OBJECTIVEWe review the targets of the deep brain and the responsive neurostimulation system (RNS) to identify the best optimal stimulation parameters and the best mode of stimulation, whether cyclical, continuous, or smarter.

DATA SOURCESThis review is based on data obtained from published articles from 1950 to 2013. To perform the PubMed literature search, the following keywords were input: deep brain stimulation (DBS), RNS, and refractory epilepsy.

STUDY SELECTIONArticles containing information related to brain stimulation or RNS for the treatment of refractory epilepsy were selected.

RESULTSThe currently available treatment options for those patients who resist multiple antiepileptic medications and surgical procedures include electric stimulation, both direct and indirect, of brain nuclei thought to be involved in epileptogenesis. The number of potential targets has increased over the years to include the anterior nucleus of the thalamus, the centromedian nucleus of the thalamus, the hippocampus, the subthalamic nucleus, the caudate nucleus, and the cerebellum, among others. The results of a randomized controlled trial and the RNS trial were published to reveal the effectiveness.

CONCLUSIONSAlthough statistically significant reductions in seizures have been observed using several different stimulation techniques, including vagus nerve stimulation, DBS, and RNS, these effects are currently only palliative and do not approach the efficacy comparable with that seen in resection in appropriately selected patients. More research is needed to determine optimal stimulation targets and techniques as well as to determine which epilepsy patients will benefit most from this technology.

Deep Brain Stimulation ; methods ; Epilepsy ; therapy ; Female ; Humans ; Male ; Vagus Nerve Stimulation ; methods

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

BACKGROUNDPrevious studies demonstrated that vagus nerve stimulation (VNS) is an effective therapy for drug-resistant epilepsy. Acupuncture is also used to treat epilepsy. This study was designed to examine the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with drug-resistant epilepsy.

METHODSA total of 50 volunteer patients with drug-resistant epilepsy were selected for a random clinical trial to observe the therapeutic effect of ta-VNS. The seizure frequency, quality of life, and severity were assessed in weeks 8, 16, and 24 of the treatment according to the percentage of seizure frequency reduction.

RESULTSIn the pilot study, 47 of the 50 epilepsy patients completed the 24-week treatment; three dropped off. After 8-week treatment, six of the 47 patients (12%) were seizure free and 12 (24%) had a reduction in seizure frequency. In week 16 of the continuous treatment, six of the 47 patients (12%) were seizure free; 17 (34%) had a reduction in seizure frequency. After 24 weeks' treatment, eight patients (16%) were seizure free; 19 (38%) had reduced seizure frequency.

CONCLUSIONSimilar to the therapeutic effect of VNS, ta-VNS can suppress epileptic seizures and is a safe, effective, economical, and widely applicable treatment option for drug-resistant epilepsy. (ChiCTR-TRC-10001023).

Adolescent ; Adult ; Epilepsy ; therapy ; Female ; Humans ; Male ; Transcutaneous Electric Nerve Stimulation ; methods ; Treatment Outcome ; Vagus Nerve Stimulation ; methods ; Young Adult

Tinnitus is defined as a perception of sound without any external sound source. Chronic tinnitus is a frequent condition that can affect the quality of life. So far, no causal cure for tinnitus has been documented, and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus' impact on the quality of life. Neuromodulation, a novel therapeutic modality, which aims at alternating nerve activity through a targeted delivery of a stimulus, has emerged as a potential option in tinnitus treatment. This review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options. The main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine. Non-invasive methods such as repetitive transcranial magnetic stimulation, transcranial electrical stimulation, neurofeedback, and transcutaneous vagus nerve stimulation were included, as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation. Some of these neuromodulation techniques revealed promising results; nevertheless, further research is needed, especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce. Various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus. Therefore, in the future, individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.
Deep Brain Stimulation/methods* ; Humans ; Neurofeedback/methods* ; Tinnitus/therapy* ; Transcranial Direct Current Stimulation/methods* ; Transcranial Magnetic Stimulation/methods* ; Vagus Nerve Stimulation/methods*

OBJECTIVE: To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI). METHODS: A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO₁₅) and Shen (CO₁₀) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain. RESULTS: After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01). CONCLUSION taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.
Brain/physiology* ; Default Mode Network ; Humans ; Magnetic Resonance Imaging/methods* ; Sleep Initiation and Maintenance Disorders/therapy* ; Vagus Nerve ; Vagus Nerve Stimulation/methods*

We evaluated the long-term outcome of vagus nerve stimulation (VNS) in 28 children with refractory epilepsy. Of these 28 children, 15 (53.6%) showed a >50% reduction in seizure frequency and 9 (32.1%) had a >75% reduction. When we compared seizure reduction rates according to seizure types (generalized vs. partial) and etiologies (symptomatic vs. cryptogenic), we found no significant differences. In addition, there was no correlation between the length of the stimulation period and treatment effect. The seizure reduction rate, however, tended to be inversely related to the seizure duration before VNS implantation and age at the time of VNS therapy. VNS also improved quality of life in this group of patients, including improved memory in 9 (32.1%), improved mood in 12 (42.9%), improved behavior in 11 (39.3%), improved altertness in 12 (42.9%), improved achievement in 6 (21.4%), and improved verbal skills in 8 (28.6%). Adverse events included hoarseness in 7 patients, dyspnea at sleep in 2 patients, and wound infection in 1 patient, but all were transient and successfully managed by careful follow-up and adjustment of parameters. These results indicate that VNS is a safe and effective alternative therapy for pediatric refractory epilepsy, without significant adverse events.
Adolescent ; Child ; Child, Preschool ; Electric Stimulation Therapy/*methods ; Epilepsy/*therapy ; Female ; Humans ; Korea ; Male ; Quality of Life ; Seizures/therapy ; Time Factors ; Treatment Outcome ; Vagus Nerve/*pathology

BACKGROUNDOver past two decades, vagus nerve stimulation (VNS) has been widely used and reported to alleviate seizure frequency worldwide, however, so far, only hundreds of patients with pharmaco-resistant epilepsy (PRE) have been treated with VNS in mainland China. The study aimed to evaluate the effectiveness of VNS for Chinese patients with PRE and compare its relationship with age cohort and gender.

METHODSWe retrospectively assessed the clinical outcome of 94 patients with PRE, who were treated with VNS at Beijing Fengtai Hospital and Beijing Tiantan Hospital between November 2008 and April 2014 from our database of 106 consecutive patients. The clinical data analysis was retrospectively examined.

RESULTSSeizure frequency significantly decreased with VNS therapy after intermittent stimulation of the vagus nerve. At last follow-up, we found McHugh classifications of Class I in 33 patients (35.1%), Class II in 27 patients (28.7%), Class III in 20 patients (21.3%), Class IV in 3 patients (3.2%), and Class V in 11 patients (11.7%). Notably, 8 (8.5%) patients were seizure-free while ≥50% seizure frequency reduction occurred in as many as 60 patients (63.8%). Furthermore, with regard to the modified Engel classification, 12 patients (12.8%) were classified as Class I, 11 patients (11.7%) were classified as Class II, 37 patients (39.4%) were classified as Class III, 34 patients (36.2%) were classified as Class IV. We also found that the factors of gender or age are not associated with clinical outcome.

CONCLUSIONSThis comparative study confirmed that VNS is a safe, well-tolerated, and effective treatment for Chinese PRE patients. VNS reduced the seizure frequency regardless of age or gender of studied patients.

Adolescent ; Adult ; Child ; Child, Preschool ; Drug Resistance ; Epilepsy ; therapy ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Vagus Nerve Stimulation ; methods ; Young Adult

BACKGROUNDIn general vagus nerve stimulation (VNS) can serve as an adjunctive treatment for patients with refractory partial-onset seizures. And we evaluated the long-term efficacy and safety of VNS in a group of Chinese patients with refractory epilepsy.

METHODSOf 127 patients with refractory epilepsy, 13 patients who were not eligible for surgical intervention were implanted with the Cyberonics VNS system. Seizure frequency, physical examination and side effects profile were recorded at follow-up visits for a minimum of 18 months.

RESULTSMean duration of treatment was 47.4 months, and the longest follow-up period was 71 months. Mean baseline seizure frequency was 26.6 seizures per month. The mean percentage reductions in convulsions were 33.2%, 47.1% and 40.0% at 6, 12 and 18 months, respectively. One patient became seizure free, and six (46%) had 50% or more reduction in seizure frequency. Response was poor (< 20% reduction) in five patients (39%). Side effects were uncommon.

CONCLUSIONSThe effectiveness of VNS was sustained and was well tolerated but benefited only a sub-group of patients with intractable convulsions.

Adolescent ; Adult ; Electric Stimulation Therapy ; methods ; Epilepsy ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Prospective Studies ; Prostheses and Implants ; Treatment Outcome ; Vagus Nerve ; physiology

BACKGROUNDVagus nerve stimulation (VNS) is an alternative treatment for drug-resistant epilepsy (DRE). The study aimed to explore the potential factors of prognosis, safety and effect of VNS treatment in patients with DRE.

METHODSWe retrospectively examined 45 cases of DRE that received VNS treatment in our center from June 2004 to June 2010 and analyzed the parameters (age of patient receiving VNS, seizure frequency before and after VNS as well as treatment duration) by Student's t test, Fisher's exact and Mann-Whitney U tests, and multivariate Logistic regression.

RESULTSThe overall response rate was 64% (29/45), 67% (6/9) for adults and 64% (23/36) for children, with no significant difference (P = 0.28). Twenty-two cases had been in VNS therapy for over 1 year with a treatment efficacy of 73% (16/22), whereas 23 cases had been in VNS therapy no more than 1 year with a treatment effecacy of 57% (13/23), and has statistically significant difference (P = 0.03). The main side effect included hoarseness of voice and cough. One patient's device was removed due to infection. One patient's VNS was half-way terminated due to seizure aggravation. One patient died due to status epilepticus.

CONCLUSIONSVNS is a safe and effective treatment for DRE. Duration of VNS therapy may be a crucial factor on prognosis.

Adolescent ; Adult ; Child ; Child, Preschool ; Epilepsy ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Retrospective Studies ; Vagus Nerve Stimulation ; methods ; Young Adult

To study the antiepileptic mechanism of vagus nerve stimulation (VNS), we used the methods of in situ hybridyzation and image analysis to detect the expression of NMDAR1 mRNA and GABAA receptor alpha 1 subunit mRNA (GABAAR alpha 1 mRNA) in the thalamic reticular nuclus. The results show that the NMDAR1 mRNA expression of rats administered pentylenetetrazole(PTZ) is higher than that of control group. By treating with VNS, it decreased. On the contrary, the expression of GABAAR alpha 1 mRNA in the thalamic reticular nuclus of PTZ group rats is lower than that of control group. For rats treated with VNS, it increased. Therefore, it is concluded that VNS may reduce the excitability of cerebral cortices by depressing the activities of glutamic acid receptors (GluR) and by promoting the activities of gamma-aminobutyric acid receptors(GABAR) in thalamic reticular nuclus. So the formation and development of seizures are inhibited.
Animals ; Electric Stimulation Therapy ; methods ; Epilepsy ; chemically induced ; therapy ; Intralaminar Thalamic Nuclei ; metabolism ; Male ; Pentylenetetrazole ; toxicity ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Wistar ; Receptors, GABA-A ; biosynthesis ; genetics ; Receptors, N-Methyl-D-Aspartate ; biosynthesis ; genetics ; Vagus Nerve ; physiopathology