An-Chao Yang

Stimulation of the anterior nucleus of the thalamus induces changes in amino acids in the hippocampi of epileptic rats

We investigated the changes in the levels of amino acids during high frequency stimulation (HFS) of the anterior nucleus of the thalamus (ANT) in epileptic rats, which had seizures induced by unilaterally stereotactic administration of kainic acid (KA). Thirty-six adult male Wistar rats were divided into three groups: the KA-stim group (KA rats received ipsilateral ANT stimulation), the KA-sham group (KA rats received sham stimulation) and the control group, which underwent stereotactic administration of saline and received ipsilateral ANT stimulation. Microdialysis probes were unilaterally lowered into the CA3 region of the hippocampus, but probes were implanted bilaterally in the KA-stim group. The concentrations of glutamate (Glu), taurine (Tau), aspartate (Asp) and γ-aminobutyric acid (GABA) in the dialysate samples were determined by high-performance liquid chromatography. The concentrations of Glu, Asp and Tau in the hippocampi of KA rats were significantly higher than that found in control rats; however, no difference in the concentrations of GABA were found. In the ipsilateral hippocampi (KA-injected) of rats in the KA-stim group, stimulation of the ANT caused decreases in concentrations of Glu and Asp, an increase in the concentration of GABA and no significant change in the concentration of Tau. Unilateral ANT stimulation did not influence the amino acids in the contralateral hippocampus. In control rats, extracellular Tau significantly increased during and after stimulation. This study demonstrated that unilateral ANT stimulation inhibited the hyperactivation of the excitatory process and promoted the inhibitory process in the ipsilateral hippocampus of KA rats.

Bilateral subthalamic nucleus stimulation in the treatment of neurodegeneration with brain iron accumulation type 1.

Background: Neurodegeneration with brain iron accumulation type 1 (NBIA1), previously called Hallervorden-Spatz disease, is a rare neurodegenerative condition with abnormal brain iron accumulation. There have been some reports of deep brain stimulation (DBS) in the treatment of NBIA1. However, the target was usually the globus pallidus internus or thalamus. Objectives/Methods: We present a case of NBIA1 in a 16-year-old male who was treated with bilateral subthalamic nucleus (STN)-DBS and explored its efficacy in the treatment of NBIA1. The patient presented with severe generalized dystonia and marked dysarthria and had previously had unsuccessful ablation surgery. MRI confirmed the diagnosis of NBIA1. Results: He had significant improvement postoperatively, and the benefit of surgery was maintained for 3 years during follow-up. Burke-Fahn-Marsden Dystonia Rating Scale score was 114/120 preoperatively, and dropped to 60/120 at 14 days, 35/120 at 1 month, 28/120 at 3 months, 14/120 at 1 year and 18/120 at 3 years postoperatively. Conclusions: Our results suggest that bilateral STN-DBS might be considered as an effective treatment for selective NBIA1 patients.

Favorable modulation in neurotransmitters: effects of chronic anterior thalamic nuclei stimulation observed in epileptic monkeys.

Anterior thalamic nuclei (ATN) stimulation has been shown to be effective in seizure reduction. Nevertheless, the underlying mechanisms remain unclear. This study investigated the changes in the amino acid levels during chronic, single-sided ATN-stimulation in the hippocampi of rhesus monkeys with mesial temporal lobe epilepsy induced by kainic acid (KA). The concentrations of glutamate, γ-aminobutyric acid, aspartate and taurine in the dialysates from bilateral hippocampi were determined at multiple time points using high-performance liquid chromatography. The results showed that after KA administration, the aspartate, γ-aminobutyric acid and taurine levels increased significantly in the sham-stimulation group, although the γ-aminobutyric acid and taurine levels gradually returned to the basal levels in the chronic stage. The glutamate level showed an initial decrease in the acute stage and a subsequent increase in the chronic stage. Chronic ATN-stimulation reversed the increases in the glutamate and aspartate levels, and maintained the initial increases in the γ-aminobutyric acid and taurine levels till the end of the experiment. These amino acid levels, however, were not affected by either contralateral KA injection or contralateral ATN-stimulation, suggesting that the observed effects of ATN-stimulation are restricted to the ipsilateral hemisphere. Our data suggest that chronic ATN-stimulation may induce favorable modulations in the amino acid levels in the hippocampi of epileptic monkeys, which may be an important mechanism underlying the effects of ATN-stimulation in epilepsy treatment.

A new choice for the treatment of epilepsy: Electrical auricula-vagus-stimulation

Preliminary reports have suggested that chronic, intermittent electrical stimulation of the cervical vagus nerve (VNS) is an effective treatment for patients who suffered from medically refractory epilepsy. But the traditional VNS is an invasive and implantable procedure that will bring some injury to the patient. Anatomic studies have confirmed the existence of auricular branch of the vagus nerve-Arnold nerve. The Arnold nerve mainly consists of afferent fibers and the superficial sites of the Arnold nerve are optimal for electrical stimulation. We hypothesized that electrical auricula-vagus-stimulation could be a new choice for the treatment of epilepsy.

Hemangiopericytomas in the spine: clinical features, classification, treatment, and long-term follow-up in 26 patients.

BACKGROUND Intraspinal hemangiopericytoma (HPC) is a rare and malignant extra-axial tumor with a strong tendency to recur and metastasize. There is a paucity in the literature of large case series of patients with intraspinal HPCs. OBJECTIVE We retrospectively analyzed the clinical radiological and histological features, classification, and treatment of 26 patients with HPCs in the spine. METHODS Twenty-six patients with HPCs in the spine were treated at our institution between 1987 and 2010. Medical records were reviewed retrospectively to collect data on the clinical features, tumor morphology, surgical resection, recurrence, and follow-up. RESULTS The 26 patients were predominantly male, and the mean age at diagnosis was 33.8 years. The intraspinal HPCs were divided into 3 types and 5 subtypes. Most of them involved the neighboring segments and/or caused bony erosion. All tumors were immunohistochemically positive for vimentin and negative for epithelial membrane antigen. All patients underwent at least 1 surgery, and most of them received postsurgical radiotherapy. The 5-year Kaplan-Meier rate of survival was 76%. The 5-year recurrence-free rate of survival was 29.4%. Only the tumor pathological grade was significantly associated with survival time and recurrence. CONCLUSION High-grade tumors had a shorter survival time and recurred earlier than low-grade tumors. Surgical removal and postoperative radiotherapy are critical for the treatment of intraspinal HPCs. However, total resection may not necessary for these tumors. Stereotactic radiosurgery may be a good alternative to control the recurrent lesions.

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 Parkinsons 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.

Potential Protective Effects of Chronic Anterior Thalamic Nucleus Stimulation on Hippocampal Neurons in Epileptic Monkeys

BACKGROUND Stimulation of the anterior nucleus of the thalamus (ANT) is effective in seizure reduction, but the mechanisms underlying the beneficial effects of ANT stimulation are unclear. OBJECTIVE To assess the beneficial effects of ANT stimulation on hippocampal neurons of epileptic monkeys. METHODS Chronic ANT stimulation was applied to kainic acid-induced epileptic monkeys. Behavioral seizures were continuously monitored. Immunohistochemical staining and western blot assays were performed to assess the hippocampal injury and the effects of ANT stimulation. RESULTS The frequency of seizures was 42.8% lower in the stimulation group compared with the sham-stimulation group. Immunohistochemical staining and western blot analyses indicated that neuronal loss and apoptosis were less severe and that neurofilament synthesis was enhanced in the stimulation monkeys compared with the sham-stimulation group. These data showed that the hippocampal injury was less severe in monkeys in the stimulation group than in those in the sham-stimulation group. CONCLUSIONS Our data suggest that chronic ANT stimulation may exert protective effects on hippocampal neurons and boost the regeneration of neuronal fibers. These effects may be closely related to the mechanisms of ANT stimulation in epilepsy treatment.

Subthalamic Deep Brain Stimulation With a New Device in Parkinson's Disease: An Open-Label Trial

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 Parkinsons disease (PD).

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.

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.