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.     

Focal interictal epileptiform discharges in idiopathic generalized epilepsy

Are idiopathic generalized epilepsies (IGEs) truly generalized? Do IGEs represent a continuum or rather distinct syndromes? Focal changes in the electroencephalography (EEG) have been reported in IGEs. The aim of this work is to investigate focal interictal epileptiform discharges (IEDs) in IGEs, and their relation to clinical variables. Forty-one IGE patients (classified according to ILAE, 2001) were recruited from a tertiary center (age 23 ± 10.938 years). Their files were reviewed and they were subjected to clinical examination and interictal EEG. Patients with focal IEDs were compared to those without focal IEDs. Nine patients had juvenile myoclonic epilepsy (JME) and 32 had idiopathic epilepsy with generalized tonic–clonic seizures only (EGTCSA). Focal IEDs were found in 20 patients, mostly in the frontal (45.5 %) and temporal (31.8 %) distribution. Patients with focal IEDs were treated with a larger number of combined antiepileptic drugs (AEDs) (p value = 0.022). No significant difference was found between the two groups regarding age, sex, age at onset, epilepsy syndrome, seizure frequency, family history, AEDs used (sodium valproate and carbamazepine) and their doses. Seventeen EGTCSA patients had focal IEDs. They were treated with larger number of combined AEDs (p value = 0.0142). No significant difference was found between the EGTCSA patients with and those without focal IEDs regarding age, sex, age at onset, seizure frequency, family history and AEDs doses. Caution must be applied in the interpretation of interictal focal IEDs. These focal changes may be related to prognosis, however this needs further investigation.     

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.     

Hemodynamic responses to interictal epileptiform discharges in children with symptomatic epilepsy

PURPOSE: Simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) (EEG-fMRI) recording is a noninvasive tool for investigating epileptogenic networks. Most EEG-fMRI studies in epilepsy have been performed in adults. Childhood epilepsies, however, differ from those in adults due to interactions between epileptogenic and developmental processes. The purpose of this study was to investigate EEG-fMRI in children with lesional epilepsies. METHODS: Thirteen children with symptomatic epilepsy underwent a 20-min EEG-fMRI acquisition at 3 T under sedation-induced sleep. Statistical analysis was performed using the timing of spikes as events, modelled with hemodynamic response functions (HRFs) that peaked at 3, 5, 7, and 9 s after the spike. RESULTS: Each spike type was analyzed separately, resulting in 25 studies. In 84% of the studies, blood oxygenation level-dependent (BOLD) responses were localized in the lesion or brain area presumably generating spikes. Activation (positive BOLD) corresponding with the lesion was seen in 20% and deactivation (negative BOLD) in 52% of the studies. In the area of spike generation, activation was found in 48% of studies and deactivation in 36%. CONCLUSIONS: Despite the necessarily short recording times (20 min), good results could be obtained from the EEG-fMRI recordings, performed in sedated children using a high field scanner and individual HRFs. In contrast to studies in adults, deactivations in the lesion and the irritative zone were more common than activations. The impact of age, sleep, and sedation on the BOLD response might explain these findings, but future studies in children should not disregard the importance of deactivations in relation to the epileptogenic network.     

Relationship of interictal epileptiform discharges to sleep depth in partial epilepsy

Non-rapid eye movement (NREM) sleep activates interictal epileptiform discharges (spikes) in many epileptic syndromes. To define this phenomenon more precisely, we studied the relationship of spikes to absolute log delta power (LDP), a continuous measure of sleep depth, in 8 patients with partial epilepsy. LDP differed significantly across visually scored sleep stages. Logistic regression analyses of spike occurrence in relation to LDP were carried out on the central-occipital channel contralateral to the dominant spike focus (C4-O2 for left and C3-O1 for right temporal focus). Within NREM sleep, spikes were more likely to occur: (1) at higher levels of LDP, (2) on the ascending limb of LDP, and (3) with more rapid rises in LDP. Spike frequency per minute was 4.6 times higher in NREM than in rapid-eye movement (REM) sleep and diminished with time from sleep onset. When the effect of LDP was controlled for in the analysis, however, there was no significant effect of REM sleep stage or time on spike occurrence. Only 1% of spikes occurred within 10 s of an arousal. These findings suggest that processes underlying the deepening of NREM sleep may contribute to spike activation in partial epilepsy.     

Effect of levetiracetam in patients with epilepsy and interictal epileptiform discharges

The effect of acute treatment with the new antiepileptic drug (AED) levetiracetam (Keppra) on the frequency of interictal epileptiform discharges (IEDs) was evaluated in a double-blind, placebo-controlled, crossover study with therapeutic drug monitoring and serial electroencephalographic (EEG) observations. Acute (500 mg twice daily) and chronic (individualized, 500-1000 mg twice daily) doses of levetiracetam were administered as an add-on to current AED treatment. Efficacy was tested by measuring the frequency of IEDs in EEG recordings and the number of seizures. A single acute dose of levetiracetam induced a reduction of IEDs in eight out of ten patients. During the acute phase, an insufficient number of seizures occurred for analysis. During chronic treatment over 8 weeks, seven patients showed a reduction in seizure frequency (responder rate), and one patient remained seizure free. No correlation was seen between levetiracetam levels and IED frequency. Doses of levetiracetam of up to 2000 mg/day were well tolerated, and no interactions were seen with concomitant AEDs.     

Cyclic alternating pattern and interictal epileptiform discharges during morning sleep after sleep deprivation in temporal lobe epilepsy

PurposeSleep deprivation (SD) increases the occurrence of interictal epileptiform discharges (IED) compared to basal EEG in temporal lobe epilepsy (TLE). In adults, EEG after SD is usually performed in the morning after SD. We aimed to evaluate whether morning sleep after SD bears additional IED-inducing effects compared with nocturnal physiological sleep, and whether changes in sleep stability (described by the cyclic alternating pattern-CAP) play a significant role.MethodsAdult patients with TLE underwent in-lab night polysomnography (n-PSG) and, within 7 days from n-PSG, they underwent also a morning EEG after night SD (SD-EEG). We included only TLE patients in which both recordings showed IED. SD-EEG consisted of waking up patients at 2:00 AM and performing video EEG at 8:00 AM. For both recordings, we obtained the following markers for the first sleep cycle: IED/h (Spike Index, SI), sleep macrostructure, microstructure (NREM CAP rate; A1, A2 and A3 Indices), and SI association with CAP variables.ResultsThe macrostructure of the first sleep cycle was similar in n-PSG and morning SD-EEG, whereas CAP rate and SI were significantly higher in SD-EEG. SI increase was selectively associated with CAP phases.ConclusionsSD increases the instability of morning recovery sleep compared with n-PSG, and particularly enhances CAP A1 phases, which are associated with the majority of IED. Thus, higher instability of morning recovery sleep may account at least in part for the increased IED yield in SD-EEG in TLE patients.     

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.     

Factors affecting interictal spike discharges in adults with epilepsy.

We investigated various factors affecting interictal spike discharges (ISDs) in standard interictal EEGs of 203 consecutive cases with seizure(s). 94 EEGs (46%) showed ISDs. Yield was maximum (68%) when recordings were done within 2 days of a seizure; beyond this period, incidence of ISD did not change with time from the last seizure. EEGs of patients having greater than 12 seizures/year were more likely to contain ISD (68%) than the records of cases with less than 12 attacks/year (37-41%; P less than 0.001). Age and neurological status at the time of EEG, etiology and anticonvulsants did not influence the frequency of ISD. Analysis of serial EEGs (n = 512) from the study group showed that if initial 3 EEGs lacked ISD, yield from further standard EEGs is small.     

The long-term course of temporal lobe epilepsy: From unilateral to bilateral interictal epileptiform discharges in repeated video-EEG monitorings

IntroductionBilateral interictal epileptiform discharges (IED) and ictal patterns are common in temporal lobe epilepsy (TLE) and have been associated with decreased chances of seizure freedom after epilepsy surgery. It is unclear whether secondary epileptogenesis, although demonstrated in experimental models, exists in humans and may account for progression of epilepsy.Material and methodsWe reviewed consecutive video-EEG recordings from 1992 to 2014 repeated at least two years apart (mean interval 6.14 years) in 100 people diagnosed with TLE.ResultsIctal EEG patterns and IED remained restricted to one hemisphere in 36 people (group 1), 46 exhibited bilateral abnormalities from the first recording (group 2), 18 progressed from unilateral to bilateral EEG pathology over time (group 3). No significant differences between the three groups were seen with respect to age at epilepsy onset, duration, or underlying pathology. Extra-temporal IED during the first EEG recording were associated with an increased risk of developing bilateral epileptiform changes over time (hazard ratio 3.67; 95% CI 1.4, 9.4).ConclusionOur findings provide some support of progression in TLE and raise the possibility of secondary epileptogenesis in humans. The development of an independent contra-lateral epileptogenic focus is known to be associated with a less favorable surgical outcome. We defined reliable EEG markers for an increased risk of progression to more widespread or independent bitemporal epileptogenicity at an early stage, thus allowing for individualized pre-surgical counselling.     

Periodic epileptiform discharges in mesial temporal lobe epilepsy with hippocampal sclerosis

PurposePeriodic epileptiform discharges (PEDs) are an uncommon, abnormal EEG pattern seen usually in patients with acute diseases and less frequently in chronic conditions, such as mesial temporal lobe epilepsy (mTLE). Evaluate the clinical histories, neuroimaging findings, and serial electrophysiological studies prior to the appearance of PEDs in patients with mTLE secondary to hippocampal sclerosis (HS).MethodsWe searched 19, 375 EEGs (2006–2012) for the presence of PEDs secondary to mTLE due to HS.Results12 patients were included. The patients with PEDs had a high prevalence of psychiatric comorbilities, including major depression (50%), interictal psychosis (16%) and dementia (8%). All of the patients had intractable epilepsy with similar clinical findings. We observed a sequential neurophysiological worsening of the EEG patterns prior to the appearance of PEDs. Five patients with PEDs underwent epilepsy surgery and four were seizure free at follow-up 15 (±9) months.ConclusionsPEDs are rare in patients with mTLE and HS and their presence in these cases could reflect clinical severity and neurophysiologic worsening, clinically manifested by intractable epilepsy and severe psychiatric comorbidities. The presence of PEDs in EEGs of patients with mTLE, however, was not associated with poor postsurgical seizure-freedom.     

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.     

额叶离断术治疗无影像学异常的难治性额叶癫痫

目的 探讨额叶离断术治疗无影像学异常的难治性额叶癫痫的可行性、有效性、并发症及适应证.方法 2006年6月至2012年1月解放军第153医院全军神经外科中心对12例无影像学异常的难治性额叶癫痫患者,采用额叶离断术治疗,对手术适应证的选择、手术方法、离断范围、额叶功能区的保护方法、手术效果以及并发症进行总结分析.12例患者中,10例行单纯额叶离断,2例一侧额叶离断后皮质脑电图(ECoG)监测发现离断部位后缘仍有癫痫波,加行胼胝体前部切开术.结果 5例术后出现短暂精神、记忆及性格改变,2例出现一侧肢体轻度偏瘫,均于1个月内恢复正常.无颅内出血、感染及严重并发症.随访1.0～5.5年,Engel Ⅰ级9例,Ⅱ级3例.结论 在术中直接皮层电刺激技术及ECoG监测下,采用额叶离断术治疗无影像学异常的难治性额叶癫痫,是一种安全有效的手术方法.     

Executive functioning in children with intractable frontal lobe or temporal lobe epilepsy

The aim of the present study was to shed light on the executive functioning deficits that might differentiate children with frontal lobe epilepsy (FLE) from children with temporal lobe epilepsy (TLE). Participants included 19 youth with intractable FLE and 47 youth with intractable TLE. Participants completed the Wisconsin Card Sorting Test (WCST), verbal fluency, Trail Making Test (Trails A and B), Digit Span Forward (DSF), and Digit Span Backward (DSB). When compared to the normative sample, the FLE group performed significantly worse on DSF, DSB, Trails B, and the WCST. Similarly, the TLE group performed significantly worse on DSF and DSB compared to the normative sample. Youth with FLE had significantly greater difficulty on the WCST compared to the TLE group. Overall, the results indicated that youth with FLE had significantly greater difficulty with concept formation compared to children with TLE. No differences between groups emerged on tasks assessing attention, working memory, mental flexibility, or rapid word retrieval. Both groups performed significantly below the normative sample levels on attention and working memory tasks. As a whole, it appears that some, although not all, executive dysfunction is specific to FLE.     

Sleep-EEG modulation of interictal epileptiform discharges in adult partial epilepsy: a spectral analysis study.

INTRODUCTION: In order to define accurately the relationship between EEG components (spindles, delta and theta frequencies) and the occurrence of interictal epileptiform discharges (IED) during sleep in partial epilepsy, a correlation study between spike overnight distribution and EEG spectral power time series was performed. METHODS: Eighteen patients (mean age: 24.7+/-5.5 years) affected by partial epilepsy underwent continuous EEG-polysomnography. The temporal series of Slow Wave Activity (SWA), Sigma Activity (SA) and Theta Band (TB), derived from spectral analysis, were obtained from a spike-free and pathologic alteration-free derivation, contralateral to the most active lead, where the IED count was performed. Relationships between SA, SWA and TB and time series of IED were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly higher correlation between IED and SWA in 12 subjects; a significantly higher correlation between IED and SA in three subjects and a significant correlation with TB in three cases. CONCLUSIONS: Data suggest that in most adult patients with partial epilepsy IED production during sleep is facilitated by the action of synchronizing mechanisms which are active during NREM sleep and lead to the appearance of EEG delta waves. Nevertheless evidence is given of two smaller groups of patients. In one of them IED are more sensitive to the promoting action of the spindle generating mechanism, active during stage 2 of NREM sleep. In the other one the promoting action of TB, characterizing EEG during stage 1 and REM sleep, is evident.