Remarkable efficacy of temozolomide for relapsed spinal myxopapillary ependymoma with multiple recurrence and cerebrospinal dissemination: a case report and literature review.

PURPOSE: Myxopapillary ependymomas are intradural tumors which grow from the terminal filum of the spinal cord. Although they are classified as WHO grade I, they sometimes cause cerebrospinal fluid dissemination or local recurrence. In this report, we describe a case in that temozolomide (TMZ) showed remarkable efficacy on a recurrent spinal myxopapillary ependymoma. CASE REPORT: A 26-year-old female underwent resection of an intradural myxopapillary ependymoma at L5 initially. Although an en bloc total resection, including the capsule, could be achieved, she needed two additional tumor resection surgeries with postoperative radiotherapy at L4 and at L3 (2 and 6 years after the initial surgery, respectively). Moreover, 4 years after the initial surgery, a disseminated metastatic tumor occurred at T11/12 and local radiotherapy was not effective. After the third surgery, an aggressive adjuvant therapy was necessary because there was a high risk of another recurrence. Therefore, TMZ was administered for 1 year. After 6 months of TMZ treatment, remarkably, the disseminated metastatic tumor at T11/12 had disappeared completely. Presently, 6 years after finishing the TMZ treatment, the follow-up MRI has shown no recurrence in the brain and whole spine. CONCLUSIONS: TMZ is usually used in the treatment of glioblastoma and, recently, it has been reported to be effective for the lower grade spinal gliomas including spinal intramedullary ependymomas. However, for myxopapillary ependymomas, there has been no report that TMZ is effective. According to our results, TMZ could be one of the possible candidates for adjuvant therapy in multiple recurrent myxopapillary ependymomas.

Microscope and Fiberscope-assisted Subarachnoid-Subarachnoid (S-S) Bypass: A Novel Surgical Technique to Reestablish Cerebrospinal Fluid Flow in Treating Dorsal Spinal Arachnoid Webs, Diagnosed by Cine-MRI.

A "dorsal spinal arachnoid web" is the thickened arachnoid band on the surface of the spinal cord which disturbs the cerebrospinal fluid (CSF) flow, known as a rare cause of thoracic myelopathy. The ideal treatment is controversial because of the risk of readhesion after simple resection of the web. A subarachnoid-subarachnoid bypass is a method to reestablish CSF flow through a silicon tube between the cranial and caudal subarachnoid space. This method is reported to be useful for traumatic syringomyelia, adhesive arachnoiditis, etc. We applied this technique for arachnoid webs with the assistance of a microscope and fiberscope. After a dura incision, the thickened arachnoid web can be seen fluttering within the CSF flow inside the arachnoid space, which partitions the subarachnoid space into cranial and caudal parts. After opening the subarachnoid space and resection of the web under a microscope, the fiberscope is inserted toward the cranial and caudal directions to check for the presence of another arachnoid web. If another web is found, it is penetrated using a guiding wire. Then, a silicone tube is inserted into the cranial and caudal normal subarachnoid space. In this paper, we would like to introduce this technique.

The impact of hypertension on the occurrence of postoperative spinal epidural hematoma following single level microscopic posterior lumbar decompression surgery in a single institute.

PURPOSE: Postoperative spinal epidural hematoma (PSEH) is one of the most hazardous complications after spine surgery. A recent study has reported that a ≥50 mmHg increase in systolic blood pressure after extubation was a significant risk factor for symptomatic PSEH. In this paper, the impact of hypertension on PSEH occurrence was investigated. METHODS: Among a total of 2468 patients who underwent single level microscopic posterior decompression surgery for lumbar spinal stenosis in a single institute, 15 (0.6%) received evacuation surgery for PSEH. Those 15 patients were investigated statistically compared with a randomly selected control group (n = 46) using the Mann-Whitney U test and multiple logistic regression analysis. RESULTS: The univariate analysis showed that there were no significant differences in age, gender, BMI, pre-operative anti-coagulant usage, intraoperative blood loss, operation time, and the rate of patients who received pre-operative hypertension treatment. However, there were significant differences in the rate of patients who showed high blood pressure at admission (66.7 vs 6.5%) and >50 mmHg increases in blood pressure after extubation (53.3 vs 17.4%) in the univariate analysis. Moreover, postoperatively, there was a statistical difference in the amount of post-operative drainage. Multiple logistic regression analysis showed that high blood pressures at admission and poor postoperative drainage were the essential risk factors. CONCLUSIONS: Our results demonstrate that the pre-operative high blood pressure value was the most essential risk factor for PSEH, although there was no difference in the preoperative hypertension treatment. Consequently, management of pre-operative blood pressure and post-operative drainage will be crucial for preventing PSEH.

Facet Preserving Technique by En Bloc Flavectomy in Microscopic Posterior Decompression Surgery for Lumbar Spinal Stenosis: Semicircumferential Decompression (SCD).

Posterior decompression surgery which enlarges the spinal canal in cases with lumbar spinal stenosis is the most fundamental technique in spine surgery, but controversy still remains for the exact technique. Because nerve roots run under the ventral side on the superior articular process (SAP), achieving both facet joint preservation and nerve root decompression is problematic. In conventional laminotomies or laminectomies, medial facetectomies are performed to decompress the nerve root, but it is ideal to preserve the facet joints completely for preserving joint stability. We handle this problem with an original decompression technique, called "semicircumferential decompression." The main features of this procedure are an en bloc flavectomy and total preservation of facet joints. The procedure is performed under the microscope with a midline approach. The flavum is detached from the ventral surface of the SAP using a currete without disturbing the SAP. The facet joints are preserved completely. The advantage of an en bloc flavectomy is that we can remove the flavum attachment to the ventral surface of SAP totally without a medial facetectomy. Since 1991, we have performed this technique in more than 5000 cases. In this paper, we will explain the tips, pitfalls, and advantages of this technique.

Extraordinary positional cervical spinal cord compression in extension position as a rare cause of postoperative progressive myelopathy after cervical posterior laminoplasty detected using the extension/flexion positional CT myelography: one case after laminectomy following failure of a single-door laminoplasty/one case after double-door laminoplasty without interlaminar spacers.

PURPOSE: Posterior cervical laminectomies and laminoplasties are common treatments for cervical spondylotic myelopathy. However, recent studies demonstrated that positional spinal cord compression occurred after cervical laminectomies and caused postoperative progressive myelopathy. Although there were no such reports after laminoplasties, we report two cases in which symptomatic extraordinary positional spinal cord compression occurred after laminoplasties in this paper. METHODS: This study included two patients who showed progressive myelopathy: one case after a laminectomy following failure of a single-door laminoplasty and one case after a double-door laminoplasty without interlaminar spacers. RESULTS: The MRIs showed mild cord compression in the neutral position in both cases. However, the patients could not extend their necks, because it triggered severe neck pain and numbness. Therefore, the positional CT myelography (CTM) was taken in the flexion and extension positions, and it showed severe spinal cord compression only in the extension position. Posterior instrumented fusions were performed for both patients, which improved their symptoms. CONCLUSIONS: This paper demonstrates that postoperative positional spinal cord compression during neck extension caused a progressive myelopathy even after laminoplasty. When myelopathy symptoms worsen after laminoplasties, we recommend positional CTM/MRI evaluation, even though there is no apparent cord compression in the neutral MRI.

C2 spondylotic radiculopathy: the nerve root impingement mechanism investigated by para-sagittal CT/MRI, dynamic rotational CT, intraoperative microscopic findings, and treated by microscopic posterior foraminotomy.

PURPOSE: C2 radiculopathy is known to cause occipito-cervical pain, but their pathology is unclear because of its rarity and unique anatomy. In this paper, we investigated the mechanism of C2 radiculopathy that underwent microscopic cervical foraminotomies (MCF). METHODS: Three cases with C2 radiculopathy treated by MCF were investigated retrospectively. The mean follow-up period was 24 months. Pre-operative symptoms, imaging studies including para-sagittal CT and MRI, rotational dynamic CT, and intraoperative findings were investigated. RESULTS: There were 1 male and 2 females. The age of patients were ranged from 50 to 79 years. All cases had intractable occipito-cervical pain elicited by the cervical rotation. C2 nerve root block was temporally effective. There was unilateral spondylosis in symptomatic side without obvious atlatoaxial instability. Para-sagittal MRI and CT showed severe foraminal stenosis at C1-C2 due to the bony spur derived from the lateral atlanto-axial joints. In one case, dynamic rotational CT showed that the symptomatic foramen became narrower on rotational position. MCF was performed in all cases, and the C2 nerve root was impinged between the inferior edge of the C1 posterior arch and bony spur from the C1-C2 joint. After surgery, occipito-cervical pain disappeared. CONCLUSION: This study demonstrated that mechanical impingement of the C2 nerve root is one of the causes of occipito-cervical pain and it was successfully treated by microscopic resection of the inferior edge of the C1 posterior arch. Para-sagittal CT and MRI, rotational dynamic CT, and nerve root block were effective for diagnosis.

The Efficacy of Intraoperative Neurophysiological Monitoring Using Transcranial Electrically Stimulated Muscle-evoked Potentials (TcE-MsEPs) for Predicting Postoperative Segmental Upper Extremity Motor Paresis After Cervical Laminoplasty.

STUDY DESIGN: Prospective study. OBJECTIVE: To investigate the efficacy of transcranial electrically stimulated muscle-evoked potentials (TcE-MsEPs) for predicting postoperative segmental upper extremity palsy following cervical laminoplasty. SUMMARY OF BACKGROUND DATA: Postoperative segmental upper extremity palsy, especially in the deltoid and biceps (so-called C5 palsy), is the most common complication following cervical laminoplasty. Some papers have reported that postoperative C5 palsy cannot be predicted by TcE-MsEPs, although others have reported that it can be predicted. METHODS: This study included 160 consecutive cases that underwent open-door laminoplasty, and TcE-MsEP monitoring was performed in the biceps brachii, triceps brachii, abductor digiti minimi, tibialis anterior, and abductor hallucis. A >50% decrease in the wave amplitude was defined as an alarm point. According to the monitoring alarm, interventions were performed, which include steroid administration, foraminotomies, etc. RESULTS: Postoperative deltoid and biceps palsy occurred in 5 cases. Among the 155 cases without segmental upper extremity palsy, there were no monitoring alarms. Among the 5 deltoid and biceps palsy cases, 3 had significant wave amplitude decreases in the biceps during surgery, and palsy occurred when the patients awoke from anesthesia (acute type). In the other 2 cases in which the palsy occurred 2 days after the operation (delayed type), there were no significant wave decreases. In all of the cases, the palsy was completely resolved within 6 months. DISCUSSION: The majority of C5 palsies have been reported to occur several days after surgery, but some of them have been reported to occur immediately after surgery. Our results demonstrated that TcE-MsEPs can predict the acute type, whereas the delayed type cannot be predicted. CONCLUSIONS: A >50% wave amplitude decrease in the biceps is useful to predict acute-type segmental upper extremity palsy. Further examination about the interventions for monitoring alarm will be essential for preventing palsy.

Clinical results of microsurgical bilateral decompression via unilateral approach for lumbar canal stenosis with multiple-level involvement.

OBJECT: Microsurgical decompression of the lumbar spine is a beneficial approach for selected patients of lumbar spinal stenosis (LSS). The purpose of this prospective study was to describe the clinical results of surgical treatment for microsurgical bilateral decompression via unilateral approach on patients with LSS with multiple-level involvement. MATERIALS AND METHODS: Seventy-three consecutive patients who had microsurgical bilateral decompression via unilateral approach of more than two spinal levels were included in this study. Seventy-seven patients who had surgery at a single level over the same time periods were compared as a single-level LSS group. RESULTS: The preoperative Japanese Orthopaedic Association scores averaged 11.7 points, and the postoperative scores averaged 21.2 points with an average recovery rate (RR) of 56% in the multiple-level LSS group. There was no significant difference in the RR between the groups. There were no major complications related to the surgery in the both groups. CONCLUSION: Microsurgical bilateral decompression via unilateral approach was a useful and safe operative procedure for LSS patients. Sufficient clinical results that were comparable to single-level LSS patients were obtained even in the patients with multiple-level LSS, if the patient were correctly selected and the microsurgical decompression surgery were carefully performed.

Long-term clinical results of microsurgical transdural discectomy with laminoplasty: follow-up results over 10 years.

OBJECT: In this retrospective analysis the authors describe the long-term clinical results of microsurgical transdural discectomy with laminoplasty (MTDL) in patients with cervical disc herniation (CDH). METHODS: Thirty patients (21 males, 9 females; mean age at surgery 55 years) with CDH had surgical treatments consisting of MTDL between 1990 and 1998. All patients demonstrated signs or symptoms of cervical myelopathy and/or radiculomyelopathy. Clinical outcomes were evaluated by the Japanese Orthopaedic Association (JOA) scoring system and by recovery rate (RR). The degenerative grades of the intervertebral discs were also evaluated based on preoperative, postoperative, and final follow-up MR images. The average follow-up period was 14.1 years (range 10-22 years). RESULTS: Twenty (67%) of the 30 patients completed the follow-up in this study. The preoperative JOA scores in these patients averaged 11.8, and the postoperative scores at the final follow-up averaged 15.5 (average RR 69.6%). None of these patients required reoperation after MTDL. Although disc degeneration progressed during the follow-up period, there were no cases of clinical deterioration, recurrence of disc herniation, or postoperative kyphotic deformity. CONCLUSIONS: Sufficient clinical results were obtained after the MTDL for a long-term follow-up period exceeding 10 years. The MTDL may be an option for an alternative procedure if the patients are correctly selected and the procedure is safely performed.

Surgical treatment of high-grade dysplastic spondylolisthesis using intraoperative electrophysiological monitoring: report of two cases and review of the literature.

Treatment of high-grade dysplastic spondylolisthesis in adolescents remains challenging. Surgical treatment of spondylolisthesis has been recommended in adolescents with pain refractory to conservative treatment, slippage progression, or severe slippage on presentation. Controversy exists as to the optimal surgical approach for high-grade spondylolisthesis. Moreover, some authors reported the incidence of L5 root palsy during the reduction procedure. We performed 2 cases of surgical treatment using intraoperative electrophysiological monitoring for patients with high-grade dysplastic spondylolisthesis in adolescence. Each patient received treatment consisting of decompression of nerve with surgical microscope, reduction, and circumferential fusion with transpedicular and monosegmental fixation surgery with intraoperative neurological monitoring with transcranial electric motor evoked potentials and continuous spontaneous electromyography recording. Intraoperative monitoring did not show any abnormal changes. The patients got well after surgery, and they showed no postoperative motor paralysis of the extremities. A postoperative radiogram showed reduction of the slippage, and computed tomogram showed bone union between L5 and S1 vertebral body. This report describes 2 cases of surgical treatment using intraoperative electrophysiological monitoring with transcranial electric motor evoked potentials and continuous spontaneous electromyography for patients with high-grade dysplastic spondylolisthesis in adolescence. We successfully perform the surgery without any neurological deficit using intraoperative electrophysiological monitoring.

Medium-term clinical results of microsurgical lumbar flavectomy that preserves facet joints in cases of lumbar degenerative spondylolisthesis: comparison of bilateral laminotomy with bilateral decompression by a unilateral approach.

STUDY DESIGN: A retrospective study of medium-term results. OBJECTIVE: To describe a technique for posterior decompression using microsurgical lumbar flavectomy (MLF) without facetectomy, which is based on the anatomic features of the ligamentum flavum, and to examine the clinical outcomes of patients with lumbar spinal spondylolisthesis with lower extremity symptoms rather than low back pain, who underwent this procedure by 2 different approaches. SUMMARY OF BACKGROUND DATA: Posterior decompression with fusion has been the optimal and standard operative treatment for lumbar degenerative spondylolisthesis. Alternatively, minimally invasive procedures have been used for the treatment of lumbar degenerative spondylolisthesis with favorable outcomes. METHODS: A bilateral laminotomy (BL group) was performed on 44 consecutive patients, and bilateral decompression by a unilateral approach (BDU group) was performed on 23 consecutive patients. The mean follow-up period was 7.0 years. The Japanese Orthopaedic Association score and recovery rate were obtained, and radiographic assessment was performed using plain radiograms on the lateral view while standing in flexion, neutral, and extension postures before surgery and at the final follow-up. RESULTS: The Japanese Orthopaedic Association score at the final follow-up was improved in the BL and BDU groups, compared with that before MLF. The mean recovery rate was 72.4% and 68.4%, respectively. The mean % slip increased at the final follow-up, compared with that before surgery in both groups, except for the % slip in the extension posture in the BDU group. However, there was no significant difference in the dynamic % slip in the flexion-extension posture between before surgery and at the final follow-up. CONCLUSIONS: Clinical and radiologic parameters were not significantly different between the 2 groups. This technique of MLF using either approach did not increase the dynamic % slip and showed favorable medium-term clinical results in cases of lumbar degenerative spondylolisthesis.

Use of prone position magnetic resonance imaging for detecting the terminal filum in patients with occult tethered cord syndrome.

OBJECT: The pathophysiology of occult tethered cord syndrome (OTCS) with no anatomical evidence of a caudally shifted conus and a normal terminal filum is hard to understand. Therefore, the diagnosis of OTCS is often difficult. The authors hypothesized that the posterior displacement of the terminal filum may become prominent in patients with OCTS who are in a prone position if filum inelasticity exists, and they investigated prone-position MRI findings. METHODS: Fourteen patients with OTCS and 12 control individuals were examined using T2-weighted axial MRI with the patients in a prone position on a flat table. On each axial view, the distance between the posterior and anterior ends of the subarachnoid space (A), the distance between the posterior end of the subarachnoid space and the terminal filum (B), the distance between the posterior end of the subarachnoid space and the dorsal-most nerve among the cauda equina (C), and the distance between the posterior end of the subarachnoid space and the ventral-most nerve (D) were measured. The location ratios of the terminal filum, the dorsal-most nerve, and the ventral-most nerve were calculated by the ratio of A to B (defined as TF = B/A), A to C (defined as DN = C/A), and A to D (defined as VN = D/A), respectively. Patients underwent sectioning of the terminal filum with the aid of a surgical microscope. The low-back pain Japanese Orthopaedic Association score was obtained before surgery and at the final follow-up visit. RESULTS: On prone-position axial MRI, the terminal filum was separated from the cauda equina and was shifted caudally to posterior in the subarachnoid space in all patients with OTCS. The locations of the caudal cauda equina shifted to ventral in the subarachnoid space. The TF values in the OTCS group were significantly lower than those in the control group at the L3-4 (p = 0.023), L-4 (p = 0.030), L4-5 (p = 0.002), and L-5 (p < 0.001) levels. In contrast, the DN values in the OTCS group were significantly higher than those of the control group at the L-2 (p = 0.003), L2-3 (p = 0.002), L-3 (p < 0.001), L3-4 (p < 0.001), L-4 (p = 0.007), L4-5 (p = 0.003), and S-1 (p = 0.014) levels, and the VN values in the OTCS group were also significantly higher than those of the control group at the L2-3 (p = 0.022), L-3 (p = 0.027), L3-4 (p = 0.002), L-4 (p = 0.011), L4-5 (p = 0.019), and L5-S1 (p = 0.040) levels. Sections were collected during surgery for histological evaluation, and a decreased elasticity within the terminal filum was suggested. Improvements in the Japanese Orthopaedic Association score were observed at the final follow-up in all patients. CONCLUSIONS: The authors' new method of using the prone position for MRI shows that the terminal filum is located significantly posterior and the cauda equina is located anterior in patients with OTCS, suggesting a difference in elasticity between the terminal filum and cauda equina.

Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice.

PURPOSE: Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress. METHODS: Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9-C10 caudal discs in 12-week-old Bach 1-/- and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1-/- and wild-type mice. RESULTS: In the age-related model, there were no significant differences between Bach 1-/- and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1-/- mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1-/- mice. CONCLUSIONS: Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

Investigation of segmental motor paralysis after cervical laminoplasty using intraoperative spinal cord monitoring with transcranial electric motor-evoked potentials.

STUDY DESIGN: A retrospective study of segmental motor paralysis after cervical laminoplasty for cervical myelopathy. OBJECTIVE: The objective of this study was to use transcranial electric motor-evoked potentials during cervical laminoplasty, to monitor and investigate the intraoperative electrophysiologic change in patients with cervical myelopathy, who subsequently develop postoperative segmental motor paralysis potentials. SUMMARY OF BACKGROUND DATA: There have been several reports about segmental motor paralysis after cervical laminoplasty for patients with cervical myelopathy. However, the pathogenesis of segmental motor paralysis of C5 myotome, so-called C5 palsy, remains unclear. METHODS: The cases of 184 consecutive patients who underwent cervical laminoplasty were analyzed to clarify the incidence of postoperative segmental motor paralysis and to monitor intraoperative change. Postoperative C5 palsy was defined as development of postoperative motor palsy of the deltoid and biceps muscles in the upper extremity by at least 1 grade in the manual muscle test without sensory disturbance or impairment of the lower extremities. All patients underwent cervical laminoplasty under intraoperative spinal cord monitoring with transcranial electric motor-evoked potentials. The evoked potentials were recorded over the deltoid, biceps, and triceps muscles in the bilateral upper extremities. RESULTS: Postoperative C5 palsy developed in 6 patients (3.3%, 5 males and 1 female) but there were no abnormal changes monitored. The incidence of C5 palsy involved 4 of 124 (3.2%) cervical spondylotic myelopathy patients, 2 of 31 (6.5%) patients with cervical ossification of the posterior longitudinal ligament. No patients with cervical disc herniation or cervical spondylotic amyotrophy developed C5 palsy. CONCLUSIONS: There were no abnormal findings on transcranial electric motor-evoked potential monitoring even in those patients who developed postoperative C5 palsy. These results indicate that the development of postoperative segmental motor paralysis after cervical laminoplasty occurs even if there are no abnormal findings during intraoperative monitoring.

Magnetic field-based delivery of human CD133⁺ cells promotes functional recovery after rat spinal cord injury.

STUDY DESIGN: Experimental animal study of spinal cord injury (SCI), using a cell delivery system. OBJECTIVE: To investigate the therapeutic effects of transplantation of peripheral blood-derived CD133 cells, with a magnetic delivery system in a rat SCI model. SUMMARY OF BACKGROUND DATA: There are no reports on intrathecal transplantation of peripheral blood-derived CD133 cells, with a magnetic cell delivery system to treat SCI. METHODS: Magnetically isolated peripheral blood-derived CD133 cells were used as the cell source. Contusion SCI was induced by an Infinite Horizon impactor in athymic nude rats. CD133 cells or phosphate-buffered saline was administered via a lumbar puncture immediately after SCI, and a magnetic field was applied to rats for 30 minutes. Animals were analyzed at specific times after transplantation by several methods to examine cell tracking, functional recovery, and histological angiogenesis and neurogenesis. RESULTS: A combination of cell transplantation and application of a magnetic field at the site of injury caused significant functional recovery. Transplantation of the cells alone in the absence of the magnetic field showed no effect beyond that observed in control rats. CONCLUSION: The combination of intrathecal transplantation of CD133 cells and application of a magnetic field at the site of injury is a possible therapeutic strategy to treat rat SCI and may therefore find application in clinical settings.

MicroRNA-223 expression in neutrophils in the early phase of secondary damage after spinal cord injury.

MicroRNA (miR)s are short non-coding RNAs that suppress the translation of target genes, and play an important role in gene regulation. Despite this prominence, there are few reports that refer to the expression of miRs after spinal cord injury (SCI). Previously, we reported on miR-223 expression after SCI in mice. The purpose of this study is to reveal the distribution of miR-223 and identify the cells that express miR-223 in the injured spinal cord. Quantitative polymerase chain reaction analysis revealed high expression of miR-223 at 12h after SCI. Double staining of in situ hybridization and immunohistochemistry showed that the signals of miR-223 merged with Gr-1 positive neutrophils. Our data indicate that miR-223 might regulate neutrophils in the early phase after SCI.

MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients.

BACKGROUND: Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients. METHODS: IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium. RESULTS: Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells. CONCLUSION: These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.

The effects of combining chondroitinase ABC and NEP1-40 on the corticospinal axon growth in organotypic co-cultures.

The area surrounding the injured spinal cord is a non-permissive milieu for axonal growth due to the inhibitory factors, especially chondroitin sulfate proteoglycan (CSPG) and Nogo. Recent studies have reported that chondroitinase ABC (ChABC) or Nogo-66(1-40) antagonist peptide (NEP1-40) promote axonal growth after spinal cord injury. But no study has addressed the effects on spinal cord injury of combining ChABC and NEP1-40. Previously, we described an organotypic co-culture system using the brain cortex and spinal cord from neonatal rats. In this study, we examined whether the combination of ChABC and NEP1-40 creates an action that promotes corticospinal axon growth in organotypic co-cultures. Organotypic co-cultures of brain and spinal cord were prepared from rats, and ChABC or NEP1-40 was delivered to them. To examine the effects of this combination these two drugs were applied together. We counted the number of labeled axons with DiI and assessed the immunoreactivity of CSPG and Nogo. Axonal growth was enhanced by infusing ChABC or NEP1-40 compared with that in the control group, whereas synergistic effects of combined administration of ChABC and NEP1-40 on axonal growth were not observed. There is a possibility that ChABC and NEP1-40 affect the same intracellular pathways and have no synergistic influence on axonal growth.

Quantitative assessment of myelopathy patients using motor evoked potentials produced by transcranial magnetic stimulation.

Motor evoked potentials (MEPs) study using transcranial magnetic stimulation (TMS) may give a functional assessment of corticospinal conduction. But there are no large studies on MEPs using TMS in myelopathy patients. The purpose of this study is to confirm the usefulness of MEPs for the assessment of the myelopathy and to investigate the use of MEPs using TMS as a screening tool for myelopathy. We measured the MEPs of 831 patients with symptoms and signs suggestive of myelopathy using TMS. The MEPs from the abductor digiti minimi (ADM) and abductor hallucis (AH) muscles were evoked by transcranial magnetic brain stimulation. Central motor conduction time (CMCT) is calculated by subtracting the peripheral conduction time from the MEP latency. Later, 349 patients had surgery for myelopathy (operative group) and 482 patients were treated conservatively (nonoperative group). CMCTs in the operative group and nonoperative group were assessed. MEPs were prolonged in 711 patients (86%) and CMCTs were prolonged in 493 patients (59%) compared with the control patients. CMCTs from the ADM and AH in the operative group were significantly more prolonged than that in the nonoperative group. All patients in the operative group showed prolongation of MEPs or CMCTs or multiphase of the MEP wave. MEP abnormalities are useful for an electrophysiological evaluation of myelopathy patients. Moreover, MEPs may be effective parameters in spinal pathology for deciding the operative treatment.