Regional neocortical thinning in mesial temporal lobe epilepsy

PURPOSE: To determine the nature and extent of regional cortical thinning in patients with mesial temporal lobe epilepsy (MTLE). METHODS: High-resolution volumetric MRIs were obtained on 21 patients with MTLE and 21 controls. Mean cortical thickness was measured within regions of interest and point-by-point across the neocortex using cortical reconstruction and parcellation software. RESULTS: Bilateral thinning was observed within frontal and lateral temporal regions in MTLE patients relative to controls. The most striking finding was bilateral cortical thinning in the precentral gyrus and immediately adjacent paracentral region and pars opercularis of the inferior frontal gyrus, extending to the orbital region. Within the temporal lobe, bilateral thinning was observed in Heschl's gyrus only. Ipsilateral only thinning was observed in the superior and middle temporal gyri, as well as in the medial orbital cortex. Greater asymmetries in cortical thickness were observed in medial temporal cortex in patients relative to controls. Individual subject analyses revealed that this asymmetry reflected significant ipsilateral thinning of medial temporal cortex in 33% of patients, whereas it reflected ipsilateral thickening in 20% of MTLEs. DISCUSSION: Patients with MTLE show widespread, bilateral pathology in neocortical regions that is not appreciated on standard imaging. Future studies are needed that elucidate the clinical implications of neocortical thinning in MTLE.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

OBJECTIVE: The goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE. METHODS: Children with symptomatic TLE (n=14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n=14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery. RESULTS: Children with MTLE with unilateral hippocampal atrophy (n=9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n=14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex. CONCLUSIONS: Similar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Hippocampal sclerosis-Origins and imaging

The association between hippocampal sclerosis (HS) and epilepsy has been known for almost two centuries. For many years, HS was studied in postmortem series; however, since the mid-20th century, surgical specimens from temporal lobe resections have provided important new knowledge. HS is the most common pathology underlying drug-resistant mesial temporal lobe epilepsy (MTLE), a syndrome with a characteristic history and seizure semiology. In the early 1990s, it was recognized that magnetic resonance imaging (MRI) could detect HS. The standard MRI protocol for temporal lobe abnormalities uses coronal slices perpendicular to the long axis of the hippocampus. The MRI features of HS include reduced hippocampal volume, increased signal intensity on T(2) -weighted imaging, and disturbed internal architecture. The histopathologic diagnosis of HS is usually straightforward, with neuronal loss and chronic fibrillary gliosis centered on the pyramidal cell layer. There are several patterns or subtypes of HS recognized from surgical series based on qualitative or quantified assessments of regional neuronal loss. The pathologic changes of HS include granule cell dispersion, mossy fiber sprouting, and alterations to interneurons. There may also be more extensive sclerosis of adjacent structures in the medial temporal lobe, including the amygdala and parahippocampal gyrus. Subtle cortical neuropathologies may accompany HS. The revised classification of dysplasias in epilepsy denotes these as focal cortical dysplasias type IIIa. Sometimes, HS occurs with a second lesion, either in the temporal lobe or extratemporal, most often ipsilateral to the HS. HS on preoperative MRI strongly predicts good seizure outcome following temporal lobe resection (TLR). If adequate MRI shows no structural correlate in patients with MTLE, functional imaging studies are valuable, especially if they are in agreement with ictal electroencephalography (EEG) findings. Focal hypometabolism on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) ipsilateral to the symptomatic temporal lobe predicts a good surgical outcome; the added value of (11) C-Flumazenil-PET (FMZ-PET) and proton magnetic resonance spectroscopy (MRS) is less clear. Surgical methods have evolved, particularly resecting less tissue, aiming to preserve function without compromising seizure outcome. Around two thirds of patients operated for MTLE with HS obtain seizure freedom. However, the best surgical approach to optimize seizure outcome remains controversial.     

Metabolic evidence for episodic memory plasticity in the nonepileptic temporal lobe of patients with mesial temporal epilepsy

Purpose: Metabolic changes have been described in the nonepileptic temporal lobe of patients with unilateral mesiotemporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). To better understand the functional correlate of this metabolic finding, we have sought to characterize brain regions in patients with MTLE that show correlation between unilateral episodic memory performances, as assessed by intracarotid amobarbital test (IAT), and interictal regional cerebral metabolism measured by [¹⁸F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Methods: Resting FDG‐PET was performed interictally in 26 patients with unilateral MTLE caused by HS (16 female, mean age: 36 years; 16 left HS). Using statistical parametric mapping (SPM8), we performed a group comparison analysis comparing brain metabolism in the patients and in 54 adult controls (27 female, mean age: 32 years), with FDG‐PET data of right HS patients being flipped. IAT scores of nonepileptic hemisphere functions (amobarbital injection ipsilateral to HS) were used as covariates of interest in a correlation analysis with regional brain metabolism. Key Findings: The group comparison analysis revealed significant hypometabolic areas in a widespread temporofrontal network ipsilateral to HS. In addition, a significant increase in metabolism was found in mesial and lateral temporal regions contralateral to HS. Significant positive correlations were found between IAT scores of nonepileptic hemisphere functions and mesial temporal metabolism in this hemisphere. Significance: This study demonstrates the existence of significant increase in relative regional cerebral glucose metabolism in mesial and lateral temporal regions contralateral to the epileptic focus in patients with unilateral MTLE associated with HS. The positive correlation in these brain regions between IAT scores and metabolism supports the role of disease‐induced plasticity mechanisms contralateral to HS in the preservation of episodic memory processes.     

Abnormal temporal lobe morphology in asymptomatic relatives of patients with hippocampal sclerosis: A replication study

We investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE+HS) and first‐degree asymptomatic relatives of patients with mTLE+HS. Using T1‐weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asymptomatic relatives of patients with mTLE+HS in an independent cohort. We performed whole‐brain MRI in 19 patients with mTLE+HS, 14 first‐degree asymptomatic relatives of mTLE+HS patients, and 32 healthy control participants. Structural alterations in patients and relatives compared to controls were assessed using automated hippocampal volumetry and cortical surface–based morphometry. We replicated previously reported cortical surface area contractions in the ipsilateral anterior temporal lobe in both patients and relatives compared to healthy controls, with asymptomatic relatives showing similar but less extensive changes than patients. These findings suggest morphologic abnormality in asymptomatic relatives of mTLE+HS patients, suggesting an inherited brain structure endophenotype.     

Neocortical thinning in "benign" mesial temporal lobe epilepsy

Purpose : In refractory mesial temporal lobe epilepsy (MTLE) extrahippocampal and neocortical abnormalities have been described in patients with or without mesial temporal sclerosis (MTS). Recently we observed gray matter reductions in regions outside the hippocampus in benign MTLE with or without MTS. Cortical thickness has been proposed as a viable methodologic alternative for assessment of neuropathologic changes in extratemporal regions. Herein, we aimed to use this technique to describe cortical abnormalities in patients with benign TLE. Methods : Whole‐brain cortical thickness analysis (FreeSurfer) was performed in 32 unrelated patients with benign TLE [16 patients with signs of MTS on magnetic resonance imaging (MRI), pMTLE; 16 without, nMTLE] and 44 healthy controls. Key Findings : In the pMTLE group, the most significant thinning was found in the sensorimotor cortex bilaterally but was more extensive in the left hemisphere (false discovery rate, p < 0.05). Other areas were localized in the occipital cortex, left supramarginal gyrus, left superior parietal gyrus, left paracentral sulcus, left inferior/middle/superior frontal gyrus, left inferior frontal sulcus, right cingulate cortex, right superior frontal gyrus, right inferior parietal gyrus, right fusiform gyrus, and cuneus/precuneus. In the nMTLE, a similar neurodegenerative pattern was detected, although not surviving correction for multiple comparisons. Direct comparison between pMTLE and nMTLE did not reveal significant changes. Significance : Patients with either benign pMTLE or nMTLE showed comparable cortical thinning, mainly confined to the sensorimotor cortex. This finding that is not appreciated on routine MRI supports the hypothesis that similar to refractory MTLE, even in benign MTLE, pathology in neocortical regions maybe implicated in the pathophysiology of this syndrome.     

Neocortical temporal FDG-PET hypometabolism correlates with temporal lobe atrophy in hippocampal sclerosis associated with microscopic cortical dysplasia

PURPOSE: Medically intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), with or without cortical dysplasia (CD), is associated with atrophy of the hippocampal formation and regional fluorodeoxyglucose positron-emission tomography (FDG-PET) hypometabolism. The relation between areas of functional and structural abnormalities is not well understood. We investigate the relation between FDG-PET metabolism and temporal lobe (TL) and hippocampal atrophy in patients with histologically proven isolated HS and HS associated with CD. METHODS: Twenty-three patients underwent en bloc resection of the mesial and anterolateral neocortical structures. Ten patients were diagnosed with isolated HS; 13 patients had associated microscopic CD. Temporal lobe volumes (TLVs) and hippocampal volumes were measured. Magnetic resonance imaging (MRI) and PET were co-registered, and regions of interest (ROIs) determined as gray matter of the mesial, lateral, and anterior temporal lobe. RESULTS: All patients (HS with or without CD) had significant ipsilateral PET hypometabolism in all three regions studied (p < 0.0001). In patients with isolated HS, the most prominent hypometabolism was in the anterior and mesial temporal lobe, whereas in dual pathology, it was in the lateral temporal lobe. TLVs and hippocampal volumes were significantly smaller on the epileptogenic side (p < 0.05). The PET asymmetries ipsilateral/contralateral to the epileptogenic zone and TLV asymmetries correlated significantly for the anterior and lateral temporal lobes (p < 0.05) in the HS+CD group, but not in the isolated HS group. Mesial temporal hypometabolism was not significantly different between the two groups. CONCLUSIONS: Temporal neocortical microscopic CD with concurrent HS is associated with more prominent lateral temporal metabolic dysfunction compared with isolated HS in TL atrophy. Further studies are needed to confirm these findings and correlate the PET hypometabolic patterns with outcome data in patients operated on for HS with or without CD.     

An optimized voxel‐based morphometric study of gray matter changes in patients with left‐sided and right‐sided mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS)

Purpose: To determine whether changes in gray matter volume (GMV) differ according to the affected side in mesial temporal lobe epilepsy/hippocampal sclerosis (MTLE/HS) syndrome, and moreover to test the hypothesis of more pronounced structural changes in right‐sided MTLE/HS. This hypothesis (especially that the contralateral thalamus is more affected in right‐sided MTLE/HS) arose from the results of our recent study, wherein more expressed structural and functional changes were observed in a small sample of patients with right‐sided MTLE/HS ( Brázdil et al., 2009 ). Methods: Twenty patients with left‐sided and 20 with right‐sided MTLE/HS and 40 sex‐ and age‐matched healthy controls were included in the study. Voxel‐based morphometry (VBM) with a modulation step was applied to magnetic resonance imaging (MRI) brain images. Statistical parametric maps were used to compare structural changes between patients and controls separately for the left‐ and right‐sided MTLE/HS subgroups. We also compared the local GMV of the brain structures (insula and thalamus) between the subgroups of patients. Results: In the subgroup with right‐sided MTLE/HS, a reduction of GMV was detected in the mesiotemporal structures and the ipsilateral thalamus (as in left‐sided MTLE/HS), but also notably in the ipsilateral insula and contralateral thalamus. A statistical analysis revealed a significantly more extensive reduction of GMV in the ipsilateral/contralateral insula and the contralateral thalamus in the subgroup with right‐sided compared to left‐sided MTLE/HS. Conclusion: We found asymmetrical morphologic changes in patients with left‐ and right‐sided MTLE/HS syndrome (more pronounced in right‐sided MTLE/HS). These differences could be theoretically explained by different neuronal networks and pathophysiologic changes in temporolimbic structures.     

Low resolution electromagnetic tomography analysis of ictal EEG patterns in mesial temporal lobe epilepsy with hippocampal sclerosis

ObjectiveTo investigate the difference in the spatial distribution of scalp initial ictal discharge (IID) patterns in mesial temporal lobe epilepsy with hippocampal sclerosis (HS–MTLE).MethodsScalp ictal EEG data in 22 seizure-free patients after temporal lobectomy with amygdalo-hippocampectomy were classified as follows: a regular 5–9 Hz rhythm with a restricted temporal/subtemporal distribution (type 1, 11 patients), or an irregular 2–5 Hz rhythm with a widespread fronto-temporal distribution (type 2, 11 patients). EEG data were fragmented into segments of 1.28 s, both at ictal onset and at baseline. The LORETA solution of three frequency bands was compared between ictal and baseline using statistical non-parametric mapping (p < 0.01).ResultsThe LORETA solution of 5–9 Hz in type 2 had wider cortical activity in the ipsilateral fronto-temporal area, compared to type 1 with activation of the ipsilateral focal mesial and lateral temporal regions. The LORETA solution of 10–13 Hz in both types showed increased activity in the fronto-temporal area, which was wider in type 2 than type 1. Increased cortical activity of <5 Hz was not observed in type 1, whereas increased cortical activity was observed in the bilateral anterior frontal area in type 2.ConclusionsThe cortical source distribution in HS–MTLE may depend on scalp IID frequency. The neural generators of 5–13 Hz may be important for the formation of the ictal onset zone in both ictal patterns.SignificanceSpatial distributions in HS–MTLE patients differ with scalp IID frequency.     

Cortical abnormalities and their cognitive correlates in patients with temporal lobe epilepsy and interictal psychosis

Purpose: To determine whether cortical abnormalities are more severe and widespread in patients with temporal lobe epilepsy (TLE) and interictal psychosis (IP) compared to those with TLE only (NIP) and healthy controls (HC), and to explore the associations between cortical parameters (area, thickness and volume), psychotic symptoms, and cognitive performance. Methods: Twenty‐two patients with IP (9 male; 10 hippocampal sclerosis, HS), 23 TLE nonpsychotic (NIP) patients (11 male; 13 HS) matched for duration of epilepsy and 20 HC participated. Surface‐based morphometry (SBM) was used to measure cortical parameters. Cognition was examined in IP and NIP patients. Associations between cortical parameters and cognition were examined using linear mixed models adjusted by age, gender, and brain volume. Key Findings: IP patients had an earlier onset of epilepsy, more status epilepticus, and worse cognitive performance than NIP patients. In IP patients, cortical thickness was reduced in the inferior frontal gyrus (IFG), and their current IQ was associated with decreases in area, but not thickness, in regions of the frontotemporal cortex. Significance: IP likely reflects the interplay of psychosis‐related genetic factors and the cumulative effects of seizure activity on the brain. Cortical thinning in the IFG, a region implicated in schizophrenia, is likely to be related to seizure activity, whereas changes in IQ, associated with reductions in area of frontotemporal cortex, may be related to the presence of psychosis.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Structural abnormalities are similar in familial and nonfamilial mesial temporal lobe epilepsy

BACKGROUND/OBJECTIVE: Diffuse temporal lobe abnormalities can be observed on MRI of patients with mesial temporal lobe epilepsy (MTLE). Our objective was to perform qualitative and quantitative analyses of temporal lobe structures in patients with familial MTLE (FMTLE) and nonfamilial MTLE. METHODS: Two groups of patients were ascertained: 67 FMTLE patients (14 with refractory seizures) and 30 patients with nonfamilial refractory MTLE. We performed qualitative analyses of MRI (with multiplanar reconstruction) and volumes of hippocampi and anterior temporal lobes in all patients, and in a normal control group of 23 individuals. We used the Chi-square test and ANOVA for statistical analyses. RESULTS: We identified anterior temporal lobe abnormalities by visual analysis in only 4% of FMTLE patients and atrophy of the anterior temporal lobe by volumetric analysis in 19%. In the group of nonfamilial MTLE patients we found anterior temporal lobe abnormalities by visual analysis in 17% of patients and anterior temporal lobe atrophy in 13%. Hippocampal atrophy was present in 90% of FMTLE and in 83% of nonfamilial MTLE. No signs of cortical dysplasia were observed. CONCLUSION: Anterior temporal lobe atrophy and other abnormalities outside the mesial portion of temporal lobes were infrequent in both familial and nonfamilial MTLE patients. Despite the genetic basis, hippocampal atrophy in FMTLE is not associated with other abnormalities outside the mesial temporal regions.     

Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes

OBJECTIVE: To determine whether MRI volumetric measurement of the entorhinal cortex could detect structural damage and lateralize the seizure focus in patients with temporal lobe epilepsy in whom no measurable hippocampal abnormalities were found. BACKGROUND: A reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy and hippocampal atrophy was recently shown. METHODS: MRI volumetric analysis of the entorhinal cortex was performed using a T1-weighted three-dimensional gradient echo sequence in 24 control subjects and 22 patients with temporal lobe epilepsy and normal hippocampal volumes. Thirteen patients underwent surgery, with a mean postoperative follow-up of 36 months. RESULTS: Group analysis (multivariate analysis of variance) showed a reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with left (p < 0.0001) and right temporal lobe epilepsy (p < 0.0001). Lateralization of the seizure focus could be done in 14 of 22 patients (64%) based on entorhinal cortex volumetry. CONCLUSION: Entorhinal cortex atrophy ipsilateral to the seizure focus supports the presence of structural damage in the mesial temporal lobe in patients with temporal lobe epilepsy and normal hippocampal volumes and emphasizes the participation of the entorhinal cortex in the pathogenesis of this disorder.     

Qualitative and quantitative imaging of the hippocampus in mesial temporal lobe epilepsy with hippocampal sclerosis

MR imaging allows the in vivo detection of hippocampal sclerosis (HS) and has been instrumental in the delineation of the syndrome of mesial temporal lobe epilepsy with HS (mTLE-HS). MR features of HS include hippocampal atrophy with an increased T2 signal. Quantitative MR imaging accurately reflects the degree of hippocampal damage.Ictal single photon emission computed tomography (SPECT) in mTLE-HS shows typical perfusion patterns of ipsilateral temporal lobe hyperperfusion, and ipsilateral frontoparietal and contralateral cerebellar hypoperfusion. Interictal 18fluoro-2-deoxyglucose positron emission tomography (PET) shows multiregional hypometabolism, involving predominantly the ipsilateral temporal lobe. 11C-flumazenil PET shows hippocampal decreases in central benzodiazepine receptor density. Future strategies to study the etiology and pathogenesis of HS should include longitudinal MR imaging studies,MR studies in families with epilepsy and febrile seizures, stratification for genetic background, coregistration with SPECT and PET, partial volume correction and statistical parametric mapping analysis of SPECT and PET images.     

Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy

OBJECTIVE: The objective of this study was to assess the volumes of medial temporal lobe structures using high resolution magnetic resonance images from patients with chronic refractory medial temporal lobe epilepsy (MTLE). METHODS: We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1 mm isotropic voxels, and applied a field non-homogeneity correction and a linear stereotaxic transformation into a standard space. The structures of interest are the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar cortex, hippocampus, and amygdala. Structures were identified by visual examination of the coronal, sagittal, and axial planes. The threshold of statistical significance was set to p<0.05. RESULTS: Patients with right and left MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients with right MTLE exhibited a significant asymmetry of all studied structures; the right hemisphere structures had smaller volume than their left side counterparts. We did not observe linear correlations between the volumes of different structures of the medial temporal lobe in patients with MTLE. CONCLUSION: Patients with refractory MTLE have damage in the temporal lobe that extends beyond the hippocampus, and affects the regions with close anatomical and functional connections to the hippocampus.     

How common is brain atrophy in patients with medial temporal lobe epilepsy?

Purpose: It is unclear whether extrahippocampal brain damage in patients with medial temporal lobe epilepsy (MTLE) is a homogeneous phenomenon, as most data relates to the average volume reduction in groups of patients. This study aimed to evaluate where and how much atrophy is to be expected in an individual patient with MTLE. Methods: High‐resolution T₁ magnetic resonance imaging (MRI) was obtained from 23 consecutive patients with unilateral MTLE and from a matched control group. Parametric tests of voxel‐based gray matter volume evaluated mean regional atrophy in MTLE compared with controls. Gray matter images were then submitted to a voxel by voxel calculation of the fitted receiver operating characteristic (ROC) curve area, plotting the sensitivity versus 1–specificity for a binary classifier (MTLE vs. controls). The area under the curve (AUC) was calculated for each voxel and a resulting three‐dimensional map of gray matter voxel‐wise AUCs was obtained. Results: On average, patients with MTLE showed atrophy in the ipsilateral hippocampus and on a limbic network. Elevated AUC was demonstrated in the ipsilateral hippocampus and medial temporal lobe, the ipsilateral thalamus and occipitotemporal cortex, the ipsilateral cerebellum, the cingulate, the contralateral insula, and the occipitoparietal and dorsolateral prefrontal cortex. Conclusion: This study suggests that the medial temporal lobe, occipitotemporal areas, the cerebellum, the cingulate cortex, the ipsilateral insula, and thalamus are more likely to be atrophied in randomly selected patients with MTLE. Structures such as the orbitofrontal cortex, the contralateral medial temporal areas and insula, the putamen, and the caudate may be atrophied, but not as consistently.     

In vivo hippocampal glucose metabolism in mesial temporal lobe epilepsy

BACKGROUND: The appearance of decreased 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) uptake in the mesial temporal region in temporal lobe epilepsy may simply reflect loss of gray matter due to hippocampal atrophy. Increased partial volume effects due to atrophic hippocampi may further increase appearance of hypometabolism. METHODS: The authors used a combination of MRI-PET coregistration, with MRI-based gray matter segmentation, and partial volume correction to improve the examination of hippocampal specific glucose uptake in FDG PET. The goal was to determine 1) if relative mesial temporal hypometabolism is an artifact of gray matter (hippocampal) atrophy, 2) whether hippocampal metabolism correlates with atrophy evaluated on MRI, and 3) if MRI-based partial volume correction influences measurement of hippocampal metabolic-volume relationships, including epilepsy lateralization. RESULTS: Findings showed that ipsilateral hippocampi of mesial temporal lobe epilepsy (MTLE) are relatively hypometabolic per unit of gray matter volume, and that hippocampal metabolism directly correlates with hippocampal volume. Specifically, partial volume corrected hippocampal metabolism correlated strongly (r = 0.613, p < 0.001) with hippocampal volume. Without partial volume correction, a weaker, but still significant, correlation was present (r = 0.482, p < 0.001). Degree of asymmetry was consistently greater and provided higher sensitivity of lateralization with partial volume vs non-partial volume corrected metabolic measurements. CONCLUSIONS: Although, decreased metabolism may occur in the absence of neuronal cell loss, hippocampal atrophy and presumed degree of neuronal cell loss appears to be a primary factor involved in the cause of decreased metabolism in epileptogenic hippocampi. Partial volume correction is recommended for optimal interpretation of hippocampal structure and function relationships.     

Pathophysiology of medial temporal lobe epilepsy: role of cerebral dysgenesis]

We studied the incidence of cerebral dysgenetic lesions(CD) in 39 operated patients with medial temporal lobe epilepsy(MTLE) who had hippocampal sclerosis. Four patients had CD, such as menigocele at the ipsilateral temporal fossa, schizencephaly in the ipsilateral peri-Rolandic area, focal cortical dysplasia in the ipsilateral inferior temporal gyrus and periventricular nodular heterotopia at the bilateral inferior horns of the lateral ventricle. Histological examinations of the resected lateral temporal lobes from 29 MTLE patients revealed the presence of microdysgenesis (microscopic cerebral dysgenesis) in 28 patients, including heterotopic white matter neuron(24 cases), molecular layer neuron(14), oligodendroglial cell cluster(11), dilated perivascular space(10). These findings suggest that the congenital factors, as well as hippocampal sclerosis, may be involved in the development of MTLE.     

Volumetric Magnetic Resonance Imaging Evidence of Bilateral Hippocampal Atrophy in Mesial Temporal Lobe Epilepsy

Summary: Purpose : We measured absolute volumes and volume differences of hippocampi in patients with mesial temporal lobe epilepsy (MTLE) using volumetric magnetic resonance imaging (MRI) to determine the extent of bilateral atrophy in MTLE and to relate hippocampal volumes (HV) to outcome of temporal lobectomy.
Methods : HV and hippocampal differences (HD) were measured in 40 patients with MTLE determined by pathology of hippocampal sclerosis (HS) and compared with those of age-matched controls. Results were matched with surgical outcome.
Results : Hippocampi contralateral to lobectomy (right hippocampi 2.96 ± 0.49 cm³, left 3.14 ± 0.51 cm³) were significantly smaller than those of controls (right hippocampi 3.73 ± 0.52 cm³, left 3.60 ± 0.51 cm³ but were significantly larger than hippocampi ipsilateral to lobectomy (right hippocampi 2.63 ± 0.61 cm³, 2.18 cm³) as compared across groups by analysis of variance (ANOVA: F = 27.2, p < 0. 0001). The smaller hippocampus was ipsilatera1 to lobectomy in 39 of 40 cases. Seven of 40 MTLE patients (18%) had bilateral atrophy, defined by volumes of each hippocampi 2 SD lower than control means. Surgical outcome was independent of hippocampal asymmetry and bilateral atrophy measured by chi-square and Fisher's exact tests.
Conclusions : We determined that most patients with MTLE have some degree of bilateral, asymmetric hippocampal pathology. However, asymmetry and bilateral atrophy have no clear relation to surgical outcome.