Neuroestimulación del nervio vago, hipocampal y de núcleos anteriores y centromedianos del tálamo en epilepsia temporal: revisión de la literatura / Neurostimulation of the vagus nerve, hippocampal and anterior and centromedian nuclei of the thalamus in temporal epilepsy: literature review

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.

Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life

Predictive factors for successful vagus nerve stimulation in patients with refractory epilepsy: real-life insights from a multicenter study

Vagus nerve stimulation (VNS) therapy is an established treatment for patients with drug-resistant epilepsy that reduces seizure frequency by at least 50% in approximately half of patients; however, the characteristics of the patients with the best response have not yet been identified. Thus, it is important to identify the profile of patients who would have the best response to guide early indications and better patient selection.

A terapia com estimulação do nervo vago (ENV) é um tratamento estabelecido para pacientes com epilepsia resistente a medicamentos que reduz a frequência de crises em pelo menos 50% em aproximadamente metade dos pacientes; entretanto, as características dos pacientes com melhor resposta ainda não foram identificadas. Assim, é importante identificar o perfil de pacientes que teriam melhor resposta para orientar indicações precoces e melhor seleção de pacientes.

Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI / 中国针灸

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.

Reducing VNS stimulation parameters: Is it safe?

Introduction Vagal nerve stimulation (VNS) is an adjuvant therapy used in the treatment of patients with refractory epilepsy who are not candidates for resective surgery or who have limited results after surgical procedures. Currently, there is enough evidence to support its use in patients with various types of epilepsy. Therefore, the present study was conducted to explore the possibility of optimizing therapy by reducing the consumption of the system's battery. Methods The prospective and double-blind analysis consisted in the evaluation of 6 patients submitted to VNS implantation for 3 months, followed by adjustment of the stimulation settings and continuity of follow-up for another month. The standard protocol was replaced by another with a frequency value of 20 Hz instead of 30 Hz to increase battery life. The safety of this procedure was evaluated through the assessment of two main variables: seizures and side effects. Results The stimulation at 20 Hz showed 68% reduction in the incidence of seizures (p»0.054) as well as low incidence of side effects. Conclusion The present study suggests that the reduction of the stimulation frequency from 30 to 20 Hz is a safe procedure, and it does not compromise the effectiveness of therapy.

Effect of transcutaneous auricular vagus nerve stimulation on nocturnal autonomic nervous function in primary insomnia patients / 中国针灸

OBJECTIVE@#To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the sleep quality and nocturnal heart rate variability (HRV) in patients with primary insomnia.@*METHODS@#Twenty-one patients with primary insomnia were included. Using SDZ-ⅡB electric acupuncture apparatus, Xin (CO15) and Shen (CO10) were stimulated with disperse-dense wave, 4 Hz/ 20 Hz in frequency, (0.2±30%) ms of pulse width and tolerable intensity. Electric stimulation was given once every morning and evening of a day, 30 min each time, for 4 weeks totally. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), objective sleep structure (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], the percentages of non-rapid eye movement period 1, 2, 3, and the percentage of rapid eye movement period to TST [N1%, N2%, N3%, REM%] ) and nocturnal HRV (high frequency [HF], low frequency [LF], the ratio of LF to HF [LF/HF], standard deviation for the normal RR intervals [SDNN], squared root of the mean sum of squares of differences between adjacent intervals RR [RMSSD], the percentage of adjacent RR intervals with differences larger than 50 ms in the entire recording [PNN50%], the mean of sinus RR intervals [NNMean] ) were compared in the patients separately.@*RESULTS@#After treatment, the score of each item and the total score of PSQI and SL were all reduced as compared with those before treatment (P<0.01, P<0.001); SE, N3%, LF, HF, LF/HF, SDNN, NNMean and RMSSD were all increased compared with those before treatment (P<0.001, P<0.01).@*CONCLUSION@#The taVNS improves the sleep quality and objective sleep structure in patients with primary insomnia, which is probably related to the regulation of autonomic nervous functions.

Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia / 中国针灸

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.

Non-invasive electrical neuromodulation techniques: analgesic effects and neural mechanisms / 生理学报

As non-pharmaceutical interventions, non-invasive electrical neuromodulation techniques are promising in pain management. With many advantages, such as low costs, high usability, and non-invasiveness, they have been exploited to treat multiple types of clinical pain. Proper use of these techniques requires a comprehensive understanding of how they work. In this article, we reviewed recent studies concerning non-invasive electrical peripheral nerve stimulation (transcutaneous electrical nerve stimulation and transcutaneous vagus/vagal nerve stimulation) as well as electrical central nerve stimulation (transcranial direct current stimulation and transcranial alternating current stimulation). Specifically, we discussed their analgesic effects on acute and chronic pain, and the neural mechanisms thereof. We then contrasted the four kinds of nerve stimulation techniques, pointing out limitations of existing studies and proposing directions for future research. With more extensive and in-depth research to overcome these limitations, we shall witness more clinical applications of non-invasive electrical nerve stimulations to alleviate patients' pain and ease the crippling medical and economic burden imposed on patients, their families, and the entire society.

Efficacy and safety of vagus nerve stimulation in the treatment of refractory epilepsy / 中南大学学报(医学版)

OBJECTIVES@#Vagus nerve stimulation (VNS) is a neuromodulative therapeutic technique for patients with drug-resistant epilepsy who are not suitable for resection or who have experienced a failed resection. This study aims to explore the efficacy and safety of VNS in patients with refractory epilepsy, and to analyze the influential factors for the efficacy.@*METHODS@#A retrospective review of clinical data were conducted for 35 patients, who were treated for refractory epilepsy through VNS surgery in the Department of Neurosurgery, Xiangya Hospital, Central South University from April 2016 to August 2019. All patients were analyzed in terms of the clinical and follow-up data.@*RESULTS@#After a mean follow-up of 26 months (6-47 months), outcome was as follows: 7 patients were MuHugh class I, 13 patients were MuHugh class II, 8 patients were MuHugh class III, and 7 patients were MuHugh class IV-V. The total efficacy rate in the short duration group was significantly higher than that in the long duration group (77.8% vs 50.0%, @*CONCLUSIONS@#VNS is a safe and effective option in treating patients with refractory epilepsy, especially for those with short duration.

Cholinergic anti-inflammatory pathway and its role in treatment of sepsis / 中南大学学报(医学版)

The cholinergic anti-inflammatory pathway (CAP) is a neuro-immunomodulatory pathway,in which acetylcholine (ACh) released by the interaction of vagal nerves with α7 nicotinic acetylcholine receptor (α7nAChR),which prevents the synthesis and release of pro-inflammatory cytokines and ultimately regulates the local or systemic inflammatory response in a feedback manner. It has been shown that there are many possible effective treatments for sepsis, including vagus nerve stimulation by physical therapy, drugs such as acetylcholine receptor agonist and ultrasound therapy.

Application of scalp electroencephalogram in treatment of refractory epilepsy with vagus nerve stimulation / 生物医学工程学杂志

Electroencephalogram (EEG) has been an important tool for scientists to study epilepsy and evaluate the treatment of epilepsy for half a century, since epilepsy seizures are caused by the diffusion of excessive discharge of brain neurons. This paper reviews the clinical application of scalp EEG in the treatment of intractable epilepsy with vagus nerve stimulation (VNS) in the past 30 years. It mainly introduces the prediction of the therapeutic effect of VNS on intractable epilepsy based on EEG characteristics and the effect of VNS on EEG of patients with intractable epilepsy, and expounds some therapeutic mechanisms of VNS. For predicting the efficacy of VNS based on EEG characteristics, EEG characteristics such as epileptiform discharge, polarity of slow cortical potential changes, changes of EEG symmetry level and changes of EEG power spectrum are described. In view of the influence of VNS treatment on patients' EEG characteristics, the change of epileptiform discharge, power spectrum, synchrony, brain network and amplitude of event-related potential P300 are described. Although no representative EEG markers have been identified for clinical promotion, this review paves the way for prospective studies of larger patient populations in the future to better apply EEG to the clinical treatment of VNS, and provides ideas for predicting VNS efficacy, assessing VNS efficacy, and understanding VNS treatment mechanisms, with broad medical and scientific implications.

The Present and Future of Vagus Nerve Stimulation

Epilepsy is one of the major chronic neurological diseases affecting many patients. Resection surgery is the most effective therapy for medically intractable epilepsy, but it is not feasible in all patients. Vagus nerve stimulation (VNS) is an adjunctive neuromodulation therapy that was approved in 1997 for the alleviation of seizures; however, efforts to control epilepsy by stimulating the vagus nerve have been studied for over 100 years. Although its exact mechanism is still under investigation, VNS is thought to affect various brain areas. Hence, VNS has a wide indication for various intractable epileptic syndromes and epilepsy-related comorbidities. Moreover, recent studies have shown anti-inflammatory effects of VNS, and the indication is expanding beyond epilepsy to rheumatoid arthritis, chronic headaches, and depression. VNS yields a more than 50% reduction in seizures in approximately 60% of recipients, with an increase in reduction rates as the follow-up duration increases. The complication rate of VNS is 3–6%, and infection is the most important complication to consider. However, revision surgery was reported to be feasible and safe with appropriate measures. Recently, noninvasive VNS (nVNS) has been introduced, which can be performed transcutaneously without implantation surgery. Although more clinical trials are being conducted, nVNS can reduce the risk of infection and subsequent device failure. In conclusion, VNS has been demonstrated to be beneficial and effective in the treatment of epilepsy and various diseases, and more development is expected in the future.

Epilepsy Surgery in 2019: A Time to Change

Epilepsy has been known to humankind since antiquity. The surgical treatment of epilepsy began in the early days of neurosurgery and has developed greatly. Many surgical procedures have stood the test of time. However, clinicians treating epilepsy patients are now witnessing a huge tide of change. In 2017, the classification system for seizure and epilepsy types was revised nearly 36 years after the previous scheme was released. The actual difference between these systems may not be large, but there have been many conceptual changes, and clinicians must bid farewell to old terminology. Paradigms in drug discovery are changing, and novel antiseizure drugs have been introduced for clinical use. In particular, drugs that target genetic changes harbor greater therapeutic potential than previous screening-based compounds. The concept of focal epilepsy has been challenged, and now epilepsy is regarded as a network disorder. With this novel concept, stereotactic electroencephalography (SEEG) is becoming increasingly popular for the evaluation of dysfunctioning neuronal networks. Minimally invasive ablative therapies using SEEG electrodes and neuromodulatory therapies such as deep brain stimulation and vagus nerve stimulation are widely applied to remedy dysfunctional epilepsy networks. The use of responsive neurostimulation is currently off-label in children with intractable epilepsy.

Neuroimmune interactions and kidney disease

The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.

Epilepsy Surgery in 2019: A Time to Change

Epilepsy has been known to humankind since antiquity. The surgical treatment of epilepsy began in the early days of neurosurgery and has developed greatly. Many surgical procedures have stood the test of time. However, clinicians treating epilepsy patients are now witnessing a huge tide of change. In 2017, the classification system for seizure and epilepsy types was revised nearly 36 years after the previous scheme was released. The actual difference between these systems may not be large, but there have been many conceptual changes, and clinicians must bid farewell to old terminology. Paradigms in drug discovery are changing, and novel antiseizure drugs have been introduced for clinical use. In particular, drugs that target genetic changes harbor greater therapeutic potential than previous screening-based compounds. The concept of focal epilepsy has been challenged, and now epilepsy is regarded as a network disorder. With this novel concept, stereotactic electroencephalography (SEEG) is becoming increasingly popular for the evaluation of dysfunctioning neuronal networks. Minimally invasive ablative therapies using SEEG electrodes and neuromodulatory therapies such as deep brain stimulation and vagus nerve stimulation are widely applied to remedy dysfunctional epilepsy networks. The use of responsive neurostimulation is currently off-label in children with intractable epilepsy.

The Present and Future of Vagus Nerve Stimulation

Epilepsy is one of the major chronic neurological diseases affecting many patients. Resection surgery is the most effective therapy for medically intractable epilepsy, but it is not feasible in all patients. Vagus nerve stimulation (VNS) is an adjunctive neuromodulation therapy that was approved in 1997 for the alleviation of seizures; however, efforts to control epilepsy by stimulating the vagus nerve have been studied for over 100 years. Although its exact mechanism is still under investigation, VNS is thought to affect various brain areas. Hence, VNS has a wide indication for various intractable epileptic syndromes and epilepsy-related comorbidities. Moreover, recent studies have shown anti-inflammatory effects of VNS, and the indication is expanding beyond epilepsy to rheumatoid arthritis, chronic headaches, and depression. VNS yields a more than 50% reduction in seizures in approximately 60% of recipients, with an increase in reduction rates as the follow-up duration increases. The complication rate of VNS is 3–6%, and infection is the most important complication to consider. However, revision surgery was reported to be feasible and safe with appropriate measures. Recently, noninvasive VNS (nVNS) has been introduced, which can be performed transcutaneously without implantation surgery. Although more clinical trials are being conducted, nVNS can reduce the risk of infection and subsequent device failure. In conclusion, VNS has been demonstrated to be beneficial and effective in the treatment of epilepsy and various diseases, and more development is expected in the future.

Video Caso Clínico: Estimulación Vagal Directa Como Maniobra Electrofisiológica Alternativa en el Diagnóstico de Taquicardia Durante Estudio Electrofisiológico / Case Report: Direct Vagal Stimulation as Alternative Electrophysiological Procedure in the Diagnosis of Tachycardias During Electrophysiological Study

INTRODUCCIÓN: El síndrome de Wolff Parkinson White se caracteriza por la conexión anómala entre la aurícula y el ventrículo durante el paso del estímulo sinusal, generalmente causada por una vía accesoria que conecta el músculo auricular con el músculo ventricular llamado haz de Kent, caracterizándose por la presencia de síntomas como: palpitaciones, sincope o muerte súbita y sumado a la presencia de onda delta, intervalo PR corto, QRS ancho y alteraciones de la repolarización ventricular en el electrocardiograma. El estudio electrofisiológico tiene como objetivo confirmar la presencia, localización y características de este haz anómalo y posteriormente, con seguridad, proceder a la ablación por radiofrecuencia eliminando esta vía accesoria, siendo considerado un procedimiento curativo en el caso del síndrome de Wolff Parkinson White. Durante el estudio se realiza estimulaciones eléctricas en los sitios específicos, tanto de la aurícula como del ventrículo, además se utiliza medicación intravenosa como la adenosina que actúa bloqueando al nódulo aurículoventricular y así observar el paso residual de la estimulación sinusal normal y/o el paso retrogrado del estímulo ventricular hacia la aurícula a través del haz de Kent, permitiendo de esta forma analizar las características de las conexiones aurículoventriculares previo a la ablación. La posibilidad de realizar una estimulación vagal selectiva de alta frecuencia y baja amplitud a nivel infraorbitario, descrita por Pachón et al [1], a través de la vena yugular interna y el consecuente bloqueo aurículoventricular transitorio que esta ocasiona, permite realizar el estudio sin necesidad de utilizar otras maniobras electrofisiológicas o medicación endovenosa

BACKGROUND: Wolff Parkinson White Syndrome is characterized by the bypass of the electrical signal through an abnormal pathway, different from the atrioventricular node that connects the atrial and ventricular muscles (Bundle of Kent). It presents with palpitations, syncope or can even cause sudden death. Electrocardiogram findings consist on Delta waves, shortened PR interval, widened QRS complex and altering of the ventricular repolarization. In the presence of Ventricular pre-excitation (Wolff Parkinson White Syndrome), the electrophysiological testing is key to confirm the presence, site and features of this accessory pathway. Later, with the certainty of the diagnosis proceed to perform the Radiofrequency Ablation, the definitive treatment to eliminate this abnormal pathway. This test is usually done with the use of electrophysiological maneuvers, stimulating key sites in the atria and the ventricle, with the help of intravenous drugs like Adenosine. The objective is to block the AV node to look how the remnants of the normal electrical signal move through the abnormal pathway, thus letting the physician analyze the characteristics previously mentioned of this pathway. After the ablation, these maneuvers are repeated to confirm the complete elimination of the accessory pathway that has direct relation with the prognostic. Based on the possibility of high frequency and low amplitude selective vagal stimulation described by Pachón et al [1], at infraorbital level through the internal jugular vein and the resulting transitory atrioventricular block. It is possible to study the abnormal pathway without the need of electrophysiological maneuvers or the use of IV drugs, either pre or post ablation.

The role of vagus nerve stimulation in refractory epilepsy / O papel da estimulação do nervo vago na epilepsia refratária

ABSTRACT Vagus nerve stimulation is an adjunctive therapy used to treat patients with refractory epilepsy who are not candidates for resective surgery or had poor results after surgical procedures. Its mechanism of action is not yet fully comprehended but it possibly involves modulation of the locus coeruleus, thalamus and limbic circuit through noradrenergic and serotonergic projections. There is sufficient evidence to support its use in patients with focal epilepsy and other seizure types. However, it should be recognized that improvement is not immediate and increases over time. The majority of adverse events is stimulation-related, temporary and decreases after adjustment of settings. Future perspectives to improve efficacy and reduce side effects, such as different approaches to increase battery life, transcutaneous stimulation and identification of prognostic factors, should be further investigated.

RESUMO A estimulação vagal é uma terapia paliativa utilizada no tratamento de pacientes com epilepsia refratária que não são candidatos à cirurgia ressectiva ou naqueles com evolução insatisfatória após o procedimento cirúrgico. Seu mecanismo de ação ainda não foi completamente elucidado mas possivelmente envolve a modulação do locus coeruleus, tálamo e circuito límbico através de projeções noradrenérgicas e serotoninérgicas. Atualmente há evidência suficiente para corroborar o uso desta terapia em pacientes com epilepsia focal e outros tipos de crise, com resultados que, apesar de não imediatos, melhoram progressivamente no longo prazo. Os eventos adversos são, em sua maioria, relacionados à estimulação e auto-limitados. Perspectivas futuras para aumentar a eficácia e reduzir os efeitos colaterais como a utilização de baterias com maior durabilidade, estimulação transcutânea e identificação de fatores prognósticos devem ser investigadas.