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Abstract Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.

ObjectiveNeurological deterioration after mild traumatic brain injury (TBI) has been recognized as a poor prognostic factor. Early detection of neurological deterioration would allow appropriate monitoring and timely therapeutic interventions to improve patient outcomes. In this study, we developed a machine learning model to predict the occurrence of neurological deterioration after mild TBI using information obtained on admission.MethodsThis was a retrospective cohort study of data from the Think FAST registry, a multicenter prospective observational study of elderly TBI patients in Japan. Patients with an admission Glasgow Coma Scale (GCS) score of 12 or below or who underwent surgical treatment immediately upon admission were excluded. Neurological deterioration was defined as a decrease of 2 or more points from a GCS score of 13 or more within 24 h of hospital admission. The model predictive accuracy was judged with the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC), and the Youden index was used to determine the cutoff value.ResultsA total of 421 of 721 patients registered in the Think FAST registry between December 2019 and May 2021 were included in our study, among whom 25 demonstrated neurological deterioration. Among several machine learning algorithms, eXtreme Gradient Boosting (XGBoost) demonstrated the highest predictive accuracy in cross-validation, with an AUROC of 0.81 (±0.07) and an AUPRC of 0.33 (±0.08). Through SHapley Additive exPlanations (SHAP) analysis, five important features (D-dimer, fibrinogen, acute subdural hematoma thickness, cerebral contusion size, and systolic blood pressure) were identified and used to construct a better performing model (cross-validation AUROC of 0.84 and AUPRC of 0.34; testing data AUROC of 0.77 and AUPRC of 0.19). At the cutoff value from the Youden index, the model showed a sensitivity, specificity, and positive predictive value of 60, 96, and 38%, respectively. When neurosurgeons attempted to predict neurological deterioration using the same testing data, their values were 20, 94, and 19%, respectively.ConclusionIn this study, our predictive model showed an acceptable performance in detecting neurological deterioration after mild TBI. Further validation through prospective studies is necessary to confirm these results.

Abstract Background Surgical intervention for cavernous sinus meningiomas remains challenging because of their anatomically complicated location. We report a case of a cavernous sinus meningioma that enlarged and caused hearing impairment due to internal auditory canal stenosis 7 years after gamma-knife radiosurgery. Case description A 38-year-old man with abducent nerve paralysis and dysesthesia on the left side of the face was diagnosed with a cavernous sinus meningioma with thickened petrous bone. After a year, the patient had mild left-sided hearing impairment, and gamma-knife radiosurgery was performed. At the age of 46, the left hearing impairment worsened, the tumor was slightly enlarged, and petrous bone thickening in the internal auditory meatus had progressed. We partially resected the tumor, which seemed to be viable, and removed the thickened petrosal bone and opened the internal auditory meatus. The tumor was pathologically diagnosed as meningothelial meningioma. The patient’s hearing impairment did not progress, and the residual tumor had not grown for four years. Conclusions Removal of the viable tumor that progressed after gamma-knife radiosurgery and opening of the internal auditory meatus were effective in stopping the worsening of hearing impairment and controlling the tumor.

Recently, thyroid autoantibodies were found to be associated with moyamoya disease (MMD). The ring finger protein 213 (RNF213) p.R4810K variant represents the most important susceptibility genotype of this disease, but its relationship with thyroid autoantibodies remains to be elucidated. Thus, in this study, we aimed to evaluate the clinical relevance of thyroid autoantibodies in each RNF213 genotype in patients with MMD. Included in this study were patients with MMD without a thyroid disease history and in euthyroid status; they were then classified into the mutated or nonmutated based on the RNF213 p.R4810K genotype and positive or negative based on thyroid autoantibody (thyroperoxidase and thyroglobulin) levels. Clinical data of each group were thereafter evaluated. Among the 209 patients, the mutated RNF213 p.R4810K variant and positive thyroid autoantibodies were detected in 155 and 41 patients, respectively. Positive thyroid autoantibodies were found to be more common in the nonmutated patients than in the mutated patients (31.5% vs. 15.5%; P = 0.011). In the mutated patients, as compared to autoantibody-negative patients, autoantibody-positive patients were determined to be more likely to have advanced disease with posterior cerebral artery involvement (54.2% vs. 29.0%; P = 0.017), white matter infarction (58.3% vs. 37.6%; P = 0.046), and a higher modified Rankin Scale at last visit (16.7% vs. 3.1%; P = 0.021). These results suggest that thyroid autoantibodies can act as an immunity inducer in patients with MMD lacking the susceptibility gene RNF213 p.R4810K variant. Moreover, the simultaneous presence of thyroid autoantibodies and the variant seems to aggravate the disease, which indicates synergy between thyroid autoantibodies and the variant.

This study aims to evaluate the academic activities of female neurosurgeons at all branch meetings of the Japan Neurosurgical Society and identify related issues they encountered. The programs of all seven branch meetings of the Japan Neurosurgical Society (Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku/Shikoku, and Kyushu) were used to determine the number of presentations and chairpersons by sex. The covered period was from January 2008 to December 2020, which was available for viewing during the survey. Of note, only the Kinki branch used data from January 2008 to December 2019. The Neurologia Medico-chirurgica (NMC), the journal of the Japan Neurosurgical Society, was also reviewed to identify publication achievements during the same period. In all seven branches, the percentage of presentations given by female physicians increased from 7.9% in 2008 to 9.6% in 2020 (p < 0.05). Conversely, the percentage of female chairpersons in all branch meetings did not change over time and it was significantly lower (1.1%) than that of female presenters (7.9%) for all branch meetings combined in over 13 years (p < 0.01). In the NMC, the number of articles with female physicians as first authors did not increase or decrease over the years. We conclude that efforts to smoothly promote female neurosurgeons as chairpersons and increase the number of female first authors are necessary to facilitate their academic activities.

Abstract We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

Abstract Purpose Epilepsy is a common complication of gliomas. The diagnosis of nonconvulsive status epilepticus (NCSE) is challenging because it causes impaired consciousness and mimics glioma progression. NCSE complication rate in the general brain tumor patient population is approximately 2%. However, there are no reports focusing on NCSE in glioma patient population. This study aimed to reveal the epidemiology and features of NCSE in glioma patients to enable appropriate diagnosis. Methods We enrolled 108 consecutive glioma patients (45 female, 63 male) who underwent their first surgery between April 2013 and May 2019 at our institution. We retrospectively investigated glioma patients diagnosed with tumor-related epilepsy (TRE) or NCSE to explore disease frequency of TRE/NCSE and patient background. NCSE treatment approaches and Karnofsky Performance Status Scale (KPS) changes following NCSE were surveyed. NCSE diagnosis was confirmed using the modified Salzburg Consensus Criteria (mSCC). Results Sixty-one out of 108 glioma patients experienced TRE (56%), and five (4.6%) were diagnosed with NCSE (2 female, 3 male; mean age, 57 years old; WHO grade II 1, grade III 2, grade IV 2). All NCSE cases were controlled by stage 2 status epilepticus treatment as recommended in the Clinical Practice Guidelines for Epilepsy by the Japan Epilepsy Society. The KPS score significantly decreased after NCSE. Conclusion Higher prevalence of NCSE in glioma patients was observed. The KPS score significantly decreased after NCSE. Actively taking electroencephalograms analyzed by mSCC may facilitate accurate NCSE diagnosis and improve the activities of daily living in glioma patients.

Cerebrospinal fluid (CSF) leakage is a major complication following endoscopic endonasal skull base surgery. Various skull base reconstruction methods are available, and the use of a vascularized nasoseptal flap (NSF) in skull base reconstruction has greatly contributed to a decrease in the CSF leak rate. A balloon catheter such as a sinus balloon or a Foley catheter is often used to support an NSF; however, in cases wherein nasal and/or paranasal structures supporting the balloon are lacking following the surgery, the NSF is not properly fixed and postoperative CSF leak may occur. Here we introduce a new technique of using multiple-balloon catheters to fix an NSF in such cases and provide the results of our analysis of the new technique's efficacy. Eight patients who underwent endonasal endoscopic surgery for the following cases were included: olfactory neuroblastoma (n = 6), recurrent craniofacial meningioma (n = 1), and recurrent chordoma (n = 1). After tumor resection, multilayered reconstruction with vascularized NSF was performed. Given that the Foley catheter was not stable to fix the flap in each case, we used an additional nasal catheter to support the Foley catheter. No complications such as postoperative CSF leak and necrosis of the vascularized flap were observed. These results suggest that the multiple-balloon catheter technique is a useful method for fixing the NSF to the skull base even when nasal cavity structures are missing due to surgical removal.

No previous study has histopathologically investigated whether a meningioma capsule presents with tumor cells. We investigated which types of tumor capsules (TCs) included tumor cells to help intraoperatively determine those TCs that do not need to be removed and have a low recurrence risk. We investigated 22 specimens of 14 newly diagnosed meningiomas from February 2011 to June 2021. The capsules were classified into three types: TC, capsule-like thickened arachnoid membrane (CAM), and extended membrane (EM). Capsule properties were scored by hardness (soft = 1, medium = 2, hard = 3) and transparency (high = 1, medium = 2, low = 3). The hardness, transparency, and score sums were compared between capsules with and without tumor invasion in the CAM and EM types. The mean follow-up duration was 40.6 months, and there was only one recurrence in a remote location from the residual capsule. Nine capsules were classified as TC, seven as CAM, and six as EM. The tumor cells invaded 88.9% of TCs, 42.9% of CAMs, and 50% of EMs. The hardness, transparency, and score sums for CAMs with tumor invasion were lower than those for CAMs without tumor invasion, although not significant (P = 0.114, P = 0.114, P = 0.057, respectively). A thickened TC or soft and highly transparent CAM indicated a high risk for tumor cell invasion; thus, such cases require a careful and long-term follow-up. Hard and low transparent residual CAMs may have had a low risk for tumor invasion; therefore, leaving such capsules that tightly adhere to the eloquent cortex can be theoretically justified to avoid damaging the brain surface.

Abstract Branch-like enhancement (BLE) on contrast-enhanced (CE) magnetic resonance imaging (MRI) was found to be effective in differentiating primary central nervous system lymphoma (PCNSL) from high-grade glioma (HGG) in the cerebellum. However, whether it can be applied to assessments of secondary central nervous system lymphoma (SCNSL), or other cerebellar lesions is unknown. Hence, we retrospectively reviewed cerebellar masses to investigate the use of BLE in differentiating cerebellar lymphoma (CL), both primary and secondary, from other lesions. Two reviewers qualitatively evaluated the presence and degree of BLE on CE-T1 weighted imaging (T1WI). If multiple views were available, we determined the view in which BLE was the most visible. Seventy-five patients with the following pathologies were identified:17 patients with CL, 30 patients with metastasis, 12 patients with hemangioblastoma, 9 patients with HGG, and 7 patients with others. Twelve patients presented with PCNSL and five with SCNSL. Of 17 patients with CL, 15 (88%) had BLE, whereas three (5%) out of 58 patients in the non-CL group showed BLE. In patients who underwent three-dimensional-CE-T1WI, BLE was the most visible on the sagittal image. In conclusion, BLE is a highly specific finding for CL and the sagittal image is important in evaluating this finding.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Purpose: Moyamoya disease (MMD) is a cerebrovascular disease associated with steno-occlusive changes in the arteries of the circle of Willis and with hemodynamic impairment. Previous studies have reported that parenchymal extracellular free water levels may be increased and the number of neurites may be decreased in patients with MMD. The aim of the present study was to investigate the postoperative changes in parenchymal free water and neurites and their relationship with cognitive improvement. Methods: Multi-shell diffusion MRI (neurite orientation dispersion and density imaging and free water imaging using a bi-tensor model) was performed in 15 hemispheres of 13 adult patients with MMD (11 female, mean age 37.9 years) who had undergone revascularization surgery as well as age- and sex-matched normal controls. Parameter maps of free water and free-water-eliminated neurites were created, and the regional parameter values were compared among controls, patients before surgery, and patients after surgery. Results: The anterior and middle cerebral artery territories of patients showed higher preoperative free water levels (P = 0.007) and lower postoperative free water levels (P = 0.001) than those of normal controls. The change in the dispersion of the white matter in the anterior cerebral artery territory correlated with cognitive improvement (r = -0.75; P = 0.004). Conclusion: Our study suggests that increased parenchymal free water levels decreased after surgery and that postoperative changes in neurite parameters are related to postoperative cognitive improvement in adult patients with MMD. Diffusion analytical methods separately calculating free water and neurites may be useful for unraveling the pathophysiology of chronic ischemia and the postoperative changes that occur after revascularization surgery in this disease population. [ABSTRACT FROM AUTHOR]

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.

Recently developed molecular targeted therapies such as bevacizumab (BEV; Avastin) therapy have therapeutic efficacy for glioblastoma. However, it is difficult to distinguish between a tumor response and nonenhancing tumor progression with conventional magnetic resonance imaging (MRI) after BEV administration. Here we present a recurrent glioblastoma case in which 11C-methionine positron emission tomography (MET-PET) provided useful information for detecting tumor recurrence after complete remission, as assessed by the Response Assessment in Neuro-Oncology criteria. A 47-year-old male with a left frontal lobe glioblastoma experienced recurrence 6 months postoperatively. We administered BEV concomitantly with temozolomide, subsequent to gamma knife surgery. Two months after starting BEV, complete remission was obtained. MET uptake on PET gradually decreased and had nearly disappeared 4 months after initiating BEV. No enhanced area was seen on MRI for 17 months after BEV initiation. Nevertheless, MET-PET revealed recurrence, visualized as nonenhancing tumor progression. MET-PET provides useful information for detecting glioblastoma recurrence, which lacks contrast enhancement on MRI after BEV therapy.

A warning prior to seizure onset can help improve the quality of life for epilepsy patients. The feasibility of a wearable system for predicting epileptic seizures using anomaly detection based on machine learning is evaluated. An original telemeter is developed for continuous measurement of R-R intervals derived from an electrocardiogram. A bespoke smartphone app calculates the indices of heart rate variability in real time from the R-R intervals, and the indices are monitored using multivariate statistical process control by the smartphone app. The proposed system was evaluated on seven epilepsy patients. The accuracy and reliability of the R-R interval measurement, which was examined in comparison with the reference electrocardiogram, showed sufficient performance for heart rate variability analysis. The results obtained using the proposed system were compared with those obtained using the existing video and electroencephalogram assessments; it was noted that the proposed method has a sensitivity of 85.7% in detecting heart rate variability change prior to seizures. The false positive rate of 0.62 times/h was not significantly different from the healthy controls. The prediction performance and practical advantages of portability and real-time operation are demonstrated in this study.

ObjectiveThe goal of this study was to demonstrate the feasibility of intraoperative photodynamic diagnosis (PDD) of malignant glioma using the fluorescence from talaporfin sodium (TS), which is used simultaneously for photodynamic therapy (PDT).MethodsPatients with suspected primary malignant glioma who were eligible for surgical removal of the tumor and PDT with TS were enrolled in this prospective study. Tissue samples were obtained from the contrast-enhanced (CE) region and from the surrounding non-contrast-enhanced (NCE) marginal tissue at the boundary between the tumor and normal tissue. The excised samples were set into a fluorescence measurement system, which consisted of a semiconductor laser with a 400-nm wavelength for excitation, and a compact spectrometer for detection, which were applied and received through a custom-made probe consisting of coaxial optical fibers. The fluorescence spectrum was obtained, and peak intensity was calculated. Tumor cellularity was histopathologically analyzed and semi-quantitatively classified into four (0–3) categories.Results86 samples from 17 surgical cases were available for fluorescence measurement and analysis. The fluorescence from TS had a single peak at 664 nm that was easily distinguished from the 400-nm excitation light. Samples from the CE regions showed higher fluorescence intensity than those from the NCE regions (P