Evidence map›Paper›PMID 33495377›Full record

ArticleNeurology2021

Association of Epileptic and Nonepileptic Seizures and Changes in Circulating Plasma Proteins Linked to Neuroinflammation.

John M Gledhill, Elizabeth J Brand, John R Pollard, Richard D St Clair, Todd M Wallach, Peter B Crino

Open access · greenAbstract read
In one paragraph

Article in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.6field-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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

John M GledhillFrom Cognizance Biomarkers (J.M.G., E.J.B., R.D.S., T.M.W.), Spring House, PA; Christiana Care (J.R.P.), Newark, DE; and Department of Neurology (P.B.C.), University of Maryland, Baltimore.
Elizabeth J BrandFrom Cognizance Biomarkers (J.M.G., E.J.B., R.D.S., T.M.W.), Spring House, PA; Christiana Care (J.R.P.), Newark, DE; and Department of Neurology (P.B.C.), University of Maryland, Baltimore.
John R PollardFrom Cognizance Biomarkers (J.M.G., E.J.B., R.D.S., T.M.W.), Spring House, PA; Christiana Care (J.R.P.), Newark, DE; and Department of Neurology (P.B.C.), University of Maryland, Baltimore.
Richard D St ClairFrom Cognizance Biomarkers (J.M.G., E.J.B., R.D.S., T.M.W.), Spring House, PA; Christiana Care (J.R.P.), Newark, DE; and Department of Neurology (P.B.C.), University of Maryland, Baltimore.
Todd M WallachFrom Cognizance Biomarkers (J.M.G., E.J.B., R.D.S., T.M.W.), Spring House, PA; Christiana Care (J.R.P.), Newark, DE; and Department of Neurology (P.B.C.), University of Maryland, Baltimore.
Peter B CrinoFrom Cognizance Biomarkers (J.M.G., E.J.B., R.D.S., T.M.W.), Spring House, PA; Christiana Care (J.R.P.), Newark, DE; and Department of Neurology (P.B.C.), University of Maryland, Baltimore. pcrino@som.umaryland.edu.
University of Maryland, Baltimore · US

Funding

Proof of Principle for a Diagnostic Blood Test of Recurrent SeizuresR43NS079029 · NINDS · COGNIZANCE BIOMARKERS, LLC · PI CRINO, PETER B, STRAUMAN, MAURA C · 2013 to 2014
$690k
NINDS NIH HHS R43 NS079029
6 · The paper itself

Abstract

objectiveTo develop a diagnostic test that stratifies epileptic seizures (ES) from psychogenic nonepileptic seizures (PNES) by developing a multimodal algorithm that integrates plasma concentrations of selected immune response-associated proteins and patient clinical risk factors for seizure.

methodsDaily blood samples were collected from patients evaluated in the epilepsy monitoring unit within 24 hours after EEG confirmed ES or PNES and plasma was isolated. Levels of 51 candidate plasma proteins were quantified using an automated, multiplexed, sandwich ELISA and then integrated and analyzed using our diagnostic algorithm.

resultsA 51-protein multiplexed ELISA panel was used to determine the plasma concentrations of patients with ES, patients with PNES, and healthy controls. A combination of protein concentrations, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein-2 (MCP-2), and tumor necrosis factor-receptor 1 (TNF-R1) indicated a probability that a patient recently experienced a seizure, with TRAIL and ICAM-1 levels higher in PNES than ES and MCP-2 and TNF-R1 levels higher in ES than PNES. The diagnostic algorithm yielded an area under the receiver operating characteristic curve (AUC) of 0.94 ± 0.07, sensitivity of 82.6% (95% confidence interval [CI] 62.9-93.0), and specificity of 91.6% (95% CI 74.2-97.7). Expanding the diagnostic algorithm to include previously identified PNES risk factors enhanced diagnostic performance, with AUC of 0.97 ± 0.05, sensitivity of 91.3% (95% CI 73.2-97.6), and specificity of 95.8% (95% CI 79.8-99.3).

conclusionsThese 4 plasma proteins could provide a rapid, cost-effective, and accurate blood-based diagnostic test to confirm recent ES or PNES. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that variable levels of 4 plasma proteins, when analyzed by a diagnostic algorithm, can distinguish PNES from ES with sensitivity of 82.6% and specificity of 91.6%.

Indexed as

AdolescentAdultAlgorithmsAnticonvulsantsArea Under CurveBlood ProteinsDiagnosis, DifferentialElectroencephalographyEncephalitisEpilepsyFemaleHumansMaleMental DisordersMiddle AgedRetrospective StudiesAnticonvulsantsBlood Proteins

Identifiers

PMID33495377
PMCPMC8055314
OpenAlexW3122481975

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.