Evidence map›Paper›PMID 42300806›Full record

ArticleAnnals of clinical and translational neurology2026

Integration of Serum Neurofilament Light Chain and Cortical Dysfunction Improves Diagnostic Accuracy in ALS.

Aicee Dawn Calma, Nathan Pavey, Yukiko Tsuji, Amirul Ab Ghapar, Mehdi A J van den Bos, Bronwen Orden, Grace Lee, Linda Mekhael, Julie Ryder, Cláudia Santos Silva and 7 more

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In one paragraph

Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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

17 authors.

Aicee Dawn CalmaBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Nathan PaveyBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Yukiko TsujiBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Amirul Ab GhaparBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Mehdi A J van den BosBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Bronwen OrdenBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Grace LeeBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Linda MekhaelBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Julie RyderBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Cláudia Santos SilvaDepartment of Neurology, Unidade Local de Saúde de Almada-Seixal, Almada, Portugal.
David McDonaldDepartment of Immunopathology, NSW Health Pathology and ICPMR, Westmead Hospital, Westmead, New South Wales, Australia.
Fakhria KakarDepartment of Immunopathology, NSW Health Pathology and ICPMR, Westmead Hospital, Westmead, New South Wales, Australia.
Con YiannikasConcord Repatriation General Hospital, Sydney, New South Wales, Australia.
Matthew C KiernanNeuroscience Research Australia, Sydney, Australia.
David A BrownDepartment of Immunopathology, NSW Health Pathology and ICPMR, Westmead Hospital, Westmead, New South Wales, Australia.
Parvathi MenonBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Steve VucicBrain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.ORCID https://orcid.org/0000-0002-8323-873X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo determine whether integration of serum neurofilament light chain (NfL) and cortical dysfunction improves diagnostic accuracy in amyotrophic lateral sclerosis (ALS) when applied alongside the Gold Coast criteria (GCC).

methodsIn this prospective study, 148 participants with suspected ALS were recruited (101 ALS and 47 with ALS mimicking disorders). Participants taking medications known to influence TMS measures were excluded. Serum NfL levels were quantified using a single-molecule array assay. Cortical function was assessed using threshold tracking transcranial magnetic stimulation, with cortical dysfunction defined by reduced mean short interval intracortical inhibition or motor cortex inexcitability. Diagnostic performance was evaluated using sensitivity, specificity, and diagnostic odds ratios (DOR), with 95% confidence intervals (CI).

resultsSerum NfL demonstrated excellent discrimination (area under the curve 0.92, p < 0.001), with cut-off ≥ 33.5 pg/mL providing a sensitivity of 0.85 (95% CI 0.77-0.91) and specificity 0.87 (95% CI 0.75-0.94). Cortical dysfunction demonstrated very good diagnostic performance (sensitivity 0.77 [95% CI 0.68-0.84], specificity 0.77 [95% CI 0.63-0.86]). The GCC achieved a sensitivity of 0.89 (95% CI 0.82-0.94) and specificity 0.89 (95% CI 0.77-0.95). Combining GCC with elevated NfL or cortical dysfunction increased the specificity to 0.98 (95% CI 0.89-1.00) while maintaining high sensitivity at 0.87 (95% CI 0.79-0.92), yielding the highest DOR.

interpretationIntegration of serum NfL and cortical dysfunction with the Gold Coast criteria improves diagnostic accuracy in ALS, particularly by increasing specificity. This multimodal approach provides a practical framework for earlier and more definitive diagnosis that may facilitate more efficient clinical trial recruitment.

Indexed as

amyotrophic lateral sclerosiscortical dysfunctionneurofilament light chain

Identifiers

PMID42300806
PMCPMC13394030

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.