Jian-guo Zhang

Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial.

OBJECTIVE We investigated the safety and efficacy of transcutaneous auricular vagus nerve stimulation (ta-VNS) for the treatment of pediatric epilepsy. METHODS Fourteen pediatric patients with intractable epilepsy were treated by ta-VNS of the bilateral auricular concha using an ear vagus nerve stimulator. The baseline seizure frequency was compared with that after 8weeks, from week 9 to 16 and from week 17 to the end of week 24, according to the seizure diaries of the patients. RESULTS One patient dropped out after 8weeks of treatment due to lack of efficacy, while the remaining 13 patients completed the 24-week study without any change in medication regimen. The mean reduction in seizure frequency relative to baseline was 31.83% after week 8, 54.13% from week 9 to 16 and 54.21% from week 17 to the end of week 24. The responder rate was 28.57% after 8weeks, 53.85% from week 9 to 16 and 53.85% from week 17 to the end of week 24. No severe adverse events were reported during treatment. CONCLUSION Transcutaneous auricular VNS may be a complementary treatment option for reducing seizure frequency in pediatric patients with intractable epilepsy and should be further studied.

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.

Atypical trigeminal neuralgia: A consequence of central sensitization?

Trigeminal neuralgia (TN) is characterized by sudden, recurrent, usually unilateral, severe brief stabbing pains in the distribution of trigeminal nerve. Although it is widely accepted that blood vessel or tumor compression contributes to paroxysms of TN, the pathogenesis of persistent background pain in atypical TN patient is unclear. Central sensitization is pain hypersensitivity caused by central neural plasticity. It is responsible for many temporal and symptomatic features of acute and chronic pain. We hypothesize that central sensitization might account for some symptoms of atypical TN. Based on this hypothesis, we postulate that early medical intervention predicts good outcomes in TN and medicines which are effective on central sensitization may be potential agents for the treatment of atypical TN.

Variable frequency stimulation of subthalamic nucleus for freezing of gait in Parkinson’s disease

High frequency stimulation (HFS) of the subthalamic nucleus (STN) provides consistent, long-term improvement of the cardinal signs of Parkinsons disease (PD), such as bradykinesia, tremor and rigidity. Freezing of gait (FOG) responds poorly to HFS and deteriorates over time, but this can be alleviated by using relatively low frequency stimulation (LFS) [1]. There are two major concerns when applying LFS in clinical practice, the first being the duration of clinical benefit. Evidence indicates that LFS-STN can improve axial signs in some but not all PD patients, but most of them experienced loss of efficacy in the short term. Then patients are left with little improvement or increasing tremor, rigidity and bradykinesia, which consists of the three main signs of PD. Thus even if axial problems can be ameliorated by LFS in the long term, patients might find deterioration of motor symptoms difficult to tolerate. Strategies to bypass this tolerance phenomenon to LFS are needed. Here, we describe a patient with FOG who received variable frequency stimulation (VFS) where the stimulation frequency was set to alternate between high and low frequencies. In August 2012 after signing informed consent, a 66-year-old man was implanted with Deep Brain Stimulation systems [2] (PINS Medical). STN was chosen for the target. He developed rigidity in his limbs in the middle of 2007 and was diagnosed with PD in September of that year. Over time, his levodopa dose was increased from 250 mg to 1000 mg per day and 0.375 mg pramipexole was added. The levodopa equivalent dosage was decreased to 750 mg/ day one month after implantation and UPDRS score decreased from 57 to 21. Six months later he developed FOG. The parameters of active contacts, amplitude and frequency were changed, but had no effect on the gait. Variable frequency stimulation was then applied with a remarkable improvement in the FOG observed with little deterioration of the limb rigidity. Parameters were 2.7 V, 60 us, 60 Hz & 130 Hz (60 Hz for 20 s and 130 Hz for 30 s per cycle) to the right side and 1.7 V, 60 us, 60 Hz & 130 Hz (60 Hz for 20 s and 130 Hz for 30 s per cycle) to the left side. A Timed go (TUG) test was conducted and videoed to show the ment in the FOG (Table 1). The patient was followed-up by telephone after 4 months of VFS, and the benefit was still remarkable compared with traditional HFS, in spite of some deterioration. Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.parkreldis.2015.10.002.

High-frequency electrical stimulation in the nucleus accumbens of morphine-treated rats suppresses neuronal firing in reward-related brain regions

Summary Background Previous studies have reported that high-frequency stimulation (HFS) in the nucleus accumbens (NAc) is a potential treatment modality for drug craving and relapse. We aimed to explore the electrophysiological changes in reward-related brain regions during NAc stimulation and reveal the effects of stimulation frequency and target changes on NAc neuronal activities. Material/Methods Twenty-eight rats were randomized into saline (n=8) and morphine (n=20) groups. The morphine group was further divided into core (n=10, only the core of the NAc was stimulated) and shell (n=10, only the shell of the NAc was stimulated) subgroups. Conditioned place preference (CPP) behavior of the rats was evaluated to confirm morphine preference after morphine injection and CPP training for 10 days. We recorded NAc neuronal responses to NAc core stimulation at different frequencies, as well as changes in VP and VTA neuronal firing during NAc core stimulation, and changes in NAc neuronal firing during NAc shell stimulation. Results The results indicate that high frequency stimulation was more effective in suppressing NAc neuronal activities than low frequency stimulation and that core stimulation was more effective than shell stimulation. Most VP neurons were inhibited by NAc core stimulation, while VTA neurons were not. Conclusions The results suggest that electrical stimulation in the NAc can suppress neuronal firing in reward-related brain regions. The stimulation might be frequency- dependent in suppressing neuronal firing. The core and shell of the NAc play different roles in suppressing NAc neuronal firing as 2 stimulating targets.

Deep brain stimulation in China: present and future.

Objective:  We reviewed the clinical applications, academic communications, and specialized training required for deep brain stimulation (DBS) in China. Current problems and possible solutions also were discussed.

Surgical outcome of gelastic epilepsy of frontal lobe origin: A case report

Gelastic seizure is an uncommon type of seizure which is characterized by recurrent bouts of unprovoked and stereotyped laughter. It is commonly observed in patients with hypothalamic hamartoma, while its association with other cerebral lesions is rare. The patient was a 15-year-old right-handed male. His chief complaints were recurrent onsets of laughter and unconsciousness for 10 years. On average, he had several to dozens of onsets per day and had failed most antiepileptic medications before admission. Presurgical evaluation included MRI, video-EEG, MEG and subdural electrode EEG. The results of MEG and subdural electrode EEG suggested that the epileptogenic focus was located on the lateral surface of the right frontal lobe, chiefly on the anterior part of the inferior frontal gyrus. The focus was removed under intraoperative ECoG monitoring which was consistent with the results of MEG and subdural electrode EEG. Histopathology revealed focal cortical dysplasia with balloon cells (type II). The patient kept seizure-free during the short-term follow up of 3 months. In the past literature, the medial frontal and basal temporal lobes, besides the hypothalamus, were thought to play major roles in the case of gelastic seizure. Our results suggest that the lateral surface of the frontal lobe might also be one part of the epileptogenic network in gelastic seizures. Removal of the epileptogenic focus under thorough pre-surgical evaluation might result in good seizure control in patients with gelastic seizures.

Whole-transcriptome screening reveals the regulatory targets and functions of long non-coding RNA H19 in epileptic rats

Understanding the molecular mechanisms mediating epileptogenesis may lead to the development of preventative therapies against epilepsy. Our previous study demonstrated that the long non-coding RNA H19 contributes to epileptogenesis by aggravating status epilepticus-induced neuronal loss, glial cell activation, mossy fiber sprouting, and cognitive impairments in epileptic rats. However, the systematic functions and downstream targets of H19 associated with epileptogenesis are still unknown. In the present study, high-throughput microarray analysis was used to explore the influence of H19 on gene expression in an epileptic rat model. A large number of genes were differentially expressed at the transcriptional level when H19 was overexpressed or knocked down. Series test of cluster analysis further distinguished genes associated with H19. Function and pathway analyses demonstrated that H19 has diverse functions related to epileptogenesis, including demyelination, immune and inflammatory responses, cell apoptosis, and activation of MAPK. This study implicates H19 in a broad spectrum of epileptogenic processes, thereby providing a range of targets for further mechanistic investigations.

Acute stepwise challenge test with levodopa in treated patients with parkinsonism

OBJECTIVE The aim of this study was to establish a new stepwise type of acute challenge test with incremental doses of levodopa/benserazide, and verify its predictive value in follow-up diagnoses and outcomes of deep-brain stimulation (DBS) in treated patients with parkinsonism. DESIGN Prospective cohort study. OUTCOMES The optimal cutoff points for UPDRS-III improvement in these stepwise levodopa tests. In this study, we established acute challenge tests with incremental doses of levodopa/benserazide (100/25mg, 150/37.5mg, 200/50mg and 300/75 mg) in treated patients with parkinsonism (n=175). The receiver operating characteristic (ROC) curves were plotted to compare peak UPDRS-III improvement of PD patients (n=112) with that of non-PD parkinsonism patients (n=63). The point on the ROC curve with the highest Youden index was defined as the optimal cutoff point in motor improvement for differential diagnoses. The results of the new tests were compared with follow-up diagnoses and the outcomes of DBS. RESULTS The optimal cutoff points for UPDRS-III improvement with maximal Youden Indices on ROC curves from the tests, with the four incremental doses of levodopa/benserazide, were 12.2% (100/25mg), 22.3% (150/37.5mg), 27.9% (200/50mg) and 33.4% (300/75 mg). The test showed significant correlation with follow-up diagnosis and the outcomes of DBS (P of Kappa <0.01). CONCLUSIONS The results suggested that the new acute stepwise levodopa challenge test is a useful tool for the diagnosis of PD.