Marina K. M. Alvim

Progression of gray matter atrophy in seizure-free patients with temporal lobe epilepsy

To investigate the presence and progression of gray matter (GM) reduction in seizure‐free patients with temporal lobe epilepsy (TLE).

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study.

Structural MRI abnormalities are inconsistently reported in epilepsy. In the largest neuroimaging study to date, Whelan et al. report robust structural alterations across and within epilepsy syndromes, including shared volume loss in the thalamus, and widespread cortical thickness differences. The resulting neuroanatomical map will guide prospective studies of disease progression.

MicroRNA hsa-miR-134 is a circulating biomarker for mesial temporal lobe epilepsy

Epilepsy is misdiagnosed in up to 25% of patients, leading to serious and long-lasting consequences. Recently, circulating microRNAs have emerged as potential biomarkers in a number of clinical scenarios. The purpose of this study was to identify and to validate circulating microRNAs that could be used as biomarkers in the diagnosis of epilepsy. Quantitative real-time PCR was used to measure plasma levels of three candidate microRNAs in two phases of study: an initial discovery phase with 14 patients with mesial temporal lobe epilepsy (MTLE), 13 with focal cortical dysplasia (FCD) and 16 controls; and a validation cohort constituted of an independent cohort of 65 patients with MTLE and 83 controls. We found hsa-miR-134 downregulated in patients with MTLE (p = 0.018) but not in patients with FCD, when compared to controls. Furthermore, hsa-miR-134 expression could be used to discriminate MTLE patients with an area under the curve (AUC) of 0.75. To further assess the robustness of hsa-miR-134 as a biomarker for MTLE, we studied an independent cohort of 65 patients with MTLE, 27 of whom MTLE patients were responsive to pharmacotherapy, and 38 patients were pharmacoresistant and 83 controls. We confirmed that hsa-miR-134 was significantly downregulated in the plasma of patients with MTLE when compared with controls (p < 0.001). In addition, hsa-miR-134 identified patients with MTLE regardless of their response to pharmacotherapy or the presence of MRI signs of hippocampal sclerosis. We revealed that decreased expression of hsa-miR-134 could be a potential non-invasive biomarker to support the diagnosis of patients with MTLE.

Is inpatient ictal video-electroencephalographic monitoring mandatory in mesial temporal lobe epilepsy with unilateral hippocampal sclerosis? A prospective study

To compare surgical outcome in mesial temporal lobe epilepsy (MTLE) patients with unilateral hippocampal sclerosis (MTLE‐HS) who had or did not have preoperative video‐electroencephalographic monitoring (VEEG).

A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information

Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in ABCB1, ABCC2, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner.

Sleep onset uncovers thalamic abnormalities in patients with idiopathic generalised epilepsy

The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC) of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed between patients and controls in somatosensory regions during wakefulness, and occipital regions during sleep. Intra-hemispheric thalamic FC was significantly higher in patients than controls following sleep onset, and disorder-dependent alterations to FC were seen in several thalamic regions always involving somatomotor and occipital regions. As interactions between thalamic sub-regions are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN), the results suggest abnormal TRN function in patients with IGE, with a regional distribution which could suggest a link with the thalamocortical networks involved in the generation of alpha rhythms. Intra-thalamic FC could be a more widely applicable marker beyond patients with IGE.

Multimodal evaluation of grey and white matter in patients with generalized epilepsy according to seizure control

Epilepsy is a neurological condition that affects approximately 50 million people. Usually, the magnetic resonance imaging (MRI) in idiopathic generalized epilepsy (IGE) patients is normal. However, several studies found conflicting results about subtle abnormalities in brain structures and cortical function of these patients after MRI quantitative and functional evaluations. The majority of them do not emphasize the relationship between seizure control by medication and the MRI results. The purpose of this project is to clinically characterize and evaluate both white and gray matter abnormalities in IGE patients according to their treatment response. The clinical response of 33 IGE patients was analyzed based on their first and last appointments at Hospital das Clinicas/Unicamp ́s Epilepsy service. The prevalence of seizure had a statistic significant decreased from the first to the last year of following, as the prevalence of generalized tonic-clonic seizure in this period. However, frequencies of absence seizure and myoclonic seizure remained. More than half of the patients presented at least one seizure in the last year of following. The results of imaging analysis showed statistic significant reduction of subcortical gray matter volume of the patient group in comparison with the control group; subgroup analyses revealed larger volumes in the refractory group. The clinical results shows that despite the significant decreased of prevalence of seizures, IGE epilepsy it is not easily control in the majority of times, and the type of seizure more difficult to control is the myoclonic seizure. As for the imaging analyses, the results were unexpected because the hypothesis was that if the thalamic volume is reduced in the patients in general, the refractory patients would have a more important reduction.

In response: Brain atrophy in seizure-free temporal lobe epilepsy: Implications for predicting pharmacoresistance.

The author has no conflicts of interest to disclose. I confirm that I have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Simon S. Keller simon.keller@liverpool.ac.uk Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; Department of Neuroradiology, Walton Centre NHS Foundation Trust, Liverpool, United Kingdom; and Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom