Authors :
Presenting Author: Ramya Talanki Manjunatha, MD – 1. University of Texas Health Sciences Center at Houston 2. UAB, Montgomery
Yash Vakilna, MS – Neurology – University of Texas Health Sciences Center at Houston; Ganne Chaitanya, MD – Resident, Neurology, University of Texas Health Sciences Center at Houston; Emilia Toth, PhD – University of Texas Health Sciences Center at Houston; Nuria Lacuey, MD, PhD – Associate Professor, Neurology, University of Texas Health Sciences Center at Houston; Nitin Tandon, MD – Professor, Neurosurgery, University of Texas Health Sciences Center at Houston; Kristen Riley, MD – Professor, Neurosurgery, University of Alabama at Birmingham; Adeel Ilyas, MD – Resident, Neurosurgery, University of Alabama at Birmingham; Sandipan Pati, MD – Associate Professor, Neurology, University of Texas Health Sciences Center at Houston
Rationale:
In the realm of epilepsy research, understanding the brain regions responsible for seizure generation is paramount. The phenomenon known as "ictogenicity" refers to the propensity of certain brain regions to induce seizures. The term ictogenic is derived from the Greek word “ictus,” meaning a sudden attack, which describes a seizure. While progress has been made in exploring cortical excitability and its contribution to seizures, the role of deep subcortical structures, particularly the thalami, remains a mystery. Drawing inspiration from the work of Sir Wilder Penfield, who shed light on the diverse excitability of various cortical regions, we embark on a journey to explore the ictogenicity of the human thalami in focal and generalized epilepsies. This study marks the first-ever systematic evaluation of different thalamic nuclei, including the anterior nucleus (ANT), centromedian nucleus (CM), mediodorsal nucleus (MD), and pulvinar (Pul), using direct electrical stimulation (DES) in patients with epilepsy.
Methods:
DES mapping was performed with stimulation parameters categorized into three frequency groups: low (1-10 Hz), intermediate (50 Hz), and high ( >100 Hz). Our study encompassed two patient cohorts: Cohort A; Prospectively recruited patients with intractable focal epilepsies undergoing stereo EEG evaluation and had thalamic implantation, specifically targeting the ANT, CM, MD, or Pul, and Cohort B; Patients with intractable generalized epilepsies who had bilateral CM DBS or RNS. This cohort allowed us to explore the ictogenic potential of the CM thalami specifically in generalized epilepsies. A stimulation trial was considered positive if it evoked an electroclinical seizure and confirmed the ictogenicity of the stimulated structure. Furthermore, within Cohort A, we compared the ictogenicity of different cortical regions with that of the thalamic subnuclei. This analysis allowed us to discern the relative contributions of cortical and thalamic regions in seizure generation within the focal epilepsy subgroup.
Results:
We conducted DES mapping on a total of 40 patients, with 28 of them diagnosed with focal epilepsy. Among this group, stimulation at 50 Hz and 1 Hz of multiple cortical structures consistently evoked seizures. However, stimulation of the CM at 50 Hz triggered habitual seizures in only two subjects. In the generalized group, stimulation at lower frequencies of the CM resulted in frontal spike-wave discharges, but there was no clear clinical correlation. The evoked electrographic changes showed inconsistency and appeared to be influenced by the patients' prestimulation states of vigilance.
Conclusions:
Our findings highlight that while rare, the CM thalami can indeed trigger habitual seizures in patients with focal epilepsies. However, in the context of generalized epilepsies, we were unable to replicate the evoked absences as reported by Jasper et al in feline models. These results underscore the complexity of seizure generation in different epilepsy subtypes and emphasize the need for further investigations to elucidate the underlying mechanisms involved.
Funding: No funding.