The vagus nerve is the 10th cranial nerve. More
than 80% of the fibers of the vagus nerve are afferent sensory fibers,
terminating in the nucleus tractus solitarius (NTS) and carrying
information to the brain from the neck, thorax, and abdomen. Vagal
afferents project bilaterally to the noradrenergic and serotonergic
neuromodulatory systems of the brain and spinal cord via the NTS.
The NTS is a main gateway and processing point for information entering
the brain in the vagus nerve and in multiple other cranial and peripheral
nerves.
Several mechanisms may explain the antiseizure
effects and other beneficial effects of vagus nerve stimulation
(VNS) Therapy™. Multiple actions of VNS Therapy are supported
by research in animal models of epilepsy and human brain anatomy
as well as human electroencephalogram, cerebrospinal fluid, and
functional brain imaging research.2,3,4,5
These studies offer insight as to the possible,
multiple mechanisms of action of VNS Therapy:
- The locus coeruleus (LC) may be involved in anticonvulsant
effect of VNS Therapy6
VNS Therapy demonstrated an anticonvulsant effect in rats
against maximal electroshock. However, after chronic and acute
chemical lesioning of the LC, VNS Therapy was no longer effective.
This study also suggested that the effect of VNS Therapy may require
norepinephrine release, a neuromodulator that has anticonvulsant
effects.
- VNS Therapy induces progressive EEG changes2
In humans, VNS Therapy resulted in the clustering of epileptiform
activity followed by progressively increased periods of spike-free
intervals.
- Significant bilateral changes in blood flow have been observed
during VNS Therapy5
In a study by Henry TR et al, 10 patients with epilepsy had
positron emission tomography (PET) measurements taken before and
during stimulation with VNS Therapy. The results demonstrated
bilateral changes in brain blood flow with stimulation. Bilateral
increased blood flow was seen in the thalamus, the hypothalamus,
and the insular cortex. Bilateral decreased blood flow was seen
in the amygdala, the hippocampus, and the posterior cingulate
gyri.
- Increased blood flow in the thalamus has been shown to have
significant correlation with long-term seizure control7
In a follow-up study, Henry et al reported that decreased
seizures correlated with increased right and left thalamic blood
flow (P<0.001) during VNS Therapy. The time-course of PET imaging
in this study analyzes the period of time during a train of VNS Therapy.
Conclusions from studies in animal models have
demonstrated various effects of VNS Therapy:
- Acute, abortive effects8
VNS terminates seizures when applied after seizure onset
- Acute, prophylactic effects9
Seizure frequency and severity are reduced between trains
of VNS
- Chronic, progressive prophylactic effects10
Seizure frequency and severity are further reduced after chronic,
long-term VNS
- Adjunctive VNS Therapy can add antiseizure effects to any AED
regimen1
Current understandings of the therapeutic
mechanisms strongly support the “common sense” interpretation
of the clinical studies: adjunctive VNS can add antiseizure effect
to any AED regimen, with no interactive toxicity, and no effect
on drug distribution and elimination.
Henry, 2002
1Henry TR. Neurology.
2002;59(suppl 4):S3-S14.
2Koo B. J Clin Neurophysiol. 2001;18:434-441.
3Sucholeiki R, et al. Seizure. 2002;11:157-162.
4Van Laere K, et al. J Nucl Med. 2002;43:733-744.
5Henry TR, et al. Epilepsia. 1998;39:983-990.
6Krahl S, et al. Epilepsia. 1998;39:709-714.
7Henry TR, et al. Neurology. 1999;52:1166-1173.
8McLachlan R, et al. Epilepsia. 1993;34:918-923.
9Takaya M, et al. Epilepsia. 1996;37:1111-1116.
10Lockard JS. Epilepsia. 1990;31(suppl 2):S20-S26.
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