SPECT is a noninvasive functional neuroimaging method widely used even in child neurology because it can be easily implemented in routine clinical studies. Normal brain perfusion SPECT images in children change with brain maturation and differ from those in adults; for example, the blood flow is lower in the cerebellum than in the cerebrum. New methods have been developed to measure the cerebral blood flow without blood sampling and to perform statistical parametric mapping after spatial normalization of SPECT images to standard brain. They are applied to functional disorders such as autism and learning disorders. Neurotransmission imagings using SPECT are also available to visualize the benzodiazepine and dopamine systems; an early application of insurance is expected.

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Magnetic resonance (MR) is a remarkably versatile technology applicable to various aspects of medical science. Currently, there are three categories of MR techniques available for probing human brain function in detail. The first category comprises the most widely utilized techniques which make use of the metabolic effects of brain activation, represented by BOLD functional magnetic resonance imaging (fMRI). The second category of techniques deals with apparent diffusion tensor in probing the cellular aspects of brain function and is represented by three dimensional anisotropy contrast (3DAC) axonograpy. The third category of techniques is the oldest and as yet the most underutilized. These techniques which include MR spectroscopy (MRS) and spectroscopic imaging (SI), are based on classical nuclear magnetic resonance (NMR) spectroscopy and are capable of providing biochemical information in vivo. Because of its inherently noninvasive nature, MR technologies are especially important for the field of pediatric neurology and developmental neuroscience.

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The diagnosis, treatment, and prognosis of childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) were reviewed with reference to 94 patients with typical absence seizures (82 with CAE, 12 with JAE) and the literature. The patients were separated into two groups based on clinical features, ag at onset of seizures, and EEG findings. There has been much discussion on the age that represents the borderline between CAE and JAE. My view is that JAE begins with puberty, i. e. at around 10 years old. The treatment of choice for CAE is valproic acid (VPA). If the seizures are not controlled with VPA, add-on therapy with ethosuximide is recommended. For patients who respond poorly to these drugs, clonazepam in often effective. Lamotrigine, which is not yet commercially available in Japan, is effective when combined with VPA. As for school performance, some patients showed excellent results. However, about half of them performed weakly. Patients followed beyond 20 years were free of absence seizures in both groups, but suffered from GTCS which occurred sporadically in CAE as well as in JAE. The social prognosis in CAE and JAE may not be as good as we believed it to be.

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What can medicine contribute to learning disabled (LD) children? In this symposium, most distinguished speakers in Japan discuss the following issues: the incidence of LD in children with preterm birth, biochemical aspect in LD children, neurophysiological examinations for LD and speech therapy for specific reading disorders. Brain dysfunctions in LD children should be clarified to facilitate remedial interventions. It is expected that medical insurance supports LD children and their family.

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The term learning disability was first used in 1962 by Kirk S A in his textbook. In Japan the term was adopted as a substitute term for MBD in the 1970s. At present many professionals, especially on education and psychology, are interested with LD. The role of child neurologist is discussed here from threeviewpoint: the term and definition, LD as a brain dysfunction, and LD in the child neurology. For collaboration with education and psychology, child neurologist should know more about LD and make efforts to find the etiology and mechanism of LD.

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The purpose of this study was to characterize learning disability (LD) in low birth weight children (VLBW). Longitudinal mental development of VLBW without major handicap was investigated using several neuropsychological tests (ITPA, BGT, WISC-R) suitable for their ages. The tests at ages of 5-6 years demonstrated delays in visual perception and visual motor integration. In the school-age, impairments of language understanding and abstraction were suggested. The process of mental development in VLBW with LD was reported in detail on the cases requiring special education. Some cases with a pervasive developmental disorder (PDD) were also presented to show difference from LD.

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We investigated the relationship between a disorder of higher brain function and the area of reduced regional cerebral blood flow (rCBF) in learning disabled (LD) children. Subjects consisted of two LD children with a specific Kanji writing disorder, one with dyslexia and dysgraphia and two with a specific verbal semantic disorder. Neuropsychological assessment batteries were used to detect higher brain disorders, and single photon emission tomography to measure rCBF. We found that the area of reduced rCBF in LD children correspond to that in adults with an acquired brain damage showing similar symptoms. These results suggest that LD is caused by a localized brain dysfunction.

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To clarify the pathophysiology of learning disability (LD), we measured the urinary levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), and phenylethylamine (PEA) in urine samples collected in a 24 hour period. Findings were compared with those obtained in age-matched controls and diseased controls including patients with attention deficit-hyperactivity disorder (ADHD), infantile autism, and mental retardation. The mean urinary level of MHPG in LD (n=6) were not significantly different from those in ADHD (n=16), mental retardation (n=4), infantile autism (n=5), and the controls (n=6), while the mean urinary levels of PEA were significantly lower in LD (n=6, 91±17.3μg/mg) and in ADHD (n=5, 65±53.6μg/mg) as compared to age-matched controls (n=3, 340±264.5μg/mg) ANOVA, (p<0.05). PEA is considered to play an important role for the pathogenesis of LD and ADHD.

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In the present study, we developed a new event-related potentials (ERPs) stimulator system applicable to simultaneous audio visual stimuli, and tested it clinically on healthy adults and patients with learning disabilities (LD), using Japanese language task stimuli: hiragana letters, kanji letters, and kanji letters with spoken words. (1) The origins of the P300 component were identified in these tasks. The sources in the former two tasks were located in different areas. In the simultaneous task stimuli, a combination of the two P300 sources was observed with dominance in the left posterior inferior temporal area. (2) In patients with learning disabilities, those with reading and writing disability showed low amplitudes in the left hemisphere in response to visual language task stimuli with kanji and hiragana letters, in contrast to healthy children and LD patients with arithmetic disability. (3) To evaluate the effect of methylphenidate (10 mg) on ADD, paired-associate ERPs were recorded. Methylphenidate increased the amplitude of P300.

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The medical staff can serve learning disabled (LD) children by ruling out progressive and regressive diseases, and by treating concurrent disorders, such as attention deficit hyperactivity disorders (ADHD). Teachers and even some medical members in Japan have confused ADHD with LD. Although looking similar, these two disorders are completely different. We should further clarify the brain dysfunction in LD children, thereby contributing to remedial education.

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The efficacy of zonisamide (ZNS) was studied in 16 patients (11 males, 5 females) with West syndrome (WS), symptomatic in 13 and cryptogenic in 3. They did not respond to pyridoxal phosphate (12 cases) or valproate (16 cases). The mean age of onset of WS was 4.4 (2-9) months. ZNS was administered from 3 to 9 months of age (mean 6.1). Four cases (2 cryptogenic and 2 symptomatic) became seizure free. Two had more than 50% seizure reduction. Ten infants remained unchanged or showed less than 50% seizure reduction. In the 4 responders, the effective dose was 4-8 mg/ kg (mean 5.8), and the serum ZNS concentration was 10- 21μg/ml (mean 13.8). One had relapse of WS after 4 months. Three with normalized EEG remained seizure-free during the follow-up period (12-26 months). One case developed a transient drowsiness, but no serious side effects were observed. These data suggest ZNS may be regarded as a therapy of choice before synthesized ACTH therapy in the management of WS.

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Lissencephaly type I is a diffuse type of migration disorder that contains agyria and/or pachygyria on the brain surface. We experienced 5 cases of this disease and evaluated their electroencephalographic findings and seizure types based on the neuroradiological classification of lissencephaly.
Ages at seizure onset ranged from 2 months to 4 months (mean 3.2 months). The patients with complete agyria had generalized tonic seizures, and those with pachygyria partial seizures or tonic spasms. The characteristic findings of complete agyria in electroencephalogram were high-voltage alfa activity. The amount of high-voltage slow waves increased with the ratio of pachygyria on the brain surface. The appearance of multifocal spikes and sharp waves suggested irregular arrangement of pachygyria on the brain surface.

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Xeroderma pigmentosum has been known to result from disturbance in the repair of injured DNA caused by the ultra violet light. According to cell fusion studies, this disease is classified into 8 groups. Among these groups, group A (A-XP) shows the most severe type of neurological disturbance. Slowly progressive diffuse impairment both in the central and the peripheral nervous systems has been reported. Although hearing loss occurs in all the patients, few papers have described the chronological changes of this disability. This study aimed to clarify the development of audiological abnormalities in A-XP patients. We recorded auditory brainstem evoked responses (ABRs) in 20 Japanese children with A-XP. All patients had homozygous intron 3 splicing mutations of xeroderma pigmentosum group A complementing gene, the most common type mutations in Japan. ABR threshold, peak latency of 5th wave and the peak interval latency between the 1st and 5th waves (I-V interpeak latency) were measured, and were compared with those obtained from age-matched controls.
ABRs were well detected in all patients examined under 4 years old. The I-V interpeak latencies became shorter with age as in the controls. In 3 ears, the 5th wave was recorded without 1st wave. In 4 ears which no ABRs were detected with 90 dBHL stimulation, the only 5th wave was detected. No waves were obtained from the patients aged over 10 years.
The current study revealed that ABR disturbance in A-XP patients became obvious after 4 years of age. In addition, no ABR was found to be identified after 10 years of age. During 4 to 10 years of age, some patients showed the elevation of the threshold of the 5th wave. In A-XP patients, the peripheral nerve was hypothesized to be affected earlier than the central pathway involved in ABR.

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[in Japanese]

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[in Japanese]

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