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

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.

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.

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.

Simulation-based Education for Endoscopic Third Ventriculostomy: A Comparison Between Virtual and Physical Training Models.

BACKGROUND: The relative educational benefits of virtual reality (VR) and physical simulation models for endoscopic third ventriculostomy (ETV) have not been evaluated "head to head." OBJECTIVE: To compare and identify the relative utility of a physical and VR ETV simulation model for use in neurosurgical training. METHODS: Twenty-three neurosurgical residents and 3 fellows performed an ETV on both a physical and VR simulation model. Trainees rated the models using 5-point Likert scales evaluating the domains of anatomy, instrument handling, procedural content, and the overall fidelity of the simulation. Paired t tests were performed for each domain's mean overall score and individual items. RESULTS: The VR model has relative benefits compared with the physical model with respect to realistic representation of intraventricular anatomy at the foramen of Monro (4.5, standard deviation [SD] = 0.7 vs 4.1, SD = 0.6; P = .04) and the third ventricle floor (4.4, SD = 0.6 vs 4.0, SD = 0.9; P = .03), although the overall anatomy score was similar (4.2, SD = 0.6 vs 4.0, SD = 0.6; P = .11). For overall instrument handling and procedural content, the physical simulator outperformed the VR model (3.7, SD = 0.8 vs 4.5; SD = 0.5, P < .001 and 3.9; SD = 0.8 vs 4.2, SD = 0.6; P = .02, respectively). Overall task fidelity across the 2 simulators was not perceived as significantly different. CONCLUSION: Simulation model selection should be based on educational objectives. Training focused on learning anatomy or decision-making for anatomic cues may be aided with the VR simulation model. A focus on developing manual dexterity and technical skills using endoscopic equipment in the operating room may be better learned on the physical simulation model.

Deep brain stimulation of the ventral intermediate nucleus of the thalamus for tremor in patients with multiple sclerosis.

BACKGROUND: Tremor is an important cause of disability in patients with multiple sclerosis (MS). Deep brain stimulation (DBS) in the ventral intermediate nucleus (VIM) of the thalamus is said to be beneficial for MS tremor. OBJECTIVE: To assess the long-term efficacy of VIM DBS for MS disabling tumor. METHODS: We treated 10 patients (4 men and 6 women) with advanced MS-related medication-resistant tremor with DBS at the VIM thalamic nucleus. DBS was unilateral in 9 patients and bilateral in 1 patient in 2 stages. Contralateral arm tremor was assessed with the Fahn-Tolosa-Marin tremor rating scale. RESULTS: At 1 year, 5 of 10 patients (5 of 11 hemispheres) had a reduction in tremor scores with stimulation compared with baseline; in 3 patients, the reduction was > 50%. After 36 months, 3 patients continued benefiting from stimulation, 2 having > 50% improvement. Of the 6 symptomatic sides that did not benefit at 1 year, 3 failed to have even initial benefit, and 3 had a transient improvement lasting < 1 year. One patient stopped using stimulation because of a lack of improvement at 5 months after surgery and was lost to follow-up. CONCLUSION: Approximately one-half of the patients derived some benefit from VIM DBS 1 year after surgery, but this benefit reached a > 50% reduction in only 30% of the patients. This level of improvement may be related to the variability of the demyelinating lesions and the superimposition of ataxia in the MS patients. Developing better treatments for MS tremor continues to be a challenge.