Neurosurgical Interventions for Refractory Symptoms in Autism Spectrum Disorder: Deep Brain Stimulation, Stereotactic Ablation, and Radiosurgery

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition that, in its most severe presentations, can be accompanied by life-threatening self-injurious behavior, pathological aggression, and debilitating obsessive-compulsive features. For patients whose symptoms prove refractory to all pharmacological and behavioral interventions, neurosurgical approaches have been explored as last-resort alternatives over the past two decades. This narrative review examines the available evidence on surgical interventions for ASD-associated refractory symptoms, encompassing deep brain stimulation (DBS), stereotactic radiofrequency ablation, and Gamma Knife radiosurgery. A literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Google Scholar, supplemented by hand-searching of reference lists. A total of 40 publications were retained, including 11 primary clinical studies encompassing 36 patients and 5 systematic reviews or meta-analyses. Deep brain stimulation targeting the nucleus accumbens, basolateral amygdala, globus pallidus internus, and posteromedial hypothalamus has demonstrated clinically meaningful reductions in self-injury and aggression. Ablative procedures and radiosurgery targeting the internal capsule, amygdala, and cingulum have also shown symptom improvement. However, the evidence base remains limited to case reports and small uncontrolled series, with no completed randomized controlled trials. Safety profiles appear favorable, though long-term data are scarce. Ethical considerations, particularly regarding informed consent in patients with limited autonomy, are discussed. Neurosurgical intervention for refractory ASD symptoms is feasible and can yield significant clinical benefits, but rigorous prospective trials with standardized outcome measures are needed.