Search

INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux‐M), as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second‐line arms, patients with EGFR‐amplified recurrent WHO grade III/IV glioma received Depatux‐M plus chemotherapy (temozolomide) or Depatux‐M alone regardless of EGFR status. In first‐line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux‐M plus chemoradiotherapy. The study was halted following lack of survival benefit with first‐line Depatux‐M in the global trial INTELLANCE‐1. The primary endpoint was 6‐month progression‐free survival (PFS) in patients with EGFR‐amplified tumors receiving second‐line Depatux‐M plus chemotherapy. Common nonocular treatment‐emergent adverse events (TEAEs) with both second‐line and first‐line Depatux‐M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second‐line Depatux‐M plus chemotherapy and all patients receiving second‐line Depatux‐M alone or first‐line Depatux‐M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6‐month PFS estimate was 25.6% (95% confidence interval [CI] 11.4‒42.6), and median PFS was 2.1 months (95% CI 1.9‒3.9) with second‐line Depatux‐M plus chemotherapy in the EGFR‐amplified subgroup. This study showed acceptable safety profile of Depatux‐M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263)., INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin, as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in Japanese patients with World Health Organization grade III/IV glioma. The results of this trial demonstrate an acceptable safety profile of depatuxizumab mafodotin, with ocular side effects being the most common adverse events that were mostly reversible. Second‐line depatuxizumab mafodotin in combination with temozolomide resulted in a 6‐month progression‐free survival estimate of 25.6% (95% confidence interval 11.4‒42.6) in patients with EGFR‐amplified tumors and showed encouraging antitumor activity in this subgroup of patients (NCT02590263).

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

A monoallelic germline alteration of ARMC5 causes primary bilateral macronodular adrenal hyperplasia (PBMAH) with Cushing’s syndrome via its subsequent somatic alteration on the other allele as the second hit. PBMAH is sometimes complicated with meningioma. Dependency of such a multi-organ disease on the second hit mechanism was reported before, but this finding has not been confirmed yet. We describe a case of a 65-year-old female with PBMAH, carrying a heterozygous germline alteration of ARMC5, p.R267*, complicated with meningioma associated with somatic loss of heterozygosity (LOH) of the unaffected allele. Pathogenic alterations of ARMC5 may also contribute to the development of meningioma by the two-hit mechanism.

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

Oligodendrogliomas with 1p/19q-codeletion are relatively slow progressive tumors that show good response to chemo-radiation therapy after resection. The median survival is about 15 years regardless of WHO grade, although recurrences are mostly inevitable and there is no standard treatment for recurrence. We experienced 5 oligodendroglioma cases who underwent re-radiation for recurrent tumors after chemo-radiation treatment. We retrospectively investigated those for response to re-radiation, the duration from first radiation to second radiation, and Karnofsky Performance Status (KPS) before and after the re-radiation. Patients were all male; the median radiation dose for primary tumor was 60Gy (54-60Gy), the median age at first radiation was 46 years (35-59), the median duration from the first radiation to re-radiation was 65 months (range 18-116 months), and the median follow-up period after re-radiation was 15 months (1-39 months). In all 5 cases, tumors showed good response to re-radiation. In 3 of the 5 cases, tumor recurred in corpus callosum and/or lateral side of cerebral hemisphere or basal ganglia contiguous with primary tumor sites and were radiated by IMRT (50Gy/25fr) . In 2 cases, tumors recurred around the fourth ventricle and posterior fossa and underwent conventional radiation (54Gy/30fr and 30Gy/10fr). In 2 of the 5 cases, the tumors re-recurred 24 months later after re-radiation, but the KPS were maintained until re-recurrence. For oligodendrogliomas, re-radiation therapy appears to be very effective to recurrent tumors after first chemo-radiation. Although evaluation for longer-term side effects is to be examined, re-radiation appears to be a good option for recurrent oligodendrogliomas after first chemo-radiation therapy.

Arteriovenous malformations (AVM) are congenital vascular lesions fed by arterial feeders originating from branches of the internal carotid artery (ICA) or vertebrobasilar artery. We experienced unique AVMs arising in the midline Galenic region, receiving blood supply from the ICA/vertebral artery systems and the external carotid artery system. We retrospectively reviewed data on eight patients who had an AVM arising in the Galenic region and were treated in the University of Tokyo Hospital between 1990 and 2019. The median age at diagnosis was 62 years. Three cases (38%) presented with obstructive hydrocephalus due to aqueduct obstruction caused by an engorged vein of Galen. In all cases, feeders from dural arteries were present and the vein of Galen was the primary drainer. All patients underwent stereotactic radiosurgery. Five patients were followed for > two years; nidus obliteration was confirmed in one, and > 75% shrinkage was confirmed in three, while one patient died due to hemorrhage. Altogether, AVMs arising in the Galenic region are rare and exhibit several peculiar characteristics including the presence of dural feeders, an older age at presentation and presentation with obstructive hydrocephalus.

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

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

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

BACKGROUND Manual segmentation of brain tumor images from a large volume of MR images generated in clinical routines is difficult and time-consuming. Hence, it is imperative to develop a machine learning model for automated segmentation of brain tumor images. PURPOSE Machine learning models for automated MR image segmentation of gliomas may be useful. However, the image differences among facilities cause performance degradation and impede successful automatic segmentation. In this study, we proposed a method to solve this issue. METHODS We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets collected from 10 facilities. Three models for tumor segmentation were developed. The BraTS model was trained on the BraTS dataset, and the JC model was trained on the JC dataset; whereas, the Fine-tuning model was a fine-tuned BraTS model using the JC dataset. RESULTS MR images of 544 patients were obtained for the JC dataset. Half of the JC dataset was used for independent testing. The Dice coefficient score of the JC model for the JC dataset was 0.779± 0.137, whereas that of the BraTS model was remarkably lower (0.717 ± 0.207). The mean of the Fine-tuning models for the JC dataset was 0.769 ± 0.138. There was a significant difference between the BraTS and JC models (P < 0.0001) and the BraTS and Fine-tuning models (P = 0.002); however, no significant difference was observed between the JC and Fine-tuning models (P = 0.673). CONCLUSIONS Application of the BraTS model to heterogeneous datasets can significantly reduce its performance; however, fine-tuning can solve this issue. Since our fine-tuning method only requires less than 20 cases, this methodology is particularly useful for a facility where there are a few glioma cases.

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

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

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

Background Tumors extending into the optic canal can cause progressive visual impairment because of optic nerve compression. Prompt surgical resection is often necessary. When the tumor is located medially in the optic canal, endoscopic transnasal surgery provides a safer, less invasive alternative to a transcranial approach. Case Description We recently encountered a case of small solitary fibrous tumor in the optic canal causing rapid visual deterioration. The radiographic findings of preoperative imaging studies were compatible with those of meningioma; however, unlike meningioma, bleeding from the tumor was profuse during the operation. The endoscopic transnasal approach was effective for handling the highly vascularized tumor in this delicate region, and gross total removal was achieved with postoperative gradual improvement in his visual function. Nevertheless, the tumor recurred after 6 months, and re-resection was performed using the same surgical corridor, followed by adjuvant radiotherapy. Conclusions Endoscopic transnasal surgery is a valuable option for aggressive lesions in the optic canal. Although the efficacy of radiotherapy for solitary fibrous tumor remains controversial, it should be considered when the tumor shows progressive features.

Introduction: Accumulating recent evidence demonstrated that even low-grade gliomas consist of heterogeneous cell populations and that recurrent tumors often demonstrated further complex clonal evolution, which lead to marked intratumoral heterogeneity. Due to such heterogeneity, the emergence of malignant clones resistant to therapy can occur easily. Therefore, understanding of the changes of the molecular profile during tumor progression is important to develop a proper treatment strategy. To this end, we performed comparative gene profile analysis between primary low-grade and recurrent gliomas. Methods: Multi “omics” analysis was performed in a large number of glioma samples that includes 26 paired samples of primary and recurrent astrocytic tumors. For “omics” analysis, we performed exome sequencing and RNA-sequencing using Illumina HiSeq, as well as epigenomic profile analysis using an Illumina Infinium 450K methylation chip. Results: By comparing somatic non-synonymous mutations of tumor samples, we observed that only a limited number of crucial driver mutations were retained in recurrent tumors in most cases, and that recurrent tumors gained many new mutations, indicating significant temporal heterogeneity. Interestingly, low-grade glioma treated by temozolomide - a common chemotherapeutic agent for glioma - acquired numerous de novo mutations accompanying mutations in mismatch repair genes and showed a “hypermutator phenotype”. Genome-wide DNA methylation analysis revealed characteristic DNA demethylation during malignant progression in a subset of IDH1/2 mutant astrocytic tumors, which initially showed the glioma CpG island methylator phenotype (G-CIMP). We labeled these tumors as “G-CIMP-demethylated”. Most demethylated loci were located outside of the CpG island. DNA demethylation accompanied the upregulation of mitosis related genes, which are considered to be related to the enhanced tumor growth of these G-CIMP-demethylated tumors. Integrated multi “omics” analysis demonstrated that G-CIMP-demethylated gliomas frequently harbor the RB pathway alterations. Conclusions: Recurrent tumors had a markedly different molecular profile from their primary tumor. The characteristic changes observed in the recurrent tumors are expected to be a future therapeutic target.

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

2065 Background: The poor prognosis of glioblastoma (GBM; WHO grade IV) results from a high rate of disease recurrence and lack of effective treatment options. Depatuxizumab mafodotin (depatux-m, ABT-414) is comprised of an EGFR-directed antibody, depatuxizumab (depatux, ABT-806), conjugated to the microtubule toxin monomethyl auristatin F (MMAF, mafodotin). Once bounded with tumor cells, depatux-m is internalized and releases the cytotoxin, resulting in cell death. Here, we report safety, pharmacokinetic (PK) and efficacy in an ongoing phase 1/2 study of Japanese patients with/without EGFR-amplified recurrent GBM (rGBM). Methods: M13-714 (INTELLANCE-J, NCT02590263) is a non-randomized, phase 1/2 study in Japanese patients. Phase 1 assessed tolerability and PK where the dose escalation of depatux-m was from 0.5 to 1.25 mg/kg/Q2W at day 1 and 15 during 28-day cycle until progression disease (PD) or intolerable toxicity. Phase 2 assessed efficacy and safety of depatux-m in EGFR-amplified, rGBM and patients received 1.0 mg/kg of depatux-m on day 1 and 15 + 150 mg/m2 temozolomide (TMZ) on days 1-5 during each 28-day cycle until PD or intolerable toxicity. Results: As of 10 Jan 2019, 38 patients (WHO grade ≥3) were enrolled (9 in phase 1, 29 in phase 2). There was no dose limiting toxicity in phase 1. The recommended phase 2 dose was 1.25 mg/kg where the most common adverse events (AEs) were punctate keratitis in 21 patients (72%); lymphopenia in 14 patients (45%), thrombocytopenia in 13 patients (41%). Grade 3/4 AEs included thrombocytopenia and lymphopenia in 20 patients (69%). Ocular AEs were reported in 27 patients (93%) including punctate keratitis (72%). PK results (31 patients) in both phases were similar to those of non-Japanese result. Progression Free Survival (PFS) of 27 patients in phase 2 for 12 and 6 months were 8% and 27.5% respectively. The median PFS was 4 months. The overall survival (OS) for 24, 12 and 6 months were 28%, 62.5% and 93% respectively. The median OS was 15.5 months. Conclusions: Preliminary safety, PK and efficacy in Japanese patients with/without EGFR-amplified, rGBM suggests depatux-m was tolerated and showed encouraging anti-GBM effects. Clinical trial information: NCT02590263.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.

Thyroid cancer is not a common primary cancer causing intracranial metastasis. Here we report a 74-year-old woman with magnetic resonance imaging (MRI) demonstrating a 4 cm round, heterogeneously enhancing mass in the trigone of the right lateral ventricle. Systemic screening by computed tomography (CT) examination detected a 20 mm nodule with calcification in the thyroid, multiple well circumscribed nodules in bilateral lung filed, and a bone metastasis to the right dorsal rib. Cerebral angiography demonstrated a hypervascular mass fed from anterior and posterior choroidal arteries. Tumor biopsy via parietal transcortical approach confirmed a thyroid carcinoma metastasis to the choroid plexus. Of the 33 reported cases of choroid plexus metastasis, 14 (42%) are from kidney and 3 (9%) from thyroid cancer, which appears to be overrepresented considering their prevalence among all brain metastasis. There may be seed-and-soil relationship between thyroid cancer and choroid plexus.

Background and Purpose— The frequency and pattern of symptomatic recurrence of spontaneous intracranial arterial dissection (IAD) are unknown. Methods— A follow-up study of 143 patients (85 men, 58 women; mean age, 50.7 [7–83] years) with spontaneous IADs at The University of Tokyo and affiliated hospitals from 1980 to 2000 was conducted. Tissue samples of IAD vessels obtained from 13 patients at various intervals from onset were also examined histologically. Results— With a mean follow-up of 8.2 years, symptomatic recurrence occurred in 47 patients (33%). Of 37 cases initially presenting with hemorrhage, 35 developed hemorrhagic recurrence with a mean interval of 4.8 days, and 2 developed nonhemorrhagic recurrences after 21 and 85 months, respectively. Of 10 patients initially presenting with nonhemorrhagic symptoms, 1 developed hemorrhagic recurrence 4 days later, and 9 developed nonhemorrhagic recurrences with a mean interval of 8.6 months. Histopathologically, the affected vessels in the acute stage of hemorrhage (days 0–6) demonstrated insufficient granulation formation within the pseudolumen, followed by marked intimal thickening around the pseudolumen and recanalizing vessel formation in the late stage (>day 30). In the late stage of brain ischemia, subintimal and subadventitial hemorrhage accompanied with intimal thickening was observed. Conclusions— These data indicate that IAD is a disease carrying a relatively high risk of symptomatic recurrence, apparently occurring in 3 phases and patterns: early hemorrhagic recurrence, late nonhemorrhagic recurrence, and chronic fusiform aneurysm transformation. Knowledge of this triphasic recurrence and corresponding histopathological characteristics help determine the treatment and follow-up strategy for IAD patients.

The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients’ treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P

Object Gamma Knife surgery (GKS) has gained increasing relevance in the treatment of metastatic brain tumors, but many metastatic tumors contain a large cystic component and often exceed the size limit for GKS. For such lesions, the authors adopted a procedure in which stereotactic aspiration is first performed and followed immediately by GKS on the same day. In this paper, the authors describe this 1-day combined procedure and evaluate its efficacy. Methods Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were examined. Results Tumor volume, including the cystic component, decreased from 8.0–64.2 cm3 (mean 20.3 cm3) to 3.0–36.2 cm3 (mean 10.3 cm3) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm3, which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11 months (range 1–27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement. Conclusions The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases.

Here we report a metastatic brain carcinosarcoma from the uterus that posed a problem on diagnosis by containing an extensive gliomatous component. A 56-year woman developed motor aphasia 3 months after hysterectomy for a uterine tumor. Magnetic resonance imaging (MRI) demonstrated a left frontal cystic tumor, which was treated by stereotactic radiosurgery. The lesion recurred 5 months later and was resected. Histological examination demonstrated neoplastic cells that were positive for glial fibrillary acidic protein (GFAP), leading to the diagnosis of high-grade glioma. This lesion recurred again after 9 months, and was resected again. The tumor tissue mostly consisted of GFAP-positive gliomatous cells, but close examination identified a sarcomatous component compatible with the metastatic lesion from the uterine sarcoma. This sarcoma component contained GFAP-negative-CD10-positive cells and GFAP-positive-CD10-negative cells. There was no clear border between those components, and, therefore, the lesion was considered to be a metastatic tumor from the uterus showing extensive neural differentiation. Although rare, uterine tumors are known to show such neural differentiation, and the histological diagnosis in such cases can be challenging.

Study design Sham-operation-controlled animal study to assess alterations in blood flow in the spinal cord in a chronic compression model. Laboratory investigation. Objective Cervical myelopathy is a common cause of disability in elderly patients. Hypothesis was made that ischemia subsequent to the spinal cord compression plays an important role in the pathogenesis of the spinal cord dysfunction. This study was undertaken to assess alterations in the blood flow of the spinal cord under chronic compression in a rat model. Summary of background data Histologic study of spinal cord from patients with spondylotic myelopathy showed ischemic tissue changes. Experimentally, spinal cord hypoperfusion in combination with chronic spinal cord compression induced myelopathy in dogs. We previously showed that chronic compression of the spinal cord in rats produces gradual deterioration of mobility of the animals accompanied by cord tissue degeneration compatible with ischemic changes. Methods Chronic compression of the cervical spinal cord was implemented by implantation of a thin urethane polymer sheet under the C5-C6 laminae, which expands by absorbing tissue water over 48-72 hours. The control group underwent sham operation. Twelve weeks later, blood flow to the C3-C4 and C5-C6 spinal cord segments were measured by fluorescent microsphere methods. Results In the control group, the blood flow in the C5-C6 segment was larger than C3-C4 segment. In the compression group, the blood flow in the C5-C6 was significantly reduced compared to the C3-C4 segment. Conclusion Under chronic focal spinal cord compression, there was a decrease of the blood flow in the compressed segment in comparison to the rostral segment. Our data are compatible with the hypothesis that alteration in the spinal cord blood flow contributes to pathogenesis of myelopathy.

Documentation of familial epilepsy is of paramount importance for identification of epilepsy-associated genes, elucidation of pathomechanisms of epilepsy, and development of treatment of epilepsy. We report a Japanese family with 5 members with lateral temporal lobe epilepsy beginning around the second decade of life. All seizures were intractable to medical treatment, and four patients underwent surgical treatment following long-term monitoring by intracranial electroencephalography with subdural electrodes, which revealed neocortical origins for the seizure. These four patients were successfully treated with surgery. The clinical features of this familial temporal lobe epilepsy seem to be different from those of previously reported types of familial temporal lobe epilepsy.

1p/19q co-deleted gliomas show good response to genotoxic treatment and majority of patients are expected to live more than 14 years. In addition, radiation therapy is frequently deferred to avoid potential cognitive function disturbance. In such cases, monitoring recurrence and hence decision to re-intervene is sometimes difficult. We have been using 11C-methionine -PET (MET-PET) to this purpose. After initial intervention, 32 patients were followed with MRI (every 4 months) and MET-PET (every 12 months and when MRI suggestive). Of those, regrowth was detected in 18 cases (mPFS 75 months). The recurrent lesion was localized and surgically removable in 15 cases, and none of the recurrent lesion was WHO grade 4. Treatment after recurrence depended on the previous treatment, but the majority (10/15) underwent chemo/radiation therapy with TMZ because the initial adjuvant therapy was with PCV therapy. Only 2 patients died in the median follow-up time of 76 months. MET-PET appears to be an useful method to confirm recurrence in 1p/19q co-deleted gliomas, allowing earlier intervention.

Object. Radiosurgery has been widely adopted for the treatment of cerebral arteriovenous malformations (AVMs) in which the practical endpoint is angiographic evidence of obliteration, presumed to be consistent with elimination of the risk of hemorrhage. To test this unverified assumption, the authors followed 236 radiosurgery-treated AVMs between 1 and 133 months (median 77 months) after angiographic evidence of obliteration. Methods. Four patients experienced hemorrhage between 16 and 51 months after angiographic confirmation of AVM obliteration, and two underwent resection. The histological findings in these patients showed occlusion of the AVM by thickening of the intimal layer with dense hyalinization as well as a small amount of residual AVM vessels and a tiny vasculature. The risks of hemorrhage from these presumaby obliterated AVMs were 0.3% for the annual bleeding risk and 2.2% for the cumulative risk over 10 years. Continuous enhancement of the nidus on computerized tomography (CT) or magnetic resonance (MR) imaging was the only significant factor positively associated with hemorrhage in the statistical analysis (p = 0.0212). Conclusions. Because the study was based on limited follow-up data, its significance for defining predictive features of hemorrhage after angiographic evidence of obliteration is still indeterminable. Nevertheless, disappearance of the AVM on angiography after radiosurgery does not always indicate total elimination of the disease, especially when CT or MR imaging continues to demonstrate an enhancing lesion. The authors therefore recommend continual follow up even after evidence of AVM obliteration on angiography.

The head-shaking method combined with cisternal irrigation has been proposed to be effective in preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) by facilitating rapid washout of the clot from the subarachnoid space. This study was conducted to evaluate the effectiveness of this method.The inclusion criteria included the following: 1) Fisher Grade 3 SAH on admission computerized tomography (CT) scans; 2) aneurysm secured within 48 hours of SAH onset; and 3) no focal deficit and ability to obey commands within 24 hours postsurgery. Two hundred thirty patients treated between 1994 and 2002 fulfilled the criteria. Because only one machine was available and it required I month of maintenance every other month, 114 patients underwent irrigation combined with the head-shaking method (head-shaking group), whereas the remaining 116 patients received cisternal irrigation alone (control group). There were no significant differences in sex, age, site of aneurysm, or preoperative grade between the two groups. The incidence of symptomatic vasospasm with or without infarction, cerebral infarction on CT scans, and permanent ischemic neurological deficit was 25.7, 17.7, and 8.8%, respectively, in the control group and 15.2, 4.5, and 2.7% in the head-shaking group. The difference was statistically significant for symptomatic vasospasm, cerebral infarction, and permanent ischemic neurological deficit (p0.05). In a multivariate backward stepwise logistic regression analysis, absence of head shaking was the only variable that was predictive of permanent ischemic neurological deficit (p = 0.061). The outcomes evaluated using the modified Rankin Scale were better in the head-shaking group (p = 0.051).The head-shaking method significantly reduced the incidence of symptomatic vasospasm, cerebral infarction, and permanent ischemic neurological deficit and improved the clinical outcomes in patients who underwent cisternal irrigation therapy after aneurysmal SAH.

A 78-year-old Japanese woman presented with adult-onset moyamoya disease manifesting as repetitive ischemic attacks over a period of 26 years. Initial ischemic attack occurred at age 52 years. Neurological status deteriorated, associated with worsening in angiographical and single photon emission computed tomography findings over the last 10 years. She suffered frequent transient attacks of aphasia and right hemiparesis. Superficial temporal-middle cerebral artery anastomosis was performed. Postoperative angiography and single photon emission computed tomography revealed a marked increase in cerebral blood flow and symptoms showed considerable improvement. Direct revascularization may be the treatment of choice even for aged patients with moyamoya disease.

Intorduction: Recent comprehensive genomic analysis have revealed many genetic alterations in diffuse gliomas, but few markers besides IDH and 1p19q are utilized for diagnosis in the CNS WHO 2016. In particular, diagnostic and/or prognostic markers for IDH-wild tumors are not defined, except for H3.1/3.3. TERT promoter mutation frequently occurs in GBMs among IDH-wild tumors, but its prognostic impact remains controversial. In order to evaluate the influence of TERT, we analyzed a large cohort of IDH wild type tumors. Materials and Methods: One hundred fifty-one grade II-III and 453 GBM cases without IDH mutations were included. All GBM cases were treated with standard radiotherapy and temozolomide. Molecular statuses including IDH, MGMT and TERT were assessed by pyrosequencing and/or Sanger sequencing using frozen tumor tissues for all cases. The survival data were analyzed with the log-rank test and univariate and multivariate Cox regression analyses.Results: In grade II-III cases, TERT mutations were observed in 54% cases and associated with shorter survival (16.1 months for TERT-mutated vs. 34.8 months for TERT-wild cases, p

BCNU wafer (BW) is known to increase risk of edema, frequently accompanied by enhancing lesions. The underlying mechanism is not clarified. We performed close histological examination including electron microscopy of the mass-effect-causing enhancing lesion resected from 4 patients (3 glioblastomas and 1 anaplastic oligodendroglioma) 2-33 months after the BW implantation. There noticed were two types of tissue damage in the resected lesions: 1) necrosis in immediate contact with the wafer or its remnant, and 2) necrosis with marked vasculopathy affecting arterial branches and venules. The former contained phagocyted or non-phagocyted crystalline structured polymer, and translucent spherical bodies with calcified core that were not surrounded by viable cells. In the latter, marked degeneration of arterioles were observed, suggesting relatively prolonged exposure to toxic substances such as the released BCNU, degraded polymer and cytokines. Similar type of vasculopathy had been observed in monkey brains implanted with the BCNU-free polymer. Our data suggest that the edema and neecrotic response induced by the BW implantation are results of not only the direct effect of the released drug, but also of inflammatory vasculopathy caused by the degraded polymer itself that occur even in later phase.

OBJECTIVES: The objective of our study was to investigate the effectiveness of reconstructing the carotid artery using a superficial femoral vein (SFV). METHODS: Ten patients with malignant tumours involving the carotid artery underwent carotid artery resection and reconstruction with the SFV. We use the SFV between the deep femoral vein and perforator branches to the great saphenous vein or deep femoral vein at the popliteal region reconstructive vessel. RESULTS: The mean length and diameter of the grafted SFVs were 13.9 and 11.2 mm, respectively. The mean time for SFV acquirement was 18 min. The mean cerebral ischaemic period was 23.1 min. Nine patients did not experience any neurological complications. One patient experienced slight temporary hemiparesis. There was no postoperative vascular graft thrombosis. Donor site complications did not occur. CONCLUSIONS: Reconstructing the carotid artery using an SFV is very effective due to the ease in harvesting the vessel and its optimal size and length for carotid artery replacement.

Incidence of von Hippel-Lindau disease among hemangioblastomas is important clinical information affecting the management of hemangioblastomas. Studies from Western countries reported 36–40% for the incidence, but no report has been made on the Japanese population. To investigate the incidence in Japan, we retrospectively analyzed all hemangioblastoma patients treated at The University of Tokyo Hospital from 1954 to 1998. By reviewing medical records and imaging studies, von Hippel-Lindau disease was diagnosed clinically following the currently suggested diagnostic criteria. There were 82 hemangioblastoma patients recorded during the period, and 14 cases (17%) were compatible with von Hippel-Lindau disease. However, when the incidence was calculated for each of the three 15-year periods, which are 1954–1968 (first), 1969–1984 (second), and 1985–1998 (third), the number increased dramatically in the later periods: 2 of 33 (6%) during the first, 4 of 26 (15%) during the second, and 8 of 22 (36%) during the third period. Such increase occurred after the introduction of whole body CT to our institution in 1981, suggesting that improvement of imaging techniques contributed to the sensitivity of diagnosis. In addition, one recent patient with multiple hemangioblastomas was found to harbor germline mutation of the VHL, thereby being diagnosed as von Hippel-Lindau disease on the basis of molecular genetics. The 40% incidence of von Hippel-Lindau disease in hemangioblastomas suggests that extensive screening for von Hippel-Lindau disease associated neoplasms, and probably molecular genetic examination, is indicated for all patients with hemangioblastomas, which should aim for earlier diagnosis and better management of this devastating hereditary disease.

An 18-year-old girl with a 5-year history of neurofibromatosis type 2, consisting of bilateral acoustic tumors and a meningioma at the planum sphenoidale, presented with an intramedullary mass at the T-1 level, and underwent total removal of the tumor. Histological examination showed that the tumor consisted of markedly elongated spindle-shaped cells, which were immunopositive for S-100 protein and glial fibrillary acidic protein. Ultrastructural examination showed microvilli-lined lumina and prominent intercellular junctions, which were characteristic ependymal features. These findings were compatible with the diagnosis of tanycytic ependymoma. This rare subtype of ependymoma appears to arise through inactivation of NF2, in addition to some typical ependymomas.

Object. The goal of this study was to determine the prevalence, characteristics, and radiosurgical outcomes of headaches associated with occipital arteriovenous malformations (AVMs).Methods. The authors reviewed the medical records of 37 consecutive patients with occipital AVMs who had been treated by radiosurgery to identify the radiological features of the AVMs before and after treatment and the clinical features and outcomes of headaches described in accordance with the criteria of the International Headache Society (IHS).Thirty-six patients (97.3%) were followed for a mean period of 46.6 months. The median volume of the AVMs was 1.9 cm3, to which a mean radiation dose of 21.6 Gy was delivered. In the entire study group, periodic headaches were found in 17 patients (45.9%), of whom seven (18.9%) suffered from migraines with the characteristic visual aura. Migraine was predominantly found in patients with right-sided (p = 0.038) or laterally located (p = 0.025) AVMs. Factors associated with a higher incidence of any type of headache included larger nidus volume (p = 0.02), tortuous change of feeding artery (p = 0.036), and cortical drainage with reflux in the superior sagittal sinus (p = 0.032). The actuarial rate of angiographic obliteration was 71.6% at 3 years. Headaches resolved or improved in 12 (70.6%) of 17 patients, including six (85.7%) of seven with migraine. The outcome of headache closely correlated with the obliteration results of the AVM (p = 0.002).Conclusions. A portion of occipital AVMs do cause headaches that satisfy the current IHS criteria for migraine, and the prevalence varies by the topography of the lesion. Radiosurgery can resolve headaches in the majority of treated patients.

OBJECTIVE—To assess the treatment results of radiosurgery for brain stem arteriovenous malformations (AVMs) and to seek optimal dose and treatment volume prescription for these lesions. METHODS—The clinical and radiological data of 30 consecutive patients with brain stem AVM treated with gamma knife radiosurgery were retrospectively reviewed with a mean follow up period of 52.2months. There were 26 patients with previous haemorrhages and 21 with neurological deficit. Seventeen AVMs were located in the midbrain, 11 in the pons, and two in the medulla oblongata. All of the lesions were small with the intra-axial component occupying less than one third of the area of brain stem parenchyma on axial section of multiplaner MRI or CT. The mean diameter of the nidus was 1.26 cm, and the nidus volume within the brain stem parenchyma ranged from 0.1 to 2.0 cm3. The mean radiation dose to the AVM margin was 18.4Gy. RESULTS—The actuarial 3 year obliteration rate was 52.2%; 69.4% in cases treated with standard doses (minimum target dose, 18-20Gy), and 14.3% in cases treated with low doses (

The authors present a case of meningeal melanocytoma arising from Meckel's cave. A coal-black, vascular tumor was partially removed by surgery. Histopathologically, the tumor lacked anaplastic features. Immunohistochemical studies confirmed that the tumor was of neuroectodermal origin and had low proliferating activity. The patient underwent gamma knife radiosurgery for the residual tumor, in which 25 Gy of radiation was delivered to the tumor margin. Three years after irradiation, the tumor showed marked shrinkage without complication.

Langerhans cell histiocytosis rarely presents as a solitary lesion in the pituitary-hypothalamic region, and is indistinguishable from germinoma, which occurs much more frequently, especially in Japanese. A 14-year-old girl and a 9-year-old girl presented with polydipsia and polyuria as the initial symptoms. Magnetic resonance (MR) imaging demonstrated a round mass at the pituitary stalk appearing as isointense on T1-weighted imaging and hyperintense on T2-weighted imaging. Endocrinological examination revealed mild hypopituitarism with central diabetes insipidus. Both patients underwent open craniotomy. Histological examination revealed granulomatous tissue with eosinophil infiltration and frequent Langerhans histiocyte clustering, compatible with the diagnosis of Langerhans cell histiocytosis. Low-dose local irradiation of 20 Gy was administered. First patient was followed up for 8 years, and her hypopituitarism gradually improved to a minimal level with only amenorrhea as the residual symptom. Recent MR imaging showed no residual mass at the region. Second patient was followed up for 15 months, and her diabetes insipidus is stable. MR imaging performed 5 months after the treatment showed marked reduction of the mass. These cases reemphasize the importance of histological diagnosis for lesions with similar neuroimaging appearances. Biopsy and low-dose irradiation are an effective treatment for this rare and essentially benign lesion, as opposed to attempting total removal of the mass.

Background and Purpose —Recent progress in noninvasive imaging techniques has resulted in increased detection of unruptured aneurysms. Although many neurosurgeons advocate surgical intervention for such unruptured aneurysms, the long-term results of surgery for unruptured aneurysms have not been carefully investigated. Methods —We analyzed 173 consecutive patients who had unruptured intracranial saccular aneurysm(s) detected by angiography that was performed for reasons other than subarachnoid hemorrhage (SAH). Of those, 115 cases were surgically treated and studied. All patients were followed up for either SAH, repeat treatment of aneurysms, or death. The median follow-up period was 8.8 years. Results —Four of the 115 patients suffered SAH either from a de novo aneurysm (2) or from regrowth of clipped aneurysm (1), or from regrowth after wrapping (1). Additionally, 1 patient also suffered SAH from an unstudied basilar aneurysm. One patient was incidentally found to have de novo aneurysm and underwent reoperation 14 years after the first operation. The cumulative risk for SAH for the 114 cases excluding the basilar aneurysm case was 1.4% in 10 years and 12.4% in 20 years. Conclusions —Although this study confirmed the long-term efficacy of clipping unruptured aneurysms, the risk of SAH was high compared with that in the general population, even after treatment. Considering the high mortality rate of SAH, long-term follow-up by angiography may be warranted for patients with surgically treated unruptured aneurysms.

Background: The popularity of snowboarding has been growing rapidly throughout the world. To date, however, the risk of head injury associated with this relatively new winter sport, especially in comparison with alpine skiing, has not been well analyzed. This study was conducted to assess the risk of head injury in snowboarding and to elucidate its features in comparison with skiing head injury. Methods: We prospectively analyzed 301 cases of head injuries related to snowboarding or skiing experienced from December of 1995 to May of 1997 at our institution, which is located close to the most popular skiing areas in Japan. Of those injuries, 143 cases were snowboard related and 158 cases were ski related. In addition to appropriate medical evaluation and medical care, detailed examination was performed on every patient to determine various factors, including sex, age, skill level, cause and mechanism of the accident, and the side of impact to the head. The data are statistically analyzed to elucidate unique features of snowboard head injury. Results: During the study period, 2.2 million snowboarders and 4.2 million skiers visited the five skiing facilities that are covered by our hospital. Thus, the incidence of head injury was 6.5 per 100,000 visits for snowboarders and 3.8 per 100,000 visits for skiers. Beginning snowboarders more frequently sustained head injuries compared with beginning skiers (60 of 142 vs. 48 of 154, p = 0.022). Likewise, frequent causes of snowboarding head injuries were fall during jumping (43 of 139 vs. 2 of 147, p < 0.0001), falling backward (67 of 127 vs. 49 of 144,p = 0.001), and occipital impact (67 of 126 vs. 49 of 147). More importantly, there were nine major head injury cases (6.3%) in snowboard head injuries in contrast to only two such cases found in skiing head injuries (1.3%). Of 11 major head injury cases, 10 were caused by occipital impact. Conclusion: These results indicate that snowboarders, particularly beginners, are at higher risk for head injury, frequently involving occipital impact, and could lead to more major head injuries. We propose that measures should be taken to protect the head, especially the occiput, in snowboarding.

The benefit and risk of whole brain radiation therapy (WBRT) compared to locally limited radiation therapy was assessed in 61 patients with solitary brain metastases from non-small cell lung cancer without an unresectable active primary lesion or systemic dissemination in the other organs. Twentythree patients received local irradiation (Group A), and 38 patients received whole brain irradiation with or without local irradiation (Group B). The survival was significantly better in Group A than in Group B (p &lt 0.05), with median survivals of 83.1 and 30.7 weeks, respectively. One-year local recurrence rates were 7% in Group A and 21% in Group B, but the difference was not statistically significant. The 1-year distant recurrence rate was similar at 18%. Radiation-induced dementia occurred in two patients in Group A (8.7%) and seven in Group B (18.4%), but was not statistically significant (p = 0.30). There is no obvious benefit and possible disadvantages of WBRT compared to local irradiation for the population of patients investigated in this study. Intraoperative radiation therapy or stereotactic radiosurgery without WBRT should be considered in the patients with solitary brain metastases.

A 57-year-old man presented with a posterior fossa hemangioblastoma associated with primary hyperparathyroidism. The hemangioblastoma was completely removed. Further imaging found parathyroid and thyroid tumors which were resected. Hyperparathyroidism might be a manifestation of von Hippel-Lindau (VHL) disease, but sequencing of the VHL gene of the constitutional deoxyribonucleic acid of the hemangioblastoma was negative. The present association is rare, but the hemangioblastoma and the parathyroid adenoma may have some germ-line mutation in common.