Abstracts

RATIONALE: Studies have shown that changes in respiratory patterns may have powerful effects on brain excitability by through end-tidal CO2 alterations. Recent reports have documented that vagal nerve stimulation (VNS) may have significant effects on respiration. With this background, we examined the effects that VNS may have on end-tidal CO2, through changes in respiratory patterns.
METHODS: We studied 14 patients (10 males; age range 17-55 years) with medically refractory epilepsy who were undergoing VNS therapy. All subjects were studied during daytime sleep in an outpatient setting. The patients underwent a polygraphic recording that consisted of a 10 channel EEG, ECG, electrooculogram, nasal airflow monitoring by thermocouple, and capnograph with nasal probe. Activation of the VNS device was monitored with an ECG lead so placed that the stimulation-induced artifact was clearly discernible. VNS parameters included current flows that ranged from 2.00-3.50 milliamperes. In all cases current flow was [dsquote]on[dsquote] for 30 sec, [dsquote]off[dsquote] for 5 min. The capnographs automatically measured end-tidal CO2 (EtCO2) and respiratory frequency (RF) with a nasal probe. Capnographic data were analyzed visually and consistency of changes in EtCO2 was assessed. In subjects with consistent drops in EtCO2 the average values of EtCO2 and RF were taken from points before and after VNS, as well as the highest/lowest peaks during VNS. One patient was excluded from analysis because of severe sleep apnea and 3 excluded from analysis of changes in EtCO2 because of severe snoring in one case (resulting in unreliable EtCO2 nasal measurements), inability to achieve sleep in another case, and constant aperiodic breathing in the third case that made association with VNS epochs unreliable.
RESULTS: Of the 10 subjects with reliable CO2 recordings, 5 showed clear and consistent drops in EtCO2 with simultaneous increases in RF, with maximal CO2 decreases ranging from 5-22% during VNS epochs. Three patients had occasional decreases in EtCO2 during VNS epochs and two others showed no VNS related CO2 changes. Twelve of the patients patients showed alterations in respiratory patterns (rhythm, amplitude, etc) that often varied considerably. There were no consistent changes in EEG, ECG, or heart rate related to VNS activation.
CONCLUSIONS: This study provides evidence that VNS may exert significant physiological effects in some patients by reducing CO2 through respiratory mechanisms. We speculate that this may be lead to intermittent, transient mild changes in neuronal excitability, and by modulating the early pre-ictal stages, such reductions may participate in the antiepileptic effects of VNS.
[Supported by: Finnish Academy, Finnish Cultural Foundation, Arvo and Lea Yippo Foundation, the University of Washington Regional Epilepsy Center.]