An adaptive behavior scale for persons with profound intellectual disability was proposed. This scale consisted of 64 items from five areas interpersonal relationship, perception, expression, interest and play, and daily life. Each item was scored on a 0-2 scale. Forty-eight institutionalized persons (23 males, 25 females) with profound intellectual disability, aged 13-69 (mean 40) years, were examined with this scale. The rating for each item was 0.02-1.81 (mean 0.88). On 69% of the items, estimates were consistent between two care-staffs. The Cronbach's alpha value was calculated to be 0.97, indicating good internal consistency. On the whole, this scale is useful in assessing adaptive behaviors of the subjects.

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Recent studies have postulated that impairment of behavior inhibition, leading to executive dysfunction in future, is the fundamental pathophysiology of attention deficit/hyperactivity disorder (AD/HD). To evaluate this, we studied two saccadic eye movement tasks: visual-and memory-guided, in 8 children with AD/HD (combined type; mean age, 9.1 years, range 6-11 years) and 16 healthy children (mean age, 9.2 years, range 6-12 years). In the memory-guided saccade task, reflexive anticipatory errors were more frequently observed in AD/HD than in controls. The children with AD/HD showed longer response latency in the memory-guided saccade task, and greater coefficient of variation in both the latency and amplitude in both the tasks. These results suggested that saccade tasks, especially the memory-guided task, may be useful in clarifying pathophysiology of AD/HD.

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Moyamoya disease is a cerebrovascular disorder of unknown etiology. Its high incidence in East Asia and accumulation in family members suggest a genetic background. A high incidence of maternal inheritance implicates genomic imprinting in this disorder. Based on this hypothesis, we studied the association between moyamoya disease and IGF2R gene on chromosome 6, but found no evidence for such association between them. On the other hand, heterogeneous expressions of IGF2R were confirmed in the lymphocytes. Some individuals showed monoallelic expression and others showed biallelic expression.

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Moyamoya disease is a well-known cerebrovascular disorder of unknown pathogenesis affecting terminal portion of internal carotid arteries and causing ischemic attacks. Its familial occurrence suggests genetic background. We hypothesized that paternally imprinted gene might be associated with this disorder. To identify the expressed sequence tags (ESTs) with monoallelic expressions on chromosome 3, we used mouse A9 hybrid cells having human chromosome 3. Two ESTs showed only maternal expression in mouse A9 hybrid cells, and four showed non-expression in the lymphocytes derived from moyamoya patients. Although these ESTs are clustered on the same 150 kb region, we finally failed to identify c DNA in this region.

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We examined 50 children in high functioning pervasive developmental disorder (HFPDD) to study the comorbidity with other clinical disorders by questionnaires. Seventy-two percentage of them met the criteria for attention deficit hyperactivity disorder (AD/HD). The majority of the children had intelligence quotient less than 90. Learning problems, motor control problems, abnormal responses to sensory stimuli and anxiety disorder frequently coexisted in the children. Since clinical symptoms of HFPDD so diverse, it is possible that some children with HFPDD may be overlooked and diagnosed as having its coexisting disorders.

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Effects of milnacipran (MIL), a selective serotonin and noradrenaline (NA) reuptake inhibitor, on the neuronal excitability and synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular and whole-cell patch-clamp recording techniques. We compared MIL and methylphenidate (MPH), a selective NA and dopamine reuptake inhibitor, as a therapeutic agent for attention deficit/hyperactivity disorder. Application of MPH (1-100μM) and MIL (1-100μM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response in LC neurons in a concentration-dependent manner. Spontaneous firing of LC neurons was blocked during the hyperpolarization. The MIL-induced hyperpolarization was blocked by yohimbine (1μM), an antagonist for α₂- adrenoceptors. These results suggest that the MIL-induced hyperpolarization is mediated by NA via α₂-adrenoceptors in LC neurons. Under the whole-cell patch-clamp condition, prolonged application of MIL produced an outward current which lasted as long as MIL existed in the ACSF. The outward current induced by NA was enhanced by MIL in LC neurons. MIL enhanced the amplitude and duration of the inhibitory postsynaptic potential, while it depressed the excitatory postsynaptic potential. The results indicated that both MIL and MPH showed almost the same effects on neuronal activity and synaptic transmission in the rat LC. These results suggest

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Mutations in a gene on the X-chromosome encoding methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome. We examined clinical symptoms of 27 patients with Rett syndrome (aged 2 to 37 years), diagnosed by the criteria of the Rett Syndrome Diagnostic Criteria Work Group, having MECP2 gene mutations. Two novel MECP2 mutations, 119 del AG resulting in amino acid frame-shift 40fs43X and C to G transversion resulting in amino acid change of F157L, were found. All patients had the most important symptoms of this syndrome, including loss of acquired purposeful hand skills followed by stereotyped hand movements. Two patients had mild perinatal abnormalities. Nine showed psychomotor delay or hypotonia before 6 months. Five patients over 4 years old did not have microcephaly. Speech was preserved in five patients. According to the criteria, 18 cases were diagnosed as Rett syndrome variants. Sixteen out of 26 patients over 3 years old were able to walk (61.5%), and 22 had epilepsy (84.6%). Mutations of the 5 patients without microcephaly were R133C, P225R, R255X, R306C and 376fs386X, whereas those of the 5 variants with preserved speech were 34fs123X, R133C, R255X and R270. Common T158M mutation was detected in 4 patients, R255X in 7 and R270X in 4. Patients with the same mutations showed different phenotypes. Patients with R133C and R306C presented a mild phenotype without microcephaly. Of the proposed diagnostic criteria, the following three may not be essential: apparently normal prenatal and perinatal period, apparently normal psychomotor development through the first 6 months, and deceleration of head growth between 5 months and 4 years.

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To minimize adverse effects and to get good efficacy of ACTH therapy against West syndrome, we tried a new 2-steps therapeutic protocol consisting of the shortened ACTH therapy and the additional ACTH therapy. In a prospective multi-institutional study, 20 patients with newly diagnosed West syndrome who had failed to respond to high-dose vitamin B₆ and zonisamide were treated by this shortened ACTH therapy. Synthetic corticotropin (ACTH-Z 0.025mg/kg/dose, max 0.25 mg) was administrated intramuscularly seven times on every other day for 14 days. At 1 month after discontinuing corticotropin, spasms and hypsarrhythmia disappeared in 10/20 (50%) and 13/17 (59%) patients respectively. Subsequently, 9 out of the 10 patients with persistent spasms received additional therapy for 1 or 2 weeks with daily intramuscular ACTH-Z, which was tapered off over a few weeks. Including the additional ACTH therapy, the disappearance of spasms and hypsarrhythmia were found in 13 patients (65%) and 13 patients (76%). Adverse effects during the shortened ACTH therapy were fewer than additional ACTH therapy but not statistically significant. Severe adverse effects were not observed in both ACTH therapy. In the 2-steps therapeutic protocol according to the response to ACTH, favorable results were obtained in seizure control, EEG findings and the degree of adverse effects.

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Alexander disease is a hereditary disorder of myelin degeneration. The pathological feature of the brain is the characteristic inclusion bodies in astrocytes called Rosenthal fibers. The major components of the Rosental fibers are known to be α B-crystallin and glial fibrillary acidic protein (GFAP). In recent years, reports have indicated mutations of the GFAP gene in patients with Alexander disease. The R239 mutation (R239C, R239H) tends to cause comparatively more severe conditions among the GFAP mutations. In this study, we examined a long-term survival case of a patient (age 25 years, 7 months) with infantile Alexander disease with an R239C mutation confirmed by DNA analysis. There are no past reports of subjects with the R239C mutation who had as prolonged a long-term survival as our case. Our subject's condition was not as severe as those with the R239H mutation. The clinical progress in those other reports also varied by case. The R239C mutation does not show as much correlation with the clinical presentation as the R239H mutation. We believe that factors such as the environment also play a part in the prognosis of the disease.

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We report here about an 8-year-old boy with parietal lobe epilepsy (PLE) and ictal laughter. At the age of 6, he began to experience drop seizures, followed by sensory fits. Interictal EEG showed frequent spikes at C3, C4, P3 and Cz. Despite treatment with antiepileptic drugs, he often fell down in seizures after feeling abnormal sensations in the right shoulder. On ictal video EEG at the age of 7 years, (1) he became motionless and complained of fear and pain in the right hand, (2) he had clonic seizures of the right upper limb and fell down to his left, (3) helaughed tho ugh he did not feel funny. Ictal EEG showed spikes which originated in Pz and then were generalized.
In many of the previously reported cases, ictal laughter is associated with hypothalamic hamartomas, infantile spasms, complex partial seizures of frontal, temporal, or parietal origin. We diagnosed the present case as having PLE. However, other localization could not be roled out because the spikes were generalized quickly. To date, there are two reported cases of ictal laughter with PLE, but ictal EEG is lacking in these patients. Ictal laughter is rare in non-lesional cryptogenic PLE, but it may imply PLE's pathogenesis.

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Anterior spinal artery syndrome is rare in children, especially in neonates. We present a girl with hydrops fetalis and hypothyroidism who developed flaccid paresis of both arms in the neonatal period (around day 25). MRI of the spine performed on day 52 revealed atrophic changes at C5-Th 1 without Gd-DTPA-induced enhancement. Nerve conduction studies were also helpful in the diagnosis; in the upper limbs, motor potential was not elicited, while sensory nerve conduction velocity was normal. These clinical and laboratory findings suggested an atypical case of anterior spinal artery syndrome.

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