Precipitation and inhibition of
seizures and epileptic discharges by sensory stimuli are receiving increasing attention because they provide insight into natural seizure generation in human
epilepsies and can identify potential nonpharmacological
therapies. We aimed to investigate modulation (provocation or inhibition) of epileptiform discharges (EDs) in mesial
temporal lobe epilepsy (MTLE) versus
idiopathic generalized epilepsy (
IGE) by olfactory stimulation (OS) compared with standard provocation methods. The underlying hypothesis was that any response would be more likely to occur in MTLE, considering the anatomical connections of the temporal lobe to the olfactory system. This multicenter, international study recruited patients with either MTLE or
IGE who were systematically compared for responses to OS using an EEG/video-EEG protocol including a 30-min baseline, twice 3-min olfactory stimulation with ylang-ylang,
hyperventilation, and intermittent photic stimulation. The 95% confidence interval (CI) for the baseline EDs in each patient was calculated, and modulation was assumed when the number of EDs during any 3-min test period was outside this CI. A total of 134 subjects (55 with MTLE, 53 with
IGE, and 26 healthy controls) were included. Epileptiform discharges were inhibited during OS in about half the patients with both MTLE and
IGE, whereas following OS, provocation was seen in 29.1% of patients with MTLE and inhibition in 28.3% of patients with
IGE. Olfactory stimulation was less provocative than standard activation methods. The frequent subclinical modulation of epileptic activity in both MTLE and
IGE is in striking contrast with the rarity of reports of
olfactory seizure precipitation and arrest. Inhibition during OS can be explained by nonspecific arousal. The delayed responses seem to be related to processing of olfactory stimuli in the temporal lobe, thalamus, and frontal cortex.