Kazuko Kishi

Regional excitatory and inhibitory amino acid concentrations in pentylenetetrazol kindling and kindled rat brain

We determined regional concentrations of excitatory and inhibitory amino acids in pentylenetetrazol (PTZ) kindling and kindled rat brains in order to investigate the mechanisms responsible for the PTZ kindling process and kindled state. Compared with control rats, PTZ kindling rats had significantly higher concentrations of aspartate in the striatum and the temporal cortex 24 h after the 14th injection of PTZ. Glutamate and GABA concentrations were also significantly higher in the brainstem of PTZ kindling rats 24 h after the 14th injection of PTZ. These findings suggest that the striatum and temporal cortex may participate in a pathway for propagation of the PTZ kindling process, and that the brainstem may be a primary site of PTZ kindling epileptogenesis or a part of the pathways for propagation. On the other hand, the concentrations of amino acids in PTZ kindled rats and controls did not differ 4 weeks after the 14th injection. This suggests that the alterations we detected in amino acid metabolism are not related to retention of the PTZ kindled state, and that some other mechanism for it must exist.

Rotavirus-associated encephalopathy with a reversible splenial lesion.

The case is reported of a 2-year-old boy with a rotavirus-induced mild encephalopathy that presented as transient intensified signal on the splenium of the corpus callosum. The boy also experienced persistent diarrhea, vomiting, fever, and sudden disturbance of consciousness. Although cerebrospinal fluid analysis did not manifest pleocytosis, electroencephalography demonstrated global diffuse slow waves and cranial magnetic resonance imaging demonstrated intensified signal on the splenium of the corpus callosum. Methylprednisolone was infused for 3 days. The disturbance of consciousness disappeared within 24 hours without any other complications, and the splenial signal and electroencephalogram returned to normal within 6 days.

Early predictors of status epilepticus-associated mortality and morbidity in children

BACKGROUND Early predictors of status epilepticus (SE)-associated mortality and morbidity have not been systematically studied in children, considerably impeding the identification of patients at risk. OBJECTIVES To determine reliable early predictors of SE-associated mortality and morbidity and identify the etiology of SE-associated sequelae in Japanese children. METHODS We conducted a prospective multicenter study of clinical findings and initial laboratory data acquired at SE onset, and assessed outcomes at the last follow-up examination. In-hospital death during the acute period and neurological sequelae were classified as poor outcomes. RESULTS Of the 201 children who experienced their first SE episode, 16 exhibited poor outcome that was most commonly associated with acute encephalopathy. Univariate analysis revealed that the following were associated with poor outcomes: young age (⩽24 months); seizure duration >90 min; seizure intractability (failure of the second anticonvulsive drug); biphasic seizures; abnormal blood glucose levels (<61 or >250 mg/dL); serum aspartate aminotransferase (AST) ⩾56 U/L; and C-reactive protein (CRP) levels >2.00 mg/dL. Multivariate analysis revealed that young age, seizure intractability, abnormal blood glucose levels, and elevated AST and CRP levels were statistically significant. CONCLUSIONS Young age and seizure intractability were highly predictive of poor outcomes in pediatric SE. Moreover, abnormal blood glucose levels and elevated AST and CRP levels were predictors that might be closely associated with the etiology, especially acute encephalopathy and severe bacterial infection (sepsis and meningitis) in Japanese children.

Effect of penicillin on GABA-gated chloride ion influx

To investigate the mechanism of penicillin-induced convulsions, we have studied the effects of penicillin G (PC-G) on GABA-gated chloride ion influx in brain ‘microsac’ preparations of mice. In the presence of 10−4 M GABA, PC-G inhibited GABA-gated chloride ion influx in a dose-dependent manner. The dose-response curve for GABA in the presence of 10−3 M PC-G was shifted rightward and there was a decrease in maximum response. The inhibitory effects of PC-G were not reversed by RO 15-1788, an antagonist of benzodiazepine (BZ) receptors, but were reversed by washing the ‘microsac’ membranes. Therefore, PC-G probably exerts its proconvulsant effect by inhibiting GABA-gated chloride ion influx. However, it appears not to act through the BZ receptor of the GABA/BZ receptor complex.

Clinical and genetic investigation of 17 Japanese patients with hyperekplexia.

The aim of the study was to determine clinical and genetic characteristics of Japanese patients with hyperekplexia.

A variant case of congenital bilateral perisylvian syndrome with asymmetric findings on neuroimaging and septum pellucidum defect.

We report a 17-year-old female patient with a variant form of congenital bilateral perisylvian syndrome (CBPS). She had pseudobulbar palsy, partial epilepsy and mild pyramidal symptoms predominantly in the left hand. Magnetic resonance imaging revealed asymmetric perisylvian and perirolandic polymicrogyric cortical dysplasia and septum pellucidum defect. The clinicoradiological findings for this patient met the criteria for CBPS. Moreover, they appeared to overlap those of congenital unilateral perisylvian syndrome. The findings in this case support the hypothesis that these two syndromes are parts of a continuous spectrum of one clinico-radiological syndrome.

A 14-year-old girl with hyperekplexia having GLRB mutations.

Hyperekplexia manifests as generalized stiffness and an excessive startle reflex to stimuli. It starts in the neonatal period and is transmitted in many cases via autosomal dominant inheritance. The etiology is an abnormality of the glycinergic neurotransmission system that is involved in inhibitory neurotransmission. Aberrations of five genes related to this neurotransmission system have been identified. The patient was a 14-year-old girl with mild mental retardation. None of her family members had a neuromuscular disease. An excessive startle reflex and generalized stiffness were noted immediately after birth and she was diagnosed with epilepsy because epileptic discharges were observed. However, the disease was resistant to various antiepileptic drugs and the startle responses persisted. GLRB gene mutations (R50X/Q216fsx222) were identified, after which the patient was diagnosed with hyperekplexia. The startle reflex improved when clonazepam treatment was initiated. When patients have a persistent startle reflex, it is necessary to consider hyperekplexia, even if epileptic discharges are observed. Only four cases with GLRB mutations, including the present patient, have been reported. To make a definite diagnosis of hyperekplexia, it may be useful to screen for genes that are involved in the glycinergic neurotransmission system.

GABA-gated chloride ion influx in brains of tremor rats

We measured the GABA-gated chloride ion influx and GABA concentrations in the cerebral cortex and the hippocampus of young (5 weeks old) and older (15 weeks old) tremor rats. GABA-gated chloride ion influx in these tremor rats was significantly greater than in the controls of both the 5 week- and 15 week-old groups. GABA concentrations in the cerebral cortex and hippocampus of the tremor rats increased compared with controls of 5 weeks and decreased compared with controls of 15 weeks. These findings suggest that the GABAergic presynaptic neurons in the cortex and hippocampus of the tremor rat are disturbed with aging. This change may be related to the appearance of absence-like seizures in the rats. The increased GABA-gated chloride ion influx in tremor rats may be a compensatory mechanism against the genetically-determined seizure susceptibility of these rats. Furthermore, the increased GABA levels and GABA-gated chloride ion influx found in 5 week-old tremor rats may be related to the tremor movements.

Regional excitatory and inhibitory amino acid concentrations in Noda epileptic rat (NER) brain.

We measured regional concentrations of excitatory and inhibitory amino acids in Noda epileptic rat (NER) brains to investigate the mechanisms responsible for spontaneous generalized seizures. Compared with Fisher 344 (F344) rats and F1 hybrid (female NER x male F344 rat) rats, NERs had significantly higher concentrations of glycine in the cerebellum. NERs and F1 hybrid rats had significantly lower concentrations of taurine in the cerebellum than did F344 rats. Although our findings do not explain sufficiently the mechanisms directly responsible for spontaneous seizures, they suggest that the cerebellum of NER may be in an excited state to dampen seizures, while the cerebellum of F1 hybrid rats may also be slightly excited to inhibit milder forms of seizures. Further studies, including microdialysis and receptor binding assays, will be required to elucidate these mechanisms.

Quality of Life in Schoolchildren and Students with Epilepsy: A Survey by Questionnaire for Nurse‐Teachers in Shimane Prefecture

Epilepsy is one of the most common chronic diseases occurring during schooldays. For the treatment of epilepsy, it is very important to improve the quality of life of patients with the disease as well as early diagnosis and therapy. We conducted this survey by questionnaires among nurse-teachers to elucidate the conditions of schoolchildren and students with epilepsy and try to improve the quality of their school life. In this paper, we will analyze the problems obtained by the survey.