Indications for a brain biopsy in neurological diseases of unknown etiology: The role of magnetic resonance imaging findings and liquid biopsy in yielding definitive pathological diagnoses.

Brain biopsies are often considered for patients who cannot be diagnosed with various laboratory test results. However, physicians tend to be hesitant regarding their application in possibly non-neoplastic brain diseases, due to the invasiveness and risks. The aim was to determine the indications for brain biopsies in cases of neurological diseases of unknown etiology. We retrospectively evaluated diagnostic accuracy, laboratory findings (including a liquid biopsy for malignant lymphoma), magnetic resonance imaging (MRI) characteristics and the post-treatment outcomes of patients undergoing brain biopsies for neurological diseases of unknown etiology. The data of patients who had undergone a brain biopsy during their admission to Niigata University Hospital, between 2011 and 2024, were reviewed. Moreover, the laboratory data and MRI findings between patients with definitive and nonspecific biopsy diagnoses were compared. Twenty-six patients underwent a brain biopsy, and a definitive diagnosis was obtained in 14 patients (53.8%). Even in cases where a nonspecific diagnosis was made, biopsy findings helped rule out malignancy and guide clinical diagnosis and treatment decisions. The liquid biopsy for malignant lymphoma was performed in eight patients, with one yielding a positive result, consistent with primary central nervous system lymphoma. The sensitivity and specificity of liquid biopsy were 0.5 and 1, respectively. Diffusely contrasted cortical lesions and the presence of mass effects on MRI, were significantly associated with a definitive diagnosis, compared to a nonspecific diagnosis. In conclusion, brain MRI and liquid biopsies can assist in determining the appropriate indications for brain biopsies in neurological diseases of unknown etiology.

[Intraoperative Monitoring During Microvascular Decompression].

During microvascular decompression(MVD)for hemifacial spasm(HFS), trigeminal neuralgia(TN), and glossopharyngeal neuralgia(GPN), brainstem auditory-evoked potential monitoring is widely used to preserve hearing function. In MVD for HFS, abnormal muscle response monitoring is useful for identifying the offending vessels compressing the facial nerve and confirming the completion of decompression intraoperatively. The amplitude of facial motor-evoked potential by transcranial electrical stimulation in the orbicularis oculi muscle is reported to decrease after completing MVD. The Z-L response(ZLR)probably confirms the true offending vessels by stimulating the culprit vessels; then, the ZLR could disappear after decompressing the offending vessels away from the compression sites. Spontaneous electromyographic activities obtained from the mentalis muscles by injection of saline into the facial nerve reportedly decreased after MVD compared with those before MVD. In MVD for the GPN, glossopharyngeal motor-evoked potential by transcranial electrical stimulation is used to preserve swallowing function and not to assess the completion of MVD. Because MVD for both the TN and GPN can result in normalization of the hyperactivity of the sensory nerve, it may be difficult to develop any monitoring to confirm the completion of MVD during surgery.

Superior Visualization of Neovascularization with Silent Magnetic Resonance Angiography Compared to Time-of-Flight Magnetic Resonance Angiography After Bypass Surgery in Moyamoya Disease.

OBJECTIVE: The evaluation of postsurgical neoangiogenesis in patients with moyamoya disease (MMD) is crucial for appropriate patient management. This study aimed to assess the visualization of neovascularization after bypass surgery using noncontrast-enhanced silent magnetic resonance angiography (MRA) with ultrashort echo time and arterial spin labeling. METHODS: After bypass surgery, 13 patients with MMD were followed up for >6 months between September 2019 and November 2022. They underwent silent MRA in the same session as time-of-flight magnetic resonance angiography (TOF-MRA) and digital subtraction angiography (DSA). Two observers independently rated the visualization of neovascularization in both types of MRA from 1 (not visible) to 4 (nearly equal to DSA), with reference to DSA images as the standard. RESULTS: The mean scores were significantly higher for silent MRA compared with TOF-MRA (3.81 ± 0.48 and 1.92 ± 0.70, respectively) (P < 0.01). The intermodality agreements were 0.83 and 0.71 for silent MRA and TOF-MRA, respectively. TOF-MRA depicted the donor artery and recipient cortical artery after direct bypass surgery, although fine neovascularization developed after indirect bypass surgery was poorly visualized. Silent MRA could reveal the developed bypass flow signal and perfused middle cerebral artery territory, which was almost equal to the DSA images. CONCLUSIONS: Silent MRA achieves better visualization of postsurgical revascularization in patients with MMD than TOF-MRA. Moreover, it may have the potential to provide visualization of the developed bypass flow equivalent to DSA.

Preoperative three-dimensional multifusion imaging aiding successful microvascular decompression of a cerebellopontine angle lipoma: associated hemifacial spasm. Illustrative case.

BACKGROUND: Cerebellopontine angle (CPA) lipoma-associated hemifacial spasm (HFS) is rare. As the removal of CPA lipomas has a high risk of worsening the neurological symptoms, surgical exploration is warranted only in selected patients. Preoperative identification of the lipoma affected site of the facial nerve, and offending artery are crucial for patient selection and successful microvascular decompression (MVD). OBSERVATIONS: Presurgical simulation using three-dimensional (3D) multifusion imaging showed a tiny CPA lipoma wedged between the facial and auditory nerves, as well as an affected facial nerve by the anterior inferior cerebellar artery (AICA) at the cisternal segment. Although a recurrent perforating artery from the AICA anchored the AICA to the lipoma, successful MVD was achieved without lipoma removal. LESSONS: The presurgical simulation using 3D multifusion imaging could identify the CPA lipoma, affected site of the facial nerve, and offending artery. It was helpful for patient selection and successful MVD.

Elevated ratio of C-type lectin-like receptor 2 level and platelet count (C2PAC) aids in the diagnosis of post-operative venous thromboembolism in IDH-wildtype gliomas.

INTRODUCTION: Podoplanin (PDPN) is known to induce platelet aggregation via interacting with the C-type lectin-like receptor-2 on platelets and is involved in postoperative venous thromboembolism (VTE) formation. In this study, we investigate the correlation between soluble C-type lectin-like receptor (sCLEC-2) levels and PDPN expression in patients with high grade gliomas and the relationship between sCLEC-2 levels and the occurrence of VTE. MATERIALS AND METHODS: Forty-four patients harboring high grade gliomas, treated surgically at the Department of Neurosurgery, Niigata University from April 2018 to August 2020, were included. Patients with high grade gliomas were divided into isocitrate dehydrogenase (IDH)- wildtype and mutant groups, and the presence or absence of VTE and the intensity of PDPN by immunohistochemistry were confirmed. Platelet counts, as well as plasma sCLEC-2 and PDPN were measured in these patients. Furthermore, the levels of sCLEC-2 concentration were divided by the platelet count (C2PAC index) for comparison. RESULTS: IDH-wildtype glioma patients highly expressed PDPN (P < 0.001) compared to IDH-mutant glioma patients. In total, 9 (20.5 %) patients were diagnosed with VTE during the follow-up period, of which 8 patients harbored IDH-wildtype gliomas, and one patient an IDH-mutant glioma. Mean sCLEC-2 levels and C2PAC index in patients with IDH-wildtype gliomas were significantly higher than that of low or no PDPN expression group, which included patients with IDH-mutant gliomas (P = 0.0004, P = 0.0002). In patients with IDH-wildtype gliomas, the C2PAC index in patients with VTE was significantly higher than in patients without VTE (P = 0.0492). The optimal cutoff point of C2PAC for predicting VTE in IDH-wildtype glioma patients was 3.7 with a sensitivity of 87.5 % and specificity of 51.9 %. CONCLUSION: Platelet activation is strongly involved in the development of VTE in patients with IDH-wildtype high grade gliomas, and C2PAC index is a potential marker to detect VTE formation after surgery.

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin.

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

Successful Treatment of Acute Uric Acid Nephropathy with Rasburicase in a Primary Central Nervous System Lymphoma Patient Showing a Dramatic Response to Methotrexate-Case Report.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. The standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSLs. CASE PRESENTATION: A 54-year-old man with a history of gout presented with a change in character and cognitive dysfunction. MRI showed a large enhancing mass spanning the bilateral frontal lobes and the right temporal lobe. After endoscopic biopsy, an MTX, procarbazine, and vincristine (MPV) regimen was initiated for the treatment of the PCNSL. After the initiation of chemotherapy, the patient experienced a gout attack, and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute uric acid nephropathy. As the dramatic effect of MTX was observed, treatment was continued despite ARF, most probably due to acute hyperuricemia due to tumor lysis, which was treated in parallel. After an improvement in renal function, MTX was resumed, and rasburicase was initiated to control hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase, and renal function was preserved. CONCLUSIONS: Acute uric acid nephropathy should be considered when ARF occurs after the initiation of MTX in PCNSLs, especially in newly diagnosed PCNSL patients with large tumors or hyperuricemia.

Elucidating the multiple genetic alterations involved in the malignant transformation of a KRAS mutant neurenteric cyst. A case report.

Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.

[Intraoperative Neuromonitoring for Skull Base Surgery].

Intraoperative neuromonitoring techniques can be used to evaluate neural functions during surgical procedures. For removal of tumors in the skull base region, we perform them for both structural mapping of the compressed cranial nerves and continuous monitoring of their preservation. The goal is to eliminate the critical irreversible damage to the neurological structures and prevent postoperative neurologic deficits. Recording techniques have been developed and neuromonitoring equipment used in the operation room with the intravenous anesthesia technique. For skull base surgery, in particular, the neuromonitoring contains motor evoked potential(MEP), brainstem auditory evoked potential(BAEP), visual evoked potential(VEP), and others. We believe that the appropriate recording and interpretation of these data can greatly improve the surgical outcomes of tumor removal and prevent postoperative neurologic deficits.

HSP90 Inhibition Overcomes Resistance to Molecular Targeted Therapy in BRAFV600E-mutant High-grade Glioma.

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 GSK3ß (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.

Clinicopathological risk factors for a poor prognosis of primary central nervous system lymphoma in elderly patients in the Tohoku and Niigata area: a multicenter, retrospective, cohort study of the Tohoku Brain Tumor Study Group.

Clinicopathological risk factors for a poor prognosis were investigated in elderly patients with malignant lymphoma of the central nervous system. A total of 82 pathologically confirmed, CD20-positive, diffuse large B-cell lymphoma patients aged 71 years or older who underwent therapeutic intervention in the Tohoku and Niigata area in Japan were retrospectively reviewed. A univariate analysis was performed by the log-rank test using the Kaplan-Meier method. A Cox proportional hazards model was used for multivariate analysis of risk factors. Of the 82 patients, 39 were male and 43 were female, and their median age at onset was 75 years. At the end of the study, there were 34 relapse-free patients (41.5%), 48 relapse cases (58.5%), median progression-free survival was 18 months, and median overall survival (OS) was 26 months; there were 41 deaths and 41 survivors. Multivariate analysis of median OS showed that Karnofsky Performance Status less than 60% 3 months after treatment (p = 0.022, hazard ratio (HR) = 2.591) was the clinical risk factor, and double expressor lymphoma (p = 0.004, HR = 3.163), expression of programmed death-ligand 1 in tumor infiltrating lymphocytes or tumor-associated macrophages (p < 0.001, HR = 5.455), and Epstein-Barr virus infection (p = 0.031, HR = 5.304) were the pathological risk factors.

Novel Repositioning Therapy for Drug-Resistant Glioblastoma: In Vivo Validation Study of Clindamycin Treatment Targeting the mTOR Pathway and Combination Therapy with Temozolomide.

Multimodal therapy including surgery, radiation treatment, and temozolomide (TMZ) is performed on glioblastoma (GBM). However, the prognosis is still poor and there is an urgent need to develop effective treatments to improve survival. Molecular biological analysis was conducted to examine the signal activation patterns in GBM specimens and remains an open problem. Advanced macrolides, such as azithromycin, reduce the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream mammalian target of rapamycin (mTOR) effector, and suppress the proliferation of T-cells. We focused on its unique profile and screened for the antitumor activity of approved macrolide antibiotics. Clindamycin (CLD) reduced the viability of GBM cells in vitro. We assessed the effects of the candidate macrolide on the mTOR pathway through Western blotting. CLD attenuated p70S6K phosphorylation in a dose-dependent manner. These effects on GBM cells were enhanced by co-treatment with TMZ. Furthermore, CLD inhibited the expression of the O6-methylguanine-DNA methyltransferase (MGMT) protein in cultured cells. In the mouse xenograft model, CLD and TMZ co-administration significantly suppressed the tumor growth and markedly decreased the number of Ki-67 (clone MIB-1)-positive cells within the tumor. These results suggest that CLD suppressed GBM cell growth by inhibiting mTOR signaling. Moreover, CLD and TMZ showed promising synergistic antitumor activity.

Visualization of cortical activation in human brain by flavoprotein fluorescence imaging.

OBJECTIVE: To develop an innovative brain mapping and neuromonitoring method during neurosurgery, the authors set out to establish intraoperative flavoprotein fluorescence imaging (iFFI) to directly visualize cortical activations in human brain. The significance of iFFI was analyzed by comparison with intraoperative perfusion-dependent imaging (iPDI), which is considered the conventional optical imaging, and by performing animal experiments. METHODS: Seven patients with intracerebral tumors were examined by iFFI and iPDI following craniotomy, using a single operative microscope equipped with a laser light source for iFFI and xenon lamp for iPDI. Images were captured by the same charge-coupled device camera. Responses to bipolar stimulation at selected points on the cortical surface were analyzed off-line, and relative signal changes were visualized by overlaying pseudocolor intensity maps onto cortical photographs. Signal changes exceeding 3 SDs from baseline were defined as significant. The authors also performed FFI and PDI on 10 mice using similar settings, and then compared signal patterns to intraoperative studies. RESULTS: Signals acquired by iFFI exhibited biphasic spatiotemporal changes consisting of an early positive signal peak (F1) and a delayed negative signal peak (F2). In contrast, iPDI signals exhibited only 1 negative peak (P1) that was significantly delayed compared to F1 (p < 0.02) and roughly in phase with F2. Compared to F2 and P1, F1 was of significantly lower amplitude (p < 0.02) and located closer to the bipolar stimulus center (p < 0.03), whereas F2 and P1 were more widespread, irregular, and partially overlapping. In mice, the spatiotemporal characteristics of FFI and PDI resembled those of iFFI and iPDI, but the early positive signal was more robust than F1. CONCLUSIONS: This is the first report in humans of successful intraoperative visualization of cortical activations by using iFFI, which showed rapid evoked cortical activity prior to perfusion-dependent signal changes. Further technical improvements can lead to establishment of iFFI as a real-time intraoperative tool.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

BACKGROUND: Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. METHODS: Patients aged ≥ 71 years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76 years and < 76 years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. CONCLUSIONS: Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.

Detection of 2-Hydroxyglutarate by 3.0-Tesla Magnetic Resonance Spectroscopy in Gliomas with Rare IDH Mutations: Making Sense of "False-Positive" Cases.

We have previously published a study on the reliable detection of 2-hydroxyglutarate (2HG) in lower-grade gliomas by magnetic resonance spectroscopy (MRS). In this short article, we re-evaluated five glioma cases originally assessed as isocitrate dehydrogenase (IDH) wildtype, which showed a high accumulation of 2HG, and were thought to be false-positives. A new primer was used for the detection of IDH2 mutation by Sanger sequencing. Adequate tissue for DNA analysis was available in 4 out of 5 cases. We found rare IDH2 mutations in two cases, with IDH2 R172W mutation in one case and IDH2 R172K mutation in another case. Both cases had very small mutant peaks, suggesting that the tumor volume was low in the tumor samples. Thus, the specificity of MRS for detecting IDH1/2 mutations was higher (81.3%) than that originally reported (72.2%). The detection of 2HG by MRS can aid in the diagnosis of rare, non-IDH1-R132H IDH1 and IDH2 mutations in gliomas.

The Japan Neurosurgical Database: Statistics Update 2018 and 2019.

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

Microvascular Decompression for Trigeminal Neuralgia: A Prospective, Multicenter Study.

BACKGROUND: Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. OBJECTIVE: To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. METHODS: We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. RESULTS: There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. CONCLUSION: In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients.

Less-invasive diagnosis of disseminated epithelioid glioblastoma harboring BRAF V600E mutation by cerebrospinal fluid analysis-A case report.

Spinal dissemination in epithelioid glioblastoma can be diagnosed by cerebrospinal fluid cytology and liquid biopsy to detect BRAF V600E mutation.

Reactive astrocytes contribute to epileptogenesis in patients with cavernous angioma.

OBJECTIVE: Patients with cavernous angioma (CA) often suffer from severe epilepsy, and surgical resection is often performed to attenuate these epileptic seizures. Several studies have suggested that surgical removal of the surrounding hemosiderin-pigmented tissues adjacent to CA achieves better seizure control than restricted lesionectomy. Pathological examination of the resected foci reveals not only hemosiderin pigmentation but also various degrees of inflammatory change, such as hemosiderin-laden macrophages, gliosis and fibrosis. However, there is some controversy regarding the epileptogenic potential of these regions due to the uncertain nature of the mechanisms contributing to these histopathological changes. METHODS: To investigate the correlations between neuron hyperexcitability and evident pathological changes, we performed ex vivo flavoprotein fluorescence imaging using surgically resected epileptogenic foci surrounding CA. The mirror surfaces of the tissues used for the physiological experiment were also subjected to morphological examination. RESULTS: Hemosiderin-laden macrophages and many gemistocytic astrocytes were observed in the area adjacent to CA, where horizontal spreading excitations were detected significantly more frequently. Outside these areas, we found fine granular iron deposits and only a few fibrillary astrocytes, and weakly propagating excitations were detected. Furthermore, areas of enhanced activation were more clearly correlated with the glial proliferation index than with iron deposition. CONCLUSION: These results suggest that the epileptogenesis in patients with CA may be based on a biological process, such as alteration of glial function, rather than direct chemical reactions involving iron deposition.