Use of accelerometry to detect varus thrust of osteoarthritic knees before and one year after high tibial osteotomy.

BACKGROUND: The purpose of this study was to determine the effects of high tibial osteotomy (HTO) on varus thrust during gait in patients with medial compartment knee osteoarthritis (KOA), and to identify factors that influence thrust before and one year after surgery. METHODS: HTO was performed in 60 KOA patients (70 knees, including 56 knees by open wedge and 14 by closed wedge). The control group comprised 28 normal, control subjects. Several parameters were evaluated before surgery and one year thereafter. Varus thrust was defined as acceleration of the thigh relative to the lower leg in the coronal plane. Knee-injury-and-osteoarthritis-outcome scores (KOOSs), knee joint angles, radiography, and mediolateral knee acceleration during free speed gait were measured and analyzed. RESULTS: One-year after HTO, KOOSs, knee extension angles, and range of knee motion were improved (p < 0.001). The hip-knee-ankle angle and joint-line-convergent angle (JLCA) had decreased (p < 0.001), and walking speed had increased (p < 0.001). Preoperatively, patient acceleration was significantly (p < 0.05) higher than that of controls, and it did not change after HTO. However, it was reduced significantly (p < 0.05) after adjusting for walking speed. Walking speed correlated significantly with acceleration preoperatively, postoperatively, and among controls. Surgical methods (open-wedge/closed-wedge HTO) and correction angle did not affect postoperative acceleration. There was a low correlation between acceleration and KOOSs (KOOSa, KOOSp), knee joint angles, or JLCA postoperatively, but no relationship was found between acceleration and these parameters in the preoperative or the control group. CONCLUSIONS: Walking speed correlated significantly with acceleration preoperatively, postoperatively, and with those of controls. Mediolateral acceleration of the thigh relative to the lower leg in patients with KOA was significantly higher than that of normal controls before surgery, and it did not change after HTO. However, after surgery it was reduced significantly after adjusting for walking speed.

Symptom-based characteristics and treatment efficacy of neuropathic pain related to spinal disorders.

BACKGROUND: Symptom-based therapeutic management is required for neuropathic pain (NeP) to achieve higher treatment efficacy. In spinal disorders, which have a high prevalence of NeP, neurological symptoms are classified into myelopathy, radiculopathy, and cauda equina syndrome. The characteristics of pain and the treatment efficacy for each of these symptoms require clarification. METHODS: A retrospective patient-based outcome study was conducted in 265 outpatients with chronic NeP (≥3 months) related to spinal disorders. The patients were classified into three groups according to their neurological symptoms: spinal cord-related pain, radicular pain, and cauda equina syndrome. Data were obtained from patient-based questionnaires using the Neuropathic Pain Symptom Inventory (NPSI) and the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP), and from clinical information. RESULTS: Most of the patients with NeP had a NPSI score >10 (moderate to severe pain) and 40% had psychiatric problems. The common subtype of NeP was spontaneous pain and paresthesia/dysesthesia in patients with radicular pain and cauda equina syndrome, whereas more severe paresthesia/dysesthesia was particularly prominent in patients with spinal cord-related pain. The pain reduction rate was significantly lower in these latter patients, especially in association with residual paresthesia/dysesthesia. CONCLUSIONS: The characteristics and treatment efficacy of NeP in patients with spinal disorders varied according to neurological symptoms. Effective treatment was difficult, especially for paresthesia/dysesthesia in patients with spinal cord-related pain. These findings enhance the understanding of the underlying mechanisms of pain and could help in design of symptom-based therapeutic management.

Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling.

The pathomechanisms of initiation and progression of ossification of the posterior longitudinal ligament (OPLL) are unclear. Indian hedgehog (Ihh) and related signaling molecules are key factors in normal enchondral ossification. The purpose of this study is to investigate the contribution of mechanical strain to OPLL and the relationship of Ihh with OPLL. Sections of the posterior longitudinal ligament (PLL) were obtained from 49 patients with OPLL and from 7 patients without OPLL. Cultured PLL cells were subjected to 24 hours of cyclic tensile strain. To identify differentially expressed genes associated with cyclic tensile strain, microarray analysis was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified upregulation of various genes, particularly of the Hedgehog signaling pathway; Ihh and related genes had increased expression compared with controls after 24-hour cyclic tensile strain. In immunoblotting analysis, Ihh, Runx2, Sox9, Gli2, Gli3, and smoothened (SMO) had significantly increased expression after 6- or 12-hour cyclic tensile strain. OPLL samples were strongly immunopositive for Ihh, Sox9, Runx2, Gli2, Gli3, and SMO in the ossification front of OPLL. These results suggest that cyclic tensile strain induces abnormal activation of Ihh and related signaling molecules, and this might be important in the ossification process in OPLL.

Role of macrophages and activated microglia in neuropathic pain associated with chronic progressive spinal cord compression.

Neuropathic pain (NeP) is commonly encountered in patients with diseases associated with spinal cord damage (e.g., spinal cord injury (SCI) and compressive myelopathy). Recent studies described persistent glial activation and neuronal hyperactivity in SCI, but the pathomechanisms of NeP in chronic compression of the spinal cord remains elusive. The purpose of the present study was to determine the roles of microglia and infiltrating macrophages in NeP. The study was conducted in chimeric spinal hyperostotic mice (ttw/ttw), characterized by chronic progressive compression of the spinal cord as a suitable model of human compressive myelopathy. The severity of spinal cord compression correlated with proportion of activated microglia and hematogenous macrophages. Spinal cord compression was associated with overexpression of mitogen-activated protein kinases (MAPKs) in infiltrating macrophages and reversible blood-spinal cord barrier (BSCB) disruption in the dorsal horns. Our results suggested that chronic neuropathic pain in long-term spinal cord compression correlates with infiltrating macrophages, activated microglial cells and the associated damage of BSCB, together with overexpression of p-38 MAPK and p-ERK1/2 in these cells. Our findings are potentially useful for the design of new therapies to alleviate chronic neuropathic pain associated with compressive myelopathy.

Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury.

The use of mesenchymal stromal cell (MSC) transplantation to repair the injured spinal cord has shown consistent benefits in preclinical models. However, the low survival rate of grafted MSC is one of the most important problems. In the injured spinal cord, transplanted cells are exposed to hypoxic conditions and exposed to nutritional deficiency caused by poor vascular supply. Also, the transplanted MSCs face cytotoxic stressors that cause cell death. The aim of this study was to compare adipose-derived MSCs (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs) isolated from individual C57BL6/J mice in relation to: (i) cellular characteristics, (ii) tolerance to hypoxia, oxidative stress and serum-free conditions, and (iii) cellular survival rates after transplantation. AD-MSCs and BM-MSCs exhibited a similar cell surface marker profile, but expressed different levels of growth factors and cytokines. To research their relative stress tolerance, both types of stromal cells were incubated at 20.5% O2 or 1.0% O2 for 7 days. Results showed that AD-MSCs were more proliferative with greater culture viability under these hypoxic conditions than BM-MSCs. The MSCs were also incubated under H2O2-induced oxidative stress and in serum-free culture medium to induce stress. AD-MSCs were better able to tolerate these stress conditions than BM-MSCs; similarly when transplanted into the spinal cord injury region in vivo, AD-MSCs demonstrated a higher survival rate post transplantation Furthermore, this increased AD-MSC survival post transplantation was associated with preservation of axons and enhanced vascularization, as delineated by increases in anti-gamma isotype of protein kinase C and CD31 immunoreactivity, compared with the BM-MSC transplanted group. Hence, our results indicate that AD-MSCs are an attractive alternative to BM-MSCs for the treatment of severe spinal cord injury. However, it should be noted that the motor function was equally improved following moderate spinal cord injury in both groups, but with no significant improvement seen unfortunately following severe spinal cord injury in either group.

Reconstruction of acetabulum in revision total hip arthroplasty for pelvic discontinuity: report of a difficult case requiring four revision arthroplasty.

BACKGROUND: Massive bone defects of the acetabulum with pelvic discontinuity are one of the major problems in revision total hip arthroplasty. Several techniques have been described for repair of acetabular defect; however, reconstruction of acetabulum with massive bone defect is still a major problem. We describe a patient who required four revision total hip arthroplasty during a 24-year period. FINDINGS: The acetabulum with pelvic discontinuity was successfully reconstructed by stabilization of the posterior column with a plate commonly used for fracture treatment, and stabilization of the anterior column by reinforcement device commonly used for acetabular reconstruction. Fixation of both acetabular columns provided significant improvement of component stability. CONCLUSIONS: In the case of pelvic discontinuity with massive acetabular bone defect, reconstruction by stabilizing both acetabular columns using reconstruction plate and KT plate is one of the better surgical options.

[Ossification of the posterior longitudinal ligament (OPLL) and the ligamentum flavum (OLF)].

The adult population is frequently sustained with ossification of the posterior longitudinal ligament (OPLL) and/or the ligamentum flavum (OLF) of the spine and the diseases may subsequently result is serious spinal cord insult with profound paralysis of the extremities. These pathologies are genetically denoted metaplasia of the elastic fibers of the ligament with consequent ectopic ossification process. The spinal cord is chronically compressed and will result in profound motor paralysis with sensory deficit. Both diseases are well imaged on CT and MRI, showing a various magnitude of spinal cord compression.

Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain.

Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (P<0.05). In contrast, the application of TENS at 1 week (TENS-1w) or 2 weeks (TENS-2w) after injury was ineffective in reducing hyperalgesia (mechanical and thermal) or activation of microglia and astrocytes. Early TENS decreased p-p38 within microglia (P<0.05), the expression levels of protein kinase C (PKC-γ), and phosphorylated anti-phospho-cyclic AMP response element-binding protein (p-CREB) in the superficial spinal dorsal horn neurons (P<0.05), mitogen-activated protein (MAP) kinases, and proinflammatory cytokines, and increased the expression levels of opioid receptors (P<0.05). The results suggested that the application of early TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-γ, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible.

Prognostic value of changes in spinal cord signal intensity on magnetic resonance imaging in patients with cervical compressive myelopathy.

BACKGROUND CONTEXT: Signal intensity on preoperative cervical magnetic resonance imaging (MRI) of the spinal cord has been shown to be a potential predictor of outcome of surgery for cervical compressive myelopathy. However, the prognostic value of such signal remains controversial. One reason for the controversy is the lack of proper quantitative methods to assess MRI signal intensity. PURPOSE: To quantify signal intensity and to correlate intramedullary signal changes on MRI T1- and T2-weighted images (WIs) with clinical outcome and prognosis. STUDY DESIGN: Retrospective case study. PATIENT SAMPLE: Patients (n=148; cervical spondylotic myelopathy, n=102 and ossified posterior longitudinal ligament, n=46) who underwent surgery for cervical compressive myelopathy and had high signal intensity change on sagittal T2-WI MRI before surgery between 2006 and 2010. OUTCOME MEASURE: Neurologic assessment was conducted with the Japanese Orthopedic Association (JOA) scoring system for cervical myelopathy. The rate of neurologic improvement was calculated with the use of preoperative and postoperative JOA scores. METHODS: Quantitative analysis of MRI signal on both T1- and T2-WIs via use of the signal intensity ratio (SIR; signal intensity of lesion relative to that at C7-T1 disc level) was performed. Correlations between SIR on T1- and T2-WIs and preoperative JOA score, JOA improvement rate, disease duration, and MRI morphologic classification (cystic or diffuse type) were analyzed. Multivariate regression analysis for JOA improvement rate was also analyzed. In a substudy, 25 patients underwent follow-up MRI starting from 6 months after surgery to analyze the relationship between changes in SIR on follow-up MRI and clinical outcome. RESULTS: SIR on T1-WIs, but not SIR on T2-WIs, correlated with postoperative neurologic improvement. The disease duration correlated negatively with SIR on T1-WIs and JOA improvement rate but not with SIR on T2-WIs. SIR on T2-WIs of "cystic type" was significantly greater than of "diffuse type," but SIR on T1-WI and JOA improvement rate were not different in the two types. Stepwise multivariate regression analysis indicated that SIR on T1-WIs and long disease duration were significant predictors of postoperative neurologic outcome. SIR on follow-up T1-WI and changes in SIR on T1-WI after surgery correlated positively with postoperative improvement rate. SIR on follow-up T2-WI and changes on T2-WI correlated negatively with postoperative neurologic improvement. CONCLUSIONS: Our results suggest that low intensity signal on preoperative T1-WIs but not T2-WIs correlated with poor postoperative neurologic outcome. Furthermore, decreased signal intensity on postoperative T1-WIs and increased signal intensity on postoperative T2-WIs are predictors of poor neurologic outcome.

Blockade of interleukin 6 signaling improves the survival rate of transplanted bone marrow stromal cells and increases locomotor function in mice with spinal cord injury.

Bone marrow stromal cells (BMSCs) have the potential to improve functional recovery in patients with spinal cord injury (SCI); however, they are limited by low survival rates after transplantation in the injured tissue. Our objective was to clarify the effects of a temporal blockade of interleukin 6 (IL-6)/IL-6 receptor (IL-6R) engagement using an anti-mouse IL-6R monoclonal antibody (MR16-1) on the survival rate of BMSCs after their transplantation in a mouse model of contusion SCI. MR16-1 cotreatment improved the survival rate of transplanted BMSCs, allowing some BMSCs to differentiate into neurons and astrocytes, and improved locomotor function recovery compared with BMSC transplantation or MR16-1 treatment alone. The death of transplanted BMSCs could be mainly related to apoptosis rather than necrosis. Transplantation of BMSC with cotreatment of MR16-1 was associated with a decrease of some proinflammatory cytokines, an increase of neurotrophic factors, decreased apoptosis rates of transplanted BMSCs, and enhanced expression of survival factors Akt and extracellular signal-regulated protein kinases 1/2. We conclude that MR16-1 treatment combined with BMSC transplants helped rescue neuronal cells and axons after contusion SCI better than BMSCs alone by modulating the inflammatory/immune responses and decreasing apoptosis.

Indian hedgehog signaling promotes chondrocyte differentiation in enchondral ossification in human cervical ossification of the posterior longitudinal ligament.

STUDY DESIGN: Histological, immunohistochemical, and immunoblot analyses of the expression of Indian hedgehog (Ihh) signaling in human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To examine the hypothesis that Ihh signaling in correlation with Sox9 and parathyroid-related peptide hormone (PTHrP) facilitates chondrocyte differentiation in enchondral ossification process in human cervical OPLL. SUMMARY OF BACKGROUND DATA: In enchondral ossification, certain transcriptional factors regulate cell differentiation. OPLL is characterized by overexpression of these factors and disturbance of the normal cell differentiation process. Ihh signaling is essential for enchondral ossification, especially in chondrocyte hypertrophy. METHODS: Samples of ossified ligaments were harvested from 45 patients who underwent anterior cervical decompressive surgery for symptomatic OPLL, and 6 control samples from patients with cervical spondylotic myelopathy/radiculopathy without OPLL. The harvested sections were stained with hematoxylin-eosin and toluidine blue, examined by transmission electron microscopy, and immunohistochemically stained for Ihh, PTHrP, Sox9, type X, XI collagen, and alkaline phosphatase. Immunoblot analysis was performed in cultured cells derived from the posterior longitudinal ligaments in the vicinity of the ossified plaque and examined for the expression of these factors. RESULTS: The ossification front in OPLL contained chondrocytes at various differentiation stages, including proliferating chondrocytes in fibrocartilaginous area, hypertrophic chondrocytes around the calcification front, and apoptotic chondrocytes near the ossified area. Immunoreactivity for Ihh and Sox9 was evident in proliferating chondrocytes and was strongly positive for PTHrP in hypertrophic chondrocytes. Mesenchymal cells with blood vessel formation were positive for Ihh, PTHrP, and Sox9. Cultured cells from OPLL tissues expressed significantly higher levels of Ihh, PTHrP, and Sox9 than those in non-OPLL cells. CONCLUSION: Our results indicated that overexpression of Ihh signaling promotes abnormal chondrocyte differentiation in enchondral ossification and enhances bone formation in OPLL.

(18)F-FDG PET/CT for Diagnosis of Osteosclerotic and Osteolytic Vertebral Metastatic Lesions: Comparison with Bone Scintigraphy.

STUDY DESIGN: A retrospective study. PURPOSE: The aims of this study were to investigate the diagnostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PET/computed tomography (CT) in the evaluation of spinal metastatic lesions. OVERVIEW OF LITERATURE: Recent studies described limitations regarding how many lesions with abnormal (18)F-FDG PET findings in the bone show corresponding morphologic abnormalities. METHODS: The subjects for this retrospective study were 227 patients with primary malignant tumors, who were suspected of having spinal metastases. They underwent combined whole-body (18)F-FDG PET/CT scanning for evaluation of known neoplasms in the whole spine. (99m)Tc-methylene diphosphonate bone scan was performed within 2 weeks following PET/CT examinations. The final diagnosis of spinal metastasis was established by histopathological examination regarding bone biopsy or magnetic resonance imaging (MRI) findings, and follow-up MRI, CT and (18)F-FDG PET for extensively wide lesions with subsequent progression. RESULTS: From a total of 504 spinal lesions in 227 patients, 224 lesions showed discordant image findings. For 122 metastatic lesions with confirmed diagnosis, the sensitivity/specificity of bone scan and FDG PET were 84%/21% and 89%/76%, respectively. In 102 true-positive metastatic lesions, the bone scan depicted predominantly osteosclerotic changes in 36% and osteolytic changes in 19%. In 109 true-positive lesions of FDG PET, osteolytic changes were depicted predominantly in 38% while osteosclerotic changes were portrayed in 15%. CONCLUSIONS: (18)F-FDG PET in PET/CT could be used as a substitute for bone scan in the evaluation of spinal metastasis, especially for patients with spinal osteolytic lesions on CT.

The prevalence and phenotype of activated microglia/macrophages within the spinal cord of the hyperostotic mouse (twy/twy) changes in response to chronic progressive spinal cord compression: implications for human cervical compressive myelopathy.

BACKGROUND: Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease. METHODS: Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass. RESULTS: The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac)-2 progressively increased. CONCLUSIONS: Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease.

Fracture of the acetabulum: a retrospective review of ninety-one patients treated at a single institution.

Acetabular fracture result in fairly good outcome after the anatomic reduction in the displaced fracture fragments and damaged joint structure, but some patients will inevitably suffer from hip joint problems during their courses after the insult. We retrospectively reviewed 91 patients with acetabular fractures to investigate the causes of clinical failure and relationship among the fracture types, selected treatment options and their courses. Ninety-one patients (73 men and 18 women) with an average age of 49 years (range 18-80) at the time of injury were followed up for an average of 8.6 years (range 2-18). Judet-Letournel classification of fracture type and Matta's rating regimen of functional and radiographic patient' assessment were conducted. Conservative treatment was provided in 20 patients, in which 19 attained excellent/good, and one fair clinical results. All achieved excellent/good radiographic outcome. Surgically treated patients (n = 71) with critical dislodgement of the fracture fragment showed that 64 (90%) attained excellent/good and 7 (10%) fair/poor clinical outcomes. Sixty-three (89%) attained excellent/good and 8 (11%) fair/poor postoperative radiographic outcome. Five patients with poor radiographic outcome after surgery subsequently required total hip arthroplasty, due to the development of hip joint osteoarthritis in 3 and femoral head avascular necrosis in 2. We conclude that displacement of the joint surface should be reduced to less than 3 mm in accordance with the selection of the most appropriate surgical approach for open reduction/fixation in each fracture type; however, comminuted fracture and avascular necrosis of the femoral head may be the cause of poor clinical results.

Dislocated intra-articular femoral head fracture associated with fracture-dislocation of the hip and acetabulum: report of 12 cases and technical notes on surgical intervention.

This report describes case series of the femoral head fractures associated with fracture-dislocation of the hip joint to evaluate the mid- and long-term outcomes and to highlight the surgical technique of fixation of the femoral head from the posterior trochanteric flip osteotomy approach. Twelve patients (6 men and 6 women) with dislocated femoral head fractures (mean age at the time of injury, 56 years; range, 23-80) were followed up for mean period of 9.7 years (range, 5-20). All dislocations were reduced within less than 6 h after the injury. The type of femoral head fracture was classified according to the Pipkin classification on radiographs and CT. Five patients were classified as type I, 2 as type II, 2 as type III, and 3 as type IV. The clinical and radiological outcomes were assessed by Thompson and Epstein's regimen. Excluding 2 patients with Pipkin type III, the outcome of 9 patients was excellent/good, and poor in 1. The latter patient sustained Pipkin type IV and developed osteoarthritis 1 year after surgery and consequently required total hip arthroplasty. We conclude that small fragment of the femoral head less than 1 cm can be removed, while larger fragments should be fixed by bioabsorbable screws or pins in all types of femoral head fractures. In Pipkin type IV fractures, surgeons should always take anatomical reduction in the acetabulum into consideration during surgery.

Changes in gait pattern and hip muscle strength after open reduction and internal fixation of acetabular fracture.

OBJECTIVES: To characterize changes in the gait pattern at 3 and 12 months after surgery for acetabular fracture, to assess the relationship between various gait parameters and hip muscle strength, and to determine the factors associated with gait disorders that correlate with gait parameters measured at 12 months after surgery. DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Patients (N=19) with acetabular fractures were treated by open reduction and internal fixation (ORIF) and examined at 3 and 12 months postoperatively. The study also included a similar number of sex- and age-matched control subjects. INTERVENTIONS: Postoperative rehabilitation program. MAIN OUTCOME MEASURES: Spatiotemporal, kinematic, and kinetic variables of gait and strength of hip flexor, adductor, and abductor muscles at 3 and 12 months after ORIF. RESULTS: Walking velocity at 3 months after ORIF was slower in the patients than in the control subjects; however, walking velocity at 12 months was similar in the 2 groups. Although most of the kinematic and kinetic variables showed recovery to control levels at 3 and 12 months after ORIF, recovery was incomplete for pelvic forward tilt and hip abduction moment even at 12 months after ORIF. The greatest loss of muscle strength was noted in the hip abductors, where the average deficit was 35.4% at 3 months and 24.6% at 12 months. There was a significant relationship between hip abductor muscle strength and hip abduction moment at 3 months (R(2)=.63); however, this relationship diminished at 12 months (R(2)=.14). The presence of associated injuries correlated with lack of recovery of the peak hip abduction moment. CONCLUSIONS: Pelvic forward tilt and peak hip abduction moment showed incomplete recovery at 12 months after ORIF with subsequent conventional and home exercise rehabilitation programs. Our results suggest that improvement of hip abductor muscle strength in the early postoperative period could improve the peak hip abduction moment.

Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury.

Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0×10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-α and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.