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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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Kazuyoshi Kobayashi, Shiro Imagama, Zenya Ito, Kei Ando, Tetsuro Hida, Kenyu Ito, Mikito Tsushima, Yoshimoto Ishikawa, Akiyuki Matsumoto, Yoshihiro Nishida, and Naoki Ishiguro

OBJECTIVE

Corrective surgery for spinal deformities can lead to neurological complications. Several reports have described spinal cord monitoring in surgery for spinal deformity, but only a few have included patients younger than 20 years with adolescent idiopathic scoliosis (AIS). The goal of this study was to evaluate the characteristics of cases with intraoperative transcranial motor evoked potential (Tc-MEP) waveform deterioration during posterior corrective fusion for AIS.

METHODS

A prospective database was reviewed, comprising 68 patients with AIS who were treated with posterior corrective fusion in a prospective database. A total of 864 muscles in the lower extremities were chosen for monitoring, and acceptable baseline responses were obtained from 819 muscles (95%). Intraoperative Tc-MEP waveform deterioration was defined as a decrease in intraoperative amplitude of ≥ 70% of the control waveform. Age, Cobb angle, flexibility, operative time, estimated blood loss (EBL), intraoperative body temperature, blood pressure, number of levels fused, and correction rate were examined in patients with and without waveform deterioration.

RESULTS

The patients (3 males and 65 females) had an average age of 14.4 years (range 11–19 years). The mean Cobb angles before and after surgery were 52.9° and 11.9°, respectively, giving a correction rate of 77.4%. Fourteen patients (20%) exhibited an intraoperative waveform change, and these occurred during incision (14%), after screw fixation (7%), during the rotation maneuver (64%), during placement of the second rod after the rotation maneuver (7%), and after intervertebral compression (7%). Most waveform changes recovered after decreased correction or rest. No patient had a motor deficit postoperatively. In multivariate analysis, EBL (OR 1.001, p = 0.085) and number of levels fused (OR 1.535, p = 0.045) were associated with waveform deterioration.

CONCLUSIONS

Waveform deterioration commonly occurred during rotation maneuvers and more frequently in patients with a larger preoperative Cobb angle. The significant relationships of EBL and number of levels fused with waveform deterioration suggest that these surgical invasions may be involved in waveform deterioration.

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Masaki Matsushita, Kenichi Mishima, Ryusaku Esaki, Naoki Ishiguro, Kinji Ohno, and Hiroshi Kitoh

OBJECTIVE

Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Foramen magnum stenosis (FMS) is one of the serious neurological complications in ACH. Through comprehensive drug screening, the authors identified that meclozine, an over-the-counter drug for motion sickness, inhibited activation of FGFR3 signaling. Oral administration of meclozine to the growing ACH mice promoted longitudinal bone growth, but it did not prevent FMS. In the current study, the authors evaluated the effects of maternal administration of meclozine on FMS in ACH mice.

METHODS

The area of the foramen magnum was measured in 17-day-old Fgfr3 ach mice and wild-type mice using micro-CT scanning. Meclozine was administered to the pregnant mice carrying Fgfr3 ach offspring from embryonic Day (ED) 14.5 to postnatal Day (PD) 4.5. Spheno-occipital and anterior intraoccipital synchondroses were histologically examined, and the bony bridges were scored on PD 4.5. In wild-type mice, tissue concentrations of meclozine in ED 17.5 fetuses and PD 6.5 pups were investigated.

RESULTS

The area of the foramen magnum was significantly smaller in 17-day-old Fgfr3 ach mice than in wild-type mice (p < 0.005). There were no bony bridges in the spheno-occipital and anterior intraoccipital synchondroses in wild-type mice, while some of the synchondroses prematurely closed in untreated Fgfr3 ach mice at PD 4.5. The average bony bridge score in the cranial base was 7.053 ± 1.393 in untreated Fgfr3 ach mice and 6.125 ± 2.029 in meclozine-treated Fgfr3 ach mice. The scores were not statistically significant between mice with and those without meclozine treatment (p = 0.12). The average tissue concentration of meclozine was significantly higher (508.88 ± 205.16 ng/g) in PD 6.5 mice than in ED 17.5 mice (56.91 ± 20.05 ng/g) (p < 0.005).

CONCLUSIONS

Maternal administration of meclozine postponed premature closure of synchondroses in some Fgfr3 ach mice, but the effect on preventing bony bridge formation was not significant, probably due to low placental transmission of the drug. Meclozine is likely to exhibit a marginal effect on premature closure of synchondroses at the cranial base in ACH.

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Kei Ando, Shiro Imagama, Zenya Ito, Kazuyoshi Kobayashi, Hideki Yagi, Tetsuro Hida, Kenyu Ito, Mikito Tsushima, Yoshimoto Ishikawa, and Naoki Ishiguro

OBJECT

Little is known about the progression of spinal schwannomas. The aim of this study was to determine the natural progression of spinal schwannomas and establish the risk of tumor growth.

METHODS

This study retrospectively analyzed data from 23 patients (12 men and 11 women, 40–89 years old) with schwannomas detected by MRI. The mean follow-up period was 5 years (range 2–10 years). The absolute and relative growth rates of the tumors were calculated.

RESULTS

The average tumor size was 1495 mm3 at the initial visit and 2224 mm3 at the final follow-up. The average absolute growth rate was 139 mm3 per year, and the average relative growth rate was 5.3% per year. Tumors were classified into 3 groups based on enhancement patterns: isointense/hyperintense (iso/high; 11 cases), rim enhancement when enhancement was peripheral (high/rim; 5 cases), and heterogeneous/heterogeneous (hetero/hetero; 7 cases) based on Gd-enhanced T2-weighted MRI. The average absolute growth rates of the 3 lesion groups were 588 mm3, 957 mm3, and 3379 mm3, respectively (p < 0.01).

CONCLUSIONS

Although the tumors classified as iso/high and high/rim on T2-weighted Gd-enhanced MR images were small and grew very little, most tumors with hetero/hetero classification increased in size. Hetero/hetero-type tumors should be followed closely and may require surgery.

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Kei Ando, Kazuyoshi Kobayashi, Masaaki Machino, Kyotaro Ota, Satoshi Tanaka, Masayoshi Morozumi, Sadayuki Ito, Shunsuke Kanbara, Taro Inoue, Naoki Ishiguro, and Shiro Imagama

OBJECTIVE

The objective of this study was to investigate the relationship between morphological changes in thoracic ossification of the posterior longitudinal ligament (T-OPLL) and postoperative neurological recovery after thoracic posterior fusion surgery. Changes of OPLL morphology and postoperative recovery in cases with T-OPLL have not been examined.

METHODS

In this prospective study, the authors evaluated data from 44 patients (23 male and 21 female) who underwent posterior decompression and fusion surgery with instrumentation for the treatment of T-OPLL at our hospital. The patients’ mean age at surgery was 50.7 years (range 38–68 years). The minimum duration of follow-up was 2 years. The location of thoracic ossification of the ligamentum flavum (T-OLF), T-OLF at the OPLL level, OPLL morphology, fusion range, estimated blood loss, operative time, pre- and postoperative Japanese Orthopaedic Association (JOA) scores, and JOA recovery rate were investigated. Reconstructed sagittal multislice CT images were obtained before and at 3 and 6 months and 1 and 2 years after surgery. The basic fusion area was 3 vertebrae above and below the OPLL lesion. All parameters were compared between patients with and without continuity across the disc space at the OPLL at 3 and 6 months after surgery.

RESULTS

The preoperative morphology of OPLL was discontinuous across the disc space between the rostral and caudal ossification regions on sagittal CT images in all but one of the patients. Postoperatively, these segments became continuous in 42 patients (97.7%; occurring by 6.6 months on average) without progression of OPLL thickness. Patients with continuity at 3 months had significantly lower rates of diabetes mellitus (p < 0.05) and motor palsy in the lower extremities (p < 0.01). The group with continuity also had significantly higher mean postoperative JOA scores at 3 (p < 0.01) and 6 (p < 0.05) months and mean JOA recovery rates at 3 and 6 months (both p < 0.01) after surgery.

CONCLUSIONS

Preoperatively, discontinuity of rostral and caudal ossified lesions was found on CT in all patients but one of this group of 44 patients who needed surgery for T-OPLL. Rigid fixation with instrumentation may have allowed these segments to connect at the OPLL. Such OPLL continuity at an early stage after surgery may accelerate spinal cord recovery.

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

Object

Postoperative C-5 palsy is a significant complication resulting from cervical decompression procedures. Moreover, when cervical degenerative diseases are treated with a combination of decompression and posterior instrumented fusion, patients are at increased risk for C-5 palsy. However, the clinical and radiological features of this condition remain unclear. Therefore, the purpose of this study was to clarify the risk factors for developing postoperative C-5 palsy.

Methods

Eighty-four patients (mean age 60.1 years) who had undergone posterior instrumented fusion using cervical pedicle screws to treat nontraumatic lesions were independently reviewed. The authors analyzed the medical records of some of these patients who developed postoperative C-5 palsy, paying particular attention to their plain radiographs, MRI studies, and CT scans. Risk factors for postoperative C-5 palsy were assessed using multivariate logistic regression analysis. The cutoff values for the pre- and postoperative width of the intervertebral foramen (C4–5) were determined by receiver operating characteristic curve analysis.

Results

Ten (11.9%) of 84 patients developed postoperative C-5 palsy. Seven patients recovered fully from the neurological complications. The pre- and postoperative C4–5 angles showed significant kyphosis in the C-5 palsy group. The pre- and postoperative diameters of the C4–5 foramen on the palsy side were significantly smaller than those on the opposite side in the C-5 palsy group and those bilaterally in the non–C5 palsy group. Risk factors identified by multivariate logistic regression analysis were as follows: 1) ossification of the posterior longitudinal ligament (relative risk [RR] 7.22 [95% CI 1.03–50.55]); 2) posterior shift of the spinal cord (C4–5) (RR 1.73 [95% CI 1.00–2.98]); and 3) postoperative width of the C-5 intervertebral foramen (RR 0.33 [95% CI 0.14–0.79]). The cutoff values of the pre- and postoperative widths of the C-5 intervertebral foramen for C-5 palsy were 2.2 and 2.3 mm, respectively.

Conclusions

Patients with preoperative foraminal stenosis, posterior shift of the spinal cord, and additional iatrogenic foraminal stenosis due to cervical alignment correction were more likely to develop postoperative C-5 palsy after posterior instrumentation with fusion. Prophylactic foraminotomy at C4–5 might be useful when preoperative foraminal stenosis is present on CT. Furthermore, it might be useful for treating postoperative C-5 palsy. To prevent excessive posterior shift of the spinal cord, the authors recommend that appropriate kyphosis reduction should be considered carefully.

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Yukihiro Matsuyama, Yoshihito Sakai, Yoshito Katayama, Shiro Imagama, Zenya Ito, Norimitsu Wakao, Koji Sato, Mitsuhiro Kamiya, Yasutsugu Yukawa, Tokumi Kanemura, Makoto Yanase, and Naoki Ishiguro

Object

The authors investigated the outcome of intramedullary spinal cord tumor surgery, focusing on the effect of preoperative neurological status on postoperative mobility and the extent of tumor excision guided by intraoperative spinal cord monitoring prospectively.

Methods

Intramedullary spinal cord tumor surgery was performed in 131 patients between 1997 and 2007. The authors compared the pre- and postoperative neurological status and examined the type of surgery in 106 of these patients. A modified McCormick Scale (Grades I–V) was used to assess ambulatory ability (I = normal ambulation; II = mild motor sensory deficit, independent without external aid; III = independent with external aid; IV = care required; and V = wheelchair required). The type of surgery was classified into 4 levels: total resection, subtotal resection, partial resection, and biopsy.

Results

The 106 patients consisted of 47 females and 59 males, whose average age was 42.5 years (range 6–75 years). The mean follow-up period was 7.3 years (range 2.5 months–21 years). The tumor types included astrocytoma (12 cases), ependymoma (46 cases), hemangioblastoma (16 cases), cavernous hemangioma (17 cases), and others (15 cases overall: gangliocytoma, 1; germ cell tumor, 1; lymphoma, 3; neurinoma, 1; meningioma, 1; oligodendroglioma, 1; sarcoidosis, 2; glioma, 1; and unknown, 4). Initial total excision, subtotal resection, partial resection, biopsy, and duraplasty were performed in 59, 12, 22, 12, and 1 patients, respectively. According to the preoperative McCormick Scale, ambulatory status was classified as Grades I, II, III, IV, and V in 41(38%), 30 (28%), 14 (13%), 19 (19%), and 2 (2%) patients, respectively. Thirty-three (31%) of 106 patients suffered postoperative neurological deterioration. The number of patients who did not lose ambulatory ability or who achieved an ambulatory status of Grade I or II postoperatively was 33 (80%), 21 (70%), 10 (71%), 8 (42%), and 1 (50%) in patients with preoperative Grades I, II, III, IV, and V, respectively. Total excision was performed in 31 (79%) of 39 patients with preoperative Grade I, 12 (40%) of 30 patients with Grade II, 7 (50%) of 14 patients with Grade III, and 9 of 21 patients (38%) with Grade IV or V, indicating that the rate of total excision was significantly higher in patients with Grade I status.

Conclusions

The postoperative ambulatory ability was excellent in patients with a good preoperative neurological status. Total excision in patients with Grade I or II ambulation was associated with a good prognosis for postoperative mobility. However, the rate of postoperative deterioration was 31.5%, which is relatively high, and patients should be fully informed of this concern prior to intramedullary spinal cord tumor surgery.

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Masaaki Machino, Kei Ando, Kazuyoshi Kobayashi, Hiroaki Nakashima, Shunsuke Kanbara, Sadayuki Ito, Taro Inoue, Hidetoshi Yamaguchi, Hiroyuki Koshimizu, Keigo Ito, Fumihiko Kato, Naoki Ishiguro, and Shiro Imagama

OBJECTIVE

Although increased signal intensity (ISI) on MRI is observed in patients with cervical spinal cord injury (SCI) without major bone injury, alterations in ISI have not been evaluated. The association between postoperative ISI and surgical outcomes remains unclear. This study elucidated whether or not the postoperative classification and alterations in MRI-based ISI of the spinal cord reflected the postoperative symptom severity and surgical outcomes in patients with SCI without major bone injury.

METHODS

One hundred consecutive patients with SCI without major bone injury (79 male and 21 female) with a mean age of 55 years (range 20–87 years) were included. All patients were treated with laminoplasty and underwent MRI pre- and postoperatively (mean 12.5 ± 0.8 months). ISI was classified into three groups on the basis of sagittal T2-weighted MRI: grade 0, none; grade 1, light (obscure); and grade 2, intense (bright). The neurological statuses were evaluated according to the Japanese Orthopaedic Association (JOA) scoring system and the American Spinal Injury Association Impairment Scale (AIS).

RESULTS

Preoperatively, 8 patients had grade 0 ISI, 49 had grade 1, and 43 had grade 2; and postoperatively, 20 patients had grade 0, 24 had grade 1, and 56 had grade 2. The postoperative JOA scores and recovery rate (RR) decreased significantly with increasing postoperative ISI grade. The postoperative ISI grade tended to increase with the postoperative AIS grade. Postoperative grade 2 ISI was observed in severely paralyzed patients. The postoperative ISI grade improved in 23 patients (23%), worsened in 25 (25%), and remained unchanged in 52 (52%). Patients with an improved ISI grade had a better RR than those with a worsened ISI grade.

CONCLUSIONS

Postoperative ISI reflected postoperative symptom severity and surgical outcomes. Alterations in ISI were seen postoperatively in 48 patients (48%) and were associated with surgical outcomes.

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Kazuyoshi Kobayashi, Kei Ando, Ryuichi Shinjo, Kenyu Ito, Mikito Tsushima, Masayoshi Morozumi, Satoshi Tanaka, Masaaki Machino, Kyotaro Ota, Naoki Ishiguro, and Shiro Imagama

OBJECTIVE

Monitoring of brain evoked muscle-action potentials (Br[E]-MsEPs) is a sensitive method that provides accurate periodic assessment of neurological status. However, occasionally this method gives a relatively high rate of false-positives, and thus hinders surgery. The alarm point is often defined based on a particular decrease in amplitude of a Br(E)-MsEP waveform, but waveform latency has not been widely examined. The purpose of this study was to evaluate onset latency in Br(E)-MsEP monitoring in spinal surgery and to examine the efficacy of an alarm point using a combination of amplitude and latency.

METHODS

A single-center, retrospective study was performed in 83 patients who underwent spine surgery using intraoperative Br(E)-MsEP monitoring. A total of 1726 muscles in extremities were chosen for monitoring, and acceptable baseline Br(E)-MsEP responses were obtained from 1640 (95%). Onset latency was defined as the period from stimulation until the waveform was detected. Relationships of postoperative motor deficit with onset latency alone and in combination with a decrease in amplitude of ≥ 70% from baseline were examined.

RESULTS

Nine of the 83 patients had postoperative motor deficits. The delay of onset latency compared to the control waveform differed significantly between patients with and without these deficits (1.09% ± 0.06% vs 1.31% ± 0.14%, p < 0.01). In ROC analysis, an intraoperative 15% delay in latency from baseline had a sensitivity of 78% and a specificity of 96% for prediction of postoperative motor deficit. In further ROC analysis, a combination of a decrease in amplitude of ≥ 70% and delay of onset latency of ≥ 10% from baseline had sensitivity of 100%, specificity of 93%, a false positive rate of 7%, a false negative rate of 0%, a positive predictive value of 64%, and a negative predictive value of 100% for this prediction.

CONCLUSIONS

In spinal cord monitoring with intraoperative Br(E)-MsEP, an alarm point using a decrease in amplitude of ≥ 70% and delay in onset latency of ≥ 10% from baseline has high specificity that reduces false positive results.