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Michael G. Fehlings and Jared T. Wilcox

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Masashi Yamazaki, Masao Koda, Minori Yoneda, Atsuomi Aiba, and Hideshige Moriya

✓ The authors report a case of a patient with Down syndrome in whom the abnormal course of the right vertebral artery (VA) at the craniovertebral junction (CVJ) was accurately demonstrated on three-dimensional (3D) computerized tomography (CT) angiography. The patient was a 5-year-old boy, who developed severe myelopathy. Bone abnormalities were also present at the CVJ, including atlantoaxial and occipitoatlantal instabilities, a hypoplastic odontoid process, and ossiculum terminale. Three-dimensional CT angiography revealed that the right VA was duplicated after emerging from the C-2 transverse foramen. One half of the duplication, an artery that was as large as the left VA, turned posteromedially and entered the spinal canal between C-1 and C-2. The other half, a very small artery, ran as usual and passed through the C-1 transverse foramen. The authors performed an occipitocervical posterior fusion and a C-1 laminectomy. Intraoperatively the course of the anomalous VA was identified on Doppler ultrasonography, and the surgical approach and bone excision were undertaken carefully to avoid VA injury. Postoperatively, resolution of myelopathy was marked. In the surgical treatment of patients with Down syndrome, surgeons should consider the possibility that a VA anomaly is present at the CVJ. With preoperative 3D CT angiography, the anomalous VA can be identified precisely and the possible risk of intraoperative VA injury predetermined.

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Macondo Mochizuki, Atsuomi Aiba, Mitsuhiro Hashimoto, Takayuki Fujiyoshi, and Masashi Yamazaki

Object

The authors assessed the clinical course in patients with a narrowed cervical spinal canal caused by ossification of the posterior longitudinal ligament (OPLL), but who have no or only mild myelopathy. Additionally, the authors analyzed the factors contributing to the development and aggravation of myelopathy in patients with OPLLinduced spinal canal stenosis.

Methods

Between 1997 and 2004, the authors selected treatments for patients with cervical OPLL in whom the residual space available for the spinal cord was ≤ 12 mm. Treatment decisions were based on the severity of myelopathy at presentation. Twenty-one patients with no or mild myelopathy (defined as a Japanese Orthopaedic Association [JOA] scale score ≥ 14 points) received conservative treatment, with a mean follow-up period of 4.5 years. In 20 patients with moderate or severe myelopathy (JOA scale score < 14 points), the authors performed surgery via an anterior approach. The clinical course in these patients was assessed with the JOA scale and the OPLL types were classified. The authors evaluated the range of motion between C-1 and C-7, the developmental segmental sagittal diameter, the percentage of spinal canal diameter occupied by the OPLL (% ratio), and the residual space available for the spinal cord on cervical radiographs; T2-weighted MR images were examined for high signal changes (HSCs).

Results

In the conservative treatment group, 8 patients showed improvement, 12 remained unchanged, and 1 patient's condition became slightly worse during the observation period. Fifteen patients in this group had mixedtype, 3 had continuous-type, 2 had localized-type, and 1 had a segmental-type OPLL. In the surgically treated group, there were 12 patients with segmental-type, 10 patients with mixed-type, and 1 with localized-type OPLL. The mean range of motion at C1–7 was 36.4° in the conservatively treated group and 46.5° in the surgical group (p < 0.05). No significant difference was seen between the groups in terms of developmental segmental sagittal diameter, % ratio, or residual space available for the cord. No HSCs were noted in the conservative group, while 17 patients in the surgical group had HSCs (p < 0.05).

Conclusions

In the present study, the authors demonstrate that the mobility of the cervical spine and the type of OPLL are important factors contributing to the development and aggravation of myelopathy in patients with OPLLinduced spinal canal stenosis. The authors advocate conservative treatment in most patients with OPLLs who have no or only mild myelopathy, even in the presence of spinal canal narrowing.

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Naoya Kikuchi, Masafumi Uesugi, Masao Koda, Tomoaki Shimizu, Kohei Murakami, Mamoru Kono, Haruka Tanaka, and Masashi Yamazaki

The use of methotrexate (MTX) to treat rheumatoid arthritis (RA) is increasing. Recently, MTX-associated lymphoproliferative disorder (MTX-LPD) has been frequently reported as lymphoma occurring during MTX therapy. The authors report their experience with a relatively rare case of MTX-LPD presenting in the lumbar spine. The patient, a 73-year-old woman who experienced low-back pain while receiving MTX therapy for RA, was suspected of having developed MTX-LPD based on her medical history, images of the L1 vertebra, and transpedicular biopsy results. One week after discontinuing MTX, the patient’s low-back pain reportedly improved. The woman was diagnosed with MTX-LPD based on histopathological findings. MTX discontinuation alone coincided with spontaneous tumor regression. Because MTX-LPD can occur in tissues other than lymph nodes, such as in bones and joints, it is a disease that should be considered when diagnosing spinal tumors in patients receiving MTX therapy.

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Masashi Yamazaki, Takana Koshi, Chikato Mannoji, Akihiko Okawa, and Masao Koda

✓ The authors report the case of a 62-year-old woman who suffered an accidental fall and complained of severe neck pain and right C-7 radiculopathy. A right C6–7 facet fracture–subluxation was diagnosed. Bone fragments impinged on the right C-7 nerve root at the neural foramen. The bilateral vertebral arteries (VAs) ascended at the anterior aspect of C-6 and C-5 and entered the transverse foramen at the C-4 level.

Based on findings of anomalous VAs, the authors applied a pedicle screw (PS)/rod system to effect surgical correction of the deformity. Intraoperatively, they successfully performed reduction of the subluxation, decompression of the impinged nerve root, and minimum single-segment fusion involving the placement of a PS/rod system. After surgery, the patient's neurological deficit dramatically improved and spinal fusion was completed without any loss of deformity correction.

Prior to surgery for cervical injuries, the possible presence of an abnormal VA course should be considered. Preoperative detection of anomalous VAs will affect decisions on the appropriate corrective surgery option in cases of cervical spine injuries.

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Mikiko Takahashi, Yusuke Tomita, Shoko Merrit Yamada, Kazuto Yamazaki, Hideaki Yokoo, Tatsuya Aso, and Masashi Kawamoto

BACKGROUND

Diffuse midline glioma H3 K27M-mutant is a distinct subtype of glial tumors newly introduced in the revised fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System. They are aggressive pediatric tumors with a poor prognosis but have also been reported in adults.

OBSERVATIONS

The authors present the case of a man in his 60s who presented with rotatory vertigo, taste disorder, and right facial paralysis. Magnetic resonance imaging showed a tumor expanding from the cerebellum to the pons, which was histologically identified as glioblastoma, grade IV, IDH wild type. After tumor resection, the patient received chemoradiotherapy but showed only a partial response. His condition gradually worsened, and he died of progressive disease 12 months postoperation, after which an autopsy was performed. Tumor cells with a high nuclear-to-cytoplasm ratio were immunohistochemically analyzed and found to test positive for H3 K27M and negative for H3 K27me3. Furthermore, mutational analysis revealed HIST1H3B K27M mutation, and the tumor was finally identified as a high-grade glioma H3 K27M-mutant. The tumor invaded widely along the cerebral ventricle and disseminated to the spinal cord.

LESSONS

When a glioblastoma shows localization or dissemination patterns different from those of typical glioblastoma, an H3 K27M-mutant glioma should be suspected.

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Tomoaki Shimizu, Masao Koda, Tetsuya Abe, Tomoyuki Asada, Kosuke Sato, Yosuke Shibao, Mamoru Kono, Fumihiko Eto, Kousei Miura, Kentaro Mataki, Hiroshi Noguchi, Hiroshi Takahashi, Toru Funayama, and Masashi Yamazaki

OBJECTIVE

The goal of this study was to clarify the clinical utility of paravertebral foramen screws (PVFSs) and to determine intraoperative indicators for appropriate screw placement during posterior cervical fusion surgery to improve its safety.

METHODS

The authors included data from 46 patients (29 men and 17 women, mean age 61.7 years) who underwent posterior cervical spine surgery with 94 PVFSs. Of the 94 PVFSs, 77 were used in C6, 9 in C3, 5 in C4, and 3 in C5. According to the cervical lateral radiographic view, the authors divided the 94 PVFSs into 3 groups as follows: a longer group, in which the tip of PVFS was located anteriorly from the line of the posterior wall of the vertebral body (> +0 mm); an intermediate group, in which the screw tip was located up to 2 mm posteriorly to the posterior wall of the vertebral body (–2 to 0 mm); and a shorter group, in which the screw tip was located more than 2 mm posteriorly (< –2 mm). The accuracy of screw placement was assessed using CT imaging in the axial plane, and the proportion of screws penetrating a vertebral foramen or a transverse foramen was compared between the 3 groups. Screw loosening was defined as a lucent zone around the screw evaluated on cervical radiography at 1 year after surgery. Complications related to PVFS insertion and revision surgery related to PVFS were evaluated.

RESULTS

The authors classified 25 PVFSs into the longer group, 43 into the intermediate group, and 26 into the shorter group. The proportion of screws penetrating a vertebral foramen was largest in the shorter group, and the proportion penetrating a transverse foramen was largest in the longer group. Screw loosening was confirmed for 3 of 94 PVFSs. One PVFS inserted in C6 unilaterally within a long construct from C2 to C7 showed loosening, but it did not cause clinical symptoms. Revision surgery was required for 2 PVFSs inserted in C3 bilaterally as the lower instrumented vertebra in occiput–cervical fusion because they pulled out. There was no neurovascular complication related to PVFS insertion.

CONCLUSIONS

PVFSs are useful for posterior cervical fusion surgery as alternative anchor screws, and the line of the posterior wall of the cervical body on lateral fluoroscopic images is a potential intraoperative reference to indicate an appropriate trajectory for PVFSs.

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Koichi Hayashi, Masayuki Hashimoto, Masao Koda, Atsuhiko T. Naito, Atsushi Murata, Akihiko Okawa, Kazuhisa Takahashi, and Masashi Yamazaki

Object

Clinical use of autologous induced pluripotent stem cells (iPSCs) could circumvent immune rejection and bioethical issues associated with embryonic stem cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting disability, and current therapeutic approaches are not satisfactory. In the present study, the authors used the neural stem sphere (NSS) method to differentiate iPSCs into astrocytes, which were evaluated after their transplantation into injured rat spinal cords.

Methods

Induced pluripotent stem cell–derived astrocytes were differentiated using the NSS method and injected 3 and 7 days after spinal contusion–based SCI. Control rats were injected with DMEM in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and locomotion tests were evaluated at 8 weeks. Immunohistological parameters were then assessed.

Results

Transplant recipients lived for 8 weeks without tumor formation. Transplanted cells stretched their processes along the longitudinal axis, but they did not merge with the processes of host GFAP-positive astrocytes. Locomotion was assessed in 3 ways, but none of the tests detected statistically significant improvements compared with DMEM-treated control rats after 8 weeks. Rather, iPSC transplantation caused even greater sensitivity to mechanical stimulus than DMEM treatment.

Conclusions

Astrocytes can be generated by serum treatment of NSS-generated cells derived from iPSCs. However, transplantation of such cells is poorly suited for repairing SCI.

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Satoshi Maki, Masaaki Aramomi, Yusuke Matsuura, Takeo Furuya, Mitsutoshi Ota, Yasushi Iijima, Junya Saito, Takane Suzuki, Chikato Mannoji, Kazuhisa Takahashi, Masashi Yamazaki, and Masao Koda

OBJECTIVE

Fusion surgery with instrumentation is a widely accepted treatment for cervical spine pathologies. The authors propose a novel technique for subaxial cervical fusion surgery using paravertebral foramen screws (PVFS). The authors consider that PVFS have equal or greater biomechanical strength than lateral mass screws (LMS). The authors’ goals of this study were to conduct a biomechanical study of PVFS, to investigate the suitability of PVFS as salvage fixation for failed LMS, and to describe this novel technique.

METHODS

The authors harvested 24 human cervical spine vertebrae (C3–6) from 6 fresh-frozen cadaver specimens from donors whose mean age was 84.3 ± 10.4 years at death. For each vertebra, one side was chosen randomly for PVFS and the other for LMS. For PVFS, a 3.2-mm drill with a stopper was advanced under lateral fluoroscopic imaging. The drill stopper was set to 12 mm, which was considered sufficiently short not to breach the transverse foramen. The drill was directed from 20° to 25° medially so that the screw could purchase the relatively hard cancellous bone around the entry zone of the pedicle. The hole was tapped and a 4.5-mm-diameter × 12-mm screw was inserted. For LMS, 3.5-mm-diameter × 14-mm screws were inserted into the lateral mass of C3–6. The pullout strength of each screw was measured. After pullout testing of LMS, a drill was inserted into the screw hole and the superior cortex of the lateral mass was pried to cause a fracture through the screw hole, simulating intraoperative fracture of the lateral mass. After the procedure, PVFS for salvage (sPVFS) were inserted on the same side and pullout strength was measured.

RESULTS

The CT scans obtained after screw insertion revealed no sign of pedicle breaching, violation of the transverse foramen, or fracture of the lateral mass. A total of 69 screws were tested (23 PVFS, 23 LMS, and 23 sPVFS). One vertebra was not used because of a fracture that occurred while the specimen was prepared. The mean bone mineral density of the specimens was 0.29 ± 0.10 g/cm3. The mean pullout strength was 234 ± 114 N for PVFS, 158 ± 91 N for LMS, and 195 ± 125 N for sPVFS. The pullout strength for PVFS tended to be greater than that for LMS. However, the difference was not quite significant (p = 0.06).

CONCLUSIONS

The authors introduce a novel fixation technique for the subaxial cervical spine. This study suggests that PVFS tend to provide stronger fixation than LMS for initial applications and fixation equal to LMS for salvage applications. If placement of LMS fails, PVFS can serve as a salvage fixation technique.

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Yutaka Nishio, Masao Koda, Takahito Kamada, Yukio Someya, Katsunori Yoshinaga, Seiji Okada, Hideki Harada, Akihiko Okawa, Hideshige Moriya, and Masashi Yamazaki

Object

The use of human umbilical cord blood (HUCB) cells has been reported to improve functional recovery in cases of central nervous system injuries such as stroke, traumatic brain injury, and spinal cord injury (SCI). The authors investigated the effects of hemopoietic stem cells that were derived from HUCB and transplanted into the injured spinal cords of rats.

Methods

One week after injury, an HUCB fraction enriched in CD34-positive cells was transplanted into the experimental group. In control animals, vehicle (Matrigel) was transplanted. Recovery of motor functions was assessed using the Basso, Beattie, and Bresnahan Locomotor Scale, and immunohistochemical examinations were performed.

Cells from HUCB that were CD34 positive improved functional recovery, reduced the area of the cystic cavity at the site of injury, increased the volume of residual white matter, and promoted the regeneration or sparing of axons in the injured spinal cord. Immunohistochemical examination revealed that transplanted CD34-positive cells survived in the host spinal cord for at least 3 weeks after transplantation but had disappeared by 5 weeks. The transplanted cells were not positive for neural markers, but they were positive for hemopoietic markers. There was no evidence of an immune reaction at the site of injury in either group.

Conclusions

These results suggest that transplantation of a CD34-positive fraction from HUCB may have therapeutic effects for SCI. The results of this study provide important preclinical data regarding HUCB stem cell–based therapy for SCI.