Electrical source imaging and intracranial recordings in epilepsy: a prospective concordance study

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• dc.contributor.author Ley Nácher, Miguel
• dc.contributor.other Rocamora Zúñiga, Rodrigo Alberto
• dc.contributor.other Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida
• dc.date.accessioned 2025-06-19T05:40:46Z
• dc.date.available 2025-06-19T05:40:46Z
• dc.date.issued 2025-06-18T15:12:43Z
• dc.date.issued 2025-06-03
• dc.date.issued 2025-12-03T02:00:00Z
• dc.date.modified 2025-06-18T20:02:09Z
• dc.description.abstract Introduction: Epilepsy is a prevalent neurological disorder affecting a significant portion of the population (prevalence of 1%). Approximately one-third of epilepsy patients exhibit drug resistance, posing challenges for effective management. In this context, both focal and generalized drug-resistant epilepsies (DRE) require specialized evaluation and treatment approaches. Patients with focal DRE can benefit from resective epilepsy surgery. A critical step in this process involves thorough presurgical evaluation. Key components include and may involve: 1. MRI (Magnetic Resonance Imaging): Structural brain imaging to identify potential epileptogenic lesions; 2. Neuropsychological Testing (NPS): Assessing cognitive function and identifying brain regions associated with language, memory, and other functions; 3. Video-EEG (video-electroencephalography) Monitoring: Recording brain activity during seizures to pinpoint the seizure onset zone (SOZ); 4. Functional Neuroimaging: In selected cases, additional imaging techniques (such as 18FDG-PET or SPECT scans) may be necessary to map brain epileptogenic regions. 5. Intracranial Recordings: Invasive intracranial electrode monitoring to precisely localize the epileptogenic focus. For patients with generalized DRE, palliative techniques can provide relief. These approaches aim to reduce seizure frequency and improve quality of life (Noachtar & Borggraefe, 2009). While surgical resection may not be feasible for generalized epilepsies, other interventions (such as vagus nerve stimulation, ketogenic diets, and responsive neurostimulation) can be considered. Electrical Source Imaging (ESI) is a non-invasive neuroimaging technique used to localize the sources of electrical activity in the brain, particularly useful in the study of epilepsy. It involves recording electrical signals from the scalp using electroencephalography (EEG) and applying advanced mathematical algorithms, such as inverse solutions, to estimate the spatial origin of the brain's electrical activity. This method helps clinicians to localize the SOZ or other brain regions involved in pathological activity, contributing to the diagnosis, presurgical evaluation, and treatment planning for patients with epilepsy and other neurological disorders. ESI typically integrates EEG data with anatomical information from MRI scans, improving its accuracy by mapping the electrical sources onto the patient's specific brain anatomy. Over recent years, software packages like BESA® and CURRY® have emerged for ESI. These tools utilize scalp EEG and/or MEG data to localize the epileptogenic tissue. ESI assists in identifying critical regions, including the interictal epileptiform discharges (IEDs) zone and the SOZ. It aids in developing precise resection hypotheses. Recent research has explored combined techniques, such as simultaneous EEG, magnetoencephalography (MEG) (Grova et al., 2016; Murakami et al., 2016), and intracranial recordings. However, ESI alone has not undergone rigorous testing with exclusive electrical data and intracranial recordings to validate dipole localization using intracerebral electrodes. The primary goal of this doctoral thesis project is to rigorously assess the accuracy of interictal ESI of IEDs in conjunction with stereoelectroencephalography (SEEG). By validating the dipole generator localization, we aim to enhance our understanding of epileptogenic networks and improve presurgical planning. In summary, advancements in evaluation techniques and innovative imaging tools offer hope for better outcomes in epilepsy management. This research contributes to our ongoing efforts to optimize patient care and surgical decision-making. Objective: The primary goal of this study was to assess the concordance between two critical approaches in epilepsy research and diagnosis: ESI of the main cluster of IEDs and intracranial recordings (specifically SEEG). We also aimed to investigate the clinical utility of the main cluster of IEDs during the presurgical evaluation of DRE, to integrate it with direct cortical stimulation (DCS) during SEEG, and to compare it with functional neuroimaging techniques like 18 FDG-PET. By integrating these methods, we aim to enhance our understanding of epileptogenic networks and improve patient care. Materials and methods Participants: This study enrolled 33 patients diagnosed with DRE studied with simultaneous SEEG+ESI. The assessments were conducted at the epilepsy monitoring unit (EMU) of Hospital del Mar. By combining these techniques, we aim to improve our understanding of the networks involved in epilepsy and enhance clinical decision-making for this challenging patient population. Methods: After initial evaluations in the outpatient clinic, patients underwent detailed assessments, including MRI, NPS testing, and video-EEG. A specific group of these patients then received additional diagnostic procedures, such as 18FDG-PET, ictal/interictal SPECT integrated with MRI (SISCOM), functional MRI, Wada tests, and voxel-based morphometry (VBM). ESI was also conducted for these patients, and its findings were compared with other neuroimaging results. The clinical relevance of the primary cluster of IEDs was evaluated. A subset of these patients was further examined using simultaneous SEEG+ESI and DCS. The outcomes of these tests were analyzed using Cohen’s Kappa index and contingency tables and by comparing postsurgical outcomes based on the Engel Class. The effectiveness of ESI in identifying the primary cluster of IEDs during presurgical assessments was further explored and compared to the results from 18FDG-PET. Study design: Prospective cohort study followed by a retrospective review to assess the concordance and distribution of IEDs related to other neuroimaging modalities using the Cramer´s V, the agreement between ESI of IEDs and SEEG using validity measures, Cohen’s Kappa index and ROC curves, the utility of the DCS during SEEG using validity measures, and the clinical utility of the main cluster of IEDs during presurgical evaluation of DRE in comparison to 18FDG-PET scan. This investigation holds significant implications for advancing our understanding of epileptogenic networks and optimizing patient care. Results We demonstrated concordance between IEDs, as captured by ESI, and results from established imaging modalities such as MRI, 18FDG-PET, and SISCOM. This concordance was statistically significant, underscoring the value of ESI in aligning with and validating the findings from these traditional methods. We validated the precision of localization in mathematical models like Standardized Low Resolution Electromagnetic Tomography (SLORETA) and Standardized Weighted Low Resolution Electromagnetic Tomography (SWLORETA). These methods showed high concordance rates with MRI and functional imaging, emphasizing their reliability in pinpointing epileptogenic zones (EZ). This precision is crucial for accurately targeting therapeutic interventions in epilepsy treatment. The utility of ESI in surgical planning was another significant aspect of this thesis. We showed how ESI's capability to localize the main cluster of IEDs plays a vital role in delineating the EZ. The integration of ESI with SEEG was explored, which provided a more comprehensive understanding of the EZ. The highest Cohen’s Kappa Index was found between interictal ESI of IEDs for the Local Autoregressive Average (LAURA). Also,we found that the Standardized Shrinking Loreta Focuss (SSLOFO) and Classical Loreta Analysis Recursively Applied (CLARA) to be the most specific inverse solutions for detecting contacts involved in IEDs generation compared to SEEG. In this sense, LAURA, SWLORETA and SLORETA displayed the best ROC curves for detecting contacts without IEDs. This combination of non-invasive and invasive techniques proved optimal for enhancing surgical outcomes by offering a detailed view of the epileptic network. This work also assessed the added value of interictal ESI compared to 18FDG-PET. The findings indicated that while 18FDG-PET effectively identifies hypometabolic regions, ESI frequently includes the main cluster of IEDs within these regions. However, in some patients, the main cluster of IEDs, as demonstrated with SEEG, and later demonstrated with ESI, was localized out of the hypometabolic region. This highlights ESI's additional benefit in bridging the gap between metabolic and electrical abnormalities in the brain. Finally, the impact of ESI on surgical outcomes was rigorously evaluated, focusing on the utility of the main cluster of IEDs in the presurgical evaluation of patients with DRE. The precise localization and subsequent resection of these zones, as identified by ESI and localized with SEEG, were associated with transitioning patients to Engel Class Ia, indicating a successful surgical outcome with the patients achieving seizure freedom. Relevance Interpreting EEG results, considered the gold standard test for epilepsy diagnosis, can be intricate, especially in patients with DRE. To address this challenge, ESI employs various strategies to tackle the EEG inverse problem. The EEG inverse problem involves localizing the electro-anatomical brain source responsible for the in the scalp recorded electrical signals. ESI meticulously analyzes EEG data, considering multiple factors such as electrode placement, head geometry, and conductivity, to unravel the hidden sources. SEEG is the new gold standard and has recently emerged as the gold standard for intracranial recordings. SEEG involves implanting depth electrodes directly into the brain tissue, providing unparalleled spatial resolution. These electrodes capture neural activity at precise locations. Clinicians rely on SEEG to map the EZ, guiding treatment decisions and surgical planning. Testing ESI with SEEG complements SEEG by offering a non-invasive perspective. Integrating ESI with intracranial recordings could significantly enhance our understanding of epileptogenic tissue localization. By combining these modalities, we bridge the gap between surface EEG and deep intracranial recordings, refining our ability to pinpoint the elusive source of seizures. Clinical implications and future directions: The development of robust electrical source localization using intracranial recordings holds immense promise. In the presurgical workup of DRE patients evaluated for surgery, ESI can aid in designing implantation schemes and refining resection hypotheses. Collaborative efforts between ESI and SEEG pave the way for personalized treatment strategies, ultimately improving patient outcomes. In summary, the synergy between ESI and SEEG empowers clinicians to navigate the intricate neural landscape, unraveling the mysteries of DRE.
• dc.description.abstract Introduccion: La epilepsia es un trastorno neurológico prevalente que afecta a una parte significativa de la población (prevalencia del 1%). Aproximadamente un tercio de los pacientes con epilepsia presentan resistencia a los fármacos, lo que plantea desafíos para su manejo efectivo. En este contexto, tanto las epilepsias focales como generalizadas resistentes a fármacos (DRE) requieren enfoques especializados de evaluación y tratamiento. Los pacientes con DRE focal pueden beneficiarse de la cirugía resectiva de epilepsia. Un paso crítico en este proceso implica una evaluación prequirúrgica exhaustiva. Los componentes clave incluyen: Resonancia Magnética (MRI): Imágenes estructurales del cerebro para identificar posibles lesiones epileptogénicas. Pruebas Neuropsicológicas (NPS): Evaluación de la función cognitiva e identificación de regiones cerebrales asociadas con el lenguaje, la memoria y otras funciones. Video-EEG: Registro de la actividad cerebral durante las crisis para localizar la zona de inicio de las crisis (SOZ). Neuroimagen Funcional: En casos seleccionados, pueden ser necesarias técnicas de imagen adicionales (como 18FDG-PET o SPECT) para mapear regiones cerebrales epileptogénicas. Registros Intracraneales: Monitoreo invasivo con electrodos intracraneales para localizar con precisión el foco epileptogénico. En los pacientes con DRE generalizada, las técnicas paliativas pueden proporcionar alivio, reduciendo la frecuencia de las crisis y mejorando la calidad de vida (Noachtar & Borggraefe, 2009). Si bien la resección quirúrgica puede no ser factible para estas epilepsias, se pueden considerar otras intervenciones como la estimulación del nervio vago, dietas cetogénicas y neuroestimulación responsiva. Electrical Source Imaging (ESI): ESI es una técnica de neuroimagen no invasiva utilizada para localizar las fuentes de actividad eléctrica en el cerebro, especialmente útil en el estudio de la epilepsia. Consiste en registrar señales eléctricas del cuero cabelludo mediante electroencefalografía (EEG) y aplicar algoritmos matemáticos avanzados, como soluciones inversas, para estimar el origen espacial de la actividad eléctrica cerebral. Este método ayuda a los clínicos a localizar la SOZ u otras regiones cerebrales implicadas en la actividad patológica, contribuyendo al diagnóstico, la evaluación prequirúrgica y la planificación del tratamiento. En los últimos años, se han desarrollado paquetes de software como BESA® y CURRY® para ESI, que integran datos de EEG y/o MEG para localizar tejido epileptogénico. ESI ayuda a identificar regiones críticas, incluida la zona de descargas epileptiformes interictales (IEDs) y la SOZ, y desarrolla hipótesis precisas de resección. Este método, combinado con técnicas como registros intracraneales, ha mostrado potencial para mejorar la planificación quirúrgica y los resultados en el tratamiento de la epilepsia. Resumen: El objetivo principal de este estudio fue evaluar la concordancia entre ESI del principal grupo de IEDs y los registros intracraneales (específicamente SEEG). También se investigó la utilidad clínica del principal grupo de IEDs durante la evaluación prequirúrgica de DRE, integrándolo con la estimulación cortical directa (DCS) durante SEEG y comparándolo con técnicas de neuroimagen funcional como 18FDG-PET. Materiales y métodos: Participantes: Se incluyeron 33 pacientes con DRE estudiados con SEEG+ESI simultáneos, evaluados en la unidad de monitoreo de epilepsia (EMU) del Hospital del Mar. Métodos: Los pacientes fueron sometidos a evaluaciones detalladas que incluyeron MRI, NPS, y video-EEG. Un subgrupo recibió procedimientos adicionales como 18FDG-PET, SPECT ictal/interictal integrado con MRI (SISCOM), fMRI, pruebas de Wada, y morfometría basada en vóxel (VBM). Se realizó ESI para estos pacientes y sus hallazgos se compararon con otros resultados de neuroimagen. La relevancia clínica del grupo principal de IEDs se evaluó en comparación con resultados quirúrgicos basados en la Clasificación de Engel. Diseńo del estudio: Estudio prospectivo de cohortes seguido de una revisión retrospectiva para evaluar la concordancia y distribución de IEDs relacionadas con otras modalidades de neuroimagen, utilizando medidas de validez, índice de Kappa de Cohen y curvas ROC. Resultados: Se demostró concordancia estadísticamente significativa entre los IEDs capturados por ESI y los resultados de métodos de imagen tradicionales como MRI, 18FDG-PET y SISCOM. ESI mostró utilidad en la planificación quirúrgica al localizar con precisión la zona epileptogénica (EZ). Las técnicas de localización matemática como SLORETA y SWLORETA mostraron altas tasas de concordancia con MRI y neuroimagen funcional. Relevancia clinica y futura direcciones: La integración de ESI con SEEG representa una combinación poderosa para comprender redes epileptogénicas y personalizar estrategias de tratamiento, optimizando los resultados quirúrgicos y mejorando el cuidado del paciente.
• dc.description.abstract Programa de Doctorat en Biomedicina
• dc.format 177 p.
• dc.format application/pdf
• dc.identifier http://hdl.handle.net/10803/694686
• dc.identifier.uri http://hdl.handle.net/10230/70721
• dc.language.iso eng
• dc.publisher Universitat Pompeu Fabra
• dc.rights ADVERTIMENT. Tots els drets reservats. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.
• dc.rights info:eu-repo/semantics/embargoedAccess
• dc.source TDX (Tesis Doctorals en Xarxa)
• dc.subject.keyword Drug-resistant epilepsy
• dc.subject.keyword Electrical source imaging
• dc.subject.keyword 18FDG-PET
• dc.subject.keyword SISCOM
• dc.subject.keyword Stereotactic-EEG
• dc.subject.keyword Epilepsy surgery
• dc.subject.keyword Epilepsia farmacorresistente
• dc.subject.keyword Imágenes de fuente eléctrica
• dc.subject.keyword EEG estereotáctico
• dc.subject.keyword Cirugía de epilepsia
• dc.subject.keyword 616.8
• dc.title Electrical source imaging and intracranial recordings in epilepsy: a prospective concordance study
• dc.type info:eu-repo/semantics/doctoralThesis
• dc.type info:eu-repo/semantics/publishedVersion