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Objective: The aim of this prospective multicenter randomized controlled trial was to compare the efficacy of silver nitrate cauterization against that of topical steroid ointment in the treatment of neonatal umbilical granuloma., Methods: An open-label, non-inferiority randomized controlled trial was conducted from January 2013 to January 2016. The primary endpoint for the silver nitrate cauterization and topical steroid ointment groups was the healing rate after 2 weeks of treatment, applying a non-inferiority margin of 10%. The healing rate was evaluated until completion of 3 weeks of treatment., Results: Participants comprised 207 neonates with newly diagnosed umbilical granuloma, randomized to receive silver nitrate cauterization (n = 104) or topical steroid ointment (n = 103). Healing rates after 2 weeks of treatment were 87.5% (91/104) in the silver nitrate cauterization and 82% (82/100) in the topical steroid ointment group group. The difference between groups was -5.5% (95% confidence interval, -19.1%, 8.4%), indicating that the non-inferiority criterion was not met. After 3 weeks of treatment, the healing rate with topical steroid ointment treatment was almost identical to that of silver nitrate cauterization (94/104 [90.4%] vs. 91/100 [91.0%]; 0.6% [-13.2 to 14.3]). No major complications occurred in either group., Conclusions: This study did not establish non-inferiority of topical steroid ointment treatment relative to silver nitrate cauterization, presumably due to lower healing rates than expected leading to an underpowered trial. However, considering that silver nitrate cauterization carries a distinct risk of chemical burns and that the overall efficacy of topical steroid ointment treatment is similar to that of silver nitrate cauterization, topical steroid ointment might be considered as a good alternative in the treatment of neonatal umbilical granuloma due to its safety and simplicity. To clarify non-inferiority, a larger study is needed.

Objective: To clarify longitudinal changes in white matter microstructures from the onset of disease in patients with West syndrome (WS) of unknown etiology., Methods: Diffusion tensor imaging (DTI) was prospectively performed at onset and at 12 and 24 months old in 17 children with WS of unknown etiology. DTI was analyzed using tract-based spatial statistics (TBSS) and tract-specific analysis (TSA) of 13 fiber tracts, and fractional anisotropy (FA) and mean diffusivity (MD) were compared with those of 42 age-matched controls. Correlations of FA and MD with developmental quotient (DQ) at age 24 months were analyzed. Multiple comparisons were adjusted for using the false discovery rate (q-value)., Results: TBSS analysis at onset showed higher FA and lower MD in the corpus callosum and brainstem in patients. TSA showed lower MD in bilateral uncinate fasciculi (UF) (right: q < 0.001; left: q = 0.03) at onset in patients. TBSS showed a negative correlation between FA at onset and DQ in the right frontal lobe, whereas FA at 24 months old exhibited a positive correlation with DQ in the diffuse white matter. MD for bilateral UF at 24 months old on TSA correlated positively with DQ (q = 0.04, both)., Significance: These findings may indicate the existence of cytotoxic edema in the immature white matter and dorsal brainstem at onset, and subsequent alterations in the diffuse white matter in WS of unknown etiology. Microstructural development in the UF might play important roles in cognitive development in WS., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objective: Epileptic spikes are associated with rapidly changing brain activation involving the epileptic foci and other brain regions in the "epileptic network". We aim to resolve these activation changes using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings., Methods: Simultaneous EEG-fMRI recordings from 9 patients with epilepsy were used in the analysis. Our method employed the whole scalp EEG data to generate regressors for the analysis of fMRI data using the general linear model., Results: We were able to resolve, with milliseconds temporal resolution, changes in activation patterns involving suspected epileptic foci and other brain regions in the epileptic network during spike and slow wave. Using summary maps (called SSWAS maps) which show the activation frequency of voxels, we found that suspected epileptic foci tend to be significantly active during this interval. SSWAS maps also enabled the detection of the epileptic foci in 4 of 5 patients where the conventional event-timing-based analysis failed to identify., Conclusion: These findings demonstrated the efficacy of the method and the potential application of SSWAS maps to identify epileptic foci., Significance: The method could help resolve activation changes during epileptic spike and could provide insights into the underlying pathophysiology of these changes., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: The characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations (KABUK1) have not yet been well documented. This is the first review to explore this., Materials & Methods: We enrolled 14 patients with KABUK1, whose median age was 13.6years (range=4.1-21.3years). Their medical records from October 1981 to May 2016 were retrospectively analyzed., Results: Epilepsy was present in 5 (36%) patients. Four of these patients presented with nonsense mutations and one with missense mutations. None presented with brain abnormalities. Four patients presented with annual or monthly focal seizures, of which three evolved to bilateral convulsive seizures. Median onset age of focal epilepsy was 11.8years (range=9.5-12.8years). One presented with monthly myoclonic seizures from age 11.2, whose mother with no other KABUK1 features, had focal epilepsy. The cumulative incidence of epilepsy related to KABUK1 up until age 13 was 45%. Interictal electroencephalogram revealed focal paroxysmal epileptiform discharges (in frontal, central, and parietal regions) in three patients, diffuse high-voltage spike-and-waves in one patient, and normal sleep record in one patient. Myoclonic seizures were rapidly controlled by levetiracetam. In contrast, focal seizures were not controlled in the early period of antiepileptic therapy., Conclusion: This long-term follow-up of patients with KABUK1 revealed a higher prevalence of epilepsy than previously reported. The age of epilepsy onset and rate of focal seizures evolving to bilateral convulsive seizures in KABUK1 were also higher than previously reported in patients with clinically diagnosed Kabuki syndrome. Although seizure outcome is reported to be favorable in Kabuki syndrome, focal seizures in patients with KABUK1 were not immediately responsive to medication., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Inherited GPI (glycosylphosphatidylinositol) deficiencies (IGDs), a recently defined group of diseases, show a broad spectrum of symptoms. Hyperphosphatasia mental retardation syndrome, also known as Mabry syndrome, is a type of IGDs. There are at least 26 genes involved in the biosynthesis and transport of GPI-anchored proteins; however, IGDs constitute a rare group of diseases, and correlations between the spectrum of symptoms and affected genes or the type of mutations have not been shown. Here, we report four newly identified and five previously described Japanese families with PIGO (phosphatidylinositol glycan anchor biosynthesis class O) deficiency. We show how the clinical severity of IGDs correlates with flow cytometric analysis of blood, functional analysis using a PIGO-deficient cell line, and the degree of hyperphosphatasia. The flow cytometric analysis and hyperphosphatasia are useful for IGD diagnosis, but the expression level of GPI-anchored proteins and the degree of hyperphosphatasia do not correlate, although functional studies do, with clinical severity. Compared with PIGA (phosphatidylinositol glycan anchor biosynthesis class A) deficiency, PIGO deficiency shows characteristic features, such as Hirschsprung disease, brachytelephalangy, and hyperphosphatasia. This report shows the precise spectrum of symptoms according to the severity of mutations and compares symptoms between different types of IGD., (© 2017 Wiley Periodicals, Inc.)

Objective: The aim of this study was to clarify the characteristics of paroxysmal nonepileptic events (PNEs) suspected as being epileptic seizures by families of children with epilepsy., Methods: The video-EEG (vEEG) recordings of habitual paroxysmal events in children with epilepsy at Nagoya University Hospital between October 2006 and January 2016 were reviewed. Based on the doctor's suspicion before the vEEG, the PNEs were divided into two groups that included PNEs suspected as epileptic seizures and PNEs suspected as PNEs. PNEs in the former group were classified based on the suspected seizure type., Results: Of 886 habitual paroxysmal events, vEEG confirmed that 83 events (68 children) were PNEs. The median age of the 68 children was 3.2 years. Concurrent epilepsies included focal epilepsies (n=33), infantile spasms (n=16), and other types (n=19). The most common types of PNEs were sleep myoclonus (n=11), followed by stereotypies (n=9), awake myoclonus (n=8), paroxysmal ocular deviations (PODs, n=8), and tonic posturing (n=8). Even after direct observation or video viewing, the doctors suspected epileptic seizures in all three of the PODs and two of the tonic posturing children. Before the vEEG, however, the accurate visual information led to the speculation that the four psychogenic and two sleep myoclonus events were all PNEs. Myoclonus, stereotypies, and head drops were often misdiagnosed as epileptic spasms, while PODs and tonic posturing were often misdiagnosed as focal seizures with motor components. Additionally, staring and motion arrest during a drowsy state were often misdiagnosed as focal dyscognitive seizures. Seven of eight patients with PODs had epileptic spasms that were concurrent with epileptic seizures. A diffuse cerebral lesion or reduced visual acuity was seen in seven patients with PODs., Conclusion: We re-emphasize that vEEG is essential for accurate diagnosis and provides evidence for listing POD in the differential diagnosis of oculomotor paroxysmal events., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In 2015, the Japanese Society of Child Neurology released new guidelines for the management of febrile seizures, the first update of such guidelines since 1996. In 1988, the Conference on Febrile Convulsions in Japan published "Guidelines for the Treatment of Febrile Seizures." The Task Committee of the Conference proposed a revised version of the guidelines in 1996; that version released in 1996 was used for the next 19years in Japan for the clinical management of children with febrile seizures. Although the guidelines were very helpful for many clinicians, new guidelines were needed to reflect changes in public health and the dissemination of new medical evidence. The Japanese Society of Child Neurology formed a working group in 2012, and published the new guidelines in March 2015. The guidelines include emergency care, application of electroencephalography, neuroimaging, prophylactic diazepam, antipyretics, drugs needing special attention, and vaccines. While the new guidelines contain updated clinical recommendations, many unsolved questions remain. These questions should be clarified by future clinical research., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Primary abscess of the iliopsoas muscle in children is uncommon, especially due to Streptococcus pyogenes (group A streptococcus: GAS), which causes a variety of diseases ranging from pharyngitis to invasive life-threatening infection. We present primary iliopsoas abscess in a nine-year-old boy presenting with fever, mild disturbance of consciousness, limp, and pain in the right loin. Magnetic resonance imaging and isolation of GAS from both blood and abscess samples led us to the confirmative diagnosis. The patient recovered after treatment comprising drainage and intravenous antibiotics. The CovRS system is one of the best-characterized systems with two-component signal transduction in the GAS, and mutations in covRS induce overproduction of various virulence factors that play a crucial role in invasive GAS infection. RopB, also known as a GAS regulator, influences the expression of multiple regulatory networks to coregulate virulence factor expression in GAS. In the present case, sequence analysis revealed the isolated GAS as emm type 6 with alterations in covS, whereas the covR and ropB genes were intact. The covS alterations might have influenced the virulence of the strain causing this severe GAS infection., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Rare progression to renal failure imposes a burden on children with IgA vasculitis (Henoch-Schönlein purpura, HSP). An abnormal urinalysis on day 7 (7d-UA) may be a surrogate marker for persistent nephritis, but this has not been established. We retrospectively analyzed the risk factors for persistent nephritis in a cohort of 138 children. Of 35 children with abnormal 7d-UA, 24 (69%) had an abnormal urinalysis 6 months after the diagnosis of HSP, which was significantly more than 6 of 103 children (6%) with normal 7d-UA ( P < 0.0001). The negative predictive values for normal urinalysis and negative proteinuria 6 months after diagnosis were 0.94 (95% confidence interval [CI], 0.90-0.97) and 0.98 (95% CI, 0.95-0.99), respectively. When children with abnormal urinalysis 6 months after diagnosis were compared with those without, the following factors were significantly associated: age at diagnosis, abnormal urinalysis at diagnosis, abnormal 7d-UA, complement C3, steroid treatment, and presence of abdominal pain. However, multivariate analysis revealed that abnormal 7d-UA was the only significant risk factor for abnormal urinalysis 6 months after diagnosis (odds ratio 54.3, 95% CI 15.3-275, P = 1.89 × 10 -6 ). Abnormal 7d-UA may be an independent risk factor for persistent nephritis, but this should be confirmed in a prospective study.

Purpose: Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy., Methods: A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB))., Results: The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration., Conclusion: LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate the outcome of ketogenic diets (KDs) in patients with glucose transport type 1 deficiency syndrome (GLUT1DS) in Japan., Methods: A nationwide survey for GLUT1DS was conducted by sending questionnaires to board-certified pediatric neurologists nationwide to obtain clinical and laboratory data., Results: Among 39 patients whose diagnosis was confirmed molecularly or by the 3-O-methylglucose uptake assay, 31 were treated with KDs for longer than 1month. Seventeen patients (55%) were on the modified Atkins diet, 11 (35%) were on the classic KD, and 3 were on the medium-chain triglyceride (MCT) diet. The median values and ranges of serum β-hydroxybutyrate levels in patients on the modified Atkins diet, classic KD and MCT diet were 2.5mM (0.75-4.1), 1.7mM (0.23-3.5) and 2.6mM (1.5-3.0), respectively. The KDs were effective on seizures (80%), aggravation after fasting (80%) and ataxia (79%). Thus, ataxia was as responsive as seizures. Two patients on the classic KD with a ketogenic ratio as low as 1:1 showed improvement in neurological symptoms. The development or intelligence quotient measured using the same psychological scales before and after the KDs in 9 patients did not show a significant improvement; the median quotients before and after the diets were 40 (12-91) and 46 (12-67)., Conclusion: The KDs were most effective on seizures, transient aggravation after fasting and ataxia. The efficacy on intellectual development was equivocal. The modified Atkins diet was more commonly used for GLUT1DS in this study, and its ketogenicity was equivalent to the classic KD., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: West syndrome is an epileptic encephalopathy characterized by epileptic spasms, a specific pattern on electroencephalography of hypsarrhythmia, and developmental regression. Our aim was to assess white matter abnormalities in West syndrome of unknown etiology. We hypothesized that diffusion tensor imaging reveals white matter abnormalities, especially in patients with poor seizure and developmental outcomes., Materials and Methods: We enrolled 23 patients with new-onset West syndrome of unknown etiology. DTI was performed at 12 and 24 months of age. Fractional anisotropy images were compared with those of controls by using tract-based spatial statistics. We compared axial, radial, and mean diffusivity between patients and controls in the fractional anisotropy skeleton. We determined correlations of these parameters with developmental quotient, electroencephalography, and seizure outcomes. We also compared DTI with hypometabolism on fluorodeoxyglucose positron-emission tomography., Results: At 12 months of age, patients showed widespread fractional anisotropy reductions and higher radial diffusivity in the fractional anisotropy skeleton with a significant difference on tract-based spatial statistics. The developmental quotient at 12 months of age correlated positively with fractional anisotropy and negatively with radial and mean diffusivity. Patients with seizure and abnormal findings on electroencephalography after initial treatments had lower fractional anisotropy and higher radial diffusivity. At 24 months, although tract-based spatial statistics did not show significant differences between patients and controls, tract-based spatial statistics in the 10 patients with a developmental quotient of <70 had significant fractional anisotropy reduction. In patients with unilateral temporal lobe hypometabolism on PET, tract-based spatial statistics showed greater fractional anisotropy reduction in the temporal lobe ipsilateral to the side of PET hypometabolism., Conclusions: Diffuse abnormal findings on DTI at 12 months of age suggest delayed myelination as a key factor underlying abnormal findings on DTI. Conversely, asymmetric abnormal findings on DTI at 24 months may reflect underlying focal pathologies., (© 2016 by American Journal of Neuroradiology.)

Objective: To clarify the clinical and radiological spectrum of posterior reversible encephalopathy syndrome (PRES) in children, and to identify the prognostic factors., Methods: The records of 40 children with PRES were reviewed. Acute clinical symptoms, MRI including apparent diffusion coefficient (ADC) maps in the acute and follow-up periods and neurological sequelae, including epilepsy, were noted., Results: Age at onset ranged from 2 to 16 years. Underlying disorders were hematological or neoplastic disorders (n = 20), renal diseases (n = 14) and others (n = 6). In the acute period, 31 patients had seizures, 25 had altered consciousness, 11 had visual disturbances and 10 had headache. Of 29 patients who had ADC maps in the acute period, 13 had reduced diffusivity as shown by ADC within PRES lesions. Of 26 patients with follow-up MRI, 13 had focal gliosis or cortical atrophy. No patients had motor impairment, and four patients had focal epilepsy. No clinical variables were associated with focal gliosis or cortical atrophy on follow-up MRI, but lesional ADC reduction in the acute period was prognostic for focal gliosis or cortical atrophy on follow-up MRI (p = 0.005)., Conclusions: To the best of our knowledge, this is the largest cohort study to date involving PRES in children. Acute symptoms in pediatric patients are similar to those reported in adults, but altered consciousness was more frequent in children. Lesional ADC reduction in the acute period was common and was a good predictor of later, irreversible MRI lesions., (Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

TUBA1A mutations cause a wide spectrum of lissencephaly and brain malformations. Here, we report two patients with severe cortical dysgeneses, one with an extremely thin cerebral parenchyma apparently looking like hydranencephaly and the other with lissencephaly accompanied by marked hydrocephalus, both harbouring novel de novo missense mutations of TUBA1A. To elucidate how the various TUBA1A mutations affect the severity of the phenotype, we examined the capacity of the mutant protein to incorporate into the endogenous microtubule network in transfected COS7 cells by measuring line density using line extraction in an immunofluorescence study. The mutants responsible for severe phenotypes were found to incorporate extensively into the network. To determine how each mutant alters the microtubule stability, we examined cold-induced microtubule depolymerisation in fibroblasts. The depolymerisation of patients' fibroblasts occurred earlier than that of control fibroblasts, suggesting that microtubules bearing mutated tubulins are unstable. Both mutations are predicted to participate in lateral interactions of microtubules. Our data suggest that the TUBA1A mutations disrupting lateral interactions have pronounced dominant-negative effects on microtubule dynamics that are associated with the severe end of the lissencephaly spectrum.

Objectives: We conducted a nationwide survey of glucose transporter type-1 deficiency syndrome (GLUT-1DS) in Japan in order to clarify its incidence as well as clinical and laboratory information., Subjects and Methods: A questionnaire to survey the number of genetically and clinically confirmed cases of GLUT-1DS was sent to 1018 board-certified pediatric neurologists, which resulted in 57 patients being reported. We obtained the clinical and laboratory data of 33 patients through a secondary questionnaire., Results: The age of the 33 patients (male: 15, female: 18) at the time of the study ranged between 3 and 35 years (mean: 13.5 years). The age of these patients at the onset of initial neurological symptoms ranged between the neonatal period and 48 months (mean: 9.4 months). GLUT-1DS was diagnosed at a mean age of 8.4 years (range: 1 year to 33 years). The initial symptom was convulsive seizures, which occurred in 15 cases, and was followed by abnormal eye movements in 7 cases and apneic or cyanotic attacks in 4 cases. The latter two symptoms most frequently occurred early in infancy. Thirty-two patients (97%) exhibited some type of epileptic seizure. Neurological findings revealed that most patients had muscle hypotonia, cerebellar ataxia, dystonia, and spastic paralysis. Mild to severe mental retardation was detected in all 33 cases. Furthermore, paroxysmal episodes of ataxia, dystonia/dyskinesia, and motor paralysis were described in approximately 1/3 of all patients. The factors that frequently aggravated these events were hunger, exercise, fever, and fatigue, in that order. The mean CSF/blood glucose ratio was 0.36 (0.28-0.48). Pathological mutations in the SLC2A1 gene were identified in 28 out of 32 cases (87.5%)., Conclusion: The results described herein provided an insight into the early diagnosis of GLUT1-DS, including unexplained paroxysmal abnormal eye movements, apneic/cyanotic attacks, and convulsive seizures in infancy, as well as uncommon paroxysmal events (ataxia, atonia, and motor paralysis) in childhood., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

In this study, we investigated the cognitive processing and language abilities of a 13-year-old boy with moderate periventricular leukomalacia (PVL), spastic diplegia and exotropia who had discrepant scores in the verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) in the Wechsler Intelligence Scale for Children, third edition (VIQ; 82 > PIQ; under 40). In the Kaufman Assessment Battery for Children and Das-Naglieri Cognitive Assessment System, his performance was poor at simultaneous processing compared to sequential processing. He could not copy three-dimensional figures, and he could place only two out of eight blocks correctly in the second level models of Benton three-dimensional block construction test, showing visuospatial impairment typical of patients with PVL. Despite the relatively high score in VIQ, there was a gap among the scores of the subtests in the Illinois Test of Psycholinguistic Abilities. He tended to get low scores in tests that required visual abilities. In addition, there was also an impairment in reading fluency tested by the Diagnostic Criteria and Medical Guideline for Specific Developmental Disorders. He was much less fluent in reading syllables, words or sentences (6.0 SD or more compared to 12-year-old boys). The relatively higher score in VIQ superficially suggests adequate language ability. However, in the present study, precise investigation revealed some discrepancies even within the field of language. Thus, defining stronger and weaker points of a patient is important in order to determine optimal medical or educational approaches.

Objective: The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types., Methods: Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings., Results: Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE., Significance: We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain network., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

The older of two siblings began to have spasms and partial seizures at 1 month of age. Head magnetic resonance imaging showed an abnormal area in the left temporo-parieto-occipital region. Interictal electroencephalogram (EEG) showed a suppression-burst pattern. Adrenocorticotropic hormone stopped the spasms, but the seizures continued. Clonazepam, carbamazepine, zonisamide, and clobazam were ineffective. She underwent focal resection at age 8 months. Postoperatively, the seizures disappeared. Histopathologically, the lesion appeared to be focal cortical dysplasia type IIa. The younger sibling had spasms from birth. Head magnetic resonance imaging showed left hemi-megalencephaly. Interictal EEG showed a suppression-burst pattern. Phenobarbital, valproic acid, and zonisamide were ineffective. He underwent hemispherotomy at age 2 months and became seizure free. The histopathological features were consistent with those of hemi-megalencephaly. The siblings' EEG and clinical courses had some similarities. These siblings' conditions may have the same genetic background., (© 2015 Japan Pediatric Society.)

Objective: To develop a score that predicts the prognosis of children with acute necrotizing encephalopathy (ANE)., Method: We retrospectively evaluated clinical variables and neurological outcome in two cohorts of children with ANE. Firstly, we developed the ANE severity score (ANE-SS) according to the clinical variables that correlated with neurological outcome in 41 children who were included in our previous reports in 2009. We then applied the scoring system to a second cohort of 32 patients who were newly collected in 2011. We investigated the correlation between the ANE-SS and neurological outcome in all 73 patients., Results: In the first cohort, brain stem lesions on MRI and state of shock at onset were significantly correlated with outcome. Age over 48 months, elevated CSF protein, and low platelet counts tended to be correlated with outcome. No types of treatment were correlated with outcome. The developed ANE-SS ranged from 0 to 9 points, with 3 points for existence of shock, 2 points for brain stem lesions, 2 points for age over 48 months, 1 point for platelet count below 100,000/μL, and 1 point for CSF protein above 60 mg/dl. Patients were classed as low risk (ANE-SS 0-1 points), medium risk (ANE-SS 2-4 points), or high risk (ANE-SS 5-9 points). ANE-SS was significantly correlated with outcome in the group of 73 patients., Conclusion: ANE-SS can be used to predict outcome in patients with ANE. More effective treatments need to be developed for high-risk patients., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Congenital myasthenic syndromes (CMS) are caused by mutations in genes expressed at the neuromuscular junction. Most CMS patients have been reported in Western and Middle Eastern countries, and only four patients with COLQ mutations have been reported in Japan. We here report six mutations in acetylcholine receptor (AChR) subunit genes in five Japanese patients. Five mutations are novel, and one mutation is shared with a European American patient but with a different haplotype. Among the observed mutations, p.Thr284Pro (p.Thr264Pro according to the legacy annotation) in the epsilon subunit causes a slow-channel CMS. Five other mutations in the delta and epsilon subunits are splice site, frameshift, null, or missense mutations causing endplate AChR deficiency. We also found a heteroallelic p.Met465Thr in the beta subunit in another patient. p.Met465Thr, however, was likely to be polymorphism, because single channel recordings showed mild shortening of channel openings without affecting cell surface expression of AChR, and the minor allelic frequency of p.Met465Thr was 5.1% in the Japanese population. Lack of shared mutant alleles between the Japanese and the other patients suggests that most mutations described here are ethnically unique or de novo in each family., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: We aimed to assess the characteristics of thalamic lesions in children with acute encephalopathy with biphasic seizures and late reduced diffusion., Methods: Using the Tokai Pediatric Neurology Society database, we identified and enrolled 18 children with acute encephalopathy with biphasic seizures and late reduced diffusion from 2008 to 2010. Using diffusion-weighted images, we identified patients with thalamic lesions and compared their clinical factors with those of patients without thalamic lesions. We analyzed the time sequence of thalamic, sucortical, and cortical lesions. To study the topography of thalamic lesions, we divided the thalamus into five sections: anterior, medial, anterolateral, posterolateral, and posterior. Subsequently, we analyzed the relationship between the topography of thalamic lesions and the presence of central-sparing., Results: Seven children presented with symmetrical thalamic lesions associated with bilateral subcortical or cortical lesions. No statistical difference in the clinical features was observed between individuals with and without thalamic lesions. These lesions were observed only when subcortical or cortical lesions were present. In 5 children, thalamic lesions were present in bilateral anterior or anterolateral sections and were associated with subcortical or cortical lesions in bilateral frontal lobes with central-sparing. In the other two children, thalamic lesions were extensive and accompanied by diffuse subcortical and cortical lesions without central-sparing., Conclusion: Thalamic lesions in patients with acute encephalopathy with biphasic seizures and late reduced diffusion involve the anterior sections. The thalamocortical network may play a role in development of thalamic lesions in patients with acute encephalopathy with biphasic seizures and late reduced diffusion., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Developmental and seizure outcomes in patients with cryptogenic West syndrome are variable. Our aim was to clarify the relationship between FDG-PET findings in infancy and long-term seizure and developmental outcome in cryptogenic West syndrome., Materials and Methods: From 1991 to 1999, we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in 27 patients. PET was performed at onset and at 10 months of age. In 2012, we evaluated the educational status, psychomotor development, and seizure outcome in 23 of the 27 patients (13-22 years of age). The correlation between PET findings and outcome was evaluated., Results: At onset, PET showed hypometabolism in 13 patients (57%). The second PET after the initial treatment revealed cortical hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on the second PET in 9 patients, it was newly revealed in 3 patients on the second PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients had intellectual impairment. The first PET did not correlate with seizure or developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients with normal findings on the second PET were free of seizures. Five of 7 patients (71%) showing hypometabolism on the second PET had intellectual impairment. Thirteen of 16 (81%) patients with normal findings on the second PET showed normal intelligence. A significant correlation was found between the second PET and long-term seizure (P = .01) or developmental outcome (P = .03)., Conclusions: Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome., (© 2014 by American Journal of Neuroradiology.)

Background and Objectives: Conventional electroencephalogram (cEEG) is a reliable predictor of outcome in term infants with hypoxic ischemic encephalopathy (HIE). Early therapeutic hypothermia initiated within 6h after birth is a beneficial treatment in these infants. However, a classification system with reduced cEEG recording time to determine early intervention has not been reported. The aim of this study is to propose a new classification of depression on cEEG with reduced recording time in infants with HIE and to examine the correlation between the classification and short-term outcome., Patients and Methods: We retrospectively investigated 20 term infants with HIE in whom cEEG was performed within 12h after birth, and deaths or outcomes at 18months of age were assessed. We determined grades 0-3 EEG depression in each 10-min epoch based on the most common EEG patterns of each 20s epoch defined by our criteria., Results: Eighteen infants could be assessed by depression grade. The Spearman's rank correlation coefficient Rs between the maximum depression grade in 10-min epochs and three-grade outcomes was 0.68 (P=0.002), and that between the minimum one and outcomes was 0.66 (P=0.003). The area under the receiver operating characteristic curve of the maximum and minimum depression grades for predicting abnormal outcome were 0.885 and 0.869, respectively., Conclusions: We demonstrated a new cEEG depression classification with a recording time of at least 10min in term infants with HIE and a good correlation with short-term outcome., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant sclerosing bone dysplasia. Typically affected females show macrocephaly, characteristic facial appearance, cleft palate, mild learning difficulties, hearing loss, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis and scapulae. Typically affected males usually die at the fetal or early neonatal stage. Because of its variable expressivity, which ranges from asymptomatic to fetal death, clinical diagnosis of OSCS can be difficult. Here, we identify a unique female patient presenting with severe macrocephaly, characteristic facial appearance, developmental delay, and hepatoblastoma. Exome sequencing identified a novel de novo nonsense mutation (c.1045C>T, p.Glu349*) in the WTX gene associated with OSCS. The OSCS diagnosis was confirmed in this patient based on the hallmark appearance of longitudinal striations in long bones when viewed by X-ray. WTX is also known as a tumor suppressor gene, and somatic mutations in that gene have been identified in Wilms tumors. In addition to this patient, although two patients with OSCS have been reported to have colorectal cancer or ovarian cancer, Wilms tumor has never been reported in association with this disorder. Tumor susceptibility in patients with OSCS is discussed., (© 2014 Wiley Periodicals, Inc.)

Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is mostly composed of an asymmetric form in which three tetramers of catalytic AChE subunits are linked to a triple helical collagen Q (ColQ). Mutations in COLQ cause endplate AChE deficiency. We report three patients with endplate AChE deficiency with five recessive COLQ mutations. Sedimentation profiles showed that p.Val322Asp and p.Arg227X, but not p.Cys444Tyr, p.Asp447His, or p.Arg452Cys, inhibit formation of triple helical ColQ. In vitro overlay of mutant ColQ-tailed AChE on muscle sections of Colq(-/-) mice revealed that p.Cys444Tyr, p.Asp447His, and p.Arg452Cys in the C-terminal domain (CTD) abrogate anchoring ColQ-tailed AChE to the NMJ. In vitro plate-binding assay similarly demonstrated that the three mutants inhibit binding of ColQ-tailed AChE to MuSK. We also confirmed the pathogenicity of p.Asp447His by treating Colq(-/-) mice with adeno-associated virus serotype 8 carrying mutant COLQ-p.Asp447His. The treated mice showed no improvement in motor functions and no anchoring of ColQ-tailed AChE at the NMJ. Electroporation of mutant COLQ harboring p.Cys444Tyr, p.Asp447His, and p.Arg452Cys into anterior tibial muscles of Colq(-/-) mice similarly failed to anchor ColQ-tailed AChE at the NMJ. We proved that the missense mutations in ColQ-CTD cause endplate AChE deficiency by compromising ColQ-MuSK interaction at the NMJ., (© 2013 WILEY PERIODICALS, INC.)

Background: Dexmedetomidine hydrochloride, a highly selective 2-adrenoceptoragonist, is used in combination with local anesthetics for sedation and analgesia. It is known to be efficacious in adult patients and is enthusiastically expected to be successful for sedation in neonates., Patient: The present case report details a term infant who was sedated by dexmedetomidine during artificial ventilation. He underwent electroencephalograms that confirmed epileptic seizures and non-epileptic abnormal movements. Twelve hours after the discontinuation of dexmedetomidine, both symptoms gradually disappeared without the use of any antiepileptic medication. After then, he had achieved normal development, with no obvious neurological abnormalities., Conclusion: Dexmedetomidine acts throughout the central nervous system and leads to a reduction in the anticonvulsant activity of the locus coeruleus. This case suggests potential adverse effects of dexmedetomidine in terms of inducing both epileptic seizures and non-epileptic movements in neonates., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: We performed diffusion tensor imaging (DTI) in children with periventricular leukomalacia (PVL) to quantify the relationship between the fractional anisotropy (FA) values of DTI and the severity of PVL., Methods: In this study, we performed DTI in 16 children (seven males, nine females) with PVL. To evaluate the FA values, we used region-of-interest (ROI) measurements and tractography-based measurements. We classified the patients into two groups based on the severity of the magnetic resonance imaging (MRI) findings: the mild group had white matter injury limited to a triangular zone around the lateral ventricle (n = 9) and the severe group had it extended forward (n = 7). Then, we performed ROI measurements for these two groups to evaluate the FA values. We also divided the patients into two groups based on their motor ability :those that could (n = 10) and could not (n = 6) stand. We used tractography-based measurements to evaluate the FA values. To reduce the bias caused by age, we divided the patients into two groups: those younger than 3 years and those 3 years of age and older. All data were analyzed using the Mann-Whitney U-test, and p < 0.05 was considered statistically significant., Results: In the ROI measurements, regardless of age, the severe group showed a more significant FA reduction in the white matter of the parietal and occipital lobes, including the middle/posterior part of the centrum ovale, superior longitudinal fasciculus, arcuate fascicullus, and thalamic radiation. In the tractography-based measurements, regardless of age, the measured FA values were significantly lower in the group that could not stand., Conclusions: This study suggested that the measured FA values could be used to evaluate the severity of PVL quantitatively, and that DTI provides much more information for understanding the pathophysiology of PVL, as compared with conventional MRI.

We report a preterm infant, who showed abnormal amplitude-integrated electroencephalogram (aEEG) findings 1 h after birth and later developed cystic periventricular leukomalacia (PVL). The patient was a girl with a gestational age of 29 weeks. She was delivered by emergency cesarean section because of placental abruption and intrauterine co-twin demise. Artificial ventilation and administration of surfactant were needed to treat respiratory distress syndrome. Her cardiovascular condition was stable with artificial ventilation. Cranial ultrasonography showed extended cystic PVL after 11 days of age. aEEG 1 h after birth showed a consistently inactive pattern that resolved completely 28 h after birth. The neurophysiological findings of this patient suggest that aEEG findings during the very early period after birth provide significant information for predicting PVL., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We report on a 4-year-old boy with transient reduced diffusion in the cortex, thalamus, and hippocampus on diffusion-weighted imaging (DWI) performed after prolonged febrile seizures (PFS). He had experienced intermittent right hemiconvulsions lasting about 90 min during the febrile illness, but his neurological symptom resolved completely after several hours. DWI performed immediately after the PFS showed abnormally high signal intensities in the left extended cortex and pulvinar of the ipsilateral thalamus. Two days later, these DWI lesions resolved completely, but abnormally high signal intensities were observed in the left hippocampus. Three months later, the DWI was normal, and no atrophy or gliosis was seen. This patient had unique lesions on DWI after PFS, but it is nevertheless important to attend to such lesions on the DWI of patients with PFS., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To clarify the prognostic value of conventional EEG for the identification of preterm infants at risk for subsequent adverse neurodevelopment in the current perinatal care and medicine setting., Methods: We studied 780 EEG records of 333 preterm infants born <34 weeks' gestation between 2002 and 2008. Serial EEG recordings were conducted during 3 time periods; at least once each within days 6 (first period), during days 7 to 19 (second period), and days 20 to 36 (third period). The presence and the grade of EEG background abnormalities were assessed according to an established classification system. Neurodevelopmental outcomes were assessed at a corrected age of 12 to 18 months., Results: Of the 333 infants, 33 (10%) had developmental delay and 34 (10%) had cerebral palsy. The presence of EEG abnormalities was significantly predictive of developmental delay and cerebral palsy at all 3 time periods: the first period (n = 265; odds ratio [OR], 4.5; 95% confidence interval [CI], 2.2-9.4), the second period (n = 278; OR, 7.6; 95% CI, 3.6-16), and the third period (n = 237; OR, 5.9; 95% CI, 2.8-13). The grade of EEG abnormalities correlated with the incidence of developmental delay or cerebral palsy in all periods (P < .001). After controlling for other clinical variables, including severe brain injury, EEG abnormality in the second period was an independent predictor of developmental delay (OR, 3.2; 95% CI, 1.1-9.7) and cerebral palsy (OR, 6.8; 95% CI 2.0-23)., Conclusions: EEG abnormalities within the first month of life significantly predict adverse neurodevelopment at a corrected age of 12 to 18 months in the current preterm survivor.

Objectives: Acute encephalopathy with reduced subcortical diffusion (AED) covers a spectrum including not only typical acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) but also atypical AESD with monophasic clinical course, or more severe subtypes. Aim of this study is to analyze prognostic factors of AED., Materials & Methods: We recruited 33 children with AED, that is, widespread diffusion restriction in cortical and subcortical structures. Their clinical courses, laboratory data, MRI, and the efficacy of treatment were analyzed retrospectively., Results: Of the 33 children, 20 were males and the mean age at diagnosis was 22 months. Eighteen children had good outcome and 15 had poor outcome. Univariate analysis showed loss of consciousness 24 h after the onset, prolonged seizure at the onset, and mechanical ventilation to be weak predictors of poor outcome. Maximal aspartate aminotransferase, alanine aminotransferase, and creatinine kinase levels were significantly higher in the poor outcome group. Multivariate analysis showed loss of consciousness 24 h after the onset and prolonged seizure at the onset to be poor predictors of AED. Treatment with steroids and/or immunoglobulins did not result in better outcome., Conclusion: Prolonged seizure at the onset and loss of consciousness 24 h after the onset were seen at early stages of severe AED. Using these features, a prospective study of early intervention in AED should be conducted to further analyze the efficacy of its treatment., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Array-based technologies have led to the identification of many novel microdeletion and microduplication syndromes demonstrating multiple congenital anomalies and intellectual disability (MCA/ID). We have used chromosomal microarray analysis for the evaluation of patients with MCA/ID and/or neonatal hypotonia. Three overlapping de novo microdeletions at 5q31.3 with the shortest region of overlap (SRO) of 370 kb were detected in three unrelated patients. These patients showed similar clinical features including severe neonatal hypotonia, neonatal feeding difficulties, respiratory distress, characteristic facial features, and severe developmental delay. These features are consistent with the 5q31.3 microdeletion syndrome originally proposed by Shimojima et al., providing further evidence that this syndrome is clinically discernible. The 370 kb SRO encompasses only four RefSeq genes including neuregulin 2 (NRG2) and purine-rich element binding protein A (PURA). NRG2 is one of the members of the neuregulin family related to neuronal and glial cell growth and differentiation, thus making NRG2 a good candidate for the observed phenotype. Moreover, PURA is also a good candidate because Pura-deficient mice demonstrate postnatal neurological manifestations., (Copyright © 2012 Wiley Periodicals, Inc.)

Introduction: To assess differences in amplitude among electrode locations on amplitude-integrated electroencephalograms (aEEGs) in preterm infants and change therein between preterm age and term-equivalent age (TEA), we investigated aEEGs in preterm infants at both 30-32 wk post-conceptional age (PCA) and TEA., Methods: The median values of upper- and lower-margin amplitudes were quantitatively calculated every 5 min (Med-UMA5 and Med-LMA5, respectively), and peak, median, and bottom values were extracted at each location for the trans-frontal, trans-central, trans-occipital, fronto-central, and centro-occipital electrodes., Results: In 38 clinically stable preterm infants studied, most measurement items showed significant differences among the electrode locations at both preterm age and TEA. At 30-32 wk PCA, the bottom of Med-LMA5 was significantly higher for the trans-frontal electrodes than for the trans-central electrodes. In contrast, all measurements for Med-LMA5 were significantly lower for the trans-frontal electrodes than for the trans-central electrodes., Discussion: Amplitudes on aEEGs were significantly different among the electrode locations in preterm infants, and locational differences in amplitude changed between preterm age and TEA. It is necessary to understand the differences in amplitudes among the electrode locations on aEEGs in infants to appropriately evaluate them.

We report the case of a 17-month-old infant who developed an isolated cystic lesion of the callosal genu as a unique lesion of traumatic axonal injury (TAI). Although one of the most common sites of TAI is the corpus callosum, there have been no reports describing the lesion seen in our patient. Brain computed tomography findings were normal on the day of the traffic accident. After 3 months, brain magnetic resonance imaging showed an isolated cystic lesion of the callosal genu that had the appearance of a cystic cavity. This lesion decreased in size 16 months later. The neuroimaging findings of this patient suggest that an isolated cystic lesion of the callosal genu could appear as a unique form of TAI in infants after traumatic brain injury (TBI), but it is nevertheless important to attend to such lesions in children with TBI., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Many types of spinocerebellar ataxias (SCAs) manifest as progressive disorders with cerebellar involvement. SCA type 27 (SCA27) is a rare type of SCA caused by mutations in the fibroblast growth factor 14 gene (FGF14). FGF14 disruption caused by a de novo reciprocal chromosomal translocation between chromosomes 13 and 21 was identified in a patient with the phenotype of paroxysmal non-kinesigenic dyskinesia (PNKD). This indicated genetic heterogeneity of PNKD, since 60% of the patients with PNKD exhibit mutations in another gene responsible for PNKD, the myofibrillogenesis regulator 1 gene (MR-1). We hypothesized that the remaining 40% of patients with PNKD may have FGF14 mutations; therefore, the nucleotide sequences of MR-1 and FGF14 were analyzed in another six patients with PNKD, but no nucleotide alterations were observed in these genes for these patients. Further studies should be conducted on the phenotypic heterogeneity of FGF14 mutations and/or haploinsufficiency in SCA27 and PNKD., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

To clarify the features of acute encephalopathy associated with 2009 pandemic flu. We identified 51 patients with acute encephalopathy with seasonal flu from the data base accumulated by Tokai Pediatric Neurology Society. We also collected 10 patients with acute encephalopathy with 2009 pandemic flu. The clinical course, laboratory data, neuroimaging findings, treatment, and the outcome of these patients were recruited using a structured research form. These data were compared between the two groups. The age was larger in the 2009 pandemic flu group (median, 109.5months) than in the seasonal flu group (median, 44months). There was no significant difference in other demographic data, neurologic symptoms, laboratory and neuroimaging findings, and treatment. Various degrees of neurologic sequelae including death were observed in 32% of the patients in the seasonal flu group, and in 50% in the 2009 pandemic flu groups. The analyses of patients with ages of 6years or older revealed that moderate or more severe sequelae were more frequent in patients with 2009 pandemic flu. Acute encephalopathy with 2009 pandemic flu occurred mainly among children with 6years of age or older, and the outcome was worse in this age group compared with acute encephalopathy with seasonal flu., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders., Methods: A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations., Key Findings: One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features., Significance: We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Objective: To investigate the accuracy of conventional electroencephalograms (cEEGs) and amplitude-integrated EEGs (aEEGs) in the evaluation of brain maturation in normal pre-term infants. In addition, extrauterine acceleration of brain maturation was investigated., Methods: A total of 129 EEGs recorded between 27 and 37 weeks of postconceptional age (PCA) from 37 clinically stable pre-term infants were analysed. One expert investigator blindly estimated PCA using cEEG and total cerebral function monitoring (CFM) score on aEEG. The estimated PCA (ePCA) on aEEG was calculated from a regression equation., Results: The linear regression analysis showed a significant correlation between chronological PCA (cPCA) and ePCA on cEEG and between cPCA and total CFM score on aEEG. The estimation gap was smaller on cEEG, which was between -2 and +2 weeks in 96.9%. No significant correlation was observed between postnatal age and the estimation gap on cEEG or aEEG., Conclusions: Estimated brain maturation was well correlated with cPCA on cEEG and aEEG. However, the evaluation of brain maturation was much more accurate on cEEG than aEEG. Extrauterine acceleration of brain maturation was not observed on either cEEG or aEEG., Significance: cEEG and aEEG will be valuable tools for evaluation of brain maturation in pre-term infants., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Rotavirus is one of the most common causes of gastroenteritis in children and is known to accompany some neurological disorders such as encephalitis/encephalopathy and seizures. Although cerebellar disorders sometime occur as a complication of rotavirus gastroenteritis in Japan, few reports have addressed these issues. Here, we report three cases of insulted cerebellums in addition to encephalitis/encephalopathy associated with rotavirus. Similar to posterior fossa syndrome after surgery, mutism was a notable symptom that lasted about 1 month. Brain diffusion-weighted imaging (DWI) revealed chronological changes, i.e., marked hyperintensity in the bilateral dentate nucleus followed by the vermis and cerebellar hemisphere. The bilateral dentate nucleus is known to be a key lesion site for mutism, and these clinical and radiological findings may be tightly connected in rotavirus-associated cerebellitis/cerebellopathy., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Purpose: 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)., Methods: 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., Results: 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., Conclusions: 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., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)

Objectives: To investigate the progression of the clinical features from symptom onset to diagnosis in children with brain tumours., Design: Retrospective case note review., Patients: Sixty children with brain tumours: 27 patients from Nagoya University Hospital diagnosed between February 2004 and April 2008, and 33 patients from Anjo Kosei Hospital diagnosed between April 1995 and December 2008., Results: Various symptoms and signs were observed. The most common initial symptoms or signs were vomiting (24.1%), headache (17.2%), unsteadiness (10.3%), and paresis (10.3%). Sixteen patients were diagnosed based on the initial symptom or sign alone; six, at routine medical check-ups or had perinatal diagnosis; and the remaining 38, based on one or more additional features following the initial symptom. Nine of the 10 patients with headache as the initial symptom subsequently developed either vomiting (in seven) or unsteadiness with cranial nerve palsies (in two). Twelve of the 14 patients with vomiting as the initial symptom subsequently developed headache (in three), unsteadiness (in five), or other manifestations of increased intracranial pressure (in four). The remaining 14 had varied initial symptoms and combinations of symptoms and signs associated with the tumour location. The median pre-diagnosis symptomatic interval was 20.5 days. There was no significant difference in the median symptomatic interval between patients with headache or vomiting as the initial symptom and those with any neurological sign., Conclusion: Paediatric brain tumours present with various initial symptoms and signs. Many are diagnosed as additional symptoms or signs develop. The clinical features exhibit several patterns of progression, which are related to the tumour location., (Copyright 2009 Elsevier B.V. All rights reserved.)

We describe two infants with subcortical leukomalacia and decreased water diffusivity in widespread white matter on magnetic resonance imaging. In both infants, diffusion-weighted imaging at age 1 day revealed a widespread increase in signal intensities, predominantly in subcortical areas. The corticospinal tract in the brainstem was not involved. Subsequently, diffusion-weighted imaging produced apparently normal results, and conventional magnetic resonance imaging indicated diffuse but subcortical-dominant white matter lesions in the subacute phase. Follow-up magnetic resonance imaging revealed a volume loss and gliosis of the white matter. In one infant, psychomotor development was mildly delayed, and epilepsy occurred. The other infant experienced normal development and no epilepsy. Neither infant developed spastic cerebral palsy. These infants represent a characteristic group with perinatal brain injury., (Copyright 2010 Elsevier Inc. All rights reserved.)

Introduction: Hemimegalencephaly is a well-known congenital malformation. However, localized megalencephaly, which may be one of the subtypes of hemimegalencephaly, has not been separately investigated. In the present study, we attempted to characterize the clinical and magnetic resonance (MR) imaging features of localized megalencephaly in comparison with ordinary diffuse hemimegalencephaly and multilobar cortical dysplasia., Methods: MR findings for 43 patients with hemimegalencephaly and ten with multilobar cortical dysplasia, which is the differential diagnosis of localized megalencephaly, were retrospectively reviewed. Clinical findings such as the onset and severity of seizures and imaging findings including the affected area of the brain, structures outside of the hemisphere, and interval morphological changes were examined., Results: Of the 43 patients, 11 showed signs of localized megalencephaly (25.6%). Localized megalencephaly was predominantly seen on the left side (72.7%) and had a tendency toward severe-grade seizures compared to multilobar cortical dysplasia. The frequencies of the extracerebral abnormalities in the diffuse hemimegalencephaly, localized megalencephaly, and multilobar cortical dysplasia groups were 84.4%, 36.4%, and 0.0%, respectively. There were three localized megalencephaly patients whose affected areas shrank and whose images were similar to those of multilobar cortical dysplasia., Conclusion: Localized megalencephaly accounts for one quarter of all hemimegalencephaly cases in this study. The incidence of extracerebral abnormalities in patients with localized hemimegalencephaly was almost half that of patients with diffuse hemimegalencephaly. Extracerebral abnormalities were absent in patients with multilobar cortical dysplasia. Associated extracerebral abnormalities may be a clue to differentiating localized megalencephaly from multilobar cortical dysplasia.

Objective: This study sought to clarify chronologic changes in neonatal electroencephalographic (EEG) findings in periventricular leukomalacia (PVL)., Methods: 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., Results: 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., Conclusions: 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.

Purpose: To assess the efficacy of diazepam suppositories at preventing febrile seizure recurrence during a single febrile illness to determine how to treat children with a febrile seizure on presentation at the hospital., Methods: We studied 203 children with febrile seizures from December 2004 through March 2006. On admission between December 2004 and May 2005, a diazepam suppository was administered to the patients. Patients seen between June 2005 and March 2006 were not treated with antiepileptic drugs on admission., Results: We saw a significant difference in the rate of recurrence of febrile seizures between children treated with diazepam and those who were not. Recurrences were observed in 2 (2.1%) of 95 children treated with diazepam and in 16 (14.8%) of 108 untreated children. For the 108 untreated patients, the median age was 22.8 months in those with recurrences and 30.6 months in those without, confirming that a younger age was related to a recurrence., Conclusions: A diazepam suppository after a febrile seizure will reduce the incidence of recurrent febrile seizures during the same febrile illness. However, a diazepam suppository after a febrile seizure should be used after carefully considering the benefits and potential adverse effects.