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Reduced wave amplitudes of brainstem auditory response in high-risk babies born at 28–32week gestation
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 7 June 2016
Source:Brain and Development
Author(s): Ze Dong Jiang, Li Li Ping
Objective To examine brainstem auditory electrophysiology in high-risk babies born at 28–32week gestation by analysing the amplitudes of wave components in maximum length sequence brainstem auditory evoked response (MLS BAER). Methods 94 preterm babies, ranging in gestation 28–32weeks, with perinatal problems (high-risk) were recruited. The amplitudes of MLS BAER wave components were studied at term age (37–42weeks postconceptional age). Results Compared with normal term controls, the amplitude in the high-risk preterm babies was significantly smaller at the highest click rate 910/s for wave I (p <0.01), at all 91–910/s for wave III (all p <0.01) and at 455 and 910/s (p <0.05 and 0.01) for wave V. Compared with age-matched low-risk preterm controls, the amplitude was significantly smaller at 455 and 910/s for wave I (p <0.05 and 0.05), 91–910/s for wave III (p <0.05–0.001), and 227–910/s (p <0.05 and 0.01) for wave V. No differences in the V/I and V/III amplitude ratios were found between the high-risk preterm babies and the controls. Conclusions The amplitudes of MLS BAER wave components, mainly more central components, were reduced in the high-risk preterm babies born at 28–32week gestation. Electrophysiological activity of the brainstem auditory neuron in such babies is depressed, mainly attributed to or related to the associated perinatal problems.
Source:Brain and Development
Author(s): Ze Dong Jiang, Li Li Ping
Objective To examine brainstem auditory electrophysiology in high-risk babies born at 28–32week gestation by analysing the amplitudes of wave components in maximum length sequence brainstem auditory evoked response (MLS BAER). Methods 94 preterm babies, ranging in gestation 28–32weeks, with perinatal problems (high-risk) were recruited. The amplitudes of MLS BAER wave components were studied at term age (37–42weeks postconceptional age). Results Compared with normal term controls, the amplitude in the high-risk preterm babies was significantly smaller at the highest click rate 910/s for wave I (p <0.01), at all 91–910/s for wave III (all p <0.01) and at 455 and 910/s (p <0.05 and 0.01) for wave V. Compared with age-matched low-risk preterm controls, the amplitude was significantly smaller at 455 and 910/s for wave I (p <0.05 and 0.05), 91–910/s for wave III (p <0.05–0.001), and 227–910/s (p <0.05 and 0.01) for wave V. No differences in the V/I and V/III amplitude ratios were found between the high-risk preterm babies and the controls. Conclusions The amplitudes of MLS BAER wave components, mainly more central components, were reduced in the high-risk preterm babies born at 28–32week gestation. Electrophysiological activity of the brainstem auditory neuron in such babies is depressed, mainly attributed to or related to the associated perinatal problems.
Frequency specific patterns of resting-state networks development from childhood to adolescence: A magnetoencephalography study
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 7 June 2016
Source:Brain and Development
Author(s): Lu Meng, Jing Xiang
Objective The present study investigated frequency dependent developmental patterns of the brain resting-state networks from childhood to adolescence. Method Magnetoencephalography (MEG) data were recorded from 20 healthy subjects at resting-state with eyes-open. The resting-state networks (RSNs) was analyzed at source-level. Brain network organization was characterized by mean clustering coefficient and average path length. The correlations between brain network measures and subjects’ age during development from childhood to adolescence were statistically analyzed in delta (1–4Hz), theta (4–8Hz), alpha (8–12Hz), and beta (12–30Hz) frequency bands. Results A significant positive correlation between functional connectivity with age was found in alpha and beta frequency bands. A significant negative correlation between average path lengths with age was found in beta frequency band. Conclusions The results suggest that there are significant developmental changes of resting-state networks from childhood to adolescence, which matures from a lattice network to a small-world network.
Source:Brain and Development
Author(s): Lu Meng, Jing Xiang
Objective The present study investigated frequency dependent developmental patterns of the brain resting-state networks from childhood to adolescence. Method Magnetoencephalography (MEG) data were recorded from 20 healthy subjects at resting-state with eyes-open. The resting-state networks (RSNs) was analyzed at source-level. Brain network organization was characterized by mean clustering coefficient and average path length. The correlations between brain network measures and subjects’ age during development from childhood to adolescence were statistically analyzed in delta (1–4Hz), theta (4–8Hz), alpha (8–12Hz), and beta (12–30Hz) frequency bands. Results A significant positive correlation between functional connectivity with age was found in alpha and beta frequency bands. A significant negative correlation between average path lengths with age was found in beta frequency band. Conclusions The results suggest that there are significant developmental changes of resting-state networks from childhood to adolescence, which matures from a lattice network to a small-world network.
Editorial Board
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Source:Brain and Development, Volume 38, Issue 6
Neurodevelopment in full-term small for gestational age infants: A nationwide Japanese population-based study
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Akihito Takeuchi, Takashi Yorifuji, Kyohei Takahashi, Makoto Nakamura, Misao Kageyama, Toshihide Kubo, Tatsuya Ogino, Hiroyuki Doi
Objective To investigate neurological development in small for gestational age (SGA) infants, with a focus on full-term SGA infants. Methods We analyzed data from a large, Japanese, nationwide, population-based longitudinal survey started in 2001. We restricted the study to participants born before 42weeks of gestation (n =46,563). Parents were asked questions about motor and language development when the children were 2.5years old, and about behavioral development at 5.5years. We analyzed the relationships between SGA status and development by logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for each outcome for full-term and preterm births, adjusting for potential infant- and parent-related confounding factors. We also calculated the population-attributable fractions to estimate the public impact of SGA births. Results SGA full-term children were more likely to demonstrate developmental delays at 2.5years, e.g., being unable to walk alone (OR 3.0, 95% CI: 1.7, 5.3), compose a two-phrase sentence (OR 1.5, 95% CI: 1.2, 1.8), or use a spoon to eat (OR 1.5, 95% CI: 1.1, 1.9). SGA status also had some degree of negative impacts on behavioral problems at 5.5years among term children, e.g., being unable to listen without fidgeting (OR 1.2, 95% CI: 1.1, 1.3), or remain patient (OR 1.1, 95% CI: 1.0, 1.2). The public health impacts were comparable between full-term and preterm SGA children at 2.5years. Conclusion SGA is a risk factor for developmental delay, even in full-term infants, with non-negligible public health impacts.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Akihito Takeuchi, Takashi Yorifuji, Kyohei Takahashi, Makoto Nakamura, Misao Kageyama, Toshihide Kubo, Tatsuya Ogino, Hiroyuki Doi
Objective To investigate neurological development in small for gestational age (SGA) infants, with a focus on full-term SGA infants. Methods We analyzed data from a large, Japanese, nationwide, population-based longitudinal survey started in 2001. We restricted the study to participants born before 42weeks of gestation (n =46,563). Parents were asked questions about motor and language development when the children were 2.5years old, and about behavioral development at 5.5years. We analyzed the relationships between SGA status and development by logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for each outcome for full-term and preterm births, adjusting for potential infant- and parent-related confounding factors. We also calculated the population-attributable fractions to estimate the public impact of SGA births. Results SGA full-term children were more likely to demonstrate developmental delays at 2.5years, e.g., being unable to walk alone (OR 3.0, 95% CI: 1.7, 5.3), compose a two-phrase sentence (OR 1.5, 95% CI: 1.2, 1.8), or use a spoon to eat (OR 1.5, 95% CI: 1.1, 1.9). SGA status also had some degree of negative impacts on behavioral problems at 5.5years among term children, e.g., being unable to listen without fidgeting (OR 1.2, 95% CI: 1.1, 1.3), or remain patient (OR 1.1, 95% CI: 1.0, 1.2). The public health impacts were comparable between full-term and preterm SGA children at 2.5years. Conclusion SGA is a risk factor for developmental delay, even in full-term infants, with non-negligible public health impacts.
Study of clinical characteristics in young subjects with Developmental coordination disorder
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Marie Farmer, Bernard Echenne, M’hamed Bentourkia
Background Developmental Coordination Disorder (DCD) is a chronic neurological disorder observed in children. DCD is characterized by slowness in activities and motor impairment that affects the children’s daily living and academic achievements, and later their professional and social behavior. Our aim in this work was to report characteristics frequencies in a group of children with DCD and to propose a subtyping of DCD characteristics. Methods Thirty three clinical DCD characteristics, the mostly reported in the literature, were assessed in 129 patients, boys and girls aged from 4years to 18years, and their subtyping was proposed. The statistical analyses were carried out with the Chi square, the t-test and the correlation for the statistical differences, and with the Ward clustering method for subtyping. Results We found that there were 3.17 boys for one girl, all patients were characterized as slow, 47% were left-handers or ambidextrous, 36% and 26% had orofacial and verbal dyspraxia, respectively, 83% were found anxious, and 84% were described as being clumsy. Conclusions It appears from these results that a child with DCD expresses more than a single difficulty. Three subtypes emerged from the statistical analysis in this study: (1) clumsiness and other characteristics except language difficulties; (2) self-esteem and peer relation without clumsiness and language difficulties; (3) language difficulties and orofacial dyspraxia.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Marie Farmer, Bernard Echenne, M’hamed Bentourkia
Background Developmental Coordination Disorder (DCD) is a chronic neurological disorder observed in children. DCD is characterized by slowness in activities and motor impairment that affects the children’s daily living and academic achievements, and later their professional and social behavior. Our aim in this work was to report characteristics frequencies in a group of children with DCD and to propose a subtyping of DCD characteristics. Methods Thirty three clinical DCD characteristics, the mostly reported in the literature, were assessed in 129 patients, boys and girls aged from 4years to 18years, and their subtyping was proposed. The statistical analyses were carried out with the Chi square, the t-test and the correlation for the statistical differences, and with the Ward clustering method for subtyping. Results We found that there were 3.17 boys for one girl, all patients were characterized as slow, 47% were left-handers or ambidextrous, 36% and 26% had orofacial and verbal dyspraxia, respectively, 83% were found anxious, and 84% were described as being clumsy. Conclusions It appears from these results that a child with DCD expresses more than a single difficulty. Three subtypes emerged from the statistical analysis in this study: (1) clumsiness and other characteristics except language difficulties; (2) self-esteem and peer relation without clumsiness and language difficulties; (3) language difficulties and orofacial dyspraxia.
Sleep health, messaging, headaches, and academic performance in high school students
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Keith Pecor, Lilia Kang, Matthew Henderson, Sunny Yin, Varsha Radhakrishnan, Xue Ming
Aim We tested for associations of bedtime, sleep duration, instant messaging, and chronic headaches with hypersomnolence and academic performance in a sample of high school students in New Jersey, USA. Methods Students were surveyed anonymously and asked to report their sleep and messaging habits, headache status, and overall grades. Results We found that greater hypersomnolence was associated with later bedtimes, shorter sleep durations, and the presence of chronic headaches, but not with messaging after lights out. Also, we found that academic performance was lower in students who messaged after lights out, but it was not affected by headache status, bedtime, or sleep duration. Conclusions These results are consistent with other studies that have demonstrated associations between headaches and hypersomnolence and between instant messaging habits and academic performance. They also add to a growing literature on the relationships among use of electronic devices, sleep health, and academic performance by adolescents.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Keith Pecor, Lilia Kang, Matthew Henderson, Sunny Yin, Varsha Radhakrishnan, Xue Ming
Aim We tested for associations of bedtime, sleep duration, instant messaging, and chronic headaches with hypersomnolence and academic performance in a sample of high school students in New Jersey, USA. Methods Students were surveyed anonymously and asked to report their sleep and messaging habits, headache status, and overall grades. Results We found that greater hypersomnolence was associated with later bedtimes, shorter sleep durations, and the presence of chronic headaches, but not with messaging after lights out. Also, we found that academic performance was lower in students who messaged after lights out, but it was not affected by headache status, bedtime, or sleep duration. Conclusions These results are consistent with other studies that have demonstrated associations between headaches and hypersomnolence and between instant messaging habits and academic performance. They also add to a growing literature on the relationships among use of electronic devices, sleep health, and academic performance by adolescents.
Cognitive-behavioral profiles in teenagers with Dravet syndrome
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Giorgia Olivieri, Domenica Battaglia, Daniella Chieffo, Roberta Rubbino, Domiziana Ranalli, Ilaria Contaldo, Charlotte Dravet, Eugenio Mercuri, Francesco Guzzetta
Aim To investigate behavior and cognitive performances of teenage patients with Dravet syndrome (DS). Methods We enrolled 20 teenage patients (12 females and 8 males) with DS, followed in the Child Neurology Unit of the Catholic University (Rome). Patients underwent a full clinical examination including behavioral and cognitive assessments (respectively, CBCL and Wechsler scales). Results All patients showed behavior disorders and mental retardation, mild in six cases, moderate in seven and severe in the remaining seven. Among mildly retarded patients visual function, particularly visuo-motor abilities resulted mostly impaired in Wechsler subtests, whereas verbal skills were relatively preserved. In contrast, a general cognitive impairment was observed in moderately and severely retarded patients. Conclusions Our teenage patients with DS compared with other series at different ages (young childhood, adulthood) suggest a progressivity of neurological and neuropsychological signs. A visuomotor default and a relative preservation of verbal skills, like what has been found in previous reports of younger patients, are still evident in mildly impaired cases. Therefore, the progression over time of these cases toward a generalized impairment may be suggested, but only longitudinal studies can confirm it. There was a possible responsibility of some epileptic disorders in worsening the neuropsychological outcome (early myoclonic seizures and atypical absences, as well as persistent EEG background slowness in the last 3years).
Source:Brain and Development, Volume 38, Issue 6
Author(s): Giorgia Olivieri, Domenica Battaglia, Daniella Chieffo, Roberta Rubbino, Domiziana Ranalli, Ilaria Contaldo, Charlotte Dravet, Eugenio Mercuri, Francesco Guzzetta
Aim To investigate behavior and cognitive performances of teenage patients with Dravet syndrome (DS). Methods We enrolled 20 teenage patients (12 females and 8 males) with DS, followed in the Child Neurology Unit of the Catholic University (Rome). Patients underwent a full clinical examination including behavioral and cognitive assessments (respectively, CBCL and Wechsler scales). Results All patients showed behavior disorders and mental retardation, mild in six cases, moderate in seven and severe in the remaining seven. Among mildly retarded patients visual function, particularly visuo-motor abilities resulted mostly impaired in Wechsler subtests, whereas verbal skills were relatively preserved. In contrast, a general cognitive impairment was observed in moderately and severely retarded patients. Conclusions Our teenage patients with DS compared with other series at different ages (young childhood, adulthood) suggest a progressivity of neurological and neuropsychological signs. A visuomotor default and a relative preservation of verbal skills, like what has been found in previous reports of younger patients, are still evident in mildly impaired cases. Therefore, the progression over time of these cases toward a generalized impairment may be suggested, but only longitudinal studies can confirm it. There was a possible responsibility of some epileptic disorders in worsening the neuropsychological outcome (early myoclonic seizures and atypical absences, as well as persistent EEG background slowness in the last 3years).
Electroclinical phenotype in Rubinstein–Taybi syndrome
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Antonella Giacobbe, Paola Francesca Ajmone, Donatella Milani, Sabrina Avignone, Fabio Triulzi, Cristina Gervasini, Francesca Menni, Federico Monti, Daniela Biffi, Katia Canavesi, Maria Antonella Costantino
Objective Rubinstein–Taybi syndrome (RSTS) is a rare congenital disorder (1:125.000) characterized by growth retardation, psychomotor developmental delay, microcephaly and dysmorphic features. In 25% of patients seizures have been described, and in about 66% a wide range of EEG abnormalities, but studies on neurological features are scant and dated. The aim of this study is to describe the electroclinical phenotype of twenty-three patients with RSTS, and to try to correlate electroclinical features with neuroradiological, cognitive and genetic features. Patients and methods Electroclinical features of twenty-three patients with RSTS (age between18months and 20years) were analyzed. Sleep and awake EEG was performed in twenty-one patients, and brain MRI in nineteen patients. All subjects received cognitive evaluation. Results EEG abnormalities were observed in 76% (16/21) of patients. A peculiar pattern prevalent in sleep, characterized by slow monomorphic activity on posterior regions was also observed in 33% (7/21) of patients. Almost no patient presented seizures. Eighty-four percentage of patients had brain MRI abnormalities, involving corpus callosum and/or posterior periventricular white matter. Average General Quotient (GQ) was 52, while average IQ was 55, corresponding to mild Intellectual Disability. The homogeneous electroclinical pattern was observed mainly in patients with more severe neuroradiologic findings and moderate Intellectual Disability/Developmental Disability (ID/DD). No genotype-phenotype correlations were found. Conclusion The specific electroclinical and neuroradiological features described may be part of a characteristic RSTS phenotype. Wider and longitudinal studies are needed to verify its significance and impact on diagnosis, prognosis and clinical management of RSTS patients.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Antonella Giacobbe, Paola Francesca Ajmone, Donatella Milani, Sabrina Avignone, Fabio Triulzi, Cristina Gervasini, Francesca Menni, Federico Monti, Daniela Biffi, Katia Canavesi, Maria Antonella Costantino
Objective Rubinstein–Taybi syndrome (RSTS) is a rare congenital disorder (1:125.000) characterized by growth retardation, psychomotor developmental delay, microcephaly and dysmorphic features. In 25% of patients seizures have been described, and in about 66% a wide range of EEG abnormalities, but studies on neurological features are scant and dated. The aim of this study is to describe the electroclinical phenotype of twenty-three patients with RSTS, and to try to correlate electroclinical features with neuroradiological, cognitive and genetic features. Patients and methods Electroclinical features of twenty-three patients with RSTS (age between18months and 20years) were analyzed. Sleep and awake EEG was performed in twenty-one patients, and brain MRI in nineteen patients. All subjects received cognitive evaluation. Results EEG abnormalities were observed in 76% (16/21) of patients. A peculiar pattern prevalent in sleep, characterized by slow monomorphic activity on posterior regions was also observed in 33% (7/21) of patients. Almost no patient presented seizures. Eighty-four percentage of patients had brain MRI abnormalities, involving corpus callosum and/or posterior periventricular white matter. Average General Quotient (GQ) was 52, while average IQ was 55, corresponding to mild Intellectual Disability. The homogeneous electroclinical pattern was observed mainly in patients with more severe neuroradiologic findings and moderate Intellectual Disability/Developmental Disability (ID/DD). No genotype-phenotype correlations were found. Conclusion The specific electroclinical and neuroradiological features described may be part of a characteristic RSTS phenotype. Wider and longitudinal studies are needed to verify its significance and impact on diagnosis, prognosis and clinical management of RSTS patients.
The magnetic resonance imaging spectrum of Pelizaeus–Merzbacher disease: A multicenter study of 19 patients
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Kaoru Sumida, Ken Inoue, Jun-ichi Takanashi, Masayuki Sasaki, Kenji Watanabe, Motomasa Suzuki, Hirokazu Kurahashi, Taku Omata, Manabu Tanaka, Kenji Yokochi, Jun Iio, Kuniaki Iyoda, Toru Kurokawa, Muneaki Matsuo, Tamotu Sato, Akiko Iwaki, Hitoshi Osaka, Kenji Kurosawa, Toshiyuki Yamamoto, Naomichi Matsumoto, Norihide Maikusa, Hiroshi Matsuda, Noriko Sato
Purpose We retrospectively evaluated the imaging spectrum of Pelizaeus–Merzbacher disease (PMD) in correlation with the clinical course and genetic abnormality. Methods We collected the magnetic resonance imaging (MRI) findings of 19 genetically proven PMD patients (all males, aged 0–29years old) using our integrated web-based MRI data collection system from 14 hospitals. The patterns of hypomyelination were determined mainly by the signals of the cerebrum, corticospinal tract, and brainstem on T2-weighted images (T2WI). We assessed the degree of myelination age on T1-weighted images (T1WI) and T2WI independently, and we evaluated cerebellar and callosal atrophy. The clinical severity and genetic abnormalities (causal mutations of the proteolipid protein gene PLP1) were analyzed together with the imaging findings. Results The clinical stage tended to be more severe when the whole brainstem, or corticospinal tract in the internal capsule showed abnormally high intensity on T2WI. Diffuse T2-high signal of brainstem was observed only in the patients with PLP1 point mutation. Myelination age “before birth” on T1WI is a second manifestation correlated with the clinically severe phenotypes. On the other hand, eight patients whose myelination ages were > 4months on T1WI were associated with mild clinical phenotypes. Four of them showed almost complete myelination on T1WI with a discrepancy in myelination age between T1WI and T2WI. A random and patchy pattern of myelination on T2WI was noted in one patient with PLP1 point mutation. Advanced myelination was observed in three of the seven followed-up patients. Four patients had atrophy of the cerebellum, and 17 patients had atrophy of the corpus callosum. Conclusion Our multicenter study has demonstrated a wide variety of imaging findings of PMD. Signal intensity of brainstem and corticospinal tract of internal capsule would be the points to presume clinical severity in PMD patients. The spectrum of MRI findings should be kept in mind to diagnose PMD and to differentiate from other demyelinating leukodystrophies.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Kaoru Sumida, Ken Inoue, Jun-ichi Takanashi, Masayuki Sasaki, Kenji Watanabe, Motomasa Suzuki, Hirokazu Kurahashi, Taku Omata, Manabu Tanaka, Kenji Yokochi, Jun Iio, Kuniaki Iyoda, Toru Kurokawa, Muneaki Matsuo, Tamotu Sato, Akiko Iwaki, Hitoshi Osaka, Kenji Kurosawa, Toshiyuki Yamamoto, Naomichi Matsumoto, Norihide Maikusa, Hiroshi Matsuda, Noriko Sato
Purpose We retrospectively evaluated the imaging spectrum of Pelizaeus–Merzbacher disease (PMD) in correlation with the clinical course and genetic abnormality. Methods We collected the magnetic resonance imaging (MRI) findings of 19 genetically proven PMD patients (all males, aged 0–29years old) using our integrated web-based MRI data collection system from 14 hospitals. The patterns of hypomyelination were determined mainly by the signals of the cerebrum, corticospinal tract, and brainstem on T2-weighted images (T2WI). We assessed the degree of myelination age on T1-weighted images (T1WI) and T2WI independently, and we evaluated cerebellar and callosal atrophy. The clinical severity and genetic abnormalities (causal mutations of the proteolipid protein gene PLP1) were analyzed together with the imaging findings. Results The clinical stage tended to be more severe when the whole brainstem, or corticospinal tract in the internal capsule showed abnormally high intensity on T2WI. Diffuse T2-high signal of brainstem was observed only in the patients with PLP1 point mutation. Myelination age “before birth” on T1WI is a second manifestation correlated with the clinically severe phenotypes. On the other hand, eight patients whose myelination ages were > 4months on T1WI were associated with mild clinical phenotypes. Four of them showed almost complete myelination on T1WI with a discrepancy in myelination age between T1WI and T2WI. A random and patchy pattern of myelination on T2WI was noted in one patient with PLP1 point mutation. Advanced myelination was observed in three of the seven followed-up patients. Four patients had atrophy of the cerebellum, and 17 patients had atrophy of the corpus callosum. Conclusion Our multicenter study has demonstrated a wide variety of imaging findings of PMD. Signal intensity of brainstem and corticospinal tract of internal capsule would be the points to presume clinical severity in PMD patients. The spectrum of MRI findings should be kept in mind to diagnose PMD and to differentiate from other demyelinating leukodystrophies.
A splicing mutation of proteolipid protein 1 in Pelizaeus-Merzbacher disease
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Taku Omata, Jun-ichi Nagai, Hiroko Shimbo, Shiro Koizume, Yohei Miyagi, Kenji Kurosawa, Sumimasa Yamashita, Hitoshi Osaka, Ken Inoue
A patient with an unusually mild form of Pelizaeus-Merzbacher disease was studied. Clinically, mild developmental delay with acquisition of assisted walking at 16months and mild spastic tetraplegia were evident, but no nystagmus, cerebellar, or extra-pyramidal signs were present. PLP1 mutation analysis revealed a nucleotide substitution adjacent to the acceptor site of intron 3, NM_000533.4:c.454-9T>G. Expression analysis using the patient’s leukocytes demonstrated an additional abnormal transcript including the last 118bp of intron 3. In silico prediction analysis suggested the reduction of wild-type acceptor activity, which presumably evokes the cryptic splicing variant. Putative cryptic transcript results in premature termination, which may explain the mild clinical phenotype observed in this patient.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Taku Omata, Jun-ichi Nagai, Hiroko Shimbo, Shiro Koizume, Yohei Miyagi, Kenji Kurosawa, Sumimasa Yamashita, Hitoshi Osaka, Ken Inoue
A patient with an unusually mild form of Pelizaeus-Merzbacher disease was studied. Clinically, mild developmental delay with acquisition of assisted walking at 16months and mild spastic tetraplegia were evident, but no nystagmus, cerebellar, or extra-pyramidal signs were present. PLP1 mutation analysis revealed a nucleotide substitution adjacent to the acceptor site of intron 3, NM_000533.4:c.454-9T>G. Expression analysis using the patient’s leukocytes demonstrated an additional abnormal transcript including the last 118bp of intron 3. In silico prediction analysis suggested the reduction of wild-type acceptor activity, which presumably evokes the cryptic splicing variant. Putative cryptic transcript results in premature termination, which may explain the mild clinical phenotype observed in this patient.
Familial pachygyria in both genders related to a DCX mutation
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Young Ok Kim, Tai-Seung Nam, Chungoo Park, Seul Kee Kim, Woong Yoon, Seok-Yong Choi, Myeong-Kyu Kim, Young Jong Woo
Doublecortin (DCX) and tubulin play critical roles in neuronal migration. DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females. We used whole-exome sequencing to investigate causative gene variants in a large family with late-childhood-onset focal epilepsy and anterior dominant pachygyria without SBH in both genders. Two potential variants were found for the genes encoding DCX and beta tubulin isotype 1 (TUBB1). The novel DCX mutation (p.D90G, NP_000546.2) appeared to be a major causative variant, whereas the novel mutation of TUBB1 (p.R62fsX, NP_110400.1) was found only in patients with more-severe intellectual disability after gender matching. We report an unusual DCX-related disorder exhibiting familial pachygyria without SBH in both genders.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Young Ok Kim, Tai-Seung Nam, Chungoo Park, Seul Kee Kim, Woong Yoon, Seok-Yong Choi, Myeong-Kyu Kim, Young Jong Woo
Doublecortin (DCX) and tubulin play critical roles in neuronal migration. DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females. We used whole-exome sequencing to investigate causative gene variants in a large family with late-childhood-onset focal epilepsy and anterior dominant pachygyria without SBH in both genders. Two potential variants were found for the genes encoding DCX and beta tubulin isotype 1 (TUBB1). The novel DCX mutation (p.D90G, NP_000546.2) appeared to be a major causative variant, whereas the novel mutation of TUBB1 (p.R62fsX, NP_110400.1) was found only in patients with more-severe intellectual disability after gender matching. We report an unusual DCX-related disorder exhibiting familial pachygyria without SBH in both genders.
Exome sequencing analysis in a pair of monozygotic twins re-evaluates the genetics behind their intellectual disability and reveals a CHD2 mutation
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Anna Maria Pinto, Laura Bianciardi, Maria Antonietta Mencarelli, Valentina Imperatore, Chiara Di Marco, Simone Furini, Agnese Suppiej, Leonardo Salviati, Romano Tenconi, Francesca Ariani, Francesca Mari, Alessandra Renieri
Background Neurodevelopmental disorders include a broad spectrum of conditions, which are characterized by delayed motor and/or cognitive milestones and by a variable range of intellectual disability with or without an autistic behavior. Several genetic factors have been implicated in intellectual disability onset and exome sequencing studies have recently identified new inherited or de novo mutations in patients with neurodevelopmental disorders. Case We report the case of two monozygotic twins who came for the first time to our attention at the age of 20months for a global neurodevelopmental delay associated with an autism spectrum disorder, hypotonia, postnatal microcephaly, stereotypic movements and circadian rhythm alterations in association with late-onset epilepsy. MECP2 sequence was normal. A CGH-array analysis revealed in both twins two maternally inherited duplications on chromosomes 8p22 and 16p13.11. The latter has been previously associated with neurodevelopmental disorders. We performed an exome sequencing analysis on one twin and her parents and identified a CHD2 mutation, previously described in association with a phenotypic spectrum overlapping our patients’ phenotype. Conclusions This work underlines the importance to consider a CHD2 involvement in children with intellectual disability and autism spectrum disorder even in the absence of epilepsy at an early age. It also highlights the necessity to re-evaluate inherited copy number variants with low penetrance and/or high phenotypic variability because an underlying de novo molecular event can be the major cause of the phenotype. This is essential in order to reach a correct diagnosis and provide the couple with a proper recurrence risk.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Anna Maria Pinto, Laura Bianciardi, Maria Antonietta Mencarelli, Valentina Imperatore, Chiara Di Marco, Simone Furini, Agnese Suppiej, Leonardo Salviati, Romano Tenconi, Francesca Ariani, Francesca Mari, Alessandra Renieri
Background Neurodevelopmental disorders include a broad spectrum of conditions, which are characterized by delayed motor and/or cognitive milestones and by a variable range of intellectual disability with or without an autistic behavior. Several genetic factors have been implicated in intellectual disability onset and exome sequencing studies have recently identified new inherited or de novo mutations in patients with neurodevelopmental disorders. Case We report the case of two monozygotic twins who came for the first time to our attention at the age of 20months for a global neurodevelopmental delay associated with an autism spectrum disorder, hypotonia, postnatal microcephaly, stereotypic movements and circadian rhythm alterations in association with late-onset epilepsy. MECP2 sequence was normal. A CGH-array analysis revealed in both twins two maternally inherited duplications on chromosomes 8p22 and 16p13.11. The latter has been previously associated with neurodevelopmental disorders. We performed an exome sequencing analysis on one twin and her parents and identified a CHD2 mutation, previously described in association with a phenotypic spectrum overlapping our patients’ phenotype. Conclusions This work underlines the importance to consider a CHD2 involvement in children with intellectual disability and autism spectrum disorder even in the absence of epilepsy at an early age. It also highlights the necessity to re-evaluate inherited copy number variants with low penetrance and/or high phenotypic variability because an underlying de novo molecular event can be the major cause of the phenotype. This is essential in order to reach a correct diagnosis and provide the couple with a proper recurrence risk.
Focal seizures and epileptic spasms in a child with Down syndrome from a family with a PRRT2 mutation
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Ayuko Igarashi, Akihisa Okumura, Keiko Shimojima, Shinpei Abe, Mitsuru Ikeno, Toshiaki Shimizu, Toshiyuki Yamamoto
We describe a girl with Down syndrome who experienced focal seizures and epileptic spasms during infancy. The patient was diagnosed as having trisomy 21 during the neonatal period. She had focal seizures at five months of age, which were controlled with phenobarbital. However, epileptic spasms appeared at seven months of age in association with hypsarrhythmia. Upon treatment with adrenocorticotropic hormone, her epileptic spasms disappeared. Her younger brother also had focal seizures at five months of age. His development and interictal electroencephalogram were normal. The patient’s father had had infantile epilepsy and paroxysmal kinesigenic dyskinesia. We performed a mutation analysis of the PRRT2 gene and found a c.841T>C mutation in the present patient, her father, and in her younger brother. We hypothesized that the focal seizures in our patient were caused by the PRRT2 mutation, whereas the epileptic spasms were attributable to trisomy 21.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Ayuko Igarashi, Akihisa Okumura, Keiko Shimojima, Shinpei Abe, Mitsuru Ikeno, Toshiaki Shimizu, Toshiyuki Yamamoto
We describe a girl with Down syndrome who experienced focal seizures and epileptic spasms during infancy. The patient was diagnosed as having trisomy 21 during the neonatal period. She had focal seizures at five months of age, which were controlled with phenobarbital. However, epileptic spasms appeared at seven months of age in association with hypsarrhythmia. Upon treatment with adrenocorticotropic hormone, her epileptic spasms disappeared. Her younger brother also had focal seizures at five months of age. His development and interictal electroencephalogram were normal. The patient’s father had had infantile epilepsy and paroxysmal kinesigenic dyskinesia. We performed a mutation analysis of the PRRT2 gene and found a c.841T>C mutation in the present patient, her father, and in her younger brother. We hypothesized that the focal seizures in our patient were caused by the PRRT2 mutation, whereas the epileptic spasms were attributable to trisomy 21.
Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Tatsuo Mori, Katsumi Imai, Taikan Oboshi, Yuh Fujiwara, Saoko Takeshita, Hirotomo Saitsu, Naomichi Matsumoto, Yukitoshi Takahashi, Yushi Inoue
Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Tatsuo Mori, Katsumi Imai, Taikan Oboshi, Yuh Fujiwara, Saoko Takeshita, Hirotomo Saitsu, Naomichi Matsumoto, Yukitoshi Takahashi, Yushi Inoue
Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI.
Autoimmune autonomic ganglionopathy in a pediatric patient presenting with acute encephalitis
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Ichiro Kuki, Hisashi Kawawaki, Shin Okazaki, Yuka Hattori, Asako Horino, Osamu Higuchi, Shunya Nakane
Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder that leads to systemic autonomic failure. Autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR) are detected in 50% of AAG patients. We report the first pediatric case of AAG presenting with acute encephalitis. The patient was a 13-year-old boy who presented with orthostatic hypotension, followed by rapidly progressing disturbance of consciousness. Cerebrospinal fluid analysis revealed significant pleocytosis and increased neopterin concentration. Head MRI showed hyperintensities in bilateral caudate nuclei, putamen, hippocampus, and insula cortex. Severe autonomic dysfunctions such as severe orthostatic hypotension, bradycardia, dysuria, prolonged constipation and vomiting appeared. These symptoms were successfully controlled by repeated immunomodulating therapy with intravenous methylprednisolone pulse therapy and intravenous immunoglobulin. Autoantibodies to the α3 subunit of gAChR were detected at neurological onset, but were undetectable five months later. This observation indicates that AAG should be suspected in patients manifesting acute encephalitis characterized by preceding and prolonged autonomic symptoms, and immunomodulating therapy from an early stage can be effective.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Ichiro Kuki, Hisashi Kawawaki, Shin Okazaki, Yuka Hattori, Asako Horino, Osamu Higuchi, Shunya Nakane
Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder that leads to systemic autonomic failure. Autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR) are detected in 50% of AAG patients. We report the first pediatric case of AAG presenting with acute encephalitis. The patient was a 13-year-old boy who presented with orthostatic hypotension, followed by rapidly progressing disturbance of consciousness. Cerebrospinal fluid analysis revealed significant pleocytosis and increased neopterin concentration. Head MRI showed hyperintensities in bilateral caudate nuclei, putamen, hippocampus, and insula cortex. Severe autonomic dysfunctions such as severe orthostatic hypotension, bradycardia, dysuria, prolonged constipation and vomiting appeared. These symptoms were successfully controlled by repeated immunomodulating therapy with intravenous methylprednisolone pulse therapy and intravenous immunoglobulin. Autoantibodies to the α3 subunit of gAChR were detected at neurological onset, but were undetectable five months later. This observation indicates that AAG should be suspected in patients manifesting acute encephalitis characterized by preceding and prolonged autonomic symptoms, and immunomodulating therapy from an early stage can be effective.
Pathological crying and emotional vasovagal syncope as symptoms of a dorsally exophytic medullary tumor
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Author(s): Kotaro Yuge, Takashi Ohya, Ikuhiko Shibuya, Shinichiro Nagamitsu, Yushiro Yamashita
A 3-year-old boy with a dorsally exophytic tumor arising from the rostral medulla presented with a chief complaint of a change in his emotional behavior, most notably anxiety and paroxysmal crying often followed by syncope. Magnetic resonance imaging revealed that the tumor pushed on the dorsal surface of the medulla and displaced the medulla anteriorly, and also displaced the cerebellar vermis upward and slightly posteriorly. Tissue from a partial resection was diagnosed as a pilocytic astrocytoma. The symptoms did not improved after surgery, but did improve clinically after chemotherapy with vincristine and carboplatin, at which time MR showed a reduction in tumor size. We diagnosed the paroxysmal crying as ‘pathological crying’ and the syncope with increased anxiety as ‘emotional vasovagal syncope’. This case stresses the importance of recognition of this rare presentation as an indication of a medullary tumor.
Source:Brain and Development, Volume 38, Issue 6
Author(s): Kotaro Yuge, Takashi Ohya, Ikuhiko Shibuya, Shinichiro Nagamitsu, Yushiro Yamashita
A 3-year-old boy with a dorsally exophytic tumor arising from the rostral medulla presented with a chief complaint of a change in his emotional behavior, most notably anxiety and paroxysmal crying often followed by syncope. Magnetic resonance imaging revealed that the tumor pushed on the dorsal surface of the medulla and displaced the medulla anteriorly, and also displaced the cerebellar vermis upward and slightly posteriorly. Tissue from a partial resection was diagnosed as a pilocytic astrocytoma. The symptoms did not improved after surgery, but did improve clinically after chemotherapy with vincristine and carboplatin, at which time MR showed a reduction in tumor size. We diagnosed the paroxysmal crying as ‘pathological crying’ and the syncope with increased anxiety as ‘emotional vasovagal syncope’. This case stresses the importance of recognition of this rare presentation as an indication of a medullary tumor.
JSCN Best Paper Awards
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Source:Brain and Development, Volume 38, Issue 6
Announcements and Reports
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Source:Brain and Development, Volume 38, Issue 6
Cover
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Source:Brain and Development, Volume 38, Issue 6
Contents
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: June 2016
Source:Brain and Development, Volume 38, Issue 6
Source:Brain and Development, Volume 38, Issue 6
Fast (40–150Hz) oscillations are associated with positive slow waves in the ictal EEGs of epileptic spasms in West syndrome
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 31 May 2016
Source:Brain and Development
Author(s): Katsuhiro Kobayashi, Tomoyuki Akiyama, Makio Oka, Fumika Endoh, Harumi Yoshinaga
Objective To elucidate the generative mechanisms of epileptic spasms (ESs) in West syndrome, we investigated the temporal relationship between scalp fast (40–150Hz) oscillations (FOs) and slow waves in the ictal electroencephalograms (EEGs) of ESs. Methods In 11 infants with WS, ictal FOs were detected in a bipolar montage based on spectral and waveform criteria. Their temporal distribution was analyzed in terms of the positive peaks (trough point, TT) of identical EEG data in a referential montage. Among six EEG data sections defined according to TT, the number of FOs, peak power values, and peak frequencies were compared. Results We identified a total of 1014 FOs (946 gamma and 68 ripple oscillations), which clustered closely at TT. The number of gamma oscillations in the 1s epoch including TT was significantly higher than those in the prior and subsequent phases. Peak power values and frequencies tended to be higher in these positive phase sections. Conclusions The temporal association of FO clustering and positive slow waves in the ictal EEGs of ES indicated that active neuronal firing related to FOs underlies the generation of ESs and their ictal slow waves.
Source:Brain and Development
Author(s): Katsuhiro Kobayashi, Tomoyuki Akiyama, Makio Oka, Fumika Endoh, Harumi Yoshinaga
Objective To elucidate the generative mechanisms of epileptic spasms (ESs) in West syndrome, we investigated the temporal relationship between scalp fast (40–150Hz) oscillations (FOs) and slow waves in the ictal electroencephalograms (EEGs) of ESs. Methods In 11 infants with WS, ictal FOs were detected in a bipolar montage based on spectral and waveform criteria. Their temporal distribution was analyzed in terms of the positive peaks (trough point, TT) of identical EEG data in a referential montage. Among six EEG data sections defined according to TT, the number of FOs, peak power values, and peak frequencies were compared. Results We identified a total of 1014 FOs (946 gamma and 68 ripple oscillations), which clustered closely at TT. The number of gamma oscillations in the 1s epoch including TT was significantly higher than those in the prior and subsequent phases. Peak power values and frequencies tended to be higher in these positive phase sections. Conclusions The temporal association of FO clustering and positive slow waves in the ictal EEGs of ES indicated that active neuronal firing related to FOs underlies the generation of ESs and their ictal slow waves.
Arts syndrome with a novel missense mutation in the PRPS1 gene: A case report
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 30 May 2016
Source:Brain and Development
Author(s): Koichi Maruyama, Shunsuke Ogaya, Naoko Kurahashi, Ayako Umemura, Keitaro Yamada, Akihiro Hashiguchi, Hiroshi Takashima, Rosa J. Torres, Kosaburo Aso
Arts syndrome is characterized by early-onset hypotonia, ataxia, intellectual disability, sensorineural hearing impairment, progressive optic atrophy, and a tendency to develop infections. Arts syndrome is an X-linked disorder caused by a loss-of-function mutation in the PRPS1 gene, which encodes phosphoribosylpyrophosphate synthetase 1. Only three families have been reported. Here, we report another family with Arts syndrome. The initial symptoms of the 1-year-old proband were hypotonia and ataxia, worsening recurrent infection-triggered muscle weakness, motor and intellectual developmental delay, and hearing loss. Both central nervous system involvement and peripheral neuropathy were demonstrated. His three maternal uncles had died before the age of 3years. A genetic analysis of PRPS1 revealed a novel missense mutation, c.367C>G (p.His123Asp). PRPS enzymatic activity was markedly reduced in the patient. His mother was supposed to be an asymptomatic carrier. Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance.
Source:Brain and Development
Author(s): Koichi Maruyama, Shunsuke Ogaya, Naoko Kurahashi, Ayako Umemura, Keitaro Yamada, Akihiro Hashiguchi, Hiroshi Takashima, Rosa J. Torres, Kosaburo Aso
Arts syndrome is characterized by early-onset hypotonia, ataxia, intellectual disability, sensorineural hearing impairment, progressive optic atrophy, and a tendency to develop infections. Arts syndrome is an X-linked disorder caused by a loss-of-function mutation in the PRPS1 gene, which encodes phosphoribosylpyrophosphate synthetase 1. Only three families have been reported. Here, we report another family with Arts syndrome. The initial symptoms of the 1-year-old proband were hypotonia and ataxia, worsening recurrent infection-triggered muscle weakness, motor and intellectual developmental delay, and hearing loss. Both central nervous system involvement and peripheral neuropathy were demonstrated. His three maternal uncles had died before the age of 3years. A genetic analysis of PRPS1 revealed a novel missense mutation, c.367C>G (p.His123Asp). PRPS enzymatic activity was markedly reduced in the patient. His mother was supposed to be an asymptomatic carrier. Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance.
Serial outcomes in acute necrotising encephalopathy of childhood: A medium and long term study
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 30 May 2016
Source:Brain and Development
Author(s): Hwee Ying Lim, Valerie Pui Yoong Ho, Tchoyoson Choie Cheio Lim, Terrence Thomas, Derrick Wei Shih Chan
Objective Acute necrotising encephalopathy (ANEC) is a severe, debilitating childhood disorder. We used the ANEC scoring system (ANE-ss) and standardised neurodevelopmental scores to objectively characterise medium and long term outcomes. Methods Retrospective review of children with ANEC at KK Women’s and Children’s Hospital, Singapore, from 2005 to 2012. ANE-ss was determined from clinical features and neuroimaging, and neurodevelopmental scores (Pediatric Glasgow Outcome Scale Extended, Pediatric Cerebral Performance Category scale and Pediatric Overall Performance Category scale) were applied at 1, 6, 12 and 24months post diagnosis. Results Seven patients with ANEC were studied. All had a viral prodrome with fever, and encephalopathy at presentation, and received immunotherapy (steroids or immunoglobulin). ANE-ss scores were medium risk in 4 patients and high risk in 3 patients. One died (high risk ANE-ss) and outcome was determined in the 6 survivors. At 1month post diagnosis, 3 patients (50%) were mildly affected and 3 (50%) were severely affected. Morbidity rates improved by 12months, with 67% and 33.3% scoring in the mildly affected and severely affected ranges, respectively. Medium risk patients did well with majority having little or no neurological deficits and good outcome scores. Conclusion Mortality and severe morbidity correlated well with high risk ANE-ss. However, our patients with medium risk ANE-ss had good neurodevelopmental sequelae. Serial disability scoring is useful in evaluating the progress of ANEC patients on follow up. Assessment at 1month post diagnosis can aid prognostication of long term outcome.
Source:Brain and Development
Author(s): Hwee Ying Lim, Valerie Pui Yoong Ho, Tchoyoson Choie Cheio Lim, Terrence Thomas, Derrick Wei Shih Chan
Objective Acute necrotising encephalopathy (ANEC) is a severe, debilitating childhood disorder. We used the ANEC scoring system (ANE-ss) and standardised neurodevelopmental scores to objectively characterise medium and long term outcomes. Methods Retrospective review of children with ANEC at KK Women’s and Children’s Hospital, Singapore, from 2005 to 2012. ANE-ss was determined from clinical features and neuroimaging, and neurodevelopmental scores (Pediatric Glasgow Outcome Scale Extended, Pediatric Cerebral Performance Category scale and Pediatric Overall Performance Category scale) were applied at 1, 6, 12 and 24months post diagnosis. Results Seven patients with ANEC were studied. All had a viral prodrome with fever, and encephalopathy at presentation, and received immunotherapy (steroids or immunoglobulin). ANE-ss scores were medium risk in 4 patients and high risk in 3 patients. One died (high risk ANE-ss) and outcome was determined in the 6 survivors. At 1month post diagnosis, 3 patients (50%) were mildly affected and 3 (50%) were severely affected. Morbidity rates improved by 12months, with 67% and 33.3% scoring in the mildly affected and severely affected ranges, respectively. Medium risk patients did well with majority having little or no neurological deficits and good outcome scores. Conclusion Mortality and severe morbidity correlated well with high risk ANE-ss. However, our patients with medium risk ANE-ss had good neurodevelopmental sequelae. Serial disability scoring is useful in evaluating the progress of ANEC patients on follow up. Assessment at 1month post diagnosis can aid prognostication of long term outcome.
Predictors of recurrence in Sydenham’s chorea: Clinical observation from a single center
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 18 May 2016
Source:Brain and Development
Author(s): Esra Gurkas, Zeynep S. Karalok, Birce D. Taskin, Ummu Aydogmus, Alev Guven, Aydan Degerliyurt, Omer Bektas, Cahide Yilmaz
Objective Sydenham’s chorea is the most common cause of acquired chorea in children and is the major manifestation for acute rheumatic fever. Despite being known as a benign, self-limiting condition, recurrences and persistence of symptoms can be seen. In this study, we aimed to evaluate retrospectively the clinical and laboratory features of patients with Sydenham’s chorea and the rate and the course of recurrences, and to assess the risk of recurrences. Methods The study was a retrospective study conducted in a tertiary hospital. Patients with Sydenham’s chorea who were admitted to our outpatient clinics between January 2013 and June 2015 were included. Both newly diagnosed and follow-up patients were enrolled during this period. We retrospectively reviewed the medical charts of the patients. Results There were 90 patients with female predominance. The mean age of onset was 11±2.4years. Complete remission was maintained in 77 patients (85.6%) at 1–6months and 4 patients had symptoms at more than 12months. Patients were followed for 6months to 9years. The recurrence rate was 16%. When we compared recurrent patients with the non-recurrent group, complete remission in 6months, the presence of persistent chorea, and regular use of prophylaxis were significantly different between the 2 groups. Conclusions Sydenham’s chorea is still an important health problem and has high morbidity in patients with recurrent and persistent chorea. The irregular usage of antibiotic prophylaxis, failure to achieve remission within 6months, and prolongation of symptoms for more than 1year are risk factors for recurrence of chorea.
Source:Brain and Development
Author(s): Esra Gurkas, Zeynep S. Karalok, Birce D. Taskin, Ummu Aydogmus, Alev Guven, Aydan Degerliyurt, Omer Bektas, Cahide Yilmaz
Objective Sydenham’s chorea is the most common cause of acquired chorea in children and is the major manifestation for acute rheumatic fever. Despite being known as a benign, self-limiting condition, recurrences and persistence of symptoms can be seen. In this study, we aimed to evaluate retrospectively the clinical and laboratory features of patients with Sydenham’s chorea and the rate and the course of recurrences, and to assess the risk of recurrences. Methods The study was a retrospective study conducted in a tertiary hospital. Patients with Sydenham’s chorea who were admitted to our outpatient clinics between January 2013 and June 2015 were included. Both newly diagnosed and follow-up patients were enrolled during this period. We retrospectively reviewed the medical charts of the patients. Results There were 90 patients with female predominance. The mean age of onset was 11±2.4years. Complete remission was maintained in 77 patients (85.6%) at 1–6months and 4 patients had symptoms at more than 12months. Patients were followed for 6months to 9years. The recurrence rate was 16%. When we compared recurrent patients with the non-recurrent group, complete remission in 6months, the presence of persistent chorea, and regular use of prophylaxis were significantly different between the 2 groups. Conclusions Sydenham’s chorea is still an important health problem and has high morbidity in patients with recurrent and persistent chorea. The irregular usage of antibiotic prophylaxis, failure to achieve remission within 6months, and prolongation of symptoms for more than 1year are risk factors for recurrence of chorea.
Neonatal screening for Menkes disease using urine HVA/VMA ratio
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 14 May 2016
Source:Brain and Development
Author(s): Muneaki Matsuo, Ryuji Tasaki, Manabu Iwanaga, Toshimitsu Takayanagi
Source:Brain and Development
Author(s): Muneaki Matsuo, Ryuji Tasaki, Manabu Iwanaga, Toshimitsu Takayanagi
A novel gene mutation in PANK2 in a patient with severe jaw-opening dystonia
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 13 May 2016
Source:Brain and Development
Author(s): Zuhal Yapici, Nihan Hande Akcakaya, Pinar Tekturk, Sibel Aylin Ugur Iseri, Ugur Ozbek
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative condition. Major clinical features include progressive dystonia, pigmentary retinopathy, spasticity, and cognitive decline. The typical MRI sign of the disease, known as “eye-of-the-tiger”, is what makes differential diagnosis possible. We here describe a 16-year-old male patient with PKAN presenting with severe and sustained jaw-opening dystonia which may be due to heterogeneous etiologies showing poor response to treatment. Herein, long-term follow-up and genetic results of a PKAN case who experienced severe jaw-opening dystonia are presented and discussed.
Source:Brain and Development
Author(s): Zuhal Yapici, Nihan Hande Akcakaya, Pinar Tekturk, Sibel Aylin Ugur Iseri, Ugur Ozbek
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative condition. Major clinical features include progressive dystonia, pigmentary retinopathy, spasticity, and cognitive decline. The typical MRI sign of the disease, known as “eye-of-the-tiger”, is what makes differential diagnosis possible. We here describe a 16-year-old male patient with PKAN presenting with severe and sustained jaw-opening dystonia which may be due to heterogeneous etiologies showing poor response to treatment. Herein, long-term follow-up and genetic results of a PKAN case who experienced severe jaw-opening dystonia are presented and discussed.
Reading difficulty in school-aged very low birth weight infants in Japan
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 10 May 2016
Source:Brain and Development
Author(s): Akihito Takeuchi, Tatsuya Koeda, Toshimitsu Takayanagi, Kazuo Sato, Noriko Sugino, Motoki Bonno, Akiko Kada, Makoto Nakamura, Misao Kageyama
Objective To investigate the prevalence of and the perinatal risk factors related to reading difficulty in school-aged very low birth weight infants (VLBWI) with normal intelligence. Methods Subjects were 79 Japanese children in the second to fourth grade of elementary school who had been born at very low birth weight and who regularly visited a follow-up clinic at one of four hospitals. All members had a full-scale IQ score of 80 or higher. Perinatal information was obtained retrospectively from medical records. Each subject underwent four reading tasks, testing monomoratic syllable reading, word reading, non-word reading and short sentence reading. Subjects with an SD reading time score greater than 2.0 in two or more tasks were considered to have reading difficulty (RD). Furthermore we investigated the relations between RD and perinatal factors using logistic regression analysis adjusted for potential confounding factors. Results Twenty-five (31.6%) out of 79 subjects had RD. We discovered that treated retinopathy of prematurity (tRoP) was a significant risk factor (adjusted OR=5.80, 95% confidence interval=1.51–22.33). Conclusion The rate of RD in school-aged VLBWI was higher than the estimated prevalence of dyslexia in Japan. Even in children with normal intelligence, long-term developmental follow-up including support for reading skills is necessary for VLBWI. Further investigation is desired to elucidate the relations between visual problems and RD in school-aged children.
Source:Brain and Development
Author(s): Akihito Takeuchi, Tatsuya Koeda, Toshimitsu Takayanagi, Kazuo Sato, Noriko Sugino, Motoki Bonno, Akiko Kada, Makoto Nakamura, Misao Kageyama
Objective To investigate the prevalence of and the perinatal risk factors related to reading difficulty in school-aged very low birth weight infants (VLBWI) with normal intelligence. Methods Subjects were 79 Japanese children in the second to fourth grade of elementary school who had been born at very low birth weight and who regularly visited a follow-up clinic at one of four hospitals. All members had a full-scale IQ score of 80 or higher. Perinatal information was obtained retrospectively from medical records. Each subject underwent four reading tasks, testing monomoratic syllable reading, word reading, non-word reading and short sentence reading. Subjects with an SD reading time score greater than 2.0 in two or more tasks were considered to have reading difficulty (RD). Furthermore we investigated the relations between RD and perinatal factors using logistic regression analysis adjusted for potential confounding factors. Results Twenty-five (31.6%) out of 79 subjects had RD. We discovered that treated retinopathy of prematurity (tRoP) was a significant risk factor (adjusted OR=5.80, 95% confidence interval=1.51–22.33). Conclusion The rate of RD in school-aged VLBWI was higher than the estimated prevalence of dyslexia in Japan. Even in children with normal intelligence, long-term developmental follow-up including support for reading skills is necessary for VLBWI. Further investigation is desired to elucidate the relations between visual problems and RD in school-aged children.
Clinical and genetic analysis of two Chinese infants with Mabry syndrome
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 10 May 2016
Source:Brain and Development
Author(s): Jiao Xue, Hui Li, Yuehua Zhang, Zhixian Yang
Objective Hyperphosphatasia mental retardation syndrome (Mabry syndrome) is an autosomal recessive disorder. We aim to analyze two Chinese patients diagnosed as Mabry syndrome. Methods The clinical manifestations, diagnosis and treatment were observed in two patients. Genetic analysis including PIGV and PIGO was examined. Results Two patients were diagnosed as Mabry syndrome clinically and genetically. Developmental delay, hyperphosphatasia and seizures were presented in both of them. Typical facial dysmorphism and hypoplastic terminal phalanges were only found in one. Some novel presentations including congenital laryngeal cartilage softening, inguinal hernia, broken palmprint, optic atrophy and skeleton dysplasia such as carpal age delay and metaphysis anomalies were observed in two patients. Molecular genetic analysis revealed compound heterozygous mutations of PIGV or PIGO in our patients, including c.615C>G (p.Asn205Lys) and c.854A>G (p.Tyr285Cys) of PIGV in patient 1, and c.458T>C (p.Phe153Ser) and c.1355_1356del (p.Ala452Glyfs*52) of PIGO in patient 2. Additionally, a heterozygous c.2926G>A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR). Conclusion To our best knowledge, this is the first time to report Chinese patients diagnosed as Mabry syndrome. For the PCDH19 mutation in our patient carrying PIGV mutations, due to lacking characteristics of EFMR and the ambiguity results in pathogenicity analysis, we were not sure how much pathogenic role PCDH19 mutation shared with PIGV mutations in this disease. The novel mutations of PIGV and PIGO, and novel clinical manifestations reported here might expand the genotype and phenotype spectrum of Mabry syndrome.
Source:Brain and Development
Author(s): Jiao Xue, Hui Li, Yuehua Zhang, Zhixian Yang
Objective Hyperphosphatasia mental retardation syndrome (Mabry syndrome) is an autosomal recessive disorder. We aim to analyze two Chinese patients diagnosed as Mabry syndrome. Methods The clinical manifestations, diagnosis and treatment were observed in two patients. Genetic analysis including PIGV and PIGO was examined. Results Two patients were diagnosed as Mabry syndrome clinically and genetically. Developmental delay, hyperphosphatasia and seizures were presented in both of them. Typical facial dysmorphism and hypoplastic terminal phalanges were only found in one. Some novel presentations including congenital laryngeal cartilage softening, inguinal hernia, broken palmprint, optic atrophy and skeleton dysplasia such as carpal age delay and metaphysis anomalies were observed in two patients. Molecular genetic analysis revealed compound heterozygous mutations of PIGV or PIGO in our patients, including c.615C>G (p.Asn205Lys) and c.854A>G (p.Tyr285Cys) of PIGV in patient 1, and c.458T>C (p.Phe153Ser) and c.1355_1356del (p.Ala452Glyfs*52) of PIGO in patient 2. Additionally, a heterozygous c.2926G>A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR). Conclusion To our best knowledge, this is the first time to report Chinese patients diagnosed as Mabry syndrome. For the PCDH19 mutation in our patient carrying PIGV mutations, due to lacking characteristics of EFMR and the ambiguity results in pathogenicity analysis, we were not sure how much pathogenic role PCDH19 mutation shared with PIGV mutations in this disease. The novel mutations of PIGV and PIGO, and novel clinical manifestations reported here might expand the genotype and phenotype spectrum of Mabry syndrome.
First Japanese variant of late infantile neuronal ceroid lipofuscinosis caused by novel CLN6 mutations
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 7 May 2016
Source:Brain and Development
Author(s): Ryo Sato, Takehiko Inui, Wakaba Endo, Yukimune Okubo, Yusuke Takezawa, Mai Anzai, Hiroyuki Morita, Hirotomo Saitsu, Naomichi Matsumoto, Kazuhiro Haginoya
The clinical phenotypes of neuronal ceroid lipofuscinoses (NCLs) have been determined based on the age of onset and clinical symptoms. NCLs with onset between age 2 and 4years are known as late infantile neuronal ceroid lipofuscinoses (LINCLs). The clinical features of LINCLs include visual loss and progressive myoclonus epilepsy (PME) characterized by myoclonus, seizures, ataxia, and both mental and motor deterioration. There have been reports of several genes associated with LINCLs, with mutations in the CLN6 gene reported to cause variant forms of LINCLs (vLINCLs). Here, we report the first Japanese vLINCL caused by novel CLN6 mutations, found in a patient diagnosed by whole-exome sequencing. Visual acuity in our patient was preserved until the early teens. It remains to be elucidated if preserved visual function is related to the novel mutations of CLN6. Our case reveals the efficacy of whole-exome sequencing for examination of PMEs and highlights the existence of the CLN6 mutation in the Japanese population.
Source:Brain and Development
Author(s): Ryo Sato, Takehiko Inui, Wakaba Endo, Yukimune Okubo, Yusuke Takezawa, Mai Anzai, Hiroyuki Morita, Hirotomo Saitsu, Naomichi Matsumoto, Kazuhiro Haginoya
The clinical phenotypes of neuronal ceroid lipofuscinoses (NCLs) have been determined based on the age of onset and clinical symptoms. NCLs with onset between age 2 and 4years are known as late infantile neuronal ceroid lipofuscinoses (LINCLs). The clinical features of LINCLs include visual loss and progressive myoclonus epilepsy (PME) characterized by myoclonus, seizures, ataxia, and both mental and motor deterioration. There have been reports of several genes associated with LINCLs, with mutations in the CLN6 gene reported to cause variant forms of LINCLs (vLINCLs). Here, we report the first Japanese vLINCL caused by novel CLN6 mutations, found in a patient diagnosed by whole-exome sequencing. Visual acuity in our patient was preserved until the early teens. It remains to be elucidated if preserved visual function is related to the novel mutations of CLN6. Our case reveals the efficacy of whole-exome sequencing for examination of PMEs and highlights the existence of the CLN6 mutation in the Japanese population.
Reversible cerebral vasoconstriction syndrome manifesting as focal seizures without a thunderclap headache: A pediatric case report
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 7 May 2016
Source:Brain and Development
Author(s): Shuji Kuga, Hironori Goto, Kazuo Okanari, Tomoki Maeda, Kenji Ihara
We report a pediatric case of reversible cerebral vasoconstriction syndrome with focal seizures without a thunderclap headache. A 7-year-old girl had a mild acute headache with nausea after swimming. She subsequently developed hemi-convulsions followed by right hemiplegia. Brain magnetic resonance angiography revealed generalized vasoconstriction of the main cerebral peripheral arteries. Her hemiplegia was spontaneously resolved within 6h. Over the next 24h she suffered from recurrent and transient headaches, which recurred on days 3 and 5. Follow-up magnetic resonance angiography on day 3 documented the multifocal narrowing of the main cerebral arteries, which was observed to have diminished at 12weeks after her initial presentation. She did not have any headaches or neurological deficits after day 5. This case indicates that reversible cerebral vasoconstriction syndrome should be considered in children with focal seizures even when they do not present with thunderclap headaches. The timely and appropriate evaluation by magnetic resonance angiography and imaging is essential for diagnosing reversible cerebral vasoconstriction syndrome.
Source:Brain and Development
Author(s): Shuji Kuga, Hironori Goto, Kazuo Okanari, Tomoki Maeda, Kenji Ihara
We report a pediatric case of reversible cerebral vasoconstriction syndrome with focal seizures without a thunderclap headache. A 7-year-old girl had a mild acute headache with nausea after swimming. She subsequently developed hemi-convulsions followed by right hemiplegia. Brain magnetic resonance angiography revealed generalized vasoconstriction of the main cerebral peripheral arteries. Her hemiplegia was spontaneously resolved within 6h. Over the next 24h she suffered from recurrent and transient headaches, which recurred on days 3 and 5. Follow-up magnetic resonance angiography on day 3 documented the multifocal narrowing of the main cerebral arteries, which was observed to have diminished at 12weeks after her initial presentation. She did not have any headaches or neurological deficits after day 5. This case indicates that reversible cerebral vasoconstriction syndrome should be considered in children with focal seizures even when they do not present with thunderclap headaches. The timely and appropriate evaluation by magnetic resonance angiography and imaging is essential for diagnosing reversible cerebral vasoconstriction syndrome.
Editorial Board
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Source:Brain and Development, Volume 38, Issue 5
Trends and tenets in relapsing and progressive opsoclonus-myoclonus syndrome
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Michael R. Pranzatelli, Elizabeth D. Tate
Despite advances in inducing remission in pediatric opsoclonus-myoclonus syndrome (OMS), relapse remains a challenge. By definition, relapse is not a characteristic of monophasic OMS, but occurs at any time in the course of multiphasic OMS. Due to variability and heterogeneity, patients are best approached and treated on a case-by-case basis, using precepts derived from clinical and scientific studies. Treatment of provocations, such as infection or immunotherapy tapering, is the short-term goal, but discovering unresolved neuroinflammation and re-configuring disease-modifying agents is crucial in the long-term. The working hypothesis is that much of the injury in OMS results from neuroinflammation involving dysregulated B cells, which may cause loss of tolerance and autoantibody production. Biomarkers of disease activity include cerebrospinal fluid (CSF) B cell frequency, oligoclonal bands (OCB), B cell attractants (CXCL13) and activating factors (BAFF). Measuring these markers comprises modern detection and characterization of neuroinflammation or verifies ‘no evidence of disease activity’. The decision making process is three-tiered: deciding if the relapse is bone fide, identifying its etiology, and formulating a therapeutic plan. Relapsing-remitting OMS is treatable, and combination multimodal/multi-mechanistic immunotherapy is improving the outcome. However, some patients progress to a refractory state with cognitive impairment and disability from failure to go into remission, multiple relapses, or more aggressive disease. This report provides new insights on underappreciated risks and pitfalls inherent in relapse, pro-active efforts to avoid progression, the need for early and sufficient treatment beyond corticosteroids and immunoglobulins, and utilization of disease activity biomarkers to identify high-risk patients and safely withdraw immunotherapy.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Michael R. Pranzatelli, Elizabeth D. Tate
Despite advances in inducing remission in pediatric opsoclonus-myoclonus syndrome (OMS), relapse remains a challenge. By definition, relapse is not a characteristic of monophasic OMS, but occurs at any time in the course of multiphasic OMS. Due to variability and heterogeneity, patients are best approached and treated on a case-by-case basis, using precepts derived from clinical and scientific studies. Treatment of provocations, such as infection or immunotherapy tapering, is the short-term goal, but discovering unresolved neuroinflammation and re-configuring disease-modifying agents is crucial in the long-term. The working hypothesis is that much of the injury in OMS results from neuroinflammation involving dysregulated B cells, which may cause loss of tolerance and autoantibody production. Biomarkers of disease activity include cerebrospinal fluid (CSF) B cell frequency, oligoclonal bands (OCB), B cell attractants (CXCL13) and activating factors (BAFF). Measuring these markers comprises modern detection and characterization of neuroinflammation or verifies ‘no evidence of disease activity’. The decision making process is three-tiered: deciding if the relapse is bone fide, identifying its etiology, and formulating a therapeutic plan. Relapsing-remitting OMS is treatable, and combination multimodal/multi-mechanistic immunotherapy is improving the outcome. However, some patients progress to a refractory state with cognitive impairment and disability from failure to go into remission, multiple relapses, or more aggressive disease. This report provides new insights on underappreciated risks and pitfalls inherent in relapse, pro-active efforts to avoid progression, the need for early and sufficient treatment beyond corticosteroids and immunoglobulins, and utilization of disease activity biomarkers to identify high-risk patients and safely withdraw immunotherapy.
Surgical versus medical treatment for children with epileptic encephalopathy in infancy and early childhood: Results of an international multicenter cohort study in Far-East Asia (the FACE study)
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Taisuke Otsuki, Heung-Dong Kim, Guoming Luan, Yushi Inoue, Hiroshi Baba, Hirokazu Oguni, Seung-Chyul Hong, Shigeki Kameyama, Katsuhiro Kobayashi, Shinichi Hirose, Hitoshi Yamamoto, Shin-ichiro Hamano, Kenji Sugai
Objective To compare the seizure and developmental outcomes in infants and young children with epileptic encephalopathy who have undergone surgical and medical treatments. Methods An international, multicenter, observational cohort study was undertaken. A total of 317 children aged <6years, who had frequent disabling seizures despite intensive medical treatments, were registered. Among the enrolled children, 250 were treated medically (medical group), 31 underwent resective surgery (resective group), and 36 underwent palliative surgery [callosotomy (n =30) or vagal nerve stimulation (n =6); palliative group] on admission. Seizure and developmental outcomes were obtained for 230 children during the 3-year follow-up period. Cox proportional hazard model was used to adjust for clinical backgrounds among treatment groups when comparing the seizure-free survival rates. Results At the 3-year follow-up, seizure-free survival was 15.7%, 32.1%, and 52.4% in the medical, palliative, and resective groups, respectively. The adjusted hazard ratios for seizure recurrence in the resective and palliative groups versus the medical group were 0.43 (95% CI, 0.21–0.87, P =0.019) and 0.82 (95% CI, 0.46–1.46, P =0.50), respectively; the former was statistically significant. Regarding the developmental outcome, the mean DQs in the resective group increased significantly compared to those in the medical group during the follow-up (P <0.01). As for subgroup analysis, better seizure and development outcomes were demonstrated in the resective group compared to the medical group in children with nonsyndromic epilepsies (those to which no known epilepsy syndromes were applicable). Significance These results suggest that surgical treatments, particularly resective surgeries, are associated with better seizure and developmental outcomes compared with successive medical treatment. The present observations may facilitate the identification of infants and young children with epileptic encephalopathy who could benefit from surgery.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Taisuke Otsuki, Heung-Dong Kim, Guoming Luan, Yushi Inoue, Hiroshi Baba, Hirokazu Oguni, Seung-Chyul Hong, Shigeki Kameyama, Katsuhiro Kobayashi, Shinichi Hirose, Hitoshi Yamamoto, Shin-ichiro Hamano, Kenji Sugai
Objective To compare the seizure and developmental outcomes in infants and young children with epileptic encephalopathy who have undergone surgical and medical treatments. Methods An international, multicenter, observational cohort study was undertaken. A total of 317 children aged <6years, who had frequent disabling seizures despite intensive medical treatments, were registered. Among the enrolled children, 250 were treated medically (medical group), 31 underwent resective surgery (resective group), and 36 underwent palliative surgery [callosotomy (n =30) or vagal nerve stimulation (n =6); palliative group] on admission. Seizure and developmental outcomes were obtained for 230 children during the 3-year follow-up period. Cox proportional hazard model was used to adjust for clinical backgrounds among treatment groups when comparing the seizure-free survival rates. Results At the 3-year follow-up, seizure-free survival was 15.7%, 32.1%, and 52.4% in the medical, palliative, and resective groups, respectively. The adjusted hazard ratios for seizure recurrence in the resective and palliative groups versus the medical group were 0.43 (95% CI, 0.21–0.87, P =0.019) and 0.82 (95% CI, 0.46–1.46, P =0.50), respectively; the former was statistically significant. Regarding the developmental outcome, the mean DQs in the resective group increased significantly compared to those in the medical group during the follow-up (P <0.01). As for subgroup analysis, better seizure and development outcomes were demonstrated in the resective group compared to the medical group in children with nonsyndromic epilepsies (those to which no known epilepsy syndromes were applicable). Significance These results suggest that surgical treatments, particularly resective surgeries, are associated with better seizure and developmental outcomes compared with successive medical treatment. The present observations may facilitate the identification of infants and young children with epileptic encephalopathy who could benefit from surgery.
Cerebral 18FluoroDeoxy-Glucose Positron Emission Tomography in paediatric anti N-methyl-d-aspartate receptor encephalitis: A case series
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Stanislas Lagarde, Anne Lepine, Emilie Caietta, Florence Pelletier, José Boucraut, Brigitte Chabrol, Mathieu Milh, Eric Guedj
Background Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a frequent and severe cause of encephalitis in children with potential efficient treatment (immunotherapy). Suggestive clinical features are behavioural troubles, seizures and movement disorders. Prompt diagnosis and treatment initiation are needed to guarantee favourable outcome. Nevertheless, diagnosis may be challenging because of the classical ancillary test (magnetic resonance imaging (MRI), electroencephalogram, standard cerebro-spinal fluid analysis) have limited sensitivity. Currently, immunological analyses are needed for the diagnostic confirmation. In adult patients, some studies suggested a potential role of cerebral 18FluoroDeoxy-Glucose Positron Emission Tomography (FDG-PET) in the evaluation of anti-NMDAR encephalitis. Nevertheless, almost no data exist in paediatric population. Method We report retrospectively clinical, ancillary tests and cerebral FDG-PET data in 6 young patients (median age=10.5years, 4 girls) with immunologically confirmed anti-NMDAR encephalitis. Results Our patients presented classical clinical features of anti-NMDAR encephalitis with severe course (notably four patients had normal MRI). Our series shows the feasibility and the good sensitivity of cerebral FDG-PET (6/6 patients with brain metabolism alteration) in paediatric population. We report some particular features in this population: extensive, symmetric cortical hypometabolism especially in posterior areas; asymmetric anterior focus of hypermetabolism; and basal ganglia hypermetabolism. We found also a good correlation between the clinical severity and the cerebral metabolism changes. Moreover, serial cerebral FDG-PET showed parallel brain metabolism and clinical improvement. Conclusion Our study reveals the existence of specific patterns of brain metabolism alteration in anti-NMDAR encephalitis in paediatric population.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Stanislas Lagarde, Anne Lepine, Emilie Caietta, Florence Pelletier, José Boucraut, Brigitte Chabrol, Mathieu Milh, Eric Guedj
Background Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a frequent and severe cause of encephalitis in children with potential efficient treatment (immunotherapy). Suggestive clinical features are behavioural troubles, seizures and movement disorders. Prompt diagnosis and treatment initiation are needed to guarantee favourable outcome. Nevertheless, diagnosis may be challenging because of the classical ancillary test (magnetic resonance imaging (MRI), electroencephalogram, standard cerebro-spinal fluid analysis) have limited sensitivity. Currently, immunological analyses are needed for the diagnostic confirmation. In adult patients, some studies suggested a potential role of cerebral 18FluoroDeoxy-Glucose Positron Emission Tomography (FDG-PET) in the evaluation of anti-NMDAR encephalitis. Nevertheless, almost no data exist in paediatric population. Method We report retrospectively clinical, ancillary tests and cerebral FDG-PET data in 6 young patients (median age=10.5years, 4 girls) with immunologically confirmed anti-NMDAR encephalitis. Results Our patients presented classical clinical features of anti-NMDAR encephalitis with severe course (notably four patients had normal MRI). Our series shows the feasibility and the good sensitivity of cerebral FDG-PET (6/6 patients with brain metabolism alteration) in paediatric population. We report some particular features in this population: extensive, symmetric cortical hypometabolism especially in posterior areas; asymmetric anterior focus of hypermetabolism; and basal ganglia hypermetabolism. We found also a good correlation between the clinical severity and the cerebral metabolism changes. Moreover, serial cerebral FDG-PET showed parallel brain metabolism and clinical improvement. Conclusion Our study reveals the existence of specific patterns of brain metabolism alteration in anti-NMDAR encephalitis in paediatric population.
Altered frontal pole development affects self-generated spatial working memory in ADHD
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Sumiyoshi Arai, Yuko Okamoto, Toru Fujioka, Keisuke Inohara, Makoto Ishitobi, Yukiko Matsumura, Minyoung Jung, Kaori Kawamura, Shinichiro Takiguchi, Akemi Tomoda, Yuji Wada, Michio Hiratani, Naomi Matsuura, Hirotaka Kosaka
Background Spatial working memory (SWM) dysfunction is a feature of attention deficit hyperactivity disorder (ADHD). Previous studies suggested that behavioral performance in self-generated SWM improves through development in children with and without ADHD. Nevertheless, developmental changes in the neural underpinnings of self-generated SWM are unknown. Method Using near-infrared spectroscopy, hemodynamic activity in the prefrontal cortex (PFC) was measured in 30 children with ADHD (9.5±1.6years-old) and 35 TD children (9.0±1.6years-old) while they performed a self-generated SWM task. We then investigated correlations between age and behavioral performance, and between age and hemodynamic activity in the PFC for each group. Results Both groups showed a negative correlation with age and number of errors [ADHD: r(28)=−0.37, p =0.040; TD: r(33)=−0.59, p <0.001], indicating that self-generated SWM improves through development. The TD group showed a positive correlation between age and oxygenated hemoglobin in the frontal pole [10ch: r(33)=0.41, p =0.013; 11ch; r(33)=0.44, p =0.008] and bilateral lateral PFC [4ch: r(33)=0.34, p =0.049; 13ch; r(33)=0.54, p =0.001], while no significant correlation was found in the ADHD group. Furthermore, regression slopes for the frontal pole significantly differed between the TD and ADHD groups [10ch: t(61)=2.35, p =0.021; 11ch: t(61)=2.05, p =0.044]. Conclusion Children with ADHD showed abnormalities in functional maturation of the frontal pole, which plays a role in manipulating and maintaining information associated with self-generated behavior.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Sumiyoshi Arai, Yuko Okamoto, Toru Fujioka, Keisuke Inohara, Makoto Ishitobi, Yukiko Matsumura, Minyoung Jung, Kaori Kawamura, Shinichiro Takiguchi, Akemi Tomoda, Yuji Wada, Michio Hiratani, Naomi Matsuura, Hirotaka Kosaka
Background Spatial working memory (SWM) dysfunction is a feature of attention deficit hyperactivity disorder (ADHD). Previous studies suggested that behavioral performance in self-generated SWM improves through development in children with and without ADHD. Nevertheless, developmental changes in the neural underpinnings of self-generated SWM are unknown. Method Using near-infrared spectroscopy, hemodynamic activity in the prefrontal cortex (PFC) was measured in 30 children with ADHD (9.5±1.6years-old) and 35 TD children (9.0±1.6years-old) while they performed a self-generated SWM task. We then investigated correlations between age and behavioral performance, and between age and hemodynamic activity in the PFC for each group. Results Both groups showed a negative correlation with age and number of errors [ADHD: r(28)=−0.37, p =0.040; TD: r(33)=−0.59, p <0.001], indicating that self-generated SWM improves through development. The TD group showed a positive correlation between age and oxygenated hemoglobin in the frontal pole [10ch: r(33)=0.41, p =0.013; 11ch; r(33)=0.44, p =0.008] and bilateral lateral PFC [4ch: r(33)=0.34, p =0.049; 13ch; r(33)=0.54, p =0.001], while no significant correlation was found in the ADHD group. Furthermore, regression slopes for the frontal pole significantly differed between the TD and ADHD groups [10ch: t(61)=2.35, p =0.021; 11ch: t(61)=2.05, p =0.044]. Conclusion Children with ADHD showed abnormalities in functional maturation of the frontal pole, which plays a role in manipulating and maintaining information associated with self-generated behavior.
Comparison of the Kyoto Scale of Psychological Development 2001 with the parent-rated Kinder Infant Development Scale (KIDS)
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Sayaka Aoki, Keiji Hashimoto, Natsuha Ikeda, Makoto Takekoh, Takeo Fujiwara, Naho Morisaki, Hidetoshi Mezawa, Yoshiyuki Tachibana, Yukihiro Ohya
Objective The purpose of the study was to extend our understanding of the Kyoto Scale of Psychological Development (KSPD) by comparison with a parent-rated scale, the Kinder Infant Development Scale (KIDS). Methods The participants of this study were 229 children aged 0–4, who were referred to the Developmental Evaluation Center of the National Center for Child Health and Development, due to a suspected developmental disorder/delay. The participants were divided into subgroups, depending on age and overall DQ. For each group separately, correlation analyses were conducted between the Developmental Quotient (DQ) of each KSPD domain and DQ of each KIDS subscale. Results For high DQ group, in all ages, the KSPD Postural-Motor (P-M) domain DQ demonstrated a high correlation with the KIDS Physical–Motor DQ, and at young ages, it was also found to be moderately or strongly associated with the KIDS Manipulation DQ. For high DQ group, the KSPD Cognitive–Adaptive (C–A) domain DQ was most consistently related to the KIDS Manipulation DQ, and was also moderately correlated with the KIDS Physical–Motor DQ, Receptive Language DQ, Social Relationship with Adults DQ, Discipline DQ, and Feeding DQ, depending on age. For high DQ group, the KSPD Language–Social (L–S) DQ most consistently showed a moderate or high correlation with the KIDS Receptive Language DQ and the Manipulation DQ, and also related to Physical–Motor DQ, Expressive Language DQ, Language Conception DQ, Social Relationship with Adults DQ, and Social Relationship with Children DQ for some age groups. The low DQ group demonstrated stronger relationships on many of the pairs of the DQ of a KSPD subdomain and the DQ of a KIDS subscale, regardless of the type of subdomains and subscales. Conclusions For high DQ group, the KSPD P-M domain was consistently related to parent-reported physical/motor development, the C–A domain primarily reflected a child’s fine motor skills and his/her ability to understand and follow verbal instructions provided by adults, while the L–S domain was associated with parent-reported language ability. For low DQ group, the effect of global delay increased overall correlations between each domain and subscale. Further studies are necessary to replicate the findings in a larger sample including typical children.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Sayaka Aoki, Keiji Hashimoto, Natsuha Ikeda, Makoto Takekoh, Takeo Fujiwara, Naho Morisaki, Hidetoshi Mezawa, Yoshiyuki Tachibana, Yukihiro Ohya
Objective The purpose of the study was to extend our understanding of the Kyoto Scale of Psychological Development (KSPD) by comparison with a parent-rated scale, the Kinder Infant Development Scale (KIDS). Methods The participants of this study were 229 children aged 0–4, who were referred to the Developmental Evaluation Center of the National Center for Child Health and Development, due to a suspected developmental disorder/delay. The participants were divided into subgroups, depending on age and overall DQ. For each group separately, correlation analyses were conducted between the Developmental Quotient (DQ) of each KSPD domain and DQ of each KIDS subscale. Results For high DQ group, in all ages, the KSPD Postural-Motor (P-M) domain DQ demonstrated a high correlation with the KIDS Physical–Motor DQ, and at young ages, it was also found to be moderately or strongly associated with the KIDS Manipulation DQ. For high DQ group, the KSPD Cognitive–Adaptive (C–A) domain DQ was most consistently related to the KIDS Manipulation DQ, and was also moderately correlated with the KIDS Physical–Motor DQ, Receptive Language DQ, Social Relationship with Adults DQ, Discipline DQ, and Feeding DQ, depending on age. For high DQ group, the KSPD Language–Social (L–S) DQ most consistently showed a moderate or high correlation with the KIDS Receptive Language DQ and the Manipulation DQ, and also related to Physical–Motor DQ, Expressive Language DQ, Language Conception DQ, Social Relationship with Adults DQ, and Social Relationship with Children DQ for some age groups. The low DQ group demonstrated stronger relationships on many of the pairs of the DQ of a KSPD subdomain and the DQ of a KIDS subscale, regardless of the type of subdomains and subscales. Conclusions For high DQ group, the KSPD P-M domain was consistently related to parent-reported physical/motor development, the C–A domain primarily reflected a child’s fine motor skills and his/her ability to understand and follow verbal instructions provided by adults, while the L–S domain was associated with parent-reported language ability. For low DQ group, the effect of global delay increased overall correlations between each domain and subscale. Further studies are necessary to replicate the findings in a larger sample including typical children.
Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Bingjuan Han, Zhiyang Cao, Liping Tian, Hui Zou, Lian Yang, Weiwei Zhu, Yingxia Liu
Objectives To estimate the incidence of MMA on newborn screening in Shandong province from May 2011 to May 2014 and summarize the clinical presentation, biochemical features, mutation analysis, and treatment regime of early-treated patients with cblC disease. Methods Between May 2011 and May 2014, 35,291 newborns were screened for MMA in Jinan maternal and Child Care Hospital, Shandong province. The levels of C3, C3/C2, methionine and tHcy were measured. Most patients received treatment with intramuscular hydroxocobalamin after diagnosis. Metabolic parameters, clinical presentation and mental development were followed up. Results Nine patients were identified among 35,291 by newborn screening, giving an estimated incidence of 1:3920 live births for MMA, and all were classified as cblC disease. Among them, five patients received treatment with intramuscular hydroxocobalamin and two patients did not receive any treatment. One patient died of metabolic crises triggered by infection at the age of 38days. Seven different mutations (c.609G>A, c.455_457delCCC, c.394C>T, c.445_446insA, c.658_660delAAG, c.452A>G and IVS1+1G>A) were detected. The mutations (c.455_457delCCC and IVS1+1G>A) are novel. Five patients who received treatment had favorable metabolic response, with both reduction of urine MMA and tHcy and increase of methionine. We obtained 7 records of DQ assessment. The five patients who received treatment presented with developmental delay and obvious neurological manifestations. In two patients who did not receive any treatment, case 8 presented with severe mental retardation and developmental delay, while case 9 had nearly normal DQ values at the age of 11/12 years. Conclusion Our study characterized variable phenotypes of neurodevelopment in early-treated cblC patients diagnosed on newborn screening. The long-term outcomes of cblC disease are unsatisfactory in spite of conventional treatment and improvement of biochemical abnormalities. Although the number of patients is too small, the information provided in this work is of value in highlighting possible genotype–phenotype correlation that influences outcomes in cblC disease by future studies.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Bingjuan Han, Zhiyang Cao, Liping Tian, Hui Zou, Lian Yang, Weiwei Zhu, Yingxia Liu
Objectives To estimate the incidence of MMA on newborn screening in Shandong province from May 2011 to May 2014 and summarize the clinical presentation, biochemical features, mutation analysis, and treatment regime of early-treated patients with cblC disease. Methods Between May 2011 and May 2014, 35,291 newborns were screened for MMA in Jinan maternal and Child Care Hospital, Shandong province. The levels of C3, C3/C2, methionine and tHcy were measured. Most patients received treatment with intramuscular hydroxocobalamin after diagnosis. Metabolic parameters, clinical presentation and mental development were followed up. Results Nine patients were identified among 35,291 by newborn screening, giving an estimated incidence of 1:3920 live births for MMA, and all were classified as cblC disease. Among them, five patients received treatment with intramuscular hydroxocobalamin and two patients did not receive any treatment. One patient died of metabolic crises triggered by infection at the age of 38days. Seven different mutations (c.609G>A, c.455_457delCCC, c.394C>T, c.445_446insA, c.658_660delAAG, c.452A>G and IVS1+1G>A) were detected. The mutations (c.455_457delCCC and IVS1+1G>A) are novel. Five patients who received treatment had favorable metabolic response, with both reduction of urine MMA and tHcy and increase of methionine. We obtained 7 records of DQ assessment. The five patients who received treatment presented with developmental delay and obvious neurological manifestations. In two patients who did not receive any treatment, case 8 presented with severe mental retardation and developmental delay, while case 9 had nearly normal DQ values at the age of 11/12 years. Conclusion Our study characterized variable phenotypes of neurodevelopment in early-treated cblC patients diagnosed on newborn screening. The long-term outcomes of cblC disease are unsatisfactory in spite of conventional treatment and improvement of biochemical abnormalities. Although the number of patients is too small, the information provided in this work is of value in highlighting possible genotype–phenotype correlation that influences outcomes in cblC disease by future studies.
Clinical and allelic heterogeneity in a pediatric cohort of 11 patients carrying MFN2 mutation
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Chloé Di Meglio, Nathalie Bonello-Palot, Christophe Boulay, Mathieu Milh, Caroline Ovaert, Nicolas Levy, Brigitte Chabrol
Introduction The Mitofusin 2 gene (MFN2), which encodes a mitochondrial membrane protein, is known to be the first cause of autosomal dominant Charcot–Marie–Tooth disease type 2 (CMT2) with early onset. This gene is involved in typical CMT2A and in more atypical phenotypes as optic atrophy or spastic paraplegia. CMT2 refers to inherited axonal polyneuropathy, which associates progressive peripheral motor and sensory neuropathy, a family history consistent mainly with autosomal dominant inheritance, and normal nerve conduction velocities. Subjects Between 1999 and 2012, the genetic diagnosis of MFN2 mutation was made in 11 children who were treated in our department for different neurological symptoms. All data including family and personal history data, results of standardized clinical and electrophysiology testing, brain magnetic resonance imaging (MRI), neuro-ophthalmic evaluation, muscle biopsy histopathology and molecular diagnosis were retrospectively analyzed. Results Five different mutations were found in 6 unrelated families. Three of them have previously been described; the two remaining are new mutations: one of them related a new phenotype. Clinical signs appeared before the age of 6years in more than half of the patients (54%). The motor deficit was predominant in 8 patients (72%). Two children presented an acute onset of disease that stabilized afterwards; the other children showed a more progressive deterioration that was managed symptomatically. Conclusion This large pediatric study describes a great interfamilial and intrafamilial phenotypic variability. We recommend screening this gene in pediatric patient with chronic neurologic symptoms such as motor deficit or optic atrophy but also in acute neurologic deficiencies such as subacute polyradiculoneuritis.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Chloé Di Meglio, Nathalie Bonello-Palot, Christophe Boulay, Mathieu Milh, Caroline Ovaert, Nicolas Levy, Brigitte Chabrol
Introduction The Mitofusin 2 gene (MFN2), which encodes a mitochondrial membrane protein, is known to be the first cause of autosomal dominant Charcot–Marie–Tooth disease type 2 (CMT2) with early onset. This gene is involved in typical CMT2A and in more atypical phenotypes as optic atrophy or spastic paraplegia. CMT2 refers to inherited axonal polyneuropathy, which associates progressive peripheral motor and sensory neuropathy, a family history consistent mainly with autosomal dominant inheritance, and normal nerve conduction velocities. Subjects Between 1999 and 2012, the genetic diagnosis of MFN2 mutation was made in 11 children who were treated in our department for different neurological symptoms. All data including family and personal history data, results of standardized clinical and electrophysiology testing, brain magnetic resonance imaging (MRI), neuro-ophthalmic evaluation, muscle biopsy histopathology and molecular diagnosis were retrospectively analyzed. Results Five different mutations were found in 6 unrelated families. Three of them have previously been described; the two remaining are new mutations: one of them related a new phenotype. Clinical signs appeared before the age of 6years in more than half of the patients (54%). The motor deficit was predominant in 8 patients (72%). Two children presented an acute onset of disease that stabilized afterwards; the other children showed a more progressive deterioration that was managed symptomatically. Conclusion This large pediatric study describes a great interfamilial and intrafamilial phenotypic variability. We recommend screening this gene in pediatric patient with chronic neurologic symptoms such as motor deficit or optic atrophy but also in acute neurologic deficiencies such as subacute polyradiculoneuritis.
Endoplasmic reticulum stress intolerance in EIF2B3 mutant oligodendrocytes is modulated by depressed autophagy
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Na Chen, Lifang Dai, Yuwu Jiang, Jingmin Wang, Hongjun Hao, Yali Ren, Xuerong Leng, Lili Zang, Ye Wu
Objective Eukaryotic translation initiation factor 2B (eIF2B) is an essential factor for the initiation of protein synthesis. Mutations in eIF2B encoded by EIF2B1-5 cause a lethal leukoencephalopathy—vanishing white matter disease (VWM). Previous studies have suggested that an improper activated unfolded protein response (UPR) after endoplasmic reticulum stress (ERS) contributed to the pathogenesis of the disease. Autophagy, an important compensatory pathway after ERS, was analyzed in this study. Methods To determine the tolerance differences to ERS, cell viability and apoptosis rates were detected in oligodendrocyte cell lines transfected with EIF2B3-c.1037T>C or the wild type. Autophagy flux was measured between groups. Autophagy inducers and inhibitors were used to identify the role of autophagy in the mutant oligodendrocytes. Results We confirmed that oligodendrocytes with mutant EIF2B3 was less tolerant to ERS than the wild type, with decreased cell viability and increased apoptosis rates. Autophagy flux was depressed in mutant oligodendrocytes under baseline condition and after ERS stimulation. Reduced expression of autophagy related gene (Atg) 3 and Atg 7 were involved in the depression of autophagy flux. The mutant oligodendrocytes pretreated with autophagy inducers showed stable cell viability and decreased apoptosis despite ERS induction, whereas the autophagy inhibitors aggravated cell apoptosis and viability declination. Conclusions Oligodendrocytes transfected with mutant EIF2B3 was less tolerant to ERS than the wild type. Depressed autophagy flux was observed in the mutant cells at baseline and after ERS stimulation. Improperly depressed autophagy played a role in the susceptibility to ERS in EIF2B3 mutant oligodendrocytes.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Na Chen, Lifang Dai, Yuwu Jiang, Jingmin Wang, Hongjun Hao, Yali Ren, Xuerong Leng, Lili Zang, Ye Wu
Objective Eukaryotic translation initiation factor 2B (eIF2B) is an essential factor for the initiation of protein synthesis. Mutations in eIF2B encoded by EIF2B1-5 cause a lethal leukoencephalopathy—vanishing white matter disease (VWM). Previous studies have suggested that an improper activated unfolded protein response (UPR) after endoplasmic reticulum stress (ERS) contributed to the pathogenesis of the disease. Autophagy, an important compensatory pathway after ERS, was analyzed in this study. Methods To determine the tolerance differences to ERS, cell viability and apoptosis rates were detected in oligodendrocyte cell lines transfected with EIF2B3-c.1037T>C or the wild type. Autophagy flux was measured between groups. Autophagy inducers and inhibitors were used to identify the role of autophagy in the mutant oligodendrocytes. Results We confirmed that oligodendrocytes with mutant EIF2B3 was less tolerant to ERS than the wild type, with decreased cell viability and increased apoptosis rates. Autophagy flux was depressed in mutant oligodendrocytes under baseline condition and after ERS stimulation. Reduced expression of autophagy related gene (Atg) 3 and Atg 7 were involved in the depression of autophagy flux. The mutant oligodendrocytes pretreated with autophagy inducers showed stable cell viability and decreased apoptosis despite ERS induction, whereas the autophagy inhibitors aggravated cell apoptosis and viability declination. Conclusions Oligodendrocytes transfected with mutant EIF2B3 was less tolerant to ERS than the wild type. Depressed autophagy flux was observed in the mutant cells at baseline and after ERS stimulation. Improperly depressed autophagy played a role in the susceptibility to ERS in EIF2B3 mutant oligodendrocytes.
“Eye of tiger sign” mimic in an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN)
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Sangeetha Yoganathan, Sniya Valsa Sudhakar, Maya Thomas, Atanu Kumar Dutta, Sumita Danda
Neurodegeneration with brain iron accumulation (NBIA) refers to an inherited heterogeneous group of disorders pathologically characterized by focal brain iron deposition. Clinical phenotype, imaging findings and genotype are variable among the different types of this disorder. In this case report, we describe the imaging finding of an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN), a subentity of NBIA. Magnetic resonance imaging of brain revealed hypointensity of globi pallidi with medial medullary lamina appearing as a hyperintense streak in T2 weighted images. Mild cerebellar atrophy in T2 weighted images and blooming of substantia nigra and globi pallidi in susceptibility weighted images were also observed. Imaging findings in patients with MPAN mimics the eye of tiger appearance in patients with pantothenate kinase associated neurodegeneration. Classical phenotype and eye of tiger sign mimic in imaging of patients with NBIA should raise the suspect for MPAN. Genetic studies helps in the confirmation of diagnosis of this neurodegenerative disorder.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Sangeetha Yoganathan, Sniya Valsa Sudhakar, Maya Thomas, Atanu Kumar Dutta, Sumita Danda
Neurodegeneration with brain iron accumulation (NBIA) refers to an inherited heterogeneous group of disorders pathologically characterized by focal brain iron deposition. Clinical phenotype, imaging findings and genotype are variable among the different types of this disorder. In this case report, we describe the imaging finding of an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN), a subentity of NBIA. Magnetic resonance imaging of brain revealed hypointensity of globi pallidi with medial medullary lamina appearing as a hyperintense streak in T2 weighted images. Mild cerebellar atrophy in T2 weighted images and blooming of substantia nigra and globi pallidi in susceptibility weighted images were also observed. Imaging findings in patients with MPAN mimics the eye of tiger appearance in patients with pantothenate kinase associated neurodegeneration. Classical phenotype and eye of tiger sign mimic in imaging of patients with NBIA should raise the suspect for MPAN. Genetic studies helps in the confirmation of diagnosis of this neurodegenerative disorder.
Two cases of early-onset myoclonic seizures with continuous parietal delta activity caused by EEF1A2 mutations
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Takehiko Inui, Satoru Kobayashi, Yuka Ashikari, Ryo Sato, Wakaba Endo, Mitsugu Uematsu, Hiroshi Oba, Hirotomo Saitsu, Naomichi Matsumoto, Shigeo Kure, Kazuhiro Haginoya
Background Mutations in the elongation factor 1 alpha 2 (EEF1A2) gene have recently been shown to cause severe intellectual disability with early-onset epilepsy. The specific manifestations of mutations in this gene remain unknown. Case report We report two cases of severe intellectual disability accompanied by early-onset epilepsy with continuous delta activity evident on electroencephalography. Both cases presented with developmental delay and repetitive myoclonic seizures in early infancy. Both cases showed continuous high-voltage delta activity over both parietal areas when awake, as revealed by interictal electroencephalograms. After the emergence of continuous delta activity, development stagnated. One case showed some development after relief of the seizures and epileptic activity, but drug resistant seizures recurred, and the development again became stagnant. In both cases, a de novo recurrent heterozygous mutation in EEF1A2 [c.364G>A (p.E122K)] was identified by whole-exome sequencing. Conclusion This report provides clinical data on epileptic encephalopathy in patients with EEF1A2 mutation. Continuous high-voltage delta activity seen over both parietal areas may be a unique manifestation of EEF1A2 mutation. Epileptic activity may aggravate the effect of the mutation on brain development.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Takehiko Inui, Satoru Kobayashi, Yuka Ashikari, Ryo Sato, Wakaba Endo, Mitsugu Uematsu, Hiroshi Oba, Hirotomo Saitsu, Naomichi Matsumoto, Shigeo Kure, Kazuhiro Haginoya
Background Mutations in the elongation factor 1 alpha 2 (EEF1A2) gene have recently been shown to cause severe intellectual disability with early-onset epilepsy. The specific manifestations of mutations in this gene remain unknown. Case report We report two cases of severe intellectual disability accompanied by early-onset epilepsy with continuous delta activity evident on electroencephalography. Both cases presented with developmental delay and repetitive myoclonic seizures in early infancy. Both cases showed continuous high-voltage delta activity over both parietal areas when awake, as revealed by interictal electroencephalograms. After the emergence of continuous delta activity, development stagnated. One case showed some development after relief of the seizures and epileptic activity, but drug resistant seizures recurred, and the development again became stagnant. In both cases, a de novo recurrent heterozygous mutation in EEF1A2 [c.364G>A (p.E122K)] was identified by whole-exome sequencing. Conclusion This report provides clinical data on epileptic encephalopathy in patients with EEF1A2 mutation. Continuous high-voltage delta activity seen over both parietal areas may be a unique manifestation of EEF1A2 mutation. Epileptic activity may aggravate the effect of the mutation on brain development.
Bilateral ophthalmoplegia in a child with migraine
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Author(s): Rachana Dubey, Biswaroop Chakrabarty, Lokesh Saini, Priyanka Madaan, Sheffali Gulati
Background In children, migraine with or without aura is a common entity, however variants like recurrent painful optic neuropathy (RPON) is rarely encountered. Case result A 9year old boy presented with headache for 1week and restricted movements and drooping in both eyes for last 3days. On examination he had bilateral ophthalmoplegia and ptosis. History of migrainous headache was present in the patient as well as his mother. His MRI brain with venogram, serum autoimmune markers, serum and urine toxicology screen and repetitive nerve stimulation test were normal. He received intravenous pulse followed by oral steroids for 6weeks and was started on antimigraine prophylaxis. Eighteen months since the attack, he has improved completely with mild asymmetric mydriasis persisting. Discussion and conclusion This may represent first attack of RPON in a child with migraine. Rarely this may herald the onset of migraine as well, index of suspicion should be high as it is a diagnosis of exclusion and a treatable entity.
Source:Brain and Development, Volume 38, Issue 5
Author(s): Rachana Dubey, Biswaroop Chakrabarty, Lokesh Saini, Priyanka Madaan, Sheffali Gulati
Background In children, migraine with or without aura is a common entity, however variants like recurrent painful optic neuropathy (RPON) is rarely encountered. Case result A 9year old boy presented with headache for 1week and restricted movements and drooping in both eyes for last 3days. On examination he had bilateral ophthalmoplegia and ptosis. History of migrainous headache was present in the patient as well as his mother. His MRI brain with venogram, serum autoimmune markers, serum and urine toxicology screen and repetitive nerve stimulation test were normal. He received intravenous pulse followed by oral steroids for 6weeks and was started on antimigraine prophylaxis. Eighteen months since the attack, he has improved completely with mild asymmetric mydriasis persisting. Discussion and conclusion This may represent first attack of RPON in a child with migraine. Rarely this may herald the onset of migraine as well, index of suspicion should be high as it is a diagnosis of exclusion and a treatable entity.
Announcements and reports
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Source:Brain and Development, Volume 38, Issue 5
Cover
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Source:Brain and Development, Volume 38, Issue 5
Contents
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: May 2016
Source:Brain and Development, Volume 38, Issue 5
Source:Brain and Development, Volume 38, Issue 5
Corrigendum to “Congenital neurogenic muscular atrophy in megaconial myopathy due to a mutation in CHKB gene” [Brain Dev. 38 (2016) 167–172]
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 29 April 2016
Source:Brain and Development
Author(s): Manuel Castro-Gago, David Dacruz-Alvarez, Elena Pintos-Martínez, Andrés Beiras-Iglesias, Joaquín Arenas, Miguel Ángel Martín, Francisco Martínez-Azorín
Source:Brain and Development
Author(s): Manuel Castro-Gago, David Dacruz-Alvarez, Elena Pintos-Martínez, Andrés Beiras-Iglesias, Joaquín Arenas, Miguel Ángel Martín, Francisco Martínez-Azorín
Ketogenic diet – A novel treatment for early epileptic encephalopathy due to PIGA deficiency
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 25 April 2016
Source:Brain and Development
Author(s): Charuta Joshi, Diana L. Kolbe, M. Adela Mansilla, Sara Mason, Richard J.H. Smith, Colleen A. Campbell
We describe the presentation and workup of two brothers with early-onset epileptic encephalopathy who became seizure-free on a ketogenic diet. Extensive testing culminated in whole exome sequencing, which led to the diagnosis of phosphatidyl inositol glycan biosynthesis class A protein (PIGA) deficiency. This familial case highlights the importance of genetic testing for early-onset epileptic encephalopathies and underscores the potential value of a ketogenic diet in the treatment of this condition.
Source:Brain and Development
Author(s): Charuta Joshi, Diana L. Kolbe, M. Adela Mansilla, Sara Mason, Richard J.H. Smith, Colleen A. Campbell
We describe the presentation and workup of two brothers with early-onset epileptic encephalopathy who became seizure-free on a ketogenic diet. Extensive testing culminated in whole exome sequencing, which led to the diagnosis of phosphatidyl inositol glycan biosynthesis class A protein (PIGA) deficiency. This familial case highlights the importance of genetic testing for early-onset epileptic encephalopathies and underscores the potential value of a ketogenic diet in the treatment of this condition.
A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 23 April 2016
Source:Brain and Development
Author(s): Asako Horino, Hisashi Kawawaki, Masataka Fukuoka, Hitomi Tsuji, Yuka Hattori, Takeshi Inoue, Megumi Nukui, Ichiro Kuki, Shin Okazaki, Kiyotaka Tomiwa, Shinichi Hirose
Background Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. Patient A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. 123I-iomazenil (IMZ) SPECT revealed a decrease in binding of 123I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. Conclusion IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients.
Source:Brain and Development
Author(s): Asako Horino, Hisashi Kawawaki, Masataka Fukuoka, Hitomi Tsuji, Yuka Hattori, Takeshi Inoue, Megumi Nukui, Ichiro Kuki, Shin Okazaki, Kiyotaka Tomiwa, Shinichi Hirose
Background Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. Patient A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. 123I-iomazenil (IMZ) SPECT revealed a decrease in binding of 123I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. Conclusion IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients.
A compound heterozygous EARS2 mutation associated with mild leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL)
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 23 April 2016
Source:Brain and Development
Author(s): Olcay Güngör, Ahmet Kağan Özkaya, Yavuz Şahin, Gülay Güngör, Cengiz Dilber, Kürşad Aydın
Mitochondrial glutamyl-tRNA synthetase is a major component of protein biosynthesis that loads tRNAs with cognate amino acids. Mutations in the gene encoding this enzyme have been associated with a variety of disorders related to oxidative phosphorylation. Here, we present a case of leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) presenting a biphasic clinical course characterized by delayed psychomotor development and seizure. High-throughput sequencing revealed a novel compound heterozygous mutation in mitochondrial glutamyl-tRNA synthetase 2 (EARS2), which appears to be causative of disease symptoms.
Source:Brain and Development
Author(s): Olcay Güngör, Ahmet Kağan Özkaya, Yavuz Şahin, Gülay Güngör, Cengiz Dilber, Kürşad Aydın
Mitochondrial glutamyl-tRNA synthetase is a major component of protein biosynthesis that loads tRNAs with cognate amino acids. Mutations in the gene encoding this enzyme have been associated with a variety of disorders related to oxidative phosphorylation. Here, we present a case of leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) presenting a biphasic clinical course characterized by delayed psychomotor development and seizure. High-throughput sequencing revealed a novel compound heterozygous mutation in mitochondrial glutamyl-tRNA synthetase 2 (EARS2), which appears to be causative of disease symptoms.
Acute encephalopathy with biphasic seizures and late reduced diffusion associated with staphylococcal toxic shock syndrome caused by burns
Σάββατο, 18 Ιουνίου 2016, 9:04:35 μμ
Publication date: Available online 23 April 2016
Source:Brain and Development
Author(s): Takaoki Yokochi, Shinpei Sakanishi, Yuuki Ishidou, Go Kawano, Toyojiro Matsuishi, Yukihiro Akita, Keizo Obu
We report a case of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with toxic shock syndrome caused by burns. A one-year-old girl was admitted to our hospital for treatment of severe burns. On day 3, she exhibited a fever, generalized rash and multiple organ failure. She was diagnosed with toxic shock syndrome after burns. She had seizures with fever twice on the same day, followed by secondary seizures on day 8 and transient deterioration of the gross motor functions involved in sitting alone and rolling over. On day 9, MRI diffusion-weighted images showed bright tree appearance (BTA). We conclude that she developed AESD.
Source:Brain and Development
Author(s): Takaoki Yokochi, Shinpei Sakanishi, Yuuki Ishidou, Go Kawano, Toyojiro Matsuishi, Yukihiro Akita, Keizo Obu
We report a case of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with toxic shock syndrome caused by burns. A one-year-old girl was admitted to our hospital for treatment of severe burns. On day 3, she exhibited a fever, generalized rash and multiple organ failure. She was diagnosed with toxic shock syndrome after burns. She had seizures with fever twice on the same day, followed by secondary seizures on day 8 and transient deterioration of the gross motor functions involved in sitting alone and rolling over. On day 9, MRI diffusion-weighted images showed bright tree appearance (BTA). We conclude that she developed AESD.
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