Basal temporal language area revisited in Japanese language with a language function density map.

We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.

Performance status improvement and advances in systemic treatment after brain metastases resection: a retrospective single-center cohort study of non-small cell lung cancer patients.

BACKGROUND: Brain metastasis (BrM) is prevalent among patients with NSCLC, and surgical resection of BrM constitutes a promising treatment strategy for local management and histopathological diagnosis, although it is offered for a select group of patients. Limited information exists concerning the improvement in performance status (PS) following BrM resection or the outcomes stratified by subsequent systemic therapy. METHODS: We conducted a retrospective single-center cohort study including NSCLC patients with surgically resected BrM and focused on the improvement in PS and subsequent therapy after BrM resection. RESULTS: 71 patients were included, and the median overall survival was 18.3 months (95% confidence interval [95% CI]: 8.7, not reached). Patients with NSCLC who underwent surgical resection of BrM showed significant improvement in PS (18% and 39% showed ECOG PS of 0-1, before and after BrM resection, respectively [p = 0.006]), and patients with PS improvement were younger than those with PS unimprovement (median, 62 years versus 66 years; p = 0.041). Regarding subsequent systemic therapy after BrM resection, 21 patients (30%) received cytotoxic chemotherapy, 14 patients (20%) received tyrosine kinase inhibitors (TKIs), 3 patients (4%) received immune checkpoint inhibitors (ICIs), and 21 patients (30%) received no subsequent therapy. The survival outcomes of patients stratified by subsequent systemic treatments suggested the tendency that those who received TKI or ICI showed better survival outcomes, although a small number of patients hindered statistical comparisons. CONCLUSIONS: We describe the outcomes of patients with NSCLC who underwent surgical resection of BrM, revealing that younger patients were more likely to anticipate improvement in PS, and patients who received TKI or ICI after BrM resection tended to exhibit a more preferable prognosis.

Vessel wall MRI in moyamoya disease: arterial wall enhancement varies depending on age, arteries, and disease progression.

OBJECTIVE: To investigate the relationship of followings for patients with moyamoya disease (MMD): arterial wall enhancement on vessel wall MRI (VW-MRI), cross-sectional area (CSA), time-of-flight MR angiography (MRA), age, locations from intracranial internal carotid artery (ICA) to proximal middle cerebral artery (MCA), disease progression, and transient ischemic attack (TIA). METHODS: Patients who underwent VW-MRI between October 2018 and December 2020 were enrolled in this retrospective study. We measured arterial wall enhancement (enhancement ratio, ER) and CSA at five sections of ICA and MCA. Also, we scored MRA findings. Multiple linear regression (MLR) analysis was performed to explore the associations between ER, age, MRA score, CSA, history of TIA, and surgical revascularization. RESULTS: We investigated 102 sides of 51 patients with MMD (35 women, 16 men, mean age 31 years ± 18 [standard deviation]). ER for MRA score 2 (signal discontinuity) was higher than ER for other scores in sections D (end of ICA) and E (proximal MCA) on MLR analysis. ER in section E was significantly higher in patients for MRA score 2 with TIA history than without. ER significantly increased as CSA increased in section E, which suggests ER becomes less in decreased CSA due to negative remodeling. CONCLUSION: Arterial wall enhancement in MMD varies by age, location, and disease progression. Arterial wall enhancement may be stronger in the progressive stage of MMD. Arterial wall enhancement increases with history of TIA at proximal MCA, which may indicate the progression of the disease. CLINICAL RELEVANCE STATEMENT: Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression, and arterial wall enhancement may be used as an imaging biomarker of moyamoya disease. KEY POINTS: It has not been clarified what arterial wall enhancement in moyamoya disease represents. Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression. Arterial wall enhancement in moyamoya disease increases as the disease progresses.

Posterior cerebral artery involvement in unilateral moyamoya disease is exclusively ipsilateral and influenced by RNF213 mutation gene dose: The SUPRA Japan study: PCA involvement in unilateral moyamoya.

OBJECTIVES: The characteristics and clinical implications of posterior cerebral artery (PCA) involvement in unilateral moyamoya disease (U-MMD), such as laterality, frequency of the RNF213 p.R4810K mutation, and clinical outcomes, have not been well studied. POPULATION AND METHODS: We analyzed a cohort of 93 patients with U-MMD who participated in the SUPRA Japan study. Clinical characteristics and radiological examinations were collected from medical records. The presence of the p.R4810K mutation was determined using a TaqMan assay. The clinical outcome was assessed using the modified Rankin Scale (mRS). Univariate and multivariate logistic regression analyses were performed to assess the associations. RESULTS: Among the patients with U-MMD, PCA involvement was observed in 60.0 % (3/5) of patients with homozygous mutation, 11.3 % (7/62) of those with heterozygous mutation, and 3.8 % (1/26) of those with wild type, showing a significant linear trend (p < 0.001 for trend). PCA involvement was observed exclusively on the same side as the affected anterior circulation. Dyslipidemia and cerebral infarction at initial onset were independently associated with mRS ≥1. Hypertension was associated with mRS ≥1 and it was also linked to infarction at initial onset, suggesting a potential confounding effect. Although PCA involvement showed a trend for higher mRS, it was not statistically significant. CONCLUSIONS: Our findings indicate a gene dose effect of the p.R4810K mutation on PCA involvement, with the homozygous state showing the most significant effect. Both genetic and modifiable factors such as dyslipidemia may influence the progression of U-MMD.

Common and distinct risk profiles of asymptomatic extra- and intracranial atherosclerosis in the Nagahama cohort.

BACKGROUND AND PURPOSE: Atherosclerotic burden increases the risk of both extracranial internal carotid artery stenosis (ICS) and intracranial large artery disease (ICAD). However, the differences in risk profiles have not been thoroughly investigated. METHODS: Participants were recruited from the Nagahama study cohort in Japan. Individuals over 60 years old who underwent 1.5-T head and neck magnetic resonance angiography (MRA) between July 2013 and February 2017 were included. ICAD was defined as WASID ≥ 50 %, and ICS was defined as NSCET ≥ 30 %. The prevalence and association of risk factors, including proatherogenic and proinflammatory factors, and the p.R4810K variant in the RNF213 gene, were investigated. Multivariable logistic regression analyses were performed. RESULTS: A total of 3089 individuals participated in the study, with a mean age of 68.1 ± 5.3 years, and 36.0 % were males. Among them, 52 (1.7 %) had ICS, 119 (3.8 %) had ICAD, and 15 (0.49 %) had both conditions. Alopecia areata was an independent predictor for both ICS (Odds ratio [OR] 3.5; 95 % CI 1.3-8.3) and ICAD (OR 2.1; 95 % CI 1.0-3.9). Diabetes (OR 3.7; 95 % CI 2.0-7.0) and older age (OR 2.4; 95 % CI 1.2-4.5) were associated only with ICS, while the RNF213 variant was associated with only ICAD (OR 5.7; 95 % CI 1.6-16.0). ICS and ICAD were also independently associated with each other. CONCLUSIONS: In this MRA-based large scale study, alopecia areata, known as a systemic inflammatory disease, was shown to be a common risk factor for ICS and ICAD. While conventional atherosclerotic factors were associated with ICS, non-atherosclerotic factors appear to contribute to ICAD in Japan.

Automatic Ischemic Core Estimation Based on Noncontrast-Enhanced Computed Tomography.

BACKGROUND: Evaluating the extent of ischemic change is an important step in deciding whether to use thrombolysis or mechanical thrombectomy, but the current standard method, Alberta Stroke Program Early CT Score, is semiquantitative and has low consistency among raters. We aim to create and test a fully automated machine learning-based ischemic core segmentation model using only noncontrast-enhanced computed tomography images. METHODS: In this multicenter retrospective study, patients with anterior circulation acute ischemic stroke who received both computed tomography (CT) and magnetic resonance imaging before thrombolysis or recanalization treatment between 2013 and 2019 were included. On CT, the ischemic core was manually delineated using the diffusion-weighted image and apparent diffusion coefficient maps. A deep learning-based ischemic core segmentation model (DL model) was developed using data from 3 institutions (n=272), and the model performance was validated using data from 3 institutions (n=106 Results: The median time ).between CT and magnetic resonance imaging in the validation cohort was 18 min. The DL model calculated ischemic core volume was significantly correlated with the reference standard (intraclass correlation coefficient, 0.90, P<0.01). Both the early time window (≤4.5 hours from onset; intraclass correlation coefficient, 0.90, P<0.01) and the late time window (>4.5 hours from onset; intraclass correlation coefficient, 0.93, P<0.01) had significant correlations. The median difference in ivolume between the model and the reference standard was 4.7 mL (interquartile range, 0.8-12.4 mL). The DL model performed well in distinguishing large ischemic cores (>70 mL), with a sensitivity of 84.2%, specificity of 97.7%, and area under the curve of 0.91. CONCLUSIONS: The deep learning-based ischemic core segmentation model, which was based on noncontrast-enhanced CT, demonstrated high accuracy in assessing ischemic core volume in patients with anterior circulation acute ischemic stroke.

Bioresorbable Poly (L-Lactic Acid) Flow Diverter Versus Cobalt-Chromium Flow Diverter: In Vitro and In Vivo Analysis.

BACKGROUND: Permanent metallic flow diverter (FD) implantation for treatment of intracranial aneurysms requires antiplatelet therapy for an unclear duration and restricts postprocedural endovascular access. Bioresorbable FDs are being developed as a solution to these issues, but the biological reactions and phenomena induced by bioresorbable FDs have not been compared with those of metallic FDs. METHODS: We have developed a bioresorbable poly (L-lactic acid) FD (PLLA-FD) and compared it with an FD composed of cobalt-chromium and platinum-tungsten (CoCr-FD). FD mechanical performance and in vitro degradation of the PLLA-FD were evaluated. For in vivo testing in a rabbit aneurysm model, FDs were implanted at the aneurysm site and the abdominal aorta in the PLLA-FD group (n=21) and CoCr-FD group (n=15). Aneurysm occlusion rate, branch patency, and thrombus formation within the FD were evaluated at 3, 6, and 12 months. Local inflammation and neointima structure were also evaluated. RESULTS: Mean strut, porosity, and pore density for the PLLA-FD were 41.7 µm, 60%, and 20 pores per mm2, respectively. The proportion of aneurysms exhibiting a neck remnant or complete occlusion did not significantly differ between the groups; however, the complete occlusion rate was significantly higher in the PLLA-FD group (48% versus 13%; P=0.0399). Branch occlusion and thrombus formation within the FD were not observed in either group. In the PLLA-FD group, CD68 immunoreactivity was significantly higher, but neointimal thickness decreased over time and did not significantly differ from that of the CoCr-FD at 12 months. Collagen fibers significantly predominated over elastic fibers in the neointima in the PLLA-FD group. The opposite was observed in the CoCr-FD group. CONCLUSIONS: The PLLA-FD was as effective as the CoCr-FD in this study and is feasible for aneurysm treatment. No morphological or pathological problems were observed with PLLA-FD over a 1-year period.

Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).

BACKGROUND: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. METHODS: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0-1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. RESULTS: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24-20.6]; P=0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P=0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62-30.7]; P=0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. CONCLUSIONS: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: UMIN000006640.

Seizure control by adding on other anti-seizure medication on seizure during levetiracetam administration in patients with glioma-related epilepsy.

BACKGROUND: Epilepsy is a major symptom in patients with glioma. Levetiracetam (LEV) is recognized as a first-line treatment for glioma-related epilepsy. Increasing the LEV dose is allowed into patients with seizure occurrence against its initial dose. However, the therapeutic efficacy of increasing the LEV dose in response to seizure occurrence remains unclear. METHODS: We retrospectively analyzed 236 glioma patients who were treated with antiseizure medications (ASMs) internally at our institute between September 2010 and December 2017. Of these, the analysis focused on 156 patients treated with LEV who had a clear history of administration. RESULTS: Seizure occurrences were observed in 21 of 75 patients (26.7%) who received LEV as first-line therapy and in 33 of 81 patients (40.7%) who received LEV as non-first-line treatment. The seizure control rate for seizure occurrence with LEV as first-line treatment was significantly higher in patients treated with addition of other ASMs (72.7%) than in those treated with increasing dose of LEV (20.0%) (p = 0.016). The seizure control rate for seizure occurrence with LEV as non-first-line treatment did not differ significantly between patients with addition of other ASMs (58.3%) and those treated with increasing dose of LEV (47.6%) (p = 0.554). CONCLUSIONS: Adding other ASMs was more effective than increasing the LEV dose for seizure control in patients treated with LEV as first-line treatment, but they demonstrated comparable efficacy in patients treated with LEV as non-first-line treatment.

Continuous and Early Progression of Carotid Intima-Media Thickness after Radiotherapy for Head and Neck Cancer: 5-Year Prospective Observational Study.

INTRODUCTION: Radiation-induced carotid artery stenosis (RI-CS) is known as one of long-term side effects of radiotherapy for head and neck cancer (HNC). However, the clinical time course after irradiation has been poorly understood. We aimed to investigate the natural history of radiation-induced carotid atherosclerosis, comparing the patients who received radiotherapy for HNC with the patients who were treated without radiotherapy. METHODS: The patients who received treatment of HNC at Department of Otolaryngology, Head and Neck Surgery of Kyoto University Hospital, from November 2012 to July 2015 were enrolled. The patients were assigned into the RT group and the control group, depending on whether radiotherapy was planned or not. Annual carotid ultrasound was performed from the enrollment to 5 years. The increase of mean intima-media thickness (IMT) at common carotid artery from the enrollment (Δmean IMT) was evaluated. RESULTS: Fifty-six patients in the RT group and 25 patients in the control group were enrolled. From 5-year follow-up data, the significant higher increase of Δmean IMT was consistently observed in the RT group than in the control group after 2 years. The RT group presented a 7.8-fold increase of mean IMT compared to the control group (0.060 mm per year in the RT group and 0.008 mm per year in the control group). Cumulative incidence curves obtained from the analysis of all vessels revealed that the RT group presented higher incidence of Δmean IMT ≥0.25 mm than the control group (p < 0.01). In the RT group, the patients with mean IMT ≥1.0 mm at enrollment exhibited significantly higher incidence of Δmean IMT ≥0.25 mm than the patients with mean IMT <1.0 mm (p < 0.01). DISCUSSION: Radiotherapy for HNC induces continuous carotid mean IMT progression. The irradiated carotid arteries with mean IMT ≥1.0 mm before radiotherapy presented earlier IMT progression than those with mean IMT <1.0 mm.

Enhanced phase-amplitude coupling of human electrocorticography selectively in the posterior cortical region during rapid eye movement sleep.

The spatiotemporal dynamics of interaction between slow (delta or infraslow) waves and fast (gamma) activities during wakefulness and sleep are yet to be elucidated in human electrocorticography (ECoG). We evaluated phase-amplitude coupling (PAC), which reflects neuronal coding in information processing, using ECoG in 11 patients with intractable focal epilepsy. PAC was observed between slow waves of 0.5-0.6 Hz and gamma activities, not only during light sleep and slow-wave sleep (SWS) but even during wakefulness and rapid eye movement (REM) sleep. While PAC was high over a large region during SWS, it was stronger in the posterior cortical region around the temporoparietal junction than in the frontal cortical region during REM sleep. PAC tended to be higher in the posterior cortical region than in the frontal cortical region even during wakefulness. Our findings suggest that the posterior cortical region has a functional role in REM sleep and may contribute to the maintenance of the dreaming experience.

Influence of Tumor Characteristics on Visual Field Outcomes After Pituitary Adenoma Surgery.

BACKGROUND: There were few reports about the influence of tumor characteristics on the postoperative visual field outcomes after transsphenoidal surgery for pituitary adenoma. The purpose of this study was to explore the tumor characteristics that influenced perioperative visual field changes. METHODS: Patients who underwent transsphenoidal surgery under a diagnosis of pituitary adenoma at the Kyoto University Hospital between April 2012 and December 2018 were retrospectively enrolled. Correlations among circumpapillary retinal nerve fiber layer thickness, preoperative and postoperative mean deviation (MD) of visual field, MD change after the surgery, and maximum tumor diameter were evaluated by measuring Pearson correlation coefficient. We evaluated the influences on postoperative MD using a generalized estimating equation for univariate and multivariate regression analyses. We also compared the characteristics of cystic and solid tumors. RESULTS: Thirty-two eyes of 18 patients were included in this study (9 male and 9 female patients). Postoperative MD positively correlated with maximum tumor diameter only in multivariate regression {ß = 0.22 (95% confidence interval [CI], 0.004-0.43), P = 0.046}, although maximum tumor diameter negatively correlated with postoperative MD in univariate regression (ß = -0.16 [95% CI, -0.58 to 0.26], P = 0.46). In the investigation of perioperative MD changes, eyes with cystic tumors showed significantly better improvement those with solid tumors (8.93 ± 7.85 vs 0.18 ± 6.56 dB, P = 0.007). CONCLUSIONS: Cystic and solid tumors show different characteristics of visual loss and visual field defects. The MD in eyes with cystic tumors improved significantly more than that in eyes with solid tumors.

"Transcallosal" periventricular anastomosis in moyamoya disease: the fourth periventricular anastomosis and a potential predictor of hemorrhage.

OBJECTIVES: Choroidal anastomosis is a risk factor for hemorrhage in moyamoya disease. One variant of choroidal anastomosis, "transcallosal anastomosis," originates from the medial posterior choroidal artery, and penetrates the corpus callosum to reconstruct the pericallosal artery. We aimed to investigate the prevalence and the bleeding rate of transcallosal anastomosis using sliding thin-slab maximum intensity projection reformatted from magnetic resonance angiography (MRA). MATERIALS AND METHODS: This study included 222 patients. We defined transcallosal anastomosis grades (0-2) and the stenosis of the anterior (ACA, 0-2), middle (MCA, 1-3), and posterior cerebral artery (PCA, 0-2) by MRA scores, independently by two coauthors. RESULTS: Grade-2 transcallosal anastomosis was detected in 21 patients (9.5 %). There were no correlations of the incidence of transcallosal anastomosis with previous bypass surgery (P = 0.23). Multivariate analysis revealed a significantly higher incidence in hemorrhagic onset and younger age (odds ratio [OR] 3.77, and 0.97). Transcallosal anastomosis had statistically significant correlation with ACA and PCA scores (P = 0.01 and 0.03), but not with MCA scores (P = 0.1). In multivariate analysis, ACA scores 1 and 2 were significantly higher (OR, 15.44 and 11.17), and PCA score 1 was also higher (OR, 3.07), but PCA score 2 was not. Interrater agreement for judgment of transcallosal anastomosis grade was strong (κ = 0.89). Two patients with Grade-2 transcallosal anastomosis had late hemorrhage in the corpus callosum (bleeding rate: 2.5 % per year). CONCLUSIONS: Transcallosal anastomosis may be associated with both advanced ACA and moderate PCA stenosis, and cause hemorrhage at the corpus callosum.

Distinct connectivity patterns in human medial parietal cortices: Evidence from standardized connectivity map using cortico-cortical evoked potential.

The medial parietal cortices are components of the default mode network (DMN), which are active in the resting state. The medial parietal cortices include the precuneus and the dorsal posterior cingulate cortex (dPCC). Few studies have mentioned differences in the connectivity in the medial parietal cortices, and these differences have not yet been precisely elucidated. Electrophysiological connectivity is essential for understanding cortical function or functional differences. Since little is known about electrophysiological connections from the medial parietal cortices in humans, we evaluated distinct connectivity patterns in the medial parietal cortices by constructing a standardized connectivity map using cortico-cortical evoked potential (CCEP). This study included nine patients with partial epilepsy or a brain tumor who underwent chronic intracranial electrode placement covering the medial parietal cortices. Single-pulse electrical stimuli were delivered to the medial parietal cortices (38 pairs of electrodes). Responses were standardized using the z-score of the baseline activity, and a response density map was constructed in the Montreal Neurological Institutes (MNI) space. The precuneus tended to connect with the inferior parietal lobule (IPL), the occipital cortex, superior parietal lobule (SPL), and the dorsal premotor area (PMd) (the four most active regions, in descending order), while the dPCC tended to connect to the middle cingulate cortex, SPL, precuneus, and IPL. The connectivity pattern differs significantly between the precuneus and dPCC stimulation (p<0.05). Regarding each part of the medial parietal cortices, the distributions of parts of CCEP responses resembled those of the functional connectivity database. Based on how the dPCC was connected to the medial frontal area, SPL, and IPL, its connectivity pattern could not be explained by DMN alone, but suggested a mixture of DMN and the frontoparietal cognitive network. These findings improve our understanding of the connectivity profile within the medial parietal cortices. The electrophysiological connectivity is the basis of propagation of electrical activities in patients with epilepsy. In addition, it helps us to better understand the epileptic network arising from the medial parietal cortices.

Chlorambucil-conjugated PI-polyamides (Chb-M'), a transcription inhibitor of RUNX family, has an anti-tumor activity against SHH-type medulloblastoma with p53 mutation.

Malignancy of medulloblastoma depends on its molecular classification. Sonic Hedgehog (SHH)-type medulloblastoma with p53 mutation was recognized as one of the most aggressive types of tumors. We developed a novel drug, chlorambucil-conjugated PI-polyamides (Chb-M'), which was designed to compete with the RUNX consensus DNA-binding site. Chb-M' specifically recognizes this consensus sequence and alkylates it to inhibit the RUNX transcriptional activity. In-silico analysis showed all the RUNX families were upregulated in the SHH-type medulloblastoma. Thus, we tested the anti-tumor effects of Chb-M' in vitro and in vivo using Daoy cell lines, which belong to SHH with p53 mutation. Chb-M' inhibited tumor growth of Daoy cells by inducing apoptosis. The same inhibitory effect was also observed by knocking down of RUNX1 or RUNX2, but not RUNX3. Apoptosis array analysis showed that Chb-M' treatment induced phosphorylation of p53 serine 15 residues. In a subcutaneous tumor model, intratumoral injection of Chb-M' induced tumor growth retardation. Chb-M' mediated inhibition of RUNX1 and RUNX2 can be a novel therapeutic strategy for SHH-type medulloblastoma with p53 mutation.

A novel SREBF1::NACC1 gene fusion in an unclassifiable intracranial tumour.

A 39-year-old man had an intracranial tumour without infiltration into the surrounding cerebral tissue. The tumour recurred seven times in 11 years but maintained a well-demarcated character. Histopathological examination of the 4th surgical specimens showed nests of tumour cells surrounding small blood vessels. The tumour cells harboured amphophilic cytoplasm and small round nuclei with fine chromatin, and perinuclear haloes and clear borders were frequently observed, which was unclassifiable histology. By the Deutsches Krebsforschungszentrum methylation classifier, the tumour was not classified into any of the methylation classes. mRNA sequencing identified a novel SREBF1::NACC1 gene fusion. This intracranial tumour could be a novel tumour entity with NACC1 rearrangement showing characteristic histological and diagnostic imaging findings.

Low-dose contrast-enhanced time-resolved angiography with stochastic trajectories with iterative reconstruction (IT-TWIST-MRA) in brain arteriovenous shunt.

OBJECTIVES: To assess the feasibility of low-dose contrast-enhanced four-dimensional (4D) time-resolved angiography with stochastic trajectories (TWIST) with iterative reconstruction (hereafter IT-TWIST-MRA) covering the whole brain and to compare IT-TWIST-MRA and TWIST-MRA with reference to digital subtraction angiography (DSA) in the evaluation of arteriovenous shunts (AVS). METHODS: Institutional Review Board approval was obtained for this observational study, and the requirement for written informed consent was waived. Twenty-nine patients with known AVS underwent TWIST-MRA on a 3-T MRI scanner, using low-dose injection (0.02 mmol/kg) of gadolinium-based contrast agent (GBCA) with each of Fourier and iterative reconstruction between September 2016 and October 2019. Visual evaluation of image quality was conducted for delineation of (a) the normal cerebral arteries and veins and (b) AVS feeder, shunt, and drainer vessels. Region-of-interest evaluation was conducted to evaluate bolus sharpness and baseline signal fluctuation in the signal intensity of the cerebral vessels. We compared the detection of AVS between TWIST-MRA and IT-TWIST-MRA. The paired-samples Wilcoxon test was used to test the differences between TWIST-MRA and IT-TWIST-MRA. RESULTS: Visualization scores for normal vasculature and AVS angioarchitecture were significantly better for images produced using IT-TWIST-MRA than those using TWIST-MRA. Peak signal and the enhancement slope of the time-intensity curve were significantly higher for IT-TWIST-MRA than for TWIST-MRA, except for the superior sagittal sinus (SSS). Baseline intensity fluctuation was significantly lower for IT-TWIST-MRA than for TWIST, except for SSS. CONCLUSIONS: IT-TWIST-MRA yields clinically feasible 4D MR-DSA images and delineates AVS even with low-dose GBCA. KEY POINTS: • Iterative reconstruction significantly improves the image quality of TWIST-MRA covering the whole brain. • The short temporal footprint and denoising effect of iterative reconstruction enhances the quality of 4D-MRA. • IT-TWIST-MRA yields clinically feasible images of AVS with low-dose GBCA.

Intra-cerebellar schwannoma with various degenerative changes: a case report and a systematic review.

BACKGROUND: Intra-cranial schwannomas account for less than 8% of brain tumors, among which more than 80% arise from the vestibular nerve. Intra-cerebellar schwannomas are extremely rare. Several cases have been previously reported but without remarkable degenerative changes on histology. CASE PRESENTATION: A 61-year-old man presented with worsening disorientation, and an imaging study revealed a cystic lesion (6.5 cm in the largest diameter) in the left hemisphere of the cerebellum accompanied by a mural nodule (2.5 cm) located just inside the skull with enhancement and focal calcification, in addition to hydrocephalus. The lesion was more than 5 mm from the left acoustic nerve. The patient underwent gross total resection. Pathological examination revealed remarkable degenerative changes with various morphological features. Tumor cells were pleomorphic with rich cytoplasm containing numerous eosinophilic granules. Blood vessels and extracellular matrix showed remarkable hyalinization. Immunohistochemical staining revealed that the tumor cells were positive for S-100 protein and negative for Olig2. The tumor was diagnosed as a schwannoma with marked degenerative changes. CONCLUSIONS: The present case is discussed with reference to a systematic review of previous reports of intra-cerebellar schwannoma. Intra-cerebellar schwannoma should be included in the differential diagnosis of cystic lesions with heterogeneous histopathological morphology in the cerebellum.

Detecting immunoglobulin G4-related intracranial arteriopathy with magnetic resonance vessel wall imaging: a preliminary experience in two cases.

BACKGROUND: Detecting immunoglobulin G4 (IgG4)-related intracranial arteriopathy, a rare neurovascular complication of IgG4-related disease, is challenging. While magnetic resonance (MR) vessel wall imaging (VWI) can visualize various neurovascular pathologies, its application to this arteriopathy has not been reported as of this writing. CASE PRESENTATION: A 74-year-old male and a 65-year-old female manifested multiple cranial nerve palsy and neck pain, respectively. Both cases exhibited multiorgan masses with markedly elevated serum IgG4 levels and were clinically diagnosed with IgG4-related disease. Three-dimensional T1-weighted black blood VWI with and without contrast agent identified intracranial vascular lesions characterized as nearly-circumferential mural thickening with homogeneous contrast enhancement in the internal carotid and vertebral arteries; some of the lesions had been unrecognized with screening MR angiography due to expansive remodeling. The former patient underwent corticosteroid therapy, and VWI after treatment revealed decreased mural thickening and enhancement. CONCLUSION: Further studies to elucidate characteristic findings of VWI might contribute to early detection of this treatable pathology.

A multicenter prospective registry of Borden type I dural arteriovenous fistula: results of a 3-year follow-up study.

PURPOSE: Although intracranial dural arteriovenous fistula (DAVF) without retrograde leptomeningeal venous drainage (Borden type I) is reported to have a benign nature, no study has prospectively determined its clinical course. Here, we report a 3-year prospective observational study of Borden type I DAVF. METHODS: From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion. RESULTS: During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02). CONCLUSION: In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction.