Keisuke Masuda

Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats

OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.

Lymphocyte Count at 4 Days Postoperatively and CRP Level at 7 Days Postoperatively: Reliable and Useful Markers for Surgical Site Infection Following Instrumented Spinal Fusion.

Study Design. A case-control study. Objective. The objective of this study is to identify biochemical markers for surgical site infection (SSI) in posterior instrumented spinal fusion that are not affected by operative circumstances and to determine diagnostic cutoffs for these markers. Summary of Background Data. Numerous biochemical markers may be used for early detection of SSI; however, these markers may be affected by operative factors. Methods. We reviewed data on C-reactive protein level and total white blood cell count and differential count before instrumented spinal fusion and at 1, 4, and 7 days postoperatively. The 141 patients in our sample were divided into an SSI group (patients who developed deep SSI) and a no-SSI group. We determined which markers differed significantly between groups and identified those not affected by operative circumstances (operating time, intraoperative blood loss, number of fusion segments) in the no-SSI group. Then, we determined diagnostic cutoffs for these unaffected markers by using receiver-operating characteristic curves. Results. Three markers were selected: lymphocyte count at 4 days postoperatively (cutoff 1180/&mgr;L, sensitivity 90.9%, specificity 65.4%, area under the curve [AUC] 0.80), lymphocyte count of at 7 days postoperatively (cutoff <1090/&mgr;L, sensitivity 63.6%, specificity 78.5%, AUC 0.77), and C-reactive protein level at 7 days postoperatively (cutoff >4.4 mg/dL, sensitivity 90.9%, specificity 89.2%, AUC 0.95). Conclusion. Lymphocyte count at 4 and 7 days postoperatively and C-reactive protein level at 7 days postoperatively are reliable markers for SSI following instrumented spinal fusion. Lymphocyte count at 4 days should be useful for screening because of its high sensitivity and because it can be measured early. C-reactive protein level at 7 days should be useful for definitive diagnosis given its high sensitivity and specificity and large AUC. Level of Evidence: 4

Comparison of neutrophil and lymphocyte at 1 and 4 days postoperatively: reliable and early detection markers for surgical site infection following instrumented spinal fusion

Introduction To identify the temporal comparison of biochemical markers for early detection of surgical site infection (SSI) following instrumented spinal fusion that are not affected by operative factors. Methods We reviewed data on C-reactive protein level and total white blood cell count and differential count before instrumented spinal fusion and at 1, 4, and 7 days postoperatively. The 141 patients in our sample were divided into an SSI group (patients who developed deep SSI) and a non-SSI group. We investigated the peak or nadir value day and identified those not affected by operative circumstances (operating time, intraoperative blood loss, and number of fusion segments) in the non-SSI group. If there was a significant difference between the peak or nadir value day and the next survey day, we considered the temporal comparison between these unaffected markers as an indicator of SSI and examined the usefulness of these indicators by calculating sensitivity and specificity. Furthermore, we investigated the usefulness of the combination of these markers (if even each one marker was recognized, we considered it positive). Results Four biochemical markers of SSI were selected: neutrophil percentage at postoperative day 4 more than day 1 (sensitivity 36%, specificity 95%), neutrophil count at postoperative day 4 more than day 1 (sensitivity 46%, specificity 93%), lymphocyte percentage at postoperative day 4 less than day 1 (sensitivity 36%, specificity 90%), and lymphocyte count at postoperative day 4 less than day 1 (sensitivity 36%, specificity 90%). The combination of these markers showed sensitivity 100%, specificity 80%, respectively. Conclusions Four markers are reliable indicators for early detection of SSI following spinal instrumented fusion because they are not affected by operative factor. The combination of each indicator had both high sensitivity and specificity. Therefore, it is reliable and much useful for early detection of SSI.

Biceps-Related Physical Findings Are Useful to Prevent Misdiagnosis of Cervical Spondylotic Amyotrophy as a Rotator Cuff Tear

Study Design Case–control study. Purpose The aim of the present study was to identify physical findings useful for differentiating between cervical spondylotic amyotrophy (CSA) and rotator cuff tears to prevent the misdiagnosis of CSA as a rotator cuff tear. Overview of Literature CSA and rotator cuff tears are often confused among patients presenting with difficulty in shoulder elevation. Methods Twenty-five patients with CSA and 27 with rotator cuff tears were enrolled. We included five physical findings specific to CSA that were observed in both CSA and rotator cuff tear patients. The findings were as follows: (1) weakness of the deltoid muscle, (2) weakness of the biceps muscle, (3) atrophy of the deltoid muscle, (4) atrophy of the biceps muscle, and (5) swallow-tail sign (assessment of the posterior fibers of the deltoid). Results Among 25 CSA patients, 10 (40.0%) were misdiagnosed with a rotator cuff tear on initial diagnosis. The sensitivity and specificity of each physical finding were as follows: (1) deltoid weakness (sensitivity, 92.0%; specificity, 55.6%), (2) biceps weakness (sensitivity, 80.0%; specificity, 100%), (3) deltoid atrophy (sensitivity, 96.0%; specificity, 77.8%), (4) biceps atrophy (sensitivity, 88.8%; specificity, 92.6%), and (5) swallow-tail sign (sensitivity, 56.0%; specificity, 74.1%). There were statistically significant differences in each physical finding. Conclusions CSA is likely to be misdiagnosed as a rotator cuff tear; however, weakness and atrophy of the biceps are useful findings for differentiating between CSA and rotator cuff tears to prevent misdiagnosis.

Post-tetanic transcranial motor evoked potentials augment the amplitude of compound muscle action potentials recorded from innervated and non-innervated muscles

BACKGROUND CONTEXT Transcranial electrical stimulation used to produce motor evoked potentials (TES-MEPs) and subsequent compound muscle action potential (CMAP) recording is widely used to monitor motor function during surgery when there is risk of damaging the spinal cord. Nonetheless, some muscles do not produce CMAP amplitudes sufficient for intraoperative monitoring. PURPOSE This study aimed to investigate the utility of tetanic stimulation at single and multiple peripheral nerve sites for augmenting CMAP amplitudes recorded from innervated and non-innervated muscles. STUDY DESIGN/SETTING A retrospective study was carried out. PATIENT SAMPLE The study sample comprised 24 patients with cervical myelopathy who underwent decompression surgery at our department between November 2005 and March 2007. OUTCOME MEASURES Compound muscle action potential amplitude was a physiological measure. METHODS We used two patterns of tetanic peripheral nerve stimulation for each patient. The first pattern consisted of tetanic stimulation of the left tibial nerve only (Pattern 1), and the second pattern consisted of tetanic stimulation of the bilateral median nerves and left tibial nerve (Pattern 2). RESULTS Compound muscle action potential amplitudes from all muscles were augmented by both tetanic stimulation patterns compared with conventional TES-MEP recording; however, Pattern 2 elicited the greatest augmentation of CMAP amplitudes, especially for CMAPs recorded from the bilateral abductor pollicis brevis muscles. CONCLUSIONS Although tetanic stimulation of a single peripheral nerve increased CMAP amplitudes recorded from both innervated and non-innervated muscles, CMAP amplitudes were best augmented when the corresponding nerve received tetanic stimulation. Additionally, tetanic stimulation of multiple nerves rather than a single nerve appears to provide better augmentation.

Increased Segmental Range of Motion is Correlated with Spondylolisthesis in the Cervical Spine after Laminoplasty.

Study Design. A retrospective study. Objective. The aim of this study was to determine the incidence of increased segmental range of motion (ROM) after laminoplasty and to clarify whether increased ROM is associated with spondylolisthesis. Finally, we explored the effect of increased segmental ROM on clinical results. Summary of Background Data. Cervical laminoplasty for cervical spondylotic myelopathy causes reduced ROM, possibly due to the unintended contracture of the facet joint or a bony union. Although it is rarely studied, ROM may also increase following laminoplasty. Thus far, there are no reports describing the correlation between increased segmental ROM and segmental spondylolisthesis after laminoplasty. Methods. We evaluated 187 segments from 39 cervical spondylotic myelopathy patients who underwent bilateral open door laminoplasty from C2 to C7. The segmental ROM and spondylolisthesis were measured using dynamic radiographs that were obtained preoperatively and 2 years postoperatively. The Japanese Orthopedic Association (JOA) score was used for clinical evaluation. To compare the clinical results, we compared the cases with increased ROM in at least one segment with the remaining cases. Results. Increased segmental ROM (i.e., ≥5° increase) was observed in 25 of 187 segments (13.4%) from 14 cases. There was a strong correlation between increased ROM and spondylolisthesis. A high preoperative disc height was associated with increased segmental ROM 2 years postoperation. Regardless of the correlation with spondylolisthesis, there was no statistically significant correlation between increased segmental ROM and JOA score. Conclusion. The decrease in segmental ROM after laminoplasty was not uniform. Approximately 13.4% of all segments showed increased ROM. The preoperative disc height might influence the risk for increased segmental ROM. Furthermore, increased ROM was correlated with spondylolisthesis in the segment, though it was not correlated with clinical results. Level of Evidence: 4

Preliminary algorithm for differential diagnosis between spinal meningioma and schwannoma using plain magnetic resonance imaging

BACKGROUND Preoperative differential diagnosis between spinal meningioma and schwannoma is critical due to the characteristic differences of the surgical treatments. Thus, we aimed to develop an algorithm for the differential diagnosis of these two lesions based on plain MRI findings. METHODS We retrospectively reviewed plain MR images from patients who had undergone surgical treatment for meningiomas and schwannomas in our hospital between 2002 and 2016. Seven findings characteristic of meningioma or schwannoma were considered: (a) low or equal signal intensity on T2-weighted images, (b) obtuse angle from the dura mater, (c) anterior location in the spinal canal, (d) cystic degeneration, (e) lumbar occurrence, (f) oval or round shape, and (g) dumbbell type. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of each MRI finding, following which the algorithm was developed using decision tree analysis. Finally, we examined the usefulness of the algorithm for differential diagnosis between the two lesions. RESULTS Twenty four patients with meningiomas and 56 with schwannomas were enrolled. The sensitivity, specificity, PPV, NPV, and accuracy of each finding were as follows: (a) [58%, 100%, 100%, 85%, 88%], (b) [67%, 89%, 73%, 86%, 83%], (c) [29%, 88%, 50%, 74%, 70%], (d) [30%, 96%, 94%, 37%, 50%], (e) [43%, 96%, 96%, 42%, 59%], (f) [33%, 88%, 73%, 57%, 60%], and (g) [25%, 96%, 93%, 35%, 46%]. Significant differences were observed with regard to (a), (b), (d), (e), and (g). The algorithm was developed using these five findings, all of which exhibited high specificity and reliability. Accuracy of the algorithm was 91.3%. CONCLUSIONS Our results indicated that plain MRI findings can be used to differentiate between spinal meningiomas and schwannomas. Furthermore, our novel algorithm exhibited high accuracy, suggesting that this algorithm may aid in the differential diagnosis of these two lesions.

Lymphopenia and Elevated Blood C-Reactive Protein Levels at Four Days Postoperatively Are Useful Markers for Early Detection of Surgical Site Infection Following Posterior Lumbar Instrumentation Surgery

Study Design Case-control study. Purpose To identify the characteristics of candidate indexes for early detection of surgical site infection (SSI). Overview of Literature SSI is a serious complication of spinal instrumentation surgery. Early diagnosis and treatment are crucial for the welfare of the patient postoperation. Methods We retrospectively reviewed laboratory data of patients who underwent posterior lumbar instrumentation surgery for degenerative spine disease. The sensitivity and specificity of six laboratory markers for early detection of SSI were calculated: greater elevation of the white blood cell count at day 7 than at day 4 postoperatively, greater elevation of the C-reactive protein (CRP) level at day 7 than at day 4 postoperatively, a CRP level of >10 mg/dL at 4 days postoperatively, neutrophil percentage of >75% at 4 days postoperatively, a lymphocyte percentage of <10% at 4 days postoperatively, and a lymphocyte count of <1,000/µL at 4 days postoperatively. Statistical analysis was via Fishers exact test and a p-value of <0.05 was considered significant. Results In total, 85 patients were enrolled. Of these, five patients developed deep SSI. The sensitivity and specificity of each index were as follows: index 1, 20.0% and 77.5%; index 2, 20.0% and 83.8%; index 3, 40.0% and 97.5%; index 4, 40.0% and 86.3%; index 5, 0% and 96.3%; and index 6, 80.0% and 80.0%. A significant difference was noted for indexes 3 and 6. Conclusions A CRP level of >10 mg/dL at 4 days postoperatively would be useful for definitive diagnosis of SSI, and a lymphocyte count of <1,000/µL at 4 days postoperatively would be a useful screening test for SSI. Although laboratory markers for early detection of SSI have been frequently reported, we believe that it is important to understand the characteristics of each index for a precise diagnosis.

Lymphopenia at 4 Days Postoperatively Is the Most Significant Laboratory Marker for Early Detection of Surgical Site Infection Following Posterior Lumbar Instrumentation Surgery

Study Design Case control study. Purpose To identify the most significant laboratory marker for early detection of surgical site infection (SSI) using multiple logistic regression analysis. Overview of Literature SSI is a serious complication of spinal instrumentation surgery. Early diagnosis and treatment are crucial. Methods We retrospectively reviewed the laboratory data of patients who underwent posterior lumbar instrumentation surgery for degenerative spinal disease from January 2003 to December 2014. Six laboratory markers for early SSI detection were considered: renewed elevation of the white blood cell count, higher at 7 than 4 days postoperatively; renewed elevation of the C-reactive protein (CRP) level, higher at 7 than 4 days postoperatively; CRP level of >10 mg/dL at 4 days postoperatively; neutrophil percentage of >75% at 4 days postoperatively; lymphocyte percentage of <10% at 4 days postoperatively; and lymphocyte count of <1,000/µL at 4 days postoperatively. Results Ninety patients were enrolled; five developed deep SSI. Multivariate regression analysis showed that a lymphocyte count of <1,000/µL at 4 days postoperatively was the sole significant independent laboratory marker for early detection of SSI (p=0.037; odds ratio, 11.9; 95% confidence interval, 1.2–122.7). Conclusions A lymphocyte count of <1,000/µL at 4 days postoperatively is the most significant laboratory marker for early detection of SSI.