Occurrence Of Interictal Epileptiform Discharges Research Articles

Subclinical Epileptiform Activity in Dementia with Lewy Bodies.

Patients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of α-synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG). However, no studies have so far investigated the occurrence of interictal epileptiform discharges (IED) in patients with DLB. To investigate if IED as measured with ear-EEG occurs with a higher frequency in patients with DLB compared to healthy controls (HC). In this longitudinal observational exploratory study, 10 patients with DLB and 15 HC were included in the analysis. Patients with DLB underwent up to three ear-EEG recordings, each lasting up to 2 days, over a period of 6 months. At baseline, IED were detected in 80% of patients with DLB and in 46.7% of HC. The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with DLB as compared to HC with a risk ratio of 2.52 (CI, 1.42-4.61; P-value = 0.001). Most IED occurred at night. Long-term outpatient ear-EEG monitoring detects IED in most patients with DLB with an increased spike frequency compared to HC. This study extends the spectrum of neurodegenerative disorders in which epileptiform discharges occurs at an elevated frequency. It is possible that epileptiform discharges are, therefore, a consequence of neurodegeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spike-microstates correlate with interictal epileptogenic discharges: a marker for hidden epileptic activity.

Objectively estimating disease severity and treatment success is a main problem in outpatient managing of epilepsy. Self-reported seizures diaries are well-known to underestimate the actual seizure count, and repeated EEGs might not show interictal epileptiform discharges (IEDs), although patients suffer from seizures. In this prospective study, we investigate the potential of microstate analysis to monitor epilepsy patients independently of their IED count. From our databank of candidates for epilepsy surgery, we included 18 patients who underwent controlled resting EEG sessions (with eyes closed, 30 min), at around the same time of the day, during at least four days (range: 4-8 days; mean: 5). Nine patients with temporal foci, six with extratemporal foci, and three with generalized epilepsy were included. Each patient's IEDs were marked and the topographic voltage maps of the IED peaks were averaged, and an individual average spike topography (AST) was created. The AST was then backfitted to each timepoint of the whole EEG resulting in the Spike-Microstate (SMS). The presence of the SMS in the residual EEG outside of the short IEDs epochs was determined for each recording session in each patient and correlated with the occurrence of the IEDs across all recording session, as well as with the drug charge of each day. Overall, SMS was much more represented in the routine EEG than the IEDs: they were identified 262 times more often than IEDs. The SMS time coverage correlated significantly with the IED occurrence rate (rho = 0.56; P < 0.001). If only patients with focal epilepsy were considered, this correlation was even higher rho = 0.69 (P < 0.001). Drug charge per day did not correlate with SMS. In this proof-of-concept study, the time coverage of SMS correlated strongly with the occurrence rate of the IEDs, they can be retrieved in the scalp EEG at a much higher occurrence rate. We conclude that SMS, once obtained for a given patient, are a more abundant marker of hidden epileptic activity than IEDs, in particular in focal epilepsy, and can be used also in absence of IEDs. Future larger studies are needed to verify its potential as monitoring tool and to determine cut-off values when drug protection becomes imperfect.

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.

Interictal discharges delay target-directed eye movements and impair attentional set-shifting in children with epilepsy.

The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye-tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy. Eleven consecutive children undergoing invasive monitoring with stereotactic electrodes for localization-related epilepsy performed an attentional set-shifting task while tandem intracranial electroencephalographic signals and eye-tracking data were recorded. Using an established algorithm, IEDs were detected across all intracranial electrodes on a trial-by-trial basis. Hierarchical mixed-effects modeling was performed to delineate associations between trial reaction time (RT), eye movements, and IEDs. Hierarchical mixed-effects modeling revealed that both the presence of an IED (β±SE=72.74± 24.21 ms, p= .003) and the frequency of epileptiform events (β±SE=67.54± 17.30 ms, p< .001) were associated with prolonged RT on the attentional set-shifting task. IED occurrence at the time of stimulus presentation was associated with delays in gaze initiation toward the visual targets (p= .017). The occurrence of epileptiform activity in close temporal association with stimulus presentation is associated with delays in target-directed gaze and prolonged response time, hallmarks of momentary lapses in attention. These findings provide novel insights into the mechanisms of transient impairments in children and support the use of visual tracking as a correlate of higher order attentional behavior.

Interictal Epileptiform Discharges are Task Dependent and are Associated with Lasting Electrocorticographic Changes.

The factors that control the occurrence of interictal epileptiform discharges (IEDs) are not well understood. We suspected that this phenomenon reflects an attention-dependent suppression of interictal epileptiform activity. We hypothesized that IEDs would occur less frequently when a subject viewed a task-relevant stimulus compared with viewing a blank screen. Furthermore, IEDs have been shown to impair memory when they occur in certain regions during the encoding or recall phases of a memory task. Although these discharges have a short duration, their impact on memory suggests that they have longer lasting electrophysiological effects. We found that IEDs were associated with an increase in low-frequency power and a change in the balance between low- and high-frequency oscillations for several seconds. We found that the occurrence of IEDs is modified by whether a subject is attending to a word displayed on screen or is observing a blank screen. In addition, we found that discharges in brain regions in every lobe impair memory. These findings elucidate the relationship between IEDs and memory impairment and reveal the task dependence of the occurrence of IEDs.

Effect of Wrist Tapping on Interhemispheric Coherence in Patients with Juvenile Myoclonic Epilepsy

The aim of this study was to assess the dynamics of interhemispheric coherence (IC) as an indicator of integration of different areas of the brain and their participation in the performance of certain functions before and after wrist tapping (WT), using the author's method in juvenile myoclonic epilepsy (JME). Methods and Results: The study included 81 subjects of working age, including 51 clinically healthy volunteers (median age of 39[21;56] years) and 30 patients (median age of 27[23;38] years) with JME. Analysis of IC in the electrode pairs Fp1-Fp2, F3-F4, C3-C4, T3-T4 was performed using a computer encephalographic complex. A coherent EEG analysis was used to identify and evaluate the relationships between different areas of the brain. Based on the change in the coherence coefficients (CCs), the level of integrative activity of brain structures was quantified. In healthy volunteers, before and after WT, we observed a statistically significant decrease in CCs for the beta-1 band in the pairs Fp1-Fp2, F3-F4, and C3-C4 (P&lt;0.05), while in the pair T3-T4, changes in CCs were not statistically significant (P&gt;0.05). At the same time, a statistically significant decrease in CCs in the alpha band was found only in the frontal regions in the pairs Fp1-Fp2 and F3-F4 (P&lt;0.05). No statistically significant changes were found in all the studied pairs in the theta band. When comparing CCs in JME patients in beta–1 and theta bands, before and after WT, we did not find statistically significant changes in CCs in all the studied electrode pairs. However, in the alpha band, we found a statistically significant decrease in CCs in the frontal region in the F3-F4 (P=0.0038) and C3-C4 electrode pairs (P=0.034). The results of the study of interhemispheric integration showed statistically significant differences between patients with JME and the control group. Conclusion: WT according to the author's method does not provoke the occurrence of interictal epileptiform discharges on the EEG and epileptic seizures in patients with JME. Coherent analysis showed positive changes in interhemispheric integrations of neurons in the beta–1 and alpha frequency ranges, mainly in the anterior hemispheres.

Epilepsy syndromes of childhood with sleep activation: Insights from functional imaging.

In epilepsy syndromes of childhood with sleep activation, defined as the spectrum of epileptic conditions going from classical benign childhood epilepsy with centrotemporal spikes (BECTS) to epileptic encephalopathy (EE) with continuous spike and waves during slow-wave sleep (CSWS) including Landau-Kleffner syndrome (LKS), a lot of functional imaging studies have been performed so far, leading to results that are not always consistent, related to the technique of neuroimaging performed and to the variability of the clinical phenotype. Most consistent findings are, depending of the method used, activations or increased regional glucose metabolism in the epileptogenic regions, and deactivations, hypometabolism or decreased functional connectivity in cortical regions that belong to the default mode network. Functional changes are either transitory, temporally related to the occurrence of interictal epileptiform discharges (IED), or permanent, persisting across IED-free periods. Some studies have shown that the more severe phenotype, i.e. EE with CSWS, displays the more profound functional disturbances. Taken together, functional imaging studies support the concept that IED impact cognition in epilepsy syndromes of childhood with sleep activation. However, the precise chronology between the occurrence of IED and the functional disturbances, the neuropsychological correlates of the functional disturbances, and the effects of the anti-epileptic treatments on IED, functional disturbances and cognition need to be further studied.

Real-time effects of interictal spikes on hippocampus and amygdala functional connectivity in unilateral temporal lobe epilepsy: An EEG-fMRI study.

To explore the real-time effects of interictal epileptiform discharges (IEDs) on hippocampus and amygdala functional connectivity (FC) in unilateral temporal lobe epilepsy (TLE). Patients with unilateral TLE were recruited and underwent simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) scanning. Simultaneous EEG was used to define the prespike (10 s before spike) and postspike (10 s after spike) periods. Dynamic FC analysis was applied using the left/right hippocampus and amygdala separately as a seed region to map the network alterations after IED occurrence. A total of 261 IED events (133 left, 128 right) from 21 patients with unilateral TLE (10 left, 11 right) were analyzed. Left IEDs had a greater influence on the hippocampus-seeded networks, whereas right IEDs affected the amygdala-seeded networks more. Left IEDs disconnected the ipsilateral hippocampus and the default mode network, which might be related to cognitive impairment in TLE. The reward-emotion network (more of the prefrontal-limbic system) and visual network also showed FC changes after left IEDs. The reward-emotion network (more of the reward system) was coactivated after right IEDs, indicating a possible mechanism of forced normalization. This study directly linked the disrupted functional networks in TLE to epileptic activities and offered a unique tool for future research to investigate mechanisms of comorbidities in TLE.

S81. The first hour sleep EEG recording predicts the occurrence of interictal epileptiform discharges during long-term video-EEG monitoring

Introduction To determine the predictive value of the first hour sleep EEG recording in identifying patients with interictal epileptiform discharges (IEDs) during long-term video-EEG monitoring in an adult epilepsy monitoring unit. Methods We retrospectively reviewed 255 consecutive patients who underwent continuous long-term video-EEG monitoring in the University of Chicago EMU. The complete video-EEG recording was reviewed, and the occurrence of IEDs was determined for each patient. We compared the occurrence of IEDs observed during the first hour sleep EEG recordings with the occurrence of IEDs observed during the complete long-term video-EEG recordings; inclusive of the first hour of sleep. Results Overall, IEDs were observed in 134(53%) of 255 patients during the full long-term video-EEG recording with a duration of 4 ± 0.8 days. IEDs were identified in the first hour sleep EEG recording in 125 (sensitivity 93%) of the 134 patients. IEDs were found in the first hour sleep EEG recording in 92 (94%) of 98 patients with temporal lobe epilepsy, 11 (92%) of 12 patients with frontal lobe epilepsy, 3 (100%) of 3 patients with parietal lobe epilepsy, 1 (50%) of the 2 patients with occipital lobe epilepsy, and 15 (88%) of the 17 patients with generalized epilepsy. The ictal onset in remaining 2 patients with multi-focal IEDs could not be localized due to muscle artifacts. The negative predictive value of the first hour EEG was 93%. Conclusion The first hour of sleep EEG recording reliably predicts the occurrence of interictal epileptiform activity in a long-term video-EEG recording, and therefore can be used efficiently for identifying patients with IEDs during long-term video-EEG recording in the adult epilepsy monitoring unit.

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

Sleep 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. Adult patients with TLE underwent in-lab night polysomnography (n-PSG) and, within 7days 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. The 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. SD 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.

Association of Interictal Epileptiform Discharges with Sleep and Anti-Epileptic Drugs

Background: The presence of interictal epileptiform discharges (IEDs) in electroencephalogram (EEG) is diagnostic of epilepsy. Latent IEDs are activated during sleep. Anti-epileptic drugs (AEDs) improve sleep. AEDs, sleep, and IEDs may interact and affect epilepsy management. Purpose: To explore the occurrence of IEDs and its association with sleep and AED status in suspected patients of epilepsy. Methods: EEG records were collected of suspected patients of epilepsy who reported to the electrophysiology laboratory of a tertiary care hospital during 1 year. The anthropometric details, clinical presentations, and AED status of the patients were recorded from the EEG records. Patients were divided into 2 categories based on whether AEDs had been started prior to the EEG evaluation (category-I) or not (category-II). The occurrences of IEDs in EEG recordings in both categories were analyzed. Results: In 1 year, 138 patients were referred for diagnostic EEG evaluation. One-hundred-two patients fulfilled the inclusion criteria, of which 57 patients (53%) belonged to category-I and 45 patients (47%) belonged to category-II. Incidence of IEDs, suggestive of definite diagnosis of epilepsy in category-I was 88% and in category-II was 69%, and this difference was statistically significant (p = 0.02). Conclusion: The increased proportion of IEDs in category-I patients may be due to high clinical suspicion or compounding interaction of AEDs and sleep. More extensive studies are required to delineate the complex interaction of AEDs, sleep, and IEDs so that judicious yet prompt management of epilepsy can be carried out.

Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy.

Patients with focal epilepsy have been shown to have reduced functional connectivity in intrinsic connectivity networks (ICNs), which has been related to neurocognitive development and outcome. However, the relationship between interictal epileptiform discharges (IEDs) and changes in ICNs remains unclear, with evidence both for and against their influence. EEG-fMRI data was obtained in 27 children with focal epilepsy (mixed localisation and aetiologies) and 17 controls. A natural stimulus task (cartoon blocks verses blocks where the subject was told "please wait") was used to enhance the connectivity within networks corresponding to ICNs while reducing potential confounds of vigilance and motion. Our primary hypothesis was that the functional connectivity within visual and attention networks would be reduced in patients with epilepsy. We further hypothesized that controlling for the effects of IEDs would increase the connectivity in the patient group. The key findings were: (1) Patients with mixed epileptic foci showed a common connectivity reduction in lateral visual and attentional networks compared with controls. (2) Having controlled for the effects of IEDs there were no connectivity differences between patients and controls. (3) A comparison within patients revealed reduced connectivity between the attentional network and basal ganglia associated with interictal epileptiform discharges. We also found that the task activations were reduced in epilepsy patients but that this was unrelated to IED occurrence. Unexpectedly, connectivity changes in ICNs were strongly associated with the transient effects of interictal epileptiform discharges. Interictal epileptiform discharges were shown to have a pervasive transient influence on the brain's functional organisation. Hum Brain Mapp 38:221-236, 2017. © 2016 Wiley Periodicals, Inc.

Epileptic networks are strongly connected with and without the effects of interictal discharges.

Epilepsy is increasingly considered as the dysfunction of a pathologic neuronal network (epileptic network) rather than a single focal source. We aimed to assess the interactions between the regions that comprise the epileptic network and to investigate their dependence on the occurrence of interictal epileptiform discharges (IEDs). We analyzed resting state simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) recordings in 10 patients with drug-resistant focal epilepsy with multifocal IED-related blood oxygen level-dependent (BOLD) responses and a maximum t-value in the IED field. We computed functional connectivity (FC) maps of the epileptic network using two types of seed: (1) a 10-mm diameter sphere centered in the global maximum of IED-related BOLD map, and (2) the independent component with highest correlation to the IED-related BOLD map, named epileptic component. For both approaches, we compared FC maps before and after regressing out the effect of IEDs in terms of maximum and mean t-values and percentage of map overlap. Maximum and mean FC maps t-values were significantly lower after regressing out IEDs at the group level (p < 0.01). Overlap extent was 85% ± 12% and 87% ± 12% when the seed was the 10-mm diameter sphere and the epileptic component, respectively. Regions involved in a specific epileptic network show coherent BOLD fluctuations independent of scalp EEG IEDs. FC topography and strength is largely preserved by removing the IED effect. This could represent a signature of a sustained pathologic network with contribution from epileptic activity invisible to the scalp EEG.

Nocturnal interictal epileptic discharges in adult Lennox-Gastaut syndrome: the effect of sleep stage and time of night.

Lennox-Gastaut syndrome (LGS) is characterized by interictal epileptiform discharges (IEDs) occurring during sleep. The aim of this study was to determine whether sleep influences not only the frequency of seizures and IEDs, but also the time-dependent evolution that may support the hypothesis of homeostatic influences on epileptic threshold. Video polysomnography data from our database were reviewed to identify adult LGS patients with at least seven hours of nocturnal recording. Thirteen patients were identified and a second polysomnography was available for nine. The number, duration and index of IEDs, relative to total sleep, sleep stages, and time during the night, were calculated. The majority of IEDs occurred during non-rapid eye movement sleep, mainly in stage 2 and slow-wave sleep. Adjusting for time spent in each sleep stage, we found 45 IEDs/hour in stage 1, 123/hour in stage 2, 106/hour in slow-wave sleep, and 26/hour in rapid eye movement sleep. The temporal distribution of IEDs showed a significant rise in the first three hours of sleep, followed by a progressive decrease at the end of the night (F=85.6; p<0.0001). Interictal epileptiform discharges occurrence in adult LGS is facilitated by non-rapid eye movement sleep with an evident effect of stage 2 and slow-wave sleep. The significant IED occurrence in the first part of the night and the subsequent decline suggests a link between epileptic threshold and homeostatic sleep mechanisms. The latter should be considered regarding choice of therapy.

Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children.

BackgroundEarly surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the “resting state”; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED); scan duration and design efficiency. This work’s motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric populationMethodsForty-six children with focal epilepsy and 20 controls (6–18) underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies (“rest sessions”), for another two sessions, subjects watched a child friendly stimulation i.e. movie (“movie sessions”). IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject.FindingsMovement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance.ConclusionsA child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising information without sedation. Our data suggest that ~20 minutes is the optimal length of scanning for EEG-fMRI studies in children with frequent IED. The efficiency of the fMRI design derived from spontaneous IED generation is an important factor for producing concordant results.

Epileptogenic networks as identified by the fMRI

Focal epilepsies are associated to the dysfunction of a pathological neuronal network (epileptic network) rather than to a single epileptogenic region. Simultaneous electroencephalogram (EEG)-functional MRI (EEG-fMRI) allows identification of hemodynamic networks associated with interictal epileptiform discharges (IEDs). Better understanding of interactions between physiological and epileptic networks, as well as exploring how this interaction is influenced by IEDs, is fundamental, considering the increasing volume of resting state functional connectivity studies. In recent works we found that drug-resistant epilepsy involves a durable non-transient re-arrangement of brain functional connectivity patterns that are present in absence of visible scalp IEDs. These are specific for each patient and occur also in non-lesional cases. The epileptic network could be considered as a new or modified “physiological” resting state networks (RSNs), additionally activated by the occurrence of IEDs. This hypothesis of new pathological RSN is corroborated by the fact that epileptic functional connectivity maps do not share the topographic pattern of typically described RSN. We can hypothesize that these epileptic networks may evolve over time from transient to more permanent connectivity changes as a result of plasticity triggered by pathological activity. How this finding impact the (re)-organization of the known physiological RSNs remains to be elucidated.

PP11.6 – 2858: ADHD predominantly inattentive subtype, interictal epileptiform discharges and use of methylphenidate for ADHD

Objective Interictal epileptiform discharges (IED) occur more often in children with attention deficit/hyperactivity disorder predominantly inattentive subtype (ADHD-I), and may contribute to the occurrence of ADHD symptoms in some cases. The aim of the present study was to investigate whether IED in children with ADHD-I influence the use of methylphenidate (MPH) during one year follow-up. Methods 517 children diagnosed with ADHD (82% male), age 5–14 years, performed routine awake EEG at ADHD assessment over 6 years period. 39 had EEG with IED. The group with IED was compared to an age and gender matched control group without IED. The groups showed no differences in using of MPH during one year follow-up. This study examined whether IED influence the use of MPH in a subgroup with ADHD-I with and without IED. Outcome measures were: initial positive response to MPH after 4–6 weeks titration, and the use of MPH at one-year follow-up. Results ADHD-I was diagnosed in 22 of 78 cases. 16 of 22 had IED, and 4 had previous history of epilepsy. Of the 16 cases with IED, 14 (87.5%) hade initial positive response to MPH, and 13 (81.3%) used MPH at one year follow-up. ADHD-I without IED was found in 6. Of the 6 cases with ADHD-I without IED, 5 (83.3%) had positive initial response to MPH, and 5 (83.3%) used MPH at one year follow-up. There was no statistic difference between the groups in using of MPH. Conclusion There is a higher occurrence of IED in ADHD-I. This study suggested that IED occurrence in ADHD-I does not influence the use of MPH during one year follow-up.

Attention deficit/hyperactivity disorder and interictal epileptiform discharges: It is safe to use methylphenidate?

PurposeThis study investigated whether interictal epileptiform discharges (IED) on a baseline routine EEG in children with ADHD was associated with the occurrence of epileptic seizures (Sz) or influenced the use of methylphenidate (MPH) during 2 years follow-up. MethodsA retrospective chart-review of 517 ADHD children with EEG revealed IED in 39 cases. These patients (IED group) were matched on age and gender with 39 patients without IED (non-IED group). We measured at baseline, 1 year and 2 years Sz occurrence, the use of MPH and antiepileptic drug (AED). ResultsAt baseline, 12 patients in the IED group had active epilepsy and three of them had Sz during the last year. 36 (92.3%) patients were treated with MPH. Initial positive response to MPH was achieved in 83.3% compared with 89.2% in the non-IED group. At 1 and 2 years follow-up, three patients who also had Sz at baseline and difficult to treat epilepsy, had Sz, without changes in seizure frequency. We found no statistically significant differences between the groups with respect to MPH use at 1 year and at 2 years. Ten patients from IED group, who did not have confirmed epilepsy diagnosis, temporarily used AEDs during the first year of follow-up. ConclusionDespite the occurrence of IED, the use of MPH was safe during 2 years follow-up. IED predict the Sz occurrence in children with previous epilepsy, but does not necessarily suggest an increased seizure risk. A caution is warranted in order not to overestimate the significance of temporarily occurrence of IED.

Therapeutic Significance of Frequency of Deep Brain Stimulation in Intractable Epilepsy

In addition to the exact placement of electrodes in the target site, the successful outcome of DBS depends largely upon correct choice of its stimulation parameters (especially voltage, frequency, pulsewidth and mode of stimulation) and optimal stimulation parameters (SPs) are those that reduce seizures optimally with minimum side effects and minimum consumption of the device-battery. The DBS in the patients with IE is commonly delivered at initial SP settings of 5-6 voltage in the frequency range of 130-180 Hz and pulse width varying from 60-90 microseconds by a monopolar intermittent mode of stimulation (1-min ON and 5-min OFF). The frequency of stimulation (FOS) selected is invariably in the high range for reasons outlined below. In the authors’ opinion, the FOS is of utmost importance in the determination of success and efficacy of the DBS as changes in FOS can potentially exercise maximum impact on the seizure profile (frequency, duration, severity of seizures and interictal epileptiform discharge rates) of the patients. It is generally agreed that analogous to vagal nerve stimulation (VNS), DBS is also effective at highfrequency stimulation (HFS) in reducing seizures [1-3], whereas low-frequency stimulation (LFS) is generally ineffective and can even exacerbate existing seizures [2]. The main objectives of selection of SPs for a successful DBS that have been postulated earlier also [4] are induction of EEGdesynchronization with reduction (or even possibly abolishment) of interictal epileptiform discharges (IEDs). This is in keeping with the generally accepted electrophysiological concept that EEGdesynchronization is associated with seizure resistance and reduction in the occurrence of IEDs and seizures. It has been suggested that LFS induces EEG synchronization, whereas HFS is associated with desynchronization, which might have a therapeutic effect in epilepsy as it has been found to be effective in both animal models and patients with epilepsy [5,6]; LFS is assumed to have anti-epileptic properties but the efficacy is highly debated [5,6] and from their study [5], the researchers have concluded that HFS at 130Hz is more effective than LFS (5Hz) in affecting excitability in epileptic rats. In 2007, a study by Boex et al. [3] also identified that HFS, but not LFS, was associated with a reduction of the interictal discharges and seizures. In Parkinson’s disease also, another neurological disorder characterized by abnormal neuronal synchrony, the usual FOS of the subthalamic nucleus is in the range of 130-180 Hz [7] and in one study [8], FOS at 90 Hz or more yielded the best results, whereas, FOS at 10 Hz or even 50 Hz failed to yield the required clinical effect. From a previous study also [9], the researchers have suggested that the effects of hippocampal DBS depend upon the frequency and topography of stimulation and a patterned stimulation with LFS and HFS resulted in desynchronization and exhibited anti-kindling effects in animal models of epilepsy. Thus, in view of the above electrophysiological findings, we suggest that the FOS in DBS plays a crucial role in determining the clinical outcome of DBS therapy in IE and the selection of optimal FOS may be based on its ability to induce EEG-desynchronization that can be assessed with a simultaneous EEG monitoring. This is especially in view of the observations that the optimal FOS may vary from patient to patient and therefore require individual settings. Admittedly, larger well-designed prospective studies are recommended that may in the course of time validate the therapeutic significance of the FOS and the utility of EEG monitoring in determining the optimal FOS.

Impact of side of lesion, seizure outcome and interictal epileptiform discharges on attention and memory after surgery in temporal lobe epilepsy

To determine the impact of side of surgery, seizure outcome and interictal epileptiform discharges (IEDs) on attention and memory in a cohort of patients with temporal lobe epilepsy who had undergone unilateral mesial temporal lobe resection. Ninety-four patients were investigated pre- and postoperatively by means of a standardised neuropsychological battery measuring subcomponents of attention, as well as short-term, working and long-term memory. The side of epilepsy surgery, seizure outcome and the presence of postoperative IEDs, as well as their possible relationship to the neuropsychological changes, were assessed. Statistical data were analysed using a repeated-measures MANOVA. The absence of seizures following surgery had a positive effect on short-term memory and attentional control. The occurrence of IEDs was found in patients with impaired figural learning. In terms of attentional control and working memory, patients who continued to present IEDs had also scored lower in these domains prior to surgery. IEDs had an effect independent of seizure presence, but were found to have a "supplementary negative effect" when the two variables were combined.