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We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior. We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma. These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.

Background We report a rare case of unruptured middle cerebral artery aneurysm associated with moyamoya disease. Case Description A 48-year-old woman with an 8-year history of moyamoya disease developed a de novo aneurysm at the bifurcation of the right middle cerebral artery. The aneurysm showed rapid enlargement in size in 1 year and surgical treatment was performed. Preoperative images could not clearly define the anatomical relationship between the aneurysm and the surrounding vessels. Intraoperative findings indicated that segmental occlusion of normal arteries that was not visualized made it difficult to define the vascular anatomy. In addition, those occlusions accompanied by improved M1 flow after administration of cilostazol was speculated to have increased hemodynamic stress, leading to the relatively rapid progress of the aneurysm. Conclusions Understanding the complexity of such process may be valuable in proper decision-making in the management of moyamoya disease patients.

Ependymomas encompass multiple, clinically relevant tumor types based on localization, genetic alterations, and epigenetic and transcriptomic profiles. Tumors belonging to the methylation class of spinal ependymoma (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, molecular data of SP-EPN are scarce, and clear treatment recommendations are lacking. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations. Yet, it remains unclear whether SP-EPN with germline or sporadic NF2 mutations or with NF2 wild type status differ clinically or molecularly. To provide a comprehensive molecular profile of SP-EPN, we integrated epigenetic, genomic, transcriptomic, and histological analyses of up to 237 cases. Clustering of methylation data revealed two distinct molecular SP-EPN subtypes. The distribution of NF2 mutated cases differed significantly across these subtypes (p

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior.We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis.By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma.These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. Comparing expression level of each genes between 19q-loss and 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Gene expression patterns of 19q-loss astrocytomas were partially different from that of 19q-intact astrocytomas. More down-regulated genes distributed on 19q and 4p, and more up-regulated genes distributed on 4q. Multiple genes associated with stem cell maintenance were down-regulated in 19q-loss astrocytomas, and genes associated with glioma progression were differentially expressed. Comparing expression patterns among 19q-loss astrocytomas and other IDH-mutant glioma subgroups using TCGA datasets by t-SNE analysis revealed that expression pattern of 19q-loss astrocytomas did not shift to that of oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas was an acquired event different from 1p/19q codeletion in oligodendrogliomas, and better prognosis morphological features in 19q-loss astrocytomas were derived from differentially expressed genes associated with stem cell maintenance and glioma progression.

BACKGROUND Mismatch Repair (MMR) Deficiency is common in recurrent gliomas from IDH-mutant and IDH-wild-type tumors. Emergence of MMR deficit is strongly associated with the chemotherapy using TMZ, and it is considered to be a key mechanism of acquiring resistance to TMZ. Several studies showed MMR protein loss detected by immunohistochemistry was well concordant with molecular genetics sequencing data, and sometimes even more reliable in detecting MMR functional deficit. Here we evaluated Mismatch Repair protein expression by immunohistrochemistry for the pairs of primary and recurrent gliomas. METHODS We investigated the expression of 4 MMR proteins (MLH1/MSH2/MSH6/PMS2) in 37 cases of paired primary-recurrent gliomas (7 grade II & III astrocytomas, 16 grade II & III oligodendrogliomas, and 14 glioblastomas). Clinical information including history of chemo-radiotherapy after primary surgery were collected retrospectively. RESULTS Except for one case of GBM, all primary tumors retained 4 MMR proteins. 10 of 37 recurrent tumors lost one or more MMR protein expression (4 GBM 3 astrocytoma, 3 oligodendroglioma), including one case in which primary tumor already had MSH2/MSH6 loss. 2 recurrent GBM lost MMR protein expression homogenously, while in other 8 tumors, the patterns of MMR protein loss were heterogenous. 8 of 10 tumors that lost MMR protein expression were recurrence after TMZ treatment. CONCLUSION Although the interpretation of the heterogenous loss of MMR protein expression is somewhat difficult, the immunohistochemical evaluation of MMR proteins appears to be feasible, and may be able to detect early phase of MMR deficiency and the rise of hypermutator phenotype.

OBJECTIVE In cervical spondylotic myelopathy (CSM), compromise of blood flow to the compressed spinal cord has been postulated to contribute to the development of myelopathy. Although decompressive surgery has been considered to improve spinal cord blood flow, evidence to support this notion is scarce. To determine whether blood flow improves after decompressive surgery for CSM, regional blood flow was measured in a model of chronic cervical compression in rats by using a fluorescent microsphere technique. METHODS Thin polyurethane sheets, measuring precisely 3 × 5 × 0.7 mm, were implanted under the C5–6 laminae in 24 rats to induce continuous compression on the cervical spinal cord. These sheets expand gradually by absorbing tissue fluid. This animal model has been demonstrated to reproduce the clinical features and histological changes of CSM, including progressive motor weakness with delayed onset and insidious tissue damage prior to symptom onset. Twenty-four rats that underwent sham operation were allocated to a control group. To confirm the development of cervical myelopathy, motor functions were measured weekly over the study period. Nine weeks after implantation of the sublaminar expanding sheets, histological studies and C5–6 decompressive surgery were conducted. Regional blood flow in the brainstem and cervical spinal cord was measured sequentially until 120 minutes after decompression. RESULTS In the CSM group, bilateral forepaw grip strength deteriorated progressively from 5 weeks after implantation. In the compressed C5–6 segment of the spinal cord, significant flattening of the cord, a decreased number of motor neurons, and vacuolations of gray matter were demonstrated. In the control group, blood flow in the brainstem and cervical spinal cord was unchanged by the decompressive surgery. In the CSM group, however, diminished blood flow and continuous blood flow increments for 120 minutes after decompression were demonstrated in the compressed C5–6 spinal cord segment. CONCLUSIONS Chronic mechanical compression induced regional spinal cord blood flow insufficiency concomitant with progressive neuronal loss and motor dysfunction in a chronic compression model in rats. Decompressive surgery increased spinal cord blood flow. These findings suggest that blood flow recovery may contribute to postoperative neurological improvement.

The Japan Neurosurgical Database (JND) is a prospective observational study registry established in 2017 by the Japan Neurosurgical Society (JNS) to visualize real-world clinical practice, promote science, and improve the quality of care and neurosurgery board certification in Japan. We summarize JND's aims and methods, and describes the 2018 survey results. The JND registered in-hospital patients' clinical data mainly from JNS training institutions in 2018. Caseload, patient demographics, and in-hospital outcomes of the overall cohort and a neurosurgical subgroup were examined according to major classifications of main diagnosis. Neurosurgical caseload per neurosurgeon in training in core hospitals in 2018 was calculated as an indicator of neurosurgical training. Of 523,283 cases (male 55.3%) registered from 1360 participating institutions, the neurosurgical subgroup comprised of 33.9%. Among the major classifications, cerebrovascular diseases comprised the largest proportion overall and in the neurosurgical subgroup (53.1%, 41.0%, respectively), followed by neurotrauma (19.1%, 25.5%), and brain tumor (10.4%, 12.8%). Functional neurosurgery (6.4%, 3.7%), spinal and peripheral nerve disorders (5.1%, 10.1%), hydrocephalus/developmental anomalies (2.9%, 5.3%), and encephalitis/infection/inflammatory and miscellaneous diseases (2.9%, 1.6%) comprised smaller proportions. Most patients were aged 70-79 years in the overall cohort and neurosurgical subgroup (27.8%, 29.4%). Neurotrauma and cerebrovascular diseases in the neurosurgical subgroup comprised a higher and lower proportion, respectively, than in the overall cohort in elderly patients (e.g. 80 years, 46.9% vs. 33.5%, 26.8% vs. 54.4%). The 2018 median neurosurgical caseload per neurosurgeon in training was 80.7 (25-75th percentile 51.5-117.5). These initial results from 2018 reveal unique aspects of neurosurgical practice in Japan.

Brain invasion by chronic lymphocytic leukemia (CLL) is very rare, and only a handful of cases have been reported. We here report a case of 61-year-old woman who had been treated for CLL for 14 years presenting with a progressive mental disturbance. Magnetic resonance imaging (MRI) showed discontinuous ring-enhancing lesions compatible with the "open ring" sign, which was considered a demyelinating disorder, in both the frontal lobes. However, on histological examination of the biopsied specimen, infiltration of small lymphocytes positive for CD5, CD20, and CD23, indicating brain invasion by CLL, was seen. The leukemia cells occupied the Virchow-Robin space and infiltrated into the brain parenchyma. The arterioles in the Virchow-Robin space were compressed and occluded with the tumor cells, while CD163-positive cells infiltrated the brain parenchyma. Myelin staining demonstrated myelinoclasis in the infiltrated brain tissue. The MRI findings in the present case probably reflected myelinoclasis, suggesting rare brain invasion by CLL. The possibility of lymphoma should not be eliminated based on the MRI findings.

Intravascular lymphoma (IVL) has been characterized in many case reports by multiple white matter lesions reflecting ischemic changes. In contrast, there are very few case reports of cerebral or cerebellar hemorrhage resulting from IVL. A 56-year-old woman was referred to our department with two-week history of headache, nausea, and poor appetite. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) showed dilated veins on the cerebellar surface. No ischemic lesions were detected on diffusion-weighted images. Three days after admission, the patient had a large cerebellar hemorrhage, prompting emergency surgery. Unfortunately, the patient died on the 11th postoperative day. Massive CD20-positive lymphoma cells were recognized in the cerebellar veins, but not in the arteries or the parenchyma of the brain. This is the rare case report of a cerebellar hemorrhage complication from IVL that might have been caused by venous congestion. The dilated veins on the cerebellar surface recognized from the Gd-enhanced T1-weighted images were specific clues in this case.

BACKGROUND Ependymomas are currently classified into 9 subgroups by DNA methylation profiles. Although spinal cord ependymoma (SP-EPN) is distinct from other tumors, diversity within SP-EPN is still unclear. Here, we used transcriptomic and epigenomic profiles to investigate the diversity among Japanese SP-EPN cases. MATERIALS AND METHODS We analyzed 57 SP-EPN patients (32 males and 25 females, aged from 18 to 78 years, median: 52), including two cases of neurofibromatosis type 2, five cases of grade 3 (WHO grade). We obtained transcriptome (RNA-seq) and DNA methylation (Infinium Methylation EPIC array) data from fresh frozen specimens of SP-EPN resected at the University of Tokyo Hospital and our collaborative groups. RESULTS Three cases had a previous intracranial ependymoma operation. Hierarchical clustering of the DNA methylation data showed that these three cases of intracranial origin as a different cluster from spinal origin. The 45 grade 2 spinal ependymoma showed a relatively homogenous methylation pattern. However, the methylation status of HOX gene cluster regions is compatible with the segment of origin, which reflects the cells of origins are derived after the determination of segment identity. RNA sequencing of 57 cases revealed two subgroups within grade 2. Gene ontology analysis of differentially expressed genes suggested the difference in metabolic state such as rRNA translation and mitochondrial respiration between the two expression subgroups. CONCLUSION Epigenetic analysis indicated the accurate body segment origin of SP-EPN. We observed that metabolic states could divide grade 2 spinal cord ependymoma into 2 subgroups and will present the relationship to clinicopathological information.

髄膜腫は最も頻度の多い脳腫瘍で，その多くは手術摘出後に再発が稀な腫瘍であるが，一部ではより高い増殖能を示すものがある．組織学的には異型性髄膜腫に分類されるもので，その頻度は診断基準であるWHO分類の変遷に伴い1993年当初数％であったものが，最近30％程度にまで増加している．しかし，臨床的には髄膜腫全体での再発率や悪性度が高くなっている証拠はない．一つの可能性として異型性髄膜腫と診断される比率が増えたことが考えられる．我々は異型性髄膜腫の組織像を詳細に検討し，臨床経過と併せて検討を行った．対象症例は2009年1月〜2014年7月における64例で，WHO grade Iが37例，異型性髄膜腫が27例であった．異型性髄膜腫は組織像によって，局所での核分裂像を示すⅡa群と，全体的での核分裂像もしくは脳浸潤を伴うⅡb群に分けることが可能であり，Ⅱa群は10例，Ⅱb群は17例であった．臨床像はⅡb群が grade I/Ⅱa群より，高齢(中央値Ⅰ：57，Ⅱa：50，Ⅱb：69歳)で男性に多く，MIB-1 labeling indexがより高値(中央値Ⅰ：3.0，Ⅱa：2.1，Ⅱb：10.3％)であった．追跡期間中にgradeⅠで1 例，Ⅱb群で5例が再発した．Ⅱa群の臨床経過は，grade Iに類似しており，臨床像としてはⅡb群が異型性髄膜腫のような，より再発を認めやすい一群であると考えられる．

Study design Basic animal research. Objective The effects of granulocyte colony-stimulating factor (G-CSF) were assessed in a rat chronic spinal cord compression model to explore the potential of G-CSF as a pharmacological treatment for cervical spondylotic myelopathy. Summary of background data G-CSF is a hematopoietic cytokine used clinically to treat neutropenia. Recently, neuroprotective effects of G-CSF have been reported in spinal cord disorders. Methods To introduce the chronic cervical cord compression, thin polyurethane sheets were implanted under C5-C6 laminae of rats and gradually expanded by absorbing water. This model reproduces delayed compressive myelopathy of the cervical spine. In sham operations, the sheets were immediately removed. G-CSF (15 μg/kg) or normal saline (NS) was administered subcutaneously 5 days a week. Experimental groups were sham operation given NS; cord compression given NS; and cord compression given G-CSF. To assess motor functions, rotarod performance, and grip strength were measured. Twenty-six weeks after surgery, cervical spinal cords were examined histopathologically. In the prevention experiment, G-CSF or NS administration was started immediately after surgery. In the treatment experiment, their administration was started 8 weeks after surgery. In another experiment, in three groups in the prevention experiment, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining was performed to assess apoptotic cell death at 8 weeks after surgery. Results In the prevention experiment, administration of G-CSF preserved the motor functions and motor neurons throughout the 26 weeks, and significantly decreased the number of apoptotic cells at 8 weeks. In the treatment experiment, G-CSF administration from 8 weeks after surgery markedly restored the motor function temporarily to a level equal to the sham group. Conclusion G-CSF prevents the decline in motor functions and preserves motor neurons in the rat chronic cord compression model. G-CSF also improves motor function in the progressive phase of compression myelopathy. Level of evidence N/A.

Hemangioblastoma is usually amenable to total surgical resection, but indication for surgery can be hampered by its location, multiplicity, or repeated recurrences frequently observed in patients with von Hippel Lindau disease (VHLD). Stereotactic radiosurgery (SRS) has been administered for such cases as an alternative therapeutic option with generally favorable clinical response, but the effect of SRS has not been underscored by histological examination of the treated hemangioblastoma. Here we present histology of VHLD-associated hemangioblastoma tissue resected three months after SRS because of cyst enlargement. It confirmed that hemangioblastoma cells totally disappeared after SRS with a marginal dose of 20 Gy. Furthermore, Electron microscope revealed that endothelial cells of the vascular structure disappeared while maintaining the basement membranes, and leakage of intraluminal contents was observed around the structure. We showed the SRS was effective for hemangioblastoma pathologically at least with the marginal dose of 20 Gy. Leakage of intraluminal contents from the damaged vascular structure losing the endothelial cells is one possible mechanism for the cyst enlargement, and it may be a reason of poor control rate of SRS for the cystic hemangioblastoma.

Background: The most common cause of intracranial subarachnoid hemorrhage (SAH) is an intracranial aneurysm or other vascular lesion; however, spinal lesions have also been implicated. Furthermore, vascular lesions rarely occur in the thoracolumbar region. We herein presented a case of intracranial SAH caused by an isolated aneurysm in the thoracic spinal artery.Case presentation: A 79-year-old woman developed the sudden onset of headaches in the parietal and occipital regions followed by vomiting. Head computed tomography (CT) scans showed SAH in the basal cistern and around the parietal lobe cortex. Cerebral angiography detected no aneurysm or vascular malformation. Spinal CT on day 1 showed extensive SAH at the posterior surface of the spinal cord, which was the most prominent at the level of T9/10, and spinal angiography subsequently revealed an aneurysm fed by the T10 radicular artery. The aneurysm was resected by T8-10 laminectomy, and the patient recovered with no long-term neurological deficit.Conclusions: A literature review revealed 17 cases of intracranial SAH from thoracolumbar vascular lesions. Most cases resulted in poor functional outcomes, which occurred in the later phase of the disease and may have been avoided with earlier diagnoses and interventions. We suggest whole spine CT as a useful tool for rapid screening of this rare lesion, and is recommended when an initial survey for intracranial lesions does not detect any likely lesions. Furthermore, ventricular reflux on head CT may lead to an accurate diagnosis in the absence of spinal symptoms.

OBJECTIVEErythropoietin (EPO) is a clinically available hematopoietic cytokine. The aim of this study was to evaluate the effect of EPO on a rat model of cervical cord compression myelopathy and to explore the possibility of its use as a pharmacological treatment.METHODSTo produce the chronic cervical cord compression model, thin polyurethane sheets were implanted under the C5-C6 laminae of rats and gradually expanded due to water absorption. In this model, motor functions significantly declined from 7 weeks after surgery. Based on the result, EPO administration was started 8 weeks after surgery. Motor function as seen with rotarod performance and grip strength was measured 16 weeks after surgery, and then motor neurons were stained with H-E and NeuN staining, and counted. Apoptotic cell death was assessed with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. To assess transfer of EPO into spinal cord tissue, the EPO level in spinal cord tissue was measured with an enzyme-linked immunosorbent assay for each group after subcutaneous injection of EPO.RESULTSHigh-dose EPO (5000 IU/kg) administered from 8 weeks after surgery markedly restored and maintained motor function in the Compression groups (P < 0.01). EPO significantly prevented loss of motor neurons in the anterior horn (P < 0.05) and significantly decreased the number of TUNEL-positive apoptotic cells (P < 0.05). The EPO level in spinal cord tissue was significantly higher in the High-dose EPO group than other groups.CONCLUSIONSEPO improves motor function in rats with progressive chronic compression myelopathy. EPO protects anterior horn motor neurons and inhibits neuronal cell apoptosis in spinal cord compression. The neuroprotective effects can be produced through transfer of EPO into spinal cord tissue. These findings suggest that EPO has high potential as a treatment for developing compression myelopathy.

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Down-regulated genes in the 19q-loss astrocytomas were heavily clustered to 19q and 4p, and up-regulated genes to 4q. It was noted that fibroblast growth factor 1 associated with stem cell maintenance was down-regulated in 19q-loss astrocytomas and genes associated with glioma progression were differentially expressed, these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, 19q-loss astrocytomas did not shift to oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas is more likely to be an acquired event rather than early event in oncogenesis like 1p/19q codeletion in oligodendrogliomas, and the biological and morphological features of 19q-loss astrocytomas were possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

Background Middle meningeal artery (MMA) embolization can be a treatment option for selected cases of chronic subdural hematoma (CSDH) patients. However, appropriate timing of this procedure or the conditions to be considered are still not standardized. Methods Between 2008 and 2018, 18 symptomatic CSDH patients underwent MMA embolization at our institution. The timing of embolization and the risk factors for recurrence of CSDH, the recurrence rate after an embolization, and the complication were thoroughly reviewed. Results Of the 18 cases, 16 patients were male. The median age at MMA embolization was 78.5 years (range, 66–98 years). The median follow-up period were eight months (range, 2–53 months). Possible risk factors for CSDH recurrence harbored by those patients were age > 74 yrs (10), brain atrophy (4), separated hematoma (3), coagulopathy (3), anticoagulant administration (3), and thrombocytopenia (1). No recurrence or complication was observed in any of the patients after the embolization. Conclusions MMA embolization is effective and safe in preventing recurrence of CSDH with high risk of recurrence, and could be a standard treatment for such cases.

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas (Otani et al. Cancer Sci 2018). The purpose of the present study was to reveal how 19q-loss contributed to better prognosis and the morphology in the subgroup. We compared expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. 136 up-regulated genes and 203 down regulated genes were extracted in 19q-loss astrocytomas compared with 19q-intact astrocytomas. Significantly changed genes distributed throughout all chromosomes, but more down-regulated genes were on 19q and 4p, and more up-regulated genes were on 4q. Genes associated with apoptosis, cell adhesion, and antigen presentation were up-regulated, and genes associated with Ras signaling pathway were down-regulated. These changes could result in better prognosis. By contrast, there was few expression changed gene associated with oligodendroglioma-like morphology although up-regulation of genes associated with axon guidance and down-regulation of genes associated with cell shape might result in the morphology or neuronal differentiation. Expression pattern of 19q-loss astrocytomas indicated no tendency of oligodendroglial differentiation. Better prognosis of 19q-loss astrocytomas was derived from expression changes associated with tumor proliferation and tumor immunity.

Brain metastasis is associated with worse prognosis in patients with non-small cell lung cancer (NSCLC). However, recent advances in molecular targeted therapy are rapidly changing the treatment strategy for NSCLC. Here, we conducted a retrospective study to clarify the prognosis and risk factors in NSCLC patients with synchronous brain metastasis. Seventy-four patients who were treated at our institute between Jan 2013 and Apr 2019 were included. The association between overall survival (OS) and clinicopathological features, such as neurological symptoms at diagnosis, histology, EGFR and ALK mutation status, number of intracranial metastases, extracranial systemic metastasis, Karnofsky performance status (KPS) at diagnosis, and initial therapy, were examined. OS was calculated from the day of diagnosis with brain metastasis or NSCLC. Of the 51 men and 23 women enrolled (median 70.0 years of age, range 40–84), 26 patients (35.1%) exhibited neurological symptoms at diagnosis. EGFR and ALK mutations were present in 24 (32.4%) patients. The median OS for all patients was 23.0 months. Factors significantly associated with worse OS in univariate analysis were symptomatic lesions and the absence of a driver mutation. Driver mutation status was only an independent prognosis factor in multivariate analysis. On lung-mol GPA score, the patients greater than or equal to 2.5 were significantly better prognosis compared with less than 2.5 (median OS: 40.0 VS 10.0 months, respectively). Our cohort of 74 NSCLC patients with synchronous brain metastasis had a median OS of 23.0 months. This much longer OS may reflect recent advances in treatment, particularly the availability of molecular targeted drugs. Lung-mol GPA score was considered as a useful tool to estimate the prognosis; thus, the information of KPS score, extracranial metastasis, brain metastases numbers, and driver mutation status are essential to build a treatment strategy for synchronous brain metastasis from NSCLC.

Background Motor evoked potential (MEP) recording is used as a method to monitor integrity of the motor system during surgery for intramedullary tumors (IMTs). Reliable sensitivity of the monitoring in predicting functional deterioration has been reported. However, we observed false positives and false negatives in our experience of 250 surgeries of IMTs. Objective To delineate specificity and sensitivity of MEP monitoring and to elucidate its limitations and usefulness. Methods From 2008 to 2011, 58 patients underwent 62 surgeries for IMTs. MEP monitoring was performed in 59 operations using transcranial electrical stimulation. Correlation with changes in muscle strength and locomotion was analyzed. A group undergoing clipping for unruptured aneurysms was compared for elicitation of MEP. Results Of 212 muscles monitored in the 59 operations, MEP was recorded in 150 (71%). Positive MEP warnings, defined as amplitude decrease below 20% of the initial level, occurred in 37 muscles, but 22 of these (59%) did not have postoperative weakness (false positive). Positive predictive value was limited to 0.41. Of 113 muscles with no MEP warnings, 8 muscles developed postoperative weakness (false negative, 7%). Negative predictive value was 0.93. MEP responses were not elicited in 58 muscles (27%). By contrast, during clipping for unruptured aneurysms, MEP was recorded in 216 of 222 muscles (96%). Conclusion MEP monitoring has a limitation in predicting postoperative weakness in surgery for IMTs. False-positive and false-negative indices were abundant, with sensitivity and specificity of 0.65 and 0.83 in predicting postoperative weakness.

Object Regional blood flow is decreased in experimental models of chronic spinal cord compression, and the alteration presumably contributes to the development of myelopathy. Cilostazol (Otsuka Pharmaceuticals Co.), a selective Type III phosphodiesterase inhibitor, has been shown to be neuroprotective in cerebral hypoperfusion animal models and clinically effective in preventing the recurrence of cerebral infarction. To investigate the neuroprotective effect of cilostazol on cervical spondylotic myelopathy, the preventive effect against progressive motor dysfunction and the loss of anterior horn motor neurons were assessed using a chronic cord compression model in rats. Methods To produce chronic cervical cord compression in male Wistar rats, thin polyurethane sheets (3 × 5 × 0.7 mm) that gradually expand over 48–72 hours by absorbing water were implanted under the C5–6 laminae. In sham operations, the sheets were momentarily placed and then immediately removed. This model has been shown to reproduce characteristic features of clinical cervical myelopathy, with progressive motor disturbances after a latency period and insidious neuronal loss preceding the onset of symptoms. In the treatment group, cilostazol (30 mg/kg/day) was orally administered to the rats once a day, starting the day after surgery and continuing through the entire observation period of 25 weeks. In the control group, vehicle solution was administered under the same protocol. Changes in motor function were monitored by measuring bilateral forepaw grip strength and the duration of forced running on a treadmill. Twenty-five weeks after surgery, cervical spinal cords were examined histopathologically. Results Cilostazol preserved both forepaw grip strength and forced running capability. The drug also preserved anterior horn motor neurons in the C5–6 spinal cord segment, which diminished in number in the untreated chronic compression group. The drug decreased the number of TUNEL-positive apoptotic cells. Conclusions These results indicate that cilostazol is neuroprotective in the chronically compressed cervical cord and is potentially useful in the treatment of cervical spondylotic myelopathy.