Page 470 - ILAE_Lectures_2015

are only experienced by about 5–10% of patients in the open studies and may be subject to
publication bias24.

Interestingly, a mortality study by Annegers25 showed that the excess mortality associated
with refractory epilepsy was lower with longer-term follow-up (standardised mortality ratio,
or SMR, of 3.6 with extended follow-up compared to the previous finding of an SMR of 5.3).
Moreover, when VNS experience was stratified by duration of use, the rate of sudden
unexpected death in epilepsy (SUDEP) was 5.5 per 1000 over the first two years and 1.7 per
1000 thereafter. This finding was not, though, confirmed in a more recent study showing that
VNS did not appear to lower the risk of premature death or rate of SUDEP26.

In a cost analysis study27, unplanned direct hospital costs before and after VNS implantation
showed an annual reduction of some $3000 US per study patient, irrespective of whether the
patient was classified as a responder (in this study defined as experiencing 25% or greater
reduction in seizure frequency). Other studies have reported a significant decrease in
epilepsy-related direct medical costs in VNS-treated patients28 and recently a large study has
confirmed a progressive and substantial reduction in healthcare costs following implantation,
with the surgery and device costs being offset by the savings by 18 months29.

Special groups

There are many case series of the use of VNS in particular syndromes, often purporting
benefit that is not necessarily replicated in other studies. Notably, a recent review concluded
that VNS could not currently be recommended in refractory status epilepticus30. There does,
though, appear to be some evidence of specific benefit in Lennox-Gastaut Syndrome2,31 and
there are repeated reports of improvement in alertness and mood, most noticeable in those
with learning difficulty. Patients with learning difficulties, both adults and children, may
therefore be especially suitable for VNS insertion32.

Future advances

A potentially promising development in VNS technology is the development of the new
Aspire SR VNS device. Aspire SR is responsive to heart rate, giving an extra stimulation
when detecting ictal tachycardia. The device is somewhat larger than the previous model,
therefore requiring a larger skin incision, and intra-operative testing can take somewhat
longer. However, the possibility of automated additional stimulation at the onset of a seizure
would seem worthwhile, especially as this facility can be deactivated if necessary

Another novel development is of transcutaneous VNS. This stimulates the auricular branch
of the vagus, which supplies the skin of the concha of the ear, and is a non-invasive device.
Benefit has been shown to seizure profile in small studies and there are minimal reported
complications or side effects33,34. However, larger studies are needed to fully evaluate the
effect of transcutaneous VNS

Summary

VNS is now established as a safe procedure with clear, clinically useful and sustained
benefits, particularly in the medium to long term. It is recommended that VNS is considered
in patients with pharmacoresistant epilepsy who are not suitable for resective surgery. VNS
may have a particular benefit in patients with learning difficulties and may also offer benefit
to mood in patients with epilepsy. Caution however should still be exercised in older
populations with potential co-existing cardiopulmonary disease where experience is still
limited