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Introduction Epilepsy associated with tuberous sclerosis complex (TSC) has very complex clinical characteristics. Scalp electroencephalogram (EEG) fast (40–200 Hz) oscillations (FOs) were recently suggested to indicate epilepsy severity. Epileptic FOs may undergo age-dependent longitudinal change in individual patients, however, and the typical pattern of such change is not yet fully clarified. We therefore investigated the age-related correspondence between clinical courses and FOs in pediatric patients with TSC-associated epilepsy. Subjects and methods FOs were semi-automatically detected from scalp sleep EEG data recorded from 23 children (15 boys, 8 girls; initial data obtained at Results The number of FOs per patient that were associated with spikes was significantly greater than that of FOs unassociated with spikes (median 145 and 5, respectively; p = 0.0001 by the Wilcoxon signed-rank test). In the eight patients who had West syndrome (WS) in infancy, FOs associated with spikes were abundant during the WS period prior to adrenocorticotropic hormone therapy, with significantly greater numbers of FOs compared to the post-WS period (median 242 and 0, respectively; p = 0.0078). As there was no such time-dependent difference regarding FOs unassociated with spikes, FOs associated with spikes were identified as epileptic. The detected FOs included both gamma and ripple oscillations with no consistent age-dependent shifts in dominant frequency. There were no apparent age-related changes in FO duration. Conclusions Epileptic scalp FOs are confirmed to correspond to severity of epileptic encephalopathy, particularly in WS, even during the long-term evolutional courses of TSC-associated epilepsy.

Summary We investigated the relationship between the scalp distribution of fast (40–150 Hz) oscillations (FOs) and epileptogenic lesions in West syndrome (WS) and related disorders. Subjects were 9 pediatric patients with surgically confirmed structural epileptogenic pathology (age at initial electroencephalogram [EEG] recording: mean 7.1 months, range 1–22 months). The diagnosis was WS in 7 patients, Ohtahara syndrome in 1, and a transitional state from Ohtahara syndrome to WS in the other. In the scalp EEG data of these patients, we conservatively detected FOs, and then examined the distribution of FOs. In five patients, the scalp distribution of FOs was consistent and concordant with the lateralization of cerebral pathology. In another patient, FOs were consistently dominant over the healthy cerebral hemisphere, and the EEG was relatively low in amplitude over the pathological atrophic hemisphere. In the remaining 3 patients, the dominance of FOs was inconsistent and, in 2 of these patients, the epileptogenic hemisphere was reduced in volume, which may result from atrophy or hypoplasia. The correspondence between the scalp distribution of FOs and the epileptogenic lesion should be studied, taking the type of lesion into account. The factors affecting scalp FOs remain to be elucidated.

Objective We explored fast (40–150 Hz) oscillations (FOs) from the ictal scalp electroencephalogram (EEG) data of myoclonic seizures in pediatric patients to obtain insight into the pathophysiological mechanisms involved in the generation of myoclonic seizures. Subjects and methods The participants were 21 children (11 boys, 10 girls; age ranging from 5 months to 17 years 2 months) with myoclonic seizures associated with generalized (poly)spike-wave bursts in the ictal EEG data. The patients had heterogeneous etiologies and epilepsy diagnoses. In the ictal data, we detected FOs that clearly showed oscillatory morphology in filtered EEG traces and an outstanding spectral blob in time-frequency analysis. Results We identified FOs in 61 (88.4%) of all 69 myoclonic seizures. Every patient had at least one myoclonic seizure-associated FO. The observed FOs were embedded in the spike component of (poly)spike-wave discharges, and they had a focal distribution with frontal predominance. They ranged in frequency from 41.0 to 123.0 Hz and involved both the gamma and ripple bands, and their spectral peak frequencies were higher in the group of patients with a genetic background free of apparent fundamental brain pathology than in the group of other patients (p = 0.019). Conclusion FOs were found to represent at least part of the cortical pathophysiological process in the generation of myoclonic seizures that should involve the thalamocortical network system.

Objective Fast oscillations (FOs) were first explored from scalp electroencephalographic (EEG) data from hypsarrhythmia in West syndrome (infantile spasms) to investigate the meaning of FOs in this epileptic encephalopathy. Methods In 17 infants with West syndrome, we conservatively detected fast frequency peaks that stood out from the time-frequency spectral background with square root power > 1µV (spectral criterion) and corresponded to clear FOs with at least 4 oscillations in the filtered EEG traces (waveform criterion) in sleep EEGs. Results We found a total of 1,519 interictal FOs that fulfilled both the spectral and waveform criteria. The FOs with a median frequency of 56.6Hz (range = 41.0–140.6Hz) were dense, with a median rate of 66 (range = 24–171) per minute before adrenocorticotropic hormone (ACTH) treatment, which was significantly higher than that in control infants without seizures (median = 1, p

Purpose: To clarify the clinical implications of the preceding positive spikes (PPSs) observed primarily in rolandic spikes, we analyzed PPSs in the rolandic and occipital spikes observed in the electroencephalograms (EEGs) of patients with two types of benign partial epilepsies (benign childhood epilepsy with centro-temporal spikes [BECT] and Panayiotopoulos syndrome [PS]) and febrile seizures (FS). Subjects and methods: We identified patients from our outpatient EEG database that were seen between 2006 and 2008 that had BECT, PS, and FS with rolandic or occipital spikes. We generated an averaged spike for each patient from the rolandic and occipital spikes that were detected using an automatic spike detection and clustering system. We compared the presence rate of the averaged spikes with the PPS among the three groups (BECT vs. PS vs. FS) using sequential mapping. Results: We identified 25 BECT, 18 PS, and 15 FS patients with rolandic spikes. Fifteen BECT and nine PS patients exhibited a PPS in their averaged rolandic spikes, whereas only four FS patients did. Three of these four FS patients later developed afebrile seizures, and one of them was diagnosed as having PS. We analyzed eight PS and six FS patients with occipital spikes. Five PS patients exhibited a PPS in their averaged occipital spikes, whereas only one FS patient did. This FS patient later developed prolonged autonomic febrile seizures. Conclusion: PPSs are observed not only in rolandic spikes associated with BECT that is related strictly to sylvian seizures, but also in rolandic and occipital spikes associated with PS. Although PPSs are rare in such spikes observed in FS, patients with FS and PPSs may have an increased risk of developing afebrile seizures or prolonged autonomic febrile seizures. Further studies are warranted to determine the diagnostic utility of PPSs as a marker of the future development of epilepsy when they are observed in FS patients.

Objective To elucidate the generative mechanisms of epileptic spasms (ESs) in West syndrome, we investigated the temporal relationship between scalp fast (40–150 Hz) oscillations (FOs) and slow waves in the ictal electroencephalograms (EEGs) of ESs. Methods In 11 infants with WS, ictal FOs were detected in a bipolar montage based on spectral and waveform criteria. Their temporal distribution was analyzed in terms of the positive peaks (trough point, T T ) of identical EEG data in a referential montage. Among six EEG data sections defined according to T T , the number of FOs, peak power values, and peak frequencies were compared. Results We identified a total of 1014 FOs (946 gamma and 68 ripple oscillations), which clustered closely at T T . The number of gamma oscillations in the 1 s epoch including T T was significantly higher than those in the prior and subsequent phases. Peak power values and frequencies tended to be higher in these positive phase sections. Conclusions The temporal association of FO clustering and positive slow waves in the ictal EEGs of ES indicated that active neuronal firing related to FOs underlies the generation of ESs and their ictal slow waves.

Purpose Epileptic spasms (ES) beyond infancy are a highly refractory type of seizures that require the development of an effective treatment. We therefore studied the efficacy and safety of topiramate (TPM), which is a drug that is indicated to be effective for intractable childhood epilepsy, for ES. Methods Out of 58 children with ES, we enrolled 33 patients treated with TPM at ≤12years of age. The administration of TPM was limited to cases of epilepsies that were resistant to any other potent treatment. We retrospectively investigated the efficacy of TPM for seizures and changes in electroencephalogram (EEG) findings. Results The median age at the start of TPM treatment was 5years, 8months. All patients had ES and 28 also had tonic seizures. As for the efficacy of TPM for all seizures, five patients became seizure-free and two had a ≥50% reduction in seizures. Seizure aggravation was observed in six patients. Of 29 patients whose EEG findings were compared before and during TPM treatment, nine showed EEG improvement with reduced epileptic discharges. Adverse effects were observed in 13 patients and included somnolence, anorexia, and irritability. In general, TPM was well tolerated. Conclusions TPM can be effective at suppressing very intractable ES in a proportion of patients who do not respond to any other treatment. The efficacy of TPM may be predictable based on EEG changes observed early in the course of treatment. TPM is promising for the treatment of extremely intractable childhood epilepsy and it has largely tolerable adverse effects.

To clarify the characteristics of the mode of appearance and morphology of epileptiform discharges before the onset of West syndrome (WS). The subjects were 25 infants whose electroencephalograms (EEGs) were recorded before the onset of WS and whose first EEG was recorded before 6 months of corrected age (CA). We extensively analyzed the chronological and topographical changes of the epileptiform discharges before the onset of WS. The location of the initial epileptiform discharges was in the posterior areas in 14 (Group O), the multiple areas in 7 (Group M), and areas other than occipital in 4 (Group non-O). Twelve of the 14 patients in Group O were premature infants, and all but one had PVL. Most patients in Group M were full-term infants or near full-term infants who had hypoxic damage. The ages at the appearance of the initial epileptiform discharges in Group O were significantly later than those in Group M: 3.0-5.9 months of CA in Group O vs. -0.1 to 2.0 months of CA in Group M. These facts suggest that the difference of brain damage is related to both the topographical characteristics and the age at the appearance of initial epileptiform discharges, and around 3 months of CA is a critical period for the appearance of occipital hyperexcitability. Hypsarrhythmia and tonic spasms appeared almost simultaneously from 4 to 6 months of CA in most patients. To predict the occurrence of WS in high-risk infants, EEG follow-ups from early infancy are very useful.

We report a patient with intractable West syndrome whose epileptic spasms (ESs) were initially bilaterally synchronous, as is typical; after a complete corpus callosotomy, however, bilaterally independent ESs originated in either hemisphere. Activity of probable cortical origin associated with ESs was detected by observing ictal gamma oscillations. Brain MRI revealed no structural abnormality before surgery. This case suggests that ESs with a hemispheric origin may appear generalized because of synchronizing effects in the corpus callosum in some patients.

Purpose To investigate whether serial electroencephalographic (EEG) findings can predict relapse of epileptic spasms after synthetic adrenocorticotropic hormone (ACTH) therapy in patients with West syndrome (WS). Subjects and methods Thirty-nine WS patients (8 cryptogenic and 31 symptomatic) were included in this study. These patients received ACTH therapy for the first time and were regularly followed up for more than three years at our hospital. Sixteen patients (41.0%) showed seizure relapse (relapse group) and 23 patients (59.0%) did not show relapse (non-relapse group). We used survival analysis to investigate the influence of etiology and presence of epileptic discharges after the ACTH therapy on seizure outcome. Results Immediately after the ACTH therapy, etiology was associated with seizure outcome ( p = 0.003). In the early stage (1 month after the ACTH therapy), only the presence of epileptic discharges ( p = 0.001) had a significant association with seizure outcome, regardless of etiology. Because all relapsed patients were in the symptomatic group, we performed the same statistical analysis on symptomatic WS patient data only. We found that the group with no epileptic discharges on EEG showed a significantly higher seizure-free rate than those with epileptic discharges in the early stage ( p = 0.0091). Conclusion This study demonstrated that serial EEG findings after ACTH therapy are significantly related to relapse of epileptic spasms.

Fast oscillations (FOs) were first explored from scalp electroencephalographic (EEG) data from hypsarrhythmia in West syndrome (infantile spasms) to investigate the meaning of FOs in this epileptic encephalopathy.In 17 infants with West syndrome, we conservatively detected fast frequency peaks that stood out from the time-frequency spectral background with square root power1µV (spectral criterion) and corresponded to clear FOs with at least 4 oscillations in the filtered EEG traces (waveform criterion) in sleep EEGs.We found a total of 1,519 interictal FOs that fulfilled both the spectral and waveform criteria. The FOs with a median frequency of 56.6Hz (range = 41.0-140.6Hz) were dense, with a median rate of 66 (range = 24-171) per minute before adrenocorticotropic hormone (ACTH) treatment, which was significantly higher than that in control infants without seizures (median = 1, p0.001). The FOs were reduced by treatment. The mean gamma and ripple oscillation rates that were detected using the waveform criterion alone were 40.62/min and 15.75/min, respectively, per channel; these results were 112.8 and 98.4 times higher, respectively, than the previously reported corresponding rates in adult epilepsy patients.The observed FOs corresponded to epileptogenicity because of their close relation to the severity of hypsarrhythmia during the course of ACTH treatment. The very high epileptic FO rates in hypsarrhythmia are thought to affect the process of neurodevelopment by interfering with physiological functions in West syndrome, taking into account that high frequencies are also important in physiological higher brain functions.

The cortical contribution for the generation of gamma rhythms detected from scalp ictal EEG was studied in unique cases of epileptic spasms and a review of the related literature was conducted. Ictal scalp gamma rhythms were investigated through time–frequency analysis in two cases with a combination of focal seizures and spasms and another case with spasms associated with cortical dysplasia. In the two patients with combined seizures, the scalp distribution of ictal gamma rhythms was related to that of focal seizure activity. In the third patient, an asymmetric distribution of the ictal scalp gamma rhythms was transiently revealed in correspondence to the dysplasic cortex during hormonal treatment. Therefore, the dominant region of scalp gamma rhythms may correspond to the epileptogenic cortical area. The current findings have reinforced the possibility of the cortical generation of ictal scalp gamma rhythms associated with spasms. The detection of high frequencies through scalp EEG is a technical challenge, however, and the clinical significance of scalp gamma rhythms may not be the same as that of invasively recorded high frequencies. Further studies on the pathophysiological mechanisms related to the generation of spasms involving high frequencies are necessary in the future, and the development of animal models of spasms will play an important role in this regard.

We investigated the effect of lamotrigine (LTG) add-on therapy in 50 patients with childhood-onset refractory epilepsy (25 males and 25 females): 15 with localization-related epilepsy, 33 with generalized epilepsy, and 2 with undetermined epilepsy. Twenty-four patients had experienced a period of West syndrome during their clinical course. Age at the start of LTG therapy ranged from 2 years 6 months to 41 years 2 months:16 years in 43 andor = 16 years in 7. Seizure frequency wasor = 1 per day in 36 patients (72%) andor = 1 per week in 14 (28%). We increased the LTG dosage every two weeks in accordance with usage recommendations. We evaluated efficacy at two points: 3 and 6 months after the start of LTG. At the 6-month point, seizure freedom was achieved in 2 patients (4%),or = 50% seizure reduction in 14 (28%), 25 to 50% seizure reduction in 20 (40%), no effect in 6 (12%), and aggravation in 4 (8%). Only 4 patients (8%) stopped LTG therapy within 6 months due to LTG-related mild skin rash in 2 and suspicion of seizure aggravation in the other 2. In terms of seizure types, seizure freedom oror = 50% seizure reduction was achieved in 29% for epileptic spasms, 32% for tonic seizures, and 29% for partial seizures. A comparison between the 3- and 6-month points revealed that the efficacy level was increased or maintained in 77% of the patients and decreased in 23%. In most cases, the highest level of efficacy appeared within 3 months with doses that were smaller than maintenance doses. Observed CNS-related adverse effects included somnolence in 16 patients, irritability in 14, and sleep disturbance in 11. Positive psychotropic effects in daily activities were seen in 28 patients (56%). These effects appeared regardless of the change in seizure frequency with doses that were smaller than maintenance doses.

In our sequential EEG study performed on 68 infants with various pre- and perinatal brain insults, we found peculiar abnormal fast activity (AFAs) in 12 patients. 9 of the 12 patients with AFAs later developed West syndrome (WS) compared with only 3 of the 56 patients without AFAs (p

Summary Objective To improve the interpretability of figures containing an amplitude-integrated electroencephalogram (aEEG), we devised a color scale that allows us to incorporate spectral edge frequency (SEF) information into aEEG figures. Preliminary clinical assessment of this novel technique, which we call aEEG/SEF, was performed using neonatal and early infantile seizure data. Methods We created aEEG, color density spectral array (DSA), and aEEG/SEF figures for focal seizures recorded in seven infants. Each seizure was paired with an interictal period from the same patient. After receiving instructions on how to interpret the figures, eight test reviewers examined each of the 72 figures displaying compressed data in aEEG, DSA, or aEEG/SEF form (12 seizures and 12 corresponding interictal periods) and attempted to identify each as a seizure or otherwise. They were not provided with any information regarding the original record. Results The median number of correctly identified seizures, out of a total of 12, was 7 (58.3%) for aEEG figures, 8 (66.7%) for DSA figures and 10 (83.3%) for aEEG/SEF figures; the differences among these are statistically significant ( p = 0.011). All reviewers concluded that aEEG/SEF figures were the easiest to interpret. Conclusion The aEEG/SEF data presentation technique is a valid option in aEEG recordings of seizures.

Summary Purpose EEG gamma rhythms, which are found in association with epileptic spasms in infants with West syndrome, were explored in the ictal EEGs of tonic seizures in older patients with Lennox–Gastaut syndrome (LGS) to investigate the pathophysiology of the disease. Methods The subjects were 20 patients with LGS (11 males, 9 females; age range: 3 years 1 month to 29 years 3 months) who had at least one digitally recorded tonic seizure with minimal artifacts. A time–frequency analysis was applied to each patient's ictal EEG data. Results A total of 54 seizures were analyzed, excluding spasms in clusters. The ictal EEGs of the tonic seizures showed only diffuse desynchronization in 10 seizures, and desynchronization followed by rhythmic activity in 21. The ictal discharges started as rhythmic activity of varying amplitude without initial desynchronization in 23 seizures. In a total of 25 seizures from 13 patients, gamma rhythms with frequencies ranging from 43 to 101.6 Hz were detected by temporal expansion of the ictal EEG traces and spectral analysis. In 24 (96%) of these seizures, gamma rhythms were observed at seizure onset corresponding to visually identified desynchronization. In the remaining seizure, gamma rhythms were found in association with transient suppression of high-amplitude rapid discharges. Conclusion The detection of gamma rhythms in the ictal EEGs of tonic seizures indicated that some tonic seizures might have generative mechanisms in common with epileptic spasms, and that these mechanisms are possibly related to desynchronization at seizure onset.

Purpose: This study was intended to clarify the relation between spasms in series and a suppression-burst (SB) EEC pattern which have a common nature of repetitive bursting activity in epileptic encephalopathy in early infancy. Methods: The ictal EEC traces of spasms were temporally compressed and expanded to study the beginning and ending phases of series along with their spectral analysis in two patients with Ohtahara syndrome (OS) and one with early myoclonic encephalopathy (EME). The EEC bursts associated with myoclonus were also investigated. Results: A mutual transition was indicated between the ictal activity of spasms and the bursts in the peri-series SB on EEC. Gamma rhythm was detected in common in the ictal activity and the peri-series and interictal bursts on EEC, and also in the bursts with myoclonus. Conclusion: The relation between the ictal activity of spasms and SB on EEC was shown to be close. The generative mechanisms of spasms and myoclonus might be linked to the bursting tendency intrinsic to immature brain function.

We report on a 4-year 8-month-old boy with Panayiotopoulos syndrome who showed atypical evolution with newly developed absence seizures and EEG exacerbation induced by carbamazepine. Soon after the introduction of carbamazepine, EEGs began to worsen, and finally absence seizures and myoclonic seizures appeared. Immediately after we discontinued carbamazepine, the seizures disappeared and the EEG improved. Carbamazepine may induce unusual electroclinical features, electrophysiologically explained by bilateral synchrony. This case provides more evidence of the close links between Panayiotopoulos syndrome and benign childhood epilepsy with centrotemporal spikes.