Evidence map›Paper›PMID 41848169›Full record

ArticleDisease models & mechanisms2026

Chiari II brain malformation is secondary to open spina bifida.

Maryam Clark, Timothy J Edwards, Dawn Savery, Gabriel L Galea, Nagaraj Samy, Erwin Pauws, Nicoletta Kessaris, Nicholas D E Greene, Andrew J Copp

Abstract read
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In one paragraph

Article in Disease models & mechanisms, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Maryam ClarkDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0009-0001-8714-2508
Timothy J EdwardsDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Dawn SaveryDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Gabriel L GaleaDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0003-2515-1342
Nagaraj SamyDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Erwin PauwsDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0003-1751-0317
Nicoletta KessarisWolfson Institute for Biomedical Research, University College London, London WC1E 6JL, UK.ORCID 0000-0003-1191-6009
Nicholas D E GreeneDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0002-4170-5248
Andrew J CoppDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0002-2544-9117

Funding

Bo Hjelt Spina Bifida FoundationGreat Ormond Street Hospital Charity V4918Hjelt FoundationsMedical Research Council UKRI2551MRC National Mouse Genetics Network, Congenital Anomalies Cluster MC_PC_21044University College London
6 · The paper itself

Abstract

Chiari II brain malformation affects 90% of children with open spina bifida. Hindbrain herniation leads to hydrocephalus, together with higher-brain anomalies including cerebral cortical defects implicated in learning disability, which affects 20-25% of children with spina bifida. The causal link between Chiari II and spina bifida has long been debated, and we aimed to determine whether Chiari II arises secondary to spina bifida, rather than as a separate effect of shared genetic or non-genetic factor(s). Pax3 gene function was conditionally deleted by Cdx2cre specifically in the lower body of mice, leaving the head genetically intact. Open spina bifida was seen in all Cdx2cre/+;Pax3fl/fl fetuses, together with many features of Chiari II in the wild-type brain and skull. These included hindbrain herniation, callosal and hippocampal hypogenesis, cortical thinning with neuronal heterotopia, a thickened ventricular zone and posterior skull defects. Hence, the brain and skull defects of Chiari II arise secondary to open spina bifida, with likely disturbance of neurogenesis and neuronal migration early in gestation. The Cdx2cre/+;Pax3fl/fl mouse provides a model for improved understanding of Chiari II pathogenesis.

Indexed as

Arnold-Chiari MalformationBrainSpina Bifida CysticaAnimalsCDX2 Transcription FactorFetusIntegrasesMicePAX3 Transcription FactorRhombencephalonSkullCdx2 protein, mouseCDX2 Transcription FactorCre recombinaseIntegrasesPax3 protein, mousePAX3 Transcription FactorFetusMouseMyelomeningoceleNeural tube defectSkullTransgenic

Identifiers

PMID41848169
PMCPMC13148473

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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.