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We provide the details of the successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia. The patient was a 27-year-old Japanese female healthcare worker who was scheduled to undergo pituitary surgery for Cushing’s disease. She had been in close contact with an undiagnosed patient infected with COVID-19 and then developed COVID-19 pneumonia. Despite a lack of known risk factors associated with severe COVID-19 infection, the patient’s dyspnea worsened and her respiratory condition deteriorated, as indicated by the need for 7 L/min oxygen supply by mask to maintain her oxygen saturation at >90%. Medical treatment was initiated to control hypercortisolism by the ‘block and replace’ regimen using steroidogenesis inhibitors and hydrocortisone. The COVID-19 pneumonia improved with multi-modal treatment including antiviral therapy. One month later, after a negative severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) test result and with appropriate protection against virus transmission to medical staff in the operating room and daily medical care nurses, trans-sphenoidal surgery was performed by our highly experienced pituitary surgeon. One month after the surgery, the patient’s basal ACTH and cortisol levels and urinary free cortisol were all under the detection limit. Surgical remission was expected. Since hypercortisolism due to active Cushing’s disease may worsen a COVID-19 infection, multi-disciplinary management that includes appropriate and prompt treatment strategies is mandatory in such cases.

The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy., The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements., All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved., A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA.

Background It is very rare for a choroid plexus tumor to occur intraparenchymally in the absence of a relation to the choroid plexus. Clinical Presentation A case of cerebral intraparenchymal choroid plexus tumor in a 30-year-old woman presenting with left hemiparesis is described. Brain magnetic resonance imaging depicted a large cystic mass in the right frontal lobe. Tumor resection was performed by right frontal craniotomy. No connection with the choroid plexus was observed during the operation. Histologically, the tumor exhibited a glandular structure with a papillary pattern suggesting a neoplasm of epithelial origin. Immunohistochemical analyses revealed the tumor as an atypical choroid plexus papilloma. Conclusion Immunohistochemical findings, especially regarding Kir7.1, are very important for the differential diagnosis of cerebral intraparenchymal choroid plexus tumors from metastatic tumors. The present case reveals that an atypical choroid plexus papilloma can occur intraparenchymally without an association with the choroid plexus. Intraparenchymal atypical choroid plexus papillomas may have previously been diagnosed incorrectly as metastatic adenocarcinomas of unknown origin.

A 24 year-old female presented with a mass lesion in the right temporal lobe. This case was difficult to diagnose using histological and immunological methods and therefore molecular analyses were applied to provide a definitive diagnosis. The tumor was well-demarcated, partially cystic, and irregularly-enhanced on gadolinium-enhanced T1-weighted magnetic resonance images. Pathologically, a large part of the tumor consisted of cells with fine cytoplasmic processes on a myxoid and mucinous background. Cells formed a microcystic structure around the mucinous tissue. Numerous eosinophilic granular bodies, but not Rosenthal fibers, were present. The solid and compact regions of the tumor were composed of fasciculation of dense fibrous glial tissues and occasional multinucleated giant cells. Tumor cells and their fragmented cytoplasmic processes were positively stained with GFAP, while eosinophilic granular bodies were both positive and negative. Xanthomatous changes were not detected and the reticulin fibers were restricted to vascular tissues. The MIB1 index was scored as approximately 10%. In molecular analyses of BRAF, the KIAA1549-BRAF (K16-B9) fusion gene was detected in all tumor regions, whereas BRAF V600E mutation was not detected by either conventional Sanger sequencing or the Eprobe-PCR method. Based on the results of the molecular analyses, this case was diagnosed as pilocytic astrocytoma.

Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors’ employment status. A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants’ first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses. Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence). Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group.

The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known.This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months.The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P.0001) and trigeminal nerve (P.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients.Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.

Objective This single-arm, open-label, Phase II study evaluated the efficacy and safety of single-agent bevacizumab, a monoclonal antibody against vascular endothelial growth factor, in Japanese patients with recurrent malignant glioma. Methods Patients with histologically confirmed, measurable glioblastoma or World Health Organization Grade III glioma, previously treated with temozolomide plus radiotherapy, received 10 mg/kg bevacizumab intravenous infusion every 2 weeks. The primary endpoint was 6-month progression-free survival in the patients with recurrent glioblastoma. Results Of the 31 patients enrolled, 29 (93.5%) had glioblastoma and 2 (6.5%) had Grade III glioma. Eleven (35.5%) patients were receiving corticosteroids at baseline; 17 (54.8%) and 14 (45.2%) patients had experienced one or two relapses, respectively. The 6-month progression-free survival rate in the 29 patients with recurrent glioblastoma was 33.9% (90% confidence interval, 19.2-48.5) and the median progression-free survival was 3.3 months. The 1-year survival rate was 34.5% with a median overall survival of 10.5 months. There were eight responders (all partial responses) giving an objective response rate of 27.6%. The disease control rate was 79.3%. Eight of the 11 patients taking corticosteroids at baseline reduced their dose or discontinued corticosteroids during the study. Bevacizumab was well-tolerated and Grade ≥3 adverse events of special interest to bevacizumab were as follows: hypertension [3 (9.7%) patients], congestive heart failure [1 (3.2%) patient] and venous thromboembolism [1 (3.2%) patient]. One asymptomatic Grade 1 cerebral hemorrhage was observed, which resolved without treatment. Conclusion Single-agent bevacizumab provides clinical benefit for Japanese patients with recurrent glioblastoma.

Health-related quality of life (HRQOL) is not only a degree of health but also reflects patient perceptions and expectations of health. For children with brain tumors, better understanding of HRQOL requires the use of complementary reports from parents and interviewer-administered reports for children. Here, we aimed to test whether or not the trait anxiety of children and the psychological distress of their parents influence children's and parents' responses to HRQOL questionnaires, and whether or not the report-administration method for children influences children's responses to HRQOL questionnaires.One hundred and thirty-four children aged 5-18 with brain tumors and one of their parents completed the Pediatric Quality of Life Inventory(™) (PedsQL(™)) Brain Tumor Module questionnaires. In addition, the children also completed the State-Trait Anxiety Inventory for Children (STAIC), and the parents also completed the Kessler-10 (K10) and health and sociodemographic characteristics questionnaires. The child questionnaires were administered either by the child (self-administered) or an interviewer. Rater-dependent perceptions about HRQOL were derived from the subscales scores of the PedsQL(™) Brain Tumor Module using structural equation modeling based on a multitrait-multimethod model. The STAIC trait-anxiety score, K10 score, report-administration method, and other health and sociodemographic factors related to each child's or parent's perceptions were identified through multiple linear regression analyses of the questionnaire responses. We used a path analysis to estimate the change in a PedsQL(™) child-reported score that occurs when interviewer-administration changes the child's perception about HRQOL.Surveys for 89 children were self-administered while those for 45 were interviewer-administered. The perceptions of the children and parents were calculated by fitting data to the model (chi-squared P = 0.087, normed fit index = 0.932, comparative fit index = 0.978, standardized root mean squared residual = 0.053, and root mean square error of approximation = 0.054). The children's perception of HRQOL was affected by their STAIC trait-anxiety score (b = -0.43, 95% CI [-0.60, -0.25]). The parent's perception was affected by their child's treatment status (b = 0.26, 95% CI [0.09, 0.43]), the parent's K10 score (b = -0.21, 95% CI [-0.37, -0.04]), and by education level (b = 0.17, 95% CI [0.00, 0.34]). The change in the child-reported PedsQL(™) score in relation to the method of administration ranged from -1.1 (95% CI: -3.5, 1.3) on the procedural anxiety subscale to -2.5 (95% CI: -7.6, 2.6) on the movement and balance subscale.Child-reporting of HRQOL is little influenced by the method of administration. Children's perception about HRQOL tended to be influenced by their trait anxiety, while parents' perception was influenced by their psychological distress, academic background, and their child's treatment status.

Purpose Personalized selection of suitable peptides for patients could offer a novel approach to developing cancer vaccines that boost anticancer immunity. We present the results of a phase I trial of 14 kinds of vaccine candidates (ITK-1) in patients with recurrent or progressive glioblastoma multiforme (GBM). Patients and Methods From January 2006 to January 2008, 12 patients from eight Japanese hospitals who were positive for human leukocyte antigen–A24, including 10 patients refractory to temozolomide (TMZ), were enrolled. The dose escalation trial included three dose groups (1, 3, and 5 mg) to determine the safety and tolerability of ITK-1 peptides. Immunologic response was monitored by measuring levels of cytotoxic T-lymphocyte precursors and peptide-specific immunoglobulin G. In another ITK-1 phase I trial for advanced prostate cancer, the vaccination schedule was skipped or discontinued in all three patients receiving the highest dose (5 mg/peptide) because of injection site reactions. This trial was therefore ended without enrollment for the highest dose, and data were analyzed by intention to treat. Results No serious adverse drug reactions were encountered, and treatment was well tolerated. The vaccine induced dose-dependent immune boosting. The recommended dose of ITK-1 peptides is 3 mg/peptide. Conclusion Personalized vaccination with ITK-1 peptides could be recommended in further stages of clinical trials. The safety and increased frequency of immune boosting offers potential clinical benefits in cases of recurrent or progressive GBM, even in TMZ-refractory settings.

Five Japanese children presented with rare xanthogranuloma located in the sellar region between 2000 and 2010 at the Department of Neurosurgery, Hokkaido University Hospital. Endocrinological examination disclosed central diabetes in four patients. Preoperative magnetic resonance (MR) imaging and computed tomography (CT) demonstrated clearly defined intra- or suprasellar masses appearing as isointense or hyperintense on T(1)-weighted MR imaging with no calcification on CT. The tumor was totally removed under preoperative diagnosis of craniopharyngioma in all cases. Histological examination found fibrous tissue with abundant cholesterol clefts and hemosiderin deposits, but no or only tiny amounts of epithelial cells in each case. Therefore, the histological diagnoses were xanthogranuloma of the sellar region, not adamantinomatous craniopharyngioma. Postoperatively, no patient recovered from endocrinological deficits, whereas visual disturbances were improved immediately after operation. Currently, whether xanthogranuloma is distinct from adamantinomatous craniopharyngioma remains unclear. Only a few clinical reports of xanthogranuloma of the sellar region have been reported in pediatric patients. Our series shows that xanthogranuloma should be included in the differential diagnosis of pediatric tumor of the sellar region.

Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that mostly occurs in early childhood and has poor prognosis despite aggressive therapy. Adult cases are rare and, as far as we are aware, only 30 cases have been reported to date. Here we present the case of a 27-year-old female with left parietal AT/RT with the chief complaint of numbness of the right superior limb. First, the tumor was surgically removed and the diagnosis was grade II glioma. With additional radiotherapy, the clinical course after surgery was favorable. After 6 years, she had an operation for recurrence and the diagnosis was grade III glioma. Temozolomide was prescribed, and a disease-free period of 2 years followed. Surgery was performed for a third time for second recurrence with histology of diffuse growth of rhabdoid cells. Immunohistochemistry was partially positive for vimentin and epithelial membrane antigen. Ki-67 labeling index was extremely high and tumor cells showed no staining of INI1 suggestive of diagnosis of AT/RT. We re-evaluated past specimens and none had immunoreactivity of INI1. Ki-67 labeling index and O-6 methylguanine DNA methyltransferase (MGMT) staining were also re-examined and both increased gradually. She is still alive without recurrence for more than 1 year. As far as we are aware, this is the second longest survival of an adult with AT/RT.

Objective: The current study was conducted to evaluate the effects of low-dose craniospinal irradiation (CSI) combined with chemotherapy on non-metastatic embryonal tumors in the central nervous system (CNS), including medulloblastoma and supra-tentorial primitive neuroectodermal tumors (ST-PNET). Methods: All patients were treated according to the following protocol. After surgery, the patients 5 years old received 18 Gy and the patients .5 years old received 24 Gy CSI. The dose to the primary tumor bed was 39.6–54 Gy. Chemotherapy consisted of ifosfamide, cisplatin and etoposide (ICE chemotherapy). Results: Sixteen patients aged 0.5–20.4 (median 6.1) years were enrolled and followed for 11–165 (median 112) months. Both 5-year actuarial overall survival (OAS) and progressionfree survival (PFS) were 81% (95% confidence interval (CI): 62–1 00%) for the 16 patients. Both 5-year OAS and PFS were 82% (CI: 59 –1 00%) for the patients with medulloblastoma and 80% (CI: 45 –1 00%) for the patients with ST-PNET. Both 5-year OAS and PFS were 75% for the eight patients 5 years old and 88% for the eight patients .5 years old. Both 5-year OAS and PFS were 100% for six average-risk patients (3 years or older, total resection and posterior fossa) and 70% for 10 poor-risk patients (others). The median total intellectual quotient at the last follow-up was 85 (ranging from 48 to 103) in 12 patients who were followed for 3 –1 45 (median 49) months. Eight patients received hormone replacement therapy. Conclusion: Low-dose CSI and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the CNS.

Central nervous system (CNS) germinoma is a curable tumor and its recurrence rate after initial therapy may be approximately 10% or higher. This study elucidates the time-course of recurrence and results of salvage therapy. Twenty-five patients with recurrent germinoma treated at Hokkaido University Hospital were retrospectively reviewed. The median age at initial treatment was 12 years (range: 8-37). All patients had been tumor-free for at least 6 months after the initial treatment. The median follow-up period was 134 months (range: 44-338). The median age at first recurrence was 18 years and the median time to the first recurrence was 50 months. Among the patients, 9 (36%) had the first recurrence at 60 months or later. The latest recurrence in a patient occurred 230 months after the initial treatment. The results of salvage therapy were estimated in all 25 patients. Seventeen patients (68%) were salvaged and were tumor-free at the final observation. The remaining 8 patients died of disease. At first recurrence, 11 patients were treated using radiation therapy with or without surgery and 7 out of the 11 patients died due to the recurrent tumor. On the other hand, 13 patients who received salvage chemotherapy and radiotherapy were tumor-free at the last follow-up. In conclusion, late recurrence is not a rare event in patients with CNS germinoma. To identify a true cure rate of this disease, a 10-year or longer observation period may be required. As a salvage therapy, platinum-based chemotherapy followed by wide-field low-dose radiation therapy appears to be effective.

Olfactory neuroblastoma is such a rare malignancy that no consensus has been reached on its management. We analyzed 17 patients with olfactory neuroblastoma treated between April 1980 and March 2004--9 men and 8 women, aged 16 to 76 years old(mean: 50.4 years). Follow-up of current survivors was 1 year 8 months to 16 years 6 months (average: 7 years 9 months). Initially, 2 were treated with surgery alone, 5 with surgery and radiotherapy, and 2 with a combination of these and chemotherapy. Without surgery, radiotherapy alone was conducted in 3 and combined of radiation and chemotherapy in 5. Three of the 5 patients treated with surgery and radiotherapy survive without locoregional recurrence as do 2 with chemotherapy added. All 5 initially treated with craniofacial resection survived more than 5 years. Combined radiotherapy and chemotherapy without surgery was effective in 2. 5- and 10-year overall survival for all patients were 75.5% and 64.7%. Overall 5-year survival of 8 patients with low-grade tumors was 87.5% and of 6 with high-grade tumors 33.3%. In conclusion, combined craniofacial resection plus radiotherapy and chemotherapy seemed to improve survival. Histopathological grading is a prognostic factors.

Congenital brain tumors, especially tumors diagnosed before birth, are very rare. This report presents a case of a congenital gemistocytic astrocytoma diagnosed by antenatal intrauterine ultrasound. An intrauterine MRI revealed hydrocephalus and a mass lesion including massive hemorrhage in the right occipital lobe of a fetus. The patient was delivered by cesarean section and a total excision of the hemorrhagic tumor was carried out on the third day of his life. The histological study revealed gemistocytic astrocytoma (WHO grade II). Neither adjuvant chemotherapy nor radiation was given after the first surgery. Ten months after his birth, a recurrent tumor was depicted on follow-up MRI. The second total excision of the recurrent tumor and chemotherapy using cisplatin and vincristine were performed. The patient is free of disease at the age of 2 years and 6 months.

Objective To determine the efficacy and safety of unilateral deep brain stimulation on the posterior subthalamic white matter, including the zona incerta (ZI) and the prelemniscal radiation (PRL), for tremor-dominant parkinsonian patients and to determine the exact location of electrodes that were most effective. Methods Eight parkinsonian patients with severe resting tremor underwent unilateral stimulation of the ZI/PRL by use of stereotactic guidance. Electrophysiological targeting was obtained by macrostimulation and by somatosensory evoked potentials recorded directly through a quadripolar deep brain stimulation lead. Postoperative computed tomographic scans and magnetic resonance images were performed to confirm anatomic location of the electrode. Parkinsonian motor disabilities were evaluated by use of the Unified Parkinson's Disease Rating Scale in the medication-off state before surgery and every 6 months after electrode implantations. Results The mean location of the clinically effective contacts was in the posterior subthalamic white matter, including the ZI and the PRL (mean, 5.6 +/- 1.2 mm posterior to the midcommissural point, 3.2 +/- 1.1 mm inferior to the anterior commissure-posterior commissure line, and 10.5 +/- 1.2 mm lateral to the midline). At 24 months after operation, ZI/PRL stimulation resulted in significant improvement in mean Unified Parkinson's Disease Rating Scale motor score by 44.3%, contralateral tremor by 78.3%, contralateral rigidity by 92.7%, and contralateral akinesia by 65.7% above the "off-stimulation" scores. Handwriting, posture, and gait were also improved. There were no or only mild adverse events. Conclusion Unilateral ZI/PRL stimulation is a reliable and long-term therapeutic modality and can be considered another surgical target for the treatment of tremor-dominant Parkinson's disease.

The priming solution using in cardiopulmonary bypass (CPB) for infants undergoing cardiac surgery includes considerable amounts of stored blood. Our objective was to test the hypothesis that ultrafiltration (UF) of the stored blood before CPB reduces the unfavorable effects of stored blood and the production of inflammatory cytokines. Fifty pediatric patients with congenital heart defects took part in this study. The patients were randomly divided into two groups: the UF (27 pediatric patients who received UF) and control (23 pediatric patients who did not receive UF) groups. UF was performed with a polysulphone ultrafiltrator before CPB. Blood samples were collected immediately before, during, and 1 h after CPB. The levels of cytokines (TNF-alpha, IL-1beta, IL-8), NH3, and bradykinin were determined. The serum concentrations of NH3 and bradykinin decreased significantly after UF. Compared with the control group, the UF group had significantly lower cytokine production. Water balance in UF group was better than that of control group. The UF group received significantly less inotropic support and shorter duration of ventilator support and ICU stay. We conclude that removal of bradykinin and a decrease in the levels of NH3, potassium, and pH play a significant role in reducing water retention and postoperative lung injury. UF of the blood used to prime the circuit for CPB is a safe and efficient method for use in open heart surgery in small pediatric patients.

The purpose of this study is to investigate a minimally invasive access to a high cervical lesion involving the internal carotid artery. Using 13 fixed cadaveric preparations, we sought to design a surgical approach that would cause minimal involvement of the surrounding structures and maximal exposure to the extreme high cervical area. This technique preserves the function and integrity of the mandible, sternocleidomastoid, posterior belly of digastric and styloid process muscles. The method uses retraction and mobilisation of those muscles, as well as decompression of the facial from the stylomastoid foramen. The internal carotid artery is exposed up to the entry point into the carotid canal. The cranial nerves IX, X, XI and XII are kept in sight up to the jugular foramen. This approach creates a wide corridor into the deep high cervical and inferior cranial base area and can be utilised for high cervical carotid lesions and tumours related to the artery.

OBJECTIVE: The P2 segment of the posterior cerebral artery has remained a challenging region to expose surgically. We establish a surgical strategy for P2-segment aneurysms. METHODS: Each segment of the posterior cerebral artery was classified according to Zeal and Rhoton's classification. Fourteen of 18 P2-segment aneurysms were surgically treated. The patient's outcome, the aneurysm location, and the surgical procedures were evaluated. A cadaveric study was performed to clarify the surgical view obtained via three different surgical approaches. RESULTS: Nine aneurysms were clipped, two were trapped, one was coated, and one was excised with parent artery reconstruction. Cerebral revascularization techniques were used for three patients. The pterional approach exposed the anterior half of the P2a segment. The subtemporal approach revealed the P2a segment, but its exposure was restricted by its localization in the ambient cistern. Via the occipital interhemispheric transtentorial approach, the P2p segment was visible and could be manipulated. When the posterior half of P2a segment was high on a coronal view of magnetic resonance imaging, it was extremely hard to access via any approach. CONCLUSION: A surgical strategy for the P2 aneurysm can be planned with accurate prediction of the aneurysm location. When the localization of an aneurysm on the posterior half of P2a segment is high, a resection of brain tissue may be required.

Purpose : To assess the efficacy and toxicity of small-field fractionated radiotherapy with or without stereotactic boost (SB) for vestibular schwannomas. Methods and materials : Thirty-nine patients with vestibular schwannoma were treated with irradiation between March 1991 and February 1996. Extra-meatal tumor diameters were under 30 mm. Thirty-three patients received small-field fractionated radiotherapy followed by SB. Basic dose schedule was 44 Gy in 22 fractions over 5 1/2 weeks plus 4 Gy in one session. Six patients received small-field fractionated radiotherapy only (40–44 Gy in 20–22 fractions over 5–5 1/2 weeks or 36 Gy in 20 fractions over 5 weeks). p>Results : Follow-up ranged from 6 to 69 months (median, 24 months). Tumors decreased in size in 13 cases (33%), were unchanged in 25 (64%), and increased in one (3%). The actuarial 2-year tumor control rate was 97%. Fifteen patients had useful hearing (Gardner–Robertson class 1–2) and 25 patients had testable hearing (class 1–4) before irradiation. The 2-year actuarial rates of useful hearing preservation (free of deterioration from class 1–2 to class 3–5) were 78%. The 2-year actuarial rates of any testable hearing preservation (free of deterioration from class 1–4 to class 5) were 96%. No permanent facial and trigeminal neuropathy developed after irradiation. The 2-year actuarial incidences of facial and trigeminal neuropathies were 8% and 16%, respectively. Conclusions : Small-field fractionated radiotherapy with or without SB provides excellent short-term local control and a relatively low incidence of complications for vestibular schwannoma, although further follow-up is necessary to evaluate the long-term results.

We studied overexpression of p53, Bcl-2, Bcl-6, c-Myc and Mdm2 proteins by immunohistochemistry for a total of 27 primary central nervous system B cell lymphomas (CNS lymphomas) in immunocompetent patients and one CNS lymphoma in an AIDS patient. The expression of Epstein-Barr (EB) virus-encoded small RNA-1 (EBER-1) was also analysed using in situ hybridisation. Overexpression (more than 20% of cells stained) of p53 protein was detected in 8 of 27 immunocompetent cases (30%); 6 cases showed a nuclear stain and 2 cases showed cytoplasmic stain (nuclear exclusion). Strong Bcl-2 or Bcl-6 immunoreactivity suggestive of overexpression was seen, respectively, in 5 (19%) and 6 (22%) cases; 2 cases were positive for both immunoreactivities. Interestingly, overexpression of Bcl-2 or Bcl-6 was not seen in the cases which showed p53 overexpression (P < 0.03; chi-square test). EBER-1 expression was not detected in any of the 27 immunocompetent cases, but was found in the AIDS-related CNS lymphoma, which also showed an overexpression of Bcl-6, but not Bcl-2. None of the cases showed c-Myc or Mdm2 overexpression. Taken together, it is suggested that CNS lymphoma in immunocompetent hosts is a distinct disease that has a different molecular profile from those of systemic lymphoma and/or AIDS-related CNS lymphoma.

While it is established that p53 mutation plays a critical role in the carcinogenesis of astrocytic brain tumors, its role remains to be clarified for other types of tumors in the central nervous system (CNS). Using a yeast-based assay which tests the ability of human p53 to activate transcription, we analyzed p53 mutations in 85 non-astrocytic CNS tumors, including 4 benign neuronal tumors (3 central neurocytomas and 1 pineocytoma), 12 primitive neuroectodermal tumors, 14 germ cell tumors (7 germinomas, 7 non-germinomatous tumors), 4 craniopharyngiomas, 14 ependymomas, 22 schwannomas, 10 primary brain lymphomas in immunocompetent patients, and 5 bone tumors of the skull. The only tumors found to contain p53 mutations were 3 malignant lymphomas. The presence of mutations in these cases was confirmed by DNA sequencing. Given the high accuracy and sensitivity of the yeast assay and previous negative results using conventional techniques, this indicates that p53 mutation is a rare event in non-astrocytic CNS tumor types examined here.

Germ cell tumours (GCTs) of the central nervous system (CNS) encompass various histological subtypes, and their optimal management has been the subject of debate. To indicate a better management strategy for each subtype, we analysed the records of 111 patients (median age 14 years), who underwent treatment since 1970. With a median follow-up duration of 86 months, the probability of surviving 5 years was: 96% for pure germinoma patients, 100% for mature teratoma, 67% for immature teratoma and 69% immature teratoma mixed with germinoma. The probability of cause-specific progression of germinomas producing human chorionic gonadotropin (HCG) was higher than that of non-producing germinomas (P < 0.01). GCTs that included a highly malignant component, such as embryonal carcinoma or yolk sac tumour, exhibited a poor prognosis with 38% chance of 5-year survival. Late adverse effects of therapy included stroke, secondary malignancy and cognitive, endocrinological, auditory and visual dysfunctions. Of 85 survivors with a median follow-up period of 99 months, 58 patients needed hormone replacement therapy, 26 patients showed poor performance status and, to date, only 1 patient has fathered children. Because the outcomes varied widely for each subtype, the traditional categories, that is, germinoma and non-germinomatous GCT as an extrapolation from the gonadal GCTs, are not suitable for appropriately selecting therapeutic regimen for CNS GCTs.

✓ This report describes a new surgical technique to improve the results of conventional hypoglossal—facial nerve anastomosis that does not necessitate the use of nerve grafts or hemihypoglossal nerve splitting. Using this technique, the mastoid process is partially resected to open the stylomastoid foramen and the descending portion of the facial nerve in the mastoid cavity is exposed by drilling to the level of the external genu and then sectioning its most proximal portion. The hypoglossal nerve beneath the internal jugular vein is exposed at the level of the axis and dissected as proximally as possible. One-half of the hypoglossal nerve is transected: use of less than one-half of the hypoglossal nerve is adequate for approximation to the distal stump of the atrophic facial nerve. The nerve endings, the proximally cut end of the hypoglossal nerve, and the distal stump of the facial nerve are approximated and anastomosed without tension. This technique was used in four patients with long-standing facial paralysis (greater than 24 months), and it provided satisfactory facial reanimation, with no evidence of hemitongue atrophy or dysfunction. Because it completely preserves glossal function, the hemihypoglossal—facial nerve anastomosis described here constitutes a successful approach in patients with long-standing facial paralysis who do not wish to have tongue function compromised.

OBJECTIVE: Radiation-induced glioma is a rare but serious complication of radiotherapy. Underlying radiation-induced mutations in oncogenes or tumor suppressor genes have not previously been described. CLINICAL PRESENTATION: A 16-year-old female patient developed a glioblastoma in the right frontal lobe 10 years after treatment of a suprasellar germ cell tumor with 50 Gy of ionizing radiation. The glioblastoma was undetectable on a high-resolution magnetic resonance image obtained 3 months before diagnosis. METHODS AND RESULTS: A p53 functional assay was used to examine the transcriptional competence of the p53 tumor suppressor gene. This assay scores the content of mutant p53 alleles in tumor and blood samples quantitatively as a percentage of red yeast colonies. The glioblastoma contained 95% mutant p53 alleles, whereas blood from the patient and her parents contained only normal background levels of red colonies. Sequencing revealed that the mutation in the tumor was a 3-base pair deletion affecting codons 238 and 239. Intragenic deletion within the p53 deoxyribonucleic acid binding domain is uncommon in sporadic tumors but would be entirely consistent with misrepair of a radiation-induced double-strand deoxyribonucleic acid break in this case. CONCLUSION: This is the first case in which a causative underlying genetic event has been identified in a radiation-induced glioblastoma. We infer that mutation of one p53 allele occurred at the time of radiotherapy, and the sudden appearance of the tumor 10 years later occurred after loss of the remaining wild-type allele and/or other genetic alterations, such as chromosome 10 loss and epidermal growth factor receptor gene amplification.

A 24-year-old female presented with basilar invagination and kyphoscoliosis of the cervical spine associated with a large intercarotid paraganglioma. She had suffered from pharyngeal discomfort from the age of 9 years due to the tumor. The tumor had originated from the right carotid body and extended in the parapharyngeal space compressing the upper cervical spine. Presumably the slowly growing tumor had caused the kyphoscoliosis and disturbed osseous development of the occipito-atlanto-axial complex, resulting in anterior basilar invagination, hypoplasia of the clivus, and aplasia of the posterior arch of the atlas.

Cerebrospinal fluid (CSF) leakage through dural sutures after craniotomy increases the risk of complications such as persistent CSF fistulas, meningitis, and subcutaneous, graft bone, or epidural infections. The effectiveness of fibrin glue for preventing CSF leakage through dural closure was investigated in 183 patients who underwent frontotemporal craniotomy for unruptured aneurysm. Fibrin glue was used in 138 patients, but not in the other 45. Computed tomography was used to evaluate postoperative extradural fluid collection as a minimal volume of low-density area. Postoperative computed tomography demonstrated transient increases in extradural fluid collection in 55 patients. However, none of these patients received a second surgery for dural repair. Fluid collection occurred in 19 of 45 patients (42%) in whom fibrin glue was not used, and in 36 of 138 patients (26%) in whom fibrin glue was used. The fibrin sealant on the dural suture was a significant factor in reducing the incidence of the fluid leakage (p < 0.05, chi-square test). Fibrin glue is a useful surgical tool for the prevention of postoperative extradural fluid collection through the dural sutures.

A 23 year-old woman presented with dysarthria, hoarseness, dysphasia, ataxia and dyspnoea. MRI showed a mass of heterogeneous intensity at the dorsal medulla oblongata. Laboratory studies revealed high serum alpha-fetoprotein (AFP) and beta-subunit human chorionic gonadotropin (beta-HCG) levels. No other tumours were found on systemic investigation. An intracranial non-germinomatous germ cell tumour (NGGCT) was strongly suspected. The patient received combination chemotherapy using ifosfamide, cisplatin, and etoposide and local irradiation to a total of 52 Gy. Serum AFP and beta-HCG levels normalized after four cycles of chemotherapy and she became asymptomatic apart from mild postural hypotension. A follow-up MRI showed only a tiny residual lesion in the medulla oblongata, which has been stable for more than three years. Surgical resection should be carefully considered in patients with brainstem tumours with elevation of serum tumour markers as chemo- and radiotherapy may be effective for brainstem NGGCT.

Ten children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor of the posterior fossa were treated with total surgical resection, radiation therapy, and ICE chemotherapy regimen with ifosfamide (900 mg/m2, days 1-5), cisplatin (20 mg/m2, days 1-5), and etoposide (60 mg/m2, days 1-5) every 4 weeks for eight cycles. Four children under 2 years old were at first treated with eight cycles of ICE chemotherapy, and then irradiated. The ICE regimen was well tolerated by all children, with no irreversible adverse effects. However, dose reductions during the eight cycles were inevitable mainly due to myelosuppression. Complete remissions were achieved in eight of 10 patients at 1 month after completion of the treatment. One child showed recurrence 21 months after complete remission. The disease-free survival rate was 70% with a mean observation period of 24 months after surgery. The ICE regimen is a useful treatment modality for children with medulloblastoma. Further study is warranted to clarify long-term outcome in a number of patients.

This phase II clinical study evaluated the use of 5-(3-3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) pretreatment to reduce cellular resistance and enhance the antitumor effects of chloroethyl nitrosoureas in 32 patients with supratentorial malignant gliomas, including 13 anaplastic astrocytoma and 19 glioblastoma multiforme. All patients received a total dose of 50-65 Gy radiation therapy after surgery. Chemotherapy consisted of DTIC (1 mg/kg) on days 1-5, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (2 mg/kg) on day 5, and vincristine (0.02 mg/kg) on days 1 and 15 every 5 weeks. One patient achieved complete response and 12 patients showed partial response. Median survival time was 18 months and median time-to-progression was 11 months. No significant toxicity was encountered. There was no significant benefit of this pretreatment to combination chemotherapy when compared with previous results. This study does not support a further role for DTIC as a depleter of O6-alkylguanine deoxyribonucleic acid alkyltransferase activity preceding chloroethyl nitrosourea-based chemotherapy.

The long-term changes during late delayed radiation-induced brain damage were investigated by serial magnetic resonance (MR) imaging of eight patients over a mean follow-up period of 45 months after irradiation. The radiation damage appeared as an enhanced lesion on T1-weighted MR images with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) at 3 to 30 months after radiotherapy (mean 12.8 months). In all patients, an abnormal high signal intensity area on T2-weighted imaging preceded the enhanced lesion. The volume and number of enhanced lesions continued to increase for 3 to 23 months (mean 10.3 months). The high signal intensity area on T2-weighted imaging simultaneously expanded. The lesions were subsequently stabilized, and in four long-term survivors, the Gd-DTPA-enhanced lesions then decreased in size, the intervals from onset to regression were 12, 13, 17, and 35 months (mean 19.3 months), respectively. However, two patients showed a relapse of the enhanced lesion with latent periods of 8 and 9 months, respectively. Finally, the radiation-damaged brain became atrophic including the high signal intensity area on T2-weighted images. Late delayed radiation-induced brain damage continues to progress for over a year and then regresses, but thereafter a relapse may occur.

MACROSCOPIC BENIGN PINEAL cysts, according to previous reports, may preferentially occur in the young population at the fourth decade; symptomatic pineal cysts have been found mainly in females. To confirm the relationship of age and sex to the incidence of pineal cysts, we reviewed 8623 consecutive magnetic resonance images in 6023 patients. Tiny and obscure cysts in the pineal gland were ignored; only the pineal cysts5 mm were examined. The cysts were encountered in 79 (1.3%) of 6023 patients evaluated. The cysts predominantly occurred in females; we found 29 cysts in 3008 males and 50 cysts in 3015 females (P0.05). Young adults had higher incidence of these cysts, with a peak incidence occurring between the ages of 21 and 30 years, then the incidence gradually decreased with age. We found no significant age distribution in males. However, among all groups, young women between the ages of 21 and 30 years had the highest frequency (5.82%). The incidence of pineal cysts among women between the ages of 21 and 30 years was significantly higher than in any other group (P0.001; 21-30 versus 51-60, 61-70, and 71-80). In females, when the incidence below the age of 41 was compared with that above or equal to 41, the z score was 4.98 (P0.001). The cystic expansion of the pineal gland in females appeared to begin at adolescence, and presumably the pineal gland decreases in size with aging. In this article, we will also speculate about the relationship of these changes to the secretory activity of the pineal glands.

Glioblastoma (GBM) is one of the worst cancers in terms of prognosis. Standard therapy consists of resection with concomitant chemoradiotherapy. Resistance to nimustine hydrochloride (ACNU), an alkylating agent, has been linked to methylguanine DNA methyltransferase (MGMT). Daily administration of procarbazine (PCZ) has been reported to decrease MGMT activity. This study investigated the efficacy of ACNU + PCZ compared to ACNU alone for GBM and anaplastic astrocytoma (AA). Patients (20–69 years) who had newly diagnosed AA and GBM were randomly assigned to receive radiotherapy with ACNU alone or with ACNU + PCZ. The primary endpoint was overall survival (OS). This was designed as a phase II/III trial with a total sample size of 310 patients and was registered as UMIN-CTR C000000108. After 111 patients from 19 centers in Japan were enrolled, this study was terminated early because temozolomide was newly approved in Japan. The median OS and median progression-free survival (PFS) with ACNU alone (n = 55) or ACNU + PCZ (n = 56) in the intention-to-treat population were 27.4 and 22.4 months (p = 0.75), and 8.6 and 6.9 months, respectively. The median OS and median PFS of the GBM subgroup treated with ACNU alone (n = 40) or ACNU + PCZ (n = 41) were 19.0 and 19.5 months, and 6.2 and 6.3 months, respectively. Grade 3/4 hematologic adverse events occurred in more than 40 % of patients in both arms, and 27 % of patients discontinued treatment because of adverse events. The addition of PCZ to ACNU was not beneficial, in comparison with ACNU alone, for patients with newly diagnosed AA and GBM.

Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of primary CNS tumors. Because of their rare incidence, previous reports on PPTs are limited in number and the useful molecular markers for deciding histological grading and even selecting chemotherapy are undetermined. In this study, we conducted immunohistochemical analysis of 12 PPT specimens, especially for expression of O⁶-methylguanine DNA methyltransferase (MGMT) to assess whether temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate differentiation (PPTIDs), and three pineoblastomas. Immunohistochemical analysis was performed using antibodies against MGMT, synaptophysin, neurofilament protein (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of 12 cases were positive for MGMT. The mean MIB-1 labeling index was less than 1% in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were positive for synaptophysin and 11 cases, except one PPTID case, showed positive for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic staining of NeuN was observed in five cases. No case was positive for p53. Eleven out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy to TMZ treatment. This is the first report showing MGMT expression in PPTs. In addition, MIB-1 labeling index correlated with WHO grade, although the immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the histological grade.

A 2-year-old female presented with a rare case of recurrent giant cell tumor affecting the frontal bone. She had already undergone partial removal twice at the ages of 14 and 18 months. The tumor was located in the frontal bone, expanding to the ethmoid and orbital bones, and invading the frontal base dura mater. The tumor was totally removed including the surrounding bone and frontal base dura mater. No local recurrence and metastasis were observed at 18 months after the last operation. Most giant cell tumors occur in the epiphyses of long bones and are rare in the cranio-facial bone. These tumors usually affect young adults and few pediatric cases are reported.

A 55-year-old woman presented with an extremely rare primary central nervous system mucosa-associated lymphoid tissue (MALT) lymphoma manifesting as seizure and was subsequently diagnosed with dural MALT lymphoma in the cranium. Magnetic resonance imaging revealed a left frontal dural mass with peritumoral edema. Histological examination of the dural mass confirmed MALT lymphoma and revealed infiltration of small cells with irregular nuclear borders and expression of a B cell marker (CD20) but absence of CD5, CD10, CD23, and cyclinD1. Reactive T-cell infiltration was also seen. Subsequently, local irradiation (40 Gy/20 fractions) was performed. Magnetic resonance imaging showed complete remission just after irradiation was completed. There was no evidence of systemic MALT lymphoma. There has been no recurrence for 3 years without additional therapy.

A 77-year-old woman with cognitive impairment and multifocal progressive lesions on brain MRI was admitted to our hospital. Analysis of blood and cerebrospinal fluid showed no evidence of infection, autoimmune disease, or metabolic abnormalities. Histological examination of biopsied tissue from a lesion in the right frontal lobe revealed an abnormally increased glial cell density with enlarged nuclei and a high MIB-1 index. These pathological findings coupled with her progressive clinical history indicated a diagnosis of gliomatosis cerebri. General characteristics of gliomatosis cerebri include diffuse infiltrative lesions in neuroimaging with or without mass effect. However, the present case showed unusual multifocal manifestations in brain MRI. Therefore, histopathological examination must be taken into account for a proper diagnosis.

A 30-year-old female presented with a central neurocytoma manifesting as positional headache. Magnetic resonance imaging showed a large calcified mass in the right lateral ventricle. The tumor was completely removed surgically. Light microscopy showed a linear arrangement of well-defined cells (beaded-string pattern) containing small round nuclei with abundant perikarya. A perinuclear halo reminiscent of oligodendroglioma was prominent in some cell groups. The tumor was entirely amitotic and free of atypia. Large, plump spheroid bodies lacking nuclei but containing coarse brown pigments were present among the tumor cells. The tumor cells were immunoreactive to neuron-specific enolase and synaptophysin but not glial fibrillary acidic protein or neurofilament. The ultrastructure of the tumor cells included abundant spheroid bodies containing secretory granules around neurons, indicating a dystrophic or aborted process of neuronal differentiation rather than a completely-differentiated central neurocytoma.

Our therapeutic strategy for the petroclival meningioma (PCM) allows for observation for asymptomatic and microsurgery for symptomatic cases. For evaluation of this strategy, functional status assessed by the Karnofsky Performance Score (KPS) in each group was retrospectively analyzed. The records of 29 patients with PCMs were reviewed. Fifteen patients were enrolled in the observation group and the median follow-up period was 40 months (range, 5-170). Eighteen patients underwent operative procedures for resection of PCMs and the median follow-up period was 65.5 months (range, 9-194). In the observation group, 60% of the cases showed radiological tumor growth during the follow-up period. There was functional deterioration in 47% of the cases. The growing tumors were unpredictable. In the microsurgery group, gross tumor resection was accomplished in 22% of the cases. The surgical morbidity rate, a KPS less than 80, at three months after surgery and at the time of the last follow-up was 56% and 6%, respectively. Postoperative KPS at three months after surgery was significantly worse than preoperative KPS. However, most of the patients with a worse KPS had recovered at the time of the last follow-up and they had a favorable functional outcome. Regarding the degree of the KPS change, there was no significant difference between the observation and the microsurgery groups during the follow-up periods. Based on the functional outcomes of each group, our therapeutic strategy for PCMs was shown to be reasonable and warranted.

(11)C-Methionine positron emission tomography (MET-PET) has been used to distinguish brain tumor recurrence from radiation necrosis. Because the spatial resolution of conventional PET scanners is low, partial volume effect (PVE) may decrease the detectability of small tumor recurrence. The aim of this study is to investigate the diagnostic value of MET-PET upon semiquantitative analyses in particular PVE-affected small lesions.First, we performed a phantom experiment to investigate what size lesion is affected by PVE. This study included 29 patients (33 lesions) suspected of recurrent brain tumors by magnetic resonance imaging (MRI) after radiation therapy. All of them received MET-PET. Semiquantitative analysis was performed using maximum standardized uptake value (SUVmax) and lesion-versus-normal ratio (L/N ratio). ROC analysis was also assessed about the diagnostic value of MET-PET.From the result of the phantom experiment, lesions smaller than 20 mm in brain mode or smaller than 30 mm in whole-body mode were defined as PVE-affected lesions. Histological analysis or clinical follow-up confirmed the diagnosis of tumor recurrence in 22 lesions, and radiation necrosis in 11 lesions. L/N ratios of recurrence and necrosis for overall lesions were 1.98 ± 0.62 and 1.27 ± 0.28, respectively (p0.01). In the PVE-affected lesions, L/N ratio for recurrence (1.72 ± 0.44) was also significantly higher than that for necrosis (1.20 ± 0.11) (p0.01). On the ROC analysis for the PVE-affected lesions, the area under the curve for L/N ratio (0.897) was significantly higher than that for SUVmax (0.718) (p0.05). These areas under the curve were almost equal to that of overall lesions for L/N ratio (0.886) and for SUVmax (0.738).Semiquantitative analysis of MET provided high diagnostic value even for PVE-affected small lesions. MET-PET enables early diagnosis of recurrence of brain tumor in the follow-up after the radiation therapy.

Peduncular hallucinosis is a rare phenomenon characterized by visual hallucination consisting of vivid, colored image of people, animals, scenes or geometric patterns. In most of the cases the hallucination is accompanied by sleeping disorder, and is by the patient recognized as not being real. It can be observed mainly in patients with thalamic/midbrain vascular disease, and is less frequently seen in brain stem tumor. The damage of the ascending reticular activating system by brain stem compression causing dream activity releasing what is normally suppressed during wakefulness is thought to be the mechanism of peduncular hallucinosis. The authors report a 13-year-old female presenting peduncular hallucinosis due to brainstem compression by a pineocytoma. The patient had a 3-month history of complex visual hallucination and slight somnolence. The hallucination mainly consisted of TV game characters, animals, and vegetables which were colorful and vivid. She was well oriented and realized that the hallucination was not real. MRI showed a pineal mass compressing the quadrigeminal plate inferiorly. There was mild obstructive hydrocephalus due to aqueduct stenosis. The tumor was totally removed and was pathologically diagnosed as pineocytoma. After the surgery, the hallucination ameliorated remarkably. Although the administration of benzodiazepine exacerbated the hallucination and sleep disorder, oral carbamazepine was clearly effective and produced nearly complete disappearance of hallucination. To the best of our knowledge, this is the first report of peduncular hallucinosis caused by quadrigeminal plate compression by a pineal tumor.

OBJECTIVE: For quick and stable identification of the primary motor area (PMA), diffusion tensor imaging (DTI) data were acquired and corticospinal tractography was mathematically visualized. METHODS: Data sets of DTI, anatomic magnetic resonance imaging, and functional magnetic resonance imaging with finger-tapping tasks were acquired during the same investigation in 30 patients with a brain lesion affecting the motor system. Off-line processing of DTI data was performed to visualize the corticospinal tract, placing a seed area in the cerebral peduncle of the midbrain, where the corticospinal tract is densely concentrated. Somatosensory evoked magnetic fields and intraoperative cortical somatosensory evoked potentials were recorded with electrical stimulation of the median nerve to confirm the results of the corticospinal tractography. RESULTS: Functional magnetic resonance imaging and somatosensory evoked magnetic fields failed to identify the PMA in eight patients (16.7%) and one patient (3.8%) investigated, respectively, because of cortical dysfunctions caused by brain lesions. DTI data were acquired within 3 minutes without patient tasks. Using the appropriate seed area and fractional anisotropy, corticospinal tractography successfully indicated the PMA location in all patients. The suspected PMA and central sulcus locations were confirmed by the cortical somatosensory evoked potentials. CONCLUSION: Corticospinal tractography enables identification of the PMA and is beneficial, particularly for patients who present with dysfunction of the PMA.

Purpose Although the effectiveness of stereotactic radiosurgery for nonacoustic schwannomas is currently being assessed, there have been few studies on the efficacy of stereotactic radiotherapy (SRT) for these tumors. We investigated the long-term outcome of SRT for nonacoustic intracranial nerve schwannomas. Methods and Materials Seventeen patients were treated between July 1994 and December 2006. Of these patients, 7 had schwannomas located in the jugular foramen, 5 in the trigeminal nerve, 4 in the facial nerve, and 1 in the oculomotor nerve. Radiotherapy was used as an initial treatment without surgery in 10 patients (59%) and after initial subtotal resection in the remaining patients. The tumor volume ranged from 0.3 to 31.3 mL (mean, 8.2 mL). The treatment dose was 40 to 54 Gy in 20 to 26 fractions. The median follow-up period was 59.5 months (range, 7.4–122.6 months). Local control was defined as stable or decreased tumor size on follow-up magnetic resonance imaging. Results Tumor size was decreased in 3 patients, stable in 13, and increased in 1 after SRT. Regarding neurologic symptoms, 8 patients (47%) had improvement and 9 patients were unchanged. One patient had an increase in tumor size and received microsurgical resection at 32 months after irradiation. No patient had worsening of pre-existing neurologic symptoms or development of new cranial nerve deficits at the last follow-up. Conclusions SRT is an effective alternative to surgical resection for patients with nonacoustic intracranial nerve schwannomas with respect to not only long-term local tumor control but also neuro-functional preservation.

Carney complex is a rare autosomal-dominant, familial tumor syndrome first described in the mid 80's. This syndrome is multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous, and neural tumor, in addition to a variety of pigmented lesions of the skin and mucosa. We report the case of a 12-year-old female patient with Carney complex who manifested a high value of serum growth hormone (s-GH), cutaneous angiomyxomas and labial pigmented lesions. Magnetic resonance imaging (MRI) revealed a cystic pituitary tumor. We carried out removal of the pituitary tumor via the transsphenoidal approach. In addition to the pituitary adenoma, pathological examination revealed the presence of a Rathke cleft cyst. So far, approximately 500 cases of this disorder have been described, but there have been no cases similar to our case described here. Therefore, the present case seems to be the first case of Carney Complex complicated with pituitary adenoma and Rathke cleft cyst.

For children with craniosynostosis presenting intracranial hypertension and facial hypoplasia, different techniques have been used. Commonly, an initial frontoorbital advancement to expand a tight cranium volume was followed by Le Fort III osteotomy to repair midface abnormalities several months later. The 2-stage surgeries were unified into a 1-step procedure to optimize treatment. We here report results of frontofacial monobloc advancement, applying gradual distraction by a rigid external distraction device. Three patients were treated with excellent functional and cosmetic outcome with high rate of patient satisfaction. There was no remarkable complication.

Sino-orbital invasive aspergillosis has been regarded as a lethal disease. The authors report a case with a successful treatment result. A 65 year-old woman, with mild diabetes mellitus, presented progressive right visual disturbance, diplopia, ptosis, and severe periorbital pain over a period of 2 weeks. MR images with gadolinium contrast showed a heterogeneously enhanced mass extending from the right orbital apex to the cavernous sinus. Despite steroid pulse therapy, her symptoms progressed. An open biopsy revealed invasive sino-orbital aspergillosis. Intravenous and oral antifungal agents were administered, but the aspergilloma gradually expanded. Her general status deteriorated due to intractable periorbital pain that was resistant to narcotic analgesics. By a craniotomy, the aspergilloma involving the orbit and cavernous sinus was radically removed leaving the internal carotid artery intact and simultaneously rhizotomy of the trigeminal nerve was carried out. The postoperative course was uneventful and the pain was remarkably ameliorated. Three years after the surgery, she has been well, receiving voriconazole and experiencing no relapse of the disease.

One-stage frontofacial monobloc advancement has been used to treat patients with craniofacial synostosis including Crouzon disease. Nishimoto et al. first applied a rigid external distraction system for two patients. However, precise surgical techniques and proper indication for this gradual distraction method have not yet been established. This report describes the advantages and detailed surgical methods of frontofacial monobloc advancement using a Rigid External Distraction (RED- II) System. Three patients with severe craniofacial synostosis including Crouzon disease and Treacher Collins syndrome were treated. The ages of patients were 9, 9, and 8 year old, respectively. The RED- II System was safely applied for these young children and cosmetic results were sufficient. No major postoperative complications occurred.

Objective It is known that functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are sensitive to the frontal and temporal language function, respectively. Therefore, we established combined use of fMRI and MEG to make reliable identification of the global language dominance in pathological brain conditions. Methods We investigated 117 patients with brain lesions whose language dominance was successfully confirmed by the Wada test. All patients were asked to generate verbs related to acoustically presented nouns (verb generation) for fMRI and to read three-letter words for fMRI and MEG. Results fMRI typically showed prominent activations in the inferior and middle frontal gyri, whereas calculated dipoles on MEG typically clustered in the superior temporal region and the fusiform gyrus of the dominant hemisphere. A total of 87 patients were further analyzed using useful data from both the combined method and the Wada test. Remarkably, we observed a 100% match of the combined method results with the results of the Wada test, including two patients who showed expressive and receptive language areas dissociated into bilateral hemispheres. Conclusion The results demonstrate that this non-invasive and repeatable method is not only highly reliable in determining language dominance, but can also locate the expressive and receptive language areas separately. The method may be a potent alternative to invasive procedures of the Wada test and useful in treating patients with brain lesions.

Temozolomide (TMZ) has demonstrated activity and acceptable toxicity for the treatment of recurrent malignant gliomas in carious prospective phase II studies. No information is, however, available on TMZ treatment for recurrent malignant glioma in Japanese patients. We report Hokkaido University Hospital experience on 35 adult patients with a recurrent malignant glioma, including 13 glioblastomas, 9 anaplastic astrocytomas, and 13 anaplastic oligondendroglial tumors. The median age was 52 years. The starting dose of TMZ was 150 mg/m2/day for 5 days. When no remarkable toxicity was observed, the dose was increased to 200 mg/m2 for subsequent cycles, every 4 week. In the 35 patients, the overall objective response rate (partial response) was 12% and 74% of the patients achieved disease stabilization. The median progression-free survival was 28 weeks and the median overall survival was 43 weeks. Although hematological toxicity was the most frequent adverse event (CTC grade 3 or 4 in 6 patients), overall toxicity was generally mild. Four patients required hospitalization due to the toxicity, but 28 patients had been treated with TMZ at our outpatient clinic. These results suggested that the reported efficacy and toxicity profile of TMZ for the treatment of Japanese patients with recurrent malignant glioma is reproducible from the setting of clinical trials in the western countries.

Objective and importance Hemifacial spasm is rarely caused by facial nerve lesions in the temporal bone. Intratemporal facial nerve hemangiomas may initially present as facial spasm. Clinical presentation A 30-year-old woman developed right hemifacial spasm. Physicians observed slight weakness on the right side of her face, in addition to the hemifacial spasm, but routine radiological examinations did not detect any abnormal findings along the course of the facial nerve. Although the patient underwent neurovascular decompression, the spasm persisted postoperatively. Two years after surgery, the right facial palsy progressed. Concurrently, the hemifacial spasm diminished. High-resolution computed tomography demonstrated a small mass lesion expanding the cortex of the right petrosal bone involving the geniculate ganglion of the facial nerve. Intervention The patient underwent a second craniotomy through a subtemporal extradural route, and the tumor was completely removed. A pathological examination demonstrated a cavernous hemangioma. Conclusion Routine radiological examinations may fail to detect small intratemporal facial nerve hemangiomas, particularly at the geniculate ganglion. Therefore, when physicians encounter atypical facial spasm, the intratemporal portion of the facial nerve should be carefully examined using high-resolution computed tomography.