Multicenter cross-sectional study of the clinical features and types of treatment of spinal cord-related pain syndrome.

BACKGROUND: We termed chronic neuropathic pain (NeP) in patients with diseases associated with spinal cord damage as "spinal cord-related pain syndrome". We conducted a survey of patients with the syndrome to assess the type and severity of NeP and its effect on QOL, and treatment modalities. METHODS: This cross-sectional study was conducted in 185 patients recruited from 15 medical institutions. We analyzed the questionnaires sent to clinicians (basic information, magnetic resonance imaging (MRI) findings, type and effectiveness of medications) and patients [modified Neuropathic Pain Symptom Inventory (NPSI) and short form (SF)-36 healthy survey]. RESULTS: The incidence of spinal cord-related pain syndrome was highest in patients with cervical spondylotic myelopathy, ossification of posterior longitudinal ligament (OPLL) and spinal cord injury. The number of patients with at-level pain was higher than those with below-level pain; dysesthesia/paresthesia, spontaneous and evoked pain types were mainly seen in patients with at-level pain and dysesthesia/paresthesia was common among those with below-level pain. NPSI score was higher than 10 in the majority of patients, and the subscore for dysesthesia/paresthesia was significantly the highest. The NPSI score was the highest in patients with severe hyperintense signal increase on MRI. The scores of all SF-36 sub-items were significantly lower than the national average. The majority of patients used non-steroid anti-inflammatory drugs and gabapentin/pregabalin; the latter was significantly effective for allodynia, compared with other medications, regardless of the pain level. CONCLUSIONS: The majority of patients with spinal cord-related pain syndrome suffered from severe NeP, which affected physical activity. The pain phenotype varied according to the level of the lesion and dysesthesia/paresthesia was the most intense. Compared with other medications, gabapentin/pregabalin was significantly effective especially for dysesthesia/paresthesia and evoked pain regardless of the pain level.

Early transplantation of mesenchymal stem cells after spinal cord injury relieves pain hypersensitivity through suppression of pain-related signaling cascades and reduced inflammatory cell recruitment.

Bone marrow-derived mesenchymal stem cells (BMSC) modulate inflammatory/immune responses and promote motor functional recovery after spinal cord injury (SCI). However, the effects of BMSC transplantation on central neuropathic pain and neuronal hyperexcitability after SCI remain elusive. This is of importance because BMSC-based therapies have been proposed for clinical treatment. We investigated the effects of BMSC transplantation on pain hypersensitivity in green fluorescent protein (GFP)-positive bone marrow-chimeric mice subjected to a contusion SCI, and the mechanisms of such effects. BMSC transplantation at day 3 post-SCI improved motor function and relieved SCI-induced hypersensitivities to mechanical and thermal stimulation. The pain improvements were mediated by suppression of protein kinase C-γ and phosphocyclic AMP response element binding protein expression in dorsal horn neurons. BMSC transplants significantly reduced levels of p-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (p-ERK1/2) in both hematogenous macrophages and resident microglia and significantly reduced the infiltration of CD11b and GFP double-positive hematogenous macrophages without decreasing the CD11b-positive and GFP-negative activated spinal-microglia population. BMSC transplants prevented hematogenous macrophages recruitment by restoration of the blood-spinal cord barrier (BSCB), which was associated with decreased levels of (a) inflammatory cytokines (tumor necrosis factor-α, interleukin-6); (b) mediators of early secondary vascular pathogenesis (matrix metallopeptidase 9); (c) macrophage recruiting factors (CCL2, CCL5, and CXCL10), but increased levels of a microglial stimulating factor (granulocyte-macrophage colony-stimulating factor). These findings support the use of BMSC transplants for SCI treatment. Furthermore, they suggest that BMSC reduce neuropathic pain through a variety of related mechanisms that include neuronal sparing and restoration of the disturbed BSCB, mediated through modulation of the activity of spinal-resident microglia and the activity and recruitment of hematogenous macrophages.

Extensive Loss of Tibialis Anterior Tendon: Surgical Repair With Split Tendon Transfer of Tibialis Posterior Tendon: A Case Report.

Extensive damage of the tibialis anterior tendon is rare and mainly caused by trauma. Surgical treatment of these injuries can become challenging owing to the limited availability of autogenous graft resources for reconstruction of the defect. In the present case report, we describe a large defect in the midfoot soft tissue after a traffic injury, which included complete loss of the tibialis anterior tendon. The tendon was reconstructed by split tendon transfer of the tibialis posterior tendon without sacrificing function, which was confirmed by the follow-up examination at 6 years after injury. We believe split tendon transfer of the tibialis posterior tendon can be one of the treatment options for patients with extensive disruption of the tibialis anterior tendon.

Intraportal GLP-1 stimulates insulin secretion predominantly through the hepatoportal-pancreatic vagal reflex pathways.

We previously reported that glucagon-like peptide-1 (GLP-1) appearance in the portal vein facilitates hepatic vagal afferent activity, and this further augments reflexively the pancreatic vagal efferents in anesthetized rats, suggesting a neuroincretin effect of GLP-1. To determine whether the GLP-1-induced vagal pathways lead to a neuronal-mediated component (NMC) of insulin secretion, we infused GLP-1 at a physiological or pharmacological dose (1 or 3 pmol·kg(-1)·min(-1), respectively) into the portal vein in conscious rats with selective hepatic vagotomy (Vagox) or sham operation (Sham). The experiments consisted of two sequential 10-min intraportal infusions (P1 and P2): glucose at a physiological rate (56 µmol·kg(-1)·min(-1)) in P1 and the glucose plus GLP-1 or vehicle in P2. Under arterial isoglycemia across the groups, the physiological GLP-1 infusion in Sham augmented promptly and markedly arterial insulin levels, approximately twofold the levels in glucose alone infusion (P < 0.005), and insulin levels in Vagox diminished apparently (P < 0.05). Almost 60% of the GLP-1-induced insulin secretion (AUC) in Sham met the NMC, i.e., difference between insulin secretion in Sham and Vagox, (AUC 976 ± 65 vs. 393 ± 94 pmol·min/l, respectively, P < 0.005). Intraportal pharmacological GLP-1 infusion further augmented insulin secretion in both groups, but the NMC remained in 46% (NS; Sham vs. Vagox). In contrast, "isoglycemic" intravenous GLP-1 infusion (3 pmol·kg(-1)·min(-1)) evoked an equal insulin secretion in both groups. Thus, the present results indicate that GLP-1 appearing in the portal vein evokes a powerful neuronal-mediated insulinotropic effect, suggesting the neuroincretin effect.

A genome-wide sib-pair linkage analysis of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common musculoskeletal disease among people after middle age. The OPLL presents with serious neurological abnormalities due to compression of the spinal cord and nerve roots. The OPLL is caused by genetic and environment factors; however, its etiology and pathogenesis still remain to be elucidated. To determine the susceptibility loci for OPLL, we performed a genome-wide linkage study using 214 affected sib-pairs of Japanese. In stratification analyses for definite cervical OPLL, we found loci with suggestive linkage on 1p21, 2p22-2p24, 7q22, 16q24 and 20p12. Fine mapping using additional markers detected the highest non-parametric linkage score (3.43, P = 0.00027) at D20S894 on chromosome 20p12 in a subgroup that had no complication of diabetes mellitus. Our result would shed a new light on genetic aspects of OPLL.

Knee laxity after staircase exercise predicts radiographic disease progression in medial compartment knee osteoarthritis.

OBJECTIVE: To evaluate whether increased laxity of the knee during daily physical activities such as stair climbing is associated with progression of knee joint osteoarthritis (OA). METHODS: During the years 2001-2003, 136 patients with bilateral primary medial compartment knee joint OA were enrolled in this prospective study. Baseline data collected were body mass index (BMI), muscle power, radiographic joint space width, mechanical axis on standing radiography, and anteroposterior (AP) knee laxity before and after physical exercise. After 8 years of followup, 84 patients were reexamined to assess radiographic changes. Radiographic disease progression was defined as progression of >1 grade on the Kellgren/Lawrence scale. RESULTS: AP knee laxity increased significantly after stair climbing. Patients with OA progression and those without progression did not differ significantly in age, sex, baseline quadriceps muscle strength, mechanical axis, joint space width, and AP knee laxity before exercise. The 2 groups of patients did, however, differ significantly in baseline BMI and change in AP knee laxity due to exercise. The risk of progression of knee OA increased 4.15-fold with each millimeter of increase in the change in AP knee laxity due to exercise and 1.24-fold with each point increase in the BMI. CONCLUSION: Our results indicate that patients with OA progression have significantly greater changes in knee joint laxity during physical activities and a higher BMI than patients without OA progression. These findings suggest that larger changes in knee laxity during repetitive physical activities and a higher BMI play significant roles in the progression of knee OA.

Modified metaphyseal-loading anterolaterally flared anatomic femoral stem: five- to nine-year prospective follow-up evaluation and results of three-dimensional finite element analysis.

We have designed a proximal-fitting, anterolaterally flared, arc-deposit hydroxyapatite-coated anatomical femoral stem (FMS-anatomic stem; KYOCERA Medical, Osaka, Japan) for cementless total hip arthroplasty (THA) for Japanese patients with dysplastic hip osteoarthritis, using a nonlinear three-dimensional finite element analysis simulating loading conditions. The Anatomic Fit stem was modified in the region of the arc-sprayed surface, to allow more proximal appearance of spot welds. The aim of the present study was to analyze the clinical and radiographic outcomes of patients who underwent THA using this stem. We reviewed 73 consecutive patients (79 hips; 13 men 16 hips; 60 women 63 hips; age at surgery, 57.6 years, range, 35-78) who underwent cementless THA using the Anatomic Fit stem, at a follow-up period of 7.1 years (range, 5.1-9.4). Harris Hip score improved from 40.7 ± 17.1 before surgery to 91.0 ± 5.2 points at follow-up. The 7.1-year stem survival rate was 100%. Radiographs at follow-up confirmed the stability of the femoral stems within the femoral canal in all cases, with sufficient bone ingrowth. None of the patients had subsidence of the stem exceeding 2.0 mm within the femoral canal or changes in varus or valgus position of more than 2.0°. The Anatomic Fit stem provided excellent results. The nonlinear three-dimensional finite element analysis demonstrated that the stem-bone relative motion was 10 µm at the proximal end of the stem and proximal load transfer. Our analysis confirmed reduced radiolucency around the stem, minimal subsidence, appropriate stress shielding, and promising medium-term stability within the femoral canal.

Effects of low frequency electromagnetic field on proliferation of human epidermal stem cells: An in vitro study.

To investigate the effects of low frequency electromagnetic fields (EMF) on the proliferation of epidermal stem cells, human epidermal stem cells (hESC) were isolated, expanded ex vivo, and then exposed to a low frequency EMF. The test and control cells were placed under the same environment. The test cells were exposed for 30 min/day to a 5 mT low frequency EMF at 1, 10, and 50 Hz for 3, 5, or 7 days. The effects of low frequency EMF on cell proliferation, cell cycle, and cell-surface antigen phenotype were investigated. Low frequency EMF significantly enhanced the proliferation of hESC in the culture medium in a frequency-dependent manner, with the highest cell proliferation rate at 50 Hz (P < 0.05). Exposure to a low frequency EMF significantly increased the percentage of cells at the S phase of the cell cycle, coupled with a decrease in the percentage of cells in the G1 phase (P < 0.05) but the effect was not frequency dependent. The percentage of CD29(+) /CD71(-) cells remained unchanged in the low frequency EMF-exposed hESC. The results suggested that low frequency EMF influenced hESC proliferation in vitro, and this effect was related to the increased proportion of cells at the S phase.

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.

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.

Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice.

BACKGROUND: Recent in vivo and in vitro studies in non-neuronal and neuronal tissues have shown that different pathways of macrophage activation result in cells with different properties. Interleukin (IL)-6 triggers the classically activated inflammatory macrophages (M1 phenotype), whereas the alternatively activated macrophages (M2 phenotype) are anti-inflammatory. The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. METHODS: MR16-1 antibodies versus isotype control antibodies or saline alone were administered immediately after thoracic SCI in mice. SC tissue repair was compared between the two groups by Luxol fast blue (LFB) staining for myelination and immunoreactivity for the neuronal markers growth-associated protein (GAP)-43 and neurofilament heavy 200 kDa (NF-H) and for locomotor function. The expression of T helper (Th)1 cytokines (interferon (IFN)-γ and tumor necrosis factor-α) and Th2 cytokines (IL-4, IL-13) was determined by immunoblot analysis. The presence of M1 (inducible nitric oxide synthase (iNOS)-positive, CD16/32-positive) and M2 (arginase 1-positive, CD206-positive) macrophages was determined by immunohistology. Using flow cytometry, we also quantified IFN-γ and IL-4 levels in neutrophils, microglia, and macrophages, and Mac-2 (macrophage antigen-2) and Mac-3 in M2 macrophages and microglia. RESULTS: LFB-positive spared myelin was increased in the MR16-1-treated group compared with the controls, and this increase correlated with enhanced positivity for GAP-43 or NF-H, and improved locomotor Basso Mouse Scale scores. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. Whereas iNOS-positive, CD16/32-positive M1 macrophages were the predominant phenotype in the injured SC of non-treated control mice, MR16-1 treatment promoted arginase 1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site. MR16-1 treatment suppressed the number of IFN-γ-positive neutrophils, and increased the number of microglia present and their positivity for IL-4. Among the arginase 1-positive M2 macrophages, MR16-1 treatment increased positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. CONCLUSION: The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages.

Clinical significance of MRI/(18)F-FDG PET fusion imaging of the spinal cord in patients with cervical compressive myelopathy.

PURPOSE: (18)F-FDG PET is used to investigate the metabolic activity of neural tissue. MRI is used to visualize morphological changes, but the relationship between intramedullary signal changes and clinical outcome remains controversial. The present study was designed to evaluate the use of 3-D MRI/(18)F-FDG PET fusion imaging for defining intramedullary signal changes on MRI scans and local glucose metabolic rate measured on (18)F-FDG PET scans in relation to clinical outcome and prognosis. METHODS: We studied 24 patients undergoing decompressive surgery for cervical compressive myelopathy. All patients underwent 3-D MRI and (18)F-FDG PET before surgery. Quantitative analysis of intramedullary signal changes on MRI scans included calculation of the signal intensity ratio (SIR) as the ratio between the increased lesional signal intensity and the signal intensity at the level of the C7/T1 disc. Using an Advantage workstation, the same slices of cervical 3-D MRI and (18)F-FDG PET images were fused. On the fused images, the maximal count of the lesion was adopted as the standardized uptake value (SUV(max)). In a similar manner to SIR, the SUV ratio (SUVR) was also calculated. Neurological assessment was conducted using the Japanese Orthopedic Association (JOA) scoring system for cervical myelopathy. RESULTS: The SIR on T1-weighted (T1-W) images, but not SIR on T2-W images, was significantly correlated with preoperative JOA score and postoperative neurological improvement. Lesion SUV(max) was significantly correlated with SIR on T1-W images, but not with SIR on T2-W images, and also with postoperative neurological outcome. The SUVR correlated better than SIR on T1-W images and lesion SUV(max) with neurological improvement. Longer symptom duration was correlated negatively with SIR on T1-W images, positively with SIR on T2-W images, and negatively with SUV(max). CONCLUSION: Our results suggest that low-intensity signal on T1-W images, but not on T2-W images, is correlated with a poor postoperative neurological outcome. SUV(max) of lesions showing increased signal intensity and SUVR measured on fusion MRI/PET scans are more sensitive parameters for predicting clinical outcome than signal intensity on the MRI scan.

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.

Anteroposterior and varus-valgus laxity of the knee increase after stair climbing in patients with mild osteoarthritis.

The aim of this study was to measure exercise-induced changes in knee joint laxity in patients with knee osteoarthritis (OA). The study subjects were 46 female patients with OA and 22 age- and sex-matched normal controls. Radiographs of the knee were taken in all subjects, and the disease severity was graded according to the Kellgren and Lawrence (K-L) grading system. The K-L grade of the control subjects (non-OA group) was 0-1. The OA patients were divided into those with mild OA (K-L grade 2, n = 20) and advanced OA (K-L grade 3-4, n = 26). The subject climbed up and down 8 steps on a staircase apparatus over a period of 10 min. The anteroposterior (A-P) translation was measured with KT2000 arthrometer, and varus-valgus (V-V) rotation was measured on stress radiographs before and after the stair climbing. The Δchange in A-P translation after the exercise was significantly larger in mild OA group than other groups (P < 0.005). The Δchange in V-V rotation after exercise was significantly larger in mild and advanced OA groups than the control (P < 0.003). There were no significant differences in A-P laxity and V-V laxity before exercise among the non-OA, mild OA and advanced OA groups. Exercise resulted in significant changes in A-P knee joint laxity in patients with mild OA relative to the control. The results suggest that daily physical activities (e.g., knee bending or squatting) play a role in the development of knee laxity, particularly in patients with mild OA, and that progression of knee OA seems to correlate with increments of A-P knee joint laxity.

Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy).

INTRODUCTION: Ossification of the posterior longitudinal ligament (OPLL) is a significantly critical pathology that can eventually cause serious myelopathy. Ossification commences in the vertebral posterior longitudinal ligaments, and intensifies and spreads with the progression of the disease, resulting in osseous projections and compression of the spinal cord. However, the paucity of histological studies the underlying mechanisms of calcification and ossification processes remain obscure. The pathological process could be simulated in the ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy). The aim of this study is to observe that enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of the posterior longitudinal ligament of twy/twy mice. MATERIALS AND METHODS: The mutant twy/twy mice (6 to 22-week-old) were used in the present study. The vertebral column was analyzed histologically and immunohistochemically. RESULTS: We observed that the enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of posterior longitudinal ligament of twy/twy mice. In this regards, the cells of the protruded hyperplastic annulus fibrosus invaded the longitudinal ligaments and induced neovascularization and metaplasia of primitive mesenchymal cells to osteoblasts in the spinal ligaments of twy/twy mice. CONCLUSION: Since genetic mechanisms could play a role in human OPLL, the age-related enlargement of the nucleus pulposus in the twy/twy mouse may primarily occur as a result of overproduction of mucopolysaccharide matrix material induced by certain genetic abnormalities.

Apoptosis of neurons and oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy): possible pathomechanism of human cervical compressive myelopathy.

INTRODUCTION: Cervical compressive myelopathy is the most serious complication of cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) and the most frequent cause of spinal cord dysfunction. There is little information on the exact pathophysiological mechanism responsible for the progressive loss of neural tissue in the spinal cord of such patients. In this study, we used the spinal hyperostotic mouse (twy/twy) as a suitable model of human spondylosis, and OPLL to investigate the cellular and molecular changes in the spinal cord. Mutant twy/twy mouse developed ossification of the ligamentum flavum at C2-C3 and exhibited progressive paralysis. MATERIALS AND METHODS: The mutant twy/twy mice, aged 16 and 24 weeks, were used in the present study. The cervical spinal cord was analyzed histologically and immunohistochemically. RESULTS: We observed that a significant correlation between the proportion of apoptotic oligodendrocytes in the compressed area of the spinal cord and the magnitude of cord compression. Immunohistochemical analysis indicated overexpression of TNFR1, CD95, and p75NTR in the twy/twy mice, which was localized by the immunofluorescence in the neurons and oligodendrocytes. CONCLUSION: The expression of such factors seems to play at least some role in the apoptotic process, which probably contributes to axonal degeneration and demyelination in the twy/twy mice spinal cords with severe compression.

Perioperative complications of anterior cervical decompression with fusion in patients with ossification of the posterior longitudinal ligament: a retrospective, multi-institutional study.

BACKGROUND: Anterior decompression with fusion (ADF) for patients with cervical ossification of the posterior longitudinal ligament (OPLL) is reportedly associated with a higher incidence of complications than is laminoplasty. However, the frequency of perioperative complications associated with ADF for cervical OPLL has not been fully established. The purpose of this study was to investigate the incidence of perioperative complications, especially neurological complications, following ADF performed to relieve compressive cervical myelopathy due to cervical OPLL. METHODS: Study participants comprised 150 patients who had undergone ADF for cervical OPLL at 27 institutions between 2005 and 2008. Perioperative--especially neurological--complications occurring within 2 weeks after ADF were analyzed. Preoperative imaging findings, including Cobb angle, between C2 and C7 and occupying ratio of OPLL were investigated. Multivariate analysis with logistic regression was performed to identify independent risk factors for neurological complications. RESULT: Three patients (2.0 %) showed deterioration of lower-extremity function after ADF. One of the three patients had not regained their preoperative level of function 6 months after surgery. Upper-extremity paresis occurred in 20 patients (13.3 %), five of whom had not returned to preoperative levels 6 months after surgery. Patients with upper-extremity paresis showed significantly higher occupying ratios of OPLL, greater blood loss, longer operation times, fusion of more segments, and higher rates of cerebrospinal fluid leakage than those without paresis. Independent risk factors for upper-extremity paresis were a high occupying ratio of OPLL and large blood loss during surgery. CONCLUSIONS: The incidences of deterioration in upper- and lower-extremity functions were 13.3 % and 2.0 %, respectively. Patients with a high occupying ratio of OPLL are at higher risk of developing neurological deterioration.

Spontaneous epidural hematoma of thoracic spine presenting as Brown-Séquard syndrome: report of a case with review of the literature.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is an uncommon clinical entity. It produces a severe neurological deficit and prompt decompression is usually the first choice of treatment. Brown-Séquard syndrome is commonly seen in the setting of spinal trauma or an extramedullary spinal neoplasm, but rarely caused by SSEH. METHODS: Case report and literature review. FINDINGS: A previously healthy man presented with Brown-Séquard syndrome below T5-T6 cord segment secondary to spontaneous epidural hematoma. He opted for conservative treatment, which was followed by rapid resolution. CONCLUSIONS: Although Brown-Séquard syndrome as a presenting feature of SSEH is rare, it does exist in exceptional case, which should be taken into consideration for differential diagnosis. Prompt surgical decompression is an absolute surgical indication widely accepted for patient with progressive neurological deficit. However, SSEH presenting with incomplete neurological insult such as Brown-Séquard syndrome might have a benign course. Successful non-operative management of this problem does not make it a standard of care, and surgical decompression remains the standard treatment for SSEH.

Microarray analysis of expression of cell death-associated genes in rat spinal cord cells exposed to cyclic tensile stresses in vitro.

BACKGROUND: The application of mechanical insults to the spinal cord results in profound cellular and molecular changes, including the induction of neuronal cell death and altered gene expression profiles. Previous studies have described alterations in gene expression following spinal cord injury, but the specificity of this response to mechanical stimuli is difficult to investigate in vivo. Therefore, we have investigated the effect of cyclic tensile stresses on cultured spinal cord cells from E15 Sprague-Dawley rats, using the FX3000 Flexercell Strain Unit. We examined cell morphology and viability over a 72 hour time course. Microarray analysis of gene expression was performed using the Affymetrix GeneChip System, where categorization of identified genes was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) systems. Changes in expression of 12 genes were validated with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The application of cyclic tensile stress reduced the viability of cultured spinal cord cells significantly in a dose- and time-dependent manner. Increasing either the strain or the strain rate independently was associated with significant decreases in spinal cord cell survival. There was no clear evidence of additive effects of strain level with strain rate. GO analysis identified 44 candidate genes which were significantly related to "apoptosis" and 17 genes related to "response to stimulus". KEGG analysis identified changes in the expression levels of 12 genes of the mitogen-activated protein kinase (MAPK) signaling pathway, which were confirmed to be upregulated by RT-PCR analysis. CONCLUSIONS: We have demonstrated that spinal cord cells undergo cell death in response to cyclic tensile stresses, which were dose- and time-dependent. In addition, we have identified the up regulation of various genes, in particular of the MAPK pathway, which may be involved in this cellular response. These data may prove useful, as the accurate knowledge of neuronal gene expression in response to cyclic tensile stress will help in the development of molecular-based therapies for spinal cord injury.

Metaphyseal-loading anterolaterally-flared femoral stem in cementless total hip arthroplasty: five- to eleven-year follow-up evaluation.

Using a nonlinear three-dimensional finite element analysis simulating loading conditions, we designed a new type of proximal-fitting, anterolaterally-flared, arc-deposit hydroxyapatite-coated anatomical femoral stem (FMS-anatomic stem; Japan Medical Materials, Osaka, Japan) for cementless total hip arthroplasty (THA) for Japanese patients with dysplastic hip osteoarthritis. The aim of the present study was to analyze the clinical and radiographic outcomes of the new stem. We reviewed 143 consecutive patients (164 hips; 13 men, 14 hips; 130 women, 150 hips; age at surgery, 56.6 +/- 7.6 years, mean +/- SD, range, 30-74) who underwent cementless THA using the FMS-anatomic stem at a single institution, with a follow-up period of 7.6 +/- 1.6 years (range, 5.3-11.0). Harris Hip score improved from 46.1 +/- 12.6 before surgery to 90.0 +/- 8.9 points post-THA. The 7.6-year survival rate of the stem was 99.0% after revision for aseptic loosening. Radiographs at follow-up confirmed the stability of the femoral stems within the femoral canal in all cases, with sufficient bone ingrowth. None of the patients had subsidence of the stem exceeding 2.0 mm within the femoral canal or changes in varus or valgus position of more than 2.0 degrees . The FMS-anatomic stem provided excellent results in patients with dysplastic hip osteoarthritis. Our analysis confirmed reduced radiolucency around the stem in Gruen zones, minimal subsidence, appropriate stress shielding, and promising medium-term stability within the femoral canal in our patients.