Authors :
Presenting Author: Erica Von Stein, MD – Stanford University
Michael Povlow, MD – Stanford University
Eric van Staalduinen, DO – Stanford University
Michael Zeineh, MD, PhD – Stanford University
Vivek Buch, MD – Stanford University
Ann Hyslop Segeren, MD – Stanford Medicine Children’s Health
Roger Chang, MD, PhD – Stanford University
Robert Fisher, MD, PhD – Stanford University
Rationale:
The nucleus reticularis thalamus (nRT) is a thin shell comprised of GABAergic neurons surrounding the dorsal thalamus. nRT receives predominantly glutamatergic inputs from the cortex, subcortical structures, and other thalamic neurons, and sends GABAergic outputs to thalamic relay nuclei, generating both strong and weak inhibitory post-synaptic currents. This circuitry modulates thalamocortical rhythms such as sleep-related potentials and epileptiform spike-waves.
Although prior animal research has primarily focused on the role of nRT in generalized seizures, the powerful inhibitory actions of nRT also position it to play a role in propagation of focal seizures through the thalamus. Few studies have examined the physiology of nRT in humans, and none of these were specifically in patients with epilepsy. In this preliminary study, we used intracranial EEG recordings from patients undergoing presurgical evaluation to determine the participation of nRT in focal electroclinical seizures. This work aims to identify novel thalamic targets for neuromodulation in refractory epilepsy.
Methods:
This retrospective study was approved by the Stanford Institutional Review Board (IRB). An epileptologist reviewed intracranial EEG recordings from 10 medically refractory epilepsy patients who had implanted depth electrodes (5 mm contact spacing) targeting the anterior (ANT) or the centromedian (CM) nucleus of the thalamus, with trajectory traversing near nRT. Neuroradiologists determined which electrode contact was closest to nRT using thin-cut postoperative brain CT co-registered with 3 Tesla MRI. Despite having a shell-like structure, nRT was visualized using FGATIR and/or FSPGR sequences and the distance to nearest electrode contact was measured.
Results:
Across the 10 subjects (5 female, 5 male) there were 41 focal seizures analyzed. In 98% of focal seizures, the electrode contact closest to nRT (average distance 1.7 mm, range 0.0 - 4.0 mm) exhibited activity temporally corresponding to discharges at the seizure onset zone. This activity in the vicinity of nRT occurred earlier than seizure propagation to ANT/CM in 24% of seizures. In 43% of focal seizures and 50% of patient cases, the ictal nRT activity appeared to be distinct in frequency, morphology, and evolution from the adjacent channels, suggesting involvement beyond volume conduction. The average time from first ictal EEG pattern at the seizure focus to distinct ictal activity in nRT was 7 seconds (range 0 - 22 seconds). nRT ictal onset patterns included rhythmical slow spikes, bursts of beta spikes, and rhythmical alpha or theta frequencies. Distinct nRT activity was seen with seizure onsets localizing to the left hippocampus, left amygdala, left insula, right posterior cingulate, and right superior temporal sulcus.
Conclusions:
These findings provide novel evidence that nRT may play a role in focal seizure networks in humans. This preliminary work supports further investigation into nRT neuromodulation as a therapeutic strategy for focal - and possibly generalized or multifocal - seizure management.
Funding:
None.