Aberrant topological patterns of brain structural network in temporal lobe epilepsy.

OBJECTIVE: 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. METHODS: We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. RESULTS: We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased 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 rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. SIGNIFICANCE: These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology.

Neurocysticercotic Calcifications and Hippocampal Sclerosis: A Case-Control Study.

OBJECTIVE: The exact role of calcified neurocysticercotic lesions (CNLs) in epilepsy is yet unknown and controversial. Although the relationship between CNLs, epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) has already been addressed, to our knowledge, no study has actually provided strong statistical evidence, nor reported the ODDS ratio for these associations. Therefore, we designed this case-control study to assess the likelihood of having MTLE-HS versus other forms of epilepsy in the presence of CNLs. METHODS: In this case-control study we included 119 consecutive patients with epilepsy and 106 disease controls (headache) with previous CT scans. We subdivided cases into MTLE-HS and other epilepsies. We used brain CT scans to define presence or absence of CNLs. After exploratory analyses, we used logistic regression to analyze the association between CNLs, epilepsy subgroups and disease controls. RESULTS: CNLs were found in 31.09% of cases and in 11.32% of controls (p<0.001). The initial analysis comparing epilepsy versus controls revealed a significant association between CNLs and epilepsy (OR = 5.32; 95%CI = 2.43-11.54; p<0.001). However, when we compared MTLE-HS versus other epilepsies versus controls we confirmed that CNLs were associated with MTLE-HS (OR = 11.27, 95%CI = 4.73-26.85; p<0.001) but other epilepsies were not. We found no difference in the CNLs load and no difference in the location of the CNLs when we compared patients with MTLE-HS, other epilepsies and disease controls. SIGNIFICANCE: The inclusion of controls allowed us to estimate the likelihood of having epilepsy in the presence of CNLs. We found that patients with CNLs were 11 times more likely to have MTLE-HS; however, the presence of CNLs did not change the odds of having other types of epilepsy. These findings raise the possibility of neurocysticercosis playing a role in the pathophysiology of MTLE-HS and need further confirmation in other series.

Longitudinal analysis of hippocampal T2 relaxometry in FMTLE.

PURPOSE: To investigate the degree of T2 relaxometry changes over time in groups of patients with familial mesial temporal lobe epilepsy (FMTLE) and asymptomatic relatives. METHODS: We conducted both cross-sectional and longitudinal analyses of T2 relaxometry with Aftervoxel, an in-house software for medical image visualization. The cross-sectional study included 35 subjects (26 with FMTLE and 9 asymptomatic relatives) and 40 controls; the longitudinal study was composed of 30 subjects (21 with FMTLE and 9 asymptomatic relatives; the mean time interval of MRIs was 4.4 ± 1.5 years) and 16 controls. To increase the size of our groups of patients and relatives, we combined data acquired in 2 scanners (2T and 3T) and obtained z-scores using their respective controls. General linear model on SPSS21® was used for statistical analysis. RESULTS: In the cross-sectional analysis, elevated T2 relaxometry was identified for subjects with seizures and intermediate values for asymptomatic relatives compared to controls. Subjects with MRI signs of hippocampal sclerosis presented elevated T2 relaxometry in the ipsilateral hippocampus, while patients and asymptomatic relatives with normal MRI presented elevated T2 values in the right hippocampus. The longitudinal analysis revealed a significant increase in T2 relaxometry for the ipsilateral hippocampus exclusively in patients with seizures. CONCLUSIONS: The longitudinal increase of T2 signal in patients with seizures suggests the existence of an interaction between ongoing seizures and the underlying pathology, causing progressive damage to the hippocampus. The identification of elevated T2 relaxometry in asymptomatic relatives and in patients with normal MRI suggests that genetic factors may be involved in the development of some mild hippocampal abnormalities in FMTLE.

Contralateral hippocampal volume influences surgical outcome in patients with MTLE and similar degree of ipsilateral hippocampal atrophy / O volume hipocampal contralatral influencia o desfecho cirúrgico de pacientes com ELTM e grau semelhante de atrofia hipocampal ipsilateral

Objective: to investigate the relationship between hippocampal atrophy (HA) and surgical outcome in patients with mesial temporal lobe epilepsy (MTLE). Methodology: we compared 34 patients free of seizure (GroupA) with 33 patients with persistent seizures after surgery (GroupB). All had preoperative diagnosis of unilateral MTLE by EEG and MRI evidence of unilateral hippocampal sclerosis (HS) by visual analysis. We performed hippocampal volumetry using high resolution T1 MRI (1mm) in all patients and in 30 healthy controls. Results: Z-score (Mean±SD) of affected hippocampus was -2.58±1.29 in GroupA and -2.57±1.47 in Group-B (p=0.98). The Z-Score of contralateral hippocampus was significantly lower in GroupB, compared to GroupA (p=0.038). Grouping all patients, smaller hippocampal volumes in the affected side were associated with history of meningitis (p=0.049), febrile seizures (p=0.049) and absence of family history of epilepsy (p=0.049). Conclusions: Ipsilateral HA was more severe in patients who had febrile seizures and meningitis, and in those without family history of epilepsy, supporting the notion that in the absence of genetic predisposition, more severe cerebral insult is necessary to induce epileptogenesis. Less favorable surgery outcome for unilateral MTLE was associated with smaller hippocampal volumes contralateral to the operated side, suggesting that surgery is less effective when bilateral damage exists, even when it is not detectable by visual MRI analysis...

Objetivo: investigar a relação entre atrofia hipocampal (AH) e resultado cirúrgico de pacientes com epilepsia de lobo temporal mesial (ELTM). Methodology: comparamos 34 pacientes livres de crises (grupoA) com 33 pacientes que permaneceram com crises após cirurgia (GrupoB). Todos apresentavam o diagnóstico pré-operatório de ELTM unilateral por EEG e RM com sinais de atrofia hipocampal (AH) unilateral na análise visual. Realizamos volumetria do hipocampo utilizando imagens T1 de RM de alta resolução (1mm) em todos os pacientes e em 30 controles sadios. Resultados: o Z-score (Média±DP) dos hipocampos afetados foi -2.58±1.29 no GrupoA e -2.57±1.47 no GrupoB (p=0.98). O Z-score dos hipocampos contralaterais foi significativamente menor no grupoB comparado ao grupoA (p=0.038). Agrupando todos os pacientes, volumes hipocampais menores no lado afetado foram associados à história de meningite (p=0.049), crises febris (p=0.049) e ausência de história familiar de epilepsia (p=0.049). Conclusão: AH ipsilateral foi mais acentuada em pacientes com antecedente de crises febris e meningite, e naqueles sem história familiar de epilepsia, reforçando a ideia de que na ausência de predisposição genética, um maior insulto cerebral seria necessário para induzir epileptogenesis. Um resultado cirúrgico menos favorável na cirurgia para ELTM unilateral foi associado a menores volumes hipocampais no lado contralateral ao lado operado, sugerindo que a cirurgia é menos efetiva quando há dano bilateral, mesmo quando não detectado por analise visual...

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.

Refractory epilepsy is highly associated with severe dentoalveolar and maxillofacial injuries.

Dental intrusion and avulsion, crown fracture and mandibular fractures are important dentofacial complications in patients with epilepsy-related traumas. The objective of the present study was to describe the occurrence of orofacial injuries in patients with epilepsy. One hundred and nine consecutive patients (60 women; mean age 38.81 ±â€Š14 years), treated for refractory epilepsy (45 with extratemporal epilepsy and 64 with temporal epilepsy) at the outpatient clinic of our University Hospital, were included in the present study. Orofacial injury occurring as a direct result of a seizure was determined by clinical examination and interview. In addition, seizure frequency, use of medication, and the occurrence and type of injury to other parts of the body, were documented. We employed regression analyses to investigate the association between teeth fractures and frequency of seizures. The majority of injuries were crown fractures (42 subjects), followed by mandibular fractures (eight subjects) and tooth avulsion (eight subjects). Sixteen patients had more than two fractured teeth. Patients with mandibular trauma also suffered concomitant injuries (teeth fracture, avulsion and dislocation). The number of fractured teeth was associated with seizure frequency (r(2) = 0.59, p < 0.001). The data suggest that there is an increased rate of dentoalveolar and maxillofacial injuries in patients with poorly controlled epileptic seizures.

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.

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 Engel's IA), worthwhile improvement group (23 patients, Engel's IB-IIA) and failure group (10 patients Engel's 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.

Hematoma subdural crônico: estudo de 161 pacientes operados e a relação com alterações no coagulograma / Chronic subdural hematoma: study of 161 patients and the relationship with coagulation abnormalities

O objetivo deste estudo é analisar a evolução de pacientes com hematoma subdural crônico em relação aos achados do coagulograma. Foram analisados 161 pacientes operados no Hospital das Clínicas-UNICAMP entre abril de 1994 e 2000. Foi detectado um predomínio do sexo masculino (86,3 por cento), da cor branca (85,1 por cento) e da faixa etária na quinta década (mediana 57 anos). O estudo mostrou mortalidade maior no período pós-operatório entre os pacientes com valores de RNI (international normalized ratio) superiores a 1,25 e/ou trombocitopenia (p<0,001 e p=0,004, respectivamente) e mortalidade menor para os pacientes com antecedente de traumatismo cranioencefálico (76 por cento) (p=0,044). Os resultados ressaltam a importância da avaliação pré-operatória com o coagulograma a fim de se corrigir possíveis alterações

[Chronic subdural hematoma: study of 161 patients and the relationship with coagulation abnormalities]. / 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.