Marcia Elisabete Morita

Dynamic changes in white and gray matter volume are associated with outcome of surgical treatment in temporal lobe epilepsy

BACKGROUND The reasons for surgical failure in 30% of patients with unilateral mesial temporal lobe epilepsy (MTLE) are still unclear. We investigated if different outcomes could be associated to different patterns of subtle gray matter atrophy (GMA) and white matter atrophy (WMA), and searched for postoperative magnetic resonance imaging (MRI) changes. METHODS We studied 69 controls and 67 operated patients with refractory unilateral MTLE. Patients were grouped as seizure-free (SF) group (34 patients Engels IA), worthwhile improvement group (23 patients, Engels IB-IIA) and failure group (10 patients Engels IIB-IV). We created a voxel-based morphometry/MATLAB code to mask the surgical lacuna, and performed t-test and paired t-test to evaluate preoperative and postoperative MRI scans. RESULTS Failure group showed a widespread pattern of preoperative GMA. On SF and improvement groups we identified a more restricted pattern of GMA. The three groups presented a widespread, bilateral pattern of WMA. In contrast, postoperative analyses showed bilateral hemispheric recovery (a relative increase of WM concentration) on SF and improvement groups, but few changes on failure group. We also identified areas with relative postoperative increase of GM on both SF and improvement groups, more widespread on SF group. CONCLUSION Areas of subtle GMA may be related to poorer surgical outcome. In addition, we demonstrated a postoperative relative increase of WM and GM concentration associated with seizure control. These changes may represent neuroplasticity related to improvement of brain function after seizure control. Further studies with a multimodal approach may help to predict surgical outcome and improve selection of patients for surgical treatment of MTLE.

Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis

BACKGROUND Half of patients who have resective brain surgery for drug-resistant epilepsy have recurrent postoperative seizures. Although several single predictors of seizure outcome have been identified, no validated method incorporates a patients complex clinical characteristics into an instrument to predict an individuals post-surgery seizure outcome. METHODS We developed nomograms to predict complete freedom from seizures and Engel score of 1 (eventual freedom from seizures allowing for some initial postoperative seizures, or seizures occurring only with physiological stress such as drug withdrawal) at 2 years and 5 years after surgery on the basis of sex, seizure frequency, secondary seizure generalisation, type of surgery, pathological cause, age at epilepsy onset, age at surgery, epilepsy duration at time of surgery, and surgical side. We designed the models from a development cohort of patients who had resective surgery at the Cleveland Clinic (Cleveland, OH, USA) between 1996 and 2011. We then tested the nomograms in an external validation cohort operated on over a similar period in four epilepsy surgery centres, in Brazil, France, Italy, and the USA. We assessed performance of the nomogram by calculating concordance statistics and assessing the calibration of predicted freedom from seizures with the reported freedom from seizures and Engel score of 1. FINDINGS The development cohort included 846 patients and the validation cohort included 604 patients. Variables included in the nomograms were sex, seizure frequency, secondary seizure generalisation, type of surgery, and pathological cause. In the development cohort, the baseline risk of complete freedom from seizures was 0·57 at 2 years and 0·40 at 5 years. The baseline risk of Engel score of 1 was 0·69 at 2 years and 0·62 at 5 years. In the validation cohort, the models had a concordance statistic of 0·60 for complete freedom from seizures and 0·61 for Engel score of 1. Calibration curves showed adequate calibration (judged by eye) of predicted and reported freedom from seizures, throughout the range of seizure outcomes. INTERPRETATION If validated in prospective cohorts, these nomograms could be used to predict seizure outcomes in patients who have been judged eligible for epilepsy surgery. FUNDING Cleveland Clinic Epilepsy Center.

Amygdala Enlargement in Patients with Mesial Temporal Lobe Epilepsy without Hippocampal Sclerosis

Purpose: Patients with mesial temporal lobe epilepsy (MTLE) without MRI abnormalities (MTLE-NL) represent a challenge for definition of underlying pathology and for presurgical evaluation. In a recent study we observed significant amygdala enlargement (AE) in 14% of MTLE patients with MRI signs of hippocampal sclerosis. Areas of gray matter volume (GMV) increase could represent structural abnormalities related to the epileptogenic zone or part of a developmental abnormality. Our objective was to look for undetected areas of increased GMV in MTLE-NL using post processing MRI techniques to better understand the pathophysiology of this condition. Methods: We evaluated 66 patients with MTLE-NL on visual analysis and 82 controls. Voxel-based morphometry (VBM) group analysis was performed with VBM8/SPM8 looking for areas of increased GMV. We then performed automatic amygdala volumetry using FreeSurfer software and T2 relaxometry to confirm VBM findings. Results: Voxel-based morphometry group-analysis demonstrated increased amygdala volume in the MTLE-NL group compared to controls. Individual volumetric analysis confirmed AE in eight (12%) patients. Overall, from all patients with AE and defined epileptic focus, four (57%) had the predominant increased volume ipsilateral to the epileptic focus. These results were cross-validated by a secondary VBM analysis including subgroups of patients according to the volumetric data. T2 relaxometry demonstrated no amygdala hyperintense signal in any individual with significant AE. There were no clinical differences between patients with and without AE. Discussion: This exploratory study demonstrates the occurrence of AE in 12% of patients with MTLE-NL. This finding supports the hypothesis that there might be a subgroup of patients with MTLE-NL in which the enlarged amygdala could be related to the epileptogenic process. Further studies are necessary but this finding could be of great importance in the understanding of MTLE-NL.

Amygdala enlargement occurs in patients with mesial temporal lobe epilepsy and hippocampal sclerosis with early epilepsy onset

Mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) is considered an electroclinical syndrome, and there is a debate whether it is a unique disease or an entity with distinct subtypes. Together with other mesial temporal structures, the amygdala is important in the epileptogenic network of patients with MTLE with HS. During automatic volumetric analysis of mesial structures in a group of 102 patients with MTLE with MRI signs of HS, we observed significant amygdala enlargement in 14 (14%) individuals compared to a group of 79 healthy subjects. The increased amygdala volume was contralateral to the epileptogenic zone and MRI signs of HS in 93% of these patients. Patients with MTLE with HS and enlarged amygdala had significantly earlier epilepsy onset than those without an increase of amygdala volumes. Mesial temporal lobe epilepsy with HS and enlarged amygdala may be a part of the spectrum of this condition.

Hematoma subdural crônico: estudo de 161 pacientes operados e a relação com alterações no coagulograma

The chronic subdural hematoma represents one of the most frequent types of intracranial hemorrhage. One hundred sixty one patients operated in the Clinical Hospital of State University of Campinas-SP (UNICAMP) from April 1994 to May 2000, were analyzed retrospectively in order to characterize the population and to study the importance of the pre-operative coagulation analysis in the outcome. The majority of the population was male (86%), white (85.1%) and in the fifth decade (median age: 57 years). A high mortality index in the postoperative period was found in patients with INR (international normalized ratio) values greater than 1.25 and/or thrombocytopenia (p<0.001 and p=0.004 respectively). Patients with previous head injury history (76%) showed a lower mortality (p=0.044). The results stand out the importance of the pre-operative evaluation with coagulation studies in order to correct possible abnormalities.

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).

Longitudinal MRI volumetric evaluation in patients with familial mesial temporal lobe epilepsy

Introduction: Studies have shown progressive cerebral damage in patients with refractory mesial temporal lobe epilepsy (MTLE). However, this has not been demonstrated in benign forms of MTLE such as familial mesial temporal lobe epilepsy (FMTLE). Purpose: To evaluate progression of hippocampal atrophy (HA) in patients with sporadic mesial temporal lobe epilepsy (SMTLE) and FMTLE by longitudinal Magnetic resonance images (MRIs) acquired with at least 7 months of interval. Method: We included 35 patients with FMTLE (25 classified as benign and 10 refractory) and 33 with SMTLE (4 benign and 29 refractory). All MRIs were analyzed by an investigator blind for clinical data. Hippocampal analyses were performed manually in coronal 3 mm thick T1 inversion recovery, using the software Scion Image®. Volumes were compared to those from a control group, and HA was determined for volumes below two standard deviations from the mean of controls. Results: The mean interval between the first (MRI1) and second MRI (MRI2) was 90 months for FMTLE and 45 months for SMTLE group. FMTLE group: volumetry demonstrated HA in 20 patients in MRI1 and in 23 patients in MRI2. There was significant progression of HA in FMTLE patients between MRIs in both benign and refractory FMTLE patients (benign FMTLE: right hippocampus, p = 0.001 and left hippocampus, p < 0.001; refractory FMTLE: right hippocampus, p = 0.022 and left hippocampus, p < 0.010). SMTLE group: volumetry demonstrated HA in 27 patients in MRI1 and in 29 patients in MRI2. In the group analysis, there was a significant reduction of the right (p < 0.0001) and left (p < 0.0001) hippocampal volumes during the follow-up period. Although the mean time between the MRIs in the FMTLE group was twice the time of the SMTLE group, the progression of volume loss was similar in both groups, indicating a slower progression in the FMTLE patients. Conclusion: FMTLE patients have progressive hippocampal volume reduction independently of seizure frequency although the progression of HA seems to be slower than in SMTLE.

Aberrant topological patterns of brain structural network in temporal lobe epilepsy

Although altered large‐scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as 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 networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy.

MRI and EEG as long-term seizure outcome predictors in familial mesial temporal lobe epilepsy

Objective: To evaluate the natural history and outcome predictors in familial mesial temporal lobe epilepsy (FMTLE). Methods: We conducted a longitudinal study of 103 individuals from 17 FMTLE families (mean follow-up: 7.6 years). We divided subjects into 3 groups: FMTLE (n = 53), unclassified seizure (n = 18), and asymptomatics (n = 32). We divided FMTLE patients into 3 subgroups: seizure-free (n = 19), infrequent (n = 17) seizures, and frequent (n = 17) seizures and further reclassified them into favorable and poor outcome. We defined hippocampal atrophy (HA) by visual MRI analysis and performed volumetry in those who had 2 MRIs. Results: FMTLE patients with infrequent seizures evolved to either frequent seizures (17.6%) or seizure freedom (23.5%). In the seizure-free group, most remained seizure-free and 21% developed infrequent seizures. All patients with frequent seizures remained in the same status or underwent surgery. Twelve percent of the asymptomatics and 22% of the unclassified-seizure group evolved to FMTLE with infrequent seizures. Predictive factors of poor outcome were presence of HA (p = 0.0192) and interictal epileptiform discharges (p = 0.0174). The relationship between initial precipitating incidents and clinical outcome was not significant although a tendency was observed (p = 0.055). Use of antiepileptic drugs and secondary generalized seizures during the patient’s lifetime did not predict poor outcome. We observed progression of HA only in the group with frequent seizures. Conclusion: Most patients with FMTLE continued in the same clinical status. However, patients with frequent seizures had progression of HA and none improved except those who underwent surgery. Interictal epileptiform discharges and HA predicted poorer outcome in FMTLE, and there was a tendency in favor of initial precipitating incidents as outcome predictors.

Memory impairment is not necessarily related to seizure frequency in mesial temporal lobe epilepsy with hippocampal sclerosis

To investigate the effect of seizure frequency on memory, we performed a cross sectional study comparing mesial temporal lobe epilepsy (MTLE) patients with frequent and infrequent seizures.