Technical Considerations in Endoscopic Lumbar Decompression.

With technical development and evolution of endoscopic instruments, endoscopic spinal surgery has become one of the standard treatments for various lumbar spinal diseases ranging from a simple contained disc to complicated cases such as highly migrated disc herniation and other pathology combined with bony degeneration to produce foraminal and canal stenosis. Favorable clinical results of endoscopic decompression for lumbar stenotic disease were reported by several authors. However, studies have also reported limitations, such as steep learning curves and a relatively high complication rate compared with conventional techniques. The endoscopic lumbar decompression technique consists of many essential skills to manage different endoscopic anatomic structures of the spine. From the perspective of surgical completion and safety, this article discusses issues related to technical considerations in endoscopic lumbar decompression.

Comparative Analysis between Three Different Lumbar Decompression Techniques (Microscopic, Tubular, and Endoscopic) in Lumbar Canal and Lateral Recess Stenosis: Preliminary Report.

PURPOSE: The purpose of our study is to compare the results of spinal decompression using the full-endoscopic interlaminar technique, tubular retractor, and a conventional microsurgical laminotomy technique and evaluate the advantages and clinical feasibility of minimally invasive spinal (MIS) lumbar decompression technique in the lumbar canal and lateral recess stenosis. METHODS: The authors retrospectively reviewed clinical and radiological data from 270 patients who received microsurgical (group E: 72 patients), tubular (group T: 34 patients), or full-endoscopic decompression surgery (group E: 164 patients) for their lumbar canal and lateral recess stenosis from June 2016 to August 2017. Clinical (VAS, ODI, and Mcnab criteria), radiologic (spinal canal diameter, segmental dynamic angle, and disc height), and surgical outcome parameters (CPK level, Operative time, blood loss, and hospital stay) were evaluated pre- and postoperatively and compared among the three groups by means of statistical analysis. Failed cases and complications were reviewed in all groups. RESULTS: The mean follow-up period was 6.38 months. The Overall clinical success rate was 89.4%. All groups showed favorable clinical outcome. The clinical and radiologic results were similar in all groups. Regarding surgical outcome, group E showed longer operation time than group M and T (group E: 84.17 minutes/level, group M: 52.22 minutes/level, and group T: 66.12 minutes/level) (p<0.05). However, groups E and T showed minimal surgical invasiveness compared with group M. Groups E and T showed less immediate postoperative back pain (VAS) (group E: 3.13, group M: 4.28, group T: 3.54) (p<0.05), less increase of serum CPK enzyme (group E: 66.38 IU/L, group M: 120 IU/L, and group T: 137.5 IU/L) (p<0.05), and shorter hospital stay (group E: 2.12 days, group M: 4.85 days, and group T: 2.83 days) (p<0.05). The rates of complications and revisions were not significantly different among the three groups. CONCLUSIONS: MIS decompression technique is clinically feasible and safe to treat the lumbar canal and lateral recess stenosis, and it has many surgical advantages such as less muscle trauma, minimal postoperative back pain, and fast recovery of the patient compared to traditional open microscopic technique.

The Usefulness of Percutaneous Endoscopic Technique in Multifocal Lumbar Pathology.

Introduction. The multifocal lumbar pathology including disc herniation and stenosis in the spinal canal or foramen has been considered the most difficult to approach surgically. It often requires mandatory dual approaches and/or fusion techniques. Traditional percutaneous endoscopic lumbar transforaminal and interlaminar approach has been focused on unifocal disc herniation. However, the development of endoscopic spinal instruments and surgical technique has broadened surgical indication and therapeutic boundary in endoscopic spine surgery. Cases Presentation. The authors present outcomes of four patients with multilumbar pathology including highly inferior migrated disc combined with lateral recess stenosis, multifocal disc herniation, bilateral disc herniations in spinal canal and foraminal disc herniation combined with central canal stenosis. They were successfully treated by percutaneous uniportal full endoscopic approach with single incision. Conclusion. Percutaneous endoscopic spine surgery is a safe and effective tool to figure out multilumbar pathology in a minimal invasive way.

Percutaneous Endoscopic Laminotomy with Flavectomy by Uniportal, Unilateral Approach for the Lumbar Canal or Lateral Recess Stenosis.

OBJECTIVE: To evaluate clinical feasibility and safety of percutaneous endoscopic decompression by a uniportal, unilateral approach for lumbar canal or lateral recess stenosis. METHODS: In this retrospective study, the procedure was performed with endoscopic instruments in the same way as conventional microscopic laminotomy and flavectomy. Clinical outcomes (visual analog scale, Oswestry Disability Index, modified MacNab criteria) were evaluated. Surgical outcomes, including operative time, hospital stay, and complications, were recorded. RESULTS: Decompression was performed in 213 patients (232 lumbar levels) for spinal canal or lateral recess stenosis (unilateral laminotomy, n = 80; bilateral laminotomy, n = 152). Mean follow-up period was 26.45 months. Mean visual analog scale for leg pain, and back pain and mean Oswestry Disability Index improved from 8.24%, 5.35%, and 67.8% at baseline to 1.93% (P < 0.001), 2.05% (P < 0.001), and 17.14% (P < 0.001) at final follow-up. Based on modified MacNab criteria, excellent or good results were obtained in 93.8% of patients. Average operative time was 105.3 ± 56 minutes. In the late period of the learning curve, mean operative time was shortened by two thirds, and mean hospital stay was 2.45 days. There were 12 cases of transient postoperative dysesthesia, 3 cases of motor weakness, and 6 cases of dural tear. No patient had postoperative infection, hematoma, or need for revision surgery for incomplete decompression. CONCLUSIONS: Percutaneous endoscopic decompression by a uniportal, unilateral approach is a safe, clinically feasible, and effective surgical technique for treatment of lumbar stenosis.

Suppression of AIMP1 protects cognition in Alzheimer's disease model mice 3xTg-AD.

Neuroinflammation has been raised as a candidate of unifying pathogenesis and a target of a disease-modifying strategy for Alzheimer's disease (AD). Aminoacyl-tRNA synthetase complex (ARS)-interacting multifunctional protein 1 (AIMP1) is a cytokine that is known to amplify the actions of tumor necrosis factor-α and to be involved in microglial activation and neuronal death. In this respect, AIMP1 could be a plausible target for the treatment of AD. Therefore, we aimed to examine whether anti-AIMP1 antibody could exert therapeutic effects against cognitive impairment using 3xTg-AD mice. Through the passive avoidance test, we found that an intraperitoneal injection of anti-AIMP1 antibody over 4 weeks was effective in protecting memory function in 3xTg-AD mice (16 weeks old). In addition, to address the translational implications of AIMP1, we measured blood AIMP1 levels in patients with AD (n=22), mild cognitive impairment (n=25), and normal cognition (n=23). Blood AIMP1 levels were associated negatively with global cognitive function and were significantly higher in individuals with a higher degree of medial temporal lobe atrophy, which is one of the representative clinical markers of AD. Our results suggested a possible association of AIMP1 with AD pathogenesis, as well as the potential of the anti-AIMP1 antibody as a novel therapeutic option for AD.

Tauroursodeoxycholic acid improves viability of artificial RBCs.

Tauroursodeoxycholic acid (TUDCA) is known to prevent apoptosis through the Bax pathway and to promote neovascularization by enhancing the mobilization of stem cells, their differentiation. This study was performed to investigate the effect of TUDCA on erythropoiesis in hematopoietic stem cells (HSCs). Since erythropoiesis of CD34(+) HSCs is divided into four phases, the total cell number, viable cell number, cell viability, cell morphology, and expressed erythroid markers in each phase were examined. The number of viable control cells and their viability did not differ from those of the TUDCA-treated cells in phase I and II. However, TUDCA increased cell viability compared to the control in phases III and IV. Cell distribution differed that the immature erythroid cell number was higher for the TUDCA-treated cells than for the control cells until phase III, but all developed into RBCs in the last. The final RBC number and viability was significantly higher in TUDCA-treated cells compared to the control cells. Taken together, we suggest that TUDCA addition to cell cultures for artificial RBC production could be used as a new protocol for improving the viability of RBCs.

Foraminoplastic Superior Vertebral Notch Approach with Reamers in Percutaneous Endoscopic Lumbar Discectomy : Technical Note and Clinical Outcome in Limited Indications of Percutaneous Endoscopic Lumbar Discectomy.

To describe the details of the foraminoplastic superior vertebral notch approach (FSVNA) with reamers in percutaneous endoscopic lumbar discectomy (PELD) and to demonstrate the clinical outcomes in limited indications of PELD. Retrospective data were collected from 64 patients who underwent PELD with FSVNA from August 2012 to April 2014. Inclusion criteria were high grade migrated disc, high canal compromised disc, and disc protrusion combined with foraminal stenosis. The clinical outcomes were assessed using by the visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified MacNab criteria. Complications related to the surgery were reviewed. The procedure used a unique approach, using the superior vertebral notch as the target and performing foraminoplasty with only reamers under C-arm control. The mean age of the 55 female and 32 male patients was 52.73 years. The mean F/U period was 12.2±4.2 months. Preoperative VAS (8.24±1.25) and ODI (67.8±15.4) score improved significantly at the last follow-up (VAS, 1.93±1.78; ODI, 17.14±15.7). Based on the modified MacNab criteria, excellent or good results were obtained in 95.3% of the patients. Postoperative transient dysthesia (n=2) and reoperation (n=1) due to recurred disc were reported. PELD with FSVNA could be a good method for treating lumbar disc herniation. This procedure may offer safe and efficacious results, especially in the relatively limited indications for PELD.

The antibody atliximab attenuates collagen-induced arthritis by neutralizing AIMP1, an inflammatory cytokine that enhances osteoclastogenesis.

ARS-interacting multifunctional protein 1 (AIMP1) induces production of inflammatory cytokines from immune cells. Since osteoclastogenesis is promoted by positive regulation of inflammatory cytokines, whether AIMP1 could promote osteoclastogenesis was investigated. AIMP1 induced osteoclastogenesis and acted synergistically with RANKL to promote osteoclastogenesis. Down-regulation of CD23, an AIMP1 receptor, abolished AIMP1-mediated osteoclastogenesis. Enzyme-linked immunosorbent assays showed that the AIMP1 level was significantly higher in the peripheral blood (PB) and synovial fluid of rheumatoid arthritis patients than in normal PB. A monoclonal antibody (clone 15B3AF) that blocked the cytokine activity of AIMP1 inhibited the AIMP1-mediated production of inflammatory cytokines. Clone 15B3AF inhibited the AIMP1-mediated osteoclastogenesis in vitro. We then cloned the complementary determining regions of clone 15B3AF and generated a chimeric antibody (atliximab). In a collagen-induced arthritis mouse model (CIA), atliximab administration significantly attenuated disease severity and improved various histopathological parameters. Three-dimensional micro-computed tomography scanning confirmed that atliximab enhanced the joint structures in CIA mice. Furthermore, atliximab decreased the expression of inflammatory cytokines in the serum and inflamed joints of CIA mice. Taken together, our findings suggest that AIMP1 exacerbates RA by promoting inflammation and osteoclastogenesis and that atliximab could be developed as a therapeutic antibody to target inflammatory diseases, including RA.

Tauroursodeoxycholic acid, a bile acid, promotes blood vessel repair by recruiting vasculogenic progenitor cells.

Although serum bile acid concentrations are approximately 10 µM in healthy subjects, the crosstalk between the biliary system and vascular repair has never been investigated. In this study, tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34(+) hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34(+) /Sca1(+) progenitors in mice peripheral blood (PB), and CD34(+) , CD31(+) , and c-kit(+) progenitors in human PB. In addition, TUDCA increased differentiation of CD34(+) HSCs into EPC lineage cells via Akt activation. EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein via Akt activation. Interestingly, TUDCA induced integration of EPCs into human aortic endothelial cells (HAECs) by increasing adhesion molecule expression. In the mouse hind limb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1(+) /CD34(+) and Sca-1(+) /c-kit(+) progenitors into damaged tissue. In GFP(+) bone marrow-transplanted hind limb ischemia, TUDCA induced recruitment of GFP(+) /c-kit(+) progenitors to the ischemic area, resulting in an increased blood perfusion ratio. Histological analysis suggested that GFP(+) progenitors mobilized from bone marrow, integrated into blood vessels, and differentiated into VEGFR(+) cells. In addition, TUDCA decreased cellular senescence by reducing levels of p53, p21, and reactive oxygen species and increased nitric oxide. Transplantation of TUDCA-primed senescent EPCs in hind limb ischemia significantly improved blood vessel regeneration, as compared with senescent EPCs. Our results suggested that TUDCA promoted neovascularization by enhancing the mobilization of stem/progenitor cells from bone marrow, their differentiation into EPCs, and their integration with preexisting endothelial cells.

Radicular compression by intraspinal epidural gas bubble occurred in distant two levels after lumbar microdiscectomy.

The authors report a case of symptomatic epidural gas accumulation 2 weeks after the multi-level lumbar surgery, causing postoperative recurrent radiculopathy. The accumulation of epidural gas compressing the dural sac and nerve root was demonstrated by CT and MRI at the distant two levels, L3-4 and L5-S1, where vacuum in disc space was observed preoperatively and both laminectomy and discectomy had been done. However, postoperative air was not identified at L4-5 level where only laminectomy had been done in same surgical field, which suggested the relationship between postoperative epidural gas and the manipulation of disc structure. Conservative treatment and needle aspiration was performed, but not effective to relieve patient's symptoms. The patient underwent revision surgery to remove the gaseous cyst. Her leg pain was improved after the second operation.

ARS-interacting multi-functional protein 1 induces proliferation of human bone marrow-derived mesenchymal stem cells by accumulation of ß-catenin via fibroblast growth factor receptor 2-mediated activation of Akt.

ARS-Interacting Multi-functional Protein 1 (AIMP1) is a cytokine that is involved in the regulation of angiogenesis, immune activation, and fibroblast proliferation. In this study, fibroblast growth factor receptor 2 (FGFR2) was isolated as a binding partner of AIMP peptide (amino acids 6-46) in affinity purification using human bone marrow-derived mesenchymal stem cells (BMMSCs). AIMP1 peptide induced the proliferation of adult BMMSCs by activating Akt, inhibiting glycogen synthase kinase-3ß, and thereby increasing the level of ß-catenin. In addition, AIMP1 peptide induced the translocation of ß-catenin to the nucleus and increased the transcription of c-myc and cyclin D1 by activating the ß-catenin/T-cell factor (TCF) complex. By contrast, transfection of dominant negative TCF abolished the effect of AIMP1. The inhibition of Akt, using LY294002, abolished the accumulation and nuclear translocation of ß-catenin induced by AIMP1, leading to a decrease in c-myc and cyclin D1 expression, which decreased the proliferation of BMMSCs. An intraperitoneal injection of AIMP1 peptide into C57/BL6 mice increased the colony formation of fibroblast-like cells. Fluorescence activated cell sorting analysis showed that the colony-forming cells were CD29(+)/CD44(+)/CD90(+)/CD105(+)/CD34(-)/CD45(-), which is characteristic of MSCs. In addition, the fibroblast-like cells differentiated into adipocytes, chondrocytes, and osteocytes. Taken together, these data suggest that AIMP1 peptide promotes the proliferation of BMMSCs by activating the ß-catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in MSCs in peripheral blood.

A new paradigm for stem cell therapy: substance-P as a stem cell-stimulating agent.

Bone marrow is a reservoir for hematopoietic stem cells, endothelial precursor cells, and bone marrow stromal cells (also generally called mesenchymal stem cells), whose positive role in tissue repair is highly anticipated. In this report, we introduce a novel function of substance-P (SP), an 11-amino-acid peptide, as an injury-inducible messenger to mobilize bone marrow stem cells to the blood and finally to engage in tissue repair. This new drug may substitute for ex vivo cell culture of therapeutic cells by stimulating cell proliferation in the bone marrow in vivo and mobilizing those therapeutic cells to the patient's own blood stream. Again, the additional role of SP in mitigating inflammation-mediated tissue damage can further rationalize the clinical development of SP-peptide as a stem cell stimulant.

Surgical management and outcome of tethered cord syndrome in school-aged children, adolescents, and young adults.

OBJECTIVE: The adolescent presentation of tethered cord syndrome (TCS) is well-recognized, but continues to pose significant diagnostic and management controversies. The authors conducted a retrospective study of clinical outcomes after surgical intervention in 24 school-aged children, adolescents, and young adults with TCS. METHODS: All 83 patients with a lipomyelomeningocele (LMMC) underwent untethering surgery for caudal cord tethering between 1987 and 2007. The clinical charts and follow-up data were reviewed. Of these patients, 24 school-aged children, adolescents, and young adults with TCS were studied with respect to the clinical, radiologic, pathologic features, and surgical outcomes. RESULTS: Untethering procedures were performed in 24 patients (age range, 7-25 years) for TCS of various origins (lipoma, lipomyelomeningocele, and tight filum terminale). Specific circumstances involving additional tugging of the already tight conus, and direct trauma to the back precipitated the onset of symptom in 50% of the patients. Diffuse and non-dermatomal leg pain, often referred to the anorectal region, was the most common presenting symptom. Progressive sensorimotor deficits in the lower extremities, as well as bladder and bowel dysfunction, were also common findings, but progressive foot and spinal deformities were noted less frequently. The most common tethered lesions were intradural lipomas, thickened filum and fibrous band adhesions into the placode sac. The surgical outcome was gratifying in relation to pain and motor weakness, but disappointing with respect to resolution of bowel and bladder dysfunction. Of the 24 patients with TCS, pre-operative deficits improved after surgery in 14 (58.3%), remained stable in 8 (33.4%), and worsened in 2 (8.3%). CONCLUSION: The pathologic lesions of tethered cord syndrome in school-aged children, adolescents, and young adults, are mostly intradural lipomas and tight filum. It is suggested that the degree of cord traction results in neurologic dysfunction in late life due to abnormal tension, aggravated by trauma or repeated tugging of the conus during exercise. Early diagnosis and adequate surgical release might be the keys to the successful outcome in school-aged children, adolescents, and young adults with TCS.

Retro-odontoid pseudotumor in diffuse idiopathic skeletal hyperostosis.

STUDY DESIGN: A rare case of retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis is presented. OBJECTIVE: To discuss the pathomechanism of retro-odontoid pseudotumor in diffuse idiopathic skeletal hyperostosis. SUMMARY OF BACKGROUND DATA: Reports describing craniovertebral manifestations of diffuse idiopathic skeletal hyperostosis are quite rare. Only two cases of an atlantoaxial subluxation and one case of an odontoid fracture have been reported. Myelopathy resulting from retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis has not been reported previously. METHODS: A 74-year-old man presented with spastic tetraparesis caused by a retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis. Transoral removal of the extradural mass combined with a dorsal atlantoaxial fusion was performed using a titanium frame with sublaminar cable wiring. RESULTS: Yellowish amorphous material extruded from between the odontoid process and the arch of C1 when the anterior capsule had been incised. The retro-odontoid mass was very firmly attached to the hypertrophied ligaments. The mass therefore had to be sharply dissected away to expose the dura. The histologic appearance of the mass consisted of poorly cell-degenerated ligament, fibrocartilage, and fibrin. There was a focal proliferation of small vessels, but no significant inflammatory component and no evidence of neoplasia. The ligaments appeared fibrillated, disintegrated, and fragmented. After surgery, the patient's neurologic function improved. CONCLUSIONS: This is the first reported case of a retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis. The secondary transfer of mechanical stress to the atlantoaxial segment was presented as a pathomechanism underlying the formation of this retro-odontoid pseudotumor.