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Takahiro Naruse, Yukihiro Matsuyama and Naoki Ishiguro

Object

Cyclooxygenase-2 (COX-2), also known as prostaglandin endoperoxide synthase, has been reported to play an important role in the tumorigenicity of many types of tumors. The expression of COX-2 in spinal ependymomas, however, has not been studied. The authors evaluated COX-2 expression in ependymoma of the spinal cord.

Methods

Sixteen ependymoma samples obtained in patients undergoing surgery between 1995 and 2004 were utilized for immunohistochemical studies to evaluate COX-2 and vascular endothelial growth factor (VEGF) expression. Intratumoral microvessels were also stained immunohistochemically using anti–human von Willebrand factor antibody and were quantified to determine the microvessel density (MVD). The clinical features were reviewed and recorded and the association with COX-2 expression was assessed.

Seven (43.8%) of the 16 ependymoma specimens expressed COX-2. All three of the myxopapillary-type ependymomas exhibited COX-2–positive staining. Excluding the three myxopapillary-type cases, COX-2 expression was identified in four (30.8%) of 13 cellular-type ependymomas. The COX-2–positive samples exhibited a significant increase in VEGF-positive staining cells and MVD compared with COX-2-negative samples. The clinical features were not associated with COX-2 expression.

Conclusions

The results of the present study indicate that COX-2 expression may promote angiogenesis through VEGF expression in ependymomas of the spinal cord. It is suggested that the use of selective COX-2 inhibitors may provide a new therapeutic strategy for spinal cord ependymomas due to their inhibition of the COX-2-mediated angiogenesis.

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Editorial

Traumatic sacral pseudomeningocele

Vincent Traynelis

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Yukihiro Matsuyama, Kazuhiro Chiba, Hisashi Iwata, Takayuki Seo and Yoshiaki Toyama

OBJECTIVE

Chemonucleolysis with condoliase has the potential to be a new, less invasive therapeutic option for patients with lumbar disc herniation (LDH). The aim of the present study was to determine the most suitable therapeutic dose of condoliase.

METHODS

Patients between 20 and 70 years of age with unilateral leg pain, positive findings on the straight leg raise test, and LDH were recruited. All eligible patients were randomly assigned to receive condoliase (1.25, 2.5, or 5 U) or placebo. The primary end point was a change in the worst leg pain from preadministration (baseline) to week 13. The secondary end points were changes from baseline in the following items: worst back pain, Oswestry Disability Index (ODI), SF-36, and neurological examination. For pharmacokinetic and pharmacodynamic analyses, plasma condoliase concentrations and serum keratan sulfate concentrations were measured. The safety end points were adverse events (AEs) and radiographic and MRI parameters. Data on leg pain, back pain, abnormal neurological findings, and imaging parameters were collected until week 52.

RESULTS

A total of 194 patients received an injection of condoliase or placebo. The mean change in worst leg pain from baseline to week 13 was −31.7 mm (placebo), −46.7 mm (1.25 U), −41.1 mm (2.5 U), and −47.6 mm (5 U). The differences were significant at week 13 in the 1.25-U group (−14.9 mm; 95% CI −28.4 to −1.4 mm; p = 0.03) and 5-U group (−15.9 mm; 95% CI −29.0 to −2.7 mm; p = 0.01) compared with the placebo group. The dose-response improvement in the worst leg pain at week 13 was not significant (p = 0.14). The decrease in the worst leg pain in all 3 condoliase groups was observed from week 1 through week 52. Regarding the other end points, the worst back pain and results of the straight leg raise test, ODI, and SF-36 showed a tendency for sustained improvement in each of the condoliase groups until week 52. In all patients at all time points, plasma condoliase concentrations were below the detectable limit (< 100 μU/ml). Serum keratan sulfate concentrations significantly increased from baseline to 6 hours and 6 weeks after administration in all 3 condoliase groups. No patient died or developed anaphylaxis or neurological sequelae. Five serious AEs occurred in 5 patients (3 patients in the condoliase groups and 2 patients in the placebo group), resolved, and were considered unrelated to the investigational drug. Severe AEs occurred in 10 patients in the condoliase groups and resolved or improved. In the condoliase groups, back pain was the most frequent AE. Modic type 1 change and decrease in disc height were frequent imaging findings. Dose-response relationships were observed for the incidence of adverse drug reactions and decrease in disc height.

CONCLUSIONS

Condoliase significantly improved clinical symptoms in patients with LDH and was well tolerated. While all 3 doses had similar efficacy, the incidence of adverse drug reactions and decrease in disc height were dose dependent, thereby suggesting that 1.25 U would be the recommended clinical dose of condoliase.

Clinical trial registration no.: NCT00634946 (clinicaltrials.gov)

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Tomohiro Banno, Tsuyoshi Ohishi, Daisuke Suzuki, Yosuke Honda, Sho Kobayashi and Yukihiro Matsuyama

Pseudomeningocele arises after spinal fracture and nerve root avulsion or after complications of spine surgery. However, traumatic pseudomeningocele with spina bifida occulta is rare. In this report, a traumatic pseudomeningocele in a patient with spina bifida occulta that required surgical treatment is documented. This 37-year-old man presented to the authors' hospital with headache and a fluctuant mass in the center of his buttocks. A CT scan with myelography and MR imaging of the sacral region revealed a large subcutaneous area of fluid retention communicating with the intradural space through a defect of the S-2 lamina. Because 3 months of conservative treatment was unsuccessful, a free fat graft was placed with fibrin glue to seal the closure of the defect, followed by 1 week of CSF drainage. This is the first report on traumatic pseudomeningocele with spina bifida occulta successfully treated in this manner.

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Masahiko Watanabe, Daisuke Sakai, Daisuke Matsuyama, Yukihiro Yamamoto, Masato Sato and Joji Mochida

Object

The purpose of this study was to identify risk factors for surgical site infection after spine surgery, noting the amount of saline used for intraoperative irrigation to minimize wound contamination.

Methods

The authors studied 223 consecutive spine operations from January 2006 through December 2006 at our institute. For a case to meet inclusion criteria as a site infection, it needed to require surgical incision and drainage and show positive intraoperative cultures. Preoperative and intraoperative data regarding each patient were collected. Patient characteristics recorded included age, sex, and body mass index (BMI). Preoperative risk factors included preoperative hospital stay, history of smoking, presence of diabetes, and an operation for a traumatized spine. Intraoperative factors that might have been risk factors for infection were collected and analyzed; these included type of procedure, estimated blood loss, duration of operation, and mean amount of saline used for irrigation per hour. Data were subjected to univariate and multivariate logistic regression analyses.

Results

The incidence of surgical site infection in this population was 6.3%. According to the univariate analysis, there was a significant difference in the mean duration of operation and intraoperative blood loss, but not in patient age, BMI, or preoperative hospital stay. The mean amount of saline used for irrigation in the infected group was less than in the noninfected group, but was not significantly different. In the multivariate analysis, sex, advanced age (> 60 years), smoking history, and obesity (BMI > 25 kg/m2) did not show significant differences. In the analysis of patient characteristics, only diabetes (patients receiving any medications or insulin therapy at the time of surgery) was independently associated with an increased risk of surgical site infection (OR 4.88). In the comparison of trauma and elective surgery, trauma showed a significant association with surgical site infection (OR 9.42). In the analysis of surgical factors, a sufficient amount of saline for irrigation (mean > 2000 ml/hour) showed a strong association with the prevention of surgical site infection (OR 0.08), but prolonged operation time (> 3 hours), high blood loss (> 300 g), and instrumentation were not associated with surgical site infection.

Conclusions

Diabetes, trauma, and insufficient intraoperative irrigation of the surgical wound were independent and direct risk factors for surgical site infection following spine surgery. To prevent surgical site infection in spine surgery, it is important to control the perioperative serum glucose levels in patients with diabetes, avoid any delay of surgery in patients with trauma, and decrease intraoperative contamination by irrigating > 2000 ml/hour of saline in all patients.

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Recurrence of hypertrophic spinal pachymeningitis

Report of two cases and review of the literature

Zenya Ito, Yoshimitsu Osawa, Yukihiro Matsuyama, Takaaki Aoki, Atsushi Harada and Naoki Ishiguro

✓Hypertrophic spinal pachymeningitis (HSP) is a comparatively rare disease characterized by hypertrophic inflammation of the dura mater and clinical symptoms that progress from local pain to myelopathy. The authors report two cases of recurrent HSP and review the English- and Japanese-language literature focusing on the recurrence of HSP.

In the first case, a man who presented at 67 years of age with lower-extremity numbness, gait disturbance, and bladder dysfunction experienced two recurrences of HSP during the 11 years of follow up after his initial laminectomy. Both recurrences were successfully treated with laminoplasty and duraplasty. Three years after his last surgical procedure, he was still able to walk with the aid of a walker. In the second case, a man who presented at 62 years of age with lower-extremity numbness and gait disturbance was initially treated successfully with steroid pulse therapy. Approximately 8 months after his initial presentation, his symptoms recurred. He underwent laminoplasty and duraplasty. At the 2.5-year follow-up examination, he had only mild neurological deficits and was still able to walk unaided.

To explore possible causes of recurrence, the authors searched the English- and Japanese-language literature for cases of HSP. Of the 96 cases identified, 11 were recurrent. Data on the presence or absence of inflammatory signs were available for 84 patients. A chi-square analysis revealed a significantly increased rate of recurrence for patients who had at least one positive inflammatory sign before surgery (six [20%] recurrent cases of 30) compared with those who had no positive inflammatory signs before surgery (two [3.7%] recurrent cases of 54) (p < 0.05). The authors conclude that HSP recurrence occurs because of active inflammation of the dura before surgery and the influence of chronic inflammation, including residual arachnoiditis.

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Tatsuya Yasuda, Tomohiko Hasegawa, Yu Yamato, Daisuke Togawa, Sho Kobayashi, Go Yoshida, Tomohiro Banno, Hideyuki Arima, Shin Oe and Yukihiro Matsuyama

OBJECTIVE

The purpose of this study was to evaluate the effect of position on lumbar lordosis (LL) in adult spinal deformity (ASD) patients.

METHODS

The authors evaluated the radiographic data of ASD patients who underwent posterior corrective fusion surgery from the thoracic spine to L5, S1, or the ilium for the treatment of ASD of the lumbar spine. The spinopelvic parameters were measured in the standing position preoperatively. LL was also evaluated in the supine position preoperatively and in the prone position on the surgical frame. Changes in LL were compared between groups.

RESULTS

Eighty-five patients were included. The average LL in standing, supine, and prone positions was 11.8°, 24.3°, and 24.0°, respectively. LL increased significantly from standing to supine or prone position (p < 0.001). In 80 patients (94.1%), the difference between supine LL and prone LL was within 5°. Change in LL from standing to prone position was significantly higher in the severe deformity group.

CONCLUSIONS

The lordotic effect of intraoperative prone positioning was remarkable in patients with severe deformities. LL in the supine position was approximately the same as that in the prone position. Therefore, assessing preoperative supine lateral lumbar radiographs enables one to plan corrective spinal surgeries in ASD patients.

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Yu Yamato, Tomohiko Hasegawa, Sho Kobayashi, Tatsuya Yasuda, Daisuke Togawa, Go Yoshida, Tomohiro Banno, Shin Oe, Yuki Mihara and Yukihiro Matsuyama

OBJECTIVE

Despite the significant incidence of rod fractures (RFs) following long-segment corrective fusion surgery, little is known about the optimal treatment strategy. The objectives of this study were to investigate the time course of clinical symptoms and treatments in patients with RFs following adult spinal deformity (ASD) surgery and to establish treatment recommendations.

METHODS

This study was a retrospective case series of patients with RFs whose data were retrieved from a prospectively collected single-center database. The authors reviewed the cases of 304 patients (mean age 62.9 years) who underwent ASD surgery. Primary symptoms, time course of symptoms, and treatments were investigated by reviewing medical records. Standing whole-spine radiographs obtained before and after RF development and at last follow-up were evaluated. Osseous union was assessed using CT scans and intraoperative findings.

RESULTS

There were 54 RFs in 53 patients (mean age 68.5 years [range 41–84 years]) occurring at a mean of 21 months (range 6–47 months) after surgery. In 1 patient RF occurred twice, with each case at a different time and level, and the symptoms and treatments for these 2 RFs were analyzed separately (1 case of revision surgery and 1 case of nonoperative treatment). The overall rate of RF observed on radiographs after a minimum follow-up of 1 year was 18.0% (54 of 300 cases). The clinical symptoms at the time of RF were pain in 77.8% (42 of 54 cases) and no onset of new symptoms in 20.5% (11 of 54 cases). The pain was temporary and had subsided in 19 of 42 cases (45%) within 2 weeks. In 36 of the 54 cases (66.7%) (including the first RF in the patient with 2 RFs), patients underwent revision surgery at a mean of 116 days (range 5–888 days) after diagnosis. In 18 cases patients received only nonoperative treatment as of the last follow-up, including 17 cases in which the patients experienced no pain and no remarkable progression of deformity (mean 18.5 months after RF development).

CONCLUSIONS

This analysis of 54 RFs in 53 patients following corrective fusion surgery for ASD demonstrates a relationship between symptoms and alignment change. Revision surgeries were performed in a total of 36 cases. Nonoperative care was offered in 18 (33.3%) of 54 cases at the last follow-up, with no additional symptoms in 17 of the 18 cases. These data offer useful information regarding informed decision making for patients in whom an RF occurs after ASD surgery.

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Kei Ando, Shiro Imagama, Norimitsu Wakao, Kenichi Hirano, Ryoji Tauchi, Akio Muramoto, Fumihiko Kato, Yasutsugu Yukawa, Noriaki Kawakami, Koji Sato, Yuji Matsubara, Tokumi Kanemura, Yukihiro Matsuyama and Naoki Ishiguro

Object

The purpose of this study was to provide the first evidence for the influence of an ossified anterior longitudinal ligament (OALL) on the clinical features and surgical outcomes in an ossified ligamentum flavum (OLF) in the thoracic region.

Methods

Sixty-three patients who underwent surgery for a 1-level thoracic OLF were identified, and preoperative symptoms, severity of symptoms and myelopathy, disease duration, MR imaging and CT findings, surgical procedure, intraoperative findings, complications, and postoperative recovery were investigated in these patients. Entities of OALLs were found on sagittal CT images to be adjacent to or at the same vertebral level as the OLF were classified into 4 types: no discernible type (Type N), one-sided (Type O), discontinuous (Type D), and continuous (Type C).

Results

The duration of symptoms was especially long for Types D and C OALLs. Patients with Type D OALLs had a significantly worse percentage of recovery, as well as worse preoperative JOA scores.

Conclusions

The authors' results showed that a Type D OALL had strong associations with preoperative severity of symptoms and surgical outcomes. These findings may allow surgeons to determine the severity of preoperative symptoms and the probable surgical outcomes from the OALL classifications. Moreover, surgery with instrumentation for Type D OALLs may produce better surgical outcomes.

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Yasutsugu Yukawa, Fumihiko Kato, Keigo Ito, Yumiko Horie, Tetsurou Hida, Masaaki Machino, Zen-ya Ito and Yukihiro Matsuyama

Object

Increased signal intensity of the spinal cord on magnetic resonance (MR) imaging was classified pre- and postoperatively in patients with cervical compressive myelopathy. It was investigated whether postoperative classification and alterations of increased signal intensity could reflect the postoperative severity of symptoms and surgical outcomes.

Methods

One hundred and four patients with cervical compressive myelopathy were prospectively enrolled. All were treated using cervical expansive laminoplasty. Magnetic resonance imaging was performed in all patients preoperatively and after an average of 39.7 months postoperatively (range 12–90 months). Increased signal intensity of the spinal cord was divided into 3 grades based on sagittal T2-weighted MR images as follows: Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). The severity of myelopathy was evaluated according to the Japanese Orthopedic Association (JOA) score for cervical myelopathy and its recovery rate (100% = full recovery).

Results

Increased signal intensity was seen in 83% of cases preoperatively and in 70% postoperatively. Preoperatively, there were 18 patients with Grade 0 increased signal intensity, 49 with Grade 1, and 37 with Grade 2; postoperatively, there were 31 with Grade 0, 31 with Grade 1, and 42 with Grade 2. The respective postoperative JOA scores and recovery rates (%) were 13.9/56.7% in patients with postoperative Grade 0, 13.2/50.7% in those with Grade 1, and 12.8/40.1% in those with Grade 2, and these differences were not statistically significant. The postoperative increased signal intensity grade was improved in 16 patients, worsened in 8, and unchanged in 80 (77%). There was no significant correlation between the alterations of increased signal intensity and surgical outcomes.

Conclusions

The postoperative increased signal intensity classification reflected postoperative symptomatology and surgical outcomes to some extent, without statistically significant differences. The alteration of increased signal intensity was seen postoperatively in 24 patients (23%) and was not correlated with surgical outcome.