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Kenichiro Yahata, Haruo Kanno, Hiroshi Ozawa, Seiji Yamaya, Satoshi Tateda, Kenta Ito, Hiroaki Shimokawa, and Eiji Itoi

OBJECTIVE

Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI.

METHODS

Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42.

RESULTS

Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in NeuN-, GFAP-, and Olig2-labeled cells. Low-energy ESWT significantly promoted CD31 and α-SMA expressions in the injured spinal cords. In addition, low-energy ESWT significantly reduced the TUNEL-positive cells in the injured spinal cords. Furthermore, the immunodensity of 5-HT–positive axons was significantly higher in the animals treated by low-energy ESWT. The areas of spared white matter were obviously larger in the SCI-SW group than in the SCI group, as indicated by Luxol fast blue staining.

CONCLUSIONS

The results of this study suggested that low-energy ESWT promotes VEGF expression in various neural cells and enhances angiogenesis in damaged neural tissue after SCI. Furthermore, the neuroprotective effect of VEGF induced by low-energy ESWT can suppress cell death and axonal damage and consequently improve locomotor and sensory functions after SCI. Thus, low-energy ESWT can be a novel therapeutic strategy for treatment of SCI.

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Toshimi Aizawa, Toshimitsu Eto, Ko Hashimoto, Haruo Kanno, Eiji Itoi, and Hiroshi Ozawa

OBJECTIVE

Thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) remains one of the most difficult-to-treat disorders for spine surgeons. In Japan, approximately 75% of patients with this condition are treated using posterior decompression with instrumented spinal fusion (PDF). In contrast, anterior decompression is the most effective method for relieving spinal cord compression. The authors treated nonambulatory patients with thoracic OPLL by either PDF or by their technique using anterior decompression through a posterior approach. In this study the surgical results of these procedures are compared.

METHODS

This was a retrospective case series. From 2008 to 2018, 9 patients with thoracic OPLL who could not walk preoperatively were treated surgically. Three patients were treated by PDF (the PDF group) and 6 patients were treated by anterior decompression through a posterior approach (the modified Ohtsuka group). The degree of surgical invasion and the neurological conditions of the patients were assessed.

RESULTS

The PDF group had a shorter operative duration (mean 477 ± 122 vs 569 ± 92 minutes) and less intraoperative blood loss (mean 613 ± 380 vs 1180 ± 614 ml), although the differences were not statistically significant. The preoperative Japanese Orthopaedic Association (JOA) score was almost identical between the two groups; however, the latest JOA score and the recovery rate were significantly better in the modified Ohtsuka group than in the PDF group (8.8 ± 1.5 vs 5.0 ± 1.7 and 71.3% ± 23.7% vs 28.3% ± 5.7%, respectively). The walking ability was evaluated using the modified Frankel scale. According to this scale, 3 patients showed three grade improvements, 2 patients showed two grade improvements, and 1 patient showed one grade improvement in the modified Ohtsuka group. Three patients in the modified Ohtsuka group could walk without any support at the final follow-up.

CONCLUSIONS

The present study clearly indicated that the surgical outcomes of the authors’ modified Ohtsuka procedure were significantly better than those of PDF for patients who could not walk preoperatively.

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Toshimi Aizawa, Toshimitsu Eto, Ko Hashimoto, Haruo Kanno, Eiji Itoi, and Hiroshi Ozawa

OBJECTIVE

Thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) remains one of the most difficult-to-treat disorders for spine surgeons. In Japan, approximately 75% of patients with this condition are treated using posterior decompression with instrumented spinal fusion (PDF). In contrast, anterior decompression is the most effective method for relieving spinal cord compression. The authors treated nonambulatory patients with thoracic OPLL by either PDF or by their technique using anterior decompression through a posterior approach. In this study the surgical results of these procedures are compared.

METHODS

This was a retrospective case series. From 2008 to 2018, 9 patients with thoracic OPLL who could not walk preoperatively were treated surgically. Three patients were treated by PDF (the PDF group) and 6 patients were treated by anterior decompression through a posterior approach (the modified Ohtsuka group). The degree of surgical invasion and the neurological conditions of the patients were assessed.

RESULTS

The PDF group had a shorter operative duration (mean 477 ± 122 vs 569 ± 92 minutes) and less intraoperative blood loss (mean 613 ± 380 vs 1180 ± 614 ml), although the differences were not statistically significant. The preoperative Japanese Orthopaedic Association (JOA) score was almost identical between the two groups; however, the latest JOA score and the recovery rate were significantly better in the modified Ohtsuka group than in the PDF group (8.8 ± 1.5 vs 5.0 ± 1.7 and 71.3% ± 23.7% vs 28.3% ± 5.7%, respectively). The walking ability was evaluated using the modified Frankel scale. According to this scale, 3 patients showed three grade improvements, 2 patients showed two grade improvements, and 1 patient showed one grade improvement in the modified Ohtsuka group. Three patients in the modified Ohtsuka group could walk without any support at the final follow-up.

CONCLUSIONS

The present study clearly indicated that the surgical outcomes of the authors’ modified Ohtsuka procedure were significantly better than those of PDF for patients who could not walk preoperatively.

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Haruo Kanno, Toshimi Aizawa, Hiroshi Ozawa, Takeshi Hoshikawa, Eiji Itoi, and Shoichi Kokubun

The authors report a rare case of tethered cord syndrome with low-placed conus medullaris complicated by a vertebral fracture that was successfully treated by a spine-shortening vertebral osteotomy. The patient was a 57-year-old woman whose neurological condition worsened after a T-12 vertebral fracture because a fracture fragment and the associated local kyphotic deformity directly compressed the tethered spinal cord. An osteotomy of the T-12 vertebra was performed in order to correct the kyphosis, remove the fracture fragment, and reduce the tension on the spinal cord. Postoperative radiographs showed the spine to be shortened by 22 mm, and the kyphosis between T-11 and L-1 improved from 23° to 0°. Two years after the surgery, the patient's neurological symptoms were resolved. The bone union was complete with no loss of correction.

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Seiji Yamaya, Hiroshi Ozawa, Haruo Kanno, Koshi N. Kishimoto, Akira Sekiguchi, Satoshi Tateda, Kenichiro Yahata, Kenta Ito, Hiroaki Shimokawa, and Eiji Itoi

Object

Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether lowenergy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI.

Methods

Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord.

Results

In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p < 0.05). The number of NeuN-positive cells in the SCI-SW group was significantly higher than that in the SCI group at 42 days after injury (p < 0.05). In addition, mRNA expressions of VEGF and Flt-1 were significantly increased in the SCI-SW group compared with the SCI group at 7 days after injury (p < 0.05). The expression of VEGF protein in the SCI-SW group was significantly higher than that in the SCI group at 7 days (p < 0.01).

Conclusions

The present study showed that low-energy ESWT significantly increased expressions of VEGF and Flt-1 in the spinal cord without any detrimental effect. Furthermore, it significantly reduced neuronal loss in damaged neural tissue and improved locomotor function after SCI. These results suggested that low-energy ESWT enhances the neuroprotective effect of VEGF in reducing secondary injury and leads to better locomotor recovery following SCI. This study provides the first evidence that low-energy ESWT can be a safe and promising therapeutic strategy for SCI.