Benign EEG variants in the sleep–wake cycle: A prospective observational study using the 10–20 system and additional electrodes

ObjectivesTo study the prevalence of benign EEG variants (BEVs) in the sleep–wake cycle among 1163 consecutive patients.MethodsProspective, observational EEG study using the 10–20 system with systematically two additional anterior-temporal electrodes. Depending on clinical indications, other electrodes were added. REM sleep identification was based on its characteristic EEG grapho-elements and rapid eye movements, clearly detectable with the additional anterior-temporal and fronto-polar electrodes due to eye proximity. The video-EEG monitoring duration was between 24 hours and eight days.ResultsWe identified 710 patients (61%) with BEVs. Positive occipital sharp transients of sleep (POSTs) were observed in 36.4% of participants, mu rhythm in 22.4%, lambda waves in 16.7%, wicket spikes (WS) in 15%, 14- and 6-Hz positive bursts in 8.3%, benign sporadic sleep spikes (BSSS) in 3.3%, rhythmic mid-temporal theta burst of drowsiness (RMTD) in 2.15%, midline theta rhythm in 2.1% and six-Hz spike and wave (SW) bursts in 0.1%. WS and RMTD were present during wakefulness, NREM (14.1%, 1.3%, respectively) and REM sleep (3.3%, 1.1%, respectively). Mu rhythm was also observed during NREM (1.5%) and REM sleep (7.7%). Fourteen- and 6-Hz positive bursts were present during NREM (4.5%) and REM sleep (6.5%). BSSS and six-Hz SW bursts were only observed during NREM sleep.ConclusionsThe prevalence of BEVs is much higher than current estimates. POSTs and WS can no longer be considered as unusual patterns but physiological patterns of NREM sleep. RMTD and mu rhythm may be observed during NREM and REM sleep.     

High-frequency oscillations in a spectrum of pediatric epilepsies characterized by sleep-activated spikes in scalp EEG

ObjectiveWe studied ripple-band (80–200 Hz) high-frequency oscillations in scalp electroencephalogram (EEG) in various pediatric epilepsies featuring sleep-activated spikes, such as epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) and investigated their characteristics.MethodsThe subjects were 94 children with epileptic disorders including idiopathic and non-idiopathic CSWS, benign epilepsy with centrotemporal spikes (BECTS), Panayiotopoulos syndrome, other types of focal epilepsies (oFE), and focal spikes without clinical seizures (Latent). We detected ripple oscillations using a semi-automatic detection tool based on localized power increase.ResultsIn the idiopathic CSWS Group, the median ratio of ripples per spike in the initial EEG was 5.73, which was significantly higher than those in the BECTS, Panayiotopoulos syndrome, oFE, and Latent Groups (0.39, 0.02, 0.35, 0, respectively, all with p < 0.01). Ripples were particularly frequent at younger ages.ConclusionsThis paper is the first to confirm a high ratio of ripples per spike in CSWS in the largest number of patients to date.SignificanceThe dense generation of ripples, which occurs through a combination of heavy loading of individual spikes with ripples and large numbers of spikes during sleep, characterizes CSWS and might be closely related to the pathophysiology of this epileptic encephalopathy.     

Electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome in children: An electroclinical evaluation according to the EEG patterns

ObjectiveThe aim of this study was to describe the electroclinical spectrum in children with electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome according to the EEG patterns.MethodsClinical data of 44 patients with ESES/CSWS syndrome who were treated and followed at least two years were analyzed. Records of EEGs of patients were reevaluated to determine two aspects of the ESES pattern: (1) the spike–wave index (SWI) on the NREM sleep EEG (Group I: typical vs. atypical ESES pattern (33/11 patients)) and (2) the area of maximum amplitude of continuous epileptic activity (Group II: anterior vs. posterior ESES pattern (33/11 patients)).ResultsSymptomatic etiology was more defined in patients with the typical ESES pattern (40%) than the group with the atypical ESES pattern (9%) by a factor of four. All patients were receiving at least two antiepileptic drug (AED) treatments. Eighteen patients (41%) received AEDs plus ACTH therapy. Complete disappearance of the ESES pattern on the EEG was observed in 18 patients (41%), more than 50% reduction was observed in five patients (11%), less than 50% reduction was observed in eight patients (18%), and no response was observed in five patients (11%). No significant difference was found when comparing the groups in terms of reduction of seizures and the SWI. Seizure outcome at the two-year follow-up was similar between the group with ESES treated with AEDs plus ACTH and the group with ESES treated with AEDs without ACTH therapy.SignificanceThis study demonstrated that the rate of the SWI (typical vs. atypical ESES) and the maximum amplitude of the ESES pattern (anterior vs. posterior) have no significant correlation with seizure control and reduction of the SWI on the EEG in children with ESES syndrome.     

Semiautomatic quantification of spiking in patients with continuous spikes and waves in sleep: sensitivity to settings and correspondence to visual assessment

ObjectiveTo define the optimal analysis protocol for semiautomatic quantification of spike index (SI) in continuous spikes and waves in sleep (CSWS).MethodsTen overnight EEGs (nine patients) with abundant spiking were used to quantify SI with a previously published semiautomatic quantification based on spike detection with BESA software. We studied (i) dependency of SI on maximal interspike interval (maxISI) defining the continuous discharge, (ii) sensitivity of SI to variations in the spike search protocol, and (iii) stability of SI over time. Finally, the semiautomatic method was compared with the quantification based on visual scoring by two neurophysiologists.ResultsMaxISI of 3 s appeared to yield the best combination of sensitivity and stability in SI quantification. The SI of the first hour of sleep did not differ significantly from the SI of the whole night. Mean error of the semiautomatic method compared to visual scoring was only seven percentage units.ConclusionsSemiautomatic quantification of SI functions well with maxISI of 3 s, and the first hour of sleep represents the whole night SI with a clinically relevant accuracy.SignificanceThis method opens a possibility for objective quantification of near-continuous epileptiform spiking during sleep, and it supports the use of shorter epochs for quantitative assessment of CSWS.     

Sleep modulation of interictal spike configuration in untreated children with partial seizures

Spontaneous changes in interictal spike morphology were evaluated before initiation of antiepileptic drug (AED) therapy in 38 children with uncontrolled partial seizures. Nonrapid eye movement (NREM) sleep during the first third of the night was associated with spikes of higher amplitude, longer duration, and lower degree of sharpness than those observed in wakefulness or REM sleep. Spike amplitude decreased in subsequent NREM epochs, but duration and sharpness remained relatively consistent. A NREM/REM modulatory pattern was identified, with REM periods exhibiting spikes of decreased amplitude, shorter duration, and increased sharpness as compared with NREM periods in each third of the night. The spike changes associated with REM sleep are similar to the alterations previously described as occurring coincidentally with attainment of seizure control and thus may reflect inherent modulation of epileptogenicity in synchrony with sleep cycles.     

Spike patterns surrounding sleep and seizures localize the seizure-onset zone in focal epilepsy

Objective

Interictal spikes help localize seizure generators as part of surgical planning for drug-resistant epilepsy. However, there are often multiple spike populations whose frequencies change over time, influenced by brain state. Understanding state changes in spike rates will improve our ability to use spikes for surgical planning. Our goal was to determine the effect of sleep and seizures on interictal spikes, and to use sleep and seizure-related changes in spikes to localize the seizure-onset zone (SOZ).

Methods

We performed a retrospective analysis of intracranial electroencephalography (EEG) data from patients with focal epilepsy. We automatically detected interictal spikes and we classified different time periods as awake or asleep based on the ratio of alpha to delta power, with a secondary analysis using the recently published SleepSEEG algorithm. We analyzed spike rates surrounding sleep and seizures. We developed a model to localize the SOZ using state-dependent spike rates.

Results

We analyzed data from 101 patients (54 women, age range 16–69). The normalized alpha-delta power ratio accurately classified wake from sleep periods (area under the curve = .90). Spikes were more frequent in sleep than wakefulness and in the post-ictal compared to the pre-ictal state. Patients with temporal lobe epilepsy had a greater wake-to-sleep and pre- to post-ictal spike rate increase compared to patients with extra-temporal epilepsy. A machine-learning classifier incorporating state-dependent spike rates accurately identified the SOZ (area under the curve = .83). Spike rates tended to be higher and better localize the seizure-onset zone in non–rapid eye movement (NREM) sleep than in wake or REM sleep.

Significance

The change in spike rates surrounding sleep and seizures differs between temporal and extra-temporal lobe epilepsy. Spikes are more frequent and better localize the SOZ in sleep, particularly in NREM sleep. Quantitative analysis of spikes may provide useful ancillary data to localize the SOZ and improve surgical planning.     

Encephalopathy related to status epilepticus during slow sleep (ESES) as atypical evolution of Panayiotopoulos syndrome: an EEG and neuropsychological study

Aim: We report two patients with Panayiotopoulos syndrome (PS) who developed encephalopathy related to status epilepticus during slow sleep (ESES) at the peak of their clinical course. Methods: Clinical charts and EEG data were reviewed. Results: The patients exhibited nocturnal autonomic seizures and occipital EEG foci, the latter of which later evolved into multifocal EEG foci with synchronous frontopolar and occipital spikes (Fp‐O EEG foci), and finally into continuous spikes‐waves during sleep (CSWS; spike‐wave index >85% based on whole‐night sleep recording) at eight years and seven years of age, respectively. The occipital spikes always preceded frontopolar spikes by 30～50 mseconds based on the analysis of CSWS. Neuropsychological ability, including IQ, deteriorated during the CSWS period in both patients. The autonomic seizures and focal to bilateral tonic‐clonic seizures were initially resistant to antiepileptic drugs (AEDs), and occurred more than 10 times in both patients. However, the seizures and EEG findings gradually resolved, and AEDs were successfully terminated in both patients. Conclusion: PS can progress to ESES if the clinical course exhibits atypical evolution. The initial autonomic symptom of the seizures and interictal Fp‐O EEG foci should be carefully monitored in patients with CSWS or ESES.     

Reduced NREM sleep instability in benign childhood epilepsy with centro-temporal spikes

ObjectiveTo analyze sleep architecture and NREM sleep instability by means of the cyclic alternating pattern (CAP) in children with benign epilepsy with rolandic spikes (BERS).MethodsTen children with BERS, drug free at the time of the study and 10 age-matched normal controls were included in this study. Sleep was visually scored for sleep architecture and CAP using standard criteria.ResultsSleep architecture in BERS showed only few significant differences vs. controls with a reduction of total sleep time, sleep efficiency, and REM sleep percentage. CAP analysis revealed several significant differences: reduced total CAP rate, mainly in sleep stage 2, and reduced EEG slow oscillations and arousals during stages N1 and N2.ConclusionsSleep architecture is not importantly affected in BERS but CAP analysis reveals a decrease of NREM instability, mainly in sleep stage 2. Since there is a spindle-related spike activation in BERS, we speculate that the decrease of CAP and of EEG slow oscillations and arousals might be linked with the inhibitory action of spindling activity and spikes on arousals.SignificanceCAP analysis discloses sleep structure abnormalities in children with BERS not shown by the classical sleep scoring. Spike activity and CAP A1 subtypes seem to be mutually exclusive probably because centro-temporal spikes disturb the physiological synchronization mechanisms needed for the generation of slow-wave components of CAP.     

Long-term follow-up of cognitive functions in patients with continuous spike–waves during sleep (CSWS)

Continuous spike–waves during sleep (CSWS) are associated with several cognitive, neurological, and psychiatric disorders, which sometimes persist after CSWS disappearance. The purpose of this retrospective study was to investigate the correlation between general (clinical and instrumental) and neuropsychological findings in CSWS, to identify variables that predispose patients to a poorer long-term neuropsychological outcome.Patients with spikes and waves during sleep with a frequency ≥ 25/min (spikes and waves frequency index — SWFI) were enrolled. There were patients presenting abnormal EEG activity corresponding to the classic CSWS and patients with paroxysmal abnormalities during sleep < 85% with SWFI ≥ 25/min that was defined as excessive spike–waves during sleep (ESWS). Clinical and instrumental features and neuropsychological findings during and after the spike and wave active phase period were considered. A statistical analysis was performed utilizing the Spearman correlation test and multivariate analysis. The study included 61 patients; the mean follow-up (i.e., the period between SWFI ≥ 25 first recording and last observation) was 7 years and 4 months.The SWFI correlated inversely with full and performance IQ during CSWS/ESWS. Longer-lasting SWFI ≥ 25 was related to worse results in verbal IQ and performance IQ after CSWS/ESWS disappearance. Other variables may influence the neuropsychological outcome, like age at SWFI ≥ 25 first recording, perinatal distress, pathologic neurologic examination, and antiepileptic drug resistance. This confirms that CSWS/ESWS are a complex pathology and that many variables contribute to its outcome.The SWFI value above all during CSWS/ESWS and long-lasting SWFI ≥ 25 after CSWS/ESWS disappearance are the most significant indexes that appear mostly to determine cognitive evolution. This finding underscores the importance of EEG recordings during sleep in children with a developmental disorder, even if seizures are not reported, as well as the importance of using therapy with an early efficacy.     

Neurobehavioral consequences of continuous spike and waves during slow sleep (CSWS) in a pediatric population: A pattern of developmental hindrance

IntroductionContinuous spike and waves during slow sleep (CSWS) is a typical EEG pattern defined as diffuse, bilateral and recently also unilateral or focal localization spike–wave occurring in slow sleep or non-rapid eye movement sleep. Literature results so far point out a progressive deterioration and decline of intellectual functioning in CSWS patients, i.e. a loss of previously normally acquired skills, as well as persistent neurobehavioral disorders, beyond seizure and EEG control. The objective of this study was to shed light on the neurobehavioral impact of CSWS and to identify the potential clinical risk factors for development.MethodsWe conducted a retrospective study involving a series of 16 CSWS idiopathic patients age 3–16 years, considering the entire duration of epilepsy from the onset to the outcome, i.e. remission of CSWS pattern. All patients were longitudinally assessed taking into account clinical (sex, age at onset, lateralization and localization of epileptiform abnormalities, spike wave index, number of antiepileptic drugs) and behavioral features. Intelligent Quotient (IQ) was measured in the whole sample, whereas visuo-spatial attention, visuo-motor skills, short term memory and academic abilities (reading and writing) were tested in 6 out of 16 patients.ResultsOur results showed that the most vulnerable from an intellectual point of view were those children who had an early-onset of CSWS whereas those with later onset resulted less affected (p = 0.004). Neuropsychological outcome was better than the behavioral one and the lexical-semantic route in reading and writing resulted more severely affected compared to the phonological route.ConclusionsCognitive deterioration is one but not the only consequence of CSWS. Especially with respect to verbal skills, CSWS is responsible of a pattern of consequences in terms of developmental hindrance, including slowing of development and stagnation, whereas deterioration is rare. Behavioral and academic problems tend to persist beyond epilepsy resolution.     

Relationship of interictal epileptiform discharges to sleep depth in partial epilepsy

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

Etomidate activates epileptic high frequency oscillations

ObjectiveThe short acting anesthetic etomidate has been shown to provoke epileptic spikes and rarely seizures. Influence of etomidate on the occurrence of epileptic HFO (high frequency oscillations) however is unknown. An HFO inducing effect of etomidate would allow further validation of the substance as a provocation measure in presurgical evaluation as well as provide insights into the common mechanisms of HFO, spike and seizure generation.MethodsWe retrospectively analyzed EEG data from four patients who underwent etomidate activation during invasive video-EEG monitoring with subdural strip electrodes. Spikes were manually selected in raw data, HFO in band pass filtered data (80–250 Hz). Rate and spatial distribution of HFO and spikes in three segments were compared: immediately after etomidate administration, as well as during slow wave sleep and while awake.ResultsRates of HFO and spikes increased significantly after etomidate administration: Overall average rates of spikes were 9.7/min during sleep, 10/min while awake and 61.4/min after etomidate. Average HFO rates were 9.5/min during sleep, 8.3/min while awake and 24.4/min after etomidate (p < 0.001, non-parametric ANOVA). Spatial distributions of HFO and spikes after administration of etomidate were consistent with the seizure onset zone (SOZ) and area of resection when available (SOZ: two patients; resection: one patient; no information: one patient). Except for spurious events, no additional HFO and spike foci were seen with activation.ConclusionsEtomidate administration activates spikes and HFO. Spatial distributions do not extend beyond electrodes showing spikes and HFO without Etomidate and seem consistent with the epileptic network.SignificanceEtomidate activation is a safe procedure to provoke not only epileptic spikes but also HFO, which were shown to have a high specificity for the SOZ.     

Magnetoencephalography localizing spike sources of atypical benign partial epilepsy

Rationale: Atypical benign partial epilepsy (ABPE) is characterized by centro-temporal electroencephalography (EEG) spikes, continuous spike and waves during sleep (CSWS), and multiple seizure types including epileptic negative myoclonus (ENM), but not tonic seizures. This study evaluated the localization of magnetoencephalography (MEG) spike sources (MEGSSs) to investigate the clinical features and mechanism underlying ABPE. Methods: We retrospectively analyzed seizure profiles, scalp video EEG (VEEG) and MEG in ABPE patients. Results: Eighteen ABPE patients were identified (nine girls and nine boys). Seizure onset ranged from 1.3 to 8.8 years (median, 2.9 years). Initial seizures consisted of focal motor seizures (15 patients) and absences/atypical absences (3). Seventeen patients had multiple seizure types including drop attacks (16), focal motor seizures (16), ENM (14), absences/atypical absences (11) and focal myoclonic seizures (10). VEEG showed centro-temporal spikes and CSWS in all patients. Magnetic resonance imaging (MRI) was reported as normal in all patients. MEGSSs were localized over the following regions: both Rolandic and sylvian (8), peri-sylvian (5), peri-Rolandic (4), parieto-occipital (1), bilateral (10) and unilateral (8). All patients were on more than two antiepileptic medications. ENM and absences/atypical absences were controlled in 14 patients treated with adjunctive ethosuximide. Conclusion: MEG localized the source of centro-temporal spikes and CSWS in the Rolandic-sylvian regions. Centro-temporal spikes, Rolandic-sylvian spike sources and focal motor seizures are evidence that ABPE presents with Rolandic-sylvian onset seizures. ABPE is therefore a unique, age-related and localization-related epilepsy with a Rolandic-sylvian epileptic focus plus possible thalamo-cortical epileptic networks in the developing brain of children.     

Cluster-based spike detection algorithm adapts to interpatient and intrapatient variation in spike morphology

Visual quantification of interictal epileptiform activity is time consuming and requires a high level of expert's vigilance. This is especially true for overnight recordings of patient suffering from epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS) as they can show tens of thousands of spikes. Automatic spike detection would be attractive for this condition, but available algorithms have methodological limitations related to variation in spike morphology both between patients and within a single recording. We propose a fully automated method of interictal spike detection that adapts to interpatient and intrapatient variation in spike morphology. The algorithm works in five steps. (1) Spikes are detected using parameters suitable for highly sensitive detection. (2) Detected spikes are separated into clusters. (3) The number of clusters is automatically adjusted. (4) Centroids are used as templates for more specific spike detections, therefore adapting to the types of spike morphology. (5) Detected spikes are summed. The algorithm was evaluated on EEG samples from 20 children suffering from epilepsy with CSWS. When compared to the manual scoring of 3 EEG experts (3 records), the algorithm demonstrated similar performance since sensitivity and selectivity were 0.3% higher and 0.4% lower, respectively. The algorithm showed little difference compared to the manual scoring of another expert for the spike-and-wave index evaluation in 17 additional records (the mean absolute difference was 3.8%). This algorithm is therefore efficient for the count of interictal spikes and determination of a spike-and-wave index.     

Spinal reflexes and lateral geniculate nucleus activity during sleep: Quantitative relationships

The relationship between monosynaptic spinal reflex (MSR) activity and monophasic spike activity of the lateral geniculate nucleus (LGN) was studied in unanesthetized, unrestrained cats during spontaneous sleep. Relative to MSR modulation during slow-wave sleep (SWS), modulation during paradoxical sleep (PS) was toward decreased reflex amplitude within 500 ms subsequent to the onset of isolated LGN spikes (t₀). These modulations, although statistically significant, were not particularly pronounced and were not always consistent for all animals. Reflex amplitude decreased in the 1 s following onset of either small (three to four spikes) or larger (≥ 5 spikes) spike bursts, but this reduction was significant only for the latter group. Consistent changes in reflex amplitude did not outlast brief spike bursts even when additional isolated spikes occurred in the extended sample interval (2.2 e post-t₀). Extended modulation (5 s post-t₀) of reflex activity was detected for bursts of ≥ 14 spikes. Whereas previous reports indicated variations in MSR activity only in association with bursts of LGN spikes, the present data suggest state-dependent modulation of such activity for isolated and low-frequency bursts as well as high-frequency spike bursts. A possible role for the caudal raphe nuclei in the generation of low frequency pontogeniculate (PGO) activity and related reflex variations is postulated, and bases for discrepancies between phasic MSR modulation during synchronized sleep in man and cat are explored.     

The epileptic syndromes with continuous spikes and waves during slow sleep: definition and management guidelines

The authors propose to define the epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) as a cognitive or behavioral impairment acquired during childhood, associated with a strong activation of the interictal epileptiform discharges during NREM sleep--whatever focal or generalized--and not related to another factor than the presence of CSWS. The type of syndrome will be defined according to the neurological and neuropsychological deficit. These syndromes have to be classified among the localization-related epileptic syndromes. Some cases are idiopathic and others are symptomatic. Guidelines for work-up and treatment are proposed.     

频繁的临床下癫痫样放电对睡眠结构的影响

目的分析临床下癫痫样放电(SED)对睡眠结构的影响。方法对44例伴中央颞区棘波的良性儿童癫痫(BECTS)患者进行脑电-多导睡眠监测研究,并应用非条件Logistic回归分析处理数据。结果BECTS患者的睡眠周期中棘波指数分布为Ⅱ期>Ⅰ期>Ⅲ/Ⅳ期>REM期;BECTS患者的睡眠REM期缩短、Ⅰ期睡眠比例增加、Ⅲ/Ⅳ睡眠比例减少;SED频率与睡眠结构失调发生呈正相关关系。结论频繁的SED(>10次/分)是引起睡眠结构失调的主要危险因素,可以引起睡眠结构的紊乱。     

Treatment with flunitrazepam of continuous spikes and waves during slow wave sleep (CSWS) in children.

We describe our treatment of two boys with continuous spikes and waves during slow wave sleep (CSWS). One of the boys was suffering from non-convulsive status epilepticus and the other from conscious disturbance with automatism. Their ictal EEG readings showed continuous diffuse spike and wave complexes, which were considered to show electrical status. The boys were diagnosed as having CSWS, and were later diagnosed with Landau-Kleffner syndrome (LKS). EEG readings returned to normal on intravenous injection of flunitazepam (FZP) at a dose of 0.02 mg/kg, suggesting that FZP is an effective treatment for CSWS.     

High‐frequency oscillations in idiopathic partial epilepsy of childhood

Purpose: We explored high‐frequency oscillations (HFOs) in scalp sleep electroencephalography (EEG) studies of patients with idiopathic partial epilepsy (IPE) of childhood in order to obtain a better understanding of the pathologic mechanisms underlying IPE. Methods: The subjects were 45 patients, including 32 with benign childhood epilepsy with centrotemporal spikes (BCECTS) and 13 with Panayiotopoulos syndrome (PS). A total of 136 EEG records were investigated through temporal expansion and filtering of traces and time‐frequency spectral analysis. Key Findings: HFOs with frequency of 93.8–152.3 Hz (mean 126.2 ± 13.6 Hz) in the band of ripples were detected in association with spikes in 97 records (71.3%). Time from last seizure to the EEG recording was significantly shorter in those with spike‐related HFOs than in the EEG recordings with spikes without HFOs (p = 0.006). Although time from last seizure reflects age, age at the time of recording was not significantly different between EEG studies with and without HFOs. Peak‐power values of the high‐frequency spots in time‐frequency spectra were significantly negatively correlated with time from last seizure (R² = 0.122, p < 0.001) but not with age at the time of recording. Peak frequencies of the high‐frequency spectral spots were not significantly correlated with age at the time of recording or with time from last seizure. Significance: The close relationship between the generation of spike‐related HFOs and the period of active seizure occurrence indicated that HFOs may tell us more about epileptogenicity in IPE than the spikes themselves. Because there is a spectrum of pediatric epileptic disorders extending from the benign end of BCECTS to the encephalopathic end of epilepsy with continuous spike‐waves during slow‐wave sleep (CSWS), and HFOs that have already been detected in association with CSWS were more prominent than HFOs in IPE, intense spike‐related HFOs may indicate poor prognosis.