Evidence map›Paper›PMID 27658852›Full record

ReviewNature reviews. Neurology2016

Pathophysiological and diagnostic implications of cortical dysfunction in ALS.

Nimeshan Geevasinga, Parvathi Menon, P Hande Özdinler, Matthew C Kiernan, Steve Vucic

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 2 pooled it
13.5field-weighted citation impact, top 1% 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

127 citing papers in PubMed, 2 syntheses or guidelines pooled it, 220 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Review
  7. Exploration of reliable assessment of respiratory function in amyotrophic lateral sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  8. Review
  9. Article
  10. Clinical utility and prospective of TMS-EEG: Updated review from an international expert group.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2026
    Review
  11. Article
  12. Review
  13. Dynamic changes in excitability and viability of sporadic andFrontiers in cell and developmental biology · 2026
    Article
  14. Review
  15. Review
  16. Article
  17. Cell Type-Specific Alterations in Excitability and Inhibition of Upper Motor Neurons in AlsinKO Mice, a Model of Juvenile Onset ALS.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  18. Article
  19. Article
  20. Article

67 more citing papers are in PubMed but not listed here.

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

5 authors at 3 institutions in 2 countries.

Nimeshan GeevasingaWestern Clinical School, University of Sydney, Westmead Hospital, Cnr Hawkesbury and Darcy Road, Wentworthville, New South Wales, 2045, Australia.
Parvathi MenonWestern Clinical School, University of Sydney, Westmead Hospital, Cnr Hawkesbury and Darcy Road, Wentworthville, New South Wales, 2045, Australia.
P Hande ÖzdinlerDavee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, 675 North St Clair Street, Suite 20-100, Chicago, Illinois 60611, USA.
Matthew C KiernanBrain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, New South Wales, 2050, Australia.
Steve VucicWestern Clinical School, University of Sydney, Westmead Hospital, Cnr Hawkesbury and Darcy Road, Wentworthville, New South Wales, 2045, Australia.
The University of Sydney · AUWestmead Hospital · AUNorthwestern University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cortical dysfunction - specifically, the development of hyperexcitability - seems to be an early and intrinsic feature of sporadic and familial amyotrophic lateral sclerosis (ALS) phenotypes, preceding the onset of lower motor neuron dysfunction and correlating with ensuing lower motor neuron dysfunction and degeneration. In fact, cortical dysfunction could provide a pathogenic basis for ALS, with corticomotor neuronal hyperexcitability mediating motor neuron degeneration via a trans-synaptic, glutamate-mediated, excitotoxic mechanism. The recent identification of C9orf72 repeat expansion as an important genetic risk factor for both ALS and frontotemporal dementia has underscored the importance of cortical function in ALS pathogenesis, and has helped to confirm that the disease forms part of a spectrum of central neurodegenerative processes. Changes in cortical function that develop in ALS could prove useful as diagnostic biomarkers, potentially enhancing the diagnosis of ALS at an early stage of the disease process. Pathophysiological and diagnostic biomarkers of cortical function might also provide insights to guide the development of future therapeutic approaches, including stem cell and genetic interventions, thereby providing potential for more-effective management of patients with ALS.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinCortical ExcitabilityHumansMotor NeuronsC9orf72 Protein

Identifiers

PMID27658852
OpenAlexW2522741011

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.