Gorodetsky Carolina, Mithani Karim, Breitbart Sara, Yan Han, Zhang Kristina, Gouveia Flavia Venetucci, Warsi Nebras, Suresh Hrishikesh, Wong Simeon M, Huber Joelene, Kerr Elizabeth N, Kulkarni Abhaya V, Taylor Margot J, P Hagopian Louis, Fasano Alfonso, Ibrahim George M
Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Biol Psychiatry. 2025 Jun 15;97(12):1116-1126. doi: 10.1016/j.biopsych.2024.12.001. Epub 2024 Dec 5.
Self-injurious behavior (SIB) consists of repetitive, nonaccidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB is 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 behaviors.
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 behaviors, 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 3 children experienced transient worsening in irritability or SIB with titration of stimulation parameters. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviors 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.
自我伤害行为（SIB）由重复性、非意外性动作组成，这些动作会导致对自身造成身体损伤，且无自杀意图。SIB在自闭症谱系障碍儿童中很普遍，可能导致永久性残疾或死亡。对与SIB相关的神经回路位点——伏隔核（NAc）进行神经调节，可能会直接影响这些行为。
我们完成了一项针对患有严重、难治性SIB儿童的伏隔核深部脑刺激（DBS）的I期开放标签临床试验（ClinicalTrials.gov标识符NCT03982888）。在进行NAc-DBS后，对参与者进行了12个月的监测，以评估安全性和可行性的主要结果。次要结果包括对SIB及与SIB相关行为的系列评估、动态活动记录仪监测以及DBS引起的脑葡萄糖代谢变化。
6名儿童（年龄7 - 14岁）接受了NAc-DBS，未发生严重不良事件。发现1名儿童在DBS电极附近出现延迟性无症状颅内出血，无需干预，3名儿童在刺激参数滴定过程中出现易怒或SIB短暂恶化。NAc-DBS导致多个标准化量表上的SIB及与SIB相关行为显著减少，同时生活质量有临床意义的改善。动态活动记录仪显示高振幅肢体运动减少，正电子发射断层扫描显示治疗导致丘脑、纹状体和颞岛叶皮质的代谢活动降低。
这项儿童首例的1期临床试验证明了NAc-DBS在有身体受伤和死亡高风险的严重难治性SIB儿童中的安全性和可行性，并支持进一步研究。
