Elsevier

World Neurosurgery

Volume 139, July 2020, Pages e70-e77
World Neurosurgery

Original Article
Variability Between Direct and Indirect Targeting of the Anterior Nucleus of the Thalamus

https://doi.org/10.1016/j.wneu.2020.03.107Get rights and content

Background

Preoperative thalamic targeting methods have historically relied on indirect targeting techniques that do not fully account for variances in anatomy or for thalamic atrophy in epilepsy. We aimed to address variability noted between traditional indirect targeting and direct targeting methods for the anterior nucleus of the thalamus (ANT).

Methods

Fifteen consecutive patients undergoing ANT deep brain stimulator placement were evaluated (30 thalamic nuclei). Direct ANT targeting was performed using a fast gray matter acquisition T1 inversion recovery sequence and compared with standard stereotactic coordinates. Thalamic volumes were calculated for each patient, and degree of thalamic volume loss was assessed compared with matched control subjects. Vertex analysis was performed to assess shape changes in the thalamus compared with age- and sex-matched subjects.

Results

There was significant variation between direct and indirect targets in the y-axis and z-axis on both sides. On the left, the direct target was located at y = 2 ± 1.3 mm and z = 9.3 ± 1.8 mm (both P = 0.02). On the right, the direct target was located at y = 2.9 ± 1.8 mm and z = 9.2 ± 2 mm (both P ≤ 0.0003). There was no significant difference in the x-coordinate on either side (P > 0.5). Additionally, there was a correlation between thalamic volume and difference between direct and indirect targets in the y-axis and the z-axis.

Conclusions

We showed a significant difference in direct and indirect targeting in the y-axis and z-axis when targeting the ANT for deep brain stimulation for epilepsy. This difference is correlated to thalamic volume, with a larger difference noted in patients with thalamic atrophy.

Introduction

Epilepsy affects 65 million people globally; approximately one-third have drug-resistant epilepsy and can be potentially helped with surgical interventions.1 Within this group is a subset of patients who are not ideal candidates for resective/ablative procedures, such as patients with seizure onset that is focal but in eloquent cortex, patients with multifocal seizure onset zones, or patients with generalized epilepsy. These patients are potentially candidates for neuromodulation,2,3 which includes therapies such as vagus nerve stimulation, responsive neurostimulation, chronic subthreshold cortical stimulation, and deep brain stimulation (DBS). DBS of the anterior nucleus of the thalamus (ANT) has recently received approval in the United States by the Food and Drug Administration and continues to gain acceptance as an effective treatment modality. However, there is little available information about what makes this therapy most effective.4 Evidence suggests that indirect targeting of the ANT for epilepsy is associated with varying precision that may affect clinical efficacy.5,6

Preoperative thalamic targeting methods have historically relied on indirect targeting mainly because individual thalamic nuclei are not well resolved with traditional neuroimaging methods. Standard target points can be identified in reference to universally applied coordinates to the anterior commissure–posterior commissure (AC-PC) line by using atlas-based methods or stereotaxy-based approaches. The variability of patient anatomy relative to imaging required adjunctive techniques, such as microelectrode recording to verify accurate lead placement in DBS. However, for ANT, microelectrode recordings are not particularly helpful for localization.7 In contrast, recently developed imaging techniques can improve localization of ANT.

Direct imaging-based targeting has been shown to be a viable alternative to indirect targeting methods for patients with movement disorders in most, but not all, cases.8 We have previously described a similar technique to directly target the ANT for patients with medically refractory epilepsy,9,10 which is especially helpful in cases of thalamic atrophy that occurs in patients with epilepsy.11 The mammillothalamic tract (MMT) terminates in the inferior one-third of the ANT and provides an ideal means of direct targeting. The MMT is a dense fiber tract that can be well imaged.12,13 This study aimed to systematically quantify the variability between traditional indirect and direct imaging-based targeting methods for the ANT in patients in whom an ANT deep brain stimulator for epilepsy was ultimately implanted.

Section snippets

Materials and Methods

A retrospective analysis of a consecutive series of patients with refractory epilepsy who underwent ANT DBS was approved by the institutional review board with a waiver of informed consent. All patients had undergone bilateral ANT deep brain stimulator placement following a consensus decision made at a multidisciplinary epilepsy review. Inclusion criteria included preoperative volumetric T1-weighted magnetic resonance imaging (MRI) for assessment of thalamic volumes and high-resolution fast

Results

Fifteen patients (30 thalamic nuclei) met inclusion criteria. The average age of patients was 32.2 ± 14.1 years (range, 18–71 years), and 56.3% were male. The mean duration of epilepsy was 15.6 ± 10.3 years (range, 2–36 years). Mean number of seizures per month was 42.8 ± 75.9 (range, 4–240). Of 15 patients, 11 had multifocal onset and the remaining 4 had generalized epilepsy. Six patients had positive MRI findings, including 3 with periventricular heterotopia, 2 with polymicrogyria, and 1 with

Discussion

Our results show significant differences in targeting of the ANT when using direct targeting versus a fixed stereotactic indirect coordinate. In particular, there were significant differences in the y-axis and z-axis compared with indirect targeting that were correlated with thalamic volume loss. Differences in the y-axis and z-axis suggest a pattern of regional atrophy in the anterior dorsal and posterior ventral thalamus (Figure 4). Recognition of the variability in ANT location in patients

Conclusions

Our data show that there is a significant difference in direct and indirect targeting in the y-axis and z-axis when targeting the ANT in patients with epilepsy Differences between targeting methods is also significantly correlated with thalamic volume. Such dependence of target location on thalamic volume highlights the potential value of direct targeting in ANT DBS, as thalamic atrophy is a common finding in epilepsy.

CRediT authorship contribution statement

Sanjeet S. Grewal: Conceptualization, Methodology, Writing - original draft, Writing - review & editing. Erik H. Middlebrooks: Conceptualization, Methodology, Visualization, Writing - original draft, Writing - review & editing. Lela Okromelidze: Methodology, Writing - review & editing. Grant P. Gosden: Data curation, Writing - review & editing. William O. Tatum: Conceptualization, Writing - review & editing. Brian N. Lundstrom: Conceptualization, Writing - review & editing. Gregory A. Worrell:

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      Such generalization of targeting does not fully account for variation in brain anatomy between patients. As an example, for ANT targeting, significant variation was present between indirect target coordinates and direct visualization of the nucleus in both the y-axis and z-axis, which correlated with thalamic volume (Grewal et al., 2020). As previously discussed, regional atrophy and shape change of the thalamus in people with epilepsy, related to the brain network(s) involved by seizures can significantly impact targeting and likely contribute to variation in outcomes.

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      ANT stimulation reduces seizure frequency in medically refractory patients,49-53 and new evidence suggests that the structural changes may also affect accuracy of surgical targeting in ANT DBS, as well as its efficacy. Grewal et al.54 have shown that variability between direct and indirect stereotactic coordinates was different in ANT DBS and dependent on the degree of thalamic atrophy. In addition, Wang et al.55 have shown that when ANT was stimulated, hippocampal sclerosis eliminated the presence of evoked potentials in the hippocampus, and this process correlates with poor ANT DBS response.

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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