Skip to main content

Advertising Disclaimer »

Main menu

  • Journals
    • Pediatrics
    • Hospital Pediatrics
    • Pediatrics in Review
    • NeoReviews
    • AAP Grand Rounds
    • AAP News
  • Authors/Reviewers
    • Submit Manuscript
    • Author Guidelines
    • Reviewer Guidelines
    • Open Access
    • Editorial Policies
  • Content
    • Current Issue
    • Online First
    • Archive
    • Blogs
    • Topic/Program Collections
    • AAP Meeting Abstracts
  • Pediatric Collections
    • COVID-19
    • Racism and Its Effects on Pediatric Health
    • More Collections...
  • AAP Policy
  • Supplements
    • Supplements
    • Publish Supplement
  • Multimedia
    • Video Abstracts
    • Pediatrics On Call Podcast
  • Subscribe
  • Alerts
  • Careers
  • Other Publications
    • American Academy of Pediatrics

User menu

  • Log in
  • My Cart

Search

  • Advanced search
American Academy of Pediatrics

AAP Gateway

Advanced Search

AAP Logo

  • Log in
  • My Cart
  • Journals
    • Pediatrics
    • Hospital Pediatrics
    • Pediatrics in Review
    • NeoReviews
    • AAP Grand Rounds
    • AAP News
  • Authors/Reviewers
    • Submit Manuscript
    • Author Guidelines
    • Reviewer Guidelines
    • Open Access
    • Editorial Policies
  • Content
    • Current Issue
    • Online First
    • Archive
    • Blogs
    • Topic/Program Collections
    • AAP Meeting Abstracts
  • Pediatric Collections
    • COVID-19
    • Racism and Its Effects on Pediatric Health
    • More Collections...
  • AAP Policy
  • Supplements
    • Supplements
    • Publish Supplement
  • Multimedia
    • Video Abstracts
    • Pediatrics On Call Podcast
  • Subscribe
  • Alerts
  • Careers

Discover Pediatric Collections on COVID-19 and Racism and Its Effects on Pediatric Health

American Academy of Pediatrics
Case Report

Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

Hilgo Bruining, Laurien Passtoors, Natalia Goriounova, Floor Jansen, Britt Hakvoort, Maretha de Jonge and Simon-Shlomo Poil
Pediatrics August 2015, 136 (2) e539-e543; DOI: https://doi.org/10.1542/peds.2014-4133
Hilgo Bruining
Departments of aTranslational Neuroscience,
bPsychiatry, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurien Passtoors
bPsychiatry, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Natalia Goriounova
cMediterranean Institute of Neurobiology (INMED), INSERM, Marseille, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Floor Jansen
dPediatric Neurology, Brain Center Rudolf Magnus, University Medical Center, Utrecht, Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Britt Hakvoort
eResearch Institute of Child Development and Education, University of Amsterdam, Amsterdam, Netherlands; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maretha de Jonge
bPsychiatry, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon-Shlomo Poil
fDepartment of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • Comments
Loading

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Download PDF

Abstract

The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders. However, strategies to select appropriate candidates for bumetanide treatment are lacking. We hypothesized that a paradoxical response to GABA-enforcing agents such as benzodiazepines may predict the efficacy of bumetanide treatment in neurodevelopmental disorders. We describe a case of a 10-year-old girl with ASD, epilepsy, cortical dysplasia, and a 15q11.2 duplication who had exhibited marked behavioral arousal after previous treatment with clobazam, a benzodiazepine. We hypothesized that this response indicated the presence of depolarizing excitatory GABA and started bumetanide treatment with monitoring of behavior, cognition, and EEG. The treatment resulted in a marked clinical improvement in sensory behaviors, rigidity, and memory performance, which was substantiated by questionnaires and cognitive assessments. At baseline, the girl’s EEG showed a depression in absolute α power, an electrographic sign previously related to ASD, which was normalized with bumetanide treatment. The effects of bumetanide on cognition and EEG seemed to mirror the “nonparadoxical” responses to benzodiazepines in healthy subjects. In addition, temporal lobe epilepsy and cortical dysplasia have both been linked to disturbed chloride homeostasis and seem to support our assumption that the observed paradoxical response was due to GABA-mediated excitation. This case highlights that a paradoxical behavioral response to GABA-enforcing drugs may constitute a framework for targeted treatment with bumetanide.

  • Accepted April 24, 2015.
  • Copyright © 2015 by the American Academy of Pediatrics

Individual Login

Log in
You will be redirected to aap.org to login or to create your account.

Institutional Login

via Institution

You may be able to gain access using your login credentials for your institution. Contact your librarian or administrator if you do not have a username and password.

Log in through your institution

If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.

Offer Reprints

PreviousNext
Back to top

Advertising Disclaimer »

In this issue

Pediatrics
Vol. 136, Issue 2
1 Aug 2015
  • Table of Contents
  • Index by author
View this article with LENS
PreviousNext
Email Article

Thank you for your interest in spreading the word on American Academy of Pediatrics.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?
(Your Name) has sent you a message from American Academy of Pediatrics
(Your Name) thought you would like to see the American Academy of Pediatrics web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Request Permissions
Article Alerts
Log in
You will be redirected to aap.org to login or to create your account.
Or Sign In to Email Alerts with your Email Address
Citation Tools
Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?
Hilgo Bruining, Laurien Passtoors, Natalia Goriounova, Floor Jansen, Britt Hakvoort, Maretha de Jonge, Simon-Shlomo Poil
Pediatrics Aug 2015, 136 (2) e539-e543; DOI: 10.1542/peds.2014-4133

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?
Hilgo Bruining, Laurien Passtoors, Natalia Goriounova, Floor Jansen, Britt Hakvoort, Maretha de Jonge, Simon-Shlomo Poil
Pediatrics Aug 2015, 136 (2) e539-e543; DOI: 10.1542/peds.2014-4133
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Print
Download PDF
Insight Alerts
  • Table of Contents

Jump to section

  • Article
    • Abstract
    • Patient Presentation
    • Methods
    • Discussion
    • Conclusions
    • Acknowledgment
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • Comments

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Respiratory Syncytial Virus Bronchiolitis Complicated by Necrotizing Enterocolitis: A Case Series
  • Inflammatory Bowel Disease Presenting With Concurrent COVID-19 Multisystem Inflammatory Syndrome
  • Guillain-Barré Syndrome in a Child With COVID-19 Infection
Show more Case Report

Similar Articles

Subjects

  • Neurology
    • Neurology
    • Neurologic Disorders
  • Developmental/Behavioral Pediatrics
    • Developmental/Behavioral Pediatrics
    • Autism/ASD
  • Journal Info
  • Editorial Board
  • Editorial Policies
  • Overview
  • Licensing Information
  • Authors/Reviewers
  • Author Guidelines
  • Submit My Manuscript
  • Open Access
  • Reviewer Guidelines
  • Librarians
  • Institutional Subscriptions
  • Usage Stats
  • Support
  • Contact Us
  • Subscribe
  • Resources
  • Media Kit
  • About
  • International Access
  • Terms of Use
  • Privacy Statement
  • FAQ
  • AAP.org
  • shopAAP
  • Follow American Academy of Pediatrics on Instagram
  • Visit American Academy of Pediatrics on Facebook
  • Follow American Academy of Pediatrics on Twitter
  • Follow American Academy of Pediatrics on Youtube
  • RSS
American Academy of Pediatrics

© 2021 American Academy of Pediatrics