Cortical and Hippocampal Volume Deficits in Temporal Lobe Epilepsy

Summary: Purpose : To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE).
Methods : Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3–mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA).
Results : As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe.
Conclusions : Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

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.     

Men may be more vulnerable to seizure-associated brain damage

BACKGROUND: Repetitive seizures may be associated with progressive neuronal damage measurable by quantitative MRI. OBJECTIVE: To investigate whether gender is a risk factor for this damage. METHODS: Sixty patients with refractory temporal lobe epilepsy (TLE) (28 men, 32 women) and 54 healthy controls (28 men, 26 women) were compared by quantitative MRI methods. RESULTS: Male patients had ipsilateral hemicranial volume loss of 12% (CI 8% to 16%) and contralateral volume loss of 7% (CI:3% to 11%) compared with male controls (p < or =0.004, analysis of variance). Female patients were 4% (CI:0.3% to 8%, p = 0.04) smaller than controls in the ipsilateral hemicranium, and not different contralaterally. The patient-to-control difference was greater in men than in women for the ipsilateral (p = 0.003) and contralateral hemicranial volume (p = 0.02). In men, 14% of the ipsilateral (F = 4.7, p = 0.004) and 16% of the contralateral (F = 5.1, p = 0.03) hemicranial volume loss could be attributed to generalized tonic clonic seizures. Compared with controls, patients averaged a 29% smaller ipsilateral and a 5% smaller contralateral hippocampus. CONCLUSION: Men with TLE have more brain atrophy than women with TLE. Seizure frequency is a factor contributing to reduced brain volumes in men but not in women. Men, therefore, may be more vulnerable to seizure-associated brain abnormalities.     

Hippocampal Atrophy Is Not a Major Determinant of Regional Hypometabolism in Temporal Lobe Epilepsy

Summary: Purpose : The pathophysiologic basis for the [¹⁸F]fluorodeoxyglucose positron-emission tomography (FDG-PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS.
Methods : Regions of interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry index for each ROI was calculated. These results were correlated with hippocampal magnetic resonance imaging (MRI) volume ratios.
Results : There was no correlation between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio for the mesial or lateral temporal regions (r =−0.09, r =−0.04). When the right/left asymmetry index was compared with the right/left hippocampal volume ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply indicated that both tests accurately reflect the side of the epileptogenic region. The concordance of the side of relative hypometabolism of the FDG-PET with the side of the hippocampal atrophy was higher for the mesial temporal region (100%) than for the lateral (77.5%).
Conclusions : The lack of correlation between the magnitudes of the ratios argues against hippocampal atrophy and cell loss having a central role in the FDG-PET temporal hypometabolism.     

Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients

Purpose: Temporal lobe epilepsy (TLE) is associated with smaller hippocampal volume and with elevated extracellular (EC) glutamate levels. We investigated the relationship between the hippocampal volume and glutamate in refractory TLE patients.
Methods: We used quantitative MRI volumetrics to measure the hippocampal volume and zero-flow microdialysis to measure the interictal glutamate, glutamine, and GABA levels in the epileptogenic hippocampus of 17 patients with medication-resistant epilepsy undergoing intracranial EEG evaluation. The relationships between hippocampal volume, neurochemical levels, and relevant clinical factors were examined.
Results: Increased EC glutamate in the epileptogenic hippocampus was significantly related to smaller ipsilateral (R²= 0.75, p < 0.0001), but not contralateral hippocampal volume when controlled for glutamine and GABA levels, and for clinical factors known to influence hippocampal volume. Glutamate in the atrophic hippocampus was significantly higher (p = 0.008, n = 9), with the threshold for hippocampal atrophy estimated as 5 μM. GABA and glutamine levels in the atrophic and nonatrophic hippocampus were comparable. Decreased hippocampal volume was related to higher seizure frequency (p = 0.008), but not to disease duration or febrile seizure history. None of these clinical factors were related to the neurochemical levels.
Conclusions: We provide evidence for a significant association between increased EC glutamate and decreased ipsilateral epileptogenic hippocampal volume in TLE. Future work will be needed to determine whether the increase in glutamate has a causal relationship with hippocampal atrophy, or whether another, yet unknown factor results in both. This work has implications for the understanding and treatment of epilepsy as well as other neurodegenerative disorders associated with hippocampal atrophy.     

Routine EEG and Temporal Lobe Epilepsy: Relation to Long-Term EEG Monitoring, Quantitative MRI, and Operative Outcome

Summary: Purpose: To investigate the relation among routine EEG, long-term EEG monitoring (LTM), quantitative magnetic resonance imaging (MRI), and surgical outcome in temporal lobe epilepsy (TLE).
Methods: We evaluated 159 patients with intractable TLE who underwent an anterior temporal lobectomy between 1988 and 1993. The epileptogenic temporal lobe was determined by ictal LTM. A single awake-sleep outpatient EEG with standard activating procedures was performed before LTM. EEGs were analyzed by a blinded investigator.
Results: MRI scans showed unilateral medial temporal atrophy (109 patients) or symmetrical hippocampal volumes (50 patients). The surgically excised epileptogenic brain tissue revealed mesial temporal sclerosis, gliosis, or no histopathologic alteration. Routine EEG revealed temporal lobe epileptiform discharges in 123 patients. Routine EEG findings correlated with the temporal lobe of seizure origin (p < 0.0001) and the results of MRI volumetric studies (p < 0.0001). Interictal epileptiform discharges were seen only during LTM in 24 patients. Routine EEG was disconcordant with interictal LTM in another 20 patients. MRI-identifed unilateral medial temporal lobe atrophy was a strong predictor of operative success (p < 0.0001). There was no significant relation between the routine EEG findings and operative outcome (p > 0.20).
Conclusions: Results of this study modified our approach in patients with TLE. Interictal epileptiform discharges localized to one temporal lobe on serial routine EEGs or during LTM may be adequate to identify the epileptogenic zone in patients with MRI-identified unilateral medial temporal lobe atrophy.     

Extratemporal ictal clinical features in hippocampal sclerosis: their relationship to the degree of hippocampal volume loss and to the outcome of temporal lobectomy

Purpose: Since extratemporal clinical features in patients with unilateral hippocampal sclerosis (HS) are likely to indicate aberrant ictal spread or a more extensive epileptogenic zone, we asked whether such features are associated with more severe HS and a worse outcome following temporal lobectomy.
Patients and methods: We reviewed all patients (174) who had undergone temporal lobectomy for histologically proven unilateral HS related temporal lobe epilepsy between 1997–2005 at the National Hospital for Neurology and Neurosurgery. We divided patients into those with severe HS (side-to-side ratio < 0.6) and those with mild HS (side-to-side ratio > 0.75). We examined all seizures recorded on electroencephalography (EEG) video telemetry in these patients for clinical features of temporal lobe epilepsy. The postsurgical outcome was classified using the Engel classification at the time of follow up (median 4.7 years, range 1–9 years).
Results: Patients (28 out 39) with severe HS had atypical features compared to 7 out of 27 in the mild HS [Chi square (χ ² ) test, p = 0.0013]. The mean number of atypical clinical features was 2.2 in the severe HS group and 0.62 in the mild HS group (Mann Whitney U Test, p < 0.001). The percentage of postsurgery seizure freedom (class 1 Engel classification) was 87%, and there was no significant effect of the presence of atypical clinical features.
Conclusions: This study shows that atypical (extratemporal) clinical features tend to occur more frequently in patients with severe HS and do not correlate with worse surgical outcome.     

Reduced hippocampal 5HT1A PET receptor binding and depression in temporal lobe epilepsy

Summary:  Purpose: To study the relation of hippocampal 5HT1A receptor binding to symptoms of depression in patients with temporal lobe epilepsy. Depression is common in people with epilepsy, and reduced 5HT1A binding has been reported in patients with primary depressive disorders.
Methods: We studied 45 patients with temporal lobe epilepsy confirmed by ictal video-EEG recording. Mood was assessed with the Beck Depression Inventory (BDI). Positron emission tomographic measurement of 5HT1A receptors was performed with 18F-FCWAY, a highly specific silent antagonist. 3D-T1-weighted MRI was used to correct for structural atrophy. Receptor distribution volume (V) was corrected for plasma tracer free fraction (f1).
Results: There was a significant inverse relation between ipsilateral hippocampal v/f1 and the BDI. For contralateral hippocampus, there was a nonsignificant trend. Patients with BDI > 20 had significantly lower ipsilateral hippocampal V/f1 than patients in the low and medium groups. There was no significant effect of the presence of mesial temporal sclerosis, focus laterality, or gender on the BDI.
Conclusions: Our study shows a relationship between hippocampal 5HT1A binding and depressive symptoms measured by the BDI in patients with epilepsy. The findings parallel results in patients with MDD.     

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.     

MRI lesion and epileptogenic focus in temporal lobe epilepsy

The spatial relationship between a circumscribed lesion in the temporal lobe detected by MRI and an epileptogenic focus identified by ictal depth EEG along with a correlation of the MRI lesion with neuropathological findings were investigated in patients with medically intractable temporal lobe epilepsy but without any focal lesion on CT. Four parameters (an areal ratio of the temporal lobe against the hemisphere, area and calculated T1, T2 values of the hippocampus) were used to determine the abnormal MRI side. An agreement was reached in 67-72% of 18 patients between the abnormal values of the hippocampal area and of calculated T1, T2 and the side of the epileptogenic focus. In 14 of 17 patients, typical hippocampal sclerosis was demonstrated in resected tissue in accordance with the MRI lesions (atrophy and/or prolonged T2 of hippocampus). These results imply: 1) MRI abnormality thus defined may, if not all, indicate the side of the epileptogenic focus, and 2) also the presence of hippocampal sclerosis. It was emphasized that the MRI lesion would be a usable instrument to explore the causal relationship of hippocampal sclerosis to a generation of epileptogenic lesions as well as for presurgical evaluation.     

Decreased dopamine D2/D3-receptor binding in temporal lobe epilepsy: an [18F]fallypride PET study

PURPOSE: Although animal data are suggestive, evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing. METHODS: To quantify D2/D3-receptor density, we studied seven patients with temporal lobe epilepsy (TLE) and nine age-matched controls with positron emission tomography (PET) by using the high-affinity dopamine D2/D3-receptor ligand [18F]Fallypride ([18F]FP) suitable for imaging extrastriatal binding. TLE was defined by interictal and ictal video-EEG, magnetic resonance imaging (MRI), and [18F]fluorodeoxyglucose ([18F]FDG)-PET and was due to hippocampal sclerosis (HS), based on histology in all patients. Primary analysis was based on regions of interest (ROIs) defined on individual MRIs. For each patient, binding potential (BP) was calculated by using the simplified reference tissue model, and the epileptogenic was compared with the unaffected hemisphere in each ROI. To confirm the results, an additional voxel-based group analysis was performed by using statistical parametric mapping. RESULTS: Compared with controls, [18F]FP BP was significantly decreased in the epileptogenic temporal lobe in all patients. On ROI analysis, this reduction was evident in areas surrounding the seizure-onset zone at the pole (-34.2%) and lateral aspects (-32.9%) of the temporal lobe. Although the hippocampus [18F]FDG uptake (-8.1%) and hippocampal MR volume (-35.1%) were significantly reduced, no significant decrease of [18F]FP BP was found. Reduction of [18F]FP BP did not correlate with hippocampal atrophy. CONCLUSIONS: D2/D3-receptor binding is reduced at the pole and in lateral aspects of the epileptogenic temporal lobe in patients with mesial TLE and HS. This area might correspond to "the irritative zone," indicating that D2/D3 receptors might play a specific role in the pathophysiology of mesial TLE.     

Volumetric MRI, pathological, and neuropsychological progression in hippocampal sclerosis

OBJECTIVE: To examine the relationships between age at onset and duration of seizure disorder with severity of hippocampal sclerosis (HS) and cognitive functioning in patients with HS and unilateral temporal lobe epilepsy. METHODS: Twenty-six subjects had left temporal lobe seizure onset; 20 had right temporal onset. Measures were age at seizure onset, duration of seizure disorder divided by age (seizure duration), history of febrile convulsion (FC), ratio of the smaller hippocampal volume to the larger (HF) as determined by volumetric MRI, and pathologic HS grade. RESULTS: Results showed that pathologic HS grade and HF were positively related to seizure duration, and negatively related to seizure onset. When subjects were divided into onset prior to age 10 versus later, subjects with earlier onset had higher mean pathologic HS grade and smaller (more asymmetric) mean HF. When subjects were divided into seizure duration <0.5 (i.e., less than half current lifetime) vs greater, subjects with seizure duration > or =0.5 had higher mean pathologic HS grade and lower mean HF. There was also evidence for earlier age at seizure onset and longer seizure duration being associated with worse performance on neuropsychological measures. FC was not related to either seizure duration or age at seizure onset, but patients with a history of FC showed higher pathologic HS grade and lower HF. A history of FC was not related to cognitive functioning. CONCLUSIONS: Unilateral HS patients with earlier seizure onset and longer duration of epilepsy have more severe HS and greater hippocampal volume asymmetry. This suggests that HS may be a progressive disorder with risk for cognitive dysfunction.     

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes

Objective

To investigate the clinical and surgical outcome correlates of preoperative hippocampal subfield volumes in patients with refractory temporal lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence segmentation technique.

Methods

We recruited 106 patients with TLE and hippocampal sclerosis (HS) who underwent conventional T1‐weighted and T2 short TI inversion recovery MRI. An automated hippocampal segmentation algorithm was used to identify twelve subfields in each hippocampus. A total of 76 patients underwent amygdalohippocampectomy and postoperative seizure outcome assessment using the standardized ILAE classification. Semiquantitative hippocampal internal architecture (HIA) ratings were correlated with hippocampal subfield volumes.

Results

Patients with left TLE had smaller volumes of the contralateral presubiculum and hippocampus‐amygdala transition area compared to those with right TLE. Patients with right TLE had reduced contralateral hippocampal tail volumes and improved outcomes. In all patients, there were no significant relationships between hippocampal subfield volumes and clinical variables such as duration and age at onset of epilepsy. There were no significant differences in any hippocampal subfield volumes between patients who were rendered seizure free and those with persistent postoperative seizure symptoms. Ipsilateral but not contralateral HIA ratings were significantly correlated with gross hippocampal and subfield volumes.

Conclusions

Our results suggest that ipsilateral hippocampal subfield volumes are not related to the chronicity/severity of TLE. We did not find any hippocampal subfield volume or HIA rating differences in patients with optimal and unfavorable outcomes. In patients with TLE and HS, sophisticated analysis of hippocampal architecture on MRI may have limited value for prediction of postoperative outcome.     

Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy

The aims of this study were to examine the relationships of hippocampal T2 (HCT2) relaxation time and magnetic resonace (MR)-based hippocampal volume (HCV) to neuronal (ND) and glial cell densities (GD) of hippocampal neuronal cell layers, and to obtain a better clinicopathological definition of hippocampal sclerosis (HS) and end folium sclerosis (EFS). Fifty-three hippocampi with HS, 6 with EFS, and 6 control hippocampi were studied. Pathologically, the HS group had a significantly higher logarithm (log) GD/ND than the controls in all hippocampal subregions, and than the EFS group in all subregions except the granule cell layer of the dentate gyrus (GCDG). The EFS group had a significantly higher log GD/ND than the control group only in the GCDG. Clinical correlations suggested that EFS may be the consequence of temporal lobe seizures and not an epileptogenic entity. Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus. An increased HCT2 was associated with damage in the CA1 and also the hilus and has a different neuropathological basis than HCV loss. MR-based HCV measurement and HCT2 mapping, therfore, give complementary information in the presurgical evaluation of temporal lobe epilepsy and longitudinal studies.     

Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: Preliminary results

Purpose:   High-resolution magnetic resonance imaging (MRI) at 4 Tesla depicts details of the internal structure of the hippocampus not visible at 1.5 Tesla, and so allows for in vivo parcellation of different hippocampal subfields. The aim of this study was to test if distinct subfield atrophy patterns can be detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) and without (TLE-no) hippocampal sclerosis.
Methods:   High-resolution T₂-weighted hippocampal images were acquired in 34 controls: 15 TLE-MTS and 18 TLE-no. Entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, and CA3, and dentate (CA3&DG) volumes were determined using a manual parcellation scheme.
Results:   TLE-MTS had significantly smaller ipsilateral CA1, CA2, CA3&DG, and total hippocampal volume than controls or TLE-no. Mean ipsilateral CA1 and CA3&DG z-scores were significantly lower than ipsilateral CA2, ERC, and SUB z-scores. There were no significant differences between the various subfield or hippocampal z-scores on either the ipsi- or the contralateral side in TLE-no. Using a z-score ≤−2.0 to identify severe volume loss, the following atrophy patterns were found in TLE-MTS: CA1 atrophy, CA3&DG atrophy, CA1 and CA3&DG atrophy, and global hippocampal atrophy. Significant subfield atrophy was found in three TLE-no: contralateral SUB atrophy, bilateral CA3&DG atrophy, and ipsilateral ERC and SUB atrophy.
Discussion:   Using a manual parcellation scheme on 4 Tesla high-resolution MRI, we found the characteristic ipsilateral CA1 and CA3&DG atrophy described in TLE-MTS. Seventeen percent of the TLE-no had subfield atrophy despite normal total hippocampal volume. These findings indicate that high-resolution MRI and subfield volumetry provide superior information compared to standard hippocampal volumetry.     

Persistent seizures following left temporal lobe surgery are associated with posterior and bilateral structural and functional brain abnormalities

PURPOSE: To perform a quantitative MRI and retrospective electrophysiological study to investigate whether persistent post-surgical seizures may be due to brain structural and functional abnormalities in temporal lobe cortex beyond the margins of resection and/or bilateral abnormalities in patients with temporal lobe epilepsy (TLE). METHODS: In 22 patients with left TLE and histopathological evidence of hippocampal sclerosis, we compared pre-surgical brain morphology between patients surgically remedied (Engel's I) and patients with persistent post-surgical seizures (PPS, Engel's II-IV) using voxel-based morphometry (VBM). Routine pre-surgical EEG and invasive and non-invasive telemetry investigations were additionally compared between patient groups. RESULTS: Results indicated widespread structural and functional abnormalities in patients with PPS relative to surgically remedied patients. In particular, patients with PPS had significantly reduced volume of the ipsilateral posterior medial temporal lobe and contralateral medial temporal lobe relative to surgically remedied patients. Furthermore, successful surgery was associated with clear anterior (89%) and unilateral (100%) temporal lobe EEG abnormalities, whilst PPS were associated with widespread ipsilateral (91%) and bilateral (82%) temporal lobe abnormalities. DISCUSSION: We suggest that these preliminary data support the hypothesis that PPS after temporal lobe surgery are due to functionally connected epileptogenic cortex remaining in the ipsilateral posterior temporal lobe and/or in temporal lobe contralateral to resection.     

Texture analysis of hippocampal sclerosis

Mesial temporal lobe epilepsy (MTLE) is frequently associated with refractory seizures and pathologic features of hippocampal sclerosis (HS). Quantitative magnetic resonance imaging (MRI) techniques can improve the detection and quantification of HS. The objective of this study was to evaluate whether MRI texture analysis can detect hippocampal abnormalities in patients with pathologically proven HS. METHODS: Nineteen consecutive patients who underwent surgery for refractory unilateral MTLE and had HS diagnosed on histopathology (12 right and seven left) had their preoperative MRIs evaluated. We performed texture analysis in 3-mm coronal T1-IR MRIs, focusing on the hippocampal head, by using the software MAZDA. Data were compared with those of a group of 78 normal hippocampi from 39 healthy adult volunteers through multivariate analysis of variance and selection of the most significant texture parameters. RESULTS: Overall, almost all parameters of texture could discriminate the group of hippocampi with HS and the group of contralateral hippocampi from the group of normal hippocampi, but the post hoc comparison showed no differences between HS and contralateral hippocampi. CONCLUSIONS: These results provide evidence of texture alteration in MRIs of hippocampi with HS and corroborate the hypothesis of bilaterality of hippocampal damage in patients with MTLE, but further studies are needed to investigate the lateralization power of texture analysis.     

Prediction of postoperative seizure control by hippocampal event-related potentials

PURPOSE: In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event-related potentials (ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process, we examined whether ERPs can help to improve the prediction of postoperative seizure control. METHODS: We recorded ERPs to words from bilateral intrahippocaampal electrodes by using a visual word-recognition paradigm in 70 patients with unilateral hippocampal pathology and related these measurements to seizure outcome after temporal lobe surgery. RESULTS: Words elicited N400 potentials, which were reduced in amplitude on repetition on the side contralateral to hippocampal sclerosis. This contralateral repetition effect, however, was significantly diminished in the group of patients who experienced seizure recurrence after the operation. Contralateral repetition effects thus permitted correct prediction of postoperative seizure control in 94% of all patients. CONCLUSIONS: Recording ERPs to words within the medial temporal lobes can improve the prediction of postoperative seizure control. Reduced repetition effects contralateral to the side of hippocampal sclerosis may indicate bilateral epileptogenicity.     

When should a resection sparing mesial structures be considered for temporal lobe epilepsy?

Anteromesial temporal lobectomy (AMTL) is an effective and safe treatment for refractory temporal lobe epilepsy (TLE) caused by hippocampal sclerosis (HS). It is possible that modifications to this procedure could offer improved seizure control or a reduction in functional consequences in some patients. Reviewed here is the issue of when it might be appropriate to perform a resection for TLE that spares the mesial structures, particularly the hippocampus and parahippocampal gyrus. This issue is particularly important for dominant hemipshere TLE and for patients without obvious HS, as these are the patients at greatest risk for verbal memory decline following AMTL. Current evidence suggests that mesial structure-sparing resections may be worth consideration for two types of patients: those with temporal lobe foreign tissue lesions outside the mesial structures, and those with temporal lobe hypometabolism on fluorodeoxyglucose positron emission tomography but a normal MRI. Patients with dual pathology (i.e., HS plus another epileptogenic lesion) are unlikely to benefit from a resection that spares the mesial temporal lobe. There is little evidence to state whether resections of this kind are worthwhile for cryptogenic TLE, or for mesial TLE with preserved memory function. There is a clear need to move beyond the field's present focus on the hippocampus and investigate new approaches to TLE that may minimize the risks of functional consequences in patients without HS.     

Measures of hippocampal volumes, diffusion and 1H MRS metabolic abnormalities in temporal lobe epilepsy provide partially complementary information

We assessed whether interictal measures of hippocampal volume, hippocampal diffusion and metabolic abnormalities yield correlated or complementary information about hippocampal pathology in patients with temporal lobe epilepsy (TLE). Volumes, apparent diffusion coefficients (ADC) and ratios of N-acetyl-aspartate (NAA) to Creatine/Phosphocreatine (Cr) and Choline (Cho) were measured from each hippocampus during one magnetic resonance imaging (MRI) session in patients with TLE. Structural MRI showed unilateral hippocampal sclerosis (HS) in 13 patients and was normal in the remaining nine patients. Pearson's correlation (two-tailed) between ADC values and NAA/(Cr + Cho) ratios was significant (P = 0.04, r = -0.45) for the hippocampus ipsilateral to the epileptogenic zone as determined on the basis of interictal and ictal scalp EEG recordings. This finding was driven by a very high correlation between the two measures in the presence of HS (P < 0.001, r = -0.96). Furthermore, ipsilateral ADC values but not NAA/(Cr + Cho) ratios were correlated with disease duration (P = 0.001, r = 0.67). Hippocampal volumes did not correlate with either ADC values, NAA/(Cr + Cho) ratios or disease duration. These data suggest that hippocampal volumes, NAA/(Cr + Cho) ratios and ADC values capture partially complementary aspects of hippocampal pathology.