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Moyamoya syndrome (MMS) refers to a rare cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches, leading to an increased risk of stroke. While prevalent in Asia, this condition is considerably less common in Western countries, including Europe. The association between MMS and Graves’ disease (GD) has been well documented, primarily in Asian and American populations, notably Latin Americans. In this report, we report the first case of GD with MMS in a Caucasian woman from Western Europe. The precise mechanisms underpinning the correlation between these two conditions remain poorly elucidated but are hypothesized to involve hemodynamic alterations, the toxic effects of anti-thyroid-stimulating hormone receptor antibodies, or a shared genetic predisposition. Our clinical case underscores the significance of thyroid disease screening in suspected MMS cases, as the management of thyroid dysfunction may suffice to improve neurological symptoms.

BackgroundNeuroinflammation is widely recognized as a key factor in the pathogenesis of Alzheimer’s disease (AD), alongside ß-amyloid deposition and the formation of neurofibrillary tangles. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, part of the innate immune system, has been implicated in the neuropathology of both preclinical amyloid and tau transgenic models. Activation of the NLRP3 pathway involves an initial priming step, which increases the expression of Nlrp3 and interleukin (IL)-1β, followed by the assembly of the NLRP3 inflammasome complex, comprising NLRP3, ASC, and caspase-1. This assembly leads to the proteolytic maturation of the pro-inflammatory cytokines IL-1β and IL-18. Additionally, the NLRP3 inflammasome induces Gasdermin D (GSDMD) cleavage, forming membrane pores through which IL-1β and IL-18 are secreted. Inhibition of NLRP3 has been shown to enhance plaque clearance by modulating microglial activation. Furthermore, blocking NLRP3 in tau transgenic mice has been found to reduce tau phosphorylation by affecting the activity of certain tau kinases and phosphatases.MethodsIn this study, organotypic brain slice cultures from P301S transgenic mice were treated with lipopolysaccharide (LPS) plus nigericin as a positive control or exposed to tau seeds (K18) to evaluate NLRP3 inflammasome activation. The effect of tau seeding on NLRP3 activity was further examined using Meso Scale Discovery (MSD) assays to measure IL1β secretion levels in the presence and absence of NLRP3 inhibitors. The role of NLRP3 activity was investigated in full-body Nlrp3 knockout mice crossbred with the tau transgenic P301S model. Additionally, full-body and microglia-selective Gsdmd knockout mice were crossbred with P301S mice, and tau pathology and neurodegeneration were evaluated at early and late stages of the disease using immunohistochemistry and biochemical assays.ResultsActivation of the NLRP3 pathway was observed in the mouse organotypic slice culture (OSC) model following stimulation with LPS and nigericin or exposure to tau seeds. However, Nlrp3 deficiency did not mitigate tauopathy or neurodegeneration in P301S mice in vivo, showing only a minor effect on plasma neurofilament (NF-L) levels. Consistently, Gsdmd deficiency did not alter tau pathology in P301S mice. Furthermore, neither full-body nor microglia-selective Gsdmd deletion had an impact on neuronal pathology or the release of pro-inflammatory cytokines.ConclusionThe absence of key components of the NLRP3 inflammasome pathway did not yield a beneficial effect on tau pathology or neurodegeneration in the preclinical Tau-P301S mouse model of AD. Nonetheless, organotypic slice cultures could serve as a valuable ex vivo mechanistic model for evaluating NLRP3 pathway activation and pharmacological inhibitors.

Introduction Research using animal models suggests that intensive motor skill training in infants under 2 years old with cerebral palsy (CP) may significantly reduce, or even prevent, maladaptive neuroplastic changes following brain injury. However, the effects of such interventions to tentatively prevent secondary neurological damages have never been assessed in infants with CP. This study aims to determine the effect of the baby Hand and Arm Bimanual Intensive Therapy Including Lower Extremities (baby HABIT-ILE) in infants with unilateral CP, compared with a control intervention.Methods and analysis This randomised controlled trial will include 48 infants with unilateral CP aged (corrected if preterm) 6–18 months at the first assessment. They will be paired by age and by aetiology of the CP, and randomised into two groups (immediate and delayed). Assessments will be performed at baseline and at 1 month, 3 months and 6 months after baseline. The immediate group will receive 50 hours of baby HABIT-ILE intervention over 2 weeks, between first and second assessment, while the delayed group will continue their usual activities. This last group will receive baby HABIT-ILE intervention after the 3-month assessment. Primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes will include behavioural assessments for gross and fine motricity, visual–cognitive–language abilities as well as MRI and kinematics measures. Moreover, parents will determine and score child-relevant goals and fill out questionnaires of participation, daily activities and mobility.Ethics and dissemination Full ethical approval has been obtained by the Comité d’éthique Hospitalo-Facultaire/Université catholique de Louvain, Brussels (2013/01MAR/069 B403201316810g). The recommendations of the ethical board and the Belgian law of 7 May 2004 concerning human experiments will be followed. Parents will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.Trial registration number NCT04698395. Registered on the International Clinical Trials Registry Platform (ICTRP) on 2 December 2020 and NIH Clinical Trials Registry on 6 January 2021. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT04698395?term=bleyenheuft&draw=1&rank=7.

Introduction Stroke causes multiple deficits including motor, sensitive and cognitive impairments, affecting also individual’s social participation and independence in activities of daily living (ADL) impacting their quality of life. It has been widely recommended to use goal-oriented interventions with a high amount of task-specific repetitions. These interventions are generally focused only on the upper or lower extremities separately, despite the impairments are observed at the whole-body level and ADL are both frequently bimanual and may require moving around. This highlights the need for interventions targeting both upper and lower extremities. This protocol presents the first adaptation of Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) for adults with acquired hemiparesis.Methods and analysis This randomised controlled trial will include 48 adults with chronic stroke, aged ≥40 years. This study will compare the effect of 50 hours of HABIT-ILE against usual motor activity and regular rehabilitation. HABIT-ILE will be provided in a 2-week, adult’s day-camp setting, promoting functional tasks and structured activities. These tasks will continuously progress by increasing their difficulty. Assessed at baseline, 3 weeks after and at 3 months, the primary outcome will be the adults-assisting-hand-assessment stroke; secondary outcomes include behavioural assessments for hand strength and dexterity, a motor learning robotic medical device for quality of bimanual motor control, walking endurance, questionnaires of ADL, stroke impact on participation and self-determined patient-relevant goals, besides neuroimaging measures.Ethics and dissemination This study has full ethical approval from the Comité d’éthique Hospitalo-Facultaire/Université catholique de Louvain, Brussels (reference number: 2013/01MAR/069) and the local medical Ethical Committee of the CHU UCL Namur-site Godinne. Recommendations of the ethical board and the Belgian law of 7 May 2004, concerning human experiments will be followed. Participants will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.Trial registration number NCT04664673.

Background: Neuroinflammation is widely recognized as a key factor in the pathogenesis of Alzheimer’s disease (AD), alongside ß-amyloid deposition and the formation of neurofibrillary tangles. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, part of the innate immune system, has been implicated in the neuropathology of both preclinical amyloid and tau transgenic models. Activation of the NLRP3 pathway involves an initial priming step, which increases the expression of Nlrp3 and interleukin (IL)-1β, followed by the assembly of the NLRP3 inflammasome complex, comprising NLRP3, ASC, and caspase-1. This assembly leads to the proteolytic maturation of the pro-inflammatory cytokines IL-1β and IL-18. Additionally, the NLRP3 inflammasome induces Gasdermin D (GSDMD) cleavage, forming membrane pores through which IL-1β and IL-18 are secreted. Inhibition of NLRP3 has been shown to enhance plaque clearance by modulating microglial activation. Furthermore, blocking NLRP3 in tau transgenic mice has been found to reduce tau phosphorylation by affecting the activity of certain tau kinases and phosphatases. Methods: In this study, organotypic brain slice cultures from P301S transgenic mice were treated with lipopolysaccharide (LPS) plus nigericin as a positive control or exposed to tau seeds (K18) to evaluate NLRP3 inflammasome activation. The effect of tau seeding on NLRP3 activity was further examined using Meso Scale Discovery (MSD) assays to measure IL1β secretion levels in the presence and absence of NLRP3 inhibitors. The role of NLRP3 activity was investigated in fullbody Nlrp3 knockout mice crossbred with the tau transgenic P301S model. Additionally, full-body and microglia-selective Gsdmd knockout mice were crossbred with P301S mice, and tau pathology and neurodegeneration were evaluated at early and late stages of the disease using immunohistochemistry and biochemical assays. Results: Activation of the NLRP3 pathway was observed in the mouse organotypic slice culture (OSC) model following stimulation with LPS and nigericin or exposure to tau seeds. However, Nlrp3 deficiency did not mitigate tauopathy or neurodegeneration in P301S mice in vivo, showing only a minor effect on plasma neurofilament (NF-L) levels. Consistently, Gsdmd deficiency did not alter tau pathology in P301S mice. Furthermore, neither full-body nor microglia-selective Gsdmd deletion had an impact on neuronal pathology or the release of pro-inflammatory cytokines. Conclusion: The absence of key components of the NLRP3 inflammasome pathway did not yield a beneficial effect on tau pathology or neurodegeneration in the preclinical Tau-P301S mouse model of AD. Nonetheless, organotypic slice cultures could serve as a valuable ex vivo mechanistic model for evaluating NLRP3 pathway activation and pharmacological inhibitors. [ABSTRACT FROM AUTHOR]

Abstract Background Most activities of daily life (ADL) require cooperative bimanual movements. A unilateral stroke may severely impair bimanual ADL. How patients with stroke (re)learn to coordinate their upper limbs (ULs) is largely unknown. The objectives are to determine whether patients with chronic supratentorial stroke could achieve bimanual motor skill learning (bim-MSkL) and to compare bim-MSkL between patients and healthy individuals (HIs). Methods Twenty-four patients and ten HIs trained over 3 consecutive days on an asymmetrical bimanual coordination task (CIRCUIT) implemented as a serious game in the REAplan® robot. With a common cursor controlled by coordinated movements of the ULs through robotic handles, they performed as many laps as possible (speed constraint) on the CIRCUIT while keeping the cursor within the track (accuracy constraint). The primary outcome was a bimanual speed/accuracy trade-off (biSAT), we used a bimanual coordination factor (biCO) and bimanual forces (biFOP) for the secondary outcomes. Several clinical scales were used to evaluate motor and cognitive functions. Results Overall, the patients showed improvements on biSAT and biCO. Based on biSAT progression, the HI achieved a larger bim-MSkL than the patients with mild to moderate impairment (Fugl-Meyer Assessment Upper Extremity (FMA-UE): 28–55, n = 15) but not significantly different from those with minimal motor impairment (FMA-UE: 66, n = 9). There was a significant positive correlation between biSAT evolution and the FMA-UE and Stroke Impact Scale. Conclusions Both HI and patients with chronic stroke training on a robotic device achieved bim-MSkL, although the more impaired patients were less efficient. Bim-MSkL with REAplan® may be interesting for neurorehabilitation after stroke. Trial registration: ClinicalTrial.gov identifier: NCT03974750. Registered 05 June 2019. https://clinicaltrials.gov/ct2/show/NCT03974750?cond=NCT03974750&draw=2&rank=1

BackgroundSince a stroke can impair bimanual activities, enhancing bimanual cooperation through motor skill learning may improve neurorehabilitation. Therefore, robotics and neuromodulation with transcranial direct current stimulation (tDCS) are promising approaches. To date, tDCS has failed to enhance bimanual motor control after stroke possibly because it was not integrating the hypothesis that the undamaged hemisphere becomes the major poststroke hub for bimanual control.ObjectiveWe tested the following hypotheses: (I) In patients with chronic hemiparetic stroke training on a robotic device, anodal tDCS applied over the primary motor cortex of the undamaged hemisphere enhances bimanual motor skill learning compared to sham tDCS. (II) The severity of impairment correlates with the effect of tDCS on bimanual motor skill learning. (III) Bimanual motor skill learning is less efficient in patients than in healthy individuals (HI).MethodsA total of 17 patients with chronic hemiparetic stroke and 7 healthy individuals learned a complex bimanual cooperation skill on the REAplan® neurorehabilitation robot. The bimanual speed/accuracy trade-off (biSAT), bimanual coordination (biCo), and bimanual force (biFOP) scores were computed for each performance. In patients, real/sham tDCS was applied in a crossover, randomized, double-blind approach.ResultsCompared to sham, real tDCS did not enhance bimanual motor skill learning, retention, or generalization in patients, and no correlation with impairment was noted. The healthy individuals performed better than patients on bimanual motor skill learning, but generalization was similar in both groups.ConclusionA short motor skill learning session with a robotic device resulted in the retention and generalization of a complex skill involving bimanual cooperation. The tDCS strategy that would best enhance bimanual motor skill learning after stroke remains unknown.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT02308852, identifier: NCT02308852.

Mowing is a crucial management strategy for conservation and restoration of semi‐natural grasslands. In the past decades, dominant mowing methods have changed from manual to mechanical, using heavy machines causing soil compaction. Whereas the negative effects of compaction are well understood in agriculture and forestry, they have received little attention so far in nature management. This study aims to investigate the effects of compaction on soil quality, arbuscular mycorrhizal fungal communities, and survival of a target plant species. We subjected seven grasslands to three contrasting mowing types: manual mowing with a brush cutter, softtrack mowing—designed to minimize soil compaction—and tractor mowing. We compared compaction, soil properties, and arbuscular mycorrhizal communities among the types. Additionally, we experimentally subjected intact grassland sods containing Devil's bit scabious (Succisa pratensis Moench), a target species of grassland conservation, to compaction levels corresponding to the three mowing types. Subsequently, we assessed plant survival. We found that soil compaction, soil nutrient availability, and toxic soil elements were significantly higher in the softtrack‐ and tractor‐mown parts of grassland sites compared to the manually mown parts. Also, the arbuscular mycorrhizal community composition differed significantly among mowing types, with the largest differences between “manual” and “tractor.” Succisa pratensis survival significantly decreased by 43 and 71% on the short term and by 71 and 86% on the longer term with increasing compaction. Consequently, mowing‐associated soil compaction compromises nature management targets via at least four mechanisms: nutrient enrichment, soil toxicity, changes in arbuscular mycorrhizal communities, and decreased survival of the target plant species. [ABSTRACT FROM AUTHOR]

Using robotic devices might improve recovery post-stroke, but the optimal way to apply robotic assistance has yet to be determined. The current study aimed to investigate whether training under the robotic active-assisted mode improves bimanual motor skill learning (biMSkL) more than training under the active mode in stroke patients. Twenty-six healthy individuals (HI) and 23 chronic hemiparetic stroke patients with a detectable lesion on MRI or CT scan, who demonstrated motor deficits in the upper limb, were randomly allocated to two parallel groups. The protocol included a two-day training on a new bimanual cooperative task, LIFT-THE-TRAY, under either the active or active-assisted modes (where assistance decreased in a pre-determined stepwise fashion) with the bimanual version of the REAplan® robotic device. The hypothesis was that the active-assisted mode would result in greater biMSkL than the active mode. The biMSkL was quantified by a speed-accuracy trade-off (SAT) before (T1) and immediately after (T2) training on days 1 and 2 (T3 and T4). The change in SAT after 2 days of training (T4/T1) indicated that both HI and stroke patients learned and retained the bimanual cooperative task. After 2 days of training, the active-assisted mode did not improve biMSkL more than the active mode (T4/T1) in HI nor stroke patients. Whereas HI generalized the learned bimanual skill to different execution speeds in both the active and active-assisted subgroups, the stroke patients generalized the learned skill only in the active subgroup. Taken together, the active-assisted mode, applied in a pre-determined stepwise decreasing fashion, did not improve biMSkL more than the active mode in HI and stroke subjects. Stroke subjects might benefit more from robotic assistance when applied “as-needed.” This study was approved by the local ethical committee (Comité d’éthique médicale, CHU UCL Namur, Mont-Godinne, Yvoir, Belgium; Internal number: 54/2010, EudraCT number: NUB B039201317382) on July 14, 2016 and was registered with ClinicalTrials.gov (Identifier: NCT03974750) on June 5, 2019.

The imbalance between production and clearance of amyloid β (Aβ) peptides and their resulting accumulation in the brain is an early and crucial step in the pathogenesis of Alzheimer's disease (AD). Therefore, Aβ is strongly positioned as a promising and extensively validated therapeutic target for AD. Investigational disease-modifying approaches aiming at reducing cerebral Aβ concentrations include prevention of de novo production of Aβ through inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and clearance of Aβ deposits via passive Aβ immunotherapy.We have developed a novel, high affinity antibody against Aβ peptides bearing a pyroglutamate residue at amino acid position 3 (3pE), an Aβ species abundantly present in plaque deposits in AD brains. Here, we describe the preclinical characterization of this antibody, and demonstrate a significant reduction in amyloid burden in the absence of microhemorrhages in different mouse models with established plaque deposition. Moreover, we combined antibody treatment with chronic BACE1 inhibitor treatment and demonstrate significant clearance of pre-existing amyloid deposits in transgenic mouse brain, without induction of microhemorrhages and other histopathological findings. Together, these data confirm significant potential for the 3pE-specific antibody to be developed as a passive immunotherapy approach that balances efficacy and safety. Moreover, our studies suggest further enhanced treatment efficacy and favorable safety after combination of the 3pE-specific antibody with BACE1 inhibitor treatment.

Abstract Background To estimate the additional impact of coping and of being dependent on caregivers, over and above the large effects of disability on utility after ischemic stroke. Methods A total of 539 patients were recruited into an observational, retrospective study when returning for a check-up between 3 and 36 months after an ischemic stroke. Patients’ modified Rankin Scale (mRS), dependency on caregivers, the Brandtstädter and Renner Coping questionnaire (with summary scores: Tenacity of Goal Pursuit (TGP) and Flexible Goal Adjustment (FGA) coping styles), EQ-5D-3 L and co-morbidities were evaluated. Results In multivariable regression, greater disability (mRS) resulted in large utility losses, between 0.06 for mRS 1 to 0.65 for mRS 5 (p

Zoonotic infections represent an uncommon phenomenon. Few people with pets realise the infectious risk this entails. This case describes a Pasteurella canis infection of a breast implant following close contact between a patient and her cat.A 59-year-old woman developed infection of her breast implant 7 months after implantation. Surgical revision was performed after failure of conservative treatment with antibiotics. Perioperative samples from the periprosthetic fluid were positive for P. canis, a Gram-negative coccobacillus that is present in the oropharyngeal commensal flora of cats and dogs. History revealed that the patient owned a cat for 2 years.This case highlights the possible risk of zoonotic infections in humans with protheses following close contact with a cat. Antibiotic therapy and surgical revision, with or without removal of the prosthesis constitute the cornerstone of treatment in such cases. Keywords: Animals, Domestic, Pasteurella, Zoonoses, Pasteurella infections