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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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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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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.

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Junko Kawabe, Masao Koda, Masayuki Hashimoto, Takayuki Fujiyoshi, Takeo Furuya, Tomonori Endo, Akihiko Okawa, and Masashi Yamazaki

Object

Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects on the CNS. The authors have previously demonstrated that G-CSF also exerts neuroprotective effects in experimental spinal cord injury (SCI) by enhancing migration of bone marrow–derived cells into the damaged spinal cord, increasing glial differentiation of bone marrow–derived cells, enhancing antiapoptotic effects on both neurons and oligodendrocytes, and by reducing demyelination and expression of inflammatory cytokines. Because the degree of angiogenesis in the subacute phase after SCI correlates with regenerative responses, it is possible that G-CSF's neuroprotective effects after SCI are due to enhancement of angiogenesis. The aim of this study was to assess the effects of G-CSF on the vascular system after SCI.

Methods

A contusive SCI rat model was used and the animals were randomly allocated to either a G-CSF–treated group or a control group. Integrity of the blood–spinal cord barrier was evaluated by measuring the degree of edema in the cord and the volume of extravasation. For histological evaluation, cryosections were immunostained with anti–von Willebrand factor and the number of vessels was counted to assess revascularization. Real-time reverse transcriptase polymerase chain reaction was performed to assess expression of angiogenic cytokines, and recovery of motor function was assessed with function tests.

Results

In the G-CSF–treated rats, the total number of vessels with a diameter > 20 μm was significantly larger and expression of angiogenic cytokines was significantly higher than those in the control group. The G-CSF–treated group showed significantly greater recovery of hindlimb function than the control group.

Conclusions

These results suggest that G-CSF exerts neuroprotective effects via promotion of angiogenesis after SCI.

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Yukio Someya, Masao Koda, Mari Dezawa, Tomoko Kadota, Masayuki Hashimoto, Takahito Kamada, Yutaka Nishio, Ryo Kadota, Chikato Mannoji, Tomohiro Miyashita, Akihiko Okawa, Katsunori Yoshinaga, and Masashi Yamazaki

Object

The authors previously reported that Schwann cells (SCs) could be derived from bone marrow stromal cells (BMSCs) in vitro and that they promoted axonal regeneration of completely transected rat spinal cords in vivo. The aim of the present study is to evaluate the efficacy of transplanted BMSC-derived SCs (BMSC-SCs) in a rat model of spinal cord contusion, which is relevant to clinical spinal cord injury.

Methods

Bone marrow stromal cells were cultured as plastic-adherent cells from the bone marrow of GFPtransgenic rats. The BMSC-SCs were derived from BMSCs in vitro with sequential treatment using beta-mercaptoethanol, all-trans-retinoic acid, forskolin, basic fibroblast growth factor, platelet derived–growth factor, and heregulin. Schwann cells were cultured from the sciatic nerve of neonatal, GFP-transgenic rats. Immunocytochemical analysis and the reverse transcriptase–polymerase chain reaction were performed to characterize the BMSC-SCs. For transplantation, contusions with the New York University impactor were delivered at T-9 in 10- to 11-week-old male Wistar rats. Four groups of rats received injections at the injury site 7 days postinjury: the first received BMSCSCs and matrigel, a second received peripheral SCs and matrigel, a third group received BMSCs and matrigel, and a fourth group received matrigel alone. Histological and immunohistochemical studies, electron microscopy, and functional assessments were performed to evaluate the therapeutic effects of BMSC-SC transplantation.

Results

Immunohistochemical analysis and reverse transcriptase–polymerase chain reaction revealed that BMSC-SCs have characteristics similar to SCs not only in their morphological characteristics but also in their immunocytochemical phenotype and genotype. Histological examination revealed that the area of the cystic cavity was significantly reduced in the BMSC-SC and SC groups compared with the control rats. Immunohistochemical analysis showed that transplanted BMSCs, BMSC-SCs, and SCs all maintained their original phenotypes. The BMSC-SC and SC groups had a larger number of tyrosine hydroxilase–positive fibers than the control group, and the BMSC-SC group had more serotonin-positive fibers than the BMSC or control group. The BMSC-SC group showed significantly better hindlimb functional recovery than in the BMSC and control group. Electron microscopy revealed that transplanted BMSC-SCs existed in association with the host axons.

Conclusions

Based on their findings, the authors concluded that BMSC-SC transplantation reduces the size of the cystic cavity, promotes axonal regeneration and sparing, results in hindlimb functional recovery, and can be a useful tool for spinal cord injury as a substitute for SCs.

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Yawara Eguchi, Masaki Norimoto, Munetaka Suzuki, Ryota Haga, Hajime Yamanaka, Hiroshi Tamai, Tatsuya Kobayashi, Sumihisa Orita, Miyako Suzuki, Kazuhide Inage, Hirohito Kanamoto, Koki Abe, Tomotaka Umimura, Takashi Sato, Yasuchika Aoki, Atsuya Watanabe, Masao Koda, Takeo Furuya, Junichi Nakamura, Tsutomu Akazawa, Kazuhisa Takahashi, and Seiji Ohtori

OBJECTIVE

The purpose of this study was to determine the relationship between vertebral bodies, psoas major morphology, and the course of lumbar nerve tracts using diffusion tensor imaging (DTI) before lateral interbody fusion (LIF) to treat spinal deformities.

METHODS

DTI findings in a group of 12 patients (all women, mean age 74.3 years) with degenerative lumbar scoliosis (DLS) were compared with those obtained in a matched control group of 10 patients (all women, mean age 69.8 years) with low-back pain but without scoliosis. A T2-weighted sagittal view was fused to tractography from L3 to L5 and separated into 6 zones (zone A, zones 1–4, and zone P) comprising equal quarters of the anteroposterior diameters, and anterior and posterior to the vertebral body, to determine the distribution of nerves at various intervertebral levels (L3–4, L4–5, and L5–S1). To determine psoas morphology, the authors examined images for a rising psoas sign at the level of L4–5, and the ratio of the anteroposterior diameter (AP) to the lateral diameter (lat), or AP/lat ratio, was calculated. They assessed the relationship between apical vertebrae, psoas major morphology, and the course of nerve tracts.

RESULTS

Although only 30% of patients in the control group showed a rising psoas sign, it was present in 100% of those in the DLS group. The psoas major was significantly extended on the concave side (AP/lat ratio: 2.1 concave side, 1.2 convex side). In 75% of patients in the DLS group, the apex of the curve was at L2 or higher (upper apex) and the psoas major was extended on the concave side. In the remaining 25%, the apex was at L3 or lower (lower apex) and the psoas major was extended on the convex side. Significant anterior shifts of lumbar nerves compared with controls were noted at each intervertebral level in patients with DLS. Nerves on the extended side of the psoas major were significantly shifted anteriorly. Nerve pathways on the convex side of the scoliotic curve were shifted posteriorly.

CONCLUSIONS

A significant anterior shift of lumbar nerves was noted at all intervertebral levels in patients with DLS in comparison with findings in controls. On the convex side, the nerves showed a posterior shift. In LIF, a convex approach is relatively safer than an approach from the concave side. Lumbar nerve course tracking with DTI is useful for assessing patients with DLS before LIF.