Publisher：Arthritis Research and Therapy  

Background: Controlling disease activity and improving physical function would be more difficult in patients with late-onset rheumatoid arthritis (LORA) who have chronic lung disease (CLD) at baseline. Our aim was to evaluate 5-year outcomes of following a treat-to-target (T2T) strategy targeting low disease activity (LDA) in LORA with CLD. Methods: Data from 197 methotrexate (MTX)-naïve LORA patients (mean age 74.4 years) from a prospective, monocentric registry were analyzed. Patients were treated with MTX if they had one or more poor prognostic features. If they had interstitial lung disease (ILD), tacrolimus could be administered instead of MTX at the discretion of the attending physician. If patients exhibited no response according to the European League Against Rheumatism criteria at week 12 or had not achieved LDA by week 24, biological disease-modifying antirheumatic drugs (bDMARDs) were started targeting LDA. The primary outcomes were the 5-year simplified disease activity index (SDAI) remission and Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5 by non-responder imputation analysis. Secondary outcomes were serious adverse events (SAEs). Results: Of the 197 LORA patients, 47 had CLD at baseline. The proportion of patients using MTX at baseline was significantly lower in those with than without CLD. Tacrolimus was initiated in 25.5% of the CLD group. The proportion of patients on bDMARDs was higher in those with CLD at year 5. Achievement of SDAI remission at year 5 was 29.8% in patients with CLD and 44.0% in those without CLD (p = 0.555). Achievement of HAQ-DI ≤ 0.5 at year 5 was 36.2% and 45.3% in patients with and without CLD, respectively (p = 0.939). Non-adherence to T2T due to comorbidities or adverse events was observed in 34.0% and 18.7% of the patients with and without CLD, respectively (p = 0.027). Infections requiring hospitalization, deterioration of extra-articular manifestations and fractures were more frequently reported as SAEs in patients with CLD, and multivariable analysis showed that patients with CLD had a higher risk of developing these SAEs (adjusted hazard ratio:2.53, 95% CI 1.60–4.00, p < 0.001). Conclusion: For LORA patients with CLD, the T2T strategy is effective, but comorbidities and SAEs make the implementation of the T2T more difficult.

DOI： 10.1186/s13075-025-03491-1

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OBJECTIVE: Carotid artery atherosclerotic plaques undergo various pathological changes during disease progression, and their characterization relies on MRI, CT, and ultrasound imaging. The diagnosis of calcified lesions using only MRI is challenging because of irregular low-signal areas across all sequences. Conventionally, a diagnosis is made by combining multiple modalities such as contrast-enhanced CT (CECT) and carotid ultrasonography. Field echo resembling CT using restricted echo-spacing (FRACTURE) is a new MRI sequence with enhanced bone contrast that uses a 3D gradient echo pulse sequence. The aim of this study was to evaluate the ability of FRACTURE to detect carotid plaque calcification by comparing its images with pathological findings from carotid endarterectomy (CEA). The study also compared the accuracy of conventional CECT and MRI plaque imaging with that of FRACTURE and assessed its accuracy in stenosis rate evaluation using fusion imaging with MR angiography (MRA). METHODS: This retrospective analysis included 21 consecutive patients (average age 74 years, 16 males) who underwent FRACTURE, CECT, and MRA (including time-of-flight and black-blood techniques) as preoperative examinations for CEA. Pathological specimens from extracted plaques were analyzed, and the calcified areas were measured and statistically compared across imaging modalities. Digital subtraction angiography (DSA) was used as the reference standard for stenosis rate evaluation. RESULTS: The sensitivity and specificity of FRACTURE in detecting calcified lesions in pathological specimens were comparable with those of CECT (sensitivity 91.7% vs 95.8%, specificity 96.6% vs 93.1%) and superior to those of MRA (sensitivity 75.0%, specificity 93.1%). Furthermore, for lesions < 2 mm2, significant differences in the measured calcified areas were observed between pathological specimens and both CECT and MRA, whereas no significant difference was found with FRACTURE, suggesting its superiority for small lesions. In stenosis rate assessment, no significant differences were found among FRACTURE/MRA, CECT, and DSA in overall stenosis measurements. However, in cases in which calcified lesions directly faced the vascular lumen, CECT tended to overestimate stenosis because of beam-hardening artifacts, while FRACTURE/MRA showed a higher agreement with DSA, indicating greater accuracy. CONCLUSIONS: FRACTURE is a useful MRI sequence with higher sensitivity and specificity than those of MRA and accuracy comparable with that of CECT for calcified lesion detection. Additionally, it may provide superior detection of small, calcified lesions and more accurate stenosis assessment in cases with calcified plaques.

DOI： 10.3171/2025.4.JNS241803

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Language：Japanese   Publisher：株式会社医学書院  

DOI： 10.11477/mf.030126030530061225

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Publisher：Journal of Geophysical Research Planets  

The successful sample return from asteroid (162173) Ryugu by Hayabusa2 has contributed to our understanding of the solar system evolution. Over the course of the initial sample analysis, various measurements were conducted, such as mineralogical observation, chemical analysis, and mechanical property measurement. These pieces of information allow us to give constraints on the essential conditions of Ryugu's formation and evolution processes (e.g., thermal environment, aqueous alteration, formation of a rubble-pile body), leading to a clearer view of the early solar system. Here, we report the initial results of the elastic properties of Ryugu particles (e.g., P- and S-wave velocities and Young's modulus) obtained via ultrasonic pulse transmission measurement. Our measurement results showed 2.15 (Formula presented.) 0.05 km/s and 1.25 (Formula presented.) 0.05 km/s for the compressional and shear waves, respectively. Regarding Young's modulus, we obtained 7.1 (Formula presented.) 0.6 GPa, consistent with the previously measured value via a nanoindentation test. Compared with the elastic properties of other carbonaceous chondrites (Tagish Lake, Tarda, Ivuna, and Murchison meteorites), we found that Ryugu had distinctly lower rigidity than Ivuna—the most similar material to Ryugu with respect to chemical and mineralogical features. Instead, Tagish Lake showed the closest elastic properties to Ryugu samples. The affinities in chemical and mineralogical features indicate the genetic relationship between Ryugu and Ivuna. On the other hand, the difference in elastic properties might indicate their formation and evolution processes proceeded differently (e.g., formation depth, degree of alteration).

DOI： 10.1029/2025JE008944

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OBJECTIVE: Optimal lesioning is essential for successful MR-guided focused ultrasound (MRgFUS) thalamotomies targeting the ventral intermediate nucleus (Vim) for tremors. This study aimed to evaluate the relationships between postoperative lesions that overlapped with the Vim and surrounding structures segmented automatically and the treatment outcomes. METHODS: This study included 48 patients who underwent MRgFUS thalamotomy targeting the Vim for essential tremors. The Clinical Rating Scale for Tremor (CRST) score was examined preoperatively as well as 1 week, 3 months, and 12 months postoperatively. Adverse effects were also assessed 1 month postoperatively. Using automatic segmentation software and fiber tracking software, the authors retrospectively segmented the Vim and surrounding structures, including the internal capsule (IC), ventrocaudal nucleus (Vc), zona incerta (ZI), and dentato-rubro-thalamic tract (DRTT), using preoperative images. Additionally, they manually delineated the coagulated lesions using images taken immediately after MRgFUS thalamotomy. The relationships between the volume and location of lesions overlapping with these structures, CRST improvement rates, and the presence of adverse effects were examined. RESULTS: The mean thalamotomy volume was 0.076 ± 0.042 cm3 (median 0.085 cm3). The median improvement in the CRST score in the affected upper limb at 12 months postoperatively was 68.8%. Although no correlation was observed between lesion volume and CRST improvement at 1 week postoperatively, a positive correlation was observed between lesion volume and CRST improvement at 3 and 12 months. At 12 months, the authors observed a moderate correlation between the volume of the lesions overlapping with the Vim and improvement in the CRST score. A slightly stronger correlation was observed between the percentage of the lesion volume and the Vim. No correlation was found between lesion volume and improvements in the IC, Vc, ZI, DRTT, or CRST score. However, the authors found that both total lesion volume and the volume of lesion within the IC were significantly associated with gait imbalance. CONCLUSIONS: The volume of the lesions immediately after MRgFUS thalamotomy was correlated with improvements in tremor during long-term follow-up. Furthermore, larger lesions within the automatically segmented Vim were associated with better outcomes. This finding supports the usefulness of the method. In contrast, gait imbalance is more likely to occur with larger lesion volumes and may be associated with IC damage.

DOI： 10.3171/2025.3.JNS241995

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PURPOSE: This study aimed to evaluate the efficacy and safety of intravenous perampanel (IV-PER) in routine clinical practice. METHODS: Patients who received IV-PER at Nagoya University Hospital or one of the 21 affiliated institutions between June 2024 and March 2025 were included. Indications for IV-PER included treatment for epileptic seizures, particularly acute symptomatic seizures, and prophylactic use before or after surgery. The primary endpoint was the seizure suppression rate within 7 days of treatment initiation, and the secondary endpoint was the incidence of adverse events (AEs). Clinical data were recorded daily, and blood tests were conducted within 2 weeks of administration. Enrolled patients were categorized into three groups based on the underlying etiology: cerebrovascular disease (CD), brain tumor (BT), and traumatic brain injury (TBI). Treatment efficacy and safety were assessed across these groups. RESULTS: Of the 237 patients, 74, 116, and 47 were classified into the CD, BT, and TBI groups, respectively. The overall seizure suppression rate within 7 days was 89.0 %. Rates by group were 87.8 % (CD), 96.6 % (BT), and 72.3 % (TBI). When stratified by indication, the rates were 99.3 % for prophylactic use, 69.4 % for focal seizures, and 74.4 % for generalized seizures. Regarding AEs, somnolence was reported in 3 patients and irritability in one. Laboratory abnormalities included anemia, elevated liver enzymes, elevated creatine kinase, and hyponatremia. A total of 71 patients experienced one of these. CONCLUSIONS: This large multicenter prospective registry demonstrates that IV-PER can be safely used for seizure management during the 7-day acute phase in real-world clinical settings.

DOI： 10.1016/j.seizure.2025.07.023

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Insular epilepsy after encephalitis is often drug-resistant and MRI-negative, limiting resection due to eloquent cortex involvement. We describe a case in which radiofrequency thermocoagulation (RFTC) was applied to disconnect the propagation network (PN) identified by stereoelectroencephalography. In a woman with focal to bilateral tonic-clonic seizures, the epileptogenic network (EN) was in the left insula and temporal operculum, and the PN spread to the perirolandic area. PN-targeted RFTC, guided by tractography, preserved the EN. At 18 months, seizures decreased by 95.6% with preserved function. Selective PN disconnection may be an option when EN resection is limited.

DOI： 10.1007/s00701-025-06652-y

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Publisher：Surgery United States  

Background: The complex procedures of ultralow anterior resection and intersphincteric resection require precise manipulation at the deepest pelvis, where the advantages of robotic surgery in particular could be leveraged, despite limited reports of such procedures. We aimed to evaluate the short-term outcomes of robot-assisted ultralow anterior resection and robot-assisted intersphincteric resection at 31 institutions in Japan. Methods: This multicenter retrospective study was performed by a total of 31 institutions with the largest number of robot-assisted rectal cancer surgeries based on the survey conducted by the Japan Society for Endoscopic Surgery. We retrospectively analyzed a cohort of patients who had undergone robot-assisted ultralow anterior resection or robot-assisted intersphincteric resection for rectal cancer between January 2020 and December 2021. Results: A total of 1,250 patients were enrolled in this study, 40 were excluded, and finally 1,210 (886 robot-assisted ultralow anterior resection and 324 robot-assisted intersphincteric resection) were included in the analysis. The median operating time was 364 minutes (interquartile range, 277–479 minutes) and blood loss 17 mL (interquartile range, 0–50 mL), and conversion to laparotomy occurred in only 1 patient in robot-assisted ultralow anterior resection. A total of 109 (9.0%) patients had postoperative complications of Clavien-Dindo grade III or higher grade within 30 days after operation, with anastomotic leakage being the most common (3.4%), followed by ileus (1.3%), and mortality within 30 days after operation was a rare event, with only 1 death. Conclusion: The ROSEMARY study demonstrated the feasibility and safety of robot-assisted ultralow anterior resection and robot-assisted intersphincteric resection for low rectal cancer.

DOI： 10.1016/j.surg.2025.109414

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Publisher：International Journal of Thermophysics  

The regolith on the shallow lunar surface was formed through micrometeorite impacts over time. Investigating the thermophysical properties of the regolith provides valuable insights into the thermal history of the Moon as recorded by these surface materials and offers critical data for future lunar exploration. In several studies, the thermophysical properties of the regolith layer and rocks have been examined, but few studies have focused on individual regolith particles because of their limited size and irregular shapes, which are generally believed to have formed following intense activities, such as micrometeorite impacts. In this study, the local thermal diffusivity of individual particles from Apollo 17 sample 70161 was measured via the lock-in thermography (LIT) technique, and subsequently, the distribution of in-plane thermal diffusivity was provided. The particle was confirmed to be a typical breccia using X-ray tomography (XCT) assisted by X-ray diffraction (XRD). The local average thermal diffusivity values ranged from 2.9 m²·s⁻¹ to 3.6 × 10⁻⁷ m²·s⁻¹ and showed an anisotropic distribution. In addition, we calculated the representative thermal conductivity and thermal inertia of the particles via the specific heat and density, which are 0.738 ± 0.088 W.m⁻¹·K⁻¹ (300 K) and (1.231 ± 0.086) × 10³J·m⁻²·s^−1/2·K⁻¹ (300 K), respectively. The specific heat was also obtained by differential scanning calorimetry (DSC) of fine samples from 70161. The density was calculated from the measured weight, and the volume was determined via XCT. On the one hand, our experimental results are in good agreement with previously reported measurements of Apollo lunar rocks (in terms of average values). On the other hand, our measurements also reveal an anisotropic distribution of thermal diffusivity within localized regions of the particle. This anisotropy is attributed to factors such as cracks and defects, which locally weaken heat conduction.

DOI： 10.1007/s10765-025-03563-z

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DOI： 10.1039/d5se00370a

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Language：English   Publisher：Journal of Dermatological Science  

Background: The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research. Objective: To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies. Methods: Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model. Results: The ML-based predictions identified drugs for Parkinson's disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor-α levels. Conclusion: This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases.

DOI： 10.1016/j.jdermsci.2025.04.012

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The 2018 Movement Disorder Society classification introduced essential tremor plus (ETP) as a category for patients with essential tremor (ET) accompanied by additional features of uncertain significance. While earlier studies have characterized clinical features of ETP, the factors that characterize the phenotypic expression of ETP remain unclear. We prospectively evaluated 70 consecutive patients with ET or ETP. Clinical and neurophysiological assessments included tremor severity (Clinical Rating Scale for Tremor, CRST), cognitive functions (Addenbrooke's Cognitive Examination Revised, ACE-R), and accelerometric analysis. Statistical analyses examined between-group differences and factors influencing tremor characteristics. The prevalence of ETP (61%) exceeded that of ET. Among ETP patients, 77% exhibited two or more additional motor and/or cognitive features. Compared to ET patients, ETP patients demonstrated significantly higher tremor severity, lower tremor frequency, older age at assessment and onset, and poorer cognitive function, despite comparable disease duration. The accelerometric analysis revealed similar tremor patterns in both groups with quantitative differences in tremor amplitude and frequency. The propensity score matching and multiple regression analyses suggested that tremor severity and frequency are more influenced by age than by disease duration or diagnostic classification of ET/ETP. ACE-R score and the presence of resting tremor were also significant predictors of tremor severity. ETP represents a heterogeneous population with diverse neurological features, and age is likely a key determinant of severity and phenotypic expression. Comprehensive analysis is needed to identify other factors that may determine phenotype and treatment responsiveness.

DOI： 10.1007/s00702-025-02941-z

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Language：Japanese   Publisher：Movement Disorder Society of Japan (MDSJ)  

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INTRODUCTION: Epilepsy is a prevalent chronic neurological disorder, with approximately one-third of patients experiencing intractable epilepsy, often necessitating surgical intervention. Deep brain stimulation (DBS) of the thalamus has been introduced as a palliative surgical option for seizure control; however, its precise mechanisms remain largely unclear. The thalamus plays a crucial role in coordinating neural networks, both in normal brain function and the propagation of epileptic activity. This study aims to investigate the involvement of the thalamus in epilepsy networks using stereoelectroencephalography (SEEG) to monitor thalamic activity during epileptic seizures in patients with drug-resistant epilepsy. METHODS AND ANALYSIS: This single-arm, non-randomised, prospective, exploratory study will be conducted at Nagoya University Hospital, involving 10 patients undergoing SEEG for presurgical evaluation of drug-resistant epilepsy. Participants must be 18 years or older, have normal cognitive function and provide informed consent. Between 7 and 14 SEEG electrodes, including 2 in the bilateral thalamus, will be implanted in key thalamic nuclei (anterior, dorsomedial, centromedian and pulvinar) using a robotic system. The primary outcome focuses on electroencephalographic findings from the thalamus, emphasising waveform and frequency changes around seizures. Secondary outcomes include postoperative seizure frequency, changes in cognitive function and neuroimaging results. SEEG data will be recorded continuously for 1-2 weeks to capture both ictal and interictal activity. Data analysis will employ t-tests to compare ictal and interictal periods, with p values <0.05 deemed statistically significant. This study seeks to characterise thalamic spectral and connectivity changes during seizures, identify the thalamic subnuclei involved in seizure propagation and explore their association with seizure outcomes, potentially contributing to future DBS candidate selection. By advancing our understanding of the thalamus in epilepsy networks, this research aims to improve DBS interventions, ultimately enhancing seizure control in patients with intractable epilepsy. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of the Nagoya University Graduate School of Medicine (Approval No. 2024-0044). All participants will provide written informed consent prior to enrolment. The results of this study will be disseminated through publication in a peer-reviewed journal and presentations at academic conferences. TRIAL REGISTRATION NUMBER: jRCT1042240024.

DOI： 10.1136/bmjopen-2024-097957

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Language：Japanese   Publisher：一般社団法人 日本臨床神経生理学会  

<p>定位的頭蓋内脳波 (SEEG) は脳深部のてんかんネットワークを解析し, 発作起始領域 (SOZ) からてんかん原性ネットワーク (EN) の推定を可能にする。本総説ではSEEGの特性や発作時脳波のアルゴリズム解析手法を紹介し, てんかんネットワークの理論に基づいたSEEGの理解を深めることを目的とする。SEEGは広範なネットワークの評価に優れるが, 空間解像度が低いため, 硬膜下電極と異なりSOZの正確な同定には制限がある。従来の目視評価によるSOZの同定は, 観察者の恣意性やバイアスの影響を受けやすく, 高周波数帯域の神経活動を十分に考慮できないという課題がある。これに対し, Epileptogenicity indexなどのアルゴリズム解析が導入されENの特性をより客観的に捉える手法が発展しつつある。さらに, 機械学習を用いたアルゴリズム解析の発展も期待されており, 今後の技術革新によりENのより精緻な推定が可能になれば, てんかん外科手術の適応や治療戦略に新たな展望をもたらすことが期待される。</p>

DOI： 10.11422/jscn.53.191

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Language：English   Publishing type：Research paper (scientific journal)  

Background/Objectives: Lasmiditan is a newly developed drug for the acute treatment of migraine attacks, but factors associated with its efficacy remain unclear. This study aimed to confirm the efficacy of lasmiditan started at 50 mg under various dosing conditions and identify factors associated with its efficacy. Methods: There are four reasons for prescribing lasmiditan: as an add-on to triptan, if triptan is ineffective, if triptan produces side effects, and when triptan is contraindicated. Lasmiditan was administered at a dose of 50 mg. The efficacy of lasmiditan was defined as the disappearance of headache or a 50% or greater reduction in headache intensity within two hours after dosing. This study included 108 patients with migraines who took lasmiditan. Results: The results for efficacy and the side effects of lasmiditan were as follows: effective without side effects (22), effective with mild side effects (32), ineffective (14), and severe side effects (40). The efficacy rate of lasmiditan 50 mg was 50.0% (54/108). The following factors were found to be associated with lasmiditan's efficacy: sex, migraine classification, calcium channel blockers, and anti-calcitonin gene-related peptide monoclonal antibody (CGRP-mAb) treatment. The overall incidence of side effects was 66.7%, and the dropout rate was 37.0%. Somnolence was more prevalent in the effective group, and other side effects were more prevalent in patients who dropped out due to the side effects of lasmiditan. Conclusions: Lasmiditan is likely to be effective in males with severe migraine classification and receiving CGRP-mAb treatment. If mild somnolence is a side effect, the drug can be continued and may be effective.

DOI： 10.3390/neurolint17050062

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OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is associated with disruptions in the temporo-amygdala-orbitofrontal (TAO) network, a key component of the limbic system. We aimed to investigate TAO network alterations in patients with MTLE using magnetoencephalography (MEG), which overcomes susceptibility artifacts that limit functional MRI analysis of the orbitofrontal cortex. METHODS: Nine seizure-free patients with MTLE post-temporal lobectomy and nine age- and sex-matched healthy controls were recruited. Preoperative MEG data were collected and segmented into frequency bands ranging from delta to ripple to assess functional connectivity (FC) between the bilateral hippocampi and TAO network. RESULTS: Patients with MTLE exhibited increased FC between the affected hippocampus and amygdala across all frequency bands. Additionally, FC between the affected hippocampus and the medial prefrontal cortex (mPFC), orbitofrontal gyrus (OFG), and amygdala was elevated in the gamma and ripple bands compared with healthy controls. Conversely, FC between the healthy hippocampus and mPFC decreased in the alpha and beta bands. Furthermore, FC within the TAO network fluctuated before and after epileptic spikes; there was a decrease in the delta band between the bilateral hippocampi and the amygdala, OFG, and thalamus, whereas FC between the hippocampus and mPFC increased in the alpha, beta, and ripple bands. SIGNIFICANCE: These findings suggest the formation of an abnormal network involving the affected hippocampus and the TAO network, particularly in the gamma-ripple bands, indicating epilepsy-induced network disruptions. Reduced FC in the healthy hippocampus and the TAO network may reflect frontal lobe dysfunction related to emotion and cognition. Additionally, both chronic and transient FC changes observed via MEG may contribute to the cognitive and psychiatric impairments experienced by patients with MTLE. This study highlights the significance of frequency-specific network alterations in understanding MTLE's pathophysiology and its impact on limbic system functions. PLAIN LANGUAGE SUMMARY: In mesial temporal lobe epilepsy, there may be abnormal connectivity between the hippocampus and the limbic system, which is involved in memory, cognition, and emotion. The changes in connectivity observed using magnetoencephalography may be implicated in cognitive and psychiatric problems experienced by patients with mesial temporal lobe epilepsy. Examining disruptions in the connectivity across brain regions in relation to epileptic activity could further the understanding of the pathophysiology of this debilitating condition and its impact on behavioral and emotional functions, among others.

DOI： 10.1002/epi4.70018

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OBJECTIVE: At our institute, most pediatric patients undergo epilepsy surgery following a thorough presurgical evaluation without intracranial electroencephalography (EEG). We conducted an initial validation of our noninvasive presurgical strategy by assessing the seizure and developmental outcomes of 135 children. METHODS: All 135 pediatric patients were <15 years old, had undergone curative surgery, and were followed for at least 2 years postoperatively. Presurgical evaluations and postoperative seizure and developmental outcomes were investigated. Thorough noninvasive evaluation included 3-T magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in all patients. Intracranial EEG was mainly indicated for patients whose MRIs were negative or subtle. We defined Engel class I as favorable and Engel classes II-IV as unfavorable seizure outcomes. Intelligence quotient (IQ) and developmental quotient (DQ) before and 2 years after surgery were used to assess developmental/neuropsychological outcomes. RESULTS: MRI was positive in 130 of 135 patients (96.3%), including 39 of 40 with focal cortical dysplasia (FCD) type II and 30 of 33 with FCD type I. FDG-PET revealed concordant localizing findings in 119 of 132 patients (90.2%). Ictal single photon emission computed tomography provided concordant localizing information in 85 of 91 patients (93.4%). Intracranial EEG was performed in only 10 of 135 patients (7.4%). Ninety-seven of 135 patients (71.9%) were seizure-free 2 years after surgery. The final seizure-free rate was 99 of 135 (73.3%). Temporal lobe surgery predicted a favorable seizure outcome by multivariate analysis, whereas FCD type I and preoperative IQ/DQ < 70 predicted an unfavorable outcome. The mean IQ change was +1.3 points, and the mean DQ change was +1.0 points. Mean DQ significantly improved following extratemporal surgery (multivariate regression, p < .05), and mean DQ significantly decreased in patients with epileptic spasms (multivariate regression, p < .01). SIGNIFICANCE: Thorough noninvasive presurgical evaluation enables detection of subtle MRI lesions and curative epilepsy surgery without intracranial EEG in most patients, including those with FCD type II and type I, and leads to favorable seizure and developmental/neuropsychological outcomes.

DOI： 10.1111/epi.18249

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Publisher：International Journal of Thermophysics  

In this study, a method employing lock-in thermography is proposed for measuring the thermal diffusivity distribution of materials with high thermal conductivity. In this method, the thermal response distribution induced by periodic laser heating is analyzed, and the thermal diffusivity in the out-of-plane direction over the material surface is mapped. An undersampling method is applied during lock-in thermography to measure the thermal diffusivity distribution of materials with low thermal resistance at high frequencies. Additionally, a principle is developed to eliminate the inherent phase lag generated by the measurement system. The accuracy of the proposed method is validated by quantitatively measuring the thermal diffusivity of a pure copper sheet that exhibits an isotropic thermal diffusivity distribution. Results reveal that its average thermal diffusivity agreed with the reference value within + 2.4 %. The proposed method is also used to measure the thermal diffusivity of an isotropic graphite sheet with an inhomogeneous thermal diffusivity distribution. Results reveal that its average thermal diffusivity agreed with the reference value within + 7.0 %, and local areas with high thermal diffusivity are successfully visualized.

DOI： 10.1007/s10765-025-03523-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Neurosurgical Society  

<p>Three anti-calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs) are available in Japan: galcanezumab, fremanezumab, and erenumab. Early-onset efficacy has been demonstrated for each CGRP-mAb in comparison with placebo, but differences among the drugs are unclear. Only galcanezumab requires 2 doses at the initial injection. This study is a multicenter, open-label, randomized, two-group comparison trial, consisting of the random selection of a CGRP-mAb and 6 consecutive injections, and then discontinuation of the CGRP-mAb after 6 injections. The primary outcome is a comparison of early-onset efficacy between galcanezumab and both fremanezumab and erenumab after the initial injection. The secondary outcomes are comparisons between galcanezumab and both fremanezumab and erenumab, and between fremanezumab and erenumab as follows: weekly number of headache days, migraine days, and acute medication use are compared to baseline during one month after initial injection; time of subjectively perceiving onset of effect after initial injection; monthly changes in headache status from baseline to after third (3rd) injections; effective rates after initial and 3rd injections; improvement rates of depression scores between baseline and after 3rd injections; changes in number of absenteeism and presenteeism days in each month from baseline to after 3rd injections; proportion of ineffective cases after 3rd injections; recurrence rates and time to recurrence after CGRP-mAb discontinuation; effective rates of CGRP-mAb re-injections; detection of clinical factors associated with effectiveness after the initial and 3rd injections. The aim of this study is to investigate differences in early-onset efficacy among the CGRP-mAbs, and when and to what extent headache symptoms recur after discontinuation.</p>

DOI： 10.2176/jns-nmc.2024-0201

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DOI： 10.1016/j.seizure.2024.12.019

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INTRODUCTION: Recent studies have reported that essential tremor (ET) presents with not only motor symptoms but also cognitive dysfunction. However, detailed pathological mechanisms remain unclear. Here, we evaluate the characteristics of cognitive changes in older patients. METHODS: Eighty-five patients aged 65 years or older with ET but without dementia were evaluated for cognitive function using the Addenbrooke Cognitive Examination Revised (ACE-R). The patients were compared with healthy controls (HCs), and the characteristics of cognitive dysfunction were examined. Age at onset and correlations with tremor severity were also investigated. Moreover, we performed resting-state network (RSNs) analysis in a subset of these patients, and the functional connectivity (FC) within the networks was compared with age-matched controls. RESULTS: Compared to HCs, older patients with ET showed a clear reduction in the total (p = 0.001), attention (p = 0.005), verbal fluency (p = 0.001), and memory (p = 0.001) ACE-R scores. Older-onset patients showed significant cognitive dysfunction compared with younger-onset patients. Verbal fluency correlated with tremor severity in the multiple regression analysis (p < 0.001). RSNs showed an increase in FC in the frontal lobes within the language network in patients with ET compared to HCs (p < 0.05, FWE-corrected). CONCLUSION: Older patients with ET showed obvious cognitive dysfunction compared to HCs, indicating that cognitive dysfunction varies by age of onset and correlates with tremor severity. The results of the RSNs analysis suggest that the pathological mechanism of cognitive dysfunction in ET patients involves network changes similar to those in the early stages of Alzheimer's disease.

DOI： 10.1016/j.parkreldis.2024.107228

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

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Publisher：Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society EMBS  

Accurate identification of an epileptogenic zone (EZ) is crucial for successful epilepsy surgery. Stereotactic intracranial electroencephalography (SEEG) has contributed to improving surgical outcomes through assessing epileptic networks prior to surgery. However, SEEG data analysis has primarily relied on visual interpretation of epileptologists and clinical features of seizure types, leading to challenges in objective and quantitative surgical planning because it is difficult to visually evaluate High-Frequency Oscillation (HFO) or other epilepsy-related waveforms. Although the Epileptogenicity Index (EI) estimates epileptogenicity quantitatively based on temporal and energy parameters of brain regions, its accuracy is not always high enough. Thus, we propose a new automatic algorithm for detecting the seizure onset, referred to as TAILOR (Tailored Algorithm for Ictal Localization and Onset pRediction), which can determine the order of seizure onsets with high temporal resolution based on each patient's power spectrum patterns for tailor-made. In addition, the epileptic network can be estimated according to the order of seizure onsets determined with the proposed TAILOR. We retrospectively analyzed the clinical SEEG using TAILOR and confirmed that the actual surgical areas were ranked first as surgical areas in six out of eight cases.Clinical Relevance - We propose TAILOR as an automated algorithm for detecting seizure onset based on the power spectrum pattern. Estimating epileptic networks according to detailed seizure onset orders is anticipated to improve the accuracy of epilepsy treatment and surgery.

DOI： 10.1109/EMBC58623.2025.11253769

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Language：Japanese   Publisher：The Japanese Society for Artificial Intelligence  

DOI： 10.11517/pjsai.jsai2025.0_1o4os18a02

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Language：Japanese   Publisher：公益社団法人 日本生体医工学会  

<p>てんかん外科手術において、発作起始領域（SOZ）やてんかん原性領域（EZ）の正確な推定が、外科的治療を成功に導くうえで不可欠である。当院では、ロボットアームを用いた定位的頭蓋内脳波（SEEG）によって、術前に個々の患者のてんかんネットワークを高精度で推定し、良好な手術成績を得ている。しかし従来は、脳波の目視判読や発作型の臨床的特徴に強く依存していたため、客観的かつ定量的な指標に基づく手術計画を立案するには至っていない。さらに、今後の電極の多チャネル化に伴い、膨大な脳波データの目視判別が一層困難になるだけでなく、High Frequency Oscillation（HFO）など従来の視覚的観察では把握しづらい特徴も考慮する必要が生じている。そこで、EZおよび発作伝播ネットワークを機械的かつ高精度に推定するアルゴリズムを開発し、術前プランニングの客観性を確保すると同時に、治療効果を最大化する新たなてんかん外科手術計画法の構築を目指している。本発表では、SEEGデータを用いた発作起始自動検出アルゴリズムによる解析結果を、後方視的に術式および臨床転機と併せて報告するとともに、より精密なてんかんネットワークの理解に基づく手術計画最適化の可能性について述べる。</p>

DOI： 10.11239/jsmbe.annual63.214_1

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Language：English   Publisher：Operative Neurosurgery  

BACKGROUND AND OBJECTIVES: – Although volume-based stereotactic radiofrequency thermocoagulation (RFTC) is being increasingly employed, data regarding its clinical outcomes and patient selection criteria remain limited. This study aimed to elucidate the current status of RFTC for epilepsy in a multicenter Japanese cohort.METHODS: – This retrospective study included 23 patients who underwent volume-based RFTC for drug-resistant focal epilepsy between January 2021 and April 2024. Preoperative and postoperative clinical data were collected and analyzed in relation to postoperative seizure outcomes.RESULTS: – The median age at surgery was 16 years, with a median follow-up of 27 months. The most frequent etiology was focal cortical dysplasia (60.9%). Surgical planning was primarily based on magnetic resonance imaging and positron emission tomography findings, supplemented by stereo-electroencephalography in most cases. The median number of ablations per patient was 23, ranging from 5 to 51. The treatment area included the insulo-opercular cortices in 11 patients and the medial temporal lobe in 5 patients. No surgical complications occurred, although transient and permanent neurological deficits were observed in 34.8% and 13.0% of patients, respectively. Seizure freedom was achieved in 59.1% of patients at 1 year and 34.8% at the last follow-up. Prior epilepsy surgery was significantly associated with poorer seizure outcomes (P = .02). No other preoperative factors demonstrated a significant association with seizure freedom.CONCLUSION: – Volume-based RFTC seems to be a safe and effective, less invasive surgical option for selected patients with drug-resistant focal epilepsy, particularly those with deep-seated lesions or those involving eloquent cortex. While short-term seizure control is encouraging, long-term outcomes remain suboptimal, underscoring the need for improved patient selection and standardized treatment protocols.

DOI： 10.1227/ons.0000000000001869

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A patient with early-onset PARK14 and novel PLA2G6 variants underwent globus pallidus internus deep brain stimulation, achieving sustained three-year motor and quality-of-life improvements. Although a literature review supports motor benefits, our case's cognitive decline highlights the need for comprehensive assessment of non-motor symptoms and quality-of-life in this rare disorder.

DOI： 10.1016/j.prdoa.2025.100377

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BACKGROUND: Early seizures after craniotomy are significant perioperative complications that can adversely impact patient outcomes. Despite current guidelines advising against the routine use of antiseizure drugs for seizure after craniotomy prevention due to limited efficacy data, many clinicians continue prescribing them. This discrepancy highlights the need for robust evidence to guide clinical practice. This multi-center, randomized clinical trial was designed to investigate the efficacy of perampanel in preventing early seizures after craniotomy. METHOD: This multi-center, open-label, randomized clinical trial will be conducted across five hospitals in Nagoya, Japan, from February 2024 to December 2026. A total of 142 seizure-naive patients with supratentorial brain tumors will be recruited and randomized (1:1) into the treatment and control groups. The treatment group will receive 2 mg of perampanel starting 2 days preoperatively and continuing for 28 days postoperatively, while the control group will receive no antiseizure drugs. The primary outcome is the incidence of seizures within 28 days after craniotomy. Secondary outcomes are length of hospital and intensive care unit stays and postoperative complications. DISCUSSION: This study addresses the critical need for evidence-based recommendations regarding antiseizure drug use for preventing early seizures after craniotomy. As the first multi-center, randomized trial evaluating perampanel's efficacy in this setting, the findings may significantly influence clinical guidelines and perioperative practices. TRIAL REGISTRATION: This trial was registered with the Japan Registry of Clinical Trials (approval number: jRCTs041230117) on December 18, 2023, a member of the Primary Registry Network of the World Health Organization's International Clinical Trials Registry Platform.

DOI： 10.1186/s13063-024-08693-7

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BACKGROUND: Abrupt discontinuation of overused medications is standard treatment for medication overuse headache (MOH), but discontinuation is difficult to maintain. The aim was to evaluate the real-world clinical results of anti-calcitonin gene-related peptide monoclonal antibody (CGRP-mAb) treatment for migraine with MOH without abrupt drug discontinuation and no hospitalization. METHODS: Data were collected before starting CGRP-mAb injections (baseline) and 1 month after each injection. The following items were compared between baseline and after the first, second, and third CGRP-mAb injections, monthly headache days (MHD), monthly migraine days (MMD), monthly acute medication use (AMU) days, monthly total amount of AMU tablets, headache impact test-6 (HIT-6), and the migraine-specific quality of life questionnaire (MSQ). Achieving reduction rates ≥50 % in the frequency of each headache and migraine was defined as a good response. Achieving reduction rates of both AMU days and tablets ≥50 % was defined as effective in reducing AMU. RESULTS: This study included 33 patients with migraine with MOH. After the third CGRP-mAb injection, MHD and MMD were significantly decreased from median 30.0 to 9.5 days, and 10.0 to 1.5 days, respectively. In addition, monthly AMU days and tablets were significantly decreased from median 28.0 to 8.0 days, and 30.0 to 9.5 tablets, respectively. After the third CGRP-mAb injection, the good MHD and MMD responder rates were 75.0 % and 85.7 %, respectively. The rate of reducing AMU was 78.6 %. HIT-6 and MSQ scores decreased significantly from baseline to after each CGRP-mAb injection. CONCLUSIONS: When CGRP-mAb was administered to migraine with MOH, frequency of headache symptoms and AMU were reduced without abrupt drug discontinuation and no hospitalization.

DOI： 10.1016/j.heliyon.2024.e40190

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Language：Japanese   Publisher：(一社)日本疼痛学会  

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BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) develops along with status epilepticus and widespread subcortical white matter edema. We aimed to evaluate the epileptic foci and networks in two patients with epilepsy after AESD using simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI). METHODS: Statistically significant blood oxygen level-dependent (BOLD) responses related to interictal epileptiform discharges (IEDs) were analyzed using an event-related design of hemodynamic response functions with multiple peaks. RESULTS: Patient 1 developed focal seizures at age 10 years, one year after AESD onset. Positive BOLD changes were observed in the bilateral frontotemporal lobes, left parietal lobe, and left insula. BOLD changes were also observed in the subcortical structures. Patient 2 developed epileptic spasms at age two years, one month after AESD onset. Following total corpus callosotomy (CC) at age three years, the epileptic spasms resolved, and neurodevelopmental improvement was observed. Before CC, positive BOLD changes were observed bilaterally in the frontotemporal lobes. BOLD changes were also observed in the subcortical structures. After CC, the positive BOLD changes were localized in the temporal lobe ipsilateral to the IEDs, and the negative BOLD changes were mainly in the cortex and subcortical structures of the hemisphere ipsilateral to IEDs. CONCLUSION: EEG-fMRI revealed multiple epileptic foci and extensive epileptic networks, including subcortical structures in two cases with post-AESD epilepsy. CC may be effective in disconnecting the bilaterally synchronous epileptic networks of epileptic spasms after AESD, and pre-and post-operative changes in EEG-fMRI may reflect improvements in epileptic symptoms.

DOI： 10.1016/j.braindev.2024.07.003

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：English   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Neurosurgical Society  

<p>Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for essential tremor (ET). However, its long-term outcomes and prognostic factors remain unclear. This study aimed to retrospectively investigate 38 patients with ET who underwent MRgFUS thalamotomy and were followed up for >2 years. The improvement in tremor was evaluated using the Clinical Rating Scale for Tremor (CRST). Adverse events were documented, and correlations with factors, such as skull density ratio (SDR), maximum mean temperature (T-max), and lesion size, were examined. Furthermore, the outcomes were compared between two groups, one that met the cutoff values, which was previously reported (preoperative CRST-B ≤ 25, T-max ≥ 52.5°C, anterior-posterior size of lesion ≥ 3.9 mm, superior-inferior [SI] size of lesion > 5.5 mm), and the other that did not. The improvement rate was 59.4% on average at the 2-year follow-up. Adverse events, such as numbness (15.8%), dysarthria (10.5%), and lower extremity weakness (2.6%), were observed even after 2 years, although these were mild. The factors correlated with tremor improvement were the T-max and SI size of the lesion (p < 0.05), whereas the SDR showed no significance. Patients who met the aforementioned cutoff values demonstrated a 69.8% improvement at the 2-year follow-up, whereas others showed a 43.6% improvement (p < 0.05). In conclusion, MRgFUS is effective even after 2 years. The higher the T-max and the larger the lesion size, the better the tremor control. Previously reported cutoff values clearly predict the 2-year prognosis, indicating the usefulness of MRgFUS.</p>

DOI： 10.2176/jns-nmc.2023-0202

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INTRODUCTION: Connector hubs are specialized brain regions that connect multiple brain networks and therefore have the potential to affect the functions of multiple systems. This study aims to examine the involvement of connector hub regions in essential tremor. METHODS: We examined whole-brain functional connectivity alterations across multiple brain networks in 27 patients with essential tremor and 27 age- and sex-matched healthy controls to identify affected hub regions using a network metric called functional connectivity overlap ratio estimated from resting-state functional MRI. We also evaluated the relationships of affected hubs with cognitive and tremor scores in all patients and with motor function improvement scores in 15 patients who underwent postoperative follow-up evaluations after focused ultrasound thalamotomy. RESULTS: We have identified affected connector hubs in the cerebellum and thalamus. Specifically, the dentate nucleus in the cerebellum and the dorsomedial thalamus exhibited more extensive connections with the sensorimotor network in patients. Moreover, the connections of the thalamic pulvinar with the visual network were also significantly widespread in the patient group. The connections of these connector hub regions with cognitive networks were negatively associated (FDR q < 0.05) with cognitive, tremor, and motor function improvement scores. CONCLUSION: In patients with essential tremor, connector hub regions within the cerebellum and thalamus exhibited widespread functional connections with sensorimotor and visual networks, leading to alternative pathways outside the classical tremor axis. Their connections with cognitive networks also affect patients' cognitive function.

DOI： 10.1016/j.parkreldis.2024.106034

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OBJECTIVE: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). METHODS: We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. RESULTS: A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non-epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. SIGNIFICANCE: The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. PLAIN LANGUAGE SUMMARY: This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non-epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non-epilepsy group.

DOI： 10.1002/epi4.12891

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BACKGROUND: The use of anchor bolts to secure electrodes to the skull can be difficult in some clinical situations. Herein, we present the boltless technique to secure electrodes to the scalp using nylon sutures to overcome the problems associated with anchor bolts. We investigated the safety, accuracy errors, and patient-related and operative factors affecting errors in the boltless technique. METHODS: This single-institution retrospective series analyzed 103 electrodes placed in 12 patients. The target-point localization error (TPLE), entry-point localization error (EPLE), radial error (RE), and depth error (DE) of the electrodes were calculated. RESULTS: The median of the mean operative time per electrode was 9.3 min. The median TPLE, EPLE, RE, and absolute DE value were 4.1 mm, 1.6 mm, 2.7 mm, and 1.9 mm, respectively. Positive correlations were observed between the preoperative scalp thickness, mean operative time per electrode, EPLE, RE, and the absolute value of DE versus TPLE (r = .228, p = .02; r = .678, p = .015; r = .228, p = .02; r = .445, p < .01; r = .630, p < .01, respectively), and electrode approach angle versus EPLE (r = .213, p = .031). Multivariate analysis revealed that the absolute value of DE had the strongest influence on the TPLE, followed by RE and preoperative scalp thickness, respectively (β = .938, .544, .060, respectively, p < .001). No complications related to SEEG insertion and monitoring were encountered. CONCLUSION: The boltless technique using our unique planning and technical method is a safe, effective, and low-cost alternative in cases where anchor bolts are contraindicated.

DOI： 10.1007/s00701-024-05889-3

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The involvement of the human amygdala in facial mimicry remains a matter of debate. We investigated neural activity in the human amygdala during a task in which an imitation task was separated in time from an observation task involving facial expressions. Neural activity in the amygdala was measured using functional magnetic resonance imaging in 18 healthy individuals and using intracranial electroencephalogram in six medically refractory patients with epilepsy. The results of functional magnetic resonance imaging experiment showed that mimicry of negative and positive expressions activated the amygdala more than mimicry of non-emotional facial movements. In intracranial electroencephalogram experiment and time-frequency analysis, emotion-related activity of the amygdala during mimicry was observed as a significant neural oscillation in the high gamma band range. Furthermore, spectral event analysis of individual trial intracranial electroencephalogram data revealed that sustained oscillation of gamma band activity originated from an increased number and longer duration of neural events in the amygdala. Based on these findings, we conclude that during facial mimicry, visual information of expressions and feedback from facial movements are combined in the amygdalar nuclei. Considering the time difference of information approaching the amygdala, responses to facial movements are likely to modulate rather than initiate affective processing in human participants.

DOI： 10.1093/cercor/bhad488

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Language：English   Publisher：The Japan Neurosurgical Society  

<p>Central poststroke pain is a chronic, intractable, central neuropathic pain. Spinal cord stimulation is a neuromodulation therapy for chronic neuropathic pain. The conventional stimulation method induces a sense of paresthesia. Fast-acting subperception therapy is one of the latest new stimulation methods without paresthesia. A case of achieving pain relief of central poststroke pain affecting both the arm and leg on one side by double-independent dual-lead spinal cord stimulation using fast-acting subperception therapy stimulation is presented. A 67-year-old woman had central poststroke pain due to a right thalamic hemorrhage. The numerical rating scale scores of the left arm and leg were 6 and 7, respectively. Using dual-lead stimulation at the Th 9-11 levels, a spinal cord stimulation trial was performed. Fast-acting subperception therapy stimulation achieved pain reduction in the left leg from 7 to 3. Therefore, a pulse generator was implanted, and the pain relief continued for 6 months. Then, two additional leads were implanted at the C 3-5 levels, and pain in the arm decreased from 6 to 4. Independent setting and adjustments of the dual-lead stimulation were required because the thresholds of paresthesia perception were significantly different. To achieve pain relief in both the arm and leg, double-independent dual-lead stimulation placed at cervical and thoracic levels is an effective treatment. Fast-acting subperception therapy stimulation may be effective for central poststroke pain, especially in cases where the paresthesia is perceived as uncomfortable or the conventional stimulation itself is ineffective.</p>

DOI： 10.2176/jns-nmc.2022-0336

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DOI： 10.1016/j.seizure.2023.09.018

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Publisher：International Journal of Thermal Sciences  

This paper proposes a new thermal contact resistance distribution measurement method using lock-in thermography. This method was used to evaluate a two-dimensional local thermal contact resistance distribution. To be able to measure the distribution, a uniform intensity laser heating system was developed. The developed system has a top-hat intensity distribution with a diameter of 30 mm. By combining this heat source and the lock-in thermography, a new measurement instrument was developed, which can evaluate local temperature behavior in the frequency domain, including the information of the contact interface in high spatial resolution of about 70 μm. Additionally, a new thermal contact resistance measurement principle was constructed based on a one-dimensional heat transfer equation that considers the reflected and transmitted temperature waves at the boundary and contact interface. The thermal contact resistance was acquired as a solution to the inverse problem of the temperature response done by fitting analyses. The validation of this method was performed quantitatively with two samples made of two bonded isotropic graphite plates. The one sample has an intentional defect area that has a slightly higher thermal resistance. The other sample has the known thermal contact resistance value measured with a validated method. Based on the results, the measurement value agreed with the referenced value. Also, the defect area was quantitatively detected clearly as a high thermal resistance region. Furthermore, as a practical example, the measurement method was applied for two different contact interface roughness samples consisting of aluminum alloys and thermal grease. Consequently, it was revealed and visualized that the contact interface with a rough surface has a high thermal resistance spot.

DOI： 10.1016/j.ijthermalsci.2023.108475

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DOI： 10.1016/j.seizure.2023.07.007

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BACKGROUND: Spinal cord stimulation (SCS) is one of the neuromodulation therapies for chronic neuropathic pain. The conventional paresthesia-based SCS involves the application of tonic stimulation that induces a sense of paresthesia. Recently, new SCS stimulation patterns without paresthesia have been developed. Differential target multiplexed (DTM) stimulation and fast-acting subperception therapy (FAST) stimulation are the latest paresthesia-free SCS patterns. METHODS: A single-center, open-label, crossover, randomized clinical trial to investigate the superiority of SCS using the latest new stimulation patterns over conventional tonic stimulation for neuropathic pain is planned. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). In the SCS trial, participants will be randomly assigned to 4 groups receiving stimulation, including tonic, DTM, and FAST. Each stimulation will then be performed for 2 days, and a visual analog scale (VAS) for pain will be evaluated before and after each stimulation pattern. A stimulation-off period for 1 day is set between each stimulation pattern to wash out the residual previous stimulation effects. Pain improvement is defined as more than 33% reduction in the pain VAS. The primary analysis will compare pain improvement between the new stimulation patterns and the conventional tonic stimulation pattern in the SCS trial. The secondary outcomes will be evaluated as follows: (1) the relationships between causative disease and improvement rate by each stimulation pattern; (2) comparison of pain improvement between the DTM and FAST stimulation patterns in all cases and by causative disease; (3) changes in assessment items preoperatively to 24 months after the implantation; (4) preoperative factors associated with long-term effects defined as continuing for more than 12 months; and (5) adverse events related to this study 3 months after the implantation. DISCUSSION: This study aims to clarify the effectiveness of the latest new stimulation patterns compared to the conventional tonic stimulation. In addition, which stimulation pattern is most effective for which kind of causative disease will be clarified. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) 1,042,220,094. Registered on 21 November 2022, and last modified on 6 January 2023. jRCT is an approved member of the Primary Registry Network of WHO ICTRP.

DOI： 10.1186/s13063-023-07637-x

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This work aimed to investigate the involvement of the thalamic nuclei in mesial temporal lobe epilepsy (MTLE) and identify the influence of interictal epileptic discharges on the neural basis of memory processing by evaluating the functional connectivity (FC) between the thalamic nuclei and default mode network-related area (DMNRA) using magnetoencephalography. Preoperative datasets of nine patients with MTLE with seizure-free status after surgery and those of nine healthy controls were analyzed. The FC between the thalamic nuclei (anterior nucleus [ANT], mediodorsal nucleus [MD], intralaminar nuclei [IL]), hippocampus, and DMNRA was examined for each of the resting, pre-spike, spike, and post-spike periods in the delta to ripple bands using magnetoencephalography. The FC between the ANT, MD, hippocampus, and medial prefrontal cortex increased in the gamma to ripple bands, whereas the FC between the ANT, IL, and DMNRA decreased in the delta to beta bands, compared with that of the healthy controls at rest. Compared with the rest period, the pre-spike period had significantly decreased FC between the ANT, MD, and DMNRA in the ripple band. Different FC changes between the thalamic nuclei, hippocampus, and DMNRA of specific connections in a particular band may reflect impairment or compensation in the memory processes.

DOI： 10.1038/s41598-023-37834-2

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BACKGROUND: Neuropathic pain after spinal cord injury (SCI), both traumatic and non-traumatic, is refractory to various treatments. Spinal cord stimulation (SCS) is one of the neuromodulation therapies for neuropathic pain, although SCS has insufficient efficacy for neuropathic pain after SCI. The reasons are presumed to be inappropriate locations of SCS leads and conventional tonic stimulation itself does not have a sufficient analgesic effect for the pain. In patients with past spinal surgical histories, the cylinder-type leads are likely to be placed on the caudal side of the SCI because of surgical adhesions. Differential target multiplexed (DTM) stimulation is one of the latest new stimulation patterns that is superior to conventional stimulation. METHODS: A single-center, open-label, randomized, two-way crossover trial is planned to investigate the efficacy of SCS using DTM stimulation placing a paddle lead at the appropriate site for neuropathic pain after SCI in patients with spinal surgical histories. The paddle-type lead delivers energy more efficiently than a cylinder-type lead. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). The primary outcome is rates of achieving pain improvement with more than 33% reduction 3 months after SCS system implantation. The secondary outcomes are to be evaluated as follows: (1) effectiveness of DTM and tonic stimulations during the SCS trial; (2) changes of assessment items from 1 to 24 months; (3) relationships between the result of the SCS trial and the effects 3 months after SCS system implantation; (4) preoperative factors associated with a long-term effect, defined as continuing for more than 12 months; and (5) whether gait function improves from 1 to 24 months. DISCUSSION: A paddle-type lead placed on the rostral side of SCI and using DTM stimulation may provide significant pain relief for patients with intractable neuropathic pain after SCI in patients with past spinal surgical histories. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCT 1042220093. Registered on 21 November 2022, and last modified on 6 January 2023. jRCT is approved as a member of the Primary Registry Network of WHO ICTRP.

DOI： 10.1186/s13063-023-07433-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Neurosurgical Society  

<p>Stereotactic electroencephalography (SEEG) is receiving increasing attention as a safe and effective technique in the invasive evaluation for epileptogenic zone (EZ) detection. The main clinical question is whether the use of SEEG truly improves outcomes. Herein, we compared outcomes in our patients after three types of intracranial EEG (iEEG): SEEG, the subdural electrode (SDE), and a combined method using depth and strip electrodes. We present here our preliminary results from two demonstrative cases. Several international reports from large epilepsy centers found the following clinical advantages of SEEG: 1) three-dimensional analysis of structures, including bilateral and multilobar structures; 2) low rate of complications; 3) less pneumoencephalopathy and less patient burden during postoperative course, which allows the initiation of video-EEG monitoring immediately after implantation and does not require resection to be performed in the same hospitalization; and 4) a higher rate of good seizure control after resection. In other words, SEEG more accurately identified the EZ than the SDE method. We obtained similar results in our preliminary experiences under limited conditions. In Japan, as of August 2022, dedicated electrodes and SEEG accessories have not been approved and the use of the robot arm is not widespread. The Japanese medical community is hopeful that these issues will soon be resolved and that the experience with SEEG in Japan will align with that of large epilepsy centers internationally.</p>

DOI： 10.2176/jns-nmc.2022-0271

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Understanding the semiology and underlying anatomy of each seizure is essential for epilepsy surgeons. According to the International League Against Epilepsy(ILAE)classification in 2017, seizure types are classified as focal, generalized, or unknown onset, all of which are further classified as motor or non-motor onset. Impairment of awareness is involved in consciousness systems(consisting of subcortical structures such as the thalamus and upper brain stem)and cortical structures(including the frontoparietal association cortices). Seizures with motor features are divided into elementary symptoms for which myoclonic, clonic, and tonic expressions reflect the somatotopy of the primary motor cortex; and integrated or gestural motor expression representing activation of the motor association cortex. A rostrocaudal gradient is demonstrated in hyperkinetic movements in frontal lobe epilepsy. Non-motor epileptic features should be understood together with auras, which correspond to focal aware seizures and hold crucial localizing semiologic values. The correlation between functional anatomy and seizure semiology is justified by invasive recordings such as stereotactic electroencephalography and subdural recordings, and also confirmed by seizure outcomes after resection of supposed epileptogenic zones. In addition to the conventional localization theory, it is necessary to consider the neural network theory for further recognition of the functionally anatomical basis in an incomprehensible demonstration of seizures.

DOI： 10.11477/mf.1436204711

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OBJECTIVE: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for essential tremor (ET) is well known; however, no prognostic factors have been established. The authors aimed to retrospectively investigate MRgFUS ablation outcomes and associated factors and to define the cutoff values for each prognostic factor. METHODS: Sixty-four Japanese patients who underwent unilateral ventral intermediate nucleus thalamotomy with MRgFUS for ET were included. Follow-up evaluations were performed at 1 week and 1, 3, 6, 12, and 24 months postoperatively. Tremor suppression was evaluated using the Clinical Rating Scale for Tremor (CRST), and adverse effects were recorded postoperatively. Outcome-associated factors were examined preoperatively, intraoperatively, and postoperatively using multivariate analyses. The cutoff values for the prognostic factors were calculated using receiver operating characteristics. RESULTS: Percentage improvements in the CRST scores of the affected upper limb were 82.4%, 72.2%, 68.6%, and 65.9% at 1, 3, 6, and 12 months, respectively. Preoperatively, a high skull density ratio (SDR) (p ≤ 0.047), low CRST part B score (used to assess tremors during several tasks) (cutoff value 25, p ≤ 0.041), and nonoccurrence of resting tremors (p = 0.027) were significantly associated with improved tremor control. An intraoperatively high maximum mean temperature (cutoff value 52.5°C, p ≤ 0.047), postoperatively large lesion (cutoff value 3.9 mm in the anterior-posterior direction, p ≤ 0.002; cutoff value 5.0-5.55 mm in the superior-inferior direction, p ≤ 0.026), and small transducer focus correction (p ≤ 0.015) were also associated with improved tremor control. No valid cutoff value was found for SDR. Adverse effects (limb weakness, sensory disturbance, ataxia/walking disturbance, dysgeusia, dysarthria, and facial swelling) occurred transiently and were associated with high SDR, high temperature, high number of sonication sessions, large lesion, and occurrence of resting tremor. Patients who developed leg weakness experienced greater percentage improvement in tremors at 3 months postoperatively than those who did not. CONCLUSIONS: MRgFUS ablation could be used to achieve good tremor control with acceptable adverse effects in Japanese patients with ET. The relatively low SDR in Asian ethnic groups as compared with that of Western populations makes treatment difficult; however, the cutoff values obtained in this study may be useful for achieving good treatment outcomes even in such patients. Clinical trial registration no.: UMIN000026952 (University Hospital Medical Information Network). ABBREVIATIONS: ACPC = anterior commissure-posterior commissure; AP = anterior to posterior; CRST = Clinical Rating Scale for Tremor; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound; PC = posterior commissure; PSA = posterior subthalamic area; RL = right to left; ROC = receiver operating characteristic; SDR = skull density ratio; SI = superior to inferior; T2WI = T2-weighted imaging; VIM = ventral intermediate nucleus.

DOI： 10.3171/2022.3.JNS212460

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Holmes tremor is a symptomatic tremor that develops secondary to central nervous system disorders. Stereotactic neuromodulation is considered when the tremors are intractable. Targeting the ventral intermediate nucleus (Vim) is common; however, the outcome is often unsatisfactory, and the posterior subthalamic area (PSA) is expected as alternative target. In this study, we report the case of a patient with intractable Holmes tremor who underwent dual-lead deep brain stimulation (DBS) to stimulate multiple locations in the PSA and thalamus. The patient was a 77-year-old female who complained of severe tremor in her left upper extremity that developed one year after her right thalamic infarction. Vim-thalamotomy using focused ultrasound therapy (FUS) was initially performed but failed to control tremor. Subsequently, we performed DBS using two leads to stimulate four different structures. Accordingly, one lead was implanted with the aim of targeting the ventral oralis nucleus (Vo)/zona incerta (Zi), and the other with the aim of targeting the Vim/prelemniscal radiation (Raprl). Electrode stimulation revealed that Raprl and Zi had obvious effects. Postoperatively, the patient achieved good tremor control without any side effects, which was maintained for two years. Considering that she demonstrated resting, postural, and intention/action tremor, and Vim-thalamotomy by FUS was insufficient for tremor control, complicated pathogenesis was presumed in her symptoms including both the cerebellothalamic and the pallidothalamic pathways. Using the dual-lead DBS technique, we have more choices to adjust the stimulation at multiple sites, where different functional networks are connected. Intractable tremors, such as Holmes tremor, may have complicated pathology, therefore, modulating multiple pathological networks is necessary. We suggest that the dual-lead DBS (Vo/Raprl and Vim/Zi) presented here is safe, technically feasible, and possibly effective for the control of Holmes tremor.

DOI： 10.3389/fnhum.2022.1065459

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OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.

DOI： 10.3171/2022.5.JNS22411

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Neurosurgical Society  

<p>Resting-state functional MRI (rs-fMRI) has been utilized to visualize large-scale brain networks. We evaluated the usefulness of multitier network analysis using rs-fMRI in patients with focal epilepsy. Structural and rs-fMRI data were retrospectively evaluated in 20 cases with medically refractory focal epilepsy, who subsequently underwent surgery. First, structural changes were examined using voxel-based morphometry analysis. Second, alterations in large-scale networks were evaluated using dual-regression analysis. Third, changes in cortical hubs were analyzed and the relationship between aberrant hubs and the epileptogenic zone (EZ) was evaluated. Finally, the relationship between the hubs and the default mode network (DMN) was examined using spectral dynamic causal modeling (spDCM). Dual-regression analysis revealed significant decrease in functional connectivity in several networks including DMN in patients, although no structural difference was seen between groups. Aberrant cortical hubs were observed in and around the EZ (EZ hubs) in 85% of the patients, and a strong degree of EZ hubs correlated to good seizure outcomes postoperatively. In spDCM analysis, facilitation was often seen from the EZ hub to the contralateral side, while inhibition was seen from the EZ hub to nodes of the DMN. Some cognition-related networks were impaired in patients with focal epilepsy. The EZ hub appeared in the vicinity of EZ facilitating connections to distant regions in the early phase, which may eventually generate secondary focus, while inhibiting connections to the DMN, which may cause cognitive deterioration. Our results demonstrate pathological network alterations in epilepsy and suggest that earlier surgical intervention may be more effective.</p>

DOI： 10.2176/nmc.oa.2021-0173

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Language：Japanese   Publisher：大阪 : てんかん治療研究振興財団  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033719786

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