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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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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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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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Hiroaki Nakashima, Yasutsugu Yukawa, Shiro Imagama, Tokumi Kanemura, Mitsuhiro Kamiya, Makoto Yanase, Keigo Ito, Masaaki Machino, Go Yoshida, Yoshimoto Ishikawa, Yukihiro Matsuyama, Naoki Ishiguro, and Fumihiko Kato

Object

The cervical pedicle screw (PS) provides strong stabilization but poses a potential risk to the neurovascular system, which may be catastrophic. In particular, vertebrae with degenerative changes complicate the process of screw insertion, and PS misplacement and subsequent complications are more frequent. The purpose of this study was to evaluate the peri- and postoperative complications of PS fixation for nontraumatic lesions and to determine the risk factors of each complication.

Methods

Eighty-four patients who underwent cervical PS fixation for nontraumatic lesions were independently reviewed to identify associated complications. The mean age of the patients was 60.1 years, and the mean follow-up period was 4.1 years (range 6–168 months). Pedicle screw malpositioning was classified on postoperative CT scans as Grade I (< 50% of the screw outside the pedicle) or Grade II (≥ 50% of the screw outside the pedicle). Risk factors of each complication were evaluated using a multivariate analysis.

Results

Three hundred ninety cervical PSs and 24 lateral mass screws were inserted. The incidence of PS misplacement was 19.5% (76 screws); in terms of malpositioning, 60 screws (15.4%) were classified as Grade I and 16 (4.1%) as Grade II. In total, 33 complications were observed. These included postoperative neurological complications in 11 patients in whom there was no evidence of screw misplacement (C-5 palsy in 10 and C-7 palsy in 1), implant failure in 11 patients (screw loosening in 5, broken screws in 4, and loss of reduction in 2), complications directly attributable to screw insertion in 5 patients (nerve root injury by PS in 3 and vertebral artery injury in 2), and other complications in 6 patients (pseudarthrosis in 2, infection in 1, transient dyspnea in 1, transient dysphagia in 1, and adjacent-segment degeneration in 1). The multivariate analysis showed that a primary diagnosis of cerebral palsy was a risk factor for postoperative implant failure (HR 10.91, p = 0.03) and that the presence of preoperative cervical spinal instability was a risk factor for both Grade I and Grade II screw misplacement (RR 2.12, p = 0.03), while there were no statistically significant risk factors for postoperative neurological complications in the absence of evidence of screw misplacement or complications directly attributable to screw insertion.

Conclusions

In the present study, misplacement of cervical PSs and associated complications occurred more often than in previous studies. The rates of screw-related neurovascular complications and neurological deterioration unrelated to PSs were high. Insertion of a PS for nontraumatic lesions is surgically more challenging than that for trauma; consequently, experienced surgeons should use PS fixation for nontraumatic cervical lesions only after thorough preoperative evaluation of each patient's cervical anatomy and after considering the risk factors specified in the present study.

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Hiroki Oba, Jun Takahashi, Sho Kobayashi, Tetsuro Ohba, Shota Ikegami, Shugo Kuraishi, Masashi Uehara, Takashi Takizawa, Ryo Munakata, Terue Hatakenaka, Michihiko Koseki, Shigeto Ebata, Hirotaka Haro, Yukihiro Matsuyama, and Hiroyuki Kato

OBJECTIVE

Unfused main thoracic (MT) curvatures occasionally increase after selective thoracolumbar/lumbar (TL/L) fusion. This study sought to identify the predictors of an unacceptable increase in MT curve (UIMT) after selective posterior fusion (SPF) of the TL/L curve in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS).

METHODS

Forty-eight consecutive patients (44 females and 4 males, mean age 15.7 ± 2.5 years, range 13–24 years) with Lenke type 5C AIS who underwent SPF of the TL/L curve were analyzed. The novel “Shinshu line” (S-line) was defined as a line connecting the centers of the concave-side pedicles of the upper instrumented vertebra (UIV) and lowest instrumented vertebra (LIV) on preoperative radiographs. The authors established an S-line tilt to the right as S-line positive (S-line+, i.e., the UIV being to the right of the LIV) and compared S-line+ and S-line− groups for thoracic apical vertebral translation (T-AVT) and MT Cobb angle preoperatively, early postoperatively, and at final follow-up. The predictors for T-AVT > 20 mm at final follow-up were evaluated as well. T-AVT > 20 mm was defined as a UIMT.

RESULTS

Among the 48 consecutively treated patients, 26 were S-line+ and 22 were S-line−. At preoperative, early postoperative, and final follow-up a minimum of 2 years later, the mean T-AVT was 12.8 mm (range −9.3 to 32.8 mm), 19.6 mm (range −13.0 to 41.0 mm), and 22.8 mm (range −1.9 to 68.7 mm) in the S-line+ group, and 10.8 mm (range −5.1 to 27.3 mm), 16.2 mm (range −11.7 to 42.1 mm), and 11.0 mm (range −6.3 to 26.9 mm) in the S-line− group, respectively. T-AVT in S-line+ patients was significantly larger than that in S-line− patients at the final follow-up. Multivariate analysis revealed S-line+ (odds ratio [OR] 23.8, p = 0.003) and preoperative MT Cobb angle (OR 7.9, p = 0.001) to be predictors of a UIMT.

CONCLUSIONS

S-line+ was defined as the UIV being to the right of the LIV. T-AVT in the S-line+ group was significantly larger than in the S-line− group at the final follow-up. S-line+ status and larger preoperative MT Cobb angle were independent predictors of a UIMT after SPF for the TL/L curve in patients with Lenke type 5C AIS. Surgeons should consider changing the UIV and/or LIV in patients exhibiting S-line+ during preoperative planning to avoid a possible increase in MT curve and revision surgery.

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Hiroki Ushirozako, Go Yoshida, Tomohiko Hasegawa, Yu Yamato, Tatsuya Yasuda, Tomohiro Banno, Hideyuki Arima, Shin Oe, Tomohiro Yamada, Koichiro Ide, Yuh Watanabe, Tadayoshi Kurita, and Yukihiro Matsuyama

OBJECTIVE

Transcranial motor evoked potential (TcMEP) monitoring may be valuable for predicting postoperative neurological complications with a high sensitivity and specificity, but one of the most frequent problems is the high false-positive rate. The purpose of this study was to clarify the differences in the risk factors for false-positive TcMEP alerts seen when performing surgery in patients with pediatric scoliosis and adult spinal deformity and to identify a method to reduce the false-positive rate.

METHODS

The authors retrospectively analyzed 393 patients (282 adult and 111 pediatric patients) who underwent TcMEP monitoring while under total intravenous anesthesia during spinal deformity surgery. They defined their cutoff (alert) point as a final TcMEP amplitude of ≤ 30% of the baseline amplitude. Patients with false-positive alerts were classified into one of two groups: a group with pediatric scoliosis and a group with adult spinal deformity.

RESULTS

There were 14 cases of false-positive alerts (13%) during pediatric scoliosis surgery and 62 cases of false-positive alerts (22%) during adult spinal deformity surgery. Compared to the true-negative cases during adult spinal deformity surgery, the false-positive cases had a significantly longer duration of surgery and greater estimated blood loss (both p < 0.001). Compared to the true-negative cases during pediatric scoliosis surgery, the false-positive cases had received a significantly higher total fentanyl dose and a higher mean propofol dose (0.75 ± 0.32 mg vs 0.51 ± 0.18 mg [p = 0.014] and 5.6 ± 0.8 mg/kg/hr vs 5.0 ± 0.7 mg/kg/hr [p = 0.009], respectively). A multivariate logistic regression analysis revealed that the duration of surgery (1-hour difference: OR 1.701; 95% CI 1.364–2.120; p < 0.001) was independently associated with false-positive alerts during adult spinal deformity surgery. A multivariate logistic regression analysis revealed that the mean propofol dose (1-mg/kg/hr difference: OR 3.117; 95% CI 1.196–8.123; p = 0.020), the total fentanyl dose (0.05-mg difference; OR 1.270; 95% CI 1.078–1.497; p = 0.004), and the duration of surgery (1-hour difference: OR 2.685; 95% CI 1.131–6.377; p = 0.025) were independently associated with false-positive alerts during pediatric scoliosis surgery.

CONCLUSIONS

Longer duration of surgery and greater blood loss are more likely to result in false-positive alerts during adult spinal deformity surgery. In particular, anesthetic doses were associated with false-positive TcMEP alerts during pediatric scoliosis surgery. The authors believe that false-positive alerts during pediatric scoliosis surgery, in particular, are caused by “anesthetic fade.”

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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.