Evidence map›Paper›PMID 41388206›Full record

ArticleJournal of neurology2025

Motor phenotypes and neurofilament light chain in genetic amyotrophic lateral sclerosis-results from a multicenter screening program.

Philipp Schmitt, Peggy Schumann, Alexander Koerbs, Hsuen-Ju Lin, Torsten Grehl, Ute Weyen, Susanne Petri, Annekathrin Rödiger, Robert Steinbach, Julian Großkreutz and 18 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

28 authors.

Philipp SchmittDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. philipp.schmitt@charite.de.ORCID http://orcid.org/0009-0008-1643-0079
Peggy SchumannDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Alexander KoerbsAmedes Genetics, Hannover, Germany.
Hsuen-Ju LinAmedes Genetics, Hannover, Germany.
Torsten GrehlDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Alfried Krupp Krankenhaus, Essen, Germany.
Ute WeyenDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum, Germany.
Susanne PetriDepartment of Neurology, Hannover Medical School, Hannover, Germany.
Annekathrin RödigerDepartment of Neurology, Jena University Hospital, Jena, Germany.
Robert SteinbachDepartment of Neurology, Jena University Hospital, Jena, Germany.
Julian GroßkreutzDepartment of Neurology, Universitätsmedizin Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Sarah BernsenDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Patrick WeydtDepartment for Neuromuscular Disorders, Bonn University, Bonn, Germany.
Joachim WolfDepartment of Neurology, Brüderklinikum Julia Lanz, Diako Mannheim, Mannheim, Germany.
René GüntherDepartment of Neurology, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Petra BaumDepartment of Neurology, University Hospital Leipzig, Leipzig, Germany.
Moritz MetelmannDepartment of Neurology, University Hospital Leipzig, Leipzig, Germany.
Jochen H WeishauptDepartment of Neurology, University of Ulm, Ulm, Germany.
Berthold StreubelInstitute for Pathology, Medical University of Wien, Vienna, Austria.
David C KasperARCHIMED Life Science GmbH, Vienna, Austria.
Yasemin KocDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Dagmar KettemannDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Jenny NordenDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Bertram WalterDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Christoph MünchDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Susanne SpittelAmbulanzpartner Soziotechnologie APST GmbH, Berlin, Germany.
André MaierDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Péter KörtvélyessyDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Thomas MeyerDepartment of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveIn genetic amyotrophic lateral sclerosis (ALS), the clinical phenotypes, disease progression and neurofilament light chain (NfL) levels are incompletely characterized.

methodsIn a total cohort of 1988 ALS patients, a subcohort of genetic ALS linked to C9orf72 (n = 137), SOD1 (n = 54), TARDBP (n = 27), and FUS (n = 19) was investigated. The phenotypes of onset region, propagation and motor neuron involvement were analyzed according to the OPM classification. Serum NfL (sNfL) was measured and related to ALS progression (ALSPR, monthly change of ALS Functional Rating Scale-Revised). To quantify NfL elevation relative to ALSPR, the logNfL(index), the log-transformed ratio of sNfL to ALSPR was calculated.

resultsC9orf72-associated ALS showed frequent bulbar onset (n = 42.6%), higher ALSPR (0.95, SD 0.84), highest NfL (116.3, SD 72.7 pg/mL) and logNfL(index) (5.02, SD 0.88). SOD1-ALS had mostly limb onset (n = 96.1%), slower ALSPR (0.57, SD 0.60), high NfL (76.1, SD 61.4 pg/mL) and a comparably high logNfL(index) (4.94, SD 1.03). FUS-ALS exhibited mostly limb onset (82.4%), lower motor neuron dysfunction (70.6%), a wide range of faster (22.2%) to slower ALSPR (55.6%), lower NfL (66.2, SD 32.9) and logNfL(4.65, SD 0.9). TARDBP-ALS displayed the lowest ALSPR (0.53, SD 0.52), the lowest NfL (43.3, SD 31.8 pg/mL) and the lowest logNfL(index) (4.40, SD 0.7).

conclusionIn C9orf72-ALS, the phenotype and NfL profile are close to typical ALS. The finding of distinct phenotypes and NfL patterns in SOD1-, FUS- and TARDBP-associated ALS underscores the relevance of genetic ALS for prognostic counseling, clinical trial design, treatment expectations and unraveling of pathogenic mechanisms in ALS.

Indexed as

Amyotrophic Lateral SclerosisNeurofilament ProteinsAdultAgedC9orf72 ProteinCohort StudiesDisease ProgressionDNA-Binding ProteinsFemaleHumansMaleMiddle AgedPhenotypeRNA-Binding Protein FUSSuperoxide Dismutase-1C9orf72 ProteinC9orf72 protein, humanDNA-Binding ProteinsFUS protein, humanneurofilament protein LNeurofilament ProteinsRNA-Binding Protein FUSSOD1 protein, humanSuperoxide Dismutase-1TARDBP protein, humanALS progressionGenetic ALSNeurofilamentPhenotype

Identifiers

PMID41388206
PMCPMC12700978

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