Deep Brain Stimulation for Treatment of Refractory Epilepsy
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.310083
Source of Support: None, Conflict of Interest: None
Keywords: Anterior nucleus of the thalamus, centromedian nucleus of the thalamus, deep brain stimulation, hippocampus, refractory epilepsy
Deep brain stimulation has been increasingly used in the treatment of refractory epilepsy and consists in the delivery of electrical current into brain structures with the purpose of modulating different pathological circuits. Efficacy of DBS for refractory epilepsy depends on the target and time of stimulation, as it appears to improve overtime. The ANT has been shown to be most efficacious for limbic seizures due to its connections in the Circuit of Papez, as well as the HIP for temporal seizures. Diversely, the CM is advocated for generalized seizures, as it diffusely modulates cortical excitability, mainly through reticulo-thalamic projections.
This video intends to describe the techniques for the surgical planning of DBS implantation in the three most widely used targets in epilepsy: the ANT, the CM, and the HIP, respectively.
Video Link: https://youtu.be/T2Z7Dn1vgTQ
Video timeline with audio transcript:
0.0–0.08 s: Titles and Introduction. The following video describes the techniques to target the three most widely used structures to treat refractory epilepsy.
0.08–0.20 s: Our first target is the ANT. The first step in planning when targeting a deep structure is to co-register the MRI sequences with the stereotactic CT.
0.21 s–1.08 min: To visualize the target, the most used sequences are STIR and T2, as the one demonstrated here. Due to great anatomical variability among subjects, indirect target should be avoided. The structure to be identified is the point where the mamilothalamic tract (MTT) enters the ANT, as this area is related to better outcomes. If one goes back and forth on the coronal slices, it is possible to distinguish first the mamillary bodies (MB), and then the MTT, as confirmed on the axial and sagittal views.
1.09–1.23 min: It is of extreme importance to address the vessels near the target as they may limit the trajectory when implanting the electrode.
1.24–1.50 min: The burr hole for entering the cortex is placed 1.5 to 3 cm lateral from the midline and 1 cm in front of the coronal suture, but these may be adjusted according to the safest trajectory. One should avoid major vascular structures and superficial and deep sulci.
1.51–2.37 min: Two approaches may be used when targeting the ANT: the paraventricular and the transventricular. The first, the paraventricular one, has the advantage of going lateral and not through the ventricle. However, as it has a very lateral entry point, it is more challenging to correctly position the electrode inside the nucleus, on the sweet spot. Therefore, we rather choose the transventricular one, as it is easier to place the interspace of the two center contacts on the target.
2.38–3.16 min: After the trajectory and the entry point are defined, it is necessary to go down from the cortex to the parenchyma to identify the main vessels that will be encountered. The first vessel is the callosomarginal artery, which may limit the trajectory medially. After the ventricle is entered, there are the lateral striatal vein, laterally, and the superior choroidal vein, medially.
3.17–4.14 min: Our next target is the CM, which is a thalamic nucleus of the intralaminar group. As it is not directly visualized on the MRI, it is necessary to identify the anterior (AC) and posterior commissures (PC) in order to define the target. After fusing the T1 sequence with the stereotactic CT, the AC is visualized on the anterior wall of the third ventricle and the PC, right above the aqueduct. It is also necessary to choose a midline point to correct the alignment of the images.
4.14–4.28 min: The CM is located 10 mm lateral from the PC, at the level of the AC-PC line.
4.29–5.08 min: Once again, the burr hole for entering the cortex is placed 1.5 to 3 cm lateral from the midline and 1 cm in front of the coronal suture, but adjustments may be needed to avoid superficial and deep sulci and major vascular structures.
5.09–5.39 min: Therefore, after defining the entry point, it is necessary to ensure no major vessel is crossed along the trajectory.
5.40–7.20 min: The last target is the HIP, and this structure is readily visualized on MRI slices. Therefore, it can be targeted with direct anatomical methods. To identify it, a T1 MRI sequence with contrast is used. The first step when planning is to define an anterior point at the most anterior part of the HIP head on the coronal slice. The following step is to determine a posterior point at the middle of the HIP body on the sagital view. After defining these two points, they are connected to generate a posterior entry point. This trajectory generally covers most of the HIP formation except from the tail, as it curves posteriorly and medially.
7.21–7.41 min: A hard cannula, as the one used for the ANT and CM, ensures not only an adequate electrode route, but also penetration within hardened structures as the sclerotic HIP.
7.42–8.23 min: After defining the entry point, it is necessary to ensure no major vascular structure or superficial and deep sulci are crossed along the trajectory. Thank you.
8.24–8.30 min: References.
Surgical planning of deep nuclei is a very detailed procedure and all steps should be carefully considered. It is essential to have a satisfactory fusion of the stereotactic CT and MRI to obtain a high level of correlation among structures. For targets that can be directly visualized on MRI images, indirect coordinates and stereotactic atlas may be used to further delineate lead position, but should not be trusted as a solely approach. During trajectory planning, sulci and vessels should be strictly avoided to reduce complications risk.
The ANT is a thalamic nucleus located in its most rostral and dorsal area. It is separated from the other thalamic nuclei by the anterior Y-shaped internal medullary lamina. The inputs from the hippocampus arrive through the postcommissural fornix, directly or through the mamilothalamic tract (MMT). The exact position of the ANT in the stereotactic space is highly variable, although its theoretical coordinates are 12 mm superior, 5-6 mm lateral and 0-2 mm anterior to the midcomissural point. The most reliable way to target the ATN, though, is by direct visualization of the MMT, which is located slightly inferior to the center of the nucleus, as seen on short tau inversion recovery (STIR) or magnetization prepared gradient echo (MPRAGE) MRI sequences.
Adequate location of the electrode's contacts is mandatory to achieve satisfactory results, and the two most superior contacts should be located inside the nucleus. Although some centers advocate placement of the lead in the anterosuperior aspect of the nucleus, others have demonstrated better outcomes when the active contact is near the anterior center of the ANT, 5 mm lateral to the wall of the third ventricle, or at the junction of the ANT and the MTT. The trajectory of the lead may also correlate with results and, due to the shape and position of the ANT, the transventricular approach proved to be more efficacious than the extraventricular one.
The CM is part of the intralaminar thalamic nuclei and displays widespread connections with the cerebral cortex, limbic circuit and basal ganglia. It appears to behave as a gateway to modulate cortical excitability through various projections, such as the reticulothalamocortical system. Its targeting is carried out using indirect coordinates (at the level of the posterior commissure, 10 mm lateral from midline), as it is not visualized on CT or standard MRI sequences. However, contemporary techniques to improve delineation of the nucleus are under investigation and demonstrate promising results, as the use of quantitative susceptibility mapping reconstructed from a 3D multi-echo gradient recalled echo (GRE) sequence. Final electrode position appears to be a predictive factor for better outcomes, as seen when contacts are positioned at the anterosuperior aspect of the ventrolateral CM.,
The position of the HIP within the Papez circuit makes it an appealing target for the treatment of mesial temporal lobe epilepsy (MTLE) and animal studies have shown the efficacy of hippocampal stimulation in decreasing epileptic activity.,, The location of the active contacts may correlate with clinical response and a precise targeting is essential for a satisfactory outcome. T1 MRI coronal slices perpendicular to the HIP axis are used to localize the most anterior part of its head, followed by the identification of another point in the middle of its body in the sagittal view. The resulting line is used to determine the entry point at the occipital bone.
DBS is a promising therapy for the treatment of well-selected epilepsy patients who are not candidates for resective surgery. The ANT, CM, and HIP are the most explored targets to date. Careful surgical planning and a precise placement of the electrode are crucial for satisfactory outcomes.
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