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This case-control study aimed to assess oxidative stress alterations in autism spectrum disorder (ASD). We used the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously, in combination with conventional oxidative stress markers to investigate the ability of this MULTIS approach as a non-behavioural diagnostic tool for children with ASD. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analysed. The ASD group showed decreased hydroxyl radical ( · OH) and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide (O 2 ·- ) and alkoxyl radical (RO · ) were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of · OH, O 2 ·- , and RO · scavenging activities predicted ASD with high odds ratio (50.4), positive likelihood (12.6), and percentage of correct classification (87.0%). Our results indicate that oxidative stress in children with ASD is not simply elevated but rather shows a compensatory shift. MULTIS measurements may serve as a very powerful non-behavioural tool for the diagnosis of ASD in children.

Background: Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation., Methods: An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses., Findings: Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children., Interpretation: Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology., Funding: This study was supported mainly by MEXT, Japan., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

A growing body of evidence has indicated that individuals with autism spectrum disorder (ASD) exhibit abnormal reactions to sensory stimuli and impaired face processing. Although behavioral studies have reported that individual differences in sensory processing patterns are correlated with performance in face processing tasks, the neural substrates underlying the association between sensory processing patterns and face processing remain unknown. Using functional magnetic resonance imaging, the present study examined the relationships between sensory processing patterns assessed with the Adolescent/Adult Sensory Profile (AASP) and brain activity during a one-back task with two types of stimuli (face or house pictures). We enrolled 18 Japanese adults with ASD and 19 age- and IQ-matched controls. Sensation Avoiding scores, which were assessed using the AASP, were positively correlated with right fusiform activity during the presentation of pictures of faces in the ASD group, but not in the control group. This suggests that abnormal sensory processing patterns in ASD are associated with abnormal face-related brain activity, possibly resulting in impaired face processing. Autism Res 2020, 13: 741-750. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Sensory abnormalities are one of the most common symptoms in people with autism spectrum disorder (ASD). This study shows that individuals with ASD who react abnormally to sensory stimuli also exhibit atypical brain activity when recognizing faces. Abnormal sensory processing may partly explain the difficulty that people diagnosed with ASD have in identifying others' faces., (© 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.)

Here we report a Japanese patient with new compound heterozygous truncating variants in the PCDH12 gene. As compared to the previously reported families who had congenital microcephaly, intrauterine growth retardation, intracranial calcification, and neonatal seizure associated with dysplasia of the midbrain-hypothalamus-optic tract, the present patient showed no midbrain-hypothalamus dysplasia or congenital/postnatal microcephaly, but dyskinetic cerebral palsy and severe intellectual disability as well as multifocal epilepsy. To understand phenotypic spectrum associated with PCDH12 variants, more reports are needed.

Objective: Several studies have suggested that objective deficits in the processing of abstract information in conjunction with an enhanced ability to process concrete information is a definitive characteristic of autism spectrum disorder (ASD). However, this cognitive imbalance is not necessarily clear in high-functioning autistic individuals who do not display absolute differences relative to typically developing (TD) populations. Thus, the purpose of this study was to identify this cognitive tendency in high-functioning autistic individuals using intra-individual cognitive comparisons., Methods: The reaction times (RTs) of TD children, children with ASD, and children with attention deficit hyperactivity disorder (AD/HD) (n=17 in each group, mean age=11.9years, age range=9.8-15.8years) were compared using the Which/How-to-Apply Tools (W/HAT) test, which consists of tasks requiring the adaptive use of novel tools and familiar tools in atypical and typical situations. Differences in RTs between the atypical and typical trials ([A-T]) were used to assess intra-individual cognitive imbalances., Results: As predicted, the [A-T] scores of the ASD group were significantly higher than those of the TD group even though the RTs in the atypical and typical trials did not differ. Additionally, the [A-T] values were significantly higher in the ASD group than in the AD/HD group, which indicates that the cognitive imbalance was specific to ASD individuals. No significant interaction was detected between the trial and subject group., Conclusions: The findings of this study demonstrate that a cognitive imbalance in ASD individuals may enhance the current understanding of the pathophysiology of this disorder, which is found in a range of individuals, including those with obvious cortical dysfunction to those with only intra-individual imbalances., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Takuto Rehabilitation Center for Children is located in Sendai, the capital of the Miyagi prefecture, and faces the Pacific Ocean. The tsunami caused by the Great East Japan Earthquake resulted in tremendous damage to this region. Many physically handicapped patients with epilepsy who are treated at our hospital could not obtain medicine. We surveyed patients with epilepsy, using a questionnaire to identify the problems during the acute phase of the Great East Japan Earthquake., Methods: After the earthquake, we mailed questionnaires to physically handicapped patients with epilepsy who are treated and prescribed medications at our hospital, or to their parents., Results: A total of 161 respondents completed the questionnaire. Overall, 68.4% of patients had seven days or less of stockpiled medication when the earthquake initially struck, and 28.6% of patients had no medication or almost no medication during the acute phase after the earthquake. Six patients were forced to stop taking their medication and nine patients experienced a worsening of seizures. Most (93.6%) patients stated they require a stockpile of medication for more than seven days: 20months after the earthquake, 76.9% patients a supply of drugs for more than seven days., Conclusions: We suggest that physically handicapped patients with epilepsy are recommended to prepare for natural disasters by stockpiling additional medication. Even if the stock of antiepileptic drugs is sufficient, stress could cause worsening of seizures. Specialized support is required after a disaster among physically handicapped patients with epilepsy., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Aim: Cerebellar injury is a characteristic injury associated with preterm infants. However, the impact of cerebellar injury on the development of preterm infants is unclear., Method: We reviewed magnetic resonance image studies of preterm infants with cerebral palsy retrospectively and evaluated the developmental outcomes., Results: Cerebellar injury was recognized in 9 (2.4%) of 381 patients with cerebral palsy who were born preterm. The median gestational age was 26 (range 23-32) weeks and the median birth weight was 938 (range 492-1450) g. Seven of the nine patients had severe symmetric injuries to the inferior cerebellar hemispheres, resulting in a pancake-like appearance of the residual upper cerebellum. Supratentorial lesions were also recognized: periventricular leukomalacia in seven; atrophy of the basal ganglia in two; and intraventricular hemorrhage in two. Importantly, the motor dysfunction was related to the reduction in the white matter volume and severity of basal ganglia atrophy, but not to the cerebellar injury. Four of the nine patients could walk without limitations despite extensive cerebellar disruption. Only four patients could speak meaningful words during the study and only one spoke two-word sentences., Interpretation: The patients with cerebellar injury might have a communication handicap, rather than altered motor function. Prematurity-related cerebellar complications require more attention in terms of cognitive and speech function, in addition to neuromotor development., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We investigated the neural mechanisms underlying the ability to cope in atypical or novel situations using tools. We hypothesized that two cognitive components support this ability: adaptive coordination (for adapting to situational demands) and cognitive inhibition (for inhibiting the incongruent actions afforded by tools). We had subjects choose novel tools for a given task or choose among familiar tools in an atypical situation, during which we examined cortical activation in their brains using functional magnetic resonance imaging. Neural activation during adaptive coordination was observed in the left lateral orbitofrontal cortex, inferior frontal gyrus and sulcus, middle and medial frontal gyrus, intraparietal sulcus, precentral sulcus, inferior temporal gyrus, supramarginal gyrus, the bilateral insula, anterior cingulate cortex, and the right callosal sulcus. Activation indicating cognitive inhibition was observed in the right middle and inferior frontal gyrus. These findings demonstrate that the left parietal region shapes basic action, whereas the right frontal region inhibits stereotypical action. The left frontal regions are thought to be linked to the processing of ambiguous actions and play key roles in coordinating actions, whereas other regions are involved in processing situational contexts. Our results may be important for understanding the neural systems underlying adaptability to daily social situations., (Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Periventricular nodular heterotopia (PNH) with overlying polymicrogyria (PMG) is a recently described, developmental brain malformation; however, the causative genes of this malformation have not yet been identified. We report on a 5-year-old Japanese male with bilateral PNH with overlying PMG. He had mild intellectual disability, distinctive facial features, short stature, and microcephaly, with cardiac disorders. No mutation was identified in Sanger sequences for FLNA and ARFGEF2; however, array comparative genomic hybridization revealed an approximately 0.8Mb gain at Xq26.1-26.2, which included three genes: IGSF1, OR13H1, and FIRRE. We identified the same 3-copy gain in his mother; despite identifying the same abnormality in the mother, it must still be considered as a possible cause for the abnormalities, as X-inactivation in the mother could have led to her not expressing the same phenotype. This case may provide important clues for identifying the genes responsible and help in the understanding of the pathogenesis of this disorder., (© 2014 Mac Keith Press.)

Background: Allan-Herndon-Dudley syndrome, an X-linked condition characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia, is associated with defects in the monocarboxylate transporter 8 gene (MCT8). The long-term prognosis of Allan-Herndon-Dudley syndrome remains uncertain., Patients: We describe the clinical features and course of four adults in a family with Allan-Herndon-Dudley syndrome with athetoid type cerebral palsy., Results: We identified an MCT8 gene mutation in this family. Two of the four affected family members died at 32 and 24 years of age., Conclusions: Individuals with Allan-Herndon-Dudley syndrome are at increased risk for recurrent infection, such as aspiration pneumonia. These individuals require careful management with consideration for this increased risk of recurrent infection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Bilateral periventricular nodular heterotopia is a neuronal migration disorder characterized by gray matter cellular rests in the periventricular regions. Megalencephaly has not been reported in children with bilateral periventricular nodular heterotopia. No other disorder with a similar phenotype has been reported. Here we report the case of a 5-year-old Japanese boy with bilateral periventricular nodular heterotopia and megalencephaly. Relative macrocephaly was evident at birth, and bilateral periventricular nodular heterotopia and megalencephaly were noted on magnetic resonance imaging (MRI). However, no hydrocephalus or indication of cerebral cortical dysplasia was seen. A mild intellectual disability was present, but the patient had no history of seizures. Genetic analysis revealed no mutation on the capillary sequences for FLNA, and no pathogenic abnormalities were evident on array comparative genomic hybridization. This case could represent a new disease entity: bilateral periventricular nodular heterotopia with megalencephaly., (© The Author(s) 2013.)

We report a six-year-old girl with Cardio-facio-cutaneous (CFC) syndrome who developed acute encephalopathy after the recurrence of status epilepticus. While epileptic encephalopathy and severe epilepsy have been mentioned as frequent complications of the CFC syndrome, no previous reports have shown a case of the CFC syndrome complicated with acute encephalopathy. Here we discuss the possibility for the linkage between the development of acute encephalopathy and CFC syndrome which is generally susceptible to seizures or epilepsy., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

The recent findings on subtraction ictal SPECT and ictal near-infrared spectroscopic topography in patients with West syndrome were summarized and its availability for presurgical evaluation was discussed. The subtraction ictal SPECT study in patients with West syndrome demonstrated the cortical epileptic region and subcortical involvement, which may consist of epilepsy networks related to the spasms. Moreover, subtraction ictal SPECT may have predictive power for short-term seizure outcome. Patients with a symmetric hyperperfusion pattern are predicted to have a better seizure outcome, whereas patients with asymmetric hyperperfusion pattern may develop poor seizure control. Importantly, asymmetric MRI findings had no predictive power for seizure outcome. Multichannel near-infrared spectroscopic topography applied to the patients with West syndrome detected an increase in regional cerebral blood volume in multiple areas which were activated either simultaneously or sequentially during spasms. Topographic changes in cerebral blood volume were closely correlated with spasm phenotype, suggesting that the cortex is involved in the generation of spasms. In conclusion, subtraction ictal SPECT may be considered as a useful tool for presurgical evaluation of patients with West syndrome and investigation of the pathophysiology of spasms. The ictal near-infrared spectroscopic topography should be more investigated to see if this is useful tool for presurgical evaluation., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We describe a boy, 3 years and 6 months old, who experienced a rolandic seizure accompanied by a cluster of atypical absence seizures, the EEGs for which corresponded to those of atypical benign partial epilepsy (ABPE). Of note, this patient suffered from developmental delay beginning in infancy and exhibited giant middle-latency somatosensory evoked potentials with action myoclonus. With the exceptions of ethosuximide, acetazolamide, and adrenocorticotropic hormone, which have been reported to be effective in ABPE, the atypical absence seizures were intractable despite extensive treatment with various anticonvulsants. The drugs that were effective led to a remarkable reduction in seizure frequency and EEG improvement, but the efficacy was temporary. The patient demonstrated moderate mental retardation without regression and could not walk with support or speak any meaningful words at the age of 3 years and 6 months. Based on thorough differential diagnosis, although further studies will be necessary, we propose that this boy may present a new phenotype of ABPE: ABPE with action myoclonus., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Aim: To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia., Method: Eighty-six patients born at term with cerebral palsy (CP) and spastic diplegia (54 males, 32 females; median age 20 y, range 7-42 y) among 829 patients with CP underwent brain MRI between 1990 and 2008. The MRI and clinical findings were analysed retrospectively. Intellectual disability was classified according to the Enjoji developmental test or the Wechsler Intelligence Scale for Children (3rd edition)., Results: The median ages at diagnosis of CP, assignment of Gross Motor Function Classification System (GMFCS) level, cognitive assessment, and MRI were 2 years (range 5 mo-8 y), 6 years (2 y 8 mo-19 y), 6 years (1 y 4 mo-19 y), and 7 years (10 mo-30 y) respectively. MRI included normal findings (41.9%), periventricular leukomalacia, hypomyelination, and porencephaly/periventricular venous infarction. The frequency of patients in GMFCS levels III to V and intellectual disability did not differ between those with normal and abnormal MRI findings. Patients with normal MRI findings had significantly fewer epileptic episodes than those with abnormal ones (p=0.001)., Interpretation: Varied MRI findings, as well as the presence of severe motor dysfunction and intellectual disability (despite normal MRI), suggest that patients born at term with spastic diplegia had heterogeneous and unidentified pathophysiology., (© The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.)

The concept of "social self" is often described as a representation of the self-reflected in the eyes or minds of others. Although the appearance of one's own face has substantial social significance for humans, neuroimaging studies have failed to link self-face recognition and the likely neural substrate of the social self, the medial prefrontal cortex (MPFC). We assumed that the social self is recruited during self-face recognition under a rich social context where multiple other faces are available for comparison of social values. Using functional magnetic resonance imaging (fMRI), we examined the modulation of neural responses to the faces of the self and of a close friend in a social context. We identified an enhanced response in the ventral MPFC and right occipitoparietal sulcus in the social context specifically for the self-face. Neural response in the right lateral parietal and inferior temporal cortices, previously claimed as self-face-specific, was unaffected for the self-face but unexpectedly enhanced for the friend's face in the social context. Self-face-specific activation in the pars triangularis of the inferior frontal gyrus, and self-face-specific reduction of activation in the left middle temporal gyrus and the right supramarginal gyrus, replicating a previous finding, were not subject to such modulation. Our results thus demonstrated the recruitment of a social self during self-face recognition in the social context. At least three brain networks for self-face-specific activation may be dissociated by different patterns of response-modulation in the social context, suggesting multiple dynamic self-other representations in the human brain., (Copyright © 2011 Wiley-Liss, Inc.)

Here, we report a male child with Schinzel-Giedion syndrome associated with intramyelinic edema detected on brain magnetic resonance imaging (MRI) and persistent suppression-burst pattern on electroencephalography (EEG) with erratic myoclonus of the extremities and face. Similar to nonketotic hyperglycinemia, Schinzel-Giedion syndrome may be recognized as another causative genetic disease of early myoclonic encephalopathy and vacuolating myelinopathy., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Mate choice is an example of sophisticated daily decision making supported by multiple componential processes. In mate-choice literature, different characteristics of the value dimensions, including the sex difference in the value dimensions, and the involvement of self-assessment due to the mutual nature of the choice, have been suggested. We examined whether the brain-activation pattern during virtual mate choice would be congruent with these characteristics in terms of stimulus selectivity and activated brain regions. In measuring brain activity, young men and women were shown two pictures of either faces or behaviors, and they indicated which person they would choose either as a spouse or as a friend. Activation selective to spouse choice was observed face-selectively in men's amygdala and behavior-selectively in women's motor system. During both partner-choice conditions, behavior-selective activation was observed in the temporoparietal regions. Taking the available knowledge of these regions into account, these results are congruent with the suggested characteristics of value dimensions for physical attractiveness, parenting resources, and beneficial personality traits for a long-lasting relationship, respectively. The medial prefrontal and posterior cingulate cortices were nonselectively activated during the partner choices, suggesting the involvement of a self-assessment process. The results thus provide neuroscientific support for the multi-component mate-choice mechanism.

Hemimegalencephaly (HME) presents as severe refractory seizures and requires early surgical treatment to prevent progression to catastrophic epilepsy. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are useful imaging techniques for the presurgical evaluation of patients with intractable epilepsy. However, the results in HME are variable and no study has compared SPECT and PET performed at around the same time. We performed SPECT and PET for nine patients with HME, which was defined as a whole or part of affected hemisphere enlargement (three males, six females; age range 0.5-20 years). The ictal and interictal states were determined based on the presence or absence of clinical seizures during all PET examinations and majority of SPECT examinations. The perfusion pattern in the malformed hemisphere was increased or equal, despite the reduced glucose metabolism in six out of nine patients. Five of the six patients who underwent early surgical treatment showed this kind of perfusion/metabolism discrepancy. Importantly, even the non-affected hemisphere in early infantile cases already lacked the normal hypoperfusion and hypometabolism patterns of immature frontal lobes, which was most prominent in case with poor surgical prognosis. In all six surgical patients, epileptic seizures appeared before 4 months of age. By contrast, none of the non-surgical patients had seizures before 4 months of age. In conclusion, although the number of patients examined is small and the result is still preliminary, the perfusion/metabolism discrepancy found in this study may show potential characteristic aspect of HME and further study with simultaneous EEG recording will make clear if this finding can be useful indicator for early surgical treatment in HME., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A girl aged 1 year 9 months had recurrent episodes of febrile status epilepticus. She recovered completely after the first three episodes. However, at 9 months she developed acute encephalopathy resulting in severe neurologic sequelae. Diffusion-weighted magnetic resonance imaging revealed diffuse high-intensity signals over the cortex and subcortical white matter in the acute phase and severe diffuse cerebral atrophy in the chronic phase. Mutations were detected in the neuronal voltage-gated sodium channel alpha subunit type 1 (SCN1A) gene. SCN1A sequence analysis revealed a truncation mutation:e x1-c.126Adel (D43fs). Our patient was likely afflicted by severe myoclonic epilepsy in infancy, and the fourth episode of status epilepticus was similar to acute encephalopathy. This report provides further insight into the molecular pathophysiology underlying acute encephalopathy.

Abdominal migraine is one subcategory of migraine-related syndromes. Migraine is sometimes associated with facial ecchymosis, which may be accounted for by trigeminovascular activation. However, the precise mechanism of this concurrence remains unknown. Here, we describe a 9-year-old girl, who presented ecchymosis of the legs and buttock associated with recurrent, severe, non-localized midline abdominal pain. The patient has positive family history of migraine. Investigations during an attack revealed no obvious abnormalities. According to the International Classification of Headache Disorders (Second Edition), she was diagnosed with abdominal migraine. Her abdominal pain was relieved with sumatriptan, a migraine-specific serotonin(1B/1D) agonist. The ecchymosis always occurred in conjunction with abdominal pain and tended to regress after pain relief. In contrast to the local trigeminovascular activation theory that explains the ecchymosis in a migraine-related condition, the findings gained from the presented patient suggest a mechanism that involves the initial activation of the visceral nerves responsible for abdominal nociception under the predisposition of visceral hypersensitivity associated with abdominal migraine. Subsequently, ecchymosis developed in the skin region innerved by the activated nerves, possibly involving dichotomizing afferent fibers and afferent-afferent interactions via sacral spinal cord pathway or a sympathetic reflex. Taken together with the probable common mechanism of migraine and abdominal migraine, we suggest that the skin changes in migraine are associated with somatic referral of migraine headache via the trigeminal nerve pathway.

Second language (L2) acquisition necessitates learning and retrieving new words in different modes. In this study, we attempted to investigate the cortical representation of an L2 vocabulary acquired in different learning modes and in cross-modal transfer between learning and retrieval. Healthy participants learned new L2 words either by written translations (text-based learning) or in real-life situations (situation-based learning). Brain activity was then measured during subsequent retrieval of these words. The right supramarginal gyrus and left middle frontal gyrus were involved in situation-based learning and text-based learning, respectively, whereas the left inferior frontal gyrus was activated when learners used L2 knowledge in a mode different from the learning mode. Our findings indicate that the brain regions that mediate L2 memory differ according to how L2 words are learned and used., (Copyright 2009 Elsevier Inc. All rights reserved.)

Agency, a feeling that the self is the cause of action, has a strong relationship to the processing of discrepancies between the predicted multi-sensory feedback from one's intended action and its actual outcome (hereafter, agency error). Although previous studies have explored the neural basis of agency by assessing the brain's response to agency error, the effects found are confounded by two types of error irrelevant to agency: a mismatch between different sensory inputs in general (sensory mismatch, SM error) and a basic response to any type of prediction error (oddball error). In this functional magnetic resonance imaging study, we identified the neural response specific to agency error by dissociating it from responses to SM and oddball errors. Subjects played a game in which they controlled an on-screen character. Neural responses to rare events of violated control and congruency between types of audio-visual feedback were compared to dissociate agency from SM error. In a separate session, subjects viewed repetitive motions of the character, and neural responses to rare events of unpredictable change in movement were identified as related to oddball error. Agency-error-specific activation was observed in the supplementary motor area (SMA), left cerebellum, right posterior parietal cortex (PPC), and right extrastriate body area (EBA). Oddball errors also activated areas near the PPC and EBA peaks. SM errors activated the pre-SMA and the right posterior superior temporal sulcus. Our results suggest that the SMA, cerebellum, and some parts of the PPC and EBA serve as the neural bases of agency., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

We successfully treated 2 pediatric cases of abdominal pain-related functional gastrointestinal disorder with sumatriptan. When 9 years old, patient 1 developed periodic abdominal pain that was intractable to medication and remitted spontaneously. She was diagnosed with abdominal migraine, categorized as H2c in the Rome III criteria for functional gastrointestinal disorders. At age 12, intranasal sumatriptan relieved her pain, and her attacks halted 2 years later. Patient 2 was a 9-year-old girl diagnosed with attention-deficit hyperactivity disorder (ADHD), who began to have intermittent abdominal pain of variable severity, which sometimes restricted daily activity. She was diagnosed with childhood functional abdominal pain syndrome, categorized as H2d1 using the Rome III criteria. Intranasal sumatriptan also relieved her pain. These cases suggest that the mechanism of pain in abdominal pain-related functional gastrointestinal disorders is similar to that of migraine, with probable central hypersensitivity, at least in a subset of cases.

Pulmonary involvement is a serious complication in Gaucher disease, as is neuronopathic involvement. Few reports are available, however, on the frequency, clinical course and therapy for pulmonary involvement in patients with Gaucher disease. We report a case of type 2 Gaucher disease with severe hepatosplenomegaly, anemia, hypertonia, and psychomotor retardation. The diagnosis of Gaucher disease was confirmed by the presence of Gaucher cells in bone marrow and low serum beta-glucocerebrosidase activity (patient, 0.8; control, 4.1-9.7 nmol/mg.protein/hr) at the age of 1 year. The patient's genotype is L444P/unknown. Enzyme replacement therapy (ERT) with intravenous imiglucerase at 78 U/kg/2weeks was started, and hepatosplenomegaly and laboratory abnormalities were markedly improved after 6 months of therapy. After 8 months of therapy, respiratory impairment appeared together with a decrease of tidal volume and low SpO2 during sleep. Serum acid phosphatase and angiotensin converting enzyme levels mildly increased, and radiological findings showed bilateral ground-glass appearance without signs of respiratory infection. With the diagnosis of progressive pulmonary involvement in Gaucher disease, we increased the dosage of imiglucerase from 50 to 75 U/kg/2 weeks. After a month, respiratory symptoms and CT findings of ground-glass appearance remarkably improved, but interlobular septal and intralobular interstitial thickening persisted. The maximum permitted dosage of imiglucerase in Japan is 60 U/kg/2 weeks. Based on our experience with this case, we propose that a higher ERT dosage would be uselul for serious pulmonary involvement.

We have experienced a case of bipolor I disorder complicated by mental retardation and autistic disorder. Acquired daily life activities such as eating, clothing and toileting without assistance were gradually lost during depressive periods, which was consistent with the previous reports. Before losing daily life skills, the patient could no longer perform daily life activities without consecutive instructions. This "waiting-for-instruction" behavior may be an early diagnostic key for major depressive episode in mentally-retarded children and adolescents.

The authors present a 14-year-old girl with 18q- syndrome combined with cyclic vomiting syndrome. Since the age of 5 years, she has been admitted to hospital 30 times. Despite trying many prophylactic treatments, no medication has inhibited the vomiting attacks successfully. Intranasal sumatriptan was effective at halting the vomiting attacks. This is the first case of 18q- syndrome combined with cyclic vomiting syndrome successfully treated with sumatriptan. This report may allow us to consider sumatriptan use in patients suffering from misery attack of cyclic vomiting syndrome combined with chromosomal abnormality of 18q- syndrome.

Daily situations involve many objects and behaviors. To comprehend the meaning of situations, the relationships between objects, behaviors, and the situational context are important. To reveal the cortical networks involved in processing these relationships we used functional magnetic resonance imaging to compare brain activation during processing of behavior-situation and object-situation relationships. Each session examined two aspects of situational relationship processing: monitoring of the situational relationship and responses to irrelevant relationships. Monitoring was analyzed by comparing cortical activation during a situational relevance judgment task with that during a physical appropriateness judgment task. Responses were analyzed by comparing neural responses to situationally irrelevant and situationally relevant components. The left medial frontal cortex, fusiform gyrus, inferior frontal gyrus, calcarine sulcus, right anterior middle temporal gyrus, orbitoinsular junction, and occipito-temporo-parietal junction were commonly activated while monitoring relationships of both types. The right anterior middle temporal gyrus and orbitoinsular junction were considered to have roles in implicit monitoring because they were more deactivated during physical judgment tasks than during the resting state; this deactivation seemed to reflect unconscious situational monitoring in the resting state. Other regions seemed to be linked to explicit conscious monitoring. Responses to irrelevance were linked to separate and category-specific cortical activation in the left medial frontal cortex and frontal pole for behavioral irrelevance and in the left orbitofrontal cortex for irrelevant objects. We demonstrated that the hierarchical structure of processing situational relationships consisted of implicit monitoring, explicit monitoring, and category-specific responses to irrelevance.

We have seen 9 moderately to severely mentally-retarded autistic children and adolescents who waited for small-step instructions to perform previously acquired daily life activities (called "waiting-for-instruction" behavior). None of these patients were capable of expressing their depressive mood. All cases were considered to meet the criteria for major depressive episode described in DSM-IN. The "waiting-for-instruction" behavior was suggested to be a diagnostic key for depressive state in mentally retarded children and adolescents. GAF scales for depressive symptoms including the "waiting-for-instruction" behavior improved in 7 of these 9 cases with fluvoxamine. Risperidone and valproate sodium were useful for these symptoms in patients who were not responsive to fluvoxamine. Therefore, there is a possibility that they met the criteria for bipolar II disorder in DSM-IV.

Humans extract behaviorally significant meaning from a situation by integrating meanings from multiple components of a complex daily environment. To determine the neural underpinnings of this ability, the authors performed functional magnetic resonance imaging of healthy subjects while the latter viewed naturalistic scenes of two people and an object, including a threatening situation of a person being attacked by an offender with an object. The authors used a two-factorial design: the object was either aversive or nonaversive, and the offender's action was either directed to the person or elsewhere. This allowed the authors to examine the neural response to object aversiveness and person-directed intention separately. A task unrelated to threat was also used to address incidental (i.e., subconscious or unintentional) detection. Assuming individual differences in incidental threat detection, the authors used a functional connectivity analysis using principal components analysis of intersubject variability. The left lateral orbitofrontal cortex and medial prefrontal cortex (MPFC) were specifically activated in response to a threatening situation. The threat-related component of intersubject variability was extracted from these data and showed a significant correlation with personality scores. There was also a correlation between threat-related intersubject variability and activation for object aversiveness in the left temporal pole and lateral orbitofrontal cortex; person-directed intention in the left superior frontal gyrus; threatening situations in the left MPFC; and independently for both factors in the right MPFC. Results demonstrate independent processing of object aversiveness and person-directed intention in the left temporal-orbitofrontal and superior frontal networks, respectively, and their integration into situational meaning in the MPFC., ((c) 2008 Wiley-Liss, Inc.)

We has been 13 cases of conduct disorder (CD) with developmental disabilities for 10 years. These cases were judged as pre-delinquent states at 8.9 years old (average) and as CD at 12.5 years old. All of these children had been maltreated by their parents. Except for 4 cases who were in juvenile reformatory or prison, 5 of 9 cases were transferred to protective custodial institutions. Custodial intervention could successfully amend CD symptoms in 4 cases. Compared with a gender-matched control group with the same developmental disabilities, the CD group showed a significantly higher rate of maltreatment and a higher divorce rate among the parents. The number of parents with psychiatric disorders was not significantly different between the two groups, although parents of the control group were receiving psychiatric treatment significantly more often than those of CD group. This study suggested that therapeutic intervention is important for preventing CD to not only in children but also in their parents. Further investigations on the measures to intervene in families with a pre-delinquent child is required.

Purposes: The aims of the study were to evaluate the detectability of focal leading activity in three cases of West syndrome having focal abnormal activity on EEG by comparing subtraction ictal images and raw ictal images, and to interpret the results in 16 cases., Methods: Subtraction images were constructed using iNeurostat (revision 2)., Results: In three cases with focal abnormal activity on EEG, subtraction ictal images reflected the EEG findings; in contrast, raw ictal images did not. Diverse degrees of cortical hyperperfusion, ranging from zero to 10 sites, seen in the other 13 cases seemed to reflect spasm pathophysiology and rapid spasm propagation. Subtraction ictal images also allowed the ready detection of hyperperfusion of subcortical structures and of a tight cortico-subcortical relationship in a subset of cases., Conclusions: We showed the superiority of subtraction ictal images in detecting the focal epileptic region and in showing propagation pathways from the cortex to subcortical structures. A subset of spasms in WS may be focal cortical-onset secondarily generalized seizures. We believe that subtraction analysis is valuable in patients with complex WS who have partial seizures and spasms simultaneously along with focal epileptic EEG activity, as they will likely be candidates for epilepsy surgery.

We report on 3-year-old Japanese twin brothers suffering from ictal vomiting during infancy. Intractable seizures, including generalized tonic-clonic convulsions, and myoclonic seizures persisted in late infancy. The diagnosis of severe myoclonic epilepsy in infancy was confirmed by detecting a mutation in the voltage-gated sodium channel alpha subunit type gene. This is the first case report addressing ictal vomiting as the initial presentation of severe myoclonic epilepsy in infancy.

To understand implicit social meanings, the interaction of literal meanings and relevant information in a situational context is important. However, previous studies have not investigated such contextual interactions. Using functional magnetic resonance imaging (fMRI), we investigated cortical mechanisms underlying the processing of implicit meanings, particularly irony, in realistic social situations, focusing on contextual interactions. Healthy subjects were shown pictures depicting daily communicative situations during judgment tasks involving situational appropriateness and literal correctness. The left medial prefrontal cortex showed significantly greater activation during tasks involving situational judgments than during literal judgments. The right temporal pole was activated task-independently during irony-specific processing. The medial orbitofrontal cortex was activated task-dependently during irony processing in situational judgment tasks. These regions have been reported to be involved in theory of mind, and have not been implicated in previous studies on the linguistic processing of implicit meanings. This suggests that the intentional assessment of situational appropriateness for task execution is carried out in the left medial prefrontal cortex, whereas irony is processed in the right temporal pole by assessing situational context automatically, and is judged based on the situational context in the medial orbitofrontal cortex. Our results show that the processing of implicit meanings and irony in contextually rich situations depends on brain mechanisms involved in the "theory of mind," based on processing relevant information in a situational context, and suggest different functions in each region.

We used tacrolimus to successfully treat a patient with childhood-onset oropharyngeal myasthenia gravis (MG). A girl (2 years, 5 months old) with oropharyngeal MG responded partially to treatment including pyridostigmine bromide, intravenous immunoglobulin, and prednisolone (2 mg/kg/day) for 7 weeks, but this resulted in worsening of her eye symptoms. By contrast, tacrolimus at 2 mg/day resulted in complete remission of the MG, which made it possible to reduce the dose of prednisolone. This is a rare report of the use of tacrolimus as an effective treatment for patients with intractable childhood-onset MG.

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare leukoencephalopathy presenting in the infantile period and characterized by diffuse cerebral hypomyelination, and atrophy of the basal ganglia and cerebellum. As patients with H-ABC lack remarkable laboratory findings, the diagnosis is based on brain magnetic resonance imaging findings alone. Only eight cases have been reported in the literature, and thus the natural course and treatment of this disease are not fully understood. We report a 35-month-old boy with H-ABC who had hemidystonia, hypomyelination, and cerebellar ataxia. We diagnosed H-ABC after considering a thorough differential diagnosis, excluding other diseases involving hemidystonia, hypomyelination, and cerebellar ataxia. Furthermore, technetium-99m ethyl cysteinate dimmer-single-photon emission computerized tomography (Tc-ECD-SPECT) and positron emission tomography with fluorodeoxyglucose (18)F (FDG-PET) revealed decreased blood flow and glucose metabolism in the bilateral lenticular nucleus, thalamus, and cerebellum. A peroral levodopa preparation containing carbidopa (levodopa-carbidopa) was effective at ameliorating and stopping the progression of the patient's dystonia (final effective doses: levodopa, 200 mg/day and carbidopa, 20 mg/day). This is the first case report of a Japanese patient with H-ABC and treatment for this disease. Levodopa-carbidopa may be an effective treatment for H-ABC.