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Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas - together with patient age - were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network., Competing Interests: FG, JG, GE, AB, AL, AL, CT, WC, RM, EF, JB, PG, PA, HY, GI, NL, AL, CH No competing interests declared, (© 2023, Gouveia, Germann et al.)

Psychiatric disorders result in great suffering of affected patients, who often have rather limited treatment options. In cases refractory to standard medical and behavioral therapy, interventional procedures may be the only feasible solution. The authors experience with Gamma Knife bilateral cingulotomy for treatment-resistant major depression disorder (5 cases) and anorexia nervosa (6 cases), and bilateral anterior capsulotomy for severe obsessive-compulsive disorder (10 cases) shows that such radiosurgical techniques may be applied both effectively and safely. During post-treatment follow-up, the vast majority of patients demonstrated gradual reduction of psychiatric symptoms and improvement of the quality of life, which was confirmed by results of regular neuropsychological testing and imaging examinations. No major side effect was observed in any case. More active application of radiosurgery (using standardized technique) for management of mental illnesses in various Gamma Knife centers worldwide should be encouraged., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is a developmental disability of the brain that can be associated to severe conductual alterations, such as self or heteroaggression and obsessive and compulsive behavior. Many of these patients do not improve with any pharmacological or behavioral therapy and represent a major social problem. We describe the outcome of patients with ASD, treated with radiofrequency brain lesions combined with Gamma Knife radiosurgery for therapy-resistant aggressiveness, obsessive thoughts, and compulsions. The ASD adapted YBOCS, PCQ and EAE scales assessed the therapeutic effect on symptoms. All patients had a significant reduction of their symptoms (YBOCS:34 and 22 PCQ 42 and 35, EAE 11 and 5.5, respectively), although all needed more than one treatment to maintain this improvement. The treatments resulted very safe for the patients and their neurological status has not change. We conclude that in these patients after surgery, there is a marked improvement in behavior, quality of life and relationship with the environment, with no evidence of secondary damage. Changes in connectivity might mediate the clinical improvement, although it is necessary to confirm these results with further studies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit., Methods: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events., Results: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects., Conclusions: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)