Vagus nerve stimulation: Outcome and predictors of seizure freedom in long-term follow-up

ObjectivesTo present long-term outcome and to identify predictors of seizure freedom after vagus nerve stimulation (VNS).MethodsAll patients who had undergone VNS implantation in the Epilepsy Centre Bethel were retrospectively reviewed. There were 144 patients who had undergone complete presurgical evaluation, including detailed clinical history, magnetic resonance imaging, and long-term video-EEG with ictal and interictal recordings. After implantation, all patients were examined at regular intervals of 4 weeks for 6–9 months. During this period the antiepileptic medication remained constant. All patients included in this study were followed up for a minimum of 2 years.ResultTen patients remained seizure-free for more than 1 year after VNS implantation (6.9%). Seizures improved in 89 patients (61.8%) but no changes were observed in 45 patients (31.3%). The following factors were significant in the univariate analysis: age at implantation, multifocal interictal epileptiform discharges, unilateral interictal epileptiform discharge, cortical dysgenesis, and psychomotor seizure. Stepwise multivariate analysis showed that unilateral interictal epileptiform discharges (IEDs), P = 0.014, HR = 0.112 (95% CIs, 0.019–0.642), cortical dysgenesis P = 0.007, HR = 0.065 (95% CIs, 0.009–0.481) and younger age at implantation P = 0.026, HR = 7.533 (95% CIs 1.28–44.50) were independent predictors of seizure freedom in the long-term follow-up.ConclusionVNS implantation may render patients with some forms of cortical dysgenesis (parietooccipital polymicrogyria, macrogyria) seizure-free. Patients with unilateral IEDs and earlier implantation achieved the most benefit from VNS.     

Role of single pulse electrical stimulation (SPES) to guide electrode implantation under general anaesthesia in presurgical assessment of epilepsy

PurposeSingle-pulse electrical stimulation (SPES) during intracranial recordings is part of the epilepsy presurgical evaluation protocol at King's College Hospital (London). Epileptiform responses correlated to the stimulus (delayed responses – DRs) tend to occur in areas of seizure onset, thereby allowing interictal identification of epileptogenic cortex in patients suffering refractory epilepsy. This preliminary study investigated the validity of SPES in the operating theatre under general anaesthesia (GA) during the implantation procedure, aiming to improve the positioning of intracranial electrodes.MethodsTwelve drug-resistant epilepsy patients implanted with depth and/or subdural electrodes were studied. SPES (1 ms pulses, 4–8 mA, 0.2 Hz) was performed during both intra-operative electrode implantation under GA and chronic intracranial ECoG recordings, and the two recordings were compared in terms of cortical responses produced by stimulation and their electrode location.ResultsIn 8/12 patients, SPES during chronic recordings produced DRs positively correlated to seizure onset and/or early seizure propagation areas. Of those eight patients, four showed DRs during electrode implantation under GA over the same electrode contacts. Among the four patients without DR during GA, three had continuous localized spontaneous epileptiform discharges, which made interpretation of SPES responses unreliable.ConclusionThis study showed that, under GA, DRs can be reliably replicated, without false positive epileptiform responses to SPES, although the method's sensitivity is greatly reduced by spontaneous discharges.Results support SPES as a complementary technique that can be used to improve electrode placement during epilepsy surgery when no profound interictal activity is present.     

The role of altered tissue osmolality on the characteristics and propagation of seizure activity in the intact isolated mouse hippocampus

ObjectivesTo study the role of altered tissue osmolality on the characteristics and propagation dynamics of seizure activity and on interictal activity, in a low-Mg⁺² artificial cerebrospinal fluid (ACSF) model of recurrent seizures, using the immature (P8–P25) intact isolated mouse hippocampus.MethodsRecordings were obtained extracellularly from a single site in the CA1 region and from multiple sites along the septotemporal axis measuring spontaneous epileptiform field activity in ACSFs of different osmolalities.ResultsIn normal osmolar ACSF (310 mOsmol), the average duration of recorded seizures was 90 ± 10 s and the average peak amplitude was 0.9 ± 0.1 mV. In a hypoosmolar ACSF (270 mOsmol), the seizures were significantly prolonged at 165 ± 20 s (p < 0.05) with a peak amplitude of 1.2 ± 0.3 mV, whereas interictal activity was suppressed. Hyperosmolar ACSF (340 mOsmol) reduced the duration (65 ± 15 s) and peak amplitude (0.6 ± 0.1 mV, p < 0.05) from control, but interictal activity was not affected. No differences in seizure recurrence rate were noted in all three osmolar states.ConclusionThe present study, the first to assess of the role of altered tissue osmolality in an intact in vitro preparation, demonstrates that changes in perfusate osmolality play a significant role on the amplitude, duration, and propagation velocity of seizure-like events, and the characteristics of interictal activity, without affecting seizure recurrence rate.SignificanceIncreasing tissue osmolality should be considered as a valid target for anticonvulsant treatment.     

Prediction of rhythmic and periodic EEG patterns and seizures on continuous EEG with early epileptiform discharges

BackgroundContinuous EEG (cEEG) is necessary to document nonconvulsive seizures (NCS), nonconvulsive status epilepticus (NCSE), as well as rhythmic and periodic EEG patterns of ‘ictal–interictal uncertainty’ (RPPIIU) including periodic discharges, rhythmic delta activity, and spike-and-wave complexes in neurological intensive care patients. However, cEEG is associated with significant recording and analysis efforts. Therefore, predictors from short-term routine EEG with a reasonably high yield are urgently needed in order to select patients for evaluation with cEEG.ObjectiveThe aim of this study was to assess the prognostic significance of early epileptiform discharges (i.e., within the first 30 min of EEG recording) on the following: (1) incidence of ictal EEG patterns and RPPIIU on subsequent cEEG, (2) occurrence of acute convulsive seizures during the ICU stay, and (3) functional outcome after 6 months of follow-up.MethodsWe conducted a separate analysis of the first 30 min and the remaining segments of prospective cEEG recordings according to the ACNS Standardized Critical Care EEG Terminology as well as NCS criteria and review of clinical data of 32 neurological critical care patients.ResultsIn 17 patients with epileptiform discharges within the first 30 min of EEG (group 1), electrographic seizures were observed in 23.5% (n = 4), rhythmic or periodic EEG patterns of ‘ictal–interictal uncertainty’ in 64.7% (n = 11), and neither electrographic seizures nor RPPIIU in 11.8% (n = 2). In 15 patients with no epileptiform discharges in the first 30 min of EEG (group 2), no electrographic seizures were recorded on subsequent cEEG, RPPIIU were seen in 26.7% (n = 4), and neither electrographic seizures nor RPPIIU in 73.3% (n = 11). The incidence of EEG patterns on cEEG was significantly different between the two groups (p = 0.008). Patients with early epileptiform discharges developed acute seizures more frequently than patients without early epileptiform discharges (p = 0.009). Finally, functional outcome six months after discharge was significantly worse in patients with early epileptiform discharges (p = 0.01).ConclusionsEpileptiform discharges within the first 30 min of EEG recording are predictive for the occurrence of ictal EEG patterns and for RPPIIU on subsequent cEEG, for acute convulsive seizures during the ICU stay, and for a worse functional outcome after 6 months of follow-up.This article is part of a Special Issue entitled Status Epilepticus.     

Do sphenoidal electrodes aid in surgical decision making in drug resistant temporal lobe epilepsy?

ObjectiveThe utility of sphenoidal electrodes (SPh) in analyzing interictal epileptiform discharges (IEDs) and ictal electrography remains controversial, despite its widespread use.MethodsOne hundred and twenty-two consecutive patients with presumed temporal lobe epilepsy (TLE) who underwent presurgical evaluation were prospectively studied. SPh and Silverman’s electrodes were placed, in addition to routine electrodes in 10–20 international system. IEDs and ictal electroencephalography (EEG) were analyzed separately in bipolar and referential montages. The proportion of patients selected for surgery after adjusting for SPh placement based on the earlier ictal onset and IEDs were analyzed.ResultsOf the 8701 IEDs in SPh, only 65% were seen over the scalp bipolar montage; 1392 (16%) IEDs were confined to SPh electrodes, and were not seen at scalp bipolar montage (p < 0.001). Spike amplitudes were highest at SPh (p < 0.001). Of the 592 seizures analyzed, 62 (61%) had simultaneous SPh and scalp onset, while in 26 (25%) SPh onset preceded the scalp.ConclusionsOut of the 35 patients with unilateral mesial temporal sclerosis (MTS) with additional neocortical changes and/or non-lateralized bitemporal IEDs and/or diffuse ictal onset (group 1), 27 were selected for surgery (77%). About 7% was selected for surgery in this group by SPh placement. Also, in patients with bilateral MTS (group 2), 25% (5/20) were chosen for anterior temporal lobectomy, SPh provided an additional benefit in 11% (p < 0.001). Patients with normal magnetic resonance imaging (group 3) and temporal plus epilepsy (group 4) had a lower surgical yield, only 12% and 9.5% could undergo surgery. They were denied surgical candidacy with SPh (p < 0.001).SignificanceOne-third of patients after SPh placement were selected for resective surgery obviating the need for invasive monitoring. The maximum yield was noted in unilateral MTS (associated with additional neocortical features or non-lateralized bilateral temporal interictal IEDs or diffuse ictal onset in scalp EEG) and in bilateral MTS. Those with normal MRI/temporal plus epilepsy could be excluded from direct resective surgery.     

Automated electrical source imaging with scalp EEG to define the insular irritative zone: Comparison with simultaneous intracranial EEG

Objective To evaluate the accuracy of automated interictal low-density electrical source imaging (LD-ESI) to define the insular irritative zone (IZ) by comparing the simultaneous interictal ESI localization with the SEEG interictal activity.Methods Long-term simultaneous scalp electroencephalography (EEG) and stereo-EEG (SEEG) with at least one depth electrode exploring the operculo-insular region(s) were analyzed. Automated interictal ESI was performed on the scalp EEG using standardized low-resolution brain electromagnetic tomography (sLORETA) and individual head models. A two-step analysis was performed: i) sublobar concordance between cluster-based ESI localization and SEEG-based IZ; ii) time-locked ESI-/SEEG analysis. Diagnostic accuracy values were calculated using SEEG as reference standard. Subgroup analysis was carried out, based on the involvement of insular contacts in the seizure onset and patterns of insular interictal activity.Results Thirty patients were included in the study. ESI showed an overall accuracy of 53% (C.I. 29–76%). Sensitivity and specificity were calculated as 53% (C.I. 29–76%), 55% (C.I. 23–83%) respectively. Higher accuracy was found in patients with frequent and dominant interictal insular spikes.Conclusions LD-ESI defines with good accuracy the insular implication in the IZ, which is not possible with classical interictal scalp EEG interpretation.SignificanceAutomated LD-ESI may be a valuable additional tool to characterize the epileptogenic zone in epilepsies with suspected insular involvement.     

Electro- and magneto-encephalographic spike source localization of small focal cortical dysplasia in the dorsal peri-rolandic region

ObjectiveSmall focal cortical dysplasia (FCD) may be ambiguous or overlooked on magnetic resonance (MR) imaging. Source localization of EEG and magnetoencephalography (MEG) spikes was evaluated to confirm the diagnosis of small FCD.MethodsThis study included 6 epilepsy patients with a single small lesion on MR imaging suggesting FCD within a single gyrus among 181 consecutive epilepsy patients admitted to our epilepsy monitoring unit over 27 months. Stereotypical interictal spikes were detected on simultaneous EEG and MEG recordings and the onset-related source of averaged spikes was estimated.ResultsAll 6 patients had unique clinical characteristics as follows: leg sensori-motor seizures in 5 patients and eye version in 1 patient; a small MR imaging lesion suggesting FCD in the dorsal peri-rolandic region, which had been overlooked until our evaluation; and both EEG and MEG dipoles were estimated adjacent to the MR imaging lesion.ConclusionsSource localization of EEG and MEG spikes can confirm the diagnosis of FCD based on a single small MR imaging lesion, which was overlooked by previous examination of MR images.SignificanceExamination of MR images should be based on spike source localization as well as seizure semiology to identify subtle MR imaging abnormalities.     

A case–control study of wicket spikes using video-EEG monitoring

PurposeTo investigate clinical characteristics associated with wicket spikes in patients undergoing long-term video-EEG monitoring.MethodsA case–control study was performed in 479 patients undergoing video-EEG monitoring, with 3 age- (±3 years) and gender-matched controls per patient with wicket spikes. Logistic regression was utilized to investigate the association between wicket spikes and other factors, including conditions that have been previously associated with wicket spikes.ResultsWicket spikes were recorded in 48 patients. There was a significantly higher prevalence of dizziness/vertigo (p = 0.002), headaches (p = 0.005), migraine (p = 0.015), and seizures (p = 0.016) in patients with wickets. The majority of patients with wicket spikes did not exhibit epileptiform activity on EEG; however, patients with history of seizures were more likely to have wickets (p = 0.017). There was no significant difference in the prevalence of psychogenic non-epileptic seizures between the groups. Wickets were more common on the left, during sleep, and more likely to be first recorded on day 1–2 of monitoring.ConclusionsPatients with wicket spikes are more likely to have dizziness/vertigo, headaches, migraine, and seizures. Patients with history of seizures are more likely to have wickets. The prevalence of psychogenic non-epileptic seizures is not significantly higher in patients with wickets.     

The role of necroptosis in status epilepticus-induced brain injury in juvenile rats

PurposeTo study the role of necroptosis in status epilepticus (SE)-induced injury in the developing brain and the possible associations of necroptosis with epileptogenesis and cognitive dysfunction.MethodsThe lithium-pilocarpine epilepsy model was reproduced in male rats at postnatal day 25. Propidium iodide (PI) staining was used to detect cell death after SE. Transmission electron microscopy (TEM) was performed to observe morphological changes in injured neurons. Western blot and immunofluorescence (IF) staining were used to investigate the expression of receptor interacting protein kinase-3 (RIP3), mixed lineage kinase domain-like (MLKL), and p-MLKL after SE. EEG was monitored during the chronic epileptic period. The Morris water maze test was performed to evaluate spatial learning and memory in juvenile rats after SE.ResultsMassive PI-positive (PI⁺) neurocytes were observed mainly in the amygdala and piriform cortex 24 h to 7 days after SE, with the most prominent changes observed after 72 h. Injured neurons observed via TEM exhibited necroptotic morphological features, including loss of ribosomes, autophagosome formations, deformed nuclei with condensed and marginated chromatin, and disruptive cell membranes. The expression of RIP3 and p-MLKL increased after 24 h, peaked at 72 h, and decreased 7 days after SE. In addition, IF staining revealed that MLKL was expressed in cell plasma membranes present in the amygdala and piriform cortex. This finding was concomitant with the fact that MLKL is involved in executing necroptosis by binding and disrupting the plasma membrane. During the chronic epileptic period, spontaneous recurrent seizures were observed behaviorally and interictal spikes and sharp waves were recorded by EEG in the SE group. The Morris water maze test revealed that in the place navigation test, the escape latency of the SE group was longer than that of the control group (p < 0.05). In the spatial probe test, the number of times the rats in the SE group passed through the original platform site was lesser than that of the rats in the control group (p < 0.05).ConclusionSE-induced brain injury leads to neuronal necroptosis in juvenile rats. MLKL may play a significant role in the execution of SE-induced necroptosis. Further studies are required to determine whether inhibiting necroptosis can prevent chronic epileptogenesis and improve cognitive ability for juvenile rats.     

Ectonucleotidase and acetylcholinesterase activities in synaptosomes from the cerebral cortex of streptozotocin-induced diabetic rats and treated with resveratrol

The aim of the present study was to investigate the effects of resveratrol (RV), an important neuroprotective compound on NTPDase, 5′-nucleotidase and acetylcholinesterase (AChE) activities in cerebral cortex synaptosomes of streptozotocin (STZ)-induced diabetic rats. The animals were divided into six groups (n = 8): control/saline; control/RV 10 mg/kg; control/RV 20 mg/kg; diabetic/saline; diabetic/RV 10 mg/kg; diabetic/RV 20 mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the cerebral cortex was removed for synaptosomes preparation and enzymatic assays. The results demonstrated that NTPDase and 5′-nucleotidase activities were significantly increased in the diabetic/saline group (p < 0.05) compared to control/saline group. Treatment with resveratrol significantly increased NTPDase, 5′-nucleotidase activities in the diabetic/RV10 and diabetic/RV20 groups (p < 0.05) compared to diabetic/saline group. When resveratrol was administered per se there was also an increase in the activities of these enzymes in the control/RV10 and control/RV20 groups (p < 0.05) compared to control/saline group. AChE activity was significantly increased in the diabetic/saline group (p < 0.05) compared to control/saline group. The treatment with resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups. In conclusion, this study demonstrated that the resveratrol interfere with the purinergic and cholinergic neurotransmission by altering NTPDase, 5′-nucleotidase and AChE activities in cerebral cortex synaptosomes of diabetic rats. In this context, we can suggest that resveratrol should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with the diabetes.     

Ictal and interictal EEG patterns in patients with nonconvulsive and subtle convulsive status epilepticus

BackgroundElectroencephalography findings in nonconvulsive or subtle convulsive status epilepticus (NCSE and SCSE, respectively) can be heterogenous. We aimed to study the different patterns on EEG in our cohort of patients.ObjectiveOur objective was to study ictal and interictal EEG patterns in patients with NCSE and SCSE.MethodsFrom January 2012 to December 2013, EEGs recorded from patients admitted for altered mental status suspected of having NCSE or SCSE were reviewed retrospectively. Electroencephalography status was defined as having (a) continuous ictal discharges lasting > 5 min or (b) > 2 discrete bursts of ictal discharges, each lasting < 5 min, without returning to previous background rhythm in between these bursts.ResultsAmong 1698 EEGs recorded for at least 30 min from hospitalized patients, 55 (3.23%) satisfied the criteria of EEG SE. The ictal onset was regional in 37 (67.2%) EEGs, multiregional independent in 8 (14.5%), and generalized in 10 (18.4%).The EEG seizure duration was > 5 min in 24 (43.6%) EEGs, between 1 and 5 min in 14 (25.4%), and less than 1 min in 17 (30.8%).Twenty (36.3%) EEGs showed one continuous prolonged seizure episode of > 5-minute duration, 15 (27.2%) had 10 or less discrete episodes, 20 (36.3%) had more than 10 episodes, and 11 (20%) had 2 or more ictal patterns.Thirty (54.5%) EEGs had onset ictal frequency of > 8 Hz whereas the rest had < 8-Hz ictal frequency. In the interictal segment, 29 patients had continuous generalized slow waves, while 12 had intermittent generalized slow waves. Eleven patients had continuous slow waves lateralized to one hemisphere, and these were ipsilateral to the ictal focus in 10 but contralateral in 1. Other interictal waves seen were PLEDS (6), sharp waves (3), suppression (5), and triphasic waves (1).The background alpha rhythm was absent in 36 patients and slow in 14, and normal background alpha was seen in the interictal period in 5 patients.ConclusionThe ictal and interictal EEG patterns in NCSE and SCSE can be varied. Further study to look for etiologic and clinical correlates of each pattern could add to its clinical value.This article is part of a Special Issue entitled “Status Epilepticus”.     

Epilepsy may cause increased pain sensitivity: Evidence from absence epileptic WAG/Rij rats

ObjectiveThe comorbidity of epilepsy and pain disorders as well as effectiveness of certain therapeutic approaches in both conditions attracted attention to epilepsy–pain interactions. This lead to the discovery of significantly shared pathophysiological mechanisms although many aspects remain largely unknown. To test the hypothesis that epilepsy may be associated with altered pain sensitivity, we analyzed interictal pain sensitivity using epilepsy prone WAG/Rij rats, a genetic model exhibiting age-related-onset absence epilepsy.MethodsTwo series of experiments were conducted. In experiment I, pain sensitivity of symptomatic WAG/Rij rats were compared with age-matched control Wistar rats. In experiment II, pain sensitivity of WAG/Rij rats were monitored longitudinally when they were presymptomatic (at 2 months) and symptomatic (after maturation, at 8 months), and compared with age-matched control Wistar rats. Pain sensitivity was assessed by applying heat stimuli to hind paws and measuring the paw-withdrawal latency using thermal plantar analgesia meter in awake and freely moving animals. All pain measurements were made during the interictal period, confirmed by simultaneous electroencephalography through intracranially implanted electrodes.ResultsIn experiment I, the interictal pain withdrawal latency of symptomatic WAG/Rij rats was significantly shorter than control Wistar rats (P < 0.01).In experiment II, WAG/Rij rats had significantly shorter latency of withdrawal response than control Wistar rats, both at presymptomatic (P < 0.05) and symptomatic stage (P < 0.0001). Matured (8 months old) control Wistar rats demonstrated significantly increased withdrawal latency compared to the 2 months animals (P < 0.01), but the WAG/Rij rats did not (P > 0.5).ConclusionEpileptic WAG/Rij rats present significantly increased pain sensitivity when compared to control Wistar rats, suggesting comorbidity of epilepsy and pain.     

Parasympathetic activation is involved in reducing epileptiform discharges when listening to Mozart music

ObjectiveListening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect. Our previous work revealed the positive effects of Mozart K.448 in reducing epileptiform discharges in children with epilepsy. However, the mechanism remains unclear. parasympathetic activation has been shown to help seizure control in many studies. In this study, we investigated the effect of Mozart music on epileptiform discharges and autonomic activity.MethodsSixty-four epileptic children with epileptiform discharges were included. They all received electroencephalogram and electrocardiogram examinations simultaneously before, during, and after listening to Mozart K.448 or K.545. The total number of epileptiform discharges during each session (before, during, and after music) were divided by the duration (in minutes) of the session and then compared. Heart rate variability including time and frequency domain analysis was used to represent the autonomic function.ResultsThe results showed that epileptiform discharges were significantly reduced during and right after listening to Mozart music (33.3 ± 31.1% reduction, p < 0.001, during Mozart K.448 and 38.6 ± 43.3% reduction, p < 0.001, during Mozart K.545) (28.1 ± 43.2% reduction, p < 0.001, after Mozart K.448 and 46.0 ± 40.5% reduction, p < 0.001, after Mozart K.545). No significant difference was noticed between the two pieces of music. The reduction was greatest in patients with generalized seizures and discharges. Significant increases in high-frequency (HF), the square root of the mean squared differences of successive RR intervals (RMSSD), the standard deviation of differences between adjacent RR intervals (SDSD), and a decrease in mean beats per minute (bpm) were found during listening to Mozart music. Most of the patients with reduced epileptiform discharges also showed a decreased LF/HF ratio, low-frequency normalized units (LF nu), mean bpm, and an increased high-frequency normalized units (HF nu).ConclusionsListening to Mozart music decreased epileptiform discharges in children with epilepsy. The majority of these patients showed an increase in parasympathetic tone during music exposure.SignificanceOur results suggested that Mozart music stimuli induced parasympathetic activation which may be involved in the effect of music in reducing epileptiform discharges and the recurrence rate of seizures.     

Simple intravenous fluid regimens to control fever in hospitalized stroke patients: A theoretical evaluation

Fever is an independent predictor of worse outcome in stroke patients. We hypothesized that a peripheral infusion of saline in chilled or ice slurry form can be a practical adjuvant therapy to maintain euthermia. We developed a theoretical model simulating systemic body cooling in response to 0 °C saline and 50% ice slurry. Temperature elevations up to 39 °C were studied with respect to the time needed to reach a core temperature of 37 °C. Mathematical modeling identified a cooling rate of 0.48 °C/hr and 0.24 °C/hr using a 450 mL/hr infusion of 50% ice slurry and chilled saline. A reduction of the infusion rate to 150 mL/hr decreased euthermia time by a factor of 3; however, the total amount of coolant remained constant. Thus, based on mathematical modeling, peripheral infusions of saline in chilled or ice slurry form can be used as an adjunct therapy to achieve euthermia and control fever. Using intravenous coolants in an on-demand, temperature-guided and supervised treatment setting seems most reasonable to avoid potentially unsafe use of extended fluid volumes and infusion times.     

Duration of electroencephalographic recordings in patients with epilepsy

PurposePrevious studies have demonstrated different diagnostic yields with electroencephalography (EEG). Due to the small sample sizes or different patient populations (outpatients or inpatients only) in these previous studies, the clinical use of routine EEG and outpatient/inpatient video-EEG monitoring (VEM) needs further clarification. In this study, we investigated EEGs obtained from patients referred by epileptologists; by comparing the results of different EEG methods, we sought to determine the optimal durations and specific types of EEG recordings for different clinical situations.MethodsThe data from 335 routine EEGs, 281 3 h outpatient VEMs, and 247 inpatient VEMs (>48 h) were reviewed. We analyzed the latency to the first epileptiform discharge or clinical event.ResultsIn patients undergoing outpatient VEMs, 48% of the first epileptiform discharges appeared within 20 min, and 64% appeared within 30 min. In patients undergoing inpatient VEMs, 21.2% had their first attack within 3 h. The second peak of event occurrence was during the 33rd–36th h. Only 3.5% of the seizures were recorded after 57 h. The detection rate of epileptiform discharges was higher for 3 h outpatient VEM than for routine EEG (54.1% versus 16.4%, p < 0.01). Epileptic and/or nonepileptic events were recorded in 45.8% of the inpatient VEMs, the diagnostic yield of which was higher than for outpatient VEMs (p < 0.01). Since the patients in this study had been selected to limit the bias between each group, the diagnostic yield of EEGs in this study are likely to have been higher than those found in routine practice. Patients with generalized epilepsy had a shorter latency to the first epileptiform discharge compared to patients with localization-related epilepsy (mean, 22.1 min versus 33.9 min, p < 0.05).ConclusionsTwo-thirds of epileptiform discharges were detected within 30 min of VEM. A 30-min recording is recommended for routine EEG examinations that aim to detect epileptiform discharges. A 3 h outpatient VEM is a reasonable option when a routine EEG fails to detect epileptiform discharges. The latency to the first epileptiform discharge was shorter in patients with generalized epilepsy than in patients with localization-related epilepsy. 48 h of inpatient VEM might be adequate for detecting the target events.     

Attention-deficit/hyperactivity disorder and attention impairment in children with benign childhood epilepsy with centrotemporal spikes

Attention-deficit/hyperactivity disorder (ADHD) is a common comorbidity in children with epilepsy and has a negative impact on behavior and learning. The purposes of this study were to quantify the prevalence of ADHD in benign childhood epilepsy with centrotemporal spikes (BCECTS) and to identify clinical factors that affect ADHD or attention impairment in patients with BCECTS.The medical records of 74 children (44 males) with neuropsychological examination from a total of 198 children diagnosed with BCECTS at Asan Medical Center were retrospectively reviewed. Electroclinical factors were compared across patients with ADHD and those without ADHD. Mean T-scores of the continuous performance test were compared across patients grouped according to various epilepsy characteristics.Forty-eight (64.9%) patients had ADHD. A history of febrile convulsion was more common in patients with ADHD than in patients without ADHD (p = 0.049). Bilateral centrotemporal spikes on electroencephalogram were more common in patients receiving ADHD medication than in patients with untreated ADHD (p = 0.004). Male patients, patients with frequent seizures prior to diagnosis, and patients with a high spike index (≥ 40/min) on sleep EEG at diagnosis had significantly lower visual selective attention (p < 0.05).Children with BCECTS had a high prevalence of ADHD, and frequent seizures or interictal epileptiform abnormalities were closely related to impairment of visual selective attention in children with BCECTS, indicating the need for ADHD or attention impairment screening in children with BCECTS.     

Impaired sleep-related consolidation of declarative memories in idiopathic focal epilepsies of childhood

ObjectiveDeclarative memory is consolidated during sleep in healthy children. We tested the hypothesis that consolidation processes are impaired in idiopathic focal epilepsies (IFE) of childhood in association with frequent interictal epileptiform discharges (IEDs) during sleep.MethodsA verbal (word-pair association) and a nonverbal (2D object location) declarative memory task were administrated to 15 children with IFEs and 8 control children 6–12 years of age. Patients had either centrotemporal (11 patients) or occipital (4 patients) IEDs. All but 3 patients had a history of unprovoked seizures, and 6 of them were treated with valproate (VPA). The learning procedure (location of object pairs presented on a grid; association of word pairs) was executed in the evening. Retrieval was tested immediately after learning and on the next morning after a night of sleep. Participants were tested twice, once in natural home conditions and one month later in the unfamiliar conditions of the sleep unit under EEG monitoring.ResultsOvernight recall performance was lower in children with IFE than in control children on both tasks (ps < 0.05). Performance in home conditions was similar to that in hospital conditions. Higher spike–wave index (SWI) during nonrapid eye movement (NREM) sleep was associated with poorer performance in the nonverbal task (p < 0.05). Valproate treatment was not associated with overnight recall performance for both tasks (ps > 0.05).ConclusionMemory consolidation is impaired in IFE of childhood. The association between higher SWI during NREM sleep and poorer nonverbal declarative memory consolidation supports the hypothesis that interictal epileptic activity could disrupt sleep memory consolidation.     

Source localization of interictal spike-locked neuromagnetic oscillations in pediatric neocortical epilepsy

ObjectiveTo evaluate the utility of an event-related beamforming (ERB) algorithm in source localization of interictal discharges.MethodsWe analyzed interictal magnetoencephalography data in 35 children with intractable neocortical epilepsy. We used a spatiotemporal beamforming method to estimate the spatial distribution of source power in individual interictal spikes. We compared ERB results to source localization using the equivalent current dipole model and to the seizure onset zones on intracranial EEG.ResultsFocal beamformer localization was observed in 66% of patients and multifocal in the remaining 34%. ERB localized within 2 cm of the equivalent current dipole cluster centroid in 77% of the patients. ERB localization was concordant with the seizure onset zone on intracranial EEG at the gyral level in 69% of patients. Focal ERB localization area was included in the resection margin in 22/23 patients. However, focal ERB localization was not statistically associated with better surgical outcome.ConclusionsERB can be used for source localization of interictal spikes and can be predictive of the ictal onset zone in a subset of patients with neocortical epilepsy.SignificanceThese results support the utility of beamformer source localization as a fast semi-automated method for source localization of interictal spikes and planning the surgical strategy.     

Sleep before and after temporal lobe epilepsy surgery

PurposePatients with epilepsy often complain of non-restorative sleep. This is the consequence of the acute effect of seizures and the chronic effect of epilepsy responsible for disrupting sleep architecture. Other factors such as antiepileptic drugs (AEDs), also play a role in the alteration of sleep organization. The aim of this study was to evaluate the specific effect of seizures and interictal epileptiform abnormalities (IEAs) on sleep, in particular to see whether reducing seizure frequency by epilepsy surgery might improve sleep organization in these patients.MethodsEleven patients with refractory mesial temporal lobe epilepsy, who underwent surgical treatment and who were seizure free at the follow-up, were included in the study. Treatment with AEDs was not significantly modified before the second year of follow-up. Patients were evaluated before surgery, at 1-year and 2-year follow-up visits with a videoEEG monitoring (24 h/24). At each follow-up visit, interictal epileptiform abnormalities and sleep macrostructure parameters were assessed.ResultsAll patients showed a reduction of their IEAs. At 1-year follow-up, total sleep time and REM sleep increased significantly (p = 0.032 and p = 0.006, respectively). At 2-year follow-up, an important increase of REM sleep was observed (p = 0.028). Most significant variations were noted 1 year after surgery. No significant variations were observed between the first and the second year after surgery.ConclusionsSurgical treatment of temporal lobe epilepsy may improve sleep macrostructure by reducing the number of seizures and of IEAs. These results indirectly confirm the role of epilepsy in disrupting sleep organization chronically.