Relationship between the change of language symptoms and the change of regional cerebral blood flow in the recovery process of two children with acquired aphasia
Publication date: June 2017 Source:Brain and Development, Volume 39, Issue 6 Author(s): Junko Kozuka, Akira Uno, Hiroshi Matsuda, Yoshiya Toyoshima, Shin-ichiro Hamano ObjectiveThis study aimed to investigate the relationship between the change of language symptoms and the change of regional cerebral blood flow (rCBF) in the recovery process of two children with acquired aphasia caused by infarctions from Moyamoya disease with an onset age of 8years.MethodsWe compared the results for the Standard Language Test of Aphasia (SLTA) with rCBF changes in 7 language regions in the left hemisphere and their homologous regions in the right hemisphere at 4 time points from 3weeks for up to 5years after the onset of aphasia, while controlling for the effect of age.ResultsIn both cases, strong correlations were seen within a hemisphere between adjacent regions or regions that are connected by neuronal fibers, and between some language regions in the left hemisphere and their homologous regions in the right hemisphere. Conversely, there were differences between the two cases in the time course of rCBF changes during their recovery process.ConclusionConsistent with previous studies, the current study suggested that both hemispheres were involved in the long-term recovery of language symptoms in children with acquired aphasia. We suggest that the differences between both cases during their recovery process might be influenced by the brain states before aphasia, by which hemisphere was affected, and by the timing of the surgical revascularization procedure. However, the changes were observed in the data obtained for rCBF with strong correlations with the changes in language performance, so it is possible that rCBF could be used as a biomarker for language symptom changes.
Childhood leukodystrophies: A literature review of updates on new definitions, classification, diagnostic approach and management
Publication date: May 2017 Source:Brain and Development, Volume 39, Issue 5 Author(s): Mahmoud Reza Ashrafi, Ali Reza Tavasoli Childhood leukodystrophies are a growing category of neurological disorders in pediatric neurology practice. With the help of new advanced genetic studies such as whole exome sequencing (WES) and whole genome sequencing (WGS), the list of childhood heritable white matter disorders has been increased to more than one hundred disorders. During the last three decades, the basic concepts and definitions, classification, diagnostic approach and medical management of these disorders much have changed. Pattern recognition based on brain magnetic resonance imaging (MRI), has played an important role in this process. We reviewed the last Global Leukodystrophy Initiative (GLIA) expert opinions in definition, new classification, diagnostic approach and medical management including emerging treatments for pediatric leukodystrophies.
Molecular biomarkers predictive of sertraline treatment response in young children with fragile X syndrome
Publication date: June 2017 Source:Brain and Development, Volume 39, Issue 6 Author(s): Reem Rafik AlOlaby, Stefan R. Sweha, Marisol Silva, Blythe Durbin-Johnson, Carolyn M. Yrigollen, Dalyir Pretto, Randi J. Hagerman, Flora Tassone ObjectivesSeveral neurotransmitters involved in brain development are altered in fragile X syndrome (FXS), the most common monogenic cause of autism spectrum disorder (ASD). Serotonin plays a vital role in synaptogenesis and postnatal brain development. Deficits in serotonin synthesis and abnormal neurogenesis were shown in young children with autism, suggesting that treating within the first years of life with a selective serotonin reuptake inhibitor might be the most effective time. In this study we aimed to identify molecular biomarkers involved in the serotonergic pathway that could predict the response to sertraline treatment in young children with FXS.MethodsGenotypes were determined for several genes involved in serotonergic pathway in 51 children with FXS, ages 24–72months. Correlations between genotypes and deviations from baseline in primary and secondary outcome measures were modeled using linear regression models.ResultsA significant association was observed between a BDNF polymorphism and improvements for several clinical measures, including the Clinical Global Impression scale (P=0.008) and the cognitive T score (P=0.017) in those treated with sertraline compared to those in the placebo group. Additionally, polymorphisms in the MAOA, Cytochrome P450 2C19 and 2D6, and in the 5-HTTLPR gene showed a significant correlation with some of the secondary measures included in this study.ConclusionThis study shows that polymorphisms of genes involved in the serotonergic pathway could play a potential role in predicting response to sertraline treatment in young children with FXS. Larger studies are warranted to confirm these initial findings.
Prenatal and lactational bisphenol A exposure does not alter serotonergic neurons morphologically in the murine dorsal raphe nucleus
Publication date: June 2017 Source:Brain and Development, Volume 39, Issue 6 Author(s): Shoko Goto, Hiroshi Ogi, Shinji Fushiki, Kyoko Itoh ObjectiveThere is concern that bisphenol A (BPA), an endocrine-disrupting chemical, affects brain development when exposed to a fetus and/or infant. We previously reported that increased serotonin (5-HT) and its metabolite (5-HIAA) in the dorsal raphe nucleus (DRN) in murine adult brains when they were prenatally exposed to low doses of BPA. This study investigates the morphological alteration of the dorsal raphe nucleus (DRN) in order to explain the disrupted serotonergic system after prenatal and lactational exposure to bisphenol A (BPA).MethodsThe murine dams were orally administrated with 500μg/kg/day of BPA from embryonic day 0 to postnatal 3weeks. The DRN, the main region of serotonin production, was morphometrically analyzed at 14weeks, using immunohistochemistry and image analysis combined with 3-dimensional reconstruction.ResultsNo significant differences were revealed in the number of tryptophan hydroxylase 2-immunoreactive neurons in any of the DRN sub-regions or the morphometric parameters, including the whole volume, ventrodorsal, longitudinal, and wing lengths of the DRN among the BPA treatment and sex groups.ConclusionsThe murine DRN was not morphologically affected by prenatal and lactational exposure to low doses of BPA. Further studies are necessary regarding the function of serotonergic neurons and the activity of different kinds of related receptors in the brain.
Aspartylglucosaminuria caused by a novel homozygous mutation in the AGA gene was identified by an exome-first approach in a patient from Japan
Publication date: May 2017 Source:Brain and Development, Volume 39, Issue 5 Author(s): Toshiyuki Yamamoto, Keiko Shimojima, Mayumi Matsufuji, Ryuichi Mashima, Eri Sakai, Torayuki Okuyama BackgroundAspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, aspartylglucosaminidase (AGA). This disorder is rare in the general population except in Finland. Since the most characteristic feature of this disorder is a progressive developmental regression, patients often show no specific symptoms in the initial stages, and thus early diagnosis is often challenging.Case reportWe encountered a 16-year-old boy who began to show difficulties in his speech at the age of 6years. Due to a mild regression in his development, he gradually lost common daily abilities. His diagnosis was first obtained through exome sequencing that identified a novel homozygous mutation in the AGA gene. This result was reasonable because of parental consanguinity. Reduced enzymatic activity of AGA was then confirmed. His urine was retrospectively screened by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and a specific pattern of abnormal metabolites was identified.ConclusionsBecause both exome sequencing and MALDI-TOF-MS screening are adaptable and comprehensive, future combinatory use of these methods would be useful for diagnosis of rare inborn errors of metabolism such as AGU.
Historical documents on epilepsy: From antiquity through the 20th century
Publication date: June 2017 Source:Brain and Development, Volume 39, Issue 6 Author(s): Christos P. Panteliadis, Photios Vassilyadi, Julia Fehlert, Christian Hagel Historical documents dating back almost 4500years have alluded to the condition of epilepsy, describing signs and symptoms that are well-known today. Epilepsy was thought to be a mystical disorder by almost all Ancient cultures, including the Babylonians, Egyptians, Greeks, Indians, Iranians and Chinese. Hippocrates was the first to de-mystify the condition of epilepsy, providing a more scientific approach to the condition. As the signs and symptoms of epilepsy occurred without an obvious cause, the idea stood that it was a mystical phenomenon of divine punishment. This portrayal persisted through the early centuries of the common era, including the Middle Ages. It was not until the 16th and 17th century that Paracelsus, le Pois and Sylvius started to investigate internal causes for epilepsy. By the beginning of the 18th century, the general opinion on epilepsy was that it was an idiopathic disease residing in the brain and other inner organs. This resulted in Tissot writing the first modern book on epilepsy. Research continued in the 19th century with Jackson describing different types of seizures and many researchers showing interest in electroencephalography (EEG). The 20th century saw more detailed research being done on epilepsy and EEG, in addition to the establishment of many epilepsy-associated medical societies. The goal of this historical documentation is to provide an overview of the most important milestones in the history of epilepsy.