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)
Masahiko Watanabe, Kazuhiro Chiba, Morio Matsumoto, Hirofumi Maruiwa, Yoshikazu Fujimura, and Yoshiaki Toyama
Object. Spinal cord herniation is a rare cause of progressive myelopathy and can be corrected surgically. In most previous reports, closure of the dural defect was the recommended procedure. The object of this paper is to describe a new procedure in which spinal cord constriction is released by enlarging the hiatus; additionally the postoperative results will be discussed.
Methods. In nine patients with spinal cord herniation, enlargement of the dural defect was performed. In eight patients, neurological deficits resolved immediately after surgery. In one patient with a severe preoperative neurological deficit whose spinal cord herniated massively, deterioration occurred postoperatively. To date, no recurrence of herniation has been observed.
Conclusions. The goals of surgery are to reduce the herniation, return the spinal cord to the normal position, and prevent the recurrence of herniation. The use of sutures to close the dural defect has been the method of choice to date. The surgical space in front of the spinal cord, however, is insufficient to accommodate this procedure safely. Because symptoms are caused by the constriction of the spinal cord at the hiatus, surgical expansion of the hiatus allows the goals of surgery to be achieved. This procedure, which is technically easier and less invasive with regard to the vulnerable spinal cord than the closure of the dural defect, could be a viable alternative for the treatment of this rare disease.
Report of four cases
Ken Ishii, Kazuhiro Chiba, Masahiko Watanabe, Hiroo Yabe, Yoshikazu Fujimura, and Yoshiaki Toyama
✓ Excision is the treatment of choice in cases of sacral chordoma. Local recurrences, however, have often been observed even after total en bloc resection. The authors assessed outcomes in four cases of tumor recurrence in patients who underwent total en bloc S2–3 resection for sacral chordomas that were located below S-3. The primary recurrences were located at either side of the lateral portion of the remaining sacrum in all patients. In two patients in whom preoperative magnetic resonance imaging indicated no invasion of the tumor into surrounding soft tissues, recurrence in the resected end of the gluteus maximus or piriformis muscle was also observed. The authors therefore recommend that the S2–3 sacrectomy should be performed over an adequate margin, including a part of sacroiliac joints at the bilateral portions of the sacrum and soft tissues such as the gluteus maximus or piriformis muscle.
Morio Matsumoto, Kazuhiro Chiba, Takashi Tsuji, Hirofumi Maruiwa, Yoshiaki Toyama, and Jun Ogawa
✓ The authors placed titanium mesh cages to achieve posterior atlantoaxial fixation in five patients with atlantoaxial instability caused by rheumatoid arthritis or os odontoideum. A mesh cage packed with autologous cancellous bone was placed between the C-1 posterior arch and the C-2 lamina and was tightly connected with titanium wires. Combined with the use of transarticular screws, this procedure provided very rigid fixation. Solid fusion was achieved in all patients without major complications. The advantages of this method include more stable fixation, better control of the atlantoaxial fixation angle, and reduced donor-site morbidity compared with a conventional atlantoaxial arthrodesis in which an autologous iliac crest graft is used.
Morio Matsumoto, Kazuhiro Chiba, Masaya Nakamura, Yuto Ogawa, Yoshiaki Toyama, and Jun Ogawa
Object. Structural interlaminar graft materials were used for atlantoaxial transarticular screw fixation (TSF), and its impact on the fusion status was investigated.
Methods. Forty-two patients (10 men, 32 women, mean age 51 years, mean follow-up period 45 months; 30 with rheumatoid arthritis, and 12 with os odontoideum) underwent TSF and modified Brooks posterior wiring involving titanium cables. As interlaminar graft materials, autologous bone from posterior iliac crest alone was used in 20 patients (Group A), and a structural spacer (13 ceramic spacers, nine titanium mesh cages) in 22 (Group B). Lateral radiographs were evaluated to determine bone fusion, alignment of the cervical spine, and wire loosening. Solid osseous fusion was obtained in 95% of Group A and 96% of Group B patients. The mean atlantoaxial angle was 19.1 ± 9.7° and 16.7 ± 10.4° before surgery (p = 0.45), and 27.4± 7.8° and 22.1 ± 5.5° after surgery (p = 0.02) in Groups A and B, respectively. Atlantoaxial hyperlordosis (atlantoaxial angle ≥ 30°) was observed in 32% of Group A and 18% of Group B patients (p = 0.26). Postoperative kyphosis occurred in 40% of Group A and 23% of Group B patients (p = 0.28). Loosening of the cable was demonstrated in 50% of Group A and 36% of Group B patients (p = 0.37). In Group B patients maintenance of cervical lordosis was more likely than in those in Group A, although the differences did not reach statistical significance.
Conclusions. These results indicate that structural interlaminar spacers can maintain proper cervical alignment without a decease in the fusion rate; the authors recommend their use in conjunction with TSF.
Morio Matsumoto, Kota Watanabe, Takashi Tsuji, Ken Ishii, Masaya Nakamura, Kazuhiro Chiba, and Yoshiaki Toyama
The object of this study was to investigate failures after spinal reconstruction following total en bloc spondylectomy (TES), related factors, and sequelae arising from such failures in patients with malignant spinal tumors.
Fifteen patients (12 males and 3 females, with a mean age of 46.5 years) with malignant spinal tumors who underwent TES and survived for more than 1 year were included in this analysis (mean follow-up 41.5 months). Seven patients had primary tumors, including giant cell tumors in 4 patients, chordoma in 2, and Ewing sarcoma in 1. Eight patients had metastatic tumors, including thyroid cancer in 6 and renal cell cancer and malignant fibrous histiocytoma in 1 patient each. Seven patients without prominent paravertebral extension of the tumor were treated using a posterior approach alone, and 8 patients who exhibited prominent anterior or anterolateral extension of the tumors into the thoracic or abdominal cavity were treated using a combined anterior and posterior approach. Spinal reconstruction after tumor resection was performed using a combination of anterior structural support and posterior instrumentation. The relationship between instrumentation failure and clinical and radiographic factors, including age, sex, history of previous surgery, preoperative radiotherapy, tumor histology, tumor level, surgical approach, number of resected vertebrae, rod diameter, number of instrumented vertebrae, and cage subsidence, was investigated.
Six patients (40%) with spinal instrumentation failure were identified: rod breakage occurred in 3 patients, and breakage of both the rod and the cage, combined cage breakage and screw back-out, and endplate fracture arising from cage subsidence occurred in 1 patient each. All of these patients experienced acute or chronic back pain, but only 1 patient with a tumor recurrence experienced neurological deterioration upon instrumentation failure. Cage subsidence (≥ 5 mm), preoperative irradiation, and the number of instrumented vertebrae (≤ 4 vertebrae) were significantly related to late instrumentation failure.
Late instrumentation failure was a frequent complication after TES. Although patients with instrumentation failure experienced back pain, the neurological sequelae were not catastrophic. For prevention, meticulous preparation of the graft site and a longer posterior fixation should be considered.
Kenya Nojiri, Morio Matsumoto, Kazuhiro Chiba, Hirofumi Maruiwa, Masaya Nakamura, Takashi Nishizawa, and Yoshiaki Toyama
The aim of this study was to establish standard values for the normal alignment of the upper cervical spine and to clarify its relationship with the lower cervical spine in terms of alignment.
Three hundred thirteen asymptomatic volunteers (155 men and 158 women) participated in this study. Lateral radiographs were obtained with the neck in neutral position, and the angles formed by the occiput (Oc) and the axis, the atlas and the axis, and C-2 to C-7 were measured. The mean Oc—C2 angle was 14.5 ± 8° in men and 16 ± 8.5° in women; the mean C1–2 angle was 26.5 ± 7° and 28.9 ± 6.7°, respectively; and the mean C2–7 angle was 16.2 ± 12.9° and 10.5 ± 10.3°, respectively. Although weak, statistically significant negative correlation was observed between Oc—C2 and C2–7 angles (r = −0.31 in men and −0.37 in women), and between C1–2 and C2–7 angles (r = −0.22 in men and −0.22 in women). The correlation coefficient between the Oc—C2 and C2–7 angles was greater than that between the C1–2 and C2–7 angles.
Such relationships between alignment of the upper and lower cervical spines should be taken into consideration when performing occipitocervical fusion.