A new strategy for treating drug-resistant focal aware seizures: thalamic specific nuclei deep brain stimulation. Illustrative case

Abstract

Background: Focal aware seizures (FASs) are relatively common and frequently pharmaco-resistant. If the seizure onset zone (SOZ) is in eloquent cortical areas, making resective surgery risky and inadvisable, deep brain stimulation (DBS) of the anterior nucleus of the thalamus, which is efficacious in less than half of the cases, has been the main alternative. New targets should be searched to address this deficiency. The present study aims to determine if DBS of different thalamic specific nuclei can modulate the abnormal electrical activity of the SOZ located in their respective cortical projection areas. Herein, the authors present the first patient in an ongoing trial.

Observations: A 60-year-old female patient presented with 25-year history of pharmaco-resistant focal aware visual seizures frequently evolving to focal impaired awareness seizures. The SOZ was in the right occipital lobe (positron emission tomography-computed tomography/video electroencephalography). Magnetic resonance imaging was normal. She underwent ipsilateral lateral geniculate nucleus (LGN) DBS procedure. After a 24-month follow-up, seizure frequency decreased by 97%, improving quality of life and daily functioning without complications.

Lessons: This is the first time the LGN has been targeted in humans. The results support the hypothesis that led to this study. This strategy represents a paradigm shift in the way of treating pharmaco-resistant FASs not amenable to resective surgery.

Keywords: deep brain stimulation; epilepsy; focal aware seizures; lateral geniculate nucleus; thalamic specific nuclei.

FIG. 1.

Preoperative sagittal (A), axial (B), and coronal (C) T2-weighted MR images obtained at the level of the calcarine sulcus, demonstrating no abnormalities. Tractography of the visual pathway (D) and the determination of the right LGN coordinates and trajectory planning on merged frameless proton density MR images and stereotactic CT images using Surgiplan software (Elekta). Axial MR image (E) obtained 4.0 mm below the anterior commissure–posterior commissure line, showing the superior colliculi, subthalamic nucleus, red nucleus, MGN, and LGN (green circle). Note the optic tract ending in the LGN. Coronal MR image (F) demonstrating trajectory planning along the major axis of the LGN (green circle), which is pointed superolaterally, while avoiding the sulci and the lateral ventricle. Postoperative sagittal (G), axial (H), and coronal (I) T2-weighted MR images confirming adequate placement of the electrode in the right LGN (white arrow).

FIG. 2.

Preoperative axial PET scans (A, B, and C) showing hypometabolism in the right occipital lobe. Postoperative axial PET scans (D, E, and F) demonstrating a further slight decrease of the metabolism in the right occipital lobe after surgery with high-frequency stimulation on (130 Hz).

FIG. 3.

A: Intraoperative scalp EEG with the patient awake and the electrodes placed only on the right side. Electrical stimulation (150 Hz, 1.0 msec, train duration of 2 seconds, 0.2 mA) of the right LGN induced the patient’s usual seizure (short-lasting), a blockage of the posterior alpha rhythm, and the recruitment of sustained ictal high-frequency activity projected over the right occipital region. B: Postoperative prolonged scalp EEG while performing test stimulation to determine the best stimulation settings. Low-frequency (but not high-frequency) monopolar stimulation, in general, induced a bilateral (right > left) recruiting response over the occipito-temporo-parietal regions characterized by high-frequency low-amplitude electrical activity. At this time, the following stimulation parameters were used: 0-C+, 60 μs, 30 Hz, 2.5 V.

FIG. 4.

Deterministic tractography obtained in a 3-T MRI scanner, showing the geniculocalcarine fibers in the right hemisphere. Note that the right primary visual area projects to the contralateral one through the splenium of the corpus callosum.