Combined nerve stimulation linked to greater seizure reductions in LGS
Two-year data tied dual therapy to larger reductions than either device alone
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Vagus nerve stimulation and deep brain stimulation use electrical signals to influence brain networks involved in seizures. (Photo from iStock)
Two nerve-stimulating devices, vagus nerve stimulation (VNS) and deep brain stimulation (DBS), were associated with similar reductions in seizure frequency over two years in people with Lennox-Gastaut syndrome (LGS), according to a Mayo Clinic study.
At two years, however, combined DBS and ongoing VNS was associated with greater seizure reductions than either treatment alone, the data showed.
The study, “Comparative Seizure Outcomes of Vagus Nerve Stimulation, Deep Brain Stimulation, and Their Combination in Lennox–Gastaut Syndrome,” was published in Annals of Neurology.
Nerve-stimulation devices offer options beyond medication
LGS is a severe form of epilepsy that begins in childhood. It is marked by several types of seizures and commonly causes intellectual disability, movement difficulties, behavioral problems, and sleep disturbances.
Because LGS is often resistant to anti-seizure medications, doctors may use other treatments, including nerve-stimulation devices such as VNS and DBS. VNS sends electrical pulses through the vagus nerve in the neck to broadly influence brain activity, whereas DBS uses electrodes placed in specific brain regions to disrupt the spread and synchronization of seizures.
However, data directly comparing the two treatments remain limited, and it is unclear whether keeping VNS active after DBS is added offers any extra benefit.
To address this gap, researchers examined the medical records of 40 patients with LGS who received VNS, DBS, or both at the Mayo Clinic between 2005 and 2024.
Before receiving a device, study participants had tried a median of seven anti-seizure medications, and most (75%) had tried the ketogenic diet. At the time of device implantation, patients were having a median of 150 seizures per month.
Median reductions in seizure frequency were 16.2% vs. 50% in the VNS and overall DBS groups, respectively, at six months; 47.2% vs. 57.1% at one year; and 50% vs. 59.2% at two years. The overall DBS group included patients receiving DBS alone and those receiving DBS with ongoing VNS.
No significant differences in seizure reduction were observed between the two groups at any time point.
Likewise, responder rates — the proportions of patients whose seizure frequency fell by at least 50% from the relevant baseline — were 30.8% with VNS vs. 63.6% with DBS at six months, 46.4% vs. 59.1% at one year, and 53.8% vs. 60% at two years. The difference was statistically significant only at six months.
Combined therapy linked to greater seizure reductions
After two years, LGS patients who received both DBS and ongoing VNS had a notably higher median seizure reduction of 81% compared with 43% for DBS alone and 50% for VNS alone. The responder rate for the combined group also stayed high throughout the study, reaching 89% at two years, compared with 54% for VNS alone and 36% for DBS alone.
Before treatment, drop attacks were reported during 76% of treatment periods. These sudden falls can be particularly disabling in LGS. After treatment, patients had no further falls in 41% of those treatment periods, with similar rates across the three groups: 40% with VNS alone, 30% with DBS alone, and 56% with combined DBS and VNS. Four patients remained seizure-free for more than a year, with seizure-free periods ranging from one to five years.
Looking more closely at individual outcomes, the combined DBS and VNS group showed the clearest improvement over time. At two years, more than half (55.6%) of patients with available data in this group had fewer than 10 seizures per month, compared with none in the DBS-alone group and 7.7% in the VNS-alone group.
This shift mainly reflected patients going from daily to weekly seizures, having more seizure-free days, and no longer experiencing seizure clusters. The researchers also found that adding DBS was associated with improvement in some patients who had not responded well to VNS alone. In one patient, seizures worsened when VNS was temporarily turned off and improved after it was turned back on.
Among patients who received DBS, seizure reduction did not differ based on which part of the brain was targeted. In a small exploratory analysis, DBS was associated with a median seizure reduction of 81% for focal seizures, which begin in a specific area of the brain, compared with 48% for VNS.
Medication use remained stable across treatment groups
Most patients stayed on a stable number of anti-seizure medications throughout the study, regardless of which device they received. Researchers found no evidence that any patient characteristics, including the underlying cause of a patient’s epilepsy, were linked to seizure-reduction outcomes.
Side effects were infrequent and included one VNS lead fracture, two mechanical complications involving DBS leads that restricted neck movement, and temporary hoarseness or coughing with VNS that improved after the device settings were adjusted. One patient in the VNS group died from an unrelated medical cause.
The team noted that patients in both DBS-treated groups had previously tried more anti-seizure medications than those who received VNS alone, suggesting that their epilepsy may have been more difficult to treat.
Overall, the researchers concluded that “Both VNS and DBS are associated with comparable, meaningful seizure reduction over a 2-year follow-up period. Combined DBS [plus] VNS therapy was associated with further improvements in seizure reduction.”
