Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury.

The adult mammalian CNS has a limited capacity to regenerate after traumatic injury. In this study, a combinatorial strategy to promote axonal regeneration and functional recovery after spinal cord injury (SCI) was evaluated in adult rats. The rats were subjected to a complete transection in the thoracic spinal cord, and multichannel scaffolds seeded with activated Schwann cells (ASCs) and/or rat bone marrow-derived mesenchymal stem cells (MSCs) were acutely grafted into the 3-mm-wide transection gap. At 4 weeks post-transplantation and thereafter, the rats receiving scaffolds seeded with ASCs and MSCs exhibited significant recovery of nerve function as shown by the Basso, Beattie and Bresnahan (BBB) score and electrophysiological test results. Immunohistochemical analyses at 4 and 8 weeks after transplantation revealed that the implanted MSCs at the lesion/graft site survived and differentiated into neuron-like cells and co-localized with host neurons. Robust bundles of regenerated fibers were identified in the lesion/graft site in the ASC and MSC co-transplantation rats, and neurofilament 200 (NF) staining confirmed that these fibers were axons. Furthermore, myelin basic protein (MBP)-positive myelin sheaths were also identified at the lesion/graft site and confirmed via electron microscopy. In addition to expressing mature neuronal markers, sparse MSC-derived neuron-like cells expressed choline acetyltransferase (ChAT) at the injury site of the ASC and MSC co-transplantation rats. These findings suggest that co-transplantation of ASCs and MSCs in a multichannel polymer scaffold may represent a novel combinatorial strategy for the treatment of spinal cord injury.

Surgical treatment of severe multilevel circumferential compressive myelopathy of the cervical spine: is circumferential procedure necessary?

OBJECTIVE: To determine the necessity of circumferential decompression and fusion in patients with severe multilevel cervical spondylotic myelopathy with circumferential cord compression. METHODS: This prospective study involved 51 patients with severe multilevel circumferential cervical myelopathy underwent two-stage circumferential procedure between July 2008 and June 2010. VAS scores, satisfaction surveys and JOA scores and imaging studies were obtained. Twenty-three patients (45.1%) underwent two-stage surgery (group A); the other 28 patients (54.9%) were satisfied with the outcomes after first-stage surgery, and the second-stage surgery was avoided (group B). Age, sex and symptom duration did not differ between the groups. RESULTS: Patients were followed up for 3-5 years (mean, 42.5 months). In group A, VAS and JOA scores significantly improved from 63.3 and 7.9 to 38.3 and 10.4, respectively, at 3 months after the first-stage operation and 10.2 and 12.7, respectively, at 3 months after the second-stage operation. In group B, the VAS and JOA scores significantly improved from 62.7 and 7.9 to 31.1 and 11.2 respectively, at 3 months and 18.2 and 12.4, respectively at 6 months. Patient satisfaction rate significantly increased from 43.5% after the first-stage operation to 82.6% after the second-stage operation in group A. In group B, this rate was 89.3%. In group A, cervical spine lordosis increased from 12.8° preoperatively to 18.5° (p < .0001) and 19.1° (p > .05) at 3 months after the first-stage and second-stage operations, respectively. In group B, lordosis significantly increased from 12.5° preoperatively to 18.8° at 3 months. The total complication rate did not significantly differ from the rates after a single surgery (either anterior or posterior). CONCLUSION: Only 45.1% patients required surgery via both approaches. Therefore, a two-stage procedure is a rational choice and safe procedure. If outcomes are unsatisfactory after the first-stage operation, a second-stage operation can be performed.

An RCT study comparing the clinical and radiological outcomes with the use of PLIF or TLIF after instrumented reduction in adult isthmic spondylolisthesis.

OBJECTIVE: We prospectively compared posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) used in adult isthmic spondylolisthesis (IS) after surgical reduction with pedicle screws. METHODS: Between January 2009 and December 2010, 66 adult patients with single-level IS were randomly assigned to two groups treated using the PLIF technique (PLIF group, n = 34) and the TLIF technique (TLIF group, n = 32). Both groups were followed up for an average of 30.5 months (range 24-48 months). Clinical outcomes were assessed using the visual analog scale (VAS), Oswestry disability index (ODI) and Japanese orthopedic association (JOA) scores. Radiographic outcomes included percentage of vertebral slippage, focal lordosis and disk height. Clinical and radiographic outcomes were compared between the two groups. RESULTS: The average operative time and blood loss during surgery were significantly more in PLIF group than in TLIF group. Spondylolisthesis, disk height and focal lordosis were significantly improved postoperatively in both groups. There was no obvious difference in clinical outcomes, as assessed using the VAS, ODI and JOA scores, and radiographic outcomes. In PLIF group, there were two cases of neuropathic pain after surgery. CONCLUSIONS: After instrumented reduction of adult IS, either PLIF or TLIF can provide good clinical and radiological outcomes. With a single cage, TLIF was superior to PLIF in terms of surgical time and blood loss, but these differences may not be clinically relevant.

Single segment of posterior lumbar interbody fusion for adult isthmic spondylolisthesis: reduction or fusion in situ.

OBJECTIVE: We prospectively compared surgical reduction or fusion in situ with posterior lumbar interbody fusion (PLIF) for adult isthmic spondylolisthesis in terms of surgical invasiveness, clinical and radiographical outcomes, and complications. METHODS: From January 2006 to June 2008, 88 adult patients with isthmic spondylolisthesis who underwent surgical treatment in our unit were randomized to reduced group (group 1, n = 45) and in situ group (group 2, n = 43), and followed up for average 32.5 months (range 24-54 months). The clinical and radiographical outcomes were compared between the two groups. RESULTS: The average operative time and blood loss during surgery showed insignificant difference (p > 0.05) between two groups. The radiological outcomes were significantly better in group 1, but there was no significant difference between two groups of clinical outcomes, depicting as VAS, ODI, JOA and patients' satisfaction surveys. Incident rate of surgical complications was similar in two groups, but in group 1 the complication seemed more severe because of two patients with neurological symptoms. CONCLUSIONS: For the adult isthmic spondylolisthesis without degenerative disease in adjacent level, single segment of PLIF with pedicle screw fixation is an effective and safe surgical procedure regardless of whether additional reduction had been conducted or not. Better radiological outcome does not mean better clinical outcome.

Continuous irrigation and drainage for early postoperative deep wound infection after posterior instrumented spinal fusion.

STUDY DESIGN: A retrospective study of clinical cases. PURPOSE: To evaluate the efficacy of continuous irrigation and drainage for early postoperative deep wound infection after posterior instrumented spinal fusion. SUMMARY OF BACKGROUND DATA: Aggressive debridement and irrigation has been recommended to treat postoperative wound infections after instrumented spinal fusion. However, this method of management, indicating repeating visits to the operating room until the wound is clean enough for closure, often results in prolonged hospitalization, increased cost, and sometimes compromise of the desired outcome. We hypothesize that repeat visits to the operating room for debridements can be avoided by aggressive debridements and primary closure with continuous irrigation and drainage for postoperative wound infections. METHODS: From 2004 to 2009, 23 patients with early postoperative deep wound infections after spinal fusion with instrumentation were surgically treated with thorough debridement and primary closure with continuous irrigation and drainage. All patients were followed up for 30.6 months (range, 24-54 mo). RESULTS: The mean duration of irrigation was 12.0 days (range, 7-16 d). In 21 patients (91.3%), the wound healed after continuous irrigation. The removal of the instrumentation or cages was not required in any case. Spinal fusion was achieved in all cases, except 1, where the patient developed a pseudoarthrosis at the L4-L5 level after L4-S1 fusion. The mean ODI for these 23 patients improved significantly from 53.4±18.7 preoperatively to 18.3±11.2 at the final follow-up visit (P<0.001). The mean JOA scores increased significantly from 15.5±4.1 preoperatively to 24.3±3.8 at the final follow-up (P<0.001). CONCLUSIONS: Continuous irrigation and drainage is an effective and safe method for the treatment of early postoperative deep wound infection after posterior instrumented spinal fusion.

Transforaminal endoscopic lumbar discectomy with targeted puncture and foraminotomy for very highly migrated disc herniation: A technique note with case series.

Background: Transforaminal endoscopic lumbar discectomy (TELD) has been widely used for lumbar disc herniation. However, in some challenging cases such as very highly migrated disc herniation (VHMDH), traditional TELD is difficult to access the pathology. Methods: From January 2016 to December 2019, 63 patients with single-level VHMDH underwent TELD using targeted puncture and foraminotomy techniques were included. All patients were followed up for 26.5 months on average (range, 24-48 months). Operative time, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and surgical complications were evaluated. Results: The operative time was 40-120 min (56.8 on average). The length of hospitalization was 2.5 days (range, 2-4 d). VAS score decreased significantly from 5.5 ± 1.3 preoperatively to 1.9 ± 1.30 (p < 0.001) 1 day postoperatively, and to 0.9 ± 0.8 (p < 0.001) at the final follow-up. ODI score improved significantly from 23.5 ± 3.2 preoperatively to 13.4 ± 3.0 (p < 0.001) 1 day postoperatively; and 3.1 ± 1.2 (p < 0.001) at the final follow-up. According to the modified MacNab criteria, 40 patients (63.5%) showed excellent results, 20 patients (31.7%) were rated as good, 2 patients (3.2%) were rated as fine, and 1 patient (1.6%) was rated as bad at the final follow-up. No residual fragments, nerve root or cauda equina injury was shown in this series. One recurrent case was resolved by open surgery. Conclusions: With modified targeted puncture and foraminotomy techniques, VHMDH can be accessed safely and effectively, and satisfactory clinical outcomes can be obtained for these patients.

Percutaneous Transforaminal Endoscopic Debridement and Drainage with Accurate Pathogen Detection for Infectious Spondylitis of the Thoracolumbar and Lumbar Spine.

OBJECTIVE: In this study, we aimed to analyze the clinical outcomes of percutaneous transforaminal endoscopic debridement and drainage (PTEDD) with accurate pathogen detection for patients with infectious spondylitis of the thoracolumbar and lumbar spines. METHODS: From January 2017 to February 2019, a consecutive series of 43 patients with infectious spondylitis of the thoracolumbar and lumbar spine were surgically treated with PTEDD. Organism culture, next-generation DNA sequencing, and pathological examination of the sample extracted from the infectious site were performed for accurate microbiological diagnosis. All patients were followed up for 24-36 months. Clinical and radiological outcomes were analyzed preoperatively and postoperatively. RESULTS: Surgeries were completed successfully on all 43 patients under local infiltration anesthesia. Positive culture of the responsible organism was obtained in 33 cases (76.7%). Among the 43 patients who underwent next-generation DNA sequencing, 42 (97.7%) had positive results. Corresponding antibiotic medication was given based on the pathogen detection. The modified Macnab criteria were found to be excellent in 32 patients (74.4%) and good in 11 (25.6%). Postoperative magnetic resonance imaging showed that the abscess and infectious area were reduced significantly at 3 months and had disappeared or almost disappeared at the final follow-up. Spontaneous fusion was obtained in 30 patients (69.8%). No patients required revision or conversion to open debridement and reconstruction. CONCLUSIONS: For patients with infectious spondylitis of the thoracolumbar and lumbar spine, PTEDD is an effective and safe treatment. Next-generation DNA sequencing is a much more sensitive method for detecting the responsible organisms.

Noncontiguous anterior decompression and fusion for multilevel cervical spondylotic myelopathy: a prospective randomized control clinical study.

Anterior decompression and fusion is an established procedure in surgical treatment for multilevel cervical spondylotic myelopathy (MCSM). However, contiguous corpectomies and fusion (CCF) often induce postoperative complications such as nonunion, graft subsidence, and loss of lordotic alignment. As an alternative, noncontiguous corpectomies or one-level corpectomy plus adjacent-level discectomy with retention of an intervening body has been developed recently. In this study, we prospectively compared noncontiguous anterior decompression and fusion (NADF) and CCF for MCSM in terms of surgical invasiveness, clinical and radiographic outcomes, and complications. From January 2005 to June 2007, 105 patients with MCSM were randomized to NADF group (n = 55) and CCF group (n = 50), and followed up for average 31.5 months (range 24-48 months). Average operative time and blood loss decreased significantly in the NADF group as compared with those in the CCF group (p < 0.05 and <0.001, respectively). For VAS, within 3 months postoperatively, there was no significant difference between the two groups. But at 6 months after surgery and final follow-up, VAS improved significantly in NADF group than that in CCF group (p < 0.05). No significant difference of JOA score was observed between the two groups at every collection time. In NADF group, all 55 cases obtained fusion at 1 year after operation (average 5.1 months). In CCF group, 48 cases achieved fusion 1 year postoperatively, but the other 2 cases were performed posterior stabilization and achieved fusion 6 months later. The differences of cervical lordosis between two groups were insignificant at the same follow-up time. But the loss of lordosis and height of fusion segments in 6 months postoperatively and final follow-up were significantly more in CFF group than in NADF group (p < 0.001). Complications were similar in both groups. But in CCF group three cases needed reoperation, one case with extradural hematoma was immediately re-operated after anterior decompression and two cases mentioned above were performed posterior stabilization at 1 year postoperatively. In conclusion, in the patients with MCSM, without developmental stenosis and continuous or combined ossification of posterior longitudinal ligaments, NADF and CCF showed an identical effect of decompression. In terms of surgical time, blood loss, VAS, fusion rate and cervical alignment, NADF was superior compared with CCF.

Novel three-dimensional nerve tissue engineering scaffolds and its biocompatibility with Schwann cells.

OBJECTIVE: To develop a novel scaffolding method for the copolymers poly lactide-co-glycolide acid (PLGA) to construct a three-dimensional (3-D) scaffold and explore its biocompatibility through culturing Schwann cells (SCs) on it. METHODS: The 3-D scaffolds were made by means of melt spinning, extension and weaving. The queueing discipline of the micro-channels were observed under a scanning electronic microscope (SEM).The sizes of the micropores and the factors of porosity were also measured. Sciatic nerves were harvested from 3-day-old Sprague Dawley (SD) rats for culture of SCs. SCs were separated, purified, and then implanted on PLGA scaffolds, gelatin sponge and poly-L-lysine (PLL)-coated tissue culture polystyrene (TCPS) were used as biomaterial and cell-supportive controls, respectively. The effect of PLGA on the adherence, proliferation and apoptosis of SCs were examined in vitro in comparison with gelatin sponge and TCPS. RESULTS: The micro-channels arrayed in parallel manners, and the pore sizes of the channels were uniform. No significant difference was found in the activity of Schwann cells cultured on PLGA and those on TCPS (P larger than 0.05), and the DNA of PLGA scaffolds was not damaged. CONCLUSION: The 3-D scaffolds developed in this study have excellent structure and biocompatibility, which may be taken as a novel scaffold candidate for nerve-tissue engineering.

Region-Restrict Astrocytes Exhibit Heterogeneous Susceptibility to Neuronal Reprogramming.

The adult CNS has poor ability to replace degenerated neurons following injury or disease. Recently, direct reprogramming of astrocytes into induced neurons has been proposed as an innovative strategy toward CNS repair. As a cell population that shows high diversity on physiological properties and functions depending on their spatiotemporal distribution, however, whether the astrocyte heterogeneity affect neuronal reprogramming is not clear. Here, we show that astrocytes derived from cortex, cerebellum, and spinal cord exhibit biological heterogeneity and possess distinct susceptibility to transcription factor-induced neuronal reprogramming. The heterogeneous expression level of NOTCH1 signaling in the different CNS regions-derived astrocytes is shown to be responsible for the neuronal reprogramming diversity. Taken together, our findings demonstrate that region-restricted astrocytes reveal different intrinsic limitation of the response to neuronal reprogramming.

Percutaneous Vertebroplasty Versus Conservative Treatment in Aged Patients With Acute Osteoporotic Vertebral Compression Fractures: A Prospective Randomized Controlled Clinical Study.

STUDY DESIGN: A prospective randomized clinical trial. OBJECTIVE: In this study, we determine whether percutaneous vertebroplasty (PVP) offers extra benefits to aged patients with acute osteoporotic vertebral compression fractures (OVCFs) over conservative therapy (CV). SUMMARY OF BACKGROUND DATA: OVCFs are common in the aged population with osteoporosis. While the optimal treatment of aged patients with acute OVCFs remains controversial, PVP, a minimally invasive procedure, is a treatment option to be considered. METHODS: Patients aged at 70 years or above with acute OVCF and severe pain from minor or mild trauma were assigned randomly to PVP and CV groups. The primary outcome was pain relief as measured by VAS score in 1-year follow-up period. The second outcome was quality of life assessed with ODI and Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Patient satisfaction surveys were also recorded. RESULTS: A total of 135 patients were enrolled, and 107 (56 in PVP group; 51 in CV group) completed 1-year follow-up. In PVP group, the vertebroplasty procedure was performed at a mean of 8.4 ±â€Š4.6 days (range, 2-21 days) after onset. Vertebroplasty resulted in much greater pain relief than did conservative treatment at postoperative day 1 (P < 0.0001). At every time point of follow-up, pain relief and quality of life were significantly improved in PVP group than in CV group at 1 week, 1 month, 3 months, 6 months, and 1 year (all P < 0.0001). The final follow-up surveys indicated that patients in PVP group were significantly more satisfied with given treatment (P < 0.0001). In addition, lower rate of complications was observed in PVP group (P < 0.0001). CONCLUSION: In aged patients with acute OVCF and severe pain, early vertebroplasty yielded faster, better pain relief and improved functional outcomes, which were maintained for 1 year. Furthermore, it showed fewer complications than conservative treatment. LEVEL OF EVIDENCE: 2.

Posterior lumbar interbody fusion for aged patients with degenerative spondylolisthesis: is intentional surgical reduction essential?

BACKGROUND CONTEXT: Surgical reduction and posterior lumbar interbody fusion (PLIF) is commonly used to recover segmental imbalance in degenerative spondylolisthesis. However, whether intentional reduction of the slipped vertebra during PLIF is essential in aged patients with degenerative spondylolisthesis remains controversial. PURPOSE: We compared the outcomes of surgical reduction and fusion in situ among aged patients who underwent PLIF for degenerative spondylolisthesis. STUDY DESIGN: A prospective randomized clinical trial on the surgical treatment of degenerative spondylolisthesis patients aged older than 70 years. PATIENT SAMPLE: Between January 2006 and December 2009, 73 patients aged 70 years or older with single-level degenerative spondylolisthesis requiring surgical treatment were included in this study. OUTCOME MEASURES: Clinical outcomes were assessed using the visual analog scale, Oswestry Disability Index, and Japanese Orthopedic Association scores. Radiographic outcomes included percentage of vertebral slippage, focal lordosis, and disc height. METHODS: The 73 patients were randomly assigned to two groups treated using surgical reduction (Group A, n=36) and fusion in situ (Group B, n=37). Both groups were followed up for an average of 33.2 months (range, 24-54 months). The clinical and radiographic outcomes were compared between the two groups. RESULTS: Surgical complications were similar in the two groups. The average operative time and blood loss during surgery did not insignificantly differ (p>.05) between the two groups. Spondylolisthesis, disc height, and focal lordosis were significantly improved postoperatively in both groups. There was no obvious difference in clinical outcomes, as assessed using the visual analog scale, Oswestry Disability Index, and Japanese Orthopedic Association scores, although the radiographic outcomes were considerably better in Group A than in Group B. CONCLUSIONS: Posterior lumbar interbody fusion with pedicle screws fixation, with or without intraoperative reduction, provides good outcomes in the surgical treatment of aged patients with degenerative spondylolisthesis. Better radiological outcomes by intentional reduction do not necessarily indicate better clinical outcomes.

Anterior Z-plate and titanic mesh fixation for acute burst thoracolumbar fracture.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate the clinical outcome, effectiveness, and security of the surgical management of acute thoracolumbar burst fracture with corpectomy, titanic mesh autograft, and Z-plate fixation by anterior approach. SUMMARY OF BACKGROUND DATA: Many surgical methods were adopted to treat acute burst thoracolumbar fracture. But the optimal surgical management remains controversial. METHODS: A retrospective review of a consecutive series of 48 patients with thoracolumbar burst fracture treated with anterior corpectomy, titanic mesh autograft, and Z-plate internal fixation was carried out. Preoperative clinical and radiographic data of all cases were originally collected. Surgical indications were motor neurologic deficit and thoracolumbar column instability. Twenty-two patients (45.8%) with acute thoracolumbar burst fractures presented with a neurologic deficit. The postoperative recovery of neural function, restoration of anterior cortex collapse, kyphotic angle, and spinal canal compromise were observed. RESULTS: The preoperative kyphotic angle was improved to a mean of 5.6°, radiographic height restored to 95.8% of the adjacent normal levels, and canal compromise was 0%. None of the patients had neurologic deterioration. Mean follow-up time was 32.4 months (range, 24-47 months). All 22 patients with neurologic deficit demonstrated at least one Frankel grade improvement on final observation, with 16 (73%) patients had accomplished complete neurologic recovery. Forty-six (96%) patients reported minimal or no pain at final follow-up observation, and 40 (83%) patients who had been working before injury returned to original work. CONCLUSION: The authors considered spinal cord decompression with anterior corpectomy and stability reconstruction with titanic mesh autograft and Z-plate fixation at same time in one incision as an effective technique for unstable thoracolumbar burst fracture with and without neurologic deficit.

Anterior debridement and bone grafting of spinal tuberculosis with one-stage instrumentation anteriorly or posteriorly.

Between 2000 and 2004, 40 cases (average age 38, range 16-65 years) of spinal tuberculosis were treated with anterior debridement and iliac bone graft with one-stage anterior or posterior instrumentation in our unit. All patients received at least 2 weeks of regular antituberculous chemotherapy before surgery. We followed up all patients for 12-48 months (mean 22 months). Local symptoms of all patients were relieved significantly 1-3 weeks postoperatively; 23 of 25 cases (92%) with neurogical deficit had excellent or good clinical results. Erythrocyte sedimentation rates (ESR) returned from 51 mm/h to 32 mm/h (average) two weeks postoperatively. Kyphosis degrees were corrected by a mean of 16 degrees . Fusion rate of the grafting bone was 72.5% one year postoperatively and 90% two years postoperatively. Severe complications did not occur. We therefore believe that patients undergoing anterior debridement and iliac bone grafting with one-stage anterior or posterior instrumentation achieve satisfactory clinical and radiographic outcomes.

The treatment for multilevel noncontiguous spinal fractures.

We report the outcome of 30 patients with multilevel noncontiguous spinal fractures treated between 2000 and 2005. Ten cases were treated conservatively (group A), eight cases were operated on at only one level (group B), and 12 cases were treated surgically at both levels (group C). All cases were followed up for 14-60 months (mean 32 months). Initial mobilisation with a wheelchair or crutches in group A was 9.2 +/- 1.1 weeks, which was significantly longer than groups B and C with 6.8+/-0.7 weeks and 3.1 +/- 0.4 weeks, respectively. Operative time and blood loss in group C were significantly more than group B. The neurological deficit improved in six cases in group A (60%), six in group B (75%) and eight in group C (80%). Correction of kyphotic deformity was significantly superior in groups C and B at the operated level, and increasing deformity occurred in groups A and B at the non-operated level. From the results we believe that three treatment strategies were suitable for multilevel noncontiguous spinal fractures, and individualised treatment should be used in these patients. In the patients treated surgically, the clinical and radiographic outcomes are much better.