Epilepsy from a network perspective
[eng] Epilepsy, as stipulated by the ILAE, is a neurological disease marked by and enduring condition that ensures the persistence of epileptic seizures. It is a very heterogenous disease, with a variety of etiologies, disease course and response to treatment. This study delves into the potential im...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/214617 |
| Acceso en línea: | https://hdl.handle.net/2445/214617 http://hdl.handle.net/10803/691799 |
| Access Level: | acceso abierto |
| Palabra clave: | Neurologia Neurocirurgia Epilèpsia Ressonància magnètica Neurology Neurosurgery Epilepsy Magnetic resonance |
| Sumario: | [eng] Epilepsy, as stipulated by the ILAE, is a neurological disease marked by and enduring condition that ensures the persistence of epileptic seizures. It is a very heterogenous disease, with a variety of etiologies, disease course and response to treatment. This study delves into the potential improvement of TLE, one of the most prevalent forms of epilepsy, through surgical intervention, while also exploring the associated costs and implications. For patients with TLE whose seizures remain uncontrolled despite drug treatment, surgery can significantly reduce seizure frequency and, in many cases, even lead to a cure. However, surgery can come with risks, and some patients may not experience improvement after the procedure or may encounter cognitive and psychiatric complications. Predicting which patients will benefit the most from surgical intervention has been a challenging task. In recent years, adopting a perspective that views TLE as a condition affecting neuronal networks has yielded some advancements in our ability to predict surgical outcomes. With the aim of predicting the response to surgery of patients with TLE at the individual level in the different domains (seizure recurrence cognitive impairment, motivational deficits), our methodology primarily encompassed the utilization of two advanced neuroimaging modalities: DTI and rs-fMRI. These techniques offer a non-invasive means to comprehensively gauge the structural and functional connectivity of the entire brain. Our data was sourced from a cohort of TLE patients who were deemed candidates for surgical intervention due to the non-efficacy of traditional pharmacological interventions. Initial data acquisition was done prior to undergo a temporal lobe resection. Afterwards, patients were monitored by neurologists, tracking of seizure recurrences during long-term follow-up, as well as assessments of cognitive and emotional outcomes. Additionally, a normative group of voluntary participants underwent the same neuroimaging protocols, thus providing a comparative baseline. In study 1 and 2 we focused on the outcome of surgery in terms of seizure recurrence. In the first study, we measured the microstructural integrity of the hippocampal subfields contralateral to resection side. Both hippocampi are known to participate in seizure generation, and we hypothesized that the degree of microstructural damage to the non-resected hippocampus could relate to seizure persistence after surgery. Our experiment revealed that patients with decreased microstructural integrity of the contralateral hippocampus were more prone to relapse after surgery. In the second study, we evaluated if the functional connectivity of the whole temporal lobe could be a marker of seizure relapse after surgery. Previous research has pointed to a whole brain network readaptation in patients with drug-resistant TLE, showing increased local and decreased long-range connectivity surrounding the area of origin of the seizures. In our study, we calculated the DC among three regions of the to be resected temporal lobe. We found that a specific reorganization in temporal lobe connectivity, with increased functional connectivity in the temporal pole and the mesial temporal area related to better prognosis after surgery, in terms of curation of having seizures. In Study 3 and 4 we aimed to study the risk of cognitive and mood disorders after resection of the temporal lobe. In the third study, we analyzed the connectivity of both hippocampi to main whole brain resting state networks involved in cognition. Centered on the connectivity pattern of both hippocampi with the resting-state networks (DMN, DAN & EXE) we found differences in the connectivity of these structures relating to verbal learning decline after surgery. Moreover, these differences were found along the longitudinal axis of both hippocampi, highlighting the differences of connectivity in this structure. Our study revealed that a distinct connectivity pattern among the anterior and posterior regions of the hippocampi with the default mode network and the dorsal attention network could identify those patients who were at risk of verbal learning decline after surgery. Finally, in the fourth study, we compared the patients who developed the novo mood disorders after surgery. Specifically investigating the functional connectivity of the NAcc and the to-be resected hippocampus, we found that patients with a decrease of connectivity between these structures were more prone to develop de novo mood disorders after a surgical resection of the mesial temporal structures. Our investigation yielded the identification of a variety of potential biomarkers, sup- ported by prior empirical evidence. Significantly, in line with the individual heterogeneity of TLE, we assessed these markers at the individual subject level, and prior to temporal resection. The result of our experiments shed light on the intricate relationships between the identified biomarkers and the post-surgery clinical outcomes. Importantly, the approach that we adopted, understanding epilepsy as a network related disease not only proved to be insightful but also generated a novel set of presurgical biomarkers key in TLE surgery. These markers hold significant promise for tailoring personalized guidance for individuals with TLE who are preparing to undergo surgical interventions. |
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