Fumika Endoh

A storm of fast (40–150Hz) oscillations during hypsarrhythmia in West syndrome

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.

Spectral analysis of EEG gamma rhythms associated with tonic seizures in Lennox–Gastaut syndrome

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 patients 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 101.6Hz 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.

Relation of Spasms and Myoclonus to Suppression-Burst on EEG in Epileptic Encephalopathy in Early Infancy

PURPOSE This study was intended to clarify the relation between spasms in series and a suppression-burst (SB) EEG pattern which have a common nature of repetitive bursting activity in epileptic encephalopathy in early infancy. METHODS The ictal EEG 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 EEG 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 EEG. Gamma rhythm was detected in common in the ictal activity and the peri-series and interictal bursts on EEG, and also in the bursts with myoclonus. CONCLUSION The relation between the ictal activity of spasms and SB on EEG was shown to be close. The generative mechanisms of spasms and myoclonus might be linked to the bursting tendency intrinsic to immature brain function.

Electroencephalographic changes before the onset of symptomatic West syndrome.

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.

Cortical contribution to scalp EEG gamma rhythms associated with epileptic spasms

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.

Amplitude-integrated EEG colored according to spectral edge frequency

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.

Predictive factors for relapse of epileptic spasms after adrenocorticotropic hormone therapy in West syndrome.

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.

Questionnaire-based assessment of behavioral problems in Japanese children with epilepsy

Behavioral problems in Japanese children with epilepsy were investigated by means of a questionnaire for parents consisting of three checklists: the Child Behavior Checklist (CBCL)/4-18 Japanese Edition, the High-Functioning Autism Spectrum Screening Questionnaire (ASSQ), and the Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-IV (ADHD-RS) for parents. The participants were the parents of 108 children aged 6-18 years with apparently normal intelligence. The CBCL indicated abnormal behavior in 10.5 to 35.6% of the children, and T scores on both the internalizing and externalizing scales had a significant positive relation with scores on the ASSQ and ADHD-RS. It was revealed through multivariate logistic regression analysis that the persistence of seizures was significantly related with abnormality on the externalizing scale of the CBCL (p=0.010, odds ratio: 3.48, 95% confidence interval: 1.34-9.02). Future studies are needed to determine whether seizure freedom improves behavior in children with epilepsy.

Occurrence of bilaterally independent epileptic spasms after a corpus callosotomy in West syndrome

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.

Efficacy of topiramate for intractable childhood generalized epilepsy with epileptic spasms: With special reference to electroencephalographic changes

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 ≤ 12 years 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 5 years, 8 months. 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.