Unlikely Western countries, only recently who are within the normal range of intelligence quotient but have specific difficulties in schoolwork have become a great interest to the general public in Japan. These difficulties are termed learning disabilities or learning disorders. Some studies about children with learning disorders reported that children with learning disorders sometimes showed the epileptic seizures and abnormalities in the electroencephalogram (EEG). My colleague and I have investigated the cognitive disorders in patients with localization related epilepsy (LRE) in childhood. As a result of our studies, we became interested in the relationship between the higher brain functional disorder and the working memory and the executive function. The working memory and the executive function are assumed to be associated with the learning disorders in children with LRE. It is suggested that the impairment of these functions can be the cause of disabilities in sentence comprehension, calculation, reasoning etc.. In this session I will summerize our neuropsychological studies in the children with LRE, present the latest research about the working memory and the executive function in the patients with LRE in childhood and discuss treatment from an educational standpoint.

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To investigate the mechanism of synaptic reorganization in epileptogenesis, we studied dentate granule cell neurogenesis and neuronal loss in the rat kainate model of temporal lobe epilepsy, and their possible association with NMDA receptor activation. In rats, kainate was microinjected into the left amygdala, and limbic status epilepticus was induced. After the kainate injection, bromodeoxyuridine (BrdU) immunohistochemistry and Nissl staining were performed. In addition, MK-801, a selective NMDA receptor antagonist, was administered systemically either once or three times. Kainate-treated rats showed a marked increase in BrdU-positive cells in the bilateral dentate gyrus, while clear neuronal loss was apparent in the CA3 and CA1 regions only on the side ipsilateral to the site of kainate injection. Single pretreatment with MK-801 had no significant effect on kainate-induced enhancement of neurogenesis, whereas treatment with MK-801 three times slightly reduced it. MK-801 also showed significant protective effects against CA1 neuronal damage, but no significant protective effects against CA3 neuronal damage. These results indicate that kainate-induced focal seizure activity enhances adult neurogenesis in the dentate gyrus, which may lead to epileptogenesis independent of hippocampal neuronal damage. The seizure-induced enhancement of neurogenesis may be partly mediated via NMDA receptor activation.

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We repeatedly performed ¹H-magnetic resonance spectroscopy in the right parietal lobe of 7 patients with West syndrome who were treated with ACTH and analyzed the influence of ACTH therapy on metabolism.
ACTH-Zn (0.015mg/kg) was injected intramuscularly every day for the first 2 weeks and was gradually decreased thereafter over six weeks. NAA/Cr ratios were decreased in all 7 patients one month after the initiation of ACTH therapy. The extent of this decrease was remarkable in patients who were younger than 12 months of age. NAA/Cr ratios almost returned to their former values 4 months after the end of ACTH therapy, but remained low in 2 patients who were both younger than 12 months of age. Cho/Cr ratios were decreased in all 5 patients younger than 12 months of age at one month after the initiation of ACTH therapy and returned to their former values 4 months after the end of ACTH therapy. No remarkable change in Cho/Cr ratios was recognized in 2 patients older than 12 months of age. These findings suggest that ACTH decreases NAA synthesis in neurons and that ACTH may induce irreversible neuronal loss. Furthermore, ACTH may also suppress myelination. These potential actions of ACTH appear to be greatest in patients younger than 12 months of age.

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Nine patients with sequelae of influenza-associated encephalitis/encephalothay from 1997 to 2002 influenza seasons were included in this study. Their clinical course and serial electroencephalographic findings were studied. In the acute phase, all patients showed frequent seizures. In the convalescent phase, epileptic seizures were observed in five patients, two symptomatic localization-related epilepsy and three symptomatic generalized epilepsy. Electroencephalogram revealed high voltage slow waves in the acute phase in all patients, and two showed periodic discharges. One to twelve months later, focal spikes developed in seven patients, and 4 to 18 months later, diffuse poly spikes or spike and waves developed. These serial electroencephalographic changes were common in our patients and might be a characteristic finding following influenza-associated encephalitis/encephalopathy. It is also important to examine electroencephalogram to recognize the neurophysiological sequelae of influenza associated encephalitis/encephalopathy.

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Landau-Kleffner syndrome (LKS) is a rare but well-known epileptic syndrome in children, occurring in children who have already developed age-appropriate speech. It is characterized by marked deterioration of language functions, especially with perceptive language impairment. We report a 9 year-old boy in which LKS was successfully treated with Ethyl loflazepate. He could speak at 3years old, but gradually lost his words. At 4 years old he was observed absent-minded and he did not understand even simple verbal commands. EEG during the awake state demonstrated multiple focal spikes and waves, and showed diffuse spikes and waves continuously during the sleep stage. Sodium valproate, clonazepam, steroid therapy are reported to be effective in some cases of LKS but our patient did not respond to these drugs. Ethyl loflazepate is a new benzodiazepate drug and recently it has been tried for pediatric intractable epilepsies. We tried Ethyl loflazepate for the treatment. Tongue and lip movements were improved and the drooling was disappeared. EEG showed marked improvement. There has been no side effect for 2years. To our knowledge, the report of Ethyl loflazepate treatment in children is few. Ethyl loflazepate is supposed to worth used for the treatment on LKS reluctant to conventional anti-epileptic drugs.

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