Receiving Vagus Nerve Stimulation Therapy Research Articles

Complications and Mortality Rate of Vagus Nerve Stimulation for Drug-Resistant Epilepsy.

The goal of this study is to evaluate the complications and mortality associated with vagus nerve stimulation (VNS). We retrospectively reviewed medical records of patients who underwent VNS implantation for the treatment of drug-resistant epilepsy (DRE) between 2000 and 2023. The mean follow-up time was 10.6 years, ranging from three months to 22 years. In total, 55 adult and pediatric patients received VNS therapy with 117 procedures performed over 23 years. The most common early complications were hoarseness and cough which were reported in eight adult patients (6.8%). Four children with intellectual disability (ID) had infection (3.4%), eight patients had lead breakage (6.8%), and two had device migration (1.7%). Fourof all patients (7.3%) demonstrated late complications due to chronic nerve stimulation including vocal cord dysfunction, late-onset severe AV block, and obstructive sleep apnea (OSA). Three patients (5.5%) had VNS deactivated permanently due to complications and/or lack of efficacy. Two patients died from probable sudden unexpected death in epilepsy (SUDEP) with an incidence of 3.4/1000 person-years. VNS therapy is safe over long-term follow-up but not without risks. Most post-operative complications are minor and transient for adults. Children with ID tend to have infection and device migration. Late-onset cardiac complications and OSA can develop in some patients during VNS therapy and should not be overlooked. The SUDEP rate may decrease with VNS therapy over time.

Effective Delivery of Vagus Nerve Stimulation Requires Many Stimulations Per Session and Many Sessions Per Week Over Many Weeks to Improve Recovery of Somatosensation.

Chronic sensory loss is a common and undertreated consequence of many forms of neurological injury. Emerging evidence indicates that vagus nerve stimulation (VNS) delivered during tactile rehabilitation promotes recovery of somatosensation. Here, we characterize the amount, intensity, frequency, and duration of VNS therapy paradigms to determine the optimal dosage for VNS-dependent enhancement of recovery in a model of peripheral nerve injury (PNI). Rats underwent transection of the medial and ulnar nerves in the forelimb, resulting in chronic sensory loss in the paw. Eight weeks after injury, rats were implanted with a VNS cuff and received tactile rehabilitation sessions consisting of repeated mechanical stimulation of the previously denervated forepaw paired with short bursts of VNS. Rats received VNS therapy in 1 of 6 systematically varied dosing schedules to identify a paradigm that balanced therapy effectiveness with a shorter regimen. Delivering 200 VNS pairings a day 4 days a week for 4 weeks produced the greatest percent improvement in somatosensory function compared to any of the 6 other groups (One Way analysis of variance at the end of therapy, F[4 70] P = .005). Our findings demonstrate that an effective VNS therapy dosage delivers many stimulations per session, with many sessions per week, over many weeks. These results provide a framework to inform the development of VNS-based therapies for sensory restoration.

Sleep disordered breathing in children receiving vagus nerve stimulation therapy

ObjectiveThe effects of vagus nerve stimulation (VNS) on sleep disordered breathing (SDB) have been reported in limited case series. Detailed studies, particularly in the pediatric population, have not been performed. The primary purpose of this study is to describe clinical characteristics, polysomnographic findings, and management of children treated with VNS. MethodsA retrospective review of medical records and polysomnography data was performed in patients ages 0–20 years old receiving VNS therapy for refractory epilepsy at Cincinnati Children's Hospital Medical Center. Results22 subjects met the inclusion criteria. 50% were male. The mean age at the time of VNS insertion was 8.4 ± 4.0 years. The mean age at the first PSG was 10.6 ± 4.3 years. Common presentations to sleep clinics included snoring (77.3%), frequent nighttime awakening (68.1%), and parasomnias (63.6%). The median apnea-hypopnea index (AHI) was 4.5/hr (IQR 3.0–13.1) and the median obstructive index (OI) was 4.1/hr (1.5–12.8). Obstructive sleep apnea (OSA) was diagnosed after VNS insertion in 19 patients (86.4%), 8 of which (36.3%) had severe OSA. Six patients (27.3%) had significant hypoventilation. For management, 6 patients (27.2%) were treated with bilevel PAP, 3 patients (13.6%) with CPAP, 2 patients (9.1%) with ventilator, 4 patients (18.2%) with upper airway surgeries, and 9 patients (40.9%) received medications only. ConclusionsSDB is common in pediatric patients with medically refractory epilepsy managed with VNS who were referred to sleep medicine clinics. Both OSA and nocturnal alveolar hypoventilation are relatively common in this population. Management of SDB often involves the use of positive airway pressure therapy or upper airway surgeries. Further studies are needed to assess the prevalence, risk factors, and the effect of treatments on epilepsy control. This study highlights the need for screening of SDB prior to and following VNS implantation.

Long‐term surveillance of SUDEP in drug‐resistant epilepsy patients treated with VNS therapy

Limited data are available regarding the evolution over time of the rate of sudden unexpected death in epilepsy patients (SUDEP) in drug-resistant epilepsy. The objective is to analyze a database of 40443patients with epilepsy implanted with vagus nerve stimulation (VNS) therapy in the United States (from 1988 to 2012) and assess whether SUDEP rates decrease during the postimplantation follow-up period. Patient vital status was ascertained using the Centers for Disease Control and Prevention's National Death Index (NDI). An expert panel adjudicated classification of cause of deaths as SUDEP based on NDI data and available narrative descriptions of deaths. We tested the hypothesis that SUDEP rates decrease with time using the Mann-Kendall nonparametric trend test and by comparing SUDEP rates of the first 2years of follow-up (years1-2) to longer follow-up (years3-10). Our cohort included 277661 person-years of follow-up and 3689deaths, including 632 SUDEP. Primary analysis demonstrated a significant decrease in age-adjusted SUDEP rate during follow-up (S=-27 P=.008), with rates of 2.47/1000 for years 1-2 and 1.68/1000 for years 3-10 (rate ratio 0.68; 95% confidence interval [CI] 0.53-0.87; P=.002). Sensitivity analyses confirm these findings. Our data suggest that SUDEP risk significantly decreases during long-term follow-up of patients with refractory epilepsy receiving VNS Therapy. This finding might reflect several factors, including the natural long-term dynamic of SUDEP rate, attrition, and the impact of VNS Therapy. The role of each of these factors cannot be confirmed due to the limitations of the study.

Theoretical Basis of Vagus Nerve Stimulation.

Despite a myriad of medical and surgical treatments for epilepsy developed over the past few decades, a large subset of patients remains refractory to treatment. Over this time period, vagus nerve stimulation (VNS) has become an accepted and viable treatment modality for this population. Since the earliest report of VNS implantation in 1988, tens of thousands of patients worldwide have received VNS therapy, and >100,000 patient-years of experience have been accrued. The mechanisms underlying the response to VNS therapy continue to be elucidated. As understanding of the VNS mechanisms of action continues to grow, more pathologies will arise as potential treatment indications. Furthermore, current treatment populations with refractory epilepsy, depression, and inflammatory diseases may enjoy improved response to stimulation.

Vagus nerve stimulation therapy in patients with autism spectrum disorder and intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry

The purpose of this study was to determine the effectiveness of vagus nerve stimulation (VNS) therapy on quality-of-life (QOL) variables among patients with both autism spectrum disorder (ASD) and persistent or recurrent intractable epilepsy. Data were obtained from the VNS therapy patient outcome registry, which was established after US FDA approval of the VNS device in 1997 as a means of capturing open-label clinical data outside of protocol. The integrity of the systems for collecting and processing registry data was authenticated by an independent auditing agency. The effect of potential selection bias, however, remains uncertain. Two cohorts were compared: 1) patients with epilepsy but without ASD (non-ASD [NASD] Group, 315 patients) who were being tracked in the registry (this cohort, which was controlled for age, included patients 20 years of age or younger); and 2) patients with a diagnosis of ASD who underwent implantation of the VNS device (ASD Group, 77 patients). Differences between the ASD and NASD groups were noted in the following categories: sex (male preponderance in ASD); normal imaging results (MR imaging results normal in ASD); depression (less common in ASD); behavioral problems (more common in ASD); neurological deficit (more common in ASD); mental retardation (more common in ASD); and developmental delay. The only QOL difference between the ASD and NASD groups was noted in mood at 12 months postimplant (mood was improved in ASD) (p = 0.04). There were no other differences in the QOL variables. Patients with ASD and intractable epilepsy respond as favorably as all other patients receiving VNS therapy. In addition, they may experience a number of QOL improvements, some of which exceed those classically observed following placement of a VNS device.

Vagus Nerve Stimulation Therapy Induces Changes in Heart Rate of Children during Sleep

This study analyzed changes in the heart rates of children receiving vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. Changes in the heart rates of ten children receiving VNS therapy for pharmacoresistant epilepsy were evaluated with polysomnographic recordings, including electrocardiogram (ECG), EEG, thoraco-abdominal distension, nasal airflow, and VNS artifacts. Measurements during stimulation were compared with those at baseline for each patient. While the VNS therapy pulse generator was delivering stimulation, the heart rates of four children increased significantly (p < 0.01), decreased for one child, and increased at the end of the stimulation for one child. The heart rates of four children did not change. Changes in heart rate varied during VNS, within stimulation cycles for individual children and from one child to another. Changes in heart rate differed between rapid eye movement (REM) and non-REM (NREM) sleep states. Respiratory changes (increases in frequency and decreases in amplitude) were concomitant with the changes in heart rate. In this case series of children with pharmacoresistant epilepsy, cardiorespiratory variations occurred while the VNS therapy pulse generator was delivering stimulation. Understanding these variations may allow further optimization of VNS parameters.

Pregnancy and delivery while receiving vagus nerve stimulation for the treatment of major depression: a case report

BackgroundDepression during pregnancy can have significant health consequences for the mother and her infant. Antidepressant medications, which pass through the placenta, may increase the risk of low birth weight and preterm delivery. The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy may induce serotonergic symptoms in the infant after delivery. Antidepressant medications in breast milk may also be passed to an infant. Vagus nerve stimulation (VNS) therapy is an effective non-pharmacologic treatment for treatment-resistant depression (TRD), but little information exists regarding the use of VNS therapy during pregnancy.Case presentationThe patient began receiving VNS therapy for TRD in March 1999. The therapy was effective, producing substantial reductions in depressive symptoms and improvement of function. In 2002, the patient reported that she was pregnant. She continued receiving VNS therapy throughout her pregnancy, labor, and delivery, which enabled the sustained remission of her depression. The pregnancy was uneventful; a healthy daughter was delivered at full term.ConclusionIn this case, VNS therapy provided effective treatment for TRD during pregnancy and delivery. VNS was safe for the patient and her child.

Vagus Nerve Stimulation Therapy after Failed Cranial Surgery for Intractable Epilepsy: Results from the Vagus Nerve Stimulation Therapy Patient Outcome Registry

To determine the effectiveness of vagus nerve stimulation (VNS) therapy among patients with persistent or recurrent seizures after lobar resection, callosotomy, and other cranial operations for intractable epilepsy. Data were obtained from the VNS therapy patient outcome registry, which was established after United States Food and Drug Administration approval of the VNS device in 1997 as a means of capturing open-label clinical data outside of protocol. The integrity of the systems for collecting and processing registry data was authenticated by an independent auditing agency. The effect of potential selection bias, however, remains uncertain. Two nonconsecutive cohorts were compared: patients tracked in the registry who had previously undergone cranial surgery for epilepsy (CS group, n = 921) and those who had not (non-CS group, n = 3822). For the CS group, the median reduction in seizure frequency was 42.5% after 3 months of VNS therapy, 42.9% at 6 months, 45.7% at 12 months, 52.0% at 18 months, and 50.5% at 24 months. For the non-CS group, analogous rates were 47.0%, 52.9%, 60.0%, 62.7%, and 66.7%, respectively. In the CS group, seizures were reduced by at least 50% in 55.1% of patients, at least 75% in 31.4% of patients, at least 90% in 17.3% of patients, and 100% in 5.1% of patients after 24 months of VNS therapy. Response rates were more pronounced in the non-CS group: at least 50% in 62.2% of patients, at least 75% in 43.7% of patients, at least 90% in 26.8% of patients, and 100% in 8.3% of patients. Patients in both groups experienced marked improvements in quality of life parameters. The effectiveness of VNS is maintained during prolonged stimulation, and overall seizure control continues to improve with time. Patients in whom prior cranial surgery had failed did not respond as favorably as all other patients receiving VNS therapy. Nonetheless, many of the former group improved substantially. Thus, on the basis of these open-label data, VNS therapy represents a potentially palliative treatment option for patients with refractory seizures after failed cranial surgery.

Vagus Nerve Stimulation Therapy for Patients with Persistent Seizures after Epilepsy Surgery

Background: This study reports the effectiveness of vagus nerve stimulation (VNS) among patients who failed cranial surgery for intractable epilepsy. Methods: Data were obtained from the Cyberonics VNS therapy patient outcome registry. The integrity of the systems for collecting and processing registry data was authenticated by an independent auditing agency. Results: Two nonconsecutive cohorts were compared: patients who had had prior cranial surgery (CS group, n = 921) and those who had not (non-CS group, n = 3,822). For the CS group, the median reduction in seizure frequency was 42.5% after 3 months of VNS therapy, 42.9% at 6 months, 45.7% at 12 months, 52.0% at 18 months and 50.5% at 24 months. For the non-CS group, analogous rates were 47.0, 52.9, 60.0, 62.7 and 66.7%, respectively. Conclusion: The effectiveness of VNS is maintained during prolonged stimulation. Patients who failed prior cranial surgery did not respond quite as favorably as all other patients receiving VNS therapy.

The effect of vagus nerve stimulation on migraines

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might reduce pain in patients with VNS device implanted for intractable seizures. One case report described possible benefits on migraines. We contacted all patients who received VNS therapy for intractable epilepsy between 1993 and 1999 at Southern Illinois University, Springfield, Illinois. Patients who had concomitant chronic pain were subsequently interviewed. Pain intensity before and after VNS implantation was rated by the patient as average, worst, and least and on numeric rating scale from 1 to 10. Current pain measurements were compared to preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who received VNS, 27 patients were interviewed; 4 patients had common migraine, and no other chronic pain syndromes were identified. All patients with migraine reported reductions in headache frequency and numeric rating scale score for average and least headache intensity. One patient reported complete relief of headaches. Improvement was reported to start 1 to 3 months after initiation of therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain relief, 2 reported a lot of pain relief, and 1 reported slight pain relief. Concomitant antiepileptic drugs were decreased in 3 patients and slightly increased in 1. VNS might be beneficial for prophylactic therapy of migraine.

Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy.

Recent studies suggest that epilepsy that is unresponsive to medical therapy is likely to be refractory from the onset. Identifying such patients early and treating them with nonpharmacologic therapies may improve their outcome. We hypothesized that patients who had adjunctive therapy with vagus nerve stimulation (VNS) earlier in the course of their epilepsy would have a better response compared with patients who had VNS therapy instituted later in the course. Patients in the VNS patient outcome registry who were more than 5 years post onset of their seizure disorder at implantation and had seizure frequency data available at both baseline and 3 months comprised the control group (n = 2785). These data were obtained retrospectively. Patients who were implanted between August 15, 2000 and July 31, 2001 who had epilepsy for 5 years or less at implantation or who had tried four or fewer standard antiepileptic drugs (AEDs) before implantation, and who were evaluated at baseline and at 3-month intervals for seizure frequency and quality of life, comprised the early adjunctive registry (EAR group; n = 120). This group was identified prospectively by participating physicians at multiple centers. The data describe patient demographics, medical history, seizure frequency, and physician-graded quality of life measures. The two populations were demographically similar except for statistically significant differences in age, duration of epilepsy, institutionalized patients, and seizure type (partial and generalized). Although the median reduction in seizure frequency for all patients at 3 months was similar between groups (48.2% control versus 50.0% EAR), 15.0% of the patients in the EAR group reported no seizures at 3 months compared with 4.4% of those in the control group (p < 0.001). In addition, significantly more patients in the EAR group (20% versus 8%; p < 0.001) reported no seizures with alteration or loss of consciousness, and 32% of EAR patients reported no complex partial seizures compared with 17% in the control group (p = 0.002). Improvements in all areas of quality of life were reported by both populations, but more patients in the EAR group were reported as "much better/better" for postictal state (p = 0.030) and seizure clustering (p = 0.002). Typically, 5% of patients report having no seizures after 3 months of VNS therapy. The proportion increased threefold, from 5% to 15%, for patients who received VNS therapy earlier in the treatment process. Patients reported even higher rates of no seizures when simple partial seizures were excluded from the analysis or when only complex partial seizures were considered. Although these results are preliminary, they offer promise of success in achieving seizure control among patients with refractory seizures who have been diagnosed with epilepsy for less than 5 years or who have tried four or fewer AEDs. We suggest future prospective studies evaluating VNS therapy versus best medical therapy after the first two to three AEDs have failed, which typically occurs within 2 years of seizure onset.