Interictal depression, anxiety, personality traits, and psychological dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE

PURPOSE: This study was performed to investigate the relation between symptoms of interictal depression, anxiety, personality traits, and psychological dissociation with the localization and lateralization of the epileptogenic zone in patients with partial epilepsy. METHODS: All patients were diagnosed according to the localization-related concept of the 1989 International League Against Epilepsy (ILAE) Classification of Epilepsies and Epileptic Syndromes, and the localization and lateralization of the epileptogenic zone was established by using the clinical criteria for noninvasive presurgical evaluation. This resulted in 67 patients with temporal lobe epilepsy (TLE) and 64 patients with extra-TLE. All patients were assessed on the various aspects of psychopathology by using a comprehensive battery of standardized diagnostic instruments. RESULTS: We did not find the hypothesized excess of psychiatric symptoms in patients with (mesial) TLE in comparison with patients with extra-TLE. We also found no differences between patients with the lateralization of epilepsy in the left versus the right hemisphere. CONCLUSIONS: TLE per se cannot be considered a risk factor in developing more or more severe symptoms of psychopathology in patients with partial epilepsy. Concomitant factors, such as the duration of epilepsy, seizure frequency, and frontal lobe dysfunction may play an additional role. Our findings support the hypothesis of a multifactorial explanation for the psychiatric symptoms in patients with epilepsy.     

Lateralization of temporal lobe epilepsy based on regional metabolic abnormalities in proton magnetic resonance spectroscopic images

Magnetic resonance spectroscopic imaging (MRSI) is capable of determining the spatial distribution in vivo of cerebral metabolites, including N-acetylaspartate (NAA), a compound found only in neurons. We used this technique in 10 patients with temporal lobe epilepsy (TLE) to determine the location of maximal neuronal/axonal loss or damage and to evaluate the potential of MRSI for presurgical lateralization. Asymmetry of the relative resonance intensity of NAA to creatine was determined for mid and posterior regions of the temporal lobes defined anatomically and also for “metabolic lesions” defined as the regions of maximal abnormality on MRSI. MRSI revealed decreased relative signal intensity in at least one temporal lobe of all patients. Two patients had a widespread reduction in NAA in both temporal lobes. The region of maximal abnormality was usually in the posterior temporal lobe but sometimes in the mid temporal lobe. The side of lowest NAA was ipsilateral to the clinical electroencephalographic lateralization in all patients. Lateralization based on NAA to creatine correlated with the atrophy of amygdala and hippocampus in 8 patients who showed this on magnetic resonance imaging volumetric measurements. MRSI can demonstrate regional neuronal loss or damage that correlates with clinical electroencephalographic and structural lateralization in temporal lobe epilepsy. The ability to identify a region of maximal metabolic abnormality on spectroscopic images may confer greater sensitivity than that available from single voxel methods. The maximal metabolic abnormality may not be located in a voxel defined a priori, and based on anatomical considerations, without knowledge of the distribution of the metabolic abnormality.     

磁共振波谱分析在难治性颞叶癫痫术前病灶综合定位中的应用研究

目的 初步探讨磁共振波谱分析(proton magnetic resonance spectroscopy,1HMRS)在难治性颞叶癫痫病灶定位中的意义.方法 采用PHLIPHS 3.0 T磁共振设备,PRESS CSI序列,对15例难治性癫痫患者和15例年龄、性别与之配对的健康志愿者分别取双侧海马40 mm×20 mm×10 mm大小区域进行多体素MRS分析,获得NAA、Cho、Cr的峰下面积,以颅内电极和术后病理为标准,探讨MRS在难治性癫痫患者病灶定位中的意义.结果 15例谱线基线稳定,信噪比较好;13例癫痫患者1 HMRS结果与正常对照组测值平均值比较发现异常,定位信息与颅内电极和病理符合.结论 多体素短回波1HMRS(PRESS序列)可以发现常规MRI阴性的TLE患者海马区脑组织代谢的异常,对颞叶癫痫术前的病灶定位有较大意义.     

Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy

Purpose: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high‐resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long‐term outcomes of consecutive true MRI‐negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. Methods: In this study we present all adult MRI‐negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high‐resolution MRI were included in this study. Results: Among the 38 patients who finally underwent surgery, at the latest follow‐up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure‐free (Engel class IA). Twenty‐one (55%) of 38 patients had poor outcomes (Engel class III–IV). Outcomes did not change compared to 12‐month follow‐up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR‐negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). Discussion: Our results suggest that epilepsy surgery outcomes in MRI‐negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long‐term also remain stable. Modern imaging techniques could further improve the postsurgical seizure‐free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.     

Relationships among hippocampal volumetry, proton magnetic resonance spectroscopy, and verbal memory in temporal lobe epilepsy

PURPOSE: To examine the relationship between hippocampal volumes, 1H magnetic resonance spectroscopy (MRS)-identified hippocampal metabolic function, and verbal memory in patients with unilateral mesial temporal lobe epilepsy (MTLE). METHODS: Hippocampal volumes, 1H MRS-derived hippocampal creatine to N-acetylaspartate (Cr/NAA), and verbal memory assessment were obtained preoperatively in 22 patients (six right, 16 left) with EEG-defined unilateral MTLE. RESULTS: Left hippocampal volume correlated significantly with left hippocampal Cr/NAA (r=-0.549, p < 0.01), whereas right volume correlated significantly with right Cr/NAA (r=-0.478, p < 0.05). Verbal memory correlated significantly with left hippocampal Cr/NAA (r=-0.594, p < 0.01), but not with left hippocampal volume or right hippocampal measures. CONCLUSIONS: Hippocampal volumes and 1H MRS-derived metabolite ratios are statistically related, but share only a small percentage of variance, suggesting separate but related pathophysiologic processes. Left hippocampal Cr/NAA appears to be more sensitive to verbal memory function than volumes.     

Lateralization of temporal lobe epilepsy using resting functional magnetic resonance imaging connectivity of hippocampal networks

Purpose: Early surgical intervention can be advantageous in the treatment of refractory temporal lobe epilepsy (TLE). The success of TLE surgery relies on accurate lateralization of the seizure onset. The purpose of this study was to determine whether resting functional MRI (fMRI) connectivity mapping of the hippocampus has the potential to complement conventional presurgical evaluations in distinguishing left from right TLE. In addition, we sought to determine whether this same network might separate patients with favorable from unfavorable postoperative outcomes. Methods: Resting fMRI acquisitions were performed on 21 patients with TLE and 15 healthy controls. The patients included seven patients with left TLE and seven patients with right TLE with seizure-free postoperative outcome, and five patients with left TLE and two patients with right TLE with recurring seizures after surgery. Functional connectivity maps to each hippocampus were determined for each subject and were compared between the controls and the seizure-free patients with left TLE and with right TLE. The one network identified was then quantified in the patients with TLE and recurring seizures. Key Findings: The resting functional connectivity between the right hippocampus and the ventral lateral nucleus of the right thalamus was the most statistically significant network to distinguish between seizure-free patients with left TLE and with right TLE with high sensitivity and specificity. This connectivity was also significantly greater in the seizure-free patients with left TLE than the healthy controls. Finally, six of the seven patients in whom seizures recurred after surgery had connectivity values in this network unlike those who were seizure-free. Significance: This study identified a region in the ventral lateral nucleus of the right thalamus whose connectivity to the hippocampi separates left from right TLE subjects. This suggests that the quantification of resting-state functional magnetic resonance imaging (MRI) connectivity across this network may be a potential indicator of lateralization of TLE that may be added to other presurgical MRI assessments. Further validation in a larger, independent cohort is required.     

Use of intraoperative magnetic resonance imaging in tailored temporal lobe surgeries for epilepsy

PURPOSE: We investigated whether intraoperative magnetic resonance imaging (MRI) was able to assess immediately the extent of a tailored temporal lobe resection for epilepsy in comparison to delayed postoperative MRI. The recently proposed concept of an individually tailored procedure, preserving tissue not involved in seizures, leads to a variety of differently shaped resections. METHODS: For intraoperative imaging we used a Magnetom Open 0.2 Tesla scanner. Fifty-eight patients undergoing temporal lobe resections for pharmacoresistant epilepsy were investigated. Half of these were nonlesional. All patients had delayed postoperative follow-up scans, which were compared with the intraoperative, postresection images. RESULTS: In 49 (84%) of 58 cases, intraoperative MRI depicted the resection cavity identical to delayed postoperative studies. Complete resection of the visible lesion was primarily proved in 23 of the 29 cases. In two patients with lesions and in one nonlesional case, the resection was extended after intraoperative imaging, thus increasing the rate of total resections in gliomas from 73 to 87%. In four patients, an extension into eloquent areas did not allow complete removal. In the nonlesional cases (n = 29), the extent of tailored temporal resections also could be exactly documented intraoperatively. CONCLUSIONS: Intraoperative MRI allowed a reliable evaluation of the localization and extent of resection in epilepsy surgery within the operative procedure. Furthermore, it provided the possibility of an image-based correction of an initially incomplete resection, particularly in lesional cases. In the majority of patients, the intraoperative images would have been able to replace delayed postoperative MRI. However, in 16%, there were postoperative changes in the resection volume.     

Interictal rhythmical midline theta differentiates frontal from temporal lobe epilepsies

Purpose:   We evaluated the role of interictal rhythmical midline theta (RMT) in the identification of frontal lobe epilepsy (FLE) and its differentiation from temporal lobe epilepsy (TLE) and nonepileptic controls.
Methods:   We included 162 individuals in the study: 54 FLE patients, 54 TLE patients, and 54 nonepileptic controls. Continuous electroencephalographic (EEG)-video monitoring was performed in all individuals. Interictal RMT was included only if it occurred during definite awake states. RMT associated with drowsiness or mental activation and ictal RMT was excluded.
Results:   We identified RMT significantly more frequently in FLE patients (48.1%, 26 of 54) than in TLE patients (3.7%, 2 of 54) (p < 0.01), and not in the control group. The average frequency was 6 Hz (range 5–7 Hz), and the average RMT bursts lasted 8 s (3–12 s). Interestingly, all mesial FLE patients (n = 4) (as established by invasive EEG recordings) showed RMT, whereas this was less frequently the case in the other FLE patients (44%, 22 of 50) (p = 0.03). Thirteen of our 54 patients with FLE (24%) did not have any interictal epileptiform discharges (IEDs), but RMT was observed in the majority of these patients (62%, 8 of 13).
Conclusion:   Interictal RMT is common and has a localizing value in patients with FLE, provided that conditions such as drowsiness and mental activation as confounding factors for RMT are excluded. RMT should be included in the evaluation of patients considered for resective epilepsy surgery.     

Lateralization of epileptic foci by magnetic resonance imaging in temporal lobe epilepsy.

A retrospective single-blind study was carried out to assess the reliability of magnetic resonance imaging (MRI) for determining lateralization of the electrographic focus in 45 patients with intractable temporal lobe epilepsy. With strictly defined MRI diagnostic criteria, the electroencephalographic (EEG) focus was correctly lateralized in 86% of patients. Excluding patients with structural lesions, the criteria provided for correct lateralization of the epileptogenic focus in 78% and false lateralization in 5%. Hippocampal atrophy on T1-weighted images and increased signal intensity from mesial structures on T2-weighted scans were highly reliable for lateralization. Postoperative outcome did not differ between the patients with normal and those with abnormal findings on MRI, but the group sample was inadequate to assess the issue of surgical outcome. These findings suggest that with appropriate techniques and strictly defined diagnostic criteria, MRI can provide reliable seizure lateralization in patients with intractable temporal lobe epilepsy.     

Proton magnetic resonance spectroscopic imaging studies in patients with newly diagnosed partial epilepsy

PURPOSE: To assess whether the N-acetyl aspartate (NAA) to creatine ratio (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful treatment of seizures with antiepileptic drugs is sufficient for normalization of NAA/Cr. PATIENTS AND METHODS: Proton magnetic resonance spectroscopic imaging (1H-MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly diagnosed epilepsy before or soon after starting medication. Six patients had follow-up 1H-MRSI examinations 7 months later. Clinical pattern of the seizures and the EEG findings suggested partial seizures in all and TLE in five patients. None of the patients had lesional epilepsy according to magnetic resonance imaging. RESULTS: Initial 1H-MRSI of the temporal lobes showed significantly low NAA/Cr values in five of eight patients. Five of six patients who had follow-up 1H-MRSI were seizure-free after using medication; the remaining patient did not take medication and continued to experience occasional auras. Wilcoxon rank sign comparison of NAA/Cr on initial 1H-MRSI examination and follow-up 1H-MRSIs showed no significant difference (Z = 135, p = 0.893, 2-tailed) for five seizure-free patients. CONCLUSIONS: Neuronal dysfunction is present at an early stage of the epileptic process. NAA/Cr recovery in seizure-free patients controlled with antiepileptic drugs is less evident, compared with successful surgical treatment. Thus, absence of seizures is not necessarily coupled with NAA/Cr improvement and observed variable response warrants further investigation.     

术中高场强MRI辅助显微外科手术治疗颞叶癫痫

目的探讨应用术中高场强MRI辅助显微外科手术治疗颞叶癫痫的效果。方法2011年6月至2012年4月,对结构性异常的颞叶癫痫患者18例,利用1．5T高场强MRI实时辅助,术前术中常规行T、T2及T1加权、弥散张量成像检查,以确定显微手术切除范围及功能区。结果术后病检结果示右侧颞叶海绵状血管瘤2例,左侧颞叶海绵状血管瘤3例,右侧颞叶弥漫性少枝星形细胞瘤2例,左侧海马硬化4例,右侧海马硬化6例,左侧颞叶胚胎发育不良性神经上皮肿瘤1例。术后复查MRI手术切除满意,无手术并发症。术后随访2个月．1年,EngelⅠ级14例,Ⅱ级4例。结论术中1．5T高场强MRI辅助显微外科手术治疗结构性异常的颞叶癫痫,可以较完全切除致痫灶,并保护神经功能,手术安全和效果好。     

Predictive value of MRI-identified mesial temporal sclerosis for surgical outcome in temporal lobe epilepsy: an intent-to-treat analysis

PURPOSE: Magnetic resonance imaging (MRI) accurately identifies mesial temporal sclerosis (MTS), but prediction of successful surgical outcome ranges from 62% to 96% in published studies. Prior investigations only used patients who had received anterior temporal lobectomy (ATL), potentially overestimating the predictive value of MRI-identified MTS (MRI-MTS). METHODS: The authors performed an intent-to-treat analysis of 90 consecutive patients assessed for possible ATL, including 13 who did not undergo ATL because of inconclusive intracranial ictal EEG. Four (31%) of these 13 patients had unilateral mesial temporal abnormalities on their MRIs. RESULTS: The positive predictive value of MRI-MTS for seizure cessation decreased from 0.69 to 0.63 after adjustment for these additional false positive results. Four previous studies had revealed a positive predictive value of 0.75 (0.72 after similar adjustment). CONCLUSIONS: The authors conclude that the predictive value of MRI-MTS for outcome from ATL may be overestimated by small retrospective studies of highly selected postoperative patients.     

Epilepsy surgery outcomes in temporal lobe epilepsy with a normal MRI

Purpose:   To determine the long-term efficacy of anterior temporal lobectomy for medically refractory temporal lobe epilepsy in patients with nonlesional magnetic resonance imaging (MRI).
Methods:   We identified a retrospective cohort of 44 patients with a nonlesional modern "seizure protocol" MRI who underwent anterior temporal lobectomy for treatment of medically refractory partial epilepsy. Postoperative seizure freedom was determined by Kaplan-Meyer survival analysis. Noninvasive preoperative diagnostic factors potentially associated with excellent surgical outcome were examined by univariate analysis in the 40 patients with follow-up of >1 year.
Results:   Engel class I outcomes (free of disabling seizures) were observed in 60% (24 of 40) patients. Preoperative factors associated with Engel class I outcome were: (1) absence of contralateral or extratemporal interictal epileptiform discharges, (2) subtraction ictal single photon emission computed tomography (SPECT) Coregistered to MRI (SISCOM) abnormality localized to the resection site, and (3) subtle nonspecific MRI findings in the mesial temporal lobe concordant to the resection.
Discussion:   In carefully selected patients with temporal lobe epilepsy and a nonlesional MRI, anterior temporal lobectomy can often render patients free of disabling seizures. This favorable rate of surgical success is likely due to the detection of concordant abnormalities that indicate unilateral temporal lobe epilepsy in patients with nonlesional MRI.     

EEG background delta activity in temporal lobe epilepsy: correlation with volumetric and spectroscopic imaging

PURPOSE: With quantitative electroencephalogram (EEG) and neuroimaging methods, we examined delta activity, atrophy, and neuronal-axonal dysfunction of the cerebral gray and white matter in patients with intractable temporal lobe epilepsy (TLE). Based on evidence that lesions of the white matter result in EEG delta activity, we postulated that background abnormalities in patients with TLE are related to changes of the temporal lobe white matter. METHODS: We measured interictal delta activity in 34 TLE patients and 10 controls. Spike-free and artifact-free EEG samples were selected by visual inspection. A spectral analysis was used to compute the energy in the delta frequency band. We compared the results of the spectral analysis to magnetic resonance imaging- (MRI) based volumes of the temporal lobe white and gray matter, the hippocampus and the amygdala; and N-acetyl aspartate (NAA) in the lateral and posterior temporal lobe by using proton magnetic resonance spectroscopic imaging (1H-MRSI). The degree of correlation between delta activity and the neuroimaging measurements was assessed by using the Pearson correlation coefficient (r). An analysis of variance (ANOVA) was used to examine the influence of the seizure-focus lateralization on the delta activity and the neuroimaging parameters. RESULTS: There was no significant difference in the amount of delta activity in the temporal lobe between the controls and patients. We found no correlation between delta activity and the neuroimaging measures (p>0.05). The ANOVA showed significant differences between the patients and controls for the volume of the gray and white matter of the temporal lobe and for the NAA in the lateral and posterior temporal lobe (p<0.002). CONCLUSIONS: The interictal background delta activity was not explained by reduced volume of the temporal lobe white matter, gray matter, or by abnormalities seen in 1H-MRSI.