3,802 results match your criteria: "UCL Queen Square Institute of Neurology[Affiliation]"

Objective: SCN2A encodes the voltage-gated sodium (Na+) channel α subunit Na1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders.

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The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

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Investigating the complementary value of OCT to MRI in cognitive impairment in relapsing-remitting multiple sclerosis.

Mult Scler

December 2024

Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.

Background: Cognitive decline in multiple sclerosis (MS) is associated with neuro-axonal loss, quantifiable by optical coherence tomography (OCT). Associations between OCT measures and cognition in relapsing-remitting MS (RRMS) remain incompletely investigated, particularly the added value of OCT when combined with magnetic resonance imaging (MRI). We investigated the contributions of OCT and MRI while applying stringent criteria to control for subclinical optic neuropathy.

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Background: ATX-FGF/SCA27A has been exclusively associated with heterozygous variants in the FGF14 gene, presenting with postural tremor, slowly progressive cerebellar ataxia, and psychiatric and behavioral disturbances.

Objectives: This study describes the first case of ATX-FGF/SCA27A linked to a biallelic frameshift variant in the FGF14 gene.

Methods: Whole-exome sequencing (WES) was conducted using the Illumina NovaSeq 6000 platform, and the identified variant was confirmed using Sanger sequencing.

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Background: Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral haemorrhage (ICH) with a high recurrence risk. Left atrial appendage occlusion (LAAO) is a method for ischaemic stroke prevention in patients with atrial fibrillation (AF), potentially reducing the risk of intracranial bleeding in CAA-associated ICH. We aimed to determine the outcomes of patients with AF with CAA-associated ICH undergoing LAAO.

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Background: Can plasma biomarkers as well as cerebrospinal fluid (CSF) perform in the separation of amyloid-beta-positive (Aβ+) vs amyloid-beta-negative (Aβ-) groups across an age range seen in an NHS cognitive disorder clinic?

Methods: As part of the routine diagnostic investigation of 111 clinic patients who had contemporaneous blood and CSF samples taken, patients were categorised into Aβ+ and Aβ- groups based on their CSF in an Aβ42/40 ratio. We then evaluated four single molecule array (Simoa) Quanterix assays, quantifying single plasma analytes and ratios (p-tau217, p-tau217/Aβ42 ratio, p-tau181, p-tau181/Aβ42 ratio and Aβ42/40 ratio) in their ability to distinguish between these groups and the effect of age.

Results: The median (range) age of participants was 66 (55-79) years with 48 females (43.

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Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial.

J Neurol Neurosurg Psychiatry

December 2024

Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.

Background: Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS).

Methods: We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks.

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Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.

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Alpha rhythm slowing in temporal lobe epilepsy across scalp EEG and MEG.

Brain Commun

December 2024

CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing, Newcastle University, NE4 5DG Newcastle upon Tyne, UK.

EEG slowing is reported in various neurological disorders including Alzheimer's, Parkinson's and Epilepsy. Here, we investigate alpha rhythm slowing in individuals with refractory temporal lobe epilepsy compared with healthy controls, using scalp EEG and magnetoencephalography. We retrospectively analysed data from 17 (46) healthy controls and 22 (24) individuals with temporal lobe epilepsy who underwent scalp EEG and magnetoencephalography recordings as part of presurgical evaluation.

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Background: Myoclonus and other jerky movement disorders are hyperkinetic disorders, the diagnosis of which heavily relies on clinical neurophysiological testing. However, formal diagnostic criteria are lacking, and recently the utility and reliability of these tests have been questioned.

Objective: The aim of this review was to assess the utilization of clinical neurophysiology testing to identify possible gaps and boundaries that might guide the development of new methods for a more precise diagnosis and in-depth understanding of myoclonus.

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Background: Stroke is the second leading cause of disability worldwide. Stroke results in focal neurological deficit and often leads to auditory problems due to its impact on the auditory pathway. Altered connections in the auditory pathway, caused by stroke, can result in hearing difficulties ranging from impaired sound detection to altered auditory perception.

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Meta-analyses uncover the genetic architecture of Idiopathic Inflammatory Myopathies.

Arthritis Rheumatol

December 2024

Institute for Clinical and Translational Research, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.

Objective: Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.

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Musicality and social cognition in dementia: clinical and anatomical associations.

Brain Commun

December 2024

Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, 1081 HZ Amsterdam, The Netherlands.

Human musicality might have co-evolved with social cognition abilities, but common neuroanatomical substrates remain largely unclear. In behavioural variant frontotemporal dementia, social cognitive abilities are profoundly impaired, whereas these are typically spared in Alzheimer's disease. If musicality indeed shares a neuroanatomical basis with social cognition, it could be hypothesized that clinical and neuroanatomical associations of musicality and social cognition should differ between these causes of dementia.

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Multicenter Validation of the Ocular Myasthenia Gravis Rating Scale Questionnaire.

Neurology

January 2025

From the Department of Neuro-Ophthalmology (S.H.W.), Moorfields Eye Hospital NHS Foundation Trust; Departments of Ophthalmology and Neurology (S.H.W.), Guy's and St Thomas' NHS Foundation Trust; Department of Ophthalmology (S.H.W.), Faculty of Life Sciences & Medicine, King's College London; Department of Clinical and Movement Neuroscience (S.H.W.), UCL Queen Square Institute of Neurology, University College London, United Kingdom; Department of Ophthalmology and Visual Sciences (R.A., W.T.C., T.D., J.R.E., C.A.A., L.B.D.L.), Kellogg Eye Center, University of Michigan, Ann Arbor; Departments of Ophthalmology, Neurology, and Neurosurgery (E.R.E., S.K.), Mayo Clinic, FL; Survey Research Center (J.R.E.), Institute for Social Research, University of Michigan, Ann Arbor; and Division of Neurology (C.B.-T.), Department of Medicine, University Health Network and University of Toronto, Ontario, Canada.

Background And Objectives: Ocular myasthenia gravis (OMG) causes disabling ocular symptoms of ptosis and diplopia, but a validated disease-specific patient-reported outcome measure (PROM) has not been reported. We sought to validate a novel PROM for OMG, OMG Rating Scale Questionnaire (OMGRate-q), as a measure of visual functioning to support patient-centered care.

Methods: This was a prospective study of patients aged 18 years and older with OMG receiving care at 3 medical centers (January 2022-October 2023).

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In many neurological conditions, early-stage neural circuit adaptation preserves relatively normal behavior. In some diseases, spinal motoneurons progressively degenerate yet movement remains initially preserved. This study investigates whether these neurons and associated microcircuits adapt in a mouse model of progressive motoneuron degeneration.

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Tyro3 and Gas6 are associated with white matter and myelin integrity in multiple sclerosis.

J Neuroinflammation

December 2024

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.

Article Synopsis
  • The study explores the Gas6/TAM receptor system's impact on neurodegeneration in multiple sclerosis (MS), focusing on how it relates to demyelination and remyelination processes.
  • Researchers analyzed cerebrospinal fluid (CSF) samples from various MS patients and healthy controls to measure soluble Gas6/TAM biomarkers and assess brain volume changes over time.
  • Findings suggest that elevated levels of Gas6 and its receptors correlate with greater white matter damage and that lower levels of these markers may indicate better remyelination, highlighting their potential role in MS progression.
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The association of polytherapy and psychiatric comorbidity in epilepsy.

Epilepsy Behav

December 2024

Neurosciences Unit, KEMRI Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya; Department of Public Health, School of Human and Health Sciences, Pwani University, P.O Box 195-80108, Kilifi, Kenya; Department of Psychiatry, University of Oxford, Oxford, United Kingdom; African Population and Health Research Centre, Nairobi, Kenya. Electronic address:

Purpose: Managing epilepsy may require using more than one anti-seizure medication (ASM). While combination therapy may help, risks, including psychiatric problems, are not fully explored in Africa. We examined the relationship between polytherapy and psychiatric comorbidities among attendees of an epilepsy community clinic.

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The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2.

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Evaluating multiple sclerosis severity loci 30 years after a clinically isolated syndrome.

Brain Commun

December 2024

NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London Queen Square Institute of Neurology, London WC1N 3BG, UK.

The first genome-wide significant multiple sclerosis severity locus, rs10191329, has been pathologically linked to cortical lesion load and brain atrophy. However, observational cohorts such as MSBase have not replicated associations with disability outcomes, instead finding other loci. We evaluated rs10191329 and MSBase loci in a unique cohort of 53 people followed for 30 years after a clinically isolated syndrome, with deep clinical phenotyping and MRI measures of inflammation and neurodegeneration.

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What do we really know about the external urethral sphincter?

Continence (Amst)

June 2024

University of Bristol, School of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, Bristol BS8 1TD, UK.

The external urethral sphincter (EUS), composed of skeletal muscle, along with a smooth muscle-lined internal urethral sphincter (IUS), have crucial roles in maintaining continence during bladder filling and facilitating urine flow during voiding. Disruption of this complex activity has profound consequences on normal lower urinary tract function during the micturition cycle. However, relatively little is known about the normal and pathological functions of these particular muscle types, how activity can be manipulated and regulated and why, for example, loss of EUS function and sarcopenia is associated with ageing.

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African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Nat Struct Mol Biol

December 2024

Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

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Myogenic fusion, primarily regulated by the Myomaker and Myomixer proteins, is essential for skeletal muscle development, yet its mechanisms remain poorly understood. This study presents the clinical and molecular details of the third and fourth reported patients with biallelic variants in MYMX, the gene that encodes Myomixer. We identified a homozygous truncating variant [c.

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Mitochondrial DNA (mtDNA) encodes genes essential for oxidative phosphorylation. The m.3243A>G mutation causes severe disease, including myopathy, lactic acidosis and stroke-like episodes (MELAS) and is the most common pathogenic mtDNA mutation in humans.

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