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Techniques for triggering neural differentiation of embryonic and induced pluripotent stem cells into neural stem cells and neurons have been established. However, neural induction of mesenchymal stem cells, including dental pulp stem cells (DPSCs), has been assessed primarily based on neural-related gene regulation, and detailed studies into the characteristics and differentiation status of cells are lacking. Therefore, this study was aimed at evaluating the cellular components and differentiation pathways of neural lineage cells obtained via neural induction of human DPSCs. Human DPSCs were induced to neural cells in monolayer culture and examined for gene expression and mechanisms underlying differentiation using microarray-based ingenuity pathway analysis. In addition, the neural lineage cells were subjected to single-cell RNA sequencing (scRNA-seq) to classify cell populations based on gene expression profiles and to elucidate their differentiation pathways. Ingenuity pathway analysis revealed that genes exhibiting marked overexpression, post-neuronal induction, such as FABP7 and ZIC1, were associated with neurogenesis. Furthermore, in canonical pathway analysis, axon guidance signals demonstrated maximum activation. The scRNA-seq and cell type annotations revealed the presence of neural progenitor cells, astrocytes, neurons, and a small number of non-neural lineage cells. Moreover, trajectory and pseudotime analyses demonstrated that the neural progenitor cells initially engendered neurons, which subsequently differentiated into astrocytes. This result indicates that the aforementioned neural induction strategy generated neural stem/progenitor cells from DPSCs, which might differentiate and proliferate to constitute neural lineage cells. Therefore, neural induction of DPSCs may present an alternative approach to pluripotent stem cell-based therapeutic interventions for nervous system disorders. [ABSTRACT FROM AUTHOR]

Background The effects of sleep deprivation on surgical performance have been well documented. However, reports on the effects of sleep deprivation on microneurosurgery are limited. This study aimed to investigate the effects of sleep deprivation on microneurosurgery. Methods Ten neurosurgeons participated in the anastomosis of a vessel model using a microscope in sleep-deprived and normal states. We evaluated the procedure time (PT), stitch time (ST), interval time (IT), number of unachieved movements (NUM), leak rate, and practical scale for anastomosis quality assessment. Each parameter was compared between normal and sleep-deprived states. Subanalyses were performed on the two groups based on PT and NUM under the normal state (proficient and nonproficient groups). Results Although no significant differences were noted in PT, ST, NUM, leak rate, or practical scale, IT was significantly prolonged under sleep deprivation compared with the normal state (mean: 258.8 ± 94.0 vs. 199.3 ± 74.9 seconds; p = 0.02). IT was significantly prolonged under sleep deprivation in the nonproficient group based on both PT and NUM (PT: 234.2 ± 71.6 vs. 321.2 ± 44.7 seconds, p = 0.04; NUM: 173.3 ± 73.6 vs. 218.7 ± 97.7; p = 0.02), whereas no significant difference was observed in the proficient group (PT: 147.0 ± 47.0 vs. 165.3 ± 61.1 seconds, p = 0.25; NUM: 173.3 ± 73.6 vs. 218.7 ± 97.7; p = 0.25). Conclusions Although IT was significantly prolonged under sleep deprivation in the nonproficient group, there was no decline in performance skills in either the proficient or nonproficient group. The effect of sleep deprivation may require caution in the nonproficient group, but it is possible that certain microneurosurgical outcomes can be achieved under sleep deprivation. [ABSTRACT FROM AUTHOR]

Purpose: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are recommended based on certain risk factors. The volume of an institution's treatment experience may be associated with good clinical outcomes. There is a dilemma between the treatment strategy based on risk factors and the experience volume. Therefore, we investigated the clinical outcomes of CAS performed at institutions that selected the treatment strategy based on risk factors and those that performed CAS at the first-line treatment. Materials and Methods: Patients who underwent CAS at 5 institutions were included in this retrospective case-control study. We defined CEA/CAS institutions as those that selected the treatment option based on risk factors, and CAS-first institutions as those that performed CAS as the first-line treatment. We investigated cases of ischemic stroke, hemorrhagic stroke, myocardial infarction, and deaths within 30 days of the intervention between the CEA/CAS- and CAS-first institution groups. One-to-one propensity score matching was performed to compare rates of ischemic and hemorrhagic strokes within 30 days of the intervention. Results: A total of 239 and 302 patients underwent CAS at the CEA/CAS institutions and CAS-first institutions, respectively; ischemic stroke occurred in 12 (5.0%) and 7 patients (2.3%), respectively (p=0.09). No differences in major ischemic strokes (0.8% vs 1.3%; p=0.59), hemorrhagic strokes (0.4% vs 0.3%; p=0.87), or deaths (0.0% vs 0.7%; p=0.21) were observed. Myocardial infarction did not occur in either group. Propensity score analysis showed that ischemic stroke (odds ratio: 1.845, 95% confidence interval: 0.601–5.668, p=0.28) and hemorrhagic stroke (odds ratio: 1.000, 95% confidence interval: 0.0061–16.418, p=1.00) were not significantly associated with either institution group. Conclusions: The CAS-specific treatment strategies for CAS can achieve the same level of outcomes as the treatment strategy based on risk factors. The CAS performed based on risk factors in CEA/CAS institutions and the treatment of more than 30 patients/year/institution in CAS-first institutions were associated with good clinical outcomes. [ABSTRACT FROM AUTHOR]

The success of cell transplantation therapy for ischemic stroke is hindered by the low cell survival rate in poststroke brain, due in part to high free radical production and ensuing oxidative stress. We have developed redox nanoparticles to eliminate reactive oxygen species. In this study, we tested the protective efficacy of these redox nanoparticles in cell culture and a mouse model of ischemic stroke. Induced human dental pulp stem cells were subjected to oxygen–glucose deprivation and reoxygenation to recapitulate ischemia and reperfusion in the penumbra surrounding a cerebral infarct. Cell viability using WST-8 assay, apoptosis using TUNEL, free radicals using MitoSOX, and inflammatory cytokines using ELISA kit were measured in the presence and absence of redox nanoparticles after oxygen–glucose deprivation and reoxygenation. The scavenging activity of redox nanoparticles against reactive oxygen species was detected by electron spin resonance. Moreover, induced cells were transplanted intracerebrally into to the distal middle cerebral artery occlusion model with and without redox nanoparticles, and the survival rate measured. Cell viability was enhanced, while apoptosis, free radical generation, and inflammatory cytokine expression levels were reduced in cultures with redox nanoparticles. Further, reduced redox nanoparticles were detected in the cytoplasm, indicating free radical scavenging. Addition of redox nanoparticles also improved the survival rate of transplanted cells after 6 weeks in vivo. These redox nanoparticles may increase the applicability and success of induced stem cell therapy for ischemic stroke patents by promoting long-term survival. [ABSTRACT FROM AUTHOR]

Stroke rehabilitation with mechanical assistance improves outcomes by facilitating repetition and relieving the care burden of therapy staff. Here, we tested the Medical Care Pit (MCP) walking assistance training device in the rehabilitation of eight acute stroke patients (median age 60.7 ± 16.3 years) who had recently suffered ischemic (three) or hemorrhagic (five) stroke (14.1 ± 6.5 days). Patients received standard rehabilitation approximately 5 days per week (weekdays only), plus MCP therapy twice a week, totaling four MCP sessions over 2 weeks. Fugl–Meyer Assessment-Lower Extremities (FMA-LE), Functional Ambulation Category (FAC), and other gait-associated parameters were measured. Over the 10.5 ± 1.6 days of therapy, MCP qualitatively assisted in gait analysis and real-time patient feedback while independent walking scores significantly improved (FAC 2.2 ± 0.8 to 3.1 ± 1.3, p = 0.020). FMA-LE scores also slightly improved but not to significance (p = 0.106). Objective burden on patients, as measured by modified Borg scale, was significantly improved (2.7 ± 1.6 to 2.0 ± 1.6, p = 0.014). In terms of questionnaires, anxiety scores for the physical therapist regarding gait training and falling with MCP significantly decreased (3.8 ± 2.3 to 1.0 ± 1.6; p = 0.027 and 3.1 ± 2.2 to 0.8 ± 1.3; p = 0.045) from the first to fourth sessions. Taken together, MCP, in addition to the usual rehabilitation program, was effective in gait rehabilitation for independent walking and relieved burdens on the patients. Such walking support systems may be an important part of acute stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Parent artery occlusion (PAO) is an effective treatment for hemorrhagic diseases associated with the internal carotid artery. There are several reports of long-term cerebral infarction or the formation of de novo cerebral aneurysms following PAO. Materials and methods: We retrospectively reviewed these complications in 38 patients who underwent PAO for therapeutic treatment. We investigated perioperative cerebral infarctions, long-term cerebral infarctions, and de novo aneurysms. Results: The mean age of the patients was 64.0 years, and 25 patients (65.8%) were female. The causative diseases were unruptured (n = 19; 50.0%) and ruptured (n = 8; 21.1%) aneurysms. PAO was performed after ischemic tolerance was assessed with balloon test occlusion (BTO), and BTO was performed in 34 patients, of whom 25 (73.5%) had ischemic tolerance. Twenty-six patients (68.4%) were treated with PAO alone, eight (23.5%) with low-flow bypass, and six (17.6%) with high-flow bypass. Perioperative complications occurred in five patients (13.2%): two of the 26 patients (7.7%) who underwent scheduled treatment and three of the 12 patients (25.0%) who underwent emergency treatment. One patient (2.6%) had long-term de novo aneurysm, and none developed cerebral infarction. Conclusions: These results showed that the assessment of ischemic tolerance by performing BTO and appropriate revascularization in scheduled treatments are important to reduce perioperative and long-term cerebral infarctions. PAO must be performed with greater caution in emergency treatment. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Parent artery occlusion is a definitive treatment method for preventing rebleeding of dissecting aneurysms. We herein report a case of a ruptured distal posterior inferior cerebellar artery (PICA) dissecting aneurysm treated with internal trapping using n-butyl-2-cyanoacrylate (NBCA). A 65-year-old man visited our hospital with a complaint of headache and neck pain that began 1 week before his arrival. He had a history of spontaneous subarachnoid hemorrhage of unknown cause. Computed tomography of the brain revealed a small amount of subarachnoid hemorrhage, and distal subtraction angiogram showed a distal PICA dissecting aneurysm. We placed a guiding catheter in the left vertebral artery and an intermediate catheter in the PICA. A microcatheter was guided toward the proximal side of the aneurysm and was wedged into the parent artery. The dissecting aneurysm was treated with parent artery occlusion using 50% NBCA. The postoperative course was uneventful, and the patient was discharged 3 weeks after treatment without any neurological deficit. Parent artery occlusion with internal trapping using NBCA could be a safe and definitive treatment method for distal PICA dissecting aneurysms. Angiographical evaluation of the collateral network in the distal branch of PICA before embolization and wedged microcatheter technique in the parent artery are important for successful embolization using NBCA. [ABSTRACT FROM AUTHOR]

Purpose: Arteriovenous fistulas (AVFs) adjacent to the clivus, such as cavernous sinus dural AVFs (CSDAVFs) and condylar AVFs, sometimes have an intraosseous shunted pouch and recruit blood supply from transosseous feeders. Precise analysis of transosseous feeders regarding the clival lesion has not yet been performed. Therefore, this study aimed to clarify the characteristics and identity of transosseous feeders in clival lesions. Methods: Patients with CSDAVFs and condylar AVFs, who underwent high-resolution cone-beam computed tomography or three-dimensional rotational angiography in our institute, were included. The frequency, type of branch, penetrating point, and termination of intraosseous feeders were retrospectively evaluated. Results: A total of 31 patients with 36 lesions in CSDAVFs and 8 patients with 8 lesions in condylar AVFs underwent angiography. For CSDAVFs, 38 transosseous feeders were detected in 23 out of 31 patients, including 22 in the pharyngeal branch of the ascending pharyngeal artery (APhA), 6 in the hypoglossal branch of the APhA, 6 in the accessory meningeal artery, 3 in the meningohypophyseal trunk (MHT), and 1 in the anterior branch of the middle meningeal artery. For condylar AVFs, 24 transosseous feeders were detected in all 8 patients, including 11 in the pharyngeal branches of the APhA, 7 in the hypoglossal branch of the APhA, 6 in the segmental artery from the vertebral artery, and 2 in the MHT. Conclusion: Transosseous feeders of AVFs around the clivus, which are frequently seen in AVFs of this area, mainly arise from ventral clival branches and from pharyngeal branches of the APhA. [ABSTRACT FROM AUTHOR]

Background : Neurosurgeons often experience increased cortical microvascularization in Moyamoya disease (MMD). However, there are no previous reports that radiologically evaluated preoperative cortical microvascularization. We investigated the development of cortical microvascularization and clinical characteristics of MMD using the maximum intensity projection (MIP) method. Methods: We enrolled 64 patients at our institution, including patients with MMD (n = 26), intracranial atherosclerotic disease (ICAD; n = 18), and unruptured cerebral aneurysms (n = 20) as the control group. All patients underwent three-dimensional rotational angiography (3D-RA). The 3D-RA images were reconstructed using partial MIP images. Cortical microvascularization was defined as the vessels that branched off from the cerebral arteries and were classified as grade 0–2 depending on their development. Results: Cortical microvascularization observed in patients with MMD was classified into grade 0 (n = 4, 8.9%), grade 1 (n = 17, 37.8%), and grade 2 (n = 24, 53.3%). The development of cortical microvascularization was more common in the MMD group than in the other groups. The inter-rater reliability measured using weighted kappa was 0.68 (95% confidence interval = 0.56–0.80). There were no significant differences in cortical microvascularization according to the onset type and hemispheres. Cortical microvascularization correlated with periventricular anastomosis. Most patients with Suzuki classifications 2–5 developed cortical microvascularization. Conclusion: Cortical microvascularization was characteristic of patients with MMD. These findings developed in the early stages of MMD and may act as a bridge to the development of periventricular anastomosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hybrid Assistive Limb (HAL) is a wearable human assistant cyborg-type robot that helps lower-leg movement based on bioelectrical signals detected from the voluntary movement of the person wearing it. In this study, we developed a novel staged HAL treatment protocol for patients with acute stroke. The Regain Program for Gait with HAL (RPG-HAL) was formulated in four steps, based on the severity of limb paralysis. Twenty-one patients with acute stroke received a combination treatment of RPG-HAL and conventional rehabilitation. The feasibility and safety of RPG-HAL were evaluated based on changes in physical function and activities of daily living (ADL). RPG-HAL yielded improvement in gait speed, cadence, step length, and functional ambulation category (FAC). The effect size was >0.8 in all measurements. FAC (1.90) and Barthel Index (BI) (1.92) exhibited the highest scores. Twelve out of 14 patients with FAC 0 before RPG-HAL reached the upper FAC. Thus, earlier intervention using RPG-HAL as improving physical function, ADL, and gait ability in patients with stroke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cell therapy for peripheral nerve injury is a promising strategy as regenerative medicine that restores neurological function. However, challenges remain in producing suitable and sufficient amounts of autologous cells for promoting nerve regeneration. This study aimed to identify the characteristics of neural lineage cells (NLCs) differentiated from dental pulp stem cells (DPSCs) and reveal their effect on functional recovery and nerve regeneration after cell transplantation into an immunodeficient rat using a nerve guide conduit. Here we report a protocol of neural induction in monolayer culture and characterize NLCs in vitro. Furthermore, NLCs were transplanted into an immunodeficient rat model with a 10-mm sciatic nerve defect, and cell survival and differentiation were investigated in vivo. Outcomes of nerve regeneration were also assessed using the remyelinated axon numbers, myelin sheath thickness, electrophysiological activities, and gastrocnemius muscle mass. NLCs comprised neuronal, astrocyte, oligodendrocyte, and neural crest lineage cells. NLCs enhanced the activities of endothelial cells, Schwann cells, and neurons in a paracrine-dependent manner in vitro. At 2 weeks post-transplantation, numerous transplanted NLCs differentiated into platelet-derived growth factor receptor alpha (PDGFRα) + oligodendrocyte progenitor cells (OPCs) and a few PDGFRα + /p75 neurotrophin receptor + Schwann cell-like cells derived from OPCs were observed. At 12 weeks post-transplantation, human Schwann cell-like cells survived, and axon growth, remyelination, electrophysiological activities, and muscle atrophy were improved. This study demonstrates the broad application of our protocol of neural induction of DPSCs and portrays the efficacy of transplantation of NLCs derived from human DPSCs as a promising strategy for peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Human mesenchymal stem cells are a promising cell source for the treatment of stroke. Their primary mechanism of action occurs via neuroprotective effects by trophic factors, anti-inflammatory effects, and immunomodulation. However, the regeneration of damaged neuronal networks by cell transplantation remains challenging. We hypothesized that cells induced to neural lineages would fit the niche, replace the lesion, and be more effective in improving symptoms compared with stem cells themselves. We investigated the characteristics of induced neural cells from human dental pulp tissue and compared the transplantation effects between these induced neural cells and uninduced dental pulp stem cells. Induced neural cells or dental pulp stem cells were intracerebrally transplanted 5 days after cerebral infarction induced by permanent middle cerebral artery occlusion in immunodeficient mice. Effects on functional recovery were also assessed through behavior testing. We used immunohistochemistry and neuron tracing to analyze the differentiation, axonal extension, and connectivity of transplanted cells to the host's neural circuit. Transplantation of induced neural cells from human dental pulp ameliorated functional recovery after cerebral infarction compared with dental pulp stem cells. The induced neural cells comprised both neurons and glia and expressed functional voltage, and they were more related to neurogenesis in terms of transcriptomics. Induced neural cells had a higher viability than did dental pulp stem cells in hypoxic culture. We showed that induced neural cells from dental pulp tissue offer a novel therapeutic approach for recovery after cerebral infarction. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Background: With a rapidly aging population in Japan, locomotive syndrome is becoming an increasingly serious social problem. Exercise therapy using the lumbar type HAL, which is a wearable robot suit that can assist voluntary hip joint motion, would be expected to cause some beneficial effects for people with locomotive syndrome. The purpose of this study was to assess whether the deterioration of low back pain and any other adverse events would occur following HAL exercise therapy. Moreover, the changes of motor ability variables were evaluated.Methods: We enrolled 33 participants (16 men, 17 women) with locomotive syndrome in this study. They received exercise training (sit-to-stand, lumbar flexion-extension, and gait training) with HAL (in total 12 sessions). We assessed the change of low back pain (lumbar VAS). More than 50% and 25 mm increase compared to baseline was defined as adverse events. One-leg standing time (OLST), 10-m walking test (10MWT), Timed Up and Go test (TUG), 1-min sit-to-stand test (1MSTS), FIM mobility scores and EQ-5D were measured.Results: Of the 33 participants, 32 (16 men, 16 women) (97.0%) completed all 12 exercise training sessions using the lumbar type HAL. One woman aged 82 years withdrew because of right upper limb pain after the second session regardless of the use of HAL. There was no participant who had deterioration of low back pain. Any other adverse events including external injuries and/or falling, skin disorders, uncontrollable cardiovascular or respiratory disorders, and other health disorders directly related to this exercise therapy did not occur. Several outcome measures of motion ability including OLST, TUG and 1MSTS, EQ VAS and lumbar pain improved significantly after this HAL training.Conclusions: Almost all patients with locomotive syndrome completed this exercise training protocol without any adverse events related to HAL. Furthermore, balance function variables including OLST, TUG and 1MSTS improved after this HAL exercise therapy even though mobility function variables including 10MWT and FIM mobility scores did not show any significant change. These findings suggest that the exercise therapy using the lumbar type HAL would be one of the options for the intervention in locomotive syndrome. [ABSTRACT FROM AUTHOR]

Background: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE.Methods: This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is "continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance." In both groups, diazepam is initially administered at 1-20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000-3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes.Discussion: The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application.Trial Registration: Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019. [ABSTRACT FROM AUTHOR]

Objective: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam vs. fosphenytoin. We compare the safety of intravenous levetiracetam and fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. Methods: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous fosphenytoin on the day of admission were defined as the fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and fosphenytoin groups. Results: The analysis examined data of 5,667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2 vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73–1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the fosphenytoin group (3.2 vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43–0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. Conclusion: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for fosphenytoin, in adult status epilepticus. [ABSTRACT FROM AUTHOR]

The myoblast-mediated delivery of angiogenic genes represents a cell-based approach for targeted induction of therapeutic collateralization. Here, we tested the superiority of myoblast-mediated co-delivery of vascular endothelial growth factor-A (VEGF) together with platelet-derived growth factor-BB (PDGF-BB) on transpial collateralization of an indirect encephalomyosynangiosis (EMS) in a model of chronic cerebral ischemia. Mouse myoblasts expressing a reporter gene alone (empty vector), VEGF, PDGF-BB or VEGF and PDGF-BB through a single bi-cistronic vector (VIP) were implanted into the temporalis muscle of an EMS following permanent ipsilateral internal carotid artery occlusion in adult, male C57BL/6N mice. Over 84 days, myoblast engraftment and gene product expression, hemodynamic impairment, transpial collateralization, angiogenesis, pericyte recruitment and post-ischemic neuroprotection were assessed. By day 42, animals that received PDGF-BB in combination with VEGF (VIP) showed superior hemodynamic recovery, EMS collateralization and ischemic protection with improved pericyte recruitment around the parenchymal vessels and EMS collaterals. Also, supplementation of PDGF-BB resulted in a striking astrocytic activation with intrinsic VEGF mobilization in the cortex below the EMS. Our findings suggest that EMS surgery together with myoblast-mediated co-delivery of VEGF/PDGF-BB may have the potential to serve as a novel treatment strategy for augmentation of collateral flow in the chronically hypoperfused brain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Optic neuropathy due to an aneurysm is relatively rare, with only a few small case series on this topic, and no randomized trials having been published until now. As such, the functional prognosis and treatment for aneurysm-induced optic neuropathy remain controversial. Objective: We quantified optic nerve injuries using an objective index (the visual impairment score) and evaluated prognostic factors of postoperative visual function. Materials and Methods: Of 960 patients treated for an unruptured intracranial aneurysm, 18 (1.9%) patients had optic neuropathy. Visual acuity and visual field were assessed before surgery and 6 months' postoperatively. Cases were classified on the basis of treatment modality (coil embolization or flow alteration [FA]) and prognostic factors of the two treatment groups. Results: Of the 18 patients with an intracranial aneurysm and optic neuropathy, 12 (67%) were treated using coil embolization and 6 (33%) were FA. Visual function improved after surgery in 8 patients (44%), 5 (42%) in the coil embolization group, and 3 (50%) in the FA group. The visual function remained stable after surgery in 6 (33%) patients and worsened in 4 (22%). Patients with an aneurysms <15 mm in size had a favorable outcome (P = 0.05). Conclusions: Surgical treatment improved vision in 44% of cases, with no difference in the prognosis of coil embolization and FA and no effect of the duration of symptoms on outcomes. Further, the prognosis of visual function recovery was better for aneurysms <15 mm in diameter. [ABSTRACT FROM AUTHOR]

Hemiparetic gait is a common condition after stroke which alters importantly the quality of life of stroke survivors. In recent years, several robotic interventions have been developed to support and enhance rehabilitation strategies for such population. The Hybrid Assistive Limb® (HAL) robot suit is a unique device able to collect in real time bioelectric signals from the patient to support and enhance voluntary gait. HAL has been used before in early stages of stroke showing gait improvement after the intervention. However, evaluation of the coordination of gait has not been done yet. Coordination is a key factor for an adequate gait performance; consequently, its changes may be closely related to gait recovery. In this study, we used planar covariation to evaluate coordination changes in hemiparetic stroke patients after early HAL intervention. Before starting, impaired intersegmental coordination for the paretic and non-paretic side was evident. HAL intervention was able to induce recovery of the covariation loop shape and deviation from the covariation plane improving intersegmental coordination. Also, there was a tendency of recovery for movement range evidenced by comparison of peak elevation angles of each limb segment of the patients before and after HAL intervention, and also when compared to healthy volunteers. Our results suggest that early HAL intervention contributed to the improvement of gait coordination in hemiparetic stroke patients by reinforcing central pattern generators and therefore reshaping their gait pattern. Trial registration: UMIN000022410 2016/05/23. [ABSTRACT FROM AUTHOR]

Gait disturbance is commonly associated with stroke, which is a serious neurological disease. With current technology, various exoskeletons have been developed to provide therapy, leading to many studies evaluating the use of such exoskeletons as an intervention tool. Although these studies report improvements in patients who had undergone robotic intervention, they are usually reported with clinical assessment, which are unable to characterize how muscle activations change in patients after robotic intervention. We believe that muscle activations can provide an objective view on gait performance of patients. To quantify improvement of lateral symmetry before and after robotic intervention, muscle synergy analysis with Non-Negative Matrix Factorization was used to evaluate patients' EMG data. Eight stroke patients in their acute phase were evaluated before and after a course of robotic intervention with the Hybrid Assistive Limb (HAL), lasting over 3 weeks. We found a significant increase in similarity between lateral synergies of patients after robotic intervention. This is associated with significant improvements in gait measures like walking speed, step cadence, stance duration percentage of gait cycle. Clinical assessments [Functional Independence Measure-Locomotion (FIM-Locomotion), FIM-Motor (General), and Fugl-Meyer Assessment-Lower Extremity (FMA-LE)] showed significant improvements as well. Our study shows that muscle synergy analysis can be a good tool to quantify the change in neuromuscular coordination of lateral symmetry during walking in stroke patients. [ABSTRACT FROM AUTHOR]

Purpose. We evaluated improvements in gait after using the Hybrid Assistive Limb (HAL®) exoskeleton robot in a patient with late-onset neurological deterioration of lower extremity function after undergoing thoracic spine surgery for a myelopathy due to ossification of the ligamentum flavum. Case Presentation. A 70-year-old man participated in ten 20 min sessions of HAL intervention, twice weekly for five weeks. The effects of each HAL session were evaluated based on changes in performance on the 10 m walk test (10 MWT), lower limb kinematics quantified from motion capture, and the activation ratio of the gastrocnemius, measured before and after the intervention. Muscle activity was recorded using surface electromyography and synchronized to measured kinematics. The HAL intervention improved gait speed and step length, with an increase in the hip flexion angle during the swing phase and a decrease in the activation ratio of the gastrocnemius. The modified Ashworth scale improved from 1+ to 1 and International Standards for Neurological and Functional Classification of Spinal Cord Injury motor scores from 34 to 49. Conclusion. Intervention using the HAL exoskeleton robot may be an effective method to improve functional ambulation in patients with chronic spinal disorders. [ABSTRACT FROM AUTHOR]

PurposeTo determine whether gait training with a hybrid assistive limb (HAL) as an exoskeleton robotic device was safe and could increase functional mobility and gait ability in subacute stroke patients.MethodsThe participants were eight patients with post-stroke hemiparesis whose walking impairment and gait recovery curves had plateaued. The intervention program was gait training using HAL and a walker for 20 min daily 5 days a week for 5 weeks. The 10-m maximum walking speed (MWS), self-selected walking speed (SWS) and 2-min-walk test (2MT) without HAL were used as primary outcome measures to determine the effects of training. The Berg Balance Scale (BBS), Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA) and functional ambulation category (FAC) were assessed as secondary outcomes. These measures were assessed before and after the 5-week intervention program and were analyzed statistically using a pairedt-test.ResultsAll eight participants completed the intervention program with no adverse events. There were significant increases in MWS, SWS and 2MT. BBS, FMA and FAC also increased, but not significantly.ConclusionThe new HAL exoskeleton robotic device was efficient and safe for improving motor function and gait in patients in the subacute stage after stroke.Implications for RehabilitationGait training using HAL will improve gait ability of individuals with post stroke.The HAL achieve intensive gait training without increase spasticity and abnormal gait pattern. [ABSTRACT FROM PUBLISHER]

I Diagnosis was Atherothrombotic Cerebral Infarction (ACI), Subcortical Hemorrhage (SH), Brain Stem Infarction (BSI), Lacunar Infarct (LI) or Atherothrombotic Brain Stem Infarction (ABSI) i . [Extracted from the article]

Reports an autopsy case of an elder patient with intracranial arterial dissections involving the vertebrobasilar artery. Medical history of the patient; Results of the clinical, pathological and histopathological examinations done on the patient; Description of the intracranial arterial dissections.