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| Author(s): |
Marina Koutsodontis Machado Alvim
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2019-01-18 |
| Examining board members: |
Fernando Cendes;
André Luis Fernandes Palmini;
Marino Muxfeldt Bianchin;
Luiz Eduardo Betting;
Marcio Luiz Figueredo Balthazar
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| Advisor: | Fernando Cendes; Ana Carolina Coan |
| Abstract | |
Introduction: Epilepsy affects 1% to 2% of the world population and temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) is the most common epilepsy in adults. Imaging studies have already demonstrated that TLE patients present diffuse gray and white matter atrophy, not restricted to hippocampal region. Inflammation perform an important role in neuroexcitability. Changes on inflammatory regulation can lead to neuronal degeneration and induce seizures. Objectives: To define the association of serum inflammatory markers and epilepsies, as well as clinical characteristics, EEG and neuroimaging patterns in patients with TLE. Subjects and Methods: The study included 490 patients with clinical and electroencephalographic (EEG) diagnosis of epilepsy and a group with 166 controls without neurological diseases. The patients were classified as TLE-HS (246) and other epilepsies. All participants were invited to perform blood sampling (blood serum for inflammatory markers) and 86 performed magnetic resonance imaging (MRI). MRI cortical thickness and subcortical structures were analyzed with FreeSurfer software. The blood serum analysis of IL-1, IL-2, IL-4, IL-6, IL-10, IL-17, TNF? ,sTNFr1, sTNFr2, BDNF, CTNF, IFN?, NGF, GDNF was performed by Enzyme-Linked Immunosorbent Assay (ELISA) and Cytometric Bead Array (CBA). Results: The inflammatory markers did not present correlation with age and gender, or with epilepsy duration. The blood serum levels of BDNF, NGF, sTNFr2 e a NT3 were higher while TNF, sTNFr1, IFN? and interleukines were reduced in patients with epilepsy, TLE-HS and other epilepsies when compared with controls. The same pattern was observed in patients with malformation of cortical development, except for sTNFr1 and IL10. The CTNF, NT4/5 and GDNF were not different between patients and controls in any group. In ROC analysis the sTNFr2 was a good marker to separate patients from controls (AUC =0,858). Considering just patients, the GDNF presented higher serum levels in patients with less interictal epileptiform activity at EEG; and blood serum IL2 and IL4 were higher in patients with more frequent seizures. TNF? presented an inverse correlation with ipsilateral thalamus volume. Discussion: Our study is one of the first to evaluate an extensive cohort of patients and perform an exploratory assessment on the relationship between inflammatory markers, clinical data and imaging. Inflammatory markers play different roles in central nervous system and their serum measurement helps in better comprehending their relationship with epilepsy. Conclusion: The inflammatory markers are associated with epilepsy, but more specific studies are necessary to determine if they are epiphenomena or consequence of seizures (AU) | |
| FAPESP's process: | 15/17066-0 - Relationship between inflammatory markers and hippocampal and extra-hippocampal atrophy patterns in patients with temporal lobe epilepsy |
| Grantee: | Marina Koutsodontis Machado Alvim |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |