Biomedical subjects

Yoko Ohtsuka

Publications and source records attributed to Yoko Ohtsuka.

At least 19 recordsLinked to original sources

PubMed2006

Epilepsy development in infancy with epileptic discharges.

As a part of the study to prevent West syndrome (WS) by early treatment, we assessed what kind of epilepsy developed in infants who showed epileptic discharges in early infancy. EEG examinations were performed on 116 infants born from 1997 to September 2004, both before and after 3 months of corrected age (CA). We divided 45 infants who showed epileptic discharges in early infancy into two groups according to the existence of periventricular leukomalacia (PVL) and retrospectively performed the course observation at the survey point on April 1 in 2005. Out of 45 infants showing epileptic discharges in early infancy, 26 developed WS. Compared with infants without PVL, infants with PVL were more likely to develop WS than infants without PVL. Furthermore, infants with PVL were more likely to develop WS than other types of epilepsy. Namely, 11 out of 17 infants with PVL developed WS at the survey point. All infants with WS showed initial epileptic discharges before 5 months of corrected age (CA), and most of them (except for five) had initial epileptic discharges before 3 months of CA. There were two infants who once developed hypsarrhythmia on EEG; however, after starting VPA therapy, they did not develop WS with the improvement of EEG findings, and one was presented here in detail. We proposed that preterm infants with PVL who showed epileptic discharges before 3 months of CA should be treated by antiepileptic drugs to prevent the onset of WS syndrome.

Age Factors↗

PubMed2006

A population-based survey of childhood epilepsy in Okayama Prefecture, Japan: reclassification by a newly proposed diagnostic scheme of epilepsies in 2001.

The purpose of this study is to clarify the usefulness and problems of the newly proposed classification of epilepsies (International League Against Epilepsy: ILAE, 2001) in the epidemiological studies of epilepsy. We previously conducted an epidemiological study in Okayama Prefecture, Japan, in 1999, using the ILAE 1989 classification. Among 250,997 children under 13 years of age, 2220 epileptic patients were ascertained. In this study, we reclassified them according to the ILAE 2001 classification, focusing on axes 2 (seizure types) and 3 (syndromes). We were able to classify 1803 (95.0%) seizure types out of 1899 with detailed clinical information. In focal seizures, the most common were secondarily generalized seizures (88.6%), which generally do not represent a unique anatomic substrate. In generalized seizures, topic-clonic seizures (40.7%) and spasms (21.0%) were the most common. We identified only 269 (12.1%) patients with specific epilepsy syndromes out of the 2220. We classified 1761 patients without specific syndromic diagnoses only by axis 2, but the new concept of epileptic seizure types, representing a unique pathophysiologic mechanism and anatomic substrate, was not very meaningful in most cases, even in those with focal seizures.

Child↗

PubMed2006

Diagnostic issues and treatment of cryptogenic or symptomatic generalized epilepsies.

To clarify the diagnostic issues and treatment of patients with cryptogenic or symptomatic generalized epilepsies, not including West syndrome (WS), we investigated electroclinical change during the clinical course, and treatment effects in these patients. The selection criteria were minor generalized seizures as their main seizure type and diffuse epileptic discharges as their main EEG findings. Regarding EEG, we included EEGs that predominantly displayed multifocal spike-waves because of the inclusion of severe epilepsy with multiple independent spike foci (SE-MISF). We divided the subjects into two groups according to their main seizure types: Group A (54 patients) with brief tonic seizures and Group B (24 patients) with myoclonic seizures and/or atypical absences. The main epileptic syndromes were considered to be Lennox-Gastaut syndrome and SE-MISF in Group A, and epilepsy with myoclonic-astatic seizures in Group B. A history of WS was often seen in Group A, but it was exceptional in Group B. During the clinical course, seizure types did not basically change in Group A. EEG patterns were changeable in both groups. Although there was some overlap in electroclinical manifestations among epileptic syndromes, a transition between the two groups was not seen. High-dose valproate and ethosuximide were the most effective in Groups A and B, respectively. Long-term prognosis was significantly more favorable in Group B than in Group A.

Adolescent↗

PubMed2006

A developmental study of scores of the Boston Qualitative Scoring System.

To elucidate developmental changes of the Summary Scores of the Boston Qualitative Scoring System (BQSS) for the Rey-Osterrieth Complex Figure (ROCF). One hundred healthy children aged 6-16 (average 9.7 +/- 2.4; 60 boys, 40 girls). The ROCF was administered and graded based on the BQSS. The subjects were classified in four age-groups: 6- and 7-year-olds; 8- and 9-year-olds; 10- and 11-year-olds; and 12- and 16-year-olds. The differences in Summary Scores were examined among age-groups. All BQSS Summary Scores except Delayed Retention showed clear developmental changes. The Copy Presence Accuracy, the Immediate Presence Accuracy, the Delayed Presence Accuracy, and the Immediate Retention showed continuous development throughout childhood, though some differences were noted in the age ranges during which each score showed the most rapid development. The Organization score showed a somewhat peculiar pattern, with rapid development during the age ranges of 8-9 and 10-11 and with no distinctive development before and after these ranges. Five of the six BQSS Summary Scores showed clear developmental changes with a different developmental pattern in each score. Especially, the Organization score was unique and was supposed to reflect a different underlying process than the other Summary Scores, which might relate to the local and global processing style. BQSS is a promising tool for the evaluation of higher brain functions in childhood.

Adolescent↗

PubMed2006

The mildest known case of Fukuyama-type congenital muscular dystrophy.

We present a 14-year-old boy with Fukuyama-type congenital muscular dystrophy (FCMD) who shows the mildest muscle weakness ever reported with this affliction and exceptionally mild mental retardation, but who has intractable epilepsy. Magnetic resonance imaging showed the typical abnormalities of FCMD. Molecular genetic analyses revealed a 3 kb insertion mutation in the fukutin gene heterozygously. We could find no mutation in the coding region of the fukutin gene in the chromosome without a 3 kb insertion. The most probable mechanism of clinical manifestation in this patient could be either a mutation in the noncoding regions of the fukutin gene on the chromosome without the ancestral founder haplotype of FCMD, or an error in the process of transcription or translation. Another possibility is the abnormalities in other genes involved in the glycosylation of alpha-dystroglycan, such as Fukutin-related protein and LARGE genes.

Adolescent↗

PubMed2006

Are pervasive developmental disorders and attention-deficit/hyperactivity disorder distinct disorders?

We studied the relationship between patients with attention-deficit/hyperactivity disorder (ADHD) and those with pervasive developmental disorders (PDD), using the High-Functioning Autism Spectrum Screening Questionnaire (ASSQ) and ADHD Rating Scale-IV. The ASSQ scores of the PDD group and the ADHD group were significantly higher than the control group. Furthermore, the PDD group scored higher than the ADHD group. Both groups also showed higher scores than the control group in all three domains, that is, restricted and repetitive behavior, social interaction, and communication problem. The PDD and the ADHD group showed no significant difference in the domains of communication problem, and restricted and repetitive behavior. The PDD group had a higher score than the ADHD group only in the social interaction domain. In total score, inattention score, and hyperactivity/impulsivity score on the ADHD Rating Scale-IV, both groups were significantly higher than the control group. Between the ADHD and the PDD groups, there was no significant difference in the three scores. The patients with strictly diagnosed ADHD had many PDD-related symptoms, and the patients with PDD had many ADHD-related symptoms. It therefore seems difficult to make a distinction between ADHD and PDD by using the present diagnostic criteria in the DSM-IV. We should evaluate each patient in terms of both sets of criteria.

Adolescent↗

PubMed2006

Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders.

To elucidate an effective therapeutic strategy for 'ESES syndrome', epilepsy with electrical status epilepticus during slow sleep (ESES) and its related epileptic disorders, we studied the effect of treatment on the EEG pattern of continuous spike-waves during slow wave sleep (CSWS) in 15 afflicted patients. Basically performed in the following order, the employed therapies included (1) high-dose valproate (VPA) therapy (serum level >100 microg/ml); (2) a combination therapy of VPA and ethosuximide (ESM); (3) short cycles of high-dose diazepam (oral or intrarectal DZP, 0.5-1 mg/kg per day for 6-7 days); and (4) intramuscular synthetic ACTH-Z therapy (0.01-0.04 mg/kg per day for 11-43 days). Regarding the initial EEG effect, a remission of CSWS was achieved by high-dose VPA therapy in 7 of 15 trials (47%), by the combination therapy of VPA and ESM in 3/7 trials (43%), by short cycles of high-dose DZP in 2/4 trials (50%), and by ACTH-Z therapy in 2/5 trials (40%). A permanent remission of ESES syndrome was achieved by high-dose VPA therapy and/or combination therapy of VPA and ESM in 10 patients (67%). The effects of short cycles of high-dose DZP and ACTH-Z therapy were at best temporary. Our strategy for the treatment of ESES syndrome is therefore considered valid.

Adolescent↗

PubMed2006

Prevalence of childhood epilepsy and distribution of epileptic syndromes: a population-based survey in Okayama, Japan.

PURPOSE: A population-based survey childhood epilepsy was undertaken in Okayama Prefecture, Japan, to determine the prevalence rate and the distribution of epilepsies and epileptic syndromes according to the International Classification (ILAE, 1989). METHODS: Information on patients younger than 13 years with active epilepsy was collected from medical records. Patients diagnosed with epilepsy according to clinical and EEG findings were put on the list even if those patients had had a single seizure or seizures occurring during febrile episodes. RESULTS: In total, 2,220 cases were identified from a background population of 250,997. The prevalence rate was 8.8 per 1,000. If we exclude patients who had experienced a single seizure or seizures occurring during febrile episodes to compare our results with previous reports, the prevalence rate was 5.3 per 1,000. Of the 2,220 cases, 2,030 (91.4%) were classified into three major categories by ILAE classification. They consisted of 1,556 (76.7%) with localization-related epilepsy, 453 (22.3%) with generalized epilepsy, and 21 (1.0%) with undetermined epilepsy. Of the 2,030 cases, 309 (15.2%) were classified into epileptic syndrome categories, and 84.8% of the total were nonspecific types of epilepsy. CONCLUSIONS: The prevalence rate of childhood epilepsy was distributed from 5.3 to 8.8 per 1,000. The appearance rate of various types of epileptic syndromes was low. Most cases could not be classified into the detailed categories of the International Classification (ILAE, 1989).

Age Factors↗

PubMed2006

EEG dipole characteristics in Panayiotopoulos syndrome.

PURPOSE: Panayiotopoulos syndrome (PS) is a type of benign childhood partial epilepsy that is frequently associated with abundant multifocal spikes other than main occipital spikes on the EEG. In this study, we investigated the characteristic features of dipoles in PS. METHODS: We performed dipole analysis of the interictal occipital spike discharges seen in 10 children with PS (group A) and in 10 children with other types of symptomatic localization-related epilepsy (group B). We analyzed the dipoles of the averaged spike in each patient. RESULTS: In group A, the averaged occipital spikes in each patient showed dense dipole locations in the mesial occipital area; in group B, widely scattered dipole locations were observed. In Group A, the geometric centers of the dipoles at each time point (such as at the main negative peak and before or after the main peak) were estimated in the neighboring locations. In contrast, they tended to be scattered in group B. CONCLUSIONS: Our study reveals that PS has high dipole stability, similar to that of rolandic epilepsy. From the electroencephalographic view, this seems to indicate a close link between these two syndromes.

Adolescent↗

PubMed2006

EEG and seizure exacerbation induced by carbamazepine in Panayiotopoulos syndrome.

We report on a 4-year 8-month-old boy with Panayiotopoulos syndrome who showed atypical evolution with newly developed absence seizures and EEG exacerbation induced by carbamazepine. Soon after the introduction of carbamazepine, EEGs began to worsen, and finally absence seizures and myoclonic seizures appeared. Immediately after we discontinued carbamazepine, the seizures disappeared and the EEG improved. Carbamazepine may induce unusual electroclinical features, electrophysiologically explained by bilateral synchrony. This case provides more evidence of the close links between Panayiotopoulos syndrome and benign childhood epilepsy with centrotemporal spikes.

Anticonvulsants↗

PubMed2006

[A case of benign neonatal sleep myoclonus].

We report on a male infant with benign neonatal sleep myoclonus (BNSM). At 12 days of age, he began to have frequent myoclonic jerks in the lower and/or upper extremities during sleep. Myoclonic jerks appeared bilaterally/synchronously and persisted for several minutes to 10 minutes. Both interictal and ictal EEG findings were normal. During follow-up, the patient did not take any medication, and his myoclonic jerks gradually decreased. They completely disappeared at 50 days of age. The patient's development was normal. BNSM is a benign disorder and myoclonic jerks generally disappear without medication. Early diagnosis is important to avoid unnecessary treatment. EEG-EMG recording is useful for diagnosis.

Electroencephalography↗

PubMed2005

Mutation screen of GABRA1, GABRB2 and GABRG2 genes in Japanese patients with absence seizures.

Absence seizures are classified into typical and atypical absences according to clinical and EEG characteristics. Although missense mutations in the GABA(A) receptor gamma2 subunits (GABRG2) gene have recently been detected in two families with typical absence seizures, no study has been carried out to clarify the relationship between atypical absence and GABA(A) receptors. We performed mutation analysis of all the coding exons of GABA(A) receptor alpha1, beta2 and gamma2 subunit (GABRA1, GABRB2 and GABRG2) genes by direct sequencing to clarify whether there was common molecular biological mechanism underlying both typical and atypical absences. We recruited 52 unrelated Japanese patients, thirty-eight with typical absences and 14 with atypical absences. They consisted of 38 with childhood absence epilepsy, three with Lennox-Gastaut syndrome, two with epilepsy with myoclonic-astatic seizures and nine with epilepsy with continuous spike-waves during slow wave sleep. All of the subjects were idiopathic or cryptogenic cases without any organic brain lesions or underlying diseases. We detected five polymorphisms (T156C in GABRA1, C1194T in GABRB2, and C315T, T588C and C1230T in GABRG2), and they are silent mutations. In conclusion, mutations in GABRA1, GABRB2 and GABRG2 do not seem to be a major genetic cause of epilepsy with typical and atypical absences in Japanese subjects.

DNA Mutational Analysis↗

PubMed2005

The Rey-Osterrieth Complex Figure as a measure of executive function in childhood.

In adults, the Rey-Osterrieth Complex Figure (ROCF) can be used for the assessment of not only visuoconstructional ability and visual memory, but also executive function in adults. We studied whether ROCF scores also correlated with executive function in childhood. The subjects consisted of 56 patients with various neurological diseases (5 years 7 months-14 years 11 months; mean: 8 years 8 months; M 42, F 14) whose full-scale IQs were 70 or higher (mean: 93.3). All subjects underwent the Wechsler Intelligence Scale for children third edition (WISC-III) and various psychological tests focusing on executive function. We evaluated the ROCF with the Boston Qualitative Scoring System (BQSS). We calculated the partial correlation coefficients between the BQSS Summary Scores and representative scores of other executive function tests, using age as the control variable. Among the scores of the various examinations, the Perseverative Errors of Nelson of the Wisconsin Card Sorting Test, the raw scores of the Mazes (WISC-III), the Digit Span (WISC-III), and the Block Design (WISC-III) were correlated significantly with two to four BQSS Summary Scores (P<0.05 or P<0.01). In contrast, the scores of the Trail Making Test, the Stroop Test, and the Commission Error of Continuous Performance Test-II did not show a significant correlation with any of the BQSS Summary Scores. The ROCF evaluated with the BQSS reflects not only visuoperceptual ability and visuoconstructional ability, but also executive function, especially planning and organization. However, a new BQSS Summary Score should be devised since no existing BQSS index specifically reflects executive functions with an outstandingly strong correlation.

Adolescent↗

PubMed2005

Relationship between severity of epilepsy and developmental outcome in Angelman syndrome.

To clarify the relationship between the degree of developmental disturbance and the severity of epilepsy in Angelman syndrome, we investigated 11 patients and measured both clinical outcomes and EEG parameters. Seven patients were followed up until after 8 years of age. Eight patients were found to have 15q11-q13 deletions. All patients experienced epileptic seizures and all but one displayed non-convulsive status epilepticus (NCSE) during the period of observation. Epileptic seizures, including NCSE, disappeared by around 8 years of age. In addition, specific epileptic discharges, as measured by EEG, tended to subside with age. Although development seemed almost normal or only slightly delayed during the first 6 months of life, all patients eventually developed severe retardation. Two patients displayed very severe retardation and were unable to comprehend language or walk independently at the last follow-up. Only one patient was able to speak a few meaningful words. In one of the most severely affected patients, who showed the earliest onset of seizures and NCSE, it is possible that the repetitive bouts of NCSE might be responsible for the severe developmental outcome. However, the other patient with particularly severe retardation did not experience NCSE, while the patient with the most favorable outcome had repetitive episodes of NCSE. Therefore, we conclude that the severity of developmental disturbance in Angelman syndrome is not necessarily related to the degree of epilepsy. However, intensive therapy for NCSE might still be justified because there are some patients in whom NCSE results in a transient and sometimes permanent decline in mental and motor functioning.

Adolescent↗

PubMed2005

Dipole analysis in panayiotopoulos syndrome.

Panayiotopoulos syndrome (PS) is a type of benign childhood partial epilepsy, which has a good prognosis despite the fact that it is frequently associated with abundant multifocal spikes on the electroencephalography (EEG). We investigated whether stable dipoles, as seen in rolandic epilepsy, were also present in PS. We performed dipole analysis of the interictal spike discharges seen in the interictal EEGs of eight children with PS. We chose more than 10 spikes for each kind of spike, and investigated whether or not more than three of these spikes showed consistently stable dipole locations. (1) We observed 15 different kinds of spikes in various regions in the EEGs of the eight children. (2) Twelve of the 15 kinds of spikes had dipoles with a high goodness of fit. Furthermore, 14 of the 15 spikes had stable dipoles with similar locations for more than three individual spikes. (3) Fourteen of the 15 spikes, including frontal spikes, showed dense dipole locations in the mesial occipital area. Thirteen of these 14 spikes also showed other dipole locations in the rolandic area and/or the vertex (Cz). Our study revealed that the various types of spikes observed in PS have similar and stable dipole locations. The dipoles showing high stability, were located in the mesial occipital area, and were accompanied by dipoles located in the rolandic area. The stability and location of these dipoles indicate that there may be a pathogenetic link between PS and rolandic epilepsy.

Action Potentials↗

PubMed2005

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.

A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.

Adolescent↗

PubMed2005

Symptoms related to ADHD observed in patients with pervasive developmental disorder.

To elucidate attention-deficit/hyperactivity disorder (ADHD)-related factors observed in high-function pervasive developmental disorder (PDD) and their impact on daily life, we classified high-function PDD patients according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD with the exception of the exclusion criteria (coexistence with PDD), and studied the relationship between ADHD-related aspects and daily behavior problems using the Child Behavior Checklist (CBCL). The subjects were divided into two groups: Group 1, eight patients less than 6 years of age; and Group II, eight patients 6 years of age and older. Six patients in Group II met the criteria for ADHD. Five of them were classified as having the predominantly inattentive type of ADHD, and the remaining patient exhibited the combined type. However, no patient in Group I met the criteria for ADHD, suggesting the low sensitivity of the DSM-IV criteria for assessing the inattentiveness of preschoolers. The analyses of the correlation between corresponding items in the DSM-IV criteria and CBCL scores suggested that ADHD-related symptoms in high-function PDD patients have an impact on their daily lives.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Dipole modeling of epileptic spikes can be accurate or misleading.

PURPOSE: We investigated the accuracy and potential for serious error when representing cortical generators of epileptic spikes with the common single-dipole model. Spike generators were realistically simulated with cortical areas of different extents. METHODS: The source was simulated by using a patch that comprised small triangles on the cortical surface, each triangle having an elementary dipole generator with a moment corresponding to real intracerebral fields of spikes. The source-patch covered various clinically important parts of the temporal and frontal lobes, with an area ranging from 6 to 120 cm2. The scalp field was computed for each source-patch by using a realistic head model and was fitted by the single-dipole model to determine the best-fit dipole and the intracerebral distribution of residual variance (RV). Dipole modeling also was performed for the simulated scalp field with additional real EEG background. RESULTS: The RV after fitting a dipole to the scalp field without noise was at most 1.34%. Scalp spikes arising from sources of 6 cm2 were of small amplitude, and the dipoles estimated for these spikes were inconsistent. Extension of the source area was associated with increase of scalp potential amplitude, only very small increase of RV, and increased consistency of the estimated dipoles. When the source was very large, the dipoles clustered at very misleading locations. CONCLUSIONS: Pitfalls in dipole source localization are caused by the procedure of fitting the simplistic dipole model to real cortical sources with spatial extent and complex configuration.

Action Potentials↗