Search results for: P. Nigel Leigh

Items from 1 to 20 out of 36 results

article

Pharmacometabolomics applied to low‐dose interleukin‐2 treatment in amyotrophic lateral sclerosis

Hugo Alarcan, Clément Bruno, Patrick Emond, Cédric Raoul, more

Annals of the New York Academy of Sciences > 1536 > 1 > 82 - 91

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The immunosuppressive functions of regulatory T lymphocytes (Tregs) are impaired in ALS, and correlate to disease progression. The phase 2a IMODALS trial reported an increase in Treg number in ALS patients following the administration of low‐dose (ld) interleukin‐2 (IL‐2). We propose a pharmacometabolomics approach to decipher...

article

Frequency and outcomes of gastrostomy insertion in a longitudinal cohort study of atypical parkinsonism

Christopher Kobylecki, Viorica Chelban, Yee Yen Goh, Emilia Michou, more

European Journal of Neurology > 31 > 6 > n/a - n/a

Background Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) show a high prevalence and rapid progression of dysphagia, which is associated with reduced survival. Despite this, the evidence base for gastrostomy is poor, and the optimal frequency and outcomes of this intervention are not known. We aimed to characterise the prevalence and outcomes of...

article

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome

David J. Whiteside, Duncan Street, Alexander G. Murley, P. Simon Jones, more

Human Brain Mapping > 44 > 11 > 4239 - 4255

There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson‐plus...

article

Genome‐wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy

Zhongbo Chen, Jason A. Chen, Aleksey Shatunov, Ashley R. Jones, more

Movement Disorders > 34 > 7 > 1049 - 1059

Background Progressive supranuclear palsy is a neurodegenerative tauopathy manifesting clinically as a progressive akinetic‐rigid syndrome. In this study, we sought to identify genetic variants influencing PSP susceptibility through a genome‐wide association analysis of a cohort of well‐characterized patients who had participated in the Neuroprotection and Natural History in Parkinson Plus Syndromes...

article

Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases

Jason A. Chen, Zhongbo Chen, Hyejung Won, Alden Y. Huang, more

Molecular Neurodegeneration > 2018 > 13 > 1 > 1-11

Background Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease for which the genetic contribution is incompletely understood. Methods We conducted a joint analysis of 5,523,934 imputed SNPs in two newly-genotyped progressive supranuclear palsy cohorts, primarily derived from two clinical trials (Allon davunetide and NNIPPS riluzole trials in PSP) and a previously published genome-wide...

article

Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial

Vincent Meininger, Angela Genge, Leonard H van den Berg, Wim Robberecht, more

The Lancet Neurology > 2017 > 16 > 3 > 208-216

Neurite outgrowth inhibitor A (Nogo-A) is thought to have a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). A monoclonal antibody against Nogo-A showed a positive effect in the SOD1^G93A mouse model of ALS, and a humanised form of this antibody (ozanezumab) was well tolerated in a first-in-human trial. Therefore, we aimed to assess the safety and efficacy of ozanezumab in patients...

article

Characterizing axonal myelination within the healthy population: a tract-by-tract mapping of effects of age and gender on the fiber g-ratio

Mara Cercignani, Giovanni Giulietti, Nick G. Dowell, Matt Gabel, more

Neurobiology of Aging > 2017 > 49 > C > 109-118

The g-ratio, equal to the ratio of the inner-to-outer diameter of a myelinated axon, is associated with the speed of conduction, and thus reflects axonal function and integrity. It is now possible to estimate an “aggregate” g-ratio in vivo using MRI. The aim of this study was to assess the variation of the MRI-derived fiber g-ratio in the brain of healthy individuals, and to characterize its variation...

article

Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study

Ammar Al-Chalabi, Andrea Calvo, Adriano Chio, Shuna Colville, more

The Lancet Neurology > 2014 > 13 > 11 > 1108-1113

Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. We generated incidence...

article

C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: A genome‐wide meta‐analysis

Frank P. Diekstra, Vivianna M. Deerlin, John C. Swieten, Ammar Al‐Chalabi, more

Annals of Neurology > 76 > 1 > 120 - 133

ObjectiveSubstantial clinical, pathological, and genetic overlap exists between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP‐43 inclusions have been found in both ALS and FTD cases (FTD‐TDP). Recently, a repeat expansion in C9orf72 was identified as the causal variant in a proportion of ALS and FTD cases. We sought to identify additional evidence for a common genetic...

article

Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeat

Ashley R. Jones, Ione Woollacott, Aleksey Shatunov, Johnathan Cooper-Knock, more

Neurobiology of Aging > 2013 > 34 > 9 > 2234.e1-2234.e7

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons. Single-nucleotide polymorphism rs3849942 is associated with ALS, tagging a hexanucleotide repeat mutation in the C9orf72 gene. It is possible that there is more than 1 disease-causing genetic variation at this locus, in which case association might remain after removal of cases carrying the mutation. DNA from patients...

article

Trimodal pattern of C9ORF72 GGGGCC normal allele repeat number in sporadic amyotrophic lateral sclerosis and lack of association with disease risk and age at onset

Ione Woollacott, Aleksey Shatunov, Ashley Jones, Karen E Morrison, more

The Lancet > 2013 > 381 > Supplement 1 > S116

Recent research has discovered a non-coding hexanucleotide repeat expansion mutation (HREM) of the chromosome 9 open reading frame 72 (C9ORF72) gene, which produces hundreds of pathological GGGGCC repeats on one allele in up to 40% of familial and 10% of patients with sporadic amyotrophic lateral sclerosis (ALS). We studied patients with sporadic ALS who had a normal number of repeats (up to 23) on...

article

Behavioural and emotional symptoms of apathy are associated with distinct patterns of brain atrophy in neurodegenerative disorders

Biba R. Stanton, P. Nigel Leigh, Robert J. Howard, Gareth J. Barker, more

Journal of Neurology > 2013 > 260 > 10 > 2481-2490

Apathy is a neurocognitive syndrome of reduced goal-directed behaviour and is an important cause of disability in neurodegenerative disorders. Frontal–subcortical dysfunction is thought to be important in apathy, but the contribution of individual brain regions to different aspects of the apathy syndrome is poorly understood. We aimed to test the hypotheses that apathy in two distinct neurodegenerative...

article

The anatomy of cognitive impairment in amyotrophic lateral sclerosis: More than frontal lobe dysfunction

Stella Tsermentseli, P. Nigel Leigh, Laura H. Goldstein

Cortex > 2012 > 48 > 2 > 166-182

Cognitive and behavioural impairments accompanying amyotrophic lateral sclerosis (ALS) have been reported since the early 20th century. Typically, these changes can be associated with a dysexecutive syndrome or manifest as a frontotemporal dementia (FTD). Although the nature of specific frontotemporal dysfunction in ALS remains to be refined, as with the clinical presentation, there is likely to be...

article

Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study

Aleksey Shatunov, Kin Mok, Stephen Newhouse, Michael E Weale, more

The Lancet Neurology > 2010 > 9 > 10 > 986-994

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons that results in progressive weakness and death from respiratory failure, commonly within about 3 years. Previous studies have shown association of a locus on chromosome 9p with ALS and linkage with ALS–frontotemporal dementia. We aimed to test whether this genomic region is also associated with ALS in an independent...

article

Nutritional factors associated with survival following enteral tube feeding in patients with motor neurone disease

A. Rio, C. Ellis, C. Shaw, E. Willey, more

Journal of Human Nutrition and Dietetics > 23 > 4 > 408 - 415

Background: Motor neurone disease (MND) is a progressive neurodegenerative disease leading to limb weakness, wasting and respiratory failure. Prolonged poor nutritional intake causes fatigue, weight loss and malnutrition. Consequently, disease progression requires decisions to be made regarding enteral tube feeding. The present study aimed to investigate the survival, nutritional status and complications...

article

Riluzole protects against glutamate-induced slowing of neurofilament axonal transport

Alison Stevenson, Darran M. Yates, Catherine Manser, Kurt J. De Vos, more

Neuroscience Letters > 2009 > 454 > 2 > 161-164

Riluzole is the only drug approved for the treatment of amyotrophic lateral sclerosis (ALS) but its precise mode of action is not properly understood. Damage to axonal transport of neurofilaments is believed to be part of the pathogenic mechanism in ALS and this has been linked to defective glutamate handling and increased phosphorylation of neurofilament side-arm domains. Here, we show that riluzole...

article

Imaging the brain during sniffing: A pilot fMRI study

Blaž Koritnik, Sheba Azam, Chris M. Andrew, P. Nigel Leigh, more

Pulmonary Pharmacology & Therapeutics > 2009 > 22 > 2 > 97-101

Whilst the act of sniffing can provide us with an indirect method to study the central mechanisms of respiratory control, functional neuroimaging now provides us with a tool to directly visualise the activity of the human brain during this voluntary action using functional magnetic resonance imaging (fMRI).We performed fMRI during sniffing in 11 healthy volunteers where all subjects executed single,...

article

Mushroom-cage gastrostomy tube placement in patients with amyotrophic lateral sclerosis: a 5-year experience in 104 patients in a single institution

Dylan Lewis, Mary-Ann Ampong, Alan Rio, Emma Willey, more

European Radiology > 2009 > 19 > 7 > 1763-1771

To review our experience of placement of a mushroom-cage gastrostomy tube (Entristar®, Tyco Healthcare, Mansfield, MA), using radiological guidance, in patients with amyotrophic lateral sclerosis (ALS). All procedures were performed under local anaesthesia without sedation. Complications were recorded as peri-procedural, early (<24 h), late (>24 h), major or minor. Deaths were recorded as related...

article

Biomarkers in amyotrophic lateral sclerosis

Martin R Turner, Matthew C Kiernan, P Nigel Leigh, Kevin Talbot

The Lancet Neurology > 2009 > 8 > 1 > 94-109

Amyotrophic lateral sclerosis (ALS; motor neuron disease) is a relentlessly progressive disorder. After half a century of trials, only one drug with modest disease-modifying potency—riluzole—has been developed. The diagnosis of this disorder is still clinical and there is a pronounced delay between the onset of symptoms and diagnosis, possibly beyond the therapeutic window. Bedside quantification...

article

Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport

Catherine Manser, Alison Stevenson, Steven Banner, Jennifer Davies, more

FEBS Letters > 2008 > 582 > 15 > 2303-2308

Neurofilaments are synthesised in neuronal cell bodies and then transported through axons. Damage to neurofilament transport is seen in amyotrophic lateral sclerosis (ALS). Here, we show that PKN1, a neurofilament head–rod domain kinase is cleaved and activated in SOD1G93A transgenic mice that are a model of ALS. Moreover, we demonstrate that glutamate, a proposed toxic mechanism in ALS leads to caspase...

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INFONA - science communication portal

Search results for: P. Nigel Leigh

Pharmacometabolomics applied to low‐dose interleukin‐2 treatment in amyotrophic lateral sclerosis

Frequency and outcomes of gastrostomy insertion in a longitudinal cohort study of atypical parkinsonism

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome

Genome‐wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy

Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases

Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial

Characterizing axonal myelination within the healthy population: a tract-by-tract mapping of effects of age and gender on the fiber g-ratio

Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study

C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: A genome‐wide meta‐analysis

Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeat

Trimodal pattern of C9ORF72 GGGGCC normal allele repeat number in sporadic amyotrophic lateral sclerosis and lack of association with disease risk and age at onset

Behavioural and emotional symptoms of apathy are associated with distinct patterns of brain atrophy in neurodegenerative disorders

The anatomy of cognitive impairment in amyotrophic lateral sclerosis: More than frontal lobe dysfunction

Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study

Nutritional factors associated with survival following enteral tube feeding in patients with motor neurone disease

Riluzole protects against glutamate-induced slowing of neurofilament axonal transport

Imaging the brain during sniffing: A pilot fMRI study

Mushroom-cage gastrostomy tube placement in patients with amyotrophic lateral sclerosis: a 5-year experience in 104 patients in a single institution

Biomarkers in amyotrophic lateral sclerosis

Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport

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