Targeting the centromedian thalamic nucleus for deep brain stimulation

Warren, Aaron E. L.; Dalic, Linda J.; Thevathasan, Wesley; Roten, Annie; Bulluss, Kristian J; Archer, John S.

doi:10.1101/19008136

Cited by 15 publications

(33 citation statements)

References 39 publications

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“…Each patient underwent bilateral CM‐DBS electrode insertion using our previously described neurosurgical targeting approach 13 . Briefly, a Medtronic Activa PC system with Medtronic model 3389 leads (4 × 1.5‐mm contacts per lead, 0.5‐mm intercontact distance) was implanted under stereotactic guidance (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, a Medtronic Activa PC system with Medtronic model 3389 leads (4 × 1.5‐mm contacts per lead, 0.5‐mm intercontact distance) was implanted under stereotactic guidance (Figure 1). The CM was identified preoperatively on patients’ 3‐T MRI scans using a magnetization‐prepared two‐rapid‐gradient‐echoes sequence that was processed using Sobel filtering to highlight intrathalamic borders, together with a three‐dimensional thalamic atlas 14 that was nonlinearly spatially warped to each patient's brain (for detailed methodological description, refer to Warren et al 13 ). All surgeries were performed under a modified anesthetic regimen combining intravenous remifentanil (0.1‐0.3 µg/kg/min) with inhalational isoflurane (0.5%‐0.7%).…”

Section: Methodsmentioning

confidence: 99%

“…DBS lead trajectories were reconstructed by coregistering postoperative CT to preoperative MRI scans using lead‐DBS software version 2.1.8.1 15 . Thalamic locations of DBS electrodes were determined by warping patients’ CT‐reconstructed lead trajectories to Montreal Neurological Institute 152 2009b template space, and then assigning each electrode to the nearest thalamic nucleus defined by the Krauth/Morel thalamic atlas 13,14 …”

Section: Methodsmentioning

confidence: 99%

“…15 Thalamic locations of DBS electrodes were determined by warping patients' CT-reconstructed lead trajectories to Montreal Neurological Institute 152 2009b template space, and then assigning each electrode to the nearest thalamic nucleus defined by the Krauth/Morel thalamic atlas. 13,14 T A B L E 1 Clinical and EEG characteristics of 12 adults with Lennox-Gastaut syndrome who underwent deep brain stimulation surgery…”

Section: Eeg Recordingsmentioning

confidence: 99%

“…For every identified discharge, PTE was measured in three brain states, each defined with respect to the discharge onset ( Figure 3): "preonset" state (spanning −1 to −0.5 seconds prior to discharge onset), "onset" state (spanning −0.5 seconds prior to discharge onset to the onset time, defined as 0 seconds), and "event" state (spanning 0 seconds to +0.5 seconds postonset). Pathways analyzed were Fp2 R CM, F8 R CM, T2 R CM, T4 R CM, and T6 R CM, where R CM was the EEG signal generated by only the subset of right-sided thalamic contacts that were confirmed by postoperative CT scans to be located within the CM 13 (Figure 1).…”

Section: Effective Connectivity Measured Using Ptementioning

confidence: 99%

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

et al. 2020

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Eeg Recordingsmentioning

confidence: 99%

Section: Effective Connectivity Measured Using Ptementioning

confidence: 99%

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

et al. 2020

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Using chronic recordings from a closed‐loop neurostimulation system to capture seizures across multiple thalamic nuclei

Kundu

Arain

Davis

et al. 2022

Ann Clin Transl Neurol

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We report the case of a patient with unilateral diffuse frontotemporal epilepsy in whom we implanted a responsive neurostimulation system with leads spanning the anterior and centromedian nucleus of the thalamus. During chronic recording, ictal activity in the centromedian nucleus consistently preceded the anterior nucleus, implying a temporally organized seizure network involving the thalamus. With stimulation, the patient had resolution of focal impaired awareness seizures and secondarily generalized seizures. This report describes chronic recordings of seizure activity from multiple thalamic nuclei within a hemisphere and demonstrates the potential efficacy of closed‐loop neurostimulation of multiple thalamic nuclei to control seizures.

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

Dalic

Warren

Bulluss

et al. 2021

Annals of Neurology

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Objective Prior uncontrolled studies have reported seizure reductions following deep brain stimulation (DBS) in patients with Lennox–Gastaut syndrome (LGS), but evidence from randomized controlled studies is lacking. We aimed to formally assess the efficacy and safety of DBS to the centromedian thalamic nucleus (CM) for the treatment of LGS. Methods We conducted a prospective, double‐blind, randomized study of continuous, cycling stimulation of CM‐DBS, in patients with LGS. Following pre‐ and post‐implantation periods, half received 3 months of stimulation (blinded phase), then all received 3 months of stimulation (unblinded phase). The primary outcome was the proportion of participants with ≥50% reduction in diary‐recorded seizures in stimulated versus control participants, measured at the end of the blinded phase. A secondary outcome was the proportion of participants with a ≥50% reduction in electrographic seizures on 24‐hour ambulatory electroencephalography (EEG) at the end of the blinded phase. Results Between November 2017 and December 2019, 20 young adults with LGS (17–37 years;13 women) underwent bilateral CM‐DBS at a single center in Australia, with 19 randomized (treatment, n = 10 and control, n = 9). Fifty percent of the stimulation group achieved ≥50% seizure reduction, compared with 22% of controls (odds ratio [OR] = 3.1, 95% confidence interval [CI] = 0.44–21.45, p = 0.25). For electrographic seizures, 59% of the stimulation group had ≥50% reduction at the end of the blinded phase, compared with none of the controls (OR= 23.25, 95% CI = 1.0–538.4, p = 0.05). Across all patients, median seizure reduction (baseline vs study exit) was 46.7% (interquartile range [IQR] = 28–67%) for diary‐recorded seizures and 53.8% (IQR = 27–73%) for electrographic seizures. Interpretation CM‐DBS in patients with LGS reduced electrographic rather than diary‐recorded seizures, after 3 months of stimulation. Fifty percent of all participants had diary‐recorded seizures reduced by half at the study exit, providing supporting evidence of the treatment effect. ANN NEUROL 2022;91:253–267

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Targeting the centromedian thalamic nucleus for deep brain stimulation

Cited by 15 publications

References 39 publications

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

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

Using chronic recordings from a closed‐loop neurostimulation system to capture seizures across multiple thalamic nuclei

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

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