Ricardo Silva Centeno

Major depressive disorder as a predictor of a worse seizure outcome one year after surgery in patients with temporal lobe epilepsy and mesial temporal sclerosis

PURPOSE The association between pre-surgical psychiatric disorders (PDs) and worse seizure outcome in patients with refractory epilepsy submitted to surgery has been increasingly recognized in the literature. The present study aimed to verify the impact of pre- and post-surgical PD on seizure outcome in a series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS). METHOD Data from 115 TLE-MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy (CAH) were analyzed. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV and ILAE criteria. The outcome subcategory Engel IA was considered as corresponding to a favorable prognosis. A multivariate logistic regression model was applied to identify possible risk factors associated with a worse seizure outcome. RESULTS Pre-surgical PDs, particularly major depressive disorder (MDD), anxiety and psychotic disorders, were common, being found in 47 patients (40.8%). Fifty-six patients (48.7%) were classified as having achieved an Engel IA one year after CAH. According to the logistic regression model, the presence of pre-surgical MDD (OR=5.23; p=0.003) appeared as the most important risk factor associated with a non-favorable seizure outcome. CONCLUSION Although epilepsy surgery may be the best treatment option for patients with refractory TLE-MTS, our findings emphasize the importance of performing a detailed psychiatric examination as part of the pre-surgical evaluation protocol.

The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis.

Purpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor κB (NFκB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control.

Pre-surgical evaluation and surgical treatment in children with extratemporal epilepsy.

IntroductionThis review summarizes some patterns of pre-surgical evaluation and surgical treatment of extratemporal epilepsy in pediatric patients with medically refractory seizures, whose ictal behavior is variable. The most effective treatment for intractable partial epilepsy is a focal cortical resection with excision of the epileptogenic zone (the area of ictal onset and initial seizure propagation). This might be risky, though, in the case of a widespread lesion, sometimes encroaching one or more lobes, given the risk to the functional cerebral cortex. An anterior temporal lobectomy might prove more effective then in preventing seizures with fewer potential complications. If partial extratemporal epilepsy is associated with pharmaco-resistant seizures, the preoperative evaluation and operative strategy are determined according to the epileptogenic zone and to the relationship between a substrate-directed disorder and eloquent areas. The pediatric treatment of extratemporal epilepsy is aimed at controlling the seizures, avoiding morbidity, and improving the patient’s quality of life through psychosocial integration. Since the immature brain is more plastic than when mature, the recovery of functions after surgery is greater in children than in adults.RecommendationEarly surgery is recommended for children with intractable epilepsy, and is now accepted as an important therapeutic modality also for children with chronic epilepsy.ConclusionTechnological advances in the last two decades, mainly in neuroimaging, have led many medical centers to consider surgical treatment of epilepsy, accuracy being granted by MRI-based neuronavigation systems—an interface between the lesion seen in the preoperative magnetic resonance imaging (MRI) and the operative field, often invisible to the surgeon.

Auras and clinical features in temporal lobe epilepsy: A new approach on the basis of voxel-based morphometry

MRI investigations in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) have demonstrated structural abnormalities extending beyond ipsilateral hippocampus which may be studied through voxel-based morphometry (VBM). We investigated brain morphology related to clinical features in patients with refractory TLE with MTS using VBM. One hundred patients with unilateral TLE with MTS (59 left) and 30 controls were enrolled. VBM5 was employed to analyze (1) hemispheric damage, (2) influence of initial precipitating injury (IPI): 23 patients with febrile seizures and 19 with status epilepticus, and (3) types of auras classified as: mesial, including psychic auras (19 patients); anterior mesio-lateral, as autonomic symptoms, specially epigastric auras (27 patients) and neocortical, which included auditory, vertiginous, somatosensory and visual auras (16 patients). (1) Left TLE patients presented more widespread gray matter volume (GMV) reductions affecting ipsilateral hippocampus, temporal neocortex, insula and also left uncus, precentral gyrus, thalamus, parietal lobule, cuneus and bilateral cingulum. (2) Febrile seizures group presented ipsilateral GMV reductions in hippocampus, neocortical temporal, frontal and occipital cortices, insula and cingulum. Status epilepticus group presented more widespread GMV reductions involving temporal and extratemporal lobes. (3) Patients with mesial auras showed significant ipsilateral GMV reductions in hippocampus and amygdala, particularly right TLE group, who presented greater extension of GMV reduction in the entorhinal cortex. Significant reductions in hippocampus, amygdala and insula were seen in patients with anterior mesio-lateral auras. This study evaluated a large number of TLE-MTS patients showing structural damage extending beyond hippocampus, and different types of IPI associated with the extension of brain damage. Subtypes of auras are related to different clusters of areas of GMV reductions in VBM. For the first time, we have demonstrated GMV reductions anatomically correspondent to psychic (mesial areas) and autonomic auras (mesial and insular areas) reproducing previous cortical stimulation studies.

Pre-surgical predictors for psychiatric disorders following epilepsy surgery in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis

Psychiatric outcomes of patients submitted to epilepsy surgery have gained particular interest given the high prevalence of pre-surgical psychiatric disorders (PD) in this population. The present study aimed to verify the possible pre-surgical predictors for psychiatric disorders following epilepsy surgery in a homogeneous series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS). Data from 115 TLE-MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy were included. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV criteria. Pre-surgical PD - particularly mood, anxiety and psychotic disorders - were diagnosed in 47 patients (40.8%). Twenty-seven patients (54% of those with pre-surgical PD) demonstrated a remission of psychiatric symptoms on post-surgical psychiatric evaluation. Eleven patients (9.6%) developed de novo PD. The presence of pre-surgical depression (OR=3.32; p=0.008), pre-surgical interictal psychosis (OR=4.39; p=0.009) and epileptiform discharges contralateral to the epileptogenic zone (OR=2.73; p=0.01) were risk factors associated with post-surgical PD. Although epilepsy surgery is considered to be the best treatment option for patients with refractory TLE-MTS, the relatively high psychiatric comorbidities observed in surgical candidates and their possible negative impact on post-surgical outcomes require a careful pre-surgical evaluation of clinical, sociodemographic and psychiatric factors.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome

OBJECTIVE To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patients clinical data and surgical outcome were reviewed. RESULTS Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). CONCLUSION Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

Can intraoperative electrocorticography patterns predict surgical outcome in patients with temporal lobe epilepsy secondary to unilateral mesial temporal sclerosis

INTRODUCTION Intraoperative electrocorticography (ECoG) can be performed in cases of temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). However, its significance and correlation with surgical outcome are still controversial. OBJECTIVES To analyze the electrophysiological characteristics of temporal lobe structures during ECoG of patients with TLE-HS, with emphasis on the comparison between pre- and post-resection recordings and surgical outcome. PATIENTS AND METHODS Seventeen patients with refractory TLE-HS submitted to corticoamigdalohipocampectomy were included in the study. Clinical variables included age at the onset, duration of epilepsy and seizure outcome. The post-operative follow-up ranged from 24 to 36 months. According to outcome subjects were divided in two subgroups: (A) individuals free of seizures (Engel 1A), and (B) individuals not-free of seizures (Engel 1B-IV). Four patterns of ECoG findings were identified: isolated discharges; high frequency spikes (HFS); continuous discharges; combination of isolated discharges and HFS. According to predominant topography ECoG was classified as mediobasal, lateral (or neocortical), mediobasal and lateral. RESULTS The progressive removal of the temporal pole and the hippocampus was associated with significant decrease of neocortical spikes. No correlation between clinical variables and seizure outcome was observed. Patients who only had isolated spikes on intraoperative ECoG presented a statistical trend for excellent surgical control. Patients who presented temporal pole blurring on MRI also had better post-surgical seizure outcome. CONCLUSIONS This study showed that out of diverse clinical and laboratory variables, only isolated discharges on intraoperative ECoG and temporal pole blurring on MRI predicted excellent post-surgical seizure outcome. However, other studies with larger number of patients are still necessary to confirm these findings.

Dysmorphic neurons in patients with temporal lobe epilepsy

We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients with medically intractable TLE and compare histological, clinical, and imaging features with ten TLE patients with classical hippocampal sclerosis without abnormal cells. Such dysmorphic neurons were observed in the hilus of the dentate gyrus and were characterized by giant or misshapen cells with abnormal cytoskeletal structure and atypical dendritic processes that resembled the dysmorphic neurons from cortical dysplasias. Specimens with dysmorphic cells also contained other cytoarchitectural abnormalities including bilamination of the dentate granular cell layer (four out seven cases), and the presence of Cajal-Retzius cells in the dentate gyrus or Ammons horn (five out seven cases). There were no statistically significant differences regarding the age at onset, duration of epilepsy, and hippocampal asymmetry ratio between patients with or without dysmorphic cells. Nevertheless, it is interesting to note that a higher proportion of patients with dysmorphic neurons continued to present auras after surgery, when compared with patients without those cells.

Sign of the Cross (Signum Crucis): observation of an uncommon ictal manifestation of mesial temporal lobe epilepsy.

The objective of the study was to describe the clinical characteristics and determine the lateralizing value of ictal Sign of the Cross (SC) as a complex hand automatism (CHA) in patients evaluated by video/EEG monitoring in a comprehensive epilepsy unit. We reviewed video/EEG data of 530 patients with epilepsy recorded in a tertiary epilepsy center from 2002 to 2008. Four patients were found to have manifested a CHA similar to the SC at least once during their complex partial seizures. All patients had unilateral right mesial temporal lobe epilepsy (TLE) refractory to medical treatment. The limbic system is often suggested as the critical site of religious experience. Moreover, it may be localized predominantly to the temporal regions of the right hemisphere. However, this rare and peculiar ictal manifestation may be related not only to the neural substrate and personality characteristics of TLE, but also to the general religious convictions of Brazilians.

Neurocysticercosis and microscopic hippocampal dysplasia in a patient with refractory mesial temporal lobe epilepsy

Epidemiologic studies suggest that neurocysticercosis (NC) is the main cause of symptomatic epilepsy in developing countries. The association between NC and mesial temporal lobe epilepsy (MTLE) has been reported by several authors. Recent data have shown that the presence of NC does not influence the clinical and pathological profile in MTLE patients and suggest that not all cysticercotic lesions are inevitably epileptogenic. We describe a 50-years-old woman with partial seizures due to NC which evolve to MTLE. The patient was submitted to a corticoamygdalohippocampectomy to treat refractory epilepsy. An immunohistochemical study using neuronal markers was made on hippocampal formation. Besides the typical aspects of Ammons horn sclerosis (AHS), the microscopic examination demonstrates cellular features of hippocampal malformation including dysmorphic neurons and focal bilamination of granular cell layer. We suggest that, in this case, a developmental disorder lowered the threshold for the NC-induced seizures and contributed to the establishment of refractory epilepsy.