Number Of Interictal Epileptiform Discharges Research Articles

Effect of Lacosamide on Interictal Epileptiform Discharges in Pediatric Patients With Newly Diagnosed Focal Epilepsy

BackgroundThe purpose of this study was to determine the efficacy of lacosamide (LCM) on interictal epileptiform discharges (IEDs) and evaluate the relationships between IEDs and seizure outcome in pediatric patients with focal epilepsy. MethodsPatient inclusion criteria included (1) newly diagnosed focal epilepsy with unknown etiology; and (2) electroencephalogram recorded twice (before and after starting LCM) under the same conditions. The difference between the highest number of IEDs over five successive minutes (IEDs/5 min) and the location of IEDs was determined. Seizure outcome was evaluated one year after achieving the maintenance dose of LCM. Responders were identified as showing a ≥50% reduction in the pre-LCM seizure frequency. ResultsOf 22 patients, 10 showed an increase in IEDs/5 min after starting LCM. The median IEDs/5 min before and after starting LCM was not significantly different, at 1.5 (interquartile range: 0, 31.75) and 10.5 (0, 80.5), respectively. No relationship was identified between the difference in IEDs/5 min and seizure outcome. Patients with multiple regional or diffuse IEDs had significantly poorer seizure outcome compared with patients without those IEDs (P = 0.036 and P = 0.039, respectively). Of 10 patients with single regional IEDs, a tendency of IEDs to disappear was observed between patients with frontal and non-frontal IEDs. ConclusionThe effects of LCM on the number of IEDs may be unrelated to seizure outcome. LCM may be ineffective at improving seizure outcomes in patients with multiple regional or diffuse IEDs.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (β±SE=49.91± 16.55 ms, p= .003) and number of IEDs (β±SE=49.84± 12.51 ms, p< .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p= .009) and improved task performance (β±SE=-107.43± 39.54 ms, p= .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

Omitting Hyperventilation in Electroencephalogram during the COVID-19 Pandemic May Reduce Interictal Epileptiform Discharges in Patients with Juvenile Myoclonic Epilepsy.

Background: To prevent the spread of coronavirus disease 2019 (COVID-19), hyperventilation (HV) activation has been avoided in electroencephalograms (EEGs) since April 2020. The influence of omitting HV in EEG on epilepsy diagnosis remains uncertain for patients with epilepsies other than child absence epilepsy. We hypothesized that EEGs with HV would show more interictal epileptiform discharges (IEDs) than EEGs without HV in patients with juvenile myoclonic epilepsy (JME). Methods: We reviewed the EEGs of seizure-free patients with JME who underwent EEG, both with and without HV, from January 2019 to October 2021, in our institution, and compared IEDs between EEG with and without HV. Results: This study analyzed 23 JME patients. The IED-positive rate was significantly higher in EEG with HV (65.2%) than in EEG without HV (34.8%, p = 0.016). The mean ± standard deviation number of IEDs per minute was significantly larger during HV (1.61 ± 2.25 × 10−1) than during non-activation of both first EEG (0.57 ± 0.93 × 10−1, p = 0.039) and second EEG (0.39 ± 0.76 × 10−1, p = 0.009). Conclusions: In JME patients, performing HV during EEG may increase IEDs and appears to facilitate the accurate diagnosis of epilepsy.

Interictal Activity Is Associated With Slower Binocular Rivalry in Idiopathic Generalized Epilepsy.

Objective: Perceptual alternations evoked by binocular rivalry (BR) reflect cortical dynamics strongly dependent on the excitatory–inhibitory balance, suggesting potential utility as a biomarker for epileptogenesis. Therefore, we investigated the characteristics of BR in patients with idiopathic generalized epilepsy (IGE) and potential associations with clinical variables.Methods: Sixty-two healthy controls (HCs) and 94 IGE patients completed BR task. Perceptual alternation rates were compared between HC and IGE groups as well as among the HC group and IGE patients stratified according to the presence or absence of interictal activity on the ambulatory electroencephalogram (EEG), termed the abnormal ambulatory EEG group (AB-AEEG, n = 64) and normal ambulatory EEG group (N-AEEG, n = 30), respectively.Results: The IGE patients demonstrated a slower rate of BR perceptual alternation than HC subjects (t = −4.364, p < 0.001). The alternation rate also differed among the HC, AB-AEEG, and N-AEEG groups (F = 44.962, df = 2, p < 0.001), and post hoc comparisons indicated a significantly slower alternation rate in the AB-AEEG group compared with the N-AEEG and HC groups (0.28 vs. 0.46, and 0.43 Hz). Stepwise linear regression revealed positive correlations between the BR alternation rate and both the ambulatory EEG status (β, 0.173; standard error, 0.022 p < 0.001) and Montreal Cognitive Assessment score (β, 0.013; standard error, 0.004; p = 0.003). Receiver operating characteristic curve analysis of the BR alternation rate distinguished AB-AEEG from N-AEEG subjects with 90.00% sensitivity and 76.90% specificity (area under the curve = 0.881; 95% confidence interval = 0.801– 0.961, cut-off = 0.319). Alternatively, Montreal Cognitive Assessment score did not accurately distinguish AB-AEEG from N-AEEG subjects and the area under the receiver operating characteristic curve combining the BR alternation rate and Montreal Cognitive Assessment score was not markedly larger than that of the BR alternation rate alone (0.894, 95% confidence interval = 0.822–0.966, p < 0.001). K-fold cross-validation was used to evaluate the predictive performance of BR alternation rate, MoCA score, and the combination of both, which yielded average AUC values of 0.870, 0.584 and 0.847, average sensitivity values of 89.36, 92.73, and 91.28%, and average specificity values of 62.25, 13.42, and 61.78%, respectively. The number of interictal epileptiform discharges was significantly correlated with the alternation rate in IGE patients (r = 0.296, p = 0.018). A forward stepwise linear regression model identified the number of interictal epileptiform discharges (β, 0.001; standard error, 0.001; p = 0.025) as an independent factor associated with BR alternation rate in these patients.Conclusion: These results suggest that interictal epileptiform discharges are associated with disruptions in perceptual awareness, and that the BR may be a useful auxiliary behavioral task to diagnosis and dynamically monitor IGE patients with interictal discharge.

Absolute spike frequency and different comorbidities in temporal lobe epilepsy

ObjectiveThe objective of this study was to examine if the absolute number of interictal epileptiform discharges (IED) is related to the presence of different comorbidities and refractivity in patients with temporal lobe epilepsy. MethodsAnalysis with scalp EEG of the IED of 30 patients with temporal epilepsy. The analysis was performed in three selected periods of the record during N2–N3 sleep. We analyzed the number of IED and the sum of the values obtained in the three selected segments to determine the absolute interictal spike frequency. ResultsThe number of IED for patients varied from 11 to 450. The absolute interictal spike frequency showed a statistically significant relation with the presence of refractivity (p < 0.05), and neurological and/or psychiatric comorbidity (p < 0.05). Patients with an absolute interictal spike frequency ≤ 60 showed little refractoriness and no comorbidity. Patients with an absolute interictal spike frequency > 60 were mostly refractory and with neurological and/or psychiatric comorbidity. No significant relation was found of absolute interictal spike frequency with age at the onset of epilepsy, number of anticonvulsant drugs used, or base pathology (MRI). ConclusionsThe absolute interictal spike frequency is capable of differentiating patients with temporal lobe epilepsy, identifying those with temporal lobe epilepsy according to the severity of the condition. Only those patients with non-frequent spikes (≤60 over the affected temporal lobe) have a low percentage of refractoriness with little or no presence of comorbidity.

Effect of Mozart K.448 on interictal epileptiform discharges in children with epilepsy: A randomized controlled pilot study

BackgroundEpilepsy is a common pediatric neurologic disease in Thailand. However, the mainstay antiepileptic pharmacotherapies can induce severe side effects. While the benefit of playing Mozart K.448 music has been studied as an alternative, supplementary, nonpharmacologic treatment for epilepsy, the literature features limited few randomized controlled trial studies of children. ObjectiveWe aimed to study the effect of Mozart K.448 for two pianos on interictal epileptiform discharges (IEDs), quantitative electroencephalogram (qEEG), and heart rate variability (HRV) in patients with epilepsy. MethodsWe employed a single-blinded randomized trial design with a placebo control. The treatment group listened to the first 8 min of Mozart K.448 for two pianos during EEG recording. The control group underwent an EEG recording of the same duration in a quiet environment. Interictal epileptiform discharges were manually counted for 8 min before, during, and after the song was plated. Quantitative electroencephalogram and HRV were analyzed in each period. ResultA total of 32 patients aged 0–18 years were enrolled. There were 12 patients in the music group and 14 patients in the control group; 67% of the patients in the former exhibited significantly decreased IEDs while listening to the music compared with 42% of the patients in the quiet group (RR [Relative Risk Reduction]: 0.72, p-value: <0.001, 95% confidence interval [CI]: 0.69–0.74). During music exposure, qEEG demonstrated an increase in the delta/theta to alpha/beta ratio relative to that of controls (median in music: +3% and control: −6%, p-value: 0.520). Heart rate variability analyses showed a decrease in the ratio of low frequency to high frequency (LF/HF), which represents parasympathetic activity during music exposure (decrease of 34%, p-value: 0.382). ConclusionThe present study showed that Mozart K.448 reduced the number of IEDs in children with epilepsy and that Mozart K.448 could enhance parasympathetic activity. However, possibly because of the small study population, statistical significance was not reached. Our study revealed the considerable potential of music in the treatment of pediatric epilepsy.

Electrical cortical stimulations modulate spike and post-spike slow-related high-frequency activities in human epileptic foci

ObjectiveUsing interictal epileptiform discharges (IEDs), consisting of spikes and post-spike slow waves (PSSs), and IED-related high-frequency activities (HFAs), we elucidated inhibitory effects of electrical cortical stimulation (ECS) on human epileptic foci. MethodsWe recruited 8 patients with intractable focal epilepsy, and 50-Hz ECS was applied to the seizure-onset zone (SOZ) and non-SOZ. Before (5-min) and after (20-min) ECS, we evaluated the number of IED, the amplitudes of spikes and PSSs, spike-related HFA power, and PSS-related low gamma (30–50 Hz) activities. ResultsSOZ stimulation significantly decreased the number of IEDs and amplitude of spikes. Spike-related HFA power values in fast ripple (200–300 Hz) and ripple (80–150 Hz) bands were significantly suppressed only by SOZ stimulation in 4 and 3 patients, respectively. Among 4 patients with discrete PSSs, the amplitude ratio of spike/PSS decreased and the PSS-related low gamma activity power increased significantly in 2 patients and marginally in 1 patient. ConclusionsECS potentially modulates cortical excitability by reducing excitation and increasing inhibition, and monitoring IED-related HFAs may help achieve the optimal effects of ECS. SignificanceIED and IED-related HFAs are dynamic, potential surrogate markers for epileptic excitability during the interictal period.

Could Rolandic spikes be a prognostic factor of the neurocognitive outcome of children with BECTS?

IntroductionRolandic epilepsy, also known as benign childhood epilepsy with centrotemporal spikes (BECTS), is one of the most common epileptic syndromes in previously healthy children. Despite what was known about the benignity of this syndrome, there is always more evidence about the involvement of the cognitive functions with different deficits in several domains to be investigated. Aim of the studyThe aim of our study was to describe prognostic electroencephalogram (EEG) pattern of an adverse cognitive development to recognize patients at higher risk of lasting cognitive deficits that could need antiepileptic drugs (AEDs) or an improved neurocognitive therapy. In addition, we wanted to investigate the existence of a possible linkage between the number of interictal epileptiform discharges (IEDs) in the EEG and the more pronounced cognitive deficits. Material and methodsWe performed a case–control study on a cohort of 16 patients (10 male and 6 female) aged 4–14, diagnosed with BECTS who underwent EEG, magnetic resonance imaging (MRI), and neurocognitive assessment at the Pediatric Neurology Unit at the Umberto I Hospital, Sapienza University of Rome. Patients were divided into two groups according to the percentage of IEDs evaluated based on their sleep EEG: group A with less than 50% of the entire EEG invaded by discharges in more than 70% of the total number of EEG performed, so-called with low or intermediate activation. On the contrary, group B had a high activation, with more than 50% of the entire EEG invaded by discharges in the same percentage of the EEG performed. All children were assessed based on a protocol designed to study neuropsychological functions with specific tests chosen depending on age (Wechsler Intelligence Scale for Children IV: WISC IV; Wechsler Preschool and Primary Scale of Intelligence III: WPPSI III). Groups were compared for cognitive outcomes achieved by each patient through Student's t-test with a significance level of p<0.05 (two-tailed). ResultsThere is no statistically significant difference in the cognitive outcomes of these patients: Student's t-test showed a statistical significance (p) for each cognitive index always higher than 0.05, demonstrating that the intellectual quotient (IQ) and all other indexes analyzed (verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI)) are not affected by the difference in EEG anomalies presented by our patients. Interestingly, all patients had an IQ equal to or greater than the Italian average (12 out of 16 patients showed an IQ>100), with selective drops, particularly significant in the WMI and also in the PSI. ConclusionsOur results clearly demonstrate the importance of a proper evaluation of patients with this kind of epilepsy, without paying attention only to those with the greatest number of IEDs or seizures because all of them had a neurocognitive impairment, especially in memory. These data may be reinforced by a larger sample for an even more significant statistical value. These results also highlight the importance of a neurocognitive therapy for these children to treat for their specific needs.

Circadian rhythm of interictal epileptiform discharges and changes of spindles in patients with temporal lobe epilepsy

Background: This study aims to explore the circadian rhythm of interictal epileptiform discharges (IEDs) and changes of spindles in patients with temporal lobe epilepsy (TLE). Methods: Subjects were divided into two groups: research group (patients diagnosed with TLE, n=50) and control group (n=30). The whole-night natural sleep of all subjects was monitored, analysis and statistics were performed on IED, and the number, amplitude and the average duration of spindles were compared between these two groups. Results: (1) In TLE patients, the number of IED was larger in non-rapid eye movement (NREM) stages 1+2 and NREM stages 3+4 than in the waking stage and rapid eye movement (REM) stage, and the differences were statistically significant (P<0.05). (2) TLE patients had bilateral asymmetric sleep spindles, and their amplitude was lower in the affected side than in the unaffected side. Furthermore, the number, amplitude and mean duration of sleep spindles in the affected side in NREM stage 2 was significantly reduced compared with that in the control group (P<0.05). Conclusions: (1) TLE patients have the highest frequency of IED in slow wave sleep, followed by NREM stages 1+2, waking and REM stages. Slow wave sleep easily induces IED. (2) The number, amplitude and mean duration of sleep spindles in the affected side in NREM stage 2 were significantly reduced, compared with that in the control group. This suggests that changes in spindles have a lateralization value.

Rapid eye movement sleep reveals epileptogenic spikes for resective surgery in children with generalized interictal discharges.

Epilepsy surgery can be successful in children with extensive congenital or early acquired focal or hemispheric brain lesion on magnetic resonance imaging (MRI) despite generalized interictal epileptiform discharges (IEDs). The aim of this study was to assess if rapid eye movement (REM) sleep reduced generalized IEDs and revealed lateralized IEDs to identify the epileptogenic hemisphere in children with generalized IEDs and normal/subtle changes on MRI. We studied 20 children with generalized IEDs on scalp electroencephalography (EEG) and normal/subtle changes on MRI who underwent intracranial video-EEG for epilepsy surgery. We assessed a minimum of 100 IEDs during REM, non-REM, and wakefulness, and assigned the distribution (generalized, left, or right hemisphere) to each IED. The number of lobes in the resected areas and seizure outcome were compared between 20 children with generalized IEDs and a comparison group of 28 children without generalized IEDs. The mean occurrence rate of generalized IEDs during REM (37%) was significantly lower than that during non-REM (67%, p < 0.001) and wakefulness (54%, p = 0.003). The number of children whose largest number of IEDs was lateralized in REM was significantly higher than that in non-REM (15 vs. 3 children, 75% vs. 15%, p < 0.001). The hemisphere with lateralized IEDs among three states corresponded with the surgical side in 16 children with generalized IEDs. Seventeen children (85%) with generalized IEDs and 27 (96%) without generalized IEDs underwent resective surgery. Multilobar resection was required for 16 children (94%) with generalized IEDs more frequently than 7 children (26%) without generalized IEDs (p < 0.001). Thirteen children (77%) with generalized IEDs and 19 (73%) without generalized IEDs were seizure-free with a mean of 3.3 years of follow-up. Our study demonstrates the importance of assessing REM in children with generalized IEDs as it reveals lateralized epileptogenic spikes. Seizure freedom may be achieved with multilobar resection in these children with generalized IEDs and normal/subtle changes on MRI. Generalized IEDs in children with normal/subtle changes on MRI should not preclude surgical resection.

Prevalence of Interictal Epileptiform Discharges in Children Less Than One Year of Age Referred for Polysomnography

ABSTRACTThis study aimed to identify the prevalence of interictal epileptiform discharges (IEDs) in patients less than one year of age referred for polysomnogram (PSG), to quantify the number of IEDs and characterize sleep stage(s) during which IEDs occur, and to relate the reason for PSG referral and IED frequency. This was a retrospective cohort study of children less than 12 months of age referred for PSG studies. Fifty study participants had sufficient EEG data, and 49 were included in the study analysis. We identified an IED prevalence rate of 28% over the 2-year study period. The mean number (Standard Deviation; SD) of IEDs per hour of total sleep time was 0.4 (1.2). IEDs occurred most frequently in non-rapid eye movement (NREM) stages 2 and 3 of sleep. The most common reason for PSG referral in this patient cohort was for obstructive sleep apnea (OSA) (42/50). We concluded that patients less than 12 months of age referred for PSG may have abnormal brain activity. The relationship of that activity to PSG findings is unclear. This study offers a systematic process of identifying IEDs that should prompt referral to a neurologist for further evaluation.

Memory consolidation in children with epilepsy: Does sleep matter?

IntroductionChildren with epilepsy have frequent sleep disturbance and challenges in learning and memory. There is little research on the consolidation of memory during sleep in this population. The goal of this pilot study was to determine whether children with epilepsy are able to consolidate memories better after a sleep versus wake period as has been demonstrated in typically developing children. MethodsThis study was a prospective evaluation of children with epilepsy to determine if sleep improved episodic memory (using word lists) as compared with memory following a wake period of similar duration. The study was conducted in patients in the Epilepsy Monitoring Unit at a single academic health science center. In the sleep recall condition, the learning trials were presented in the evening, and delayed recall of the words was tested in the morning. In the wake condition, the learning took place in the morning, and the delayed recall took place later in the day. Subjects wore an actigraph to evaluate sleep/wake patterns. Data regarding the children's epilepsy, antiepileptic medications, and frequency of interictal epileptiform discharges were also documented. ResultsTen children (agd 8–17years) participated in the study. For the entire sample, recall after sleep was better than recall after awake (p=0.03), and 7 of the 10 children showed this effect. However, reanalyses removing an outlier showed no difference between the two recall conditions. The mean number of interictal epileptiform discharges was 8.8 during the recall after sleep and 7.8 during the recall after awake. Three children had seizures during the evaluation. ConclusionIn this pilot study, we demonstrated that a small cohort of children with epilepsy, with similar interictal epileptiform discharges during sleep and wake, showed no advantage in memory for a word list after a period of sleep than after a period of being awake. This finding requires further study in a larger cohort. Poor memory consolidation during sleep may contribute to the cognitive deficits in children with epilepsy.

The Relationship between Sleep-Activated Interictal Epileptiform Discharges and Intelligence in Children

ABSTRACT.This study investigates the relationship between interictal epileptiform discharges (IEDs) during sleep in children with benign rolandic epilepsy (BRE) and cognitive test scores as measured by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) with the hypothesis that, as IEDs increase, cognitive test scores decrease. Studies have shown that generalized seizures and status epilepticus can negatively impact cognition (Dodrill 2004), that children with epilepsy have lower cognitive function on average than children without epilepsy and that children with epilepsy and abnormal electroencephalograms (EEGs) have lower cognitive function than children with epilepsy and normal EEGs (Bailet et al. 2000). Studies have also indicated that as IEDs decrease, neurocognitive test scores increase (Baglietto et al. 2001). The current study evaluated sleep-activated IEDs in children with the specific syndrome of benign rolandic epilepsy based on the frequency of IEDs in sleep in relation to cognitive test scores. Neuropsychological test scores from the WISC-IV were gathered along with the number of spikes per minute detected in EEG recordings. Statistical analysis revealed a negative correlation between spike frequency and both processing speed and coding scores, though the relationship did not reach statistical significance. This study concludes that there may be correlations between increased spike density and cognitive test scores, or there might be other factors impacting cognition in BRE, but a larger sample is needed to further investigate. In addition, it is possible that a negative result in the present study represents good news, that the number of IEDs in BRE does not harm the brain by negatively impacting cognition.

Interictal epileptiform discharges and phasic phenomena of REM sleep

The objective of this study was to assess the effect of phasic rapid eye movement (REM) sleep events on interictal epileptiform discharges (IEDs). Twelve patients with focal epilepsy and IEDs during REM sleep were examined by video-EEG monitoring. The number of IEDs was calculated in different REM sleep episodes according to the rate of rapid eye movements. A negative correlation was identified between the occurrence of rapid eye movements and IEDs, indicating that the suppression of propagation of IEDs during REM sleep is enhanced by phasic REM sleep events, probably as a result of phasic activation of cholinergic neurons of the ponto-mesencephalic tegmentum. This study demonstrates that the degree of EEG desynchronization and IEDs is influenced by REM density.

Effect of chronic vagal nerve stimulation on interictal epileptiform discharges

We evaluated the effect of vagus nerve stimulation (VNS) on interictal epileptiform discharges (IEDs) in 32 epileptic patients (18 females; 14 males) with an average age of 42.2 ± 11.4 years, all of whom had been suffering from epilepsy for an average of 29.2 ± 14.5 years. All of the patients had received VNS for 5 years. The first EEG was performed prior to the initiation of stimulation; the second EEG was performed at the 5-year follow-up visit. The duration of each EEG was 30 min. We compared these two EEGs in terms of the number of IEDs present in each patient and correlated them to other variables. The average total number of IEDs during EEG and the total number of seconds in which IEDs were present decreased significantly after 5 years of stimulation from 97.3 ± 106.9 resp. 80.6 ± 86.1 to 49.4 ± 94.0 resp. 37.8 ± 65.0. Although there was no positive correlation between the reduction of IEDs and the percent of seizure reduction, we found a greater decrease of IEDs in patients who responded to VNS in comparison to those who did not. The decrease of IEDs was more pronounced in patients suffering from temporal lobe epilepsy than in patients suffering from extratemporal epilepsy. No other significant correlations were found. VNS reduced IEDs in patients chronically simulated for epilepsy. The reduction of IEDs was greater in patients who responded to VNS and in patients suffering from temporal lobe epilepsy.

Comparison of analytical strategies for EEG-correlated fMRI data in patients with epilepsy

The simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can be used to localize interictal epileptiform discharges (IEDs). Previous studies have reported varying degrees of concordance of EEG-fMRI with electroclinical findings. The aim of the present study is to evaluate to what extent this variability is determined by the analytical strategy or by the properties of the EEG data. For that purpose, 42 IED sets obtained in 29 patients with epilepsy were reanalyzed using a finite impulse response approach, which estimates the hemodynamic response function (HRF) from the data and allows non-causal effects. Cardiac effects were treated as additional confounders in the model. This approach was compared to the classical approach assuming a fixed HRF for each voxel in the brain. The performance of each method was assessed by comparing the fMRI results to the EEG focus. The flexible model revealed more significantly activated voxels, which resulted in more activated brain regions concordant with the EEG focus (26 vs. 16). Correction for cardiac effects improved the results in 7 out of the 42 data sets. Furthermore, design theory for event-related experiments was applied in order to determine the influence of the number of IEDs and their temporal distribution on the success of an experiment. It appeared that this success is highly dependent upon the number of IEDs present during the recording and less on their temporal spacing. We conclude that the outcome of EEG-fMRI can be improved by using an optimized analytical strategy, but also depends on the number of IEDs occurring during the recording.

Long-term effect of vagus nerve stimulation on interictal epileptiform discharges in refractory epilepsy

BackgroundVagus nerve stimulation (VNS) therapy has been widely recognized as an effective alternative for the treatment of refractory epilepsy. However, the precise mechanism of VNS is poorly understood. The purpose of this study was to observe the long-term interictal EEG changes induced by VNS, and to investigate the probable mechanism of action of VNS in achieving seizure control. MethodsEight patients with VNS were selected from two epilepsy centers in China (Harbin and Shanghai) between 2001 and 2004. We studied the clinical efficacy by long-term follow-up, ranging from 37 to 81 months (mean 55.8 months). Moreover, serial EEGs were performed at the different time (preoperative baseline, 3, 6, 12, and 24 months after VNS initiation) and the different states of VNS stimulator (“activation”, “deactivation” and “reactivation”). ResultsA ≥50% seizure reduction was achieved in 12.5%, 62.5%, 75%, 62.5% and 75% of the total patients (n=8) at 6, 12, 18, 24 and 36 months of post-VNS, respectively. The results revealed a statistically significant progressive decrease in the number of IEDs (interictal epileptiform discharges) on EEG with time (P<0.01). Significant correlation had been highlighted after 6 months of VNS stimulation, between the reduction of seizure frequency and the decreasing of IEDs (P<0.01). Furthermore, statistically significant difference of IEDs was seen when comparing the state of “deactivation” with the states of “activation” and “reactivation”, respectively (P<0.01). However, there was no significant difference in IEDs between “activation” and “reactivation” (P>0.05). ConclusionsVNS is an efficient, well-tolerated therapy for refractory epilepsy. It can induce progressive electrophysiological effect on epileptiform activity over time. This may reflect the mechanism of chronic action of VNS with desynchronization of EEG in achieving seizure control.

Effects of ketogenic diet on epileptiform activity in children with therapy resistant epilepsy

The purpose was to quantify changes of epileptiform activity during ketogenic diet (KD) treatment in children with therapy resistant epilepsy, and evaluate how these changes are related to activity stage and to clinical effects on seizure frequency, seizure severity, attentional behaviour, quality of life (QOL), and beta-hydroxybutyrate (betaOHb). Eighteen children were investigated with 24h ambulatory EEG monitoring 1 week prior to KD initiation and, after 3 months of KD treatment. Epileptiform activity was evaluated by automated spike detection. This data was compared with data presented in a previous study published in Epilepsia 2006, on sleep structure and different activity stages, clinical data on seizure frequency, seizure severity, QOL and attentional behaviour on the same children [Hallbook, T., Lundgren, J., Rosén, I., 2007. Ketogenic diet improves sleep quality in children with therapy resistant epilepsy. Epilepsia 48, 59-65]. After 3 months of KD treatment the number of interictal epileptiform discharges (IEDs) was significantly reduced (p<0.001). When considering the four activity stages separately, the reduction was significant during non-rapid eye movement sleep stage 2, slow wave sleep (SWS) and rapid eye movement (REM) sleep (p=0.001, 0.001, 0.002), and not significantly so during awake (p=0.07). Beta-hydroxybutyrate was significantly increased (p<0.001). There was a significant correlation between the reduction in IEDs and clinical seizures (Spearman r=0.6, p=0.005) and between improvement in attentional behaviour and the increase in betaOHb (Spearman r=0.5, p=0.03). There was no significant correlation between changes in attentional behaviour and IEDs or clinical seizures. This study shows that KD reduces the number of IEDs, especially during sleep. It shows a correlation between reduction in epileptiform activity and clinical seizures. There were no correlations between reduction in epileptiform activity and clinical seizures and improvement in QOL or attention. The increase in betaOHb correlated with improvement in attention.

Low-frequency electric cortical stimulation decreases interictal and ictal activity in human epilepsy

We previously reported that low-frequency electric cortical stimulation (LFECS) directly applied to the epileptic focus by means of subdural electrodes decreased the number of interictal epileptiform discharges in patients with intractable partial epilepsy. In the present study, LFECS was applied to the epileptic foci directly in four patients with medically intractable partial epilepsy through subdural electrodes and evaluated its effect on the number of interictal epileptiform discharges as well as simple partial seizures. We used alternating electric current of 0.3 ms duration presented at 0.9 Hz frequency for 250 s. LFECS did not induce seizures in any of the four patients. In one patient, the number of interictal epileptiform discharge decreased significantly by LFECS, which is in conformity with our previous report. In addition, LFECS applied to the seizure onset zone decreased the frequency of simple partial seizures in one patient. These results suggest that LFECS has an inhibitory effect not only on the interictal but also the ictal activities in patients with intractable partial epilepsy. Further study is required to determine the inhibitory effect of LFECS more in details.

Long term effects on epileptiform activity with vagus nerve stimulation in children

We report long-term effects of vagus nerve stimulation (VNS) on epileptiform activity in 15 children, and how these changes are related to activity stage and to clinical effects on seizure reduction, seizure severity (NHS3) and quality of life (QOL). Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with 24 h ambulatory EEG monitoring for spike detection. The number of interictal epileptiform discharges (IEDs) and the inter spike intervals (ISIs) were analysed during 2 h in the awake state, and 1h of rapid eye movement (REM)-, spindle- and delta-sleep, respectively. Total number and duration of electrographic seizure episodes were also analysed. At 9 months the total number of IEDs was significantly reduced (p=0.04). There was a tendency of reduction in all activity stages, and significantly so in delta-sleep (p=0.008). Total electrographic seizure number was significantly reduced in the 24 h EEG at 3 and 9 months (p=0.03, 0.05). There was a significant concordance in direction of changes in epileptiform activity and electrographic seizures at 9 months (p=0.04). Concordance in direction of changes was seen in 9 of 15 children between clinical seizures and IED (p>0.3), in 10 of 15 children between QOL and IED (p=0.3) and in 8 of 15 children between NHS3 and IED (p>0.3). There was no direct correlation between the extent of improvement in these clinical data and the degree of spike reduction. This study shows that VNS reduces IEDs especially in REM and delta sleep, as well as the number of electrographic seizures. It also shows a concordance between reduction in IEDs and electrographic seizures.