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.