Approximately 50% of patients with tuberous sclerosis complex (TSC) present intractable epilepsy, and surgery is an option for those patients. Hereby, we analyze long-term seizure control and neuropsychological outcomes of epilepsy surgery in patients with TSC. Clinical data were retrospectively collected from 66 patients with TSC and epilepsy followed up over 5 years, 51 of whom underwent epilepsy surgery between 2001 and 2011. Reductions in the number of seizures were analyzed at 1-year (1FU), 5-year (5FU), and 10-year (10FU) follow-ups visits after the operation. Influential factors on postoperative seizure free and intelligence quotient (IQ) and quality-of-life (QOL) outcomes were evaluated at 5FU. Resective procedures included 26 tuber resections, 15 lobectomies, and 10 tuber resections and lobectomies. Corpus callosotomies were performed as the adjunctive approach in 11 cases with low IQ. The percentages of seizure-free cases were 74.5% at 1FU, 58.8% at 5FU, and 47.8% at 10FU, and the predictive factor for long-term postoperative seizure freedom was the history of preoperative seizures and preoperative full-scale IQ. Significant improvements were found in performance IQ, full-scale IQ, and QOL in patients from the surgery group, particularly those who were seizure free after the operation. Our study showed that epilepsy surgery in TSC with epilepsy rendered improvements in seizure control, full-scale IQ, and QOL. Satisfactory long-term seizure control was often achieved with an early operation and without mental retardation, and improvements in QOL and IQ were frequently observed in postoperative patients who remained seizure free.
Background/Aims: Osteoporosis is a commonly occurring condition marked by a loss of bone density. Previous evidence has highlighted the roles played by microRNAs as potential treatment tools for the disease. At present, the influence of long non-coding RNAs (lncRNAs) on the progression of osteoporosis remains largely unclear. Thus, an investigation was conducted into the target relationship between LINC00311, which has been reported to be highly expressed in osteoporosis, and delta-like 3 (DLL3), which is involved in the Notch signaling pathway, in connection with a series of bioinformatic methods. An osteoporotic rat model was established by means of ovariectomy (OVX) to evaluate the influence exerted by DLL3-binding LINC00311 on osteoclasts through the Notch signaling pathway. Methods: Osteoclasts were extracted from osteoporotic rats and transfected with the LINC00311-vector, shRNA-LINC00311, Notch activator, or a combination of the Notch activator and LINC00311-vector. Western blotting and RT-qPCR techniques were applied to determine the expression levels of LINC00311, DLL3, Notch1, Notch2, Jagged1, Hes-1 and TRAP in tissues and cells, while cell activity was detected by MTT assay. The cell cycle as well as the rate of apoptosis was detected by flow cytometry. The successfully established osteoporotic rats were designated into the OVX-siRNA, OVX-LINC00311 and OVX-control groups to observe the effects of LINC00311 on the proliferation and differentiation of osteoclasts. Results: Cells transfected with the LINC00311-vector exhibited increased expression levels of Notch2 and TRPA as well as increased cell activity, while decreased expression levels of DLL3, Notch1, Jagged1 and Hes-1, along with a decreased cell apoptosis rate, were observed. The opposite tendencies of these parameters were observed in the cells treated with shRNA-LINC00311. A key observation was made when the Notch signaling pathway was activated, in that the cell activity was decreased while the rate of apoptosis increased. In comparison with the OVX-control group, the expression levels of LINC00311, Notch2 and TRAP as well as the positive expression rate of TRAP all exhibited reductions, while those of DLL3, Jagged1 and Notch1 were elevated in the OVX-siRNA group. Compared with those in the sham group, in the OVX-control and OVX-LINC00311 groups, LINC00311 and the expression levels of Notch2 and TRAP were increased; however, decreased levels of DLL3, Jagged1 and Notch1 were noted. Conclusions: Taken together, the key findings of the present study suggest that LINC00311 induces proliferation and inhibits apoptosis of osteoclasts via the regulation of the Notch signaling pathway by inhibiting DLL3 expression, ultimately demonstrating that LINC00311 and its target gene DLL3 may serve as independent factors in cases of osteoporosis.
OBJECT The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes. METHODS Two hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes. RESULTS Fifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients. CONCLUSIONS The iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery.
Automatic seizure termination is likely due to the fact that a portion of the inhibitory neurons and synapses are upregulated in the seizure-onset cortices. This mechanism may create novel therapeutic strategies to treat intractable epilepsy, such as the simultaneous upregulation of cortical inhibitory neurons and their output synapses.
Background: Deep brain stimulation (DBS) is considered an effective treatment option for Parkinson's disease (PD). Several studies have demonstrated the efficacy of neurostimulation in patients with advanced PD. The subthalamic nucleus (STN), the internal globus pallidus (GPi), ventral intermediate nucleus (Vim), and pedunculopontine nucleus (PPN) are reportedly effective DBS targets for control of Parkinsonian tremors. However, there is no consensus on the ideal target for DBS in patients with Parkinson's disease. Only a few studies have directly compared the efficacy of DBS of the Vim, STN, and GPi. Therefore, we searched PubMed, Embase, Cochrane Library, and other databases for observational studies, extracted data on unified Parkinson's disease rating scale (UPDRS) scores and performed a comprehensive network meta-analysis of different strategies of DBS and compared the efficiency of DBS at different targets. Methods: Forest plot was used to examine the overall efficiency of DBS; cumulative probability value was used to rank the strategies under examination. A node-splitting model was employed to assess consistency of reported outcomes inconsistency. A total of 16 studies which focused on UPDRS improvement were included in the network meta-analysis. Results: By comparing the overall efficiency associated with each target, we confirmed the efficacy of DBS therapy in PD. Our findings revealed similar efficacy of DBS targeted at GPi and STN in the on-medication phase [GPi-3.9 (95% CI −7.0 to −0.96); STN-3.1 (−5.9 to −0.38)]; however, in the off-medication phase, Vim-targeted DBS was associated with better improvement in UPDRS scores and could be a choice as a DBS target for tremor-dominant Parkinsonism. Conclusions: Our findings will help improve clinical application of DBS.
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