Traumatic sacral pseudomeningocele
Takahiro Naruse, Yukihiro Matsuyama, and Naoki Ishiguro
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.
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.
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.
Yukihiro Matsuyama, Kazuhiro Chiba, Hisashi Iwata, Takayuki Seo, and Yoshiaki Toyama
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.
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.
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.
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)
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.
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.
Masahiko Watanabe, Daisuke Sakai, Daisuke Matsuyama, Yukihiro Yamamoto, Masato Sato, and Joji Mochida
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.
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.
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.
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.
Go Yoshida, Mituhiro Kamiya, Hisatake Yoshihara, Tokumi Kanemura, Fumihiko Kato, Yasutugu Yukawa, Keigo Ito, Yukihiro Matsuyama, and Yoshihito Sakai
The purpose of this study was to evaluate the effect of a fixed atlantoaxial angle on subaxial sagittal alignment, and that of atlantoaxial fixation on adjacent-segment motion and degeneration.
The authors retrospectively reviewed 65 patients in whom atlantoaxial instability was treated with atlantoaxial fixation by C-1 lateral mass and C-2 pedicle screw fixation (30 patients, Goel-Harms [GH] group) or a combination of transarticular screw fixation and posterior wiring (35 patients, Magerl-Brooks [MB] group). Angles of Oc–C1, C1–2, C2–3, and C2–7 were determined based on an upright lateral radiograph in flexion, neutral, and extension positions. The range of motion (ROM) at Oc–C1 and C2–3 was also determined. All patients were examined before and 2 years after surgery.
The mean preoperative atlantoaxial angles in the GH and MB groups were 20.9 ± 8.3° and 18.3 ± 7.2°, respectively, and the mean postoperative atlantoaxial angles in the same groups were 23.5 ± 5.6° and 29.7 ± 6.3°, respectively, with a statistically significant difference between the 2 groups (p < 0.05). The mean preoperative angles of C2–7 in the GH and MB groups were 15.4 ± 7.8° and 13.7 ± 9.5°, respectively, and after surgery, the angles were 11.8 ± 12° and 2.48 ± 12°, respectively, with a statistically significant difference between the 2 groups (p < 0.05). The postoperative angle of C1–2 showed a negative correlation with the extent of change observed in the C2–7 angle preand postoperatively in each of these 2 surgical procedures. The Oc–C1 ROM increased after surgery in both groups, but the difference was not statistically significant (p = 0.38). The C2–3 ROM decreased after surgery in both groups, and the difference was statistically significant (p < 0.05).
Atlantoaxial fixation in a hyperlordotic position produced kyphotic sagittal alignment after surgery in both GH and MB groups. Reduction of the atlantoaxial joint can be easily achieved through screw fixation at an optimal angle, thereby ameliorating the risk for subsequent subaxial kyphosis. Degeneration of lower adjacent segments appeared to be less with this procedure compared with using a combination of transarticular screw fixation and posterior wiring.
Yu Yamato, Tomohiko Hasegawa, Sho Kobayashi, Tatsuya Yasuda, Daisuke Togawa, Go Yoshida, Tomohiro Banno, Shin Oe, Yuki Mihara, and Yukihiro Matsuyama
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.
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.
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).
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.
Hideyuki Arima, Steven D. Glassman, Keith Bridwell, Yu Yamato, Mitsuru Yagi, Kota Watanabe, Morio Matsumoto, Satoshi Inami, Hiroshi Taneichi, Yukihiro Matsuyama, and Leah Y. Carreon
The Scoliosis Research Society-22r questionnaire (SRS-22r) has been shown to be reliable, valid, and responsive to change in patients with adult spinal deformity (ASD) undergoing surgery. The minimal clinically important difference (MCID) is the smallest difference in a health-related quality of life score that is considered to be worthwhile or clinically important to the individual. The authors hypothesized that the proportion of patients with ASD achieving an MCID in the SRS-22r score would be different between two culturally different cohorts. The purpose of this study was to compare the proportion of patients with ASD achieving MCID for the SRS-22r domains in North American (NA) and Japanese cohorts.
A total of 137 patients from North America (123 women, mean age 60.0 years) and 60 patients from Japan (56 women, mean age 65.5 years) with at least 2 years of follow-up after corrective spine surgery for ASD were included. Except for self-image, published Japanese MCID values of SRS-22r for ASD were higher (function = 0.90, pain = 0.85, self-image = 1.05, subtotal = 1.05) than the published NA MCID values (function = 0.60, pain = 0.40, self-image = 1.23, subtotal = 0.43).
There was a statistically significant improvement in all SRS-22r domain scores at 2 years compared to baseline in both cohorts. Except for mental health (NA = 0.32, Japanese = 0.72, p = 0.005), the mean improvement from baseline to 2 years was similar between the NA and Japanese cohorts. The proportion of patients achieving MCID was higher in North America for function (NA = 51%, Japanese = 30%, p = 0.006), pain (NA = 80%, Japanese = 47%, p < 0.001), and subtotal (NA = 72%, Japanese = 35%, p < 0.001), while there was no significant difference for self-image (NA = 53%, Japanese = 58%, p = 0.454).
Despite similar improvements in SRS-22r domain scores from baseline to 2 years postoperatively, the proportion of patients reaching SRS-22r MCID for function, pain, and subtotal after ASD surgery was higher in the NA cohort than in the Japanese cohort. This may imply that patients in North America and Japan may value observed changes in clinical status differently.
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
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.
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.
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.
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.