Treatment of CHO cells with Taxol and reversine improves micronucleation and microcell-mediated chromosome transfer efficiency.

Microcell-mediated chromosome transfer is an attractive technique for transferring chromosomes from donor cells to recipient cells and has enabled the generation of cell lines and humanized animal models that contain megabase-sized gene(s). However, improvements in chromosomal transfer efficiency are still needed to accelerate the production of these cells and animals. The chromosomal transfer protocol consists of micronucleation, microcell formation, and fusion of donor cells with recipient cells. We found that the combination of Taxol (paclitaxel) and reversine rather than the conventional reagent colcemid resulted in highly efficient micronucleation and substantially improved chromosomal transfer efficiency from Chinese hamster ovary donor cells to HT1080 and NIH3T3 recipient cells by up to 18.3- and 4.9-fold, respectively. Furthermore, chromosome transfer efficiency to human induced pluripotent stem cells, which rarely occurred with colcemid, was also clearly improved after Taxol and reversine treatment. These results might be related to Taxol increasing the number of spindle poles, leading to multinucleation and delaying mitosis, and reversine inducing mitotic slippage and decreasing the duration of mitosis. Here, we demonstrated that an alternative optimized protocol improved chromosome transfer efficiency into various cell lines. These data advance chromosomal engineering technology and the use of human artificial chromosomes in genetic and regenerative medical research.

Characterization of human anti-EpCAM antibodies for developing an antibody-drug conjugate.

We previously generated fully human antibody-producing TC-mAb mice for obtaining potential therapeutic monoclonal antibodies (mAbs). In this study, we investigated 377 clones of fully human mAbs against a tumor antigen, epithelial cell adhesion molecule (EpCAM), to determine their antigen binding properties. We revealed that a wide variety of mAbs against EpCAM can be obtained from TC-mAb mice by the combination of epitope mapping analysis of mAbs to EpCAM and native conformational recognition analysis. Analysis of 72 mAbs reacting with the native form of EpCAM indicated that the EpCL region (amino acids 24-80) is more antigenic than the EpRE region (81-265), consistent with numerous previous studies. To evaluate the potential of mAbs against antibody-drug conjugates, mAbs were directly labeled with DM1, a maytansine derivative, using an affinity peptide-based chemical conjugation (CCAP) method. The cytotoxicity of the conjugates against a human colon cancer cell line could be clearly detected with high-affinity as well as low-affinity mAbs by the CCAP method, suggesting the advantage of this method. Thus, this study demonstrated that TC-mAb mice can provide a wide variety of antibodies and revealed an effective way of identifying candidates for fully human ADC therapeutics.

Influence of MDR1 gene polymorphism (2677G>T) on expression and function of P-glycoprotein at the blood-brain barrier: utilizing novel P-glycoprotein humanized mice with mutation.

P-glycoprotein, the encoded product of the MDR1 / ABCB1 gene in humans, is expressed in numerous tissues including brain capillary endothelial cells and restricts the distribution of xenobiotics into the brain as an efflux pump. Although a large number of single nucleotide polymorphisms in the MDR1 gene have been identified, the influence of the nonsynonymous 2677G>T/A single nucleotide polymorphism on P-glycoprotein at the blood-brain barrier has remained unclear. In the present study, we developed a novel P-glycoprotein humanized mouse line carrying the 2677G>T mutation by utilizing a mouse artificial chromosome vector constructed by genetic engineering technology and we evaluated the influence of 2677G>T on the expression and function of P-glycoprotein at the blood-brain barrier in vivo . The results of this study showed that the introduction of the 2677G>T mutation does not alter the expression levels of P-glycoprotein protein in the brain capillary fraction. On the other hand, the brain penetration of verapamil, a representative substrate of P-glycoprotein, was increased by the introduction of the 2677G>T mutation. These results suggested that the 2677G>T single nucleotide polymorphism may attenuate the function of P-glycoprotein, resulting in increased brain penetration of P-glycoprotein substrates, without altering the expression levels of P-glycoprotein protein in the blood-brain barrier. This mutant mouse line is a useful model for elucidating the influence of an MDR1 gene single nucleotide polymorphism on the expression and function of P-glycoprotein at the blood-brain barrier.

Efficient human-like antibody repertoire and hybridoma production in trans-chromosomic mice carrying megabase-sized human immunoglobulin loci.

Trans-chromosomic (Tc) mice carrying mini-chromosomes with megabase-sized human immunoglobulin (Ig) loci have contributed to the development of fully human therapeutic monoclonal antibodies, but mitotic instability of human mini-chromosomes in mice may limit the efficiency of hybridoma production. Here, we establish human antibody-producing Tc mice (TC-mAb mice) that stably maintain a mouse-derived, engineered chromosome containing the entire human Ig heavy and kappa chain loci in a mouse Ig-knockout background. Comprehensive, high-throughput DNA sequencing shows that the human Ig repertoire, including variable gene usage, is well recapitulated in TC-mAb mice. Despite slightly altered B cell development and a delayed immune response, TC-mAb mice have more subsets of antigen-specific plasmablast and plasma cells than wild-type mice, leading to efficient hybridoma production. Our results thus suggest that TC-mAb mice offer a valuable platform for obtaining fully human therapeutic antibodies, and a useful model for elucidating the regulation of human Ig repertoire formation.

Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice.

Mammalian artificial chromosomes derived from native chromosomes have been applied to biomedical research and development by generating cell sources and transchromosomic (Tc) animals. Human artificial chromosome (HAC) is a precedent chromosomal vector which achieved generation of valuable humanized animal models for fully human antibody production and human pharmacokinetics. While humanized Tc animals created by HAC vector have attained significant contributions, there was a potential issue to be addressed regarding stability in mouse tissues, especially highly proliferating hematopoietic cells. Mouse artificial chromosome (MAC) vectors derived from native mouse chromosome 11 demonstrated improved stability, and they were utilized for humanized Tc mouse production as a standard vector. In mouse, however, stability of MAC vector derived from native mouse chromosome other than mouse chromosome 11 remains to be evaluated. To clarify the potential of mouse centromeres in the additional chromosomes, we constructed a new MAC vector from native mouse chromosome 10 to evaluate the stability in Tc mice. The new MAC vector was transmitted through germline and stably maintained in the mouse tissues without any apparent abnormalities. Through this study, the potential of additional mouse centromere was demonstrated for Tc mouse production, and new MAC is expected to be used for various applications.

Transchromosomic technology for genomically humanized animals.

"Genomically" humanized animals are invaluable tools for generating human disease models and for biomedical research. Humanized animal models have generally been developed via conventional transgenic technologies; however, conventional gene delivery vectors such as viruses, plasmids, bacterial artificial chromosomes, P1 phase-derived artificial chromosomes, and yeast artificial chromosomes have limitations for transgenic animal creation as their loading gene capacity is restricted, and the expression of transgenes is unstable. Transchromosomic (Tc) techniques using mammalian artificial chromosomes, including human chromosome fragments, human artificial chromosomes, and mouse artificial chromosomes, have overcome these limitations. These tools can carry multiple genes or Mb-sized genomic loci and their associated regulatory elements, which has facilitated the creation of more useful and complex transgenic models for human disease, drug development, and humanized animal research. This review describes the history of Tc animal development, the applications of Tc animals, and future prospects.

A Sufficient Surgical Window for Deep-Seated Extracranial Schwannomas in the Craniocervical Junction by the Anterolateral Approach.

Care should be taken regarding surrounding anatomic structures during access to deepseated extracranial schwannomas in the craniocervical junction (CCJ). Herein, we present surgical tips for extracranial schwannomas in the CCJ using the anterolateral approach. A retrospective review was performed of 3 cases of surgical treatment of extracranial schwannomas in the CCJ by the anterolateral approach, which is a presternomastoid retrojugular route to the CCJ. The combination of neck rotation and reflection of the sternocleidomastoid muscle presented a sufficient, shallow surgical field for the CCJ. We could identify tumors along the accessory nerves and internal jugular veins, and had sufficient rostrocaudal working space to resect the tumors. Two cases were enucleated total resection and 1 was subtotal resection. Two patients experienced transient postoperative vocal cord partial paralysis and 1 had transient dysphagia. These neurological complications improved within 1 month. The anterolateral approach can provide a shallow and sufficient rostral and caudal surgical window.

Five factors can reconstitute all three phases of microtubule polymerization dynamics.

Cytoplasmic microtubules (MTs) undergo growth, shrinkage, and pausing. However, how MT polymerization cycles are produced and spatiotemporally regulated at a molecular level is unclear, as the entire cycle has not been recapitulated in vitro with defined components. In this study, we reconstituted dynamic MT plus end behavior involving all three phases by mixing tubulin with five Drosophila melanogaster proteins (EB1, XMAP215Msps, Sentin, kinesin-13Klp10A, and CLASPMast/Orbit). When singly mixed with tubulin, CLASPMast/Orbit strongly inhibited MT catastrophe and reduced the growth rate. However, in the presence of the other four factors, CLASPMast/Orbit acted as an inducer of pausing. The mitotic kinase Plk1Polo modulated the activity of CLASPMast/Orbit and kinesin-13Klp10A and increased the dynamic instability of MTs, reminiscent of mitotic cells. These results suggest that five conserved proteins constitute the core factors for creating dynamic MTs in cells and that Plk1-dependent phosphorylation is a crucial event for switching from the interphase to mitotic mode.

A Pilot Clinical Study of Olfactory Mucosa Autograft for Chronic Complete Spinal Cord Injury.

Recent studies of spinal cord axon regeneration have reported good long-term results using various types of tissue scaffolds. Olfactory tissue allows autologous transplantation and can easily be obtained by a simple biopsy that is performed through the external nares. We performed a clinical pilot study of olfactory mucosa autograft (OMA) for chronic complete spinal cord injury in eight patients according to the procedure outlined by Lima et al. Our results showed no serious adverse events and improvement in both the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade and ASIA motor score in five patients. The preoperative post-rehabilitation ASIA motor score improved from 50 in all cases to 52 in case 2, 60 in case 4, 52 in case 6, 55 in case 7, and 58 in case 8 at 96 weeks after OMA. The AIS improved from A to C in four cases and from B to C in one case. Motor evoked potentials (MEPs) were also seen in one patient, reflecting conductivity in the central nervous system, including the corticospinal tract. The MEPs induced with transcranial magnetic stimulation allow objective assessment of the integrity of the motor circuitry comprising both the corticospinal tract and the peripheral motor nerves.We show the feasibility of OMA for chronic complete spinal cord injury.

Motor evoked potential and voluntary EMG activity after olfactory mucosal autograft transplantation in a case of chronic, complete spinal cord injury: case report.

The efficacy of olfactory mucosal autografts (OMAs) for chronic spinal cord injury (SCI) has been reported, but there is no report documenting electrophysiological conductivity via the emergence of motor evoked potentials (MEPs). We report the case of a 39-year-old man with chronic, complete SCI at T8, who exhibited MEPs after OMA transplantation, and, with intensive rehabilitation, was ultimately able to ambulate with short leg braces and Lofstrand crutches. The initial injury occurred in a motor vehicle accident in November 1999 and resulted in a complete loss of sensorimotor function below T8. OMA transplantation to the injury site was performed in March 2010 in combination with intensive pre- and postoperative rehabilitation. The patient exhibited voluntary electromyograph (EMG) activity and MEPs at 96 and 144 weeks after transplantation and he was was ambulatory with short leg braces and Lofstrand crutches at 144 weeks after transplantation. We were able to elicit MEPs after OMA with intensive rehabilitation. To our knowledge, this is the first report of recovery of electrophysiological conductivity in the spinal cord after any type of treatment for chronic, complete SCI.

Extramedullary Conus Ependymoma Involving a Lumbar Nerve Root with Filum Terminale Attachment.

PURPOSE: In the current report, we describe a case of an extramedullary ependymoma involving a lumbar nerve root near conus medullaris. Spinal ependymomas commonly present as intramedullary tumors in the cervical or thoracic cord or as tumors arising from the conus medullaris or the filum terminale. In this case, we showed an extramedullary conus ependymoma involving a lumbar nerve root with filum terminale attachment. CASE PRESENTATION: A 69-year-old woman presented with lower back pain, but without sensory disturbance or motor weakness in her lower extremities. CLINICAL ASSESSMENT: Magnetic resonance imaging revealed an intradural mass at T12-L1 at the conus medullaris, which was totally resected. Histopathology revealed a non-myxopapillary ependymoma (WHO grade 2). Postoperatively, the patient did well and displayed no neurological deficits. Moreover, no radiotherapy was required. CONCLUSIONS: This report documented a rare case of intradural extramedullary ependymoma located at the conus medullaris, involving the lumbar nerve root, and attached to the filum terminale. Although extramedullary ependymomas at this region are more frequently classified as myxopapillary, histopathological examination revealed this tumor as a non-myxopapillary ependymoma.

Isolation of human adult olfactory sphere cells as a cell source of neural progenitors.

Olfactory stem cells are generated from olfactory mucosa. Various culture conditions generate olfactory stem cells that differ according to species and developmental stage and have different progenitor or stem cell characteristics. Olfactory spheres (OSs) are clusters of progenitor or stem cells generated from olfactory mucosa in suspension culture. In this study, adult human OSs were generated and their characteristics analyzed. Human OSs were adequately produced from olfactory mucosa with area over 40 mm(2). Immunocytochemistry (ICC) and fluorescence-activated cell sorting showed that human OSs were AN2 and A2B5-positive. Immunofluorescence analysis of cell type-specific ICC indicated that the number of Tuj1-positive OS cells was significantly elevated. Tuj1-positive cells displayed typical neuronal soma and dendritic morphology. Human OS cells were also immunopositive for MAP2. By contrast, few RIP-, O4-, and GFAP-positive cells were present. These RIP, O4, and GFAP-positive cells did not resemble bona fide oligodendrocytes and astrocytes morphologically. In culture to induce differentiation of oligodendrocytes, human OS cells also expressed neuronal markers, but neither oligodendrocyte or astrocyte markers. These findings suggest that human OS cells autonomously differentiate into neurons in our culture condition and have potential to be used as a cell source of neural progenitors for their own regenerative grafts, avoiding the need for immunosuppression and ethical controversies.

Differences between Cervical Schwannomas of the Anterior and Posterior Nerve Roots in Relation to the Incidence of Postoperative Radicular Dysfunction.

STUDY DESIGN: A retrospective study. PURPOSE: To assess the case files of patients who underwent surgery for cervical dumbbell schwannoma for determining the differences between schwannomas of the anterior and posterior nerve roots with respect to the incidence of postoperative radicular dysfunction. OVERVIEW OF LITERATURE: The spinal roots giving origin to schwannoma are frequently nonfunctional, but there is a risk of postoperative neurological deficit once these roots are resected during surgery. METHODS: Fifteen patients with cervical dumbbell schwannomas were treated surgically. Ten men and 5 women, who were 35-79 years old (mean age, 61.5 years), presented with neck pain (n=6), radiculopathy (n=10), and myelopathy (n=11). RESULTS: Fourteen patients underwent gross total resection and exhibited no recurrence. Follow-ups were performed for a period of 6-66 months (mean, 28 months). Preoperative symptoms resolved in 11 patients (73.3%) but they persisted partially in 4 patients (26.7%). Six patients had tumors of anterior nerve root origin, and 9 patients had tumors of posterior nerve root origin. Two patients who underwent total resection of anterior nerve root tumors (33.3%) displayed minor postoperative motor weakness. One patient who underwent total resection of a posterior nerve root tumor (11.1%) showed postoperative numbness. CONCLUSIONS: Appropriate tumor removal improved the neurological symptoms. In this study, the incidence of radicular dysfunction was higher in patients who underwent resection of anterior nerve root tumors than in patients who underwent resection of posterior nerve root tumors.

Olfactory sphere cells are a cell source for γ-aminobutyric acid-producing neurons.

Olfactory sphere cells (OSCs) are stem cells generated by culturing olfactory mucosa. Adult rat OSCs express oligodendrocyte progenitor cell (OPC) markers and differentiate into mature oligodendrocytes. Although OSCs also express nestin, a marker of neural stem cells (NSCs), it remains unclear whether adult rat OSCs are multipotent and capable of giving rise to neurons as well as oligodendrocytes. Valproic acid (VPA) is a histone deacetylase inhibitor that has the contradictory capacity to induce both differentiation of NSCs and dedifferentiation of OPCs. This study investigates a potential role for VPA in inducing either differentiation or dedifferentiation of adult rat OSCs. Treatment of OSCs with VPA induced hyperacetylation of histones and decreased cell proliferation in the absence of changes in the number of nestin-positive cells. Furthermore, VPA promoted the genesis of γ-aminobutyric acid (GABA)-producing neurons identified by expression of Tuj1/GAD67/GABA while repressing oligodendrocyte production. These findings suggest that OSCs treated with VPA did not exhibit stem cell properties indicative of dedifferentiation but rather switched to a neuronal identity during their terminal differentiation. OSCs were then transplanted into the hippocampus of rats with kainic acid-induced temporal lobe epilepsy and were systemically given VPA. Although grafted OSCs expressed Tuj1 and GAD67, these cells did not sufficiently inhibit epileptic activity. These results suggest that OSCs are a transplantable cell source for GABA-producing neurons that can be modulated by VPA. However, further investigation is required to develop them for clinical applications.

Soybean DREB1/CBF-type transcription factors function in heat and drought as well as cold stress-responsive gene expression.

Soybean (Glycine max) is a globally important crop, and its growth and yield are severely reduced by abiotic stresses, such as drought, heat, and cold. The cis-acting element DRE (dehydration-responsive element)/CRT plays an important role in activating gene expression in response to these stresses. The Arabidopsis DREB1/CBF genes that encode DRE-binding proteins function as transcriptional activators in the cold stress responsive gene expression. In this study, we identified 14 DREB1-type transcription factors (GmDREB1s) from a soybean genome database. The expression of most GmDREB1 genes in soybean was strongly induced by a variety of abiotic stresses, such as cold, drought, high salt, and heat. The GmDREB1 proteins activated transcription via DREs (dehydration-responsive element) in Arabidopsis and soybean protoplasts. Transcriptome analyses using transgenic Arabidopsis plants overexpressing GmDREB1s indicated that many of the downstream genes are cold-inducible and overlap with those of Arabidopsis DREB1A. We then comprehensively analyzed the downstream genes of GmDREB1B;1, which is closely related to DREB1A, using a transient expression system in soybean protoplasts. The expression of numerous genes induced by various abiotic stresses were increased by overexpressing GmDREB1B;1 in soybean, and DREs were the most conserved element in the promoters of these genes. The downstream genes of GmDREB1B;1 included numerous soybean-specific stress-inducible genes that encode an ABA receptor family protein, GmPYL21, and translation-related genes, such as ribosomal proteins. We confirmed that GmDREB1B;1 directly activates GmPYL21 expression and enhances ABRE-mediated gene expression in an ABA-independent manner. These results suggest that GmDREB1 proteins activate the expression of numerous soybean-specific stress-responsive genes under diverse abiotic stress conditions.

Syringomyelia associated with spinal arachnoiditis treated by partial arachnoid dissection and syrinx-far distal subarachnoid shunt.

The authors describe a new modified surgical approach to minimize the postoperative recurrence of a syrinx after surgery to treat syringomyelia associated with spinal adhesive arachnoiditis in two cases. Both patients presented with progressive gait disturbance without any remarkable history, and spinal magnetic resonance imaging revealed a syrinx and broad irregular disappearance of the subarachnoid space and/or deformity of the cord. We successfully performed a partial arachnoid dissection and syrinx-far distal subarachnoid shunt for both cases.

Presence of trans-synaptic neurons derived from olfactory mucosa transplanted after spinal cord injury.

STUDY DESIGN: Using biotinylated dextran amine (BDA) and wheat germ agglutinin (WGA) tracers, we measured the effectiveness of olfactory mucosa (OM) transplantation as a scaffold in a rat model of chronic spinal cord injury (SCI). OBJECTIVE: We examined whether OM transplantation for chronic SCI in rats results in reconstruction of neuronal pathways by both regeneration of the remaining axons and supply of OM-derived trans-synaptic neurons. SUMMARY OF BACKGROUND DATA: OM is one of the ideal scaffolds for axonal regeneration after chronic SCI. METHODS: Rats received a mild contusion at vertebral level T6-T7. Two weeks after SCI, enhanced green fluorescent protein rat-derived OM, respiratory mucosa, and phosphate-buffered saline were transplanted into each group of SCI rats. Ten weeks after SCI, BDA was injected into the right sensorimotor cortex. Eleven weeks after SCI, WGA was injected into the L1-L2 posterior column to label the corticospinal tract retrogradely and trans-synaptically. Twelve weeks after SCI, rats were killed and their spinal cords were divided into cervical (area a), thoracic-injured (area b), and lower thoracic portions (area c). Immunohistochemically, sections of area (b) were evaluated by counting cells positive for enhanced green fluorescent protein, 4',6-diamidino-2-phenylindole, WGA, and BDA (OM and respiratory mucosa groups). Axonal regenerations were estimated by counting WGA- and BDA-positive dots in transverse sections of area (a) and area (c). RESULTS: Compared with respiratory mucosa and phosphate-buffered saline transplantation, OM transplantation increased the number of WGA-positive dots in area (a), and the number of BDA-positive dots in area (c) was more after OM transplantation than after phosphate-buffered saline transplantation. Furthermore, the number of quadruple-positive cells in area (b) was much higher after OM transplantation. CONCLUSION: Our results provide both indirect and direct evidence for the presence of trans-synaptic neurons. OM transplantation in rats with chronic SCI resulted in reconstruction of neural pathways by both providing trans-synaptic neurons and supporting regeneration of remaining axons. The olfactory mucosa is thought to be an efficacious scaffold to produce the relay neuron in chronic spinal cord injury.

Primary olfactory mucosal cells promote axonal outgrowth in a three-dimensional assay.

Among the possible sources of autologous cells and tissues for use in spinal cord injury grafts, one promising source is the olfactory mucosa containing olfactory ensheathing cells and neural progenitor cells. Olfactory mucosa transplantation for spinal cord injury has been effective in animal models and in pilot clinical trials. However, the contributions of olfactory ensheathing cells and neurons in olfactory mucosa are unclear. For the present study, we prepared primary olfactory mucosal cells and used a cortex-Matrigel coculture assay system to examine the axonal outgrowth of olfactory mucosa. Axonal outgrowth from cortical slices was significantly enhanced in olfactory mucosal cells compared with noncell controls and respiratory mucosal cells, which have few olfactory ensheathing cells and neurons. Axonal outgrowth was severely reduced after treatment with an antineurotrophin cocktail. A conditioned medium in the olfactory mucosa-derived cell group contained neurotrophin-3. Some olfactory ensheathing cells and almost all neurons were immunopositive for neurotrophin-3. Axons originating from cortical slices targeted mainly the astrocyte-like olfactory ensheathing cells. Our findings demonstrate that the axonal outgrowth effect of olfactory mucosa is supported by both olfactory ensheathing cells and neurons in olfactory mucosa.

Adult olfactory sphere cells are a source of oligodendrocyte and Schwann cell progenitors.

The olfactory epithelial layer contains multipotent horizontal basal cells (HBCs) that differentiate into olfactory sensory neurons. Here, we show that rat HBCs express oligodendrocyte progenitor cell (OPC) and astrocyte markers. We generated olfactory sphere (OS) cells in cultures that were derived from adult rat olfactory mucosa. Fluorescence-activated cell sorting and immunofluorescence analyses showed that OS cells also express OPC and astrocyte markers. Interestingly, OS cells underwent oligodendrocyte differentiation in vitro. To study oligodendrocyte differentiation in vivo, OS cells were transplanted into injured rat spinal cords. The transplanted cells integrated into host tissue and differentiated into oligodendrocytes. When transected saphenous nerve ends were encased in collagen-containing silicone tubes with or without OS cells, the transplanted OS cells differentiated into Schwann cells. Our data provide new insights into of the stemness of OS cells.

Intradural extramedullary spinal ependymoma: a case report of malignant transformation occurring.

Intradural extramedullary spinal ependymomas are extremely rare. Herein, we describe a lesion-type spinal ependymoma that followed a malignant course, and discuss its clinical presentation, etiopathogenesis, and treatment. We present a patient who was diagnosed with an intradural extramedullary spinal tumor at T4-T6. The patient underwent gross total resection of the tumor without damage to the spinal cord. Histological examination, classified the lesion as a World Health Organization (WHO)-grade 2 ependymoma. One and a half years later, magnetic resonance imaging detected a recurring tumor at T4-T5. The tumor was removed and classified as a WHO-grade 3 anaplastic ependymoma. The patient was started on a course of regional spinal cord radiotherapy. The patient achieved tumoral control and clinical stabilization after the recurrence. We must consider the differential diagnosis of intradural extramedullary spinal tumors. The best treatment for this lesion is gross total resection and adjunctive radiotherapy is necessary in cases of malignant-change.