Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.

BACKGROUND: Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection. METHODS: Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment. RESULTS: 807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups. CONCLUSIONS: Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.

Multimodal assessment of mitochondrial function in Parkinson's disease.

The heterogenous aetiology of Parkinson's disease is increasingly recognized; both mitochondrial and lysosomal dysfunction have been implicated. Powerful, clinically applicable tools are required to enable mechanistic stratification for future precision medicine approaches. The aim of this study was to characterize bioenergetic dysfunction in Parkinson's disease by applying a multimodal approach, combining standardized clinical assessment with midbrain and putaminal 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and deep phenotyping of mitochondrial and lysosomal function in peripheral tissue in patients with recent-onset Parkinson's disease and control subjects. Sixty participants (35 patients with Parkinson's disease and 25 healthy controls) underwent 31P-MRS for quantification of energy-rich metabolites [ATP, inorganic phosphate (Pi) and phosphocreatine] in putamen and midbrain. In parallel, skin biopsies were obtained from all research participants to establish fibroblast cell lines for subsequent quantification of total intracellular ATP and mitochondrial membrane potential (MMP) as well as mitochondrial and lysosomal morphology, using high content live cell imaging. Lower MMP correlated with higher intracellular ATP (r = -0.55, P = 0.0016), higher mitochondrial counts (r = -0.72, P < 0.0001) and higher lysosomal counts (r = -0.62, P = 0.0002) in Parkinson's disease patient-derived fibroblasts only, consistent with impaired mitophagy and mitochondrial uncoupling. 31P-MRS-derived posterior putaminal Pi/ATP ratio variance was considerably greater in Parkinson's disease than in healthy controls (F-tests, P = 0.0036). Furthermore, elevated 31P-MRS-derived putaminal, but not midbrain Pi/ATP ratios (indicative of impaired oxidative phosphorylation) correlated with both greater mitochondrial (r = 0.37, P = 0.0319) and lysosomal counts (r = 0.48, P = 0.0044) as well as lower MMP in both short (r = -0.52, P = 0.0016) and long (r = -0.47, P = 0.0052) mitochondria in Parkinson's disease. Higher 31P-MRS midbrain phosphocreatine correlated with greater risk of rapid disease progression (r = 0.47, P = 0.0384). Our data suggest that impaired oxidative phosphorylation in the striatal dopaminergic nerve terminals exceeds mitochondrial dysfunction in the midbrain of patients with early Parkinson's disease. Our data further support the hypothesis of a prominent link between impaired mitophagy and impaired striatal energy homeostasis as a key event in early Parkinson's disease.

Investigation of the wake region behind a hemispherical turret via laser Rayleigh scattering.

Planar and volumetric density measurements in the wake region behind a mounted hemispherical turret are obtained using laser Rayleigh scattering. The measurements are conducted in a Mach 2 wind tunnel facility at the Kirtland Air Force Base. Quantitative measurements of density and contour plots with lines of constant density are computed, thus enabling visualization of the turret wake's fluid dynamics. A new, to the best of our knowledge, laser diagnostic methodology and configuration for capturing laser images is also presented. This methodology enables further suppression of background light scattering. Multi-dimensional single-shot and time-average measurements are recorded at multiple axial locations behind the turret. The images acquired reveal turbulent regions of the wake flow, and a discussion of the observed phenomena is presented.

Adverse developmental impacts in progeny of zebrafish exposed to the agricultural herbicide atrazine during embryogenesis.

Atrazine (ATZ) is an herbicide commonly used on crops in the Midwestern US and other select global regions. The US Environmental Protection Agency ATZ regulatory limit is 3 parts per billion (ppb; µg/L), but this limit is often exceeded. ATZ has a long half-life, is a common contaminant of drinking water sources, and is indicated as an endocrine disrupting chemical in multiple species. The zebrafish was used to test the hypothesis that an embryonic parental ATZ exposure alters protein levels leading to modifications in morphology and behavior in developing progeny. Zebrafish embryos (F1) were collected from adults (F0) exposed to 0, 0.3, 3, or 30 ppb ATZ during embryogenesis. Differential proteomics, morphology, and behavior assays were completed with offspring aged 120 or 144 h with no additional chemical treatment. Proteomic analysis identified differential expression of proteins associated with neurological development and disease; and organ and organismal morphology, development, and injury, specifically the skeletomuscular system. Head length and ratio of head length to total length was significantly increased in the F1 of 0.3 and 30 ppb ATZ groups (p < 0.05). Based on molecular pathway alterations, further craniofacial morphology assessment found decreased distance for cartilaginous structures, decreased surface area and distance between saccular otoliths, and a more posteriorly positioned notochord (p < 0.05), indicating delayed ossification and skeletal growth. The visual motor response assay showed hyperactivity in progeny of the 30 ppb treatment group for distance moved and of the 0.3 and 30 ppb treatment groups for time spent moving (p < 0.05). Due to the changes in saccular otoliths, an acoustic startle assay was completed and showed decreased response in the 0.3 and 30 ppb treatments (p < 0.05). These findings suggest that a single embryonic parental exposure alters cellular pathways in their progeny that lead to perturbations in craniofacial development and behavior.

Evaluating the Rumen Degradation of Novel Protected Gelatin Capsules Containing Fish Oil Fed to Lactating Dairy Cows.

The objective of this study was to assess the effects of feeding gelatin capsules containing fish oil, treated with alcoholic solutions of flavoring agents followed by drying, on lactation performance, rumen fatty acids content and milk enrichment of fatty acids. In Trial 1, four multiparous ruminally fistulated Holstein cows were randomly assigned to one of four dietary treatments sequences in a 4 × 4 Latin square design. Treatments consisted of (1) Control with no capsules, (2) Control plus 200 untreated capsules per cow/day, mixed with the TMR, (3) Control plus 200 treated capsules per cow/day placed directly into the rumen, (4) Control plus 200 treated capsules per cow/day, mixed with the TMR. In Trial 2, three fistulated Holstein and three fistulated Jersey multiparous cows were randomly assigned to three dietary treatments sequences in a replicated 3 × 3 Latin square design. Treatments consisted of (1) Control with no capsules fed to the cows, (2) Control plus 180 untreated capsules per cow/day, (3) Control plus 180 treated capsules per cow/day. Compared to control, feeding fish oil capsules significantly (Trial 1) or numerically (Trial 2) reduced milk fat concentration and yield. Furthermore, in both trials, the feeding of untreated or treated capsules had no effect on animal performance or milk composition. In both trials, compared to controls, supplementing the diet with fish oil capsules consistently increased total trans C18:1 isomers and DHA concentration in the rumen and milk fat. However, for both trials, capsule protection treatment had a minimal effect on the concentration of any of the reported rumen and milk fatty acids. When assessed under laboratory control conditions, due to water absorption, the treated capsule weight was increased by 40% while resistance to pressure decreased by 84% after 2 h of incubation in water. The results of this study suggest that due to a reduction in the capsule shell's resistance to abrasion, treated capsules marginally prevented the release of fish oil in the rumen.

Tendon-derived matrix crosslinking techniques for electrospun multi-layered scaffolds.

Tendon tears are common and healing often occurs incompletely and by fibrosis. Tissue engineering seeks to improve repair, and one approach under investigation uses cell-seeded scaffolds containing biomimetic factors. Retention of biomimetic factors on the scaffolds is likely critical to maximize their benefit, while minimizing the risk of adverse effects, and without losing the beneficial effects of the biomimetic factors. The aim of the current study was to evaluate cross-linking methods to enhance the retention of tendon-derived matrix (TDM) on electrospun poly(ε-caprolactone) (PCL) scaffolds. We tested the effects of ultraviolet (UV) or carbodiimide (EDC:NHS:COOH) crosslinking methods to better retain TDM to the scaffolds and stimulate tendon-like matrix synthesis. Initially, we tested various crosslinking configurations of carbodiimide (2.5:1:1, 5:2:1, and 10:4:1 EDC:NHS:COOH ratios) and UV (30 s 1 J/cm2 , 60 s 1 J/cm2 , and 60 s 4 J/cm2 ) on PCL films compared to un-crosslinked TDM. We found that no crosslinking tested retained more TDM than coating alone (Kruskal-Wallis: p > .05), but that human adipose stem cells (hASCs) spread most on the 60 s 1 J/cm2 UV- and 2.5:1:1 EDC-crosslinked films (Kruskal-Wallis: p < .05). Next, we compared the effects of 60 s 1 J/cm2 UV- and 2.5:1:1 EDC-crosslinked to TDM-coated and untreated PCL scaffolds on hASC-induced tendon-like differentiation. UV-crosslinked scaffolds had greater modulus and stiffness than PCL or TDM scaffolds, and hASCs spread more on UV-crosslinked scaffolds (ANOVA: p < .05). Fourier transform infrared spectra revealed that UV- or EDC-crosslinking TDM did not affect the peaks at wavenumbers characteristic of tendon. Crosslinking TDM to electrospun scaffolds improves tendon-like matrix synthesis, providing a viable strategy for improving retention of TDM on electrospun PCL scaffolds.

A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease.

BACKGROUND: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. OBJECTIVES: To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. METHODS: The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS: UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS: High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effects of porous media thickness and its hydraulic gradient history on the formation of sand boils: Experimental investigation.

Sand boils occur where groundwater discharges to the land surface under sufficient hydraulic gradient to cause internal erosion and the upward transport of particles. A proper understanding of sand boil processes is essential in evaluating a wide range of geomechanical and sediment transport situations under which groundwater seepage occurs, such as the effects of groundwater discharge on beach stability. Although various empirical methods have been developed to estimate the critical hydraulic gradient (icr) leading to sand liquefaction, a prerequisite for sand boil occurrence, the effect of sand layer thickness and the implications of driving head fluctuations on the formation and reformation of sand boils have not been explored previously. This paper uses laboratory experiments to study sand boil formation and reformation for various sand thicknesses and hydraulic gradients to fill this knowledge gap. Sand layer thicknesses of 90 mm, 180 mm and 360 mm were adopted in evaluating sand boil reactivation, which was created by imposing hydraulic head fluctuations. While the first experiment (i.e., 90 mm sand layer) yielded a value for icr smaller (by 5%) than Terzaghi's (1922) value, the same theory underestimated icr by 12% and 4% for 180 mm and 360 mm sand layers, respectively. Moreover, icr needed for the reformation of sand boils decreased by 22%, 22% and 26% (relative to icr applicable to the initial sand boil) for the 90 mm, 180 mm and 360 mm sand layer thicknesses, respectively. We conclude that the formation of sand boils requires consideration of sand depth and the history of sand boil formation, particularly in relation to sand boils that form (and potentially reform) under oscillating pressures (e.g., tidal beaches).

Genetically Confirmed Malignant Hyperthermia in a Six-Week-Old Infant: A Case Report.

A six-week-old 3.9-kg infant presented for microlaryngoscopy and diaphragmatic hernia repair. While positioning for laparoscopy after microlaryngoscopy, the infant developed muscle rigidity, worsening hypercarbia, tachycardia, and early hyperthermia. Sevoflurane was discontinued, and the clinical picture indicating malignant hyperthermia (MH) resolved without dantrolene. Subsequent genetic testing revealed that both the patient and his father carried a mutation in the RYR1 gene that is diagnostic for MH. This is the second youngest genetically confirmed case of MH. This case adds to a limited body of evidence regarding MH presentation and diagnosis in neonates and infants.

Motor neuron disease mimics in practice: a case series.

In the majority of cases of motor neuron disease (MND), diagnosis is clinical and unambiguous. However, given the gravity of the diagnosis, it is crucial that treatable mimics are differentiated accurately. We present three cases referred to our clinic with possible MND with unusual features that led to an alternative diagnosis. (1) A middle-aged man with swallowing, then speech problems and foot drop. Tongue movements were slow and electromyography (EMG) showed fibrillations/positive sharp waves. Following investigation, a tonsillar tumour involving the tongue root was identified, and the foot drop improved, suggesting unrelated common peroneal nerve palsy (related to weight loss) or lumbar radiculopathy. (2) An elderly man presenting with progressive unilateral leg weakness and localised fasciculations on EMG. Following investigation, a high-grade brain glioma was diagnosed. (3) An elderly woman presenting with progressive quadriparesis over 18 months with fibrillations and chronic denervation on EMG. Symmetrical weakness and short duration response to immunotherapy led to further serological investigation and a diagnosis of anti-GD1a motor neuropathy. She was treated successfully with intravenous immunoglobulin, cyclophosphamide and rituximab and is now in remission.

COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.

BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course. METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation. RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.

Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain.

The routine clinical integration of individualized objective markers of disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multicentre, clinic-based, longitudinal cohort was used to systematically appraise the leading candidate biofluid biomarkers in the stratification and potential therapeutic assessment of those with amyotrophic lateral sclerosis. Incident patients diagnosed with amyotrophic lateral sclerosis (n = 258), other neurological diseases (n = 80) and healthy control participants (n = 101), were recruited and followed at intervals of 3-6 months for up to 30 months. Cerebrospinal fluid neurofilament light chain and chitotriosidase 1 and blood neurofilament light chain, creatine kinase, ferritin, complement C3 and C4 and C-reactive protein were measured. Blood neurofilament light chain, creatine kinase, serum ferritin, C3 and cerebrospinal fluid neurofilament light chain and chitotriosidase 1 were all significantly elevated in amyotrophic lateral sclerosis patients. First-visit plasma neurofilament light chain level was additionally strongly associated with survival (hazard ratio for one standard deviation increase in log10 plasma neurofilament light chain 2.99, 95% confidence interval 1.65-5.41, P = 0.016) and rate of disability progression, independent of other prognostic factors. A small increase in level was noted within the first 12 months after reported symptom onset (slope 0.031 log10 units per month, 95% confidence interval 0.012-0.049, P = 0.006). Modelling the inclusion of plasma neurofilament light chain as a therapeutic trial outcome measure demonstrated that a significant reduction in sample size and earlier detection of disease-slowing is possible, compared with using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. This study provides strong evidence that blood neurofilament light chain levels outperform conventional measures of disease activity at the group level. The application of blood neurofilament light chain has the potential to radically reduce the duration and cost of therapeutic trials. It might also offer a first step towards the goal of more personalized objective disease activity monitoring for those living with amyotrophic lateral sclerosis.

Reinnervation as measured by the motor unit size index is associated with preservation of muscle strength in amyotrophic lateral sclerosis, but not all muscles reinnervate.

INTRODUCTION/AIMS: The motor unit size index (MUSIX) may provide insight into reinnervation patterns in diseases such as amyotrophic lateral sclerosis (ALS). However, it is not known whether MUSIX detects clinically relevant changes in reinnervation, or if all muscles manifest changes in MUSIX in response to reinnervation after motor unit loss. METHODS: Fifty-seven patients with ALS were assessed at 3-month intervals for 12 months in four centers. Muscles examined were abductor pollicis brevis, abductor digiti minimi, biceps brachii, and tibialis anterior. Results were split into two groups: muscles with increases in MUSIX and those without increases. Longitudinal changes in MUSIX, motor unit number index (MUNIX), compound muscle action potential amplitude, and Medical Research Council strength score were investigated. RESULTS: One hundred thirty-three muscles were examined. Fifty-nine percent of the muscles exhibited an increase in MUSIX during the study. Muscles with MUSIX increases lost more motor units (58% decline in MUNIX at 12 months, P < .001) than muscles that did not increase MUSIX (34.6% decline in MUNIX at 12 months, P < .001). However, longitudinal changes in muscle strength were similar. When motor unit loss was similar, the absence of a MUSIX increase was associated with a significantly greater loss of muscle strength (P = .002). DISCUSSION: MUSIX increases are associated with greater motor unit loss but relative preservation of muscle strength. Thus, MUSIX appears to be measuring a clinically relevant response that can provide a quantitative outcome measure of reinnervation in clinical trials. Furthermore, MUSIX suggests that reinnervation may play a major role in determining the progression of weakness.

Assessment of the Precision in Measuring Glutathione at 3 T With a MEGA-PRESS Sequence in Primary Motor Cortex and Occipital Cortex.

BACKGROUND: Glutathione (GSH) is an important brain antioxidant and a number of studies have reported its measurement by edited and nonedited localized 1 H spectroscopy techniques within a range of applications in healthy volunteers and disease states. Good test-retest reproducibility is key when assessing the efficacy of treatments aimed at modulating GSH levels within the central nervous system or when noninvasively assessing changes in GSH content over time. PURPOSE: To evaluate the intraday (in vitro and in vivo) and 1-month apart (in vivo) test-retest reproducibility of GSH measurements from GSH-edited MEGA-PRESS acquisitions at 3 T in a phantom and in the brain of a cohort of middle-aged and older healthy volunteers. STUDY TYPE: Prospective. SUBJECTS/PHANTOMS: A phantom containing physiological concentrations of GSH and metabolites with overlapping spectral signatures and 10 healthy volunteers (4 F, 6 M, 55 ± 14 years old). FIELD STRENGTH/SEQUENCE: GSH-edited spectra were acquired at 3 T using the MEGA-PRESS sequence. ASSESSMENT: The phantom was scanned twice and the healthy subjects were scanned three times (on two separate days, 1 month apart). GSH was quantified from each acquisition, with the in vivo voxels placed at the primary motor cortex (PMC) and the occipital cortex (OCC). STATISTICAL TESTS: Mean coefficients of variation (CV) were used to assess short-term (in vitro and in vivo) and longer-term (in vivo) test-retest reproducibility. RESULTS: In vitro, the CV was 2.3%. In vivo, the mean intraday CV was 3.3% in the PMC and 2.4% in the OCC, while the CVs at 1 month apart were 4.6% in the PMC and 7.8% in the OCC. DATA CONCLUSION: GSH-edited MEGA-PRESS spectroscopy allows measurement of GSH with excellent precision. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

VoxelHop: Successive Subspace Learning for ALS Disease Classification Using Structural MRI.

Deep learning has great potential for accurate detection and classification of diseases with medical imaging data, but the performance is often limited by the number of training datasets and memory requirements. In addition, many deep learning models are considered a "black-box," thereby often limiting their adoption in clinical applications. To address this, we present a successive subspace learning model, termed VoxelHop, for accurate classification of Amyotrophic Lateral Sclerosis (ALS) using T2-weighted structural MRI data. Compared with popular convolutional neural network (CNN) architectures, VoxelHop has modular and transparent structures with fewer parameters without any backpropagation, so it is well-suited to small dataset size and 3D imaging data. Our VoxelHop has four key components, including (1) sequential expansion of near-to-far neighborhood for multi-channel 3D data; (2) subspace approximation for unsupervised dimension reduction; (3) label-assisted regression for supervised dimension reduction; and (4) concatenation of features and classification between controls and patients. Our experimental results demonstrate that our framework using a total of 20 controls and 26 patients achieves an accuracy of 93.48 % and an AUC score of 0.9394 in differentiating patients from controls, even with a relatively small number of datasets, showing its robustness and effectiveness. Our thorough evaluations also show its validity and superiority to the state-of-the-art 3D CNN classification approaches. Our framework can easily be generalized to other classification tasks using different imaging modalities.

Muscle MRI in motor neuron diseases: a systematic review.

Objective: To summarize applications of muscle magnetic resonance imaging (MRI) in cross-sectional assessment and longitudinal monitoring of motor neuron diseases and evaluate associations with clinical assessment techniques.Methods: PubMed and Scopus were searched for research published up to May 2021 relating to muscle MRI in motor neuron diseases, according to predefined inclusion and exclusion criteria. Studies were systematically appraised for bias and data were extracted for discussion.Results: Twenty-eight papers met inclusion criteria. The studies assessed muscle T1- and T2-weighted signal, diffusion, muscle volume, and fat infiltration, employing quantitative, qualitative, and semi-quantitative approaches. Various regions of interest were considered; changes in thigh and calf muscles were most frequently reported. Preliminary evidence of concordance between clinical and radiological findings and utility as an objective longitudinal biomarker is emerging.Conclusion: Muscle MRI appears a promising objective, versatile, and practical biomarker to assess motor neuron diseases.

Characterizing Progression to Neovascular AMD in Fellow Eyes of Patients Treated With Intravitreal Anti-VEGF Injections.

BACKGROUND AND OBJECTIVE: The purpose of this study was to assess the real-world incidence of conversion to bilateral neovascular age-related macular degeneration (nAMD) following treatment initiation of nAMD in the initial eye. PATIENTS AND METHODS: This was a retrospective cohort of electronic health records from retinal centers across the United States (Vestrum Database) of all patients with unilateral nAMD treated with anti-vascular endothelial growth factor therapy. RESULTS: A total of 22,553 patients with unilateral nAMD were included. Fellow eyes of 8,522 patients (38%) converted to nAMD. Among these, 2,639 (12%), 2,030 (9%), and 1,802 (8%) patients converted in Years 1, 2, and 3, respectively, after diagnosis in the first eye. Fellow eyes had better vision at conversion and 1 year following conversion. CONCLUSIONS: The fellow eye should be monitored at regular intervals to detect signs of neovascularization. Fellow eyes presented with significantly better vision at diagnosis than the initial eye and maintained better visual acuity with less injections. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:123-128.].

Value of systematic genetic screening of patients with amyotrophic lateral sclerosis.

OBJECTIVE: The clinical utility of routine genetic sequencing in amyotrophic lateral sclerosis (ALS) is uncertain. Our aim was to determine whether routine targeted sequencing of 44 ALS-relevant genes would have a significant impact on disease subclassification and clinical care. METHODS: We performed targeted sequencing of a 44-gene panel in a prospective case series of 100 patients with ALS recruited consecutively from the Sheffield Motor Neuron Disorders Clinic, UK. All participants were diagnosed with ALS by a specialist Consultant Neurologist. 7/100 patients had familial ALS, but the majority were apparently sporadic cases. RESULTS: 21% of patients with ALS carried a confirmed pathogenic or likely pathogenic mutation, of whom 93% had no family history of ALS. 15% met the inclusion criteria for a current ALS genetic-therapy trial. 5/21 patients with a pathogenic mutation had an additional variant of uncertain significance (VUS). An additional 21% of patients with ALS carried a VUS in an ALS-associated gene. Overall, 13% of patients carried more than one genetic variant (pathogenic or VUS). Patients with ALS carrying two variants developed disease at a significantly earlier age compared with patients with a single variant (median age of onset=56 vs 60 years, p=0.0074). CONCLUSIONS: Routine screening for ALS-associated pathogenic mutations in a specialised ALS referral clinic will impact clinical care in 21% of cases. An additional 21% of patients have variants in the ALS gene panel currently of unconfirmed significance after removing non-specific or predicted benign variants. Overall, variants within known ALS-linked genes are of potential clinical importance in 42% of patients.

A plea for equitable global access to COVID-19 diagnostics, vaccination and therapy: The NeuroCOVID-19 Task Force of the European Academy of Neurology.

Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.