Evidence map›Paper›PMID 31002412›Full record

ArticleNeuropathology and applied neurobiology2019

White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis.

J Mollink, M Hiemstra, K L Miller, I N Huszar, M Jenkinson, J Raaphorst, M Wiesmann, O Ansorge, M Pallebage-Gamarallage, A M van Cappellen van Walsum

Open access · hybridAbstract read
In one paragraph

Article in Neuropathology and applied neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 10% 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

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.

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  17. Mapping the trigeminal root entry zone and its pontine fibre distribution patterns.Cephalalgia : an international journal of headache · 2020
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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

10 authors at 3 institutions in 2 countries.

J MollinkDepartment of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0003-1199-324X
M HiemstraDepartment of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
K L MillerWellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK.
I N HuszarWellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK.
M JenkinsonWellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK.
J RaaphorstDepartment of Neurology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
M WiesmannDepartment of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
O AnsorgeNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
M Pallebage-GamarallageNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
A M van Cappellen van WalsumDepartment of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
University of Oxford · GBRadboud University Nijmegen · NLAmsterdam University Medical Centers · NL

Funding

Medical Research Council G1000691Medical Research Council MR/K02213X/1Medical Research Council MR/L022656/1
6 · The paper itself

Abstract

objectiveThe aim of this study was to test the hypothesis that white matter degeneration of the perforant path - as part of the Papez circuit - is a key feature of amyotrophic lateral sclerosis (ALS), even in the absence of frontotemporal dementia (FTD) or deposition of pTDP-43 inclusions in hippocampal granule cells.

methodsWe used diffusion Magnetic Resonance Imaging (dMRI), polarized light imaging (PLI) and immunohistochemical analysis of post mortem hippocampus specimens from controls (n = 5) and ALS patients (n = 14) to study white matter degeneration in the perforant path.

resultsdiffusion Magnetic Resonance Imaging demonstrated a decrease in fractional anisotropy (P = 0.01) and an increase in mean diffusivity (P = 0.01) in the perforant path in ALS compared to controls. PLI-myelin density was lower in ALS (P = 0.05) and correlated with fractional anisotropy (r = 0.52, P = 0.03). These results were confirmed by immunohistochemistry; both myelin (proteolipid protein, P = 0.03) and neurofilaments (SMI-312, P = 0.02) were lower in ALS. Two out of the fourteen ALS cases showed pTDP-43 pathology in the dentate gyrus, but with comparable myelination levels in the perforant path to other ALS cases.

conclusionWe conclude that degeneration of the perforant path occurs in ALS patients and that this may occur before, or independent of, pTDP-43 aggregation in the dentate gyrus of the hippocampus. Future research should focus on correlating the degree of cognitive decline to the amount of white matter atrophy in the perforant path.

Indexed as

AgedAged, 80 and overAmyotrophic Lateral SclerosisDiffusion Magnetic Resonance ImagingFemaleHippocampusHumansMaleMiddle AgedPerforant PathwayWhite Matteramyotrophic lateral sclerosisdiffusion MRIfrontotemporal dementiahippocampusperforant pathpolarized light imaging

Identifiers

PMID31002412
PMCPMC6852107
OpenAlexW2912082114

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.