Vagus nerve stimulation was approved in Europe in 1994 and in the United States and
Canada in 1997 for therapy of epilepsy, based upon pivotal trials in patients with partial and
secondarily generalized seizures in patients over 12 years of age
666768
. Retrospective
studies of 440 patients implanted for 2–3 years
69
and for greater than ten years
70
. VNS has
been shown to be effective for partial and secondarily generalized seizures in pediatric
populations
717273
. Small trials
74
have suggested efficacy of VNS for some generalized
seizures.
The clinical VNS device allows a noninvasive paddle held near the device to program
current intensity, individual pulse duration, pulse frequency, on-off cycle time and intensity
and duration of an extra pulse triggered by a magnet held over the stimulator. Tecoma and
Iragui
75
reviewed value of varying these stimulation parameters. Pulse width of 0.25 ms
may be better tolerated than those of 0.5, with similar efficacy, but 0.13 ms pulses are less
effective. Stimulation at frequencies below 20 per second may allow increased stimulation
of unmyelinated C-fibers, with more autonomic side effects. A controlled study of on-off
cycle durations (DeGiorgio
76
showed no differences in efficacy; however, some non-responders improved when the on-cycle was later increased. No stimulation parameter set
has yet been shown conclusively to be better than those used in the pivotal trials,
recognizing that individual patients may respond to various parameter changes.
Vagus nerve stimulation technology continues to be under development. Size of the device
is decreasing, such that the Demipulse device is smaller and has improved monitoring of
battery life
77
. High-field MRI has recently been shown safe, with a 3T GE Signa scanner
using a specific T/R head coil
78
, but more experience with safety is needed for other
systems. Externally rechargeable devices are under development, so the battery need not be
replaced every few years. Development of remote monitoring and telemedicine capabilities
for the vagus stimulator is in progress. The ADNS-300 stimulator system
79
can record VNS
compound action potentials, affording possible enhancement of understanding of the
physiology of vagus stimulation for epilepsy and perhaps better individualization of
stimulation parameters. Recording from the VNS also holds the possibility of early detection
or even anticipation of seizures. In rats with pentylenetetrazol-induced tonic seizures
80
, a
measure of energy in the nerve could be used to predict behavioral seizures. Some patients
benefit from using a magnet to turn VNS on at start of a seizure. A trial has begun at Ghent
University in Belgium of using ictal tachycardia to trigger stimulation
81
.
One retrospective study
82
found that unilateral interictal discharges, cortical dysplasia and
younger age were predictive of better outcomes. However, most reviews have concluded
that it is difficult to predict who will benefit from VNS
7075
. For that reason, external
stimulation paradigms are of interest as noninvasive screens for whether an implanted
stimulating device is likely to be of value. An auricular branch, called the Arnold nerve has
been hypothesized to be a potentially useful test stimulation site prior to device
implantation
83
. A randomized study of electroacupuncture for pain effectively used
stimulation at this superficial vagal auricular site
84
. Transcutaneous stimulation of the left
vagus nerve under the tragus of the ear was shown to influence MRI BOLD signals in the
left locus coeruleus, left thalamus, left cingulate, left insula, left prefrontal cortex, and
bilateral postcentral gyrus
85
. DeGiorgio
86
used superficial stimulation of the supraorbital
nerve to identify responders, who are implanted with a subcutaneous supraorbital nerve
stimulator. In an unblinded paradigm, seizure frequency was reduced relative to baseline by
66% at 3 months, 56% at 6 months and 59% at 12 months. Efficacy will need to be validated
in a larger controlled, blinded study.