Evidence map›Paper›PMID 38810181›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2024

Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE).

Aurélie Hanin, Le Zhang, Anita J Huttner, Isabelle Plu, Bertrand Mathon, Franck Bielle, Vincent Navarro, Lawrence J Hirsch, David A Hafler

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In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Aurélie HaninFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.ORCID 0000-0002-5912-9998
Le ZhangFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.ORCID 0000-0002-4860-831X
Anita J HuttnerFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.
Isabelle PluFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.
Bertrand MathonFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.ORCID 0000-0002-9182-5846
Franck BielleFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.ORCID 0000-0001-6564-6388
Vincent NavarroFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.ORCID 0000-0003-0077-8114
Lawrence J HirschFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.ORCID 0000-0002-6333-832X
David A HaflerFrom the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.ORCID 0000-0003-4664-535X

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

BACKGROUND AND

objectivesNew-onset refractory status epilepticus (NORSE) occurs in previously healthy children or adults, often followed by refractory epilepsy and poor outcomes. The mechanisms that transform a normal brain into an epileptic one capable of seizing for prolonged periods despite treatment remain unclear. Nonetheless, several pieces of evidence suggest that immune dysregulation could contribute to hyperexcitability and modulate NORSE sequelae.

methodsWe used single-nucleus RNA sequencing to delineate the composition and phenotypic states of the CNS of 4 patients with NORSE, to better understand the relationship between hyperexcitability and immune disturbances. We compared them with 4 patients with chronic temporal lobe epilepsy (TLE) and 2 controls with no known neurologic disorder.

resultsPatients with NORSE and TLE exhibited a significantly higher proportion of excitatory neurons compared with controls, with no discernible difference in inhibitory GABAergic neurons. When examining the ratio between excitatory neurons and GABAergic neurons for each patient individually, we observed a higher ratio in patients with acute NORSE or TLE compared with controls. Furthermore, a negative correlation was found between the ratio of excitatory to GABAergic neurons and the proportion of GABAergic neurons. The ratio between excitatory neurons and GABAergic neurons correlated with the proportion of resident or infiltrating macrophages, suggesting the influence of microglial reactivity on neuronal excitability. Both patients with NORSE and TLE exhibited increased expression of genes associated with microglia activation, phagocytic activity, and NLRP3 inflammasome activation. However, patients with NORSE had decreased expression of genes related to the downregulation of the inflammatory response, potentially explaining the severity of their presentation. Microglial activation in patients with NORSE also correlated with astrocyte reactivity, possibly leading to higher degrees of demyelination. DISCUSSION: Our study sheds light on the complex cellular dynamics in NORSE, revealing the potential roles of microglia, infiltrating macrophages, and astrocytes in hyperexcitability and demyelination, offering potential avenues for future research targeting the identified pathways.

Indexed as

BrainDrug Resistant EpilepsySingle-Cell AnalysisStatus EpilepticusAdolescentAdultChildEpilepsy, Temporal LobeFemaleGABAergic NeuronsGene Expression ProfilingHumansMaleMicrogliaMiddle AgedTranscriptome

Identifiers

PMID38810181
PMCPMC11139018

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