記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s10143-024-03019-2

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その他リンク： https://link.springer.com/article/10.1007/s10143-024-03019-2/fulltext.html

記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：日本脳神経漢方医学会  

片頭痛に対するCGRP関連抗体薬（CGRP mAbs）と漢方薬（五苓散・呉茱萸湯）の併用療法に関し，安全性と効能を検討した後方視的観察研究である。漢方薬はCGRP mAbsと安全に併用可能であることが示唆された。CGRP mAbs導入前から漢方薬を使用していた患者では漢方薬の継続率が高く，約3割では症状改善により漢方薬の投薬が終了した。しかし，CGRP mAbs治療後に新たに漢方薬を導入した場合には，併用療法の効果が劣る可能性が示唆された。五苓散は天候変動に伴う頭痛やめまい症，呉茱萸湯は薬剤の使用過多を有する患者で併用療法が有用である症例が存在する。

DOI： 10.57364/kmnn.9.1_12

CiNii Research

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: The influence of the age at which complete corpus callosotomy (CC) surgery is performed on seizure outcomes remains unclear. This study aimed to evaluate the age-dependent aspects of long-term seizure outcomes after complete CC. METHODS: We reviewed 41 patients who underwent one-stage complete CC. Seizure outcomes were analyzed for age at epilepsy onset and at complete CC, focal MRI abnormality, and etiology. RESULTS: The median age was 7 months at epilepsy onset and 93 months at complete CC. The median follow-up duration was 67 months. Sixteen patients had focal MRI lesions and 4 had only general atrophy. Etiology was identified in 20 patients. For overall seizure outcomes (N = 41), complete seizure freedom was achieved in 5 patients, excellent seizure reduction (>80%) in 11, good (50%-80%) in 5, and poor (<50%) in 20. Freedom was correlated with younger age at complete CC and unknown etiology (P ≤ .05). Freedom was only achieved in patients aged younger than 7 years. Worthwhile (≥50%, freedom, excellent, and good) and not worthwhile (<50%, poor) overall seizure reduction showed no statistical difference in age at complete CC. No related factor was found for worthwhile overall seizure reduction. For drop attack outcomes (N = 31), freedom was achieved in 22 cases, excellent in 5, and poor in 4. Freedom was correlated with younger age at complete CC (P < .05) although freedom was achieved in 4 of 7 patients older than 20 years. Age at complete CC showed no statistical difference between worthwhile (≥50%) and not worthwhile (<50%) drop attack reduction. Worthwhile drop attack reduction was correlated with unknown etiology (P < .05). Complications were mild and transient. CONCLUSION: Complete CC is an excellent surgical option based on favorable seizure outcomes and acceptable complications in our present study.

DOI： 10.1227/neu.0000000000003092

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

SIGNIFICANCE: The initiation of goal-directed actions is a complex process involving the medial prefrontal cortex and dopaminergic inputs through the mesocortical pathway. However, it is unclear what information the mesocortical pathway conveys and how it impacts action initiation. In this study, we unveiled the indispensable role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions. AIM: To investigate the role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions. APPROACH: We designed a lever-press task in which mice internally determine the timing of the press, receiving a larger reward for longer waiting periods. RESULTS: Our study revealed that self-initiated actions depend on dopaminergic signaling mediated by D2 receptors, whereas sensory-triggered lever-press actions do not involve D2 signaling. Microprism-mediated two-photon calcium imaging further demonstrated ramping activity in mesocortical axon terminals approximately 0.5 s before the self-initiated lever press. Remarkably, the ramping patterns remained consistent whether the mice responded to cues immediately for a smaller reward or held their response for a larger reward. CONCLUSIONS: We conclude that mesocortical dopamine axon terminals encode the timing of self-initiated actions, shedding light on a crucial aspect of the intricate neural mechanisms governing goal-directed behavior.

DOI： 10.1117/1.NPh.11.3.033408

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. METHODS: A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2',7'-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. RESULTS: CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. CONCLUSION: Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways.

DOI： 10.1186/s12576-024-00928-1

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.

DOI： 10.1111/cas.16243

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

近年、てんかん性脳症の概念が拡張され、発達性てんかん性脳症(DEE)が定義された。本稿では、視床下部過誤腫による笑い発作の成因、てんかん原性、そして治療介入前後の認知機能障害を通じて、DEEの科学的な理解を深めることを目指した。視床下部過誤腫の成因は、胎生初期の体細胞変異によるShhシグナルの異常が一因とされる。変異が発生する時期によって脳の構造異常の程度が異なり、重度の場合は発達性脳症へとつながることがある。視床下部過誤腫の内因性てんかん原性には、Ca2+透過性AMPA型グルタミン酸受容体の異常発現が関与している。視床下部過誤腫を正常脳から外科的に離断すると、笑い発作が制御され、術後の認知機能障害や行動異常も改善し、てんかん性脳症の病態を示唆している。視床下部過誤腫に伴う認知機能障害はDEEとして位置付けられ、さらに社会的要因や薬剤の副作用が修飾する。神経発達症の観点からも早期診断と早期治療が重要と考えられる。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞I はじめに OTA(occipital transtentorial approach)は松果体部近傍への代表的な手術アプローチであり,ほかにinfratentorial supracerebellar approach,transcallosal interforniceal approach,parietal transcortical trans/sub-choroidal approachなどが用いられる.OTAはテント切痕上下および小脳テント直下の手術に対応でき,中脳視蓋,松果体,内大脳静脈(internal cerebral vein:ICV)下面,中間帆槽,モンロー孔直下の第三脳室側壁・後半部までの広い範囲を視野に収め,これらに発生する種々の病変に対処できる汎用性の高い術式である.OTAを用いた自験例83症例(89手技)では,germ cell tumorが36例で最も頻度が多く(43.4%),続いて松果体実質腫瘍15例(18.1%),毛様細胞性星細胞腫11例(13.3%),その他のグリオーマ8例(9.6%)の順であった(Table 1).OTAでは,頭尾側方向のcorridorを用いる.Parietooccipital interhemispheric routeを用いることで,中脳水道周囲から第四脳室上部,視蓋およびcerebellomesencephalic fissureの病変に対処する.逆にoccipital interhemispheric/occipitobasal/transtentorial routeでは,視床枕やモンロー孔より後方の第三脳室,脳梁膨大部から上方へ進展する病変,さらに中脳被蓋から視蓋に進展した病変に対処できる.テント下に向けた視軸では,"transtentorial"の名称が示すとおり,テント切開部を経由して視野を確保するというのが教科書的なコンセプトである.しかし,実際の手術では,十分なテント切開によって可動化した大脳鎌を対側後頭葉に向かって圧排偏位させることで,両側のテント縁や迂回槽での視軸を確保し,静脈や腫瘍の剥離操作を行いやすくすることがテント切開のもう1つの意義となっている.

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J01228&link_issn=&doc_id=20240531170023&doc_link_id=1390863252064058624&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390863252064058624&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

This article describes the concept and technical aspects of the occipital transtentorial approach(OTA)for tumor extraction in the pineal region, based on the author's experience and literature review. Awareness of the successful completion of each surgical step is essential. Preoperative preparation and imaging evaluations, with particular attention to the veins and venous sinuses, are especially important. It is also helpful to perform a complete dura incision and inversion up to the edge of confluence, superior sagittal sinus, and transverse sinus. Subsequently, it is necessary to understand the usefulness of adequate dissection in the vicinity of the corpus callosum and internal occipital vein(IOV)so that the occipital lobe can be moved without difficulty. Furthermore, development of the IOV with adequate tentoriotomy facilitates contralateral work. Finally, complete understanding of each step during the bilateral, ambient cistern and cerebellomesencephalic fissure dissection process, where the cerebellar vermis can be moved without difficulty, is necessary for a safe OTA to pineal region tumor extraction.

DOI： 10.11477/mf.1436204958

PubMed

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Takotsubo cardiomyopathy (TC) is a well-known complication of subarachnoid haemorrhage (SAH), often accompanied by neurogenic myocardial dysfunction. Although TC has been reported to be associated with higher morbidity and mortality among patients with aneurysmal SAH (aSAH), some patients have been reported to recover, the profiles and follow-up outcomes of these survivors remain unclear. MATERIALS AND METHODS: To characterize the profiles of patients with aSAH complicated by TC who experienced favourable outcomes using long-term follow-up data, a consecutive series of patients with aSAH were enrolled and TC diagnosis was based on the revised version of the Mayo Clinic criteria. Clinical outcomes were assessed at 6 months according to modified Rankin Scale scores. RESULTS: Among 165 consecutive patients with aSAH, 15 cases were complicated by TC, corresponding to an occurrence rate of 9.0%. Five patients with aSAH complicated by TC (33.3%) experienced a favourable outcome, and the mean value of systolic blood pressure on arrival was significantly lower than in those who experienced an unfavourable outcome (p = 0.032). CONCLUSION: According to analysis, it is possible cardiac dysfunction with decreased cerebral perfusion pressure and catecholamine toxicity transiently worsens conscious disturbance in aSAH complicated by TC. Therefore, it is important to carefully screen patients with aSAH to identify those complicated by TC, and for close collaboration of the multidisciplinary team to design appropriate treatment strategies.

DOI： 10.1080/02688697.2024.2334432

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction Preoperative embolization can potentially facilitate surgical resection of challenging tumors in the intracranial and facial regions; however, its clinical efficacy remains controversial, mainly due to potential morbidity risks. We explored negative factors of the combined treatment of preoperative embolization and tumor resection that affect neurological prognosis. Method This retrospective study used clinical data from 132 consecutive tumors that underwent combined treatment at multiple facilities between January 2016 and May 2021. Basic patient information, tumor characteristics, and treatment details were assessed to identify predictors of deterioration as measured using the modified Rankin scale (mRS) score at three months post-treatment. Results Among the 126 eligible combined treatments, a deterioration in the postoperative mRS score was observed in 19/126 (15.1%). Complications related to embolization and tumor resection occurred in 8/126 (6.3%) and 19/125 (15.2%) of procedures, respectively. Multivariate analyses indicated significant associations between migration of embolic material (adjusted odds ratio 13.80; 95% confidence interval 1.25-152.52; p=0.03), elevated intraoperative blood loss (p=0.04), and deterioration of postoperative mRS score. Embolic material migration was identified as the primary prognostic factor for the deterioration of score. An analysis of 192 procedures, excluding those that exclusively used coils, identified embolization targeting the accessory meningeal artery (p=0.046) and the third segment of the internal maxillary artery (p=0.03) as a risk factor for embolic material migration. Conclusions Embolic material migration is the predominant factor associated with declining neurological outcome that persists into the chronic phase after combined treatment. Given that preoperative embolization is a supplementary treatment option, a thorough understanding of vascular anatomy and striving safe procedure are critical.

DOI： 10.7759/cureus.57315

PubMed

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記述言語：英語   出版者・発行元：(一社)日本病理学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.52874

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記述言語：日本語   出版者・発行元：(一社)日本定位・機能神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Carotid artery stenting embolic protection devices offer various options, among which distal filter protection is the simplest and easiest to handle. However, compared to balloon protection systems, distal filter protection has more embolic complications. Therefore, we explored the risk factors of distal filter protection, intending to achieve a safer carotid artery stenting. This retrospective study was conducted to identify prognostic factors following carotid artery stenting with only distal filter protection from July 2010 to June 2021. METHODS: Information on patient background, procedures and devices, and complications was collected using medical records. The data pertaining to 187 patients were analyzed after excluding the data of patients in whom other protection devices (8 cases) were used. We used FilterWire EZ as the first choice for embolic protection device and SpiderFX when the patients had difficult-to-cross lesions. RESULTS: The patients' mean age was 71.9 ± 6.9 years, and 72 (38.5%) were symptomatic. Symptomatic (odds ratio: 2.02, p = 0.035) and difficult-to-cross lesions (odds ratio: 3.63, p = 0.0013) were factors independently associated with symptomatic complications. CONCLUSION: This retrospective single-center study established independent prognostic factors for carotid artery stenting with distal filter protection. For patients with symptomatic lesions and severe stenosis or bends that are difficult to pass through, it is necessary to be careful when performing carotid artery stenting with distal filter protection.

DOI： 10.5797/jnet.oa.2023-0096

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Vertebral artery (VA) stenosis can be caused by several factors, including arteriosclerosis, arterial dissection, and mechanical compression. Symptomatic vertebrobasilar insufficiency caused by VA stenosis due to mechanical compression associated with head rotation is well-known as Bow Hunter's syndrome. However, an accurate diagnosis of asymptomatic osteophyte compression-induced nonrotational VA stenosis is difficult. We report a case of left posterior inferior cerebellar artery aneurysm with severe left VA stenosis, treated with stent-assisted coil embolization following appropriate diagnosis. CASE DESCRIPTION: A 72-year-old female patient was found to have severe asymptomatic VA stenosis at the V2 segment (C4-5 level of the cervical spine) on cerebral angiography. Osteophyte compression-induced VA stenosis was suspected, which was confirmed by cone-beam computed tomography. The VA stenosis improved by flexing the neck and fixing the head position, following which the endovascular treatment was successfully completed. CONCLUSION: The site of the VA stenosis is critical in determining the etiology. Atherosclerotic VA stenosis often occurs at the origin of the artery or V4 segment, whereas bony compression-induced stenosis is more likely to occur at the V2 segment. Diagnosis and appropriate management of VA stenosis is based on determining the site.

DOI： 10.25259/SNI_772_2024

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The use of anti-epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence. METHODS: Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 (n = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019. RESULTS: Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459-0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups. DISCUSSION: Among patients newly diagnosed with epilepsy, compared to non-use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted. HIGHLIGHTS: Anti-epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence.Identifying the epileptic phenotype was crucial for justifying early AED use in DD.AED use with an epilepsy diagnosis did not pose an additional risk of DD.The potential contribution of combination drug therapy to the strategy was noted.

DOI： 10.1002/trc2.70001

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The superiority and usefulness of liquid material over particles for embolization have been a topic of debate due to differences in materials and techniques. This study aimed to identify the complications and outcomes associated with both embolization materials. METHODS: This retrospective multicenter cohort study included 93 patients from an endovascular treatment registry, treated from January 1, 2018 to May 31, 2022. It included patients who underwent preoperative embolization for meningioma, solitary fibrous tumor/hemangiopericytoma, and hemangioblastoma. Data for patient characteristics, procedural factors, complications, and outcomes were collected from medical records. RESULTS: A tortuous access route was the only factor independently associated with complications (p = 0.020). Although liquid material was more frequently used for embolization in relatively high-risk conditions, complication rates did not differ significantly between the groups (p = 0.999). In the liquid material group, the tip of the microcatheter could be guided closer to the tumor (p <0.001) using a distal access catheter and flow-guide microcatheters. The subgroup middle meningeal artery embolization had less operative bleeding in the liquid material group (p <0.001), whereas the particles group exhibited less intraoperative blood loss than the liquid material group (p = 0.006). CONCLUSION: The vascular tortuosity of the access route was only associated with complications in preoperative tumor embolization. Liquid material and particles showed no difference in complication rates. The use of particles in embolization may reduce intraoperative bleeding, but not in all cases can it be used safely. Therefore, a thorough understanding of the characteristics of both approaches and their relative advantages in clinical practice is essential to opt for the appropriate material according to the case.

DOI： 10.5797/jnet.oa.2023-0083

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Isolated abducens nerve palsy (IANP), caused by secondary communicating hydrocephalus, has been rarely documented; in addition, its mechanism and appropriate treatment are not understood well. This study presents a case of bilateral IANP with hydrocephalus in a 62-year-old man who was successfully treated with cerebrospinal fluid (CSF) diversion to correct an enlarged retroclival space during the follow-up of recurrent brain tumor in the right parieto-occipital lobe. The patient was treated with three resections, temozolomide, and irradiation before developing IANP. Magnetic resonance imaging (MRI) revealed a recurrent tumor and ventriculomegaly with an expanded retroclival cisternal space. The patient underwent subtotal tumor resection and external ventricular drain placement in the anterior horn of the lateral ventricle. His bilateral IANP persisted for 4 days after surgery but gradually improved and disappeared by Day 7. Four weeks later, the patient underwent ventriculoperitoneal (VP) shunt surgery to establish a permanent CSF diversion that continued to control the symptoms. Retrospective MRI review revealed the distance between the clivus and pontomedullary junction on the sagittal section (retroclival-pontomedullary distance; RPD) of 9.0, 12.8, 10.7, and 10.6 mm before IANP, on IANP onset, on postoperative Day 4, and post VP shunt surgery, respectively. In conclusion, VP shunt surgery was an appropriate approach for IANP with communicating hydrocephalus to correct the enlarged retroclival cisternal space. RPD thus may be used as one of possible evaluation methods for IANP with hydrocephalus, which can be caused by various factors.

DOI： 10.2176/jns-nmc.2024-0092

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

DOI： 10.1227/ons.0000000000000879

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain elusive. Here, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2R172K and TP53R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recurrent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2R172K and TP53R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astrocytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.

DOI： 10.1186/s40478-023-01683-x

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Using a network meta-analysis, this study aimed to compare the risks of C5 palsy after three different procedures of anterior cervical decompression. SUMMARY OF BACKGROUND DATA: C5 palsy is a well-known complication affecting quality of life after anterior procedures. Due to the limited evidence on the various procedures available, we evaluate the basis for selection to prevent palsy and achieve maximal decompression in cases spanning 3-6 levels. METHODS: We conducted a comprehensive search for C5 palsy and complications after three representative procedures, including anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and their combination (Hybrid), involving 3-6 intervertebral levels. The incidence of C5 palsy was compared using a network meta-analysis. RESULTS: We identified 1655 patients in 11 studies that met inclusion criteria. Sixty-nine patients (4.2%) developed delayed C5 palsies. The incidences among ACDF, ACCF, and Hybrid cases were 2.3% (16/684, 95% confidence interval [CI] 1.4-3.8%), 6.4% (39/613, 95%CI 4.7-8.6%), and 3.9% (14/358, 95%CI 2.3-6.5%), respectively (P<0.01). A network meta-analysis was performed for 15 pairwise comparisons across the three procedure arms: ACDF versus Hybrid, 7/232 (3.0%) versus 11/234 (4.7%); Hybrid versus ACCF, 14/301 (4.3%) versus 18/224 (8.0%); ACCF versus ACDF, 38/523 (7.8%) versus 16/619 (2.6%). Compared with ACDF, the risk of C5 palsy was significantly higher in ACCF (odds ratio [OR] 2.72, 95%CI 1.47-5.01), while ACDF versus Hybrid did not significantly differ in risk (OR 1.56, 95%CI 0.68-3.60). CONCLUSION: We determined that ACCF was associated with a higher risk of postoperative C5 palsy than ACDF in cases spanning 3-6 intervertebral levels. If practicable, ACDF surgery may be an appropriate choice for cases requiring anterior decompression of 3-6 levels. LEVEL OF EVIDENCE: 3.

DOI： 10.1097/BRS.0000000000004865

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Intraosseous clival arteriovenous fistulas (AVFs), in which the shunt drains extracranially from the posterior and anterior condylar veins rather than from the cavernous sinus (CS), are rare. Targeting embolization of an intraosseous clival AVF is challenging because of its complex venous and skull base anatomy; therefore, a therapeutic strategy based on detailed preoperative radiological findings is required to achieve a favorable outcome. Here, the authors report the successful targeted embolization of an intraosseous clival AVF using an ingenious access route. OBSERVATIONS: A 74-year-old woman presented with left-sided visual impairment, oculomotor nerve palsy, and right facial pain. A fusion image of three-dimensional rotational angiography and cone-beam computed tomography revealed a left CS dural AVF and a right intraosseous clival AVF. The shunt flow of the clival AVF drained extracranially from the posterior and anterior condylar veins via the intraosseous venous route. Transvenous embolization was performed by devising suboccipital, posterior condylar, and intraosseous access routes. The symptoms resolved after the bilateral AVFs were treated. LESSONS: Accurate diagnosis and proper transvenous access based on detailed intraosseous and craniocervical venous information obtained from advanced imaging modalities are key to resolving intraosseous clival AVF.

DOI： 10.3171/CASE23492

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Since majority of adult malignant brain tumors are gliomas and primary central nervous system lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. Additionally, diffuse gliomas require molecular information on single nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen section (FS) diagnosis through incorporation of a quantitative polymerase chain reaction (qPCR)-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid immunohistochemistry, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined based on the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patientswith glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

DOI： 10.1158/1078-0432.CCR-23-1660

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: For patients who undergo endovascular treatment for acute ischemic stroke, the total time for treatment may increase during off-duty hours leading to worse outcomes. The present study compared endovascular treatment outcomes for on-duty and off-duty hours and examined factors that could be responsible for the prolonged treatment of patients in a multicenter registry. METHODS: The study group comprised 1571 patients listed in the multicenter stroke registry (K-NET) who had undergone endovascular treatment between January 2018 and June 2020. The modified Rankin Scale (mRS), evaluated at 90 days after stroke onset, was utilized as the primary outcome. Patients were divided into on-duty and off-duty patients based on admission time. Multivariate logistic regression analysis was used to identify the independent factors that increased the time from admission to puncture during the off-duty period. RESULTS: The mean mRS score at 90 days after stroke onset was 2.9, similar in both on-duty and off-duty patients, with no significant difference (p = 0.77); however, significant differences were observed in time from door-to-puncture (74.7 vs. 88.8, p < 0.01). Additionally, the mRS score at 90 days worsened significantly for door-to-puncture time >60 min in the off-duty period. Multivariate logistic regression analysis revealed that a low National Institute of Health Stroke Scale (NIHSS) score, high pre-mRS score, posterior circulation, and diabetes were independent indicators of door-to-puncture time >60 min during the off-duty period. CONCLUSION: Door-to-puncture time >60 min during off-duty hours was associated with poor outcomes related to low NIHSS, high pre-mRS, posterior circulation, and diabetes.

DOI： 10.1177/15910199231205050

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

DOI： 10.1227/ons.0000000000000879

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：英語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Carotid artery stenting is sometimes adapted for some at-risk cases; however, appropriate treatment timing with stroke onset is controversial. This study aims to identify factors that have an impact on complications and outcomes, especially in patients at high risk. MATERIALS AND METHODS: We examined the characteristics of 152 consecutive patients treated by carotid artery stenting between January 2018 and March 2022 and retrospectively analyzed the risk factors for complications and poor outcomes (modified-Rankin-Scale deterioration), such as patient background, carotid artery stenting risks (access route tortuosity, severe calcification, vulnerable plaque, estimated glomerular filtration rate <30 mL/min/1.73 m2, etc.), characteristics of the stenosis, details of treatment, and treatment timing. RESULTS: The average North American Symptomatic Carotid Endarterectomy Trial criteria score was 68.3% and the lesion length was 20.5±9.7mm. Among patients, 107 (70.4%) had a carotid artery stenting risk. In high-risk carotid artery stenting cases, symptomatic complications occurred in 32 (30.0%), and the 90-day modified Rankin scale score deteriorated in 15 cases (14.0%). Multivariate analysis showed that cases with triple antithrombotic therapy (p=0.003), stenting within 7 days (p=0.0032), and after 28+ days (p=0.0035) of stroke onset were independently associated factors for complications. CONCLUSIONS: This study showed that among risk factors, triple antithrombotic therapy in particular was a risk factor for perioperative complications. Carotid artery stenting for patients with stroke after 28 days of onset affects the prognosis. Therefore, although further study is warranted, waiting more than one month for treatment in patients requiring carotid artery stenting is a potential risk.

DOI： 10.1016/j.jstrokecerebrovasdis.2023.107329

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2-3 using real-world data. METHODS: Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4-5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0-3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0-3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only. RESULTS: After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2-3). A 90-day mRS score of 0-3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2-3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0-3. CONCLUSION: Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.

DOI： 10.1177/15910199231185637

PubMed

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

症例は58歳女性で、15年前に左顔面がしびれる感覚発作を経験し、10年前から同様の発作が定期的に出現するようになった。近医の画像診断で海綿状血管奇形(CM)を指摘されて、抗てんかん薬による治療が開始され感覚発作は消失した。しかし、7年前から頸部の間代発作を呈するようになり、薬剤抵抗性に発作が持続したため7ヵ月前に当科紹介となり、包括的てんかん精査を経て手術のため入院した。てんかん原性領域はCMの内側で、機能的には発作症候の始まりである頸部の支配領域に位置すると推定してCMおよびその内側の皮質の切除を計画した。電極留置12日後に焦点切除術を施行し、切除外側はヘモジデリン沈着部を残したCMの核出にとどめ、内側ではCM周辺のヘモジデリンの沈着した皮質に切除を加えた。術前に3剤内服していた抗てんかん薬は漸減し、ラモトリギン単剤で術後2年以上発作は抑制されている。

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

DOI： 10.1093/noajnl/vdad043

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Common carotid artery (CCA) occlusion (CCAO) is a rare cause of ischemic stroke and bypass surgery is the common treatment approach. However, safer alternatives should be developed to treat CCAO. A 68-year-old male was diagnosed with left-sided CCAO with decreased left visual acuity due to neck radiation therapy for laryngeal cancer. Recanalization therapy using a pull-through technique was initiated because cerebral blood flow progressively decreased during the follow-up period. First, after a short sheath was inserted into the CCA, the occluded CCA was retrogradely penetrated through the sheath. Second, a micro-guidewire was guided to the aorta from the femoral sheath where it was caught using a snare wire guided from the cervical sheath. Subsequently, the micro-guidewire was gently pulled out from the cervical sheath, penetrated the occluded lesion, and was secured to the femoral and cervical sheaths. Finally, the occluded lesion was dilated using a balloon, and the stent was placed. Five days postprocedure, the patient was discharged uneventfully and exhibited improved left visual acuity. In terms of reliable penetration of obstructive lesions and reduction of embolic and hemorrhagic complications, combined endovascular antegrade and direct retrograde carotid artery stenting is a versatile and minimally invasive treatment option for CCAO.

DOI： 10.2176/jns-nmc.2022-0397

PubMed

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.heliyon.2023.e14712

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. CASE PRESENTATION: The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient's symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient's condition. CONCLUSION: If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient's condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

DOI： 10.1186/s12245-023-00490-4

PubMed

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掲載種別：研究論文（学術雑誌）  

Background: Risk-benefit analysis results for the treatment of unruptured aneurysms smaller than 5 mm are controversial. This study aimed to identify the outcomes and complication associated with treating such unruptured aneurysms. Methods: This was a retrospective study of 165 consecutive patients who underwent endovascular procedures for unruptured cerebral aneurysms of a maximum diameter 5 mm between January 2018 and March 2021. Patient background, aneurysm characteristics, adjuvant technique, volume embolization rate (VER), symptomatic complications, and modified Rankin Scale (mRS) scores were examined. Results: Sixty patients with sufficient data were included in the study. The mean age was 62.1 ± 14.6 years, and the median follow-up period was 12 months. The mean maximum diameter was 4.16 ± 0.63 mm, the neck diameter was 2.73 ± 0.82 mm, and 90% of patients had anterior circulation. Complete occlusion was achieved in 34 cases (57.6%). Although there were no intraoperative ruptures, complications were observed in four patients (6.7%), and one patient (1.7%) had worsened mRS score. Only one patient (1.7%) required retreatment. The first coil VER was independently associated with complete occlusion after endovascular treatment. Univariate analysis of complications showed an association between hypertension, hyperlipidaemia, and the estimated glomerular filtration rate. Conclusions: No patient experienced mRS score deterioration, and only one patient developed permanent disability due to ischemic complications; hence, we could safely treat small unruptured aneurysms. Complications are not related to procedural factors such as coiling adjuvant technique. However, lifestyle-related diseases are related to complications, and we suggest that physicians should remain vigilant of the indication for coiling when treating patients with underlying diseases.

DOI： 10.1016/j.inat.2022.101678

Scopus

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS: Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS: The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

DOI： 10.3171/2022.12.JNS221221

PubMed

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記述言語：英語  

OBJECTIVES: A foreign body granuloma after an endovascular intervention is a rare complication. Some cases of foreign body granulomas, especially after coil embolization, have been reported. However, only four cases of foreign body granulomas after mechanical thrombectomy (MT) have previously been reported. The current study reports two cases of post-MT foreign body granulomas, including a biopsy-proven case. MATERIAL AND METHODS: Case 1: A 73-year-old woman presented with complete occlusion of the right middle cerebral artery. Cerebral angiography and MT were successfully performed with improvement in clinical symptoms. Left hemiparesis and a disturbance in attention appeared after discharge and progressed slowly. She was re-admitted to our hospital 120 days after cerebral infarction owing to foreign body granulomas diagnosed on biopsy. Case 2: A 78-year-old man presented with occlusion of the left cervical internal carotid artery and the left middle cerebral artery. Cerebral angiography, percutaneous transluminal angioplasty, and MT were successfully performed. On the 34th day, he experienced progressive consciousness disorder because of foreign body granulomas. Both cases were successfully treated with steroid therapy. RESULTS: MRI after steroid treatment showed the disappearance of most nodular lesions and improvement of the encephalopathy. CONCLUSIONS: The cause of the granuloma may be an allergic reaction to the hydrophilic polymers that peel from endovascular devices. Steroid therapy is an effective treatment; therefore, neurologists should consider this complication when neurological symptoms or signs on image appears or worsens. A reliable diagnosis is important for prompt treatment.

DOI： 10.1016/j.jstrokecerebrovasdis.2023.106990

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: There have been several reports of central nervous system impairments associated with severe coronavirus disease 2019 (COVID-19) infection on head magnetic resonance imaging and angiography (MRI/A). However, head MRI/A is rarely performed in mild cases, and there have been few reports on intracranial changes after COVID-19 infection in these cases. Here, we report a comparative examination of the findings seen in common head MRI/A sequences in mild cases of COVID-19. METHODS: Of the 15,376 patients who underwent head MRI/A examination called "Brain Dock" between June 2020 and June 2021, 746 patients who received a COVID-19 antibody test were evaluated. Positive and negative patients were comparatively examined for head MRI/A findings such as cerebral white matter lesions, ischemic changes, cerebral microbleeds, cerebral aneurysms, arterial stenosis, sinusitis, and other abnormal findings. RESULTS: Overall, 31 (4.2%) patients were COVID-19 positive, and all of them had mild infections not requiring hospitalization. There was no significant difference in patient characteristics and head MRI/A findings between positive and negative patients. All positive patients showed no particular abnormalities in the nasal findings such as olfactory bulb atrophy or thickening of the olfactory mucosa. CONCLUSION: Intracranial lesions in mild patients do not show a clear difference from those in negative patients. This indicates that findings seen in common MRI/A sequences of severe patients are not likely in mild patients, supporting that there is relatively no damage to the central nervous system in mild patients.

DOI： 10.7759/cureus.34229

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：The Japanese Society for Neuroendovascular Therapy  

DOI： 10.5797/jnet.oa.2022-0043

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記述言語：英語  

BACKGROUND: Brain metastases with hematoma are clinically important as they indicate the potential for rapid neurological deterioration. Non-uterine leiomyosarcoma-derived brain metastases are particularly rare, and their clinical features, including the bleeding rate, are unclear. Herein, we present a rare case of thigh leiomyosarcoma-derived brain metastasis with intratumoral hematoma and review previous case reports. CASE DESCRIPTION: A 68-year-old man with a right thigh leiomyosarcoma presented with multiple brain metastases. The patient received stereotactic radiotherapy; however, he reported sudden right-sided hemiparesis. We found a right frontal irradiated lesion with intratumoral hemorrhage and performed gross total tumor resection. Histopathological examination showed highly atypical cells with prominent necrosis and hemorrhage. Abnormal thin-walled vessels were prominent within the brain tumor, and vascular endothelial growth factor was diffusely expressed immunohistopathologically. To date, 11 cases of brain metastasis from non-uterine leiomyosarcoma, including the present case, have been reported. Of note, six patients had hemorrhage. Three out of six patients presented with hemorrhage before therapeutic intervention, three cases were from residual sites after surgery or radiation. CONCLUSION: More than half the patients with non-uterine leiomyosarcoma-derived brain metastases presented with intracerebral hemorrhage. Furthermore, these patients are at risk of developing rapid neurological deterioration due to intracerebral hemorrhage.

DOI： 10.25259/SNI_113_2023

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1227/neuopn.0000000000000019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Observation is the first management option in asymptomatic meningiomas, but when an enlargement or mass effect is observed, surgery is indicated. This study is aimed at exploring risk factors for complications and recurrence after surgery for asymptomatic meningioma. We also examined the impact of preoperative tumor embolization, which is considered controversial. METHODS: We retrospectively reviewed 109 patients with primary asymptomatic meningiomas surgically treated at our institute between April 2007 and March 2021. Patients who only had headaches as a nonspecific complaint were included in the asymptomatic group. Complications, time to recurrence, and Glasgow Outcome Scale (GOS) score were the endpoints of the study. Risk factors for complications and recurrence were explored. Moreover, the effect of the resection on nonspecific headaches was also explored. RESULTS: The permanent postoperative complication rate related to the surgical procedure was 1.8%. Of the total, 107 patients (98.2%) with asymptomatic meningiomas who were surgically treated achieved a GOS score of 5 1 year after the operation. Preoperative headache was present in 31 patients and improved postoperatively in 21 patients. Multivariate analysis using the Cox proportional hazard model showed that preoperative tumor embolization with > 80% resolution of tumor staining (p < 0.001) was negatively related to recurrence, whereas age (p = 0.046) and Simpson grade IV resection (p = 0.041) were positively related to recurrence. CONCLUSION: Although surgery for asymptomatic meningiomas can, in many cases, be safe, it is not free of complications Thus, surgical intervention for asymptomatic meningiomas should be considered cautiously. However, more than half the patients with headaches showed improvement. Simpson grade IV resection cases should be assessed for recurrence, and preoperative tumor embolization might be effective in controlling recurrence.

DOI： 10.1007/s00701-022-05420-6

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

DOI： 10.3390/brainsci12101381

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Stereotactic ablation surgeries including radiofrequency thermocoagulation (RFTC) and laser interstitial thermal therapy are recent less invasive treatment methods for insular epilepsy. Volume-based RFTC after stereoelectroencephalography was first proposed by a French group as a more effective method for seizure relief in insular epilepsy patients than stereoelectroencephalography-guided RFTC. OBJECTIVE: To describe the feasibility and technical details about volume-based RFTC in patients with insulo-opercular epilepsy. METHODS: We successfully treated 3- and 6-year-old patients with medically refractory insulo-opercular epilepsy with volume-based RFTC, in which the target volume of coagulation was flexibly designed by combining multiple spherical models of 5-mm diameter which is smaller than reported previously. RESULTS: The insula was targeted by oblique trajectory from the frontoparietal area in one case, and the opercular cortex was targeted by perpendicular trajectories from the perisylvian cortex in the other case. The use of the small sphere model required more trajectories and manipulations but enabled more exhaustive coagulation of the epileptogenic zone, with 70% to 78% of the planned target volume coagulated without complications, and daily seizures disappeared after RFTC in both patients. CONCLUSION: Volume-based RFTC planned with small multiple sphere models may improve the completeness of lesioning for patients with insulo-opercular epilepsy. Careful planning is necessary to reduce the risks of vascular injuries.

DOI： 10.1227/ons.0000000000000294

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Meningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence. METHODS: We retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects. RESULTS: Preoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003). CONCLUSIONS: After controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications.

DOI： 10.1136/neurintsurg-2022-019080

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.inat.2022.101583

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Molecular targeted therapy using BRAF and/or MEK inhibitors has been applied to BRAFV600E-mutant high-grade gliomas (HGG); however, the therapeutic effect is limited by the emergence of drug resistance. EXPERIMENTAL DESIGN: We established multiple paired BRAFV600E-mutant HGG patient-derived xenograft models based on tissues collected prior to and at relapse after molecular targeted therapy. Using these models, we dissected treatment-resistant mechanisms for molecular targeted therapy and explored therapeutic targets to overcome resistance in BRAFV600E HGG models in vitro and in vivo. RESULTS: We found that, despite causing no major genetic and epigenetic changes, BRAF and/or MEK inhibitor treatment deregulated multiple negative feedback mechanisms, which led to the reactivation of the MAPK pathway through c-Raf and AKT signaling. This altered oncogenic signaling primarily mediated resistance to molecular targeted therapy in BRAFV600E-mutant HGG. To overcome this resistance mechanism, we performed a high-throughput drug screening to identify therapeutic agents that potently induce additive cytotoxicity with BRAF and MEK inhibitors. We discovered that HSP90 inhibition combined with BRAF/MEK inhibition coordinately deactivated the MAPK and AKT/mTOR pathways, and subsequently induced apoptosis via dephosphorylation of GSK3β (Ser9) and inhibition of Bcl-2 family proteins. This mediated potent cytotoxicity in vitro and in vivo in refractory models with acquired resistance to molecular targeted therapy. CONCLUSIONS: The combination of an HSP90 inhibitor with BRAF or MEK inhibitors can overcome the limitations of the current therapeutic strategies for BRAFV600E-mutant HGG.

DOI： 10.1158/1078-0432.CCR-21-3622

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000525229

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The use of mechanical thrombectomy (MT) for treatment of acute large vessel occlusion has recently increased. Prompt and timely guiding catheter (GC) induction is necessary to improve prognosis of MT and reduce the time for recanalization. However, difficulties in GC induction are encountered in some patients. This GC induction depends mainly on the aortic arch structure. Therefore, this study focused on assessing presence of tracheal shift on chest X-ray images as pre-treatment evaluation method for GC induction due to its wide availability as an indicator for status of the mediastinum. METHODS: We retrospectively examined 33 patients who underwent MT at our facilities between April 2017 and March 2021. The patients were divided into two groups according to presence or absence of tracheal shift on chest X-ray images. Background characteristics and treatment courses in these two groups were compared. RESULTS: Among 33 patients, tracheal shift was observed on the chest X-ray images of 14 patients. Furthermore, tracheal shift was positively correlated with the time of GC induction (32.9 min vs. 11.6 min, [p < 0.05]) and the female sex (p = 0.03). Additionally, tracheal shift exhibited correlations with multiple risk factors of atherosclerosis (p = 0.04). CONCLUSIONS: In patients with tracheal shift, GC induction could be expectedly difficult. Therefore, advanced disinfection of the right upper arm and affected side of the neck during MT in preparation for changing an approach route is required.

DOI： 10.1177/19714009221084237

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recovery time after corpus callosotomy (CC) is known to be longer in elderly than in younger patients. OBJECTIVE: To evaluate the relationship between patient age and recovery time of activities of daily living (ADL) after 1-stage complete CC. METHODS: This study included 41 patients (22 women; aged 13 months-34 years, median 7 years) who underwent 1-stage complete CC for medically intractable seizures with drop attacks, infantile spasms, and/or bilaterally synchronized electroencephalographic discharges between August 2009 and April 2019. The timing of restart of competence in 5 ADL categories and surgical outcomes were recorded. RESULTS: Patients (1) restarted speech at 2.2 ± 1.3 (mean ± 2 standard deviations; range 1-5) days, (2) restarted replying with their own name on request at 5.5 ± 8.6 (2-33) days, (3) restarted oral intake at 1.6 ± 1.7 (1-11) days, (5) discontinued intravenous feeding at 6.0 ± 3.0 (2-16) days, and (5) restarted ambulation or wheelchair movement at 5.8 ± 3.4 (2-10) days. Younger patients showed significantly (P < .0223) earlier recovery of ambulation or wheelchair movement, but no age difference was found in the other 4 ADL categories. Overall seizure freedom was achieved in 5 patients, excellent (>80%) seizure reduction in 11, good (50%-80%) seizure reduction in 5, and poor (<50%) seizure reduction in 20. CONCLUSION: Early ADL recovery after 1-stage complete CC is favorable in both young and adult patients. These findings, with good surgical outcomes, will encourage more positive consideration of 1-stage complete CC in both pediatric and adult patients.

DOI： 10.1227/neu.0000000000001871

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Parent artery occlusion (PAO) is an effective treatment for hemorrhagic diseases associated with the internal carotid artery. There are several reports of long-term cerebral infarction or the formation of de novo cerebral aneurysms following PAO. MATERIALS AND METHODS: We retrospectively reviewed these complications in 38 patients who underwent PAO for therapeutic treatment. We investigated perioperative cerebral infarctions, long-term cerebral infarctions, and de novo aneurysms. RESULTS: The mean age of the patients was 64.0 years, and 25 patients (65.8%) were female. The causative diseases were unruptured (n = 19; 50.0%) and ruptured (n = 8; 21.1%) aneurysms. PAO was performed after ischemic tolerance was assessed with balloon test occlusion (BTO), and BTO was performed in 34 patients, of whom 25 (73.5%) had ischemic tolerance. Twenty-six patients (68.4%) were treated with PAO alone, eight (23.5%) with low-flow bypass, and six (17.6%) with high-flow bypass. Perioperative complications occurred in five patients (13.2%): two of the 26 patients (7.7%) who underwent scheduled treatment and three of the 12 patients (25.0%) who underwent emergency treatment. One patient (2.6%) had long-term de novo aneurysm, and none developed cerebral infarction. CONCLUSIONS: These results showed that the assessment of ischemic tolerance by performing BTO and appropriate revascularization in scheduled treatments are important to reduce perioperative and long-term cerebral infarctions. PAO must be performed with greater caution in emergency treatment.

DOI： 10.1177/15910199221095786

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a WHO grade II and III tumor arising from pineal parenchymal cells. PPTID is a rare tumor accounting for less than 1% of all primary central nervous system neoplasms. Therefore, reports describing the clinical characteristics and biological features of PPTID are lacking. Moreover, the therapeutic strategy remains controversial. The current study aimed to evaluate treatment results and problems of contemporary therapeutic modalities of PPTID based on its features compared with other pineal parenchymal tumors. A comprehensive systematic literature review of 69 articles was performed, including articles on PPTID (389 patients) and similar tumors. Patient demographics, disease presentation, imaging characteristics, biological features, and current therapeutic options and their results were reviewed. We found that histopathological findings based on current WHO classification are well associated with survival; however, identifying and treating aggressive PPTID cases with uncommon features could be problematic. A molecular and genetic approach may help improve diagnostic accuracy. Therapeutic strategy, especially for grade III and aforementioned uncommon and aggressive tumors, remains controversial. A combination therapy involving maximum tumor resection, chemotherapy, and radiotherapy could be the first line of treatment. However, although challenging, a large prospective study would be required to identify ways to improve the clinical results of PPTID treatment.

DOI： 10.1007/s10143-021-01674-3

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Scholar  

Background:

It is not well-known that contralateral vertebral artery dissecting aneurysms (VADA) may be newly revealed after parental artery occlusion for unilateral VADA. However, the optimal treatment strategies and perioperative management have not been established. In this report, we present the case of a patient who required reconstructive embolization in the subacute stage for contralateral VADA developed after endovascular internal trapping of the ruptured VADA.

Case Description:

A 61-year-old man developed subsequent disturbance of consciousness. Head CT showed a diffuse and symmetrical SAH. 3DCT revealed a fusiform aneurysm of the left intracranial vertebral artery with bleb formation. We performed emergency endovascular parent artery occlusion of the left vertebral artery. A digital subtraction angiography on postoperative day 16 showed continued occlusion of the left VA, and a fusiform aneurysm was noted at the right VA. We performed reconstructive embolization and the patient eventually recovered with minimal persistent symptoms.

Conclusion:

Since the outcomes of contralateral VAD complicated by infarction or hemorrhage are poor, and most cases develop within 7–14 days after endovascular internal trapping for unilateral VAD, performing bilateral radiographic reinspection within this time frame is recommended for early detection and preventive treatment of possible contralateral VADs.

DOI： 10.25259/sni_19_2022

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その他リンク： http://surgicalneurologyint.com/surgicalint-articles/reconstructive-embolization-for-contralateral-vertebral-artery-dissecting-aneurysm-that-developed-after-internal-trapping-of-ruptured-vertebral-artery-dissection-a-case-report-and-literature-review/

記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Through the progression of devices, the adaptation of carotid artery stenting (CAS) has been expanded according to the non-inferiority of CAS for carotid endarterectomy reported by several randomized control trials. To maintain favorable outcomes, identifying prognostic factors is essential for optimizing treatment indications and periprocedural management. This study focused on the prognostic factors of CAS using real-world data. METHODS: This retrospective multicenter cohort study aimed to identify the prognostic factors after CAS using real-world data from the stroke registry of Yokohama (STrOke Registry of Yokohama; STORY) from January 1, 2018 to May 31, 2021. Patient characteristics, procedural factors, complications, and prognoses were collected using medical records. RESULTS: Data from 107 patients were enrolled in this study after excluding those with insufficient data (2 cases). The mean participant age was 74.9±8.2 years, and 66 patients (61.7%) were symptomatic. Symptomatic lesions were a significant prognostic factor in the overall analysis (p=0.003). A multivariate analysis showed that the estimated glomerular filtration rate (eGFR) (odds ratio: 1.11, p=0.003) and staged CAS (odds ratio: 38.9, p=0.04) were independent prognostic factors. The odds ratio and relative risk of mRS deterioration when eGFR was under 49 mL/min/1.73 m2 compared with when eGFR was above 49 mL/min/1.73 m2 were 5.2 and 3.74, respectively. CONCLUSIONS: In this real-world multicenter study, we established independent prognostic factors for CAS using high totality data. For patients with symptomatic lesions and low eGFR (≤49 mL/min/1.73 m2), indication for treatment should be considered strictly.

DOI： 10.1016/j.jstrokecerebrovasdis.2021.106269

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Brain metastasis is rare in ovarian cancer patients. The results of Gamma Knife radiosurgery (GKRS) for the treatment of patients with brain metastases from ovarian cancer were retrospectively analyzed to derive the efficacy and prognostic factors for survival and local tumor control. Further histopathological analysis was also performed. METHODS: The authors retrospectively reviewed the medical records of 118 patients with 566 tumors who had undergone GKRS at the 10 GKRS institutions in Japan. RESULTS: After the initial GKRS, the median overall survival time was 18.1 months. Multivariate analysis showed that uncontrolled primary cancer (p = 0.003) and multiple intracranial metastases (p = 0.034) were significant unfavorable factors. Ten patients died of uncontrolled brain metastases at a median of 17.1 months. The 6-, 12-, and 24-month neurological death rates were 3.2%, 4.6%, and 11.9%, respectively. The 6-, 12-, and 24-month neurological deterioration rates were 7.2%, 13.5%, and 31.4%, respectively. The 6-, 12-, and 24-month distant brain control failure rates were 20.6%, 40.2%, and 42.3%, respectively. Median tumor volume was 1.6 cm3 and marginal dose was 20 Gy. The 6-, 12-, and 24-month local tumor control rates were 97.6%, 95.2%, and 88.0%, respectively. Peritumoral edema (p = 0.043), more than 7-cm3 volume (p = 0.021), and prescription dose less than 18 Gy (p = 0.014) were factors that were significantly correlated in local tumor control failure. Eight patients had symptomatic radiation injury. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 7.8%, and 12.2%, respectively. Primary ovarian cancer was histopathologically diagnosed for 313 tumors in 69 patients. Serous adenocarcinoma was found in 37 patients and other types in 32 patients. Median survival times were 32.3 months for the serous type and 17.4 months for other types after initial GKRS. Patients with serous-type tumors survived significantly longer than patients with other types (p = 0.039). The 6-, 12-, and 24-month local tumor control rates were 100%, 98.8%, and 98.8%, respectively. Serous-type tumors were a significantly good prognosis factor for local tumor control after GKRS (p = 0.005). CONCLUSIONS: This study established a relationship between the efficacy of GKRS treatment for brain metastases and the histological type of primary ovarian cancer. GKRS for ovarian cancer brain metastasis can provide satisfactory survival and local control, especially in cases of serous adenocarcinoma.

DOI： 10.3171/2021.12.JNS212239

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Endovascular embolization using standalone coils is the preferred treatment option for ruptured cerebral aneurysms to avoid the use of dual antiplatelet therapy with stent coiling or endoluminal flow diversion devices. However, it has been reported that patients undergoing the standalone coiling approach are at risk for periprocedural thromboembolism. Therefore, this systematic review and meta-analysis was performed to clarify the risks and benefits of antiplatelet therapy (AT) during coiling procedures performed to treat ruptured aneurysms, including the incidence of early thromboembolic events, hemorrhagic and delayed ischemic events, as well as clinical outcomes. METHODS: A comprehensive search of three databases was performed for articles from inception to June 2021. After fulfilling the inclusion criteria, five studies were included in this meta-analysis and 462 patients with aneurysmal subarachnoid hemorrhage (aSAH) were identified who underwent endovascular standalone coiling treatment. Aneurysm location, patient characteristics, and aSAH grades were comparable between the AT and non-AT groups. RESULTS: AT significantly decreased the incidence of thromboembolic events immediately after the coiling procedures compared with non-AT (OR 3.42; 95% CI 1.77 to 6.61, p<0.001). The incidences of hemorrhage, delayed ischemia, and clinical outcomes with or without AT were not significantly different between groups. CONCLUSIONS: Although this study showed no beneficial effect of AT on clinical outcomes, the results suggest that AT could be combined with standalone coiling to avoid thromboembolism during the perioperative period. A large prospective study and/or an additional meta-analysis would be required to further investigate how AT benefits standalone coil embolization in aSAH.

DOI： 10.1136/neurintsurg-2021-018346

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed. METHODS: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastrointestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients' background information. RESULTS: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. CONCLUSIONS: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587.

DOI： 10.1111/den.13945

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Meningioma is the most common primary neoplasm of the central nervous system (CNS). Generally, these tumors are benign and have a good prognosis. However, treatment can be challenging in cases with aggressive variants and poor prognoses. Among various prognostic factors that have been clinically investigated, bone invasion remains controversial owing to a limited number of assessments. Recent study reported that bone invasion was not associated with WHO grades, progression, or recurrence. Whereas, patients with longer-recurrence tended to have a higher incidence of bone invasion. Furthermore, bone invasion may be a primary preoperative predictor of the extent of surgical resection. Increasing such evidence highlights the potential of translational studies to understand bone invasion as a prognostic factor of meningiomas. Therefore, this mini-review summarizes recent advances in pathophysiology and diagnostic modalities and discusses future research directions and therapeutic strategies for meningiomas with bone invasion.

DOI： 10.3389/fonc.2022.895374

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor is a major component of neurotransmission. Although elevated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated currents initiate epileptic discharges. We have recently developed the first PET tracer for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, [11C]K-2, to visualize and quantify the density of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.

DOI： 10.1093/braincomms/fcac023

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jiph.2021.08.016

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記述言語：英語  

BACKGROUND: The pathogenesis and endovascular treatment strategy for spontaneously thrombosed unruptured cerebral aneurysms have not yet been comprehensively described. OBSERVATIONS: The authors reported on a 78-year-old woman who had large bilateral unruptured cavernous carotid artery aneurysms that induced chronic disseminated intravascular coagulation and acquired factor XIII deficiency. The right aneurysm was symptomatic and partially thrombosed. Hemorrhagic diathesis and abnormal values of laboratory data improved after administration of recombinant human thrombomodulin followed by endovascular treatment in which three pipeline embolization devices were deployed for the right aneurysm. LESSONS: To the best of the authors' knowledge, this was the first report of an unruptured cerebral aneurysm leading to coagulation disorders with clinical manifestation that was treated successfully by endovascular intervention after intensive perioperative management.

DOI： 10.3171/CASE21288

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).

DOI： 10.1016/j.ctrv.2021.102209

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

DOI： 10.1016/j.wneu.2021.04.041

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Primary central nervous system lymphoma (PCNSL) is a highly aggressive, extra-nodal non-Hodgkin lymphoma that is confined to the central nervous system (CNS) and the eyes. Most PCNSLs arise in immunocompetent older patients and less frequently in immunocompromised patients with Epstein-Barr virus infection. Although a patient's initial response to chemotherapy and radiation therapy is favorable, the clinical outcome of PCNSL remains poor compared to that of systemic lymphoma. Radiation-induced neurotoxicity is also a critical problem for patients with PCNSL. Therefore, a novel therapeutic strategy is required to overcome these challenges. Recent studies have largely uncovered the genomic landscape and associated histopathological features of PCNSL. Based on this background, novel therapeutic agents, such as Bruton's tyrosine kinase inhibitors and immune checkpoint inhibitors, have been introduced for patients with PCNSL. Here, we provide an overview of the updated histopathological and genomic characterization of PCNSL and summarize the current therapeutic strategies. We also review current preclinical PCNSL models for translational research.

DOI： 10.1007/s10014-021-00408-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

ABSTRACT: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs 1037.0 minutes, P < .001).Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.

DOI： 10.1097/MD.0000000000026161

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Implantation of subdural electrodes on the brain surface is still widely performed as one of the "gold standard methods" for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. However, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.

DOI： 10.3390/brainsci11030307

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

DOI： 10.1093/jnen/nlaa161

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

DOI： 10.1093/jnen/nlaa141

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioblastoma multiforme (GBM), the most common brain tumor in adults, has an extremely poor prognosis, which is attributed to the aggressive properties of GBM cells, such as dysregulated proliferation and disseminative migration. We recently found that peptide TNIIIA2, derived from tenascin-C (TNC), which is highly expressed in GBM, contributes to the acquisition of these aggressive properties through β1-integrin activation. In general, cancer cells often acquire an additional malignant property that confers resistance to apoptosis due to loss of adhesion to the extracellular matrix, termed anoikis resistance. Our present results show that regulation of β1-integrin activation also plays a key role in both the development and loss of anoikis resistance in GBM cells. Despite being derived from a GBM with an extremely poor prognosis, the human GBM cell line T98G was susceptible to anoikis but became anoikis resistant via treatment with peptide TNIIIA2, which is able to activate β1-integrin. The TNIIIA2-conferred anoikis resistance of T98G cells was disrupted by further addition of peptide FNIII14, which has the ability to inactivate β1-integrin. Moreover, anchorage-independent survival of GBM cells in suspension culture was abrogated by peptide FNIII14, but not by RGD and CS-1 peptides, which are antagonistic for integrins α5β1, αvβ3, and α4β1. These results suggest that GBM cells develop anoikis resistance through activation of β1-integrin by TNC-derived peptide TNIIIA2, which is abundantly released into the tumor microenvironment of GBM. Inactivation of β1-integrin may provide a promising strategy to overcome the apoptosis resistance of cancer cells, including GBM.

DOI： 10.1016/j.bbrc.2020.12.050

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記述言語：英語  

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is induced by common neurosurgical conditions, for example, trauma, stroke, tumors, and surgical interventions in the brain. The aggressiveness of the treatment for NCSE depends on its neurological prognosis. Aphasic status epilepticus (ASE) is a subtype of focal NCSE without consciousness impairment. The impact of ASE on neurological prognosis is poorly documented. We describe a case of postoperative ASE resulting in verbal and memory deficits. CASE DESCRIPTION: A 54-year-old, right-handed man with focal impaired awareness seizures underwent partial resection for a left temporal lobe tumor. No neurological deficits were observed immediately after surgery. Three days later, however, a focal to bilateral tonic-clonic seizure (FBTCS) occurred, followed by aphasia. Electroencephalography revealed 1.5 Hz left-sided periodic discharges. He was diagnosed with ASE. Multiple anti-seizure drugs were ineffective for the resolution of the patient's verbal disturbance. Nine days after the FBTCS, deep sedation with intravenous anesthetics was performed and the ASE stopped. Thereafter, his symptoms gradually improved. However, the prolonged ASE resulted in verbal and memory deficits. Automated hippocampal volumetry revealed an approximate decrease of 20% on the diseased side on magnetic resonance imaging 3 months after surgery. CONCLUSION: Prolonged ASE can induce verbal and memory deficits. Early intervention with intravenous anesthetics is required to obtain a favorable neurological prognosis.

DOI： 10.25259/SNI_1120_2021

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記述言語：英語  

Dermatofibrosarcoma protuberans (DFSP) originates from the dermal layer of the skin; the optimum treatment is an extended marginal resection. We describe a case of DFSP of the scalp with a skull invasive defect that was thoroughly examined pathologically to determine the optimum length of surgical margins. The tumor cells infiltrated up to 26 mm into the dermal tissues, whereas no infiltrating tumor cells were present in the skull, indicating the combination of marginal resection of the dermal tissues and lower of the skull can be a clinically relevant strategy for treatment of DFSP cases with skull invasion.

DOI： 10.2176/nmccrj.cr.2020-0297

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記述言語：英語  

Meningiomas are the most common intracranial primary neoplasm in adults, and show various histological subtypes, indicating heterogeneous clinical and molecular genetic characteristics. Different subtypes of meningioma coexisting independently within the main tumor of another different subtype is a quite rare clinical situation. A 69-year-old woman presented with a several- year history of dizziness as a non-specific complaint. Magnetic resonance imaging (MRI) revealed an extra-axial mass lesion in the left parieto-occipital region including two well-demarcated, round mass components. Total resection was performed via left parieto-occipital craniotomy. Two white masses were identified within the main tumor, with neither showing dural attachments. Pathological findings showed the main mass represented meningothelial meningioma and the demarcated mass lesions were both fibrous meningiomas. No transitional features existed between these subtypes. No differences in genetic characteristics were evident between subtypes of meningioma. We have described, apparently for the first time, a case of two fibrous meningiomas coexisting in an isolated manner in meningothelial meningioma with the similar molecular genetic profile.

DOI： 10.2176/nmccrj.cr.2020-0159

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Epidemiological contact tracing is a powerful tool to rapidly detect SARS-CoV-2 infection in persons with a close contact history with COVID-19-affected patients. However, it remains unclear whom and when should be PCR tested among the close contact subjects. Methods: We retrospectively analyzed 817 close contact subjects, including 144 potentially SARS-CoV-2-infected persons. The patient characteristics and contact type, duration between the date of the close contact and specimen sampling, and PCR test results in PCR positive and negative persons were compared. Results: We found that male gender {adjusted odds ratio 1.747 [95% confidence interval (CI) 1.180-2.608]}, age ≥ 60 [1.749 (95% CI 1.07-2.812)], and household contact [2.14 (95% CI 1.388-3.371)] are independent risk factors for close contact SARS-CoV-2 infection. Symptomatic subjects were predicted 6.179 (95% CI 3.985-9.61) times more likely to be infected compared to asymptomatic ones. We could observe PCR test positivity between days 1 and 17 after close contact. However, no subject could be found with a Ct-value <30, considered less infective, after day 14 of close contact. Conclusions: Based on our results, we suggest that contact tracing should be performed on the high-risk subjects between days 3 and 13 after close contacts.

DOI： 10.3389/fpubh.2021.690006

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記述言語：英語  

Cognitive decline is a well-known chronic side effect of multidisciplinary treatment of pineal region tumors, whereas epilepsy is an under-reported chronic consequence caused by multiple potential factors including radiotherapy, surgery, or chemotherapy. Some long-term survivors have suffered drug-resistant epilepsy after treatment, which impaired the quality of life. We report five consecutive patients with drug-resistant epilepsy after combined treatment of pineal region tumor (5 men, aged 21-42 years) among 1201 epilepsy patients who underwent comprehensive evaluation in our tertiary epilepsy center from 2011 to 2018. The comprehensive epilepsy evaluation included medical interview, long-term video electroencephalography (EEG) monitoring (VEM), and magnetic resonance (MR) imaging. The patients started to have seizures at 2-22 years after initial treatment for the tumor. Four of the five patients had focal impaired awareness seizures, whereas one patient had only visual aura. All patients had EEG seizures during VEM, which confirmed the diagnosis of focal epilepsy, but three patients had no interictal epileptiform discharges (IEDs). Two patients had diagnoses of focal epilepsy arising from the left occipital region based on ictal EEG findings. Both patients had MR imaging lesion in the left occipital lobe, radiation-induced cavernoma, or surgical injury. The remaining three patients showed poor localization of epileptogenic foci based on VEM and MR imaging. Drug-resistant epilepsy after multidisciplinary treatment of pineal region tumor is characterized by focal impaired awareness seizures with poorly localized EEG onset or rare interictal spikes.

DOI： 10.2176/nmccrj.cr.2021-0093

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記述言語：英語  

Background: Intraventricular tumors can generally result in obstructive hydrocephalus as they grow. Rarely, however, some intraventricular tumors develop superficial siderosis (SS) and trigger hydrocephalus, even though the tumor has hardly grown. Here, we present an illustrative case of SS and nonocclusive hydrocephalus caused by subependymoma of the lateral ventricles. Case Description: A 78-year-old man with an intraventricular tumor diagnosed 7 years ago had been suffering from gait disturbance for 2 years. He also developed cognitive impairment. Intraventricular tumors showed little growth on annual magnetic resonance imaging (MRI). MRI T2-star weighted images (T2*WI) captured small intratumoral hemorrhages from the beginning of the follow-up. Three years before, at the same time as the onset of ventricular enlargement, T2*WI revealed low intensity in the whole tumor and cerebral surface. Subsequent follow-up revealed that this hemosiderin deposition had spread to the brain stem and cerebellar surface, and the ventricles had expanded further. Cerebrospinal fluid (CSF) examination revealed xanthochromia. The tumor was completely removed en bloc. Histopathological findings were consistent with those of subependymoma. Although CSF findings improved, SS and hydrocephalus did not improve. Therefore, the patient underwent a lumboperitoneal shunt for CSF diversion after tumor resection. Conclusion: Some intraventricular tumors cause SS and nonobstructive hydrocephalus due to microbleeding, even in the absence of tumor growth. T2*WI and, if necessary, timely CSF examination can allow identification of presymptomatic SS. This follow-up strategy may provide a favorable course by facilitating early intervention in patients with intraventricular lesions, not just subependymomas.

DOI： 10.25259/SNI_868_2021

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Primary central nervous system lymphoma (PCNSL) is an isolated type of lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations of MYD88 and CD79B in immunocompetent PCNSL, whereas LMP1 activation is commonly observed in Epstein-Barr virus (EBV)-positive PCNSL. However, a lack of clinically representative preclinical models has hampered our understanding of the pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here, we establish a panel of 12 orthotopic, patient-derived xenograft (PDX) models from both immunocompetent and EBV-positive PCNSL and secondary CNSL biopsy specimens. PDXs faithfully retained their phenotypic, metabolic, and genetic features, with 100% concordance of MYD88 and CD79B mutations present in PCNSL in immunocompetent patients. These models revealed a convergent functional dependency upon a deregulated RelA/p65-hexokinase 2 signaling axis, codriven by either mutated MYD88/CD79B or LMP1 with Pin1 overactivation in immunocompetent PCNSL and EBV-positive PCNSL, respectively. Notably, distinct molecular alterations used by immunocompetent and EBV-positive PCNSL converged to deregulate RelA/p65 expression and to drive glycolysis, which is critical for intracerebral tumor progression and FDG-PET imaging characteristics. Genetic and pharmacologic inhibition of this key signaling axis potently suppressed PCNSL growth in vitro and in vivo. These patient-derived models offer a platform for predicting clinical chemotherapeutics efficacy and provide critical insights into PCNSL pathogenic mechanisms, accelerating therapeutic discovery for this aggressive disease. SIGNIFICANCE: A set of clinically relevant CNSL xenografts identifies a hyperactive RelA/p65-hexokinase 2 signaling axis as a driver of progression and potential therapeutic target for treatment and provides a foundational preclinical platform. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5330/F1.large.jpg.

DOI： 10.1158/0008-5472.CAN-20-2425

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We retrospectively assessed the effectiveness and safety of Gamma Knife radiosurgery (GKRS) for asymptomatic obstructive hydrocephalus associated with posterior fossa metastases, which was known empirically but not well discussed. METHODS: We reviewed the medical records of 27 patients who underwent GKRS for asymptomatic obstructive hydrocephalus related to posterior fossa metastases. RESULTS: Cumulative control rates of hydrocephalus were 11.1%, 51.9%, 70.4%, and 74.6% at 1, 2, 3, and 6 months after GKRS. Primary gastrointestinal tract cancer (P = 0.001) was significantly correlated with unfavorable management. Evans ratio at GKRS (median 0.31) improved significantly compared with that at 1-3 months after GKRS (median 0.26) (P < 0.0001) and maintained at 6 to 12 months. Cumulative local tumor control rates were 91.7%, 70.8%, and 64.4% at 3, 6, and 12 months after GKRS. Primary gastrointestinal tract cancer (P = 0.018) and no conventional systemic agents (P = 0.027) were significantly correlated with unfavorable control. Cumulative incidence rates of adverse radiation effects were 0.0%, 16.7%, and 24.2% at 6, 9, and 12 months after GKRS. Primary gastrointestinal tract cancer (P < 0.0001) and single and 2- or 3-fraction GKRS (P < 0.0001) were significantly correlated with unfavorable outcomes. All but 1 patient avoided surgical procedure for hydrocephalus after GKRS. CONCLUSIONS: The present findings suggest that GKRS is an effective and safe treatment for asymptomatic obstructive hydrocephalus caused by posterior fossa metastases, and all but 1 could avoid invasive surgical procedures for hydrocephalus. Posterior fossa metastases from gastrointestinal tract cancer resulted in unsatisfactory outcomes for control of hydrocephalus, tumor progression, and adverse radiation effects.

DOI： 10.1016/j.wneu.2020.09.059

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recurrent RELA and YAP1 fusions are intimately associated with tumorigenesis in supratentorial ependymomas. Chromothripsis and focal copy number alterations involving 11q are hallmarks of these tumors. However, it is unknown whether the chromosomal alterations are a direct causal event resulting in fusion transcripts. In addition, the biological significance of the RELA fusion variants and YAP1 fusions is not yet fully characterized. In this study, we generated gene rearrangements on 11q with the CRISPR/Cas9 system and investigated the formation of oncogenic ependymoma fusion genes. Further, we examined the oncogenic potential of RELA fusion variants and YAP1 fusions in a lentiviral gene transfer model. We observed that endogenous RELA fusion events were successfully induced by CRISPR/Cas9-mediated genome rearrangement in cultured cells. In vivo genome editing in mouse brain resulted in the development of ependymoma-like brain tumors that harbored the Rela fusion gene. All RELA fusion variants tested, except a variant lacking the Rel homology domain, were able to induce tumor formation, albeit with different efficacy. Furthermore, expression of YAP1-FAM118B and YAP1-MAMLD1 fusions induced the formation of spindle-cell-like tumors at varying efficacy. Our results indicate that chromosomal rearrangements involving the Rela locus are the causal event for the formation of Rela fusion-driven ependymomas in mice. Furthermore, the type of RELA. fusion might affect the aggressiveness of tumors and that the Rel homology domain is essential for the oncogenic functions of RELA. fusions. The YAP1 fusion genes are also oncogenic when expressed in mice.

DOI： 10.1186/s40478-020-01080-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

STUDY DESIGN: A systematic review and meta-analysis were performed with the literature including the case of C5 palsy following anterior cervical decompression surgery. OBJECTIVE: The aim of this study was to compare three reconstructive procedures of anterior cervical decompression, the incidences of delayed C5 palsy and other complications were assessed. SUMMARY OF BACKGROUND DATA: Delayed C5 palsy is now a well-known complication after cervical decompression surgery. The etiology of C5 palsy has been studied, especially after posterior surgery. However, in anterior surgery there has been a lack of investigation due to procedure variation. Additionally, limited evidence exists regarding the risk of C5 palsy in surgical procedures. METHODS: We performed an extensive literature search for C5 palsy and other complications with ACDF, ACCF, and their combination (Hybrid). Gross incidences of C5 palsy after these three procedures were compared, and specific superiorities (or inferiorities) were investigated via comparison of binary outcomes between two of three groups using odds ratios (OR). RESULTS: Twenty-six studies met the inclusion criteria. A total of 3098 patients were included and 5.8% of those developed C5 palsy. Meta-analyses demonstrated that ACDF had a lower risk of palsy than ACCF (OR 0.36, 95% confidence interval [CI] 0.16-0.78), whereas ACDF versus Hybrid (OR 0.60, 95% CI 0.24-1.51) and Hybrid versus ACCF (OR 1.11, 95% CI 0.29-4.32) were not significantly different. Although these differences were not observed in shorter lesion subgroups, there were significant differences between the three procedures in longer lesion subgroups (P = 0.0005). Meta-analyses revealed that in longer lesions, ACDF had a significantly lower incidence than ACCF (OR 0.42, 95% CI 0.22-0.82). Additionally, Hybrid surgery was noninferior for palsy occurrence compared to ACCF, and suggested a trend for reduced rates of other complications compared to ACCF. CONCLUSION: ACDF may yield better outcomes than Hybrid and ACCF. Furthermore, Hybrid may have advantages over ACCF in terms of surgical complications. LEVEL OF EVIDENCE: 3.

DOI： 10.1097/BRS.0000000000003637

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

小児後頭蓋窩上衣腫で、播種を伴い多発に再発した場合の治療については一定の見解はない。本症例は第四脳室に発生した退形成性上衣腫の6歳女児で、3回の手術で全摘出後に後頭蓋窩照射するも、その後播種を伴い再発を繰返した。定位照射により各腫瘍は1年程度制御でき、合計14回の手術と11回の定位照射で発症から60ヵ月は良好なQOLを保つことができた。再発時の治療は再手術や追加照射を繰り返すことになり、患児の負担が大きい。定位照射は手術回数を減らしQOLを維持する目的で、治療オプションと成り得ると考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00650&link_issn=&doc_id=20210115260006&doc_link_id=%2Fco2socie%2F2020%2F004504%2F006%2F0358-0364%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fco2socie%2F2020%2F004504%2F006%2F0358-0364%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語  

DOI： 10.1002/pbc.28618

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cerebral bypass surgery, such as the superficial temporal artery-middle cerebral artery bypass, is one of the essential procedures for cerebral revascularization. However, very narrow or thin blood vessels will increase the risk of anastomotic problems, such as occurs in Moyamoya disease. For such vessels, we have devised a "lifting method" in the recipient arteriotomy. In the present study, we have introduced this novel optional technique and evaluated its effects. METHODS: The lifting method is a procedure of lifting the incision edge of a linear incision on the recipient vessel to widen the ostium. We attempted the lifting method in 23 consecutive patients (41 arteries) and, as a historical control, compared the results with those from the conventional method in 25 consecutive patients (37 arteries) for the previous 3 years. We compared patient age, years of surgical experience, recipient vessel diameter, anastomotic events, and final patency. As a subanalysis, the same evaluations were performed separately for patients with Moyamoya disease. Furthermore, the time required for the lifting procedure was measured retrospectively. RESULTS: The incidence of anastomotic events with the conventional method was 13.5% overall and 19% in those with Moyamoya disease. No adverse events occurred with the lifting method (P < 0.05). No statistically significant differences were found for the other factors, including final patency between the 2 groups. The time required for the lifting procedure averaged 1 minute, 15 seconds. CONCLUSIONS: Use of the lifting method widens and secures the ostium in a recipient vessel and greatly facilitates operability. We have found it to be a foolproof method enabling safe and reliable anastomosis even with narrow or thin vessels.

DOI： 10.1016/j.wneu.2020.06.077

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily.

DOI： 10.1007/s12565-020-00545-z

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.

DOI： 10.1186/s40478-020-01023-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Cognitive risk associated with insular cortex resection is not well understood. The authors reviewed cognitive and developmental outcomes in pediatric patients who underwent resection of the epileptogenic zone involving the insula. METHODS: A review was conducted of 15 patients who underwent resective epilepsy surgery involving the insular cortex for focal cortical dysplasia, with a minimum follow-up of 12 months. The median age at surgery was 5.6 years (range 0.3-13.6 years). Developmental/intelligence quotient (DQ/IQ) scores were evaluated before surgery, within 4 months after surgery, and at 12 months or more after surgery. Repeated measures multivariate ANOVA was used to evaluate the effects on outcomes of the within-subject factor (time) and between-subject factors (resection side, anterior insular resection, seizure control, and antiepileptic drug [AED] reduction). RESULTS: The mean preoperative DQ/IQ score was 60.7 ± 22.8. Left-side resection and anterior insular resection were performed in 9 patients each. Favorable seizure control (International League Against Epilepsy class 1-3) was achieved in 8 patients. Postoperative motor deficits were observed in 9 patients (permanent in 6, transient in 3). Within-subject changes in DQ/IQ were not significantly affected by insular resection (p = 0.13). Postoperative changes in DQ/IQ were not significantly affected by surgical side, anterior insular resection, AED reduction, or seizure outcome. Only verbal function showed no significant changes before and after surgery and no significant effects of within-subject factors. CONCLUSIONS: Resection involving the insula in children with impaired development or intelligence can be performed without significant reduction in DQ/IQ, but carries the risk of postoperative motor deficits.

DOI： 10.3171/2020.5.PEDS2058

PubMed

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Flow diverters (FDs) have marked the beginning of innovations in the endovascular treatment of large unruptured intracranial aneurysms, but no multi-institutional studies have been conducted on these devices from both the clinical and economic perspectives. OBJECTIVE: To compare retreatment rates and healthcare expenditures between FDs and conventional coiling-based treatments in all eligible cases in Japan. METHODS: We identified patients who had undergone endovascular treatments during the study period (October 2015-March 2018) from a national-level claims database. The outcome measures were retreatment rates and 1-yr total healthcare expenditures, which were compared among patients who had undergone FD, coiling, and stent-assisted coiling (SAC) treatments. The coiling and SAC groups were further categorized according to the number of coils used. Retreatment rates were analyzed using Cox proportional hazards models, and total expenditures were analyzed using multilevel mixed-effects generalized linear models. RESULTS: The study sample comprised 512 FD patients, 1499 coiling patients, and 711 SAC patients. The coiling groups with ≥10 coils and ≥9 coils had significantly higher retreatment rates than the FD group with hazard ratios of 2.75 (1.30-5.82) and 2.52 (1.24-5.09), respectively. In addition, the coiling group with ≥10 coils and SAC group with ≥10 coils had significantly higher 1-year expenditures than the FD group with cost ratios (95% CI) of 1.30 (1.13-1.49) and 1.31 (1.15-1.50), respectively. CONCLUSION: In this national-level study, FDs demonstrated significantly lower retreatment rates and total expenditures than conventional coiling with ≥ 9 coils.

DOI： 10.1093/neuros/nyz377

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中の外科学会  

症例は31歳男性で、発熱を主訴に外来を受診した。僧帽弁に疣贅を認め、血液培養からα-hemolytic Streptococcusが検出され、感染性心内膜炎と診断され入院となった。入院翌日に心臓血管外科で僧帽弁置換術を施行され、頭部MRIで左後大脳動脈末端に紡錘状の動脈瘤を認めた。抗生剤投与にもかかわらず動脈瘤が消退しないため血管内治療となった。全身麻酔下に視覚誘発電位(VEP)の術中モニタリングを行い、バルーンを拡張、造影を行うと後頭葉の造影欠損を認め、直後から左後頭葉のVEP振幅が低下し始めた。そこで、left parieto-occipital arteryを温存しつつleft calcarine arteryの起始拡張部をコイル塞栓することにした。術後はアスピリン100mg/日とクロピドグレル300mg/日の内服を開始し、クロピドグレルは75mg/日で維持を行った。MRAで動脈瘤は消失し、MRI拡散強調画像で新規梗塞はなかった。視野欠損なく独歩で退院した。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J02079&link_issn=&doc_id=20200527210009&doc_link_id=%2Fcp4strok%2F2020%2F004802%2F009%2F0134-0138%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcp4strok%2F2020%2F004802%2F009%2F0134-0138%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The adult mammalian central nervous system (CNS) rarely recovers from injury. Myelin fragments contain axonal growth inhibitors that limit axonal regeneration, thus playing a major role in determining neural recovery. Nogo receptor-1 (NgR1) and its ligands are among the inhibitors that limit axonal regeneration. It has been previously shown that the endogenous protein, lateral olfactory tract usher substance (LOTUS), antagonizes NgR1-mediated signaling and accelerates neuronal plasticity after spinal cord injury and cerebral ischemia in mice. However, it remained unclear whether LOTUS-mediated reorganization of descending motor pathways in the adult brain is physiologically functional and contributes to functional recovery. Here, we generated LOTUS-overexpressing transgenic (LOTUS-Tg) rats to investigate the role of LOTUS in neuronal function after damage. After unilateral pyramidotomy, motor function in LOTUS-Tg rats recovered significantly compared to that in wild-type animals. In a retrograde tracing study, labeled axons spanning from the impaired side of the cervical spinal cord to the unlesioned hemisphere of the red nucleus and sensorimotor cortex were increased in LOTUS-Tg rats. Anterograde tracing from the unlesioned cortex also revealed enhanced ipsilateral connectivity to the impaired side of the cervical spinal cord in LOTUS-Tg rats. Moreover, electrophysiological analysis showed that contralesional cortex stimulation significantly increased ipsilateral forelimb movement in LOTUS-Tg rats, which was consistent with the histological findings. According to these data, LOTUS overexpression accelerates ipsilateral projection from the unlesioned cortex and promotes functional recovery after unilateral pyramidotomy. LOTUS could be a future therapeutic option for CNS injury.

DOI： 10.1016/j.expneurol.2019.113068

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

42歳男性.誘因なく頭痛,めまい,嘔吐が出現した.頭部MRI検査では両側椎骨動脈(VA)から脳底動脈の描出不良を認め,両側小脳,脳幹に梗塞巣を認めた.左VAは大動脈弓部から起始していた.患者は抗血栓療法により増悪なく経過し,両側VAは経時的変化により再開通したことなどから,両側VA解離と診断した.両側VA解離は比較的稀であり,左VA大動脈起始に合併した例は渉猟した限り認めなかった.両側発生の原因として,一側の解離の対側進展や,一側の解離による血流低下が対側の血流増加をもたらし解離を誘発することが推測されている.さらに,大動脈弓から起始している左VAは解離の危険性が高いことが報告されている.このことから,特に左VA大動脈起始例では,右VA解離により左VA解離を起こす可能性もしくは潜在性に起こしている可能性が推測され,本例はそれを支持する症例と考えられた.(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01786&link_issn=&doc_id=20201201360005&doc_link_id=%2Fdh3strok%2F2020%2F004206%2F005%2F0523-0527%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdh3strok%2F2020%2F004206%2F005%2F0523-0527%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：一般社団法人 日本脳卒中の外科学会  

<p>Introduction: Magnetic resonance imaging (MRI) and spinal digital subtraction angiography (DSA) are considered the gold standard for the screening and diagnosis of spinal dural arteriovenous fistula (SPDAVF). However, the flow-void signals of abnormal vessels are not always reported, even when spinal cord edema is detected with the MRI, rendering the diagnosis in such cases difficult. Similarly, although selective spinal DSA is useful for the definite diagnosis of SPDAVF, it can be a lengthy procedure requiring technical proficiency. Here, we introduce an effective diagnostic procedure with MRI (3T MRI 3D T2 Cube), followed by reconstruction of the 3D-CTA (64 row multistring detector CT).</p><p>Material and Methods: A total of 15 consecutive cases of SPDAVF present in the departmental database from April 2006 to June 2017 were reviewed in this study. Of these, we enrolled 5 patients who conducted the 3T MRI 3D T2 Cube and/or 3D-CTA with the analysis application VINCENT®.</p><p>Result: Of the 5 SPDAVF cases analyzed, 4 showed flow-void signals around the spinal cord in the 1.5T MRI T2WI. In contrast, all cases showed engorged vessels around the spinal cord with the 3D-CTA reconstructed VINCENT® image. The entry point of the influx vessels can be easily identified, resulting in simple and efficient selective spinal DSA. Furthermore, the 3D-CTA reconstructed image was helpful as a surgical simulation tool.</p><p>Conclusion: The diagnostic procedure of the 3T MRI 3D T2 Cube followed by the reconstructed 3D-CTA image markedly contributes to the diagnosis of SPDAVF and the identification of the entry point of the influx vessels and is helpful for both efficient spinal DSA and surgical simulation.</p>

DOI： 10.2335/scs.48.42

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記述言語：英語  

DOI： 10.1002/pbc.27995

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担当区分：最終著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.4103/ajns.ajns_158_19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cortical plasticity is fundamental to motor recovery following cortical perturbation. However, it is still unclear how this plasticity is induced at a functional circuit level. Here, we investigated motor recovery and underlying neural plasticity upon optogenetic suppression of a cortical area for eye movement. Using a visually-guided eye movement task in mice, we suppressed a portion of the secondary motor cortex (MOs) that encodes contraversive eye movement. Optogenetic unilateral suppression severely impaired contraversive movement on the first day. However, on subsequent days the suppression became inefficient and capability for the movement was restored. Longitudinal two-photon calcium imaging revealed that the regained capability was accompanied by an increased number of neurons encoding for ipsiversive movement in the unsuppressed contralateral MOs. Additional suppression of the contralateral MOs impaired the recovered movement again, indicating a compensatory mechanism. Our findings demonstrate that repeated optogenetic suppression leads to functional recovery mediated by the contralateral hemisphere.

DOI： 10.7554/eLife.50855

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Intractable epilepsy patients with ulegyria could be candidates for resective surgery. Complete resection of ulegyria in the epileptogenic hemisphere is associated with favorable seizure outcome, although the risk of postoperative functional deficits is higher. The authors evaluated the extent of resection and postsurgical outcomes in epilepsy patients with ulegyria who underwent intracranial electroencephalography (iEEG) monitoring prior to resection to clarify the efficacy of iEEG-guided partial resection of ulegyria. METHODS: Ten consecutive epilepsy patients with ulegyria (7 males and 3 females, age range at surgery 7-34 years) underwent iEEG prior to resective surgery between 2011 and 2017 with a minimum follow-up of 12 months (range 12-72 months). The diagnosis of ulegyria was based on the typical pattern of cortical atrophy especially at the bottom of the sulcus on MRI. An iEEG study was indicated after comprehensive preoperative evaluations, including high-field MRI, long-term video-EEG, magnetoencephalography, and FDG-PET. The resection planning was based on iEEG analysis. Total lesionectomy was not always performed, as preservation of cortical function was prioritized. RESULTS: Ulegyria was seen in the occipital and/or parietal lobe in 9 patients and bilaterally in 5 patients. Ictal EEG onset involved the temporal neocortex in 6 patients. Intracranial electrodes were implanted unilaterally in all except 1 patient with bilateral lesions. The extent of MRI lesion was covered by the electrodes. Seizure onset zones (SOZs) and irritative zones (IZs) were identified in all patients. SOZs and IZs were completely resected in 8 patients but were only partially removed in the remaining 2 patients because the eloquent cortices and the epileptogenic zones overlapped. Ulegyria of the epileptogenic side was totally resected in 1 patient. Seizure freedom was achieved in 4 patients, including 3 after partial lesionectomy. Extended resection of the temporal neocortex was performed in 4 patients, although postoperative seizure freedom was achieved only in 1 of these patients. Visual field deficit was seen in 4 patients. Three of 5 patients with bilateral lesions achieved seizure freedom after unilateral resective surgery. CONCLUSIONS: Intracranial EEG-guided partial lesionectomy provides a reasonable chance of postoperative seizure freedom with a lower risk of functional deficits. Patients with bilateral ulegyria should not be excluded from consideration as surgical candidates.

DOI： 10.3171/2019.8.JNS191642

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Device-related infection frequently becomes a serious problem after deep brain stimulation(DBS)surgery and DBS device removal is usually the only effective treatment option. In this study, we examined risk factors for infection related to DBS devices at our institution. METHODS: We retrospectively investigated 80 DBS surgeries performed between March 2009 and September 2017 at our institution. We examined the relationship between DBS device-related infection and the following items:duration of electrode placement surgery, total number of tracks of microelectrode recordings(MER), period between surgeries, highest body temperature until implantable pulse generator(IPG)implantation, and patient background characteristics. RESULTS: Four(5.0%)patients developed device-related infection after DBS surgery. Three of them required device removal, whereas one improved following antibiotic treatment alone. We did not identify any specific trend or risk factor for infection. DISCUSSION: We perform DBS surgery in two stages. Patients were implanted with an IPG 2-3 days after electrode placement until August 2016, and at 6-8 days starting in September 2016. All cases of infection developed before September 2016, and no cases of infection have occurred since September 2016. We believe that lengthy surgical electrode placement affects the general status of patients and performing surgery before stabilization might confer a risk of infection. CONCLUSION: Device-related infection after DBS surgery does not seem to be associated with any risk factors. However, a shorter period between two-staged surgeries might affect infection rates.

DOI： 10.11477/mf.1436204070

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oxidative stress is known to play a critical role in the pathogenesis of various disorders, especially in ischemia/reperfusion (I/R) injury. We identified an apoptosis-inducing humoral factor and named this novel post translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) "oxidative stress-responsive apoptosis inducing protein" (ORAIP). The purpose of this study was to investigate the role of ORAIP in the mechanisms of cerebral I/R injury. Hypoxia/reoxygenation induced expression of ORAIP in cultured rat cerebral neurons, resulting in extensive apoptosis of these cells, which was largely suppressed by neutralizing anti-ORAIP monoclonal antibody (mAb) in vitro. Recombinant-ORAIP induced extensive apoptosis of cerebral neurons. Cerebral I/R induced expression of ORAIP in many neurons in a rat tandem occlusion model in vivo. In addition, we analyzed the effects of intracerebroventricular administration of neutralizing anti-ORAIP mAb on the development of cerebral infarction. Cerebral I/R significantly increased ORAIP levels in cerebrospinal fluid. Treatment with intracerebroventricular administration of neutralizing anti-ORAIP mAb reduced infarct volume by 72%, and by 55% even when started after reperfusion. These data strongly suggest that ORAIP plays a pivotal role and will offer a critical therapeutic target for cerebral I/R injury induced by thrombolysis and thrombectomy for acute ischemic stroke.

DOI： 10.1038/s41598-019-50073-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The suction decompression (SD) method, which proactively aspirates the blood flowing into the aneurysm and reduces the internal pressure of the aneurysm, is useful for clipping surgery of large and giant cerebral aneurysm. However, there has been little discussion on re-utilization of blood aspirated during SD. This study aimed to examine the safety, convenience, and usefulness of autologous transfusion of aspirated blood using a transfusion bag. At the time of craniotomy, the cervical carotid artery is fully exposed. An angiocatheter sheath was inserted into the carotid artery and placed in the internal carotid artery. In SD, blood was aspirated from the sheath at a constant speed and quickly stored in a blood transfusion storage bag. Blood aspiration was repeated with a new syringe; once the transfusion bag was full, the blood was re-administered to the patient. Changes in vital sign and hemoglobin/hematocrit values before and after SD were examined in five cases performed in this procedure. The aspirated blood volumes of five cases ranged from 130 to 400 mL, and all aspirated blood was successfully re-transfused. There was no critical change in vital sign, and no significant decrease in the hemoglobin/hematocrit value. No findings suggestive of complications of thrombus formation, infection, and hemolysis were noted. Re-transfusion of aspirated blood during SD using a transfusion bag is a simple and safe method, which can minimize potential risk of re-utilizing aspirated blood, and enables the safe and easy execution of SD regardless of aspirated blood volume.

DOI： 10.2176/nmc.tn.2018-0299

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tenascin-C is a member of the matricellular protein family, and its expression level is correlated to poor prognosis in cancer, including glioblastoma, whereas its substantial role in tumor formation and malignant progression remains controversial. We reported previously that peptide TNIIIA2 derived from the cancer-associated alternative splicing domain of tenascin-C molecule has an ability to activate β1-integrin strongly and to maintain it for a long time. Here, we demonstrate that β1-integrin activation by TNIIIA2 causes acquisition of aggressive behavior, dysregulated proliferation, and migration, characteristic of glioblastoma cells. TNIIIA2 hyperstimulated the platelet-derived growth factor-dependent cell survival and proliferation in an anchorage-independent as well as -dependent manner in glioblastoma cells. TNIIIA2 also strongly promoted glioblastoma multiforme cell migration, which was accompanied by an epithelial-mesenchymal transition-like morphologic change on the fibronectin substrate. Notably, acquisition of these aggressive properties by TNIIIA2 in glioblastoma cells was abrogated by peptide FNIII14 that is capable of inducing inactivation in β1-integrin activation. Moreover, FNIII14 significantly inhibited tumor growth in a mouse xenograft glioblastoma model. More importantly, FNIII14 sensitized glioblastoma cells to temozolomide via downregulation of O6-methylguanine-DNA methyltransferase expression. Consequently, FNIII14 augmented the antitumor activity of temozolomide in a mouse xenograft glioblastoma model. Taken altogether, the present study provides not only an interpretation for the critical role of tenascin-C/TNIIIA2 in aggressive behavior of glioblastoma cells, but also an important strategy for glioblastoma chemotherapy. Inhibition of the tenascin-C/β1-integrin axis may be a therapeutic target for glioblastoma, and peptide FNIII14 may represent a new approach for glioblastoma chemotherapy. SIGNIFICANCE: These findings provide a proposal of new strategy for glioblastoma chemotherapy based on integrin inactivation.

DOI： 10.1158/1535-7163.MCT-18-1251

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Oligodendroglioma has a relatively favorable prognosis, however, often undergoes malignant progression. We hypothesized that preclinical models of oligodendroglioma could facilitate identification of therapeutic targets in progressive oligodendroglioma. We established multiple oligodendroglioma xenografts to determine if the PI3K/AKT/mTOR signaling pathway drives tumor progression. EXPERIMENTAL DESIGN: Two anatomically distinct tumor samples from a patient who developed progressive anaplastic oligodendroglioma (AOD) were collected for orthotopic transplantation in mice. We additionally implanted 13 tumors to investigate the relationship between PI3K/AKT/mTOR pathway alterations and oligodendroglioma xenograft formation. Pharmacologic vulnerabilities were tested in newly developed AOD models in vitro and in vivo. RESULTS: A specimen from the tumor site that subsequently manifested rapid clinical progression contained a PIK3CA mutation E542K, and yielded propagating xenografts that retained the OD/AOD-defining genomic alterations (IDH1 R132H and 1p/19q codeletion) and PIK3CA E542K, and displayed characteristic sensitivity to alkylating chemotherapeutic agents. In contrast, a xenograft did not engraft from the region that was clinically stable and had wild-type PIK3CA. In our panel of OD/AOD xenografts, the presence of activating mutations in the PI3K/AKT/mTOR pathway was consistently associated with xenograft establishment (6/6, 100%). OD/AOD that failed to generate xenografts did not have activating PI3K/AKT/mTOR alterations (0/9, P < 0.0001). Importantly, mutant PIK3CA oligodendroglioma xenografts were vulnerable to PI3K/AKT/mTOR pathway inhibitors in vitro and in vivo-evidence that mutant PIK3CA is a tumorigenic driver in oligodendroglioma. CONCLUSIONS: Activation of the PI3K/AKT/mTOR pathway is an oncogenic driver and is associated with xenograft formation in oligodendrogliomas. These findings have implications for therapeutic targeting of PI3K/AKT/mTOR pathway activation in progressive oligodendrogliomas.

DOI： 10.1158/1078-0432.CCR-18-4144

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Transvenous embolization (TVE) via occluded sinus is one option for the treatment of dural arteriovenous fistulas. Understanding of the anatomical characteristics of the occluded sinus is difficult. It is often hard to reach the shunt point because of some risk of vessel perforation. METHODS: We assessed usefulness of T1 Volumetric Isotropic TSE Acquisition (VISTA) Black Blood (BB) and 3D-T1 Fast Field Echo (FFE) for the evaluation and visualization of an occluded sinus. Evaluation of T1 VISTA BB and 3D-T1 FFE was performed preoperatively. TVE was performed via the occluded sinus while referring to the visualized reconstruction image. RESULTS: Fourteen cases of TVE were performed between 2009 and 2015. The entire occluded sinus, including both thrombus and blood flow, was seen as the high-intensity region on 3D FFE T1 gadlinium (Gd). On the other hand, thrombus was seen as the iso- or high-intensity region and blood flow as the low-intensity region on T1 VISTA BB. The maximum intensity projection reconstruction image of 3D FFE T1Gd could visualize the whole occluded sinus and was useful for microcatheter maneuver. Total shunt obliteration was achieved in 13 cases (92.8%) except for one. CONCLUSIONS: Magnetic resonance imaging evaluation of the occluded sinus using both T1 VISTA BB and 3D FFE T1Gd gives us valuable information of the occluded sinus regarding the development and the course of the occluded sinus, the length of the thrombotic occlusion, and leads to safer catheter maneuvers in TVE.

DOI： 10.1016/j.wneu.2019.02.250

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Expression level of tenascin-C is closely correlated to poor prognosis in glioblastoma patients, while the substantial role of tenascin-C responsible for aggressive progression in glioblastoma cells has not been clarified. We previously found that peptide TNIIIA2, which is derived from the tumor-associated tenascin-C variants, has the ability to promote cell adhesion by activating β1-integrins. Our recent study demonstrated that potentiated activation of integrin α5β1 by TNIIIA2 causes not only a dysregulated proliferation in a platelet-derived growth factor (PDGF)-dependent manner, but also disseminative migration in glioblastoma cells. Here, we show that TNIIIA2 enhances the proliferation in glioblastoma cells expressing PDGF-receptorβ, even without exogenous PDGF. Mechanistically, TNIIIA2 induced upregulated expression of PDGF, which in turn stimulated the expression of tenascin-C, a parental molecule of TNIIIA2. Moreover, in glioblastoma cells and rat brain-derived fibroblasts, tenascin-C upregulated matrix metalloproteinase-2, which has the potential to release TNIIIA2 from tenascin-C. Thus, it was shown that autocrine production of PDGF triggered by TNIIIA2 functions to continuously generate a functional amount of PDGF through a positive spiral loop, which might contribute to hyper-proliferation in glioblastoma cells. TNIIIA2 also enhanced in vitro disseminative migration of glioblastoma cells via the PKCα signaling. Collectively, the tenascin-C/TNIIIA2 could be a potential therapeutic target for glioblastoma.

DOI： 10.3390/ijms20133183

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pediatric low-grade gliomas (PLGGs) have relatively favorable prognosis and some resectable PLGGs, such as cerebellar pilocytic astrocytoma, can be cured by surgery alone. However, many PLGG cases are unresectable and some of them undergo tumor progression. Therefore, a multidisciplinary approach is necessary to treat PLGG patients. Recent genomic analysis revealed a broad genomic landscape underlying PLGG. Notably, the majority of PLGGs present MAPK pathway-associated genomic alterations and MAPK signaling-dependent tumor progression. Following preclinical evidence, many clinical trials based on molecular target therapy have been conducted on PLGG patients, some of whom exhibited durable response to target therapy. Here, we provide an overview of PLGG genetics and the evidence supporting the application of molecular target therapy in these patients.

DOI： 10.1007/s10014-019-00340-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vestibular schwannomas usually originate in the internal acoustic meatus, and gradually extends into the cerebellopontine cistern. Invasive growth into the petrous bone is extremely rare. We describe a case of a vestibular schwannoma that aggressively extended into the petrous bone and extracranial space. This may have arisen because of an unusually peripheral site of origin on the vestibular nerve.

DOI： 10.1080/02688697.2019.1588226

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11477/mf.1436203922

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記述言語：英語  

In the revised World Health Organization classification 2016, anaplastic pleomorphic xanthoastrocytoma (PXA) has been newly defined as a variant of the PXA entity. Furthermore, some anaplastic PXA were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome-wide molecular analysis, we show an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile. A full implementation of the molecular approach is the key to predict prognosis and decide the treatment strategy for anaplastic PXA.

DOI： 10.1111/cas.13903

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01228&link_issn=&doc_id=20190304180016&doc_link_id=1390001288148606464&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001288148606464&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS: To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS: High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION: EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.

DOI： 10.1371/journal.pone.0214351

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This retrospective study included 65 patients who underwent multidetector computed tomography (MDCT) carotid angiography; 28 patients were <70 years old (group 1), and 37 were ≥70 years old (group 2). Each low-attenuation (<30 Hounsfield units [HU]) plaque volume (LPV) and total uncalcified plaque volume ([TUPV] ≤150 HU) were semiautomatically measured on each aortic arch and internal carotid artery (ICA) curved planar reformations (CPR), using MDCT angiographic data. Correlation coefficients were employed to assess the impact of each plaque volume on various factors including ICA stenosis. The correlations (r > 0.5) were observed between aortic LPV and each ICA stenosis ratio and >30% stenosis in group 1, between aortic TUPV and male gender in group 1, and between ICA-TUPV and each aortic TUPV or the largest plaque thickness in group 2. Marginal correlations were observed between hyperlipidemia and aortic LPV and ICA-TUPV in group 1. There was no association between cerebral infarction and the aortic and ICA plaques. Both the aortic arch and ICA plaque volumes can be measured clinically. The increasing aortic LPV may be a significant factor associated with the development of ICA stenosis in patients younger than 70 years old.

DOI： 10.1155/2019/5817534

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVEAlthough the conformity index (CI) and the gradient index (GI), which were proposed by Paddick and colleagues, are both logically considered to correlate with good posttreatment results after stereotactic radiosurgery (SRS), this hypothesis has not been confirmed clinically. The authors' aim was to reappraise whether high CI values correlate with reduced tumor progression rates, and whether low GI values correlate with reduced complication incidences.METHODSThis was an institutional review board-approved, retrospective cohort study conducted using a prospectively accumulated database including 3271 patients who underwent Gamma Knife SRS for brain metastases (BMs) during the 1998-2016 period. Among the 3271 patients, 925 with a single BM at the time of SRS (335 women and 590 men, mean age 66 [range 24-93] years) were studied. The mean/median CIs were 0.62/0.66 (interquartile range [IQR] 0.53-0.74, range 0.08-0.88) and the mean/median GIs were 3.20/3.09 (IQR 2.83-3.39, range 2.27-11.4).RESULTSSRS-related complications occurred in 38 patients (4.1%), with a median post-SRS interval of 11.5 (IQR 6.0-25.8, maximum 118.0) months. Cumulative incidences of post-SRS complications determined by a competing risk analysis were 2.2%, 3.2%, 3.6%, 3.8%, and 3.9% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed that only two clinical factors (i.e., peripheral doses and brain volume receiving ≥ 12 Gy) correlated with complication rates. However, neither CIs nor GIs impacted the incidences of complications. Among the 925 patients, post-SRS MRI was performed at least once in 716 of them, who were thus eligible for local progression evaluation. Among these 716 patients, local progression was confirmed in 96 (13.4%), with a median post-SRS interval of 10.8 (IQR 6.7-19.5, maximum 59.8) months. Cumulative incidences of local progression determined by a competing risk analysis were 7.7%, 12.6%, 14.2%, 14.8%, and 15.3% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed neurological symptoms, extracerebral metastases, repeat SRS, and CIs to correlate with incidences of local progression, whereas GIs had no impact on local tumor progression. Particularly, cumulative incidences of local progression were significantly lower in patients with CIs < 0.65 than in those with CIs ≥ 0.65 (adjusted hazard ratio 1.870, 95% confidence interval 1.299-2.843; p = 0.0034).CONCLUSIONSTo the authors' knowledge, this is the first analysis to focus on the clinical significance of CI and GI based on a large series of patients with BM. Contrary to the majority opinion that dose planning with higher CI and lower GI results in good post-SRS outcomes (i.e., low local progression rates and minimal complications), this study clearly showed that the lower the CIs were, the lower the local progression rates were, and that the GI did not impact complication rates.

DOI： 10.3171/2018.6.GKS181314

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Endovascular surgery for vertebral artery dissections (VADs) carries the risk of spinal cord infarction (SCI). Although SCI in the region of the anterior spinal artery (ASA) has been reported, SCI in the region of the posterior spinal artery (PSA) is rare. OBJECTIVE: To investigate PSA infarction after endovascular surgery for VAD. METHODS: Infarction in the region of the PSA after endovascular surgery for VADs carried out in consecutive 21 cases was investigated. The variables of aneurysmal location, status, intra-aneurysmal thrombosis, antithrombotic therapy, and endovascular procedure were investigated in relation to the occurrence of spinal cord or brain stem infarction. RESULTS: Thirteen cases were unruptured aneurysms, and 8, ruptured aneurysms. The endovascular surgical method was internal trapping in 10 cases, stent-assisted coil embolization in 8 cases, and proximal occlusion (PO) in 3 cases. Periprocedural symptomatic infarction was detected in 4 of the 21 cases (19%): 3 SCIs and 1 lower medulla infarction, after 1 stent-assisted coil embolization and 3 PO. All 3 symptomatic SCIs were PSA infarction. On univariate analysis, the variables of posterior inferior cerebellar artery-involved-type, PO, and intraprocedural proximal flow arrest were significantly correlated with occurrence of PSA infarction. CONCLUSION: PSA infarction after endovascular surgery for VAD seems not to be a rare potential complication. Insufficiency of collateral blood flow and artery-to-artery embolism due to intraprocedural flow stagnation of the VA seem to be the possible mechanisms of PSA infarction in addition to previously reported mechanisms such as direct obliteration by the embolic materials and extended thrombosis of the VA stump.

DOI： 10.1093/ons/opy026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Postoperative C5 palsy is a well-known complication after cervical decompression with either a posterior or an anterior approach. Its cause has been discussed more regarding the posterior approach. The main hypothesis is that postoperative spinal cord shift causes root traction and palsy. However, the pathogenesis in anterior cases has not been fully described. Therefore, the purpose of this study was to clarify the risk factors for C5 palsy in the anterior approach through our C5 palsy cases. METHODS: A total of 149 surgical patients with an anterior cervical lesion were treated by a specific spinal surgeon under consistent same treatment strategy. Of these patients, 88 who satisfied the evaluation criteria were enrolled. Postoperative C5 palsy was defined as postoperative weakness of the deltoid with or without weakness of the biceps brachii. Risk factors of C5 palsy were extracted from clinical backgrounds, surgical approaches, and radiologic findings from patients with palsy. RESULTS: Four sides of 3 individuals (4.6%) who underwent multiple corpectomy developed C5 palsy. All paralyses became evident several days after the surgery and recovered. Older age, multiple corpectomy, postoperative spinal cord shift, and foraminal stenosis of C4-5 and C5-6 were statistically extracted as causative factor of C5 palsy. In the patients with palsy, distortion of the anterior nerve root as a result of a residual vertebral spur was observed with anterior spinal cord shift after anterior corpectomy. CONCLUSIONS: Multiple corpectomy for patients with longer anterior lesions and locally developed kyphosis is related to a larger postoperative cord shift, which can cause the occurrence of C5 palsy. Moreover, C4-5 or C5-6 foraminal stenosis can accelerate tethering of the C5 or C6 nerve root. Older patients undergoing multiple corpectomy are susceptible to these risks of palsy. Appropriate patient selection and sufficient additional foraminotomy should be considered for extensive anterior lesions and locally developed kyphosis to avoid postoperative C5 palsy.

DOI： 10.1016/j.wneu.2018.08.240

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We previously reported the efficacy of anti-cancer therapy with hyperthermia using an alternating magnetic field (AMF) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase (AMPK) inhibitor, although this compound is not magnetic. Therefore, we examined the cellular mechanism of AMF-induced cytotoxicity of Compound C in cultured human glioblastoma (GB) cells. An AMF (280 kHz, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro. The AMF also increased Compound C-induced cell-cycle arrest of GB cells at the G2 phase and, thus, inhibited cell proliferation. The AMF increased Compound C-induced reactive oxygen species production. Furthermore, the AMF decreased ERK phosphorylation in the presence of Compound C and suppressed the protective autophagy induced by this compound. The application of an AMF in cancer chemotherapy may be a simple and promising method, which might reduce the doses of drugs used in future cancer treatment and, therefore, the associated side effects.

DOI： 10.1111/cas.13781

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Complications after stereotactic radiosurgery (SRS) for brain metastases (BMs) were analyzed in detail using our database including nearly 3000 BM patients. MATERIALS AND METHODS: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 3271 consecutive patients who underwent gamma knife SRS for BMs during the 1998-2016 period. Excluding four patients lost to follow-up, 112 with three-staged treatment and 189 with post-operative irradiation, 2966 who underwent a single-session of SRS only as radical irradiation were studied. RESULTS: The overall median survival time after SRS was 7.8 (95% CI; 7.4-8.1) months. Post-SRS complications occurred in 86 patients (2.9%) 1.9-211.4 (median; 24.0, IQR; 12.0-64.6) months after treatment. RTOG neurotoxicity grades were 2, 3 and 4 in 58, 25 and 3 patients, respectively. Cumulative incidences determined with a competing risk analysis were 1.4%, 2.2%, 2.4%, 2.6% and 2.9% at the 12th, 24th, 36th, 48th and 60th post-SRS month, respectively. Among various pre-SRS clinical factors and radiosurgical parameters, multivariable analyses demonstrated solitary tumor (Adjusted HR; 0.584, 95% CI; 0.381-0.894, p = 0.0133), controlled primary cancer (Adjusted HR; 2.595, 95% CI; 1.646-4.091, p < 0.0001), no extra-cerebral metastases (Adjusted HR; 1.608, 95% CI; 1.028-2.514, p = 0.0374), KPS ≥80% (Adjusted HR; 2.715, 95% CI; 1.245-5.924, p = 0.0121) and largest tumor volume ≥3.3 cc (Adjusted HR; 0.516, 95% CI; 0.318-0.836, p = 0.0072) to be independently significant predictors of a higher incidence of complications. CONCLUSION: The post-SRS complication incidence is acceptably low (2.9%). Meticulous long-term follow-up after SRS is crucial for all patients.

DOI： 10.1016/j.radonc.2018.08.018

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Cryptococcosis is a fungal infection that mainly occurs in immunocompromised patients. We present the first case of cryptococcal meningitis in a patient who was being administered everolimus for breast cancer. Everolimus, a selective inhibitor of mammalian target of rapamycin, is a molecular targeting agent that is administered not only as an immunosuppressive agent, but also as an anticancer therapeutic. A 72-year-old woman with recurrent breast cancer had been receiving everolimus. She was admitted to our hospital with headache and vomiting. Lumbar puncture revealed high opening pressure, and cerebrospinal fluid (CSF) evaluation diagnosed cryptococcal meningitis. She was administered liposomal amphotericin-B, followed by fosfluconazole. Daily lumbar puncture was insufficient to reduce the high intracranial pressure; thus, continuous lumbar drainage was needed to improve her symptoms. The indwelling catheter was replaced regularly to prevent bacterial infection. She was treated successfully with extracorporeal CSF drainage for 86 days and fosfluconazole administration over 17 weeks. The patient recovered fully and was discharged on day 153 of hospitalization. As patients who receive everolimus are potentially immunocompromised hosts, we recommend that the medicine be administered with caution considering opportunistic infections when used in patients with cancer. (Received April 19, 2018; Accepted August 9, 2018; Published November 1, 2018).

DOI： 10.11477/mf.1416201178

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Preoperative embolization for intracranial meningioma has remained controversial for several decades. In this study, we retrospectively reviewed our experience of embolization using particulate embolic material and coil to clarify the therapeutic efficacy, safety, and risk of complication. Methods  We reviewed 69 patients who underwent embolization with particulate embolic material followed by surgical resection. An additional 6 procedures were included for patients in whom recurrence was treated, for a total of 75 procedures of preoperative embolization. We analyzed the following clinical data: age, sex, tumor size pathology, complications related to embolization, and surgeon's opinion on the intraoperative ease of debulking and blood transfusion. Embolization was performed mainly from the branches of the external carotid artery. Results  No allogenic blood transfusions were needed for any patients. The surgeon had the opinion that whitening and softening of the tumor allowed for easy debulking during decompression of the tumor in most of the patients. Hemorrhagic complications were seen in two patients after embolization. Emergency tumor removal was performed in both of those patients, and they were recovered well after surgery. Transient cranial nerve palsy was seen in one patient. One ischemic complication and one allergic complication occurred. Conclusion  Preoperative embolization could give us an advantage in surgery for meningioma. The procedure reduces intraoperative blood loss and operating time by softening the tumor consistency. However, we must pay attention to the possibility of embolic complications and keep the preparation of emergency craniotomy, particularly in patients with large meningiomas.

DOI： 10.1055/s-0038-1667043

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The utility of surgical simulation with three-dimensional multimodality fusion imaging (3D-MFI) has been demonstrated. However, its potential in deep-seated brain lesions remains unknown. The aim of this study was to investigate the impact of 3D-MFI in deep-seated meningioma operations. MATERIAL AND METHODS: Fourteen patients with deeply located meningiomas were included in this study. We constructed 3D-MFIs by fusing high-resolution magnetic resonance (MR) and computed tomography (CT) images with a rotational digital subtraction angiogram (DSA) in all patients. The surgical procedure was simulated by 3D-MFI prior to operation. To assess the impact on neurosurgical education, the objective values of surgical simulation by 3D-MFIs/virtual reality (VR) video were evaluated. To validate the quality of 3D-MFIs, intraoperative findings were compared. The identification rate (IR) and positive predictive value (PPV) for the tumor feeding arteries and involved perforating arteries and veins were also assessed for quality assessment of 3D-MFI. RESULTS: After surgical simulation by 3D-MFIs, near-total resection was achieved in 13 of 14 (92.9%) patients without neurological complications. 3D-MFIs significantly contributed to the understanding of surgical anatomy and optimal surgical view (p < .0001) and learning how to preserve critical vessels (p < .0001) and resect tumors safety and extensively (p < .0001) by neurosurgical residents/fellows. The IR of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 100% and 92.9%, respectively. The PPV of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 98.8% and 76.5%, respectively. CONCLUSIONS: 3D-MFI contributed to learn skull base meningioma surgery. Also, 3D-MFI provided high quality to identify critical anatomical structures within or adjacent to deep-seated meningiomas. Thus, 3D-MFI is promising educational and surgical planning tool for meningiomas in deep-seated regions.

DOI： 10.1080/02688697.2018.1485877

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a rare case of a ruptured dissecting internal carotid aneurysm caused epistaxis without a history of trauma or infection. An 89-year-old woman experienced epistaxis and suffered from hemorrhagic shock at her previous hospital. Head computed tomography(CT)images revealed a ruptured internal carotid aneurysm protruding into the Onodi cell, the most posterior ethmoidal sinus, which extends superolaterally to the sphenoid sinus. Cerebral angiography demonstrated a multilobular-shaped dissecting aneurysm with a maximal diameter of 6.7mm at the cavernous portion of the internal carotid artery(ICA). Overlapping stenting was performed to prevent recanalization. However, a fatal subarachnoid hemorrhage occurred 2 days after the procedure due to the progression of the dissection to the intracranial ICA. The anatomical characteristics of the ethmoidal sinus could be associated with the occurrence of epistaxis. A ruptured small ICA aneurysm with an Onodi cell might cause epistaxis without a history of trauma or infection.

DOI： 10.11477/mf.1436203815

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記述言語：日本語   出版者・発行元：(株)医学書院  

89歳女。鼻出血のみで発症し、動脈瘤径は最大径6.7mmと比較的小型であった。小型動脈瘤が鼻出血で発症した理由として本例の頭蓋底部の特殊構造が影響している可能性が考えられた。すなわち本例の篩骨洞は、蝶形骨洞に騎乗するように後上方に広く腔が形成され、視神経管・内頸動脈に接していた。この篩骨洞の形状パターンは"Onodi cell"と呼ばれ、Onodi cellをもつ患者においては約2割が先天的に篩骨洞外壁に裂溝を形成し、内頸動脈が篩骨洞内へ露出していると報告されている。本例に対する治療法は、ハイフローバイパス+トラッピング術が必要と考えられたが、高齢であるため低侵襲性を優先して親血管を温存した血管内治療を選択した。コイルによる瘤内塞栓に加え、頭蓋内ステントEnterprise VRDを2本用いたオーバーラッピングステントで瘤内への血流減少を企図したが、遠位型への解離の進展と思われる動脈瘤破裂によって第42病日に死亡した。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01228&link_issn=&doc_id=20180925050010&doc_link_id=1390002184880588416&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390002184880588416&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: MRI scans obtained within 48-72 hours (early postoperative MRI [epMRI]), prior to any postoperative reactive changes, are recommended for the accurate assessment of the extent of resection (EOR) after glioma surgery. Diffusion-weighted imaging (DWI) enables ischemic lesions to be detected and distinguished from the residual tumor. Prior studies, however, revealed that postoperative reactive changes were often present, even in epMRI. Although intraoperative MRI (iMRI) is widely used to maximize safe resection during glioma surgery, it is unclear whether iMRI is superior to epMRI when evaluating the EOR, because it theoretically shows fewer postoperative reactive changes. In addition, the ability to detect ischemic lesions using iMRI has not been investigated. METHODS: The authors retrospectively analyzed prospectively collected data in 30 patients with glioma (22 and 8 patients with enhancing and nonenhancing lesions, respectively) who underwent tumor resection. These patients had received preoperative MRI within 24 hours prior to surgery, postresection radiological evaluation with iMRI during surgery, and epMRI within 24 hours after surgery, with all neuroimaging performed using identical 1.5T MRI scanners. The authors compared iMRI or epMRI with preoperative MRI, and defined a postoperative reactive change as a new postoperative enhancement or T2 high-intensity area (HIA), if this lesion was outside of the preoperative original tumor location. In addition, postoperative ischemia was evaluated on DWI. The iMRI and epMRI findings were compared in terms of 1) postoperative reactive changes, 2) evaluation of the EOR, and 3) presence of ischemic lesion on DWI. RESULTS: In patients with enhancing lesions, a new enhancement was seen in 8 of 22 patients (36.4%) on iMRI and in 12 of 22 patients (54.5%) on epMRI. In patients with nonenhancing lesions, a new T2 HIA was seen in 4 of 8 patients (50.0%) on iMRI and in 7 of 8 patients (87.5%) on epMRI. A discrepancy between the EOR measured on iMRI and epMRI was noted in 5 of the 22 patients (22.7%) with enhancing lesions, and in 3 of the 8 patients (37.5%) with nonenhancing lesions. The occurrence of ischemic lesions on DWI was found in 5 of 30 patients (16.7%) on iMRI, whereas it was found in 16 of 30 patients (53.3%) on epMRI (p = 0.003); ischemic lesions were underestimated on iMRI in 11 patients. CONCLUSIONS: Overall, given the lower incidence of postoperative reactive changes on iMRI, it was superior to epMRI in evaluating the EOR in patients with glioma, both with enhancing and nonenhancing lesions. However, because ischemic lesions can be overlooked on iMRI, the authors recommend only the additional DWI scan during the early postoperative period. Clinicians need to be mindful about not overestimating the presence of residual tumor on epMRI due to the high incidence of postoperative reactive changes.

DOI： 10.3171/2018.3.JNS172516

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Primary central nervous system lymphoma(PCNSL)is a primary brain tumor, which appears commonly and occupies around 4.6% of all primary brain tumors. The standard therapy for this tumor is high-dose methotrexate chemotherapy(HD-MTX)and whole-brain irradiation. No salvage therapies for HD-MTX therapy-refractory or recurrent PCNSLs have been standardized. In our institution, ESHAP therapy(high-dose cytarabine:2,000mg, cisplatin:25mg/m², etoposide:40mg/m², methylprednisolone:500mg)was administered as a secondary chemotherapy, and the efficiency was examined. METHODS: We administered ESHAP therapy as secondary chemotherapy for patients with refractory/recurrent PCNSL after HD-MTX therapy. Patients with PCNSL who were diagnosed and treated at our institute since 1996 were retrospectively studied. Clinical evaluations were performed based on Karnofsky Performance Status and overall survival, and the effect of ESHAP therapy was evaluated using the Response Assessment in Neuro-Oncology criteria. RESULTS: The number of patients with refractory/recurrent PCNSLs were 18(28-77 years of age, median age of 58.5 years). The response rate(RR)after the first course of salvage ESHAP therapy was 77.8%(14 cases), and complete response(CR)was achieved in 6 cases. The RR after the final course of ESHAP therapy was as high as 61.1%(11 cases), and 4 patients retained CR status. In patients with refractory PCNSL who were treated with HD-MTX, the RR in the final course of salvage ESHAP therapy was as high as 77.8%(7 cases), and 3 patients retained CR status during the periods. The occurrence rate of Grade 3 or higher adverse events, according to the Common Terminology Criteria for Adverse Events version 4.0, was 66.7%(12 cases);all events that were associated with blood and lymphatic system disorders were quickly alleviated, and no fatal adverse events occurred. CONCLUSION: In this study, we retrospectively examined the efficacy of ESHAP therapy as a secondary chemotherapy for patients with refractory/recurrent PCNSL after receiving HD-MTX therapy. Based on our findings, we suggest that ESHAP therapy should be considered as an encouraging secondary chemotherapy for patients with refractory/recurrent PCNSL.

DOI： 10.11477/mf.1436203773

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tumor angiogenesis has attracted increasing attention because of its potential as a valuable marker in the differential diagnosis of brain tumors as well as a novel therapeutic target. Prostate-specific membrane antigen (PSMA) is expressed by the neovasculature endothelium of some tumors, with little to no expression by the tumor cells or normal vasculature endothelium. The aim of this study was to investigate the potential of PSMA for the evaluation of the tumor neovasculature of various brain tumors and the possibility of detecting PSMA expression in brain tumors using PET imaging with 89Zr-Df-IAB2M (anti-PSMA minibody). Eighty-three tissue specimens including gliomas, metastatic brain tumors, primary central nervous system lymphomas (PCNSL), or radiation necroses were analyzed by immunohistochemical staining with PSMA antibody. 89Zr-Df-IAB2M PET scans were performed in three patients with recurrent high-grade gliomas or metastatic brain tumor. PSMA was highly expressed in the vascular endothelium of high-grade glioma and metastatic brain tumor, whereas PSMA was poorly expressed in the vascular endothelium of PCNSL and radiation necrosis. PSMA expression in high-grade gliomas and a metastatic brain tumor was clearly visualized by PET imaging with 89Zr-Df-IAB2M. Furthermore, a trend toward a positive correlation between the degree of 89Zr-Df-IAB2M uptake and PSMA expression levels in tumor specimens was observed. PET imaging of PSMA using 89Zr-Df-IAB2M may have potential value in the differential diagnosis of high-grade glioma from PCNSL or radiation necrosis as well as in the prediction of treatment efficacy and assessment of treatment response to bevacizumab therapy for high-grade glioma.

DOI： 10.1007/s11060-018-2825-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non-taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M-phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation-induced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patient-derived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas.

DOI： 10.1111/cas.13637

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Paragangliomas are generally benign, slow-growing tumors. However, approximately 10%-20% are malignant, characterized by distant metastasis. Recently, a germ line mutation in succinate dehydrogenase B subunit (SDHB) has been shown to be associated with malignant behavior in paraganglioma. Here we present a case of SDHB-negative malignant paraganglioma of the jugular foramen with a pseudohypoxic microenvironment and unique imaging features on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography ([18F]-FDG PET), and discuss the significance of SDHB immunohistochemistry and the potential of [18F]-FDG PET for clinical management. CASE DESCRIPTION: A 55-year-old woman was diagnosed with jugular foramen paraganglioma. Initial surgical resection was performed; however, follow-up [18F]-FDG PET indicated multiple uptake regions throughout the body. Biopsies for multiple recurrent lesions revealed consistent pathological features, suggesting distant metastasis. Immunohistochemical analysis revealed a lack of SDHB immunostaining in all specimens. Pseudohypoxic markers, including hypoxia-inducible factor-1α and downstream glycolysis enzymes, were strongly expressed. [18F]-FDG PET demonstrated increased uptake in the lesions, and the patient died 3 years after initial metastasis. CONCLUSION: In patients with head and neck paraganglioma without SDHB expression, close follow-up should be considered because of the risk for metastasis. In such cases, [18F]-FDG PET might be useful for detecting metastasis due to atypical accumulation from pseudohypoxia-induced glycolysis.

DOI： 10.1016/j.wneu.2018.02.147

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ons/opx168

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記述言語：英語  

Acetabular fracture usually is related to high-energy traumatic injury or falls from heights and directly caused by seizures without trauma is extremely rare. We report a 71-years-old man who sustained a left acetabular fracture secondary to generalized seizure after clipping of an unruptured aneurysm without trauma and any risk for fracture. The patient had an aneurysm was arising from the bifurcation of the left internal carotid artery and the posterior communicating artery. After the clipping, the patient had three times tonic-clonic seizures for 1 min and resulted in an acetabular fracture. In our case, acetabular fracture might relate to expose of massive stress generated by strong muscle contraction. Acetabular fracture causes severe complication, such as pelvic hemorrhage and organ injury. Therefore, early recognition and diagnosis of such fracture and risk factor provide an opportunity to secure a better outcome.

DOI： 10.2176/nmccrj.cr.2017-0143

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88 L265P mutation, which is related to NF-κB signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor. METHODS: Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88 L265P mutation was evaluated by polymerase chain reaction and direct sequencing. RESULTS: The MyD88 L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88 L265P mutation nor age >65 years alone significantly predicted overall survival relative to MyD88 wild type and age <65. The MyD88 L265P mutation was predominantly present in patients aged >65 years. Among age >65 patients, the MyD88 L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P < 0.04). CONCLUSION: The MyD88 L265P mutation predicted a poor prognosis in elderly PCNSL patients. A new tailor-made treatment strategy might be needed for these patients.

DOI： 10.1016/j.wneu.2017.12.028

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Despite cumulative evidence supporting the idea that gross total resection (GTR) contributes to prolonged survival of patients with glioblastoma (GBM), the survival outcome of such patients remains unsatisfactory. To develop more effective postoperative therapeutic strategies for patients who underwent GTR, identification of prognostic factors influencing survival is urgently needed. Here we retrospectively analyzed prognostic factors for patients who underwent GTR of newly diagnosed GBM, with a particular focus on the influence of the subventricular zone (SVZ) as the tumor location. Forty-eight consecutive patients with newly diagnosed GBM who underwent GTR during the initial operation were investigated. Tumor involvement of the SVZ was significantly associated with overall survival (OS). The SVZ-positive group had a significantly shorter median OS of 12.2 months, compared to 34.9 months for the SVZ-negative group. The occurrence of leptomeningeal dissemination was significantly influenced by tumor involvement of the SVZ, but was not significantly influenced by ventricular opening during surgery. We observed a statistically significant difference in OS according to radiation modality. The median OS was 36.9 months for patients treated with high-dose proton beam therapy, compared with 26.2 months for patients treated with conventional radiotherapy. We demonstrated that tumor involvement of the SVZ was associated with poor survival of patients who underwent GTR of newly diagnosed GBM, suggesting the potential need for therapeutic strategies that specifically target tumors in the SVZ. Further prospective studies to evaluate whether radiotherapy targeting the SVZ improves survival of patients with tumor involvement of the SVZ who had undergone GTR are warranted.

DOI： 10.1016/j.jocn.2018.01.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the current article, we provide in vitro efficacy evaluation of a unique accelerator-based neutron source, constructed at the Budker Institute of Nuclear Physics (Novosibirsk, Russian Federation), for boron neutron capture therapy (BNCT), which is particularly effective in the case of invasive cancers. U251MG, CHO-K1 and V79 cells were incubated and irradiated in various concentrations of boric acid with epithermal neutrons for 2-3 h in a plexiglass phantom, using 2.0 MeV proton energy and 1.5-3.0 mA proton current, resulting in a neutron fluence of 2.16 × 1012 cm-2. The survival curves of cells loaded with boron were normalized to those irradiated without boron (to exclude the influence of the fast neutron and gamma dose components) and fit to the linear-quadratic (LQ) model. Colony formation assays showed the following cell survival rates (means ± SDs): CHO-K1: 0.348 ± 0.069 (10 ppm), 0.058 ± 0.017 (20 ppm), 0.018 ± 0.005 (40 ppm); V79: 0.476 ± 0.160 (10 ppm), 0.346 ± 0.053 (20 ppm), 0.078 ± 0.015 (40 ppm); and U251MG: 0.311 ± 0.061 (10 ppm), 0.131 ± 0.022 (20 ppm), 0.020 ± 0.010 (40 ppm). The difference between treated cells and controls was significant in all cases (P < 0.01) and confirmed that the neutron source and irradiation regimen were sufficient for control over cell colony formation. We believe our study will serve as a model for ongoing in vitro experiments on neutron capture therapy to advance in this area for further development of accelerator-based BNCT into the clinical phase.

DOI： 10.1093/jrr/rrx071

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本脳卒中学会  

脳卒中急性期において、ロボットスーツHALが効果的な病態を把握するために、HAL介入試験のプロトコルの実行可能性と安全性を評価するとともに、HALによる介入効果を検証した。【方法】脳卒中急性期患者36例に対し、HALの段階的治療プログラムの実行可能性と安全性、および身体機能、日常生活動作の評価を行った。【結果】HAL介入前後において、歩行速度、12段階片麻痺機能評価、NIHSS、Barthel index、motor FIMの有意な改善を認めた。それらは、HALによる歩行動作介入の開始と、25m/min以上の歩行速度の獲得に有意に関係していた。【考察と結語】脳卒中急性期において、HALによる段階的治療プログラムを安全に実行することができた。身体機能と日常生活動作の評価は、HALによる立位・歩行介入の効果を評価するうえで、有用であった。(著者抄録)

DOI： 10.3995/jstroke.10522

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this report, we propose a new polyborate fragment synthesis strategy along the whole chain of the polysaccharide hyaluronic acid (HA) to produce boron neutron capture therapy (BNCT) compounds. Under high pressure and deformatory solid-state conditions, polymolecular system formation takes place due to association of phase-specific transition components into a more or less distinct microscopic organization. Fourier transform infrared (FTIR) spectroscopy shows that HA and polyborates form a network of cyclic polychelate complexes. HA acts as a multidentate ligand using carboxylic and hydroxyl proton donor groups to link oxygen atoms in B⁻O⁻B bonds and borate-anions B⁻O(-): O⁻H···O, O⁻H···(-)O. With free electron pairs in heteroatoms ⁻O(:)···B, ⁻N(:)···B, HA can act simultaneously as an electron donor. Nuclear magnetic resonance (NMR) with 13C and ¹H reveals a preserved complex interaction after both solubilizing and attenuating the HA-polyborate system. Stability of the product in water, low cost, ease of synthesis and scalability of manufacturing indicate that HA-polyborate complexes might have advantages over current chemotherapeutic approaches in creating therapeutic agents for BNCT.

DOI： 10.3390/polym10020181

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

CASE: A 71-year-old woman was receiving dialysis for microscopic polyangiitis(MPA). She was transported to the emergency room after developing a headache and losing consciousness. She was in a coma and had dense left paralysis. Head computed tomography(CT)showed a subarachnoid hemorrhage. Head three-dimensional CT angiography showed an aneurysm proximal to the right M2(inferior trunk), which was considered as the source of bleeding. We performed an emergency aneurysm clipping surgery. However, we placed a permanent clip on the arterial wall defect when the clip detached from the parent artery. Pathological examination of the aneurysm revealed that the layered structure of the artery was damaged because of fibrin degeneration, suggesting that the aneurysm was caused by vasculitis. Coma persisted after surgery, and the patient was transferred to another hospital. DISCUSSION: We found only one report demonstrating an association between a cerebral aneurysm and MPA. Aneurysms resulting from vasculitis are common at the periphery, rather than at vessel bifurcations. Cyclic inflammatory activity causes progressive destruction of the blood vessel wall, further expanding the lumen and forming an aneurysm. Therefore, such aneurysms are more fragile than true aneurysms, and are more likely to be damaged or detached during surgery, as in the present case. Trapping of the parent artery should be considered when the aneurysm is damaged or detached. Accordingly, preoperative planning could anticipate the need for superficial temporal artery to middle cerebral artery bypass.

DOI： 10.11477/mf.1436203686

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

79歳男性。発症時間不明の右片麻痺、全失語を発症した。NIHSS14点、心電図上は心房細動を認めた。MRI拡散強調画像では左中大脳動脈領域の散在性脳梗塞、MRAでは左内頸動脈領域に若干の信号強度低下を認めた。頸動脈エコーでは左内頸動脈起始部に浮動性血栓と高度狭窄の所見を認め、内頸動脈浮動性血栓による脳梗塞と診断された。血管造影検査では両側内頸動脈の強い屈曲と左内頸動脈起始部に浮動性血栓を認めたが、順行性血流は保たれていた。屈曲血管に血栓がトラップされた状態となっており、脳梗塞再発予防のため血栓回収療法を行うこととした。Proximal flow controlとして血栓を回収し、TICI 2bで手技を終了した。術翌日のMRIでは梗塞巣の拡大はなく、神経症状の悪化も見られなかった。頸動脈の屈曲は稀な形態異常ではないが、血栓が屈曲血管にトラップされて順行性の血流が維持されることはきわめて稀である。屈曲血管においては有効血管径が実際の血管径よりも狭小化することが今回の発症機序に関わったものと考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01786&link_issn=&doc_id=20180202580004&doc_link_id=%2Fdh3strok%2F2018%2F004001%2F004%2F0019-0023%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdh3strok%2F2018%2F004001%2F004%2F0019-0023%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Multiple phase II clinical trials on the use of tumor vaccines in cases of high-grade gliomas (HGG), in particular autologous formalin-fixed tumor vaccine (AFTV), demonstrated the safety and potential efficacy of such therapy. There is evidence that maximal resection of neoplasm provides optimal conditions for enhancement of the tumor-specific immune reactions induced by vaccine administration, and thus aggressive surgery may be an important prerequisite for treatment success. Irradiation and chemotherapy may also enhance the effectiveness of vaccines, particularly through modulation of the tumor microenvironment. Nevertheless, the most effective combinations of vaccine therapies with surgery, irradiation, chemotherapy, antiangiogenic therapy, or other modes of immunotherapy in cases of HGG are still unclear and likely to be an active area of research in the future.

DOI： 10.1159/000469684

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We conducted a retrospective analysis of patients younger than 60 years (N = 10, median age 54.5) with newly diagnosed primary central nervous system lymphoma (PCNSL) at the University of Tsukuba Hospital from January 2008 to November 2016. All the patients were scheduled to receive a single regimen without registration to any clinical trials. This was based on a phase 2 study by Memorial Sloan-Kettering Cancer Center (MSKCC); induction chemotherapy with rituximab, methotrexate, procarbazine, and vincristine (R-MPV) (five to seven cycles), followed by whole-brain radiotherapy (rd-WBRT) (23.4 Gy) and two high-dose cytarabine (HD-AC) cycles as a consolidation. The median age was 54.5 years, and median follow up duration was 33.1 months. The 3-year overall survival (OS) and progression-free survival (PFS) were 69% (95% CI 31-89%) and 56% (95% CI 20-81%). The median OS and PFS were not reached, respectively. Acute and delayed toxicities were manageable. In particular, OS and PFS of seven patients who achieved CR by the R-MPV induction chemotherapy were significantly superb (3-year OS, 100%; 3-year PFS, 80%), implying that a large proportion of patients in CR after the completion of this treatment may achieve durable disease control. On the other hand, all of the three patients who had progressive disease during this treatment died of disease progression within 1 year after diagnosis without achieving CR. Identifying the patients having a risk of failure in the R-MPV induction chemotherapy is important, and may allow us to consider a potentially more effective regimen.

DOI： 10.3960/jslrt.17012

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Although Terson's syndrome is a well-known cause of vision loss due to intracerebral aneurysm rupture, optic nerve neuropathy can also occur because of other causes. Here, we report such a case, i.e., a ruptured anterior communicating artery aneurysm accompanied by vision loss and visual field disturbances due to a cause other than Terson's syndrome. A 47-year-old man presented with right superior altitudinal hemianopia. Computed tomography (CT) showed subarachnoid hemorrhage (SAH), and three-dimensional CT angiography revealed an anterior communicating artery aneurysm. Coil embolization was performed. Right visual acuity degenerated to blindness in the acute stage. MRI performed on day 7 post-admission revealed that the aneurysm had swollen and made contact with the right optic disk. On the basis of the patient's clinical course, we believe that the deterioration in his visual acuity could have been due to ischemic optic neuropathy (ION) resulting from SAH, and the subsequent edema and poor blood perfusion may be attributed to spasm. In cases of visual disturbance associated with SAH, as in our case, it is important to perform MRI to evaluate the damage or risk to the optic nerve as soon as possible. (Received December 26, 2016; Accepted June 9, 2017; Published October 1, 2017).

DOI： 10.11477/mf.1416200883

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ependymomas are primary neuroepithelial malignancies that mainly occur during childhood, and arise from ependymal cells along the ventricular systems of the CNS. Recently, it was elucidated that two-thirds of supratentorial (ST) ependymomas harbor oncogenic fusions of RELA, whose protein product is the principal effector of canonical NF-κB signaling. RELA fusion proteins activate signaling for tumor proliferation and malignant progression, resulting in poorer prognoses in these patients compared to those in patients with other ST ependymomas. In this study, we encountered a case of C11orf-RelA fusion-positive ST anaplastic ependymoma that was diagnosed in first tumor resection surgery of multi-staged gross total resection with molecular evidence. In ependymomas, regardless of tumor location or pathological grade, subtotal resection is associated with higher rates of mortality compared with GTR. Molecular analysis based on the application of recent molecular knowledge for ST ependymomas performs a role in appropriate and individualized treatment strategies.

DOI： 10.1007/s10014-017-0297-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The rate of childhood cancer survival has recently reached >80%. Various adverse events among childhood cancer survivors (CCS) have been reported. Proton beams are able to avoid unnecessary irradiation to normal/vital organs. We conducted a quality of life (QOL) study for CCS who were treated with proton beam therapy (PBT). METHODS: We included those patients treated with PBT to the brain, head, or neck and who were ≤15 years old at the University of Tsukuba Hospital between 1983 and 2011. Clinical information was collected from medical records. Questionnaires including the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (which assess health-related quality of life) were sent to the families/patients. RESULTS: Sixty patients were included. Median age at treatment was 6.2 years. The number of patients with status alive/dead/unknown was 32/24/4. Median follow-up period was 63.0 months (range, 48-340 months) for survivors. Questionnaires were sent to 25 families/patients and 19 were returned. PedsQL was assessed for 17 patients. Eleven of 32 living patients had at least one comorbidity grade 3/4. Average QOL score was above that for Japanese schoolchildren and adolescents. There was no correlation with comorbidity, and only longer time from treatment was correlated with a higher PedsQL score (P = 0.006). CONCLUSION: CCS who were treated with multimodal treatment using PBT had a higher QOL score. Higher score was related to longer time since treatment, regardless of comorbidity.

DOI： 10.1111/ped.13323

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

再発下垂体腺腫に対し経鼻内視鏡手術を行った42例(機能性腺腫7例、非機能性腺腫35例)を対象に、腫瘍摘出率、視機能および合併症を調査し、初回手術201例と比較した。また、単変量解析を用いて全摘出困難となる因子を検討した。その結果、腫瘍摘出率は全摘出11例(26%)、亜全摘出(摘出率>95%)25例(60%)、部分摘出6例(14%)であった。初回手術では全摘出170例(76%)であり、再手術例の方が有意に低い全摘出率であった。再手術において視機能は改善16例(38%)、不変26例(62%)で、悪化例はなかった。再手術後の合併症は症候性後出血2例(5%)で、術後3ヵ月評価では1例が術前より改善、他の1例は術前と同程度に改善していた。また、永続的尿崩症を1例(2%)に認めた。術後合併症の発生率は初回手術との間に有意差はなかった。単変量解析では、腫瘍最大径40mm以上の巨大腺腫の有無、鞍隔膜上伸展の有無が全摘出困難となる因子として抽出された。

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

成長ホルモン(GH)産生下垂体腺腫に対し経鼻内視鏡手術を行い術中に海綿静脈洞浸潤を認めた20例を対象に、MRI上のKnosp gradeと術中所見の対比、腫瘍摘出率、寛解率を調査した。寛解率に関しては、コルチナコンセンサスに基づく寛解率も算出した。更に、海綿静脈洞非浸潤例31例の寛解率との比較も行った。その結果、海綿静脈洞浸潤を認めた20例のKnosp gradeは0:0例、1:3例、2:6例、3:6例、4:5例であった。腫瘍摘出率は全摘出が75%、亜全摘出が20%、部分摘出が5%で、Knosp grade 4以外は全例が全摘出であった。寛解率は45%で、海綿静脈洞非浸潤例の寛解率84%に比べ有意に低かった。また、寛解率はKnosp grade 0～3では60%であったが、Knosp grade 4では0%であった。なお、コルチナコンセンサスに基づく寛解率は60%であった。合併症は髄液漏が1例で、頸動脈損傷や外眼筋麻痺は認めなかった。術中出血量は平均197ml(0～1200ml)で、輸血を要した症例はなかった。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01160&link_issn=&doc_id=20171106430001&doc_link_id=10.1507%2Fendocrine.93.S.HPT_5&url=https%3A%2F%2Fdoi.org%2F10.1507%2Fendocrine.93.S.HPT_5&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although a rerupture after surgical clipping of ruptured intracranial aneurysms is rare, it is associated with high morbidity and mortality. The causes for retreatment and rupture after surgical clipping are not clearly defined. METHODS: From a prospectively maintained database of 244 patients who had undergone surgical clipping of ruptured intracranial aneurysms, we selected patients who experienced retreatment or rerupture within 30 days after surgical clipping. Aneurysm occlusions were examined by microvascular Doppler ultrasonography and indocyanine green video-angiography. Indications for retreatment included rerupture and partial occlusion. We analyzed the characteristics and causes of early retreatment. RESULTS: Six patients (2.5%, 95% CI 0.9 to 5.3%) were retreated within 30 days after surgical clipping, including two patients (0.8%, 95% CI 0.1 to 2.9%) who experienced a rerupture. The retreated aneurysms were found in the anterior communicating artery (AcomA) (n = 5) and basilar artery (n = 1). Retreatment of the AcomA (7.5%) was performed significantly more frequently than that of other arteries (0.56%) (p < 0.01). A laterally projected AcomA aneurysm (17.4%) was more frequently retreated than were other aneurysm types (2.3%). Cases of laterally projecting AcomA aneurysms tended to result from an incomplete clip placed using a pterional approach from the opposite side of the aneurysm projection. CONCLUSIONS: Despite developments, the rates of retreatment and rerupture after surgical clipping remain similar to those reported previously. Retreatment of the AcomA was significantly more frequent than was retreatment of other arteries. Patients underwent retreatment more frequently when they were originally treated for lateral type aneurysms using a pterional approach from the opposite side of the aneurysm projection. The treatment method and evaluation modalities should be considered carefully for AcomA aneurysms in particular.

DOI： 10.1007/s00701-017-3245-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Reperfusion therapy by mechanical thrombectomy is used to treat acute ischemic stroke. However, reactive oxygen species generation after reperfusion therapy causes cerebral ischemia-reperfusion injury, which aggravates cerebral infarction. There is limited evidence for clinical efficacy in stroke for antioxidants. Here, we developed a novel core-shell type nanoparticle containing 4-amino-4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (nitroxide radical-containing nanoparticles [RNPs]) and investigated its ability to scavenge reactive oxygen species and confer neuroprotection. METHODS: C57BL/6J mice underwent transient middle cerebral artery occlusion and then received RNPs (9 mg/kg) through the common carotid artery. Infarction size, neurological scale, and blood-brain barrier damage were visualized by Evans blue extravasation 24 hours after reperfusion. RNP distribution was detected by rhodamine labeling. Blood-brain barrier damage, neuronal apoptosis, and oxidative neuronal cell damage were evaluated in ischemic brains. Multiple free radical-scavenging capacities were analyzed by an electron paramagnetic resonance-based method. RESULTS: RNPs were detected in endothelial cells and around neuronal cells in the ischemic lesion. Infarction size, neurological scale, and Evans blue extravasation were significantly lower after RNP treatment. RNP treatment preserved the endothelium and endothelial tight junctions in the ischemic brain; neuronal apoptosis, O2- production, and gene oxidation were significantly suppressed. Reactive oxygen species scavenging capacities against OH, ROO, and O2- improved by RNP treatment. CONCLUSIONS: An intra-arterial RNP injection after cerebral ischemia-reperfusion injury reduced blood-brain barrier damage and infarction volume by improving multiple reactive oxygen species scavenging capacities. Therefore, RNPs can provide neurovascular unit protection.

DOI： 10.1161/STROKEAHA.116.016356

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer is a major cause of childhood death, with central nervous system (CNS) neoplasms being the second most common pediatric malignancy, following hematological cancer. Treatment of pediatric CNS malignancies requires multimodal treatment using a combination of surgery, chemotherapy, and radiotherapy, and advances in these treatments have given favorable results and longer survival. However, treatment-related toxicities have also occurred, particularly for radiotherapy, after which secondary cancer, reduced function of irradiated organs, and retarded growth are significant problems. Proton beam therapy (PBT) is a particle radiotherapy with excellent dose localization that permits treatment of liver and lung cancer by administration of a high dose to the tumor while minimizing damage to surrounding normal tissues. Thus, PBT has the potential advantages for pediatric cancer. In this context, we review the current knowledge on PBT for treatment of pediatric CNS malignancies.

DOI： 10.2176/nmc.ra.2017-0003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To date, clinical trials of various vaccine therapies using autologous tumor antigens or tumor-associated/specific antigen peptide with adjuvants have been performed to treat patients with high-grade gliomas (HGG). Furthermore, immune checkpoint pathway-targeted therapies including anti- programmed cell death 1 (PD-1) antibody have been remarkably effective in other neoplasms, and various clinical trials with anti-PD-1 antibody in patients with HGG have started to date. It is possible that up-regulation of immune checkpoint molecules in tumor tissues after vaccine therapy may be one of the mechanisms of vaccine failure. Multiple preclinical studies indicate that combination therapy with vaccination and immune checkpoint blockade is effective for the treatment of malignant tumors including HGG. Thus, immunotherapy, especially combination therapy with vaccine and immune checkpoint inhibitors, may be a promising strategy for treatment of patients with HGG.

DOI： 10.2176/nmc.nmc.ra.2016-0334

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記述言語：英語  

We report a unique case of delayed brain swelling following craniectomy that improved rapidly after cranioplasty, and discuss the potential mechanism underlying this delayed and reversible brain swelling. A 22-year-old woman developed surgical site infection after removal of a convexity meningioma. Magnetic resonance imaging revealed an epidural abscess around the surgical site. Subsequently, the abscess was evacuated, and the bone flap was removed. Later, brain edema around the skull defect emerged and progressed gradually, despite resolution of the infection. The edematous brain developed focal swelling outward through the bone defect without ventricle dilatation. Because we suspected that the edema and swelling were caused by the state of the bone defect, we performed a cranioplasty 10 weeks after the bone flap removal, and brain edema improved rapidly. We hypothesized that the brain edema was initially caused by surgical stress and inflammation, followed by compression of cortical veins between the dural edge and brain tissue, leading to disruption of venous return and exacerbation of brain edema. When delayed focal brain edema and external swelling progress gradually after bone flap removal, after excluding other pathological conditions, cranioplasty should be considered to improve cortical venous congestion caused by postsurgical adhesion.

DOI： 10.1055/s-0037-1606315

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記述言語：日本語   出版者・発行元：(株)三輪書店  

DOI： 10.11477/mf.5002200673

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The efficacy of mechanical thrombectomy with stent retrievers for emergent large vessel occlusion has been proved by randomized trials. Mechanical thrombectomy is increasingly being adopted in Japan since stent retrievers were first approved in 2014. An urgent clinical task is to offer structured systems of care to provide this treatment in a timely fashion to all patients with emergent large vessel occlusion. Treatment with flow-diverting stents is currently a preferred treatment option worldwide for large and giant unruptured aneurysms. Initial studies reported high rates of complete aneurysm occlusion, even in large and giant aneurysms, without delayed aneurysmal recanalization and/or growth. The Pipeline Embolic Device is a flow diverter recently approved in Japan for the treatment of large and giant wide-neck unruptured aneurysms in the internal carotid artery, from the petrous to superior hypophyseal segments. Carotid artery stenting is the preferred treatment approach for carotid stenosis in Japan, whereas it remains an alternative for carotid endarterectomy in Europe and the United States. Carotid artery stenting with embolic protection and plaque imaging is effective in achieving favorable outcomes. The design and conclusions of a randomized trial of unruptured brain arteriovenous malformations (ARUBA) trial, which compared medical management alone and medical management with interventional therapy in patients with an unruptured arteriovenous brain malformation, are controversial. However, the annual bleeding rate (2.2%) of the medical management group obtained from this study is worthy of consideration when deciding treatment strategy.

DOI： 10.2176/nmc.ra.2017-0027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier B.V.  

Objective: We aimed to clarify the optimal timing for the fluorescence imaging of brain tumor tissue differentiated from brain edema after the administration of photosensitizers. Methods: We have performed an in vivo study of the kinetics of 5-aminolevulinic acid (5-ALA) in comparison with talaporfin sodium using the rat brain tumor model and rat vasogenic edema model produced by cold injury. The in vivo kinetics of 5-ALA and talaporfin sodium in brain tumor model and the vasogenic edema model was determined by a fluorescence macroscope and a microplate reader. Results: The in vivo kinetic study of 5-ALA showed mild fluorescence intensity of protoporphyrin IX (PpIX) in brain tumor differentiated from vasogenic edema. The mean lesion-to-normal-brain ratio (L/N ratio) in the group of brain tumor model 2 h after the administration of 5-ALA was 7.78 ± 4.61, which was significantly higher (P &lt
0.01) than that of the vasogenic edema 2 h after the administration of 5-ALA (2.75 ± 1.12). In vivo kinetic study of talaporfin sodium showed high fluorescence intensity and retention in brain tumor differentiated from vasogenic edema. The mean L/N ratio of the fluorescence intensity in the group of brain tumor model 12 h after the administration of talaporfin sodium was 23.1 ± 11.9, which was significantly higher (P &lt
0.01) than that of the vasogenic edema 12 h after the administration (8.93 ± 8.03). Conclusions: The optimization of fluorescence imaging of brain tumors differentiated from brain edema is possible in the case of 5-ALA within 6 h, and also possible in the case of talaporfin sodium beyond 12 h. © 2009 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.pdpdt.2009.03.005

Scopus

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: It is unclear whether or not bevacizumab(Bev)has a curative ability in newly diagnosed glioblastoma(GBM) patients with low Karnofsky performance status(KPS). MATERIALS AND METHODS: Four of 14 patients with newly diagnosed GBM received combination therapy with extended local radiation, temozolomide(TMZ), and Bev after partialremovalor biopsy of the tumor. RESULTS: The average patient age was 77.2 years(range 67-85)and the male-to-female ratio was 1:3. In all cases, magnetic resonance imaging showed that combination therapy decreased tumor volume and peritumoral edema volume. The therapy was successfully administered to 3 patients without decreasing their KPS. However, 1 patient with seeding lesions dropped out of therapy because of deteriorating consciousness and decreasing KPS. DISCUSSION: Subgroup analysis in a randomized control study(AVAglio)showed that patients with a PS score of 1-2(corresponding to a KPS score of 60-80)tended to have prolonged survival after Bev treatment compared with those with a PS score of 0(corresponding to a KPS score of 90-100). In the present study, radiochemotherapy with Bev decreased lesion and edema volumes in all patients, and led to maintained or improved KPS in 3 patients. These results suggest that the treatment is potentially effective for patients with newly diagnosed GBM and lower KPS.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location. Thirty-one consecutive patients with recurrent malignant gliomas who were treated with bevacizumab were investigated. The treatment response and survival benefit from bevacizumab were analyzed in association with age, sex, Karnofsky performance status, prior pathological diagnosis, prior recurrence pattern, primary location of tumor, recurrence status, and expression of angiogenic and hypoxic markers. The group with leptomeningeal dissemination had a significantly shorter median overall survival with bevacizumab (OSBev) (6.0months, 95% confidence interval (CI) 1.4-10.7) compared to those in the local/distant group (11.8months, 95% CI 6.1-17.4). The median OSBev of the infratentorial tumor group and supratentorial tumor group were 9.2months (95% CI 5.0-13.4) and 10.4months (95% CI 6.6-14.3), respectively. With multivariate analysis, the prior recurrence pattern was the only independent prognostic factor of OSBev. Patients with leptomeningeal dissemination of recurrent malignant glioma experienced minimal benefit from bevacizumab. Therefore, in the context of cost effectiveness, bevacizumab is not recommended for patients with leptomeningeal dissemination.

DOI： 10.1016/j.jocn.2017.02.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma. We investigated 16 patients, ranging in age from 14 to 65 years, with histologically verified WHO grade IV GBM, whose original tumor was resected between 2008 and 2014, and treated with fractionated radiotherapy and temozolomide. Four patients who were treated with immunotherapy using autologous formalin-fixed tumor vaccine were enrolled. All of the patients underwent secondary resection after tumor recurrence within 24 months. We carried out an immunohistochemical examination of the initial and secondary resected tumors from patients using a panel of immune system molecular markers, and assessed whether marker expression correlated with clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was significantly increased in secondary resected specimens compared with initially resected specimens (p ≤ 0.05). All patients expressed PD-L1 on tumor cells in initial and secondary resection specimens. Patients were divided into high or low expression group by median IHC score of PD-1 on initial or secondary resected specimens. No significant differences in patient outcomes were observed between high and low PD-1 or PD-L1 groups of initially resected specimens. In high expression group of secondary resected specimens, most patients score had increased which compared with initial resected tumor specimens. The PD-1 high expression score group of secondary resected specimens was associated with long progression-free survival and short survival after recurrence. PD-L1 expression was detected in almost all initial and secondary specimens. Patients with high PD-1 expression of secondary specimen had bad prognosis after secondary resection. PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of glioblastoma.

DOI： 10.1007/s11060-017-2451-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.pdpdt.2016.12.008

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

DOI： 10.1111/bjh.14080

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11477/mf.1436203508

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: It was reported that proton beam therapy (PBT) reduced the normal brain dose compared with X-ray therapy for pediatric brain tumors. We considered whether there was not the condition that PBT was more disadvantageous than intensity modulated photon radiotherapy (IMRT) and 3D conventional radiotherapy (3D-CRT) for treatment of pediatric brain tumors about the dose reduction for the normal brain when the tumor location or tumor size were different. METHODS: The subjects were 12 patients treated with PBT at our institute, including 6 cases of ependymoma treated by local irradiation and 6 cases of germinoma treated by irradiation of all four cerebral ventricles. IMRT and 3D-CRT treatment plans were made for these 12 cases, with optimization using the same planning conditions as those for PBT. Model cases were also compared using sphere targets with different diameters or locations in the brain, and the normal brain doses with PBT, IMRT and 3D-CRT were compared using the same planning conditions. RESULTS: PBT significantly reduced the average dose to normal brain tissue compared to 3D-CRT and IMRT in all cases. There was no difference between 3D-CRT and IMRT. The average normal brain doses for PBT, 3D-CRT, and IMRT were 5.1-34.8% (median 14.9%), 11.0-48.5% (23.8%), and 11.5-53.1% (23.5%), respectively, in ependymoma cases; and 42.3-61.2% (48.9%), 54.5-74.0% (62.8%), and 56.3-72.1% (61.2%), respectively, in germinoma cases. In the model cases, PBT significantly reduced the average normal brain dose for larger tumors and for tumors located at the periphery of the brain. CONCLUSION: PBT reduces the average dose to normal brain tissue, compared with 3D-CRT and IMRT. The effect is higher for a tumor that is larger or located laterally.

DOI： 10.1186/s13014-017-0775-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Anti-angiogenic therapy represents a promising, new therapeutic modality for malignant gliomas. The present study was designed to define the malignant glioma cases most suitable for anti-angiogenic therapy and to demonstrate the efficacy of anti-angiogenic therapy using soluble-form Flt1 (sFlt1) gene delivery in mice. In human malignant glioma samples (39 glioblastomas, 21 anaplastic astrocytomas and 4 anaplastic oligoastrocytomas), protein expression of VEGF, and its specific natural inhibitor, sFlt1, as well as vessel architecture were assessed. Among these variables, VEGF >1000 ng/ml, VEGF/sFlt1 ratio >1, vessel density >30, and vessel area >7% were prognostic factors for malignant gliomas. VEGF/sFlt1 ratio >1 was the most powerful prognostic marker for survival in multivariate analysis. The sFlt1 gene was also successfully introduced into U87 glioma cells in vitro, resulting in 31% tumor growth inhibition in vivo. sFlt1-transfected tumor demonstrated high sFlt-1 expression along with diminished vessel density and area compared with the control tumor. In transfected tumor, VEGF expression was decreased in the viable area, but still high in the hypoxic area. sFlt1 and VEGF expression was re-evaluated in vitro using glioma cells under normoxic and hypoxic conditions. For sFlt1-transfected cells, VEGF expression was upregulated, but sFlt1 expression was downregulated, resulting in an increase of VEGF/sFlt1 ratio in hypoxic conditions. We conclude that malignant gliomas with a high VEGF/sFlt1 ratio and large vessel area are good candidates for anti-angiogenic therapy. Soluble Flt1 gene delivery was demonstrated to inhibit glioma growth, but this was limited in hypoxic areas.

DOI： 10.3892/ijo.2016.3810

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

ObjectiveWithdrawal of cabergoline is generally challenging, especially in patients with large or invasive macroprolactinomas. Therefore, we aimed to assess long-term results of cabergoline therapy for macroprolactinomas and remission achievement results after withdrawal in patients with macroprolactinomas. We also investigated clinical characteristics and factors related to remission after withdrawal.
MethodsThis was an institutional review board-approved retrospective analysis. We studied 46 macroprolactinoma patients who had taken cabergoline during the period from 2003 through 2013. Administration of cabergoline was maintained for 5 years before withdrawal.
ResultsMedian follow-up after the initiation of cabergoline therapy was 543 (range 53 to 1372) months. Recurrences of hyperprolactinaemia were observed in 3 of 11 (27%) postwithdrawal patients at a median time of 30 (range; 29-112) months, indicating that a high percentage (73%) maintained remission for at least 12 months after cabergoline cessation. Factors significantly associated with remission were analysed in 21 patients receiving long-term cabergoline administration. On multivariate analysis, the absence of cavernous sinus invasion on pretreatment MRI (3/4 tumour encasement of the intracavernous internal carotid artery) (HR; 2194, 95% CI; 206-10710, P = 0006), initial PRL &lt;1327 ng/ml (HR; 828, 95% CI; 124-1996, P = 003) and nadir PRL &lt;19 ng/ml during cabergoline therapy (HR; 514, 95% CI; 110-3902, P = 004) showed statistically significant correlations with remission after withdrawal.
ConclusionsCabergoline therapy can achieve a high percentage (73% in this series) of remission maintenance for at least 12 months after cessation of a 5-year course of therapy, even in patients with macroprolactinomas. The absence of cavernous sinus invasion, serum PRL level lower than 1327 ng/ml before cabergoline therapy or nadir serum PRL below 19 ng/ml were related to more frequent remission after withdrawal of cabergoline in patients receiving this medication for 5 years.

DOI： 10.1111/cen.13240

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記述言語：日本語   出版者・発行元：(一社)日本脳神経外傷学会  

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記述言語：英語  

We report the case of a 40-year-old man presenting with focal headache and a bulge at the right parietal bone, diagnosed as an intradiploic arachnoid cyst. The cyst wall included "meningothelial hyperplasia," which is a rare finding. While over 40 cases of intradiploic arachnoid cysts have been reported to date, meningothelial hyperplasia in an intradiploic arachnoid cyst does not appear to have been reported. We also discuss the pathological findings of arachnoid cysts with meningothelial hyperplasia and mechanisms of enlargement of the arachnoid cyst.

DOI： 10.2176/nmccrj.cr.2016-0147

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

We aimed to reappraise whether post-stereotactic radiosurgery (SRS) results for brain metastases differ between patients with and without neurological symptoms. This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 2825 consecutive BM patients undergoing gamma knife SRS alone during the 15-year period since July 1998. The 2825 patients were divided into two groups; neurologically asymptomatic [group A, 1374 patients (48.6 %)] and neurologically symptomatic [group B, 1451 (51.4 %)]. Because there was considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study was conducted. Ultimately, 1644 patients (822 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival. Competing risk analysis was applied to estimate cumulative incidences of neurological death, neurological deterioration, local recurrence, re-SRS for new lesions and SRS-induced complications. Post-SRS median survival times (MSTs) did not differ between the two groups; 7.8 months in group A versus 7.4 months in group B patients (HR 1.064, 95 % CI 0.963-1.177, p = 0.22). However, cumulative incidences of neurological death (HR 1.637, 95 % CI 1.174-2.281, p = 0.0036) and neurological deterioration (HR 1.425, 95 % CI 1.073-1.894, p = 0.014) were significantly lower in the group A than in the group B patients. Neurologically asymptomatic patients undergoing SRS for BM had better results than symptomatic patients in terms of both maintenance of good neurological state and prolonged neurological survival. Thus, we conclude that screening computed tomography/magnetic resonance imaging is highly beneficial for managing cancer patients.

DOI： 10.1007/s11060-016-2264-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

OBJECTIVE The aim of this study was to reappraise long-term treatment outcomes of stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs). The authors used a database that included patients who underwent SRS with a unique dose-planning technique, i.e., partial tumor coverage designed to avoid excess irradiation of the facial and cochlear nerves, focusing on tumor control and hearing preservation. Clinical factors associated with post-SRS tumor control and long-term hearing preservation were also analyzed.
METHODS This institutional review board approved, retrospective cohort study used the authors' prospectively accumulated database. Among 207 patients who underwent Gamma Knife SRS for VSs between 1990 and 2005, 183 (who were followed up for at least 36 post-SRS months) were studied. The median tumor volume was 2.0 cm3 (range 0.05-26.2 cm3). The median prescribed dose at the tumor periphery was 12.0 Gy (range 8.8-15.0 Gy; 12.0 Gy was used in 171 patients [93%]), whereas tumor portions facing the facial and cochlear nerves were irradiated with 10.0 Gy. As a result, 72%-99% of each tumor was irradiated with the prescribed dose. The mean cochlear doses ranged from 2.3 to 5.7 Gy (median 4.1 Gy).
RESULTS The median durations of imaging and audiometric follow-up were 114 months (interquartile range 73-144 months) and 59 months (interquartile range 33-109 months), respectively. Tumor shrinkage was documented in 110 (61%), no change in 48 (27%), and enlargement in the other 22 (12%) patients. A further procedure (FP) was required in 15 (8%) patients. Thus, the tumor growth control rate was 88% and the clinical control rate (i.e., no need for an FP) was 92%. The cumulative FP-free rates were 96%, 93%, and 87% at the 60th, 120th, and 180th post-SRS month, respectively. Six (3%) patients experienced facial pain, and 2 developed transient facial palsy. Serviceable hearing was defined as a pure tone audiogram result better than 50 dB. Among the 66 patients with serviceable hearing before SRS who were followed up, hearing acuity was preserved in 23 (35%). Actuarial serviceable hearing preservation rates were 49%, 24%, and 12% at the 60th, 120th, and 180th post-SRS month, respectively. On univariable analysis, only cystic-type tumor (HR 3.36, 95% CI 1.18-9.36; p = 0.02) was shown to have a significantly unfavorable association with FR Multivariable analysis followed by univariable analysis revealed that higher age 65 years: HR 2.66, 95% CI 1.16-5.92; p = 0.02), larger tumor volume 8 cm': HR 5.36, 95% CI 1.20-17.4; p = 0.03), and higher cochlear dose (mean cochlear dose &gt; 4.2 Gy: HR 2.22, 95% CI 1.07-4.77; p = 0.03) were unfavorable factors for hearing preservation.
CONCLUSIONS Stereotactic radiosurgery achieved good long-term results in this series. Tumor control was acceptable, and there were few serious complications in patients with small-to medium-sized VSs. Unfortunately, hearing preservation was not satisfactory. However, the longer the observation period; the more important it becomes to compare post-SRS hearing decreases with the natural decline in untreated cases.

DOI： 10.3171/2016.7.GKS161494

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

OBJECTIVE Stereotactic radiosurgery (SRS) without upfront whole-brain radiotherapy (WBRT) has influenced recent treatment recommendations for brain metastasis patients. However, in brain metastasis patients who undergo SRS alone, new brain metastases inevitably appear with relatively high incidences during post-SRS follow-up. However, little is known about the second SRS results. The treatment results of second SRS were retrospectively reviewed, mainly for newly developed or, uncommonly, for recurrent brain metastases in order to reappraise the efficacy of this treatment strategy with a special focus on the maintenance of neurological status and safety.
METHODS This was an institutional review board approved, retrospective cohort study that used a prospectively accumulated database, including 3102 consecutive patients with brain metastases who underwent SRS between July 1998 and June 2015. Among these 3102 patients, 859 (376 female patients; median age 64 years; range 21-88 years) who underwent a second SRS without WBRT were studied with a focus on overall survival, neurological death, neurological deterioration, local recurrence, salvage SRS, and SRS-induced complications after the second SRS. Before the second SRS., the authors also investigated the clinical factors and radiosurgical parameters likely to influence these clinical outcomes. For the statistical analysis, the standard Kaplan-Meier method was used to determine post second SRS survival and neurological death. A competing risk analysis was applied to estimate post second SRS cumulative incidences of local recurrence, neurological deterioration, salvage SRS, and SRS-induced complications.
RESULTS The post second SRS median survival time was 7.4 months (95% CI 7.0-8.2 months). The actuarial survival rates were 58.2% and 34.7% at 6 and 12 months after the second SRS, respectively. Among 789 deceased patients, the causes of death could not be determined in 24 patients, but were confirmed in the remaining 765 patients to be nonbrain diseases in 654 (85.5%) patients and brain diseases in 111 (14.5%) patients. The actuarial neurological death free survival rates were 94.4% and 86.6% at 6 and 12 months following the second SRS. Multivariable analysis revealed female sex, Karnofsky Performance Scale score of 80% or greater, better modified recursive partitioning analysis class, smaller tumor numbers, and higher peripheral dose to be significant predictive factors for longer survival. The cumulative incidences of local recurrence were 11.2% and 14.9% at 12 and 24 months after the second SRS. The crude incidence of neurological deterioration was 7.1%, and the respective cumulative incidences were 4.5%, 5.8%, 6.7%, 7.2%, and 7.5% at 12, 24, 36, 48, and 60 months after the second SRS. SRS-induced complications occurred in 25 patients (2.9%) after a median post second SRS period of 16.8 months (range 0.6-95.0 months; interquartile range 5.6-29.3 months). The cumulative incidences of complications were 1.4%, 2.0%, 2.4%, 3.0%, and 3.0% at 12, 24, 36, 48, and 60 months after the second SRS, respectively.
CONCLUSIONS Carefully selected patients with recurrent tumors either new or locally recurrent are favorable candidates for a second SRS, particularly in terms of neurological status maintenance and the safety of this treatment strategy.

DOI： 10.3171/2016.6.GKS161404

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

To evaluate the safety and efficacy of postoperative proton beam therapy (PBT) combined with nimustine hydrochloride (ACNU) or temozolomide (TMZ) for glioblastoma multiforme (GBM). The subjects were 46 patients with GBM who were treated with high dose (96.6 GyE) PBT. There were 24 males and 22 females, and the median age was 58 years old (range 24-76). The Karnofsky performance status was 60, 70, 80, 90 and 100 in 5, 10, 12, 11 and 8 patients, respectively. Total resection, partial resection, and biopsy were performed for 31, 14 and 1 patients, respectively. Photon beams were delivered to high intensity areas on T2-weighted magnetic resonance imaging (MRI) in the morning (50.4 Gy in 28 fractions). More than 6 h later, PBT was delivered to the enhanced area plus a 10 mm margin in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume in the second half (23.1 GyE in 14 fraction). Concurrent chemotherapy with ACNU during weeks 1 and 4 or daily TMZ was administered in 23 and 23 patients, respectively. The overall 1 and 2 year survival rates were 82.6 and 47.6 %, respectively. Median survival was 21.1 months (95 % CI 13.1-29.2), with no significant difference in survival between the ACNU and TMZ groups. The patient characteristics were similar in the two groups. Late radiation necrosis occurred in 11 patients (six ACNU, five TMZ), but was controlled by necrotomy and therapy including bevacizumab. PBT concurrent with ACNU or TMZ was tolerable and beneficial for carefully selected patients with GBM.

DOI： 10.1007/s11060-016-2228-4

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J04871&link_issn=&doc_id=20160822300014&doc_link_id=1390846634924220032&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390846634924220032&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

頭蓋咽頭腫連続30例(17歳以下の小児9例を含む)を対象に、摘出術後の肥満・認知機能障害を検討した。手術方法は経鼻内視鏡19例、経頭蓋8例、経鼻内視鏡+経頭蓋3例で、いずれも最低限片側の視床下部を温存した。その結果、術後新たに過体重・肥満を呈したもしくは成人例でBMIが9%以上の増加を呈した症例は8例(26.6%)であった。この8例と、術前後で標準体重であった16例を比較し、年齢、性別、平均腫瘍体積、摘出度、経頭蓋手術の割合、鞍隔膜下腫瘍の割合、内分泌機能について相関を解析したところ、男性、術後内分泌機能がgrade4の症例で有意に術後肥満・過体重・BMI9%増加の発生率が高かった。術後、新たな認知機能障害の発生はなく、術前の認知機能障害が悪化したのは1例であった。

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

BACKGROUND: Hemifacial spasm (HFS) caused by a contralateral tumor is extremely rare, and all previously reported cases involved tumors at the cerebellopontine angle. We provide the first report to our knowledge of HFS caused by a contralateral foramen magnum meningioma, which improved after tumor removal without microvascular decompression.
CASE DESCRIPTION: An 80-year-old woman presented with HFS caused by a contralateral foramen magnum meningioma. She had a 3-year history of gradual worsening of right-sided HFS. Magnetic resonance imaging showed a homogeneous gadolinium-enhancing tumor occupying the left ventrolateral portion of the foramen magnum. The loop of the right anterior inferior cerebellar artery extended into the right pontomedullary junction, compressing the root exit zone (REZ) of the right facial nerve. After tumor removal, with no attempt of confirmation of vascular compression of the right facial nerve REZ, facial spasm gradually decreased and eventually almost disappeared. Postoperative magnetic resonance imaging revealed that the loop of anterior inferior cerebellar artery had shifted away from the right facial nerve REZ. Dorsal shift of the anterior inferior cerebellar artery loop toward the facial nerve REZ along with dorsal shift of the vertebral and basilar arteries secondary to the huge contralateral mass located in the ventrolateral portion of the foramen magnum was suggested to represent the main cause of facial spasm.
CONCLUSIONS: Although an extremely rare condition, facial spasm can develop as a result of contralateral tumors in locations other than the cerebellopontine angle.

DOI： 10.1016/j.wneu.2016.01.039

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

The molecular subgrouping of diffuse gliomas was recently found to stratify patients into prognostically distinct groups better than histological classification. Among several molecular parameters, the key molecules for the subtype diagnosis of diffuse gliomas are IDH mutation, 1p/19q co-deletion, and ATRX mutation; 1p/19q co-deletion is undetectable by immunohistochemistry, but is mutually exclusive with ATRX and p53 mutation in IDH mutant gliomas. Therefore, we applied ATRX and p53 immunohistochemistry instead of 1p/19q co-deletion analysis. The prognostic value of immunohistochemical diagnosis for Grade III gliomas was subsequently investigated. Then, the same immunohistochmical diagnostic approach was expanded for the evaluation of Grade II and IV diffuse glioma prognosis. The results indicate immunohistochemical analysis including IDH1/2, ATRX, p53, and Ki-67 index is valuable for the classification of diffuse gliomas, which is useful for the evaluation of prognosis, especially Grade III gliomas and lower-grade gliomas (i.e., Grade II and III).

DOI： 10.1007/s10014-016-0260-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

BACKGROUND: Appropriate hemostasis is essential for clear visualization of the neural structures and cleavage planes. It is also essential for avoiding heat-induced injury, minimizing blood loss, and reducing operative time. OBJECTIVE: To determine the role of cerebrospinal fluid (CSF) in platelet-dependent hemostasis during neurosurgery. METHODS: The amplification of aggregation, activation of integrin aIIbb3, intrinsic and extrinsic coagulation pathways, and activation of signaling cascades in platelets were evaluated. For comparison, various concentrations of a commercially available artificial CSF solution (aCSF), an artificial CSF solution prepared by the authors, and normal saline (NS) were used. Differences between aCSF and NS in obtaining in vivo hemostasis were assessed by measuring the tail vein bleeding time in C57BL/6N mice. RESULTS: Platelet aggregation was directly amplified by the addition of aCSF through increased activation of integrin αIIbβ3, phosphatidylserine exposure, and P-selectin expression. However, the prothrombin time and activated partial thromboplastin time were not primarily related to coagulation activity with the addition of aCSF. Activation of Src kinase was related to platelet activation by aCSF. The elimination of sodium bicarbonate from aCSF and the addition of the selective inhibitor of the HCO3 -/Cl- exchanger, 4,49-diisothiocya natostilbene-2,29-disulfonic acid disodium salt, significantly inhibited platelet aggregation. The bleeding time in aCSF-treatedmice was significantly shorter than that in NS-treatedmice. CONCLUSION: Sodium bicarbonate facilitates hemostasis through the amplification of platelet aggregation function. The existence of CSF and irrigation with aCSF provide better conditions for physiological hemostasis and they have the potential of improving hemostasis by bipolar coagulation or with irrigation during neuroendoscopic procedures.

DOI： 10.1227/NEU.0000000000001058

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

最大径40mm以上の巨大下垂体腺腫21例(A群)と、40mm未満の非巨大下垂体腺腫138例(B群)を対象に、手術成績を後方視的に比較した。摘出率は術後1週間のMRI画像で評価し、視機能と合併症は術後1年まで調査した。術式はA群で17例が経鼻内視鏡単独手術、1例が開頭手術、3例が経鼻内視鏡+開頭同時手術であり、B群で全例が顕微鏡下経蝶形骨洞手術であった。その結果、全摘出率はA群で6/21例(28.6%)、B群で101/138例(73.2%)であり、A群で有意に低かった。視機能の改善率はA群で15/18例(83.3%)、B群で68/79例(86.1%)であり、有意差がなかった。術後合併症は髄液漏、後出血、視機能悪化、鼻出血、永続的尿崩症などの頻度で有意差を認めなかった。巨大下垂体腺腫は経鼻内視鏡を軸とした手術方法を選択することで、依然全摘出が困難な症例は多いが許容できる全摘出率であり、高い視機能改善率と低い合併症率を達成できると考えられた。

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Background: We experienced a case of intraorbital pseudotumor associated with IgG4-related disease, for which we successfully performed an endoscopic endonasal transethmoidal biopsy for the intraorbital pseudotumor as well as endoscopic sinus surgery for a refractory pansinusitis at the same time. Case report: A 59-year-old man was referred to our hospital because of an intraorbital mass lesion. MRI showed 2 mass lesions: a large intraconal lesion encasing the left optic nerve on the orbital apex, and a small extraconal lesion medial to the left medial rectus muscle extending into the anterior ethmoid canal. In addition, CT showed severe pansinusitis. A blood test showed a marked elevation of lgG4. lgG4-related pseudotumor was suspected, but lgG4-related MALT lymphoma was an alternative diagnosis, and a biopsy of the mass lesion was required. We successfully performed both, an endoscopic endonasal transethmoidal biopsy for the mass lesion and endoscopic sinus surgery for the refractory pansinusitis at the same time. The pathological diagnosis was an lgG4-related pseudotumor. Conclusion: Endoscopic endonasal transethmoidal biopsy is an effective and minimally invasive method for making a definitive diagnosis of lgG4-related intraorbital pseudotumor. Using this method, refractory pansinusitis frequently associated with this disease can be treated. For successful treatment, interdisciplinary decision making and collaborative team surgery are crucial.

DOI： 10.11477/mf.1436203206

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Concomitant use of temozolomide (TMZ) and radiotherapy, which is the standard therapy for patients with high-grade glioma, involves a unique regimen with multiple-day, long-term administration. In a previous study, we showed not only higher incidence rates of chemotherapy-induced nausea and vomiting (CINV) during the overall study period, but also substantially higher incidence rates of moderate/severe nausea and particularly severe appetite suppression during the late phase of the treatment. Here, we prospectively evaluated the efficacy of a combination of palonosetron, aprepitant, and dexamethasone for CINV in patients treated with concomitant TMZ and radiotherapy. Twenty-one consecutive patients with newly diagnosed high-grade glioma were enrolled. CINV was recorded using a daily diary and included nausea assessment, emetic episodes, degree of appetite suppression, and use of antiemetic medication. The percentage of patients with a complete response in the overall period was 76.2%. The percentages of patients with no moderate/severe nausea were 90.5, 100, and 90.5% in the early phase, late phase, and overall period, respectively. Severe appetite suppression throughout the overall period completely disappeared. The combination of palonosetron, aprepitant, and dexamethasone was highly effective and well tolerated in patients treated with concomitant TMZ and radiotherapy. This combination of antiemetic therapy focused on delayed as well as acute CINV and may have the potential to overcome CINV associated with a multiple-day, long-term chemotherapy regimen.

DOI： 10.2176/nmc.oa.2016-0177

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JPN SOC MAGNETIC RESONANCE IN MEDICINE  

Background: Carmustine (BCNU) wafer (Gliadel (R) Wafer) implantation after tumor resection is an approved treatment for high-grade glioma (HGG). These wafers change various characteristics on early postoperative magnetic resonance imaging (ep-MRI) including slight expansion of high-intensity areas on T-2-weighted imaging (ep-T-2-HIAs) into adjacent parenchyma without restricted diffusivity. We assessed the frequency of the ep-T-2-HIAs after BCNU wafer implantation in HGG patients. Moreover, we focused on ep-T-2-HIA expansion and its relation to delayed cerebral edema.
Methods: Twenty-five consecutive HGG patients who underwent BCNU wafer implantation were assessed. First, patients were divided into ep-T-2-HIA and non-ep-T-2-HIA groups, and the incidence of delayed adverse effects was compared between the two groups. Subsequently, the patients were divided into delayed edema and non-delayed edema groups, and pre-, intra-, and postoperative data were compared between the two groups.
Results: The ep-T-2-HIA expansion and the delayed edema were evident in 9 cases (36%) and 12 cases (48%), respectively. In comparison of the ep-T-2-HIA and non-ep-T-2-HIA groups, delayed edema was the only delayed adverse effect associated with ep-T-2-HIA expansion (P = 0.004). Univariate analysis showed a significantly higher ratio of delayed edema in the subgroups with maximal diameter of removed cavity &lt;= 40 mm (P = 0.047) and the ep-T-2-HIA expansion in comparison of the delayed edema and non-delayed edema groups. Multivariate analysis showed that the ep-T-2-HIA expansion was the only independent factor associated with delayed edema (P = 0.021).
Conclusion: In BCNU wafer implantation cases, ep-T-2-HIA expansion was a predictive factor for delayed cerebral edema.

DOI： 10.2463/mrms.mp.2015-0054

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本医学物理学会  

<p>The magnetic resonance imaging (MRI) is established as the imaging technique that is essential to the imaging of the central nervous system disease. Above all, the diffusion weighted image (DWI) is known as the tool which can diagnose acute ischemic stroke with high accuracy in a short time. DTI, an applied form of DWI, was devised as a technique to image the structure of the brain white matter. In clinical sites, this technique is used for pathologic elucidation such as the intracerebral tissue injury or mental disorder. Additionally, diffusion tensor tractography (DTT), which is a technique to build three-dimensional structure of the neural fiber tracts, is used for grasping the relations between a brain tumor and the fibers tract. Therefore, these techniques may be useful imaging tools in the central nerve region.</p>

DOI： 10.11323/jjmp.36.2_97

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記述言語：日本語   掲載種別：研究論文（その他学術会議資料等）   出版者・発行元：(公社)日本医学物理学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J03418&link_issn=&doc_id=20161005320002&doc_link_id=130005312335&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130005312335&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本医学物理学会  

<p>¹H-MRS (proton magnetic resonance spectroscopy) is a method for analyzing material components using the difference of the frequency (chemical shift) in magnetic resonance. ¹H-MRS for human body is able to diagnose the clinical conditions by non-invasive analysis of materials in organs. However, the mechanical limitations and complexity in analyses prevented it from becoming popular as MRI (magnetic resonance imaging). Recently, an ideal environment for ¹H-MRS is commonly available such as stronger magnetic field and improved software, yet we still lack common knowledges about ¹H-MRS which makes whom plans to start it difficult. In this article, the principle, tips, clinical applications and spectrum evaluations were explained focusing on novice users.</p>

DOI： 10.11323/jjmp.36.2_85

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

In this report, we are describing a rare case of dural arteriovenous fistula(DAVF)followed by an isolated symptom of bilateral visual acuity disturbance. The patient was a 67-year-old man suffering from progressive bilateral visual acuity disturbance. Angiography revealed a diffuse arteriovenous fistula in the left transverse-sigmoid sinus affected by severe venous congestion. Visual acuity disturbance is likely to have been caused by increased intracranial pressure(IICP). Venous congestion as well as visual acuity were gradually improved following three transarterial embolizations. It is possible that a gradual progression of the clinical condition has caused only visual acuity disturbance without any other IICP symptoms, which is similar to pseudotumor cerebri. Should an unexplained visual acuity loss occur, the case should be investigated by considering DAVF.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Congress of Neurological Surgeons  

Photodynamic therapy (PDT) for primary malignant brain tumors has now been approved for coverage under Japanese national health insurance. In this therapy, talaporfin sodium (Laserphyrin®) is used as a photosensitizer to be used along with an exclusively developed laser beam source. PDT is a tumor-selective, bimodal treatment, that is based on various photodynamic reactions involving molecular oxygen and oxygenated products, which are harmful for tumor tissue. After administration, the photosensitizer is accumulated and localized in the tumor tissue, which is then exposed to a laser beam with a wavelength appropriate for absorption by the sensitizer, providing photodynamic reactions. The treatment rationale, characteristics of talaporfin sodium and the laser source used for PDT of malignant brain tumors are also described.

DOI： 10.7887/jcns.25.905

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ltd  

Because of its fast metabolism gadolinium as a commercial drug was not considered to be suitable for neutron capture therapy. We studied additive effect of gadolinium and boron co-administration using colony forming assay. As a result, the survival of tumor cells with additional 5 ppm of Gd-DTPA decreased to 1/10 compared to the cells with boron only. Using gadolinium to increase the effect of BNCT instead of additional X-ray irradiation might be beneficial, as such combination complies with the short-time irradiation regimen at the accelerator-based neutron source.

DOI： 10.1016/j.apradiso.2015.07.030

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

OBJECTIVE: To evaluate a cranial base repair method using the dural suturing technique in combination with a mucosal flap in the endoscopic endonasal approach.
METHODS: We analyzed 190 patients (mean age, 52.3 years; age range, 3-86 years) who underwent 194 endoscopic endonasal approaches. The degree of intraoperative cerebrospinal fluid (CSF) leakage was graded based on previously published criteria: grade 0, absent; grade 1, small; grade 2, moderate; and grade 3, large. Cranial base repair using the dural suturing technique was performed according to the grade of CSF leakage: grades 1 and 2, autologous fat graft anchored by dural suturing covered with a sphenoid sinus mucosal flap, and grade 3, multilayered, inlay sutured and onlay nonsutured fascial grafts covered with a nasoseptal flap.
RESULTS: Intraoperative CSF leakage was observed in 125 of 194 cases (64.4%). The degree of CSF leakage was grade 0 in 69 cases, grade 1 in 51 cases, grade 2 in 30 cases, and grade 3 in 44 cases. A postoperative CSF leak was encountered in 2 of 125 repaired cases (1.6%). Both cases with CSF leak involved grade 3 CSF leak (4.5%), and both were successfully treated with lumbar drainage.
CONCLUSION: Our graded cranial base repair method using the dural suturing technique is simple and reliable.

DOI： 10.1016/j.wneu.2015.08.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18 mu gB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20 min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2015.07.035

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

BACKGROUND: Treatment of cystic craniopharyngiomas is often complicated because of adherence of craniopharyngiomas to adjacent brain structures. A strategy involving neuroendoscopic procedures followed by stereotactic radiotherapy is less invasive, avoiding brain damage. However, long-term follow-up of this strategy has not been investigated in depth.
METHODS: Cystic craniopharyngiomas in 9 patients were treated with neuroendoscopic cyst aspiration and fenestration, followed by fractionated stereotactic radiotherapy (FSRT). The neuroendoscopic procedure focused on widening of cyst fenestration and extensive irrigation of the cyst contents. FSRT was performed using 6 fixed beams, an 8-mm margin to cover the gross tumor volume with a 95% isodose line, and a target delivered dose of 50.4 Gy in 28 fractions.
RESULTS: The median follow-up period was 72.9 months. Tumor control was achieved in 8 of 9 patients (88.9%). Marked tumor volume reduction was obtained with the neuroendoscopic procedure alone (26.1%) at 6 months (20.4%), 1 year (11.0%), and 2 years (3.1%). One recurrent case showed multilobulated cysts, and a second surgery was required 1 year after the treatment. Clinical symptoms such as headache and visual disruption were rapidly alleviated after the neuroendoscopic procedure. No new visual disturbances, endocrinopathy, or hypothalamic dysfunction was observed during follow up.
CONCLUSIONS: Neuroendoscopic cyst aspiration and fenestration followed by FSRT is a less invasive, powerful strategy for treating adult cystic craniopharyngiomas.

DOI： 10.1016/j.wneu.2015.06.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

We evaluated the feasibility of 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) in the biopsy for primary central nervous system lymphoma (PCNSL). 5-ALA (20 mg kg(-1)) was administered orally 4 hours preoperatively. Forty-one biopsies obtained under PDD in 47 consecutive biopsies (46 patients) that were finally pathologically diagnosed as PCNSL were evaluated. Positive fluorescence was observed in 34 of those 41 biopsies (82.9%). An intraoperative pathological diagnosis (IOD) of suspected PCNSL was made in 21 of the biopsies with positive fluorescence (61.8%). However, the eight IODs in the remaining 13 biopsies (23.5%) were not correct (atypical cell, 4; high-grade glioma, 1; gliosis, 1; unremarkable, 2). In those 8 biopsies, PCNSL was confirmed by the final pathological diagnosis. There was no difference in the mean Mib-1 labeling index between the biopsies with positive fluorescence (86.5%) and those without positive fluorescence (90.0%). IOD was not performed in 6 biopsies; however, 5 of those biopsies (83.3%) showed positive fluorescence and were finally pathologically diagnosed as PCNSL. Use of PDD in biopsies for patients with suspected PCNSL is a reliable way of obtaining specimens of adequate quality for the final pathological diagnosis and may lead to improved diagnostic yield in the biopsy of PCNSL.

DOI： 10.1111/php.12510

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Rosette-forming glioneuronal tumors (RGNT) of the fourth ventricle are slow-growing tumors that primarily involve the fourth ventricular region. We here report the first patient, an 8-year-old girl, with an RGNT originating in the hypothalamus and manifesting with precocious puberty. After partial removal, the remaining tumor showed rapid enlargement, and the pathologic diagnosis at the second surgery revealed histopathologic features similar to those found in the initial samples, including biphasic patterns of neurocytic rosettes and GFAP-stained astrocytic components. These tumor cells had mildly atypical nuclei; however, mitotic figures and necrosis were absent. Eosinophilic granular bodies and a glomeruloid vasculature were found, but Rosenthal fibers were absent. The Ki-67 proliferative index was 3.5 % (vs 1.1 % at the initial surgery). No recurrence was recorded during the 3-year period after the proton radiotherapy.

DOI： 10.1007/s10014-015-0226-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER WIEN  

Too few cases of isolated abducent nerve palsy caused by neurovascular compression syndrome have been reported. We here report on a case of abducent nerve palsy caused by neurovascular compression syndrome that was successfully treated by microvascular decompression (MVD). A 46-year-old male presented with a 6-month history of right-sided persistent abducent nerve palsy. High-resolution magnetic resonance imaging revealed a neurovascular contact of the vertebral artery with the right abducent nerve. MVD was performed via a retrosigmoid craniotomy, with remarkable improvement of the palsy. Our report suggests that MVD might be considered as an optional treatment if the symptoms progress or persist.

DOI： 10.1007/s00701-015-2530-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

OBJECTIVE: To evaluate the role of neoadjuvant chemotherapy and radiotherapy in the treatment of central nervous system germinomas in 38 patients who received definitive treatment and were followed-up &gt;5 years between 1980 and 2009.
METHODS: The median age at diagnosis and follow-up period were 16.5 years and 128.3 months, respectively. Treatment was irradiation alone or adjuvant platinum-based chemotherapy followed by reduced-dose local irradiation. Seven patients progressed at 12.9-133.9 months and 1 died of disease 89.3 months after therapy initiation.
RESULTS: The treatment strategies were divided into 3 groups: group A (1980-1988, n=5), whole brain with local irradiation; group B (1989-2002, n=16), chemotherapy with or without reduced irradiation dose; and group C (2003-2009, n=17): neoadjuvant chemotherapy (3 courses) followed by 30.6 Gy of whole ventricle irradiation for patients with localized complete response, and additional local boost of 19.8 Gy for others. There were 7 recurrent cases, all in group B. The progression-free survival was significantly longer in groups A and C versus group B (P&lt; 0.001). Decreased Karnofsky performance status was observed in 2 (40%), 6 (37.5%), and 0 cases in groups A-C, respectively. The main reasons for the good results in group C might be the neoadjuvant chemotherapy with whole ventricle radiotherapy and introduction of neuroendoscopy, especially for pineal lesions, resulting in a substantial reduction of time from the diagnosis to first treatment.
CONCLUSIONS: Chemotherapy followed by whole ventricle radiotherapy, with or without local boost, and with use of neuroendoscopy results in good disease control without late complications in patients with germinomas.

DOI： 10.1016/j.wneu.2015.06.029

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Temozolomide (TMZ) as a concomitant and adjuvant chemotherapy to radiotherapy following maximal surgical resection is the established standard therapy for patients with newly diagnosed high-grade glioma. However, detailed analysis of chemotherapy-induced nausea and vomiting (CINV) associated with concomitant TMZ has not been sufficiently described. We prospectively analyzed the profile of CINV associated with concomitant TMZ. Eighteen consecutive patients with newly diagnosed high-grade glioma treated with concomitant chemoradiotherapy including TMZ were enrolled. CINV was recorded using a daily diary including nausea assessment, emetic episodes, degree of appetite suppression, and antiemetic medication use. The observed incidence rates of all grade nausea, moderate/severe (CTC grade 2, 3) nausea, emetic episodes, and appetite suppression for the overall period were 89%, 39%, 39%, and 83%, respectively. Moderate/severe nausea and severe (CTC grade 3) appetite suppression were frequently observed during the delayed phase of the treatment. Emetic episodes and moderate/severe nausea were significantly correlated with female gender. Moderate/severe nausea and severe appetite suppression were significantly correlated with low lymphocyte counts before chemoradiotherapy. For CINV associated with concomitant TMZ, enhanced antiemetic therapy focused on the delayed phase of the treatment will likely be beneficial, especially in female patients with a low lymphocyte count before chemoradiotherapy.

DOI： 10.2176/nmc.oa.2014-0413

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background The aim of this study was to evaluate the efficacy of proton beam therapy for pediatric patients with ependymoma. Methods Proton beam therapy was conducted for six patients (three boys and three girls
age, 2-6 years
median, 5 years) with ependymoma. The tumors were WHO grades 2 and 3 in two and four patients, respectively. All patients underwent surgery (subtotal and gross total resection in three patients each) and proton beam therapy at doses of 50.4-61.2 GyE (median, 56.7 GyE). The mean doses to normal brain tissue in proton beam therapy and photon radiotherapy were simulated using the same treatment planning computed tomography images. Results All patients completed the planned irradiation. The follow-up period was 13-44 months (median, 24.5 months) from completion of proton beam therapy and all patients were alive at the end of this period. Local recurrence in the treatment field occurred in one patient at 4 months after proton beam therapy at 50.4 GyE. Alopecia and mild dermatitis occurred in all patients, but there was no severe toxicity. One patient had a once-off seizure after proton beam therapy and alopecia persisted in another patient for 31 months, but no patients had difficulty with daily life. The simulation showed that proton beam therapy reduces the dose to normal brain tissue by approximately half compared with photon radiotherapy. Conclusions Proton beam therapy for pediatric ependymoma is safe, does not have specific toxicities, and can reduce irradiation of normal brain tissue.

DOI： 10.1111/ped.12624

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Introduction: A high-field ceiling-mounted and movable intraoperative MR imaging (iMRI) can minimize additional risks for MRI and enhance safety by not moving the patient. In this system, hanging the heavy magnet from the ceiling requires structural stability; this stability was confirmed in earlier studies, but not proved during a seismic event.
Objective: We have installed a 1.5 T movable iMRI system with an incorporated seismic system in our hospital in Japan, a seismic event-prone region. This arrangement is the first in the world, to our knowledge. The objective of this study was to describe the mechanism of this seismic system and the first clinical experience using this system.
Methods: The seismic system consists of a stabilizer pad that is mounted directly under the magnet, in addition to the structural stability. The seismic system was tested with using a shaker table testing at a test laboratory.
Results: Ninety-one patients underwent neurosurgical intervention using this iMRI and seismic system at our hospital. In all patients, intra-, pre, and/or postoperative MR images were successfully obtained, and image quality was excellent. The workflow of moving the magnet and scanning were smooth and unproblematic. We had 169 seismic events in our city during this time period, but had no incidental or accidental events related to the seismic events.
Conclusion: With the use of the seismic system, a ceiling-mounted, movable iMRI system can be more safely used. This seismic system may contribute to the spread of movable iMRI systems in countries where seismic events occur. (C) 2015 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.clineuro.2015.05.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Isocitrate dehydrogenase (IDH) mutation is a valuable prognostic marker and a tool for decision-making for glioma treatment. An algorithm for IDH mutation screening was recently proposed-it consists of a two-step process of an initial search for the most common IDH1-R132H mutation using immunohistochemistry (IHC)-based assay, followed by DNA-based analysis of IHC-negative or -equivocal cases. Here, we report that immunohistochemistry using two mutation-specific anti-IDH monoclonal antibodies (mAbs)-an IDH1-R132H-specific mAb (clone HMab-1) and a multi-specific mAb (clone MsMab-1)-is easy and reliable for IDH mutation screening. We investigated the IDH status of 54 grade III gliomas. For the first screening, we used HMab-1 IHC and for the second, (of HMab-1-negative cases) we used MsMab-1 IHC. The double IHC screening results were confirmed using sequence analysis (100 % specificity and 100 % sensitivity). Thirty of 54 cases (55.6 %) had IDH mutations and the remaining 24 were of the IDH wild type; moreover, the screening results predicted grade III glioma prognosis. IDH sequencing procedures are popular but inconsistent across laboratories. By contrast, double IHC screening using HMab-1 and MsMab-1 is very reliable for detecting IDH1/2 mutations and can predict survival in grade III glioma patients.

DOI： 10.1007/s10014-015-0214-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

A 48-year-old man with right hemi-facial palsy and cerebellar ataxia was referred to our hospital. Three years and 10 months earlier he had undergone gamma knife radiosurgery (GKRS) at the referring hospital for an 18 mm right vestibular schwannoma. Slight tumor enlargement had been observed on MRI performed at the referring hospital 3 years after the GKRS. On close follow-up after another 6 months an MRI showed an obvious enlargement of the tumor. An MRI on admission revealed an iso-intense mass lesion measuring 36 mm in maximum diameter at the right cerebellopontine angle. A two stage surgery was conducted using a retrosigmoid approach because bleeding from the tumor wall was difficult to control intraoperatively during the first operation. At the second operation, the majority of the tumor capsule had converted to necrotic tissue. A large hematoma cavity was present inside the tumor capsule which explained the rapid increase in size over a short period of time. Near total removal was achieved. Histopathological examination revealed massive intratumoral hemorrhage within a typical vestibular schwannoma with no malignancy. The complication of intratumoral hemorrhage is very rare and the utility of stereotactic radiation surgery/therapy, including GKRS, for vestibular schwannoma is well known. However, we must emphasize that careful follow-up is still required, even after several years. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2014.12.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Objective: Criteria for motor evoked potential (MEP) monitoring include the amplitude criterion and threshold criterion. The aim of our study for the amplitude criterion during removal of brain lesions was to determine a suitable stimulus intensity that can reduce the variability in amplitudes. We also assessed the usefulness of the threshold criterion and amplitude criterion by comparing the variability between the two methods as a preliminary study.Methods: Seventeen patients including 12 cases with no neurological deterioration after surgery were enrolled in this study. The amplitudes in various stimulus intensities and the stimulation threshold (ST) were repeatedly measured during surgery. The stimulus intensities used in the amplitude criterion are described as 'the ST just after dura opening (ST(0)) + additional intensity'. The variability was assessed with the coefficient of variation (CV).Results: With direct cortical stimulation (DCS), the CVs of amplitudes were significantly lower at stimulus intensities of more than ST(0) + 4 mA, with the smallest at ST(0) + 10 mA. The CV of STs was significantly smaller than that of amplitudes.Conclusions: The variability in the amplitude criterion was significantly reduced using stimulus intensities of more than ST(0) + 4 mA. The variability in the threshold criterion was significantly smaller than that of the amplitude criterion, even when using a strong stimulus intensity.Significance: The maximal stimulus intensity with no body motion should be used in the amplitude criterion for intraoperative MEP elicited by DCS. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.clinph.2014.10.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Objective: The objective of this study was to elucidate the influence on quantitative analysis using LCModel with the condition of echo time (TE) longer than the recommended values in the spectrum acquisition specifications.
Methods: A 3 T magnetic resonance system was used to perform proton magnetic resonance spectroscopy. The participants were 5 healthy volunteers and 11 patients with glioma. Data were collected at TE of 72, 144 and 288 ms. LCModel was used to quantify several metabolites (N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds). The results were compared with quantitative values obtained by using the T2-corrected internal reference method.
Results: In healthy volunteers, when TE was long, the quantitative values obtained using LCModel were up to 6.8-fold larger (p &lt; 0.05) than those obtained using the T2-corrected internal reference method. The ratios of the quantitative values obtained by the two methods differed between metabolites (p &lt; 0.05). In patients with glioma, the ratios of quantitative values obtained by the two methods tended to be larger at longer TE, similarly to the case of healthy volunteers, and large between-individual variation in the ratios was observed.
Conclusions: In clinical practice, TE is sometimes set longer than the value recommended for LCModel. If TE is long, LCModel overestimates the quantitative value since it cannot compensate for signal attenuation, and this effect is different for each metabolite and condition. Therefore, if TE is longer than recommended, it is necessary to account for the possibly reduced reliability of quantitative values calculated using LCModel. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.mri.2015.01.015

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders Ltd  

Introduction: The intent of this study was to differentiate intracranial tumors using the metabolite concentrations obtained by quantification with correction for T2 relaxation time, and to analyze whether the spectrum peak was generated by the existence of metabolites in proton magnetic resonance spectroscopy (MRS). Methods: All proton MRS studies were performed on a clinical 1.5T MR system. 7 normal volunteers and 57 patients (gliomas, metastases, meningiomas, acoustic neuromas, and pituitary adenomas) underwent single voxel proton MRS with different echo times (TE: 68, 136, 272ms) for T2 correction of signal derived from metabolites and tissue water. With tissue water employed as an internal reference, the concentrations of metabolite (i.e. N-acetylaspartate (NAA), total creatine (t-Cr) and choline-containing compounds (Cho)) were calculated. Moreover, proton MRS data of previously published typical literatures were critically reviewed and compared with our data. Results: Extramedullary tumors were characterized by absence of NAA compared with intramedullary tumors. High-grade glioma differed from low-grade glioma by lower t-Cr concentrations. Metastasis differed from cystic glioblastoma by higher Cho concentrations, lower t-Cr concentrations, an absence of NAA, and a prominent Lipids peak. Based on these results and review of previous reports, we suggest a clinical pathway for the differentiation of intracranial tumors. Conclusion: The metabolite concentrations obtained by quantification with correction for T2 relaxation time, and to analyze whether the spectrum peak was generated by the existence of metabolites in proton MRS is useful for the diagnosis of the intracranial tumors.

DOI： 10.1016/j.radi.2014.06.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medknow Publications  

Background: The authors report a continuous case series of navigation-guided rigid endoscopic biopsy via the transcortical route for intraparenchymal brain lesions to assess the feasibility and efficacy of the method. Methods: Thirty-four patients with intraparenchymal brain lesions found on neurovisualization underwent navigation-guided rigid endoscopic biopsy. Most of the preoperative diagnoses were glioma WHO Grade II-IV (16 cases) or malignant lymphoma (15 cases). Intraoperative photodynamic diagnosis and intraoperative pathological diagnosis were used in 28 and 29 cases, respectively. In 2 cases with small and deep lesions, intraoperative magnetic resonance imaging was used for confirming the accuracy of the biopsy point. Results: The sampling accuracy determined by postoperative imaging and the definitive diagnosis ratio were 94% (32 out of 34 cases) and 97% (33 out of 34 cases), respectively. There was no postoperative mortality. In 2 patients, mild postoperative permanent morbidity (5.9%), presumably related to this technique, was observed in the early cases in the current group (34 case series). Conclusion: The method was estimated as safe and feasible for diagnostic tissue sampling of intraparenchymal brain lesions.

DOI： 10.4103/2152-7806.165764

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Marfan syndrome can demonstrate tortuous and elongated intracranial arteries. However, these arteries rarely cause neurovascular compression resulting in hemifacial spasm or trigeminal neuralgia. The authors report a 33-year-old woman who was diagnosed as Marfan syndrome, suffered from trigeminal neuralgia. Magnetic resonance (MR) angiography showed tortuous and elongated left vertebral artery (VA). The coronal section of three dimensional (3D) MR cisternography with contrast enhancement showed that the left trigeminal nerve was compressed from underneath by the tortuous and elongated left VA. After successful surgery of microvascular decompression, the patient's symptom resolved and no recurrence was encountered. Neurosurgeons should not only be aware of hemifacial spasm but also of trigeminal neuralgia caused by elongated vessels in a patient with Marfan syndrome, although it is an extremely rare condition. In addition, offending vessel is not atherosclerotic in younger patients unlike usual cases of trigeminal neuralgia. Thus, microvascular decompression can be easier than usual cases. Care should be taken to prevent arterial dissection during transposition by using some technical tips.

DOI： 10.2176/nmc.cr.2013-0072

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Purpose: Although conventional x-ray therapy of 60 Gy in 30 fractions is generally used in our institute as well as others, the prognosis of patients with glioblastoma multiforme (GBM) is poor. The purpose of this study was to evaluate the characteristics of long-term GBM survivors after postoperative hyperfractionated concomitant boost x-ray radiation therapy and proton beam therapy.Methods and materials: Twenty-three of 81 GBM patients who met the eligible criteria and consented to the protocol were treated with x-ray radiation therapy (50.4 Gy in 28 fractions in T2high areas) and proton beam therapy (46.2 GyE in 28 fractions in gadolinium-enhanced volumes >6 hours after x-ray radiation therapy) concurrent with nimustine hydrochloride or temozolomide.Results: Treatment was completed in all patients within 38-50 days (median, 43 days). Six currently living patients (median follow-up period, 70.9 months) developed radiation necrosis without tumor recurrence. Of these, 5 underwent necrotomy and 2 received bevacizumab after necrotomy. Compared with the pretreatment status, the Karnofsky performance scale (KPS) for the 6 survivors decreased by 10%-30% at the last follow-up. However, radiation necrosis had been well controlled and 5 of 6 patients maintained a stable KPS without hospital care.Conclusions: The results suggest that high-dose proton beam therapy could control GBM pathogenesis if the treatment area completely covers tumor infiltration. Although radiation necrosis was inevitable, the remaining brain volume was fairly well preserved in the long-term survivors. (C) 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.prro.2014.03.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

It is generally accepted that the first choice of treatment for spinal meningiomas is "radical" surgical removal. However, Simpson grade I removal is sometimes difficult, especially in cases with ventral dural attachment, because of the risk of spinal cord damage or the difficulty of dural repair after radical resection. In addition, there is no consensus on a surgical strategy for radicality, whether or not Simpson grade I resection should be performed in all cases of spinal meningioma. In this study, we retrospectively analyzed clinical and radiological data of surgically treated 14 patients with spinal meningioma, to assess the influence of the Simpson grade to tumor recurrences during long-term follow-up (median 8.2 years, 1.3-27.9). The number of patients in Simpson grades I, II, III, and IV were 2, 8, 0, and 3, respectively; Simpson grading was not applicable to one patient with non-dura-based meningioma. No postoperative permanent neurological worsening was encountered. The recurrence rate was 21.4% (3 out of 14 cases). Of these 3 recurrent cases, 1 was a case of non-dura-based meningioma and another was a case of neurofibromatosis type 2 (NF2); both of them are known as risk factors for recurrence after surgical removal of spinal meningiomas. Considering this background of these two recurrences, the clinical results of the present study are consistent with previous results. Therefore, we propose that surgeons do not always have to achieve Simpson grade I removal if dural repair is complicated and postoperative cerebrospinal fluid (CSF) leakage or neurological worsening are estimated after resection of dural attachment and repair of dural defect.

DOI： 10.2176/nmc.oa.2013-0311

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. Recently, an increasing number of patients with brain metastases, even patients over 80 years of age, have been treated with stereotactic radiosurgery (SRS). However, there is little information on SRS treatment results for patients with brain metastases 80 years of age and older. The authors undertook this study to reappraise whether SRS treatment results for patients 80 years of age or older differ from those of patients who are 65-79 years old.
Methods. This was an institutional review board approved, retrospective cohort study. Among 2552 consecutive brain metastasis patients who underwent SRS during the 1998-2011 period, we studied 165 who were 80 years of age or older (Group A) and 1181 who were age 65-79 years old (Group B). Because of the remarkable disproportion in patient numbers between the 2 groups and considerable differences in pre-SRS clinical factors, the authors conducted a case-matched study using the propensity score matching method. Ultimately, 330 patients (165 from each group, A and B) were selected. For time-to-event outcomes, the Kaplan-Meier method was used to estimate overall survival and competing risk analysis was used to estimate other study end points, as appropriate.
Results. Although the case-matched study showed that post-SRS median survival time (MST, months) was shorter in Group A patients (5.3 months, 95% CI 3.9-7.0 months) than in Group B patients (6.9 months, 95% Cl 5.0-8.1 months), this difference was not statistically significant (HR 1.147, 95% CI 0.921-1.429, p = 0.22). Incidences of neurological death and deterioration were slightly lower in Group A than in Group B patients (6.3% vs 11.8% and 8.5% vs 13.9%), but these differences did not reach statistical significance (p = 0.11 and p = 0.16). Furthermore, competing risk analyses showed that the 2 groups did not differ significantly in cumulative incidence of local recurrence (HR 0.830,95% CI 0.268-2.573, p = 0.75), rates of repeat SRS (HR 0.738,95% Cl 0.438-1.242, p = 0.25), or incidence of SRS-related complications (HR 0.616,95% CI 0.152-2.495, p = 0.49). Among the Group A patients, post-SRS MSTs were 11.6 months (95% CI 7.8-19.6 months), 7.9 months (95% CI 5.2-10.9 months), and 2.8 months (95% CI; 2.4-4.6 months) in patients whose disease status was modified recursive partitioning analysis (RPA) Class(es) I+IIa, IIb, and IIc+III, respectively (p &lt;0.001).
Conclusions. Our results suggest that patients 80 years of age or older are not unfavorable candidates for SRS as compared with those 65-79 years old. Particularly, even among patients 80 years and older, those with modified-RPA Class I+IIa or lIb disease are considered to be favorable candidates for more aggressive treatment of brain metastases.

DOI： 10.3171/2014.6.JNS132790

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Interferon-beta (IFN-beta) has been used clinically for malignant glioma growth inhibition. Recently IFN-beta is re-evaluated for its sensitization mechanism to the chemotherapeutic agent temozolomide, because angiogenesis is essential for malignant glioma growth. In this study, we investigated new mechanisms of inhibition of glioma angiogenesis by IFN-beta. Three malignant glioma cell lines, U87, TK2 and Becker, were used for in vitro study. The effect of IFN-beta for these cell lines were evaluated by means of proliferation (MTT assay), conditioned medium induced HUVEC migration, VEGF and interferon inducible protein 10 (IP10, angiogenesis inhibitor) expression by RT-PCR and western blot analysis. SCID mouse U87 subcutaneous model and U87 implant cranial window model were used for in vivo study. The effect of IFN-beta with the models was evaluated by means of tumor growth, tumor tissue expression for VEGF and IP10, tumor tissue CD31 positive vessel densities, apoptosis and tumor microcirculation (blood velocity, interaction between leukocytes and endothelial cells). In vitro, IFN-beta upregulated IP10 expression and downregulated VEGF expression time-(4-48 h) and dose-(10-5,000 U/ml) dependently. At the same dose, glioma cell-induced HUVEC migration was inhibited, but cell proliferation was not affected. IFN-beta local and systemic injection at 10(5)U and at 5x10(5)U/day, for 15 days inhibited U87 subcutaneous growth significantly. In the tumor tissues, VEGF expression and vessel densities were downregulated, but IP10 expression and apoptosis index upregulated. In addition, IFN-beta local injection increased collagen fiber deposition in the tumor tissues. IFN-beta 5x10(5) U/day, s.c. injection for 7 days reversed the decreased leukocyte adhesion to endothelial cells, but did not affect blood velocity and vessel images. One of the important roles of IFN-beta for malignant glioma growth inhibition was anti-angiogenesis by directly inhibiting angiogenesis through downregulation of VEGF and upregulation of IP-10 and indirectly changing the tumor microcirculation and regulating the interstitial pressure.

DOI： 10.3892/ijo.2014.2620

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM.
Methods. Twenty-four patients (age 16-75 years, Karnofsky Performance Scale score &gt;= 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle.
Results. This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) &gt;= 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response.
Conclusions. The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients.

DOI： 10.3171/2014.5.JNS132392

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

プロラクチノーマ51例に対しカベルゴリン(CAB)治療を行い、長期治療成績、再発について検討した。CAB投与後の観察期間は中央値50ヵ月であった。CABによるプロラクチン(PRL)正常化率は86%と良好であり、正常化に要する期間の中央値は2.6ヵ月で、57%が3ヵ月以内であった。腫瘍サイズは、消失44%、縮小46%、不変11%であった。サルベージの経蝶形骨洞手術は4例で行われた。CABを終了できたのは14例(27%)で、内服期間は中央値60ヵ月であった。CAB終了14例の再発率は29%で、再発までの期間は中央値3.5ヵ月と1年以内が多かった。CAB終了後1年間PRL正常であった寛解例は8例、寛解率は68%で、累積での無再発率は1年88%、3年68%であった。再発と関連する因子の分析では、治療前海綿静脈洞浸潤、治療前Knosp分類が有意な相関を示した。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01160&link_issn=&doc_id=20141002460006&doc_link_id=10.1507%2Fendocrine.90.Suppl.HPT_22&url=https%3A%2F%2Fdoi.org%2F10.1507%2Fendocrine.90.Suppl.HPT_22&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Due to the rarity of skull Langerhans cell histiocytosis (LCH), correlations between abnormalities on magnetic resonance imaging (MRI) and pathological findings have not been fully evaluated. Only a few reports have as yet compared MRI of LCH infiltration and histological diagnostic features. A 22-year-old man with an unremarkable past medical history presented with headache followed by a nodular mass in the right parietal area. Gadolinium (Gd)-enhanced T1-weighted images showed a "mushroom-shaped" extension, extending from the subcutaneous to the intracranial space. The galeal tissue, the dura mater, and the cranium adjacent to the lesion showed enhancement on Gd-enhanced T1-weighted MRI. Histologically, diagnosis was LCH, with immunohistochemical positivity for S-100, CD68, and CD1a, and showed a MIB-1 labeling index of 29.5 %. By immunostaining, we confirmed LCH cells to be present in the galea with Gd enhancement and the skull without Gd enhancement on MRI. LCH cells might exist in the marginal cranium, if MRI shows only slight intensity change without Gd enhancement. Further evaluation to determine pathologically proven extent of LCH and its relation with neuroradiological diagnosis as well as clinical outcome is needed to understand heterogeneous response to surgical and/or nonsurgical treatment in LCH.

DOI： 10.1007/s10014-014-0182-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

The present retrospective data analysis was performed to determine whether intraoperative pathological diagnosis (IOD) using frozen section (FS) could clearly distinguish high-grade glioma from WHO grade II gliomas. IOD was retrospectively compared to the pathological diagnosis using permanent paraffin sections (PS) of 205 glioma cases out of 356 brain tumor cases in the pre-Carmustine (BCNU) wafer era in Japan. The sensitivity and specificity of IOD regarding the whole glioma category were 96.1 and 98.0 %, respectively. The positive predictive value and the underestimation ratio of glioma grading by IOD were 51.5 and 43.5 % in all glioma cases. In addition, 54.5 % of grade II glioma cases determined with IOD (grade II(FS)) were actually grade III or IV according to the PS pathology (grade III(PS) or IV(PS) cases). Recurrent cases and older age (a parts per thousand yen50 years old) were predictive factors that resulted in underestimated grade II(FS) group (grade II(FS)/III(PS) + IV(PS)). The grade II(FS)/III(PS) group tended to more frequently contain non-astrocytic tumors compared to the grade II(FS)/II(PS) + IV(PS) groups, although the difference was not statistically significant. In conclusion, the temporary WHO grade by IOD is underestimated in approximately half of glioma cases. We should pay attention to underestimation with IOD.

DOI： 10.1007/s10014-014-0177-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

BPA used in BNCT has a similar structure to some essential amino acids and is transported into tumor cells by amino acid transport systems. Previous study groups have tried various techniques of loading BPA to increase intracellular boron concentration. CHO-K1 cells demonstrate system L (LAT1) activity and are suitable for specifying the transport system of a neutral amino acid. In this study, we examined the intracellular accumulation of boron in CHO-K1 cells by amino acid transport control, which involves co-loading with L-type amino acid esters. Intracellular boron accumulation in CHO-K1 cells showed the greatest increased upon co-loading 1.0 mM BPA, with 1.0 mM L-Tyr-O-Et and incubating for 60 min. This increase is caused by activation of a system L amino acid exchanger between BPA and L-Tyr. The amino acid esters are metabolized to amino acids by intracellular hydrolytic enzymes that increase the concentrations of intracellular amino acids and stimulate exchange transportation. We expect that this amino acid transport control will be useful for enhancing intracellular boron accumulation. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2013.12.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

clarify the intra tumor distribution of gadlinium containing fullerene (Gd@C-82), micro particle induced X-ray emission (Micro-PIXE) analysis were performed. The tumor bearing BALB/c mice were injected Gd@C-82 and subcutaneous tumors were taken from 48 h after the intravenous injection. Using the Micro-PIXE method, we could visualize Gd intra tumor distribution. Therefore our results indicate the possibility that Micro-PIXE is useful technique for imaging the bioditribution of Gd, and Gd@C-82 is potentially useful Gd carrier for NCT. (C) 2014 Published by Elsevier Ltd.

DOI： 10.1016/j.apradiso.2013.12.037

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1200/jco.2014.32.15_suppl.e13029

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Neurosurgical Society  

DOI： 10.2176/nmc.oa2013-0112

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Migration and invasion of malignant glioma play a major role in tumor progression and can be increased by low doses of gamma or X-ray irradiation, especially when the migrated tumor cells are located at a distance from the main tumor mass or postoperative cavity and are irradiated in fractions. We studied the influence of proton beam irradiation on migration and invasion of human U87 malignant glioma (U87MG) cells. Irradiation at 4 and 8 Gy increased cell migration by 9.8% (+/- 4, P = 0.032) and 11.6% (+/- 6.6, P = 0.031) and invasion by 45.1% (+/- 16.5, P = 0.04) and 40.5% (+/- 12.7, P = 0.041), respectively. After irradiation at 2 and 16 Gy, cell motility did not differ from that at 0 Gy. We determined that an increase in proton beam irradiation dose to over 16 Gy might provide tumor growth control, although additional specific treatment might be necessary to prevent the potentially increased motility of glioma cells during proton beam therapy.

DOI： 10.1093/jrr/rrt119

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Emerging evidence suggests that the chemokine CXCL12 and its receptor CXCR4, which are expressed by glioma stem cells (GSCs), play an important role in tumorigenesis. To provide evidence for establishing a new therapy targeting the CXCL12/CXCR4 pathway, we investigated whether CXCL12 secreted from GSCs contributed to their proliferation and promoted angiogenesis in murine GSCs. Angiogenetic functions and proliferation of GSCs with or without CXCL12 inhibitors were evaluated in an in vitro model using tube formation assays, RT-PCR, and proliferation, as well as in an in vivo syngenic model. In endothelial culture, the morphology and gene expression of GSCs changed from stem cell-like characteristics to endothelial cell-like features. CXCL12 expression increased in endothelial cell-like GSCs. CXCL12 blockage with siRNA or shRNA markedly inhibited cell proliferation in vitro. CXCL12 knockdown with shRNA also inhibited tumor growth in vivo. On the other hand, CXCL12/CXCR4 blockage affected neither tube formation in vitro nor angiogenesis in vivo. The CXCL12 secreted from GSCs (autocrine/paracrine CXCL12) regulates their proliferation, but probably not angiogenesis.

DOI： 10.1007/s11060-014-1364-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DOVE MEDICAL PRESS LTD  

An antiangiogenic approach is especially suitable for the treatment of malignant gliomas. Recently, two large clinical trials in newly diagnosed glioblastoma (the Avastin in Glioblastoma study and Radiation Therapy Oncology Group 0825 study) showed a 3- to 4-month prolongation of progression-free survival (PFS) with bevacizumab, but no significant effect on overall survival (OS). Japan is the first, and so far only, country to approve the use of bevacizumab in newly diagnosed glioblastoma in combination with radiotherapy and temozolomide chemotherapy. The drug is also approved for use as monotherapy for recurrent glioblastoma and certain other types of high-grade glioma after previous therapy. The effectiveness of bevacizumab on Japanese malignant glioma patients was reviewed. The Phase II clinical trial demonstrated that the PFS with bevacizumab alone was 34% at 6 months and 3.3 months at median for 32 patients with recurrent malignant gliomas. In the Avastin in Glioblastoma study, 44 Japanese patients were registered from Japan. PFS and OS for bevacizumab combined with standard temozolomide and radiotherapy were 12.2 months and 29.2 months at median, respectively, for the patients with newly diagnosed glioblastoma. PFS and OS tended to be longer for those treated with bevacizumab than for those not treated with the drug. In addition, biomarkers of bevacizumab effectiveness were investigated in Japanese patients. Vascular endothelial growth factor concentration, matrix metalloproteinase 9 activities in urine, and apparent diffusion coefficient values on magnetic resonance imaging may be biomarkers that predict patient prognosis. Finally, novel experiments for vascular endothelial growth factor antibody action were described; these include the induction of glioma cell apoptosis, an antibody treatment failure model, and a study of the synergistic effect with chemotherapeutic agents.

DOI： 10.2147/OTT.S67621

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI PUBLISHING CORPORATION  

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in solid tumors. However, its role in angiogenesis in pituitary adenoma is controversial. Angiogenesis in solid tumors including pituitary adenoma is commonly evaluated by microvascular density (MVD). Here, we evaluated MVD and the role of VEGF in vascular architecture in 51 pituitary adenomas (24 nonfunctioning, 13 prolactin-secreting, 10 growth hormone-secreting, 3 adrenocorticotropic hormone-secreting, and 1 thyroid-stimulating hormone-secreting). Paraffin sections were stained with CD34 and VEGF. MVD and vascular architecture parameters (vessel area, diameter, perimeter, and roundness) were evaluated in CD34-stained sections. Immunohistochemistry showed 27/51 tumors (53%) were VEGF-positive. There were no significant differences in MVD, any vascular parameter, or adenoma volume between VEGF-positive and VEGF-negative tumors. VEGF mRNA expression was significantly higher in VEGF-positive tumors. There were no significant correlations between VEGF mRNA expression and MVD or vascular parameters. However, vessel diameter and perimeter were significantly larger in prolactin-secreting than nonfunctioning and growth hormone-secreting macroadenomas. The difference in vessel diameter was observed among both VEGF-positive and all adenomas (micro- and macroadenoma). Thus, VEGF may have limited roles in the development of vascular architecture and tumor angiogenesis in pituitary adenomas, but the differences in vessel architecture by histotype (i.e., larger vessel diameter and perimeter in prolactin-secreting adenomas) suggest the hormonal regulation of vessel architecture rather than angiogenesis

DOI： 10.1155/2014/989574

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI LTD  

The entity of pituitary (sellar or parasellar) lymphoma includes primary pituitary lymphoma (PPL) and secondary pituitary lymphoma (SPL). The latter has an involvement of systemic lymphoma. Both of these lymphomas are extremely rare. We describe a patient with SPL showing a good prognosis. A 78-year-old woman presented with diplopia, left ptosis, and back pain. Magnetic resonance (MR) imaging revealed a parasellar mass lesion extending to the upper clivus and anothermass lesion with compression fracture of the Th3 vertebral body. Transsphenoidal exploration was performed, and it showed diffuse large B-cell lymphoma. Based on the positive tumor cells in the following bonemarrow aspiration and hepatosplenomegaly in computed tomography (CT) findings, this patient was diagnosed as having a pituitary involvement of systemic lymphoma. After chemotherapy, she achieved complete remission for 4 years. The entity of pituitary lymphoma is extremely rare. Nineteen cases of PPL and 16 cases of SPL have been reported. Generally, clinical and radiological diagnosis was difficult because there are no specific findings. Therefore, biopsy was necessary in all of the cases. T2 hypointensity of a lesion in MR imaging in addition to an elevated serum level of soluble interleukin-2 receptor (sIL-2R) in a patient with a sellar lesion can be useful clues for the differential diagnosis of this rare disease.

DOI： 10.1155/2014/747280

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOSCIENTIFICA LTD  

Gastrointestinal perforation is a complication associated with steroid therapy or hypercortisolism, but it is rarely observed in patients with Cushing's disease in clinical practice, and only one case has been reported as a presenting symptom. Herein, we report a rare case of Cushing's disease in which a patient presented with gastrointestinal perforation as a symptom. A 79-year-old man complained of discomfort in the lower abdomen for 6 months. Based on the endocrinological and gastroenterological examinations, he was diagnosed with Cushing's disease with a perforation of the descending colon. After consultation with a gastroenterological surgeon, it was decided that colonic perforation could be conservatively observed without any oral intake and treated with parenteral administration of antibiotics because of the mild systemic inflammation and lack of abdominal guarding. Despite the marked elevated levels of serum cortisol, oral medication was not an option because of colonic perforation. Therefore, the patient was submitted to endonasal adenomectomy to normalize the levels of serum cortisol. Subsequently, a colostomy was successfully performed. Despite its rarity, physicians should be aware that gastrointestinal perforation may be associated with hypercortisolism, especially in elderly patients, and immediate diagnosis and treatment of this life-threatening condition are essential. If a perforation can be conservatively observed, endonasal adenomectomy prior to laparotomy is an alternative treatment option for hypercortisolism.

DOI： 10.1530/EDM-13-0064

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Human U251 malignant glioma cells were treated with 8 or 50 nm gold nanoparticles (GNPs) at 15, 30 and 45 g/ml gold concentrations in the culture medium and irradiated with 2, 4 and 8 Gy X-rays (150 kV, 20 mA). Both 8 and 50 nm GNPs showed concentration-dependent accumulation and were visualized in the cytoplasm of U251 malignant glioma cells. Effective radiosensitization of glioma cells was achieved at 8 Gy keV-X-ray irradiation at 37.7 (±1.6) and 53.7 (±2.8) g gold/106 cells with 8 nm GNPs and 17.1 (±1.3), 28.7 (±0.4) and 41.4 (±0.9) g gold/106 cells with 50 nm GNPs. On transmission electron microscopy both 8 and 50 nm GNPs were observed in the cell cytoplasm. As 50 nm GNPs showed more significant radiosensitization effect at 30 and 45 g gold/ml and less cytotoxicity at higher (60-150 g/ml) gold concentrations, the 50 nm GNPs are suggested to be more eligible for glioma radiosensitization, and further studies in this area are required. Copyright © 2013 American Scientific Publishers All rights reserved.

DOI： 10.1166/nnl.2013.1646

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer-Verlag Berlin Heidelberg  

Percutaneous transluminal angioplasty (PTA) and stenting are widely used methods for the treatment of vascular stenosis and much less invasive than surgery, but restenosis still occurs in 30-60 % of coronary artery cases, in no less than 5 % of carotid artery cases, and in 10-40 % of intracranial artery cases treated with PTA or stenting. Restenosis remains as the main limitation of vascular angioplasty, though the introduction of drug-eluting stents and brachytherapy has improved the restenosis rate. BNCT (boron neutron capture therapy) might be superior to beta or gamma-beam brachytherapy from the standpoint of normal structure injury, since the destructive effects of boron particles are limited to boron-containing cells. The possible application of BNCT for preventing restenosis after angioplasty was indicated in our preliminary study with a rat carotid artery model. Further investigation of the boron distribution in vascular and normal structures, development of appropriate boron compounds, and evaluation of the tolerability of BNCT for prevention of restenosis will be needed before BNCT can be applied clinically to prevent restenosis after stenting.

DOI： 10.1007/978-3-642-31334-9_30

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Benign spinal meningiomas have good prognoses, with low rates of recurrence and no cerebrospinal fluid (CSF) dissemination. However, we experienced an extremely rare case of initially benign non-dura-based spinal meningioma that showed multiple CSF disseminated lesions, which progressed for 14 years. A 29-year-old woman without neurofibromatosis presented with progressing dysesthesia in her lower limbs, low back pain, and intermittent claudication. Magnetic resonance imaging (MRI) showed an intradural extramedullary mass lesion at the Th10/11 level. The patient underwent a tumor resection. Intraoperative findings indicated that the tumor had no dural attachment. Histopathological diagnosis after gross total removal was microcystic meningioma (grade I, WHO 2007). Seven years after the first operation, other lesions appeared at the levels of Th11/12, L1, and L2/3 in MRI. These tumors were slow growing and became symptomatic; thus, a second surgery was performed 14 years after the first operation. The histopathological diagnosis was atypical meningioma (grade II, WHO 2007). Benign spinal meningiomas show CSF dissemination extremely rarely, although some authors have reported non-dura-based intraspinal clear-cell meningiomas showing CSF dissemination. However, even in cases of WHO grade I, neurosurgeons should pay attention to late CSF dissemination and malignant transformation after surgical removal of non-dura-based intraspinal meningiomas.

DOI： 10.1007/s10014-012-0116-y

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記述言語：日本語   出版者・発行元：(一社)茨城県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Postoperative cerebrospinal fluid (CSF) leakage is a major problematic complication after extended transsphenoidal surgery (TSS). Watertight closure of the sellar dura with a fascial patch graft is a method of choice for preventing CSF leakage
however, suturing and knotting in a deep and narrow operative field is technically challenging and time consuming. To present a simple and effective knotting technique named the 'sliding-lock-knot' technique, in which the knot can easily be slid to the suturing point and tied automatically using only a single string, without loosening. Methods: We use a 6-0 nylon suture and Mosquito forceps. At first, after putting a stitch, a single knot is made by hand out of the nasal cavity. Then the 'sliding-lock-knot' is made using a forceps as shown in the illustration. The knot slides deep into the operative field through the nostril and it is automatically tied only by pulling a string. Results: A 73-year-old woman presented with progressive visual deterioration. She had an intra-And suprasellar craniopharyngioma that was compressing the optic chiasm. She underwent an extended TSS, and the tumor was totally resected. The dural defect was closed with a fascial patch graft sutured on the dura using this technique, then covered with a vascularized mucoseptal flap. Neither CSF leakage nor meningitis was encountered during the postoperative period. Conclusion: The 'sliding-lock-knot' technique is simple and useful for dural suturing in microscopic/endoscopic extended TSS. This technique is a helpful tool for preventing CSF leakage after this challenging surgical procedure. Copyright © 2013 Sakamoto N.

DOI： 10.4103/2152-7806.107546

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 40-year-old bilingual man underwent removal of glioblastoma multiforme with intraoperative language mapping, mainly using the picture-naming and auditory responsive-naming tasks under cortical stimulation. Multiple language areas were identified, including one located in the middle of the inferior temporal cortex (ITC). Individual mapping for glioma patients must be performed because language areas might be located in various and unexpected regions, including the ITC.

DOI： 10.2176/nmc.53.256

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2013/305039.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Clinically, recurrent glioblastoma multiforme (GBM) is often associated with communicating hydrocephalus. We hypothesized that there are specific magnetic resonance (MR) imaging findings at the diagnosis of recurrent GBM that predict subsequent hydrocephalus. Various clinical characteristics were investigated including outcome and MR imaging findings in 12 patients with recurrent GBM followed by hydrocephalus (Hydro group) and 21 patients with recurrent GBM without hydrocephalus (Non-hydro group). Patient age and presence of communicating hydrocephalus were significantly associated with poor outcome. Median survival with recurrent GBM was longer in the Non-hydro group than in the Hydro group. Low Karnofsky performance status (KPS) and poor recursive partitioning analysis (RPA) class (RPA class 3, 5, 6, or 7) at the diagnosis of recurrent GBM were associated with the presence of hydrocephalus. The incidence of leptomeningeal dissemination after recurrent GBM was higher in the Hydro group than in the Non-hydro group. Evans index and fractional anisotropy value showed no difference at the diagnosis of recurrent GBM, but some MR imaging findings indicated that lesion attached to the basal cistern and/or ventricle was closely associated with subsequent hydrocephalus. We recommend careful monitoring of the ventricle size and leptomeningeal dissemination, especially in patients with low KPS and/or poor RPA class, if MR imaging indicates that the lesion is attached to the basal cistern and/or ventricle at recurrence of GBM.

DOI： 10.2176/nmc.53.474

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その他リンク： http://orcid.org/0000-0002-6833-9866

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Intracranial hemangioblastomas (HBs) are hypervascular neoplasms mainly located in the posterior fossa of the central nervous system. Preoperative embolization of the feeding arteries is one proposal for reduction of intraoperative hemorrhage, although indications for the procedures should be evaluated carefully due to the potential complications. This retrospective study investigated clinical outcomes and complications of 15 patients with HBs in the posterior fossa to evaluate the safety and effectiveness of endovascular procedures as well as angiographical procedures. Surgical excision without presurgical embolization was performed in 8 cases, and excision with presurgical embolization was performed in 7 cases, using Guglielmi detachable coils with or without polyvinyl alcohol (GDC +/- PVA) in 4 cases and only n-butyl 2-cyanoacrylate (NBCA) in 3 cases. The embolization was applied for selected cases in which feeding arteries were located in a deep site and hard to coagulate surgically. Partial embolization was achieved in 5 cases, and all feeders were successfully embolized in 2 cases. Total removal was achieved in 12 cases, and subtotal/partial removal was achieved in 3 cases. Subarachnoid hemorrhage with intratumoral hemorrhage occurred in 1 case during the angiographic procedure and in 1 case during the embolization procedures. The mean volume of intraoperative blood loss was clearly less in the NBCA group than in the GDC +/- PVA group. HBs are mainly located in the posterior cranial fossa, so the risk of severe clinical complication may be high if vascular problems occur. In our series, presurgical embolization using NBCA made tumor removal safe and reduced bleeding volume in posterior fossa HBs.

DOI： 10.2176/nmc.52.878

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer-Verlag Berlin Heidelberg  

Despite the recent improvements in multimodal therapies that include surgery, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) easily recurs and continues to have a median overall survival time of less than 1.5 year. Eight nonrandomized prospective external beam BNCT trials have been performed over 15 years. The p-dihydroxyboryl-phenylalanine (BPA)-mediated BNCT was performed in the Brookhaven National Laboratory (BNL) trial, the trial of Harvard/MIT, the trial of University of Helsinki and VTT (Technical Research Centre of Finland), and the trial of Studsvik. The sulfhydryl borane Na2B12H11SH (BSH)-mediated BNCT was performed in the European Organisation for Research and Treatment of Cancer (EORTC) 11961 trial and the trial of Nuclear Research Institute (NRI) in Rez. The combination of BPA and BSH was used in the trial of Osaka Medical College and the trial of University of Tsukuba and JAEA. In the trial of Studsvik and Osaka Medical College, the long-term infusion of BPA was employed. Additional photon irradiation was performed in the trial of Osaka Medical College and the trial of University of Tsukuba and Japan Atomic Energy Agency (JAEA). Four of eight studies, even in subgroups of the patient population, suggest that external beam BNCT may improve survival in newly diagnosed GBM. Of these eight studies, four primarily phase I trials demonstrated only modest toxicity. The median time to progression and the median survival time vary from 6 to 12 months and 12 to 27 months, respectively.

DOI： 10.1007/978-3-642-31334-9_20

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. For several decades, clinicians have predicted intraparenchymal brain pressure or brain tissue compression indirectly based on the degree of distortion of the midline structures (midline shift) and ventricle wall (ventriculomegaly) observed on conventional MRI. However, this method has several limitations. Diffusion tensor imaging (DTI) is a novel MRI technique that can provide information about the microstructural properties of compressed tissue. In this study, the authors evaluated whether DTI can precisely define the degree of tissue compression in patients with chronic subdural hematoma (CSDH).
Methods. The study sample consisted of 18 patients (mean age 71 years, 10 men and 8 women) with unilateral CSDH and 12 age-matched volunteers. Diffusion tensor imaging results were acquired before and after the surgical irrigation in the CSDH group. Subdural pressure during the operation was also measured. Fractional anisotropy (FA) values were evaluated at several locations, including the gray matter.
Results. The FA values of the gray matter, especially in the caudate nucleus and putamen, were increased in the patients with CSDH compared with the control group. The change in FA data before and after surgery (Delta FA) correlated with the degree of tissue compression evaluated by measurement of the subdural pressure. Furthermore, the increased FA values in patients with CSDH decreased after surgery.
Conclusions. These findings indicate that FA values of the gray matter, especially in the caudate nucleus and putamen, may be important markers of tissue compression. The assessment of FA values of the gray matter will result in a new, less-invasive diagnostic technique to evaluate the degree of brain compression. (http://thejns.org/doi/abs/10.3171/2012.4.JNS112305)

DOI： 10.3171/2012.4.JNS112305

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Isocitrate dehydrogenase 1 (IDH1) mutations, which are early and frequent genetic alterations in astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas, are specific to arginine 132 (R132). Recently, we established monoclonal antibodies (mAbs) against IDH1 mutations: anti-IDH1-R132H and anti-IDH1-R132S. However, the importance of immunohistochemistry using the combination of those mAbs has not been elucidated. For this study, 164 cases of glioma were evaluated immunohistochemically for IDH1 mutations (R132H and R132S) using anti-IDH1 mAbs (HMab-1 and SMab-1). IDH1 mutation was detected, respectively, in 9.7%, 63.6%, 51.7%, and 77.8% of primary grade IV, secondary grade IV, grade III, and grade II gliomas. For each grade of glioma, prognostic factors for progression-free survival and overall survival were evaluated using clinical and pathological parameters in addition to IDH1 immunohistochemistry. IDH1 mutation, p53 overexpression, and internexin expression, as evaluated using immunohistochemistry with clinical parameters such as degree of surgical removal and preoperative Karnofsky Performance Status (KPS), might be of greater prognostic significance than histological grading alone in grade III as well as IDH1 mutation in grade IV gliomas.

DOI： 10.1007/s11060-012-0837-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

A 54-year-old man was admitted to our hospital with complaint of sudden headache. The patient had suffered two episodes of transient headache before admission. Computed tomography (CT) revealed acute subdural hematoma (ASDH) on the right side of the cerebral convexity with bilateral extension along the tentorium cerebelli without signs of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH). Three-dimensional CT angiography and conventional cerebral angiography revealed a left A1-A2 junction aneurysm. Neck clipping of the aneurysm was performed. The aneurysm extended inferiorly, with the dome embedded in the chiasmatic cistern and tightly adhered to the arachnoid membrane. There was no evidence of hematoma in the subarachnoid space. The patient was discharged without neurological deficit. Ruptured aneurysms resulting in ASDH without SAH or ICH are very rare. Radiological investigation such as three-dimensional CT angiography should be performed to find the causative aneurysm in a patient with ASDH with a history of repeated headaches and without traumatic signs or episodes, and the appropriate treatment should be planned with expediency.

DOI： 10.2176/nmc.52.430

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Antiangiogenic strategy is promising for malignant glioma. Histone deacetylase inhibitors (HDACIs) are unique anticancer agents that exhibit antiangiogenic effects. The in vitro and in vivo antiangiogenic effects of HDACIs, valproic acid (VPA), were investigated in malignant glioma in the brain. In vitro, VPA preferentially inhibited endothelial cell proliferation compared to glioma cell proliferation at the optimum concentration in a dose-dependent manner. VPA reduced vascular endothelial growth factor (VEGF) secretion of glioma cells in a dose-dependent manner under both normoxic and hypoxic conditions. VPA was also found to inhibit tube formation in the angiogenesis assay. In vivo, treatment with VPA combined with irinotecan reduced the number of vessels expressing factor VIII in the brain tumor model. VPA inhibits glioma angiogenesis by direct (inhibition of endothelial cell proliferation and tube formation) and indirect (decreased secretion of VEGF by glioma cells) mechanisms. These data suggest a potential role for VPA as an adjuvant therapy for patients with malignant glioma.

DOI： 10.2176/nmc.52.186

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Combined vaccines containing GL261 murine glioma cells and F-2 murine endothelial cells fixed with glutaraldehyde-phosphate buffered saline were injected into the intradermal tissue of the tail base of C57BL/6 mice. After the vaccination, GL261 cells were injected subcutaneously into the left flank of the mice. Vaccination with fixed F-2 cells induced the development of relatively high amounts of interferon-gamma-releasing cells after in vitro re-stimulation with vascular endothelial growth factor-receptor 2 peptide. Tumor growth was inhibited after preventive use of the combined vaccine, prepared from GL261 and F-2 cells. Tumor specimens obtained from the combined vaccine group in a therapeutic experiment showed significantly decreased vessel count. Glioma immunotherapy with a combined vaccine prepared from tumor cells and endothelial cells might represent a new clinical strategy, as such combinations may theoretically affect both high-grade glioma cells and their environment.

DOI： 10.2176/nmc.52.194

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: In navigation-guided endoscopic surgery performed via a single port, the interference of surgical instruments often disturbs the resection and hemostasis. Case Description: With regard to this, we designed a dual-port technique for navigation-guided endoscopic surgery in a 62-year-old man, with intraparenchymal anaplastic astrocytoma. Two transparent sheaths with Nelaton tubes were inserted in the front of the target lesion via an infinity-shaped burr hole, under the control of the navigation system. The lesion was removed partially using a rigid endoscope and several surgical tools through the bilateral ports. Using the new method, it was convenient to perform hemostasis with bipolar coagulation and aspiration, without any interference from the surgical instruments during the surgery. Conclusion: The offered dual-port technique may be included in surgery planning for elderly patients or patients in particular conditions, with intraparenchymal brain tumors. Copyright © 2012 Masuda Y.

DOI： 10.4103/2152-7806.94033

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The authors report a case of intraparenchymal germinoma pathologically diagnosed using navigation-guided endoscopic biopsy. Case Description: A 27-year-old man had mild left hemiparesis, transcortical motor aphasia, and amnesia. Magnetic resonance (MR) imaging revealed an intraparenchymal mass lesion near the left ventricular trigone. Navigation-guided endoscopic biopsy was performed, and histopathology revealed large neoplastic cells immunohistochemically positive for germinoma-specific antigens, which were diagnosed as pure germinoma. Chemotherapy with whole-brain radiotherapy was performed, and the neurological symptoms did not change during the treatment. Follow-up MR imaging 1 year after the surgery showed no evidence of recurrence or dissemination. Conclusions: Navigation-guided endoscopic biopsy can be a useful technique in such intraparenchymal germinoma cases. Copyright © 2012 Onuma K.

DOI： 10.4103/2152-7806.92177

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI LTD  

Intracranial nongerminomatous germ cell tumors (NGGCTs) in unusual locations are extremely rare. Here, we report a case of a yolk sac tumor in the frontal lobe in a middle-aged patient. A 42-year-old man was admitted to our hospital for headache and nausea. Magnetic resonance imaging (MRI) showed an enhanced mass lesion with a marked cyst component. The serum alpha-fetoprotein (alpha FP) level was extremely high. Histological examination of specimens after subtotal removal revealed a primary mixed germ cell tumor with extensive yolk sac tumor elements, often referred to as an intracranial "yolk sac tumor." The preoperative diagnosis of NGGCTs in unusual age and locations is extremely difficult. Clinicians should consider the possibility of NGGCTs, including yolk sac tumors, when intracranial tumors with unusual MRI findings are encountered.

DOI： 10.1155/2012/473790

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

To evaluate the efficacy of intraparenchymal brain tumor biopsy using endoscopy and a navigation system (navigation-guided endoscopic biopsy) as a diagnostic tool, a case series of intraparenchymal tumor biopsies was reviewed. Navigation-guided endoscopic biopsy was applied in 9 cases, stereotactic needle biopsy in 16 cases, and open biopsy with or without navigation system in 34 cases. In all biopsy cases, 84.7% of biopsy points were sampled accurately, and 93.2% of diagnoses by biopsy were correct. Comparison of each type of biopsy showed that the resected volumes in navigation-guided endoscopic biopsy and open biopsy tended to be larger than those in stereotactic biopsy, and the mean operation time for the open biopsy procedure was the longest. To define the most applicable device or examination method to increase sampling accuracy, various factors were analyzed in 59 procedures. Navigation-guided endoscopic biopsy was the most accurate of the three types of biopsy, although the statistical difference was not significant. Older patients, histological diagnosis of high-grade glioma or malignant lymphoma, positive photodynamic diagnosis, and positive intraoperative pathology were significant factors in improving the sampling accuracy. Navigation-guided endoscopic biopsy could provide a larger sample volume within a relatively short operation time. The biopsy can be easily combined with both photodynamic diagnosis and intraoperative pathology, significantly improving the histological diagnostic yield.

DOI： 10.2176/nmc.51.694

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(NPO)日本レーザー医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01213&link_issn=&doc_id=20111003460035&doc_link_id=%2Fcd0rezae%2F2011%2F003202%2F044%2F0233-0233%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcd0rezae%2F2011%2F003202%2F044%2F0233-0233%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme.
Methods. Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done-one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment.
Results. The median duration of overall survival was 21.4 months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p &lt; 0.05); progression-free survival showed a statistically significant association with p53 staining index (p &lt; 0.05) and size of DTH-2 response (p &lt; 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection.
Conclusions. The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted. (DOI: 10.3171/2011.4-JNS10377)

DOI： 10.3171/2011.4.JNS10377

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PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a case, in which quantitative 1H-MR spectroscopy (MRS) was useful for the differentiation between radiation necrosis and a recurrent tumor. The present case is a 44-year-old man who underwent the subtotal removal of a mass lesion in the left frontal lobe. The histological diagnosis was anaplastic oligodendroglioma (WHO grade III). Postoperatively, a fractionated radiotherapy (total 64Gy) and chemotherapy were performed. MRI after the radiotherapy showed no contrast enhancing lesion. MRI, 5 years after the radiotherapy, showed a growing enhancing lesion and a T1 hypointensity lesion without enhancement, both of which indicated a recurrent tumor. MR spectroscopy was performed for the differential diagnosis of these lesions. The spectrum was acquired by the point resolved spectroscopy (PRESS) method by TR/TE=2,000 ms/68 ms, 136 ms, and 272 ms and evaluated with peak pattern and quantification value of metabolite. MRS of the enhancing lesion demonstrated a decrease of the Choline-containing compounds (Cho) concentration, disappearance of N-acetylaspartate (NAA), decrease of Creatine/ Phosphocreatine (t-Cr) and presence of Lipids (Lip) and Lactate (Lac), all of which are characteristic finding of a radiation necrosis. The histological diagnosis of this lesion showed evidence also of radiation necrosis. On the other hand. MRS of the T1 hypointensity lesion without enhancement showed, a marked high peak of the Cho concentration, which is characteristic for a recurrent tumor. The histological findings of this lesion showed a diffuse proliferation of recurrent tumor cells. Quantitative 1H-MRS is a useful tool for the differentiation between radiation necrosis and recurrent tumors.

Scopus

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The hemagglutinating virus of Japan envelope (HVJ-E) vector derived from inactivated replication-defective Sendai virus enhances anti-tumor immunity through activation of effector T cells and natural killer (NK) cells and inhibition of regulatory T cells (Tregs). Interleukin (IL)-2 enhances T cell proliferation and activates T cells and NK cells. However, recent studies have revealed that the application of IL-2 also has immune suppressive effects through expansion of Tregs. Here, we investigated the efficacy of IL-2 gene therapy using immunomodulating HVJ-E vector in murine malignant glioma models. A single intratumoral injection of HVJ-E containing pVAX-mIL-2 significantly suppressed tumor growth of intracranial gliomas, resulting in prolonged survival. Furthermore, HVJ-E, following intracavitary administration, delivered genes into post-operative residual tumor cells. Consequently, prolonged survival resulted from a single intracavitary administration of HVJ-E containing pVAX-mIL-2 following tumor removal. IL-2 gene therapy delivered via the HVJ-E vector significantly inhibited the expansion of Tregs in tumors compared to IL-2 gene transfer using retroviral vector and resulted in marked infiltration of CD4(+) and CD8(+) T cells into tumors. Through inhibition of Treg-mediated immunosuppression, HVJ-E enhanced effector T cell-mediated anti-tumor immunity induced by IL-2. This combination of an immunomodulating vector and immunostimulating cytokine gene shows promise as an attractive, novel immunogene therapy for malignant glioma.

DOI： 10.1007/s11060-010-0355-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

DOI： 10.1007/s10014-011-0028-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Temozolomide (TMZ), an alkylating agent widely used for patients with glioblastoma multiforme (GBM), has the potential to enhance the acquired immune response to GBM. Here, we describe 3 cases of GBM patients treated with autologous formalin-fixed tumor vaccine (AFTV) combined with TMZ. All cases demonstrated pathological changes associated with the therapy. After a 4-week break from the standard initial treatments, 1 patient with primary GBM and 2 patients with secondary GBM received adjuvant TMZ for 5 days combined with AFTV injection and were subsequently treated with multiple cycles of adjuvant TMZ for 5 days every 28 days (AFTV/TMZ therapy). Adverse effects related to AFTV plus TMZ were very minor in all patients. Magnetic resonance imaging revealed partial response in 2 patients. CD3(+)CD8(+) lymphocytes were frequently detected in surgical specimens and MIB-1 labeling index in 2 cases decreased after AFTV/TMZ therapy. AFTV/TMZ therapy is suitable for larger scale clinical trials.

DOI： 10.2176/nmc.51.319

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Isocitrate dehydrogenase 1 (IDH1) mutations have recently been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas, as well as secondary glioblastomas, whereas primary glioblastomas very rarely contain IDH1 mutations. Furthermore, a specific monoclonal antibody, IMab-1, which recognizes IDH1-R132H-the most frequent IDH1 mutation-has been generated. IMab-1 has been reported to react with the IDH1-R132H protein, but not the wild-type IDH1 or the other IDH1 mutant proteins in Western-blot analysis. However, the importance of immunohistochemistry using IMab-1 has not yet been elucidated. In this study, we compared the findings from IMab-1 immunohistochemistry and direct DNA sequencing using 49 glioma samples. IMab-1 detected 12 out of 49 cases; however, only nine cases were found to be IDH1-R132H by direct DNA sequencing because of a small population of IDH1-R132H mutation-possessing tumor cells, indicating that IMab-1 immunohistochemistry is useful for detecting IDH1-R132H. We conducted immunohistochemical detection in 52 cases of grade III astrocytomas. The median time to progression (TTP) was significantly longer in the cases with the IDH1 mutation (86.7 months) compared to the cases without the IDH1 mutation (wild type, 10.4 months) (p &lt; 0.01). In conclusion, the anti-IDH1-R132H-specific monoclonal antibody IMab-1 is very useful for detecting IDH1-R132H in immunohistochemistry, and predicting the time to progression in grade III anaplastic astrocytomas. Therefore, IMab-1 is likely to be useful for the diagnosis of mutation-bearing gliomas and for determining the treatment strategy of grade III gliomas.

DOI： 10.1007/s10014-011-0023-7

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PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Hypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha expression were investigated immunohistochemically as determinants of prognosis in 42 cases of astrocytic tumors associated with necrosis grade on magnetic resonance (MR) imaging. Expression of HIF-1 alpha was determined immunohistologically. The degree of necrosis on MR images was divided into four grades. Kaplan-Meier analysis revealed a significant effect of necrosis grade on MR images on cumulative overall survival. Median survival times were 26, 14, and 13 months for patients with necrosis grades 1, 2, and 3, respectively (not defined for grade 0). Kaplan-Meier analysis revealed a significant effect of HIF-1 alpha expression on cumulative overall survival. Median survival time of patients with HIF-1 alpha expression was 17 months, whereas it was 80 months for patients without HIF-1 alpha expression. However, overexpression of HIF-2 alpha did not correlate with malignant features, for example angiogenesis or necrosis, and had no impact on overall survival of patients with glial tumors. In conclusion, HIF-1 alpha, but not HIF-2 alpha, is a useful prognostic factor in astrocytic tumor associated with necrosis on MR images.

DOI： 10.1007/s11060-010-0292-8

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記述言語：日本語   出版者・発行元：(一社)茨城県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome with a very particular clinical course. Three patients with MERS were evaluated by various sequences of magnetic resonance imaging with diffusion tensor imaging. Initial diffusion-weighted imaging showed reduction in the apparent diffusion coefficient values in the lesions, which completely resolved with the elimination of symptoms. However, diffusion anisotropy of the lesions showed no remarkable abnormalities in the early or delayed phases. These results may indicate that white matter architecture is preserved in both early and delayed phases in MERS.

DOI： 10.2176/nmc.50.1118

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOHN WILEY & SONS LTD  

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