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.     

Different structural correlates for verbal memory impairment in temporal lobe epilepsy with and without mesial temporal lobe sclerosis

Objectives: Memory impairment is one of the most prominent cognitive deficits in temporal lobe epilepsy (TLE). The overall goal of this study was to explore the contribution of cortical and hippocampal (subfield) damage to impairment of auditory immediate recall (AIMrecall), auditory delayed recall (ADMrecall), and auditory delayed recognition (ADMrecog) of the Wechsler Memory Scale III (WMS‐III) in TLE with (TLE–MTS) and without hippocampal sclerosis (TLE‐no). It was hypothesized that volume loss in different subfields determines memory impairment in TLE–MTS and temporal neocortical thinning in TLE‐no. Methods: T1 whole brain and T2‐weighted hippocampal magnetic resonance imaging and WMS‐III were acquired in 22 controls, 18 TLE–MTS, and 25 TLE‐no. Hippocampal subfields were determined on the T2 image. Free surfer was used to obtain cortical thickness averages of temporal, frontal, and parietal cortical regions of interest (ROI). MANOVA and stepwise regression analysis were used to identify hippocampal subfields and cortical ROI significantly contributing to AIMrecall, ADMrecall, and ADMrecog. Results: In TLE–MTS, AIMrecall was associated with cornu ammonis 3 (CA3) and dentate (CA3&DG) and pars opercularis, ADMrecall with CA1 and pars triangularis, and ADMrecog with CA1. In TLE‐no, AIMrecall was associated with CA3&DG and fusiform gyrus (FUSI), and ADMrecall and ADMrecog were associated with FUSI. Conclusion: The study provided the evidence for different structural correlates of the verbal memory impairment in TLE–MTS and TLE‐no. In TLE–MTS, the memory impairment was mainly associated by subfield‐specific hippocampal and inferior frontal cortical damage. In TLE‐no, the impairment was associated by mesial–temporal cortical and to a lesser degree hippocampal damage. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Voxel-based T2 relaxation rate measurements in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis

INTRODUCTION: Quantitative measurements of T(2) relaxation in the hippocampus for focus lateralization in mesial temporal lobe epilepsy (mTLE) are well established. Less is known to what degree such relaxation abnormalities also affect regions beyond the ipsilateral hippocampus. Therefore, the aim of this study was to characterize extent and distribution pattern of extrahippocampal relaxation abnormalities in TLE with (TLE-MTS) and without MRI evidence of mesial-temporal sclerosis (TLE-no). METHODS: Double spin echo images (TE1/2: 20/80 ms) acquired in 24 TLE-MTS and 18 TLE-no were used to calculate relaxation rate maps. These maps were analyzed by SPM2 and by selecting regions of interest (ROI) in the hippocampus and several extrahippocampal brain regions. RESULTS: In TLE-MTS, the results of the SPM and ROI analysis were in good agreement and showed the most severe relaxation rate decreases in the ipsilateral hippocampus but also in other ipsilateral temporal regions, orbitofrontal, and parietal regions and to a lesser degree in contralateral frontal regions. The relaxation rate decreases in TLE-no were confined to small regions in the ipsilateral anterior inferior and medial temporal lobe in the SPM analysis while ROI analysis showed additional regions in the ipsilateral hippocampus, amygdala, and anterior cingulate. CONCLUSION: TLE-MTS showed extensive, widespread but predominantly ipsilateral temporal and also extratemporal T(2) relaxation rate decreases. In contrast, the findings of the SPM and ROI analyses in TLE-no suggested that if relaxation rate decreases are present, they are less uniform and generally milder than in TLE-MTS. This further supports the hypothesis that TLE-no is a distinct clinicopathological entity from TLE-MTS and probably heterogeneous in itself.     

Myoinositol abnormalities in temporal lobe epilepsy

PURPOSE: This study used magnetic resonance spectroscopy (MRS) to examine metabolite abnormalities in the temporal and frontal lobe of patients with temporal lobe epilepsy (TLE) of differing severity. METHODS: We investigated myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO-TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short-echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and analyzed by using LCModel. RESULTS: The temporal lobe ipsilateral to seizure origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated myoinositol (MI; HS-TLE NA, 7.8 +/- 1.9 mM, control NA, 9.2 +/- 1.3 mM; p < 0.05; HS-TLE MI, 6.1 +/- 1.6 mM, control mI 4.9 +/- 0.8 mM, p< 0.05). Frontal lobe MI was low in both patient groups (LO-TLE, 4.3 +/- 0.8 mM; p < 0.05; HS-TLE, 3.6 +/-.05 mM; p < 0.001; controls, 4.8 +/- 0.5 mM). Ipsilateral frontal lobes had lower MI (3.8 +/- 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 +/- 0.8 mM; p < 0.05). CONCLUSIONS: MI changes may distinguish between the seizure focus, where MI is increased, and areas of seizure spread where MI is decreased.     

Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis

PURPOSE: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLE-no. METHODS: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 +/- 9.7 years), 17 TLE-no (mean age, 35.6 +/- 11.1 years), and 30 healthy controls (mean age, 30.3 +/- 11.1 years). RESULTS: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi- and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS. CONCLUSIONS: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi- and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself.     

Amygdala gene expression of NMDA and GABAA receptors in patients with mesial temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real‐time PCR to quantify the expression of GABA_A (subunits α1, β1, β2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in α1, β1, and β2 subunits of GABA_A receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE. © 2010 Wiley Periodicals, Inc., Inc.     

Neocortical abnormalities of [11C]-flumazenil PET in mesial temporal lobe epilepsy

OBJECTIVE: To characterize abnormalities in neocortical central benzodiazepine receptor (cBZR) binding in patients with mesial temporal lobe epilepsy (mTLE) with unilateral hippocampal sclerosis (HS) using [(11)C]-flumazenil-(FMZ) PET and complementary voxel-based and quantitative volume-of-interest (VOI) methods. METHODS: The authors studied 13 control subjects and 15 patients with refractory mTLE and unilateral HS with [(11)C]-FMZ PET. Data were corrected for partial volume effect in the interactively outlined hippocampus and in 28 cortical VOI using an individualized template. A voxel-based analysis was also performed using statistical parametric mapping (SPM). RESULTS: Fourteen patients with mTLE had reduced [(11)C]-FMZ volume distribution (V(d)) in the hippocampus ipsilateral to the EEG focus, extending into the amygdala in four. Five patients showed additional significant neocortical abnormalities of [(11)C]-FMZ binding: temporal neocortical increases (1), extratemporal decreases (2), extratemporal increases only (1), and temporal and extratemporal neocortical increases (1). Group VOI analysis revealed significant reductions only in the ipsilateral hippocampus. SPM showed decreased [(11)C]-FMZ-V(d) in the ipsilateral hippocampus in 13 of 15 patients, extending into the amygdala in eight. Five patients showed additional neocortical abnormalities: temporal neocortical increases only (3), extratemporal decreases (1), or both temporal neocortical and extratemporal decreases (1). Group analysis showed significant reductions in the ipsilateral hippocampus only. CONCLUSIONS: A combination of VOI- and voxel-based analysis of [(11)C]-FMZ PET detected extrahippocampal changes of cBZR binding in eight of 15 patients with mTLE due to HS. The finding of abnormalities in patients who were thought to have unilateral HS only based on MRI suggests that more widespread abnormalities are present in HS.     

Benign mesial temporal lobe epilepsy

Benign mesial temporal lobe epilepsy (bMTLE), which is defined as at least 24 months of seizure freedom with or without antiepileptic medication, has probably been under-recognized because of a literature bias toward refractory epilepsy cases. Seizure onset in bMTLE tends to be in adolescence or adulthood, and patients frequently have a family history of febrile seizures and epilepsy. Long-term seizure freedom is observed with or without antiepileptic medication. On brain MRI, nearly 40% of patients with long-standing bMTLE show evidence of hippocampal sclerosis, a feature usually associated with refractory temporal lobe epilepsy. Prospective studies are needed to determine the features that allow prediction of a benign course, and to clarify the significance of hippocampal MRI changes.     

Identification of abnormal neuronal metabolism outside the seizure focus in temporal lobe epilepsy

PURPOSE: The aim of this study was to identify metabolically abnormal extrahippocampal brain regions in patients with temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) magnetic resonance imaging (MRI) evidence for mesial-temporal sclerosis (MTS) and to assess their value for focus lateralization by using multislice 1H magnetic resonance spectroscopic imaging (MRSI). METHODS: MRSI in combination with tissue segmentation was performed on 14 TLE-MTS and seven TLE-no and 12 age-matched controls. In controls, N-acetylaspartate/(creatine + choline) [NAA/(Cr+Cho)] of all voxels of a given lobe was expressed as a function of white matter content to determine the 95% prediction interval for any additional voxel of a given tissue composition. Voxels with NAA/(Cr+Cho) below the lower limit of the 95% prediction interval were defined as "pathological" in patients and controls. Z-scores were used to identify regions with a higher percentage of pathological voxels than those in controls. Results: Reduced NAA/(Cr+Cho) was found in ipsilateral temporal and parietal lobes and bilaterally in insula and frontal lobes. Temporal abnormalities identified the epileptogenic focus in 70% in TLE-MTS and 83% of TLE-no. Extratemporal abnormalities identified the epileptogenic focus in 78% of TLE-MTS but in only 17% of TLE-no. Conclusions: TLE is associated with extrahippocampal reductions of NAA/(Cr+Cho) in several lobes consistent with those brain areas involved in seizure spread. Temporal and extratemporal NAA/(Cr+Cho) reductions might be helpful for focus lateralization.     

Atypical handedness in mesial temporal lobe epilepsy

ObjectiveThe main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population.MethodsHandedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated.ResultsWe found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p = 0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8 years of age [median; min-max 0.5–17] in left-handers versus 15 years of age [median; min-max 3–30] in right-handers (p < 0.001).ConclusionsLeft-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

Superselective anterior temporal resection in mesial temporal lobe epilepsy

We report the case of a patient with pharmacoresistant mesial temporal lobe epilepsy presenting psychomotor seizures with onset at early childhood. MRI showed a blurred internal structure of the right hippocampus and right mammillary body atrophy. Neuropsychological testing revealed deficits in selective attention and visual planning. Non-invasive recording was not sufficient to precisely detect the seizure onset zone. Invasive recording showed seizure onset in the temporo-polar neocortex, with spread to the amygdalum and hippocampus. A superselective resection of the temporal pole and amygdalum was performed with preservation of the hippocampus. Histology revealed the presence of focal cortical dysplasia (Palmini type Ib). Seizure frequency was reduced after surgery, and seizure freedom for two years was achieved with optimisation of the antiepileptic drug regime. Memory functions were preserved, and selective attention and visual planning improved following limited resection. This case suggests that, in selected cases, highly targeted resections with preservation of memory-relevant structures may be the best choice considering both seizure control and unimpaired cognitive functioning.     

颞叶新皮质癫痫手术的疗效分析

目的分析总结颞叶新皮质癫痫患者临床特征、术前评估、手术方法和疗效。方法对36例颞叶新皮质癫痫行神经电生理、MRI,正电子发射计算断层显像计算机体层扫描（PET—CT）定位,术中皮层电极和深部电极描记,联合采用不同术式以及术后随访6个月至2年的疗效观察。结果疗效按谭启富的标准分类：Ⅰ级12例,Ⅱ级11例,Ⅲ级8例,Ⅳ级5例,Ⅴ级0例。病理报告：胶质增生23例;微小血管畸形5例;灰质异位1例,无异常发现7例。无手术致残和死亡。结论联合采取不同术式,如：行海马及杏仁核部分切除,对颞叶新皮质癫痫可达到良好的治疗效果,且无严重手术并发症。     

Dysmorphic neurons in patients with temporal lobe epilepsy

We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients with medically intractable TLE and compare histological, clinical, and imaging features with ten TLE patients with classical hippocampal sclerosis without abnormal cells. Such dysmorphic neurons were observed in the hilus of the dentate gyrus and were characterized by giant or misshapen cells with abnormal cytoskeletal structure and atypical dendritic processes that resembled the dysmorphic neurons from cortical dysplasias. Specimens with dysmorphic cells also contained other cytoarchitectural abnormalities including bilamination of the dentate granular cell layer (four out seven cases), and the presence of Cajal-Retzius cells in the dentate gyrus or Ammon's horn (five out seven cases). There were no statistically significant differences regarding the age at onset, duration of epilepsy, and hippocampal asymmetry ratio between patients with or without dysmorphic cells. Nevertheless, it is interesting to note that a higher proportion of patients with dysmorphic neurons continued to present auras after surgery, when compared with patients without those cells.