[Show abstract][Hide abstract] ABSTRACT: Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 mutations in abnormal corticogenesis of MSS. SIL1-silencing caused neuronal migration delay during corticogenesis ex vivo. While RNAi-resistant SIL1 rescued the defects, three MSS-causing SIL1 mutants tested did not. These mutants had lower affinities to HSPA5 in vitro, and SIL1-HSPA5 interaction as well as HSPA5 function was found to be crucial for neuronal migration ex vivo. Furthermore time-lapse imaging revealed morphological disorganization associated with abnormal migration of SIL1-deficient neurons. These results suggest that the mutations prevent SIL1 from interacting with and regulating HSPA5, leading to abnormal neuronal morphology and migration. Consistent with this, when SIL1 was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed. Taken together, abnormal neuronal migration and interhemispheric axon development may contribute to MR in MSS.
EMBO Molecular Medicine 01/2014; · 7.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Epilepsies with an onset during the early infantile period are relatively rare and their characteristics are not well recognized. The aim of this study was to determine the clinical characteristics of epilepsies with an onset during the early infantile period. Methods: Clinical information on 73 patients with the onset of epilepsy within the first four months was collected from hospitals affiliated with Nagoya University. Patients were categorized into three groups: the idiopathic (20 patients), cryptogenic (19 patients), and symptomatic groups (34 patients). Results: Fourteen (70%) of the 20 patients in the idiopathic group, nine (47%) of the 19 patients in the cryptogenic group, and 10 (29%) of the 34 patients in the symptomatic group had their first seizure within the first month of life. All patients in the idiopathic group, 12 patients (63%) in the cryptogenic group, and 18 patients (53%) in the symptomatic group had partial seizures (PS) alone throughout their clinical course. Four patients in the cryptogenic group and nine in the symptomatic group had PS at the onset, but evolved into spasms later. All patients in the idiopathic group, 13 patients (68%) in the cryptogenic group, and 13 patients (38%) in symptomatic group had experienced no seizures for at least one year at the time of the last follow-up. Conclusions: In patients with non-idiopathic epilepsy, an age-dependent evolution of seizure types was often observed. Recognition of this subgroup of patients could be important for the identification of appropriate candidates for early epilepsy surgery.
[Show abstract][Hide abstract] ABSTRACT: To investigate the survival rate and causes of death in patients with severe motor and intellectual disabilities (SMIDs) that necessitated tracheotomy, we retrospectively analyzed 90 patients who underwent tracheotomy between 1990 and 2009. Indications for tracheotomy in these patients were upper airway obstruction (44 patients), recurrent aspiration pneumonia (28 patients), retained secretions (23 patients), prolonged mechanical ventilation (18 patients), chronic respiratory failure (9 patients), central respiratory failure (5 patients), and gastroesophageal reflux (8 patients). Most of the patients underwent tracheotomy at the age of 0-5 years or 10-19 years. As of April 1, 2010, 28 patients had died. The survival rate was 0.91 at 1 year, 0.74 at 5 years, 0.59 at 10 years, 0.54 at 15 years, and 0.40 at 19 years after tracheotomy. Massive tracheal bleeding due to development of tracheo-innominate artery fistulas occurred in 5 patients, and 4 of them died. They were thirteen years of age or older when they underwent tracheotomy, and developed fistulas after 2 weeks or later. In contrast, 7 patients at high risk for fistula formation, including those that had developed severe tracheomalacia associated with granulation or warning hemorrhages, underwent preventive resection of the innominate artery, and all of them had survived. It is important to regularly evaluate patients with SMIDs who have undergone tracheotomy by using bronchofiberscopy to identify risk factors for tracheoinnominate artery fistulas, a preventable cause of death.
No to hattatsu. Brain and development 01/2012; 44(1):25-8.
[Show abstract][Hide abstract] ABSTRACT: This study was performed to clarify the relationship between prolonged depression of electroencephalography (EEG) in term and near-term infants with hypoxic ischemic encephalopathy (HIE) and the later development of West syndrome (WS).
We investigated 17 term and near-term infants with HIE. Inclusion criteria were as follows: ≥35 weeks of gestation, clinical signs of HIE, magnetic resonance imaging (MRI) lesions corresponding to HIE, assessment of outcome at >18 months of age, depression of EEG, and serial EEG examinations. The 17 infants were divided into the following two groups: Group A (n = 4) with prolonged EEG depression over 21 days of age, and group B (n = 13) with disappearance of EEG depression by 21 days of age.
WS developed in all four infants in group A, but in only one of 13 infants in group B. WS occurred significantly more frequently in group A than in group B. For the prediction of subsequent development of WS, prolonged EEG depression over 21 days of age showed sensitivity of 0.80 and specificity of 1.0. In both groups, abnormal irregular faster waves with or without EEG depression were seen in 11 infants between 2 and 28 days of age. They had no significant relationship with WS, but were significantly related to an adverse developmental outcome.
Prolonged depression of EEG over 21 days of age in term or near-term infants with HIE is a valuable predictor of the later development of WS.
[Show abstract][Hide abstract] ABSTRACT: SLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in SLC19A3 cause two distinct clinical phenotypes, biotin-responsive basal ganglia disease and Wernicke's-like encephalopathy. Biotin and/or thiamin are effective therapies for both diseases.
We conducted on the detailed clinical, brain MRI and molecular genetic analysis of four Japanese patients in a Japanese pedigree who presented with epileptic spasms in early infancy, severe psychomotor retardation, and characteristic brain MRI findings of progressive brain atrophy and bilateral thalami and basal ganglia lesions.
Genome-wide linkage analysis revealed a disease locus at chromosome 2q35-37, which enabled identification of the causative mutation in the gene SLC19A3. A pathogenic homozygous mutation (c.958G > C, [p.E320Q]) in SLC19A3 was identified in all four patients and their parents were heterozygous for the mutation. Administration of a high dose of biotin for one year improved neither the neurological symptoms nor the brain MRI findings in one patient.
Our cases broaden the phenotypic spectrum of disorders associated with SLC19A3 mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.
BMC Medical Genetics 01/2010; 11:171. · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study sought to clarify chronologic changes in neonatal electroencephalographic (EEG) findings in periventricular leukomalacia (PVL).
We obtained serial EEG findings for all premature infants who were admitted to our hospital at gestational age of < or =33 weeks between 1997 and 2006. EEG recordings were obtained on days 1 to 4, 5 to 14, 15 to 28, 29 to 56, and 57 to 84. Abnormal EEG findings were classified as acute-stage abnormalities (ASAs) or chronic-stage abnormalities (CSAs) and were subclassified as mild, moderate, or severe. PVL was classified as noncystic, localized cystic, or extensive cystic. The final diagnosis of PVL was made through neurologic assessment and MRI findings at 24 months.
Fifty-five infants were diagnosed as having PVL, including 23 with noncystic PVL, 9 with localized cystic PVL, and 23 with extensive cystic PVL. ASAs were observed most frequently on days 1 to 4 and were observed rarely thereafter in all groups. CSAs were observed most frequently on days 5 to 14, were most severe on days 5 to 14, and then resolved within 1 to 2 months in all groups. CSAs in patients with extensive cystic PVL were more severe and persisted longer, compared with other groups. ASA and CSA severity was correlated with PVL severity.
EEG findings in PVL differed according to the severity of PVL and the time of recording. To detect PVL, > or =2 EEG recordings are recommended, 1 within 48 hours after birth, to detect ASAs, and 1 in the second week of life, to detect CSAs.
[Show abstract][Hide abstract] ABSTRACT: We retrospectively reviewed electroencephalography and magnetic resonance imaging findings for 21 children exhibiting delirious behavior during febrile illness. Among these, five patients had transient callosal lesions with or without white matter lesions on diffusion-weighted images. We compared the clinical characteristics, duration, and components of delirious behavior, the duration and severity of reduced consciousness, and EEG findings among patients with or without callosal lesions. No significant differences were detected in these items according to the presence or absence of callosal lesions. Adding insight into the pathogenesis of this condition, our study revealed that callosal lesions are not uncommon in patients exhibiting delirious behavior during febrile illness.
Brain & development 02/2009; 31(2):158-62. · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe the clinical, EEG, and MRI features of children with reduced diffusion in the unilateral hemispheres. Seven patients with reduced diffusion in the subcortical white matter of the unilateral hemisphere alone were identified. Their median age was 32 months. Human herpesvirus 6 infection was virologically proven in 2 patients and human herpesvirus 7 in 1. The initial neurological symptom was a prolonged seizure in 4, a brief seizure in 2, and delirious behavior in 1. Three patients had biphasic clinical course. Laboratory tests were unremarkable in most patients. MRI showed no abnormal findings during the acute phase, whereas reduced diffusivity in the unilateral hemisphere was seen during the subacute phase. EEG during the acute phase demonstrated marked slowing in the affected hemisphere in 1 patient, mild slowing in 4, and relatively low voltage in 1. No patients died, but 6 patients had various degrees of neurological sequelae. Acute encephalopathy with reduced diffusion in the unilateral hemisphere may be one of the representative phenotypes of acute encephalopathy.
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 07/2008; 13(2):154-9. · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to clarify the characteristics of ictal EEG findings of neonatal seizures in preterm infants. Seizures associated with ictal EEG changes were recognized in nine infants with gestational age of less than 37 weeks. Propagation, migration, shifting, changes in morphology of ictal EEG discharges were evaluated. Seizure manifestation was divided into the following categories; motor seizure, apneic seizure, automatic seizure and seizure without clinical symptoms. The types of the seizures were motor seizures in five infants, apneic in two, automatic in one and those without clinical symptoms in five. All seizures were of focal onset. The foci of seizures were temporal in six infants, occipital in two, central in one, and frontal in one. The morphology of ictal discharges was low voltage spikes or sharp waves in six infants, spikes in two, theta waves in one and high-voltage spiky theta in one. The propagation of ictal discharges was focal in five infants and regional in five. The migration of ictal discharges was observed in two infants and a shift in two. There was no clear relation between seizure manifestation and ictal EEG foci, duration of seizures and morphology or propagation of ictal discharges.
Brain and Development 05/2008; 30(4):261-8. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the usability of our MRI interpretation scheme among pediatricians with different skill levels in evaluating MRI of patients with cerebral palsy. We divided MRI findings into three groups: no abnormalities, pre/perinatally acquired lesions, and other abnormalities. Pre/perinatally acquired lesions were divided into six subgroups. Other abnormalities included brain malformations, ventriculomegaly, atrophic changes, and other unclassifiable abnormalities. We compared the interpretations of eight participants, i.e., three nonexpert pediatricians, two junior pediatric neurologists, and three senior pediatric neurologists, in evaluating magnetic resonance images of 73 children with cerebral palsy. The degree of agreement was substantial or near perfect for all participants. When limited to pre/perinatally acquired lesions, the degree of agreement was near perfect for all but one participant. The rate of correct diagnosis did not differ greatly according to participants' experience with pre/perinatally acquired lesions. For patients with basal ganglia thalamic lesions, multicystic encephalomalacia, and posthemorrhagic porencephaly, the rate of correct diagnosis increased according to participants' experience. Pre/perinatally acquired lesions can be appropriately interpreted by nonexpert pediatricians utilizing our interpretation scheme.
[Show abstract][Hide abstract] ABSTRACT: We studied the relation among serum cytokine levels, EEG changes, and mild neurological complications (delirium and febrile seizure) in children with influenza. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble tumor necrosis factor receptor-1 (sTNFR-1) were measured in 27 children with proven influenza infection with mild neurological complications (10 patients with delirium and 17 with febrile seizures) and seven control children. EEG was recorded in 14 children with neurological complications. EEG showed focal slowing in four of nine patients with delirium and in four of five with febrile seizures. Generalized slowing was observed in one patient with delirium. The median serum IL-6 level was 31.2+/-15.1 pg/ml (range, 7.5-64.5 pg/ml) in the delirium group, 42.3+/-44.0 pg/ml (range, 8.0-196.0 pg/ml) in the febrile seizure group, and 15.4+/-7.0 pg/ml (range, 7.2-28.0 pg/ml) in the control group. Serum TNF-alpha and sTNFR-1 levels were not different among three groups. Mild neurological complications associated with influenza were related to the mildly abnormal serum IL-6 levels and EEG findings. The combination of these parameters will be useful for early diagnosis and differentiation of neurological complications in children with influenza. Further studies will be necessary for investigating that IL-6 has the diagnostic value for differentiation between severe encephalopathy and mild neurological complications in children with influenza.
Brain and Development 09/2007; 29(7):425-30. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Children with sequelae of perinatal hypoxic-ischemic encephalopathy (HIE) occasionally suffer from cytokine-related disease. We investigated 12 children with perinatal HIE sequelae, who died in childhood, concerning (1) the incidence of cytokine-related disease as the cause of death, and (2) the characteristics of the cytokine-related disease. Six (50%) of the 12 patients died from cytokine-related disease:two had virus-associated hemophagocytic syndrome (VAHS) ; one had acute encephalopathy;one had systemic inflammatory response syndrome (SIRS); and two had severe pneumonia/acute respiratory distress syndrome (ARDS). These six patients presented with increased liver transaminase, LDH, and CK, and decreased platelet count and albumin. This study shows the high incidence of cytokine-related disease as the cause of death in children with perinatal HIE sequelae. Further investigation is needed to clarify the pathogenesis of this disease.
No to hattatsu. Brain and development 12/2006; 38(6):439-42.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the long-term outcome of children with benign partial epilepsy in infancy (BPEI).
A telephone-interview survey using a structured questionnaire was conducted with patients who were diagnosed as having possible BPEI at age 2 years and who were 8 years or older at the time of the survey. The data from 39 of 48 patients were available. The median age at the time of the survey was 11.3 years; 18 boys and 21 girls were included.
Three patients had a recurrence of unprovoked seizure beyond age 2 years. Four patients had cognitive problems (mild mental retardation in three and Asperger syndrome in one). An association of paroxysmal kinesigenic choreoathetosis was observed in three patients, and another three had experienced seizures associated with mild gastroenteritis. Major behavioral problems were not recognized in any patients. Four patients were excluded from having definite BPEI at age 5 years, and another two were excluded for having definite BPEI at the last follow-up. Eventually, 33 of 39 patients were categorized as having definite BPEI beyond 8 years of age.
A large majority of patients diagnosed as possibly having BPEI at age 2 years did not have a recurrence of unprovoked seizures and cognitive problems beyond 8 years of age.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to clarify the incidence and clinical features of prolonged unconsciousness and delirious behavior in children with febrile seizures. We studied 213 consecutive febrile seizures during 208 febrile episodes in 203 patients. The seizure manifestations, the duration of seizures, the duration of unconsciousness, and the presence or absence of delirious behavior were determined on the basis of interviews with the parents with the assistance of medical records. The duration of seizures was less than 5 minutes in 90.2% of the seizures. The duration of unconsciousness was less than 30 minutes in 93% of the seizures. Delirious behavior was observed in 2.0% of the patients. Delirious behavior appeared before febrile seizures, and its duration was not long. On multiple regression analysis, nongeneralized seizures, seizures of >/=5 minutes, and intravenous diazepam were demonstrated to be independently associated with prolonged unconsciousness. In conclusion, prolonged unconsciousness and delirious behavior are rare in children with febrile seizures. Careful diagnostic evaluation is necessary when a child with febrile seizures has associated prolonged unconsciousness or delirious behavior.
[Show abstract][Hide abstract] ABSTRACT: To determine the clinical significance of abnormal sharp transients other than positive rolandic sharp waves (PRS), electroencephalograms were used for the diagnosis of periventricular leukomalacia (PVL).
We evaluated 126 electroencephalograms from 93 preterm infants; 31 infants had PVL, and 62 were control infants. Frontal sharp waves (FS) were defined as sharp transients of positive polarity with an amplitude >100 microV. Occipital sharp waves (OS) were defined as those of negative polarity with an amplitude >150 microV. FS, OS, or PRS were considered to be present when there were >0.1 per minute.
The number of FS per minute was significantly higher in the PVL group than in the control group during days 0 to 4 and 5 to 7. The number of OS per minute was also significantly higher in the PVL group than in the control group during days 0 to 4, 5 to 7, and 8 to 14. The sensitivity of FS or OS was relatively high but that of PRS was low. The presence of two or more types of abnormal sharp transients was correlated with a poor outcome.
FS or OS may be useful for predicting which infant will have PVL.
Journal of Pediatrics 07/2003; 143(1):26-30. · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to elucidate a predictive value of electroencephalogram (EEG) during early infancy for later development of West syndrome (WS) in premature infants with cystic periventricular leukomalacia (PVL).
The subjects of this study were 19 infants with cystic PVL born between 1992 and 1996. EEGs were recorded at 3 months of corrected age (CA) in all of them. We divided these 19 infants into the following two groups; group A (n = 9), no paroxysmal discharge was recognized; and group B (n = 10), paroxysmal discharges were recognized.
In none of the infants in group A did WS develop. Subsequent EEGs were normal in all infants in group A. WS developed in seven of 10 infants in group B. The occurrence of WS is significantly higher in group B than in group A. The mean age at the onset of WS was 6 months of CA. Paroxysmal discharges in infants in group B were observed as irregular spikes-and-waves and polyspikes-and-waves, mainly in bilateral parietooccipital areas. In seven of eight patients with severe MRI findings in group B, WS developed.
Paroxysmal discharges during early infancy were correlated with later development of WS in infants with cystic PVL. The possibility of developing WS had increased in the children with the combination with EEG and MRI findings.