Deep Brain Stimulation of the Nucleus Accumbens for Severe Self-Injurious Behaviour in Children: A Phase I Pilot Trial.

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Self-injurious behaviours (SIB) are repetitive, non-accidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB are prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviours. We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov Identifier NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB and SIB-associated behaviours, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS. Six children (ages 7-14 years) underwent NAc-DBS without serious adverse events. One child was found to have a delayed asymptomatic intracranial hemorrhage adjacent to a DBS electrode that did not require intervention, and three children experienced transient worsening in irritability or SIB with titration of stimulation parameters. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviours across multiple standardized scales, concurrent with clinically meaningful improvements in quality-of-life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex. This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.