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Nitric oxide (NO) is historically well known as a toxic gas but now recognized as a physiological cellular mediator acting at very low concentrations. It is biosynthesized within the body, and modulates many signal transduction processes. For investigation of the functions of this gaseous mediator, it is necessary to use chemical donors that release NO specifically, and it is highly advantageous if the release can be made with precise spatiotemporal control. For this purpose, we have developed caged NO (photocontrollable NO-releasing compounds) with unique releasing mechanisms. One employs the photoinduced rearrangement of an arylnitro group and subsequent release of NO, and another uses photoinduced electron transfer to release NO. One of our caged NO was confirmed to induce a NO-dependent cellular response in vivo under photocontrol. Photocontrollable NO releasers are expected to become indispensable tools for physiological experiments, and are also potential therapeutic agents for photodynamic therapy.

A 30-year-old man was admitted to Osaka University Hospital for the treatment of gastric varices and assessment of indication for liver transplant. When he was 6 years old, liver dysfunction was pointed out and diagnosed as chronic inactive hepatitis by liver biopsy. At 13 years of age, the second liver biopsy proved congenital hepatic fibrosis (CHF). The third liver biopsy was performed when he was 30 years old, and the progression of hepatic fibrosis was confirmed. Besides CHF, we recognized oligophrenia, cerebellar ataxia, hypoplasia of cerebellar vermis and coloboma, leading to the diagnosis of COACH syndrome. COACH syndrome is quite rare, and our case is especially valuable because he was diagnosed as an adult case and the progression of hepatic fibrosis could be followed through several liver biopsies. We should be aware of COACH syndrome in mind when we encounter CHF patients.

The ARX gene is involved in the development of GABAergic interneurons in the forebrain. Loss-of-function mutations, such as nonsense or frameshifts mutation, of ARX cause a group of brain malformations, such as hydranencephaly, lissencephaly, and agenesis of the corpus callosum, while expansion mutations of the polyalanine tracts of ARX, supposed to be gain-of-function mutations, result in a non-malformation group, such as non-syndromic mental retardation, mental retardation with dystonia, West syndrome, and Ohtahara syndrome. A variety of phenotypes caused by pleiotropic mutations of the ARX gene are considered to share a common pathological mechanism connected with the structural and functional disturbance of interneurons, designated as 'interneuronopathies'. We identified the second gene responsible for Ohtahara syndrome, STXBP1, which is essential for synaptic vesicle release. Molecular studies of the diseases will reveal the relationships between the structure and function of the brain. It is indispensable to clarify the etiology of hereditary diseases and identify new approaches to treatment.

Etiologies and risk factors of 569 patients with cerebral palsy (CP) in Shiga Prefecture born during 1977-2000 were investigated. The patients with CP born at preterm and at term were separately analyzed. The main etiologies or risk factors for CP in preterm children were periventricular leukomalacia (PVL, 58%), multiple births (25%) and mechanical ventilation (45%). The prevalence rates of these increased in the latter half of the study period. The main etiologies or risk factors for CP in term children were brain dysplasia (17%), fetal brain vascular disorders (15%), hypoxic ischemic encephalopathy (14%), PVL (8%) and intrauterine growth retardation (19%). The prevalence rates among etiologies did not change during the study period.

Cortical dysplasia (CD) is a malformation predominantly affected cerebral neocortex, resulting in disorganized brain cytoarchitecture. Normal cortical lamination is disturbed and neurons are abnormally located. Adjacent white matter is often involved. Chronic seizures are a clinical feature of developmental disorders of the brain, including CD and agenesis of the corpus callosum. A morphologically distinct form of CD is focal cortical dysplasia (FCD) characterized by the presence of cytomegalic neurons, seen in specimens resected from patients with partial epilepsy. The abnormal area usually appears normal externally, but may on occasion be represented by a wilder than normal gyrus, while the cut surface shows blurred grey-and white-matter demarcation. MR images of FCD show blurred grey-and white-matter demarcation and T2 elongation in the white matter. In our cases of FCD, no calcifications or mass effects were observed. The lesions of FCD also bear some resemblance to those of a forme fruste of tuberous sclerosis (solitary cortical tuber). The cytoarchitectual abnormalities in cortical tubers are, however, much more extensive and a characteristic feature of cortical tubers is the presence of subpial clusters of giant astrocytes and sheaves of astrocytic processes. CT images of a solitary cortical tuber show abnormal cortex with high density and frequently associated with calcifications and mass effect. An abnormal dilatated and oriented cerebral fissure is often observed around the lesion. White matter bands and blurred grey-and white-matter discrimination are occasionally seen in the white matter near the lesion. FCD is a different lesion from a solitary cortical tuber.

Clinical and electroencephalographic features of epilepsy and the prognosis of intelligence were investigated in 156 children with hydrocephalus. Of these 53 (34.0%) had epilepsy. The incidence and outcome of epilepsy were determined by the etiology of hydrocephalus. The incidence was high in children with hydrocephalus caused by intra-cranial infection and dysgenetic hydrocephalus without dysraphism. Furthermore, it was difficult to control the epileptic seizures in these patients. In contrast, children with dysgenetic hydrocephalus caused by dysraphism and simple hydrocephalus had lower incidence of epilepsy and epileptic seizures had been well controlled in these cases. In hydrocephalic children, localization-related epilepsy was the most common. Complex partial seizures and focal motor seizures were frequently observed. Common electroencephalographic findings were focal spikes or multi-focal spikes. The intelligence quotient was significantly lower in children with epilepsy than in those without epilepsy. All these findings suggest that the incidence of epilepsy may be a crucial prognostic factor in children with hydrocephalus.

Schizencephalyis a rare disorder of brain development resulting in the formation of abnormal unilateral or bilateral clefts in the cerebral hemispheres. One patient is described with psychotic symptoms with unilateral schizencephaly. The implications of the association between schizencephaly and psychosis in these patients for understanding the biology of the psychoses are discussed.

Two months-old girl with psychomotor retardation had aminophylline-resistant apnea attacks and was investigated by video-EEG recording. She had hypogenesis of cerebral cortex and cerebellum and complete agenesis of corpus callosum. Left hemispheric 2 Hz rhythmic delta wave burst originating from the posterior temporal area lasted about 20 seconds, and was followed by an apnea attack persisting for 30 seconds. During the apnea attack, the basic activity of EEG was suppressed. The diagnosis of epileptic apnea was made, and the attacks were controlled with valproate sodium. Reports of cases of brain anomaly presenting with epileptic apnea are rare and this interesting case provided a clue to the pathomechanism of this condition.

We report a case of a dermoid cyst in the parasellar area associated with porencephaly. A 22-year-old man presented with headache and visual disturbance. Non-enhanced brain CT showed a high density mass in the parasellar area and a low density area in the left temporal lobe. On gadolinium-enhanced T1-weighted images, a partial rim enhancement was present in the parasellar region. A presumptive diagnosis of Rathke cleft cyst, craniopharyngioma, non-function pituitary adenoma, or germ cell tumor was considered. A left frontotemporal craniotomy was performed and the tumor was removed almost totally. The tumor was well-capsulated and contained whitish, milky debris. The histologic diagnosis was dermoid cyst. The temporal lobe lesion was porencephaly. The postoperative course was uneventful. Their most typical aspect is the presence of a low-density mass on CT, allowing an easy radiologic diagnosis of dermoid cyst containing lipids. Enhancement following contrast administration is uncommon. The hyperdensity may be related to the high protein content of the lesion. The hyperdense aspect of the lesion on CT, and the presence of rim enhancement made the radiologic diagnosis of a dermoid cyst difficult in this case. A case of dermoid cyst associated with porencephaly has not yet been reported in the literature.

We report two adult cases of unilateral schizencephaly manifesting as minor neurological signs. Case 1 was a 52-year-old female with an attack of partial seizure. CT demonstrated a closed cleft in the left frontal lobe. MRI revealed that the cleft was covered with gray matter, and was extending to the ventricular wall. Her epileptic seizure was successfully controlled by medication. Case 2 was a 58-year-old female with a history of mild right hemiparesis from her birth. CT demonstrated a closed cleft in the left peri-Rolandic area. MRI revealed a cortical infolding which extended to the lateral ventricle, and complication with polymicrogyria. Two patients were diagnosed as having normal intelligence, and unilateral schizencephalies with closed-lip. There has appeared to be more reports in the recent literature dealing with unilateral schizencephaly with mildly neurologic dysfunction. It is sufficiently capable of making such a diagnosis for schizencephaly by initial CT evaluation of a detailed radiographic assessment, in which characteristic findings with focal enlargement of cortical sulci or appearance of cortical infolding extending to deep white matter will be detected, though MRI is considered to be useful for a more detailed neuroanatomical evaluation.

Twin embolization syndrome (TES) is a complication of monozygotic twining following in utero demise of the co-twin. Passage of thromboplastic materials into the circulation of the surviving fetus results in ischemic structural defects of various systemic organs including the central nervous system (CNS). In our case of monozygotic twining prenatal sonography at the 18th week of gestation revealed intracranial abnormality and demise of the co-twin. Postnatal MRI demonstrates localized cerebral parenchymal defects (porencephalic cysts) in the bilateral hemispheres, which probably were the sequelae to the occlusion of the peripheral branches of the bilateral middle cerebral arteries. She developed physio-mental retardation and subsequently West syndrome. At the 6th months, right porencephalic cyst-peritoneal shunt was performed for progressive enlargement of the head. While the enlargement of the head was well controlled, no changes in her epileptic symptoms were noted. The development of generalized epilepsy in our case may indicate that the involvement of the CNS with TES in our case is not restricted to the porencephalic cysts and their surrounding areas.

We studied the incidence of cerebral dysgenetic lesions(CD) in 39 operated patients with medial temporal lobe epilepsy(MTLE) who had hippocampal sclerosis. Four patients had CD, such as menigocele at the ipsilateral temporal fossa, schizencephaly in the ipsilateral peri-Rolandic area, focal cortical dysplasia in the ipsilateral inferior temporal gyrus and periventricular nodular heterotopia at the bilateral inferior horns of the lateral ventricle. Histological examinations of the resected lateral temporal lobes from 29 MTLE patients revealed the presence of microdysgenesis (microscopic cerebral dysgenesis) in 28 patients, including heterotopic white matter neuron(24 cases), molecular layer neuron(14), oligodendroglial cell cluster(11), dilated perivascular space(10). These findings suggest that the congenital factors, as well as hippocampal sclerosis, may be involved in the development of MTLE.

Our experience with modified functional hemispherectomy in 14 infants are presented. The etiology of intractable epilepsy was cortical dysgenesis in all of the cases. We applied our new surgical method, transopercular hemispherotomy, in which the frontal operculum was resected en bloc including the upper half of the insula. The corpus callosum was totally sectioned through the lateral ventricle. The resection cavity was communicated to the inferior ventricle, and the medial temporal structures were resected. Finally, the horizontal fibers emerging from the frontal lobe were sectioned along the posterior edge of the ala minor ossis sphenoidalis. There was no mortality or morbidity during and immediately after operation. In 12 cases with more than 1 year follow-up, remarkable seizure reduction was obtained in 75% of the cases and worthwhile improvement in the remaining 25%. No major complications were encountered, except for hydrocephalus in 3 cases and incomplete section of the callosum in 3. In cases showing catch-up of psychomotor development after surgery, swelling of the unaffected hemisphere was observed.

A 24-year-old male of medial temporal lobe epilepsy associated with schizencephaly was presented. He developed complex partial seizure after head trauma at the age of a year and 7 months, which became intractable at the age of 13 year. MRI demonstrated a schizencephalic cleft in the right peri-Rolandic area, cortical dysplasia in the right medical parietal and occipital lobes, and right hippocampal atrophy. Scalp-recorded EEG failed to localize the ictal onset zone. Interictal FDG-PET and ECD-SPECT indicated hypometabolism and hypoperfusion of the right entire temporal lobe, and ictal ECD-SPECT increased perfusion of this area. Chronic subdural electrode recording clearly demonstrated that ictal onset zone was located not on the schizencephalic cleft or its surrounding cortex but on the right medial temporal lobe. Following right anterior temporal lobectomy with hipppocampectomy, seizure control became easy. For the identification of the epileptogenic zone in patients with schizencephaly, chronic subdural electrode recording is mandatory.

In this report, we describe a one-year-old girl of the Miller-Dieker syndrome(MDS) with lissencephaly, seizures, microcephaly and mental disorders. Cytogenetic studies of this patient confirmed the presence of a 46,XX, 17ps+ chromosome karyotype, but it could not find the microdeletion of 17p13.3. Fluorescence in situ hybridization(FISH) studies confirmed a terminal deletion in the patient using the LIS1 gene probe which mapped to 17p13.3. Further it was also found the satellite on 17p13(17ps) in the patient who was rare associated with MDS. These findings suggest that FISH analysis may be useful method to detect microdeletion of LIS1 gene as 17-specific probe in the investigation of MDS patients.

To determine the occurrence, outcome, and prognostic factors of West syndrome (WS), we performed a retrospective epidemiological study of WS occurred in 47 children (26 boys and 21 girls) in Nagasaki prefecture during a recent 10-year period from 1989 to 1998. The incidence of WS was 3.1/10,000 live births. The mean age at onset of spasm is 6.3 months (range: 2 to 12 months). Thirty-nine patients (83%) had symptomatic WS, in which the prenatal causes (patients) were most frequent, followed by low-birth weight infants (patients), perinatal (patients) and postnatal (patients). The brain CT was performed in 37 patients, and revealed congenital brain malformations (9 patients), destructive brain disorders (12 patients), and no structural abnormalities (16 patients). The seizure outcome was worse in the symptomatic WS than in the cryptogenic WS; seizure/disappeared in 39% of the former and in 75% of the latter/developmental delay before the onset of WS, relapse of WS and persistence of seizures were associated with poor seizure outcomes. Among the remaining seizures at the time of this surveillance, a tonic seizure was most frequently observed, followed by the partial seizures. Lennox-Gastaut syndrome was observed in 2 patients only. Epileptic discharge in the latest interictal EEG were diffuse in 4.3%, focal or multifocal in 60.7%, and absent in 35%, suggesting that many patients with WS had cortical epileptogenic foci. The developmental outcome was very poor in both the symptomatic and cryptogenic WS. The mean DQ in all the patients was 25, and only 4 patients (11%) had a normal DQ (> 75). DQ was lower in patients with congenital brain malformations than in those with destructive brain disorders.

There have recently been a number of new pathological findings of specimens from epileptic foci that have increasingly been highlighted as opportunities for surgical treatment. These findings include a wide range from hippocampal sclerosis-related lesions of temporal lobe epilepsy to newly established malformative lesions. As to the former, special interest has been paid to additional knowledge regarding the pathology inside and outside the medial temporal regions, such as the significance of 1) accumulation of corpora amylacea in hippocampal sclerotic lesions, 2) dispersion of the granular layer of the dentate gyrus, 3) various pathologic features in the lateral temporal lobe, and 4) dual pathology in extratemporal areas. As increasing opportunities for surgical treatment of intractable epilepsy, new categories of malformative lesions are being established, including focal cortical dysplasia and microdysgenesis, the latter of which can be diagnosed only by pathological examination after surgery. In the field of surgical pathology of epilepsy patients, further clues to clarify the pathomechanism of epilepsy remain to be discovered.

For the treatment of intractable generalized epilepsies, two-staged total callosotomy was performed in five patients. In all patients, preceded anterior callosotomy failed to obtain satisfactory seizure control. All patients showed mental retardation with various degrees. Mean age at the first operation was 10.2 years and 4 patients were operated in their childhood. All patients showed various types of seizures; drop attack (DA) in 3 patients, tonic seizure (TS) in 2, myoclonus (MY) in 2, complex partial seizure (CPS) in 2, atypical absence (AA) in 1, and head drop (HD) in 2. After anterior callosotomy, complete cessation of CPS and 50-80% reduction of DA was obtained in one, respectively. However, only less than 50% reduction of seizures was obtained in other types of seizures. Two years after anterior callosotomy, posterior portion of the corpus callosum was divided. After staged total callosotomy, complete cessation of DA was obtained in all patients and 80-100% reduction of AA was obtained in one patient. One adult patient showed the disconnection syndrome which did not affect activities of his daily life. Our study revealed the efficacy of posterior callosotomy in DA patients with unsatisfactory results after anterior callosotomy. This strategy should be considered especially in childhood cases, since obvious complication was not observed in such cases.

Schizencephaly is an extremely rare congenital disease caused by abnormal neuronal migration. The etiology of schizencephaly is not established but vascular disturbance in early childhood could cause this condition. We have cared of a patient with schizencephaly. The patient was 47 year old male. He had focal motor seizure with secondary generalization. Neurological examination revealed, mild left hemiparesis, left pyramidal signs with no sensory impairment, left hemiatrophy, and mirror movement. MRI findings showed schizencephaly, open lip type(type II) in right cerebral hemisphere. His epileptic seizure was controlled by administration of sodium valproate. The possible mechanism of this mirror movement in his left hand and leg could be reorganization of non-affected brain and disinhibition on homolateral pyramidal tract in non-affected left cerebral hemisphere by the transcallosal inhibitory pathyway from affected right cerebral hemisphere. Sodium valpronate can not suppress this mirror movement.

We report here 38 Japanese patients with hemimegalencephaly collected by a national survey study. All the patients were sporadic. There was no familial occurrence or sex difference. Some patients had basic diseases: hypomelanosis of Ito in 3 cases and organic nevus syndromes in 8. Most patients had hemiparesis, and 11 were bed-ridden. All except for 3 patients had mental retardation, being profound in half of them. There was no correlation between the side of hemimegalencephaly and clinical symptoms. All patients had epileptic seizures, which first appeared within 24 hours after birth in 4 cases, within 7 days in 7, within a month in 2, within 6 months in 10, and within a year in 4. Antiepileptic drugs were not very effective for controlling seizures. In 7 patients, however, functional hemispherectomy resulted in seizure control and improved development. The patients whose epileptic symptom occurred earlier tended to be more severe in clinical symptoms.