Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox‐Gastaut syndrome

Abstract

We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox-Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype) trial. Methods: Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM-DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range = 10-34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity [GPFA] and slow spike-and-wave [SSW]) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM-DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events. Results: GPFA was captured in eight of 12 patients (total event number across patients = 168, cumulative duration = 358 seconds). Eighty-six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98 milliseconds (interquartile range = 78.5 milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75 milliseconds (interquartile range = 228 milliseconds). One to 0.5 seconds and 0.5-0 seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1-3 Hz) frequency band. For alpha (8-12 Hz) and beta (13-30 Hz) frequencies, PTE was greatest 1-0.5 seconds before GPFA onset. Significance: Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEGfunctional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.

Ictal Electroencephalographic Characteristics of Nodding Syndrome: A Comparative Case‐Series from South Sudan, Tanzania, and Uganda

“…We found that there is a statistically significant increase in gamma frequency that could be recorded on scalp EEG during the ictal period of head drops, a phenomenon that has been reported in other developmental and epileptic encephalopathies 9,11 . The presence of diffuse ictal cortical high frequency rhythms suggest recruitment of a widely distributed epileptic network, involving multifocal cortical areas and deep brain structures including thalamus and brainstem as reported in infantile spasms and Lennox–Gastaut syndrome 15 , 16 …”

DBS of Thalamic Centromedian Nucleus for Lennox–Gastaut Syndrome (ESTEL Trial)

“…16,18 All surgeries were performed under a modified anesthetic regimen combining intravenous remifentanil (0.1-0.3μg/kg/min) with inhalational isoflurane (0.5-0.7%), permitting intra-operative simultaneous EEG recordings from the thalamus and scalp. 19 Up to 1 day postoperatively, a brain computed tomography (CT) scan was acquired to confirm accurate DBS electrode positioning. DBS lead contact positions were established by coregistering postoperative CT to pre-operative MRI scans (see Fig 2).…”

“…The CM was identified preoperatively on patients’ 3T magnetic resonance imaging (MRI) scans using a magnetization‐prepared 2‐rapid‐gradient‐echoes (MP2RAGEs) sequence that was post‐processed using Sobel filtering to highlight intrathalamic borders, together with the 3‐dimensional Krauth/Morel thalamic atlas 17 that was nonlinearly spatially warped to each patient's brain 16,18 . All surgeries were performed under a modified anesthetic regimen combining intravenous remifentanil (0.1–0.3μg/kg/min) with inhalational isoflurane (0.5–0.7%), permitting intra‐operative simultaneous EEG recordings from the thalamus and scalp 19 . Up to 1 day postoperatively, a brain computed tomography (CT) scan was acquired to confirm accurate DBS electrode positioning.…”

Successful Hemispherotomy in a Patient with Encephalopathy with Continuous Spikes and Waves during Sleep Related to Neonatal Thalamic Hemorrhage: A Case Report with Intracranial Electroencephalogram Findings

“…However, controversy remains regarding whether the trigger of the epileptic seizures lies in the thalamus or cortex. For example, Dalic et al recently analyzed EEG findings in patients with Lennox-Gastaut syndrome (LGS) with simultaneous recordings from depth electrodes placed in the thalamic centromedian nucleus (CM) and scalp electrodes and found that most of the onsets of generalized fast activities were observed earlier in the scalp electrodes, whereas the onset of slow spikes and waves were variable [15]. Velasco et al analyzed the EEG onset of various types of seizures observed in patients with LGS using the depth electrodes placed in the CM and scalp electrodes and reported that the onset of generalized tonic, tonic-clonic, and atypical absence seizures occurred simultaneously in the CM and cortex; however, the EEG onset of myoclonic seizures was observed earlier in the CM [16].…”