Abstracts

RATIONALE: Vagus Nerve Stimulation (VNS) is a novel adjunctive therapy used in patients with epilepsy refractory to pharmacological treatments. The vagus is a mixed nerve containing visceral afferent and efferent fibers. The anticonvulsant effect of the procedure is likely to be related to the stimulation of the afferent fibers that project to various brain regions via the brainstem. The effects of stimulation of the efferent fibers in patients with epilepsy are not known. Clinical studies have reported no significant effects that could be attributed to the peripheral effects of VNS. However, the efferent vagus is known to play important roles in parasympathetic autonomic regulation of the cardiac, gastrointestinal, and pancreatic activity. Pancreatic polypeptide (PP) is a newly discovered hormone released from the endocrine pancreas after ingestion of a meal via vagal-dependent mechanisms. Recent evidence suggest that the circulating PP may have important central actions including mediating the feedback neural control of the exocrine pancreatic function at the level of the brainstem, and modulating food intake in mice. Experimental studies have shown that stimulation of the vagus nerve by sham feeding increases the plasma concentrations of PP in humans. On the other hand, cooling of the nerve appears to reduce the plasma PP response to insulin infusions in dogs. The purpose of this study was to investigate a possible modulatory action of VNS on PP release in patients with intractable epilepsy.
METHODS: A total of 12 patients with intractable epilepsy were enrolled in the study. Fasting plasma samples were obtained from 6 patients 3-6 months after the initiation of VNS treatment, and from 6 comparable control patients treated with anti-epileptic drugs only. Plasma PP levels were measured, using a radioimmunoessay (Quest Diagnostics, Nichols Institute). A comparison of the levels between the VNS and control groups was made, using Student[scquote]s t test to determine statistically significant differences.
RESULTS: Mean ([plusminus] SEM) plasma concentration of PP was 124.7 [plusminus] 22.9 pg/ml in the control group, and 241.0 [plusminus] 48.5 pg/ml in the VNS group. Statistical analysis showed a trend (p [lt] 0.1)for higher concentration of PP in the VNS group.
CONCLUSIONS: These results suggest that VNS may increase PP release from the pancreas in patients with intractable epilepsy. PP has been found in the central nervous system, localized in neurons immuno-reactive for GABA, a neurotransmitter of prime importance in the neurochemical mechanisms of epileptogenesis. The contribution of the peripheral effects of VNS to its anticonvulsant action warrants further investigation.
Support: This study was supported by NIH NCRR GCRC Grant 5 MO1 RRO997.