Stereoelectroencephalography (SEEG) forms a key part of the pre-surgical evaluation in children who may be candidates for epilepsy surgery. It can help delineate the location of the putative epileptogenic zone, guiding further treatments including resective, disconnective and ablative epilepsy surgery techniques. However, less than 35% of children undergoing SEEG end up becoming seizure free following further treatment. Open and closed loop stimulation of thalamic nuclei via deep brain stimulation (DBS) and responsive neurostimulation (RNS) are emerging treatment options for epilepsy. Thalamic target nuclei vary between studies and there are currently no gold standard personalised methods for choosing a target. This stems from the limited systematic neurophysiological recordings from thalamic nuclei; investigators currently do not understand the ictal and interictal thalamic signatures of involvement in epilepsy and do not understand how functional connectivity can be altered within and between patients. In this prospective study, the investigators aim to recruit 30 patients undergoing SEEG as part of their pre-surgical evaluation for drug resistant epilepsy at Great Ormond Street Hospital over a period of 3 years. Once recruited, the investigators will target 3 nuclei bilaterally in each patient - the anterior, centromedian and pulvinar nuclei - using additional SEEG electrodes. Following clinical recording, the investigators will conduct two stimulation experiments, the first using single pulse electrical stimulation to measure effective connectivity between the thalamus and cortical regions and the second to study the effects of simulated DBS currents on cortical local field potential signatures. This study will lay the foundation for a personalised approach to thalamic neuromodulation for drug-resistant epilepsy by identifying neurophysiological biomarkers of thalamic involvement in epilepsy, paving the way for closed loop neuromodulation strategies that aim to optimise response using these biomarkers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
30
The centromedian, anterior and pulvinar nuclei on each side will be chosen as target for new electrodes; up to 6 additional electrodes may be added but, where possible, existing electrode trajectories will be extended to facilitate recording. At the beginning of the recording process, usually within the first 24-48 hours of implantation, we will conduct 2 study-specific stimulation experiments: 1. Single pulse electrical stimulation (SPES): 2. N-of-1 trials of simulated DBS: We will simulate high (130Hz) and low (6Hz) frequency DBS currents from each pair of thalamic nuclei (always bilateral) and record spontaneous interictal neuronal activity in all other cortical contacts for 15 minutes. We will also record SPES from each of the cortical contacts.
Great Ormond Street Hospital for Children
London, United Kingdom
RECRUITINGIctal thalamic involvement
Experienced neurophysiologists will assess, during ictal activity, whether each of the nuclei are involved in the seizure and, if so, the latency between first cortical contact onset and thalamic nucleus onset.
Time frame: Hospital discharge (maximum one month from SEEG implantation)
Epileptogenicity index
We will quantify ictal involvement by measuring the epileptogenicity index in each nucleus.
Time frame: Hospital discharge (maximum one month from SEEG implantation)
Interictal power distribution
To assess interictal signatures, we will assess power at different frequencies in the nuclei using the 'fitting oscillations \& one over f' (FOOOF) method.
Time frame: Hospital discharge (maximum one month from SEEG implantation)
Single pulse electrical stimulation (SPES):
We will systematically conduct SPES from all cortical and thalamic contacts and record responses in all other contacts. This measures the effective connectivity.
Time frame: Hospital discharge (maximum one month from SEEG implantation)
Incidence of bleeding
Radiological evidence of bleeding or clinically new neurological symptoms during SEEG implantation
Time frame: Hospital discharge (maximum one month from SEEG implantation)
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