“Worldwide Heterogeneity in Stereo-EEG Theory and Practice: Do all Roads Lead to Rome?”

Abstract

Investigating Current Clinical Opinions in Stereoelectroencephalography-Informed Epilepsy Surgery.

Thomas J, Abdallah C, Cai Z, Jaber K, Gotman J, Beniczky S, Frauscher B. Epilepsia. 2024 Sep;65(9):2662-2672. doi: 10.1111/epi.18076. Epub 2024 Aug 3. PMID: 39096434.

Objective: Stereoelectroencephalography (SEEG) is increasingly utilized worldwide in epilepsy surgery planning. International guidelines for SEEG terminology and interpretation are yet to be proposed. There are worldwide differences in SEEG definitions, application of features in epilepsy surgery planning, and interpretation of surgical outcomes. This hinders the clinical interpretation of SEEG findings and collaborative research. We aimed to assess the global perspectives on SEEG terminology, differences in the application of presurgical features, and variability in the interpretation of surgery outcome scores, and analyze how clinical expert demographics influenced these opinions. Methods: We assessed the practices and opinions of epileptologists with specialized training in SEEG using a survey. Data were qualitatively analyzed, and subgroups were examined based on geographical regions and years of experience. Primary outcomes included opinions on SEEG terminology, features used for epilepsy surgery, and interpretation of outcome scores. Additionally, we conducted a multilevel regression and poststratification analysis to characterize the nonresponders. Results: A total of 321 expert responses from 39 countries were analyzed. We observed substantial differences in terminology, practices, and use of presurgical features across geographical regions and SEEG expertise levels. The majority of experts (220, 68.5%) favored the Lüders epileptogenic zone definition. Experts were divided regarding the seizure onset zone definition, with 179 (55.8%) favoring onset alone and 135 (42.1%) supporting onset and early propagation. In terms of presurgical SEEG features, a clear preference was found for ictal features over interictal features. Seizure onset patterns were identified as the most important features by 265 experts (82.5%). We found similar trends after correcting for nonresponders using regression analysis. Significance: This study underscores the need for standardized terminology, interpretation, and outcome assessment in SEEG-informed epilepsy surgery. By highlighting the diverse perspectives and practices in SEEG, this research lays a solid foundation for developing globally accepted terminology and guidelines, advancing the field toward improved communication and standardization in epilepsy surgery.

Commentary

If you are reading this commentary, chances are that epilepsy surgery, and hence stereo-electroencephalography (SEEG), is near and dear to your heart. If you are a trainee rotating through the intracranial monitoring service, you may have found yourself struggling to differentiate between seizure onset and its early propagation. If you are an epileptologist or neurosurgeon participating in the multidisciplinary epilepsy surgery conference, you may have found yourself contemplating the necessity of an additional electrode and its trajectory. If you are a general neurologist or allied health care provider or scientist attending an epilepsy conference, you may have found yourself puzzled with the debate around the epileptogenic zone definition and the best way to identify it. Guess what; as this article ¹ suggests, you are not the only one!

Epilepsy surgery has been operationalized since the second half of the 20th century. Historically, two divergent schools of thought have guided generations of trainees dispersed around the world: the Franco-Italian school of the epileptogenic “network,” championed by Bancaud and founded predominantly on SEEG investigations, and the Anglo-Saxon school of the seizure “focus,” championed by Lüders and founded predominantly on subdural electrodes investigations. ² Due to its advantages in investigating deep-seated epileptogenic zones, and its better tolerability and safety profile, ³ SEEG has gradually prevailed as the most popular tool of intracranial EEG monitoring. ⁴ Yet, its worldwide adoption has not been accompanied by analogous standardization. ⁵

This article ¹ examined the global perspectives about the theoretical underpinnings and practical applications of SEEG. By surveying 321 experts from 39 countries, the authors identified remarkable heterogeneity in SEEG concepts and habits. While most experts agreed upon the significance of ictal findings over interictal findings, the value of seizure onset patterns and the scales used for surgical outcomes, there was a dichotomy between mere seizure onset versus seizure onset plus early propagation, when a definition of the seizure onset zone was requested. Although more than 2/3 of the experts aligned with the Lüders definition of the epileptogenic zone, approximately 1/3 of them were confused about the distinction between the seizure onset zone and the epileptogenic zone, and another 14% of them were unsure if they were confused! Not surprisingly, there was no consensus opinion on an alternative terminology. Despite occasional geographical preferences, there were no major discrepancies based on responders’ demographics, beyond those attributed to local training and practice patterns. Similar trends were also identified when correcting for nonresponders with a regression analysis. ¹

This is a commendable research endeavor as it investigated the spectrum of beliefs and applications of a visionary methodology that enjoyed peaked appreciation and somewhat anarchical expansion over the past decade. As such, it lays the groundwork for standardization. The major advantage of the study ¹ was the focus on experts in the field of SEEG and the wide representation over several continents, increasing the survey's credibility and participation rate. The survey was designed according to well-accepted research standards, and it was piloted by a subgroup of authors. It was distributed both in a targeted fashion as well as through leading organizations in the field with broad outreach. The content incorporated conceptual aspects of SEEG, in addition to practical applications related to recording parameters, interpretation, and outcome ascertainment. The collection of detailed demographics allowed for evaluation of regional associations among the responders and for further analysis of potential bias related to the nonresponders. ¹

Nevertheless, there are inescapable drawbacks to acknowledge. Although the emphasis was on expert epileptologists in the field, that was defined as at least 6 months of specialized training in SEEG and the majority were engaged in 1–2 SEEG cases per month, resulting inevitably in a diverse spectrum of expertise. Some of the questions were open to variable interpretation or did not have mutually exclusive answers. Certain aspects of SEEG utilization (eg adult vs pediatric, in isolation or in combination with other evaluations), implantation planning (eg neurosurgeon vs epileptologist vs both, number, type, and direction of electrodes, use of multimodal imaging, etc), implantation management (eg frame-based or robotic-assisted approaches, intraoperative electrocorticography, electrodes nomenclature and coregistration, choice of reference and montaging, addition of scalp electrodes, stimulation timing and parameters, nursing care, safety measures, medication management and activation maneuvers, duration of monitoring, etc), explantation (eg bedside vs in the operating room, follow-up imaging) and intervention (eg type and timing) were not explicitly investigated. As is commonly the case with surveys, responses may have been predominantly derived by those inherently biased towards the use of that technology compared to alternatives, and the responses may have been skewed towards mentorship directives and institutional traditions.

Notwithstanding these limitations, this survey ¹ highlights the striking variability in SEEG practice around the world. That has been also demonstrated in prior literature that focused on similar evaluations of SEEG related practices at a national^4,6 or international ⁷ level. Why is this important? After all, there are many ways to achieve a goal and what really matters is whether one of them does it more efficiently. The peril, though, with the rapid and untamed adoption of SEEG practice is its relegation from a philosophy to a technique, with potentially detrimental repercussions in its safety and efficacy. Rather than focusing on deconstructing anatomo-electro-clinical correlations through carefully thought-out, custom-made, three-dimensional cerebral exploration, ⁸ the risk of a cultural shift towards reckless fishing expeditions with an array of depth electrodes is lurking. Standardizing this process through well-accepted guidelines can partially prevent this predicament by means of setting clear indications and limits on the planning and execution of SEEG implantations, the technical requirements, management, and interpretation of the recordings and associated procedures, as well as interventions before and after explantation. ⁹ Technical and clinical standardization should be paralleled with structured training of newer adoptees of this methodology in the spirit of its founding fathers, and it should foster international, multi-institutional research collaborations to improve our understanding of the derived signals. ⁵ Hopefully, such developments will eventually translate into better seizure outcomes, increased referrals for and improved access to epilepsy surgery worldwide. ¹⁰

Yet, guidelines can only address common denominators, and an unyielding, resource-demanding and technologically-intensive strategy cannot be universally mandated. ⁴ Standardization should not be synonymous with a rigid, cookie-cutter approach. SEEG can be biased by electrode sampling and is full of challenges, quandaries and controversies ⁸ ; hence, it should be practiced with an open mind and a broader dialogue of shared experiences. ⁵ The debate on the epileptogenic zone should surpass etymology ² and focus on reliable, easy-to-use, readily and freely available tools to identify it. ¹¹

Regardless of which theoretical or practical framework is applied, the ultimate judge of success is seizure freedom and improved quality of life postoperatively. Getting to that Rome is the goal, but if you lose or misuse your SEEG compass, some roads may not lead to it!