Abstract Germ cell tumor (GCT) is a rare juvenile CNS tumor that is more frequent in eastern Asia. Most survivors require continuous medical care for hormone replacement, maintenance of shunting devices, and late radiation-induced effects. In the present study, we retrospectively analyzed medical records of long-term GCT survivors, and make the health and social issues clear. Ninety-two GCT patients were treated in our institute from 1982 to 2018, and 81 patients, of which medical records are available, are included. The median follow-up period is 12.2 years, and 47 patients (58.1%) are followed for more than ten years. The overall survival rate is gradually decreasing more than ten years follow-up, such as 10-, 15- and 25-years survival are 92.3, 87.7, and 73.3%, respectively. In the long-term follow-up, eight subsequent malignancy and seven cerebrovascular events are recorded. These events occurred 20 years or more after the treatments, and six CNS malignancies were observed in survivors irradiated with 50Gy or more. As social issues, forty-two of 50 adult survivors had been employed after the treatments, but only thirty-four (70.8%) are still working. Of note, only nine (18.8% of adults) survivors got married. All four married women require any hormone replacement, while only one of 4 men requires the replacement. Long-term follow-up of GCT survivors revealed subsequent malignancy and social problems. A recent attempt to decrease the dose of irradiation might overcome some issues. As a conclusion, GCT survivors require a supporting program for not only health but also social issues.

Germ cell tumor (GCT) is a juvenile tumor, completely cured by adequate treatments, including radiation therapy and chemotherapy. However, survivors require continuous medical treatment mostly due to hypopituitarism, and several issues could be observed during follow-up. In the present report, we analyzed medical records of long-term GCT survivors, retrospectively, and make the issues clear. Of ninety-three, 82 GCT patients with several medical and social information are included in the analysis. Median follow-up time is 11.95 years, and 47 patients followed more than ten years. Fifteen deaths are recorded, and 8 are tumor-progression, and 7 are treatment-related long-term events, including four subsequent gliomas, one cerebral vascular disease, one renal cancer, and one sudden death. Seven survivors developed subsequent malignancy, and all lived more than 19 years and received more than 50Gy of irradiation. The overall survival rate is gradually decreasing more than ten years follow-up, such as 10-, 15- and 25-years survival are 92.3, 87.7 and 73.3%, respectively. Long-term follow-up also clarified several social issues. Forty-two of 50 adult survivors had a job after the treatments, but only thirty-four (70.8%) are still working. Of note, only nine (18.8% of adults) survivors got married. All four women require any hormone replacement, while only one of 4 men requires the replacement. Long-term follow-up of GCT survivors revealed subsequent malignancy and social problems. Recent attempt to decrease radiation dose and to give adequate hormone replacement might overcome these problems. Clinicians still observed GCT patients closely.

OBJECTIVE The neurological prognostic score (NPS) was recently proposed as a means for predicting neurological outcomes, such as the preservation of neurological function and the prevention of neurological death, in brain metastasis patients treated with Gamma Knife radiosurgery (GKRS). NPS consists of 2 groups: Group A patients were expected to have better neurological outcomes, and Group B patients were expected to have poorer outcomes. NPS robustness was tested in various situations. METHODS In total, 3040 patients with brain metastases that were treated with GKRS were analyzed. The cumulative incidence of the loss of neurological function independence (i.e., neurological deterioration) was estimated using competing risk analysis, and NPS was compared between Groups A and B by employing Gray's model. NPS was tested to determine if it can be applied to 5 cancer categories-non-small cell lung cancer, small cell lung cancer, gastrointestinal tract cancer, breast cancer, and other cancers-as well as if it can be incorporated into the 5 major grading systems: recursive partitioning analysis (RPA), score index for stereotactic radiosurgery (SIR), basic score for brain metastases (BSBM), graded prognostic assessment (GPA), and modified-RPA (M-RPA). RESULTS There were 2263 patients in NPS Group A and 777 patients in Group B. Neurological deterioration was observed in 586 patients (19.2%). The cumulative incidences of neurological deterioration were 9.5% versus 21.0%, 14.1% versus 25.4%, and 17.6% versus 27.8% in NPS Groups A and B at 1, 2, and 5 years, respectively. Significant differences were detected between the NPS groups in all cancer categories. There were significant differences between NPS Groups A and B for all classes in terms of the BSBM, GPA, and M-RPA systems, but the differences failed to reach statistical significance in terms of RPA Class I and SIR Class 0 to 3. CONCLUSIONS The NPS was verified as being highly applicable to all cancer categories and almost all classes for the 5 grading systems in terms of neurological function independence. This NPS system appears to be quite robust in various situations for brain metastasis patients treated with GKRS.

BACKGROUND: Hypomethylation of genomic DNA induces stem-cell properties in cancer cells and contributes to the treatment resistance of various malignancies. OBJECTIVE: To examine the correlation between the methylation status of stem-cell-related genes and the treatment outcomes in patients with glioblastoma (GBM). METHODS: The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between a group of patients with good prognosis (survival > 4 yr) and a group with poor prognosis (survival < 1 yr). Immunohistochemistry for proteins translated from hypomethylated genes, including alkaline phosphatase (ALPL), CD133, and CD44, was performed in 70 GBMs and 60 oligodendroglial tumors. RESULTS: The genomic DNA in refractory GBM was more hypomethylated than in GBM from patients with relatively long survival ( P = .0111). Stem-cell-related genes including ALPL, CD133, and CD44 were also significantly hypomethylated. A validation study using immunohistochemistry showed that DNA hypomethylation was strongly correlated with high protein expression of ALPL, CD133, and CD44. GBM patients with short survival showed high expression of these stem-cell markers. Multivariate analysis confirmed that co-expression of ALPL + CD133 or ALPL + CD44 was a strong predictor of short survival. Anaplastic oligodendroglial tumors without isocitrate dehydrogenase 1 mutation were significantly correlated with high ALPL expression and poor survival. CONCLUSION: Accumulation of stem-cell properties due to aberrant DNA hypomethylation is associated with the refractory nature of GBM.

Invasion into surrounding normal brain and resistance to genotoxic therapies are the main devastating aspects of glioblastoma (GBM). These biological features may be associated with the stem cell phenotype, which can be induced through a dedifferentiation process known as epithelial-mesenchymal transition (EMT). We show here that tumor cells around pseudopalisading necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor (TGF-β), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF-β around necrotic regions was significantly correlated with shorter progression-free survival and overall survival in patients with GBM. High expression of stem cell markers, ALPL, CD133, and CD44 was also correlated with poor outcomes. These results collectively support the hypothesis that tissue hypoxia induces the stem cell phenotype through TGF-β-related EMT and contributes to the poor outcome of GBM patients.

Objective Chromosome 1p/19q deletion is an established prognostic and predictive marker in the WHO grade III oligodendroglial tumours (OT). To estimate the genetic status preoperatively, the authors investigated the correlation between the uptake of 11C-methionine in positron emission tomography (PET) and the 1p/19q status in grades II and III OT. Methods We retrospectively reviewed 144 patients with gliomas who received 11C-methionine PET. 66 cases with grades II–III oligodendrogliomas or oligoastrocytomas underwent fluorescence in situ hybridisation to determine the 1p/19q status. The tissue uptake of 11C-methionine was expressed as the ratio of the maximum standardised uptake value (SUVmax) in tumour areas to the mean SUV (SUVmean) in the contralateral normal brain (tumour-to-normal tissue (T/N) ratio). Results The T/N ratio in 11C-methionine PET was significantly higher in grade III OT than in grade II tumours. The mean T/N ratio of the grade II tumours without 1p/19q deletion was significantly higher than that of the grade II tumours with 1p/19q deletion (mean 2.67 vs 1.94, respectively; p=0.0457). In grade III tumours, the mean T/N ratio of the tumours without 1p/19q deletion was also significantly higher than that of the tumours with 1p/19q deletion (mean 4.83 vs 3.49, respectively; p=0.0261). The rate of IDH1 mutation was lower and the rate of contrast enhancement on MRIs was higher in the 1p/19q non-deleted OT than those with 1p/19q deletion, which may contribute to the high T/N ratio. Conclusions Among suspected OT, 11C-methionine PET may help us preoperatively discriminate tumours with and without 1p/19q deletion.

Objectives: Manual shaping of a straight microcatheter is required when guiding or retention of a microcatheter with a pre-shaped tip is difficult. According to the manufacturer’s instructions, it is recommended that the microcatheter be shaped by steaming “for 30s” and “25 mm away from the steam source”. However, insufficient shaping and blunting can occasionally occur during the procedure. In this technical note, we present the optimal conditions of shaping for a microcatheter system.

Gliomas arising in the brain parenchyma infiltrate into the surrounding brain and break down established complex neuron-glia networks. However, mounting evidence suggests that initially the network microenvironment of the adult central nervous system (CNS) is innately non-permissive to glioma cell invasion. The main players are inhibitory molecules in CNS myelin, as well as proteoglycans associated with astrocytes. Neural stem cells, and neurons themselves, possess inhibitory functions against neighboring tumor cells. These mechanisms have evolved to protect the established neuron-glia network, which is necessary for brain function. Greater insight into the interaction between glioma cells and the surrounding neuron-glia network is crucial for developing new therapies for treating these devastating tumors while preserving the important and complex neural functions of patients.

The efficacy of stereotactic radiosurgery (SRS) instead of whole brain radiotherapy (WBRT) following high-dose methotrexate (HD-MTX) for primary central nervous system lymphoma (PCNSL) is unclear. To clarify whether SRS in combination with up-front HD-MTX supplements the effect of HD-MTX in remaining or refractory lesions after initial HD-MTX treatment. The authors conducted a retrospective review for newly diagnosed PCNSL patients who underwent SRS after HD-MTX as a first-line treatment. The local control (LC), the progression-free survival (PFS), the recurrence patterns, the salvage treatments, the overall survival (OS), the Karnofsky Performance Status (KPS), the activities of daily living (ADL) were analyzed as well as radiosurgical parameters. Twenty patients underwent SRS for 51 lesions with the median volume of 0.45 cm3. The median age at SRS was 67 (range 37–82). The median KPS at SRS was 90. The LC rate at 2 years was 86.0 %, the median PFS after SRS was 17 months, necessitating additional SRS and chemotherapy. The median OS was 52 months. No significant side effects related to SRS were observed. During follow-up period, the good ADL preservation was achieved for 13 months from SRS. Patients with KPS ≥ 90 at SRS demonstrated longer ADL preservation (32 months from SRS). SRS following up-front HD-MTX without WBRT provided excellent LC, acceptable OS and the long ADL preservation period. These benefits may be more emphasized especially in patients with good KPS, but should be validated in a large patient population.

Background: Because circulating antibodies against a variety of antigens have been detected in patients with coronary heart disease, carotid atherosclerosis and those who have suffered a stroke, it is suspected that immune response may be one of the mechanisms of atherogenesis The objective of this study is to identify novel antibodies in ischemic stroke patients by screening the expressed recombinant proteins using a human cDNA library (SEREX).Methods: To identify the candidate antigens, cDNA library was screened by SEREX using plasma from ten patients with ischemic stroke. Subsequently, via ELISA using recombinant proteins and synthetic peptides, the serum antibody levels were measured in two independent patient/healthy donor (HD) cohorts (142 and 78 in the 2nd screening and a validation cohort, respectively).Results: The initial screening resulted in the identification of six candidate antigens. Of these antigens, replication protein A2 (RPA2) was determined to be the antigen associated with stroke (P < 0.05) by ELISA with 2nd screening and validation cohort. Multifactorial logistic regression analysis showed that the increased levels of the RPA2 antibodies (RPA2-Abs) associated with stroke independent of other risk factors for stroke (P < 0.05). Receiver operating curve analysis demonstrated that the area under the curve from ELISA using GST fusion RPA2 and synthetic peptides (bRPA2-132) were 0.867 (95% CI: 0.798-0.936) and 0.971 (95% CI: 0.940-1.00), respectively. If the cut-off value of the bRPA2-132-Ab level was determined to be 0.334, the sensitivity and specificity of the antibody level as the diagnostic marker for stroke were 0.323 (95% CI: 0.209-0.453) and 1.00 (95% CI: 0.713-1.00), respectively.Conclusions: SEREX identified RPA2 as the antigen associated with ischemic stroke and serum auto-antibodies against RPA2 elevates in stroke patients. RPA2-Abs could become a biomarker for the evaluation of ischemic stroke at risk.

Some tumor-specific near-infrared (NIR) fluorescent dyes such as indocyanine green (ICG), IDRye800CW, and 5-aminolevulinic acid have been used clinically for detecting tumor margins or micro-cancer lesions. In this study, we evaluated the physicochemical properties of liposomally formulated phospholipid-conjugated ICG, denoted by LP-iDOPE, as a clinically translatable NIR imaging nanoparticle for brain tumors. We also confirmed its brain-tumor-specific biodistribution and its characteristics as the intra-operative NIR imaging nanoparticles for brain tumor surgery. These properties of LP-iDOPE may enable neurosurgeons to achieve more accurate identification and more complete resection of brain tumor.

The first nationwide survey for nontraumatic intracranial vertebrobasilar dissection (VAD) was conducted in Japan 20 years previously. The optimal treatment for ischemic VAD is still a controversial topic. We conducted a nationwide study over a 1-year period (2011) to examine the present status of management, outcomes, and factors influencing the outcome.The response rate for this survey was 15.6% (172 responses/1104 total facilities). Of the 632 patients with VAD that were enrolled to this study, 209 patients had ischemic VAD. The median age at onset was 50 (21-85) years and 78.5% of the patients were men. In this cohort, 56.7% of the patients experienced headache at the onset. Wallenberg syndrome, motor paresis, sensory disturbance, and cranial nerve symptoms were also observed in 36.9%, 22.4%, 46.7%, and 25.8% of the patients, respectively. Symptomatic deterioration and recurrence were observed in 44 patients (21.1%).With regard to patient management, 78.5% of the patients were treated with antithrombotic therapy. These treated patients had relatively severe neurological symptoms. No subarachnoid hemorrhage was observed in the ischemic VAD patients during the follow-up period. At the final follow-up, 72.4% of the patients achieved a favorable outcome (modified Rankin scale 0 to 1). Basilar artery dissection was related to clinical deterioration during the treatment, and diabetes mellitus was associated with a poor final outcome.The clinical feature, radiological findings, and outcomes were found to be similar between the present and previous reports. In the current management of ischemic VAD patients in Japan, there is considerable variability in the use of antithrombotics. Patients with severe symptoms and/or supratentorial infarction frequently received antithrombotic therapy. To evaluate the efficacy of antithrombotic in the treatment of ischemic VAD, a prospective study is necessary. Moreover, the treatment selection bias can hardly be eliminated in a non-randomized trial.

To investigate the current status of management and outcomes in patients with non-traumatic hemorrhage after intracranial vertebrobasilar artery dissection (VAD), we conducted a nationwide study over a period of 1 year (2011) in Japan.Of 632 patients with VAD, 193 patients were enrolled for the onset of hemorrhage. The following patient characteristics were recorded: age, gender, location of arterial dissection, radiographic findings, presence or absence of rebleeding, treatment, follow-up periods, and mid-term outcomes. The outcomes were evaluated using modified Rankin scale (mRS), and a good outcome was defined as an mRS score of 0-2.Regarding disease severity, Hunt and Kosnik (HK) grade-4 or grade-5 disease was observed in 48.2% of the patients. Hydrocephalus was detected in 43.6% of the patients. Rebleeding was observed in 21.5% and usually occurred within 24 hours after the onset of hemorrhage. For the prevention of rebleeding, surgical treatment, including 33 craniotomies (group C) and 127 endovascular surgeries (group E), was administered to 160 patients (82.9%). Conservative or medical treatment was administered to the remaining 33 patients (group M). Trapping was the most frequent procedure performed for the patients in groups C and E. Bypass surgery was performed in 11 patients (6.9%). Postoperative intracranial complications occurred in 23.8%, and the most common complication was ischemic events. In group C, a higher incidence of ischemic complication was observed in patients treated with trapping than in those treated by proximal occlusion. However, in group E, the incidence of ischemic events did not differ between patients treated by trapping and those treated by proximal occlusion.At the final follow-up, 56.5% of the patients achieved a good final outcome (mRS score, 0-2) and 25.9% of the patients died during the follow-up. After the treatment, 54.5% of the patients in group C, 60.6% in group E, and 42.4% in the medical treatment group showed good outcomes.Advanced age, hydrocephalus, rebleeding, posterior inferior cerebellar artery dissection, and a high HK grade were associated with poor outcomes.Endovascular surgery has been a highly common treatment option during last 2 decades. The outcomes and prognostic factors of hemorrhage in the VAD patients were similar to those previously reported.

Dmbx1 is a brain-specific homeodomain transcription factor expressed primarily during embryogenesis, and its systemic disruption (Dmbx1(-/-)) in the ICR mouse strain resulted in leanness associated with impaired long-lasting orexigenic effect of agouti-related peptide (AgRP). Because spatial and temporal expression patterns of Dmbx1 change dramatically during embryogenesis, it remains unknown when and where Dmbx1 plays a critical role in energy homeostasis. In the present study, the physiological roles of Dmbx1 were examined by its conditional disruption (Dmbx1(loxP/loxP)) in the C57BL/6 mouse strain. Although Dmbx1 disruption in fetal brain resulted in neonatal lethality, its disruption by synapsin promoter-driven Cre recombinase, which eliminated Dmbx1 expression postnatally, exempted the mice (Syn-Cre;Dmbx1(loxP/loxP) mice) from lethality. Syn-Cre;Dmbx1(loxP/loxP) mice show mild leanness and impaired long-lasting orexigenic action of AgRP, demonstrating the physiological relevance of Dmbx1 in the adult. Visualization of Dmbx1-expressing neurons in adult brain using the mice harboring tamoxifen-inducible Cre recombinase in the Dmbx1 locus (Dmbx1(CreERT2/+) mice) revealed Dmbx1 expression in small numbers of neurons in restricted regions, including the lateral parabrachial nucleus (LPB). Notably, c-Fos expression in LPB was increased at 48 hours after AgRP administration in Dmbx1(loxP/loxP) mice but not in Syn-Cre;Dmbx1(loxP/loxP) mice. These c-Fos-positive neurons in LPB did not coincide with neurons expressing Dmbx1 or melanocortin 4 receptor but did coincide with those expressing calcitonin gene-related peptide. Accordingly, Dmbx1 in the adult LPB is required for the long-lasting orexigenic effect of AgRP via the neural circuitry involving calcitonin gene-related peptide neurons.

Symptomatic glioma is usually not curable due to its invasive nature into surrounding normal brain. Establishment of serum biomarkers for gliomas would be beneficial both for early diagnosis and adequate post-operative monitoring. We searched for novel glioma antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found three independent proteins including filamin C (FLNC), SH3-domain GRB2-like 1 (SH3GL1), and pyruvate kinase M2 (PKM2) as candidate proteins. We analyzed with ELISA 131 glioma patients' sera along with 77 sera from healthy volunteers, 19 sera from patients with meningioma, and 24 patients with cerebral infarction. All the levels of serum autoantibodies to these proteins were significantly higher in low-grade gliomas than in high-grade gliomas, the healthy volunteers and the patients with other benign disease. In contrast, these proteins were expressed in glioma tissues and its level got higher as tumor grade advanced. The discrepancy was caused by the immunosuppressive microenvironments due to mesenchymal cell infiltration, which was verified by immunohistochemistry and ELISA for the mesenchymal cell-specific proteins. The rat glioma models using C6 and 9L also confirmed the increase of autoantibody levels for the SEREX-identified proteins in the early stage and the suppression in the late stage. These proteins were involved in the oncogenic process of gliomas and effectively elicit autologous antibody responses in the glioma patients without immunosuppression. The immunological reaction to some glioma antigens would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.

ObjectiveThe pulsed laser-induced liquid jet (LILJ) system is an emerging surgical instrument intended to assist both maximal removal of the lesion and functional maintenance through preservation of fine vessels and minimal damage to the surrounding tissue. The system ejects the minimum required amount of pulsed water through a handy bayonet-shaped catheter. We have already shown a significant increase in removal rate, in addition to a noteworthy reduction of intraoperative blood loss and procedure time in the treatment of large pituitary and skull base tumors in a single-institution series. The present study evaluated the safety of the system in multiple institutions.MethodsThe study included 46 patients, 29 men and 17 women (mean age: 59.1 years) who underwent microsurgical/endoscopic resection of lesions in or in the vicinity of the pituitary fossa through the transsphenoidal approach between October 2011 and June 2012 at six institutions. The histologic diagnoses were pituitary adenoma (31 cases), meningioma (4), craniopharyngioma (3), cavernous angioma (2), and Rathke cyst cleft (1). Lesion volume ranged from 2.0 to 30.4 cm(3) (mean: 3.7 cm(3)). Cavernous sinus invasion was observed in 11 cases and suprasellar extension in 29 cases.ResultsPreservation of intralesional arteries (diameter: 150 mu m) was achieved in all situations in>80% of cases. Intended surgical steps were achieved except for some restrictions in motion due to the use of an optical quartz fiber. No complications occurred directly related to the use of the device.ConclusionsThe LILJ system can be used for safe removal of lesions in or in the vicinity of the pituitary fossa.

A nationwide study (VAD 2013) was conducted over a year (January 1 to December 31, 2011) to elucidate the recent trends of the clinical features, radiographic findings, treatment, and outcomes of non-traumatic intracranial arterial dissection in the vertebrobasilar system. Here, we present the outline of the study.In this study, 632 patients from 172 neurosurgical institutes were enrolled. They were divided into 3 groups: (1) hemorrhage group consisting of 193 (30.5%) patients with subarachnoid hemorrhage; (2) ischemia group consisting of 209 (33.1%) patients with brain infarction or transient ischemic attack; and (3) headache group consisting of 230 (36.4%) patients. The following patient characteristics were recorded: age, sex, location of arterial dissection, initial radiographic findings, and serial changes in these findings, treatment, follow-up periods, and mid-term outcomes. The outcomes were evaluated using the modified Rankin scale (mRS), and a good outcome was defined as an mRS score of 0-2.Results: (1) Age and sex: The median age of the patients was 53, 52, and 50 in the hemorrhage, ischemia, and headache groups, respectively. Men outnumbered women in all the 3 groups; especially, in the ischemia group, the number of men was remarkably higher than that of women. (2) Location of arterial dissection: The vertebral artery was affected in 85% of the patients in both the hemorrhage and ischemia groups, and in 97% of the patients in the headache group. (3) Radiographic findings: Fusiform dilatation and pearl-and-string sign were the common findings in the hemorrhage group, whereas tapering string and occlusion were more frequent in the ischemia group. Regarding serial changes of the radiographic findings, improvement of the finding was the most common, followed by no change in both the ischemia and headache groups.(4) Treatment: Surgical treatment was administered to 82% of the patients, and endovascular surgery was the main procedure adopted for the hemorrhage group. In contrast, conservative treatment was administered to a majority of the patients in the ischemia and headache groups. Antithrombotic therapy was administered to 79% of the patients in the ischemia group, and to 17% in the headache group. (5) Follow-up periods: The median follow-up period was 5, 10, and 12 months in the hemorrhage, ischemia, and headache group, respectively. (6) Mid-term outcomes: Good outcomes were observed in 57% of the patients in the hemorrhage group; however, 26% of the patients in this group died. Furthermore, good outcomes were observed in 85% and 98% of the patients in the ischemia and headache group, respectively; the mortality rate in these 2 groups was rather low.These data were compared to those of the previous studies, such as the nationwide study in 1995-96 by Yamaura et al. The number of patients in the headache group was higher in this than in the previous studies. The number of patients with hemorrhage who received surgical treatment, especially endovascular surgery, was higher in this than in the previous studies. Furthermore, the number of patients in the ischemia and headache groups who received antithrombotic therapy was higher in this than in the previous studies. However, the clinical features, radiographic findings, and outcomes did not differ significantly between the present study and the previous studies.

Although lumbar drainage (LD) is widely used in skull base surgery (SBS), no cases with intracranial hypotension (IH) following LD-assisted SBS have been reported, and skull base surgeons lack awareness of this potentially life-threatening condition. We report two cases of IH after LD-assisted SBS, a spheno-orbital meningioma and an osteosarcoma in the orbit. Despite a minimal amount of cerebrospinal fluid (CSF) drainage and early LD removal, severe postural headache and even a deteriorating consciousness level were observed in the early postoperative course. Neuroimages demonstrated epidural fluid collections, severe midline shift, and tonsillar sag compatible with IH. Epidural blood patch (EBP) immediately and completely reversed the clinical and radiologic findings in both patients. IH should be included in the differential diagnosis of postural headache after LD-assisted SBS that can be managed successfully with EBP. Persistent leakage of CSF at the LD-inserted site leads to IH. Broad dural dissection and wide removal of bony structure may be involved in the midline shift. EBP should be performed soon after conservative management fails. Further reports will determine the risk factors for IH development following LD-assisted SBS.

Despite accumulating knowledge regarding molecular backgrounds, the optimal management strategy for low-grade gliomas remains controversial. One reason is the marked heterogeneity in the clinical course. To establish an accurate subclassification of low-grade gliomas, we retrospectively evaluated isocitrate dehydrogenase-1 (IDH1) mutation in clinical specimens of diffuse astrocytomas (DA) and oligodendroglial tumors separately. No patients were treated with early radiotherapy, and modified PCV chemotherapy was used for postoperative residual tumors or recurrence in oligodendroglial tumors. Immunohistochemical evaluation of IDH status, p53 status, O6-methylguanine methyltransferase expression, and the MIB-1 index were performed. The 1p and 19q status was analyzed with fluorescence in situ hybridization. Ninety-four patients were followed for a median period of 8.5 years. For DAs, p53 was prognostic for progression- free survival (PFS) and IDH1 was significant for overall survival (OS) with multivariate analysis. In contrast, for oligodendroglial tumors, none of the parameters was significant for PFS or OS. Thus, the significance of IDH1 mutation is not clear in oligodendroglial tumors that are homogeneously indolent and chemosensitive. In contrast, DAs are heterogeneous tumors including some potentially malignant tumors that can be predicted by examining the IDH1 mutation status.