Olfactory stimulation induces delayed responses in epilepsy

Abstract

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.

Behavioral and EEGraphic Characterization of the Anticonvulsant Effects of the Predator Odor (TMT) in the Amygdala Rapid Kindling, a Model of Temporal Lobe Epilepsy

“…Taken together, the results of this study are associated to the multinational research consortium Epilepsies with External Modification of Ictogenesis ( EpExMo ), aimed at collaborating with the knowledge associated to basic mechanisms and clinical features of epilepsy inhibited or triggered by external sensory or cognitive stimuli. Our current experiments are in fact absolutely coherent with previous studies ( 7 , 8 , 15 – 18 , 20 , 57 , 90 – 92 ), adding consistent data to the literature. Furthermore, our findings certainly represent a partial component that will collaborate to the understanding of efficacy of odorants in the seizure response, with potential translational impact.…”

“…The latter report was strongly supported by our experimental findings, confirming the TOL anticonvulsant effects, in the acute and chronic (kindled) audiogenic seizures, in Wistar Audiogenic Rat (WAR) animals (18). Conversely, the induction of seizures by olfactory stimulation has also been reported, in both animal models and in the clinic (19)(20)(21)(22). In fact, the neurophysiological mechanisms of both anti-and pro-convulsant modulations are little understood.…”

Intense olfactory stimulation blocks seizures in an experimental model of epilepsy

“…At present, the neurophysiological mechanisms and the knowledge needed to understand epilepsy treatment with odorants are still unknown [29]. In that direction, our current findings add to the limited data of the literature which indicate that the olfactory stimulation modulates the epileptic activity, suppressing or inhibiting it [9,10,20,[26][27][28][29][30][31][32]43].…”

“…The involvement of olfactory structures with TLE is known for quite some time [20,21]. Some studies have shown that olfactory sensations could indicate the paroxystic seizure onset in patients with TLE, a symptom described as aura [20][21][22][23][24], and that the peripheral sensory stimulation, such as an olfactory stimulus is able to modulate those seizures: suppressing or inhibiting [9,10,20,[25][26][27][28][29][30][31][32] or even inducing them, such as in the reflex epilepsies [29,[33][34][35][36][37][38][39][40][41][42].…”

Epilepsy and the Sensory Systems

“…However, a recent systematic investigation of the effect of olfactory stimuli on epileptiform EEG discharge revealed delayed responses in the minutes following exposure to an aromatic smell in about one-half of the patients. These responses were bi-directional (14): in IGE, they were inhibitory twice as often as excitatory, whereas in TLE, the relation was the reverse (40).…”