Abstract: 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.

Abstract: Hyperekplexia is primarily an autosomal dominant disease characterized by exaggerated startle reflex and neonatal hypertonia. It can be associated with, if untreated, sudden infant death from apnea or aspiration pneumonia and serious injuries and loss of ambulation from frequent falls. Different mutations in the α1 subunit of inhibitory glycine receptor (GLRA1) gene have been identified in many affected families. The most common mutation is Arg271 reported in at least 12 independent families. These mutations uncouple the ligand binding and chloride channel function of inhibitory glycine receptor and result in increased excitability in pontomedullary reticular neurons and abnormal spinal reciprocal inhibition. Three mouse models from spontaneous mutations in GLRA1 and β subunit of inhibitory glycine receptor (GLRB) genes and two transgenic mouse models are valuable for the study of the pathophysiology and the genotype–phenotype correlation of the disease. The disease caused by mutation in GLRB in mice supports the notion that human hyperekplexia with no detectable mutations in GLRA1 may harbor mutations in GLRB. Clonazepam, a gamma aminobutyric acid (GABA) receptor agonist, is highly effective and is the drug of choice. It enhances the GABA-gated chloride channel function and presumably compensates for the defective glycine-gated chloride channel in hyperekplexia. Recognition of the disease will lead to appropriate treatment and genetic counseling.

Abstract: Muscle biopsy was examined in 20 children with cerebral palsy, using immunohistochemical methods for marker of denervation neural cell adhesion molecules (N-CAM) in addition to standard techniques. Histological and histochemical study showed mild myopathic changes, type 1 predominance, and type 1 and type 2 hypotrophy, in accord with previous observations. Immunohistochemical study showed N-CAM expression in most biopsies (15/20), usually in scattered fibers, whereas in four patients aged less than 6 years it was expressed in grouped fibers. Our study supports the hypothesis of motor unit remodeling as a consequence of spasticity, especially in early phases of the disease.

Abstract: Rhythmic movement disorder (RMD) is classified as a sleep–wake transition disorder. However, some RMD patients show rhythmic movements during rapid-eye-movement (REM) sleep, during which muscle activity is completely absent. In order to determine the sleep stages in which episodes of RMD occur, we investigated two children with RMD by means of polysomnography, and also summarized the polysomnographic reports on patients with RMD. We also quantified the REM sleep atonia in our patients using the tonic and phasic inhibition indices (TII and PII). In addition, to examine the involvement of the basal ganglia in RMD patients, we studied the frequency of gross movements (GMs) during sleep in each sleep stage. Both patients showed rhythmic movements in all sleep stages, i.e. including REM sleep. Few rhythmic movements occurred during sleep–wake transition periods. Both patients showed normal TII and PII scores as well as a normal pattern for the sleep stage-dependent modulation of GMs during sleep. Eighteen of the 33 reported RMD patients, including ours, experienced episodes during REM sleep, while the other 15 patients had no episodes during REM sleep. Among the 18 patients who had episodes during REM sleep, eight experienced the episodes exclusively during REM sleep. It is unlikely that the neuronal mechanisms that underlie RMD episodes were the same in the 15 patients who had no RMD episodes during REM sleep and the eight who had them only during REM sleep. We propose that RMD can be divided into several subgroups according to the differences in the underlying neuronal mechanisms.

Abstract: The aim of the study was to assess early neuromotor development in 20 congenitally blind or severely visually impaired children, nine without (B) and 11 with associated handicaps (B + H), in order to develop a strategy for early intervention in these subjects. The mean age at first observation was 11.4 months (range: 4-30 months). The mean follow-up duration was 16.9 months (range: 3-36 months). Assessment included developmental history, neurological examination, video-recording of spontaneous activity and administration of the Reynell-Zinkin Scales and neuroradiological and neurophysiological investigations. All B children walked independently (mean age 19.8 months) and 55.5% crawled (mean age 15 months); the B + H subjects displayed absence of almost all neuromotor functions, except one who walked at 20 months. All the B and just one (9%) of the B + H children developed satisfactory fine motor abilities. 'Reach on sound' at distance was achieved by all the B children by the age of 14.2 months while in the B + H group it was achieved by only two subjects at a median age of 19.5 months. We conclude that it is possible to describe the profile of neuromotor development in B and B + H children; strategies to help postural-motor development and 'reach on sound' appear to be fundamental in early intervention in these subjects.

Abstract: We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24-72 months (median of 47 months), six (43%) were seizure-free, six achieved>90% reduction, one achieved 50-90% reduction, and one achieved 0-50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring >50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring <10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50, two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion.

Abstract: Magnetic resonance imaging (MRI) has had an enormous impact on the practice of medicine, and especially, on the clinical neurosciences. One area in which MRI has had a particularly large impact has been on the analysis and understanding of cerebral malformations. This manuscript describes the manner in which MRI in conjunction with modern molecular biology has helped to shed new light on our understanding and classification of cerebral malformations.

Abstract: Data on features of regression and pre-regression developmental history in a case series of 53 girls and women with Rett syndrome are presented. Consistent with the diagnostic criteria, hand skills and verbal or non-verbal communication skills were the most common skills lost during regression. Play and motor skills were also lost in half the cases. Regression most commonly occurred between 12 and 18 months of age but was noted in a few cases before 6 months or after 36 months. Pre-regression developmental delays or abnormalities were noted in over two-thirds of cases, increasing to 85% of the youngest cases where parental reporting was likely to be more accurate. Age at regression was not associated with severity of physical and growth symptoms, and thus did not appear to be an index of neurological severity. There is a continuing need to further elucidate the pre- and post-regression features of Rett syndrome in order to aid early identification, diagnosis and referral for genotype mutation analysis.

Abstract: To search for the origin of frontal lobe dysfunction identified by the Wisconsin card sorting test (WCST) in temporal lobe epilepsy (TLE) patients, we investigated the WCST performance among 19 children with TLE (with hippocampal atrophy (HA group N=12), without structural lesions (NSL group N=7)), 15 patients with frontal lobe epilepsy (FLE group), and age-matched normal controls (N group). The paired verbal association learning test (PVALT) and Benton visual retention test (BVRT) were also performed. HA group and FLE groups achieved significantly fewer categories and demonstrated more perseverative errors on the WCST than NSL and N groups. In addition, category achievement in WCST showed significant inverse correlation to age at the initial status convulsivus in the HA group (P 0.05). Thus, the frontal lobe dysfunction in the HA group is found to exist as early as 7 years old, when they seem to have only a short seizure history or to receive a little electrical interference from the temporal lobe focus to the frontal region. These facts would underscore the importance of prefrontal dysfunction persisting from the early insults and only becoming apparent after maturation of the prefrontal region in patients with mesial TLE.

Abstract: We report a 4-year-old child who developed hemiplegia 6 months after varicella-zoster virus (VZV) infection. Cerebral angiography showed complete occlusion of the right middle cerebral artery with basal moyamoya vessels. Elevation of anti-VZV antibody in the cerebrospinal fluid indicated central nervous system involvement. The association between VZV cerebral angitis and unilateral occlusion of right middle cerebral artery is discussed.

Abstract: The aims of the study were to compare the clinical types, electroencephalogram (EEG) and cranial magnetic resonance imaging/computed tomography findings of epileptic and non-epileptic cerebral palsy (CP) patients. Seventy-four patients with CP were evaluated in 2 years. Tetraplegic CP had a higher incidence of epilepsy (60.5%). EEG was confirmed abnormal in epileptic CP as 90.3%, and in non-epileptic CP as 39.5%. Focal epileptiform activity, generalized slowing, and multifocal epileptiform activity were significantly frequent in epileptic CP. There were cranial imaging abnormalities of 74.2% in epileptic and 48.8% in non-epileptic CP. Although there was not any statistically significant difference between the two groups, epileptic group revealed more structural abnormalities. Further studies concerning a possible risk of epilepsy development and its relations with the EEG and cranial imaging findings are needed in presenting the other risk factors involved and the factors affecting the CP prognosis.

Abstract: We examined three autopsy cases of globoid cell leukodystrophy (GLD) with different survival, using immunohistochemistry and in situ nick end labeling (ISEL). The white matter lesion was pronounced in the corona radiata, corpus callosum and cerebellar peduncles in three cases, where a spongy state developed, in addition to the neuronal loss in the thalamus, cerebellum and inferior olivary nucleus. Ramified microglia, being immunoreactive for ferritin and HLA-DR alpha, were scattered in the white matter, and some of them also had immunoreactivity for TNF-alpha. Both the small-sized and large-sized globoid cells showed immunoreactivity for ferritin KP-1 and NCAM, while some of the small-sized globoid cells were also immunoreactive for HLA-DR alpha and TNF-alpha. As the survival became longer, the occurrence of the globoid cells decreased, however, they were commonly observed in the corpus callosum and cerebellar peduncle in three cases. T lymphocytes immunoreactive for LCA, UCHL-1 and CD3 were increased around the vessels in the white matter. ISEL stained nuclei of mononuclear cells in the white matter in two cases with short survival, although the cell origin was not verified. ISEL also visualized a few nuclei of the small-sized globoid cells in one case. On the other hand, immunostainings against cell death proteins such as bcl-2 family members and p53 failed to identify any significant changes. These data suggest that the immunological step and to a lesser extent the apoptotic process may partly be involved in the myelin breakdown and glial pathology in GLD, as reported in the twitcher mouse, a murine model of GLD.

Abstract: This study was performed to assess the predictive value of ultrasonography and electroencephalography (EEG) in order to identify infants with periventricular leukomalacia (PVL) during the early neonatal period, especially non-cystic cases, and to clarify the combination of ultrasonographic and EEG findings that are the most useful. We studied 288 eligible infants, whose gestational ages ranged between 27 and 32 weeks. PVL was observed in 49 infants (26 cystic PVL and 23 non-cystic PVL). On ultrasonography, 31 infants with PVL were detected on the basis of definite periventricular echodensity (PVE). Thirty-seven infants had at least one of equivocal or definite PVE or cystic changes, but the other 12 did not have any of them. The sensitivity and specificity were 0.76 and 0.81, respectively. In EEG findings, acute stage abnormalities (ASA) of grade II or more were recognized in 31 infants with PVL. The sensitivity and specificity were 0.63 and 0.91, respectively. Equivocal or definite chronic stage abnormalities (CSA) were seen in 43 infants, the sensitivity and specificity being 0.88 and 0.84. The sensitivity of CSA was higher than that of ASA, and the specificity of ASA was higher than that of CSA. When these EEG findings were combined, 45 infants with PVL were detected. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.92, 0.77, 0.45, and 0.98, respectively. Moreover, ultrasonographic and EEG findings were combined, 46 out of the 49 infants with PVL were detected with a sensitivity of 0.94 and a specificity of 0.64. The results indicated that EEG may be suitable for detecting infants at risk for development of PVL on the basis of its high sensitivity, and ultrasonography may be useful for confirming the presence of PVL on the grounds of its high specificity. Appropriate use of these measurements will make an early diagnosis of infants with PVL possible, even in non-cystic cases.

Abstract: Genetic defects have been recently identified in certain inherited epilepsy syndromes in which the phenotypes are similar to common idiopathic epilepsies. Mutations in the neuronal nicotinic acetylcholine receptor 4 and 2 subunit genes have been detected in families with autosomal dominant nocturnal frontal lobe epilepsy. Both receptors are components of neuronal acetylcholine receptor, a ligand-gated ion channel in the brain. Furthermore, mutations of two K+-channel genes were also identified as the underlying genetic abnormalities of benign familial neonatal convulsions. Mutations in the voltage-gated Na+-channel 1, 2 and 1 and the gamma aminobutyric acid (GABAA) receptor 2 subunit genes were found as a cause of generalized epilepsy with febrile seizures plus, a clinical subset of febrile convulsions. Na+-channels, GABAA receptor and their auxiliaries may be involved in the pathogenesis of this subtype and even in simple febrile convulsions. Mutation of a voltage-gated K+-channel gene can cause partial seizures associated with periodic ataxia type 1 and some forms of juvenile myoclonic epilepsy and idiopathic generalized epilepsy can result from mutations of a Ca2+-channel. This line of evidence suggests the involvement of channels expressed in the brain in the pathogenesis of certain types of epilepsy. Our working hypothesis is to view certain idiopathic epilepsies as disorders of ion channels, i.e. 'channelopathies'. Such hypothesis should provide a new insight to our understanding of the genetic background of epilepsy.

Abstract: We report on two patients with congenital cytomegalovirus (CMV) infection asymptomatic at birth that was diagnosed retrospectively by polymerase chain reaction (PCR) of CMV DNA using blood stored on Guthrie cards. Neuroimaging studies showed abnormal myelination without any gray matter abnormalities. In the differential diagnosis of patients with abnormal white matter lesions and sensorineural hearing loss, one should consider congenital CMV infection. When investigating the etiology of patients with behavioral problems, migrational disorder, or white matter disease, PCR analysis of CMV DNA using blood stored on Guthrie cards might be helpful.

Abstract: A clinical survey of Japanese patients with mitochondrial fatty acid β-oxidation and related disorders (FAODs) was performed with questionnaires sent to 187 institutions, where inborn errors of metabolism could be managed in Japan, including a search of related literature published between 1985 and 2000. Sixty-four patients with ten types of FAODs were found. Carnitine palmitoyltransferase 2 deficiency and glutaric aciduria type 2 were most common (17 and 14 patients, respectively). As of 2000, there were no patients with medium-chain acyl-CoA dehydrogenase deficiency, which is common in Caucasians. Age at onset was under 2 years in 38 (59%) of the patients. Eight (13%) patients had neonatal onset. Twenty-one (55%) of the 38 children with an initial attack under 2 years of age had acute encephalopathy or a Reye syndrome-like illness. Half of the patients presented within 2 years of birth died or were handicapped. On the other hand, 19 (79%) of the 24 with onset after 2 years of age had muscle symptoms and 23 (96%) of the 24 grew and developed normally. Though the precise incidence of FAODs in Japan is still unknown, as a consequence of the development of diagnostic procedures the number of FAOD cases being diagnosed appears to have increased. Mass screening for FAODs during the neonatal period will greatly aid in prevention of attacks and related effects.

Abstract: Carrier detection for 12 women and prenatal diagnosis for six fetuses in Japanese families with a patient with Menkes disease (MNK) were performed by gene analysis and/or measurement of the copper concentration in cultured cells. Six out of eight mothers of MNK patients were carriers while two (25%) were not carriers. Two unrelated patients showed the same mutation (R986X): one patient's mother was a carrier while the other was not. One male and three female fetuses did not have the same mutant allele as the respective MNK proband and have been healthy since birth. One female fetus had the same mutant allele as her affected brother. Gene analysis is very useful and reliable, although such examination is only indicated in families in which a mutation has been identified. In one family in which a mutation in ATP7A was not found, cultured amniocytes from a male fetus had a high copper concentration. Thus after his birth, the biochemical findings confirmed the presence of MNK and early treatment was started. As his early treatment with parenteral copper-histidine prevented the neurological disorders effectively, prenatal diagnosis is very important.

Abstract: The prevalence of cerebral palsy (CP) in 6-year-old children in Shiga Prefecture, Japan, born between 1977 and 1991, was compared in three successive 5-year periods: period I (1977-1981), period II (1982-1986) and period III (1987-1991). Data on the accumulated age-specific prevalence of CP were collected and analyzed. During the study period, 242293 children entered elementary school, and 325 cases (194 boys, 131 girls) of CP were ascertained in Shiga Prefecture. The overall prevalence of CP per 1000 6-year-old children was 1.34. The prevalence of CP for 6-year-old children increased from period II to period III, although it did not vary from period I to period II. The proportion of low birth weight (LBW) infants and preterm infants among those with CP increased with time during the study periods. The prevalence of CP in infants born at term and with birth weight > or =2500 g did not vary over the study period. The prevalence of CP in preterm and LBW infants, especially in infants with gestational age<32 weeks and birth weight<1500 g, increased from period II to period III, while the prevalence did not increase from period I to period II. Multiple births and use of mechanical ventilation increased from period II to period III. The changes in the prevalence of CP in Shiga Prefecture may have been due to increased survival of preterm and LBW infants in period II owing to better obstetric and neonatal care, and to further improvement in the survival of very small babies receiving intensive care, which increased the prevalence of CP in period III. Further improvement of perinatal care might decrease the incidence of CP in Shiga Prefecture in the future.

Abstract: Childhood autism is a developmental disability of unknown origin with probable multiple etiologies. The purpose of this study was to compare the changes of regional cerebral blood flow (rCBF) in autistic and non-autistic controls, and to determine the relationship between rCBF on 99m Tc-hexamethylpropylene amine oxime (HMPAO) brain SPECT and the scores of the Ritvo–Freeman Real Life Rating Scale (RLRS), IQ levels, and age of autistic children. Eighteen autistic children (four girls, 14 boys; mean age: 6.13±1.99 years) and 11 non-autistic controls (five girls, six boys, mean age: 6.5±3.39 years) were examined using 99m Tc-HMPAO brain SPECT. All the children satisfying DSM-IV criteria for autistic disorder were taken into evaluation, and scored by the Ritvo–Freeman RLRS. IQ levels of these children were determined by Goodenough IQ test. Six cortical regions of interest (ROIs; frontal (F), parietal (P), frontotemporal (FT), temporal (T), temporo-occipital (TO), and occipital (O)) were obtained on transaxial slices for count data acquisition. The ratio of average counts in each ROI to whole-slice counts for the autistic children was correlated with the scores of Ritvo–Freeman RLRS. Hypoperfusion in rCBF in autistic children compared with the control group were identified in bilateral F, FT, T, and TO regions. We found no relationship between rCBF on 99m Tc-HMPAO brain SPECT and the scores of the Ritvo–Freeman RLRS. There was a relationship between bilateral F regions perfusion on 99m Tc-HMPAO brain SPECT and the age of autistic children. There was also a negative correlation between IQ levels and the scores of sensory responses, social relationship to people, and sensory-motor responses. Our results suggest that 99m Tc-HMPAO brain SPECT is helpful to locate the perfusion abnormalities but no correlation is found between rCBF on 99m Tc-HMPAO brain SPECT and the scores of Ritvo–Freeman RLRS.

Abstract: A 12-month-old boy with progressive cranial nerve palsies followed by ventilatory failure demanding artificial ventilation, generalized muscle weakness, and rapid progression to death at the age of 21 months is described. The patient had normal early development and also apparently normal hearing at presentation of illness but, after 6 months of the onset of the disease, hearing loss was documented by brainstem auditory evoked potentials (BAEP). Although the initial clinical and laboratory findings of this infant could fit with the diagnosis of progressive childhood bulbar palsy or Fazio-Londe (FL) disease, the subsequent appearance of hearing loss suggests that this patient represents a case of progressive bulbar palsy with perceptive deafness or Brown-Vialetto-Van Laere (BVVL) syndrome. To our knowledge, this case of BVVL syndrome with severe clinical features and rapid deterioration leading to death is the youngest one reported in the literature. Furthermore, this case emphasizes the need for repeated auditory examinations, including the performance of BAEP in all cases, especially infants and young children with progressive bulbar palsy.

Abstract: We present an autopsy case of ornithine transcarbamylase (OTC) deficiency with grumose degeneration in the dentate nucleus of the cerebellum. The patient had intractable neonatal convulsions and hyperammonemia from the 3rd day after birth. Diagnosis of OTC deficiency was made based on null activity of the enzyme and four-base deletions in exon 9 of the OTC gene. Death was due to sepsis as well as disseminated intravascular coagulation at 1 year and 2 months of age. Neuropathology showed multiple cystic changes and ulegyria in the bilateral frontal and parietal lobes. Multiple cysts were associated with the region, which was infiltrated with macrophages surrounded by astroglia showing palisading pattern. Ferrugination was marked in the thalamus and severe neuronal loss with astrogliotic change in the CA1-2 area of the hippocampus. Grumose degeneration was noted in the dentate nucleus of the cerebellum. This is the first report of grumose degeneration in OTC deficiency.

Abstract: To evaluate central nervous system functioning involvement in nocturnal enuresis, P300 and N200 event-related brain potentials and brainstem auditory-evoked potentials (BAER) were assessed in a group of 35 enuretic boys aged 7-9 years. The measurements of enuretic group were compared to those of age and sex matched non-entireties. P300 latency in the enuretic group was significantly longer than in non-enuretic group (420 ms at parietal scalp (Pz), 414 ms at central scalp (Cz) versus 386 ms at Pz, 376 ms at Cz; P < 0.01 and P < 0.01, respectively). Both enuretic and non-enuretic subjects were divided into three subgroups his age. There was no significant difference in terms of both P300 amplitude and N200 latency and N200 amplitude between non-enuretic age subgroups. But, P300 latency over central scalp in 8 years old non-enuretic subgroup was significantly longer than in 9 years old non-enuretic subgroup (P < 0.01). No significant difference was found in latency and amplitude of P300 and N200 latency between enuretic subgroups. However, N200 amplitude at Cz in 8 years old enuretic subgroup was significantly lower than both in 7 years old enuretic subgroup and in 9 years old enuretic subgroup (P < 0.01 and P < 0.01, respectively). There were significant topographical differences in latency and amplitude of P300 and in N200 latency in enuretic age subgroups, only. There was no significant difference in interpeak latencies I-III, I-V and III-V and wave latencies I, III and V of BAERs between enuretic group and non-enuretic subgroup. Longer interpeak and wave latencies of BAERs were found both in 8 years old enuretic subgroup and 8 years old non-enuretic subgroup. Conclusion: Longer P300 latency in primer enuretics compare to non-enuretics is an evidence of a maturational delay of central nervous system functioning.

Abstract: The serial MR image and MR spectroscopy in the brain were examined in a young male diagnosed as having juvenile Alexander disease. He had megalencephaly, psychomotor retardation, seizures, and increasing elevation of increasing alpha-B crystallin and heat shock protein 27 in the cerebrospinal fluid. Serial MR images demonstrated increased demyelination of the bilateral frontal region to left occipital region over several years. The myo-inositol/creatine ratio was significantly increased in both the demyelinated white matter and normal area in the MR spectroscopy. These results suggested that demyelination very slowly progressed from the frontal to occipital region and that glial degeneration may occur even in the unaffected white matter of patients with juvenile Alexander disease.

Abstract: This study was conducted to determine if alterations in hippocampal protein kinase C (PKC) gamma is one of the cellular mechanisms by which conventional antiepileptic drugs affect learning and memory. Wistar Rats (21-day-old) were divided into five groups: (1) control (no training and drugs); (2) training group (no drugs); (3) phenobarbital (PB) group; (4) carbamazepine (CBZ) group; and (5) valproate (VPA) group. A hippocampus dependent learning task (spatial changing learning) was used in the latter four groups lasting a total of 10 days. Correct responding rate of training group was significantly higher (P < 0.05) than in the PB, CBZ and VPA group. The PKC gamma staining intensity in hippocampal CA1-2 region of training group was significant greater than that of the control and PB group. There was no difference in staining intensities between the CBZ, VPA group or training group. The amount of PKC gamma located in plasma membrane of hippocampal neurons was significantly higher in the training group (P < 0.05) than the control, PB and VPA groups. No differences were found between the training and CBZ group. Lastly, the amount of PKC gamma in cytosol of hippocampus did not significantly differ between any of the five groups. These results indicate that the three antiepileptic drugs used in this study all disturbed the spatial learning of immature rats. Spatial learning was concomitant with activation of PKC gamma in hippocampal neurons. PB and VPA likely adversely affect learning and memory by interfering with PKC gamma activation, whereas CBZ may act by a different mechanism, possibly in the post-translocation process or by a PKC gamma independent pathway.

Abstract: Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome characterized by development of unusual tumor-like growths. Involvement of the brain is associated with the most problematic clinical manifestations of TSC, including intellectual retardation, epilepsy and abnormal behaviors. Until now, over 300 mutations of TSC1 and TSC2 were reported. Here, we report one novel mutation of TSC1 (Q897X) and five novel mutations of TSC2 (c.336+1 G>A, L345R, E700K, R905G, K914K) identified in Japanese patients with TSC. We also identified three new polymorphisms in TSC2 (N331N, A431A, S802G). The TSC1 mutation was predicted to cause a nonsense substitution whereas all of the five TSC2 mutations were predicted to cause either a splicing error or a missense substitution. In accordance with previous findings, the patients with TSC1 mutations had milder clinical manifestations than those with TSC2 mutations.

Abstract: A severely handicapped 14-year-old Japanese girl had epilepsy and was treated with sodium valproate (SV) from the age of 7 years. Although the epileptic seizures were well controlled, she sometimes had a fever and hypokalemia from the age of 13 years. Laboratory examinations revealed metabolic acidosis, hypouricemia, hypophosphatemia, glycosuria, proteinuria and aminoaciduria, thus suggesting Fanconi syndrome. Gallium scanning showed marked renal uptake. A renal biopsy revealed interstitial nephritis without immuno-deposition. SV was replaced since it was considered to be the most probable cause of the renal involvement. Thereafter, she showed marked improvement of the clinical symptoms and the laboratory data gradually, and she never had a fever. Although SV is an effective anti-epileptic drug, we have to pay attention to adverse renal effects such as Fanconi syndrome and interstitial nephritis.

Abstract: We report a 1-year-old girl with a type I Chiari malformation who presented with sleep apnea syndrome. Our patient experienced a change in characteristics of sleep apnea from obstructive to central after adenoidectomy was performed under general anesthesia. The patient also developed dysphagia, which worsened after adenoidectomy. Both disorders greatly diminished after posterior fossa decompression. Our results suggest that type I Chiari malformation should be considered in children with sleep apnea syndrome even when obstructive characteristics predominate. When the malformation is present, timely surgery can prevent irreversible neurologic damage.

Abstract: To study the electroclinical characteristics of patients with childhood-onset epilepsy who showed polymicrogyria (PMG) on MRI, we classified 15 patients according to the location of PMG on MRI. The composition of the subjects was as follows: four patients with PMG in both hemispheres; three with localized PMG in one hemisphere associated with other lesions such as porencephaly; and eight with only localized PMG in one hemisphere. We investigated the electroclinical characteristics of the epileptic syndromes associated with these different types of PMG. Four patients suffered from infantile spasms during their clinical course. Five patients suffered from epilepsy with electrical status epilepticus during slow sleep (ESES) and ESES-related epilepsy. The other six patients had only localization-related epilepsy throughout their clinical course. Patients with PMG in both hemispheres, and localized PMG in one hemisphere associated with other lesions tended to have early-onset intractable seizures, especially infantile spasms. On the other hand, patients with only localized PMG in one hemisphere had ESES and ESES-related epilepsy or localization-related epilepsy, and their seizure prognosis was relatively favorable. These findings are useful in predicting the outcome of patients with PMG.

Abstract: Four patients with leukoencephalopathy with vanishing white matter from three unrelated Brazilian families are reported. In all cases the initial symptoms occurred in the three first years of life. In three cases the onset was acute and at least in two patients the involvement of the white matter preceded the clinical symptoms. Only cerebellar and pyramidal signs were present and persisted throughout the evolution. An episodic course with worsening of the symptoms during febrile illnesses was noted in one patient. In three patients a significant deceleration of the head growth was noted. In one family, brother and sister were affected but the twin brother of the boy was free from the disease. In another family, the patient had a sister who died at 13 years of age from an identical disease not diagnosed at that time. In one family, the parents were first cousins. In all patients, serial magnetic resonance imaging and magnetic resonance spectroscopy showed the characteristic picture of the involvement of the white matter with increasing signal intensity close to that of the cerebrospinal fluid.