Eiji Oka

Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy.

To investigate the possible correlation between genotype and phenotype of epilepsy, we analyzed the voltage-gated sodium channel alpha1-subunit (SCN1A) gene, beta1-subunit (SCN1B) gene, and gamma-aminobutyric acid(A) receptor gamma2-subunit (GABRG2) gene in DNAs from peripheral blood cells of 29 patients with severe myoclonic epilepsy in infancy (SME) and 11 patients with other types of epilepsy. Mutations of the SCN1A gene were detected in 24 of the 29 patients (82.7%) with SME, although none with other types of epilepsy. The mutations included deletion, insertion, missense, and nonsense mutations. We could not find any mutations of the SCN1B and GABRG2 genes in all patients. Our data suggested that the SCN1A mutations were significantly correlated with SME (p<.0001). As we could not find SCN1A mutations in their parents, one of critical causes of SME may be de novo mutation of the SCN1A gene occurred in the course of meiosis in the parents.

The Early-Infantile Epileptic Encephalopathy with Suppression-Burst: Developmental Aspects

A clinico-electroencephalographic study on 14 cases of the early-infantile epileptic encephalopathy with suppression-burst (EIEE) including long-term follow-up studies for one year 8 months to 12 years 2 months disclosed the specificity of EIEE in its developmental aspects. With age, clinical evolution from EIEE to the West syndrome was observed in as many as 10 cases, among which two cases showed further transition to the Lennox-Gastaut syndrome. Electroencephalographically, suppression-burst pattern gradually began to disappear from age of 3 months and disappeared by 6 months in all the cases, transforming to hypsarhythmia in 10 cases from 2 to 6 months of age, showing further transition to diffuse slow spike-and-waves in 2 cases at one year and one month and at 3 years and one month of age, respectively. Changing pattern of EEG were classifiable into two types which strongly related to the prognosis. These findings indicated EIEE to be an independent epileptic syndrome as the earliest form of the age-dependent epileptic encephalopathy.

Very Fast Rhythmic Activity on Scalp EEG Associated with Epileptic Spasms

Summary:  Purpose: Very fast activity was investigated on the ictal EEGs of epileptic spasms to elucidate the pathophysiology of West syndrome (WS) and related disorders from a novel point of view.

Prevalence of childhood epilepsy and distribution of epileptic syndromes: a population-based survey in Okayama, Japan.

Summary:  Methods: Information on patients younger than 13 years with active epilepsy was collected from medical records. Patients diagnosed with epilepsy according to clinical and EEG findings were put on the list even if those patients had had a single seizure or seizures occurring during febrile episodes.

Epilepsy with Electrical Status Epilepticus During Slow Sleep and Secondary Bilateral Synchrony

Summary: In 3 children with “epilepsy with electrical status epilepticus during slow sleep” (ESES), we estimated interhemispheric small time differences (TDs) during spike‐wave activity in EEG by coherence and phase analysis by the two‐dimensional autoregressive model to differentiate their continuous diffuse spike‐waves during slow‐wave sleep (CSWS) between primary bilateral synchrony and secondary bilateral synchrony (SBS). Maximal TDs at onset of apparently bilateral synchronous spike‐wave bursts (BSSWs) during slow‐wave sleep were 12·0–26·5 ms (mean 20·3 ms) with consistent leading hemispheres in eight bursts of the 3 patients, indicating SBS as pathophysiology of their CSWS. This suggestion was supported by their clinico‐EEG findings, including the effect of a single oral dose of clobazam (CLB) on EEG. Three ictal BSSWs of atypical absence seizures in 2 patients were also analyzed to obtain maximal TDs of 17·9–41·7 ms (mean 26·3 ms) at onset, with the same leading sides as in sleep, also indicating SBS. Examination of intraburst TD variations showed no consistent disappearance of TDs during the latter part of the bursts, in either sleep or the ictal EEGs of atypical absences, and a role of the corpus callosum was suggested in the generation of SBS in ESES.

The effects of age on the N200 component of the auditory event-related potentials

This study was undertaken to determine the effects of development and aging on N200 of event-related potentials from childhood to adulthood. Event-related potentials were recorded from 164 normal subjects ranging in age from 4 to 77 years. A total of 127 of the 164 subjects demonstrated N200 peaks. N200 showed marked developmental changes. During childhood, the N200 latency decreased rapidly with age to the minimum (217 +/- 17.3 ms) at 16 years of age, while it was prolonged gradually with age during adulthood. The latency/age slope in the subjects from 5 to 15 years of age was -9.03 ms/year, while +0.97 ms/year in those from 16 to 77. The N200-P300 interpeak latency remained constant in all age groups and showed no age-related changes. The N200 amplitude decreased as age increased. Nineteen young cases showed N200 peaks to the frequent stimuli. Their ages ranged from 5 to 17 years. Our study suggests that N200 is valuable in evaluating the developmental and aging processes in the central nervous system. The results of this study could be used as normative data in clinical practices.

Primary and secondary bilateral synchrony in epilepsy: differentiation by estimation of interhemispheric small time differences during short spike-wave activity ☆

Estimation of interhemispheric small time differences (TDs) during spike-wave bursts in the EEG by coherence and phase analysis is useful for differentiation between primary bilateral synchrony (PBS) and secondary bilateral synchrony (SBS) in epilepsy. Because the previous method via Fast Fourier Transform needed long bursts for reliable analysis, a method using a 2-dimensional autoregressive model was newly developed to enable estimation of TDs even in 1.2 sec bursts, and applied to 19 epileptic patients with apparently bilaterally synchronous spike-wave bursts. At the onsets of bursts, estimated maximal TDs were 5.8 msec or less and inconsistent in leading hemispheres in 10 patients with a clinical diagnosis of idiopathic, cryptogenic or symptomatic generalized epilepsy indicating PBS, while the maximal TDs were 9.3-41.5 msec and consistent in leading in 7 patients with clinically symptomatic partial epilepsy and also in two with idiopathic and symptomatic generalized epilepsy suggesting SBS. Among 8 patients with bursts which suggested SBS and long enough for evaluation of intra-burst TD variation, TDs tended to disappear in the middle to end parts of the bursts in 5 cases, but not in the other 3, suggesting 2 different pathophysiological mechanisms in SBS.

Neuroepidemiological Study of Childhood Epilepsy by Application of International Classification of Epilepsies and Epileptic Syndromes (ILAE, 1989)

Summary: A population‐based survey of childhood epilepsy was made in 1975 on the total population of children aged >10 years living in Okayama Prefecture (n = 2,378 patients). Using the data obtained, we attempted to re‐classify the various types of epilepsy according to the international classification (ILAE, 1989). Reclassification was possible in 1,872 (78.7%) of the 2,378 cases. The 1,872 cases consisted of 1,045 (55.8%) with localization‐related epilepsies, 824 (44.0%) with generalized epilepsies, and 3 (0.2%) with epilepsies undetermined whether focal or generalized. Classification of the epilepsies in a population‐based survey using the international classification involves difficulties, because both clinical and EEG findings are essential. However, if an appropriate area is selected, classification of epilepsies and epileptic syndromes in a population‐based survey is possible by referring to all medical records stored at every hospital and practitioners clinic that administers treatment to patients with epilepsy in the area.

Benefit of simultaneous recording of EEG and MEG in dipole localization

Summary:  Purpose: In this study, we tried to show that EEG and magnetoencephalography (MEG) are clinically complementary to each other and that a combination of both technologies is useful for the precise diagnosis of epileptic focus.

Treatment of Intractable Childhood Epilepsy with High-Dose Valproate

Summary: Forty‐six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high‐dose (serum level above 100 μg/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 μg/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow‐up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow‐up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High‐dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike‐waves during slow‐wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.