A new review of studies on the use of vagus nerve stimulation (VNS) for epilepsy says the therapy can be effective as adjunctive treatment for partial or generalized epilepsy and for Lennox-Gastaut syndrome (LGS) in not only adults, but also both young and older children. The AAN Guideline Development Subcommittee updated a 1999 AAN guideline on VNS, finding that in adults with epilepsy, VNS can have the added effect of improving mood problems, such as depression.
Up to now, VNS was generally used as adjunctive therapy for partial-onset seizures in children over the age of 12, but the new review says that electrical stimulation has the potential for significantly reducing seizures in a broader group of children.
The guideline was based on an assessment of 216 scientific articles from 1996 to February 2012. The review of the published research by an AAN panel — published in the Aug. 28 online edition of Neurology — found that the efficacy of VNS may improve over time, meaning that patients undergoing VNS may experience fewer seizures as time goes on.
Neurology Today talked with George L. Morris III, MD, medical director of the Aurora Regional Epilepsy Center at Aurora St. Luke's Medical Center in Milwaukee, WI, who is the lead author of the guideline. He discussed what is new in the guideline and the implications for clinical care. [For the levels of evidence on which the committee based their recommendations, see “AAN Evidence Review: Recommendations.”]
WHY WAS IT TIME TO UPDATE THE GUIDELINE ON VNS FOR EPILEPSY?
It's been over a decade since the last guideline and there has been a lot of research that has been published since then. We wanted to know whether there was new or different evidence about the use of VNS and whether there are any additional safety issues that need to be addressed. In particular there are a lot more data on children now. The FDA-approved indication for the use of VNS goes down to the age of 12, but there is substantial new data on the use of VNS in children younger than 12.
We also were interested in the question of what settings — rapid stimulation versus standard — were most effective in improving seizure frequency. And we wanted to look at whether there are areas in which we can expand the use of VNS. One question focused on the issue of mood because there is research to suggest VNS could be advantageous in improving mood in people with epilepsy. It seemed time to give the whole thing a look-over.
WHAT ARE SOME OF THE NEW KEY POINTS IN THE GUIDELINE?
We really do believe that treatment with VNS can be applied to both partial and generalized seizures. It appears that generalized seizures responded, particularly in the case of the childhood syndrome, LGS. This is a very tough childhood syndrome and it isn't unusual for patients to require multiple medications and have types of seizures that can cause them severe injury. These episodes are scary for parents and they occur in a very rapid fashion. One of the big benefits VNS may offer is that it may reduce the frequency of these very disturbing types of seizures. That's very good news for parents.
In this review of literature, we found that “VNS is possibly effective in achieving >50 % seizure reduction” in children. The guideline states that “VNS may be considered as adjunctive treatment for children with partial or generalized epilepsy.”
Another new point has to do with magnet activation. We looked at studies that suggested that activation of the VNS magnet could stop an ongoing seizure, and we found there is credible evidence to support that. If you're a person with epilepsy, it's important to know that “Yes, there is an opportunity to intervene at the moment of the seizure.”
The guideline states that magnet-activation “may be expected to abort seizures one-fourth to two-thirds of the time when used during seizures auras.” Many people do not have a warning that a seizure is coming so this would not be an important issue for all patients.
ARE THERE SAFETY CONCERNS WITH USING VNS IN CHILDREN?
We did want to make the point that children do tend to have a slightly different profile of adverse events. Wound infection may be more of a problem for children than adults potentially because of their tendency to touch and fiddle. The guideline suggests that clinicians may want to be extra vigilant in monitoring children for wound infections.
ARE THERE ANY NEW CONCERNS WITH SIDE EFFECTS?
As we discussed, children experience a higher rate of infection. We made the recommendation that clinicians should pay extra attention to that possibility. In adults, we know we've had issues of bradycardia and slow heartbeat, associated with the surgical step of implantation. The review found that there were a couple of individuals who, after 20 months of having the implant, complained of having a slowing of their heartbeat.
It's important for clinicians to address patient concerns about the possibility that they are experiencing symptoms of bradycardia, such as a sudden loss of consciousness, a fainting spell. The guideline noted that it can be difficult to distinguish a cardiac-related disturbance from a seizure-related event. Physicians are advised to consider testing if new events occur.
HOW MIGHT VNS HELP WITH MOOD PROBLEMS IN PEOPLE WITH EPILEPSY?
The review suggests that VNS may provide the added benefit of improving mood. Depression is a common comorbidity for people with epilepsy. The new guideline notes that “in adult patients receiving VNS for epilepsy, improvement in mood may be an additional benefit.” It's a benefit for patients that they can treat two problems using one thing. It might seem logical to conclude that VNS would be an effective primary treatment for mood problems in people with epilepsy, but we do not have evidence to support that approach.
WHY MIGHT THE EFFICACY OF VNS IMPROVE THE LONGER IT IS USED?
We know that electrical stimulation is effective for reducing seizure activity, but we don't know what its mechanism is. How does electrical stimulation modify the brain relative to a drug is something that needs to be studied more aggressively. One question is whether there is a long-term change in the behavior of brain cells in response to the stimulation. We have some very tangential information that might be the case, but that needs to be studied more. Other studies suggest that the electrical stimulation itself might be the key — it may induce the brain into a state where it's always trying to inhibit stimulation.
DOES VNS OFFER ADVANTAGES OVER EPILEPSY SURGERY?
It's clear from the latest review that the evidence supporting surgical intervention is significantly stronger in respect to efficacy outcomes than it is for VNS. Surgery appears to have a stronger likelihood of a good outcome. When people are not candidates for surgery and have not responded to multiple medications, VNS is an option to consider.
WHAT ISSUES RELATED TO VNS NEED FURTHER RESEARCH?
There are clearly things we don't know. We'd love to know more about what's the optimal setting. There is insufficient evidence say whether rapid stimulation (7 second on, 30 seconds off) offers advantages over standard stimulation (30 seconds on, 5 minutes off). Unlike with a drug, where we can measure levels in the blood, we don't know the optimal level of VNS for reducing seizure occurrence.
We also don't know whether VNS would be an appropriate treatment for patients when they first develop epilepsy. It has advantages because it is a self-delivering therapy. In a population of patients in which memory is sometimes affected and remembering to take medications is a challenge, VNS might be a good treatment choice, but our guideline did not review evidence for VNS as initial therapy. But any study of VNS as an initial treatment would face barriers because there are medical options proven to work.
AAN EVIDENCE REVIEW: RECOMMENDATIONS
- Vagus nerve stimulation (VNS) may be considered as adjunctive treatment for children with partial or generalized epilepsy (Level C).
- VNS may be considered in patients with Lennox-Gastaut syndrome (Level C).
- In adult patients receiving VNS for epilepsy, improvement in mood may be an additional benefit (Level C).
- VNS may be considered progressively effective in patients over multiple years of exposure (Level C).
- Optimal VNS settings are still unknown, and the evidence is insufficient to support a recommendation for the use of standard stimulation versus rapid stimulation to reduce seizure occurrence (Level U).
- Patients may be counseled that VNS magnet activation may be associated with seizure abortion when used at the time of seizure auras (Level C) and that seizure abortion with magnet use may be associated with overall response to VNS treatment (Level C).