RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders.
The authors found that MER can be adequately performed while the patient receives a desflurane anesthetic, and the results can serve as a guide for STN electrode implantation. This may be a good alternative surgical method in patients with PD who are unable to tolerate deep brain stimulation surgery with local anesthesia.
When taking spatial influence into consideration, the neuropsychological effects of chronic STN-DBS were related to a significant anteriorly located active contact within the ventral STN in this preliminary study. This might suggest the existence of topography of STN in patients with Parkinson's disease concerning limbic and associative circuits.
Background: The efficacy and feasibility of bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) under general anesthesia (GA) has not been evaluated. Objective: We compared the outcome of patients under GA with those who were operated on under local anesthesia (LA). Material and Methods: Thirty-three patients were assigned to the GA group (desflurane) and 19 patients were assigned to the LA group. Microelectrode recording (MER) was performed in both groups. The surgical outcomes of the patients were evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) after at least 12 months after surgery. Results: Postoperatively, there was no significant difference on the UPDRS scores in either groups. A significant deterioration in cognitive function in the GA group was observed (p = 0.017). The recorded electrode coordinates, the average tracts for the MER, and STN depth were comparable in both groups. The overall incidence of adverse effects did not show any difference except that the incidence of sialorrhea and dysarthria was significantly higher in the GA group. Conclusion: Desflurane GA was shown to be a good alternative anesthetic method for PD patients undergoing DBS. Although the motor outcomes were comparable, a significant cognitive decline may be seen in the GA group with a higher occurrence of stimulation side effects.
Background/Aims: Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to have long-term benefits in Parkinson’s disease (PD). Through analyzing different variables, this study identified prognostic factors for the short- and long-term effects of STN-DBS. Methods: Thirty-six PD patients underwent bilateral STN-DBS. Clinical evaluations were performed 1 month before and 3 months after surgery, with additional follow-up examinations for a mean of 31.3 months. Results: There was a trend for long-term STN-DBS-induced improvements in the Unified Parkinson’s Disease Rating Scale (UPDRS) part II and part III measures to be greater in younger patients. Preoperative levodopa responsiveness only led to consistent UPDRS part III improvement from STN-DBS at 3 months, and this predictive value did not exist in the long term. The preoperative levodopa response of tremor and axial symptoms in motor disability predicted long-term DBS effect only. Preoperative cognitive function positively correlated with postoperative improvement from DBS in UPDRS part III during long-term follow-up only. Conclusions: The prognostic factors for STN-DBS benefit were different for short- and long-term follow-ups. Good prognostic factors for long-term STN-DBS for PD patients were good cognitive function and tremor dominance. Poor prognostic factors were related to older age and non-dopaminergic-responsive axial disability.
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