BACKGROUND/AIM: Standard treatment options for primary central nervous system lymphoma (PCNSL) include high-dose methotrexate (HD-MTX)-based drug therapy and whole-brain radiation therapy. However, there are many cases in which these standard treatment options are not tolerated for various reasons. In the present study, five cases of refractory/relapsed PCNSL that are difficult to treat with standard treatment were successfully treated by tirabrutinib. PATIENTS AND METHODS: A total of 5 patients (4 women, 1 man) with refractory (n=3) and relapsed (n=2) PCNSL were included. The patients had a median age of 76 years and a median Karnofsky performance status (KPS) of 40. The reasons why standard treatment cannot be given to these patients are the low KPS, renal dysfunction, and resistance to HD-MTX. Administration of a drug via the oral route was challenging in three patients; thus, these patients were administered tirabrutinib in suspension through a nasogastric tube. RESULTS: Imaging findings showed that the patients achieved a 100% response rate to tirabrutinib, with a median survival of 8 months. As symptoms improved, 2 of the 3 patients who were initially administered tirabrutinib via a nasogastric tube were able to receive the drug via the oral route. Three patients developed adverse reactions; however, treatment was not interrupted because they were manageable. CONCLUSION: Tirabrutinib was effective in the treatment of patients who were unable to receive standard treatment options. Tirabrutinib may be considered one of the novel treatment strategies that could improve the prognosis of PCNSL patients in the future.

高齢発症てんかん(A)は初回発作後の再発が高率であると報告されているが、発作自体は少量の抗てんかん薬で比較的コントロール可能である。そのため、Aによる機能的予後の悪化を防ぐには可及的早期の治療介入を目指すべきであるが、非専門医によるAの診断は困難であり、多数の症例が潜在化している可能性がある。そこで、潜在するAを顕在化させるために簡便な調査票を用いたスクリーニングを行い、有効性が認められたので報告した。調査票の内容は以下の8項目とした。1)突然の動作停止と反応性の低下を認める。2)無自覚な口部自動症、体幹・四肢の揺れがある。3)意識を失っても倒れない。4)動作停止後、数十秒～数分で何事もなかったように動作再開する。5)意識消失時のことを何も覚えていない。6)意識改善後も数分～数時間は虚ろである。7)易怒性が高い。8)目の焦点が合わないことがある。

We report that tirabrutinib was administered via nasogastric tubes to treat an elderly patient with primary central nervous system lymphoma (PCNSL). The patient was a 76-year-old woman who underwent endoscopic biopsy of multiple intracerebral masses, which resulted in the diagnosis of diffuse large B-cell lymphoma. The patient was diagnosed with PCNSL and was started on an induction regimen of systemic chemotherapy with rituximab in combination with high-dose methotrexate. However, after the second cycle of chemotherapy, the tumor grew rapidly, and the patient went into a coma. As a result, the treatment was changed to nasogastric tube administration of tirabrutinib suspension. After 1 week of tirabrutinib administration, the patient's level of consciousness improved, and furthermore, after 2 weeks of tirabrutinib administration, the patient was able to take tirabrutinib orally. Although oral administration is the standard route of administration for tirabrutinib, this case study showed that the nasogastric tube administration of tirabrutinib suspension is a therapeutic option for patients with impaired consciousness or dysphagia.

BACKGROUND/AIM: Leptomeningeal carcinomatosis (LMC) with hydrocephalus is particularly difficult to treat, and its prognosis is extremely poor. The therapeutic outcomes of 14 patients with LMC-associated hydrocephalus who were treated with cerebrospinal fluid shunting are reported. PATIENTS AND METHODS: The study subjects were 14 LMC patients with solid primary cancer who had developed hydrocephalus. RESULTS: Postoperatively, both symptoms and Karnofsky performance status improved in 100% of patients. Postoperative therapy consisted of whole-brain radiotherapy in 4 cases and molecular targeted therapy in 4, with 6 patients not receiving any postoperative treatment. Median overall survival was 3.7 months, with no significant difference between those who underwent postoperative therapy and those who did not. However, two of those who received molecular targeted therapy survived for more than one year. CONCLUSION: Cerebrospinal fluid shunting for LMC-associated hydrocephalus is an effective therapeutic procedure from the palliative viewpoint. Patients for whom molecular targeted therapy is indicated may have better long-term survival.

BACKGROUND/AIM: Recent advances in systemic chemotherapy, including molecularly targeted therapy, have dramatically improved survival for patients with advanced non-small cell lung cancer. We retrospectively analyzed the clinical outcomes of surgical resection for brain metastases of non-small cell lung cancer cases performed at the Department of Neurosurgery of Kindai University Hospital, Osaka, Japan. PATIENTS AND METHODS: Craniotomy and tumor resection were performed for 56 patients with brain metastases of non-small cell lung cancer. Adenocarcinoma was the most common histological type, appearing in 40 cases, of which 18 were positive for driver gene mutations. RESULTS: Median survival for all 56 patients was 14.5 months, and single brain metastasis and adenocarcinoma were identified as favorable prognostic factors. Analysis limited to the 40 cases of adenocarcinoma identified single brain metastasis as a favorable prognostic factor. Although no significant difference was found for systemic chemotherapy, patients who received molecularly targeted therapy showed a better prognosis than those who received cytotoxic chemotherapy. Analyses of both the entire group and of adenocarcinoma patients alone found that whole-brain radiotherapy showed no significant association with survival. CONCLUSION: Single brain metastasis and adenocarcinoma were identified as favorable prognostic factors, but did not confirm any benefit from whole-brain radiotherapy. These results suggest that multimodal treatment strategies utilizing various methods of treatment, including systemic chemotherapy, may help prolong patient survival in the future.

BACKGROUND: Glioblastoma multiforme (GBM) is a malignant brain tumor with an extremely poor prognosis. GBM tissues frequently express mesenchymal-epithelial transition factor (MET), which induces cell division, growth and migration. In addition, angiogenesis is a significant feature of GBM, attributable to the overexpression of vascular endothelial growth factor (VEGF). Although the VEGF inhibitor bevacizumab was recently highlighted as the second-line drug for GBM treatment, GBMs often recur even with bevacizumab therapy. Based on these findings, we hypothesized that inhibition of both MET and VEGF would exhibit a synergistic effect on MET-overexpressing GBM. MATERIALS AND METHODS: As we observed MET expression at high levels in some patients with GBM, we designed GL261 murine glioma-based experiments. GL261 cells were transfected with siRNAs specific for MET and VEGF in vitro, and the cell growth ratios were evaluated. Simultaneously, transfected GL261 cells were transplanted into the brain of C57BL/6 mice, and their survival was monitored. RESULTS: GBM tissues frequently overexpressed MET protein at high levels compared with lower-grade gliomas. These GBMs at first responded to bevacizumab, but often eventually recurred. When GL261 cells were co-transfected with both MET-specific siRNA and VEGF-specific siRNA, the in vitro tumor cell growth significantly decelerated compared to single siRNA transfection. Consistently, when mice were transplanted with co-transfected GL261 cells, their survival was significantly prolonged compared to those given cells transfected with single siRNA. CONCLUSION: The current data indicate that the inhibition of both MET and VEGF exhibits efficient therapeutic effects of GBM-bearing hosts.

BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent and the most malignant tumor among adult brain tumors. Previous reports led us to hypothesize that the proto-oncogene mesenchymal-epithelial transition (MET) expressed in glioma stem cell-like cells (GSCs) would be a potent therapeutic target for GBM. PATIENTS AND METHODS: To address this question, we analyzed 113 original samples of tumors from patients based on immunohistochemistry. During this process, we were able to establish GSC lines from patients with GBM that were MET-positive and MET-negative. Using these cells, we tested the therapeutic impact of a MET inhibitor, crizotinib, both in vitro and in vivo. RESULTS: Patients with MET-positive GBM exhibited poor survival. GSC-based experiments revealed that treatment with crizotinib, both in vitro and in vivo, exhibited therapeutic efficacy particularly against MET-positive GSCs. CONCLUSION: Based on these findings, we conclude that MET expressed in GSCs might be a potent therapeutic target for GBM.

BACKGROUND: Sylvian dissection is an essential microneurosurgical skill for neurosurgeons. The safe and accurate opening of the sylvian fissure is desirable for a good prognosis. METHODS: The aim of this report is to demonstrate the use of indocyanine green (ICG) videoangiography to recognize the superficial sylvian vein (SSV) and thus enable a wide opening of the sylvian fissure, especially in patients with subarachnoid hemorrhage (SAH). RESULTS: The small tributary flowing into the SSV was distinguishable from a passing one, which deeply entered the insula. In addition, an entering point of a tributary to the SSV, which ran perpendicular to the insula, was occasionally determined. SSV, which was barely discernable in a reddish SAH involving the sylvian fissure, was clearly demarcated using ICG videoangiography. Two representative cases of sylvian dissection are herein presented. CONCLUSION: The performance of ICG videoangiography before sylvian dissection is a simple and useful method for identifying a vital approach route for safe and accurate sylvian dissection, and it reduces the risk of causing any accidental injury to the veins in the sylvian fissure.

BACKGROUND: The preoperative imaging diagnosis of the distal portion of the internal carotid artery (ICA) is extremely important for carotid endarterectomy (CEA). Herein the authors defined a line from the C1 transverse process to the hyoid bone (C1-H line) and evaluated whether the line can be used to predict an accessible ICA in CEA. METHODS: A cross point between the C1-H line and distal ICA was analyzed using three-dimensional computerized tomographic angiography (3D-CTA) in 20 patients. The C1-H line was compared to the line drawn from the mastoid process to the mandible (M-M line). Intraoperative exposure of the distal ICA was evaluated using both lines. Furthermore, the distance of each line from the C2 vertebra was measured to identify the distance difference of each line in relation to the cervical posture. RESULTS: A distal ICA exposed at a cross point of the C1-H line corresponded well with the intraoperative findings. The cross point between the C1-H line and distal ICA was positioned at an average of 7.0 ± 0.7 mm cranially in comparison to the M-M line. The C1-H line showed smaller distance differences at different cervical positions than the M-M line. The C1-H line moved an average of 2.8 ± 2.5 mm from a cervical neutral position to an extensional one in the perpendicular direction. CONCLUSION: The C1-H line measured by 3D-CTA is a simple and useful indicator of the distal ICA exposure in the preoperative diagnosis for CEA.

Moyamoya disease is commonly diagnosed in children, and requires various vascular reconstruction to improve symptoms. Therefore, scar widening and hair loss after craniotomy, which sometimes occurs in this disease, are serious problems for patients. A variety of plastic surgical techniques in scalp have been reported to minimize the scar widening and hair loss. However, any neurosurgical reports describing this purpose have never been published for moyamoya disease. The objective of this study was to investigate whether these plastic surgical techniques could be applied to bypass surgery without any compromise of vascular reconstruction for moyamoya disease. We performed direct and indirect vascular reconstruction in six hemispheres of moyamoya disease patients not only in the middle cerebral artery territory but also in the anterior cerebral artery territory. The scalp incision was designed not parallel to the hair stream, and the bevelled incision was conducted not to jeopardize the hair follicles. The scar and hair loss were effectively camouflaged throughout the postoperative period in all cases. This study demonstrates that our design of scalp incision achieve effective vascular reconstruction and obscure the scar and hair loss.

神経膠腫幹細胞様細胞(GSC)は多剤耐性を示すアデノシン三リン酸結合カセット(ABC)ファミリートランスポーターのメンバーを過剰に発現することが知られている。ヒトにおけるGSCは神経膠芽腫(GBM)発症に重要な役割を果たす。Sleeping Beautyトランスポゾン媒介自発性GBMからマウスGSC株を派生させた。これら細胞株を用いて、GSC動態におけるABCトランスポーターの重要性を細胞形態学的アッセイ、フローサイトメトリー、RT-PCRによるmRNA発現の定量により調べた。siRNAを介するABCG2阻害はGSCのテモゾロミド(TMZ)に対する感受性を増強し、スフェロイド形成能を低下させた。Abcg2特異的siRNAでGSCを処理するとTMZに感受性になり、そのスフェロイド形成能が低下した。GSCの薬物トランスポーターを標的とする治療はGSCの化学感受性を増強し、GBMの長期にわたる寛解達成に有望な戦略であることが示唆された。

BACKGROUND: We verified the effectiveness of training in endoscopic endonasal transsphenoidal surgery (eETSS) techniques using chicken eggs and a skull model. METHODS: We verified the area of eggshell removed by drilling when five residents and four experts used the chicken eggs and a skull model. RESULTS: When residents performed drilling on 10 eggs, a mean (± standard deviation [SD]) area of 31.2 ± 17.5 mm2 was removed from the first egg, and 104.8 ± 3.3 mm2 from the tenth and final egg, representing an increase in area and a decrease in SD. The experts performed the same drilling operation on a single egg, and removed a mean area of 257± 31.7 mm2. These results demonstrated that skills improved as a result of this training, and suggested that this method was also capable of overcoming the initial individual differences in the amount of force applied and ability. An obvious difference between residents and experts was seen in the area removed (p = 0.00011); however, this was attributed to differences in endoscopic manipulation, rather than drilling skill. CONCLUSION: Our findings suggest that this training method could be adequate for acquiring eETSS techniques. Although experts showed superior endoscopic manipulation, residents may also be able to acquire adequate endoscopic skills through further training, and our training method appears to offer an effective means of improving eETSS techniques.

BACKGROUND: An outstanding issue regarding the surgical treatment of cyst-type metastatic brain tumors is the incomplete resection of cyst walls. Herein we propose a novel surgical technique that can overcome this issue. During a surgical procedure for cystic tumors, autologous fibrin glue is to be injected into the tumor cysts, which solidifies the cyst lumens and cyst walls en bloc with reducing the tumor size. As a result, tumor masses and cyst walls can be removed completely in an en bloc fashion in all cases. METHODS: The illustrative case presented in this report is a patient with metastatic brain tumors in the frontal lobe. When we reached the tumor wall surgically, we first suctioned out the cyst content and subsequently injected autologous fibrin glue into the cyst lumen. The autologous fibrin glue solidified the tumor en bloc, and we resected the tumor mass and the cyst walls in an en bloc fashion. RESULTS: We have applied this technique to four cases with cyst-type metastatic brain tumors. This approach made it possible to perform ideal en bloc resection in all cases. There were no adverse events due to the autologous fibrin glue. CONCLUSION: We developed a novel surgical technique to solidify cyst-type metastatic brain tumors using autologous fibrin glue, which allows en bloc resection of tumor masses and cyst walls quite safely using inexpensive materials. Given these advantages, it appears a promising surgical strategy for cyst-type metastatic brain tumors.

We have developed a technique of fluorescence-guided surgery using high-dose fluorescein sodium (20mg/kg) with excitation and barrier filters for glioblastoma multiforme surgery. This technique was used in 10 patients, with surgery proceeding as expected in all patients. There were no complications or permanent side effects. This method uses filters to help distinguish between the usually invisible tumor and the brain surface, as well as allowing a detailed assessment of the positional relationships with tumor vessels and the surrounding normal vessels. As sufficient yellow staining was present even without filters, delicate microsurgery was also possible under a normal white-light microscope. Both environments could be used as necessary during surgery according to the requirements of resection, thereby improving the reliability and safety of surgery.

Intrathecal baclofen (ITB) therapy is a treatment for intractable spasticity due to a variety of causes. Continuous intrathecal administration of baclofen, an agonist of the inhibitory neurotransmitter γ-aminobutyric acid, inhibits excitation of motor neurons at the spinal level and thus suppresses spasticity. This therapy was introduced clinically in the Europe and the United States in the 1990s, and was finally approved by the Japanese Ministry of Health, Labour and Welfare in Japan in 2005. Clinical use has been permitted since 2006, and reports of therapeutic efficacy are now appearing in Japan. ITB therapy is a non-destructive treatment that enables administration of baclofen from an implantable pump under the control of a programmer, and represents an outstanding treatment method offering both reversibility and adjustability. Indications for ITB therapy have been expanding in recent years to include not only spasticity, but also various causes dystonia. And ITB therapy can greatly improve activities of daily living and quality of life, and this treatment is attracting attention as a neuromodulatory therapy that also affects metabolic and respiratory functions and even state of consciousness. We here report the surgical methods and therapeutic outcomes for 22 patients who underwent ITB therapy for spastic and dystonic patients in our hospital, together with an investigation of the effects on metabolic and respiratory functions.