Increase of ceramide monohexoside and dipalmitoyl glycerophospholipids in the brain of Zellweger syndrome.

The lipid composition and molecular species of phospholipids were examined in the brain of a patient with Zellweger syndrome (ZS), and were compared with those of control infants. In the cerebral gray matter of the ZS patient, the amounts of ceramide monohexoside and cholesterol ester were larger than those of controls. By contrast, the amount of ceramide monohexoside in the white matter was smaller in the ZS patient than that in the age-matched control. Although the amount of phosphatidylcholine (PC) plus phosphatidylserine (PS) was the same, dipalmitoyl PC and PS were increased in both the gray and white matter of the ZS cerebrum. These alterations in the molecular species of brain lipids may play crucial roles in the pathogenesis of ZS.

Alterations in the molecular species of plasmalogen phospholipids and glycolipids due to peroxisomal dysfunction in Chinese hamster ovary-mutant Z65 cells by FABMS method.

Changes in the molecular species of lipids associated with Pex2 gene-mutation were investigated to elucidate the pathogeneses of peroxisome biogenesis disorders. Although no differences were observed in the concentrations of cholesterol and phosphatidyl choline between mutated Z65 and control CHO-K1 cells, the amounts of cholesterol esters and glycolipids in Z65 cells were twice those in CHO-K1 cells, but phosphatidyl ethanolamine (PE), particularly 1-O-octadec-1'-enyl-2-oleoyl PE, was absent in Z65 cells by FABMS. Enhanced synthesis of glycolipids in Z65 cells was associated with an abundance of lignoceric acid-containing ones, suggesting a role of glycolipids in the retention of longer saturated fatty acids.

[Non-verbal learning disabilities].

In 1975, Myklebust proposed a special form of learning disabilities characterizes by impairment of spatial cognition, social interaction and conceptualization, and named it as non-verbal learning disabilities (NLD). Since the brain locus for spatial cognition was thought to be localized in the right hemisphere, NLD was regarded as a disorder of the right hemispheric function. The clinical characteristics of NLD are almost identical to those of Asperger syndrome (AS), which was introduced in English literature in 1981. Since Asperger syndrome is regarded as one of the autistic spectrum disorders, and autism was once regarded as the left hemispheric dysfunction, it has long been believed that NLD and AS are clinically different entities. However, their clinical similarities have raised a growing opinion that these two disorders are probably identical or at least closely related.

Influence of sleep-onset time on the development of 18-month-old infants: Japan Children's cohort study.

OBJECTIVE: We report here the influence of sleep patterns on the development of infants in Japan. A total of 479 infants were registered in two different Japanese cities. Direct neurological observations were performed by licensed pediatric neurologists. METHOD: We designed a prospective cohort study and identified the sleep factors of children showing atypical development. The Kinder Infant Developmental Scale (KIDS) was used to evaluate the infant developmental quotient (DQ); we also applied a neurobehavioral screening battery. Neurobehavioral observations in 18-month-old infants were designed to check all developmental categories within the three areas of motor function, language, and social function. Based on the observations, each infant was classified as having "atypical development" or "typical development". RESULT: We found that later sleep onset time (>22:00 h), and longer naps during the day each had significant positive correlations with atypical development patterns in 18-month-old infants. For each hour the infant sleep-onset time extended past 22:00 h, the infants showed worse neurodevelopmental outcomes, at an odds ratio increase of 2.944. CONCLUSION: Although our results may be confounded by sleep problems resulting from pre-existing developmental disabilities, we can safely conclude that appropriate sleeping habits are important for healthy development in 18-month-old infants.

Increased right auditory cortex activity in absolute pitch possessors.

We recorded the auditory-evoked magnetic fields from children and adults with absolute pitch during the following tasks: (1) hearing 1000 Hz pure tones inattentively, (2) hearing eight random tones inattentively and (3) listening to eight random tones and identifying each tone. In children with absolute pitch, there was no significant positive correlation between the appearance rate of N100m and the kinds of tasks. In adults with absolute pitch, only the right N100m dipole moments increased significantly in tasks (1) and (2). The present results suggest that the circuit for labeling in the right auditory cortex may lose a function from childhood to adulthood, which reveals neuroplasticity in the development of absolute pitch ability.

Severe gastrointestinal dysmotility in a patient with congenital myopathy: causal relationship to decrease of interstitial cells of Cajal.

Interstitial cells of Cajal (ICC) are known to be essential regulators of gastrointestinal (GI) motility. Here, we report the clinical course and abnormalities of intestinal ICC distribution in a 5-year-old patient with congenital fiber type disproportion myopathy who demonstrated long-term GI dismotility. Full thickness biopsies of the small intestine and colon showed a normal enteric muscle layer and myenteric plexus. However, the density of ICC was strikingly decreased around the myenteric plexus compared to that in autopsied cases without GI tract disease. These findings suggest that a decline in ICC may contribute to disturbed GI motility in our patient with congenital myopathy.

A magnetoencephalographic study of negative myoclonus in a patient with atypical benign partial epilepsy.

PURPOSE: To clarify the neurophysiological mechanism of epileptic negative myoclonus (NM) of a patient with atypical benign partial epilepsy whose NM was completely suppressed with ethosuximide. METHODS: Polygraphic recordings of whole-head type magnetoencephalography (MEG), EEG and electromyography were made during NM of the bilateral hands. The silent period of 200-400 ms duration in the bilateral biceps muscles was associated with paroxysmal spikes on EEG and MEG. Single equivalent current dipoles (ECD) were calculated for each spike component associated with NM and the estimated generator sources of spikes were superimposed on the patient's head MRI. RESULTS: The magnetic fields of each peak associated with NM showed clear single dipole pattern and ECDs of each peak were located in the neck and orofacial division of the primary motor cortex. CONCLUSIONS: Abnormal firing of the neck and orofacial division of the primary motor cortex was associated with NM generation. Taking the beneficial effect of ethosuximide (a T-type Ca2+ channel blocker in thalamic neurons and the corresponding cortex) and the MEG result together, it is suggested that abnormal interaction of the thalamo-cortical network might be closely related to the pathogenesis of NM.

Efficacy and safety of immunization for pre- and post- liver transplant children.

BACKGROUND: Infection is a serious complication after liver transplantation. Immunization is one means of controlling infections. The objective of this study was to investigate the efficacy and safety of simultaneous administration of several vaccines before transplantation and the efficacy and safety of administration under immunosuppressive conditions after transplantation. METHODS: Fifty-eight patients who underwent living-related liver transplantation between April 1994 and March 2000 were included in this study. Simultaneous administration of a maximum of six vaccines was performed in a short period of time before transplantation. We also readministered vaccines to 15 patients with waning antibody titers after transplantation from June 1999. We investigated whether patients could seroconvert for measles, rubella, mumps, and varicella after immunization and how long antibody titers could be retained by measuring them several times throughout the period before and after transplantation. We also examined side effects caused by immunization. RESULTS: The rates of seroconversion against measles, rubella, mumps, and varicella after the pretransplantation vaccination were 82%, 100%, 90%, and 95%, respectively. The rates of reseroconversion against measles, rubella, mumps, and varicella after the posttransplantation revaccination were 85%, 100%, 100%, and 71%, respectively. Although antibody titers against these viruses generally waned with time, no patient exhibited any serious illness or side effects. CONCLUSION: Although 12 of 58 patients (21%) had an infection, pretransplantation immunization was effective to prevent serious illness, especially for the 6 months after transplantation. Posttransplantation live-vaccine administration under immunosuppressive conditions is effective and safe.

Children are sensitive to averted eyes at the earliest stage of gaze processing.

Event-related responses to a face with forward gaze or averted gaze (gaze task) and two equiluminous mosaic images (mosaic task) were recorded from healthy children aged 8-12 years and adults, using MEG and EEG. In children, a clear occipito-temporal magnetic field activity (P1m, around 140 ms) was observed bilaterally, and the right P1m amplitude was increased when viewing a face with averted gaze compared with that when viewing a face with forward gaze. This effect was not observed in adults. Furthermore, the source for the right P1m in children in the gaze task was mainly located around the putative human MT/V5 area. These data suggest that the early occipito-temporal brain response observed as the P1m is a gaze-sensitive component in children.

N100m in adults possessing absolute pitch.

We recorded the auditory evoked magnetic fields from adults with and without absolute pitch under the following conditions: hearing 1000 Hz pure tones inattentively (single tone session) and listening to eight random tones and identifying each tone (labeling session). In the adults with absolute pitch, the bilateral N100m dipole moments increased significantly in the labeling session. While, in the adults without absolute pitch, the left N100m dipole moment alone increased in the labeling session. These results suggest that the adults with absolute pitch execute the labeling task in the bilateral auditory cortices with interhemispheric cooperation, which does not operate in the adults without absolute pitch.

N100m in children possessing absolute pitch.

We recorded the auditory evoked magnetic fields from children with and without absolute pitch under the following conditions: (a) hearing 1000 Hz pure tones inattentively, (b) hearing eight random tones inattentively and (c) listening to eight random tones and identifying each tone. We calculated the appearance rate of N100m as the ratio of the subjects who had N100m. There was a significant positive correlation between the appearance rate of N100m and age in both groups. There was also a significant positive correlation between the appearance rate of N100m and the kinds of the task only in children without absolute pitch. These results suggest that, in the children with absolute pitch, N100m was elicited equally in every session because of their automatically driven auditory attention. No significant correlation was found between the appearance rate of N100m and the possession of absolute pitch.

People with absolute pitch process tones with producing P300.

We recorded a P300 component of event-related potentials associated with auditory oddball tasks in nine absolute pitch (AP) possessors and seven non-AP possessors. The previous studies demonstrated that AP possessors did not appear to employ working memory during auditory oddball tasks because they have a fixed tonal template in their memories. However, the present findings showed that the AP possessors exhibited similar P300 as the non-AP possessors and did update the tonal context in the auditory oddball tasks. This result suggests that the AP possessors do not always refer to the fixed tonal template in their memories when executing the oddball tasks and they employ working memory properly according to the difficulty of the auditory tasks.

Magnetoencephalographic analysis of rolandic discharges in a patient with rolandic epilepsy associated with oromotor deficits.

The purpose of this study was to clarify the neurophysiologic basis of oromotor deficits in a patient with atypical rolandic epilepsy. We investigated magnetoencephalographic analysis of rolandic discharges with right predominance before and during clonazepam therapy. Before clonazepam administration, current sources of rolandic discharges were broadly distributed in the secondary sensory cortex, superior temporal gyrus, and parietal association area in addition to hand and orofacial division of the primary somatosensory cortex. During clonazepam therapy, oromotor deficits were improved, along with a decrease in rolandic discharge, and current sources of residual right-sided rolandic discharges were shifted to the right superior parietal lobule. Taking the clinical course and magnetoencephalographic findings together, the distributed rolandic discharge focus might be closely related to oromotor deficits, and clonazepam was effective for the disorder.

Beneficial effect of L-arginine for stroke-like episode in MELAS.

We here reported the clinical course and therapeutic details of a 16-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who had had five stroke-like episodes (two episodes were clinically mild, while the three subsequent episodes were severe). Among the three episodes, the symptoms improved earliest and magnetic resonance spectroscopy abnormality was minimal when given L-arginine in addition to prednisolone, glycerol and edalavone. L-arginine administration during the acute phase of MELAS might be a potential therapy to reduce brain damage due to mitochondrial dysfunction.

A magnetoencephalographic study of astatic seizure in myoclonic astatic epilepsy.

To study the pathophysiologic mechanism of astatic seizures in a patient with myoclonic astatic epilepsy of early childhood, ictal magnetoencephalography was recorded and the neuronal pathway involved was analyzed. The patient was a 12-year-old female who developed myoclonic and astatic seizures including nodding and sudden falling at the age of 4. The current source of spikes during nodding attacks was located in the bilateral frontal area with left predominance, possibly in the premotor cortex. Although we could not claim, on the basis of our findings, that myoclonic astatic epilepsy of early childhood is a type of focal epilepsy, it seems likely that the premotor cortex might be more excitable than other areas. Thus we speculate that the functionally altered premotor-reticulospinal tract which normally controls postural adjustment might play an important role in the generation of myoclonic astatic seizures. Furthermore, the underlying mechanism in the brainstem seems to be common, at least in part, for infantile spasms when considering the efficacy of synthetic adrenocorticotropic hormone for nodding seizures.

Alterations of fatty acid metabolism and membrane fluidity in peroxisome-defective mutant ZP102 cells.

We investigated lipid composition and FA metabolism in Chinese hamster ovary CHO-K1) cells and Pex5-mutated CHO-K1 (ZP102) cells to clarify the biochemical bases of peroxisome biogenesis disorders (PBD). ZP102 cells have defective peroxisomes and exhibit impairments of peroxisomal beta-oxidation of FA and plasmalogen biosynthesis. In addition, we identified FA metabolic alterations in the synthesis of several classes of lipids in ZP102 cells. The concentration of FFA in ZP102 cells was twice that in CHO-K1 cells, but methyl esters and TAG were decreased in ZP102 cells in comparison with control cells. Also, ceramide monohexoside (CMH) concentration with ZP102 cells was significantly increased compared with the control cells. The FA molecular species, particularly the saturated to unsaturated ratios, of individual lipids also differed between the two cell types. The rate of incorporation of [14C]-labeled saturated acids into sphingomyelin (SM) and CMH in ZP102 cells was higher than that in CHO-K1 cells. Lignoceric acid incorporated into cells was predominantly utilized for the synthesis of SM at 24 h after removal of [14C]lignoceric acid from the culture medium. ZP102 cells showed higher fluorescence anisotropy of 1,3,5-diphenylhexatriene, corresponding to lower membrane mobility than in CHO-K1 cells. In particular, alteration of lipid metabolism by a Pex5 mutation enhanced metabolism of saturated FA and sphingolipids. This may be related to the reduced membrane fluidity of ZP102 cells, which has been implicated in the dysfunction of membrane-linked processes in PBD.

[A case of focal epilepsy associated with focal cortical dysplasia and crossed cerebellar diaschisis].

We here reported a 24-year-old woman who presented complex partial seizure from 15 years of age. Her brain MRI showed the right perirolandic focal cortical dysplasia (FCD) corresponding to the orofacial division of the primary sensori-motor area. On SPECT (Tc-99 mECD) study, hypoperfusion was demonstrated at the FCD, the right pons and the left cerebellum (crossed cerebellar diaschisis (CCD)). Magnetoencephalography disclosed the current source of the focal spikes was localized on the FCD. To our knowledge, no previous report of a case associated with FCD and CCD was found. We speculated the pathomechanism of the CCD might be related to the persistent epileptogenic firing which inhibited the cerebellar metabolism transsynaptically through cortico (FCD)-ponto-cerebellar pathway.