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The relaxation time deduced experimentally from the ac response in amorphous As2Se3 is not consistent with the theoretical prediction of dielectric relaxation or hop-down motion in localized tail states (e.g. ≈10−8 s at 100 K). It is suggested that some other mechanisms, e.g. defect-related hopping, should be involved in the ac photo-response in a-As2Se3. Validity of the physical parameters deduced from the dc and ac photoconductivities are discussed. [Copyright &y& Elsevier]

Background: Status epilepticus, characterized by the temporal neurological deficits, often mimics acute ischemic stroke. We investigated the usefulness of magnetic resonance imaging for differentiation of status epilepticus from acute ischemic stroke., Methods: A retrospective case series of patients with status epilepticus who underwent brain magnetic resonance imaging. For comparative analysis, a series of patients with acute ischemic stroke caused by unilateral middle cerebral artery occlusion was used., Results: Ten patients (4 females and 6 males) with status epilepticus who underwent brain magnetic resonance imaging were included. The median age at diagnosis was 82 years (age range, 70-90 years). In all ten patients, hyperintensities in diffusion-weighted imaging with decreased apparent diffusion coefficient values, decreased venous intensity in susceptibility-weighted imaging, and hyperperfusion in arterial spin labeling perfusion were detected in the cortex of the affected side. Four patients showed an additional diffusion restriction in the thalamus. The apparent diffusion coefficient value of the lesional area was 13.1% less than the contralateral, which was less than one-third as acute ischemic stroke. Status epilepticus patients showed no change in medullary venous intensity of the affected area in susceptibility-weighted imaging, whereas acute ischemic stroke patients showed increased cortical and medullary venous intensity in affected hemisphere. Seven of eight patients with status epilepticus who underwent magnetic resonance angiography showed dilation of the cerebral arteries in the ipsilateral side., Conclusions: The combined use of diffusion-weighted imaging, susceptibility-weighted imaging, and arterial spin labeling perfusion may help accurate and prompt diagnosis of status epilepticus., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A , SCN10A , and SCN9A , which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A , SCN10A , and SCN9A . In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A , SCN10A , and SCN9A , respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.

Abstract: Welwalk is a one-leg robotic-assisted gait system for stroke hemiplegic patients. This study examined the feasibility and efficacy of gait training using Welwalk (Welwalk training) for hemiplegic patients in the early phase after stroke onset, via cooperation between acute care and rehabilitation hospitals. Seven acute stroke patients (mean number of days from onset = 7.9) with severe lower extremity paralysis participated. Patients underwent Welwalk training for 40 min/d, 5 d/wk in an acute care hospital, then 7 d/wk in a rehabilitation hospital with a seamless transition. Functional Independence Measure scores for walking were assessed weekly. The endpoint was reaching Functional Independence Measure walk score of 5 (supervision level). The primary outcome was improvement efficiency of Functional Independence Measure walk, which was the increase in Functional Independence Measure walk score divided by the number of weeks required. Functional Independence Measure walk score for all patients improved from 1.1 to 5 ( P = 0.01, r = 0.96). The mean number of weeks to achieve Functional Independence Measure walk score of 5 was 5 wks, and the improvement efficiency of Functional Independence Measure walk had a mean value of 0.9. No adverse events were reported during Welwalk training. Hemiparetic patients' gait independence may be safely and rapidly improved by starting Welwalk training in the early phase after stroke onset., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

[Purpose] Belt electrode-skeletal muscle electrical stimulation (B-SES) is a novel electrical muscle stimulation treatment that causes less pain and discomfort and induces contraction in a wider skeletal muscle area than conventional electrodes. However, the stimulation intensity depends on patients' subjectivity. In the present study, B-SES and an expiratory gas device were combined to analyze the kinesiophysiological data associated with changes in subjective intensity. [Participants and Methods] Seventeen healthy participants were recruited. The subjective intensities were set to four conditions (weak, normal, strong, and maximum tolerated intensity), and the stimulation was performed in each condition in the "metabolic mode" (frequency, 4 Hz; pulse width, 250 µs). The primary outcome was metabolic equivalents (METs), and this data were compared for each condition. [Results] METs generated by B-SES were 2.0 (1.0) for weak intensity, 2.7 (1.2) for normal intensity, 3.9 (1.3) for strong intensity, and 5.0 (1.3) for the tolerance limit intensity; differences detected between all subjective intensities were statistically significant. [Conclusion] These findings show that objective intensities of >3 METs, as recommended in rehabilitation prescriptions, can be achieved when the subjective intensity is set at strong or maximum tolerated. Treatment with B-SES may provide a viable alternative to therapeutic exercise., Competing Interests: All authors have no conflict of interest or financial to declare., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Objective: To investigate the effect of a wearable integrated volitional control electrical stimulation (WIVES) device that has been developed as more compact and simpler to use in daily life compared with conventional integrated volitional control electrical stimulation (IVES) devices., Design: Randomized controlled non-inferiority trial., Setting: Convalescent rehabilitation ward., Participants: Patients with paresis of the upper extremity (UE) after early subacute stroke (N=20)., Interventions: Eligible patients were randomized to receive IVES treatment or WIVES treatment for 8 hours per day for 28 days in daily living, in addition to standard rehabilitation treatment. In both groups, the extensor digitorum communis on the affected side was the target muscle for stimulation., Main Outcome Measure: Primary outcomes were assessed with Fugl-Meyer Assessment of the UE (FMA-UE) before and after treatment. Non-inferiority was determined with a specified margin of non-inferiority., Results: Twenty patients completed the trial (IVES group: n=10, WIVES group: n=10). FMA-UE improved in both groups. The mean change in FMA-UE was 4.7 for the IVES group and 6.0 for the WIVES group (P>.05, 95% confidence interval: -6.73 to 4.13). The mean difference between the groups was 1.3, and the upper 95% confidence interval did not exceed the non-inferiority margin., Conclusion: The effectiveness of WIVES treatment is non-inferior to that of IVES treatment. As a portable device, IVES may facilitate the use of affected upper extremities in daily living and may help improve paresis of the UE., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Disruption of the circadian rhythm and sleep-wake cycles is a consequence of aging and is associated with the cognitive decline and many neurodegenerative conditions. We investigated the bedtime, wake-up time, sleep timing (midpoint between bedtime and wake-up time), and sleep timing standard deviation (SD) using the actigraphy among 80 consecutive volunteers aged ≥ 60 years. Global cognitive function and executive function of detailed cognitive domains were evaluated using the mini-mental state examination (MMSE) and Wisconsin card sorting test (WCST) and subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). The category achievement (CA), total errors (TE), perseverative errors of Nelson (PEN), non-perseverative errors (NPE), and difficulties in maintaining set (DMS) on the WCST were significantly correlated with sleep timing SD (CA: r  = - 0.276, p  = 0.013, TE: r  = 0.311, p  = 0.005, PEN: r  = 0.241, p  = 0.032, NPE: r  = 0.250, p  = 0.025, DMS: r  = 0.235, p  = 0.036), but not with the MMSE score. Multiple regression analyses with the stepwise forward selection method including age, ESS score, bedtime, sleep timing, and sleep timing SD , revealed that the ESS score, and sleep timing SD were significant factors related to CA on the WCST (ESS score: β  = - 0.322, p  = 0.004; sleep timing SD: β  = - 0.250, p  = 0.022). Assessment of sleep-wake rhythms, daytime sleepiness, and cognitive function using the MMSE and WCST is valuable for the prediction of cognitive decline in the geriatric population., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Patients with established rheumatoid arthritis (RA) are at risk of developing secondary sarcopenia. Both pharmacological and exercise interventions are essential for treatment. However, for such patients, exercise loads may lead to the progression of joint destruction and worsening of pain. The purpose of this report was to assess the feasibility of a home-based, low-intensity resistance exercise programme. The case was a 70-year-old female patient with sarcopenia secondary to RA. She was diagnosed with RA at 57 years of age and began medication, maintaining remission of disease activity. However, she did not exercise habitually and was relatively inactive in her daily life. Furthermore, she had kinesiophobia associated with her RA-related symptoms. We suggested implementing a home-based low-intensity resistance exercise programme >3 months, with the goal of exercising the lower extremities daily. The patient was asked to self-monitor using an exercise diary and attend monthly outpatient visits for repeat counselling and feedback. As a result, she was able to perform the exercise programme safely with high compliance, improving her kinesiophobia as well as physical inactivity, although her skeletal muscle mass did not change. Regular exercise and increased physical activity may help prevent the onset of sarcopenia. These results demonstrate the feasibility of implementing our exercise programme and support its potential for preventing the progression of sarcopenia. While questions remain in terms of treating sarcopenia, we believe that our findings will lead to the establishment of an exercise programme for patients with sarcopenia secondary to established rheumatoid arthritis., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hishikawa N, Sawada K, Shono S, Sakurai M, Yokozeki M, Maeda H, Ohashi S, Ueshima K, Mikami Y. Accurate diagnosis of sarcopenia without using a body composition analyzer in a convalescent rehabilitation ward. Jpn J Compr Rehabil Sci 2023; 14: 26-32., Objective: The Asian Working Group for Sarcopenia 2019 recommends diagnosing sarcopenia without using a body composition analyzer and initiating treatment early. The present study aimed to investigate the accuracy of diagnosing sarcopenia without a body composition analyzer in a convalescent rehabilitation ward., Methods: Eighty-five patients admitted to a convalescent rehabilitation ward were included, and sarcopenia diagnoses were performed with and without a body composition analyzer. To assess the accuracy of diagnosing sarcopenia without using a body composition analyzer, sensitivity, specificity, positive predictive value, and negative predictive value were calculated relative to sarcopenia diagnoses made using a body composition analyzer., Results: The sensitivity of the technique for diagnosing sarcopenia was 0.94, specificity was 0.77, positive predictive value was 0.86, and negative predictive value was 0.90., Conclusion: The accuracy of diagnosing sarcopenia without using a body composition analyzer was high. However, this technique may miss sarcopenia cases in patients with increased calf circumference due to adipose tissue and/or edema., Competing Interests: Conflicts of interest: The authors have no conflicts of interest or financial interests to declare., (©Kaifukuki Rehabilitation Ward Association 2023.)

Objectives: Patients with rheumatoid arthritis (RA)-related foot impairment have a high rate of sarcopenia. Treatment using a foot orthosis (FO) enables not only a reduction in pain while walking but also an increase in physical activity, helping to prevent further loss of muscle mass. However, the primary goal of treating RA is to maximize patients' long-term quality of life (QOL). We investigated whether FO treatment both increases physical activity and improves QOL., Methods: Among 31 patients with RA-related foot impairment, 15 with sarcopenia were treated with an FO for 6 months. Foot-specific QOL (measuring using the Self-Administered Foot Evaluation Questionnaire), foot pain, activities of daily living, and physical activity (walking-intensity activity and moderate- to vigorous-intensity activity) were compared before treatment and after 6 months of treatment., Results: Ten patients who completed 6 months of follow-up were analyzed. Significant QOL improvements were found in the Pain and Pain-Related category and the Physical Functioning and Daily Living category (P = 0.02-0.04); however, no significant changes were found in the Social Functioning, General Health and Well-Being, or Shoe-Related categories (P = 0.09-0.21). Foot pain and activities of daily living significantly improved (P = 0.01-0.04). Physical activity significantly increased for walking-intensity activity (P = 0.04) but did not change for moderate- to vigorous-intensity activity (P = 1.00)., Conclusions: FO treatment in patients with RA-related foot impairment and sarcopenia increased light-intensity physical activity such as walking and improved physical QOL., Competing Interests: CONFLICTS OF INTEREST: The authors have no financial or other competing interests to declare., (2022 The Japanese Association of Rehabilitation Medicine.)

Objectives: Foot impairment in rheumatoid arthritis (RA) may exacerbate sarcopenia from physical inactivity because of foot pain while walking. The present study aimed to investigate the prevalence of sarcopenia in patients with RA-associated foot impairment, and whether treatment with a foot orthosis improved physical activity and muscle quantity., Methods: Thirty-two patients with RA were diagnosed as sarcopenic or nonsarcopenic, and the prevalence of sarcopenia was determined. Eleven patients with sarcopenia were treated with a foot orthosis. The following parameters were compared between baseline and after 6 months of treatment: physical activity (walking, moderate-intensity activity, and vigorous-intensity activity), foot pain while walking, Health Assessment Questionnaire (HAQ) score, and body composition parameters, including muscle quantity., Results: Sarcopenia was present in 25/32 patients (78.1%). The use of a foot orthosis improved walking activity ( p  = .02), foot pain while walking ( p  = .02), and HAQ score ( p  = .02). However, there were no significant changes in moderate- or vigorous-intensity activities or body composition parameters, including muscle quantity., Conclusion: Patients with RA-associated foot impairment had a high rate of sarcopenia. Treatment with a foot orthosis increases light-intensity physical activity such as walking, but does not enhance moderate-to-vigorous-intensity activities or increase muscle quantity.

Due to an increasing number of dementia patients, the development of a rapid and sensitive method for cognitive assessment is awaited. Here, we examined the usefulness of a novel and short (3 min) eye tracking device to evaluate the cognitive function of normal control (NC, n = 52), mild cognitive impairment (MCI, n = 52), and Alzheimer's disease (AD, n = 70) subjects. Eye tracking total score declined significantly in MCI (**p < 0.01 vs NC) and AD (**p < 0.01 vs NC, ## p < 0.01 vs MCI), and correlated well with the mini-mental state examination (MMSE) score (r = 0.57, *p < 0.05). Furthermore, the eye tracking test, especially memory and deductive reasoning tasks, effectively discriminated NC, MCI and AD. The present novel eye tracking test clearly discriminated cognitive functions among NC, MCI, and AD subjects, thereby providing an advantage for the early detection of MCI and AD in screening., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We herein report a 75-year-old man who developed disturbed consciousness with polynuclear cell dominant pleocytosis and low glucose and extremely high interleukin (IL)-6 levels in his cerebrospinal fluid. The biopsy specimen from his right supraclavicular lymph node showed the infiltration of inflammatory cells positive for IgG, IgG4 and IL-6. Prednisolone and azathioprine administered under suspicion of IgG4-related disease (IgG4-RD) or multicentric Castleman's disease (MCD) successfully remitted the symptoms. However, he developed myelodysplastic syndrome (MDS) and died 18 months later. The extremely high IL-6 may have been related to the rare neurological manifestations and development of MDS in the present case.

White matter lesions (WMLs) caused by cerebral chronic hypoperfusion (CCH) may contribute to the pathophysiology of Alzheimer's disease (AD). However, the underlying mechanisms and therapeutic approaches have yet to be totally identified. In the present study, we investigated a potential therapeutic effect of the free radical scavenger edaravone (EDA) on WMLs in our previously reported novel mouse model of AD (APP23) plus CCH with motor and cognitive deficits. Relative to AD with CCH mice at 12 months (M) of age, EDA strongly improved CCH-induced WMLs in the corpus callosum of APP23 mice at 12 M by improving the disruption of white matter integrity, enhancing the proliferation of oligodendrocyte progenitor cells, attenuating endothelium/astrocyte unit dysfunction, and reducing neuroinflammation and oxidative stress. The present study demonstrates that the long-term administration of EDA may provide a promising therapeutic approach for WMLs in AD plus CCH disease with cognitive deficits.

Objective : Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Hypoxic stress is suspected as the pathogenesis of ALS, however, no positron emission tomography (PET) study for hypoxic stress has been conducted in the spinal cord of ALS patients. Methods : In the present study, we examined cervical spinal hypoxic stress of nineALS patients with upper extremity (U/E) atrophy by 18 F-fluoromisonidazole (FMISO) PET. Results : On the ipsilateral side of C1 and C5 levels, 18 F-FMISO uptake increased significantly compared with the contralateral side (* p < 0.05) and the control subject (** p < 0.01). In addition, a strong correlation was found between 18 F-FMISO uptake of the C5 level and the rate of progression of the ALS FRS-R score (R = 0.781, * p = 0.013). Conclusion : These results indicate that hypoxic stress increased in the spinal cord of ALS patients with a close link to ALS progression. Both hypoxic stress and a compromised response to hypoxia, which may lead to subsequent motor neuron death, could be a potential therapeutic target for ALS.

Cu-diacetyl-bis (N4-methylthiosemicarbazone) (CuATSM) has both anti-oxidative and anti-inflammatory activities, but its therapeutic efficacy for oxidative stress has not been thoroughly investigated in acute ischemic stroke. Here, the present study was designed to assess the efficacies of CuATSM in acute ischemic stroke by comparing with the standard neuroprotective reagent edaravone. Mice were subjected to transient middle cerebral occlusion (tMCAO) for 60 min, and then intravenously administrated with CuATSM (1.5 mg/kg) or edaravone (3 mg/kg) just after the reperfusion, and examined at 1 and 3 d. Compared with the vehicle group, CuATSM treatment decreased infarct volumes and oxidative stress at 3d after tMCAO, which was further enhanced by combined CuATSM + edaravone treatment as compared with single CuATSM group, but not improve neurobehaviors. The present study demonstrated that CuATSM showed strong antioxidative and neuroprotective effects in acute ischemic stroke, which was enhanced by the combination with edaravone., Competing Interests: Declaration of Competing Interest The authors disclose no potential conflict of interests., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Objectives: The relationship between stroke etiology and clot pathology remains controversial., Materials and Methods: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed., Results: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots., Conclusions: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Combined central and peripheral demyelination (CCPD) causes demyelination in both the central and peripheral nervous systems. Anti-neurofascin 155 antibody plays an important pathogenic role in CCPD, but evidence concerning an association between this antibody and CCPD remains inconclusive. Although there have been no reports of precedent optic neuritis developing into CCPD, we herein report a Japanese man in whom optic neuritis recurred four times over nine years and who developed CCPD without positive anti-neurofascin 155 antibody. This case suggests the possibility of developing CCPD after optic nerve neuritis and the existence of an unknown antibody that induces CCPD.

Background: Cost-effective and noninvasive methods for in vivo imaging of amyloid deposition are needed to screen Alzheimer's disease (AD). Although retinal amyloid is a possible diagnostic marker of AD, there are very few studies on in vivo retinal amyloid imaging., Objective: To examine the usefulness of in vivo imaging of retinal amyloid in AD patients., Methods: To examine amyloid deposition, 30 Japanese subjects (10 normal control (NC), 7 with mild cognitive impairment (MCI), and 13 with AD) underwent a complete ophthalmic examination, including fundus imaging by scanning laser ophthalmoscopy before and after oral curcumin intake., Results: Retinal amyloid deposition was greater in AD than in NC subjects (*p < 0.05) while MCI showed a slight but insignificant increase of retinal amyloid deposition relative to NC subjects. Retinal amyloid deposition was correlated with whole gray matter atrophy (r = 0.51, *p < 0.05) but not with the cognitive score of the Mini-Mental State Examination, nor with medial temporal lobe atrophy., Conclusion: The present noninvasive in vivo detection of retinal amyloid deposition is useful for screening AD patients.

Tocilizumab (TCZ; Actemra/RoActemra) is an anti-interleukin (IL)-6 receptor antibody for the treatment of rheumatoid arthritis (RA) and other autoimmune diseases and cytokine storms. The present case is a 63-year-old female well-controlled RA patient, who presented with a progressive cognitive impairment after 34 months of TCZ administration. Brain magnetic resonance imaging (MRI) showed leukencephalopathy with a lactic acid peak in magnetic resonance spectroscopy (MRS), a decreased blood flow in single photon emission computed tomography (SPECT), and a decreased accumulation in fluorodeoxyglucose positron emission tomography (FDG-PET). The discontinuation of TCZ improved her cognitive function and brain MRI findings at 3 months after drug cessation. The present case suggests that TCZ may sometimes cause leukoencephalopathy after long-term administration, and thus the early discontinuation of TCZ is recommended to achieve a good prognosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0 × 10 4 cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients.

Mechanical thrombectomy (MT) is a standard treatment for acute ischemic stroke that could cause hemorrhagic complications. We aimed to evaluate the pathology of MT-induced arterial damage and neurovascular unit (NVU) disruption in relation to tissue-type plasminogen activator (tPA) injection for acute ischemic stroke. We induced transient middle cerebral artery occlusion in male SHR/Izm rats for 2 hr. This was followed by reperfusion with/without tPA (3 mg/kg) and "rough suture" insertion that mimicked MT once or thrice (MT1 or MT3). Compared with the control group, the tPA + MT3 group presented with an increase in the cerebral infarct and hemorrhage with severer IgG leakage. Moreover, structural damage reaching the tunica media was detected in the MT3 and tPA + MT3 groups. The tPA + MT3 group presented with increased matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression with some MMP9-positive cells expressing a neutrophil marker myeloperoxidase. Furthermore, basal lamina detachment from astrocyte foot processes was observed in the tPA + MT1 and tPA + MT3 groups. These findings suggest that MT causes direct arterial damage, as well as VEGF and MMP9 upregulation, which results in NVU disruption and hemorrhagic complications in acute ischemic stroke, especially when combined with tPA., (© 2020 Wiley Periodicals, Inc.)

The aggregation and cellular mislocalization of several RNA-binding proteins (RBPs) have been identified as the major hallmarks of neurodegenerative diseases such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, it remains obscure whether these pathological changes also occur during cerebral ischemia. In this study, we report that RBPs increased significantly compared with the sham group (*p < 0.05 and ** p < 0.01 vs sham), with nuclear depletion and cytoplasmic deposition in neurons in the acute phase of cerebral ischemia. On the other hand, such nucleocytoplasmic mislocalization were not observed in astrocytes. We provide evidence of the alteration of these neurodegeneration-related RBPs after cerebral ischemia, suggesting a potential association between cerebral ischemia and neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The free radical scavenger edaravone is a proven neuroprotective drug for patients with amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the therapeutic effects of edaravone for oxidative stress and anti-oxidative activity in ALS patients., Methods: Twenty-two ALS patients with a disease duration of 2 years, treated by edaravone, and 25 control participants were evaluated according to their clinical scores, including ALS functional rating scale-revised (ALSFRS-R), and serum and cerebrospinal fluid (CSF) markers of oxidative stress dROM and anti-oxidative activity OXY., Results: Serum and CSF markers of anti-oxidative activity OXY were significantly decreased in ALS patients at pre-treatment compared with controls ( ## p < .01), which was improved in the course of edaravone treatment. Both serum and CSF OXY were significantly correlated with ALS clinical scores including ALSFRS-R (*p < .05, **p < .01, ***p < .001). Furthermore, serum OXY at pre-treatment was significantly correlated with a change in the ALSFRS-R score in the sixth cycle of edaravone treatment (*p < .05)., Conclusions: The present study suggests significant correlations between anti-oxidative activity and ALS clinical severity, and the therapeutic efficacy of edaravone for decreased anti-oxidative activity in ALS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)