Evidence map›Paper›PMID 33484486›Full record

ArticleAnnals of clinical and translational neurology2021

CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis.

Roberta Magliozzi, Marco Pitteri, Stefano Ziccardi, Anna Isabella Pisani, Luigi Montibeller, Damiano Marastoni, Stefania Rossi, Valentina Mazziotti, Maddalena Guandalini, Caterina Dapor and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  13. Regulation of the E/I-balance by the neural matrisome.Frontiers in molecular neuroscience · 2023
    Review
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  17. Article
  18. Regionally restricted modulation ofFrontiers in molecular neuroscience · 2022
    Article
  19. Neuroinflammation: 2022 update.Free neuropathology · 2022
    Article
  20. Review
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

15 authors at 4 institutions in 3 countries.

Roberta MagliozziNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.ORCID 0000-0001-8284-7763
Marco PitteriNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.ORCID 0000-0001-8093-4548
Stefano ZiccardiNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Anna Isabella PisaniNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Luigi MontibellerNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Damiano MarastoniNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Stefania RossiDepartment of Oncology and Molecular Oncology, Istituto Superiore di Sanità, Rome, Italy.
Valentina MazziottiNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Maddalena GuandaliniNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Caterina DaporNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Gianmarco SchiaviNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Agnese TamantiNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Richard NicholasDivision of Neuroscience, Department of Brain Sciences, Imperial College London, London, United Kingdom.ORCID 0000-0003-0414-1225
Richard ReynoldsDivision of Neuroscience, Department of Brain Sciences, Imperial College London, London, United Kingdom.
Massimiliano CalabreseNeurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
University of Verona · ITImperial College London · GBIstituto Superiore di Sanità · ITZero to Three · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

INTRODUCTION AND

methodsIn order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis.

resultsPVALB gene expression was downregulated in MS (fold change = 3.7 ± 1.2, P < 0.001 compared to controls) reflecting the significant reduction of PVALB+ cell density in cortical lesions, to a greater extent in MS patients with high meningeal inflammation (51.8, P < 0.001). Likewise, post-mortem CSF-PVALB levels were higher in MS compared to controls (fold change = 196 ± 36, P < 0.001) and correlated with decreased PVALB+ cell density (r = -0.64, P < 0.001) and increased MHC-II+ microglia density (r = 0.74, P < 0.01), as well as with early age of onset (r = -0.69, P < 0.05), shorter time to wheelchair (r = -0.49, P < 0.05) and early age of death (r = -0.65, P < 0.01). Increased CSF-PVALB levels were detected in MS patients at diagnosis compared to controls (P = 0.002). Significant correlation was found between CSF-PVALB levels and cortical lesion number on MRI (R = 0.28, P = 0.006) and global cortical thickness (R = -0.46, P < 0.001), better than Nf-L levels. CSF-PVALB levels increased in MS patients with severe cognitive impairment (mean ± SEM:25.2 ± 7.5 ng/mL) compared to both cognitively normal (10.9 ± 2.4, P = 0.049) and mild cognitive impaired (10.1 ± 2.9, P = 0.024) patients.

conclusionsCSF-PVALB levels reflect loss of cortical interneurons in MS patients with more severe disease course and might represent an early, new MS-specific biomarker of cortical neurodegeneration, atrophy, and cognitive decline.

Indexed as

AdultAutopsyBiomarkersCerebral CortexDown-RegulationFemaleGene ExpressionHumansInterneuronsMagnetic Resonance ImagingMaleMotor CortexMultiple Sclerosis, Chronic ProgressiveNeurofilament ProteinsParvalbuminsYoung AdultBiomarkersneurofilament protein LNeurofilament ProteinsParvalbuminsPVALB protein, human

Identifiers

PMID33484486
PMCPMC7951111
OpenAlexW3125035486

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.