Yoshiko Haga

Severe myoclonic epilepsy in infancy: evolution of seizures

Changes in seizure type of severe myoclonic epilepsy (SME) in infancy were reviewed retrospectively in 14 patients (11 males and 3 females) who were followed-up to the age of 7 years or more. The observation period ranged from 5 to 16 years with a mean of 10 years. During the follow-up, three or four types of seizures were seen per patient, but the pattern of appearance and disappearance of each seizure type varied considerably among the patients. Tonic-clonic convulsion, either generalized or unilateral, was seen most consistently through the entire course, and it continued to the end of follow-up in 11 patients (79%). On the contrary, myoclonic seizure, complex partial seizure, and atypical absence often disappeared and reappeared repeatedly during the course. In SME, seizure symptoms varied widely among patients in comparison with other neurological symptoms, and the most consistent core seizure type was tonic-clonic convulsions.

Association of nonsense mutation in GABRG2 with abnormal trafficking of GABAA receptors in severe epilepsy

Mutations in GABRG2, which encodes the γ2 subunit of GABAA receptors, can cause both genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. Most GABRG2 truncating mutations associated with Dravet syndrome result in premature termination codons (PTCs) and are stably translated into mutant proteins with potential dominant-negative effects. This study involved search for mutations in candidate genes for Dravet syndrome, namely SCN1A, 2A, 1B, 2B, GABRA1, B2, and G2. A heterozygous nonsense mutation (c.118C>T, p.Q40X) in GABRG2 was identified in dizygotic twin girls with Dravet syndrome and their apparently healthy father. Electrophysiological studies with the reconstituted GABAA receptors in HEK cells showed reduced GABA-induced currents when mutated γ2 DNA was cotransfected with wild-type α1 and β2 subunits. In this case, immunohistochemistry using antibodies to the α1 and γ2 subunits of GABAA receptor showed granular staining in the soma. In addition, microinjection of mutated γ2 subunit cDNA into HEK cells severely inhibited intracellular trafficking of GABAA receptor subunits α1 and β2, and retention of these proteins in the endoplasmic reticulum. The mutated γ2 subunit-expressing neurons also showed impaired axonal transport of the α1 and β2 subunits. Our findings suggested that different phenotypes of epilepsy, e.g., GEFS+ and Dravet syndrome (which share similar abnormalities in causative genes) are likely due to impaired axonal transport associated with the dominant-negative effects of GABRG2.

Transient focal cortical hypometabolism in idiopathic West syndrome

Positron emission tomography (PET) using 18F-labeled 2-deoxy-D-glucose was performed serially in 5 infants with idiopathic West syndrome. While tonic spasms persisted, 2 infants had hypometabolism in the bilateral temporo-parieto-occipital regions, which disappeared after cessation of spasms. In 2 other infants, PET revealed focal hypometabolism in the temporal region a few months after the disappearance of tonic spasms, but subsequent PET studies were normal. PET can detect transient metabolic abnormalities of the cerebral cortex which may be associated with the pathophysiology of West syndrome.

Do ictal, clinical, and electroencephalographic features predict outcome in West syndrome?

Ictal electroencephalographic/video recordings of 42 patients with West syndrome (WS) were reviewed to define the relation between ictal, clinical, and EEG features and etiology or prognosis. The duration and type of spasms, the number of spasms per cluster, and the interval between spasms did not correlate with the etiology or the short-term prognosis. However, eye deviation, asymmetric spasms, and partial seizures concomitant with spasms were observed only in symptomatic WS patients with poor outcome. In particular, all 8 patients with concurrent partial seizures had severe psychomotor retardation. The ictal EEG characteristics did not correlate with etiology and prognosis. There was no significant difference between the patients with persistence or reappearance of hypsarrhythmia and the patients without interspasm hypsarrhythmia.

Photosensitive epilepsy in children

We performed a retrospective analysis of 17 children with photosensitive seizures (PSS) who had been followed for more than 3 years (mean: 9 years). PSS were verified in all patients by simultaneous video-EEG monitoring. The seizures were precipitated by flickering stroboscopes (14 patients) or were induced by patients themselves (3) with head-nodding in front of illumination, blinking at television or close viewing of striped patterns. PSS consisted of myoclonic seizures (eight patients), generalized tonic-clonic convulsions (5), partial seizures (3) or atypical absence (1). According to the International Classification of Epileptic Syndrome, three patients were classified as having severe myoclonic epilepsy in infancy and five as having juvenile myoclonic epilepsy. The remaining nine could not be categorized as any specific epileptic syndrome. Children with age of the onset of epilepsy at 7 years or younger tended to suffer intellectual deficit in addition to intractable seizures.

Simultaneous EEG-VTR and transverse topographical analyses of absence seizures in children: Some prognostic implications

The clinical symptoms and electroencephalographic (EEG) features of typical absence seizures, including transverse topographical analysis (TTA), were studied retrospectively using a simultaneous EEG-VTR system in 36 children aged between 3 and 17 years. Complex absences were more common than simple, and oral automatisms were the most frequent complex symptoms. Occurrence of complex symptoms was directly proportional to the length of seizures. There was no association between lateral TTA type and simple absences. Prognosis was favorable in patients with long seizure duration (P < 0.01), bilaterally synchronous monomorphic spike-waves throughout the seizure discharges (BSMTSD) (P < 0.005) and lateral TTA type (P < 0.05). Two different mechanisms of origin for BSMTSD/non-BSMTSD and lateral/non-lateral TTA types are probably responsible for the difference in prognosis. Favorable prognosis in patients with long seizures is discussed in relation to the duration of the illness. EEGs with BSMTSD and lateral TTA type may indicate a favorable prognosis in children with absence seizures.

Asymmetric spasms in west syndrome

Abstract We studied 6 patients with asymmetric spasms who comprised 16.2% of 37 patients with West syndrome (WS) who demonstrated clusters of tonic spasms on simultaneous video-EEG recordings. Neuroimaging studies showed diffuse cerebral abnormalities in 3 of 6 patients and unilateral hemispheric lesions in the remaining 3. In 3, the clusters of spasms occurred soon after a preceding partial seizure. Lateral dominance of seizures alternated in each patient, and the dominant side of the spasms also varied in relation to the preceding partial seizures. In the remaining 3, tonic spasms were constantly dominant on the side contralateral to the hemispheric lesions. In most of these 6 patients, the seizures were intractable and psychomotor outcome was poor. In particular, 3 patients had severe psychomotor retardation. These results lend support to the notion that cerebral cortex plays an important role in generating clusters of tonic spasms.

Ictal electroencephalographic findings of spasms in West syndrome

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Epilepsies of Neonatal Onset

Although neonatal seizures are classified as an epileptic syndrome with both generalized and focal seizures in the recent classification, etiologies are very diverse. Most neonatal seizures are caused by acute brain insults, and such seizures cannot be called epilepsy, a chronic brain disorder characterized by repeated attacks. In this paper, we evaluated epilepsies of neonatal onset, i.e., neonatal seizures excluding those due to acute brain insults.

Child Epilepsy: Optimal ACTH Dosage for Treating West Syndrome

The study comprised 50 patients with West syndrome who were treated at our hospital from January 1975 to January 1990. The ratio of boys to girls was 27:23. The age at onset of infantile spasms (IS) ranged from 2 months to 1 year and 10 months (mean age 6.9 months). The 50 patients were classified into the following four groups: cryptogenic patients receiving 0.025 mg/kg ACTH per day (4 patients) (I-C), symptomatic patients receiving 0.025 mg/kg of ACTH per day (25 patients) (I-S), cryptogenic patients receiving 0.015 mg/kg of ACTH per day ( 5 cases)(II-C), and symptomatic cases receiving 0.015 mg/ kg of ACTH per day (16 cases)(II-S). Children with normal development and no abnormalities on neurological tests and imaging studies at the time of onset were classified under the cryptogenic group, while all the others were symptomatic. Treatment was discontinued depending on the response to treatment or the appearance of side effects. Seizure recurrence was assessed 16 months after the treatment.