A study at Emory University has shown that vagus nerve stimulation (VNS therapy), the only FDA-approved, implantable, electrical stimulation therapy for epilepsy, may activate many areas of the brain for longer periods - up to months or longer - than previously thought. The researchers measured neuronal activity before and after long-term VNS, and found more seizures were reduced when higher levels of stimulation were used. The results are published in the September issue of the journal Epilepsia.
Epilepsy is a chronic neurological disorder that produces brief disturbances in the normal electrical functions of the brain, causing recurrent seizures. More than 2.5 million Americans suffer from the condition. Patients who suffer from partial seizures (seizures that begin as electrical discharges in a small part of the brain), who do not respond well to antiepileptic medications, and who are not suitable for brain surgery to reduce seizures are all good candidates for VNS.
"Based on an earlier study of VNS, we measured regional synaptic activity and cerebral blood-flow (CBF) before beginning stimulation and then again within the first 20 hours of stimulation," says Thomas Henry, MD, professor of neurology, Emory University School of Medicine. "Then we looked again at synaptic activity and CBF after three months of VNS. By comparing the two, we were able to determine what parts of the brain changed in information processing and just how effective VNS can be immediately following stimulation and for longer periods of time."
Using positron emission tomography (PET) scans, 10 Emory patients were scanned before receiving stimulation and then again within 20 hours of treatment (immediate-effect study). The scans were repeated three months later (prolonged study). Half of the participants received high levels of stimulation (stimulation on more than off), while the other half received low levels of stimulation (stimulation off more than on).
In the immediate-effect study, cerebral blood flow changes showed increased synaptic activity in the so-called "sensory strip" of the brain's cortex, which was expected because the patients felt mild sensations during stimulation. Interestingly, VNS also activated the thalamus and other brain areas that are involved in memory, thinking, alertness, arousal and emotional processing. With higher levels of stimulation, blood flow was increased more than at low stimulation in these areas.
In the prolonged study, researchers again found CBF changes were similar between the high and low stimulation groups, but the volumes of significant changes in synaptic activity tended to be larger in the high stimulation group. Participants in each stimulation group showed some sites had significant VNS-induced CBF change, both in the immediate-effect study and prolonged study. But in general, the volumes of significant VNS-induced CBF change were reduced after three months of VNS versus the volumes of significant CBF change that occurred acutely. During prolonged studies, CBF changes were not observed in any regions that did not have CBF changes during immediate-effect studies. The thalamus, which is considered a major center of anti-seizure effects of VNS, was activated both in the immediate-effect and the prolonged studies.
Throughout the first three months of VNS, the frequency of seizures decreased by 25 percent in the entire epilepsy group. Mean seizure frequency decreased by 35 percent in the high stimulation group and by 15 percent in the low stimulation group. "These findings show that CBF changes in various areas of the brain help in reducing seizures when activated by VNS," Dr. Henry explains. "Some types of seizures start in the thalamus, but this research suggests that we may be able to control widespread seizures that begin in other areas of the brain with VNS."