Evidence map›Paper›PMID 25009280›Full record

ArticleJournal of neurology, neurosurgery, and psychiatry2015

Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study.

Ching-Hua Lu, Axel Petzold, Jo Topping, Kezia Allen, Corrie Macdonald-Wallis, Jan Clarke, Neil Pearce, Jens Kuhle, Gavin Giovannoni, Pietro Fratta and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, neurosurgery, and psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.

  1. Pooled it
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  4. Neurofilament as a potential biomarker for spinal muscular atrophy.Annals of clinical and translational neurology · 2019
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  6. Concomitant presence of a novel ARPP21 variant and CNVs in Chinese familial amyotrophic lateral sclerosis-frontotemporal dementia patients.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 7 institutions in 1 country.

Ching-Hua LuCentre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.
Axel PetzoldDepartment of Neuroinflammation, UCL Institute of Neurology, London, UK.
Jo ToppingCentre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Kezia AllenBasildon and Thurrock University Hospitals NHS Foundation Trust, Essex, UK.
Corrie Macdonald-WallisMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Jan ClarkeNational Hospital for Neurology and Neurosurgery, London, UK.
Neil PearceDepartment of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
Jens KuhleCentre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Gavin GiovannoniCentre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Pietro FrattaDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
Katie SidleDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Mark FishClinical Trial Unit, Musgrove Park Hospital, Taunton, UK.
Richard OrrellNational Hospital for Neurology and Neurosurgery, London, UK Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
Robin HowardMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Linda GreensmithSobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK.
Andrea MalaspinaCentre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK Basildon and Thurrock University Hospitals NHS Foundation Trust, Essex, UK North-East London and Essex MND Care and Research Centre, London, UK.
Queen Mary University of London · GBUniversity College London · GBMRC Epidemiology Unit · GBBasildon and Thurrock University Hospitals NHS Foundation Trust · GBLondon School of Hygiene & Tropical Medicine · GBMusgrove Park Hospital · GBNational Hospital for Neurology and Neurosurgery · GB

Funding

Medical Research Council G1000287Medical Research Council MR/M008606/1Motor Neurone Disease Association FRATTA/JAN15/946-795
6 · The paper itself

Abstract

objectiveTo investigate the role of longitudinal plasma neurofilament heavy chain protein (NfH) levels as an indicator of clinical progression and survival in amyotrophic lateral sclerosis (ALS).

methodsA cross-sectional study involving 136 clinically heterogeneous patients with ALS and 104 healthy and neurological controls was extended to include a prospective analysis of 74 of these ALS cases, with samplings at approximately 3-month intervals in a follow-up period of up to 3 years. We analysed the correlation between longitudinal NfH-phosphoform levels and disease progression. Temporal patterns of NfH changes were evaluated using multilevel linear regression.

resultsBaseline plasma NfH levels were higher than controls only in patients with ALS with short disease duration to baseline sampling. Compared with controls, fast-progressing patients with ALS, particularly those with a short diagnostic latency and disease duration, had higher plasma NfH levels at an early stage and lower levels closer to end-stage disease. Lower NfH levels between visits were associated with rapid functional deterioration. We also detected antibodies against NfH, NfH aggregates and NfH cleavage products.

conclusionsDisease progression in ALS involves defined trajectories of plasma NfH levels, reflecting speed of neurological decline and survival. Intervisit plasma NfH changes are also indicative of disease progression. This study confirms that longitudinal measurements of NfH plasma levels are more informative than cross-sectional studies, where the time of sampling may represent a bias in the interpretation of the results. Autoantibodies against NfH aggregates and NfH cleavage products may explain the variable expression of plasma NfH with disease progression. TRAIL REGISTRATION NUMBER: NIHRID6160.

Indexed as

Disease ProgressionAmyotrophic Lateral SclerosisAutoantibodiesCase-Control StudiesCross-Sectional StudiesFemaleHumansLongitudinal StudiesMaleMiddle AgedNeurofilament ProteinsAutoantibodiesNeurofilament ProteinsALSMotor Neuron DiseaseNeuroimmunology

Identifiers

PMID25009280
PMCPMC4413806
OpenAlexW2158562257

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.