Mitochondrial Calcium Uniporter (MCU) is Involved in an Ischemic Postconditioning Effect Against Ischemic Reperfusion Brain Injury in Mice.

The phenomenon of ischemic postconditioning (PostC) is known to be neuroprotective against ischemic reperfusion (I/R) injury. One of the key processes in PostC is the opening of the mitochondrial ATP-dependent potassium (mito-KATP) channel and depolarization of the mitochondrial membrane, triggering the release of calcium ions from mitochondria through low-conductance opening of the mitochondrial permeability transition pore. Mitochondrial calcium uniporter (MCU) is known as a highly sensitive transporter for the uptake of Ca2+ present on the inner mitochondrial membrane. The MCU has attracted attention as a new target for treatment in diseases, such as neurodegenerative diseases, cancer, and ischemic stroke. We considered that the MCU may be involved in PostC and trigger its mechanisms. This research used the whole-cell patch-clamp technique on hippocampal CA1 pyramidal cells from C57BL mice and measured changes in spontaneous excitatory post-synaptic currents (sEPSCs), intracellular Ca2+ concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents under inhibition of MCU by ruthenium red 265 (Ru265) in PostC. Inhibition of MCU increased the occurrence of sEPSCs (p = 0.014), NMDAR currents (p < 0.001), intracellular Ca2+ concentration (p < 0.001), and dead cells (p < 0.001) significantly after reperfusion, reflecting removal of the neuroprotective effects in PostC. Moreover, mitochondrial depolarization in PostC with Ru265 was weakened, compared to PostC (p = 0.004). These results suggest that MCU affects mitochondrial depolarization in PostC to suppress NMDAR over-activation and prevent elevation of intracellular Ca2+ concentrations against I/R injury.

Thin Calcification Predicts Lipid Component in Carotid Plaque-Relationship Between Lipid Distribution and Thin Calcification.

BACKGROUND: Accurately evaluating plaque characteristics is essential because lesions with lipid-rich plaque put patients at risk of thromboembolic complications from carotid artery stenting. Near-infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near-infrared absorption pattern but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography and the lipid core distribution derived from NIRS. METHODS: Participants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52-89 years) who underwent carotid artery stenting in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative computed tomography angiography and analyzed the relationship with maximum lipid core burden index (max-LCBI) from NIRS. RESULTS: Strong negative linear correlations were observed between the thickness of calcification and max-LCBI at Area (any segment in a target lesion) (r = -0.795, P < 0.001), max-LCBI at minimal lumen area (r = -0.795, P < 0.001) and lipid core burden index (LCBI) at lesion (rate of LCBI in entire plaque lesion) (r = -0.788, P < 0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at area (r = -0.429, P = 0.01), max-LCBI at minimal lumen area (r = -0.373, P = 0.027), and LCBI at lesion (r = -0.443, P = 0.008). CONCLUSIONS: Thin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability.

Clinical Results and Hematologic Predictors of Linear Accelerator-Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis in Patients Aged 75 Years or Older: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between January 2011 and November 2021, 101 consecutive EPs with BM were treated by LINAC-based SRS or fSRT using LINAC with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years. RESULTS: The tumors originated from the lungs (n = 90; 89.1%), colon (n = 2; 2.0%), and others (n = 9; 8.8%) in these EPs. The median pretreatment Karnofsky Performance Status was 80 (range, 40-100). The median follow-up time was 10 months (range, 0-76), as was the median survival. The 6-month, 1-year, and 2-year survival in the EP group was 58.3%, 43.2%, and 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years was 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs was 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (P < 0.001). In the EPs, the prognostic factors associated with prolonged survival in the Cox proportional hazards model were being female and a good pretreatment Karnofsky Performance Status. CONCLUSIONS: The findings of our study highlight the efficacy of LINAC-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. Neutrophil/lymphocyte ratio can be an important factor in treatment decisions for EPs with BMs.

Malignant Transformation and Leptomeningeal Melanomatosis in a Primary Meningeal Melanocytoma: A Case Report and Review of Literature.

Meningeal melanocytomas of the central nervous system, although typically benign, rarely undergo malignant transformations. A 46-year-old man presented with headache and nausea 4 years after gross total resection of a craniovertebral junction meningeal melanocytoma at another hospital. The initial clinical course was previously reported.1) Computed tomography revealed the presence of multiple intracranial mass lesions. Furthermore, magnetic resonance imaging showed multiple intracranial lesions and meningeal dissemination. A biopsy was performed for a circumflex lesion located in the right frontal lobe. Pathological examination showed anaplastic changes and a Ki-67 index of 33%. Based on the pleomorphic changes and high mitotic activity, the patient was diagnosed with primary cerebral malignant melanoma. The patient received four cycles of nivolumab (80 mg) and ipilimumab (165 mg), followed by whole-brain radiotherapy (37.5 Gy). However, the disease progressed after the third cycle. Genome analysis revealed GNAQ Q209P and SF3B1 R625C mutations, but no treatments related to these gene mutations were available. Despite the seven cycles of nivolumab therapy, the patient eventually passed away 9 months after surgery. This case was a rare example of malignant transformation and leptomeningeal melanomatosis in a meningeal melanocytoma. It highlights the importance of careful follow up after gross total resection. Identification of molecular alterations can lead to better detection of melanocytic melanomas with poor prognosis and high risk of recurrence and metastasis. It can also facilitate the development of novel therapeutic options for these patients.

Late In-Stent Thrombosis After Carotid Artery Stenting for Symptomatic Internal Carotid Artery Stenosis in a Patient With JAK2 V617F-Positive Essential Thrombocythemia: An Illustrative Case Report.

Essential thrombocythemia (ET) is a myeloproliferative disorder complicated by thrombosis in 13% of cases. The Janus kinase 2 (JAK2) V617Fmutation is present in 60% of ET cases, and it has recently been reported that the mutation itself is a significant contributor to ischemic stroke. Here, we present an illustrative case of late in-stent thrombosis following carotid artery stenting (CAS) in a patient with ET and the JAK2 V617F mutation presenting with symptomatic internal carotid artery (ICA) stenosis. An 80-year-old man with a history of JAK2 V617F-positive ET suffered from left upper motor weakness and numbness. Magnetic resonance imaging/magnetic resonance angiography revealed multiple acute cerebral infarctions scattered in the right frontal and parietal lobes and right ICA stenosis. Despite continued antiplatelet therapy, plaque size did not decrease. CAS was performed one month later; however, five months after the procedure, in-stent thrombus growth was observed, leading to severe stenosis despite administering antiplatelet or anticoagulant drugs. The thrombus was eventually resolved with increased doses of hydroxyurea and aspirin administration. In conclusion, controlling platelets and inflammation with hydroxyurea and aspirin may help improve the condition in case of rapid thrombosis due to the JAK2 V617F mutation, unlike other thromboses. This case highlights the importance of careful follow-up after CAS.

Effect of Sevoflurane Anesthesia on Intraoperative Spikes, High-Frequency Oscillations, and Phase-Amplitude Coupling in MRI-Normal Hippocampus.

INTRODUCTION: The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFOs), and phase-amplitude coupling using a modulation index in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography in identifying the epileptogenic hippocampus during sevoflurane administration. METHODS: Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography evaluation. Patients were assigned to the Ictal (+) or Ictal (-) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. Intraoperative electrocorticography was performed under 0.5 and 1.5 minimum alveolar concentration of sevoflurane. The rates of spikes, ripples, fast ripples (FRs), ripples on spikes, FRs on spikes, and MI HFO(3-4 Hz) were evaluated. RESULTS: During the intraoperative electrocorticography procedure, sevoflurane administration was found to significantly increase the rate of spikes, ripples on spikes, fast ripples on spikes, and MI HFO(3-4 Hz) in the Ictal (+) group (P < 0.01). By contrast, the Ictal (-) group exhibited a paradoxical increase in the rate of ripples and fast ripple (P < 0.05). CONCLUSIONS: Our findings indicate that the administration of sevoflurane during intraoperative electrocorticography in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, ripples on spikes, fast ripples on spikes, and MI (HFO 3-4)) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and fast ripple in the nonepileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the nonepileptogenic hippocampus.

Therapeutic Anti-KIR Antibody of 1-7F9 Attenuates the Antitumor Effects of Expanded and Activated Human Primary Natural Killer Cells on In Vitro Glioblastoma-like Cells and Orthotopic Tumors Derived Therefrom.

Glioblastoma (GBM) is the leading malignant intracranial tumor, where prognosis for which has remained extremely poor for two decades. Immunotherapy has recently drawn attention as a cancer treatment, including for GBM. Natural killer (NK) cells are immune cells that attack cancer cells directly and produce antitumor immunity-related cytokines. The adoptive transfer of expanded and activated NK cells is expected to be a promising GBM immunotherapy. We previously established an efficient expansion method that produced highly purified, activated primary human NK cells, which we designated genuine induced NK cells (GiNKs). The GiNKs demonstrated antitumor effects in vitro and in vivo, which were less affected by blockade of the inhibitory checkpoint receptor programmed death 1 (PD-1). In the present study, we assessed the antitumor effects of GiNKs, both alone and combined with an antibody targeting killer Ig-like receptor 2DLs (KIR2DL1 and DL2/3, both inhibitory checkpoint receptors of NK cells) in vitro and in vivo with U87MG GBM-like cells and the T98G GBM cell line. Impedance-based real-time cell growth assays and apoptosis detection assays revealed that the GiNKs exhibited growth inhibitory effects on U87MG and T98G cells by inducing apoptosis. KIR2DL1 blockade attenuated the growth inhibition of the cell lines in vitro. The intracranial administration of GiNKs prolonged the overall survival of the U87MG-derived orthotopic xenograft brain tumor model. The KIR2DL1 blockade did not enhance the antitumor effects; rather, it attenuated it in the same manner as in the in vitro experiment. GiNK immunotherapy directly administered to the brain could be a promising immunotherapeutic alternative for patients with GBM. Furthermore, KIR2DL1 blockade appeared to require caution when used concomitantly with GiNKs.

CIS deletion by CRISPR/Cas9 enhances human primary natural killer cell functions against allogeneic glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor and has "immunologically cold" features. Changing GBM to an "immunologically hot" tumor requires a strong trigger that induces initial immune responses in GBM. Allogeneic natural killer cells (NKCs) have gained considerable attention as promising immunotherapeutic tools against cancer, where gene-edited NKCs would result in effective anti-cancer treatment. The present study focused on the immune checkpoint molecule cytokine-inducible SH2-containing protein (CISH, or CIS) as a critical negative regulator in NKCs. METHODS: The GBM tumor environment featured with immunological aspect was analyzed with Cancer immunogram and GlioVis. We generated human primary CIS-deleted NKCs (NK dCIS) using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) with single guide RNA targeting genome sites on CIS coding exons. The genome-edited NKCs underwent microarray with differential expression analysis and gene set enrichment analysis (GSEA). The anti-GBM activity of the genome-edited NKCs was evaluated by apoptosis induction effects against allogeneic GBM cells and spheroids. We further detected in vivo antitumor effects using xenograft brain tumor mice. RESULTS: We successfully induced human CIS-deleted NKCs (NK dCIS) by combining our specific human NKC expansion method available for clinical application and genome editing technology. CIS gene-specific guide RNA/Cas9 protein complex suppressed CIS expression in the expanded NKCs with high expansion efficacy. Comprehensive gene expression analysis demonstrated increased expression of 265 genes and decreased expression of 86 genes in the NK dCIS. Gene set enrichment analysis revealed that the enriched genes were involved in NKC effector functions. Functional analysis revealed that the NK dCIS had increased interferon (IFN)ɤ and tumor necrosis factor (TNF) production. CIS deletion enhanced NKC-mediated apoptosis induction against allogeneic GBM cells and spheroids. Intracranial administration of the allogeneic NKCs prolonged the overall survival of xenograft brain tumor mice. Furthermore, the NK dCIS extended the overall survival of the mice. CONCLUSION: The findings demonstrated the successful induction of human primary NK dCIS with CRISPR/Cas9 with efficient expansion. CIS deletion enhanced the NKC-mediated anti-tumor effects in allogeneic GBM and could be a promising immunotherapeutic alternative for patients with GBM.

Case report: Giant pituitary neuroendocrine tumor presented along with acute visual loss due to pituitary apoplexy after receiving COVID-19 vaccination.

Objective: A case of giant pituitary neuroendocrine tumor presented along with acute visual loss due to pituitary apoplexy after receiving a COVID-19 vaccination is reported. Case presentation: A 45-year-old man was referred for a giant pituitary tumor with bitemporal hemianopsia. A surgical procedure was planned and then delayed due to the COVID-19 outbreak in Japan, with a Pfizer/BioNTech vaccine administered while awaiting surgery. Three days after the second COVID-19 vaccination the patient noted a progressively worsening headache that caused pituitary apoplexy and then a decrease in vision. Emergency surgery was thus performed. Conclusion: Pituitary apoplexy is a rare and life-threatening complication that may occur after undergoing a COVID-19 vaccination.

Three-dimensional reconstruction imaging by C-arm computed tomography accurately visualizes in-stent neointimal formation in patients with stent-assisted coil embolization.

Background: Stent apposition to the vessel wall and in-stent neointimal formation after stent-assisted coil embolization for intracranial aneurysm are important factors associated with postoperative thromboembolic complications. No assessment methods have been established to depict 3-dimensional (3D) all-round in-stent neointimal formation. Objective: To demonstrate the superiority of Dyna-3D imaging assessment as a modality for all-round ISNF in comparison with conventional two-dimensional digital subtraction angiography (2D-DSA). Methods: Consecutive patients who underwent braided stent-assisted coil embolization for unruptured aneurysm between November 2016 and September 2021 were enrolled. Radiological assessments for stent apposition to the parent vessel after stent deployment and in-stent neointimal formation after 3 months were obtained. Dyna-3D was reconstructed by overlapping a plain image showing stent struts with a rotational DSA image showing the vessel lumen. Reconstructed Dyna-3D images can be rotated to any angle on the screen to evaluate to stent apposition around the vessel and in-stent neointimal formation in 3D, for comparison with 2D-DSA evaluations. Results: Among the 73 patients enrolled, 70 patients (96%) showed complete stent wall apposition on Dyna-3D. Higher intra-rater agreement was confirmed on assessment of in-stent neointimal formation with Dyna-3D (Cohen's κ = 0.811) than with conventional 2D-DSA (Cohen's κ = 0.517). in-stent neointimal formation could not be confirmed on conventional imaging in 9 cases (16%) and on Dyna-3D in 2 cases (3%). The number of in-stent neointimal formations rated as stent wire completely outside the endothelial line was significantly higher with Dyna-3D than with 2D-DSA (p = 0.0001). Conclusion: All-round 3D evaluation by Dyna-3D imaging appears useful for confirming in-stent neointimal formation after braided stent deployment in patients after stent-assisted coil embolization.

Local administration of shikonin improved the overall survival in orthotopic murine glioblastoma models with temozolomide resistance.

BACKGROUND: Glioblastoma is a type of intracranial malignancy. Shikonin, a Chinese traditional medicine, has been shown to have anti-tumor efficacy toward human glioblastoma cells in vitro. However, shikonin cannot easily cross the blood-brain barrier. To address this issue, we evaluated the anti-tumor effects of direct intracranial infusion of shikonin in in vivo orthotopic syngeneic murine glioblastoma models using C57BL/6 mice. MATERIALS AND METHODS: The cytotoxic effects of shikonin against murine glioblastoma cells, SB28 and CT-2A, were reported resistance to temozolomide, were evaluated using an allophycocyanin-conjugated annexin V and propidium iodide assay with flow cytometry. Impedance-based real-time cell analysis (RTCA) was used to analyze the inhibitory effects of shikonin on growth and proliferation. To evaluate the anti-tumor activity of shikonin in vivo, we used orthotopic syngeneic murine glioblastoma models with SB28 and CT-2A cells. RESULTS: In flow cytometry-based cytotoxic assays, shikonin induced apoptosis. RTCA indicated that shikonin decreased the cell index of murine glioblastoma cells, SB28 and CT-2A, in a dose-dependent manner (p < 0.0001 for both cell lines), while temozolomide did not (p = 0.91 and 0.82, respectively). In murine glioblastoma models, SB28 and CT-2A, direct intracranial infusion of shikonin, as a local chemotherapy, improved the overall survival of mice in a dose-dependent manner compared with control groups (p < 0.0001 and p = 0.02, respectively). While temozolomide did not (p = 0.48 and 0.52, respectively). CONCLUSIONS: The direct intracranial infusion of shikonin has potential as a local therapy for patients with glioblastoma.

Parenchymal Blood Volume Changes Immediately After Endovascular Thrombectomy Predict Futile Recanalization in Patients with Emergent Large Vessel Occlusion.

OBJECTIVE: More than one third of acute ischemic stroke (AIS) patients do not recover to functional independence even if endovascular thrombectomy (EVT) is performed rapidly and successfully. This suggests that angiographic recanalization does not necessarily lead to tissue reperfusion. Although recognition of reperfusion status after EVT is pivotal for optimal postoperative management, reperfusion imaging assessment immediately after recanalization has not been fully investigated. The present study aimed to evaluate whether reperfusion status based on parenchymal blood volume (PBV) assessment after angiographic recanalization influences infarct growth and functional outcome in patients who have undergone EVT following AIS. METHODS: Seventy-nine patients who underwent successful EVT for AIS were retrospectively analyzed. PBV maps were acquired from flat-panel detector computed tomography (CT) perfusion images before and after angiographic recanalization. Reperfusion status was assessed from PBV values and their changes in regions of interest and collateral score. RESULTS: Post-EVT PBV ratio and ΔPBV ratio, as PBV parameters indicating the degree of reperfusion, were significantly lower in the unfavorable prognosis group (P < 0.01 each). Poor reperfusion on PBV mapping was associated with significantly longer puncture-to-recanalization time, lower collateral score, and higher frequency of infarct growth. Logistic regression analysis identified low collateral score and low ΔPBV ratio as associated with poor prognosis after EVT (odds ratios, 2.48, 3.72; 95% confidence intervals, 1.06-5.81, 1.20-11.53; P = 0.04, 0.02, respectively). CONCLUSIONS: Poor reperfusion in severely hypoperfused territories on PBV mapping immediately after recanalization may predict infarct growth and unfavorable prognosis in patients who undergo EVT following AIS.

Extensive Roles and Technical Advances of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.

Chronic subdural hematoma (CSDH) is a common pathology that typically affects the elderly in Japan, an aging society. Burr-hole irrigation is the standard treatment, but middle meningeal artery (MMA) embolization is a minimally invasive alternative. MMA embolization for CSDH has frequently been reported in recent years, and many technical innovations to improve clinical outcomes have been described. Embolic materials reaching more distally are found to avoid recurrences after MMA embolization. As a result, various studies have described the superiority of embolizing the anterior and posterior branches of the MMA, the advantages of embolic materials reaching beyond the midline, and a high degree of distal penetration using a "sugar rush technique" in which 5% soluble glucose is injected through an intermediate catheter during MMA embolization. Radiographically, reports have described the importance of a "bright falx" sign obtained by infiltrating embolic material beyond the midline and post-embolization enhancement of the dura, capsular membrane, septations, and subdural hematoma fluid as indicators of the spread of embolic materials. This review provides an overview of the current status and future challenges in MMA embolization for CSDH, focusing on technical aspects to improve clinical outcomes.

An efficient feeder-free and chemically-defined expansion strategy for highly purified natural killer cells derived from human cord blood.

Introduction: Natural killer cells (NKCs) are immune cells that can attack cancer cells through the direct recognition of ligands without prior sensitization. Cord blood-derived NKCs (CBNKCs) represent a promising tool for allogenic NKC-based cancer immunotherapy. Efficient NKC expansion and decreased T cell inclusion are crucial for the success of allogeneic NKC-based immunotherapy without inducing graft-versus-host reactions. We previously established an efficient ex vivo expansion system consisting of highly purified-NKCs derived from human peripheral blood. Herein, we evaluated the performance of the NKC expansion system using CB and characterized the expanded populations. Methods: Frozen CB mononuclear cells (CBMCs), with T cells removed, were cultured with recombinant human interleukin (rhIL)-18 and rhIL-2 under conditions where anti-NKp46 and anti-CD16 antibodies were immobilized. Following 7, 14, and 21 days of expansion, the purity, fold-expansion rates of NKCs, and the expression levels of NK activating and inhibitory receptors were assessed. The ability of these NKCs to inhibit the growth of T98G, a glioblastoma (GBM) cell line sensitive to NK activity, was also examined. Results: All expanded T cell-depleted CBMCs were included in over 80%, 98%, and 99% of CD3-CD56+ NKCs at 7, 14, and 21 days of expansion, respectively. The NK activating receptors LFA-1, NKG2D, DNAM-1, NKp30, NKp44, NKp46, FcγRIII and NK inhibitory receptors TIM-3, TIGIT, TACTILE, NKG2A were expressed on the expanded-CBNKCs. Two out of three of the expanded-CBNKCs weakly expressed PD-1, yet gradually expressed PD-1 according to expansion period. One of the three expanded CBNKCs almost lacked PD-1 expression during the expansion period. LAG-3 expression was variable among donors, and no consistent changes were identified during the expansion period. All of the expanded CBNKCs elicited distinct cytotoxicity-mediated growth inhibition on T98G cells. The level of cytotoxicity was gradually decreased based on the prolonged expansion period. Conclusions: Our established feeder-free expansion system yielded large scale highly purified and cytotoxic NKCs derived from human CB. The system provides a stable supply of clinical grade off-the-shelf NKCs and may be feasible for allogeneic NKC-based immunotherapy for cancers, including GBM.

Neuronal Loss in the Bilateral Medial Frontal Lobe Revealed by 123I-iomazenil Single-photon Emission Computed Tomography in Patients with Moyamoya Disease: The First Report from Cognitive Dysfunction Survey of Japanese Patients with Moyamoya Disease (COSMO-Japan Study).

Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had <85 in each index were 27.8%-33.3% in the WAIS-III and 16.7%-47.2% in the Wechsler Memory Scale-Revised. The group analysis of iomazenil SPECT demonstrated a decreased accumulation in the bilateral medial frontal areas in comparison with the normal control, whereas there were no specific characteristics on conventional imaging in the cohort. Iomazenil SPECT is a possible universal diagnostic method for the extraction of patients with cognitive impairment in MMD.

[External Ocular Movement(EOM)Monitoring].

The intraoperative monitoring of extraocular motor nerves allows optimal skull base surgery by protecting the cranial nerves. For detecting cranial nerve function, several methods, such as external ocular movement monitoring with an electrooculogram(EOG), electromyogram(EMG), and piezoelectric device sensors, are present. While being valuable and useful, several problems related to its accurate monitoring persist when scanning from inside the tumor, which might be far from the cranial nerves. Here, we described three modalities, free-run EOG monitoring, trigger EMG monitoring, and piezoelectric sensor monitoring for monitoring external ocular movement. Improvement of these processes is essential for appropriately conducting these procedures during neurosurgical operations without harming the extraocular motor nerves.

Facet Articular Irregularity Is the Most Relevant Risk Factor for Rapidly Progressive Degenerative Cervical Myelopathy.

OBJECTIVE: Facet articular irregularity is associated with rapidly progressive degenerative cervical myelopathy (DCM). However, its significance compared with other known risk factors remains unknown. Therefore, this retrospective study aimed to clarify the potential impact of facet articular irregularity as a risk factor for rapid DCM progression. METHODS: This study included 141 consecutive patients with DCM who underwent surgical treatment at our institution. Clinical variables and radiological findings related to DCM progression were collected. Imaging findings were analyzed at the segmental level of myelopathy in each case. The patients were divided into 2 groups based on the presence or absence of rapid DCM progression, and independent risk factors were determined using logistic regression analyses. RESULTS: Overall, 131 patients with a mean age of 63.9 ± 12.6 years were analyzed; 27 patients (20.6%) were classified into the rapid DCM progression group. The mean age was significantly higher in the rapid progression group than in the slow progression group (72.4 ± 9.6 vs. 61.7 ± 12.4, p < 0.001). According to univariate analysis, facet articular irregularity, dynamic segmental translation (≥ 1.6 mm), upper cervical spine involvement above C4-5, history of cerebrovascular events, preceding minor trauma, local lordotic angle (≥ 4.5°), diabetes, hypertension, ligamentum flavum hypertrophy, and age were independent risk factors. Additionally, multivariate analysis showed that facet articular irregularity was the highest risk factor for rapid DCM progression (p = 0.001). CONCLUSION: Facet articular irregularity is the most clinically significant finding among the known risk factors in patients with rapid DCM progression.

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study.

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.