Jun-Yeong Seo

Effects of Therapeutic Hypothermia on Apoptosis and Autophagy After Spinal Cord Injury in Rats.

Study Design. Animal study. Objective. To further investigate the effects of therapeutic hypothermia (TH), the present study compared autophagy and apoptosis after treatment with either therapeutic moderate systemic hypothermia or methylprednisolone sodium succinate (MP) in a rat model of acute spinal cord injury (SCI). Summary of Background Data. The neuroprotective effects of TH have recently become an important topic in the field of SCI research. Methods. All rats were subjected to a 25-g/cm spinal cord contusion over the ninth thoracic vertebrae. After the induction of SCI, the control group did not receive any further treatment, TH group immediately received moderate systemic hypothermia for 4 hours, and MP group was administered high-dose MP. The rats were killed either 2 or 7 days after SCI, and the injured spinal cord tissues were obtained. Apoptosis and autophagy were assessed by immunohistochemical analyses and Western blot analyses. In addition, the microarchitecture of the autophagosomes was evaluated using transmission electron microscopy, and the motor activity of the rats was assessed using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Results. Compared with controls, there was a significant reduction in the expression levels of cleaved caspase-8, −9, and −3 in the TH- and MP-treated groups 2 days after SCI. Moreover, compared with the control group, the expression of LC3II and Beclin-1 exhibited a significant decrease on day 2 after treatment with TH. The numbers of transferase dUTP nicked-end labeling and LC3-positive cells were significantly lower on days 2 and 7. The Basso-Beattie-Bresnahan ratings were significantly higher 6 weeks after SCI in both the TH- and MP-treated groups than in the control group. Conclusion. Both TH and MP have neuroprotective effects on injured spinal cord tissues via the inhibition of apoptosis and autophagy. Thus, the application of moderate systemic hypothermia may be a useful treatment modality after acute SCI. Level of Evidence: N/A

Posterior dynamic stabilization in the treatment of degenerative lumbar stenosis: validity of its rationale

OBJECT The authors undertook this study to investigate the validity of the rationale for posterior dynamic stabilization using the Device for Intervertebral Assisted Motion (DIAM) in the treatment of degenerative lumbar stenosis. METHODS A cohort of 31 patients who underwent single-level decompression and DIAM placement for degenerative lumbar stenosis were followed up for at least 2 years and data pertaining to their cases were analyzed prospectively. Of these patients, 7 had retrolisthesis. Preoperative and postoperative plain lumbar radiographs obtained in all patients and CT images obtained in 14 patients were analyzed. Posterior disc heights; range of motion (ROM) of proximal, distal, and implant segments; lordotic angles of implant segments; percentage of retrolisthesis; and cross-sectional area and heights of intervertebral foramina on CT sagittal images were analyzed. Clinical outcomes were evaluated using visual analog scale scores and Oswestry Disability Index scores. RESULTS The mean values for posterior disc height before surgery, at 1 week after surgery, and at the final follow-up visits were 6.4 ± 2.0 mm, 9.7 ± 2.8 mm, and 6.8 ± 2.5 mm, respectively. The mean lordotic angles at the implant levels before surgery, at 1 week after surgery, and at the final follow-up visits were 7.1° ± 3.3°, 4.1° ± 2.7°, and 7.0° ± 3.7°, respectively. No statistically significant difference was found between the preoperative values and values from final follow-up visits for posterior disc height and lordotic angles at implant levels (p = 0.17 and p = 0.10, respectively). There was no statistically significant difference between the preoperative and final follow-up visit values for intervertebral foramen cross-sectional area and heights on CT images. The ROMs of proximal and distal segments also showed no significant decrease (p = 0.98 and p = 0.92, respectively). However, the ROMs of implant segments decreased significantly (p = 0.02). The average 31.4-month improvement for all clinical outcome measures was significant (p < 0.001). CONCLUSIONS Based on radiological findings, the DIAM failed to show validity in terms of the rationale of indirect decompression, but it did restrict motion at the instrumented level without significant change in adjacent-segment ROM. The clinical condition of the patients, however, was improved, and improvement was maintained despite progressive loss of posterior disc height after surgery.

Fate of Posterior Osteophytes in Fused Segments After Anterior Cervical Discectomy and Fusion

Study Design. Prospective cohort study. Objective. To investigate the fate of posterior osteophytes after anterior cervical discectomy and fusion (ACDF) using computed tomography. Summary of Background Data. As a method of ACDF, indirect decompression through interbody height distraction and spontaneous posterior osteophyte resorption has the advantage of reducing complications that can occur during direct decompression. However, the outcome of resorption, of the posterior osteophytes, has not been considered to be satisfactory. Methods. Thirty-one patients underwent ACDF with plate fixation for cervical spondylotic radiculomyelopathy. The areas and lengths of the most prominent posterior osteophytes in each patient and the anteroposterior diameter of the intervertebral foramen were measured from computed tomographic images using commercial software. Results. Among 31 patients, the posterior osteophytes decreased in 7 (23%), increased in 5 (16%), and were unchanged in 19 (61%). The mean change of area of prominent posterior osteophytes (&Dgr;Area5 years-3 months) was −0.42 ± 4.21 mm2. There was no statistically significant change between Area3 months and Area5 years (P = 0.82). The mean change of length (&Dgr;Length5 years-3 months) was −0.02 ± 0.41 mm. There was no statistically significant difference between Length3 months and Length5 years (P = 0.84). The mean anteroposterior diameter of each intervertebral foramen of fused segments did not change significantly between 3 months and 5 years postoperatively on oblique foraminal images (C5 Rt. P = 0.31, Lt. P = 0.56; C6 Rt. P = 0.61, Lt. P = 0.49) and axial images (C5 Rt. P = 0.61, Lt. P = 0.49; C6 Rt. P = 0.71, Lt. P = 0.51). Conclusion. Contrary to previous reports, there was no evidence of consistent posterior osteophyte resorption during 5 years of follow-up.

Apoptosis in the Sequestrated Nucleus Pulposus Compared to the Remaining Nucleus Pulposus in the Same Patient

Study Design. Both sequestrated nucleus pulposus (SNP) and the remaining nucleus pulposus (RNP) were studied from the discs of the same patient to evaluate apoptosis using immunohistochemical staining. Objective. To compare apoptosis of the SNP and the RNP in the disc of the same patient. Summary of Background Data. Many studies have been conducted on the natural history and apoptosis of the herniated nucleus pulposus; however, apoptosis of the remaining nucleus cells, after removal of the sequestrated disc, in the same patient, has not been reported. Materials and Methods. Eight samples of SNP and RNP from the disc of the same patient were obtained. The TUNEL stain was performed to confirm the occurrence of apoptosis in disc cells. Immunohistochemistry staining and Western blot analysis were performed to determine the presence of proteins, including caspase-3,-8,-9, and Bid. Results. TUNEL-positive chondrocytes were identified in all of the SNP and RNP samples; the apoptotic index was 5.8 ± 1.9% and 5.9 ± 1.2%, respectively (P = 0.60). Caspase-3,-8,-9, and Bid were expressed in the SNP and the RNP of the cytoplasm and the nucleus by the immunohistochemical staining. The expression of active caspase-3,-8,-9, and Bid in the RNP of the disc and the SNP was different in each patient. Conclusion. The frequency of chondrocyte apoptosis in the SNP and the RNP was not different in the disc. The pathways involved in chondrocyte apoptosis of the SNP and the RNP differed among individuals and included intrinsic and/or extrinsic pathways.

Percutaneous posterior instrumentation followed by direct lateral interbody fusion for lumbar infectious spondylitis.

Study Design: Retrospective study. Objectives: To investigate the clinical feasibility and outcomes from direct lateral interbody fusion (DLIF) using autogenous bone grafts and percutaneous posterior instrumentation (PPI) for infectious spondylitis. Summary of Background Data: As one of the minimally invasive techniques, PPI has been attempted for various degenerative lumbar spine disorders combined with anterior lumbar interbody fusion or transforaminal lumbar interbody fusion. PPI has been played more roles recently as an internal fixation method for infectious spondylitis. However, the clinical outcomes of DLIF using an autogenous bone graft combined with PPI for infectious spondylitis have been rarely reported. Materials and Methods: Sixteen patients (mean age, 60.3±18.8 y) who suffered from pyogenic spondylitis underwent single-stage DLIF using an autogenous iliac bone graft combined with PPI. Clinical and radiologic outcomes were evaluated by visual analog scale (VAS), Oswestry Disability Index (ODI), and eradication of primary disease. Radiologic outcomes were evaluated by changes of affected segmental lordosis and fusion status. Results: Bony fusion and eradication of primary disease were obtained in all patient except 1 case during the follow-up (mean, 31.3±13.1 mo; range 14–46 mo). Preoperative VAS (7±1.2) and ODI (61.3±5.4) scores improved significantly at the last follow-up (VAS, 3.4±1.5; ODI, 32.3±15.4). C-reactive protein normalized at postoperative 20.1±0.7 days (range, 15–28 d). Although height and lordosis in the affected segment were restored by surgery, all patients showed loss of the restored lordosis and height at the final follow-up. Loss of the restored lordosis and height were related to subsidence of the grafted bone. Conclusions: Minimally invasive PPI followed by debridement and DLIF was a feasible surgical alternative in our consecutive 16 cases of pyogenic spondylitis. In most cases, however the subsidence of anteriorly grafted fusion was inevitable despite successful fusion and eradication of the primary lesion.

Does Extracorporeal Shock Wave Introduce Alteration of Microenvironment in Cell Therapy for Chronic Spinal Cord Injury

Study Design. Animal experimental study. Objective. To present experimental evidence for cell therapy for spinal cord injury (SCI). Summary of Background Data. In chronic SCI, the efficacy of cell engraftment has been known to be low due to its distinct pathology. Alteration of microenvironment was tried using extracorporeal shock waves (ESW) for chronic SCI, and the efficacy of cell therapy was investigated. Methods. A chronic contusive SCI model was made in 36 Sprague-Dawley rats. The rats were allocated into (1) control group (SCI only), (2) ESW control group (SCI + ESW), (3) IV group (SCI + intravenous transplantation of mesenchymal stem cells; MSCs), and (4) ESW + IV group (SCI + MSCs IV transplantation after ESW). ESW were applied at the energy determined by our preliminary trials. Engraftment of the cells and expressions of growth factors (brain-derived neurotrophic factor, neuronal growth factor) and cytokines (SDF-1, CXCR4, VEGF) at the epicenter were assessed. The Basso, Beattie, and Bresnahan locomotor scale was used for the clinical assessment. Results. The mean numbers of engrafted cells were higher in the ESW+ IV than that in the IV with a statistical significance. The expression of SDF-1 was higher in the ESW groups than that in the control or IV group. CXCR4 was highly expressed in the transplanted groups. The expressions of growth factors in the treated group were higher in the treated group than those in the control group. However, various statistical significances were noted. The improvement of locomotor was higher in the transplanted groups than that in the control and ESW only group. Conclusion. At a given energy level, ESW presented more engraftment of the transplanted MSCs without any clinical deterioration in a chronic SCI. Based on this promising result and possible explanations, ESW may cause an alteration of the microenvironment for the cell therapy in chronic SCI. Level of Evidence: N/A

Spinal cord compression by B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma in a patient seropositive for human immunodeficiency virus: a case report

IntroductionAlthough non-Hodgkin’s lymphoma is one of the most common and frequently fatal of the acquired immune deficiency syndrome-defining illnesses, survival has improved significantly since the introduction of antiretroviral therapy. Patients with spinal cord compression resulting from non-Hodgkin’s lymphoma present with clinically acute or rapidly progressive neurologic deficits. The purpose of this case report is to present a case of a patient seropositive for human immunodeficiency virus with spinal cord compression due to B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.Case presentationA 40-year-old Asian man, who was seropositive for human immunodeficiency virus, presented with progressive neurological deficits. Magnetic resonance images of his thoracic spine showed an epidural mass from T2 to T4, resulting in severe cord compression. Emergent surgical decompression and biopsy were performed, followed by palliative radiation therapy. The pathologic findings showed that the specimen was compatible with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Palliative radiation therapy was performed; however, leptomeningeal seeding and pulmonary embolism led to his death.ConclusionsWhen a patient infected with human immunodeficiency virus presents with a rapidly progressive spinal tumor accompanying paraplegia, non-Hodgkin’s lymphoma should be considered, and surgical decompression should be weighed with respect to the patient’s general condition and the subtype/prognosis of the lymphoma.

Bone Cement Augmentation Procedures for Spinal Pathologic Fractures by Multiple Myeloma

Efficacy and safety of bone cement augmentations for spinal pathologic fractures related to multiple myeloma, and usefulness of radionuclide studies for surgical decision were retrospectively evaluated. Forty eight vertebrae from 27 patients for bone cement augmentation procedures and 48 vertebrae from 29 patients for conservative treatment were enrolled. Clinical results using visual analogue scale (VAS) and Oswestry disability index (ODI), and radiologic results were assessed. For clinical decisions on treatment of spinal pathologic fracture, bone scan or single photon emission computed tomography was done for 20 patients who underwent surgery. Mean follow-up was 16.8 months. In terms of clinical results, immediate pain relief was superior in the operated group to that in the conservative group. ODI, maintenance of vertebral height and local kyphotic angle at the last follow-up were superior in the operated group in comparison to the conservative group. At one year follow-up, cumulative survival rate were 77.4% and 74.7% in the operated and conservative groups, respectively (log rank test> 0.05). Leakage of bone cement was noted at 10 treated vertebrae. Bone cement augmentations presented short-term pain relief for spinal pathologic fractures by myeloma with relative safety in highly selected patients, and radionuclide imaging studies were useful for the surgical decision on these procedures. Graphical Abstract

Thoracic Disc Herniation of the Adjacent Segment With Acutely Progressing Myelopathy

We report a case of a 66-year-old woman with progressing myelopathy. Her history revealed instrumented fusion from T10 to S1 for degenerative lumbar kyphosis and spinal stenosis. The plain radiographs showed narrowing of the intervertebral disc space with a gas shadow and sclerotic end-plate changes at T9-T10. Magnetic resonance imaging revealed a posterolateral mass compressing the spinal cord at the T9-T10 level. The patient was treated with a discectomy through the posterior approach combined with posterior instrumentation. The patients symptoms and myelopathy resolved completely after the discectomy and instrumented fusion. The thoracic disc herniation might have been caused by the increased motion and stress concentration at the adjacent segment.

Treatment for Multiple Aspergillus Spondylitis Including a Hip Joint

Multiple aspergillus spondylitis (AS) is a life threatening infection that occurs more commonly in immunocompromised patients, and is commonly treated with antifungal agents. However, there is relatively little information available on the treatment of multiple AS. The authors encountered a 46-year-old man suffering from low back and neck pain with radiculomyelopathy after a liver transplant. The patient had concomitant multiple AS in the cervico-thoraco-lumbar spine and right hip joint, as confirmed by radiologic imaging studies. The pathological examination of a biopsy specimen revealed fungal hyphae at the cervical and lumbar spine. Anterior decompression and interbody fusion were performed for the cervical and lumbar lesions, which showed instability and related neurological symptoms. Additional antifungal therapy was also performed. The patient was treated successfully with remission of his symptoms.