Yasuko Yamatogi

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.

Epileptic encephalopathies in early infancy with suppression-burst.

Early infantile epileptic encephalopathy with suppression-burst, or Ohtahara syndrome (OS), and early myoclonic encephalopathy (EME) are epileptic encephalopathies with onset of frequent seizures in the neonatal and early infancy period and with a characteristic EEG pattern, namely, suppression-burst, in which higher-voltage bursts of slow waves mixed with multifocal spikes alternate with isoelectric suppression phase. Their nosologic independence is now widely accepted, although some controversy initially occurred because of their common characteristics such as age of onset, EEG features, seizure intractability, and poor prognosis. Major differences between the two syndromes include (1) tonic spasms in OS versus partial seizures and erratic myoclonias in EME, (2) continuous suppression-burst pattern in both waking and sleeping states in OS versus this EEG pattern almost limited to sleep in EME, and (3) static structural brain damage in OS versus genetic or metabolic disorders in EME. The most important differentiating point is their evolutional pattern with age, which may reflect their pathophysiologic difference. Ohtahara syndrome evolves to West syndrome and further to Lennox-Gastaut syndrome with age, but EME demonstrates no unique evolution; namely, it continues as such for a long time or changes into partial epilepsy or severe epilepsy with multiple independent spike foci.

Early-infantile epileptic encephalopathy with suppression-bursts, Ohtahara syndrome; its overview referring to our 16 cases

Ohtahara syndrome (OS) is characterized by frequent tonic spasms, with or without clustering, of early onset within a few months of life, and a suppression-burst (S-B) pattern in electroencephalography (EEG). Tonic spasms occur in not only waking but also sleeping state in most cases. Partial seizures are observed in about one-third of cases. Brain imagings reveal structural abnormalities including malformations, notably asymmetric lesions in most cases.S-B pattern is persistently observed regardless of circadian cycle. Bursts of 1-3s duration alternate with nearly flat suppression phase of 2-5s at an approximately regular rate; 5-10s of burst-burst interval. Some asymmetry in S-B is noted in about two-thirds of cases. Ictal EEG of tonic spasms shows principally desynchronization with or without initial rapid activity. Tonic spasms appear concomitant with bursts. Characteristic age-dependent evolution from OS to West syndrome (WS) in many cases, and further from WS to Lennox-Gastaut syndrome (LGS) in some, proceed concomitantly with EEG transition from S-B to hypsarrhythmia at around age 3-6 months, and further from hypsarrhythmia to diffuse slow spike-waves at around age 1. Under the inclusive concept of the age-dependent epileptic encephalopathy, OS, WS, and LGS have common characteristics such as age preference, frequent minor generalized seizures, and continuous massive epileptic EEG abnormality. Mutual transition suggests the same pathophysiology among three syndromes and the age factor should be considered as the common denominator responsible for the manifestation of each of their own specific clinico-electrical features. Namely, these syndromes may be the age-specific epileptic reaction to various non-specific exogenous brain insults, acting at the specific developmental stages.

Ohtahara syndrome: With special reference to its developmental aspects for differentiating from early myoclonic encephalopathy

UNLABELLED Ohtahara syndrome (OS) is well known as a peculiar early onset epileptic syndrome with serious prognosis. The outline of OS, mainly in relation to the evolution with age, and differentiation from related conditions, particularly early myoclonic encephalopathy (EME) were mentioned. RESULTS Etiologically, structural brain lesions are most probable in OS, and non-structural/metabolic disorders in EME. Clinically, tonic spasms are the main seizures in OS, while myoclonia and frequent partial motor seizures in EME. Another difference is noted in EEG findings: suppression-bursts (SB) are consistently observed in both waking and sleeping states in OS, but suppression-bursts become more apparent in sleep in EME. The course observation clarifies differences between both syndromes; SBs evolve to hypsarrhythmia around 3-4 months of age, and sometimes further to diffuse slow spike-waves in OS. In contrast, in EME suppression-bursts may persist up to late childhood after a transient evolution to hypsarryhtmia in the middle to late infancy. Transition between syndromes is also specific; OS evolves to West syndrome, and further to Lennox-Gastaut syndrome with age, but EME persists long without such evolution excepting a transient phase of West syndrome. CONCLUSION These clinicoelectrical characteristics and differential points strongly indicate the efficiency of the developmental study to delineate both syndromes.

Predictors and underlying causes of medically intractable localization-related epilepsy in childhood.

The goal of this study is to clarify the prognostic factors in childhood localization-related epilepsy in a tertiary medical center. Children (n = 113) with symptomatic and cryptogenic localization-related epilepsy were divided into groups of intractable patients (average seizure frequency: one or more per month during the 6 months before the last follow-up; n = 40) and well-controlled patients (no seizures for at least 1 year before the last follow-up; n = 73). Clinical and electroencephalogram (EEG) factors were examined to elucidate prognostic factors. The subtypes of epilepsies and causes were also investigated. Univariate analyses indicated that the following factors were correlated with seizure outcome: (1) seizure type at the first visit; (2) seizure frequency; (3) underlying cause; (4) age at onset of epilepsy; (5) status epilepticus occurring as the first seizure and before the first visit; and (6) diffuse epileptic discharges on first visit interictal EEGs. Multivariate analyses revealed that seizure type at the first visit, seizure frequency, status epilepticus before the first visit, and underlying causes were significant independent predictive factors. The rate of intractable patients was highest in multilobar epilepsy, followed by frontal-lobe epilepsy. Regarding etiologies, the intractable group contained nine patients with encephalitis of unknown origin and three each with localized cortical malformation and mesial temporal sclerosis.

Age-dependent epileptic encephalopathy : a longitudinal study

Abstract: A longitudinal clinico‐electroencephalographic study was conducted on 484 cases of age‐dependent epileptic encephalopathy; early‐infantile epileptic encephalopathy with suppression‐burst (Ohtahara) (EIEE), the West and Lennox syndromes. 1) The three types had the same kind of etiologic heterogeneity. 2) An evolutional change with age was noted from EIEE to the West and from the West to the Lennox syndromes, with the change from suppression‐burst to hypsarhythmia, and from hypsarhythmia to the diffuse slow spike‐waves. 3) The core ictal EEG pattern of tonic spasms was the desynchronization in EIEE and the West syndrome, with the rapid synchronization and recruiting rhythm in the Lennox syndrome. In the same cases, the changes from desynchronization to hypersynchronization were observed with age. These facts suggest that the three syndromes are based on the same pathophysiology, strongly related to the subcortical mechanism, and that their clinico‐electrical manifestations are modified by the degree of brain maturation.

Severe epilepsy with multiple independent spike foci.

Severe epilepsy with multiple independent spike foci is an electroclinical entity with the following characteristics: (1) EEG showing multiple independent spike foci (three or more foci in both hemisphere, i.e., at least one in each hemisphere) and diffuse slowing of the background activity, (2) very frequent multiple types of seizures but mainly generalized minor seizures, (3) frequent association with mental retardation and neurologic abnormalities, (4) underlying causes of various nonspecific prenatal, perinatal, and postnatal cerebral conditions, and (5) poor prognoses for seizures and psychomotor development. It represents a diffuse encephalopathy with mutual transition between other age-dependent epileptic encephalopathies. This electroclinical condition may be appropriately named Markand-Blume-Ohtahara syndrome, after Markand and Blume, who initially described in detail the EEG pattern of multifocal spike discharges with its major clinical correlates, and Ohtahara, who extensively studied the group of patients with both clinical and EEG characteristics and proposed the concept of severe epilepsy with multiple independent spike foci, classifying it as one type of generalized epilepsy.

Simple and rapid analysis of lamotrigine, a novel antiepileptic, in human serum by high-performance liquid chromatography using a solid-phase extraction technique

A simple and rapid method for the quantitation of concentrations of lamotrigine, a novel antiepileptic, in human serum was developed with high-performance liquid chromatography, using a solid-phase extraction technique. The mobile phase was composed of acetonitrile-10 mM phosphate buffer (pH 3.5) containing 5 mM sodium octanesulphonate (27:73, v/v), and components were detected at 265 nm. Retention times of acetanilide as an internal standard and lamotrigine were 3.4 and 10.3 min, respectively. The coefficients of variation were 3.1-4.5% and 4.4-9.8% for the within-day and between-day precision estimates, respectively. The extraction recovery of lamotrigine added to blank serum was 86-107%. The quantitation limit of lamotrigine was ca. 0.2 microgram/ml in 100 microliters of serum. These results suggest that the method employed in this study is useful for the routine monitoring of serum concentrations of lamotrigine in epileptic patients.

Child Epilepsy: The Epileptic Syndrome Sharing Common Characteristics during Early Childhood with Severe Myoclonic Epilepsy in Infancy

As previously reported, severe myoclonic epilepsy in infancy (SME)I2 has the following characteristics before the onset of myoclonic seizures and atypical absences3; ( 1 ) a high incidence of family history of convulsive disorders, (2) the onset in early to middle infancy with generalized and/or alternating hemiconvulsions which are easily precipitated by fever or hot baths, ( 3 ) additional appearance of characteristic complex partial seizures around one year of age, ( 4 ) easy development to convulsive status epilepticus during infancy, ( 5 ) difficulty in detecting epileptic EEG discharges in infancy, (6) strong resistance against AED treatment, and ( 7 ) no developmental retardation prior to the onset. In part of the cases with these characteristics in infancy, however, neither myoclonic seizures nor atypical absences developed f ~ r t h e r . ~ Clinical and electroencephalographic evaluations of this group of patients were undertaken in this paper.

Severe Myoclonic Epilepsy in Infancy: A Long‐Term Follow‐Up Study

It is well known that severe epilepsy in infancy (SME) has my oclonic a specific age-dependent course, namely, the onset of convulsive seizures in infancy along with myoclonic seizures and atypical absences in early chi1dhood.l However, long-term follow-up studies after the appearance of myoclonic seizures and atypical absences have been rarely carried out. We, therefore, conducted a prospective long-term follow-up study of SME.