Ana Carolina Coan

Gray matter atrophy associated with duration of temporal lobe epilepsy.

Hippocampal sclerosis is the most common abnormality associated with medial temporal lobe epilepsy (MTLE). Converging evidence supports that hippocampal sclerosis progresses with time. However, it is unclear whether extrahippocampal atrophy in patients with MTLE, similarly to hippocampal sclerosis, is an unremitting progressive process. In this article, we investigate the relationship between duration of epilepsy and gray matter concentration reduction in patients with MTLE within and outside the hippocampus. We employed a voxel-based morphometry study of MRI of the entire brain of 36 patients with drug refractory MTLE and 49 neurologically healthy age-matched controls. We performed a voxel-based parametric and nonparametric investigation of the association between gray matter concentration, age and duration of epilepsy. We complemented the investigation by extracting the gray matter concentration of regions of interest (ROIs) within the limbic system, and we investigated the association between the gray matter concentration on the ROIs and duration of epilepsy. Patients with MTLE exhibited gray matter concentration reduction that is negatively correlated with the duration of epilepsy within the ipsilateral hippocampus, temporal lobes as well as extratemporal limbic structures that are closely connected with the hippocampus. In conclusion, longer duration of refractory epilepsy was associated with a more intense hippocampal and extrahippocampal atrophy in patients with MTLE. The mechanism of progressive neuronal damage in MTLE may be related to active seizure activity within a limbic network, and early seizure control may prevent further brain atrophy in patients with refractory MTLE.

Seizure frequency and lateralization affect progression of atrophy in temporal lobe epilepsy

Background: It is unclear which factors lead to progressive neuronal damage in mesial temporal lobe epilepsy (MTLE). The objective of this study was to evaluate whether progressive hippocampal and extrahippocampal atrophy occur in patients with MTLE and whether this atrophy is related to seizures. Method: We performed 2 MRI scans in 33 patients with clinical and electroencephalographic diagnosis of MTLE and in 24 healthy controls. MRI was performed in a 2-T scanner, and a T1-weighted gradient-echo sequence with 1 mm thickness was used for voxel-based morphometry analysis. Follow-up images were obtained at least 7 months after the first baseline MRI. Comparisons between the patient’s follow-up and baseline MRIs, and between patients and controls, were performed. A corrected p value of 0.05 was set as the threshold for the statistical analysis. Results: Follow-up MRI was performed after a median interval of 39 months (range 7–85 months). Three patients were seizure-free between the first and second MRIs. We observed progressive white and gray matter atrophy (p < 0.05) in patients with MTLE. This progression was more intense in patients with left MTLE compared with right MTLE. A higher frequency of seizures and a longer duration of epilepsy were associated with progression of gray and white matter atrophy in patients with MTLE. Conclusion: The progression of white and gray matter atrophy in patients with mesial temporal lobe epilepsy (MTLE) was more intense in patients with left MTLE and was associated with poorer seizure control and a longer duration of epilepsy.

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Neuropsychiatric syndromes are highly prevalent in Alzheimers disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or “resting‐state” analysis, may help to clarify this issue. Using such approaches, alterations in the default‐mode and salience networks (SNs) have been described in Alzheimers, although their relationship with specific symptoms remains unclear. We therefore carried out resting‐state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimers patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default‐mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy. Hum Brain Mapp 35:1237–1246, 2014.

3T MRI Quantification of Hippocampal Volume and Signal in Mesial Temporal Lobe Epilepsy Improves Detection of Hippocampal Sclerosis

BACKGROUND AND PURPOSE: In mesial temporal lobe epilepsy, MR imaging quantification of hippocampal volume and T2 signal can improve the sensitivity for detecting hippocampal sclerosis. However, the current contributions of these analyses for the diagnosis of hippocampal sclerosis in 3T MRI are not clear. Our aim was to compare visual analysis, volumetry, and signal quantification of the hippocampus for detecting hippocampal sclerosis in 3T MRI. MATERIALS AND METHODS: Two hundred three patients with mesial temporal lobe epilepsy defined by clinical and electroencephalogram criteria had 3T MRI visually analyzed by imaging epilepsy experts. As a second step, we performed automatic quantification of hippocampal volumes with FreeSurfer and T2 relaxometry with an in-house software. MRI of 79 healthy controls was used for comparison. RESULTS: Visual analysis classified 125 patients (62%) as having signs of hippocampal sclerosis and 78 (38%) as having normal MRI findings. Automatic volumetry detected atrophy in 119 (95%) patients with visually detected hippocampal sclerosis and in 10 (13%) with visually normal MR imaging findings. Relaxometry analysis detected hyperintense T2 signal in 103 (82%) patients with visually detected hippocampal sclerosis and in 15 (19%) with visually normal MR imaging findings. Considered together, volumetry plus relaxometry detected signs of hippocampal sclerosis in all except 1 (99%) patient with visually detected hippocampal sclerosis and in 22 (28%) with visually normal MR imaging findings. CONCLUSIONS: In 3T MRI visually inspected by experts, quantification of hippocampal volume and signal can increase the detection of hippocampal sclerosis in 28% of patients with mesial temporal lobe epilepsy.

Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

Objective Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS). Methods We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures. Results Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions. Conclusion Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process.

Hippocampal abnormalities and seizure recurrence after antiepileptic drug withdrawal

The authors performed hippocampal volumetry and T2 relaxometry in 84 consecutive patients with partial epilepsy from a protocol for antiepileptic drug (AED) withdrawal after at least 2 years of seizure control. Seizure recurrence after AED withdrawal was more frequent among patients with hippocampal atrophy and abnormal hippocampal T2 signal.

Patterns of hippocampal abnormalities in malformations of cortical development

Objective: To assess whether different types of malformation of cortical development (MCD) are associated with specific patterns of hippocampal abnormalities. Methods: A total of 122 consecutive patients with MRI diagnosis of MCD (53 males, age range 1–58 years) were included in the study. Hippocampal measurements were made on 1–3 mm coronal T1-weighted MRIs and compared with MRIs of normal controls. Results: A total of 39 patients had focal cortical dysplasia, 5 had hemimegalencephaly, 5 had lissencephaly-agyria-pachygyria, 11 had SLH, 11 had PNH, 12 had bilateral contiguous PNH, 5 had schizencephaly, and 34 had polymicrogyria. The frequency of hippocampal abnormalities in these patients with MCD was 29.5%. A small hippocampus was present in all types of MCD. Only patients with lissencephaly and SLH had an enlarged hippocampus. Abnormalities in hippocampal rotation and shape were present in all types of MCD; however, these predominated in PNH. None of the patients with lissencephaly-agyria-pachygyria or SLH had hyperintense signal on T2 or FLAIR images or abnormal hippocampal internal architecture. Conclusion: A small hippocampus was present in all types of MCD; however, the classic MRI characteristics of hippocampal sclerosis were often lacking. Abnormal enlargement of the hippocampus was associated with only diffuse MCD due to abnormal neuronal migration (lissencephaly-agyria-pachygyria and SLH).

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.

White matter abnormalities associate with type and localization of focal epileptogenic lesions

To evaluate white matter (WM) integrity of distinct groups of patients with antiepileptic drug (AED)–resistant localization‐related epilepsies.

Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large‐scale RSNs is differently affected in patients with right‐ and left‐MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting‐state functional‐MRIs of 99 subjects (52 controls, 26 right‐ and 21 left‐MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF2C‐toolbox, which provided ROI‐wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right‐MTLE. Both groups showed abnormal correlation between the dorsal‐DMN and the posterior salience, as well as between the dorsal‐DMN and the executive‐control network. Patients with left‐MTLE also showed reduced correlation between the dorsal‐DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left‐MTLE expressed a low cluster coefficient, whereas the altered connections on right‐MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right‐ and left‐MTLE patients with HS have widespread abnormal interactions of large‐scale brain networks; however, all parameters evaluated indicate that left‐MTLE has a more intricate bihemispheric dysfunction compared to right‐MTLE. Hum Brain Mapp 37:3137–3152, 2016.