for LDS with ≥ 3 years' follow-up were retrospectively reviewed. The control group comprised 78 patients who underwent single-level TLIF (T group). The analyzed variables included global alignment, radiological parameters of fused segments, asymptomatic and symptomatic ASD incidence, clinical outcomes at 3 years postoperatively using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire data, visual analogue scale scores for low back pain, lower extremity pain, and lower extremity numbness. There was no significant change in global alignment between the two groups. The rate of improvement in anterior intervertebral disc height was not significantly different between the groups at 1-month postoperatively. However, at the final evaluation, the anterior intervertebral disc height and incidence of asymptomatic ASD were significantly higher in the O group. There was no significant difference in symptomatic ASD, reoperation cases, or clinical results between groups. Thus, single-level OLIF can maintain the corrected disc height, but as it has no effect on global alignment, its benefit is limited.

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study.

PURPOSE: In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. MATERIALS AND METHODS: Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1-2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5-7 months after the administration of romosozumab. RESULTS: A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1-2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5-7 months after romosozumab administration; and a significant increase only observed in the lumbar spine. CONCLUSION: Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

Background factors for chronic low back pain resistant to cognitive behavioral therapy.

This study examined the factors that inhibit the therapeutic effects of cognitive behavioral therapy (CBT) and clarify the adaptation judgment criteria of CBT. We included patients with chronic low back pain and allocated them to the adaptation (with visual analog scale [VAS] improvement) or non-adaptation group (without VAS improvement). The patients were analyzed using various psychological tests. CBT improved depressive symptoms and catastrophic thinking; however, they were not correlated with the VAS and did not directly affect low back pain improvement. The non-adaptation group showed an unexplainable/vague sense of anxiety; an excessive focus on searching for pain; a strong intimacy desire; a strong tendency of medical dependency; and fantasy or distortion of the actual experience, especially self-image. Moreover, the patients showed a low ability to objectively express or attribute meaning to pain due to poor language skills, attention-deficit hyperactivity disorder, and emotional value judgment. Individuals with the aforementioned characteristics of pre-CBT psychological tests should select a different treatment approach given the high poor-adaption possibility. Even patients with depressive or anxious symptoms are not necessarily adaptable for CBT. Therefore, pre-CBT tests for treatment suitability are necessary. Future studies should establish a protocol for psychotherapy suitable for the non-adaptation group.

Effects of Nintendo Ring Fit Adventure Exergame on Pain and Psychological Factors in Patients with Chronic Low Back Pain.

Objective: In recent years, there has been an increase in research on the therapeutic effects of exergaming, but there have been few studies on these types of interventions for chronic low back pain. In this study, we hypothesized that the Nintendo Ring Fit Adventure (RFA) exergame would be effective for patients with chronic low back pain, and we conducted a randomized prospective longitudinal study. Materials and Methods: Patients with chronic low back pain were included in this study. Twenty randomly selected patients (9 males and 11 females, mean age 49.3 years) were included in the RFA group, and RFA exergaming was performed once a week for 40 minutes for 8 weeks. Twenty patients (12 males and 8 females, mean age 55.60 years) served as the control group and received oral treatment for 8 weeks. Pain and psychological scores (pain self-efficacy, pain catastrophizing, and kinesiophobia) were measured and analyzed before and after 8 weeks of treatment in both groups. Results: In the RFA group, low back pain, buttock pain, and pain self-efficacy were significantly improved after 8 weeks of RFA exergaming, but there was no significant improvement in lower limb numbness, pain catastrophizing, or kinesiophobia. In the control group, no significant improvement was observed after 8 weeks of oral treatment. Conclusion: RFA exergaming increased pain self-efficacy and reduced pain in patients with chronic low back pain. Future treatment protocols should be developed to improve pain self-efficacy. Approval code: 2894, School of Medicine, Chiba University.

Gene expression profiling of the spinal cord at the chronic pain phase identified CDKL5 as a candidate gene for neural remodeling.

BACKGROUND: Chronic pain is a highly refractory and complicated condition that persists even without nociception. Several genome-wide gene expression analyses have shown that the immune response and inflammatory cytokines affect chronic pain establishment in the acute pain phase. However, compared with the acute phase, the chronic phase has a poorly elucidated gene expression profile. This study aimed to determine the gene expression profile in the spinal cord of a neuropathic pain mouse model in the chronic phase to elucidate the chronic pain characteristics. METHODS: We established a sciatic nerve cuff mouse model as a neuropathic pain model by placing a 2-mm section of a split PE-20 polyethylene tube around the sciatic nerve. The spinal cord was harvested at the L4-6 level at 28 postoperative days. Next, we examined differentially expressed genes (DEGs) through RNA sequencing (RNA-seq) compared with the sham group; moreover, we conducted enrichment analyses of the expressed genes. To reveal the chronic pain characteristics, we compared the gene expression profiles of the spinal cord between the acute and chronic phases in the neuropathic pain model. Among the chronic pain-related genes categorized in the dendrites, we focused on cyclin-dependent kinase-like 5 (CDKL5). We analyzed CDKL5 expression and function using real-time polymerase chain reaction (PCR), immunohistochemistry, and neurite extension assay in Neuro 2a (N2a) cells. We used three types of CDKL5 plasmids: wild type, nuclear localization signal-attached, and K42R kinase-dead CDKL5. RESULTS: We identified 403 DEGs, including 104 upregulated and 43 downregulated genes (false discovery rate < 0.01). Rather than inflammation or immune response, the most enriched terms in the chronic phase were "regulation of plasma membrane-bounded cell projection organization" and "dendrite." Real-time PCR assay confirmed increased CDKL5 expression in the ipsilateral dorsal horn. CDKL5 was broadly expressed in the ipsilateral dorsal horn across all layers. The neurite extension assay revealed that the cytoplasmic kinase function of CDKL5 was necessary for neurite outgrowth in N2a cells. CONCLUSION: RNA-seq of the spinal cord revealed that the most enriched genes during the chronic pain phase were involved in regulating axon and dendrite morphogenesis, including CDKL5. Our findings suggest that neural remodeling affects chronic pain establishment. Since patients with CDKL5 mutations have shown reduced pain perception, our findings suggest that CDKL5 in the spinal cord could result in neural remodeling during the chronic pain phase through cytoplasmic kinase activity.

Percutaneously-quantified advanced glycation end-products (AGEs) accumulation associates with low back pain and lower extremity symptoms in middle-aged low back pain patients.

Advanced glycation end-products (AGEs) have been reported as a possible biomarker of ageing and metabolic diseases; however, its role in the clinical progression of these diseases remains unclear. We aimed to evaluate how AGEs are associated with clinical symptoms and comorbidities in lower back pain (LBP) patients. This prospective cohort study enrolled 636 LBP patients. They were subjected to quantified AGE (qAGE) analysis using skin autofluorescence, and their clinical symptoms and comorbidities, such as diabetes, renal failure with haemodialysis treatment, and osteoporosis, were measured. LBP, lower extremity pain, and numbness were evaluated using a visual analogue scale (VAS). The measured qAGE was significantly higher in subjects with any comorbidity. Age also showed a strong positive correlation with qAGE. qAGE and VAS for leg numbness were positively correlated. Furthermore, in LBP patients under 50-years-old, qAGE was positively correlated with VAS for LBP, lower extremity pain, and numbness. In conclusion, qAGE, as measured by skin autofluorescence measurement, was significantly higher in LBP patients with diabetes and dialysis, as well as in osteoporosis patients. Furthermore, qAGE showed potential as a biomarker for LBP, lower extremity pain, and numbness in patients under 50-years-old. If accumulated AGEs are identified at a young age, researchers should be vigilant for the development of osteoporosis and LBP-related clinical symptoms later in life.

Frequency of Adverse Drug Reactions and Analgesic Effects of Mirogabalin during Treatment of Peripheral Neuropathic Pain: A Retrospective Clinical Investigation.

INTRODUCTION: Mirogabalin should be equivalent to pregabalin, but with fewer incidences of adverse drug reactions (ADRs). To verify these benefits in actual clinical trials, our study investigated the frequency of ADRs and mirogabalin's analgesic effects during treatment of peripheral neuropathic pain. METHODS: This study included 74 patients with lower limb pain. We surveyed patient reports of ADRs during the follow-up period as the primary endpoint and examined the visual analog scale (VAS) reported for lower limb pain as the secondary endpoint (before administration, and two and four weeks after administration). RESULTS: The occurrence of ADR was 27.0%, like the frequency of ADRs in the clinical trials for other disorders. However, the discontinuation rate of administration was 10.8%, which was significantly lower than the frequency of ADR occurrences. When the analgesic effect was assessed, a significant decrease in the temporal change of VAS for lower limb pain was observed before administration, and two and four weeks after administration. CONCLUSIONS: In this study, the occurrence of ADRs reported by the patients was like the frequency of ADRs reported in the clinical trials for other disorders. When assessing the analgesic effect, the temporal change of VAS for lower limb pain was found to decrease significantly before administration, and two and four weeks after administration.

Temporal expression profiling of DAMPs-related genes revealed the biphasic post-ischemic inflammation in the experimental stroke model.

The neuroinflammation in the ischemic brain could occur as sterile inflammation in response to damage-associated molecular patterns (DAMPs). However, its long-term dynamic transcriptional changes remain poorly understood. It is also unknown whether this neuroinflammation contributes to the recovery or just deteriorates the outcome. The purpose of this study is to characterize the temporal transcriptional changes in the post-stroke brain focusing on DAMPs-related genes by RNA-sequencing during the period of 28 days. We conducted the RNA-sequencing on day 1, 3, 7, 14, 28 post-stroke in the mouse photothrombosis model. The gross morphological observation showed the ischemic lesion on the ipsilateral cortex turned into a scar with the clearance of cellular debris by day 28. The transcriptome analyses indicated that post-stroke period of 28 days was classified into four categories (I Baseline, II Acute, III Sub-acute-#1, IV Sub-acute-#2 phase). During this period, the well-known genes for DAMPs, receptors, downstream cascades, pro-inflammatory cytokines, and phagocytosis were transcriptionally increased. The gene ontology (GO) analysis of biological process indicated that differentially expressed genes (DEGs) are genetically programmed to achieve immune and inflammatory pathways. Interestingly, we found the biphasic induction of various genes, including DAMPs and pro-inflammatory factors, peaking at acute and sub-acute phases. At the sub-acute phase, we also observed the induction of genes for phagocytosis as well as regulatory and growth factors. Further, we found the activation of CREB (cAMP-response element binding protein), one of the key players for neuronal plasticity, in peri-ischemic neurons by immunohistochemistry at this phase. Taken together, these findings raise the possibility the recurrent inflammation occurs at the sub-acute phase in the post-stroke brain, which could be involved in the debris clearance as well as neural reorganization.

Diagnosis of lumbar radiculopathy using simultaneous MR neurography and apparent T2 mapping.

We sought to assess the utility of simultaneous apparent T2 mapping and neurography with the nerve-sheath signal increased by inked rest-tissue rapid acquisition of relaxation-enhancement imaging (SHINKEI-Quant) for the quantitative evaluation of compressed nerves in patients with lumbar radiculopathy. Thirty-two patients with lumbar radiculopathy and 5 healthy subjects underwent simultaneous apparent T2 mapping and neurography with SHINKEI-Quant. Regions of interest (ROIs) were placed in the lumbar dorsal root ganglia (DRG) and the spinal nerves distal to the lumbar nerves bilaterally at L4-S1. The T2 relaxation times were measured on the affected and unaffected sides. The T2 ratio was calculated as the affected side/unaffected side. Pearson correlation coefficients were calculated to determine the correlation between the T2 relaxation times or T2 ratio and clinical symptoms. An ROC curve was used to examine the diagnostic accuracy and threshold of the T2 relaxation times and T2 ratio. We observed no significant differences in the T2 relaxation times between the nerve roots on the left and right at each spinal level in healthy subjects. In patients, lumbar neurography revealed swelling of the involved nerve, and prolonged T2 relaxation times compared with that of the contralateral nerve. The T2 ratio correlated with leg pain. The ROC analysis revealed that the T2 relaxation time threshold was 127 ms and the T2 ratio threshold was 1.07. To our knowledge, this is the first study to show the utility of SHINKEI-Quant for the quantitative evaluation of lumbar radiculopathy.

Successful salvage surgery for failed transforaminal lumbosacral interbody fusion using the anterior transperitoneal approach.

Transforaminal lumbar interbody fusion (TLIF) is a popular posterior spinal fusion technique, but sometimes require salvage surgery when implant failure occurs, which involves possible neural damage due to postoperative adhesion. The current report deals with successful anterior transperitoneal salvage surgery for failed L5-S TLIF with less neural invasiveness.