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Topiramate impairs language in patients with epilepsy and migraine: cognitive and functional magnetic resonance assessment

Grant number: 16/16355-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2016
Effective date (End): November 30, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fernando Cendes
Grantee:Akari Ishikawa
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology, AP.CEPID

Abstract

Cognitive changes are common in patients with epilepsy and may be aggravated by antiepileptic drugs (AEDs) such as topiramate (TPM), which has been associated specifically with memory and language dysfunction. Word finding difficulties are the most commonly reported side effect (and studied), and may occur in subjects with and without epilepsy. Despite evidences supporting these side effects, the pathophysiological mechanisms have not been fully elucidated. This project aims to investigate the effects of TPM in the language through cognitive tests (we are going to measure language using verbal fluency test, handedness dominance with Edinburgh handedness inventory and memory using Digit Span) and functional magnetic resonance imaging to detect differences in the patterns of activation / deactivation, as well as changes in efficiency in cerebral connectivity (we will apply Graph Theory analysis to evaluate brain connectivity during language task). We intend to compare 3 groups with a total of 80 subjects: 1) volunteers not taking TPM 2) patients with epilepsy using TPM and 3) subjects with headache using TPM for prophylaxis. The third group is essential to avoid the bias generated by the interaction between epilepsy x drug (present in group 2). We will apply language tests (verbal and categorical fluency) and conduct examination of language functional magnetic resonance (block design, alternating rest, categorical and verbal fluency) The images will be analyzed with MATLAB / SPM12: after preprocessing, we will extract individual maps of activation and deactivation during the tasks (verbal fluency, categorical fluency and rest); later we will perform group comparisons using statistical tools of SPM12. Graph Theory analysis of connectivity will be implemented in MATLAB combining available software (Brain Connectivity Toolbox) with new routines that will be developed by the candidate. Our hypothesis is that TPM change both activation and deactivation patterns in a similar way for subjects with and without epilepsy; Furthermore, we expect to see lower efficiency in brain connectivity of these groups compared to control group. (AU)