Search

The cognitive dysfunction caused by antiepileptic drugs (AEDs) has been extensively described, although the mechanisms underlying such collateral effects are still poorly understood. The combination of functional magnetic resonance imaging (fMRI) studies with pharmacological intervention (pharmaco-MRI or ph-MRI) offers the opportunity to investigate the effect of drugs such as AEDs on brain activity, including cognitive tasks. Here we review the studies that investigated the effects of AEDs [topiramate (TPM), lamotrigine (LMT), carbamazepine (CBZ), pregabalin (PGB), valproate (VPA) and levetiracetam (LEV)] on cognitive fMRI tasks. Despite the scarcity of fMRI studies focusing on the impact of AEDs on cognitive task, the results of recent work have provided important information about specific drug-related changes of brain function.

Agradecimentos: This study was supported by the Canadian Institute of Health Research (DWG, CB, and CLY); CEPID–FAPESP: "The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN)," grant 2013/07559-3; and Brazilian National Council for Scientific and Technological Development (CNPq)–(GCB) Abstract: Objective: Although altered large-scale brain network organization in patients withtemporal lobe epilepsy (TLE) has been shown using morphologic measurements suchas cortical thickness, these studies, have not included critical subcortical structures(such as hippocampus and amygdala) and have had relatively small sample sizes. Here,we investigated differences in topological organization of the brain volumetric net-works between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hip-pocampal atrophy. Methods: We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLEpatients, and 116 controls. RTLE and LTLE groups were balanced for gender(p=0.64), seizure frequency (Mann-WhitneyUtest, p=0.94), age (p=0.39), age ofseizure onset (p=0.21), and duration of disease (p=0.69). Brain networks were con-structed by thresholding correlation matrices of volumes from 80 cortical/subcorticalregions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) thatwere then analyzed using graph theoretical approaches. Results: We identified reduced cortical/subcortical connectivity including bilateral hip-pocampus in both TLE groups, with the most significant interregional correlationincreases occurring within the limbic system in LTLE and contralateral hemisphere inRTLE. Both TLE groups demonstrated less optimal topological organization, withdecreased global efficiency and increased local efficiency and clustering coefficient.LTLE also displayed a more pronounced network disruption. Contrary to controls,hub nodes in both TLE groups were not distributed across whole brain, but ratherfound primarily in the paralimbic/limbic and temporal association cortices. Regionswith increased centrality were concentrated in occipital lobes for LTLE and contralat-eral limbic/temporal areas for RTLE.Significance:These findings provide first evidence of altered topological organizationof the whole brain volumetric network in TLE, with disruption of the coordinated pat-terns of cortical/subcortical morphology FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Objective To evaluate white matter (WM) integrity of distinct groups of patients with antiepileptic drug (AED)-resistant localization-related epilepsies. Methods We used diffusion tensor imaging (DTI) fiber-tractography and voxel-based morphometry (VBM) to investigate differences of WM micro- and macrostructural integrity in patients with different drug-resistant localization-related epilepsies: 17 with temporal lobe epilepsy with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 17 with TLE and normal MRI (TLE-NL), 14 with frontal lobe epilepsy and subtle MRI signs of focal cortical dysplasia (FLE-FCD), and 112 healthy controls. We performed fiber-tractography using a semiautomatic deterministic method to yield average fractional anisotropy (FA), axial (AD), and radial (RD) diffusivity ipsilateral and contralateral to the epileptogenic zone of the following tracts based on their functional and anatomic relevance: body of fornix (BoF), body of cingulum (BoC), inferior frontal occipital (IFO), and uncinate fasciculi (UF). In addition, we performed VBM of the WM maps to assess macrostructural integrity differences among groups. Results TLE-HS had ipsilateral and contralateral decreased FA and increased RD for all tracts. VBM showed WM alterations mainly in the ipsilateral parahippocampal region and contralateral superior temporal gyrus. FLE-FCD showed bilateral FA decreases only in the BoC and ipsilateral RD increases also in the BoC. VBM showed WM reduction mainly in the ipsilateral precuneus and posterior and anterior cingulum. No significant WM alterations were found in the TLE-NL in DTI or VBM analysis. Significance WM abnormalities differ in distinct AED-resistant localization-related epilepsies. The diverse distribution of the WM damage in these patients suggests that the localization of the epileptic networks may play a role in the WM burden. However, the distinct degree of this damage, more accentuated in TLE-HS, also suggests that the underlying cause of the epilepsy is probably an additional factor to explain this WM damage FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP Aberto

Purpose: To compare relative N-acetylaspartate (NAA) measurements in temporal lobe epilepsy (TLE) patients with good response to the first trial of antiepileptic drugs (AEDs) (an important prognostic factor) to TLE patients who failed the first AED monotherapy and required further AED trials with monotherapy or polytherapy. We studied 25 consecutive TLE patients who responded to first AED (responders) and 21 who did not (failure-group), as well as 27 controls. Patients were seen regularly in our Epilepsy Service and underwent electroencephalography (EEG) investigation, high-resolution magnetic resonance imaging (MRI), and single-voxel proton MR spectroscopy. Voxels were tailored to the medial temporal region on each side and involved the anterior hippocampus. Analysis of variance (ANOVA) demonstrated significant variation of NAA/creatine (NAA/Cr) values in both hippocampi, ipsilateral and contralateral to the EEG focus (p < 0.001 and p = 0.021) across the groups. Pairwise post hoc comparisons showed reduced NAA/Cr in both hippocampi of failure-group compared to controls (p < 0.001) and compared to responders (p < 0.05), but not between the controls and responders. Individual analyses showed NAA/Cr ratios lower than 2 SDs (standard deviations) below the mean of controls in 9 of 21 patients (42.8%) in the failure-group (6 with unilateral and 3 with bilateral reduction) but in none of the responders. These results indicate that patients with TLE who respond well to the first AED have significantly less evidence of neuronal and axonal damage/dysfunction compared to those who are refractory to the first AED trial FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP Fechado

OBJECTIVES: To study pre and postoperative WMA in MTLE patients. METHODS: We performed Voxel-Based Morphometry (VBM) with volume of interest (VOI) in 69 controls (mean age, 34.3±11.1 years) and 67 operated patients (mean age, 34.1±10.4 years) with unilateral MTLE. 34 became seizure-free (SzFree-Group), 23 improved (Engel IB-IIA [Partial recovery-group]) and 10 did not improve (Engel III-IV [Failure-Group]). All had pre and postoperative MRIs (one year minimum). We flipped MRIs of right MTLE patients in order to avoid right-to-left analysis cancelation. VBM was performed on SPM2/MATLAB7.0 with individual masks for surgical lacunae and 1% false-discovery-rate to control for multiple comparisons. We used MARSbar routine to select ROIs and t-test for statistical analyses. RESULTS: Mean postoperative follow-up was 60.2 (±SD 30.7) months. On baseline MRI, SzFree-Group showed White Matter Atrophy (WMA) involving temporal lobes [TL], ipsilateral occipital, parietal and frontal regions, with areas of significant recovery of WMA on postoperative MRI. Partial recovery-Group presented a more restricted pattern of WMA, involving ipsilateral temporal lobe, contralateral superior temporal gyrus and few areas in bilateral cingulated and orbitofrontal areas. In this group we also identified areas with relative increase of WM after surgery. By contrast, Failure-Group showed more widespread bi-hemispheric areas of WMA on baseline MRI without postoperative improvement. CONCLUSIONS: Although we have identified some differences in baseline WMA, we were unable to correlate a more widespread pattern with a worse prognosis, as SzFree-Group, also presented a bilateral distribution of WMA. The recovery of WMA in SzFree-Group and Partial recovery-group is in agreement with previous MRS and PET studies and suggests that a network of neuronal dysfunction in MTLE can be, at least in part, reversible after successful postoperative seizure control.