Abstracts

Rationale: Epilepsy is associated with hyperexcitability and glutamatergic excitotoxicity and neuronal damage. Transcranial focal electrical stimulation (TFS), applied through tripolar concentric ring electrodes (TCREs) shows positive results in preclinical models of seizure activity. Indeed, TFS decreased glutamate over-release in a preclinical model of status epilepticus (Santana-Gomez et al. 2015) and was safe in rats. To translate to humans, we developed a computer human head model to determine TFS parameters needed to activate human cortex from the scalp. For this pilot study, we investigated TFS long-term effects on expression of seizure activity in patients with epilepsy. We also investigated the acute effect of TFS on the glutamate over-release in synaptic terminals obtained from patients with drug-resistant epilepsy (DRE) submitted to surgery. Electroencephalography (EEG) was recorded with TCREs (tEEG).


Methods: The computer model showed that 45 mA would modulate cortex of humans. Patients (n=6) with focal epilepsy were recruited for both studies. In study one, the patients came to the Institute of Neurology and Neurosurgery five weekdays for four weeks. The patients received 5-minutes of TFS each day. Seizure counts were compared, pre-,during-, and post-TFS. In study two, EEG recordings were made for 15-minutes and stimulated prior to surgical resection of the epileptic focus. After resected, the tissue was used to obtain synaptic terminals (synaptosomes). Synaptosomes were divided in two fractions, to estimate by HPLC the glutamate release under basal conditions and with addition of KCL. The tEEG and EEG were processed to produce spectrograms as well as power spectrums.

Results: Three patients were stimulated prior to surgery over the region that was to be resected and three different patients have completed the month-long TFS protocol. The TFS did not cause any seizures, pain, headaches, or adverse events. The average number of seizures of the three patients the month prior to starting the study was 7.7. The first- and second-months post TFS averages were 9.7 and 5, respectively. One of the three patients only had one seizure during the three months of the study and had four seizures the month prior to entering the study. These three patients reported some somnolence after TFS. In two of the three surgical patients we were able to record 15-minutes of EEG. The power spectrums pre-TFS have high power in the high-frequencies whereas post-TFS the high-frequencies are attenuated immensely. For the tissue analysis, the average basal glutamate release was 105 nmol/mg and for the KCl induced release it was 50 nmol/mg.


Conclusions: The TFS was safe and tolerable. The EEG shows that TFS modulated brain activity to lower frequencies. The average seizure count decreased the second month after TFS. Acute exposure to TFS avoids the glutamate over-release evoked by high KCL from cortical synaptic terminals obtained from patients with DRE. This finding suggests that TFS reduces the hyperexcitability of the epileptic tissue.


Santana-Gómez et al. Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus, Epilepsy & Behav, 2015


Funding: None