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We reported the main results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 4, a nationwide surveillance of therapy (NET) in Japan from January 2015 to December 2019. JR-NET 4 registered consecutive patients who underwent NETs by Japan Society of Neuroendovascular Therapy (JSNET)-certified specialists. The primary endpoint was functional independence (mRS score of 0-2) at 30 days post-NET, with secondary endpoints focusing on technical success and major adverse events within 30 days. A total of 63,230 patients and 60,354 NET procedures from 166 participating centers were analyzed. During the study period, NET cases have consistently increased, with an increase in the proportion of elderly patients. A significant trend shift was observed in the distribution of NET procedures, with endovascular treatment for acute ischemic stroke that showed a dramatic increase in 5 years. This trend aligns with key randomized clinical trials from 2015 that presented the efficacy of this treatment. Clinical outcomes at 30 days posttreatment revealed that endovascular treatment for acute ischemic stroke and other NETs maintained safety and effectiveness despite varying prevalence of functional independence between target diseases. The study also observed a steady increase in emergency treatment cases, reflecting the increase in acute ischemic stroke, a time-sensitive medical condition. This comprehensive surveillance highlights the trend of NET practices in Japan, driven by clinical evidence and advancements in treatment devices. Although these findings were specific to Japan, they offer valuable insights into the broader trends in NETs and acute stroke care.

Immediate postcraniotomy headache frequently occurs within the first 48 h after surgery. The mechanisms underlying immediate postcraniotomy headache are not yet fully understood, and effective treatments are not yet established. This study aimed to identify the factors associated with immediate postcraniotomy headache in patients who underwent clipping surgery with frontotemporal craniotomy and to examine the effects of these factors on postcraniotomy headache. A total of 51 patients were included in this study. Immediate postcraniotomy headache was defined as pain with numerical rating scale score 4 on postoperative day 7. Sixteen patients (31.4%) had immediate postcraniotomy headache. The headache-positive group had a higher incidence of preoperative analgesic use (50.0% vs. 5.7%, respectively, p < 0.001), increased temporal muscle swelling ratio (137.0%±30.2% vs. 112.5%±30.5%, respectively, p = 0.01), and higher postoperative analgesic use (12.9±5.8 vs. 6.7±5.2, respectively, p < 0.001) than the headache-negative group. The risk factors independently associated with immediate postcraniotomy headache were preoperative analgesic use and temporal muscle swelling by >115.15% compared with the contralateral side in the receiver operating characteristic analysis. Postcraniotomy headache was significantly more common in patients with preoperative analgesic use and temporal muscle swelling than in those without (p < 0.001 and p = 0.002, respectively). Altogether, patients with immediate postcraniotomy headache had greater preoperative analgesic use, greater temporal muscle swelling ratio, and higher postoperative analgesic use than those without. Thus, temporal muscle swelling is a key response to immediate postcraniotomy headache.

In the transsylvian (TS) approach, as characterized by clipping surgery, the presurgical visualization of the superficial middle cerebral vein (SMCV) can help change the surgical approach to ensure safe microsurgery. Nevertheless, identifying preoperatively the venous structures that are involved in this approach is difficult. In this study, we investigated the venous structures that are involved in the TS approach using three-dimensional (3D) rotational venography (3D-RV) and evaluated the effectiveness of this method for presurgical simulation. Patients who underwent 3D-RV between August 2018 and June 2020 were involved in this retrospective study. The 3D-RV and partial maximum intensity projection images with a thickness of 5 mm were computationally reconstructed. The venous structures were subdivided into the following three portions according to the anatomic location: superficial, intermediate, and basal portions. In the superficial portion, predominant frontosylvian veins were observed on 31 (41%) sides, predominant temporosylvian veins on seven (9%) sides, and equivalent fronto- and temporosylvian veins on 28 (37%) sides. The veins in the intermediate (deep middle cerebral and uncal veins) and basal portions (frontobasal bridging veins) emptied into the SMCV on 57 (75%) and 34 (45%) sides, respectively. The 3D-RV images were highly representative of the venous structures observed during microsurgery. In this study, 3D-RV was utilized to capture the details of the venous structures from the superficial to the deep portions. Presurgical simulation of the venous structures that are involved in the TS approach using 3D-RV may increase the safety of microsurgical approaches.

Background: Traditional brain activity monitoring via scalp electroencephalography (EEG) offers limited resolution and is susceptible to artifacts. Endovascular electroencephalography (eEEG) emerged in the 1990s. Despite early successes and potential for detecting epileptiform activity, eEEG has remained clinically unutilized. This study aimed to further test the capabilities of eEEG in detecting lateralized epileptic discharges in animal models. We hypothesized that eEEG would be able to detect lateralization. The purpose of this study was to measure epileptiform discharges with eEEG in animal models with lateralization in epileptogenicity. Materials and methods: We inserted eEEG electrodes into the transverse sinuses of three pigs, and subdural electrodes (SDs) on the surfaces of the left and right hemispheres. We induced epileptogenicity with penicillin in the left brain of pigs F00001 and F00003, and in the right brain of pig F00002. The resulting epileptiform discharges were measured by eEEG electrodes placed in the left and right transverse sinuses, and conducted comparisons with epileptiform discharges from SDs. We also had 12 neurological physicians interpret measurement results from eEEG alone and determine the side (left or right) of epileptogenicity. Results: Three pigs were evaluated for epileptiform discharge detection using eEEG: F00001 (7 months old, 14.0 kg), F00002 (8 months old, 15.6 kg), and F00003 (8 months old, 14.4 kg). The eEEG readings were compared with results from SDs, showing significant alignment across all subjects (p 0.93) and PPV (>0.95) that appear equivalent to those of subdural EEG in the three pigs. This lateralization was also discernible by neurological physicians on visual inspection.

Background and Purpose Differences in measurement of the extent of acute ischemic stroke using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) by non-contrast computed tomography (CT-ASPECTS stratum) and diffusion-weighted imaging (DWI-ASPECTS stratum) may impact the efficacy of endovascular therapy (EVT) in patients with a large ischemic core. Methods The RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan–Large IscheMIc core Trial) was a multicenter, open-label, randomized clinical trial that evaluated the efficacy and safety of EVT in patients with ASPECTS of 3–5. CT-ASPECTS was prioritized when both CT-ASPECTS and DWI-ASPECTS were measured. The effects of EVT on the modified Rankin Scale (mRS) score at 90 days were assessed separately for each stratum. Results Among 183 patients, 112 (EVT group, 53; No-EVT group, 59) were in the CT-ASPECTS stratum and 71 (EVT group, 40; No-EVT group, 31) in the DWI-ASPECTS stratum. The common odds ratio (OR) (95% confidence interval) of the EVT group for one scale shift of the mRS score toward 0 was 1.29 (0.65–2.54) compared to the No-EVT group in CT-ASPECTS stratum, and 6.15 (2.46–16.3) in DWI-ASPECTS stratum with significant interaction between treatment assignment and mode of imaging study (P=0.002). There were significant interactions in the improvement of the National Institutes of Health Stroke Scale score at 48 hours (CT-ASPECTS stratum: OR, 1.95; DWIASPECTS stratum: OR, 14.5; interaction P=0.035) and mortality at 90 days (CT-ASPECTS stratum: OR, 2.07; DWI-ASPECTS stratum: OR, 0.23; interaction P=0.008). Conclusion Patients with ASPECTS of 3–5 on MRI benefitted more from EVT than those with ASPECTS of 3–5 on CT.

The influence of aneurysm size on the outcomes of endovascular management (EM) for aneurysmal subarachnoid hemorrhages (aSAH) is poorly understood. To evaluate the outcomes of EM for ruptured large cerebral aneurysms, we retrospectively analyzed the medical records of patients with aSAH that were treated with coiling between 2013 and 2020 and compared the differences in outcomes depending on aneurysm size. A total of 469 patients with aSAH were included; 73 patients had aneurysms measuring 10 mm in diameter (group L), and 396 had aneurysms measuring

Background The effectiveness of endovascular thrombectomy (EVT) has been proven even in patients with large cerebral infarction in the early time window. However, the association of the time course with the treatment effect is unknown. The aim of this analysis was to evaluate the influence of the time course from stroke onset to reperfusion on the therapeutic effect of EVT. Methods The subjects were patients with occlusion of large vessels and sizable strokes on imaging (Alberta Stroke Program Early Computed Tomographic score 3–5) in RESCUE–Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism–Japan Large Ischemic Core Trial), a multicenter, randomized, clinical open‐label trial of EVT versus medical care alone. In the current analysis, the clinical and time course characteristics associated with a favorable outcome (modified Rankin scale [mRS] score of 0–2 and 0–3 at 90 days) were examined in patients treated with EVT. Results The analysis included 71 patients (median age, 77 years; median National Institutes of Health Stroke Scale score on admission, 21). Occlusion sites were the internal carotid artery (48%), proximal segment of the middle cerebral artery (72%) and tandem lesions (20%). Of these patients, 23 (32%) had an mRS score of 0 to 3 and 12 (17%) had an mRS score of 0 to 2 at 90 days. In multivariate analysis, there were independent associations of onset to reperfusion time (odds ratio [OR], 0.991 [95% CI, 0.984–0.999]; P=0.01) and puncture to reperfusion time (OR , 0.952 [95% CI, 0.917–0.988]; P

Background It remains unclear whether intravenous thrombolysis (IVT) influences the incidence of the first pass effect (FPE) in patients with acute large vessel occlusion treated with mechanical thrombectomy (MT). Therefore, this study investigated the effects of IVT on FPE in patients treated with MT. Methods This is a post hoc analysis of the SKIP (Direct Mechanical Thrombectomy in Acute LVO Stroke) study, which was an investigator‐initiated, multicenter, randomized, open‐label clinical trial performed in 23 hospital networks in Japan from January 1, 2017, to July 31, 2019. Among 204 patients, 24 were excluded because they did not undergo MT. Patients treated with MT alone were compared with those treated with MT+IVT for the incidence of FPE (achieving a modified treatment in cerebral ischemia score of 2c or 3 after the first MT pass). Additional subgroup analyses were performed to investigate factors more closely related to the association between IVT and FPE. Results Among the 180 patients, 91 were treated with MT alone and 89 were treated with MT+IVT. FPE was achieved in 56 patients (31.1%). The incidence of FPE was significantly higher in patients treated with MT+IVT than in those treated with MT alone (39.3% versus 23.0%, respectively; P=0.02). In the subgroup analyses, IVT markedly increased FPE in female patients and tended to increase FPE in patients with first‐segment middle cerebral artery distal occlusion and onset to hospital arrival time >100 minutes. Conclusion IVT using alteplase increased the incidence of FPE in Japanese patients with acute ischemic stroke treated with MT. Trial Registration : Trial registration umin.ac.jp/ctr identifier: UMIN000021488

This study aimed to measure the impact of the COVID-19 pandemic on the volumes of annual stroke admissions compared with those before the pandemic in Japan. We conducted an observational, retrospective nationwide survey across 542 primary stroke centers in Japan. The annual admission volumes for acute stroke within 7 days from onset between 2019 as the pre-pandemic period and 2020 as the pandemic period were compared as a whole and separately by months during which the epidemic was serious and prefectures of high numbers of infected persons. The number of stroke patients declined from 182,660 in 2019 to 178,083 in 2020, with a reduction rate of 2.51% (95% confidence interval [CI], 2.58%-2.44%). The reduction rates were 1.92% (95% CI, 1.85%-2.00%; 127,979-125,522) for ischemic stroke, 3.88% (95% CI, 3.70%-4.07%, 41,906-40,278) for intracerebral hemorrhage, and 4.58% (95% CI, 4.23%-4.95%; 13,020-12,424) for subarachnoid hemorrhage. The admission volume declined by 5.60% (95% CI, 5.46%-5.74%) during the 7 months of 2020 when the epidemic was serious, whereas it increased in the remaining 5 months (2.01%; 95% CI, 1.91%-2.11%). The annual decline in the admission volume was predominant in the five prefectures with the largest numbers of infected people per million population (4.72%; 95% CI, 4.53%-4.92%). In conclusion, the acute stroke admission volume declined by 2.51% in 2020 relative to 2019 in Japan, especially during the months of high infection, and in highly infected prefectures. Overwhelmed healthcare systems and infection control practices may have been associated with the decline in the stroke admission volume during the COVID-19 pandemic.

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.

Abstract The number of patients with traumatic intracranial hemorrhage (tICH) that are taking antithrombotics (ATs), antiplatelets (APs) and/or anticoagulants (ACs), has increased, but the influence of it for outcome remains unclear. This study aimed to evaluate an influence of AT for tICH. We retrospectively reviewed all patients with tICH treated between 2012 and 2019, and analyzed demographics, neurological status, clinical course, radiological findings, and outcome data. A total of 393 patients with tICH were included; 117 were on AT therapy (group A) and 276 were not (group B). Fifty-one (43.6%) and 159 (57.6%) patients in groups A and B, respectively, exhibited mRS of 0–2 at discharge (p = 0.0113). Mortality at 30 days was significantly higher in group A than in group B (25.6% vs 16.3%, p = 0.0356). Multivariate analysis revealed that higher age (OR 32.7, p

In myoelectrical pattern recognition (PR), the feature extraction methods for stroke-oriented applications are challenging and remain discordant due to a lack of hemiplegic data and limited knowledge of skeletomuscular function. Additionally, technical and clinical barriers create the need for robust, subject-independent feature generation while using supervised learning (SL). To the best of our knowledge, we are the first study to investigate the brute-force analysis of individual and combinational feature vectors for acute stroke gesture recognition using surface electromyography (EMG) of 19 patients. Moreover, post-brute-force singular vectors were concatenated via a Fibonacci-like spiral net ranking as a novel, broadly applicable concept for feature selection. This semi-brute-force navigated amalgamation in linkage (SNAiL) of EMG features revealed an explicit classification rate performance advantage of 10–17% compared to canonical feature sets, which can drastically extend PR capabilities in biosignal processing.

Abstract Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time–outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospective registry of stroke patients with acute cerebral large-vessel occlusion at 46 centers, we analyzed the data of 1010 patients with successful reperfusion after endovascular therapy (mTICI of 2b or 3). In 3 age subgroups (

Introduction JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset.Methods and analysis This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5–20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×108 (cohort 1) to 3 x 108 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95.Ethics and dissemination The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal.Trial registration number NCT04608838; JapicCTI-194570 and Clinical Trials. gov.

Abstract As the goal of mechanical thrombectomy is shifting toward mTICI-3 rather than mTICI-2b, we sought to clarify the limitation of the effect of mTICI-3. A post-hoc analysis of a registry of large-vessel occlusion stroke from 46 centers was conducted. Among 2,420 registered patients, 725 patients with anterior circulation occlusion who achieved successful reperfusion were analyzed. We compared outcomes between patients with mTICI-3 and mTICI-2b, and investigated how the effect of mTICI-3 changed according to baseline characteristics and time course. The proportion of patients with favorable outcomes (mRS 0–2 at day 90) was higher among patients with mTICI-3 compared to those with mTICI-2b (adjusted OR, 2.10; 95% CI, 1.49–2.97). There was no heterogeneity in the effect of mTICI-3 with respect to age, neurological deficit, alteplase use, occluded vessels, or infarct size. mTICI-3 was associated with favorable outcomes when the puncture-to-reperfusion time was

Introduction: In Japan, there are more board‐certified neurosurgeons than board‐certified neurologists, and a significant part of stroke practice is provided by neurosurgeons. In neuroendovascular therapy practice, the trend of neurosurgeons to be in majority is more pronounced. The most of neuroendovascular therapy specialists (n = 1,586) certified by the Japanese Society for Neuroendovascular Therapy (JSNET) consists of neurosurgeons, and the proportion of neurologists/internists is only 8% (n = 128) as of April 2021. The aim of this study is to investigate the current status and roles of interventional neurologists, the minority providing neuroendovascular therapy, in Japanese clinical setting. Methods: Between 16th and 28th February 2021, the Japan Society of Vascular and Interventional Neurology (JSVIN) conducted a survey for society‐member neurologists and internists using questionnaires on Google Forms. The questionnaires consisted of 11 items regarding years after graduation, facility location, department, work style (full‐time or concurrent interventionalist), diseases for which respondents were engaged, disease/procedure preferences which respondents would treat by themselves, respondents’ roles in their own neuroendovascular therapy team, and others. Results: Replies were obtained from 112 (67.1%) out of all JSVIN‐member neurologists and internists (n = 167). The respondents included 71 JSNET‐certified specialists and they consisted of 56.3% of all the JSNET‐certified neurologists/internists. The departments to where the respondents belonged were Neurology in 66%, Cerebrovascular medicine in 25%, Neuroendovascular therapy in 4%, and Neurosurgery in 3%. The median years after graduation was 15 years (interquartile range, 10 – 21 years) and the proportion of respondents who have graduated 10 years or less was 30%. Respondents’ facilities were distributed around 27 prefectures of all 47 Japanese prefectures and a significant proportion of those was located in urban area; 20% in Osaka and 13% in Tokyo. The number of full‐time interventionalist was only 1. Sixty‐three (56%) were concurrently engaged in general neurology practice, and 33 (30%) in stroke neurology practice. The proportions of diseases for which the respondents were engaged were ischemic cerebrovascular diseases (acute large vessel occlusion strokes, carotid stenoses, and others) in 100%, hemorrhagic cerebrovascular diseases (cerebral aneurysms, arteriovenous shunts, and others) in 44%, and other diseases (tumors, spinal vascular disorders, and others) in 28%. The proportions of disease/procedure preferences which respondents would treat by themselves were acute stroke thrombectomy in 90%, carotid/intracranial stenoses in 87%, ruptured cerebral aneurysms in 38%, unruptured cerebral aneurysms in 31%, cerebral arteriovenous shunts in 33%, brain tumors in 29%, spinal vascular disorders in 13%, and pediatric diseases in 3%. Respondents’ roles in their own neuroendovascular therapy team were diagnostic performances based on neurologist’s skills in 89%, comorbidity assessment and management based on internist’s skills in 88%, precise neurological evaluation in 77%, neurosonological evaluation in 75%, and establishments of in‐hospital workflow/multi‐disciplinary collaboration in 71%. Conclusions: Most of interventional neurologists in Japan were engaged in neuroendovascular therapy mainly for ischemic cerebrovascular diseases in parallel with general neurology and/or stroke neurology practices. Interventional neurologists’ skill set developed in neurology/internist trainings and practices might contribute to the quality improvement of neuroendovascular therapy in Japan.

In clinical practice, acute post-stroke paresis of the extremities fundamentally complicates timely rehabilitation of motor functions; however, recently, residual and distorted musculoskeletal signals have been used to initiate feedback-driven solutions for establishing motor rehabilitation. Here, we investigate the possibilities of basic hand gesture recognition in acute stroke patients with hand paresis using a novel, acute stroke, four-component multidomain feature set (ASF-4) with feature vector weight additions (ASF-14NP, ASF-24P) and supervised learning algorithms trained only by surface electromyography (sEMG). A total of 19 (65.9 ± 12.4 years old; 12 men, seven women) acute stroke survivors (12.4 ± 6.3 days since onset) with hand paresis (Brunnstrom stage 4 ± 1/4 ± 1, SIAS 3 ± 1/3 ± 2, FMA-UE 40 ± 20) performed 10 repetitive hand movements reflecting basic activities of daily living (ADLs): rest, fist, pinch, wrist flexion, wrist extension, finger spread, and thumb up. Signals were recorded using an eight-channel, portable sEMG device with electrode placement on the forearms and thenar areas of both limbs (four sensors on each extremity). Using data preprocessing, semi-automatic segmentation, and a set of extracted feature vectors, support vector machine (SVM), linear discriminant analysis (LDA), and k-nearest neighbors (k-NN) classifiers for statistical comparison and validity (paired t-tests, p-value < 0.05), we were able to discriminate myoelectrical patterns for each gesture on both paretic and non-paretic sides. Despite any post-stroke conditions, the evaluated total accuracy rate by the 10-fold cross-validation using SVM among four-, five-, six-, and seven-gesture models were 96.62%, 94.20%, 94.45%, and 95.57% for non-paretic and 90.37%, 88.48%, 88.60%, and 89.75% for paretic limbs, respectively. LDA had competitive results using PCA whereas k-NN was a less efficient classifier in gesture prediction. Thus, we demonstrate partial efficacy of the combination of sEMG and supervised learning for upper-limb rehabilitation procedures for early acute stroke motor recovery and various treatment applications.

We hypothesized that gait treatment with a wearable cyborg Hybrid Assistive Limb (HAL) would improve the walking ability of patients with hemiparesis after stroke. This study aims to evaluate the efficacy and safety of gait treatment using HAL versus conventional gait training (CGT) in hemiplegic patients with acute stroke and establish a protocol for doctor-initiated clinical trials for acute stroke. We will enroll patients with acute stroke at the University of Tsukuba Hospital. This study is a single-center, randomized, parallel-group, controlled trial (HAL group, n = 20; control group, n = 20) that will include three phases: (1) pre-observation phase (patient enrollment, baseline assessment, and randomization); (2) treatment phase (nine sessions, twice or thrice per week over 3−4 weeks; the HAL and control groups will perform gait treatment using HAL or CGT, respectively, and finally (3) post-treatment evaluation phase. The Functional Ambulation Category score will be the primary outcome measure, and the following secondary outcome measures will be assessed: Mini-Mental State Examination, Brunnstrom recovery stage of lower limbs, Fugl–Meyer assessment of lower limbs, 6-min walking distance, comfortable gait speed, step length, cadence, Barthel Index, Functional Independence Measure, gait posture, motion analysis (muscle activity), amount of activity (evaluated using an activity meter), stroke-specific QOL, and modified Rankin Scale score. The baseline assessment, post-treatment evaluation, and follow-up assessment will evaluate the overall outcome measures; for other evaluations, physical function evaluation centered on walking will be performed exclusively, excluding ADL and QOL scores. This study is a randomized controlled trial that aims to clarify the efficacy and safety of gait treatment using HAL compared with CGT in hemiplegic patients with acute stroke. In addition, we aim to establish a protocol for doctor-initiated clinical trials for acute stroke based on the study results. If our results demonstrate the effectiveness of the proposed treatment regarding outcomes of patients with hemiplegic acute stroke, this study will promote the treatment of these patients using the HAL system as an effective tool in future stroke rehabilitation programs. The study protocol was registered with the Japan Registry of Clinical Trials on October 14, 2020 (jRCTs032200151).

Introduction: We hypothesized that an endovascular electroencephalogram (eEEG) can detect subdural electrode (SDE)-detectable, scalp EEG-undetectable epileptiform discharges. The purpose of this study is, therefore, to measure SDE-detectable, scalp EEG-undetectable epileptiform discharges by an eEEG on a pig. Methods: A pig under general anesthesia was utilized to measure an artificially generated epileptic field by an eEEG that was able to be detected by an SDE, but not a scalp EEG as a primary outcome. We also compared the phase lag of each epileptiform discharge that was detected by the eEEG and SDE as a secondary outcome. Results: The eEEG electrode detected 113 (97%) epileptiform discharges (97% sensitivity). Epileptiform discharges that were localized within the three contacts (contacts two, three and four), but not spread to other parts, were detected by the eEEG with a 92% sensitivity. The latency between peaks of the eEEG and right SDE earliest epileptiform discharge ranged from 0 to 48 ms (mean, 13.3 ms; median, 11 ms; standard deviation, 9.0 ms). Conclusion: In a pig, an eEEG could detect epileptiform discharges that an SDE could detect, but that a scalp EEG could not.

We hypothesized that a single-leg version of the Hybrid Assistive Limb (HAL) system could improve the gait and physical function of patients with hemiparesis following a stroke. In this pilot study, we therefore compared the efficacy of HAL-based gait training with that of conventional gait training (CGT) in patients with acute stroke. Patients admitted to the participating university hospital were assigned to the HAL group, whereas those admitted to outside teaching hospitals under the same rehabilitation program who did not use the HAL were assigned to the control group. Over 3 weeks, all participants completed nine 20 min sessions of gait training, using either HAL (i.e., the single-leg version of HAL on the paretic side) or conventional methods (i.e., walking aids and gait orthoses). Outcome measures were evaluated before and after the nine training sessions. The Functional Ambulation Category (FAC) was the primary outcome measure, but the following secondary outcome measures were also assessed: National Institutes of Health Stroke Scale, Fugl–Meyer Assessment (Lower Extremity), comfortable walking speed, step length, cadence, 6-min walk distance, Barthel Index, and Functional Independence Measure. In total, 22 post-stroke participants completed the clinical trial: 12 in the HAL group and 10 in the CGT group. No serious adverse events occurred in either group. The HAL group showed significant improvement in FAC after nine sessions when compared with the CGT group (P = 0.014). However, secondary outcomes did not differ significantly between the groups. Our results demonstrate that HAL-based gait therapy may improve independent walking in patients with acute stroke hemiplegia who are dependent on ambulatory assistance. A larger-scale randomized controlled trial is needed to clarify the effectiveness of single-leg HAL therapy.Clinical Trial Registration: UMIN Clinical Trials Registry, identifier UMIN000022410.

PurposeRecent reports have posed doubts about the effect of preradiosurgical embolization in brain arteriovenous malformation (AVM) because it makes the planning of stereotactic radiosurgery (SRS) difficult and has the risk of recanalization out of the target. We investigated whether the performance and quality of embolization may influence the success of SRS based on a retrospective case cohort study.Materials and MethodsSeventy-three patients who underwent embolization followed by SRS between 2003 and 2012 in eight institutes with neurointerventionists were considered. They were divided into the following two groups at 3 years of follow up after the final SRS: “successful occlusion group” (S group), with radiologically complete occlusion of AVM; and “non-successful occlusion group” (N group) with persistent remnant nidus or abnormal vascular networks. Patient background, AVM profile, embolization performance grade and complications were compared in each group. The quality of embolization was evaluated with the new grading system: embolization performance grade (E grade), specializing the achievement of nidus embolization. E grade A was defined as sufficient nidus embolization with more than half of the total number of feeders achieving nidus penetration. E grade B was defined as less than half achievement of nidus embolization, and E grade C was defines as failure to perform nidus embolization.ResultsForty-three patients were included in the S group, and 29 patients were included in the N group. The size and Spetzler-Martin grade of AVM and the rate of diffuse type was higher in the N group without statistical significance. The embolization performance level according to E grade indicated a significantly higher rate of successful embolization with more than 50% of nidus penetration in the S group (P

BackgroundEndovascular therapy has been shown to be effective in patients with acute cerebral large‐vessel occlusion, but real‐world efficacies are unknown. Methods and ResultsWe conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large‐vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score–matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score–matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively (P=0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10–1.86, P=0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses. ConclusionsEndovascular therapy decreased disabilities at 90 days in real‐world patients with acute cerebral large‐vessel occlusion. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02419794.

Spontaneous intracerebral hematomas usually produce the sudden onset of devastating neurological symptoms. We describe a case showing slowly progressive clinical symptoms followed by a sudden deterioration caused by two different types of intracerebral hematomas coexisting in the adjacent area. A 72-year-old female with a 2-year history of Alzheimer’s disease and a 3-month history of occasional headache and vomiting was admitted after she experienced the sudden onset of right hemiparesis and a speech disturbance. Neuroradiological examinations demonstrated two different types of intracerebral hematomas coexisting in the left temporal lobe. The patient underwent a left frontotemporal craniotomy. A solid hematoma was found immediately below the cortex and a large hematoma cavity, which contained degraded bloody fluid, was found below the solid hematoma. Histological study demonstrated an arteriovenous malformation (AVM). The AVM may have been responsible for the pathogenesis of these two different types of intracerebral hematomas. Initially, a silent intracerebral hemorrhage from the AVM and liquefaction of the hematoma probably formed the cavity and repeated small subclinical hemorrhages into the cavity during a prolonged period of time may have caused the growth of the inner hematoma. The sudden rupture of the AVM most likely caused the outer solid hematoma, resulting in the abrupt onset of hemiparesis and speech disturbance. This is the first case to demonstrate two different types of intracerebral hematomas coexisting in the adjacent area. A possible mechanism for this rare condition is discussed.

Background Atherothrombotic stroke-related large vessel occlusion (AT-LVO) is caused by two etiologies, the intracranial artery occlusion due to in situ occlusion (intracranial group) or due to embolism from cervical carotid occlusion or stenosis (tandem group). The prognosis and reocclusion rate of each etiology after endovascular therapy (EVT) is unclear. Methods We conducted a historical multicenter registry study at 51 Japanese centers to compare the prognoses of AT-LVO between two etiologies. The primary outcome was the incidence of recurrent ischemic stroke or reocclusion of the treated vessels within 90 days after EVT. Each of the primary outcome means the incidence of recurrent ischemic stroke and reocclusion of the treated vessels within 90 days after EVT. Results We analyzed 582 patients (338 in the intracranial group and 244 in the tandem group). Patients in the intracranial group were younger (mean 71.9 vs 74.5, p=0.003), more of them were female and fewer of them were current smokers than those in the tandem group. In the tandem group, the patients' National Institutes of Health Stroke Scale score on admission was higher (13 vs 15, p=0.006), onset to puncture time was shorter (299 [145-631] vs 232 [144-459] minutes, p=0.03) and Alberta Stroke Program Early CT Score (ASPECTS) was lower (8 [7-9] vs 8 [6-9], p=0.0002). The primary outcome was higher in the intracranial group (22.5% vs 8.2%, p<0.0001). However, any ICH and death were not significantly different in the two groups. Conclusions The incidence of recurrent ischemic stroke or reocclusion after EVT for AT-LVO was higher in the intracranial group. [ABSTRACT FROM AUTHOR]

Background The optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between duration of DAPT and incidence of ischemic stroke in patients with cerebral aneurysm. Methods We registered patients with cerebral aneurysm who underwent SACE in 27 hospitals in Japan. Those treated with DAPT (aspirin and clopidogrel) were eligible for inclusion in a previously reported randomized control trial (RCT). Patients who were ineligible or refused to participate to the RCT were followed-up for 15 months after SACE as the non-RCT cohort. Our study examined both the RCT and non-RCT cohorts. The primary and secondary outcomes were ischemic stroke and hemorrhagic events. Results Among the 313 patients registered, 296 were included for analysis (of these, 136 were RCT patients and 160 were non-RCT patients). Patients who were treated with DAPT for more than 6 months (n=191) were classified as the long-term DAPT group. Those treated less than 6 months (n=105) were classified as the short-term group. The incidence of ischemic stroke did not significantly differ between the long-term group (2.5 per 100 person-years) and the short-term group (3.2 per 100 person-years); nor did incidence of hemorrhagic events (0.8 and 3.2 per 100 person-years, respectively). The period of DAPT was not significantly associated with incidence rates of ischemic stroke or hemorrhagic events. Conclusions Duration of DAPT was not associated with the incidence of ischemic stroke in the first 15 months after SACE. [ABSTRACT FROM AUTHOR]

Background During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, p

Objective To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. Methods We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. Results We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. Conclusions The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT. [ABSTRACT FROM AUTHOR]

Background The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual Antiplatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. Methods Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). Results A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. lschemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). Conclusions ln this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT. [ABSTRACT FROM AUTHOR]

Objective: Intraoperative rebleeding during endovascular treatment for ruptured intracranial aneurysms is associated with poor prognosis. Lumbar drainage is performed preoperatively to control intracranial pressure; however, it is associated with a risk of brain herniation or rebleeding because intracranial pressure may change rapidly. Therefore, this study aimed to examine the efficacy and safety of preoperative lumbar drainage. Methods: This retrospective study enrolled 375 patients who underwent endovascular treatment of ruptured intracranial aneurysms at our institution between April 2013 and March 2018. The incidence of rebleeding and clinical outcomes were compared between patients who did and did not undergo preoperative lumbar drainage. Results: Among the 375 patients with ruptured intracranial aneurysms, 324 (86.0%) and 51 (14.0%) patients did and did not undergo lumbar drainage, respectively. The incidence of rebleeding was 11/324 (3.4%) and 2/51 (3.9%) in lumbar drainage and nonlumbar drainage groups, respectively, with no statistical differences (p = 0.98). Of the rebleeding cases, 9/11 (81%) and 2/2 (100%) in lumbar drainage and nonlumbar drainage groups, respectively, were due to intraoperative bleeding, and 2/11 (19%) in the lumbar drainage group, the causes of the rebleeding were undetermined. The incidence of symptomatic vasospasm did not differ significantly between the groups (13.2% vs. 11.8%, P = 0.776), while the incidence of hydrocephalus (24.6% vs. 11.8%, P = 0.043) and meningitis (15.2% vs. 5.9%, P = 0.075) were slightly higher in the lumbar drainage group. Favorable clinical outcomes (modified Rankin Scale score <2) at discharge were less frequent in the lumbar drainage group (55.3% vs. 70.0%, P = 0.051). No significant differences were observed in the propensity score-matched analysis. Conclusion: Lumbar drainage before endovascular treatment for ruptured intracranial aneurysms is a safe procedure that does not increase the incidence of rebleeding. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Several astronauts have experienced severe headaches during spaceflight, but no studies have examined the associated brain microstructure and functional changes. Head-down-tilted bed rest (HDBR) is a well-established method for studying the physical effects of microgravity on the ground. In this study, we analyzed the changes in brain microstructure and function during headache caused by HDBR using diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging (R-fMRI). METHODS: We imaged 28 healthy subjects with DTI and R-fMRI in the horizontal supine position and HDBR. Using Tract-Based Spatial Statistics, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were compared between the headache and non-headache groups. Additionally, an analysis of functional connectivity (FC) was performed, followed by a correlation analysis between FC and numerical rating scale. RESULTS: HDBR caused headaches in 21 of 28 subjects. DTI analysis showed no significant change in fractional anisotropy after HDBR, whereas axial diffusivity, radial diffusivity, and mean diffusivity increased significantly. R-fMRI analysis showed a significant decrease in FC in several areas after HDBR. The headache group showed significantly higher FC before HDBR, and both groups showed higher FC after HDBR. Correlation analysis showed a positive correlation between FC and numerical rating scale before HDBR but negative after HDBR. DISCUSSION: We demonstrated the image change in the acute phase of space headache by HDBR using DTI and R-fMRI. Changes in brain microstructure and function specific to patients developing headaches may be evaluated by imaging. [ABSTRACT FROM AUTHOR]