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.     

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.     

Interictal epileptiform discharges relate to 1H-MRS-detected metabolic abnormalities in mesial temporal lobe epilepsy

PURPOSE: To examine whether the distribution of interictal epileptiform discharges (IEDs) recorded from foramen ovale electrodes (FOEs) correlates with metabolite levels in medial structures of the temporal lobes in patients with mesial temporal lobe epilepsy (MTLE). METHODS: We studied 34 patients with MTLE. The lateralization ratio of IEDs was calculated after counting IEDs recorded from FOEs during prolonged video-EEG monitoring. Metabolite ratio between N-acetylaspartate (NAA) and creatine (Cr) was calculated in each medial temporal structure. The correlation between the lateralization ratio of IEDs and metabolic ratio was evaluated. RESULTS: The asymmetry indexes of IEDs correlated with the asymmetry index of NAA/Cr ratio in the medial temporal structure (rho = -0.380; p = 0.027). Analysis of IEDs and metabolite ratio revealed a significant inverse relation in the contralateral side to the major epileptogenic focus (rho = -0.360; p = 0.037); however, this significance was not present in the ipsilateral side (rho = -0.018; p = 0.921). CONCLUSIONS: There is a correlation between the neuronal dysfunction or damage detected by MRS and the epileptic activity in the contralateral medial temporal structure. Our results suggest that the pathomechanism underlying the contralateral reduction of NAA/Cr ratio, frequently observed in patients with MTLE, might be related to the process of epileptogenesis generating the independent contralateral IEDs.     

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.     

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.     

Source localization of mesial temporal interictal epileptiform discharges: Correlation with intracranial foramen ovale electrode recordings

OBJECTIVE: We have investigated the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) on a statistical basis by using clinical electroencephalographic (EEG) data of simultaneous scalp and intracranial foramen ovale (FO) electrode recordings. METHODS: We retrospectively analyzed the IED of 15 patients who underwent presurgical assessment for intractable temporal lobe epilepsy. All patients have subsequently undergone amygdalohippocampectomy. The scalp signals were averaged time-locked to the peak activity in bilateral 10-contact FO electrode recordings. Source modeling was carried out by using statistical non-parametric mapping (SNPM) of LORETA values and by calculating raw LORETA values of averaged IED. The results were compared to intracranial data obtained from FO electrode recordings. RESULTS: Two thousand six hundred and fifteen discharges could be attributed to 19 different patterns of intracranial mesial temporal IED. SNPM of LORETA revealed confined ipsilateral mesial temporal solutions for 14 (73.7%) and no significant solutions for five (26.3%) of these patterns. Raw LORETA current density distributions of the 19 averaged IED patterns revealed ipsilateral basal to lateral temporal solutions for the 14 IED patterns with a sufficient signal to noise ratio (SNR), but spurious results for those five IED with a low SNR. CONCLUSIONS: SNPM of LORETA but not LORETA analysis of averaged IED patterns accurately localizes the source generators of mesial temporal IEDs. SIGNIFICANCE: SNPM of raw LORETA values might be appropriate for localizing restricted mesial temporal lobe sources.     

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.     

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.     

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.     

The prognostic significance of interictal epileptiform activity in postoperative EEGs of patients with mesial temporal lobe epilepsy.

It has not been established whether electroencephalography (EEG) is a contributing factor in predicting the outcome of surgery for epilepsy. We conducted a prospective study on 26 patients (M/F 14/12, age: 33 +/- 7.5 years, range 19-48) with mesial temporal lobe epilepsy (MTLE) who were followed for 2 years after surgery and who underwent routine EEG recordings 5.6 +/- 3 months (range 3-12) postoperatively. Interictal epileptiform activity (IEA) on the EEG was compared in 17 seizure-free patients to 9 patients with recurrent seizures. The two groups were similar in gender, age, febrile convulsions, trauma, family history, seizure frequency prior to surgery, epilepsy duration and number of antiepileptic drugs. Following surgery, 17 study patients (65%) became seizure free; 9 (35%) had seizure recurrence. Post-operative EEG recordings showed IEA in 8/26 study patients (31%), 3 of whom were from the seizure-free group (3/17, 18%); 5 had seizure recurrence (5/9, 56%) (p=0.078). IEAs in postoperative EEGs were less frequently demonstrated in patients who were seizure free, but the presence of postoperative IEAs does not preclude successful surgical outcome.     

Factors underlying scalp-EEG interictal epileptiform discharges in intractable frontal lobe epilepsy.

AIMS: Scalp-EEG interictal epileptiform discharges (IEDs) may be less predictive of the outcome of frontal lobe epilepsy surgery than of temporal lobe epilepsy surgery. We identified factors associated with the location of scalp-EEG IEDs in intractable frontal lobe epilepsy. METHODS: Ten factors were assessed in a retrospective review of 53 patients with either concordant (frontal lobe seizure focus) or discordant (generalized or outside frontal seizure focus) IED or both, who had excellent surgical outcomes. The Fisher exact test and the Wilcoxon rank sum test determined statistically significant associations. RESULTS: Thirty-six patients (68%) had concordant IED, 24 (45%) discordant IED, and 17 (32%) both. Younger age at onset was significantly associated with discordant IED (mean, 7.5 years versus 17 years for patients without discordant IED; P < 0.01), whereas duration of epilepsy was not. Seizure foci at the frontal convexity were associated with concordant IED. About 72% of patients with a convexity seizure focus had concordant IED, compared with only 33% of patients with mesial frontal foci having concordant IED (P = 0.06). CONCLUSIONS: Early seizure onset in intractable frontal lobe epilepsy is associated with IEDs discordant with seizure focus. Frontal convexity seizure foci are more likely than mesial frontal seizure foci to be associated with concordant discharges.     

Benign epileptiform discharges in Rolandic region with mesial temporal lobe epilepsy: MEG, scalp and intracranial EEG features

AIM OF THE STUDY: To report benign epileptiform discharges (BEDs) in the Rolandic region, coexisting in a pediatric patient with intractable localization-related epilepsy, secondary to hippocampal sclerosis. METHODS: We describe the clinical features, MRI, scalp video EEG, magnetoencephalography (MEG) and intracranial video EEG findings, and surgical outcome in a 9-year-old boy with BEDs and intractable complex partial seizures. RESULTS: MRI showed left hippocampal sclerosis. Scalp video EEG interictally demonstrated left temporal spike and sharply contoured slow waves, and right fronto-centro-temporal spike and waves. Ictal scalp video EEG showed left temporal rhythmic sharp waves after the clinical onset of epigastric aura, followed by staring. MEG showed interictal dipoles in the bilateral Rolandic regions with a uniform orientation and right hemispheric predominance. Intracranial video EEG, with bilateral mesial temporal depth and fronto-temporo-parietal strip electrodes, interictally showed polyspikes and slow waves with superimposed low-amplitude fast waves in the left mesial and posterior lateral temporal regions, and spike and waves in the bilateral fronto-parietal regions. Ictal onset was marked by low-amplitude fast waves in the left mesial and posterior lateral temporal regions. He underwent left anterior temporal lobectomy with hippocampectomy. Pathology was hippocampal sclerosis. Predominant right fronto-centro-temporal spike and waves and MEG right Rolandic dipoles persisted after surgery. He was seizure-free 14 months after surgery. CONCLUSION: This is the first report on MEG and intracranial video EEG features of BEDs in the Rolandic region, coexisting with hippocampal sclerosis. Persistence of contralateral benign MEG Rolandic dipoles after surgery indicates that BEDs are coincidental in mesial temporal lobe epilepsy. MEG identified Rolandic dipoles, although was unable to localize the deep and focal epileptogenic dipoles from the hippocampal sclerosis.     

Interictal temporal lobe epileptiform discharges and their relationship to secondarily generalized epilepsy

In a previous study of epileptic phenomena in 19 patients with partial complex seizures, it was noted that seizures of left temporal lobe origin had a higher incidence of secondary generalization. To evaluate this observation further, we retrospectively reviewed reports of EEGs for evidence of focal interictal epileptiform discharges (FIED) of temporal lobe origin and correlated this finding with seizure type. Of 3,276 EEG reports reviewed, 195 showed FIED. The medical records of these patients were reviewed and 79 had sufficient information therein to enable seizure classification. Of 79 patients, 61 had secondary generalized seizures, 45 with left temporal FIED, 16 with right FIED. Of 79 patients, 18 had partial seizures, 13 with right temporal FIED, 5 with left FIED (p less than 0.001). These findings suggest that seizures of left temporal lobe origin may have a higher incidence of secondary generalization. The significance of this observation and its relevance to medical and surgical treatment of complex partial seizures is discussed.     

Comparison of sphenoidal, foramen ovale and anterior temporal placements for detecting interictal epileptiform discharges in presurgical assessment for temporal lobe epilepsy.

OBJECTIVES: Some authors have recently stressed that the position of the tip of the sphenoidal electrode plays a crucial role in its efficacy to detect mesio-basal spikes. We have tested this hypothesis by comparing the sensitivity of a contact of a foramen ovale bundle located at the foramen ovale (CFO) with scalp electrodes in detecting interictal epileptiform discharges. We have also compared deep and superficial foramen ovale contacts in the same bundle in order to establish whether deeper contacts can detect epileptiform discharges not seen at the foramen ovale or on the scalp. METHODS: The sensitivity for detecting epileptiform discharges of simultaneous intracranial and scalp EEG recordings from 20 patients under telemetric presurgical assessment for temporal lobe epilepsy were compared. RESULTS: Out of 2280 epileptiform discharges evaluated, about 70% were seen only at the deep foramen ovale contacts. Out of the 722 discharges recorded by CFO and/or scalp electrodes, 698 were seen at the CFO and 690 at the scalp anterior temporal electrode. Only on 29 occasions (4.15%) were discharges recorded at the CFO and not at the anterior temporal electrode. On 21 occasions (3.04%) CFO failed to detect discharges seen at the anterior temporal electrode. CONCLUSIONS: Our findings confirm previous results suggesting that sphenoidal electrodes, however accurately positioned, offer no significant increase in detection sensitivity compared with anterior temporal scalp electrodes. In addition, these results confirm that a large proportion of discharges seen at the deepest foramen ovale contacts are not seen either on the scalp nor at the superficial foramen ovale contacts.