Henrique Carrete

Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis

OBJECTIVE We assessed the cognitive performance of patients with temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis (HS), in comparison with that of matched, healthy controls. We report the relationship between cognitive measures and duration of epilepsy, correlating with hippocampal volumes, and the impact of educational level on cognitive decline. METHODS This study involved 61 outpatients (40 with < or = 8 years and 21 with >8 years of formal education) with unilateral HS and 61 controls. Volumetric MRI was performed on all patients and 10 controls. The results (mean, SD) of the neuropsychological tests of healthy subjects and patients were compared using the Student t and Mann-Whitney tests. RESULTS Patients performed worse than controls in the neuropsychological evaluation. When adjusted z scores were used to calculate the impairment index, patients had a greater percentage of abnormal tests compared with controls. The cognitive decline, assessed through the impairment index, correlated with duration of epilepsy. Higher level of education did not protect against this decline, thus not supporting the hypothesis of cerebral reserve in this population. A significant correlation between hippocampal volumetric measures and duration of epilepsy was observed only in patients with left HS. CONCLUSION Patients with TLE caused by HS present with cognitive morbidity that extends beyond memory deficits. Cognitive decline is associated with duration of epilepsy, and in patients with left-sided HS, duration may correlate with volumetric hippocampal loss.

Magnetic resonance spectroscopy reveals an epileptic network in juvenile myoclonic epilepsy

Purpose:  To investigate the cerebral metabolic differences between patients with juvenile myoclonic epilepsy (JME) and normal controls and to evaluate to what extent these metabolic alterations reflect involvement of an epileptic network.

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.

Brain Magnetic Resonance Imaging Abnormalities in Adult Patients With Sickle Cell Disease Correlation With Transcranial Doppler Findings

Background and Purpose— Brain imaging abnormalities were reported in up to 44% of children with sickle cell disease (SCD). The prevalence of neuroimaging abnormalities in adult patients with SCD and their relationship to transcranial Doppler is still unclear. Our objectives were to study the frequency of MRI and MR angiography abnormalities in adults with SCD and to define what transcranial Doppler velocities are associated with intracranial stenoses detected by MR angiography. Methods— We examined all adult patients (>16 years) with SCD followed in the hematology outpatient clinic at our university hospital with MRI, MR angiography, and transcranial Doppler. Results— We evaluated 50 patients. The overall prevalence of MRI abnormalities was 60%. Abnormal MRI findings were more frequent when vessel tortuosity or stenoses were present on MR angiography (P<0.01). Patients with intracranial stenoses had significantly higher time-averaged maximum mean velocities (P=0.01). A time-averaged maximum mean velocity of 123.5 cm/s allowed the diagnosis of middle cerebral artery or internal carotid artery intracranial stenosis with sensitivity of 100% and specificity of 73% with an area under the receiver operator characteristic curve of 0.91 (CI, 0.79 to 1.00). Conclusions— The frequency of brain imaging abnormalities detected by MRI/MR angiography in adults with SCD was higher than that described for children. Transcranial Doppler velocities in adult patients with intracranial stenoses were lower than those described for the pediatric population with SCD.

Are personality traits of juvenile myoclonic epilepsy related to frontal lobe dysfunctions? A proton MRS study

Purpose:  Personality traits characterized by emotional instability and immaturity, unsteadiness, lack of discipline, hedonism, frequent and rapid mood changes, and indifference toward one’s disease have been associated with patients who have juvenile myoclonic epilepsy (JME). Literature data demonstrate worse seizure control and more psychosocial dysfunctions among patients with JME who have those traits. In this controlled study we performed a correlation analysis of psychiatric scores with magnetic resonance spectroscopy (MRS) values across JME patients, aiming to verify the existence of a possible relation between frontal lobe dysfunction and the prevalence of personality disorders (PDs) in JME.

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.

Mutation in Filamin A Causes Periventricular Heterotopia, Developmental Regression, and West Syndrome in Males

Summary:  Purpose: Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray‐matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X‐linked dominant pattern. Heterozygotic female patients usually remain asymptomatic until the second or third decade of life, when they may have predominantly focal seizures, whereas hemizygotic male fetuses typically die in utero. Recent studies have also reported mutations in FLNA in male patients with PH who are cognitively normal. We describe PH in three male siblings with PH due to FLNA, severe developmental regression, and West syndrome.

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.

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.