Vagus Nerve Stimulation Implantation Research Articles

First-in-human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation.

Vagus nerve stimulation (VNS) is an effective treatment for people with drug-resistant epilepsy. However, its mechanisms of action are poorly understood, including which nerve fibers are activated in humans during VNS in typical clinical settings and which are required for clinical efficacy. In particular, there have been no intraneural recordings of vagus nerve fiber activation in awake humans undergoing chronic VNS. In this study, for the first time, we report recordings from the vagus nerve in this setting. The recordings were performed using a sterile tungsten microelectrode inserted percutaneously into the cervical vagus nerve under ultrasound guidance. The clinical VNS systems were used to deliver stimulation while activity in the vagus nerve was recorded. In addition to activating myelinated axons at low currents, we provide evidence that VNS can also activate unmyelinated C fibers in the vagus nerve at currents <1 mA. These results add to our understanding of how VNS exerts its beneficial effects in drug-resistant epilepsy. Here we describe for the first time, electrical recordings from the vagus nerve in awake drug-resistant epilepsy patients with an implanted vagus nerve stimulation (VNS) device. We found that the VNS device was able to activate both myelinated and unmyelinated fibers within the vagus nerve, whichcontributes to our understanding of how VNS works in the context of drug-resistant epilepsy.

Baseline characteristics and predictors for early implantation of vagus nerve stimulation therapy in people with drug-resistant epilepsy: Observations from an international prospective outcomes registry (CORE-VNS).

Vagus nerve stimulation (VNS) Therapy is routinely indicated for people with drug-resistant epilepsy (DRE). We analyzed the baseline characteristics of individuals receiving the recently released VNS models and identified factors associated with early or late implantation. The Comprehensive Outcomes Registry of subjects with Epilepsy (CORE-VNS), a prospective observational study evaluating the clinical and psychosocial outcomes of VNS Therapy®, is following participants for up to 60 months after VNS implantation. In this analysis, we used Cox proportional hazards model to identify baseline characteristics associated with the time from diagnosis to first implantation. Of the 819 enrolled, 792 (96.7%) participants implanted with a VNS device were evaluated. 529 (64.6%) underwent the first implantation and 263 (32.1%) a re-implantation. Participants' median age at first implant was 24 years; 492 (62.1%) were ≥18 years old and 166 (20.3%) were < 12 years old. The average number of failed ASMs prior to VNS implantation was 7.1, and 145 (17.7%) had undergone previous epilepsy-related surgery. Epilepsy was classified as focal in 47.7% of participants, generalized in 16.1% and combined focal and generalized in 34.2%. Many of the participants (40.9%) had epilepsy of unknown etiology. The median time from diagnosis to first implantation was 10.33 years and was significantly shorter in participants with combined focal and generalized epilepsy compared to those with focal epilepsy alone, and in participants with genetic and immune epilepsy compared to those with unknown etiologies. In people with DRE, VNS Therapy is provided after multiple failures of ASMs and after failure of epilepsy surgery in one in six individuals. Time from diagnosis to first implantation is associated with epilepsy type and etiology, likely reflecting variable treatment pathways. Clearer guidelines on when and how non-drug therapies should be deployed in people with DRE related to different epilepsy factors are needed. Neuromodulation can be a very helpful treatment in people who have seizures that do not respond to medications. The most widely utilized neuromodulation therapy is vagus nerve stimulation (VNS). We present data from a large, global study to show that people use an average of seven anti-seizure medications before attempting VNS Therapy and that it takes about 10 years for people to get their first VNS implant. We advocate for clearer treatment guidelines on how and when to consider VNS Therapy in people with seizures that are resistant to medication.

Vagus Nerve Stimulation Paired With Rehabilitation for Chronic Stroke: Characterizing Responders.

Implantable vagus nerve stimulation (VNS) paired with volitional upper extremity rehabilitation can improve impairment and function among moderately to severely impaired, chronic stroke survivors. This study is a retrospective analysis of the in-clinic rehabilitation phase of the blinded, placebo-controlled, randomized pivotal VNS-REHAB trial to determine whether dosing parameters during in-clinic paired VNS therapy were associated with responder status and whether covariates might impact that determination. Data were limited to 53 participants in the active VNS group who had received VNS implants prior to undergoing 6weeks of in-clinic rehabilitation paired with VNS. Tasks were standardized across all participants. Dosing parameters included number of stimulations and task time. The primary outcome was the Fugl-Meyer Upper Extremity Assessment (FMA-UE), evaluated at the end of 6weeks (Post-1). Participants were classified a priori as responders based on an improvement of≥6 points on the FMA-UE from baseline to Post-1. Dosing parameters were not associated with FMA-UE responder status at the end of 6weeks. Covariates including age, gender, paretic hand, baseline severity, and chronicity of stroke were also not significant associations of response. While responders to VNS could be defined, therapy dosing and participant attributes did not provide greater specification for association of responder status. Limitations of this study include small sample size and non-linearity of the FMA-UE. Future studies will include reassessing responder categorization using more linear scales and examining stroke lesion characteristics to determine whether these measures are more sensitive to dosing parameters. for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://www.w3.org/1999/xlink ).

Stimulated Vocal Fold Immobility After Vagal Nerve Stimulator Placement: A Case Series.

Vagal nerve stimulator (VNS) implantation is a vital therapy for epilepsy refractory to other treatments; however, it is associated with a very high rate of voice changes. Relatively few of these patients are evaluated for vocal fold motion impairments. In this series, we evaluate 5 such patients with a novel phenotype of forced abduction with VNS stimulation. Retrospective case series. Five patients with a VNS implant who underwent operative direct or in-office rigid laryngoscopy and had vocal fold motion impairment associated with VNS activation are included. All 5 patients had vocal fold mobility with VNS off and a fixed with activation. All patients exhibited vocal fold abduction with VNS activation. Patient 2 has since undergone laryngeal reinnervation, which helped her intermittent dysphonia but left a small glottic gap. A type 1 thyroplasty corrected this gap and improved her voice further. Patient 3 has undergone laryngeal reinnervation for which early results show improvement in perceptual and patient reported outcomes. Patients 4 and 5 have both undergone laryngeal reinnervation with improvement in voice. Previous reported cases of stimulated immobility associated with VNS use describe only adduction of the vocal fold. This series expands the previous work showing the VNS activation can also cause stimulated immobility in an abducted position, for which reinnervation and other medialization procedures offer promising treatment.

Outcomes of surgical resection and vagus nerve stimulation in patients with medically refractory epilepsy and glutamic acid decarboxylase 65 antibody positivity.

Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.

Vagus nerve stimulation in pediatric patients with drug-resistant epilepsy: a step-by-step video.

Vagus nerve stimulation (VNS) is a neuromodulatory treatment involving chronic intermittent electrical stimulation of the left vagus nerve, administered through a programmable pulse generator implanted subcutaneously in the chest. This generator connects to a bipolar lead, with electrodes wrapped around the vagus nerve in the neck. Primarily used as an adjunct therapy for patients with refractory epilepsy who cannot undergo or have not benefitted from resective surgery, VNS is generally well tolerated with few severe side effects. Herein is presented an educational surgical video providing a detailed, step-by-step technical description of VNS implantation. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID244.

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.

Vagal Nerve Stimulation in the Pediatric Population and Correlation Between Family and Treatment Team Perspectives: Single-center Experience.

Vagal nerve stimulation (VNS) is an adjunctive therapy to pharmacological treatment in patients with drug-resistant epilepsy. This study aimed to assess the efficacy of VNS therapy for seizure frequency reduction and improving quality of life (QOL) measures in children with refractory epilepsy and to evaluate the correlation between the perspectives of families and those of the treating team. This was a prospective cohort study conducted at Abha Maternity and Children's Hospital, Saudi Arabia, from 2018 to 2022. A total of 21 pediatric patients who completed one year of follow-up after VNS implantation were included. Patients were aged between 2 and 14 years, with a mean age of 8.14 ± 3.92; 11 (52.4%) patients were female. Family and physician assessments were collected blinded to each other using Clinical Global Impression of Improvement (CGI-I) scores and QOL assessments to evaluate the correlation between the families' and treating team's perspectives on VNS outcomes. In this study involving 21 patients with intractable epilepsy, VNS showed significant efficacy in reducing the frequency of seizures. VNS significantly reduced the number of seizures per week from a baseline median of 35 to a median of 0.25 at the end of the follow-up period, representing a dramatic reduction of 99.3% (p < 0.001). The number of emergency department visits per year decreased from a baseline median of 12 to a median of 2, a reduction of 83.3% (p < 0.001), whereas the number of hospital admissions per year decreased from a baseline median of 3 to a median of 1, a 66.7% decrease (p < 0.001). The number of antiepileptic medications taken decreased from a median of 4 to 3 (p < 0.001). Notably, 28.57% of the patients achieved complete seizure freedom, and 38% exhibited significant improvement, with at least 50% reduction in seizure frequency. Importantly, none of the patients experienced an escalation in seizure frequency following VNS treatment. The family and physician assessments showed varying degrees of alignment in perceptions, with "concentration" exhibiting a significant positive correlation (r = 0.498, p = 0.022), indicating noteworthy agreement, whereas verbal communication did not show a substantial correlation (r = -0.062, p = 0.791), indicating a divergence of views. VNS is a promising and well-tolerated therapy for individuals with intractable seizures, offering clinical benefits and potential enhancements in various aspects of QOL. The varying perceptions between family and physician assessments highlight the importance of considering multiple perspectives when evaluating treatment outcomes.

Electroencephalogram synchronization measure as a predictive biomarker of Vagus nerve stimulation response in refractory epilepsy: A retrospective study.

There are currently no established biomarkers for predicting the therapeutic effectiveness of Vagus Nerve Stimulation (VNS). Given that neural desynchronization is a pivotal mechanism underlying VNS action, EEG synchronization measures could potentially serve as predictive biomarkers of VNS response. Notably, an increased brain synchronization in delta band has been observed during sleep-potentially due to an activation of thalamocortical circuitry, and interictal epileptiform discharges are more frequently observed during sleep. Therefore, investigation of EEG synchronization metrics during sleep could provide a valuable insight into the excitatory-inhibitory balance in a pro-epileptogenic state, that could be pathological in patients exhibiting a poor response to VNS. A 19-channel-standard EEG system was used to collect data from 38 individuals with Drug-Resistant Epilepsy (DRE) who were candidates for VNS implantation. An EEG synchronization metric-the Weighted Phase Lag Index (wPLI)-was extracted before VNS implantation and compared between sleep and wakefulness, and between responders (R) and non-responders (NR). In the delta band, a higher wPLI was found during wakefulness compared to sleep in NR only. However, in this band, no synchronization difference in any state was found between R and NR. During sleep and within the alpha band, a negative correlation was found between wPLI and the percentage of seizure reduction after VNS implantation. Overall, our results suggest that patients exhibiting a poor VNS efficacy may present a more pathological thalamocortical circuitry before VNS implantation. EEG synchronization measures could provide interesting insights into the prerequisites for responding to VNS, in order to avoid unnecessary implantations in patients showing a poor therapeutic efficacy.

Vagus Nerve Stimulation Paired With Upper Extremity Rehabilitation for Chronic Ischemic Stroke: Contribution of Dosage Parameters

Background Vagus nerve stimulation (VNS) combined with rehabilitation is a Food and Drug Administration approved intervention for moderate to severe upper extremity deficits in chronic ischemic stroke patients. Previous studies demonstrated that VNS improves upper extremity motor impairments, using the Fugl Meyer Assessment of Upper Extremity (FMA-UE); however, delineating where these improvements occur, and the role of VNS dosage parameters were not reported. Objective This study explored the relationship between dosing (time over which task repetitions were executed and number of VNS stimulations) and changes within proximal and distal components of the FMA-UE. Methods Participants underwent VNS implantation, with 1 group receiving VNS paired with rehabilitation (Active VNS) and the other group receiving rehabilitation with sham stimulation (Controls). Both groups received 6 weeks of in-clinic therapy followed by a 90-day at-home, self-rehabilitation program. Participants who completed at least 12 of 18 in-clinic sessions were included in the analyses (n = l06). Pearson correlations and analysis of covariance were used to investigate the relationship between dosing and FMA-UE outcome change along with the effect of covariates including baseline severity, time since stroke, age, and paretic side. Results Compared to Controls, active VNS favorably influenced distal function with sustained improvement after the home program. Significant improvements were observed in only distal components (FMdist) at both post day-1 (1.80 points, 95% Cl [0.85, 2.73], P < .001) and post-day 90 (1.62 points, 95% CI [0.45, 2.80], P < .007). Conclusions VNS paired with rehabilitation resulted in significant improvements in wrist and hand impairment compared to Controls, despite similar in-clinic dosing across both groups. NCT03131960

241 Disparities in Access to Epilepsy Surgery Care in Children With Drug Resistant Epilepsy: Implications For Long-Term Survival Outcomes

INTRODUCTION: Our recent publication in Lancet Child and Adolescent Health examined long-term survival rates for pediatric patients with drug-resistant epilepsy (DRE) treated with antiseizure medications (ASMs) only, ASMs plus vagus nerve stimulation (VNS), and ASMs plus cranial epilepsy surgery in a large United States (US) administrative database. The difference in survival probabilities was statistically significant (p &lt; .001). Adjusted probabilities of survival beyond 10 years were 89.27% for the ASMs only cohort (95%CI, 87.71%-90.85%), 92.65% for VNS cohort (95%CI, 90.62%-94.72%), and 98.45% for cranial surgery cohort (95%CI, 97.53%-99.38%). METHODS: Patients aged 0-17 years with DRE between 01/01/2004-31/12/2020 were identified from the Pediatric Health Information System data set across 49 US pediatric hospitals. Patients treated with ASMs only or ASMs plus VNS or ASMs plus cranial epilepsy surgery were included. Chi-square tests determined associations between treatment time and preoperative factors such as treatment type, age, sex, race/ethnicity, insurance type, geographic region, epilepsy type, and medical complexity (presence of pediatric complex chronic conditions [PCCCs]). RESULTS: 18,292 total patients were included: 10,240 patients treated with ASMs only, 5,019 patients with ASMs plus VNS, 3,033 patients with ASMs plus cranial epilepsy surgery. There were significant differences in age, geographic region, race/ethnicity, presence of PCCCs, diagnosis, and insurance type (p &lt; 0.001). Those treated surgically, either with VNS implantation or cranial epilepsy surgery, were 2 years older than ASMs only. ASMs only patients were less ikely to be reported as non-Hispanic white (51.78%), less likely have a focal/partial epilepsy diagnosis (8.74%), and less likely carry private medical insurance (35.82%). CONCLUSIONS: We show a link of disparities in pediatric epilepsy surgery care and survival outcomes. Focused strategies are needed to expand access to comprehensive epilepsy care with neurosurgical evaluation and offerings when appropriate.

Vagus Nerve Stimulation as an Alternative to Maintenance Electroconvulsive Therapy for Difficult-to-Treat Depression.

Vagus nerve stimulation (VNS), an implantable neurostimulator, provides a valuable long-term treatment option for patients with difficult-to-treat depression. It has been reported that previous response to electroconvulsive therapy (ECT) might predict a better response to VNS and that VNS could reduce or eliminate the need for maintenance ECT in some patients. We present the case of a patient who received a total of more than 120 sessions of ECT over the course of 13 years because of a major depressive disorder, with favorable response but without achieving full remission. After implantation of VNS, ECT was discontinued, and her depressive symptoms improved, achieving remission within 12 months. This case supports VNS as an alternative to maintenance ECT in patients with difficult-to-treat depression who have shown previous response to ECT treatment.

Impact of Adjunctive VNS on Drug Load, Depression Severity, and Number of Neuromodulatory Maintenance Treatments.

Vagus nerve stimulation (VNS) is a long-term adjunctive treatment option in patients with difficult-to-treat depression (DTD). A total of n = 20 patients (mean age 52.6 years) were included in the multicenter, prospective, observational, naturalistic RESTORE-LIFE study and were treated with adjunctive VNS as an add-on to treatment as usual. Exploratory and secondary outcome parameters from a single center were investigated for this present analysis. The overall mean drug load slightly decreased from 4.5 at baseline to 4.4 at 12 months (Z = -0.534, p = 0.594). The drug load was lower in previous electroconvulsive therapy (ECT) responders than in non-responders. There was a reduction in the mean number of hospitalizations per month after VNS implantation (Z = 1.975, p = 0.048) and a significant decrease in the mean Montgomery Åsberg Depression Rating Scale (MADRS) score from 27.3 at baseline to 15.3 at 12 months (T = 4.230, degree of freedom (df) = 19, p = 0.001). A history of ECT response at baseline was associated with greater improvement in the MADRS score after 12 months of VNS (F = 8.171, p = 0.013). The number of neuromodulatory maintenance treatments decreased during the follow-up period. In summary, there was an alleviation in the burden of illness among DTD patients treated with VNS.

Vagus nerve stimulation allows to cease maintenance electroconvulsive therapy in treatment-resistant depression: a retrospective monocentric case series.

The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization. We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression. Seven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/- 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27-68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/- 9.8 weeks between sessions after VNS vs. 2.9 +/- 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians. VNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists' knowledge on this therapy.

Efficacy of vagus nerve stimulation for children with drug-resistant epilepsy: Retrospective study

IntroductionAccording to current investigations, there are controversy in our knowledge regarding the safety and efficacy of Vagus Nerve Stimulation (VNS) in children younger than 12 years old. Therefore, we performed this study and aimed to better evaluate the safety and efficacy of VNS in children younger than 12 years. MethodThe retrospective study comprised two groups. In the first group, patients (N = 19) underwent VNS implantation procedure and second group, (N = 21) received no VNS implantation. The main study parameters are as follows: (1) Primary outcome evaluated the proportion of cases with >50 % reduction of seizures at the last follow-up. (2) Changes in patients’ status in VNS group after procedure compared to before procedure. (3) Patient's complaints in VNS group compared to control group. ResultsOur results demonstrated that there was a significant reduction in the frequency of seizures (per month) in patients 6 months after VNS surgery compared to before VNS surgery (1044.3 ± 1526.7 VS 220.7 ± 421.6; P value = 0.028). 57.9 % of patients underwent VNS showed the response rate of 50 % reduction in seizure frequency. There was significant improvement in memory problem, work/ school limitation, social limitation, and tachycardia 6 months after VNS procedure compared to before VNS procedure in patients. The most common reported side effects were difficulty swallowing (31.5 %) and coughing (31.5 %) followed by stomach discomfort (15.8 %). ConclusionConsidering the significant reduction in the frequency of seizures and improvement of life aspects including in memory problem, work/ school limitation, social limitation, we recommend VNS as an effective treatment modality for drug-resistant epilepsy in children. However, the combination of VNS with other treatment modalities that could improve other aspects of quality such as energy levels, sleep pattern, and feeling management of life is recommended.

Vagus nerve stimulation for the treatment of narcolepsy

Background and objectiveNo study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. MethodsIn our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. ResultsCompared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. ConclusionIn this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.

Unveiling of vagus nerve anatomical assessment with ultrasonography before vagus nerve stimulation implantation

Unveiling of vagus nerve anatomical assessment with ultrasonography before vagus nerve stimulation implantation

Making Sense of Vagus Nerve Stimulation for Stroke.

Implantable vagus nerve stimulation, paired with high-dose occupational therapy, has been shown to be effective in improving upper limb function among patients with stroke and received regulatory approval from the US Food and Drug Administration and the Centers for Medicare & Medicaid Services. Combining nonsurgical and surgical approaches of vagus nerve stimulation in recent meta-analyses has resulted in misleading reports on the efficacy of each type of stimulation among patients with stroke. This article aims to clarify the confusion surrounding implantable vagus nerve stimulation as a poststroke treatment option, highlighting the importance of distinguishing between transcutaneous auricular vagus nerve stimulation and implantable vagus nerve stimulation. Recent meta-analyses on vagus nerve stimulation have inappropriately combined studies of fundamentally different interventions, outcome measures, and participant selection, which do not conform to methodological best practices and, hence, cannot be used to deduce the relative efficacy of the different types of vagus nerve stimulation for stroke rehabilitation. Health care providers, patients, and insurers should rely on appropriately designed research to guide well-informed decisions.

Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug-resistant epilepsy.

To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years. The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years. The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs. Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs. Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.

Long-term effects of vagus nerve stimulation therapy on cognitive functioning in patients with drug-resistant epilepsy.

Despite the increasing use of vagus nerve stimulation (VNS) for drug-resistant epilepsy, its impact on cognitive functioning remains insufficiently investigated. We aimed to comprehensively assess changes in cognition after long-term VNS therapy in a prospective sample of adults with epilepsy. Between December 2019 and March 2023, patients scheduled for VNS implantation were invited for neuropsychological assessment, including tests of executive functions, working and short-term memory (recall of a verbal logical story and the Rey-Osterrieth complex figure (ROCF)), and social cognition. Participants were re-evaluated after a year of VNS therapy and the pre- and postoperative scores were compared by means of the Student's t or Wilcoxon's signed rank tests for paired samples. Patients available only after a longer follow-up (more than 24 months) were also re-examined and included in a secondary analysis. The study included 28 PWE (16, 57.1% female, average age 33.7 ± 10.0 years). Twenty-two PWE followed-up at 14.5 ± 4.8 months had worse categorical verbal fluency than preoperatively (t = 2.613, p = 0.016). After including patients with long follow-up (n = 28, 21.6 ± 11.4 months), the group scored better on the delayed recall of the ROCF (17.09 ± 8.84 to 20.65 ± 8.32 points, t(22) = - 2.618, p = 0.016) and the Happé strange stories test (5.0 ± 2.6 to 6.1 ± 2.1 points, t(14) = - 3.281, p = 0.005). No significant changes were observed in other cognitive domains (p > 0.05). We suggest improvements in a task of social cognition and short-term visual memory after longer use of VNS therapy. Such findings should be confirmed in larger trials after controlling for changes in ictal or interictal activity.