Improved bone bonding of hydroxyapatite spacers with a high porosity in a quantitative computed tomography-image pixel analysis: A prospective 1-year comparative study of the consecutive cohort undergoing double-door cervical laminoplasty.

Laminoplasty using hydroxyapatite (HA) spacers is widely performed in patients with cervical myelopathy. However, spacer dislocation is a critical complication caused by bone absorption and inadequate bone conductivity, and can result in dural damage and restenosis. We thus designed a prospective cohort study to clarify the feasibility of increased porosity HA spacers for double-door laminoplasty by analyzing computed tomography (CT) images. Forty-seven patients underwent cervical laminoplasty. Two different types of CERATITE HA spacer were used, either high porosity (50%) or low porosity (35%). These HA spacers were placed in an alternating manner into the laminae in each patient. In total, 85 high-porosity (50%) HA spacers and 84 low-porosity (35%) HA spacers were implanted. At postoperative 2 weeks, 3 months, 6 months, and 1 year, CT images were obtained. In both groups, the percentage of bone-bonding boundary area of the HA spacer in contact with laminae and bone volume of the spinous process relative to the 2-week value were calculated by a 3D and 2D CT-image pixel analysis. The bone-bonding ratio was significantly higher in high-porosity (50%) than low-porosity (35%) HA spacers at 3 months and thereafter (1 year, 69.3 ± 27.8% and 49.7 ± 32.9% respectively, P < .01). The bone volume in both groups significantly decreased with time (1 year, 73.2 ± 29.8% and 69.0 ± 30.4% respectively, P < .01), indicating bone absorption. This showed no significant difference between the HA spacers (P = .15) but was higher in high-porosity (50%) than low-porosity (35%) HA spacers throughout the study period. Meanwhile, spacer breakage was found in 4.7% of high-porosity (50%) HA spacers and 1.2% of low-porosity (35%) HA spacers (P = .37). In summary, high-porosity (50%) HA spacers have the advantages of accelerated bone bonding and relatively decelerated bone absorption compared to low-porosity (35%) HA spacers; however, possibly more frequent breakage of HA spacers with a high porosity (50%) requires careful, extended postoperative follow-up.

Lumbar spondylolysis: A report of four cases from two generations of a family.

Spondylolysis is a major cause of back pain in children and adolescents. The prevalence of spondylolysis depends on the sex, race, and congenital abnormality. These biases suggest hereditary predisposition as an etiology of spondylolysis. However, no conclusive evidence still exists regarding the inheritance for spondylolysis. Herein, we report rare cases with familial occurrence of lumbar spondylolysis. In two generations of a Japanese family, three brothers including identical twins complained of back pain related to sports activities. Clinical, radiographic, and computed tomographic examinations identified spondylolysis at L4 and L5 in all these boys. The father experienced long-term back pain and had spondylolisthesis at L4-L5 and healed spondylolysis at L5. The daughter and mother did not show any lumbar spondylolysis. The frequent development of spondylolysis at L4, a rarely affected segment, in four of six family members (66.7%) support that lumbar spondylolysis has an underlying genetic etiology, primarily autosomal dominant inheritance.

Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study.

PURPOSE: Palliative surgery for patients with spinal metastasis provides good clinical outcomes. However, there have been few studies on quality of life (QOL) and cost-utility of this surgery. We aimed to elucidate QOL and cost-utility of surgical treatment for spinal metastasis. METHODS: We prospectively analyzed 47 patients with spinal metastasis from 2010 to 2014 who had a surgical indication. Thirty-one patients who desired surgery underwent spinal surgery (surgery group). Sixteen patients who did not want to undergo spinal surgery (non-surgery group). The EuroQol 5D (EQ-5D) and relevant costs were measured at one, three, six, and 12 months after study enrollment. Health state values were obtained by Japanese EQ-5D scoring and quality-adjusted life years (QALY) gained were calculated for each group. Cost-utility was expressed as the incremental cost-utility ratio (ICUR). RESULTS: Health state values improved from 0.036 at study enrollment to 0.448 at 12 months in the surgery group, but deteriorated from 0.056 to 0.019 in the non-surgery group, with a significant difference between groups (P < 0.05). The mean QALY gained at 12 months were 0.433 in the surgery group and 0.024 in the non-surgery group. The mean total cost per patient in the surgery group was $25,770 compared with $8615 in the non-surgery group. The ICUR using oneyear follow-up data was $42,003/QALY gained. CONCLUSIONS: Surgical treatment for spinal metastases is associated with significant improvement in health state value. In orthopaedic surgery, an ICUR less than $50,000/QALY gained is considered acceptable cost-effectiveness. Our results indicate that surgical treatment could be cost-effective.

Thoracic compression myelopathy due to the progression of dystrophic scoliosis, the presence of a paraspinal tumor, and high and excessive amplitude movement of the shoulder.

The authors present a case of 45-year-old man with neurofibromatosis type 1 (NF-1) and thoracic scoliosis, previously undergoing fusion surgery, who developed myelopathy. This patient further complained of lightning pain when he extended and horizontally abducted the convex-side shoulder. Radiological examination revealed the progression of dystrophic scoliosis with opened spinal canals and the presence of a neurofibroma behind the spinal cord at the apical levels. Delayed development of spinal instability can occur due to dystrophy even postoperatively in patients with NF-1. After tumor resection, he had rapid recovery from myelopathy and no recurrence of radiating pain despite shoulder movement. These findings provide a speculation that high, intense amplitude movement of the shoulder toward the spinal canal causes the impingement on the neurofibroma, resulting in indirect compression of the exposed spinal cord. This is the first report describing thoracic compression myelopathy associated with paraspinal displacement of the scapula.

Prospective Cohort Study of Performance Status and Activities of Daily Living After Surgery for Spinal Metastasis.

STUDY DESIGN: A prospective cohort study of performance status (PS) and activities of daily living (ADL) in patients with spinal metastasis. OBJECTIVE: To identify the effect of spinal surgery on PS and ADL in patients with spinal metastasis. SUMMARY OF BACKGROUND DATA: Spinal metastasis causes severe neurological deficits, resulting in drastic loss of patients' PS and ADL. However, the effect of spine surgery on PS and ADL is not well known. MATERIALS AND METHODS: Seventy patients with spinal metastasis were enrolled in this study. Forty-six patients desired and underwent spine surgery ("surgery" group) and 24 patients did not desire surgery ("nonsurgery" group). Both groups received optimal treatments, including radiation, chemotherapy, and palliative care services. Evaluation was performed at 1, 3, and 6 months after study enrollment using the Eastern Cooperative Oncology Group PS, the Barthel index (BI) for ADL, and Frankel classification for neurological status. RESULTS: There was no significant difference in baseline PS, the BI, or Frankel classification between the groups. The surgery group showed significant improvement in PS, maintaining grade 2 or less throughout the duration of the study, as well as in ADL, exceeding 70 points of the BI, compared with the nonsurgery group (P<0.05). Significantly improved neurological condition was also observed in the surgery group over the following 6 months. More than 95% of patients who underwent surgery improved their PS, the BI, and neurological status. Furthermore, >80% of these patients maintained improvement in PS, the BI, and neurological status for at least 6 months. In contrast, PS, the BI, and neurological status of patients in the "nonsurgery" group deteriorated throughout the study period. CONCLUSIONS: Spine surgery improves PS, ADL, and neurological status in patients with spinal metastasis for a minimum 6 months. This indicates that these patients can acquire an independent daily life.

Expression of adiponectin receptors in human and rat intervertebral disc cells and changes in receptor expression during disc degeneration using a rat tail temporary static compression model.

BACKGROUND: Adipose tissue is a large endocrine organ known to secret adiponectin, which has anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Adiponectin is widely involved in systemic disease, diabetes mellitus, and cardiac infraction. This study aimed to investigate the involvement of adiponectin in intervertebral disc (IVD) degeneration. METHODS: Adipose and IVD tissues were obtained from human patients undergoing surgery (n = 4) and from skeletally mature Sprague-Dawley rats (n = 21). Tissues were stained immunohistochemically for adiponectin and adiponectin receptors AdipoR1 and AdipoR2. Changes in adiponectin receptor expression with IVD degeneration severity were then investigated using a rat tail temporary compression model. Rat IVD tissues were stained immunohistochemically with AdipoR1 or AdipoR2, and immunopositive cell percentages were calculated. Rat nucleus pulposus (NP) and annulus fibrosus (AF) tissues were isolated separately and treated with recombinant adiponectin (Ad 0.1 or 1.0 µg/ml) and/or interleukin-1 beta (IL-1ß) (0.2 µg/ml) for 24 h. The four groups were as follows: control group (no treatment), IL-1ß group (IL-1ß-only treatment), IL-1ß+Ad (0.1) group (IL-1ß and adiponectin [0.1 µg/ml] treatment), and IL-1ß+Ad (1.0) group (IL-1ß and adiponectin [1.0 µg/ml]). Real-time reverse transcription-polymerase chain reaction was performed to evaluate messenger-RNA (mRNA) expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). RESULTS: Adiponectin was widely expressed in human subcutaneous and epidural adipose tissue. In rat IVD tissue, adiponectin was not observed in NP and AF. However, both AdipoR1 and AdipoR2 were widely expressed in both human and rat IVD tissues, with no significant differences in expression levels between receptors. Furthermore, expression levels of AdipoR1 and AdipoR2 were gradually decreased with increased IVD degeneration severity. Interestingly, mRNA expression levels of TNF-α and IL-6 were significantly upregulated by IL-1ß stimulation. TNF-α expression in the IL-1ß+Ad 1.0 group was significantly lower than that in the IL-1ß group in both NP and AF cells (P < 0.05). Finally, IL-6 expression was not affected by adiponectin treatment in IVD cells. CONCLUSIONS: This study investigated for the first time the expression of adiponectin receptors in human and rat IVD cells. The findings indicate that adiponectin produced by the systemic or epidural adipose tissue may be involved in the pathomechanism of IVD degeneration.

Surgical debridement with retention of spinal instrumentation and long-term antimicrobial therapy for multidrug-resistant surgical site infections after spinal surgery: a case series.

PURPOSE: Post-operative surgical site infection (SSI) is one of the most significant complications after instrumented spinal surgery. However, implant retention feasibility for early-onset multidrug-resistant SSI is still controversial. We aimed to verify our therapeutic strategy, surgical debridement with implant retention and long-term antimicrobial therapy for post-operative early-onset multidrug-resistant SSI. METHODS: We retrospectively analyzed the clinical course of 11 cases [eight men and three women, with a mean age of 70.4 (54-82) years] with early-onset multidrug-resistant SSI out of 409 consecutive cases of spinal instrumentation surgery performed between 2007 and 2013 at our institution. RESULTS: The median duration of follow-up was 868 (178-1,922) days. All SSIs were controlled, without recurrence during follow-up. The microbial pathogens were methicillin-resistant Staphylococcus aureus (seven cases), multidrug-resistant Corynebacterium (two cases), methicillin-resistant Staphylococcus epidermidis (one case), and methicillin-resistant coagulase-negative Staphylococcus aureus (one case). The mean duration from SSI diagnosis to surgery was 2.9 (1-6) days. Ten patients underwent surgical debridement with implant retention. No patients required multiple operations. All patients were given antimicrobial treatments. Mean duration of intravenous antimicrobials (vancomycin, vancomycin+ piperacillin/tazobactam, or gentamicin) was 66.5 (12-352) days and 336 (89-1,673) days for oral antimicrobials (rifampicin + sulfamethoxazole/trimethoprim, sulfamethoxazole/trimethoprim, or minomycin). The mean duration of clinical signs and symptom recovery was 31.0 (7-73) days, and the mean time for normalization of C-reactive protein was 54.5 (7-105) days. CONCLUSIONS: Early-onset multidrug-resistant SSI was successfully treated by surgical debridement with implant retention and long-term antimicrobial therapy.

Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells.

INTRODUCTION: Nutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells. Therefore, we conducted an in vitro study using human IVD nucleus pulposus (NP) cells. METHODS: Thirty-two IVD specimens were obtained from patients who underwent surgical intervention and were categorized based on Pfirrmann IVD degeneration grades. Cells were isolated from the NP and cultured in the presence of recombinant human SIRT1 (rhSIRT1) under different serum conditions, including 10 % (v/v) fetal bovine serum (FBS) as normal nutrition (N) and 1 % (v/v) FBS as low nutrition (LN). 3-Methyladenine (3-MA) was used to inhibit autophagy. Autophagic activity was assessed by measuring the absorbance of monodansylcadaverine and immunostaining and Western blotting for light chain 3 and p62/SQSTM1. Apoptosis and pathway analyses were performed by flow cytometry and Western blotting. RESULTS: Cells cultured under LN conditions decreased in number and exhibited enhanced autophagy compared with the N condition. Medium supplementation with rhSIRT1 inhibited this decrease in cell number and induced an additional increase in autophagic activity (P < 0.05), whereas the combined use of rhSIRT1 and 3-MA resulted in drastic decreases in cell number and autophagy (P < 0.05). The incidence of apoptotic cell death increased under the LN condition, which was decreased by rhSIRT1 (P < 0.05) but increased further by a combination of rhSIRT1 and 3-MA (P < 0.05). Under LN conditions, NP cells showed a decrease in antiapoptotic Bcl-2 and an increase in proapoptotic Bax, cleaved caspase 3, and cleaved caspase 9, indicating apoptosis induction via the mitochondrial pathway. These changes were suppressed by rhSIRT1 but elevated further by rhSIRT1 with 3-MA, suggesting an effect of rhSIRT1-induced autophagy on apoptosis inhibition. Furthermore, the observed autophagy and apoptosis were more remarkable in cells from IVDs of Pfirrmann grade IV than in those from IVDs of Pfirrmann grade II. CONCLUSIONS: SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human IVD NP cells, suggesting that rhSIRT1 may be a potent treatment agent for human degenerative IVD disease.

Functional impact of integrin α5ß1 on the homeostasis of intervertebral discs: a study of mechanotransduction pathways using a novel dynamic loading organ culture system.

BACKGROUND CONTEXT: Intervertebral disc (IVD) degeneration, a major cause of low back pain, is considered to be induced by daily mechanical loading. Mechanical stress is widely known to affect cell survival and extracellular matrix metabolism in many cell types. Although the involvement of integrin α5ß1 transmembrane mechanoreceptor in IVD degeneration has been reported, the precise function of integrin α5ß1 remains obscure. PURPOSE: To reflect IVD tissue response to mechanical stress using a dynamic loading organ culture system and elucidate the functional impact of integrin α5ß1 on the pathomechanism of IVD degeneration. STUDY DESIGN: An ex vivo study using a dynamic loading organ culture system. METHODS: Ninety-six rat IVD explants were examined. Intervertebral discs were subjected to 1.3 MPa, 1.0 Hz dynamic compressive load in the presence or absence of an Arg-Gly-Asp (RGD) peptide with affinity to the fibronectin binding-site of integrin α5ß1. Cell viability and histomorphology were assessed. The localization of integrin α5ß1 in the IVD was assessed by immunohistochemistry. Gene expression levels of IVD cells were evaluated using real-time reverse transcription-polymerase chain reaction. RESULTS: In the nucleus pulposus (NP), cell density and viability were reduced by dynamic compressive load. Histologic degenerative alterations, mainly seen in the NP, were the morphologic changes of NP cells. In both NP and annulus fibrosus (AF), immunohistochemistry revealed localization of integrin α5ß1 and that the messenger-RNA expression of integrin α5ß1 was increased by dynamic load. Dynamic load induced a catabolic effect, the stimulation of matrix metalloproteinase-3 and -13 gene expressions by NP and AF cells. The RGD peptide partially blocked the histologic alterations and the catabolic effect. CONCLUSIONS: The dynamic loading organ culture system simulated cellular responses to mechanical loading of the IVD. Our results suggest that IVD cells recognize the mechanical stress through RGD integrins, particularly the α5ß1 subtype that is highly expressed in NP and AF cells. Further experiments using this system will provide information about pathomechanisms of IVD degeneration through the mechanotransduction pathways.

Symptomatic perineural cyst: report of two cases treated with cyst-subarachnoid shunts.

INTRODUCTION: Symptomatic perineural cysts are rare. Resection and closure of such cysts sometimes results in postoperative neurological deficits and they can recur. We report two cases of symptomatic perineural cysts treated with subarachnoid shunts. MATERIALS AND METHODS: Case 1: A 62-year-old woman presented with bladder dysfunction. We identified a cyst communicating with the subarachnoid space adjacent to the S2 nerve root and implanted a subarachnoid shunt. Seven years after this surgery, her bladder dysfunction had not recurred. Case 2: A 35-year-old woman had low back pain, radiculopathy and bladder dysfunction. We identified a cyst adjacent to the S1 nerve root and implanted a subarachnoid shunt. Her low back pain and radiculopathy improved immediately and she experienced neither postoperative neurological deficits nor recurrence. CONCLUSION: Cyst-subarachnoid shunts are a useful treatment option for symptomatic perineural cysts.

Surgical treatment for recurrent solitary fibrous tumor invading atlas.

BACKGROUND: Solitary fibrous tumor (SFT), a rare neoplasm, usually originates in the pleura. Extrapleural SFTs occasionally occur in the head and neck. METHODS: In this study, the extirpation of a rare case of recurrent SFT invading the atlas is discussed. RESULTS: Ten years after surgical resection of an SFT in the right parapharyngeal space, the patient returned with a complaint of swelling sensation in the right neck. MRI and CT showed an enhanced lobulated mass invading the right lateral C1 vertebral body and canal and encasing the right vertebral artery. Extirpation of the recurrent tumor with a combined transcervical and midline posterior approach was successful. The surgical margin was negative for cancer and the postoperative course was uneventful. CONCLUSION: Although an SFT is generally benign, recurrence can occur even after several years, therefore, careful long-term follow-up is essential for early detection. A combined transcervical and midline posterior approach proved useful for resection of the atlas body.

Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model.

INTRODUCTION: The intervertebral disc has a complex structure originating developmentally from both the mesenchyme and notochord. Notochordal cells disappear during adolescence, which is also when human discs begin to show degenerative signs. During degeneration later in life, disc cells decline because of apoptosis. Although many animal models have been developed to simulate human disc degeneration, few studies have explored the long-term changes in cell population and phenotype. Our objective was to elucidate the time-dependent notochordal cell disappearance and apoptotic cell death in a rat tail static compression-induced disc degeneration model. METHODS: Twenty-four 12-week-old male Sprague-Dawley rat tails were instrumented with an Ilizarov-type device and loaded statically at 1.3 MPa for up to 56 days. Loaded and distal-unloaded discs were harvested. Changes in cell number and phenotype were assessed with histomorphology and immunofluorescence. Apoptosis involvement was determined with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry. RESULTS: The number of disc nucleus pulposus and annulus fibrosus cells decreased with the loading period; particularly, the decrease was notable at day 7 in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, indicating notochordal origin. Subsequently, the proportion of cells positive for TUNEL and cleaved caspase-3, markers of apoptosis induction, increased from day 7 through day 56. Although the percentage of cells immunopositive for cleaved caspase-8, a marker of apoptosis initiation through the death-receptor pathway, increased only at day 7, the percentage of cells immunopositive for cleaved caspase-9 and p53-regulated apoptosis-inducing protein 1 (p53AIP1), markers of apoptosis initiation through the p53-mediated mitochondrial pathway, increased from day 7 through day 56. The percentage of cells immunopositive for B-cell lymphoma 2 (Bcl-2) and silent mating type information regulation 2 homolog 1 (SIRT1), antiapoptotic proteins, decreased consistently with compression. CONCLUSIONS: This rat tail model mimics notochordal cell disappearance and apoptotic cell death in human disc aging and degeneration. Sustained static compression induces transient activation of apoptosis through the death-receptor pathway and persistent activation of apoptosis through the p53-mediated mitochondrial pathway in disc cells. The increased proapoptotic and decreased antiapoptotic proteins observed at all time points signify static compression-induced disc cell death and degeneration.

A case of parathyroid adenoma adjacent to the thoracic spine in a hemodialysis patient.

Ectopic parathyroid glands are detected occasionally, especially in cases of recurrent hyperparathyroidism after initial parathyroidectomy. Their ectopic locations usually result from faulty migration during embryogenesis. Ectopic parathyroid glands can be found within the thyroid gland, thymus, mediastinum, carotid sheath, or retropharynx, which lie along the path of their normal migration. Here we report a rare case of parathyroid adenoma adjacent to the thoracic spine in a hemodialysis patient who had undergone parathyroidectomy previously. A 67-year-old woman on maintenance hemodialysis since 1993 developed hyperparathyroidism. She underwent total parathyroidectomy with autotransplantation in 2007. Histological examination of the parathyroid glands showed hyperplasia in three glands and adenoma in one. Serum parathyroid hormone levels gradually increased after a year. Ultrasonography of the neck and upper limbs was negative, but technetium-99-sestamibi scanning showed focal uptake in the posterior mediastinum. Computed tomography and magnetic resonance imaging confirmed a tumor adjacent to the left costovertebral junction of the third thoracic vertebra. A tumor resection was performed in 2010, and histopathological examination showed a parathyroid adenoma. Parathyroid adenoma adjacent to the thoracic spine has not been reported previously, and our case suggests that technetium-9-sestamibi scanning is useful for the correct preoperative diagnosis of such rare cases of ectopic parathyroid glands.

A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

Outcomes of surgical intervention for cervical spondylotic myelopathy accompanying local kyphosis (comparison between laminoplasty alone and posterior reconstruction surgery using the screw-rod system).

PURPOSE: The surgical strategy for cervical spondylotic myelopathy (CSM) accompanying local kyphosis is controversial. The purpose of the present study was to compare and evaluate the outcomes of two types of surgery for CSM accompanying local kyphosis: (1) laminoplasty alone (LP) and (2) posterior reconstruction surgery (PR) in which we corrected the local kyphosis using a pedicle screw or lateral mass screw. METHODS: Sixty patients who presented with local kyphosis exceeding 5° were enrolled. LP and PR were each performed on a group of 30 of these patients; 30 CSM patients without local kyphosis, who had undergone LP, were used as controls. The follow-up period was 2 years or longer. Preoperative local kyphosis angles in LP and PR were 8.3° ± 4.4° and 8.8° ± 5.7°, respectively. Preoperative C2-7 angles in LP, PR and controls were -1.7° ± 9.6°, -0.4° ± 7.2° and -12.0° ± 5.6°, respectively. The recovery rate of the JOA score, local kyphosis angle and C2-7 angle at post-op and follow-up were compared between the groups. RESULTS: The recovery rate of the JOA score in the LP group (32.6 %) was significantly worse than that in the PR group (44.5 %) and that of controls (53.8 %). Local kyphosis angles in the PR and LP groups at follow-up were 4.0° ± 8.6° and 8.0° ± 6.0°, respectively. However, although the C2-7 angle at follow-up was improved to -11.1° ± 12.7° in PR, and maintained at -11.6° ± 6.2° in controls, it deteriorated to 0.5° ± 12.7° in LP. CONCLUSIONS: The present study is the first to compare the outcomes between LP alone and PR for CSM accompanying local kyphosis. It revealed that PR resulted in a better clinical outcome than did LP alone. This result may be due to reduction of local kyphosis, stabilization of the unstable segment, and/or the maintenance of C2-7 angle until follow-up in the PR group.

C1 laminectomy for retro-odontoid pseudotumor without atlantoaxial subluxation: review of seven consecutive cases.

PURPOSE: A retro-odontoid pseudotumor is usually a reactive fibrocartilaginous mass associated with atlantoaxial subluxation (AAS). However, a retro-odontoid pseudotumor not associated with AAS, which undergoes spontaneous regression following C1 laminoplasty, has been reported. The purpose of this study was to report surgical outcomes of C1 laminectomy for retro-odontoid pseudotumor without AAS. MATERIALS AND METHODS: The cases of seven patients (mean age 75.6 ± 7.6 years-old) with retro-odontoid pseudotumor without AAS were reviewed. The mean follow up time was 52.3 ± 25.5 months. Each patient underwent a C1 laminectomy with an additional C3-6 expansion laminoplasty in three patients. The Japanese Orthopaedic Association score (JOA score) was used for neurological assessment. Pseudotumor size and additional AAS were analyzed using MRI and radiography. RESULTS: All patients exhibited neurological improvement following surgery, the JOA score improved from 7.2 ± 3.2 to 14.1 ± 2.6. The mean O-C2 and C2-7 angle decreased from -3.2 ± 2.1° to -3.9 ± 1.7°, showing a slight kyphotic change. Postoperative AAS was not observed. All pseudotumors spontaneously resolved, and recurrence and regrowth were not observed. Five patients had MRIs after gadolinium administration; four patients who showed enhancement of the pseudotumor had almost complete reduction within 1 year following surgery. DISCUSSION: Our study, assessing the outcome of C1 laminectomy for retro-odontoid pseudotumor, found neurological improvement in all cases. Since all pseudotumors were reduced and additional AAS was not observed, C1 laminectomy for retro-odontoid pseudotumor, in the absence of AAS, is recommended as a therapeutic strategy.

Efficacy of hemostasis for epidural venous plexus and safety for neural structure using soft coagulation system in spinal surgery: a laboratory investigation using a porcine model.

STUDY DESIGN: A laboratory investigation using porcine model. OBJECTIVE: To clarify the effectiveness of the soft coagulation system for stopping bleeding from the epidural vein using different outputs and the safety in terms of tissue damage including spinal cord injury. SUMMARY OF BACKGROUND DATA: Problems associated with coagulation using an electrosurgical device, such as carbonization of tissue or adhesion to the electrode, have been highlighted. So called "soft coagulation" has been developed to solve these problems. Its' utility as well as the safety of the neural structure in spine surgery has never been reported. METHODS: A total of 3 animals and 45 spinal segments were used. Total laminectomy was performed to expose the dural tube and epidural venous plexus. Stable bleeding was induced by a 22 G needle puncture. Soft coagulation monopolar output (SCM), soft coagulation bipolar output (SCB), and conventional bipolar output (CB) were used as the coagulators. Valid hemostasis was defined as macroscopically complete bleeding stoppage by coagulation within 3 minutes. The neurological assessment was evaluated by somatosensory evoked potential. Histologic analysis was performed to determine the area of thermal damage. RESULTS: Valid hemostasis ratio was 75.0% of SCM group, 68.8% of SCB group, and 30.8% of CB group. Somatosensory evoked potential monitoring revealed that spinal cord injury was observed in 4 lesions (25%) of the SCM group. Neither bipolar groups (SCB and CB) showed any changes in waveform pattern. Histologic analysis revealed that severe thermal damages were observed in the epidural space of the SCM group. CONCLUSIONS: The usefulness of soft coagulation is revealed in terms of bleeding stoppage from epidural vessels and reduced soft-tissue damage compared with the conventional electric device. However, assessing the potential risk of severe neural tissue damage including spinal cord injury, a bipolar soft coagulation is strongly recommended for use in spine surgery.

Fas ligand plays an important role for the production of pro-inflammatory cytokines in intervertebral disc nucleus pulposus cells.

It is suggested that pro-inflammatory cytokines, which are produced by interaction of the intervertebral nucleus pulposus cells and macrophages, may be linked to the cause of pain of the intervertebral disc herniation. This study carries out the in vitro experiments to examine the mechanism, with the use of the co-culture of an immortalized cell line of nucleus pulposus of the human intervertebral disc and the macrophage cell line. As a result, it is found that the production of pro-inflammatory cytokines is significantly larger at the co-culture group than at the independent culture group. Also, at the co-culture group of macrophages and intervertebral nucleus pulposus cells with over-expression of fas ligand (FasL), the production of pro-inflammatory cytokines is found to be far larger. Furthermore, it is found that these pro-inflammatory cytokines are produced mainly by the intervertebral nucleus pulposus cells with over-expression of FasL, and that the expression of a disintegrin and metalloproteinase (ADAM) 10, which controls the expression of FasL and activates reverse signaling inside cells, also increases. From these findings, it is suggested that FasL and ADAM10 play an important role in the production of pro-inflammatory cytokines coming from interaction of the intervertebral nucleus pulposus cells and macrophages.

Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration.

INTRODUCTION: The longitudinal degradation mechanism of extracellular matrix (ECM) in the interbertebral disc remains unclear. Our objective was to elucidate catabolic and anabolic gene expression profiles and their balances in intervertebral disc degeneration using a static compression model. METHODS: Forty-eight 12-week-old male Sprague-Dawley rat tails were instrumented with an Ilizarov-type device with springs and loaded statically at 1.3 MPa for up to 56 days. Experimental loaded and distal-unloaded control discs were harvested and analyzed by real-time reverse transcription-polymerase chain reaction (PCR) messenger RNA quantification for catabolic genes [matrix metalloproteinase (MMP)-1a, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5], anti-catabolic genes [tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, and TIMP-3], ECM genes [aggrecan-1, collagen type 1-α1, and collagen type 2-α1], and pro-inflammatory cytokine genes [tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1ß, and IL-6]. Immunohistochemistry for MMP-3, ADAMTS-4, ADAMTS-5, TIMP-1, TIMP-2, and TIMP-3 was performed to assess their protein expression level and distribution. The presence of MMP- and aggrecanase-cleaved aggrecan neoepitopes was similarly investigated to evaluate aggrecanolytic activity. RESULTS: Quantitative PCR demonstrated up-regulation of all MMPs and ADAMTS-4 but not ADAMTS-5. TIMP-1 and TIMP-2 were almost unchanged while TIMP-3 was down-regulated. Down-regulation of aggrecan-1 and collagen type 2-α1 and up-regulation of collagen type 1-α1 were observed. Despite TNF-α elevation, ILs developed little to no up-regulation. Immunohistochemistry showed, in the nucleus pulposus, the percentage of immunopositive cells of MMP-cleaved aggrecan neoepitope increased from 7 through 56 days with increased MMP-3 and decreased TIMP-1 and TIMP-2 immunopositivity. The percentage of immunopositive cells of aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with decreased TIMP-3 immunopositivity. In the annulus fibrosus, MMP-cleaved aggrecan neoepitope presented much the same expression pattern. Aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with increased ADAMTS-4 and ADAMTS-5 immunopositivity. CONCLUSIONS: This rat tail sustained static compression model mimics ECM metabolic imbalances of MMPs, aggrecanases, and TIMPs in human degenerative discs. A dominant imbalance of MMP-3/TIMP-1 and TIMP-2 relative to ADAMTS-4 and ADAMTS-5/TIMP-3 signifies an advanced stage of intervertebral disc degeneration.

Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats.

OBJECTIVE: The expression of proinflammatory factors such as tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-8, and prostaglandin E(2) (PGE(2) ) is significantly correlated with the symptoms of herniated disc disease. Among the different types of immune cells, macrophages are frequently noted in the herniated disc tissue. We undertook this study to clarify the interaction of the intervertebral disc (IVD) and macrophages with regard to the production of TNFα, IL-6, IL-8, and PGE(2) . METHODS: We developed 2 animal models to assess the interactions of IVDs with macrophages in terms of TNFα, IL-6, IL-8, and PGE(2) production and pain-related behavior. We also cocultured IVDs and macrophages to assess the role of TNFα in IL-6, IL-8, and PGE(2) production. RESULTS: IVD autografts induced TNFα, IL-6, IL-8, and cyclooxygenase 2 (COX-2) messenger RNA (mRNA) up-regulation; macrophage infiltration was seen shortly after the autograft was implanted. A significant decrease was noted in the mechanical threshold of the ipsilateral paw following the up-regulation of TNFα, IL-6, IL-8, and COX-2 mRNA. Only IVD and macrophage cocultures resulted in IL-8 and PGE(2) up-regulation. TNFα up-regulation was maximized before that of IL-6 and IL-8. TNFα neutralization attenuated production of IL-6 and PGE(2) , but not that of IL-8. Neutralization of TNFα and IL-8 significantly increased the paw withdrawal mechanical threshold in the IVD autograft and spinal nerve ligation model. CONCLUSION: IVD-macrophage interaction plays a major role in sciatica and in the production of TNFα, IL-6, IL-8, and PGE(2) . TNFα is required for IL-6 and PGE(2) production, but not for IL-8 production, during IVD-macrophage interaction. Neutralization of TNFα and IL-8 can be a valuable therapy for herniated disc disease.