Skip to main content
Skip to main content

AAP Gateway

Advanced Search »

User menu

  • Login
  • AAP Policy
  • Topic/Program Collections
  • Submit Manuscript
  • Alerts
  • Subscribe
  • aap.org

Menu

  • AAP Grand Rounds
  • AAP News
  • Hospital Pediatrics
  • NeoReviews
  • Pediatrics
  • Pediatrics in Review
  • Current AAP Policy
  • Journal CME
  • AAP Career Center
  • Pediatric Collections
  • AAP Journals Catalog

Sections

    • Login
    • AAP Policy
    • Topic/Program Collections
    • Submit Manuscript
    • Alerts
    • Subscribe
    • aap.org

    Get Involved! Pediatrics is accepting nominations for Editorial Board positions.

    Sign up for Insight Alerts highlighting editor-chosen studies with the greatest impact on clinical care.
    Video Abstracts -- brief videos summarizing key findings of new articles
    Watch the Features Video to learn more about Pediatrics.

    Advertising Disclaimer »

    Tools and Links

    Pediatrics
    August 2015, VOLUME 136 / ISSUE 2
    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, Simon-Shlomo Poil
    • Article
    • Figures & Data
    • Info & Metrics
    • Comments
    Loading
    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
    View Full Text
    PreviousNext

     

    Advertising Disclaimer »

    View this article with LENS
    PreviousNext
    Email

    Thank you for your interest in spreading the word on 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 Pediatrics
    (Your Name) thought you would like to see the Pediatrics web site.

    Alerts
    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 Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
    Print
    PDF
    Insight Alerts
    • Table of Contents
    • Current Policy
    • Early Release
    • Current Issue
    • Past Issues
    • Editorial Board
    • Editorial Policies
    • Overview
    • Features Video
    • Open Access
    • Pediatric Collections
    • Video Abstracts
    • Author Guidelines
    • Reviewer Guidelines
    • Submit My Manuscript

    Subjects

    • Neurology
      • Neurology
      • Neurologic Disorders
    • Developmental/Behavioral Pediatrics
      • Developmental/Behavioral Pediatrics
      • Autism/ASD
    Back to top

                

    Copyright © 2019 by American Academy of Pediatrics

    International Access »

    Terms of Use
    The American Academy of Pediatrics (AAP) takes the issue of privacy very seriously. See our Privacy Statement for information about how AAP collects, uses, safeguards and discloses the information collected on our Website from visitors and by means of technology.
    FAQ

     

    AAP Pediatrics