Abstracts

Rationale: Temporal lobe epilepsy is a chronic neurological disorder characterized by a high resistance to pharmacological treatments. Transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) is a non-invasive experimental proposal to treat pharmacoresistant epilepsy. The present study aims to investigate the effect of transcranial focal electrical stimulation (TFS) applied via tripolar concentric ring electrodes (TCRE) in responsive and preventive manner on electrical amygdaloid kindling (AK) in freely moving cats.Methods: Nine adult cats were stereotaxically implanted in both amygdalae (AM) and prefrontal cortices (PFC). Additionally, in preventive-TFS group (n=3), one TCRE was placed over the vertex and in the responsive-TFS group (n=3), over the temporal bone ipsilateral to the kindled AM. Daily AK (60 Hz, 1 ms monophasic square pulses for 1 s) was applied until all animals reached three consecutive kindling stage VI. In preventive-TFS group, TFS (300 Hz, 200 ms biphasic square pulses) was delivered for 40 minutes prior to AK. In responsive-TFS group, TFS was administered for 2 minutes after the AK onset for 40 days, then only AK was applied. Control group only received AK stimulation. Sepectral power analysis was performed from both PFC and AM and band-pass filtered in frequency bands (1-4 Hz, 4-9 Hz, 10-14 Hz and 15-30 Hz).Results: Responsive-TFS treated animals reached AK stage VI after 84.3±4.25 stimulations, Preventive-TFS treated animals 25.33±3.75 and Control animals were fully kindled after 26.66±1.20 AK stimulations. Responsive-TFS application over the epileptogenic area significantly retarded the fully-kindled state compare to control and Preventive-TFS (P<0.05). Also, significantly delayed the progression of behavioral AK seizure stages (P<0.05) and decreased the afterdischarge duration during kindling acquisition (P<0.05). This suppressive effect was so strong that treated animals remained at focal seizure stages for the next 20 days after the TFS cessation, and needed a three-fold number of AK stimulations to reach the fully-kindled state. Preventive-TFS administration over vertex do not protect against epileptogenesis induced by AK in cats. In addition, preventive administration of TFS produced a continued decrease in postictal spectral power, mainly in high frequency bands of secondarily generalized seizures, that last less than 24 hours.Conclusions: TFS via TCRE applied during seizures over the epileptogenic area reduces the seizures severity and retards epileptogenesis in cats, while TFS application before the seizures onset, exhibits long seizures duration and an augmented postictal depression. These findings indicate the potential therapeutic effect of TFS against inctractable epilepsy in humans, as do the neurostimulation techniques currently used in clinic, but with the advantage of its non-invasive application.