Tatsuya Koeda

Visuo-perceptual impairment and cerebral lesions in spastic diplegia with preterm birth

Eighteen cases of spastic diplegia (SD) ranging in age from 5 year 4 month to 9 year 5 month with preterm birth were studied to clarify the relationship between visuo-perceptual impairment and their cerebral lesions. All underwent neuropsychological examinations including the Frostig developmental test of visual perception, Tanaka-Binet or Suzuki-Binet intelligence test, and MRI examination. Cerebral lesions were detected in all subjects, and the volume of the peritrigonal white matter of the parietal and occipital lobes was significantly correlated with the visuo-perceptual impairment (r = 0.74, in the axial plane; r = 0.64, in the coronal plane). We propose that visuo-perceptual impairment is caused by cerebral lesions and that the measurement of peritrigonal white matter by MRI is useful for detecting potential visuo-perceptual impairment at an early age.

MR imaging of spastic diplegia

SummaryEighteen children (eleven preterm birth and seven term birth) with clinical evidence of spastic diplegia (SD) were studied to clarify the differences of the lesions between preterm and term SD on MR imaging. All with preterm birth showed similar abnormalities of the periventricular white matter represented by high intensity in T2-weighted imaging and low intensity in T1 imaging. It seemed that the lesions were periventricular leukomalacia (PVL) and dysmyelination pathologically and correlated well clinically with spastic diplegia. SD with term birth group showed various lesions, two brain anomalies (schizencephaly and corpocephaly), one PVL, four showed no lesions. We suggested that SD with preterm birth is not only a clinical but also a pathological entity.

Neural substrates of sarcasm: A functional magnetic-resonance imaging study

The understanding of sarcasm reflects a complex process, which involves recognizing the beliefs of the speaker. There is a clear association between deficits in mentalizing, which is the ability to understand other peoples behavior in terms of their mental state, and the understanding of sarcasm in individuals with autistic spectrum disorders. This suggests that mentalizing is important in pragmatic non-literal language comprehension. To highlight the neural substrates of sarcasm, 20 normal adult volunteers underwent functional magnetic-resonance imaging. We used scenario-reading tasks, in which sentences describing a certain situation were presented, followed by the protagonists comments regarding that situation. Depending on the situation, the semantic content of the comments was classified as sarcastic, non-sarcastic, or contextually unconnected. As the combination of the first and second sentences represented discourse-level information that was not encoded in the individual sentences, sarcasm detection was represented as the differential activation induced by the second sentences. Sarcasm detection activated the left temporal pole, the superior temporal sulcus, the medial prefrontal cortex, and the inferior frontal gyrus (Brodmanns area [BA] 47). The left BA 47 was activated more prominently by sarcasm detection than by the first sentence. These findings indicate that the detection of sarcasm recruits the medial prefrontal cortex, which is part of the mentalizing system, as well as the neural substrates involved in reading sentences. The left BA 47 might therefore be where mentalizing and language processes interact during sarcasm detection.

Central Motor Reorganization in Cerebral Palsy Patients with Bilateral Cerebral Lesions

Transcranial magnetic stimulation (TMS) has been used to describe cortical plasticity after unilateral cerebral lesions. The objective of this study was to find out whether cortical plasticity occurs after bilateral cerebral lesions. We investigated central motor reorganization for the arm and leg muscles in cerebral palsy (CP) patients with bilateral cerebral lesions using TMS. Seventeen patients (12 with spastic diplegia, 1 with spastic hemiplegia, and 4 with athetoid CP) and 10 normal subjects, were studied. On CT/MRI, bilateral periventricular leukomalacia was observed in all spastic patients with preterm birth. In two normal subjects, motor responses were induced in the ipsilateral tibialis anterior, but no responses were induced in any normal subject in the ipsilateral abductor pollicis brevis (APB) or biceps brachii (BB). Ipsilateral responses were more common among CP patients, especially in TMS of the less damaged hemisphere in patients with marked asymmetries in brain damage: in 3 abductor pollicis brevis, in 6 BBs, and in 15 tibialis anteriors. The cortical mapping of the sites of highest excitability demonstrated that the abductor pollicis brevis and BB sites in CP patients were nearly identical to those of the normal subjects. In patients with spastic CP born prematurely, a significant lateral shift was found for the excitability sites for the tibialis anterior. No similar lateral shift was observed in the other CP patients. These findings suggest that ipsilateral motor pathways are reinforced in both spastic and athetoid CP patients, and that a lateral shift of the motor cortical area for the leg muscle may occur in spastic CP patients with preterm birth.

The metaphor and sarcasm scenario test: a new instrument to help differentiate high functioning pervasive developmental disorder from attention deficit/hyperactivity disorder

It is sometimes difficult to discriminate high functioning pervasive developmental disorders (HFPDD) from attention deficit/hyperactivity disorders (AD/HD) in young children because of the behavioral similarities between the two. For adequate diagnosis, understanding fundamental differences in their social cognitive abilities might become significant. In order to detect the differences in social cognitive abilities between AD/HD and HFPDD, a new test, the Metaphor and Sarcasm Scenario Test (MSST) was developed. One hundred and ninety-nine normal school children (the control group), 29 AD/HD children and 54 HFPDD children were involved. The results showed that the inability to understand a sarcastic situation was specific to children with HFPDD, both children with AD/HD and HFPDD could not equally understand metaphor. The correlation between the comprehension of sarcasm and success in the theory of mind task was remarkably high but not for comprehension of metaphor. In conclusion, the MSST has the potential to discriminate HFPDD from AD/HD in young children.

Quantitative electroencephalogram analysis in dementia with Lewy bodies and Alzheimer's disease.

Clinicopathophysiological differences between dementia with Lewy bodies (DLB) and Alzheimers disease (AD) remain obscure. Our goals were to determine whether characteristic findings of electroencephalogram (EEG) power and coherence in DLB and a differential pathophysiological mechanism of quantitative EEG existed between DLB and AD. The group consisted of 15 patients with AD or DLB and 12 age-matched controls. Original EEG signals were recorded from 14 scalp electrodes positioned according to the International 10-20 System, using digitally linked earlobes as a reference. Although EEG power spectral analysis showed increasing EEG power density in patients with DLB in the delta and theta bands, such a difference did not exist in patients with AD. Compared with AD, the delta and theta band intrahemispheric coherence values in the fronto-temporo-central regions were higher in DLB. In the beta band, AD was lower than DLB in almost all temporo-centro-parieto-occipital regions. Comparing the mean power value between patients with/without donepezil treatment, there was a significantly lower EEG power density in the delta and theta bands in DLB subjects taking donepezil than in subjects not taking donepezil, whereas there was no significant difference in AD patients. These results suggest that cholinergic dysfunction is stronger in DLB than AD.

Distinction between the literal and intended meanings of sentences: A functional magnetic resonance imaging study of metaphor and sarcasm

To comprehend figurative utterances such as metaphor or sarcasm, a listener must both judge the literal meaning of the statement and infer the speakers intended meaning (mentalizing; Amodio and Frith, 2006). To delineate the neural substrates of pragmatic comprehension, we conducted functional magnetic resonance imaging (fMRI) with 20 normal adult volunteers. Participants read short stories followed by a target sentence. Depending on the context provided by the preceding stories, the target sentences were classified as follows: (1) metaphor versus literally coherent; (2) metaphor versus literally incoherent; (3) sarcasm versus literally coherent; and (4) sarcasm versus literally incoherent. For each task pair, we directly compared the activations evoked by the same target sentences in the different contexts. The contrast images were incorporated into a 2 (metaphor and sarcasm)×2 (literal coherency and incoherency) design. Metaphor-specific activation was found in the head of the caudate, which might be involved in associating statements with potential meanings, and restricting sentence meanings within a set of possible candidates for what the speaker intended. Sarcasm-specific activation was found in the left amygdala, which is an important component of the neural substrates of social behavior. Conjunction analysis revealed that both metaphor and sarcasm activated the anterior rostral medial frontal cortex (arMFC), which is a key node of mentalizing. A distinct literal coherency effect was found in the orbital MFC, which is thought to be involved in monitoring. These mesial frontal areas are jointly involved in monitoring literal coherency and mentalizing within social contexts in order to comprehend the pragmatic meanings of utterances.

Unilateral occlusion of the middle cerebral artery after varicella-zoster virus infection

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.

Non-radioactive DNA diagnosis for the fragile X syndrome in mentally retarded Japanese males

A rapid screening test was developed to detect CGG repeat expansion of the FMR-1 gene causing the fragile X syndrome by a non-radioisotope PCR technique. A biotin-labeled primer was initially used and the biotin-labeled PCR product was detected by means of chemiluminescence. The normal PCR product of around 300 bp was not created in the abnormal FMR-1 gene sample with this method. Four positive samples were found among those from 226 mentally retarded males, but the CGG repeat expansion was shown on Southern blot analysis in only one sample. To eliminate false-positive samples, a hybridization method involving a biotin-labeled (CGG)s oligonucleotide was developed for the PCR product and the CGG repeat expansion could be detected. Finally, 256 mentally retarded males in Japan were examined and only 2 abnormal samples were detected. The prevalence of this abnormality was less than 1%, which is relatively lower than those reported previously.

A randomized, double-blind, placebo-controlled study of atomoxetine in Japanese children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVES Until the recent approval of methylphenidate (MPH), Japan had no approved treatment for attention-deficit/hyperactivity disorder (ADHD). The need still exists for an effective, safe, nonstimulant treatment. This first placebo-controlled Japan study of an ADHD nonstimulant therapy assessed atomoxetine efficacy and safety to determine the optimal dose for controlling ADHD symptoms in children and adolescents. METHODS A total of 245 Japanese children and adolescents, aged 6-17 years and diagnosed with ADHD, were randomly assigned to receive placebo or one of three atomoxetine doses (0.5, 1.2, and 1.8 mg/kg per day) over 8 weeks. Symptoms were assessed with the Japanese Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator scored and integrated with teacher reports (ADHD RS-IV-J:I/Sch). Adverse events, vital signs, laboratory tests, and electrocardiograms (ECGs) were obtained for safety analysis. RESULTS In all, 234 patients completed the study. Atomoxetine at 1.8 mg/kg per day was significantly superior to placebo in reducing ADHD symptoms (p = 0.01; one-sided). Decreased appetite and vomiting were significantly greater in the atomoxetine treatment groups; however, no clinically significant differences were observed. Two patients discontinued due to affect lability and headache. A linear dose-response and vital signs similar to those from other atomoxetine studies were observed. CONCLUSION Atomoxetine provides an effective and safe nonstimulant option for the treatment of Japanese pediatric patients with ADHD.