Transition of Akabane virus genogroups and its association with changes in the nature of disease in Japan.

Akabane virus (AKAV) is teratogenic to the foetus of domestic ruminants and causes a significant reproduction loss in cattle in Japan. In several past epizootics in cattle, AKAV was also associated with post-natal encephalomyelitis, mainly in calves and young stock. Previously analysed AKAV isolates in East Asia form two major clusters, genogroups I and II, with isolates involved in encephalomyelitis belonging mainly to the former. Between 2007 and 2013, AKAV epizootics were regularly observed in Japan during the summer/autumn season, and abnormal deliveries and post-natal encephalomyelitis caused by the virus in cattle were reported. During this period, 30 AKAV isolates were obtained from diseased and sentinel cattle, a piglet and Culicoides biting midges throughout Japan and were subjected to genetic comparison and phylogenetic analysis with previous isolates. In 2007, 2011 and 2013, AKAV belonging to genogroup I was identified in the central nervous systems of calves showing neurological disorders. Notably, a total of 165 cases of bovine encephalomyelitis were reported in 2011 and the isolated viruses from affected animals shared high genetic identities with a South Korean isolate that was associated with a large outbreak in 2010, suggesting some epidemiological linkage between these epizootics. Epizootics of genogroup II were observed in 2008 and 2010, but bovine post-natal encephalomyelitis cases rarely occurred. Our findings suggest that the frequent incursion of genogroup I isolates has increased the frequency of post-natal encephalomyelitis cases in Japan in recent years. Infection by genogroup I virus was also identified in piglets with neurological disorders or congenital malformations in 2011 and 2013. The aetiological role of AKAV in pigs should be elucidated in the future.

A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors.

PURPOSE: Binimetinib is a potent, selective MEK1/2 inhibitor with demonstrated efficacy against BRAF- and RAS-mutant tumors. Retinal adverse events associated with MEK inhibitors have been reported in some cases. The aim of this study was to assess single-agent binimetinib, with detailed ophthalmologic monitoring, in Japanese patients with advanced solid tumors. METHODS: This was an open-label phase I dose-escalation and dose-expansion study (NCT01469130). Adult patients with histologically confirmed, evaluable, advanced solid tumors were enrolled and treated with binimetinib 30 or 45 mg twice daily (BID). The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of single-agent binimetinib in Japanese patients. RESULTS: Twenty-one patients were enrolled; 3 and 8 patients had documented BRAF and KRAS mutations, respectively. Two of 6 patients (33 %) receiving binimetinib 45 mg BID in dose-escalation experienced recurrent grade 2 retinal adverse events (AEs) which were reversible, and this dose was declared the MTD and RP2D. All patients experienced ≥1 AE suspected to be treatment related; the most common (>50 %) were blood creatine phosphokinase increase (76 %), retinal detachment and aspartate aminotransferase increase (62 % each), and diarrhea (52 %). There were no complete or partial responses; 14 patients (67 %) had stable disease, which lasted >180 days in 5 patients. Expression of phospho-ERK decreased in the skin following binimetinib treatment at both dose levels, indicating target inhibition. CONCLUSIONS: Binimetinib demonstrated efficacy and acceptable safety in Japanese patients with solid tumors, supporting the 45 mg BID dose of binimetinib as the RP2D.

Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species.

OBJECTIVE: In ovarian cancer cases, recurrence after chemotherapy is frequently observed, suggesting the involvement of ovarian cancer stem-like cells (CSCs). The chemoresistance of ovarian clear cell carcinomas is particularly strong in comparison to other epithelial ovarian cancer subtypes. We investigated the relationship between a CSC marker, aldehyde dehydrogenase 1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. METHODS: Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. RESULTS: High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. CONCLUSIONS: ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.

Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region.

All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML-RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPɛ and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML.

Effects of bevacizumab on plasma concentration of irinotecan and its metabolites in advanced colorectal cancer patients receiving FOLFIRI with bevacizumab as second-line chemotherapy.

PURPOSE: Bevacizumab (BV) prolongs the survival of colorectal cancer patients when combined with irinotecan (CPT-11)-based regimens. In the AVF2107g study, the area under the curve (AUC) ratio for bolus CPT-11/5-fluorouracil (5-FU)/leucovorin (LV) (IFL) with the BV arm to bolus IFL with placebo indicated that SN-38 concentrations may have been increased in subjects receiving BV. However, the mechanism underlying such increase remains unclear, and the difference might be caused by an imbalance between the two arms and a possible inter-subject variability of CPT-11 metabolism. Within-subject comparisons were used to evaluate the effect of BV on advanced colorectal cancer patients when administered with the FOLFIRI regimen as second-line chemotherapy. METHODS: Ten advanced colorectal cancer patients received the FOLFIRI regimen every 2 weeks. At cycle 1, BV was administered following FOLFIRI administration to allow baseline pharmacokinetic (PK) analysis of CPT-11 and its metabolites. From cycle 2, BV was administered just before FOLFIRI administration. Plasma samples were collected under the same condition (at cycle 3). RESULTS: There were no significant differences in the Cmax and AUC0-infinity of CPT-11, SN-38, and SN-38G between cycle 1 (without BV) and cycle 3 (with BV). PK parameters of CPT-11, SN-38, and SN-38G were not significantly affected by BV. There were no significant differences in the changes in the AUC ratio of CPT-11 to SN-38 between cycles 1 and 3, as well as in the ratio of SN-38 to SN-38G. CONCLUSION: BV does not affect the plasma concentration of CPT-11 and its metabolites on FOLFIRI regimen.

A new operative technique for the resection of gastric tube cancer by means of lifting the anterior chest wall and videoscope-assisted surgery.

The prolonged survival of patients receiving surgery for esophageal cancer has led to an increased incidence of adenocarcinoma arising in the gastric tube used for reconstruction (gastric tube cancer). In patients with advanced gastric tube cancer, resection of the gastric tube should be considered, but currently available procedures are very invasive. In patients undergoing curative surgery for gastric tube cancer that has developed after reconstruction through the retrosternal route, the gastric tube is usually resected through a median sternotomy, followed by reconstruction with the colon. However, postoperative complications often occur and treatment outcomes remain poor. We developed a new surgical technique for gastric tube resection without performing a sternotomy in patients with gastric tube cancer who had previously undergone reconstruction through the retrosternal route. Our technique was used to treat two patients. Two Kirschner wires were passed subcutaneously through the anterior chest; the chest was lifted to extend the retrosternal space and secure an adequate surgical field. The stomach was separated from the surrounding tissue under videoscopic guidance. Total resection of the gastric tube was done. The retrosternal space was used to lift the jejunum. Roux-en-Y reconstruction was performed. Neither patient had suture line failure or surgical site infection. Their recovery was uneventful. Our surgical technique has several potential advantages including (i) reduced surgical stress; (ii) the ability to use the retrosternal space for reconstruction after gastric tube resection; and (iii) a reduced risk of serious infections such as osteomyelitis in patients with suture line failure. Our findings require confirmation by additional studies.

Chemosensitivity of patients with recurrent esophageal cancer receiving perioperative chemotherapy.

Perioperative chemotherapy (CT) and chemoradiotherapy are widely used for advanced esophageal cancer. We evaluated the chemosensitivity of patients displaying recurrent esophageal cancer after esophagectomy with perioperative CT. From the database at National Cancer Center Hospital in Tokyo, we extracted recurrent esophageal cancer cases after perioperative CT and evaluated the effectiveness of the first CT against the recurrent disease according to the duration between termination of the original perioperative CT and recurrence with treatment-free intervals (TFIs) 6 months. Systemic CT for their recurrent disease was performed for 30 esophageal cancer patients after perioperative CT. All patients received 5-fluorouracil and cisplatin as perioperative CT, with relapses occurring at TFIs 6 months in 19 patients (all received platinum-containing regimens). The response rate of patients experiencing a recurrence at TFIs 6 months was 0 and 37% (P = 0.029), the median progression-free survival was 2.8 and 4.8 months (log-rank P = 0.001) and the median overall survival was 6.1 and 10.2 months (log-rank P = 0.012), respectively. Recurrence at the TFI

Minimum leakage rate (0.5%) of stapled esophagojejunostomy with sacrifice of a small part of the jejunum after total gastrectomy in 390 consecutive patients.

BACKGROUND: The development of new surgical instruments and devices has facilitated the performance of esophagojejunostomy after total gastrectomy. However, total prevention of dehiscence of anastomoses remains difficult. We introduced a new procedure for esophagojejunostomy using a circular stapler, requiring sacrifice of only a small part of the jejunum. METHODS: The study group comprised 390 consecutive patients who underwent reconstruction by Roux-en-Y esophagojejunostomy, performed with a circular stapler, sacrificing a small part of the jejunum after total gastrectomy. We assessed anastomotic leakage and anastomotic stenosis after surgery. RESULTS: Only 2 patients (0.5%) had leakage and 4 (1.0%) had anastomotic stenosis after reconstruction. All the patients were cured by conservative therapy. CONCLUSIONS: Esophagojejunostomy performed with a circular stapler after total gastrectomy, with sacrifice of only a small part of the jejunum, is a useful and easy procedure, with a leakage rate of 0.5%.

Effect of arachnoid plasty using fibrin glue membrane after clipping of ruptured aneurysm on the occurrence of complications and outcome in the elderly patients.

BACKGROUND: In elderly patients with aneurysmal subarachnoid hemorrhage (SAH), complications including vasosopasm, subdural effusion, and late hydrocephalus, are liable to occur even after aneurysmal surgery. We examined prospectively the efficacy of arachnoid plasty using fibrin glue membrane during surgery of ruptured aneurysms in the elderly patients for preventing complications. The effects on the modified Rankin scale (mRS) and the Glasgow outcome scale (GOS) 3 months after SAH were noted. METHODS: Total of 31 patients aged more than 70 years selected from a consecutive series of patients with aneurysmal SAH, were divided into two groups alternately, a group with arachnoid plasty (n = 16) and a control group without arachnoid plasty (n = 15). Statistical analyses were performed to assess relationships among various clinical and neuroradiological variables, especially between arachnoid plasty and occurrence of symptomatic vasospasm, subdural effusion, late hydrocephalus, or outcome such as mRS and GOS 3 months after onset. FINDINGS: Statistical analyses revealed that arachnoid plasty were associated with late hydrocephalus and subdural effusion negatively, but with better mRS at 3 months after SAH. A tendency to be associated with less frequent symptomatic vasospasm was also noted. CONCLUSION: Arachnoid plasty using fibrin glue is suggested to be effective in preventing complications associated with SAH and aneurysmal surgery. A better outcome in the elderly patients can be achieved.

Efficacy of a navigation system in neuro-endoscopic surgery.

OBJECTIVE: Neuro-endoscopy is playing a greater role in the diagnosis and treatment of several types of lesions, especially in the ventricular system. However, surgical planning and intraoperative orientation during endoscopic surgery are sometimes difficult. The efficacy of a neurosurgical navigation system using three-dimensional computer graphics of magnetic resonance (MR) images in neuro-endoscopic surgery was evaluated in this study. METHODS: We have developed a navigational endoscopic system designed to monitor the tip and direction of the endoscope, with the mirror marker of the navigation connected to a rigid endoscope. Eight patients, 3 cases of aqueductal stenting for isolated fourth ventricle, 3 cases of cystostomy for ependymal cyst, 1 case of septostomy for isolated lateral ventricle, and 1 case of ventricular tap in narrow ventricles, underwent endoscopic surgery using the present system. RESULTS: All patients underwent successful procedures with good outcomes. The present system was very useful in the cases of an accurate ventricular tap in narrow ventricles, identification of anatomic structures, and determining the appropriate route to the target point. CONCLUSIONS: This navigational endoscopic system improved the safety and accuracy of neuro-endoscopic surgery.

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.

A case of delayed brain abscess due to a retained intracranial wooden foreign body: a case report and review of the last 20 years.

A 13-year-old female is presented. When she was six years old, she had fallen, holding wooden chopsticks and got stuck with a chopstick in the right upper eyelid. She was brought to a physician immediately, but a residual foreign body was missed and no particular symptom had developed during 7 years. She visited our department with fever and headache, and a brain abscess and an intracranial foreign body were found on computed tomography (CT) and magnetic resonance image (MRI) 7 years after the penetrating injury. She underwent removal of the object and abscess by craniotomy and recovered without neurological abnormalities. Since intracranial retained wooden foreign bodies frequently cause delayed complications of severe central nervous system infection, surgical removal is necessary even in the absence of symptoms.

Association of pontine small infarction (lacuna) with disturbance of postural stability.

Neuronal degeneration within the brainstem has been reported in patients with impaired postural stability. However, the functional significance of these abnormalities is unknown at present. In the present study, we evaluated the relationship between the presence of pontine lacunae and postural stability measured by stabilometry. A total of 209 consecutive patients without neurological signs were divided into three groups according to the territory of lacunae on magnetic resonance imaging: (1) non-lacunar group, (2) pontine lacunar group, and (3) non-pontine lacunar group. Stabilometry was performed and statokinesigram measures including each Romberg quotient were compared among the three groups. Using multivariate analysis, postural stability was found to be disturbed in the pontine lacunar group compared with the other groups. The data of stabilometry in this group were compatible with disturbance of the central controlling system for keeping postural stability. Pontine lacuna is associated with patients with postural instability. This result may be related to the deterioration of the central coordination system for posture and locomotion.

Insulin down-regulates insulin receptor substrate-2 expression through the phosphatidylinositol 3-kinase/Akt pathway.

Insulin receptor substrate (IRS)-1 and IRS-2 are the major substrates that mediate insulin action. Insulin itself regulates the expression of the IRS protein in the liver, but the underlying mechanisms of IRS-1 and IRS-2 regulation are not fully understood. Here we report that insulin suppressed the expression of both IRS-1 and IRS-2 proteins in Fao hepatoma cells. The decrease in IRS-1 protein occurred via proteasomal degradation without any change in IRS-1 mRNA, whereas the insulin-induced suppression of IRS-2 protein was associated with a parallel decrease in IRS-2 mRNA without changing IRS-2 mRNA half-life. The insulin-induced suppression of IRS-2 mRNA and protein was blocked by the phosphatidylinositol (PI) 3-kinase inhibitor, LY294002, but not by the MAP kinase-ERK kinase (MEK) inhibitor, PD098059. Inhibition of Akt by overexpression of dominant-negative Akt also caused complete attenuation of the insulin-induced decrease in IRS-2 protein and partial attenuation of its mRNA down-regulation. Some nuclear proteins bound to the insulin response element (IRE) sequence on the IRS-2 gene in an insulin-dependent manner in vitro, and the binding was also blocked by the PI 3-kinase inhibitor. Reporter gene assay showed that insulin suppressed the activity of both human and rat IRS-2 gene promoters through the IRE in a PI 3-kinase-dependent manner. Our results indicate that insulin regulates IRS-1 and IRS-2 through different mechanisms and that insulin represses IRS-2 gene expression via a PI 3-kinase/Akt pathway.

Determination of indices of the corpus callosum associated with normal aging in Japanese individuals.

Indices of the corpus callosum with normal aging and their sex differences were elucidated using quantitative MRI. We studied 94 Japanese men (mean+/-SD 57.3+/-20.8 years, range 6-90 years) and 111 Japanese women (mean+/-SD 61.2+/-17.6 years, range 9-86 years) who had no intracranial lesions on MRI and no history of neurological illness. The widths of the rostrum, body and splenium, the anterior to posterior length, and the maximum height in the midsagittal image were selected for measurement. The Evans index, which is the relative ratio of lateral ventricle expansion, and the maximum width of the third ventricle in the axial image were also estimated for comparison. The widths of rostrum, body and splenium of the corpus callosum became thinner with age. Conversely, the anterior to posterior length and the maximum height of the corpus callosum increased with age. The ratio of the width of the body to the length of the corpus callosum and the ratio of the width of the body to the height of the corpus callosum are best correlated with age. No sex differences in regional size of corpus callosum, including these two ratios, were observed in any raw measures, although ventricular indices were larger in men than women. Evaluation of the ratio of the width of the body to its length and the ratio of the width of the body to its height may enable accurate estimation of normal or pathological changes of the corpus callosum. Aging and pathological atrophy of corpus callosum can be evaluated without any adjustment for gender.

Insulin down-regulates resistin mRNA through the synthesis of protein(s) that could accelerate the degradation of resistin mRNA in 3T3-L1 adipocytes.

AIMS/HYPOTHESIS: Resistin is a peptide secreted by adipocytes and recognized as a hormone that could link obesity to insulin resistance. This study was designed to examine the effect and mechanism(s) of insulin on resistin expression in 3T3-L1 adipocytes. METHODS: Differentiated 3T3-L1 adipocytes were stimulated with insulin and resistin mRNA expression was examined by Northern blot analysis. In some experiments, the insulin signal was blocked by several chemical inhibitors or overexpression of a dominant negative form (Deltap85) of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase). RESULTS: Insulin treatment caused a reduction of resistin mRNA in time-dependent and dose-dependent manners in 3T3-L1 adipocytes. Pre-treatment with PD98059, an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, or SB203580, an inhibitor of p38 mitogen-activated protein-kinase (p38 MAP-kinase) pathway, did not influence insulin-induced reduction of resistin mRNA. Inhibition of PI 3-kinase by LY294002 or Deltap85 also failed to block insulin-induced reduction of resistin mRNA. Cycloheximide, a protein synthesis inhibitor, completely blocked insulin-induced reduction of resistin mRNA. Actinomycin D, a RNA synthesis inhibitor, also blocked insulin-induced reduction of resistin mRNA, and the decreasing rate of resistin mRNA in cells treated with insulin alone was faster than that with actinomycin D. CONCLUSION/INTERPRETATION: Insulin downregulates resistin mRNA via PI 3-kinase, ERK or p38 MAP-kinase independent pathways in 3T3-L1 adipocytes. The downregulation mechanism of resistin mRNA by insulin would be an indirect event through the synthesis of novel protein(s) that could accelerate the degradation of resistin mRNA.

Heterozygous knockout of the IRS-1 gene in mice enhances obesity-linked insulin resistance: a possible model for the development of type 2 diabetes.

Insulin receptor substrate 1 (IRS-1) gene polymorphisms have been identified in type 2 diabetic patients; however, it is unclear how such polymorphisms contribute to the development of diabetes. Here we introduced obesity in heterozygous IRS-1 knockout (IRS-1(+/-)) mice by gold-thioglucose (GTG) injection and studied the impact of reduced IRS-1 expression on obesity-linked insulin resistance. GTG injection resulted in approximately 30% weight gain in IRS-1(+/-) and wild type (WT) mice, compared with saline-injected controls. There was no difference in insulin sensitivity between lean IRS-1(+/-) and lean WT. Elevated fasting insulin levels but no change in fasting glucose were noted in obese IRS-1(+/-) and WT compared with the respective lean controls. Importantly, fasting insulin in obese IRS-1(+/-) was 1.5-fold higher (P<0.05) than in obese WT, and an insulin tolerance test showed a profound insulin resistance in obese IRS-1(+/-) compared with obese WT. The islets of obese IRS-1(+/-) were 1.4-fold larger than those of obese WT. The expression of insulin receptor and IRS-1 and IRS-2 was decreased in obese IRS-1(+/-), which could in part explain the profound insulin resistance in these mice. Our results suggest that IRS-1 is the suspected gene for type 2 diabetes and its polymorphisms could worsen insulin resistance in the presence of other additional factors, such as obesity.

[A case of craniopharyngioma with chemical meningitis as an initial symptom].

We reported a rare case of craniopharyngioma with chemical meningitis due to spontaneous rupture of the tumor. A 50-year-old woman was admitted with high fever, headache, and nausea. On physical examination, she had nuchal rigidity. The examination of her cerebral spinal fluid(CSF) revealed pleocytosis(mononuclear cell dominant), low value of glucose level and high content of protein. The feature of her CSF findings suggested tuberculosis or fungal meningitis, but bacteriologic culture of the CSF was negative. The CT scan showed an isodensity mass in the suprasellar region and a spotty calcification in the third ventricle. The MRI with gadolinium enhancement suggested that the tumor must be craniopharyngioma and that meningitis was a type of chemical meningitis due to spontaneous rupture of craniopharyngioma. The corticosteroid therapy was rather effective to the symptoms of fever and headache. Then the operation was performed by neurosurgeons, and the diagnosis of craniopharyngioma was pathologically confirmed. Spontaneous rupture of craniopharyngioma rarely occurred and was followed by chemical meningitis. This case was an extremely rare condition that presented with chemical meningitis as an initial symptom.