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.     

Asymmetric cortical surface area and morphology changes in mesial temporal lobe epilepsy with hippocampal sclerosis

Purpose: To date, magnetic resonance imaging (MRI)–based studies of the cerebral cortex in mesial temporal lobe epilepsy (MTLE) have focused primarily on investigating cortical volume and thickness. However, volume is a composite of surface area and thickness, each reflecting distinct neurobiologic and genetic processes. The goal of this study was to investigate cerebral cortex (1) surface area, (2) surface geometric distortion, and (3) thickness in MTLE with hippocampal sclerosis (HS). Methods: Seventy patients with “sporadic” unilateral MTLE + HS and 40 healthy controls underwent T₁‐weighted MRI. Processing MR images using an automated cortical surface reconstruction method (FreeSurfer), we quantified cortical surface area, surface geometric distortion (metric distortion), and thickness at each vertex across the entire cortex. Differences between patients and controls were determined using generalized linear models. Separate linear regression models were employed to assess the relationship between cortical surface area and hippocampal volume as well as a series of important clinical features of the condition. Key Findings: We detected an asymmetric reduction in cortical surface area, predominantly in ipsilateral mesial and anterior temporal lobe subregions, of patients with MTLE + HS. Changes in surface geometric features were also evident and closely mirrored surface area patterns. In contrast, cortical thinning appeared dispersed across the cortex bilaterally. The regression models revealed that ipsilateral hippocampal volume was a significant predictor of temporal lobe surface area changes. Significance: Our findings indicate that contraction in surface area, rather than cortical thinning, explains ipsilateral mesial and anterior temporal lobe atrophy in patients with MTLE with HS. Furthermore, the alterations in surface geometry indicate folding abnormality involving the same regions. Cortical surface changes may represent sequelae of the disease or deviant cortical development.     

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.     

Prognostic factors for the surgery for mesial temporal lobe epilepsy: longitudinal analysis

PURPOSE: Determining long-term prognostic factors of surgery for mesial temporal lobe epilepsy (MTLE) is important for identifying ideal candidates and predicting the prognosis for individual patients. We tried to identify the prognostic factors of anterior temporal lobectomy (ATL) for MTLE with longitudinal multivariate analysis. METHODS: Two hundred twenty-seven patients with MTLE were included in this study. The primary outcome variable was patient status 1-5 years after surgery: seizure free, or not. Clinical characteristics and recent diagnostic modalities were considered as prognostic factors. Univariate and standard multiple logistic-regression analysis for outcome at 1 and 5 years after surgery and the generalized estimation equation (GEE) model for longitudinal multiple logistic regression of the 5-year follow-up period were used. RESULTS: The seizure-free rate at 1 year was 81.1% and decreased to 75.2% at 5 years after surgery. By the univariate or standard multiple logistic-regression analysis, age at surgery or hippocampal sclerosis on magnetic resonance imaging (MRI) ipsilateral to surgery was significant for the postsurgical outcome. However, the longitudinal analysis by the GEE model revealed that younger age at surgery [odds ratio (OR), 0.59; 95% confidence interval (CI), 0.43-0.81], absence of secondarily generalized tonic-clonic seizure (2 degrees GTCS; OR, 0.45; 95% CI, 0.26-0.79), and hippocampal sclerosis on MRI (OR, 2.44; 95% CI, 1.11-5.26) were significant predictors of a good surgical outcome. CONCLUSIONS: Age at surgery, presence of 2 degrees GTCS, and hippocampal sclerosis on MRI are independent prognostic factors for ATL in MTLE. These findings suggest that MTLE is a progressive disorder, and surgical outcome is better when early ATL is performed.     

Surgical treatment for temporal lobe epilepsy in childhood]

We retrospectively analyzed 5 children (11-15 year) with intractable temporal lobe epilepsy (TLE) who underwent the anterior temporal lobectomy with hippocampectomy. Cases 1-3 had medial TLE (MTLE) with histologically verified hippocampal sclerosis, Case 4 had lateral TLE, and Case 5 had MTLE with old hemorrhagic lesion in the lateral temporal lobe. In Cases 3-5, chronic invasive electrocorticography recording using subdural electrodes was obtained, while in Cases 1 and 2, the epileptogenic region was defined by noninvasive preoperative evaluation. Postoperatively, Cases 1-3 became seizure free. All patients had psychosocial problems after the onset of their epilepsy, which was not improved even after the surgical control of epilepsy. Since most patients had morphological change and perfusional and metabolic disturbance outside the hippocampus at the time of surgery, earlier surgical consideration may be necessary.     

Non-invasive examinations successfully select patients with medial temporal lobe epilepsy for anterior temporal lobectomy]

We retrospectively analyzed 8 patients with intractable medial temporal lobe epilepsy (MTLE) who underwent the anterior temporal lobectomy with hippocampectomy (ATL) without invasive examinations such as chronic subdural electrode recording. Five patients had a history of febrile convulsion. While all 8 patients had oral automatism, automatism of ipsilateral limbs with dystonic posture of contralateral limbs was demonstrated in 2 patients. Bilateral temporal paroxysmal activities on interictal EEG was observed in 4 patients and all patients had clear ictal onset zone on unilateral anterior temporal region. MRI demonstrated unilateral hippocampal sclerosis in 5 cases. Interictal FDG-PET depicted hypometabolism of the unilateral temporal lobe in all cases, however, ECD-SPECT failed to reveal the hypoperfusion of the unilateral temporal lobe in a case. Postoperatively, 7 cases became seizure free, and one had rare seizure. Non-invasive examinations, especially ictal EEG and concordant FDG-PET findings, in patients with oral automatism in seizure semiology, successfully select patients with MTLE for ATL.     

Sex differences in patients with mesial temporal lobe epilepsy

Possible sex differences in the pattern of interictalhypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobehypometabolism ipsilateral to the seizure onset (p<0.0001) and aspread of epileptiform activity to this region (p=0.001). By contrast,female patients more often exhibited hypometabolism (p=0.0052) and anictal spread to the contralateral temporal lobe (p=0.0097). Thesefindings suggest sex differences in spatial distribution of braindysfunction in MTLE, perhaps reflecting sexual dimorphism in regionalcerebral connectivity.

     

Regional Cerebral Blood Flow During Temporal Lobe Seizures Associated with Ictal Vomiting: An Ictal SPECT Study in Two Patients

PURPOSE: Ictal vomiting represents a rare clinical manifestation during seizures originating from the temporal lobes of the nondominant hemisphere. The precise anatomic structures responsible for generation of ictal vomiting remain to be clarified. Ictal single photon emission computed tomography (SPECT), which allows one to visualize the three-dimensional dynamic changes of regional cerebral blood flow (rCBF) associated with the ongoing epileptic activity, should be useful to study the brain areas activated during ictal vomiting. METHODS: We performed ictal Tc-HMPAO SPECT scans in two patients with mesial temporal lobe epilepsy (MTLE) whose seizures were characterized by ictal retching and vomiting. MTLE was documented by typical clinical seizure semiology, interictal and ictal EEG findings, hippocampal atrophy on magnetic resonance imaging (MRI) scan, and a seizure-free outcome after selective amydalohippocampectomy. In both patients, seizures originated in the nondominant temporal lobe. We obtained accurate anatomic reference of rCBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. We used ictal SPECT studies in 10 patients with MTLE who had seizures without ictal vomiting as controls. RESULTS: In the two patients with ictal vomiting, we found a significant hyperperfusion of the nondominant temporal lobe (inferior, medial, and lateral superior) and of the occipital region on ictal SPECT. In patients without ictal vomiting, on the contrary, these brain regions never were hyperperfused simultaneously. CONCLUSIONS: Ictal SPECT provides further evidence that activation of a complex cortical network, including the medial and lateral superior aspects of the temporal lobe, and maybe the occipital lobes, is responsible for the generation of ictal vomiting.     

Hippocampal atrophy in temporal lobe epilepsy: the 'generator' and 'receiver'

Bonilha L, Halford JJ, Morgan PS, Edwards JC. Hippocampal atrophy in temporal lobe epilepsy: the ‘generator’ and ‘receiver’.
Acta Neurol Scand: 2012: 125: 105–110.
© 2011 John Wiley & Sons A/S. Objective – Some patients with unilateral medial temporal lobe epilepsy (MTLE) display bilateral hippocampal atrophy on MRI, even though seizures originate in only one hippocampus. The correct identification of the epileptogenic hippocampus (the ‘generator’) vs the non‐epileptogenic (the ‘receiver’) may lead to better surgical planning and results. Materials and Methods – We studied 14 patients with MTLE (eight left and six right) who became seizure free after unilateral hippocampal resection, with hippocampal sclerosis confirmed by histology. Hippocampal tridimensional morphometry was performed comparing patients and healthy controls employing a voxel‐wise Wilcoxon test. Results were corrected for multiple comparisons with the application of a False Discovery Rate (FDR)‐corrected threshold for q < 0.05. Results – Patients with MTLE showed atrophy involving the ipsilateral hippocampus and the contralateral hippocampus, more pronouncedly within the ipsilateral hippocampus in the anterior–inferior aspect of the hippocampal head (left MTLE, left hippocampus x = ?28, y = ?16, z = ?24, Z = 3.6; right MTLE, right hippocampus x = 22, y = ?11, z = ?27, Z = 2.9). On the contralateral hippocampus, the atrophy was more noticeable in the posterior head and body areas. Conclusion – The epileptogenic hippocampal atrophy has an anatomically distinct pattern compared with the contralateral hippocampus. This information may help guide the presurgical assessment of MTLE.     

Surgical treatment for temporal lobe epilepsy in patients over age 50 years]

We retrospectively analyzed 4 patients over age 50 (52 - 57) years with intractable medial temporal lobe epilepsy(MTLE) who underwent the anterior temporal lobectomy with hippocampectomy. Case 1 had MTLE with old brain abscess in the left lateral temporal lobe and Cases 2 - 4 had MTLE with histologically verified hippocampal sclerosis. In Cases 2 - 4, although the onset of seizures occurred 26 to 37 years prior to the time of surgery, there was no mental problem (IQ = 87 - 100). In Cases 1, chronic invasive electrocorticography recording using subdural electrodes was obtained, while in Case 2 - 4, the epileptogenic region was defined by noninvasive preoperative evaluation. Postoperatively, all patients obtained a meaningful improvement, becoming either free from seizures or only experiencing a rare seizure, and returned to work or usual activities without surgical complications. Surgery for MTLE appears to be effective for older individuals and carries a small risk of postoperative complications.     

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.     

Short-term cognitive changes after surgery in patients with unilateral mesial temporal lobe epilepsy associated with hippocampal sclerosis

We investigated the short-term postoperative cognitive function of patients with unilateral mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS). Fourteen unilateral MTLE/HS patients who had undergone selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) were enrolled. Cognitive functions related to the frontal and temporal lobes were evaluated using a battery of neuropsychological tests administered before surgery and 3 months after surgery. The battery included the Verbal Fluency Test (VFT), Boston Naming Test (BNT), Stroop Color-Word Test (TST), Trail Making Test (TMT) and Wechsler Memory Scale (WMS). MTLE/HS patients demonstrated significantly improved postoperative performance on the TST regardless of the surgical method or side of resection. There was no significant difference in any of the other neuropsychological tests before and after surgery. After left-side resection, performance on the VFT and the TMT-B was worse than at baseline. After right-side resection, performance on the VFT and WMS short-term memory improved; however, these differences were not statistically significant. SAH patients exhibited improved TST performance but worse TMT-A performance; however, performance on all tests was not significantly different after surgery in ATL patients. In summary, MTLE/HS patients demonstrated improved frontal lobe-related cognitive function after surgery, but no such improvement in temporal lobe-related function was observed. Based on cognitive evaluation, right-sided MTLE/HS patients may be more appropriate surgical candidates than left-sided MTLE/HS patients. SAH may not be better than ATL in improving cognitive function. We hypothesise that postoperative cognitive changes depend on whether the excised cerebral regions are related to the neuropsychological functions examined by specific assessment instruments.     

Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures

Background It has been hypothesised that seizure induced neuronal loss and axonal damage in medial temporal lobe epilepsy (MTLE) may lead to the development of aberrant connections between limbic structures and eventually result in the reorganisation of the limbic network. In this study, limbic structural connectivity in patients with MTLE was investigated, using diffusion tensor MRI, probabilistic tractography and graph theory based network analysis. Methods 12 patients with unilateral MTLE and hippocampal sclerosis (five left and seven right MTLE) and 26 healthy controls were studied. The connectivity of 10 bilateral limbic regions of interest was mapped with probabilistic tractography, and the probabilistic fibre density between each pair of regions was used as the measure of their weighted structural connectivity. Binary connectivity matrices were then obtained from the weighted connectivity matrix using a range of fixed density thresholds. Graph theory based properties of nodes (degree, local efficiency, clustering coefficient and betweenness centrality) and the network (global efficiency and average clustering coefficient) were calculated from the weight and binary connectivity matrices of each subject and compared between patients and controls. Results MTLE was associated with a regional reduction in fibre density compared with controls. Paradoxically, patients exhibited (1) increased limbic network clustering and (2) increased nodal efficiency, degree and clustering coefficient in the ipsilateral insula, superior temporal region and thalamus. There was also a significant reduction in clustering coefficient and efficiency of the ipsilateral hippocampus, accompanied by increased nodal degree. Conclusions These results suggest that MTLE is associated with reorganisation of the limbic system. These results corroborate the concept of MTLE as a network disease, and may contribute to the understanding of network excitability dynamics in epilepsy and MTLE.     

Clinical features of neocoritcal temporal lobe epilepsy

Few Studies have examined the clinical features of neocortical temporal lobe epilepsy (NTLE) in carefully selected patients. We reviewed records from 21 patients wtih NTLE, defined by intracranial electroencephal9ogram (EEG), who have been seizure free for 1 year or more following temporal lobectomy. The mean age of onset at the time of first seizure was 14 years (range, 1–41 years). Febrile seizures were reported in only 2 patients (9.5%). In contrast to prior mesial temporal lobe epilepsy (MTLE) studies, seizure-free intervals between the initial cerebral insult or first seizure and habitual seizures were uncommon. Possible or known risk factors for epilepsy were reported in 13 of 21 patients (62%). Fifteen (71%) patients reproted auras, with experiential phenomena being the most common type. Magnetic resonance imaging was normal or nospecific in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and resonance imaging was normal or nospecifc in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and heterotopic gray matter and hippocampal atrophy in 1, and cortical dysgensis in 1. Neuropsychological testing showed deficits consistent with the seizure focus in 13 patients (62%), and Wada test showed ipsilateral memory deficits in 10 (48%). The most common behavioral manifestatin was a motionless stare at ictal onset (48%). In contrast to prior studies of MTLE, only 1 NTLE patient had frequent independent, contralateral temporal lobe epileptiform spikes on scalp EEG.     

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.     

Thalamic hypometabolism on 18FDG-positron emission tomography in medial temporal lobe epilepsy

OBJECTIVES: Degree of hypometabolism in the thalamus on (18)Fluorodeoxyglucose-positron emission tomography (FDG-PET) was compared with those of medial and lateral temporal lobes in patients with medial temporal lobe epilepsy (mTLE), and its relationship with post-operative seizure outcomes was investigated. METHODS: Twenty-six patients with mTLE who underwent anterior temporal lobectomy were included. Post-operatively, 13 patients became completely seizure-free and 13 showed residual seizure, regardless of frequency (five patients became almost seizure-free, six had rare seizures and two showed significant improvements). Degrees of hypometabolism in bilateral thalamus, ipsilateral medial and lateral temporal lobes were evaluated visually and semi-quantitatively by determining the asymmetry index (AI), a value indicating 100 x (ipsilateral - contralateral)/[1/2 x (ipsilateral + contralateral)] and the region-to-cerebral hemisphere ratio (R/C ratio) being the ratio between averaged counts in each area and those in the cerebral hemisphere of the same side. RESULTS: Hypometabolism in the medial temporal lobe was visually observed in all patients. Hypometabolism in the lateral temporal lobe was observed in 20 patients and was semi-quantitatively more prominent than that of the medial temporal lobe. Pathologically, hippocampal sclerosis and prominent astrogliosis of the lateral temporal lobe were present in all cases. However, while thalamic hypometabolism was visually observed in nine patients (in the ipsilateral side of four cases, contralateral side of three and on both sides of two), no significant thalamic hypometabolism was semi-quantitatively observed. No significant differences in metabolic rate in any area except for the lateral temporal lobe between seizure-free patients and residual seizure patients were seen semi-quantitatively. DISCUSSION: Data indicated that metabolism in the lateral temporal lobe of patients with mTLE significantly decreased and revealed pathologic glial changes. Thalamic hypometabolism was quite mild and did not correlate with post-operative seizure outcome.     

Postoperative changes in cerebral metabolism in temporal lobe epilepsy

BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452     

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.     

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.     

Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy

Purpose: Medial temporal epilepsy (MTLE) is associated with extrahippocampal brain atrophy. The mechanisms underlying brain damage in MTLE are unknown. Seizures may lead to neuronal damage, but another possible explanation is deafferentation from loss of hippocampal connections. This study aimed to investigate the relationship between hippocampal deafferentation and brain atrophy in MTLE. Methods: Three different MRI studies were performed involving 23 patients with unilateral MTLE (8 left and 15 right) and 34 healthy controls: (1) voxel‐based morphometry (VBM), (2) diffusion tensor imaging (DTI) and (3) probabilistic tractography (PT). VBM was employed to define differences in regional gray matter volume (GMV) between controls and patients. Voxel‐wise analyses of DTI evaluated differences in fractional anisotropy (FA), mean diffusivity (MD) and hippocampal PT. Z‐scores were computed for regions‐of‐interest (ROI) GMV and peri‐hippocampal FA and MD (to quantify hippocampal fiber integrity). The relationship between hippocampal deafferentation and regional GMV was investigated through the association between ROI Z scores and hippocampal fiber integrity. Results: Patients with MTLE exhibited a significant reduction in GMV and FA in perihippocampal and limbic areas. There was a decrease in hippocampal PT in patients with MTLE in limbic areas. A significant relationship between loss of hippocampal connections and regional GMV atrophy was found involving the putamen, pallidum, middle and inferior temporal areas, amygdala and ceberellar hemisphere. Discussion: There is a relationship between hippocampal disconnection and regional brain atrophy in MTLE. These results indicate that hippocampal deafferentation plays a contributory role in extrahippocampal brain damage in MTLE.