• Contreras LopezWilliam OmarWONemod Research Group, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia; Division of Functional Neurosurgery, Department of Neurosurgery, FOSCAL Clinic, Bucaramanga, Colombia. Electronic address: wcontreras127@unab.ed, Paula Alejandra Navarro, Flavia Venetucci Gouveia, Erich Talamoni Fonoff, Ivo Lebrun, Aline V V Auada, Lopes AlhoEduardo JoaquimEJDepartment of Neurology, University of São Paulo School of Medicine and Integrated Clinic of Neuroscience, São Paulo, Brazil., and Raquel C R Martinez.
• Nemod Research Group, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia; Division of Functional Neurosurgery, Department of Neurosurgery, FOSCAL Clinic, Bucaramanga, Colombia. Electronic address: wcontreras127@unab.edu.co.
• World Neurosurg. 2021 Nov 1; 155: e19-e33.

BackgroundIntermittent explosive disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behavior. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS. We sought to evaluate efficacy and safety of pHyp-DBS using 8-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters.MethodsThis was a prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with 8-contact directional electrodes. Follow-up was performed at 3, 6, and 12 months after surgery.ResultsFour patients (3 men, mean age 27 ± 2.8 years) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one had a co-diagnosis of infantile autism, and the fourth presented with drug-resistant epilepsy. There was a marked increase in the levels of gamma-aminobutyric acid and glycine during intraoperative stimulation. The average improvement in aggressive behavior in the last follow-up was 6 points (Δ: 50%, P = 0.003) while also documenting an important improvement of the Short Form Health Survey in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed.ConclusionsThis is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with rIED and to demonstrate the corresponding mechanism of action through increases in gamma-aminobutyric acid and glycine concentration in the pHyp.Copyright © 2021 Elsevier Inc. All rights reserved.

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