Brain and Development RSS feed: Current Issue. Brain and Development is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor's discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome. Announcement Request for assignment of copyrights on previously published articles in Brain and Development http://www.brainanddevelopment.com/?rss=yesElsevier Inc.en © 2012 The Japanese Society of Child Neurology. Published by Elsevier Inc. All rights reserved. Brain and Development0387-7604346June 2012 © 2012 The Japanese Society of Child Neurology. Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.brainanddevelopment.com/article/PIIS0387760412001003/abstract?rss=yesEditorial Board10.1016/S0387-7604(12)00100-3Brain and Development 34, 6 (2012)2012-06-01Brain and Development2012-06-01346S0387-7604(12)X0005-6IFCIFChttp://www.brainanddevelopment.com/article/PIIS0387760411002518/abstract?rss=yesAbstract: Ohtahara syndrome or Early Infantile Epileptic Encephalopathy (EIEE) with Suppression-Burst, is the most severe and the earliest developing age-related epileptic encephalopathy. Clinically, the syndrome is characterized by early onset tonic spasms associated with a severe and continuous pattern of burst activity. It is a debilitating and early progressive neurological disorder, resulting in intractable seizures and severe mental retardation. Specific mutations in at least four genes (whose protein products are essential in lower brain’s neuronal and interneuronal functions, including mitochondrial respiratory chains have been identified in unrelated individuals with EIEE and include: (a) the ARX (aristaless-related) homeobox gene at Xp22.13 (EIEE-1 variant); (b) the CDKL5 (SYK9) gene at Xp22 (EIEE-2 variant); (c) the SLC25A22 (GC1) gene at 11p15.5 (EIEE-3 variant); and (d) the Stxbp1 (MUNC18-1) gene at 9q34-1 (EIEE-4 variant). A yet unresolved issue involves the relationship between early myoclonic encephalopathy (EME–ErbB4 mutations) versus the EIEE spectrum of disorders.Ohtahara syndrome with emphasis on recent genetic discoveryPiero Pavone, Alberto Spalice, Agata Polizzi, Pasquale Parisi, Martino Ruggieri10.1016/j.braindev.2011.09.004Brain and Development 34, 6 (2012)2011-10-04Brain and Development2011-10-04346S0387-7604(12)X0005-6Mini review459468http://www.brainanddevelopment.com/article/PIIS0387760411002440/abstract?rss=yesAbstract: Dravet syndrome (DS) is a severe epileptic encephalopathy beginning in infancy in which children have difficult to control seizures and cognitive impairment. The majority of children with DS carry mutations of the gene Scn1a, which codes for the alpha subunit of the type 1 voltage-gated sodium channel and is important for the function of interneurons. Interneurons have a critical role in the generation of brain rhythms involved in cognitive processing. We hypothesized that children with DS with Scn1a mutations would have abnormal oscillatory activity. To address this hypothesis, we used EEG power spectral analysis during the wakening to determine if frequency and power are altered in 23 EEGs from 12 children with DS compared to 18 age-matched controls. While there were few differences between the EEG power spectra in DS and controls in children under 2years, in older children group differences were apparent. In DS children between 3 and 5years there were significant decreases in percentage of alpha power compared to controls and in DS children over age 6years there was a marked increase of theta and decrease of alpha compared to controls. Developmental status paralleled the power spectral analysis with an increasing likelihood of having severe cognitive problems with increasing age. These results demonstrate that Scn1a mutations result in an age-dependent alteration in oscillatory process. Such abnormalities in developmental progression of oscillations may play an important role in poor cognitive development in children with DS.Maturation of EEG oscillations in children with sodium channel mutationsGregory L. Holmes, Alex C. Bender, Edie X. Wu, Rod C. Scott, Pierre Pascal Lenck-Santini, Richard P. Morse10.1016/j.braindev.2011.08.009Brain and Development 34, 6 (2012)2011-09-22Brain and Development2011-09-22346S0387-7604(12)X0005-6Original articles469477http://www.brainanddevelopment.com/article/PIIS0387760411002488/abstract?rss=yesAbstract: Purpose: To elucidate the functional characteristics of cortical tubers that might be responsible for epilepsy in tuberous sclerosis complex (TSC), proton magnetic resonance spectroscopy (1H-MRS) and [123I] iomazenil (123I-IMZ) single photon emission computed tomography (SPECT) were performed.Methods: 1H-MRS using a clinical 3-tesla magnetic resonance imager was performed in four children with TSC and 10 age-and sex-matched healthy control subjects. A single voxel was set on the right parietal lobe in control subjects. In patients with TSC, a single voxel was set on the epileptogenic tuber in the parietal or temporal lobe, and another voxel was set on the contralateral normal-appearing brain region. N-Acetylaspartate (NAA), myo-Inositol (mIns) and Glutamate (Glu) were analyzed using a conventional STEAM (Stimulated Echo Acquisition Mode) method. The concentration of gamma-aminobutyric acid (GABA) was quantified using MEGA-Point Resolved Spectroscopy (PRESS). Interictal 123I-IMZ SPECT was examined in all four patients with TSC.Results: A significant decrease in the NAA concentration and significant increases in the mIns and GABA concentrations were detected in the cortical tubers of all 4 patients. No significant difference was observed in Glu concentrations. In all of the cortical tubers detected by magnetic resonance imaging, 123I-IMZ binding was significantly decreased.Conclusion: Epileptogenesis in TSC might be caused by decreased inhibition secondary to the decrease in GABA receptors in dysplastic neurons of cortical tubers. An increase in the GABA concentration may compensate for decreased inhibition.Decreased benzodiazepine receptor and increased GABA level in cortical tubers in tuberous sclerosis complexKenji Mori, Tatsuo Mori, Yoshihiro Toda, Emiko Fujii, Masahito Miyazaki, Masafumi Harada, Shoji Kagami10.1016/j.braindev.2011.09.001Brain and Development 34, 6 (2012)2011-09-28Brain and Development2011-09-28346S0387-7604(12)X0005-6Original articles478486http://www.brainanddevelopment.com/article/PIIS038776041100249X/abstract?rss=yesAbstract: Background: Mutations in the MECP2 gene (methyl-CpG-binding protein-2) are responsible for 60–95% of cases of Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder affecting mostly girls. Classic RTT is characterized by normal early development followed by psychomotor regression and onset of microcephaly, although variant forms are also observed. MECP2 has also been implicated in variable mental retardation (MR) phenotypes, including X-linked Mental Retardation (XLMR), Fragile-X-like Syndrome (FXS) and Angelman-like (AS) phenotypes. Aim: The aim of the study was: (a) to evaluate the incidence and spectrum of MECP2 mutations in children with RTT and variant MR; (b) to evaluate phenotype-genotype correlations. Methods: Exons 3–4 were analyzed for mutations in 281 MR patients (aged 13months–27years old, 144 males–137 females) consisting of 88 patients referred for RTT and 193 patients referred for AS-like and FXS-like types of MR. Statistical analysis included correlation between classic MECP2-positive and MECP2-negative and variant RTT patients, and frequency of MECP2 mutations in the various categories. Results: Mutations were detected in ≈70% of classic and ≈21% of variant RTT, respectively. Amongst MR cases, 2.1% carried MECP2 mutations. MECP2-positive females had more problems in ambulation, muscle tone, tremor and ataxia, respiratory disturbances, head growth, hand use and stereotypies. Classic RTT-positive versus negative had significant respiratory and sitting problems and versus variant RTT-positive females ambulatory, hand and stereotypies problems. Conclusion: The analysis of the MECP2 gene could provide a diagnostic tool for RTT and non-specific MR research.MECP2 mutations and clinical correlations in Greek children with Rett syndrome and associated neurodevelopmental disordersStavroula Psoni, Christalena Sofocleous, Joanne Traeger-Synodinos, Sophia Kitsiou-Tzeli, Emmanuel Kanavakis, Helen Fryssira-Kanioura10.1016/j.braindev.2011.09.002Brain and Development 34, 6 (2012)2011-10-10Brain and Development2011-10-10346S0387-7604(12)X0005-6Original articles487495http://www.brainanddevelopment.com/article/PIIS0387760411002506/abstract?rss=yesAbstract: Patients with epilepsy after encephalitis/encephalopathy (EAE) often have refractory seizures, resulting in polytherapy with the risk of adverse reactions due to anti-epileptic drugs (AEDs). We focused on the characteristics of cutaneous adverse reaction (CAR).In this retrospective study, the medical records of 67 patients who were diagnosed as having EAE in our hospital were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1 (s-TNFR 1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in 22 patients. CARs attributed to AEDs were observed in 16 of 67 EAE patients (23.9%) (CAR group). High CAR rates were observed with phenytoin, lamotrigine, phenobarbital, and carbamazepine. Severe CARs were found in three of 67 patients (4.5%). The frequencies of CARs were significantly higher in patients with encephalitis onset older than five years of age. CAR occurred only in patients who had onset of EAE within 6 months after encephalitis. The durations from acute encephalitis to CARs were within one year for almost all AEDs, except lamotrigine. The proportion of patients with serumregulated on activation normal T cell expressed and secreted (RANTES) levels higher than the upper limit of normal range was significantly higher in CAR group than in non-CAR group. Patients in the early stage of EAE and patients with encephalitis onset older than five years of age may be at higher risk of CARs to AEDs, especially to phenytoin, lamotrigine, phenobarbital, and carbamazepine. RANTES may be a biomarker for susceptibility to CARs in EAE patients.Cutaneous adverse drug reaction in patients with epilepsy after acute encephalitisYukiko Mogami, Yukitoshi Takahashi, Rumiko Takayama, Hideyuki Ohtani, Hiroko Ikeda, Katsumi Imai, Hideo Shigematu, Yushi Inoue10.1016/j.braindev.2011.09.003Brain and Development 34, 6 (2012)2011-10-13Brain and Development2011-10-13346S0387-7604(12)X0005-6Original articles496503http://www.brainanddevelopment.com/article/PIIS0387760411002464/abstract?rss=yesAbstract: Background: Epilepsy is a chronic disorder that significantly affects learning and behavior. Children with epilepsy are much more vulnerable for educational problems than with any other chronic illness. Objectives: The study was conducted to assess the extent of educational problems and factors associated with educational underachievement in Indian children with epilepsy. Methods: It was a case control study and included 100 cases of 6–16years age of epilepsy, 50 healthy children (control A) and 50 children with persistent asthma (control B). Their demographic and disease variables were evaluated. The educational performance was assessed by using a predesigned semi structured open ended questionnaire to parents and by teacher’s report. Psychological evaluation was done in first step by using a standard questionnaire, childhood psychopathology measurement schedule. In second step, those have shown poor educational performance or significant score in standard questionnaire underwent detailed psychiatric evaluation. Results: Educational problems were reported in cases (36%), control A (2%) and control B (16%). Demographic or disease variables were not associated with educational problems in cases except that boys were more affected than girls. On psychiatric evaluation psychopathological illnesses (47%) like attention deficit hyperkinetic disorder, conduct disorder and depression were found to be commonly associated with poor educational performance (47%) followed by decreased learning opportunities (22.2%) and borderline intelligence (19.4%) in children with epilepsy. Conclusion: Educational problems are commoner in children with epilepsy than with asthma. Psychopathological problems are commonly associated with educational underachievement in children with epilepsy. Therefore periodic psychosocial assessment, counseling and support must be provided to improve the psychosocial adjustment in children with epilepsy.A study of educational underachievement in Indian children with epilepsyHarpal Singh, Satinder Aneja, K.E.S. Unni, Anju Seth, Virendra Kumar10.1016/j.braindev.2011.08.011Brain and Development 34, 6 (2012)2011-09-28Brain and Development2011-09-28346S0387-7604(12)X0005-6Original articles504510http://www.brainanddevelopment.com/article/PIIS0387760411002543/abstract?rss=yesAbstract: Purpose: To describe the clinical and electroencephalographic features, treatment strategies and outcome in a series of children with the atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic-BECTS).Material and methods: Out of the 148 patients with BECTS reviewed from January 2005 to June 2010 in our Institute, there were seven (5%) with atonic-BECTS. All underwent video EEG, high-resolution magnetic resonance imaging (MRI), neuropsychological evaluation and language assessment. Their progress was followed. In addition to sodium valproate, three were treated with steroids, followed by intravenous immunoglobulin (IVIG) when the seizures relapsed while tapering or after stopping the steroids.Results: All of the children had earlier onset (mean=2.4years), increased frequency and increased duration of focal seizures compared to typical BECTS. Head drop and truncal sway due to axial or axiorhizomelic atonia occurring several times per day or week was the key manifestation. The atonic seizures worsened with carbamazepine in three, clonazepam in two and clobazam in one. When the atypical seizures commenced, some children developed one or more of the following problems: hyperactivity, attention deficit, clumsy gait, and mild cognitive or language dysfunction. Three children became seizure free, one on steroids and the other two on IVIG.Conclusions: BECTS in children with an early age of onset and frequent and prolonged seizures is more likely to evolve into atonic-BECTS. Carbamazepine and some benzodiazepines may worsen these seizures. Three children became seizure free with immunomodulatory therapy, one on steroids and the other two on IVIG, and had complete resolution of the transient motor and cognitive impairment. Atonic-BECTS needs to be differentiated from Lennox–Gastaut syndrome since it is potentially treatable and children recover with no sequel. Although all the children in this series continued to be on treatment with sodium valproate it is currently undetermined whether they would have required to do so if followed up for an extended period of time.Atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic-BECTS): A distinct electro-clinical syndromeAjith Cherian, Neeraj N. Baheti, Ramshekhar N. Menon, Rajesh S. Iyer, Chaturbhuj Rathore, Ashalatha Radhakrishnan10.1016/j.braindev.2011.09.007Brain and Development 34, 6 (2012)2011-10-10Brain and Development2011-10-10346S0387-7604(12)X0005-6Original articles511519http://www.brainanddevelopment.com/article/PIIS038776041100252X/abstract?rss=yesAbstract: This is the first study to report differences between Japanese children with and without dyslexia in the way string-length and lexicality effects are manifested when reading Japanese kana. These children were asked to read kana words and non-words consisting of either two or five kana characters. The results showed that the error rates of the normal Preschoolers and Primary-School children with dyslexia were higher than those of the normal Primary-School children. Further, the reading latencies of the normal Preschoolers, First-graders and dyslexics were significantly longer than those of the normal Second, Third and Fifth/Sixth graders. Moreover, reading latencies became shorter as the age of the participants increased. Both normal and dyslexic children showed significant effects of length and lexicality on reading latencies. However, the interaction between the length and lexicality was only seen in normal children from the Second-grade onwards. These results suggest that (1) normal First-graders reach a ceiling in terms of reading accuracy and that (2) as Japanese normal children become older, they become better at lexical reading processes, which leads to fluent kana reading, but that (3) the dyslexics, even at Fifth/Sixth grades, have not developed sufficient lexical reading processes.An investigation into kana reading development in normal and dyslexic Japanese children using length and lexicality effectsAmi Sambai, Akira Uno, Suzuko Kurokawa, Noriko Haruhara, Masato Kaneko, Noriko Awaya, Junko Kozuka, Takashi Goto, Eishi Tsutamori, Kazumi Nakagawa, Taeko N. Wydell10.1016/j.braindev.2011.09.005Brain and Development 34, 6 (2012)2011-10-13Brain and Development2011-10-13346S0387-7604(12)X0005-6Original articles520528http://www.brainanddevelopment.com/article/PIIS0387760411002452/abstract?rss=yesAbstract: Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) encompasses a group of encephalopathy characterized by biphasic seizures and disturbance of consciousness in the acute stage followed in the subacute stage by reduced diffusion in the subcortical white matter on magnetic resonance imaging. The etiology of AESD is viral infection and associated pathological changes. Here we report the first case of AESD caused by bacterial infection (Streptococcus pneumoniae meningitis) in a 1-year-old boy.A case of acute encephalopathy with biphasic seizures and late reduced diffusion associated with Streptococcus pneumoniae meningoencephalitisSeiko Kuwata, Hideaki Senzaki, Yasuko Urushibara, Mihiro Toriyama, Shingo Kobayashi, Kyoko Hoshino, Hiroshi Arakawa, Masanori Tamura10.1016/j.braindev.2011.08.010Brain and Development 34, 6 (2012)2011-09-21Brain and Development2011-09-21346S0387-7604(12)X0005-6Case Reports529532http://www.brainanddevelopment.com/article/PIIS0387760411002531/abstract?rss=yesAbstract: Background: Farber disease (MIM 228000) is a rare autosomal recessive condition caused by deficiency of lysosomal acid ceramidase (EC 3.5.1.23). The disease presents classically during the infantile period with a characteristic triad of clinical manifestations: (a) painful joints, (b) subcutaneous nodules, and (c) progressive hoarseness due to laryngeal involvement. All cases reported in the literature to date have presented with the above features, except for the neonatal-visceral subtype. Methods: Here we describe a 2-year-old female, a product of a non-consanguineous Emirati union, who was quite well until 8months of age when presented with failure to thrive, developmental delay with relative sparing of cognitive function, cherry-red spot, painful joint, progressive limitation of joint movement, and hoarseness of voice. The sibling of patient died with similar presentation and the nerve biopsy of deceased sibling showed features consistent with Farber disease. Results: Gene sequencing of the ASAHI gene confirmed the diagnosis of Farber disease. Our patient has two heterozygous novel mutations, one in exon 8 (c.533 T>C) and the other in exon 13 (c.1144 A>C). The carrier status of the parents was confirmed. Conclusions: Farber disease is well known for its striking unique triad of symptoms. This study demonstrates that not all the cases essentially present with subcutaneous nodules which is considered a hallmark of the disease.A novel mutation in an atypical presentation of the rare infantile Farber diseaseFatma Al Jasmi10.1016/j.braindev.2011.09.006Brain and Development 34, 6 (2012)2011-10-10Brain and Development2011-10-10346S0387-7604(12)X0005-6Case Reports533535http://www.brainanddevelopment.com/article/PIIS0387760411002841/abstract?rss=yesAbstract: Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a neurodegenerative disorder caused by pantothenate kinase (PANK2) gene mutations. Brain magnetic resonance imaging (MRI) typically shows the “eye-of-the-tiger” sign, i.e. bilateral pallidal T2 hypointensity with a small central region of T2-hyperintensity. Aims: To describe clinical and MRI findings of a boy with early-onset neurodegeneration with brain iron accumulation due to PANK2 mutation. Methods: Clinical, neuroradiological and molecular investigations have been performed. Results: At first observation (2years and 10months) the boy presented only with developmental delay and toe-walking and isolated T2 hyperintensity within globi pallidi on brain MRI. One year later, small rounded areas of markedly low signal within the globi pallidi on T2∗- weighted images appeared in association with mild dystonia. PANK2 gene homozygous mutation confirmed the diagnosis of PKAN. Conclusions: In young children, PKAN should be suspected also before clinical and neuroradiological picture is fully indicative, to avoid delayed diagnosis of a genetic disease for which therapeutical options could be potentially useful if administered in paucisymptomatic subjects.Early-onset neurodegeneration with brain iron accumulation due to PANK2 mutationDaniela Rossi, Elisa De Grandis, Chiara Barzaghi, Monica Mascaretti, Barbara Garavaglia, Elisabetta Zanotto, Giovanni Morana, Roberta Biancheri10.1016/j.braindev.2011.09.010Brain and Development 34, 6 (2012)2011-10-17Brain and Development2011-10-17346S0387-7604(12)X0005-6Case Reports536538http://www.brainanddevelopment.com/article/PIIS0387760412000344/abstract?rss=yesWe read with great interest the recent publication by Mizuno Y. et al. in the Brain and Development . They reported a patient with intracranial calcification, cerebellar hypoplasia, growth retardation, progressive pancytopenia, interstitial pneumonia and immune abnormality. We suspect that the findings in their case are quite similar to those in CRMCC (cerebroretinal microangiopathy with calcifications and cysts)/Revesz syndrome, although the presence of retinopathy was not mentioned. The CRMCC/Revesz syndrome is a rare congenital systemic disorder that was first described by Revesz et al. . This syndrome is characterized by intrauterine growth retardation, bilateral exudative retinopathy, intracranial calcification and cysts, leukoencephalopathy, sparse hair, nail dystrophy, skeletal defects and the development of hematological disorders, which is considered to be atypical phenotype of dyskeratosis congenita (DKC). Since the patient described by Mizuno Y. et al. died early at 1year and 3months old, it is possible that clinical features such as exudative retinopathy and hair/nail abnormalities were not yet actualized. Recently, CRMCC and DKC are known to be characteristic for shortened telomere length and gene mutation of the TINF2, which encodes TIN2 (a regulator of telomere length in human cells) . Although DKC1 mutation was already excluded in their patient, we think that it is useful to perform flow-fish analysis for the measurement of telomere length in order to rule out the possibility of CRMCC. If the telomere length is shortened, genetic analysis of the genes related to DKC/CRMCC including TINF2 is highly recommended.Comments on the article by Mizuno Y. et al. entitled “Congenital infection-like syndrome with intracranial calcification”Daisuke Asai, Toshihiko Imamura, Hajime Hosoi10.1016/j.braindev.2012.02.002Brain and Development 34, 6 (2012)2012-02-27Brain and Development2012-02-27346S0387-7604(12)X0005-6Letters to the Editor539539http://www.brainanddevelopment.com/article/PIIS0387760412000691/abstract?rss=yesWe appreciate the comments of Asai et al. on our case report of congenital infection-like syndrome with intracranial calcification . They suggested the diagnostic possibility of cerebroretinal microangiopathy with calcifications and cysts (CRMCC)/Revesz syndrome in this patient. To the best of our knowledge, only one case of this syndrome has previously been reported in Japan .Congenital infection-like syndrome with intracranial calcification: Absence of TINF2 mutationYoko Mizuno, Kan Takahashi, Takashi Igarashi, Makiko Saito, Masashi Mizuguchi10.1016/j.braindev.2012.02.014Brain and Development 34, 6 (2012)2012-04-05Brain and Development2012-04-05346S0387-7604(12)X0005-6Letters to the Editor540540http://www.brainanddevelopment.com/article/PIIS0387760412001222/abstract?rss=yesAnnouncements and reports10.1016/S0387-7604(12)00122-2Brain and Development 34, 6 (2012)2012-06-01Brain and Development2012-06-01346S0387-7604(12)X0005-6IVIhttp://www.brainanddevelopment.com/article/PIIS0387760412001052/abstract?rss=yesContents10.1016/S0387-7604(12)00105-2Brain and Development 34, 6 (2012)2012-06-01Brain and Development2012-06-01346S0387-7604(12)X0005-6OBCOBC