Ryoji Tauchi

Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

Intraoperative, full-rotation, three-dimensional image (O-arm)–based navigation system for cervical pedicle screw insertion

OBJECT The aim of this study was to retrospectively evaluate the reliability and accuracy of cervical pedicle screw (CPS) placement using an intraoperative, full-rotation, 3D image (O-arm)-based navigation system and to assess the advantages and disadvantages of the system. METHODS The study involved 21 consecutive patients undergoing posterior stabilization surgery of the cervical spine between April and December 2009. The patients, in whom 108 CPSs had been inserted, underwent screw placement based on intraoperative 3D imaging and navigation using the O-arm system. Cervical pedicle screw positions were classified into 4 grades, according to pedicle-wall perforations, by using postoperative CT. RESULTS Of the 108 CPSs, 96 (88.9%) were classified as Grade 0 (no perforation), 9 (8.3%) as Grade 1 (perforations < 2 mm, CPS exposed, and < 50% of screw diameter outside the pedicle), and 3 (2.8%) as Grade 2 (perforations between ≥ 2 and < 4 mm, CPS breached the pedicle wall, and > 50% of screw diameter outside the pedicle). No screw was classified as Grade 3 (perforation > 4 mm, complete perforation). No neurovascular complications occurred because of CPS placement. CONCLUSIONS The O-arm offers high-resolution 2D or 3D images, facilitates accurate and safe CPS insertion with high-quality navigation, and provides other substantial benefits for cervical spinal instrumentation. Even with current optimized technology, however, CPS perforation cannot be completely prevented, with 8.3% instances of minor violations, which do not cause significant complications, and 2.8% instances of major pedicle violations, which may cause catastrophic complications. Therefore, a combination of intraoperative 3D image-based navigation with other techniques may result in more accurate CPS placement.

Bone union rate with autologous iliac bone versus local bone graft in posterior lumbar interbody fusion.

Study Design. A retrospective clinical study with a long-term follow-up in a single facility. Objective. The purpose of this study is to compare bone union rate between autologous iliac crest bone graft and local bone graft in patients treated by posterior lumbar interbody fusion (PLIF) using carbon cage for single-level interbody fusion. Summary of Background Data. Recently, a number of authors have reported on local bone grafting using bone that is obtained from laminectomy, and have indicated that the achieved fusion rate is similar to that of autologous iliac bone grafting. However, there is no report comparing the fusion rates between autologous iliac bone and local bone graft with a detailed follow-up of fusion progression. Methods. The subjects were 101 patients whose course could be observed for at least 2 years. The diagnosis was lumbar spinal canal stenosis in 14 patients, herniated lumbar disc in 19 patients, and degenerative spondylolisthesis in 68 patients. Single interbody PLIF was performed using iliac bone graft in 54 patients and local bone graft in 47 patients. Existence of pseudarthrosis on X-P (anteroposterior and lateral view) was investigated during the same follow-up period. Results. No significant differences were found in operation time and blood loss. Significant differences were also not observed in fusion grade at any follow-up period or in fusion progression between the 2 groups. Donor site pain continued for more than 3 months in 6 cases (11%). The final fusion rate was 94.5% versus 95.8%. Conclusion. Fusion results from the local bone group and the autologous iliac bone group were nearly identical. Furthermore, fusion progression was nearly identical. Complications at donor sites were seen in 17% of the cases. From the aforementioned results, it was concluded that local bone graft is as beneficial as autologous iliac bone graft for PLIF at a single level.

Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury

Chondroitin sulfate (CS) proteoglycans are strong inhibitors of structural rearrangement after injuries of the adult CNS. In addition to CS chains, keratan sulfate (KS) chains are also covalently attached to some proteoglycans. CS and KS sometimes share the same core protein, but exist as independent sugar chains. However, the biological significance of KS remains elusive. Here, we addressed the question of whether KS is involved in plasticity after spinal cord injury. Keratanase II (K-II) specifically degraded KS, i.e., not CS, in vivo. This enzyme digestion promoted the recovery of motor and sensory function after spinal cord injury in rats. Consistent with this, axonal regeneration/sprouting was enhanced in K-II-treated rats. K-II and the CS-degrading enzyme chondroitinase ABC exerted comparable effects in vivo and in vitro. However, these two enzymes worked neither additively nor synergistically. These data and further in vitro studies involving artificial proteoglycans (KS/CS-albumin) and heat-denatured or reduced/alkylated proteoglycans suggested that all three components of the proteoglycan moiety, i.e., the core protein, CS chains, and KS chains, were required for the inhibitory activity of proteoglycans. We conclude that KS is essential for, and has an impact comparable to that of CS on, postinjury plasticity. Our study also established that KS and CS are independent requirements for the proteoglycan-mediated inhibition of axonal regeneration/sprouting.

Adjacent Segment Disease After Posterior Lumbar Interbody Fusion: Based on Cases With a Minimum of 10 Years of Follow-up.

Study Design. Retrospective case-controlled study. Objective. To investigate the incidence of adjacent segment degeneration (ASD) and the associated risk factors during a period of at least 10 years after posterior lumbar interbody fusion (PLIF). Summary of Background Data. ASD is a problematic sequelae after spinal fusion surgery. Few long-term follow-up studies have investigated ASD after PLIF; thus, magnetic resonance imaging (MRI) data available for the evaluation of postoperative changes associated with ASD are limited. Method. One hundred one patients were retrospectively enrolled. The minimum follow-up was 10 years after surgery. Preoperative and postoperative (2, 5, and 10 yr after surgery) Radiographs and MRI images were evaluated. Disc height, vertebral slip, and intervertebral angle were examined on radiographical images. Disc degeneration and spinal stenosis on MRI images were evaluated. Risk factors for developing early-onset radiographical ASD were evaluated using a multivariate logistic regression analysis. Result. The degenerative changes in disc height, vertebral slip, and intervertebral angle on radiographs 10 years after surgery were found in 12, 36, and 17 cases, respectively, at the cranial-adjacent level and in 3, 6, and 11 cases, respectively, at the caudal-adjacent level. Increased disc degeneration and spinal stenosis worsening were observed in 62 and 68 cases, respectively, at the cranial-adjacent level and in 25 and 12 cases, respectively, at the caudal-adjacent level on MRI 10 years after surgery. Ten patients (9.9%) required reoperation, and 80% of revision surgeries were performed more than 5 years after the initial surgery. High pelvic incidence was a risk factor for developing early-onset radiographical ASD. Conclusion. The majority of the reoperations for ASD were performed more than 5 years after the initial lumbar fusion surgery, although the progression of radiographical ASD began in the early postoperative period. A high degree of pelvic incidence was a risk factor for developing early-onset radiographical ASD. Obtaining appropriate lumbar lordosis in PLIF is important for preventing ASD. Level of Evidence: 4

The cutoff amplitude of transcranial motor evoked potentials for transient postoperative motor deficits in intramedullary spinal cord tumor surgery.

Study Design. Retrospective clinical study of intraoperative transcranial motor evoked potential (TcMEP) amplitudes and postoperative motor deficits (PMDs). Objective. To determine the quantifiable cutoff amplitude of TcMEP for predicting transient PMDs in intramedullary spinal cord tumor (IMSCT) surgery. Summary of Background Data. The “presence or absence” criterion is reliable and widely used the alarm criterion for preventing permanent PMDs in IMSCT surgery. However, we wanted to prevent PMDs even if it is transient. The cutoff amplitude for transient PMDs should be identified. Methods. We conducted a retrospective study to identify the cutoff amplitude for predicting transient PMDs in IMSCT surgery. Thirty-seven patients were included in the study. We examined intraoperative electrophysiological changes and perioperative motor status in these patients. Receiver operating characteristic analyses were performed to identify the cutoff amplitudes for predicting transient PMDs in IMSCT surgery. The incidence of PMDs and cutoff TcMEP amplitude in cervical and thoracic lesions were compared. Results. Thirteen cases demonstrated transient PMDs. Among 280 monitorable muscles in 37 cases, 51 muscles in 13 patients showed PMDs. Through receiver operating characteristic analysis, the relative and the absolute cutoff amplitudes at the intraoperative point of deterioration were identified to be 12% residual of baseline amplitude and 3.2 &mgr;V, respectively. Sensitivity/specificity for those cutoff points are 86%/74% and 88%/78%, respectively. The incidence of PMD was significantly higher, and the cutoff amplitude was lower in the thoracic lesions than in the cervical lesions. Conclusion. We determined the cutoff TcMEP amplitude for predicting transient PMDs in IMSCT surgery. The cutoff amplitude for the cervical lesions was higher than that for the thoracic lesions. The results suggest the need for setting different alarm criteria in different level of spine. Level of Evidence: 3

Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats

Hyaluronan is a component of the extracellular matrix of the central nervous system, and forms perineuronal nets around neurons. It has been recently reported that the hyaluronan-degrading enzyme hyaluronidase promotes lateral mobility of AMPA-type glutamate receptors and enhances synaptic plasticity. However, the biological significance of hyaluronan-degrading products (oligosaccharides) has not been studied in depth. Here we investigated the effects of hyaluronan oligosaccharides on motor function recovery after spinal cord injury in rats. The disaccharide HA2 and especially the tetrasaccharide HA4, significantly improved motor function, unlike the case with oligosaccharides composed of 6-12 saccharides. Consistent with this finding, HA4 treatment enhanced axonal regeneration/sprouting, as assessed by corticospinal tract tracer fiber counts. HA4 treatment also significantly suppressed accumulation of Iba-1-positive cells in a lesion two weeks after injury. In vitro experiments demonstrated that NMDA-induced neuronal cell death was partly blocked by HA4, but not by other oligosaccharides, whereas proteoglycan-mediated inhibition of neurite outgrowth was not affected by treatment with any oligosaccharide examined. Taken together, the present results revealed that due in part to its neuroprotective activity, HA4 promotes motor function recovery after spinal cord injury.

The cutoff amplitude of transcranial motor-evoked potentials for predicting postoperative motor deficits in thoracic spine surgery.

Study Design. Prospective clinical study of intraoperative transcranial motor-evoked potentials (TcMEP) amplitudes and postoperative motor deficits. Objective. To determine the cutoff amplitude during intraoperative TcMEP monitoring for predicting postoperative motor deficits after thoracic spine surgery. Summary of Background Data. Several alarm points when monitoring with TcMEP have been advocated, but there have been no reports on an actual cutoff amplitude of TcMEP for predicting the occurrence of postoperative motor deficits. Methods. Among 80 consecutive surgical cases, 28 had a deterioration in TcMEP amplitude in at least 1 monitored muscle during surgery. We examined intraoperative electrophysiological changes and postoperative motor deficits in 270 monitorable muscles in those 28 patients. Through receiver operating characteristic curve analysis, we identified the cutoff amplitudes at the intraoperative point of deterioration and at the end of surgery for predicting postoperative motor deficits in both relative and absolute values. Results. The relative and the absolute cutoff amplitudes of TcMEP at the intraoperative point of deterioration and at the end of thoracic spine surgery were 12% of control amplitude and 1.9 &mgr;V and 25% of control amplitude and 3.6 &mgr;V, respectively. Sensitivity/specificity for those cutoff points are 88%/64%, 69%/83%, 90%/64%, and 70%/82%, respectively. Conclusion. We determined the cutoff amplitude for predicting postoperative motor deficits in thoracic spine surgery. The results may help establish the alarm criteria for thoracic spine surgery.

ADAMTS-13 is produced by glial cells and upregulated after spinal cord injury

ADAMTS-13, a member of the family of disintegrins and metalloproteinases with thrombospondin motifs, is produced primarily in the liver, particularly by hepatic stellate cells. This metalloproteinase cleaves von Willebrand factor multimers and thereby regulates blood coagulation. Here, we investigated the expression of ADAMTS-13 in the central nervous system. ADAMTS-13 mRNA was expressed in cultured astrocytes and microglia but not in neurons. The protein production of ADAMTS-13 was also detected in these cultured glial cells. Furthermore, we found that the expression of ADAMTS-13 was significantly increased in the rat spinal cord after injury. Supporting the in vivo data, ADAMTS-13 protein was detected in GFAP- and CD11b-positive glial cells in injured spinal cord. Consistent with this, the proteolytic activity of ADAMTS-13 was increased after spinal cord injury. Our data suggest that ADAMTS-13 may have a critical role in the central nervous system, particularly after neuronal injuries.

A new criterion for the alarm point for compound muscle action potentials.

OBJECT The purpose of this study was to review the present criteria for the compound muscle action potential (CMAP) alert and for safe spinal surgery. METHODS The authors conducted a retrospective study of 295 patients in whom spinal cord monitoring had been performed during spinal surgery. The waveforms observed during spinal surgery were divided into the following 4 grades: Grade 0, normal; Grade 1, amplitude decrease of 50% or more and latency delay of 10% or more; Grade 2, multiphase pattern; and Grade 3, loss of amplitude. Waveform grading, its relationship with postoperative motor deficit, and CMAP sensitivity and specificity were analyzed. Whenever any wave abnormality occurred, the surgeon was notified and the surgical procedures were temporarily suspended. If no improvements were seen, the surgery was terminated. RESULTS Compound muscle action potential wave changes occurred in 38.6% of cases. With Grade 1 or 2 changes, no paresis was detected. Postoperative motor deficits were seen in 8 patients, all with Grade 3 waveform changes. Among the 287 patients without postoperative motor deficits, CMAP changes were not seen in 181, with a specificity of 63%. The false-positive rate was 37% (106 of 287). However, when a Grade 2 change was set as the alarm point, sensitivity was 100% and specificity was 79.4%. The false-positive rate was 20% (59 of 295). CONCLUSIONS Neither the Grade 1 nor the Grade 2 groups included patients who demonstrated a motor deficit. All pareses occurred in cases showing a Grade 3 change. Therefore, the authors propose a Grade 2 change (multiphasic waveform) as a new alarm point. With the application of this criterion, the false-positive rate can be reduced to 20%.