Vagal Nerve Stimulation for Refractory Epilepsy a Brief Review
Introduction
The field of bioelectric neuromodulation is growing as a complementary intervention to pharmaceuticals. While pharmaceuticals deliver a dose of pocket-size molecules that are circulated throughout the body, neuromodulation devices deliver targeted doses of electric stimulation to the torso's neural circuitry which tin can be implemented to treat a wide array of disorders. New terms for this field such as bioelectric medicines and electroceuticals highlight the similarities between neuromodulatory and pharmaceutical interventions. Despite these similarities, neuromodulation offers key advantages in terms of reversible, targeted therapy with minimal long-term side effects and adherence issues.
Communication in the course of electrical signals travels bidirectionally between the peripheral and key nervous arrangement with the vagus nerve being i of the largest and longest transmission lines connecting much of the torso's internal organs to the brain. Therefore, it is no surprise that modulation of the vagus nerve is the near studied and targeted peripheral nerve in the field of neuromodulation. In the past decade, over ii,500 articles on vagus nerve stimulation (VNS) have been published, and VNS has been investigated in a broad range of disorders including epilepsy, depression, center failure, stroke, tinnitus, inflammation, and more.
Vagus nervus stimulation therapy received U.Southward. Food and Drug Administration (FDA) approving every bit an adjunctive treatment for drug resistant epilepsy (DRE) in 1997 as well as treatment resistant depression in 2005. Over the past ii decades, VNS Therapy® has been implanted in over 100,000 people with DRE, and a big latitude of evidence has since formed confirming the rubber and efficacy of VNS in DRE. Neuromodulation therapies have been on the rise, and VNS Therapy® for DRE has evolved into a smarter and more than versatile therapy. Patients and healthcare providers can now benefit from airtight-loop, responsive VNS and advanced features that enable more personalized therapy and streamlined dosing.
Vagus nervus stimulation clinics have formed at epilepsy centers across the world which counsel, manage and treat DRE patients with VNS as well as DRE patients that may do good from VNS. Advanced Do Providers (APPs), which includes nurse practitioners, dr. administration and clinical nurse specialists, accept go increasingly integral in the commitment of neurological care (1) including that in epilepsy (2). Advanced Do Providers oftentimes play a key role in VNS clinics past improving access and promoting continuity of care through patient and family pedagogy, managing patient therapy and providing essential follow-up care to VNS patients. Kennedy and Schallert published a nursing review on VNS in 2001 summarizing VNS Therapy®, guiding nurses in the daily handling of patients with VNS devices (3). This commodity provides an update on the Kennedy and Schallert nursing review past detailing the approach to a dedicated VNS clinic, a discussion of the closed-loop nature of VNS including improved understanding of dosing, advanced features, and troubleshooting techniques that aid in improved patient management by APPs practicing in epilepsy clinics. The goal is to provide guidance to APPs new to VNS Therapy® equally well as those already managing VNS patients or clinics.
Traditional VNS
The VNS Therapy® system includes a pulse generator surgically implanted below the left clavicle which connects to a wired lead that is tunneled to the neck and terminates with electrodes wrapped around the left cervical vagus nerve. The generator sends electrical pulses through the pb and electrode to the vagus nerve. The goal of electrical stimulation is to activate vagal afferent fibers that project to the nucleus tractus solitarii (NTS) which sends signals to other brainstem nuclei including the raphe nucleus (serotonergic neurons) and locus coeruleus (noradrenergic neurons). Neuromodulation of electrical and chemical signaling through these brain regions is idea to be responsible for the anti-seizure effect of VNS (4).
Traditional VNS includes two modes of stimulation: normal way (open-loop) and magnet mode (on-demand). Normal fashion stimulation is the primary operating way in which the device continually cycles between on and off periods (e.yard., 30 due south on and v min off). Magnet mode stimulation allows the patient or caregiver to deliver on-demand stimulation triggered by swiping a magnet over the area of the implanted pulse generator.
Five clinical trials (E01–E05) evaluating traditional VNS were conducted between 1988 and 1997 which enrolled a total of 454 patients with DRE. The ii randomized, blinded, active controlled trials, E03 and E05, compared a cohort receiving traditional VNS (high-stimulation group) to a cohort receiving presumably subtherapeutic VNS (depression-stimulation group). After 3 months, the high-stimulation group had a significantly higher mean seizure frequency reduction than the low-stimulation grouping [24.5 vs. vi.i% in the E03 trial (5) and 27.nine vs. 15.2% in the E05 written report (6)]. Long-term, open-label follow-up of the subjects enrolled in the E01–E05 clinical studies showed seizure reduction continued to meliorate over time with mean seizure frequency reductions of 44% later 2–three years of VNS Therapy® (7).
More recently, a retrospective analysis of 436 patients treated with traditional VNS showed a mean seizure reduction of 55.viii% after a mean follow-up of 5 years (8). Of those patients with > 10 years of follow-up (n = 65), seizure-reduction connected to improve with follow-up elapsing to 75.5% after 8 years (nine). A systematic review of 2,869 patients across 78 studies and VNS registry data from 5,554 patients, revealed ~threescore% of patients accomplished a ≥50% seizure reduction after 2–4 years, with a seizure-freedom rate of 8% (10).
In improver to improvements in seizure command, VNS has shown to amend quality of life. In the VNS Therapy Patient Issue Registry, quality of life metrics were assessed by providers in over 5,000 patients at diverse follow-up visits. Providers reported improvements in alacrity (58–63% of patients, range over follow-up period), mail service-ictal country (55–62%), cluster seizures (48–56%), mood change (43–49%), verbal communication (38–45%), school/professional achievements (29–39%), and memory (29–38%) (11). Reports of improvements in mood associated with VNS (12, xiii) led to the investigation of VNS in handling resistant depression (14) which was afterward FDA approved in 2005.
Mod VNS
Acute benefits of on-demand VNS were observed past manually swiping a magnet over the pulse generator prior to or during a seizure (fifteen). Therefore, closed-loop or responsive VNS was developed to automatically deliver VNS in the absence of the ability to perform a magnet swipe. Since ~82% of people with epilepsy feel increased heart rate during seizures, divers equally ictal tachycardia (sixteen), a cardiac based seizure detection algorithm was implemented. Although this detection system does not have the ability to place ictal events, it uses heart rate increases every bit a surrogate marker for seizures. This third mode of VNS is known as AutoStim and is available with generator models 106 AspireSR® and 1000 SenTiva®.
AutoStim was first clinically evaluated with the model 106 AspireSR® generator in a multicenter East-36 study in Europe (17) and E-37 report in the Us (18). Combined, 51 patients were implanted with VNS and observed in the epilepsy monitoring unit with AutoStim enabled. A full of 155 seizures were recorded from 32 patients. AutoStim was triggered during 48 of the 155 (31%) seizures. During the period of AutoStim existence delivered, 29/48 (60%) of seizures ended. Responder rates at 12 months were thirty% (viii/27) in the E-36 study and 50% (10/20) in the E-37 study.
The AutoStim feature works by comparing the heart charge per unit over the last ten-s (foreground) with the centre rate over the previous 5-min (background). Triggering of AutoStim occurs when the foreground eye rate exceeds the background heart rate past a programmer-defined threshold which tin be set betwixt 20 and 70% in 10% increments. The AutoStim threshold setting impacts the sensitivity of triggering an automatic stimulation based on heart rate changes, the rate of nonseizure-related automatic stimulations, and latency in triggering stimulation relative to the seizure onset. The lowest AutoStim threshold of 20% is associated with the highest sensitivity, capturing ~lxxx% of seizures, and highest false positive rate of ~7 nonseizure-related stimulations per hr. The AutoStim feature is designed to limit the patient from getting stimulation at an unsafe duty cycle. As AutoStim threshold increases, sensitivity decreases as well every bit the number of faux positives. Data from the E-36 and E-37 studies showed that lower AutoStim thresholds corresponded to shorter latency between seizure onset and triggering of AutoStim, and shorter latencies were associated with shorter seizure durations. Therefore, lower AutoStim thresholds have the potential to detect more than elevations in middle charge per unit associated with seizures with an earlier response time just too deliver more nonseizure-related stimulations which will increment the overall duty cycle (19). In the E-37 study, AutoStim was associated with a v% increase in duty bike (xi% without AutoStim compared to 16% with AutoStim) (xviii).
V separate studies (xx–24) reported long-term outcomes in patients starting on AutoStim, either via a new VNS implant or a replacement with an AutoStim capable generator. Combining these datasets resulted in fourscore patients who received new VNS implants and 151 patients receiving a generator replacement. Sixty percent of patients newly implanted with AutoStim VNS enabled were considered responders with a ≥50% reduction in seizure frequency afterwards a hateful follow-up catamenia of xiii months. For those on traditional VNS receiving a generator replacement with AutoStim enabled, more 1-3rd of patients experienced additional improvement in seizure frequency past adding AutoStim (Figure 1).
Figure 1. Summary of data reported on patients with traditional VNS after replacement with a modern VNS generator with AutoStim enabled (xx–24). The bar graph on the far right represents collated information from all five studies.
Dosing VNS Therapy®
Vagus nervus stimulation is an electroceutical, and dosing is like to that of a pharmaceutical. Instead of dosing in milligrams, VNS is dosed in milliamps (mA) of electric electric current, and it is often true that higher output currents increase the likelihood that vagus nerve fibers volition exist activated (25, 26). Similar to a medication, the output current of VNS needs to be titrated upward to achieve a therapeutic event. Titration typically begins 2 weeks afterwards implantation giving the patient some time to heal from surgery. The goal of titration is to optimize output current to a therapeutic level that is well-tolerated past the patient. Suggested programming involves starting at a normal mode output current of 0.25 mA and increasing output current by 0.25 mA every 2 weeks to a maximal tolerated current, typically with a goal of 1.5–2.25 mA. This is ofttimes considered the "therapeutic dose." The speed of titration can vary and depends on the condolement level of the healthcare provider, patient, and caregiver. Patient tolerability relates to the degree at which the patient feels sensations or experiences side effects associated with VNS. The virtually common stimulation associated side effects are hoarseness and vocalisation alterations (seven, 27). Paresthesia, cough, and shortness of breath are the adjacent most common side effects. Other less common side effects include dyspepsia (indigestion), airsickness, increased incidence of obstructive sleep apnea, and hiccups. It is important that increases in output current are conducted at a charge per unit that is tolerable and comfortable to the patient, however, patients are known to have better outcomes when they reach a dose of 1.5–2.25 mA (26, 28). Over time, patients meliorate tolerate VNS and the side effect profile diminishes (7, 27).
Once activated, VNS delivers a train of pulses with the pulse amplitude being the output current. Other programmed parameters include the pulse width (μs) and bespeak frequency (Hz) which represents the number of pulses per second. The level of vagus nerve activation is dependent on the combination of these three parameters which exhibit a conventional strength-duration human relationship (29). Therefore, shorter pulse widths may require higher output currents to achieve a similar response. Default settings for pulse width and bespeak frequency are 250 μs and 20 Hz for the model thousand SenTiva® generator while previous generators defaulted to 500 μs and xxx Hz. The use of lower pulse width and frequency settings of 250 μs and 20 Hz have been reported to result in like efficacy with improved battery life as compared to higher settings of 500 μs and 30 Hz (26, 28). Lower pulse width and frequency settings are also oft programmed to manage stimulation associated side furnishings (28). Feel with programming VNS, combined with these changes in default settings, have led to a shift in programmed pulse width and frequency settings. For patients implanted with VNS in 2018 with 12 or more months follow-upwards, ~seventy% were programmed to 20 Hz and ~80% were programmed to 250 μs (Figure 2). Prior to 2018, the percent of patients programmed to 20 or xxx Hz were carve up fairly evenly. Since 2010, the usage of a 250 μs has increased from ~threescore to lxxx%.
Figure 2. Trends in programming VNS (A) frequency and (B) pulse width settings. The data represent programming information collected at least 12 months afterward being implanted with VNS (data on file at LivaNova).
Vagus nerve stimulation therapy delivers stimulation at set intervals throughout the solar day and nighttime. The total percentage of fourth dimension VNS Therapy® is on for an individual patient is called the duty cycle. Patients typically begin with a normal way stimulation on fourth dimension of xxx s and off fourth dimension of 5 min, equating to a 10% duty cycle. While some patients tin can reach benefits at a x% duty cycle, others volition feel additional do good from increasing the duty cycle, typically by shortening the VNS off time. An instance would be to maintain the normal mode stimulation on time of 30 s and decrease the off time to three min, equating to a 16% duty cycle. Farther increasing the duty bicycle and reducing the off fourth dimension to ≤ 1.1 min, has shown to provide additional benefit to those still having seizures at lower duty cycles (30, 31). Shorter off times are associated with a lower number of AutoStims (xix), and for off times <1 min, Autostim cannot exist enabled.
Magnet style output current is typically set 0.25 mA higher than normal mode. When VNS is initially activated, the normal mode output current is 0.25 mA and the magnet mode output current is set to 0.v mA. Equally the output current is increased past 0.25 mA, the magnet current is besides increased by 0.25 mA. The patient can ofttimes feel the magnet mode stimulation at this college setting and may have minimal merely tolerable side effects such every bit vocalism changes. Tolerability of the higher magnet mode setting tin can also exist an indication the patient has acclimated to the side by side step up in dosage. For example, during the titration menstruum, the patient can be asked to swipe the magnet multiple times to prepare for the next increase in output electric current. The magnet mode is typically programmed with a pulse width of 250 or 500 united states and the on time is typically sixty s, although some patients may be set to 30 due south or less. Magnet way stimulation trumps all VNS modes and will deliver stimulation whenever the device is activated using the magnet.
AutoStim works in conjunction with normal and magnet modes. AutoStim output current is typically set up 0.125 mA college than that of normal manner, unless normal fashion output current is ii mA or college, in which case the AutoStim current should equal the normal mode output current. The AutoStim pulse width is typically prepare to the same equally that of normal manner, most commonly 250 μs, and the on time is typically 60 s, although some patients are set to xxx s. The sensitivity of the eye rate measurement is ready in the operating room betwixt 1 and five, with 1 being the least sensitive. This should be verified prior to activation past comparing the patient's heart rate to the heart rate detected by the generator. An boosted setting to be programed is the threshold for AutoStim. This typically starts at 40%, although added benefits may exist seen in patients be decreasing the threshold to 30 or xx%. Once the center charge per unit increases by at least the per centum prepare equally threshold, an AutoStim is delivered. This is followed past the normal way off time, which can be no less than the AutoStim on time duration. Immediately following an AutoStim, at that place is an enforced off fourth dimension equal to the AutoStim on time where an AutoStim cannot exist triggered in order to avoid over stimulation of the nerve.
Advanced Features
The model g SenTiva® generator has advanced features bachelor to simplify dosing, individualize therapy, and collect information (Figure 3). To assistance in simplifying and standardizing dosing, Guided Mode is available which allows the developer to adjust settings with a single push button. The steps in output current follow an FDA approved protocol based on published guidelines (28) known every bit the Standard Protocol (Table i). A Custom Protocol can exist created to adapt pulse width and frequency for each stimulation style, accommodate the normal manner duty cycle, or adjust the output electric current pace size to 0.125 mA. The step size in output current cannot exceed 0.25 mA. Another added benefit of using the Standard or Custom Protocol is the ability to use Scheduled Programming which enables titration without required office visits. With Scheduled Programming, the healthcare provider can schedule the device to automobile-titrate upward to multiple steps on prepare days and times. The interval between steps is express to 0.125 mA every 7 days or 0.25 mA every ii weeks. This is particularly useful for patients who have difficulty making office visits due to distance, limited mobility, or pandemic-related access or travel limitations. If telemedicine visits are an selection, these can exist set up on the same twenty-four hour period or day after the machine-titration to assess tolerability and side effects remotely. It is important for the patient to have the magnet accessible when undergoing scheduled programming in case the patient experiences discomfort with increased levels of stimulation and therapy needs to be turned off.
Figure 3. Mod VNS allows boosted features to traditional VNS including airtight-loop AutoStim, Guided Programming, Scheduled Programming, Twenty-four hour period-Night Programming, and Events and Trends data.
Tabular array ane. Standard protocol dosing steps.
The Solar day/Dark Programming feature enables the commitment of dissimilar VNS parameters for two different time periods within a 24-h cycle. This feature is non bachelor in Guided Way and the programmer must be in Manual Mode. This characteristic is useful to mitigate side effects or provide a higher dose of VNS during certain times of the day or nighttime. For example, if a patient has well-controlled daytime seizures but continues to predominantly have seizures at night, this feature may exist used to evangelize college current at dark. For patients with obstructive sleep apnea, this characteristic may be beneficial in scheduling reduced pulse width, frequency and/or current at night. For patients receiving AutoStim who practice on a regular basis, Day/Night Programming can exist used to turn off AutoStim or increment the AutoStim threshold during a specific timeframe to minimize or eliminate AutoStim associated with practise induced heart rate increases. It is of import to note that this setting does not adjust for daylight savings time or changes in time zones.
The developer has an Events tab to view Events (summary data from contempo part visits; Figure 4A) and Trends (daily and hourly trends of data; Figure 4B). Events displays a pie chart showing the daily distribution of normal manner, magnet style, AutoStim, and Off time, as well equally daily boilerplate number of stimulations for each fashion. Overall duty cycle tin can besides be viewed, combining total corporeality of time the normal, magnet and AutoStim features are active in a patient. Trends displays the daily or hourly number of tachycardia detections, AutoStims, and magnet fashion stimulations. This tin help guide future programming and patient education. For case, if the patient or caregiver study magnet activations that are not seen upon interrogation, additional counseling regarding the proper technique to actuate the device should exist reviewed. If the average AutoStims per twenty-four hour period is low, yous may desire to lower the Autostim threshold to determine if lower thresholds pb to an increase in the average number of AutoStims and an associated subtract in either seizure frequency or duration.
Effigy 4. The (A) Events tab displays a pie chart showing the distribution of daily Normal, AutoStim, and Magnet stimulations as well as boilerplate number of stimulations per twenty-four hours. The (B) Trends tab displays daily event counts for tachycardia detections, AutoStims, Magnet mode stimulations, prone position detections, and low heart rate detections.
The device tin as well be fix to detect and track depression middle rate and decumbent positioning which can be setup in the tachycardia detection window. The depression heart rate threshold can be set to 30, 40, 50, or sixty beats per minute. Turning on prone position detection requires a simple calibration of the accelerometer within the generator. The generator volition but sense for a low heart charge per unit detection and prone positioning 7.5 min following an AutoStim or Magnet style stimulation. A timestamp for these events tin then be seen in the events and trends window. Decumbent position detection tin simply be used when tachycardia detection is enabled. This feature is currently only used for reporting purposes with no real-time notification or alarm in place when these events are detected. The results can exist used to enhance your discussion of Sudden Unexplained Death in Epilepsy (SUDEP) with your patients and caregivers.
Magnetic resonance imaging (MRI) compatibility has expanded with the latest VNS devices, increasing access to high quality MRI scans. Patients implanted with functional unmarried-pin leads and generator models 103 Demipulse®, 105 AspireHC®, 106 AspireSR®, or one thousand SenTiva® implanted in the typical upper chest location at or in a higher place the armpit surface area (higher up rib 4) can safely receive scans using a transmit body coil as long every bit its iso-center is outside C7-L3 (Group A in Effigy 5). There are no restrictions on the type of receive coil that can be used. Use of a transmit body coil enables use of high channel count receive-only head coils which can be used to collect high quality MRI or functional MRI brain scans. Older generators, dual-pin generators, broken leads, or atypical generator implant locations are not uniform with transmit body coils and require use of extremity transmit/receive coils with the iso-heart outside C7-T8 (Group B in Figure 5).
Figure five. MRI weather with VNS TherapyⓇ.
Applied Management of VNS Clinics
Development of a dedicated VNS clinic by an APP can lead to improved patient selection, patient teaching, and development of expertise past a core grouping of clinicians. Patients who are considered for VNS Therapy® are often presented at a multidisciplinary surgical example conference that includes neurology, neurosurgery, neuroradiology, neuropsychology, psychology, and other experts. In one case the team determines the patient is a candidate for VNS, the patient should be scheduled to see the APP in a VNS clinic for a pre-VNS evaluation to discuss risks, benefits, side effects, dosing, and frequency of visits. Information technology is of import for the patient and family to sympathise the importance of follow-up and dosing subsequently implantation because results depend on proper dosing to a therapeutic level (26, 28). The side event profile of VNS Therapy® is unique in that information technology is does not cause cardinal nervous system side furnishings seen with many anti-seizure medications (27). Treatment options that practise not cause sedation or cognitive side effects are important to patients. While VNS is an adjunctive handling along with anti-seizure medications, it is possible at times to reduce polypharmacy when VNS Therapy® is effective. Although few patients are rendered seizure-free with VNS Therapy®, the potential for reduction in seizure frequency, seizure elapsing, seizure clusters as well equally the potential for other improvements in quality of life should be reviewed. Discussion of surgical risks should include take a chance of infection too equally the rare complexity of vocal string paralysis. Magnetic resonance imaging restrictions should be reviewed and a thorough review of the patient'due south medical history will help with direct counseling on potential contraindications associated with MRI. Patients with a history of reflux, apnea, arrythmia or bradycardia need to sympathise the potential for worsening symptoms. Evaluation by a cardiologist is recommended for patients with predisposed dysfunction of cardiac conduction systems.
Patients should exist fabricated aware that the generator will need to exist replaced periodically as the battery life is typically betwixt 5 and 10 years and depends on the level of VNS settings. More frequent follow-upwardly, such as every 3 months, may be required after the VNS generator has been in identify for several years in order to monitor battery life. The lead volition exist left in place unless there is a serious reason for removal. Removal of the lead and electrode tin can be done, yet in that location is a gamble of damaging the vagus nerve, and generally should not be undertaken unless the benefit of removal conspicuously outweighs the risk of the process. Analogous a pre-VNS counseling session with an evaluation by neurosurgery allows for a potent handoff to the surgeon with VNS relevant data provided by the APP. Information technology also provides a more than comprehensive approach to ensure the patient and guardians have adequate data to make an informed decision about proceeding with VNS placement. Once a patient or guardian elects to move forward with VNS placement, informed consent is obtained, surgery is scheduled, and a follow upwardly visit in the VNS dispensary should exist scheduled for two weeks after implantation. The patient is typically given a magnet kit upon implantation that should exist brought to each follow up visit.
At the VNS activation visit, the APP begins by assessing the incisions to ensure they are healing without signs of infection. At the time of activation, patients will oftentimes feel a voice change characterized by a deepened tone or a warble to their vox during VNS on time, or the patient may coughing at the onset of stimulation. Patients who experience throat clearing or a balmy cough frequently find that the symptoms subside within ane to 2 days, however this can be a dose limiting side consequence in the first of therapy. Over time patients tend to better tolerate VNS settings as side effects resolve and further dose titration is possible. Voice changes can likewise improve with time, but tin can get more pronounced with subsequent increases in current. Although this is a common side effect, it typically does non limit the ability to titrate therapy. With each dose titration, the APP should monitor for signs of discomfort, coughing, or other intolerable side effects, and be prepared to decrease the dosing parameters if needed. For newly implanted patients, the APP can increment the dose in a stepwise fashion such as that in Table 1 and monitor the patient for side effects during the visit. It is often possible to increase the output current multiple steps during the first visit. If side effects of cough or voice modify occur while slowly titrating the dose over a 30 min flow, then the APP tin can footstep dorsum to the last previously tolerated output electric current.
Once activated, patients and caregivers should be instructed in the proper employ of the magnet. Discussion effectually the times to employ the magnet, frequency of magnet activation for a unmarried event, and the proper technique to turn off the device with the magnet should be reviewed. Those nowadays at the visit should also demonstrate the proper technique to employ the magnet. It can be helpful to review magnet activations recorded by the device to come across if the patient and family are correctly using the magnet at domicile. Information technology is as well helpful to provide a letter for all caregivers to explicate the employ of the magnet, as well as magnet restrictions.
Monitoring battery life throughout follow-up is important in club to properly plan for a generator replacement procedure prior to battery depletion. As the bombardment becomes low, device diagnostics volition show the following battery life indicators: Intensified Follow-upward Indicator (IFI), Near Cease of Service (NEOS) and End of Service (EOS) when the battery life is 8–18%, 0–8%, and 0%, respectively. When the bombardment life indicator is displaying IFI, information technology is recommended to schedule more frequent follow-upward visits with the patient, such as every iii months, in order to closely monitor battery life. The full benefits from VNS may take years to fully appreciate (seven), and benefits may be lost acutely or gradually, and possibly permanently after EOS (32). It is therefore important to weigh all potential benefits of VNS in addition to seizure command when considering generator replacement, including effects on alertness, post-ictal state, cluster seizures, mood, and memory. Generator replacement should be done prior to EOS to ensure long-term treatment. Patients should also be informed that if they experience a sudden alter in seizure frequency, decreased perception of stimulation, or loss of other VNS-induced effects after existence implanted for several years, the device should be checked to run into if the battery is about cease of service. For patients with older generation dual-pin leads, a dual-pin uniform generator is required for replacement, such equally the model 104 generator. If a dual-pin compatible generator is not available in a specific region, and then a lead replacement would exist required during the generator replacement process. If discontinuation of therapy is being considered due to lack of efficacy or intolerable side effects, VNS Therapy® tin be turned off for an extended period of time, such equally six months, to make up one's mind if seizure activeness or other potential VNS-induced benefits modify. If it is determined that VNS was not beneficial to the patient, the device may remain implanted merely with all output current settings programmed to zero, or for patients who adopt, the VNS system tin be fully or partially explanted (33, 34).
Troubleshooting
The benefit of a trained APP is the knowledge to troubleshoot and ability to run across patients for urgent visits should problems arise. Difficulties with interrogation can occur. If this arises the battery power of the wand should be assessed and batteries should exist replaced if needed. If the bombardment light on the wand is green, reposition the wand to endeavour interrogation. If the Bluetooth connexion between the wand and tablet are not adequate, connect the wand to the tablet via the string provided with the device. In some cases, repositioning of the patient's arm or placing the patient supine is needed to brand the device more than accessible to the wand.
When interrogating the device, a high or depression atomic number 82 impendence may be detected. This tin can occur with atomic number 82 aperture, disconnection or fibrosis. If a high impedance error message comes upward presently later surgery this could be due to the setscrew or atomic number 82 pin non being fully inserted into the generator. If a high lead impedance message occurs in an established patient, this could point a lead interruption and all output currents should be turned off. Obtaining an x-ray to visualize the lead is often indicated if there is a high or low pb impedance, however it is possible for the break in the pb to be small and not visible on 10-ray.
Other than technical difficulties, an appropriate understanding of managing side effects is imperative for whatsoever provider running a VNS clinic. Many dose related side furnishings, such as reflux, coughing, voice change and sleep apnea tin be addressed past adjusting the settings. This includes decreasing the output current, signal frequency, pulse width or duty cycle. For patients who are unable to tolerate a higher output current, the duty cycle can exist increased and may provide additional benefit. Some patients are bothered by the noticeable departure in normal manner and AutoStim output current. In these cases, AutoStim can be set at the same output electric current every bit normal mode. Taping the magnet in place to temporarily turn off VNS Therapy® can be done during eating for patients who note difficulty in swallowing or can be washed during singing or public speaking in patients who experience stimulation induced voice alterations. In these situations, the magnet should exist removed immediately after eating, singing, or public speaking is complete. It is important to know that no stimulation volition occur if the magnet is taped or continually held in identify over the VNS. This technique of placing the magnet over the generator can also be used if there is business organisation the VNS is not tolerated equally evidenced past painful stimulation, intense neck hurting, or trouble animate. The magnet can exist taped in identify until the patient is able to obtain medical attending.
In rare cases, patients have reported discomfort along the track of the lead, just interrogation failed to reveal any abnormality. Intraoperative examination has revealed degradation of the casing around the wire, which caused the patient pain without triggering an abnormal diagnostic. If a patient consistently reports a problem, the provider must consider that there may be something incorrect that is not detectable by standard interrogation, and refer the patient back to the surgeon.
Vagus nerve stimulation is an efficacious intervention for DRE, simply it will non do good every patient. At that place may be times when patients do not feel they take benefitted from the device, and they wish to have information technology removed. Every center will institute its ain criteria for explanting a VNS, but it is reasonable to wait until the patient has had it on reasonably optimized settings for 2 years, and every attempt should be made during that fourth dimension to ensure the best settings the patient tin tolerate are achieved. If the patient and care team recall VNS removal is warranted due to lack of efficacy, they may wish to consider simply turning off the device for 6 months earlier explanting it. This gives the patient a take chances to meet if mayhap the VNS was providing more benefit that previously realized. Tracking cognitive abilities, mood, and quality of life scores during this time would exist helpful in determining if the patient notices any deterioration in these metrics without the VNS on.
Conclusion
Vagus nervus stimulation is a well-established adjunctive treatment in reducing seizure frequency in patients with DRE, and VNS has evolved into a smarter technology over the past decade with the addition of closed-loop stimulation and features the enable guided and scheduled dosing and more individualized therapy. Advanced Practise Providers play a critical role in dedicated VNS clinics which provide value to patients and caregivers through improved admission, instruction, and continuity of care. Continued education on the practical employ of traditional and modern VNS features as described in this review is important to maximize benefit to VNS patients.
Author Contributions
All authors contributed to the outset 5 sections describing VNS Therapy®. The sections PRACTICAL Management OF VNS CLINICS and TROUBLESHOOTING were written exclusively by the avant-garde practice provider authors BF, JD, EK, and SM.
Conflict of Interest
SW is an employee of LivaNova PLC.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Source: https://www.frontiersin.org/articles/10.3389/fneur.2020.610379/full
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