Significance of interictal bilateral temporal hypometabolism in temporal lobe epilepsy

OBJECTIVE: To assess the clinical implications and the pathophysiologic determinants of interictal bitemporal hypometabolism (BTH) in temporal lobe epilepsy (TLE) not associated with bilateral MRI abnormalities or intracranial space-occupying lesions. METHODS: The authors compared the clinical, interictal, and ictal EEG, Wada test, and neuropsychology data of 15 patients with intractable complex partial seizures of temporal lobe origin and BTH with those of 13 consecutive patients with unilateral TLE associated with unilateral temporal hypometabolism (UTH) who remained seizure free for more than 3 years after anterior temporal lobectomy. 18F-fluorodeoxyglucose PET scans were analyzed visually and semiquantitatively, and ratios of counts in individual temporal areas to the rest of the cerebrum were compared with the corresponding values from 11 normal control subjects and with the nonepileptogenic hemisphere of the 13 patients with UTH. BTH was defined as more than 2.5 SDs below control values for two or more temporal areas on each side irrespective of any asymmetry. RESULTS: BTH reflected bilateral independent seizure onset in eight patients (53%). The topography of the metabolic depression was not a reliable predictor of epileptogenicity, but involvement of the inferior temporal gyrus was related specifically to ipsilateral seizure onset (70% sensitivity, 100% specificity). In patients with unilateral TLE, contralateral hypometabolism was associated with longer disease duration and worst memory performance during the Wada test, which amounted to global amnesia after ipsilateral injection in three patients, precluding surgical treatment. Contralateral seizure spread in the ictal EEG was significantly faster in patients with BTH. CONCLUSIONS: In TLE, symmetric or asymmetric BTH may signal bilateral independent seizure onset in approximately half the patients, especially when involving the inferior temporal gyrus. Alternatively, it may reflect an advanced stage of the disease process, characterized by a breakdown of the inhibitory mechanisms in the contralateral hemisphere, and secondary memory deficit associated with higher risk of postoperative memory decline. Patients with TLE and BTH but without bilateral MRI changes may still be operated on successfully, but surgical suitability should be proved by comprehensive intracranial EEG studies and Wada test.     

Areas of interictal spiking are associated with metabolic dysfunction in MRI-negative temporal lobe epilepsy

PURPOSE: The objective of our study was to determine noninvasively whether metabolic dysfunction is present in focal areas of interictal electrophysiologic abnormality and whether metabolic dysfunction correlates with frequency of spiking. METHODS: We used a prospective, power analysis-driven, age-matched design to study 20 subjects with nonlesional temporal lobe epilepsy by using magnetoencephalography (MEG) and proton magnetic resonance spectroscopy (1H-MRS). MEG was used to localize the source area of interictal spikes. 1H-MRS measured integrated peak areas for N-acetyl compounds (NAA) and choline-containing compounds (Cho) in both hippocampi, the MEG spike zone, and the region contralateral to the MEG spike zone in all subjects. 1H-MRS was performed in seven controls. RESULTS: Fifteen of 20 subjects had a lower NAA/Cho ratio in the MEG spike zone compared with the contralateral homologous region. NAA/Cho was significantly decreased in the MEG spike zone (p < 0.01). NAA/Cho ratios were not significantly different between the hippocampus ipsilateral and contralateral to the spike activity, or from control hippocampi. NAA/Cho ratios did not correlate with spike frequency. CONCLUSIONS: Metabolic dysfunction is present in focal areas of interictal spiking in nonlesional temporal lobe epilepsy. These findings confirm that functional abnormalities can be detected in vivo in radiographically normal-appearing cortex exhibiting abnormal excitability.     

Dipole source localization of interictal epileptiform activity in temporal lobe epilepsy with medial temporal lesion

Dipole sources of interictal epileptiform activities recorded by conventional electroencephalogram (EEG) were estimated using the dipole tracing method. Four cases of temporal lobe epilepsy with medial temporal lesions were studied. Two patients with hippocampal sclerosis, one patient with granulation in the hippocampus and one patient with cavernous angioma were involved in the study. Interictal epileptiform activities were classified into two patterns according to the topography of spikes. They were widespread spikes over the parasagittal electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes (temporal spikes). Dipole sources of parasagittal spikes were localized in the medio-basal temporal lobe with vertically orientated vector moment. Dipole sources of temporal spikes were localized in the medio-basal temporal lobe with horizontally orientated vector moment. Locations of dipoles and directions of vector moments were consistent with topography and polarity of spikes. The difference in the two patterns of interictal epileptiform activities was derived from the difference in the direction of the vector moment of dipole sources. There was no difference in the location of dipole sources. Both the dipole sources and the lesions were localized in the same medio-basal temporal lobe. Dipole tracing was very useful in localizing the dipole sources of interictal epileptiform activities and in understanding the neurophysiological background.     

Localization of magnetic interictal discharges in temporal lobe epilepsy

Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping of simultaneously recorded magnetoencephalographic signals produced dipolar patterns from which the three-dimensional locations of equivalent current dipoles were calculated, whereas the mapping of EEG spikes showed single regions of electronegativity. The magnetic spikes were localized to the anterotemporal lobe, and the EEG spikes were localized somewhat anterior or posterior to the magnetic spikes. The magnetoencephalographic findings corresponded well with intraoperative electrocorticographic and depth-electrode findings of discharging areas located over the lateral temporal lobe and on the basal and mesial surfaces of the temporal cortex.     

Spatiotemporal relationship between seizure activity and interictal spikes in temporal lobe epilepsy.

PURPOSE: To analyze the spatio-temporal relationship between seizure propagation and interictal epileptiform discharges (IEDs) in patients with bitemporal epilepsy. METHODS: We investigated 18 adult patients with intractable temporal lobe epilepsy (TLE) who had undergone continuous video-EEG monitoring during presurgical evaluation. Only those patients were selected who had independent IEDs over both temporal lobes. Two authors evaluated the ictal and interictal EEG data independently. RESULTS: We analyzed 52 lateralized seizures of 18 patients. Thirty-one seizures showed ipsilateral seizure spread exclusively, whereas in 21 seizures the contralateral hemisphere was also involved. In lateralized seizures without contralateral propagation, we found that spikes ipsilateral to the seizure onset occurred postictally in a greater ratio than preictally (P<0.001). In lateralized seizures with contralateral propagation, we found no significant changes in the postictal spike distribution. CONCLUSIONS: Our findings showed that the lateralization of IEDs may depend on the brain areas involved by the preceding seizures, suggesting that spikes can be influenced by the seizure activity, and are not independent signs of epileptogenicity.     

Cortical current density reconstruction of interictal epileptiform activity in temporal lobe epilepsy.

OBJECTIVE: To investigate the value of cortical current density (CCD) reconstruction in localizing intracranial generators of interictal epileptiform activity in mesial and lateral temporal lobe epilepsy (TLE). METHODS: Non-linear minimum L(1)-norm CCD reconstruction (with current sources restricted to the individual cortical surface and a realistic boundary element method (BEM) head model) was used to localize and to study the propagation of interictal epileptiform EEG activity in 13 pre-surgical patients with TLE. RESULTS: In all but one patient with mesial temporal lesions, an initial activation maximum corresponding to the ascending part of averaged sharp waves was found in the ipsilateral anterior basolateral temporal lobe, mostly extending up to the affected mesial structures whose resection rendered the patients seizure-free. In all 3 patients with lateral temporal lesions, the activation was initially confined to temporal neocortex immediately adjacent to the epileptogenic lesion. Towards the peak of sharp waves, two patients showed a propagation of interictal activity to anterior and posterior and partly contralateral temporal regions. A conventional EEG analysis based on amplitude maxima or phase reversal would have missed the initial onset zone. CONCLUSIONS: The findings demonstrate that CCD reconstruction can be a valuable additional non-invasive component in the multimodal pre-surgical evaluation of epilepsy patients.     

The interictal behavior syndrome of temporal lobe epilepsy.

A distinct syndrome of interictal behavior changes occurs in many patients with temporal lobe epilepsy. These changes include alterations in sexual behavior, religiosity, and a tendency toward extensive, and in some cases compulsive, writing and drawing. The concomitants of abnormal limbic acitivity therefore include behavior alterations as well as manifest seizures. The demonstration of interictal spike activity in temporal structures provides a pathophysiologic basis for this syndrome. The constellation of behavioral changes may be of great diagnostic value. In addition, it provides an example of a human behavioral syndrome assocaited with dysfunction at specific anatomic loci. The behavior syndrome of temporal lobe epilepsy may prove to be a useful model in studies on the neural substrates for behavior.     

Focus laterality and interictal psychiatric disorder in temporal lobe epilepsy

The current study was carried out in order to find the possible associations between foci laterality and kind of prevailed psychopathological disorder in patients with temporal lobe epilepsy (TLE). One hundred and ten patients with TLE (40 men and 70 women) were included into the study. Among all studied patients the left-focus activity was detected in 67 patients, right-sided foci-in 43 patients. No relationships between chronology variables of epilepsy (age, age at epilepsy onset, epilepsy duration) and different subtypes of psychopathology in studied patients were revealed. Diagnosis of organic affective disorder was observed more frequently in patients with right-sided foci, while diagnosis of organic anxiety disorder-in patients with left-sided foci (chi(2)=7.0, p=0.0081; Fisher's exact test p=0.018). The comparison of dysphoric disorder with anxiety or affective disorder could not reveal any statistically significant association with focus laterality. Obtained results are discussed in terms of association between the different subtypes of studied psychiatric disorders and foci laterality in patients with TLE.     

In vivo hippocampal metabolic dysfunction in human temporal lobe epilepsy

BACKGROUND: The nature of functional metabolic disturbances in mesial temporal lobe epilepsy remains unclear. OBJECTIVES: To compare in vivo measures of hippocampal metabolic abnormalities in mesial temporal lobe epilepsy, as acquired with fludeoxyglucose F 18 positron emission tomography and proton magnetic resonance spectroscopic imaging, and to determine the relationship between N-acetylaspartate (NAA) disturbances and well-established derangements of glucose metabolism. DESIGN: Measures of hippocampal glucose metabolism from fludeoxyglucose F 18 positron emission tomography were normalized to whole brain counts to provide a glucose uptake metabolic index. Proton magnetic resonance spectroscopic imaging was performed at 4.1 T, and measures of creatinine/NAA ratio were made from mostly hippocampal-only voxels. Direct comparisons and correlation analysis of measures were performed. SETTING: Presurgical evaluations for treatment of intractable epilepsy. PATIENTS: Twenty-nine patients between July 1994 and June 1996 who were candidates for anterior-medial temporal lobectomy at the epilepsy centers of the University of Alabama at Birmingham and Vanderbilt University schools of medicine were studied. RESULTS: The mean ipsilateral hippocampal glucose metabolic index (0.85) was normal, while the contralateral metabolic index (0.95) was nearly significant for an abnormally elevated measure. The mean ipsilateral hippocampal creatinine/NAA (1.26) was abnormally elevated; the mean contralateral creatinine/NAA (0.88) was normal. Hippocampal glucose and creatinine/NAA measures did not correlate; asymmetry measures also did not correlate. CONCLUSIONS: Hippocampal metabolic disturbances in mesial temporal lobe epilepsy as measured by fludeoxyglucose F 18 positron emission tomography vs proton magnetic resonance spectroscopic imaging reflect different mechanisms of biochemical dysfunction. This lack of correlation is hypothesized to reflect a differential effect of varying degrees of disturbed cellular energy metabolism on mechanisms of glucose use and biosynthesis of NAA.     

颞叶癫痫患者发作间期脑活动的静息态脑磁图研究

目的用脑磁图合成孔径磁场测定(SAMg2)技术分析左侧颞叶癫痫患者与正常对照者的脑电活动差异,评估左侧颞叶癫痫患者发作间期脑活动的改变。方法给20例左侧颞叶癫痫患者及20名健康志愿者(正常对照组)进行静息态脑磁图检查,通过CTF软件中的合成孔径磁场测定技术计算所有受试者的SAMg2值;计算后,使每位受试者的SAMg2值与其对应的3D-MRI进行融合。结果与正常对照组比较,左侧颞叶癫痫患者颞叶及其内侧结构的SAMg2值显著升高,而双侧视觉皮质等颞叶以外脑区的SAMg2值降低。左侧颞叶癫痫患者异常区域的脑活动与癫痫发作频率密切相关,而性别、年龄的影响无统计学意义。结论左侧颞叶癫痫是一种多灶性的网络疾病,具有复杂的癫痫网络和脑功能缺失网络。     

Frequency of bitemporal independent interictal epileptiform discharges in temporal lobe epilepsy

PURPOSE: Bitemporal interictal epileptiform discharges (IEDs) occur in < or =42% of scalp EEGs in patients with temporal lobe epilepsy (TLE) studied with routine EEGs or partial analysis of long-term recordings. METHODS: Twenty-eight patients with TLE demonstrating exclusively unilateral temporal IEDs on routine EEGs underwent 24-h continuous recording. The entire record was visually inspected for epileptiform discharges. We used continuous EEG to assess the significance of long-term recording in detecting bilateral IEDs. RESULTS: Twenty-two patients had left temporal IEDs; 21 had right temporal IEDs. Seventeen (61%) patients had IEDs originating from both the right and left temporal lobes. The probability of detecting bilateral independent IEDs was correlated with the duration of continuous EEG recording. There was no correlation between the number of IEDs originating from one side and the probability of detecting independent IEDs on the other side. The frequencies of IEDs were not correlated with the length of time since onset of epilepsy. CONCLUSIONS: The findings suggest that when long-term recordings are performed, the incidence of bilateral discharges in TLE is higher than previously reported in the literature and supports the view that TLE is commonly a bilateral disease.     

Multifactorial etiology of interictal behavior in frontal and temporal lobe epilepsy

Purpose: Based on discussions on the so called “epileptic personality” in patients with epilepsy, interictal behavioral impairments in frontal and temporal lobe epilepsies were examined in a multivariate approach that took demographic, clinical, and neuropsychological determinants into consideration. Methods: A total of 428 patients with epilepsies originating from the temporal (TLE; 84%) or frontal (FLE; 16%) lobes were examined in regard to personality (Fragebogen zur Persönlichkeit bei zerebralen Erkrankungen [FPZ], a clinical personality questionnaire) and mood (Beck Depression Inventory [BDI I]). Prevalence of impaired behavioral domains was determined. Etiologically relevant determinants of behavioral problems were identified via multiple regression analyses. Key Findings: Elevated depression scores (BDI) were evident in 42% of the patients, and not different in TLE and FLE. In regard to personality, introversion together with low mood, sociability, and self‐determination, as well as problems with interpersonal communication were frequent. The TLE group tended to show greater neuroticism and introversion, while FLE appeared more associated with behavioral aspects of an organic psychosyndrome. Multivariate analyses revealed demographic characteristics (age, gender, education), clinical aspects (psychiatric history, affected hemisphere, mesial pathology, seizure frequency, cognitive functions), and treatment (antiepileptic drug treatment) as relevant determinants, explaining up to 30% of the behavior. Significance: Behavioral abnormalities in patients with frontal or temporal lobe epilepsy are common but on the average mostly mild. Within a multivariate etiological model, localization (mesial yes/no) and lateralization (left > right) dependent behavioral problems in TLE and FLE seem to be overshadowed by other variables, of which patients’ and their families’ psychiatric history, patient characteristics and pharmacological treatment appear of major importance. Better education and cognitive capabilities may be discussed as protective features.     

Neuroaminidase reduces interictal spikes in a rat temporal lobe epilepsy model

Interictal spikes have been implicated in epileptogenesis and cognitive dysfunction in epilepsy. Unfortunately, antiepileptic drugs have shown poor efficacy in suppressing interictal discharges; novel therapies are needed. Surface charge on neuronal membranes provides a novel target for abolishing interictal spikes. This property can be modulated through the use of neuraminidase, an enzyme that decreases the amount of negatively charged sialic acid. In the present report we determined whether applying neuraminidase to brains of rats with a history of status epilepticus would reduce number of interictal discharges. Following pilocarpine-induced status epilepticus, rats received intrahippocampal injections of neuraminidase, which significantly decreased the number of interictal spikes recorded in the CA1 region. This study provides evidence that sialic acid degradation can reduce the number of interictal spikes. Furthermore, the results suggest that modifying surface charge created by negatively charged sialic acid may provide new opportunities for reducing aberrant epileptiform events in epilepsy.     

基于颞叶癫痫发作间期脑电数据图论的初步研究

目的对颞叶癫痫(TLE)患者发作间期清醒期和睡眠期视频EEG(V-EEG)数据进行分析,研究TLE患者左右侧颞区网络节点属性的改变及全脑平均路径长度的变化。方法收集32例TLE患者,将32例TLE患者进一步分为左侧17例和右侧15例,与24名性别、年龄相匹配的正常对照者清醒期及睡眠期脑电数据进行对比研究。分析颞区清醒期β节律、睡眠期δ节律,应用Matlab软件计算出相应节点不同时期的聚类系数及全脑平均路径长度的变化特点,将数据使用图论的方式表示出来,使网络特点可视化。结果TLE患者清醒期与睡眠期颞区的聚类系数、全脑平均路径长度均较正常组升高(均P<0.05)。致痫侧的聚类系数较非致痫侧的聚类系数升高(P<0.05)。TLE患者致痫区域部分节点的连接密度增加,传输性能及效率降低。结论TLE患者发作间期清醒期、睡眠期局部节点属性发生改变,且与致痫侧变化明显。     

Running down phenomenon and acute interictal psychosis in medial temporal lobe epilepsy

PURPOSE: To examine the relationship between presurgical acute interictal psychosis and postsurgical running down phenomenon in a strictly homogeneous group with medial temporal lobe epilepsy. METHODS: Forty patients with mesial temporal sclerosis and an ultimate excellent surgical outcome, were divided into running down positive and negative groups. Various clinical and laboratory data, including presurgical psychotic episodes, were analyzed in the two groups. RESULTS: Patients in the running down positive group exhibited a significantly high incidence of presurgical history of acute interictal psychosis. CONCLUSION: We hypothesize that areas of secondary epileptogenesis beyond the scope of the primary epileptogenic zone, suggested by postsurgical running down phenomenon, may play an important role in the blockage and shift of the habitual propagation of seizure activity from the primary epileptogenic zone, to which Wolf attributed acute interictal psychosis.