Cerebral Amyloid Angiopathy and Risk of Isolated Nontraumatic Subdural Hemorrhage.

Importance: Cerebral amyloid angiopathy (CAA) is a common cause of spontaneous intracerebral hemorrhage in older patients. Although other types of intracranial hemorrhage can occur in conjunction with CAA-related intracerebral hemorrhage, the association between CAA and other subtypes of intracranial hemorrhage, particularly in the absence of intracerebral hemorrhage, remains poorly understood.

Objective: To determine whether CAA is an independent risk factor for isolated nontraumatic subdural hemorrhage (SDH).

Patent Foramen Ovale Management for Secondary Stroke Prevention: State-of-the-Art Appraisal of Current Evidence.

Patent foramen ovale (PFO) is frequently identified in young patients with ischemic stroke. Randomized controlled trials provide robust evidence supporting PFO closure in selected patients with cryptogenic ischemic stroke; however, several questions remain unanswered. This report summarizes current knowledge on the epidemiology of PFO-associated stroke, the role of PFO as a cause of stroke, and anatomic high-risk features.

Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain.

2,6-di--butylphenol (2,6-DTBP) ameliorates mechanical allodynia and thermal hyperalgesia produced by partial sciatic nerve ligation in mice, and selectively inhibits HCN1 channel gating. We hypothesized that the clinically utilized non-anesthetic dimerized congener of 2,6-DTBP, probucol (2,6-di--butyl-4-[2-(3,5-di--butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol), would relieve the neuropathic phenotype that results from peripheral nerve damage, and that the anti-hyperalgesic efficacy would correlate with HCN1 channel inhibition A single oral dose of probucol (800 mg/kg) relieved mechanical allodynia and thermal hyperalgesia in a mouse spared-nerve injury neuropathic pain model. While the low aqueous solubility of probucol precluded assessment of its possible interaction with HCN1 channels, our results, in conjunction with recent data demonstrating that probucol reduces lipopolysaccharide-induced mechanical allodynia and thermal hyperalgesia, support the testing/development of probucol as a non-opioid, oral antihyperalgesic albeit one of unknown mechanistic action.

An Empirical Comparison of Commonly Used Universal Rating Scales for Dystonia.

Background: There are several widely used clinical rating scales for documenting the severity and distribution of various types of dystonia.

Objectives: The goal of this study was to evaluate the performance of the most commonly used scales in a large group of adults with the most common types of isolated dystonia.

Methods: Global Dystonia Rating Scale (GDRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores were obtained for 3067 participants.

Corrigendum: PlexinD1 signaling controls domain-specific dendritic development in newborn neurons in the postnatal olfactory bulb.

[This corrects the article DOI: 10.3389/fnins.2023.

National- and State-Level Trends in Medicare Hospice Beneficiaries for Stroke During 2013 to 2019 in the United States.

Background: Stroke is the fifth leading cause of death in the United States, one of the leading contributors to Medicare cost, including through Medicare hospice benefits, and the rate of stroke mortality has been increasing since 2013. We hypothesized that hospice utilization among Medicare beneficiaries with stroke has increased over time and that the increase is associated with trends in stroke death rate.

Methods: Using Medicare Part A claims data and Centers for Disease Control mortality data at a national and state level from 2013 to 2019, we report the proportion and count of Medicare hospice beneficiaries with stroke as well as the stroke death rate (per 100 000) in Medicare-eligible individuals aged ≥65 years.

WarpDrive: Improving spatial normalization using manual refinements.

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration.

Sex-specific modulation of amyloid-β on tau phosphorylation underlies faster tangle accumulation in females.

Females are disproportionately affected by dementia due to Alzheimer's disease. Despite a similar amyloid-β (Aβ) load, a higher load of neurofibrillary tangles (NFTs) is seen in females than males. Previous literature has proposed that Aβ and phosphorylated-tau (p-tau) synergism accelerates tau tangle formation, yet the effect of biological sex in this process has been overlooked.

Obesity-induced Ly6C and Ly6C monocyte subset changes abolish post-ischemic limb conditioning benefits in stroke recovery.

Remote limb conditioning (RLC), performed by intermittent interruption of blood flow to a limb, triggers endogenous tolerance mechanisms and improves stroke outcomes. The underlying mechanism for the protective effect involves a shift of circulating monocytes to a Ly6C proinflammatory subset in normal metabolic conditions. The current study investigates the effect of RLC on stroke outcomes in subjects with obesity, a vascular comorbidity.

Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.

Purpose: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

Methods: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

Results: Biallelic variants in CRELD1 were found in 18 participants from 14 families.

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial.

Objective: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness.

Design: Phase 3b multicentre, double-blind, randomised placebo-controlled trial.

Setting: Twenty-one hospitals in the UK.

Novel utilization of deep brain stimulation in the pedunculopontine nucleus with globus pallidus internus for treatment of childhood-onset dystonia.

Introduction: Deep brain stimulation (DBS) is a well-documented therapy for dystonia utilized in many adult and pediatric movement disorders. Pedunculopontine nucleus (PPN) has been investigated as a DBS target primarily in adult patients with dystonia or dyskinesias from Parkinson's disease, showing improvement in postural instability and gait dysfunction. Due to the difficulty in targeting PPN using standard techniques, it is not commonly chosen as a target for adult or pediatric pathology.

Association between substantia nigra degeneration and functional outcome in patients with basal ganglia infarction.

Background And Purpose: Cerebral infarction in the basal ganglia may cause secondary and delayed neuronal degeneration in the substantia nigra (SN). However, the clinical significance of SN degeneration remains poorly understood.

Methods: This retrospective observational study included patients with acute ischemic stroke in the basal ganglia on initial diffusion-weighted imaging who underwent follow-up diffusion-weighted imaging between 4 and 30 days after symptom onset.

Atrial Fibrillation In Patients With Stroke Attributed to Large- or Small-Vessel Disease: 3-Year Results From the STROKE AF Randomized Clinical Trial.

Importance: The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown.

Objectives: To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD.

Illusory optical defocus generated by shaded surface texture.

The human visual system is tasked with the problem of extracting information about the world from images that contain a conflated mixture of environmental sources and optical artifacts generated by the focal properties of our eyes. In most contexts, our brains manage to distinguish these sources, but this is not always the case. Recent work showed that shading gradients generated by smooth three-dimensional (3D) surfaces can elicit strong illusory percepts of optical defocus - the perception of illusory blur is only eliminated when the surface appears attached to self-occluding contours, surface discontinuities, or sharp specular reflections, which all generate sharp ('high spatial frequency') image structure.

Roadmap for C9ORF72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: Report on the C9ORF72 FTD/ALS Summit.

A summit held March 2023 in Scottsdale, Arizona (USA) focused on the intronic hexanucleotide expansion in the C9ORF72 gene and its relevance in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS; C9ORF72-FTD/ALS). The goal of this summit was to connect basic scientists, clinical researchers, drug developers, and individuals affected by C9ORF72-FTD/ALS to evaluate how collaborative efforts across the FTD-ALS disease spectrum might break down existing disease silos. Presentations and discussions covered recent discoveries in C9ORF72-FTD/ALS disease mechanisms, availability of disease biomarkers and recent advances in therapeutic development, and clinical trial design for prevention and treatment for individuals affected by C9ORF72-FTD/ALS and asymptomatic pathological expansion carriers.

Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease.

Importance: Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.

Objective: To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.

Design, Setting, And Participants: This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).

Effects of oral anticoagulation in people with atrial fibrillation after spontaneous intracranial haemorrhage (COCROACH): prospective, individual participant data meta-analysis of randomised trials.

Background: The safety and efficacy of oral anticoagulation for prevention of major adverse cardiovascular events in people with atrial fibrillation and spontaneous intracranial haemorrhage are uncertain. We planned to estimate the effects of starting versus avoiding oral anticoagulation in people with spontaneous intracranial haemorrhage and atrial fibrillation.

Methods: In this prospective meta-analysis, we searched bibliographic databases and trial registries using the strategies of a Cochrane systematic review (CD012144) on June 23, 2023.

Adults with Cerebral Palsy: Navigating the Complexities of Aging.

The goal of this narrative review is to highlight the healthcare challenges faced by adults with cerebral palsy, including the management of long-term motor deficits, difficulty finding clinicians with expertise in these long-term impairments, and scarcity of rehabilitation options. Additionally, this narrative review seeks to examine potential methods for maintaining functional independence, promoting social integration, and community participation. Although the brain lesion that causes the movement disorder is non-progressive, the neurodevelopmental disorder worsens from secondary complications of existing sensory, motor, and cognitive impairments.

Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.

Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats.

Enhancing Enrollment in Acute Stroke Trials: Current State and Consensus Recommendations.

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each.

Spinal cord injury regulates circular RNA expression in axons.

Introduction: Neurons transport mRNA and translational machinery to axons for local translation. After spinal cord injury (SCI), translation is assumed to enable neurorepair. Knowledge of the identity of axonal mRNAs that participate in neurorepair after SCI is limited.

Secondary prevention of stroke. A telehealth-delivered physical activity and diet pilot randomized trial (ENAbLE-pilot).

Background: Improving physical activity levels and diet quality are important for secondary stroke prevention.

Aim: To test the feasibility and safety of 6-month, co-designed telehealth-delivered interventions to increase physical activity and improve diet quality.

Methods: A 2 × 2 factorial trial (physical activity (PA); diet (DIET); PA + DIET; control) randomized, open-label, blinded endpoint trial.