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 g-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 a 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. PATIENT PRESENTATIONThe patient, a 10-year-old girl, was the fourth child of nonconsanguineous healthy parents. The family history was unremarkable, and the pregnancy and birth were uneventful. The child displayed an apparently normal development up to 4 years of age, when she began experiencing epileptic seizures. She was diagnosed with focal epilepsy with right temporoparietal localization, with focal seizures occurring in clusters.An MRI revealed a focal cortical dysplasia of the right temporal lobe. Coinciding with the onset of epilepsy, learning difficulty and behavioral rigidity emerged but were not evaluated at that time by a child psychiatrist. At the age of 8 years, she was referred to our clinic for diagnostic evaluation of increasing learning disability, behavioral inflexibility, and emotional disturbance. We observed a delay in language development, rigidity, and repetitive behaviors with peculiar