Long-Term Follow-Up on Bilateral Posterior Hypothalamic Deep Brain Stimulation for Treating Refractory Aggressive Behavior in a Patient with Cri du Chat Syndrome: Analysis of Clinical Data, Intraoperative Microdialysis, and Imaging Connectomics

Abstract

Posterior hypothalamic-deep brain stimulation (pHyp-DBS) has been reported as a successful treatment for reducing refractory aggressive behaviors in patients with distinct primary diagnoses. Here, we report on a patient with cri du chat syndrome presenting severe self-injury and aggressive behaviors toward others, who was treated with pHyp-DBS. Positive results were observed at long-term follow-up in aggressive behavior and quality of life. Intraoperative microdialysis and imaging connectomics analysis were performed to investigate possible mechanisms of action. Our results suggest the involvement of limbic and motor areas and alterations in main neurotransmitter levels in the targeted area that are associated with positive results following treatment.

Reduction of aggressive behaviour following hypothalamic deep brain stimulation: involvement of 5-HT1Aand testosterone

“…Refractoriness to treatment is especially observed in patients with severe intellectual disabilities who often cannot receive behavioural therapies [15,16]. Neuromodulation therapies, including deep brain stimulation (DBS), have been investigated as alternative treatment modalities in this selected group of refractory patients [17][18][19][20][21][22][23][24].…”

“…Overall, DBS has been shown to induce focal and widespread changes in neuronal activity along with the development of multiple forms of plasticity [25,26,[29][30][31]. In clinical trials including a small number of patients, DBS targeting the posterior area of the hypothalamus (pHyp) was associated with an important reduction in aggressiveness [17][18][19][20][21][22][23]. To date, the mechanisms through which DBS exerts its anti-aggressive effects remain largely unknown.…”

Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours

“…Despite their efficacy, a substantial proportion (30%) of patients fail to respond and are considered to be treatment refractory Adler et al, 2015 ; Gouveia et al, 2020 ; Gouveia et al, 2021b . For these patients, neuromodulation therapies, such as deep brain stimulation (DBS), have been investigated Gouveia et al, 2019 ; Gouveia et al, 2021c ; Contreras Lopez et al, 2021 ; Benedetti-Isaac et al, 2015 ; Torres et al, 2020 ; Micieli et al, 2017 ; López Ríos et al, 2023 . DBS is a neurosurgical therapy in which implanted electrodes are used to adjustably deliver electrical current to specific brain targets Jakobs et al, 2019 .…”

“…To date, DBS for refractory aggressive behavior has primarily targeted the posterior hypothalamic region Gouveia et al, 2019 ; Gouveia et al, 2021c ; Contreras Lopez et al, 2021 ; Benedetti-Isaac et al, 2015 ; Torres et al, 2020 ; Micieli et al, 2017 ; López Ríos et al, 2023 . The hypothalamus is a diencephalic structure with well-established roles in the control of homeostasis and motivated behaviors and is a key area in a broader neurocircuitry regulating aggressive behavior that also involves the orbitofrontal cortex, hippocampus, amygdala and periaqueductal gray Dudás, 2013 ; Blair, 2016 ; Miczek et al, 2007 .…”

“…More recently, DBS of the pHyp (pHyp-DBS) has also been shown to reduce aggressive symptoms in humans, with variable outcomes Gouveia et al, 2021c ; Contreras Lopez et al, 2021 ; Benedetti-Isaac et al, 2015 ; Torres et al, 2020 ; Franzini et al, 2010 ; Torres et al, 2013 ; López Ríos et al, 2023 . At present, only 21patients diagnosed with autism spectrum disorder (ASD), intellectual disability, obsessive-compulsive disorder, epilepsy and schizophrenia with ages ranging from 10 to 51 years have been reported, mostly as individual cases or small case series.…”