Delayed vagal nerve compressive neuropathy following placement of vagal nerve stimulator: case report.

Vagal neuropathy causing vocal fold palsy is an uncommon complication of vagal nerve stimulator (VNS) placement. It may be associated with intraoperative nerve injury or with device stimulation. Here we present the first case of delayed, compressive vagal neuropathy associated with VNS coil placement which presented with progressive hoarseness and vocal cord paralysis. Coil removal and vagal neurolysis was performed to relieve the compression. Larger 3 mm VNS coils were placed for continuation of therapy. Coils with a larger inner diameter should be employed where possible to prevent this complication. The frequency of VNS-associated vagal nerve compression may warrant further investigation.

Neuromodulation for the treatment of Prader-Willi syndrome - A systematic review.

Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field.

Feasibility study of microburst VNS therapy in drug-resistant focal and generalized epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. OBJECTIVE: To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called "Microburst VNS" (µVNS). µVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. METHODS: Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of µVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. RESULTS: The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of µVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). CONCLUSION: Overall, µVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.

Wireless optoelectronic devices for vagus nerve stimulation in mice.

Objective.Vagus nerve stimulation (VNS) is a promising approach for the treatment of a wide variety of debilitating conditions, including autoimmune diseases and intractable epilepsy. Much remains to be learned about the molecular mechanisms involved in vagus nerve regulation of organ function. Despite an abundance of well-characterized rodent models of common chronic diseases, currently available technologies are rarely suitable for the required long-term experiments in freely moving animals, particularly experimental mice. Due to challenging anatomical limitations, many relevant experiments require miniaturized, less invasive, and wireless devices for precise stimulation of the vagus nerve and other peripheral nerves of interest. Our objective is to outline possible solutions to this problem by using nongenetic light-based stimulation.Approach.We describe how to design and benchmark new microstimulation devices that are based on transcutaneous photovoltaic stimulation. The approach is to use wired multielectrode cuffs to test different stimulation patterns, and then build photovoltaic stimulators to generate the most optimal patterns. We validate stimulation through heart rate analysis.Main results.A range of different stimulation geometries are explored with large differences in performance. Two types of photovoltaic devices are fabricated to deliver stimulation: photocapacitors and photovoltaic flags. The former is simple and more compact, but has limited efficiency. The photovoltaic flag approach is more elaborate, but highly efficient. Both can be used for wireless actuation of the vagus nerve using light impulses.Significance.These approaches can enable studies in small animals that were previously challenging, such as long-termin vivostudies for mapping functional vagus nerve innervation. This new knowledge may have potential to support clinical translation of VNS for treatment of select inflammatory and neurologic diseases.

Estimulación del nervio vago para epilepsia resistente / Vagus nerve stimulation for resistant epilepsy

CONTEXTO: La epilepsia constituye un trastorno neurológico crónico caracterizado por la afectación paroxística y repetida de la actividad eléctrica cerebral. Se estima que el 1% de la población general presenta epilepsia, y que aproximadamente el 70% de estos pacientes permanecen sin convulsiones utilizando solamente medicación antiepiléptica.La epilepsia resistente (ER), previamente llamada refractaria, afecta aproximadamente a una cuarta parte de los pacientes con epilepsia. La Liga internacional contra la Epilepsia (ILAE, su sigla del inglês International League Against Epilepsy) la define como aquella en la cual se ha producido el fracasso a dos fármacos antiepilépticos (FAE), en monoterapia o en combinación, tolerados, apropriadamente elegidos y empleados de forma adecuada, para conseguir la "ausencia mantenida de crisis". Se considera ausencia mantenida de crisis un periodo de un año o, en caso de crisis muy esporádicas, un periodo de al menos el triple al mayor intervalo intercrisis pre tratamiento, escogiéndose el que sea mayor de ellos.3 Como consecuencia del mal control de las crisis, pacientes con ER tienen aumentado el riesgo de muerte prematura, traumatismos y/o alteraciones psicosociales, así como una calidad de vida reducida. Aunque la epilepsia refractaria pudiera remitir temporalmente em aproximadamente un 4% de los casos, la reaparición de las crisis epilépticas es frecuente. TECNOLOGÍA: El estimulador del nervio vago (ENV) es un dispositivo, similar a un marcapasos, que se implanta debajo de la piel del tórax alrededor del nervio vago emitiendo de forma periódica un estímulo y asciende siguiendo el trayecto de susfibras aferentes. El nervio vago tiene un 80 % de fibras aferentes que proyectan hacia el tronco cerebral y el encéfalo, con múltiples conexiones corticales. El otro 20 % son fibras eferentes e inervan, entre otras, a la musculatura de laringe y faringe, lo que condiciona la mayoría de efectossecundarios. El ENV se implanta en el nervio vago izquierdo para evitar la mayor influencia del vago derecho sobre el ritmo cardiaco. Al programar el dispositivo, se puede variar la frecuencia, intensidad y duración de la estimulación, permitiendo además inducir una estimulación extra con el imán externo aplicándolo sobre el generador. La batería tiene una duración aproximada entre 3 a 8 años y se puede reemplazar con anestesia local. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de estimulación del nervio vago para pacientes con epilepsia resistente al tratamiento farmacológico no plausible de tratamento quirúrgico. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron una RS, dos ECAs, un estudio de cohorte, cuatro GPC, tres evaluaciones económicas, y 13 informes de políticas de cobertura de tecnología para indicación. CONCLUSIONES: Evidencia de alta calidad muestra que la estimulación del nervio vago produce un beneficio neto mayor porque reduce en más del 50% la cantidad de crisis epilépticas en aproximadamente la mitad de los adultos y niños con epilepsia resistente. Asimismo, mejora la puntuación en la escala de depresión. La estimulación del nervio vago puede reducir también la tasa de muerte súbita inesperada en la epilepsia. No se reportaron efectos adversos graves. Las guías de práctica clínica reveladas recomiendan la estimulación del nervio vago para adultos y niños con epilepsia resistente que no tienen indicación de resección quirúrgica. La mayoría de los financiadores relevados brindan cobertura a esta tecnología y en Argentina es plausible de reintegro en mayores de 12 años. Las evaluaciones económicas relevadas indican que es una tecnología costo efectiva, pero depende del umbral de cada país para su incorporación. No se encontraron estudios locales de costo-efectividad, por lo que esta dimensión al momento es incierta.

Vagal Nerve Stimulator Placement by a Vascular Surgeon.

BACKGROUND: Refractory seizure activity represents a difficult problem for both patients and practitioners. Implantation of the vagal nerve stimulator has been posited as an effective treatment for refractory seizure activity. These devices are inserted by placing leads into the carotid sheath along the vagus nerve. We evaluated a vascular surgeon's experience placing vagal nerve stimulators. METHODS: We examined all patients treated with placement of vagal nerve stimulator by a single surgeon from October 2016 to October 2018. Data collected included demographics, medical and surgical history, intraoperative variables, and complications. RESULTS: Thirty-four patients underwent placement of a vagal nerve stimulator. About 29.4% had a previous vagal nerve stimulator placed on the ipsilateral side. Intraoperative bradycardia was seen in 1 patient. Postoperative complications were identified in 5 patients, all of which were transient dysphagia or changes in voice quality which did not require intervention. There was no significant difference between patients with the previous operation and those without for developing postoperative complications (P = .138). Average blood loss was higher in patients who had undergone previous stimulator placement than those who had not (P = .0223), and the operative time was longer (P ≤ .0001). DISCUSSION: Given the anatomical location of placement, vascular surgeons may be called upon to place these devices. In our single surgeon series, we found that the placement was safe, with minimal complications. Intraoperatively, this case appears to be more difficult (with higher blood loss and longer operative time) in patients who have had previous device placement, but this does not appear to lead to increased complications.

Vagal nerve stimulation as a possible non-invasive treatment for chronic widespread pain in Gulf Veterans with Gulf War Illness.

AIMS: Widespread pain and headache are common in Gulf War Illness with suboptimal treatments available. We tested the efficacy of non-invasive, transcutaneous vagal nerve stimulation (nVNS) for relief of widespread pain and migraine in Gulf War Veterans with GWI. MAIN METHODS: A 10-week double-blind, randomized controlled trial of nVNS used the gammaCore (ElectroCore, Inc.) compared to sham stimulation with the same device followed by a 10-week open-label follow up with active nVNS. The primary outcome was a numerical pain rating at the end of the blinded period. Secondary outcomes included physical function, migraine frequency and severity, and impression of change during the blinded and open-label periods. Two-factor MANOVA models tested for significant differences between groups from baseline to end of the blinded period and during the open-label period. KEY FINDINGS: Among 27 participants enrolled and issued a nVNS device, there was a slight improvement in pain ratings from baseline to the end of the blinded phase [6.18 (±0.82) vs. 5.05 (±2.3); p = 0.040] which did not differ between active and sham nVNS. Physical function was also slightly improved overall without group differences. There were no significant changes in migraine frequency or severity during the blinded period. Twenty participants started in the open-label phase; no statistically significant changes in pain, physical function, migraine measures, or impression of change were noted during this phase. SIGNIFICANCE: Veterans with GWI actively treated with nVNS reported no improvement in either widespread pain or migraine frequency or severity relative to Veterans with GWI who received sham nVNS.

Technology-Dependent Children.

There are a growing number of medically complex children with implanted devices. Emergency physicians with a basic knowledge of these devices can troubleshoot and fix many of the issues that may arise. Recognition of malfunction of these devices can reduce morbidity and mortality among this special population. In this article, we review common issues that may arise in children with gastrostomy tubes, central nervous system shunts, cochlear implants, and vagal nerve stimulators.

The feasibility of vagal nerve stimulation revision surgery and surgical techniques: a retrospective review.

BACKGROUND: With the large number of VNS implants performed worldwide, the need for removal or replacement of the device in selected cases is emerging, this removal or replacement of VNS can be challenging. AIMS/OBJECTIVE: To describe the feasibility and safety of revising vagal nerve stimulation surgery in terms of the indications, surgical techniques, and outcomes. MATERIALS AND METHODS: A retrospective study, a series of eight cases with VNS implants that needed revision surgery have been reviewed, four devices were completely removed and four were only revised. The revision surgery was performed after a range of 7 months to 6 years, due to different reasons. Initial surgeries and revisions were performed at the otolaryngology department in a major tertiary center. CONCLUSIONS AND SIGNIFICANCE: We concluded that the previously implanted vagal nerve stimulation electrodes can be completely removed without any significant sequelae on the nerve. It may also be re-implanted safely at the previously used segment of the vagus nerve with a similar outcome in seizure control as the initial implantation.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.

Development and characterization of a chronic implant mouse model for vagus nerve stimulation.

Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies. The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus. However, there are several unanswered mechanistic questions about the effects of chronic VNS, which require solving numerous technical challenges for a long-term interface with the vagus in mice. Here, we describe a scalable model for long-term VNS in mice developed and validated in four research laboratories. We observed significant heart rate responses for at least 4 weeks in 60-90% of animals. Device implantation did not impair vagus-mediated reflexes. VNS using this implant significantly suppressed TNF levels in endotoxemia. Histological examination of implanted nerves revealed fibrotic encapsulation without axonal pathology. This model may be useful to study the physiology of the vagus and provides a tool to systematically investigate long-term VNS as therapy for chronic diseases modeled in mice.

High lead impedances requiring revision during vagal nerve stimulator generator replacement.

OBJECTIVE: Vagal nerve stimulation (VNS) therapy is among the growing options in the treatment of intractable epilepsy. The phenomenon of surprise lead impedance issues found at the time of surgery resulting in unplanned lead revision is a challenge with this type of device. We reviewed our experience with VNS revisions. MATERIAL AND METHODS: We retrospectively reviewed the records of all adult and pediatric patients between January 2009 and September 2018 who underwent surgery for VNS therapy, including revision surgery. Office and operative notes were reviewed to obtain the indications and operative details for VNS placement. RESULTS: A total of 570 operations were reviewed. The indication was intractable epilepsy in all cases. Primary implantation was performed in 232 patients, while the remaining 338 cases were revision cases of various natures. Surprise high lead impedance was found in 10 (3%) of these cases, resulting in a significantly increased complexity of surgery in those instances. CONCLUSION: Lead impedance issues can be caused by disconnection, electrode fracture, hardware failure, or tissue scarring but ultimately require a more extended surgery than may be initially planned. Anticipating the potential for a more extensive operation than a simple generator replacement may prevent perioperative frustrations on both sides.

Noninvasive vagal nerve stimulation for gastroenterology pain disorders.

Abdominal pain continues to be a major challenge and unmet need in clinical practice. Normalization of bidirectional gut-brain signaling has generated much interest as a therapeutic approach to treat chronic abdominal pain. Vagal nerve stimulation (VNS) is emerging as a potential non-pharmacologic strategy for the treatment of abdominal pain. In this review paper, we will summarize the etiologies of chronic pain in gastrointestinal disorders and discuss the rational for VNS as a therapeutic approach to chronic abdominal pain, with particular emphasis in the gammaCore stimulator which allows for noninvasive VNS.

Salvage therapy for vagal nerve stimulator infection; Literature review and report of a delayed recurrence.

BACKGROUND: Vagal Nerve Stimulation (VNS) is one of the most common neuro-modulation based approaches for the treatment of medically intractable epilepsy. Despite advances in technology and surgical techniques, hardware infection remains a recognized and feared complication in VNS placement. Management of such infections is scarce in the literature with the majority of data available in case reports. It ranges from immediate removal of the VNS device to conservative treatment with antibiotics in an attempt to salvage the device, particularly in patients who demonstrated significant improvement in seizure frequency and quality of life. METHODS: We performed a review of the literature in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify reported cases of salvaged VNS infection. A literature search for relevant English articles was conducted using Medline. References of relevant articles were also reviewed. Articles that comprised an attempt to salvage an infected VNS were included. RESULTS: We obtained 12 articles describing an attempt to salvage an infected VNS. Out of a total of 62 reported VNS infections and 43 salvage attempts using a variety of antibiotic-based approaches, 17 cases were successfully salvaged and 26 cases failed the salvage attempt and had to be explanted eventually. Moreover, we report a case of an 18-year-old male with Lennox-Gastaut syndrome who presented21 days after VNS placement with a MRSA deep tissue infection. An attempt was made to treat the infection with long-term culture-based intravenous antibiotics, but it recurred three years later with neck wound dehiscence and positive wound culture for the same organism, and ex-plantation was thus performed. CONCLUSION: The management of VNS infections remains a dilemma for neurosurgeons. Although the idea of salvaging an infected VNS seems appealing, hardware removal seems to be inevitable despite adequate antibiotic treatment.

Transcutaneous auricular vagus nerve stimulation enhances learning of novel letter-sound relationships in adults.

BACKGROUND: Reading is a critical skill in modern society but is significantly more difficult to acquire during adulthood. Many adults are required to learn a new orthography after this window closes for personal or vocational reasons and while many programs and training methods exist for learning to read in adulthood, none result in native-like fluency. Implantable cervical vagus nerve stimulation is capable of driving neural plasticity but is invasive and not practical as a reading intervention. OBJECTIVE: The goal of the current study was to evaluate whether non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) is effective at enhancing novel orthography acquisition in young adults. METHODS: We enrolled 37 typically developing participants and randomly assigned them to a computer control, device sham control, earlobe stimulation control, or experimental transcutaneous auricular stimulation (taVNS) group. Participants then learned novel letter-sound correspondences in Hebrew over five training lessons. Performance was assessed using three measures to evaluate various aspects of reading: Letter ID, Automaticity, and Decoding. RESULTS: The taVNS group significantly outperformed the three control groups on both the Automaticity and Decoding tasks. There was no difference on the Letter ID task. CONCLUSIONS: These results demonstrate, for the first time, that taVNS is capable of improving aspects of reading acquisition in adults. These findings have potential implications for a wide range of cognitive tasks.

Eficacia y seguridad del dispositivo estimulador del nervio vago para pacientes con epilepsia refractaria multifocal candidatos a cirugía de epilepsia / Efficacy and safety of the vagus nerve stimulator device for patients with multifocal refractory epilepsy candidates for surgery. epilepsy

INTRODUCCIÓN: Este documento técnico se realiza a solicitud del Instituto Nacional de Ciencias Neurológicas. a. Cuadro clínico La epilepsia es una de las principales enfermedades neurológicas crónicas y no transmisibles, que consiste en una alteración de la función de las neuronas de la corteza cerebral. Epilepsia refractaria (ER) es aquella con fracaso a dos fármacos antiepilépticos, en monoterapia o combinación, tolerados, apropiadamente elegidos y empleados para conseguir la ausencia mantenida de crisis epilépticas. La cirugía resectiva de epilepsia, es la mejor alternativa para lograr la ausencia de crisis hasta en 80% de pacientes con epilepsia temporal farmacorresistente. Sin embargo, existen nuevas opciones de manejo como la neuroestimulación donde se encuentra la técnica de estimulación del nervio vago (ENV). b. Tecnología sanitaria La estimulación del nervio vago (ENV) es un procedimiento en el que se realiza una incisión en el lado izquierdo del cuello y se encuentra al nervio entre la arteria carótida común y la vena yugular interna, donde se ancla el dispositivo helicoidal y se posicionan los electrodos, los cuales deben colocarse en la zona inferior a las ramas cardiacas del nervio vago para evitar los efectos adversos cardiovasculares. Los mecanismos por los cuales la ENV causa cambios neuroquímicos y previene las convulsiones aún no son del todo conocidos, aunque la evidencia sugiere que el nervio vago juega un rol en las convulsiones, en las regiones susceptibles a alta excitabilidad. Estas regiones incluyen al Sistema límbico, el tálamo, las proyecciones tálamo-cortical. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura del dispositivo estimulador del nervio vago para pacientes con epilepsia refractaria multifocal candidatos a cirugía de epilepsia. METODOLOGÍA Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE, LILACS, COCHRANE, así como en buscadores genéricos de Internet incluyendo Google Scholar y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales de neurología, y agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS Se seleccionaron una revisión panorámica, una revisión sistemática de estudios observacionales, siete GPC y cinco ETS. No se encontraron evaluaciones económicas de la región. Una RS panorámica (2018) evaluó las opciones de neuroestimulación para ER. En al que se incluyeron 9 RS, 31 estudios prospectivos y 17 estudios de registro cuya búsqueda culminó en diciembre del 2017. Para los objetivos del presente documento, se describirán solamente los estudios concernientes a la ENV. En la evaluación de eficacia se toma en cuenta un metaanálisis (3 ECAs en adultos, 1 ECA en niños). En la población adulta, se encontró que los pacientes tratados con ENV (dosis terapéutica) lograron al menos un 50% de reducción en la frecuencia de convulsiones que los pacientes tratados con dosis sub-terapéutica odds ratio (OR) de 1.95 [95% intervalo de confianza (IC): 1.16­3.27]. Otros 2 ECA revisados reportaron disminución significativa de la frecuencia de convulsiones en el grupo con dosis terapéutica, en comparación al grupo de dosis subterapéutica. En el grupo de niños no se pudo demostrar la efectividad de la ENV, con un estudio de baja calidad de evidencia. Otra RS incluida en este documento demostró una disminución del 50% de frecuencias de convulsiones a favor del uso de dosis terapéutica a comparación de dosis sub-terapéuticas OR de 1.73 (95% IC: 1.13­2.64). El mismo estudio evaluó la seguridad de ENV estimando el riesgo relativo (RR) de los eventos adversos en ambos grupos comparados; basado en 3 ECAs se encontraron un RR de 2.17 (99% IC: 1.47­3.17) para alteración de la voz o ronquera y un RR de 1.09 (99% IC: 0.74­ 1.62) para tos, ambos con moderada calidad de evidencia. Otros 2 ECA mostraron RR de 2.45 (99% IC: 1.07­5.60) para disnea y un RR de 1.01 (99% IC: 0.60­1.68) y 0.78 (99% CI: 0.39­1.53) para dolor y parestesias, respectivamente. Otro ECA incluido demostró un efecto no estadísticamente significativo para el grupo ENV en comparación al grupo con dosis sub-terapéuticas. Una RS (2019) incluyó 26 estudios (reportes de casos y series de casos) con un total de 45 pacientes para evaluar la ENV en ER. La búsqueda incluyó estudios hasta el año 2019. El implante agudo de la ENV estuvo asociado con cese de estatus epiléptico refractario y super refractario en 74% (28/38) de los casos agudos, no hubo cese de episodio en 18% (7/38). En 3 casos, sólo los resultados a largo plazo se reportaron y la asociación entre implante agudo de ENV y cese del episodio no estuvo definido. Resultados positivos (cese de los episodios después del implante de ENV, sin reporte de muerte o reducción significativa: 50% en el tipo de convulsión más debilitante o desaparición de convulsiones/ no recurrencia) se reportaron en 82% (31/38) de los casos. La duración del estatus epiléptico refractario y super refractario pre y post colocación de ENV fue reportado en 34% (13/38) y 50% (19/38) de los casos respectivamente. La duración media de los episodios antes del implante de ENV fue 18 días (rango de 3-1680 días) y una duración media post implante de ENV de 8 días (3-84 días). No se reportaron eventos adversos en todos los estudios incluidos. Siete GPC (Colombia 2019, España 2016, Perú 2015) mencionan a la tecnología dentro de las opciones para manejo de ER sin mencionar una tecnología por sobre otra. Otras GPC (Perú 2016, Chile 2014, Reino Unido 2012) la mencionan como opción en ER como alternativa paliativa para pacientes no candidatos a cirugía. Una GPC (EEUU 2013) recomienda ENV como una opción de manejo de población pediátrica. Una ETS (EEUU 2020, Perú 2017, Canadá 2013 y Reino Unido 2011) recomiendan el uso de ENV para ER, considerándola dentro de sus políticas de cobertura. Otra ETS (Perú 2019) para población pediátrica menciona que la evidencia es escasa, pero recomienda el uso de ENV como una alternativa terapêutica. CONCLUSIONES: La evidencia con respecto a ENV para ER es abundante. Basado en ECAs y estudios observacionales se puede demostrar que la ENV disminuye la frecuencia de convulsiones comparado con dosis sub-terapeúticas y además demuestra adecuada seguridad. No se ha identificado ECAs que comparen a la tecnología con otra opción para el manejo de ER directamente. Los documentos de ETS y GPC identificados coinciden en recomendar la tecnología y considerarla dentro de sus políticas de cobertura para el manejo de ER ya sea en uso paliativo en población no candidata a cirugía o como otra opción de tratamiento en candidatos a cirugía.

Preparation of Peripheral Nerve Stimulation Electrodes for Chronic Implantation in Rats.

Peripheral nerve cuff electrodes have long been used in the neurosciences and related fields for stimulation of, for example, vagus or sciatic nerves. Several recent studies have demonstrated the effectiveness of chronic VNS in enhancing central nervous system plasticity to improve motor rehabilitation, extinction learning, and sensory discrimination. Construction of chronically implantable devices for use in such studies is challenging due to rats' small size, and typical protocols require extensive training of personnel and time-consuming microfabrication methods. Alternatively, commercially available implantable cuff electrodes can be purchased at a significantly higher cost. In this protocol, we present a simple, low-cost method for construction of small, chronically implantable peripheral nerve cuff electrodes for use in rats. We validate the short and long-term reliability of our cuff electrodes by demonstrating that VNS in ketamine/xylazine anesthetized rats produces decreases in breathing rate consistent with activation of the Hering-Breuer reflex, both at the time of implantation and up to 10 weeks after device implantation. We further demonstrate the suitability of the cuff electrodes for use in chronic stimulation studies by pairing VNS with skilled lever press performance to induce motor cortical map plasticity.

Vagus nerve stimulation with tachycardia detection provides additional seizure reduction compared to traditional vagus nerve stimulation.

PURPOSE: This study investigates the clinical and cost effectiveness of switching from traditional vagus nerve stimulation (VNS) to responsive VNS (rVNS), which has an additional ictal tachycardia detection and stimulation (AutoStim) mode. METHODS: Retrospective chart review was used to collect data from patients with medically refractory epilepsy who underwent generator replacements. Patients with confounding factors such as medication changes were excluded. Vagus nerve stimulation parameters, seizure frequency, and healthcare costs were collected for the 1-year period following generator replacement with the rVNS device. RESULTS: Documented seizure frequency was available for twenty-five patients. After implant with rVNS, 28% of patients had an additional ≥50% seizure reduction. There was a significant decrease in the average monthly seizure count (p = 0.039). In patients who were not already free of disabling seizures (n = 17), 41.2% had ≥50% additional seizure reduction. There was no difference in healthcare costs during the 1-year follow-up after the rVNS implant compared with one year prior. CONCLUSIONS: Ictal tachycardia detection and stimulation provided a significant clinical benefit in patients who were not free of disabling seizures with treatment from traditional VNS. There was no additional increase in healthcare costs during the first year after device replacement.

Bradyarrhythmia secondary to vagus nerve stimulator 7 years after placement.

We present a case of a 38-year-old man with a previous medical history of asthma and refractory epilepsy requiring vagal nerve stimulator (VNS) placement 7 years prior to the presentation who was found to be in atrial fibrillation with a rapid ventricular response during a preoperative evaluation, which prompted transoesophageal echocardiography and subsequent cardioversion. In preparation for cardioversion, the VNS was turned off and the patient was cardioverted to normal sinus rhythm. Following cardioversion, the VNS was activated again. During recovery, the patient was experiencing several episodes of first-degree and second-degree Mobitz type-II atrioventricular (AV) block. In response, the VNS was deactivated indefinitely. On interrogation of a loop recorder 2 weeks after discharge, the patient did not have any further evidence of AV conduction delay.

Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy.

BACKGROUND: For patients with generalized epilepsy who do not respond to antiseizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy-resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox-Gastaut Syndrome (LGS) and genetic generalized epilepsy (GGE). METHODS: We identified patients with a diagnosis of generalized epilepsy (including LGS and GGE), who underwent VNS implantation at the London Health Sciences Centre and Western University, London, Ontario, since this treatment became available in Canada in 1997 until July 2018. We assessed response to the treatment, including admissions to hospital and complications. RESULTS: A total of 46 patients were included in this study with a history of therapy-resistant generalized epilepsy. The mean age at implantation was 24 years (interquartile range [IQR] = 17.8-31 years), significantly younger in the LGS group (p = 0.02) and 50% (n = 23) were female. The most common etiologies were GGE in 37% (n = 17) and LGS in 63% (n = 29). Median follow-up since VNS implantation was 63 months (IQR: 31-112.8 months). Of the LGS group 41.7% (n = 12) of patients had an overall seizure reduction of 50% or more, and 64.7% (n = 11) in the GGE group without statistical significance between the groups. The best response in seizure reduction was seen in generalized tonic-clonic seizures, with a significant reduction in the GGE group (p = 0.043). There was a reduction of seizure-related hospital admissions from 91.3% (N = 42) preimplantation, to 43.5% (N = 20) postimplantation (p < 0.05). The frequency of side effects due to the stimulation was almost equal in both groups (62.1% in LGS and 64.7% in GGE). CONCLUSIONS: Vagus nerve stimulation should be considered as a treatment in patients with therapy-resistant generalized epilepsy, especially in cases with GGE.