The electroclinical features and surgical outcomes of inferior perisylvian epilepsy.

OBJECTIVE: To summarize the clinical and electrophysiological observations of epilepsy originating from the inferior perisylvian cortex, and analyze the potential epileptic networks underlying the semiological manifestations. METHODS: We retrospectively analyzed patients with refractory inferior perisylvian epilepsy (IPE) who had undergone resective surgery, and then reviewed the demographic, clinical, neuroelectrophysiological, neuroimaging, surgical, histopathological, and follow-up data of the patients from the respective medical records. The selected patients were then categorized in accordance with the results of semiological analysis. Quantitative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) analysis was performed to investigate the underlying neural network. RESULTS: Of the 18 IPE patients assessed in this study, ipsilateral frontotemporal epileptic discharges or its onsets were the dominant interictal or ictal scalp EEG observations. In addition, oroalimentary or manual automatism was the most frequently documented manifestation, followed by facial tonic or clonic movements. Moreover, the semiological analysis identified and classified the patients into 2 patterns, and the PET statistical analyses conducted on these 2 groups revealed differences in the neural network between them. CONCLUSION: Inferior perisylvian epilepsy possesses semiological manifestations similar to those of mesial temporal lobe epilepsy or rolandic opercular epilepsy, hence these conditions should be carefully differentiated. Performing lesionectomy or cortectomy, sparing the mesial temporal structures, was found to be an effective and safe treatment modality for IPE.

Abnormal hippocampal functional network and related memory impairment in pilocarpine-treated rats.

OBJECTIVE: Although abnormal hippocampal structure and impaired spatial memory have been revealed in a pilocarpine rat model of temporal lobe epilepsy (TLE), the brain functional network changes are still unclear. The aim of the present study was to investigate the changes of brain functional connectivity related to the hippocampus and the associated memory impairment in a pilocarpine model of TLE. METHODS: Functional magnetic resonance imaging signals were recorded in pilocarpine-treated rats and controls by using a 7.0 T magnetic resonance scanner, and independent component analysis was performed to determine the hippocampal functional network. Behavioral tests, including novel location test, novel object test, and episodic memory test, were utilized to evaluate different aspects of memory impairment. RESULTS: Memory impairment was observed in the TLE group in all three behavior tests. As compared to control, decreased connectivity of the hippocampal functional network was observed in the anterior dorsal hippocampus, the amygdala, the thalamus, the motor cortex, and the somatosensory cortex in the TLE group. Meanwhile, increased connectivity was found in the visual cortex, the mesencephalon, and the insula in the TLE group. Correlation analysis revealed that functional connections between the hippocampal network and brain regions such as the dorsal hippocampus and the thalamus specifically relate to the spatial memory behavior, whereas connections between the hippocampal network and regions such as the amygdala, the motor cortex, the somatosensory cortex, and the mesencephalon relate to both the spatial and the object memory performance. SIGNIFICANCE: Our results indicated a trend of decreased connectivity in the hippocampal functional network, as well as spatial, object, and episodic memory impairment in the pilocarpine-induced TLE rat. Moreover, connections within the hippocampal network showed a relationship with spatial memory, and connections between the hippocampal network and regions in other networks revealed an association with both spatial and object memory.

The ability of anterior thalamic signals to predict seizures in temporal lobe epilepsy in kainate-treated rats.

OBJECTIVE: To analyze the local field potential (LFP) of the anterior nucleus of the thalamus (ANT) of epileptic rats using the Generic Osorio-Frei algorithm (GOFA), and to determine the ability of the ANT LFP to predict clinical seizures in temporal lobe epilepsy. METHODS: GOFA is an advanced real-time technique used to detect and predict seizures. In this article, GOFA was utilized to process the electrical signals of ANT and the motor cortex recorded in 12 rat models of temporal lobe epilepsy (TLE) induced via the injection of kainic acid into the unilateral hippocampus. The electroencephalography (EEG) data included (1) 161 clinical seizures (each contained a 10-min segment) involving the ANT and cortical regions and (2) one hundred three 10-min segments of randomly selected interictal (no seizure) data. RESULTS: Minimal false-positives (0.51 ± 0.36/h) and no false-negatives were detected based on the ANT LFP data processed using GOFA. In ANT LFP, the delay from electrographic onset (EO) to automated onset (AO) was 1.24 ± 0.47 s, and the delay from AO to clinical onset (CO) was 7.73 ± 3.23 s. The AO time occurred significantly earlier in the ANT than in the cortex (p = 0.001). In 75.2% of the clinical onsets predicted by ANT LFP, it was 1.37 ± 0.82 s ahead of the prediction of cortical potentials (CPs), and the remainder were 0.84 ± 0.31 s slower than the prediction of CPs. SIGNIFICANCE: ANT LFP appears to be an optimal option for the prediction of seizures in temporal lobe epilepsy. It was possible to upgrade the responsive neurostimulation system to emit electrical stimulation in response to the prediction of epileptic seizures based on the changes in the ANT LFP.

Subthalamic deep brain stimulation with a new device in Parkinson's disease: an open-label trial.

OBJECTIVE: We aimed to evaluate the safety and efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) with a new stimulator (Beijing PINS Medical Co., Ltd, PNS 1101) in Parkinson's disease (PD). MATERIALS AND METHODS: Forty patients received a PINS device implantation in the subthalamic nucleus. The effects of stimulation on motor score, activities of daily living, good-quality on-time, and the levodopa-equivalent dose were analyzed for all 40 patients with PD treated with bilateral or unilateral STN-DBS. The scores were collected at baseline in two conditions (on/off medication) and at 3, 6, 9, 12, and 24 months of follow-up with stimulation in the absence or presence of medication. The patients were followed up for two years. RESULTS: At 3, 6, 9, 12, and 24 months of follow-up, our results showed a significant increase from baseline in both activities of daily living and motor scores (p < 0.001) and good-quality on-time (p < 0.001); the daily levodopa-equivalent dose decreased compared with baseline (p < 0.01). No patient died during the study, and none of the adverse effects were classified as severe. All of the adverse events were resolved or improved by the end of the study. CONCLUSIONS: STN-DBS with the PINS device significantly improved the symptoms of PD when compared with baseline in this trial. This new device may be recommended for the treatment of patients with advanced PD; however, a randomized, double-blinding trial will be required.

[Surgical techniques and efficacies of deep brain stimulation in the treatment of essential tremor].

OBJECTIVE: To explore the surgical techniques and efficacies of deep brain stimulation (DBS) in the treatment of the patients with essential tremor (ET). METHODS: A total of 6 ET patients from January 2004 to June 2011 at Department of Neurosurgery, Beijing Tiantan Hospital were recruited to receive DBS at ventral intermediate nucleus of thalamus (Vim-DBS) (n = 5) and subthalamic nucleus (STN-DBS) (n = 1). All underwent stereotactically guided DBS procedures utilizing atlas of neuroanatomy and neurophysiology, pre-operative magnetic resonance imaging (MRI), microelectrode recording and intra-operative testing for target-locating. Postoperative computed tomography (CT) and/or MRI scan were performed after implantation. Such stimulation parameters as stimulus voltage, frequency, pulse width and polarity configuration were adjusted postoperatively to optimize tremor control and maximize battery life. The patients were followed by further consultations or telephone for a comprehensive evaluation of their therapeutic efficacies. RESULTS: All patients showed typical electrical signal and relief of tremor symptoms with significant tremor control. No severe adverse events, such as infection, hemorrhage, paresthesia, dysarthria, cognitive deficits, imbalance and diplopia, appeared after the implantation of DBS electrodes. CONCLUSION: Vim-DBS and STN-DBS are both safe and effective for the controls of unilateral and bilateral tremors.

[Changes of glutamate and γ-aminobutyric acid of extracellular fluid in hippocampus during electrical stimulation of anterior nucleus thalamus in rats].

OBJECTIVE: To explore the changes of extracellular glutamate (Glu) and γ-aminobutyric acid (GABA) in hippocampus during the high-frequency stimulation of anterior nucleus thalamus (ANT) in epileptic rats. METHODS: A total of 30 rats were divided equally into 2 groups:epilepsy model and normal control (n = 15 each). Concentric bipolar electrodes were stereotaxically implanted in bilateral ANT. A high-frequency stimulation of 130 Hz was applied in the epilepsy group. Microdialysis probes were unilaterally lowered into hippocampus. The concentrations of Glu and GABA in dialysate samples were determined by high-performance liquid chromatography (HPLC). RESULTS: Electrical stimulation of ANT induced an increase of GABA and a decrease of Glu in hippocampus. CONCLUSION: An increase of GABA and a decrease of Glu during the electrical stimulation of ANT play an important role in the therapy of epilepsy.

Modulation of the rat hippocampal-cortex network and episodic-like memory performance following entorhinal cortex stimulation.

AIMS: Entorhinal cortex (EC) deep brain stimulation (DBS) has shown a memory enhancement effect. However, its brain network modulation mechanisms remain unclear. The present study aimed to investigate the functional connectivity in the rat hippocampal-cortex network and episodic-like memory performance following EC-DBS. METHODS: 7.0 T functional MRI (fMRI) scans and episodic-like memory tests were performed 3 days and 28 days after EC-DBS in healthy rats. The fMRI data processing was focused on the power spectra, functional connectivity, and causality relationships in the hippocampal-cortex network. In addition, the exploration ratio for each object and the discrimination ratio of the "when" and "where" factors were calculated in the behavioral tests. RESULTS: EC-DBS increased the power spectra and the functional connectivity in the prefrontal- and hippocampal-related networks 3 days after stimulation and recovered 4 weeks later. Both networks exhibited a strengthened connection with the EC after EC-DBS. Further seed-based functional connectivity comparisons showed increased connectivity among the prefrontal cortex, hippocampus and EC, especially on the ipsilateral side of DBS. The dentate gyrus is a hub region closely related to both the EC and the prefrontal cortex and receives information flow from both. Moreover, acute EC-DBS also enhanced the discrimination ratio of the "where" factor in the episodic-like memory test on Day 3. CONCLUSION: EC-DBS caused a reversible modulation effect on functional connectivity in the hippocampal-cortex network and episodic-like memory performance.

Application of the robot-assisted implantation in deep brain stimulation.

Introduction: This work aims to assess the accuracy of robotic assistance guided by a videometric tracker in deep brain stimulation (DBS). Methods: We retrospectively reviewed a total of 30 DBS electrode implantations, assisted by the Remebot robotic system, with a novel frameless videometric registration workflow. Then we selected 30 PD patients who used stereotactic frame surgery to implant electrodes during the same period. For each electrode, accuracy was assessed using radial and axial error. Results: The average radial error of the robot-assisted electrode implantation was 1.28 ± 0.36 mm, and the average axial error was 1.20 ± 0.40 mm. No deaths or associated hemorrhages, infections or poor incision healing occurred. Conclusion: Robot-assisted implantation guided by a videometric tracker is accurate and safe.

Voxel-Based Morphometric MRI Postprocessing-Assisted Laser Interstitial Thermal Therapy for Focal Cortical Dysplasia-Suspected Lesions: Technique and Outcomes.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) is a novel treatment modality for focal cortical dysplasia (FCD). However, identifying the location and extent of subtle FCD by visual analysis during MRgLITT remains challenging. OBJECTIVE: To introduce voxel-based morphometric MRI postprocessing into the procedure of MRgLITT for FCD-suspected lesions and assess the complementary value of the MRI postprocessing technique for the trajectory design and thermal parameter setting of MRgLITT. METHODS: Junction and normalized fluid-attenuated inversion recovery signal intensity images were used to detect the gray-white matter junction blurring and cortical fluid-attenuated inversion recovery hyperintensity, respectively. According to the 2 postprocessing images, the region of interest (ROI) for ablation was drawn. The main principle of presurgical planning is that the trajectory of the laser fiber was designed as far as possible along the long axis of the ROI while the extent of planned ablation covered the entire ROI. The subsequent intraoperative procedure was performed under the guidance of the presurgical plan. RESULTS: Nine patients with epilepsy with FCD-suspected lesions underwent MRgLITT with the assistance of MRI postprocessing images. Among them, 4 patients were junction positive, 2 patients were normalized fluid-attenuated inversion recovery signal intensity positive, and the remaining 3 patients were positive for both. Postsurgical MRI demonstrated that the ROIs were ablated entirely in 7 patients. Engel Ia, Ib, and IV scores were obtained at 1-year follow-up for 6, 1, and 2 patients, respectively. CONCLUSION: MRI postprocessing provides complementary information for designing the laser fiber trajectory and subsequent ablation for FCDs.

Synchronized Intracranial Electrical Activity and Gait Recording in Parkinson's Disease Patients With Freezing of Gait.

Background: This study aimed to describe a synchronized intracranial electroencephalogram (EEG) recording and motion capture system, which was designed to explore the neural dynamics during walking of Parkinson's disease (PD) patients with freezing of gait (FOG). Preliminary analysis was performed to test the reliability of this system. Methods: A total of 8 patients were enrolled in the study. All patients underwent bilateral STN-DBS surgery and were implanted with a right subdural electrode covering premotor and motor area. Synchronized electrophysiological and gait data were collected using the Nihon Kohden EEG amplifier and Codamotion system when subjects performed the Timed Up and Go (TUG) test. To verify the reliability of the acquisition system and data quality, we calculated and compared the FOG index between freezing and non-freezing periods during walking. For electrophysiological data, we first manually reviewed the scaled (five levels) quality during waking. Spectra comprising broadband electrocorticography (ECoG) and local field potential (LFP) were also compared between the FOG and non-FOG states. Lastly, connectivity analysis using coherence between cortical and STN electrodes were conducted. In addition, we also use machine learning approaches to classified FOG and non-FOG. Results: A total of 8 patients completed 41 walking tests, 30 of which had frozen episodes, and 21 of the 30 raw data were level 1 or 2 in quality (70%). The mean ± SD walking time for the TUG test was 85.94 ± 47.68 s (range: 38 to 190.14 s); the mean ± SD freezing duration was 12.25 ± 7.35 s (range: 1.71 to 27.50 s). The FOG index significantly increased during the manually labeled FOG period (P < 0.05). The beta power of STN LFP in the FOG period was significantly higher than that in the non-FOG period (P < 0.05), while the band power of ECoG did not exhibit a significant difference between walking states. The coherence between the ECoG and STN LFP was significantly greater in high beta and gamma bands during the FOG period compared with the shuffled surrogates (P < 0.05). Lastly, STN-LFP band power features showed above-chance performance (p < 0.01, permutation test) in identifying FOG epochs. Conclusion: In this study, we established and verified the synchronized ECoG/LFP and gait recording system in PD patients with FOG. Further neural substrates underlying FOG could be explored using the current system.

[Application of intracranial electrode for locating epileptogenic zone for temporal lobe epilepsy surgery].

OBJECTIVE: To explore the application of intracranial electrodes (IE) for temporal lobe epilepsy (TLE) surgery and assess the clinical utility of intracranial video electroencephalography (IVEEG). METHODS: The clinical data of 60 TLE patients undergoing implantation of IE were reviewed retrospectively. Cortical subdural strip, grids and depth electrodes were implanted by sphenotresia, bone disc craniotomy or stereotactic technology. RESULTS: The implanted electrodes were as follows: frontal-temporal lobe cortical strip (n = 34), frontal-anterior temporal-occipitotemporal lobe cortical strip (n = 7), bilateral temporal lobe cortical strip (n = 7), combined temporal lobe strip & depth (n = 7), anterior temporal-occipitotemporal junction cortical strip (n = 3) and combined strip & grid (n = 2). The following procedures were performed: anterior temporal lobectomy (ATL) (n = 50), combined ATL & frontal focal cortical resection (n = 7), combined ATL & callosotomy (n = 1) and combined neocortex epileptogenic focus resection & amygdalohippocampectomy (n = 2). CONCLUSION: IVEEG is effective and important for the localization of epileptogenic focus in patients with intractable temporal lobe epilepsy.

The Clinical Application of Robot-Assisted Ventriculoperitoneal Shunting in the Treatment of Hydrocephalus.

BACKGROUND: This work aims to assess the effectiveness and safety of robotic assistance in ventriculoperitoneal shunting and to compare the results with data from traditional surgery. METHODS: We retrospectively analyzed 60 patients who had undergone ventriculoperitoneal shunting, of which shunts were implanted using a robot in 20 patients and using traditional surgical methods in the other 40 patients. Data related to surgery were compared between the two groups, and the accuracy of the drainage tube in the robot-assisted group was assessed. RESULTS: In the robot-assisted surgery group, the operation duration was 29.75 ± 6.38 min, intraoperative blood loss was 10.0 ± 3.98 ml, the success rate of a single puncture was 100%, and the bone hole diameter was 4.0 ± 0.3 mm. On the other hand, the operation duration was 48.63 ± 6.60 min, intraoperative blood loss was 22.25 ± 4.52 ml, the success rate of a single puncture was 77.5%, and the bone hole diameter was 11.0 ± 0.2 mm in the traditional surgery group. The above are statistically different between the two groups (P < 0.05). Only one case of surgery-related complications occurred in the robot-assisted group, while 13 cases occurred in the traditional surgery group. There was no significant difference in the hospitalization time. In the robot-assisted surgery group, the average radial error was 2.4 ± 1.5 mm and the average axial error was 1.9 ± 2.1 mm. CONCLUSION: In summary, robot-assisted implantation is accurate, simple to operate, and practical; the duration of surgery is short; trauma to the patient is reduced; and fewer postoperative complications related to surgery are reported.

Clinical Application of a Neurosurgical Robot in Intracranial Ommaya Reservoir Implantation.

Background: The Ommaya reservoir implantation technique allows for bypass of the blood-brain barrier. It can be continuously administered locally and be used to repeatedly flush the intracranial cavity to achieve the purpose of treatment. Accurate, fast, and minimally invasive placement of the drainage tube is essential during the Ommaya reservoir implantation technique, which can be achieved with the assistance of robots. Methods: We retrospectively analyzed a total of 100 patients undergoing Ommaya reservoir implantation, of which 50 were implanted using a robot, and the remaining 50 were implanted using conventional surgical methods. We then compared the data related to surgery between the two groups and calculated the accuracy of the drainage tube of the robot-assisted group. Results: The average operation time of robot-assisted surgery groups was 41.17 ± 11.09 min, the bone hole diameter was 4.1 ± 0.5 mm, the intraoperative blood loss was 11.1 ± 3.08 ml, and the average hospitalization time was 3.9 ± 1.2 days. All of the Ommaya reservoirs were successful in one pass, and there were no complications such as infection or incorrect placement of the tube. In the conventional Ommaya reservoir implantation group, the average operation time was 65 ± 14.32 min, the bone hole diameter was 11.3 ± 0.3 mm, the intraoperative blood loss was 19.9 ± 3.98 ml, and the average hospitalization time was 4.1 ± 0.5 days. In the robot-assisted surgery group, the radial error was 2.14 ± 0.99 mm and the axial error was 1.69 ± 1.24 mm. Conclusions: Robot-assisted stereotactic Ommaya reservoir implantation is quick, effective, and minimally invasive. The technique effectively negates the inefficiencies of craniotomy and provides a novel treatment for intracranial lesions.

A Bulk Retrospective Study of Robot-Assisted Stereotactic Biopsies of Intracranial Lesions Guided by Videometric Tracker.

Background: Biopsies play an important role in the diagnosis of intracranial lesions, and robot-assisted procedures are increasingly common in neurosurgery centers. This research investigates the diagnoses, complications, and technology yield of 700 robotic frameless intracranial stereotactic biopsies conducted with the Remebot system. Method: This research considered 700 robotic biopsies performed between 2016 and 2020 by surgeons from the Department of Functional Neurosurgery in Beijing's Tiantan Hospital. The data collected included histological diagnoses, postoperative complications, operation times, and the accuracy of robotic manipulation. Results: Among the 700 surgeries, the positive rate of the biopsies was 98.2%. The most common histological diagnoses were gliomas, which accounted for 62.7% of cases (439/700), followed by lymphoma and germinoma, which accounted for 18.7% (131/700) and 7.6% (53/700). Bleeding was found in 14 patients (2%) by post-operation computed tomography scans. A total of 29 (4.14%) patients had clinical impairments after the operation, and 9 (1.29%) experienced epilepsy during the operation. The post-biopsy mortality rate was 0.43%. Operation time-from marking the cranial point to suturing the skin-was 16.78 ± 3.31 min (range 12-26 min). The target error was 1.13 ± 0.30 mm, and the entry point error was 0.99 ± 0.24 mm. Conclusion: A robot-assisted frameless intracranial stereotactic biopsy guided by a videometric tracker is an efficient, safe, and accurate method for biopsies.

Microstructure and functional connectivity-based evidence for memory-related regional impairments in the brains of pilocarpine-treated rats.

Patients with temporal lobe epilepsy (TLE) frequently suffer from memory disorders, and the pathological changes show widespread regional impairments in the brain. In lithium-pilocarpine (LIP)-treated rats with TLE, an abnormal hippocampal microstructure and functional connectivity have been observed. However, changes in other brain regions are still unclear. In the present study, diffusion tensor imaging and functional magnetic resonance imaging (MRI) signals were collected in LIP-TLE rats and controls using a 7.0 T MRI. Microstructural parameters and functional connectivity were calculated among regions of interest (ROIs), including the bilateral prefrontal cortex, amygdala, hippocampus and entorhinal cortex. A correlation analysis was further performed between the neuroimaging results and the behavioral performance in the novel object and novel location memory tests. In our results, TLE rats showed increased fractional anisotropy (FA) values in the hippocampus and decreased FA values in the amygdala and entorhinal cortex. In addition, decreased functional connectivity between the amygdala and the CA3, and increased connectivity between the prefrontal cortex and the CA1 were observed in the TLE rats compared to control rats. Moreover, FA values in the amygdala, the hippocampus and the entorhinal cortex, as well as the amygdala-CA3 and the prefrontal-CA1 connectivity correlated with the memory performance. Based on our results, both the microstructure and functional connections were impaired in memory-related brain regions of LIP-TLE rats. Furthermore, the abnormal changes in the microstructure and functional connectivity were related to behavioral deficits in object and location memory.

Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy.

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) has been shown to be effective and safe in the long-term treatment of refractory epilepsy. However, the mechanisms by which ANT-DBS controls epilepsy at the gene expression level (e.g., which regulatory mechanisms are altered) is not well understood. Nine rats were randomly assigned to the control group, the kainic acid (KA) group, and the DBS group. Temporal lobe epilepsy in rats was induced by a stereotaxic KA injection (KA group). The DBS group received the KA injection followed by treatment with ANT-DBS. Video-electroencephalogram (EEG) was used to monitor seizures. Total RNA samples were isolated from the hippocampus of three groups. Microarray was used to detect differentially regulated mRNAs. GO and pathway analysis were performed to analyze the functional categories and affected pathways. qPCR was used to prove the reliability of the microarray results. The differentially expressed genes the KA group and the DBS group, relative to the control group, were screened and a total of 2910 genes were identified. These genes were involved in functional categories such as ion channel activity (P = 5.01 × 10-8), gated channel activity (P = 1.42 × 10-7), lipid binding (P = 4.97 × 10-5), and hydrolase activity (P = 5.02 × 10-5) and pathways such as calcium signaling pathway (P = 2.09 × 10-8), glutamatergic synapse (P = 4.09 × 10-8) and NOD-like receptor signaling pathway (P = 2.70 × 10-6). Differentially expressed mRNAs might play a role in the pathogenesis of temporal lobe epilepsy. Calcium signaling pathways, synaptic glutamate, and NOD-like receptor signaling pathway play a central role in normal-epilepsy-ANT-DBS treatment series. ANT-DBS achieves its antiepileptic effects by modulating target genes involved in a variety of functions and pathways.

Stimulation of Anterior Thalamic Nuclei Protects Against Seizures and Neuronal Apoptosis in Hippocampal CA3 Region of Kainic Acid-induced Epileptic Rats.

BACKGROUND: The antiepileptic effect of the anterior thalamic nuclei (ANT) stimulation has been demonstrated; however, its underlying mechanism remains unclear. The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis. METHODS: Sixty-four rats were divided into four groups: The control group, the kainic acid (KA) group, the sham-deep brain stimulation (DBS) group, and the DBS group. KA was used to induce epilepsy. Seizure count and latency to the first spontaneous seizures were calculated. Nissl staining was used to analyze hippocampal neuronal loss. Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 (Casp3), B-cell lymphoma-2 (Bcl2), and Bcl2-associated X protein (Bax) in the hippocampal CA3 region. One-way analysis of variance was used to determine the differences between the four groups. RESULTS: The latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group (27.50 ± 8.05 vs. 16.38 ± 7.25 days, P = 0.0005). The total seizure number in the DBS group was also significantly reduced (DBS vs. KA group: 11.75 ± 6.80 vs. 23.25 ± 7.72, P = 0.0002). Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region (DBS vs. KA group: 23.58 ± 6.34 vs. 13.13 ± 4.00, P = 0.0012). After chronic DBS, the relative mRNA expression level of Casp3 was decreased (DBS vs. KA group: 1.18 ± 0.37 vs. 2.09 ± 0.46, P = 0.0003), and the relative mRNA expression level of Bcl2 was increased (DBS vs. KA group: 0.92 ± 0.21 vs. 0.48 ± 0.16, P = 0.0004). The protein expression levels of CASP3 (DBS vs. KA group: 1.25 ± 0.26 vs. 2.49 ± 0.38, P < 0.0001) and BAX (DBS vs. KA group: 1.57 ± 0.49 vs. 2.80 ± 0.63, P = 0.0012) both declined in the DBS group whereas the protein expression level of BCL2 (DBS vs. KA group: 0.78 ± 0.32 vs. 0.36 ± 0.17, P = 0.0086) increased in the DBS group. CONCLUSIONS: This study demonstrated that chronic ANT stimulation could exert a neuroprotective effect on hippocampal neurons. This neuroprotective effect is likely to be mediated by the inhibition of apoptosis in the epileptic hippocampus.

Deep brain stimulation of the subthalamic and pedunculopontine nucleus in a patient with Parkinson's disease.

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel therapy developed to treat Parkinson's disease. We report a patient who underwent bilateral DBS of the PPN and subthalamic nucleus (STN). He suffered from freezing of gait (FOG), bradykinesia, rigidity and mild tremors. The patient underwent bilateral DBS of the PPN and STN. We compared the benefits of PPN-DBS and STN-DBS using motor and gait subscores. The PPN-DBS provided modest improvements in the gait disorder and freezing episodes, while the STN-DBS failed to improve the dominant problems. This special case suggests that PPN-DBS may have a unique role in ameliorating the locomotor symptoms and has the potential to provide improvement in FOG.

Pathological alterations and stress responses near DBS electrodes after MRI scans at 7.0T, 3.0T and 1.5T: an in vivo comparative study.

OBJECTIVE: The purpose of this study was to investigate the pathological alterations and the stress responses around deep brain stimulation (DBS) electrodes after magnetic resonance imaging (MRI) scans at 7.0T, 3.0T and 1.5T. MATERIALS AND METHODS: DBS devices were stereotactically implanted into the brains of New Zealand rabbits, targeting the left nucleus ventralis posterior thalami, while on the right side, a puncture passage pointing to the same target was made. MRI scans at 7.0T, 3.0T and 1.5T were performed using transmit/receive head coils. The pathological alterations of the surrounding tissue were evaluated by hematoxylin and eosin staining (H&E staining) and transmission electron microscopy (TEM). The levels of the 70 kDa heat shock protein (HSP-70), Neuronal Nuclei (NeuN) and Caspase-3 were determined by western-blotting and quantitative polymerase chain reaction (QPCR) to assess the stress responses near the DBS electrodes. RESULTS: H&E staining and TEM showed that the injury around the DBS electrodes was featured by a central puncture passage with gradually weakened injurious alterations. Comparisons of the injury across the groups manifested similar pathological alterations near the DBS electrodes in each group. Moreover, western-blotting and QPCR assay showed that the level of HSP-70 was not elevated by MRI scans (p>0.05), and the levels of NeuN and Caspase-3 were equal in each group, regardless of the field strengths applied (p>0.05). CONCLUSIONS: Based on these findings, it is reasonable to conclude that in this study the MRI scans at multiple levels failed to induce additional tissue injury around the DBS electrodes. These preliminary data furthered our understanding of MRI-related DBS heating and encouraged revisions of the current MRI guidelines for patients with DBS devices.

A rat model of hemidystonia induced by 3-nitropropionic acid.

OBJECTIVE: Secondary dystonia commonly presents as hemidystonia and is often refractory to current treatments. We aimed to establish an inducible rat model of hemidystonia utilizing 3-nitropropionic acid (3-NP) and to determine the pathophysiology of this model. METHODS: Two different doses of 3-NP were stereotactically administered into the ipsilateral caudate putamen (CPu) of Wistar rats. Behavioral changes and alterations in the neurotransmitter levels in the basal ganglia were analyzed. We also performed an electromyogram, 7.0-T magnetic resonance imaging and transmission electron microscopy examination to determine the pathophysiology of the model. RESULTS: In the CPu region, 3-NP produced mitochondrial cristae rupture, axonal degeneration, increased excitatory synaptic vesicles and necrosis. The extracellular concentrations of excitatory amino acids increased, whereas the inhibitory amino acids decreased in the CPu. Furthermore, an imbalance of neurotransmitters was found in other regions of the basal ganglia with the exception of the external globus pallidus. This study demonstrated that 3-NP administration results in CPu damage, and combined with a neurotransmitter imbalance in the basal ganglia, it produces specific neurobehavioral changes in rats. Right limb (contralateral side of CPu lesion) and trunk dystonic postures, shortened step length and ipsiversive dystonic posturing were observed in these rats. Furthermore, EMG recordings confirmed that co-contraction of the agonist and antagonist muscles could be seen for several seconds in right limbs. CONCLUSIONS: Stereotactic injection of 3-NP into the ipsilateral CPu of rats established an inducible model for hemidystonia. This effect might result from an imbalance of neurotransmitter levels, which induce dysfunctional activity of the basal ganglia mainly via the cortico-striato-GPi direct pathway. Symptoms in this model were present for 1 week. Activation of the cortico-striato-GPe indirect pathway and rebalance of neurotransmitters may lead to recovery. This rat model may be a suitable tool used to understand and further investigate the pathophysiology of dystonia.