Evidence map›Paper›PMID 30187162›Full record

ArticleJournal of neurology2018

Significance of CSF NfL and tau in ALS.

Stefanie Schreiber, Nicola Spotorno, Frank Schreiber, Julio Acosta-Cabronero, Jörn Kaufmann, Judith Machts, Grazyna Debska-Vielhaber, Cornelia Garz, Daniel Bittner, Nathalie Hensiek and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
5.3field-weighted citation impact, top 4% 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

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.

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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

14 authors at 5 institutions in 3 countries.

Stefanie SchreiberDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany. stefanie.schreiber@med.ovgu.de.ORCID http://orcid.org/0000-0003-4439-4374
Nicola SpotornoGerman Center for Neurodegenerative Diseases (DZNE) Within the Helmholtz Association, Leipziger Straße 44, 39120, Magdeburg, Germany.
Frank SchreiberDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
Julio Acosta-CabroneroGerman Center for Neurodegenerative Diseases (DZNE) Within the Helmholtz Association, Leipziger Straße 44, 39120, Magdeburg, Germany.
Jörn KaufmannDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
Judith MachtsDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
Grazyna Debska-VielhaberDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
Cornelia GarzDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
Daniel BittnerDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
Nathalie HensiekDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
Reinhard DenglerDepartment of Neurology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Susanne PetriDepartment of Neurology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Peter J NestorGerman Center for Neurodegenerative Diseases (DZNE) Within the Helmholtz Association, Leipziger Straße 44, 39120, Magdeburg, Germany.
Stefan VielhaberDepartment of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.
German Center for Neurodegenerative Diseases · DEOtto-von-Guericke-Universität Magdeburg · DEMedizinische Hochschule Hannover · DEThe University of Queensland · AUWellcome Centre for Human Neuroimaging · GB

Funding

Foundation of Medical Research 02728/STVOtto-von-Guericke University Magdeburg Grant for Young Scientists 2016
6 · The paper itself

Abstract

Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has emerged as putative diagnostic biomarker in amyotrophic lateral sclerosis (ALS), but it remains a matter of debate, whether CSF total tau (ttau), tau phosphorylated at threonine 181 (ptau) and the ptau/ttau ratio could serve as diagnostic biomarker in ALS as well. Moreover, the relationship between CSF NfL and tau measures to further axonal and (neuro)degeneration markers still needs to be elucidated. Our analysis included 89 ALS patients [median (range) age 63 (33-83) years, 61% male, disease duration 10 (0.2-190) months] and 33 age- and sex-matched disease controls [60 (32-76), 49%]. NfL was higher and the ptau/ttau ratio was lower in ALS compared to controls [8343 (1795-35,945) pg/ml vs. 1193 (612-2616), H(1) = 70.8, p < 0.001; mean (SD) 0.17 (0.04) vs. 0.2 (0.03), F(1) = 14.3, p < 0.001], as well as in upper motor neuron dominant (UMND, n = 10) compared to classic (n = 46) or lower motor neuron dominant ALS [n = 31; for NfL: 16,076 (7447-35,945) vs. 8205 (2651-35,138) vs. 8057 (1795-34,951)], Z ≥ 2.5, p ≤ 0.01; for the ptau/ttau ratio: [0.13 (0.04) vs. 0.17 (0.04) vs. 0.18 (0.03), p ≤ 0.02]. In ALS, NfL and the ptau/ttau ratio were related to corticospinal tract (CST) fractional anisotropy (FA) and radial diffusivity (ROI-based approach and whole-brain voxelwise analysis). Factor analysis of mixed data revealed a co-variance pattern between NfL (factor load - 0.6), the ptau/ttau ratio (0.7), CST FA (0.8) and UMND ALS phenotype (- 2.8). NfL did not relate to any further neuroaxonal injury marker (brain volumes, precentral gyrus thickness, peripheral motor amplitudes, sonographic cross-sectional nerve area), but a lower ptau/ttau ratio was associated with whole-brain gray matter atrophy and widespread white matter integrity loss. Higher NfL baseline levels were associated with greater UMN disease burden, more rapid disease progression, a twofold to threefold greater hazard of death and shorter survival times. The findings that higher CSF NfL levels and a reduced ptau/ttau ratio are more associated with clinical UMN involvement and with reduced CST FA offer strong converging evidence that both are markers of central motor degeneration. Furthermore, NfL is a marker of poor prognosis, while a low ptau/ttau ratio indicates extramotor pathology in ALS.

Indexed as

AdultAgedAged, 80 and overAmyotrophic Lateral SclerosisBiomarkersBrainCross-Sectional StudiesDisease ProgressionFemaleFollow-Up StudiesHumansMaleMiddle AgedNeurofilament ProteinsPhosphorylationRetrospective StudiesBiomarkersMAPT protein, humanneurofilament protein LNeurofilament Proteinstau ProteinsAmyotrophic lateral sclerosisCerebrospinal fluidDiffusion tensor imagingMRINeurofilament light chainPtau/ttau ratioTau phosphorylated at threonine 181 (ptau)Ttau

Identifiers

PMID30187162
OpenAlexW2890542093

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.