Trial reportPloS one2012
Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology.
Trial report in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00821132 (Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.), which is not on this map. Cited by 163 papers, 9 of them syntheses that pooled 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.
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.
Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.
Who cites it
163 citing papers in PubMed, 9 syntheses or guidelines pooled it, 292 citations in OpenAlex.
- Neuroimaging findings in preclinical amyotrophic lateral sclerosis models-How well do they mimic the clinical phenotype? A systematic review.Frontiers in veterinary science · 2023Pooled it
- Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases-A systematic review and meta-analysis.Frontiers in neurology · 2022Pooled it
- The imaging signature of C9orf72 hexanucleotide repeat expansions: implications for clinical trials and therapy development.Brain imaging and behavior · 2021Pooled it
- Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases.Frontiers in neuroscience · 2021Pooled it
- MatchingFrontiers in neuroanatomy · 2019Pooled it
- Present and Future of Ultra-High Field MRI in Neurodegenerative Disorders.Current neurology and neuroscience reports · 2018Pooled it
- The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review.BMC neurology · 2016Pooled it
- Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation.Neurosciences (Riyadh, Saudi Arabia) · 2016Pooled it
- Mutations in the HFE gene and sporadic amyotrophic lateral sclerosis risk: a meta-analysis of observational studies.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2014Pooled it
- Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis?Antioxidants & redox signaling · 2018Trial
- Review
- In-vivo iron mapping in patients with Parkinson's disease using deep learning-based susceptibility source separation MRI.NPJ Parkinson's disease · 2026Article
- Multimodal ultra-high-field MRI, clinical, cognitive, and genetic profiles across the ALS-FTD spectrum.Scientific data · 2026Article
- Disappearing corticospinal tract on routine MRI: dynamic signal evolution in primary lateral sclerosis.BMJ case reports · 2026Article
- Metabolic signatures of ferritin and TDP-43 co-pathology provide a mechanistic basis for stratified therapeutic approaches in ALS.bioRxiv : the preprint server for biology · 2026Article
- Voxel-Wise Whole-Brain Analysis in Quantitative Susceptibility Mapping: A Narrative Review.Human brain mapping · 2026Review
- Individualized phenotyping of functional amyotrophic lateral sclerosis pathology in sensorimotor cortex.Brain communications · 2026Article
- Role of iron in brain development, aging, and neurodegenerative diseases.Annals of medicine · 2025Review
- Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- Labile iron overload reprograms microglia and neurons for lipid droplet synthesis in the aging brain.bioRxiv : the preprint server for biology · 2025Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T(2)-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2)(*)-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.
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Registered trials
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.