Evidence map›Paper›PMID 32152460›Full record

ReviewNature reviews. Neurology2020

Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets.

Jason K Karimy, Benjamin C Reeves, Eyiyemisi Damisah, Phan Q Duy, Prince Antwi, Wyatt David, Kevin Wang, Steven J Schiff, David D Limbrick, Seth L Alper and 4 more

Registry-linked trialOpen access · greenAbstract readReview
In one paragraph

Review in Nature reviews. Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07662174 (VENTURE-PHH), which is not on this map. Cited by 129 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 3 pooled it
12.2field-weighted citation impact, top 1% 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.

NCT07662174 phase1 / phase2not yet recruitingnot on this mapstarted 2027, after this paper: background citation

VENTURE-PHH: Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage

TypeinterventionalSponsorMassachusetts General HospitalRan2027 to 2027Enrolled15ConditionsPost-hemorrhagic Hydrocephalus (PHH)ArmsSirolimus (Rapamune®)
3 · Its place in the literature

Who cites it

129 citing papers in PubMed, 3 syntheses or guidelines pooled it, 224 citations in OpenAlex.

  1. Pooled it
  2. Pathophysiologic mechanisms and strategies for the treatment of post-hemorrhagic hydrocephalus of prematurity.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022
    Pooled it
  3. Pooled it
  4. Trial
  5. Comparative study between ventriculosubgaleal shunt and external ventricular drain for management of post infective hydrocephalus among pediatrics.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024
    Trial
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  20. Frontiers in medicine · 2026
    Article

69 more citing papers are in PubMed but not listed here.

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 7 institutions in 2 countries.

Jason K Karimy *Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Benjamin C Reeves *Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-5924-6991
Eyiyemisi Damisah *Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0001-8854-1335
Phan Q DuyDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Prince AntwiDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Wyatt DavidDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Kevin WangDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-4911-4848
Steven J SchiffDepartments of Neurosurgery, Engineering Science & Mechanics, and Physics; Center for Neural Engineering, The Pennsylvania State University, University Park, PA, USA.ORCID 0000-0003-2623-3614
David D LimbrickDepartments of Neurosurgery and Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Seth L AlperDivision of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA, USA.
Benjamin C WarfDepartment of Neurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Maiken NedergaardCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA.
J Marc SimardDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Kristopher T KahleDepartments of Neurosurgery, Pediatrics, and Cellular & Molecular Physiology and Yale-Rockefeller NIH Centers for Mendelian Genomics, Yale School of Medicine, New Haven, CT, USA. kristopher.kahle@yale.edu.ORCID 0000-0002-5922-7547
Yale University · USBeth Israel Deaconess Medical Center · USBoston Children's Hospital · USPennsylvania State University · USUniversity of Copenhagen · DKUniversity of Maryland, Baltimore · USWashington University in St. Louis · US

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
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Predictive Personalized Public Health (P3H): A Novel Paradigm to Treat Infectious DiseaseR01AI145057 · NIAID · YALE UNIVERSITY · PI SCHIFF, STEVEN J · 2018 to 2022
$8.1M
Sulfonylurea receptor 1 (SUR1)- A novel therapeutic target in ischemic strokeR01HL082517 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI SIMARD, J. MARC · 2006 to 2021
$5.6M
Neurocognitive outcomes and changes in brain and CSF volume after treatment of post-infectious hydrocephalus in Ugandan infants by shunting or ETV/CPC: a randomized prospective trialR01HD085853 · NICHD · YALE UNIVERSITY · PI KULKARNI, ABHAYA V, SCHIFF, STEVEN JOHN · 2015 to 2025
$4.7M
Control of the Neonatal Septisome and Hydrocephalus in sub-Saharan AfricaDP1HD086071 · NICHD · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SCHIFF, STEVEN J · 2015 to 2019
$4.1M
Para-Vascular Basis of Small Vessel DiseaseR01NS100366 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2016 to 2020
$3.8M
Characterizing the glymphatic peri-vascular connectome and its disruption in ADRF1AG053991 · NIA · YALE UNIVERSITY · PI BENVENISTE, HELENE D, NEDERGAARD, MAIKEN · 2016 to 2016
$3.4M
Spinal cord injury, progressive hemorrhagic necrosis and the NC(Ca-ATP) channelR01NS060801 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI SIMARD, J. MARC · 2009 to 2018
$3.3M
Age and AD related bottlenecks in glymphatic-lymphatic waste transportRF1AG057575 · NIA · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2017 to 2017
$3.2M
Capillary hyperemia in white matter: Novel mechanistic insight and effect of hypertension and agingRF1NS110049 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN, WAN, JIANDI · 2018 to 2018
$2.9M
Improving infant hydrocephalus outcomes in Uganda: Predicting developmental outcomes and identifying patients at risk for early treatment failure after ETV/CPCR01HD096693 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI LIN, PEI-YI, WARF, BENJAMIN CURTIS · 2018 to 2022
$2.8M
BLRD VA I01 BX002889NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL082517NIAID NIH HHS R01 AI145057NIA NIH HHS RF1 AG053991NIA NIH HHS RF1 AG057575NICHD NIH HHS DP1 HD086071NICHD NIH HHS R01 HD085853NICHD NIH HHS R01 HD096693NIGMS NIH HHS T32 GM007205NINDS NIH HHS R01 NS060801NINDS NIH HHS R01 NS100366NINDS NIH HHS R01 NS102589NINDS NIH HHS R01 NS105633NINDS NIH HHS R01 NS109358NINDS NIH HHS RF1 NS110049
6 · The paper itself

Abstract

Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation - driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways - contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia-lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.

Indexed as

AnimalsEncephalitisHumansHydrocephalusInflammation MediatorsInflammation Mediators

Identifiers

PMID32152460
PMCPMC7375440
OpenAlexW3010263513

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Registered trials

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.