Huan-Guang Liu

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.

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.

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.

Long-term Effects of Subthalamic Nucleus Deep Brain Stimulation in Tardive Dystonia

To the Editor: Tardive dystonia (TD) is a specific type of secondary dystonia caused primarily by the chronic application of dopamine receptors antagonists.[1] Deep brain stimulation (DBS) has been becoming a promising therapy to treat dystonia. Here, we report the long-term effect of subthalamic nucleus (STN) stimulation for a TD patient after a 12-year follow-up. A 28-year-old woman was diagnosed with TD in May 2000. The history of illness, physical examination, and auxiliary examination were precisely described in our previous report.[2] The Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) total score was 98.5 (motor score: 70.5, disability score: 28.0) in May 2003 [Figure ​[Figure1a1a and ​and1b].1b]. In July 2003, she underwent bilateral STN electrodes implantation. After stimulation, the patient showed distinct improvement of the motor symptoms without any side effects. Three months after the operation, BFMDRS total score was 8.0 (motor score: 6.0, disability score: 2.0) [Figure 1c]. The involuntary movement disappeared. There was only slight elevation of right shoulder and slightly tremor of hands. Six years after the operation, BFMDRS total score decreased to 0 [Figure 1d]. She could walk for 1–2 h with the IPG turned off in the morning. Nine years after the operation, her right leg had slight stiffness. BFMDRS total score was 3.0 (motor score: 2.0, disability score: 1.0) [Figure 1e]. She could also turn off the stimulation for several hours every day without any serious symptoms. Twelve years after operation, the gait disturbance disappeared. BFMDRS total score was 0 [Figure 1f]. The off time of stimulation markedly increased from several hours to several days. She could live with DBS off when sitting, eating, and even doing physical exercises. She turned on the stimulation only when she felt tired. Except the psychiatric episodes that the patient experienced before surgery, she did not have any extra psychiatric complications in the 12 years follow-up. Figure 1 Clinical pictures of the patient before surgery and in the long-term follow-up. (a and b) Prior to operation, the patient cannot sit and walk steadily. (c) Three months after the operation, the patient can walk and run in a natural manner. (d) Six years ... In the treatment of dystonia, globus pallidus internus (GPi) is the preferred target. However, STN-DBS also could produce 77% of improvement of BFMDRS scores and remarkable improvement in the quality of life in primary dystonia without any psychiatric complications.[3] Here, we demonstrated that STN-DBS also worked perfectly in TD patients. The promising results in our patient were that the time of DBS interruption gradually increased, and the patient could perform daily activities independent of stimulation. Although Gruber et al.[4] reported that sudden cessation of stimulation after long-term stimulation of GPi would result in a severe relapse of the symptoms within minutes to hours in TD patients, we did not observe this phenomenon in our patient after 12 years of STN-DBS treatment. The sustained effect of DBS in our patient may be maintained by converting the maladaptive plasticity to normal plasticity in the pathological brain. It is promising that our patient could stop the stimulation completely in the future. Therefore, STN is promising to become an optimal target for TD patients. However, large cohorts studies are needed to fully evaluate the efficacy of STN-DBS for TD in future. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship This study was supported by a grant from the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (No. ZYLX201305). Conflicts of interest There are no conflicts of interest.

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.

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

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.