Subjects -> MEDICAL SCIENCES (Total: 8669 journals)
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MEDICAL SCIENCES (2406 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 201 - 400 of 3562 Journals sorted alphabetically
Asian Biomedicine     Open Access   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 6)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 5)
Asian Journal of Medical and Pharmaceutical Researches     Open Access   (Followers: 2)
Asian Journal of Medical Sciences     Open Access   (Followers: 2)
Asian Journal of Medicine and Health     Open Access   (Followers: 1)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access   (Followers: 1)
Asian Journal of Scientific Research     Open Access   (Followers: 3)
Asian Journal of Transfusion Science     Open Access   (Followers: 1)
Asian Medicine     Hybrid Journal   (Followers: 5)
Asian Pacific Journal of Cancer Prevention     Open Access  
Asian Pacific Journal of Health Sciences     Open Access   (Followers: 11)
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
Atención Familiar     Open Access  
Atención Primaria     Open Access   (Followers: 2)
Atención Primaria Práctica     Open Access   (Followers: 1)
Atti della Accademia Peloritana dei Pericolanti - Classe di Scienze Medico-Biologiche     Open Access  
Audiology - Communication Research     Open Access   (Followers: 10)
AUP Advances     Open Access   (Followers: 7)
Auris Nasus Larynx     Full-text available via subscription  
Australasian Journal of Ultrasound in Medicine (AJUM)     Hybrid Journal   (Followers: 1)
Australian Coeliac     Full-text available via subscription   (Followers: 2)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 3)
Autopsy and Case Reports     Open Access  
Avicenna     Open Access   (Followers: 3)
Avicenna Journal of Clinical Medicine     Open Access  
Avicenna Journal of Medicine     Open Access   (Followers: 1)
Bangabandhu Sheikh Mujib Medical University Journal     Open Access   (Followers: 1)
Bangladesh Journal of Anatomy     Open Access   (Followers: 2)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 4)
Bangladesh Journal of Medical Education     Open Access   (Followers: 2)
Bangladesh Journal of Medical Microbiology     Open Access   (Followers: 4)
Bangladesh Journal of Medical Physics     Open Access   (Followers: 1)
Bangladesh Journal of Medical Science     Open Access  
Bangladesh Journal of Medicine     Open Access   (Followers: 1)
Bangladesh Journal of Physiology and Pharmacology     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Bangladesh Medical Journal     Open Access  
Bangladesh Medical Journal Khulna     Open Access  
Basal Ganglia     Hybrid Journal  
Basic Sciences of Medicine     Open Access   (Followers: 1)
Batı Karadeniz Tıp Dergisi / Medical Journal of Western Black Sea     Open Access  
Baylor University Medical Center Proceedings     Hybrid Journal  
BBA Clinical     Open Access  
BC Medical Journal     Free  
Benha Medical Journal     Open Access  
Beni-Suef University Journal of Basic and Applied Sciences     Open Access   (Followers: 3)
Bijblijven     Hybrid Journal  
Bijzijn     Hybrid Journal   (Followers: 1)
Bijzijn XL     Hybrid Journal  
Bio-Algorithms and Med-Systems     Hybrid Journal   (Followers: 2)
BioDiscovery     Open Access   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 2)
Bioelectronic Medicine     Open Access   (Followers: 1)
Bioengineering & Translational Medicine     Open Access  
Bioethics     Hybrid Journal   (Followers: 19)
Bioethics Research Notes     Full-text available via subscription   (Followers: 15)
Biologics in Therapy     Open Access  
Biology of Sex Differences     Open Access   (Followers: 2)
Biomarker Research     Open Access   (Followers: 3)
Biomarkers in Medicine     Hybrid Journal   (Followers: 2)
BioMed Research International     Open Access   (Followers: 5)
Biomédica     Open Access  
Biomedical & Life Sciences Collection     Full-text available via subscription   (Followers: 3)
Biomedical and Biotechnology Research Journal     Open Access   (Followers: 1)
Biomedical Engineering     Hybrid Journal   (Followers: 16)
Biomedical Engineering and Computational Biology     Open Access   (Followers: 13)
Biomedical Engineering Letters     Hybrid Journal   (Followers: 6)
Biomedical Engineering Research     Open Access   (Followers: 7)
Biomedical Informatics Insights     Open Access   (Followers: 9)
Biomedical Journal     Open Access   (Followers: 4)
Biomedical Materials     Hybrid Journal   (Followers: 7)
Biomedical Microdevices     Hybrid Journal   (Followers: 9)
Biomedical Optics Express     Open Access   (Followers: 6)
Biomedical Photonics     Open Access  
Biomedical Reports     Full-text available via subscription  
Biomedical Research Reports     Full-text available via subscription   (Followers: 2)
Biomedical Safety & Standards     Full-text available via subscription   (Followers: 9)
Biomedical Science and Engineering     Open Access   (Followers: 7)
BioMedicine     Open Access  
Biomedicine Hub     Open Access  
Biomedicines     Open Access   (Followers: 1)
Biomedika     Open Access  
Biomolecular and Health Science Journal     Open Access   (Followers: 1)
Biophysics Reports     Open Access  
BioPsychoSocial Medicine     Open Access   (Followers: 8)
Biosafety and Health     Open Access   (Followers: 2)
Biosalud     Open Access   (Followers: 1)
Biostatistics & Epidemiology     Hybrid Journal   (Followers: 2)
Birat Journal of Health Sciences     Open Access  
BIRDEM Medical Journal     Open Access   (Followers: 1)
Birth Defects Research     Hybrid Journal  
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 3)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal  
BJR|Open     Open Access   (Followers: 1)
BJS Open     Open Access   (Followers: 1)
Black Sea Journal of Health Science     Open Access  
BLDE University Journal of Health Sciences     Open Access  
Blickpunkt Medizin     Hybrid Journal  
BMC Biomedical Engineering     Open Access  
BMC Medical Ethics     Open Access   (Followers: 22)
BMC Medical Research Methodology     Open Access   (Followers: 9)
BMC Medicine     Open Access   (Followers: 14)
BMC Obesity     Open Access   (Followers: 7)
BMC Proceedings     Full-text available via subscription   (Followers: 2)
BMC Research Notes     Open Access   (Followers: 4)
BMC Sports Science, Medicine and Rehabilitation     Open Access   (Followers: 34)
BMH Medical Journal     Open Access   (Followers: 2)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access  
BMJ     Hybrid Journal   (Followers: 1888)
BMJ Case Reports     Hybrid Journal   (Followers: 28)
BMJ Evidence-Based Medicine     Hybrid Journal   (Followers: 4)
BMJ Global Health     Open Access   (Followers: 3)
BMJ Innovations     Hybrid Journal   (Followers: 6)
BMJ Leader     Hybrid Journal  
BMJ Open     Open Access   (Followers: 44)
BMJ Open Quality     Open Access   (Followers: 19)
BMJ Open Science     Open Access   (Followers: 1)
BMJ Sexual & Reproductive Health     Hybrid Journal   (Followers: 2)
BMJ Surgery, Interventions, & Health Technologies     Open Access  
Bodine Journal     Open Access  
Boletín del Consejo Académico de Ética en Medicina     Open Access  
Boletín del ECEMC     Open Access  
Boletin Médico de Postgrado     Open Access  
Boletín Médico del Hospital Infantil de México     Open Access  
Bone     Hybrid Journal   (Followers: 18)
Bone and Tissue Regeneration Insights     Open Access   (Followers: 2)
Bone Marrow Research     Open Access   (Followers: 2)
Bone Reports     Open Access  
Bosnian Journal of Basic Medical Sciences     Open Access  
Bozok Tıp Dergisi / Bozok Medical Journal     Open Access  
Brachytherapy     Full-text available via subscription   (Followers: 6)
Brain and Development     Full-text available via subscription   (Followers: 5)
Brain Communications     Open Access   (Followers: 2)
Brain Connectivity     Hybrid Journal   (Followers: 5)
Brain Impairment     Full-text available via subscription   (Followers: 2)
Brazilian Journal of Medical and Biological Research     Open Access  
Brazilian Journal of Medicine and Human Health     Open Access  
Brazilian Journal of Pain (BrJP)     Open Access  
Brazilian Journal of Physical Therapy     Open Access   (Followers: 2)
Breastfeeding Review     Full-text available via subscription   (Followers: 19)
British Journal of Biomedical Science     Full-text available via subscription   (Followers: 7)
British Journal of General Practice     Full-text available via subscription   (Followers: 39)
British Journal of Hospital Medicine     Full-text available via subscription   (Followers: 16)
British Medical Bulletin     Hybrid Journal   (Followers: 6)
Buddhachinaraj Medical Journal     Open Access  
Bulletin Amades     Open Access  
Bulletin de la Société de pathologie exotique     Hybrid Journal   (Followers: 1)
Bulletin of Legal Medicine     Open Access  
Bulletin of Medical Sciences     Open Access  
Bulletin of the History of Medicine     Full-text available via subscription   (Followers: 21)
Bulletin of the Menninger Clinic     Full-text available via subscription  
Bulletin of The Royal College of Surgeons of England     Free  
Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products     Open Access  
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz     Hybrid Journal   (Followers: 6)
Burapha Journal of Medicine     Open Access  
Burns     Hybrid Journal   (Followers: 10)
Cadernos de Naturologia e Terapias Complementares     Open Access   (Followers: 1)
Calcified Tissue International     Hybrid Journal   (Followers: 2)
Canadian Bulletin of Medical History     Hybrid Journal   (Followers: 1)
Canadian Family Physician     Partially Free   (Followers: 13)
Canadian Journal of Pain     Open Access   (Followers: 2)
Canadian Journal of Rural Medicine     Full-text available via subscription   (Followers: 1)
Canadian Medical Association Journal     Open Access   (Followers: 18)
Canadian Medical Education Journal     Open Access   (Followers: 10)
Canadian Prosthetics & Orthotics Journal     Open Access  
Cannabis and Cannabinoid Research     Hybrid Journal   (Followers: 1)
Cardiac Electrophysiology Clinics     Full-text available via subscription   (Followers: 1)
Care Management Journals     Hybrid Journal   (Followers: 5)
Case Reports     Open Access  
Case Reports in Acute Medicine     Open Access   (Followers: 2)
Case Reports in Clinical Medicine     Open Access   (Followers: 2)
Case Reports in Clinical Nutrition     Open Access   (Followers: 1)
Case Reports in Clinical Pathology     Open Access   (Followers: 1)
Case Reports in Medicine     Open Access   (Followers: 3)
Case Reports in Transplantation     Open Access  
Case Reports in Vascular Medicine     Open Access  
Case Reports in Women's Health     Open Access   (Followers: 4)
Case Study and Case Report     Open Access   (Followers: 5)
CASUS : Revista de Investigación y Casos en Salud     Open Access   (Followers: 1)
CBU International Conference Proceedings     Open Access   (Followers: 3)
Cell & Bioscience     Open Access   (Followers: 6)
Cell Adhesion & Migration     Open Access   (Followers: 9)
Cell and Molecular Response to Stress     Full-text available via subscription   (Followers: 2)
Cell and Tissue Transplantation and Therapy     Open Access   (Followers: 2)
Cell Cycle     Full-text available via subscription   (Followers: 6)
Cell Death and Differentiation     Hybrid Journal   (Followers: 8)
Cell Death Discovery     Open Access   (Followers: 1)
Cell Health and Cytoskeleton     Open Access   (Followers: 1)
Cell Medicine     Open Access   (Followers: 6)
Cell Research     Hybrid Journal   (Followers: 8)
Cell Transplantation     Open Access   (Followers: 4)
CEN Case Reports     Hybrid Journal  
Central African Journal of Medicine     Full-text available via subscription  
Cephalalgia Reports     Open Access   (Followers: 2)
Ceylon Journal of Medical Science     Open Access  

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Journal Cover
Brain and Development
Journal Prestige (SJR): 0.686
Citation Impact (citeScore): 2
Number of Followers: 5  
  Full-text available via subscription Subscription journal
ISSN (Print) 0387-7604
Published by Elsevier Homepage  [3203 journals]
  • Spontaneous spinal epidural hematoma mimicking Guillain-Barre Syndrome
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Aya Kondo, Hiroshi Yamaguchi, Yusuke Ishida, Daisaku Toyoshima, Mai Azumi, Nobuyuki Akutsu, Junji Koyama, Hiroshi Kurosawa, Atushi Kawamura, Azusa MaruyamaAbstractBackgroundThe initial symptoms of Guillain-Barre Syndrome (GBS) can be similar to a case of spontaneous spinal epidural hematoma (SSEH) located at the cervicothoracic junction. Therefore, SSEH may be misdiagnosed as GBS. Case Report: A previously healthy 6-year-old girl presented with a 2-day history of progressive pain in the lower extremities and an inability to walk. On initial evaluation, she was completely paraparetic in the lower extremities. Deep tendon reflexes were absent in the lower extremities, and Babinski reflexes were positive on both sides. She exhibited reduced response to light touch and pinprick with a sensory level below T10, and experienced difficulty during urination. However, the strength, sensation and flexion of upper extremities were normal. Because her presentation and examinations were consistent with GBS, we initiated intravenous immunoglobulin therapy. The next day, she also developed pain and muscle weakness of the right upper extremity. Three days after admission, respiratory depression progressed rapidly. Spinal MRI showed a mass extending from the level of C7-T3, with spinal cord compression. The patient underwent an emergency laminectomy with evacuation of hematoma, and was diagnosed with SSEH. Sixty days after admission, she was transferred to the rehabilitation hospital with severe neurologic sequelae of paralysis in both legs. Conclusion: SSEH might have severe consequences, including neurologic deficits and risk of death. This case report serves to raise the awareness of SSEH that mimics the initial presentation of GBS.
  • Ketogenic diet as a successful early treatment modality for SCN2A mutation
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Dilsad Turkdogan, Gulten Thomas, Birsen DemirelAbstractSCN2A mutations have been described in a very broad spectrum of clinical phenotypes including benign (familial) neonatal/infantile seizures and early infantile epileptic encephalopathies (EIEE) as Ohtahara syndrome (OS), Dravet syndrome (DS), epilepsy of infancy with migrating focal seizures and West syndrome (WS). Treatment modalities for epilepsy caused by SCN2A mutations mainly consist of sodium channel blockers but ketogenic diet (KD) is also considered as an option of treatment for intractible seizures caused by SCN2A mutations. Because of the wide nature of the heterogeneity of mutations related to SCN2A gene, the clinical phenotypes vary in severity and treatment response to KD has been reported to be controversial.We present a patient diagnosed with OS associated with a novel SCN2A mutation (c.408G > A, p.Met136lle; OMIM®: 182390) who had a complete resolution of seizures and EEG abnormalities with KD commenced at 39 days of age.As far as we are aware our case is the youngest patient with SCN2A mutation treated with KD with complete resolution of epilepsy at an early age and has been seizure free of antiepileptic medications for a long duration.
  • Neonatal methionine adenosyltransferase I/III deficiency with abnormal
           signal intensity in the central tegmental tract
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Jun Kido, Takaaki Sawada, Ken Momosaki, Yosuke Suzuki, Hiroyuki Uetani, Mika Kitajima, Hiroshi Mitsubuchi, Kimitoshi Nakamura, Shirou MatsumotoAbstractMethionine adenosyltransferase I/III (MAT I/III) deficiency is characterized by persistent hypermethioninemia. The clinical manifestations in cases with MAT I/III deficiency vary from a complete lack of symptoms to neurological problems associated with brain demyelination. We experienced a neonatal case with MAT I/III deficiency, in which severe hypermethioninemia was detected during the newborn screening test. The patient gradually showed hyperreflexia, foot clonus, and irritability from the age of 1 month onwards, and his brain magnetic resonance imaging scans showed abnormal signal intensity in the bilateral central tegmental tracts. His neurological manifestations improved after the S-adenosylmethionine (SAMe) treatment, deteriorated after discontinuation of SAMe, and re-improved owing to re-administration of SAMe. He achieved normal neurodevelopment through SAMe and methionine restriction therapy. Lack of SAMe as well as severe hypermethioninemia were thought to contribute towards the clinical psychophysical state. Moreover, impaired MAT I/III activity contributed to the development of neurological disorder from the early neonatal period.
  • An acute encephalopathy with reduced diffusion in BRAF-associated
           cardio-facio-cutaneous syndrome
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Sayaka Okuzono, Ryoko Fukai, Marie Noda, Noriko Miyake, Sooyoung Lee, Noriyuki Kaku, Masafumi Sanefuji, Satoshi Akamine, Shunsuke Kanno, Yoshito Ishizaki, Hiroyuki Torisu, Ryutaro Kira, Naomichi Matsumoto, Yasunari Sakai, Shouichi OhgaAbstractBackgroundCardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder characterized by cardiovascular anomalies, dysmorphic faces, ectodermal abnormalities and developmental delays. Mutations in BRAF and other RAS-MAPK pathway-associated genes are commonly identified in patients with CFCS. While this molecular pathway is known to be associated with neuro-inflammatory conditions, only one case with CFCS has been reported thus far to develop acute encephalopathy in childhood.Case reportA 3-year-old boy with dysmorphic features and mild psychomotor delay developed acute encephalopathy. After a 45-min long, generalized seizure, the magnetic resonance imaging revealed that the restricted diffusion signals spread to the bilateral subcortical white matters on day 1 of illness. Despite the 14 days of intensive care, the acute symptoms of encephalopathy left him intractable epilepsy and severe neurocognitive impairments. The whole-exome sequencing analysis identified a de novo heterozygous mutation of BRAF (NM_004333:p.Thr241Met) in this case.ConclusionThe present case suggests that the hyperactive condition of ERK signals might augment the development of acute encephalopathy and post-encephalopathic epilepsy in childhood.
  • Fulminant acute disseminated encephalomyelitis in children
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Yukako Yae, Go Kawano, Takaoki Yokochi, Toru Imagi, Yukihiro Akita, Keizo Ohbu, Toyojiro MatsuishiAbstractAcute disseminated encephalomyelitis (ADEM) is a typically monophasic inflammatory demyelinating disease of the central nervous system with a favorable outcome. However, 2% of ADEM involves acute hemorrhagic leukoencephalitis (AHLE), which is a fulminant and hyperacute variant of ADEM with a poor outcome and high mortality. There are limited case reports of fulminant ADEM including AHLE in children. Herein, we report two pediatric cases of fulminant ADEM. Both cases had a rapid deterioration of consciousness, repetitive seizures, and brain edema on neuroimaging, in addition to atypical neuroradiological findings on magnetic resonance imaging (MRI), a reversible splenial lesion in case 1, and bilateral frontal and occipital cortical lesions in case 2. Both cases were treated with early high-dose methyl-prednisolone and immunoglobulin, while therapeutic hypothermia was also initiated in case 2 after the patient exhibited a decerebrate posture and irregular breathing pattern. Both cases had a favorable outcome. Further case reports on pediatric fulminant ADEM are required to clarify the various clinical types, and to examine the efficacy of various treatment modalities for fulminant ADEM and AHLE in children.
  • Announcements and reports
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s):
  • Resting energy expenditure prediction using bioelectrical impedance
           analysis in patients with severe motor and intellectual disabilities
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Naoki Hashizume, Yoshiaki Tanaka, Motomu Yoshida, Suguru Fukahori, Shinji Ishii, Nobuyuki Saikusa, Daisuke Masui, Naruki Higashidate, Saki Sakamoto, Shiori Tsuruhisa, Kotaro Yuge, Takashi Ohya, Minoru Yagi, Yushiro YamashitaAbstractIntroductionResting energy expenditure (REE) is expected to be lower in with severe motor and intellectual disabilities (SMID) patients than in healthy subjects because of their relatively low fat-free mass (FFM). Therefore, an REE predictive equation for SMID patients may be required. The aim of this study was to validate existing REE predictive weight-based equations (Harris-Benedict, WHO, Mifflin, Owen, Schofield) and FFM-based REE equations (Mifflin, Owen and Cunningham) and to develop a new SMID patient-specific FFM-based REE equation.MethodsTwenty-eight (22 males, 6 females) SMID patients over 18 years of age were included. The REE was measured using indirect calorimetry. FFM were measured using bioelectrical impedance analysis. A multiple linear regression analysis was used to develop a new FFM-based REE predictive equation. The accurate predictions compared the measured REE and root mean square error.ResultsThe median measured REE was 950 (25th,75th percentile:712.75, 1102.75) kcal/day. The new FFM-based equation was as follows: REE (kcal/day) = 550.62 + 16.62 FFM (kg). The new FFM-based REE resulted in the highest percentage of accurate predictions within 10% of measured REE (42.9%). The root mean square errors were the smallest for the new FFM-based REE and largest for Harris-Benedict (91.00 and 185.22 kcal/day).ConclusionFor SMID patients, the REE cannot accurately be predicted using the existing weight-based REE equations. Furthermore, the existing FFM-based REE equations are less accurate with regard to the measured REE than the new FFM-based REE equation. The new FFM-based equation is advised for use in SMID patients.
  • Sensory processing in children with autism spectrum disorder and the
           mental health of primary caregivers
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Kanae Suzuki, Shu Takagai, Masatsugu Tsujii, Hiroyuki Ito, Tomoko Nishimura, Kenji J. TsuchiyaAbstractBackgroundSensory processing difficulties, which commonly occur in autism spectrum disorder (ASD), are expected to have negative effects on the primary caregiver’s mental health. The aim of this study was to examine the association between sensory processing difficulties in children with ASD and the mental health of primary caregivers.MethodsA total of 707 primary caregivers (mothers in the present study) and their children with ASD (4–18 years of age) participated in this study. Sensory processing difficulties were indexed using the Short Sensory Profile (SSP). The mental health of primary caregivers was indexed using the General Health Questionnaire (GHQ12).ResultsHigher scores on Auditory Filtering as measured with the SSP were associated with poorer mental health of primary caregivers, even after an adjustment for ASD symptom severity. Analyses of two age sub-groups, a young (4–10 years) and an old age group (11–18 years), revealed that higher scores on Tactile Sensitivity and Auditory Filtering were associated with poorer mental health of primary caregivers in younger children, whereas only higher scores on Auditory Filtering were associated with poorer mental health of primary caregivers in older children.ConclusionsOur findings suggest that practitioners who support primary caregivers of children with ASD need to focus not only on the social and communication-related symptoms of the child but also on their specific sensory processing difficulties.
  • Novel method using Hjorth mobility analysis for diagnosing
           attention-deficit hyperactivity disorder in girls
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Julie Chi Chow, Chen-Sen Ouyang, Ching-Tai Chiang, Rei-Cheng Yang, Rong-Ching Wu, Hui-Chuan Wu, Lung-Chang LinAbstractBackgroundAttention-deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder. Diagnosis of ADHD is based on core symptoms or checklists; however, practitioner subjectivity inevitably results in instances of over- or under-diagnosis. Although an elevated theta/beta ratio (TBR) of the electroencephalography (EEG) band has been approved by the Food and Drug Administration as a factor that may be used in diagnosis of ADHD, several studies have reported no significant differences between the TBR of patients with ADHD and controls.PurposeIn this study, a method was developed based on Hjorth Mobility (M) analysis of EEG to compare patients with ADHD and controls.MethodsDifferences in the presentations of ADHD between boys and girls are well established; therefore, separate investigations are required. The present study enrolled 30 girls with ADHD and 30 age-matched controls.ResultsThe results revealed that the control group had significantly higher Hjorth M values in most brain areas in EEG readings compared with the values for the ADHD group. Compared with TBR, our method revealed a greater number of more significant differences between the girls in the ADHD group and the controls. Moreover, our method can produce the higher average sensitivity (0.796), average specificity (0.796), average accuracy (0.792), and average area under the curve of receiver operating characteristic curve (AUC) value (0.885). Therefore, compared with TBR, Hjorth M possessed the better potential for differentiating between girls with ADHD and controls.ConclusionThe proposed method was more accurate than the TBR in diagnosing ADHD. Therefore, Hjorth M may be a promising tool for differentiating between children with ADHD and controls.
  • Age related signal changes of the pituitary stalk on thin-slice magnetic
           resonance imaging in infants
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Takashi Okazaki, Tetsu Niwa, Keiji Suzuki, Shuhei Shibukawa, Yutaka ImaiAbstractPurposeSignals of some brain regions change along with development in T1-weighted imaging (T1WI) in infants. This study aimed to assess the association of the signal intensity of the pituitary stalk on thin-slice T1WI with infant age.MethodsThis retrospective study was performed in 89 infants (gestational age [GA], 25–41 weeks; postmenstrual age [PMA], 36–46 weeks; chronological age [CA], 4–141 days) without intracranial abnormalities. The signal ratio of the pituitary stalk/pons on thin-slice T1WI was calculated, and its correlations with GA, PMA, and CA were assessed. Additionally, the signal ratio of the anterior pituitary gland/pons was calculated, and its correlation with that of the pituitary stalk was assessed. The signal intensity and distribution of the pituitary stalk were visually rated, and their correlations with GA, PMA, and CA were assessed.ResultsThe signal ratio of the pituitary stalk was significantly positively correlated with GA (P 
  • A longer body length and larger head circumference at term significantly
           influences a better subsequent psychomotor development in
           very-low-birth-weight infants
    • Abstract: Publication date: April 2019Source: Brain and Development, Volume 41, Issue 4Author(s): Tomoko Egashira, Mizuko Hashimoto, Tada-aki Shiraishi, Akinori Shichijo, Masakazu Egashira, Tomoko Mizukami, Toshimitsu TakayanagiAbstractAimTo clarify the influence of intra- and extra-uterine growth on subsequent psychomotor development in very-low-birth-weight (VLBW) infants.MethodsTwo hundred and eighty VLBW infants (28.4 ± 2.6 weeks, 1000 ± 294 g) were enrolled. Psychomotor development was determined at 37.1 ± 2.1 months after birth using the Kyoto Scale of Psychological Development (KSPD), which includes Postural-Motor (P-M), Cognitive-Adaptive (C-A) and Language-Social (L-S) subscales. Subjects were divided into two groups based on whether each developmental quotient (DQ) was ≥85, and the perinatal variables that contributed to a DQ of ≥85 (for each DQ) were determined. The twelve variables that were evaluated included the z scores for body weight (zBW), body length (zBL), head circumference (zHC), which were obtained at birth and at term.ResultsThe median P-M, C-A, L-S values and total DQ were 92, 83, 81 and 83, respectively, and the percentage of patients with a DQ of ≥85 were 53%, 44%, 35% and 39%, respectively. A multivariate analysis revealed significant associations between the following variables and the DQs: P-M ≥ 85, GA [odds ratio; OR = 1.11] and zBL at term [OR = 1.26]; C-A ≥ 85, male gender [OR = 0.30], GA [OR = 1.14] and zHC at term [OR = 1.84]; L-S ≥ 85, male gender [OR = 0.55], GA [ OR = 1.20] and zHC at term [OR = 1.45]; total DQ ≥ 85, male gender [OR = 0.39], GA [OR = 1.19] and zBL at term [OR = 1.69].ConclusionIn addition to less prematurity and female gender, a longer body length and larger head circumference at term were important indicators that influenced better psychomotor development in VLBW infants at three years of chronological age.
  • Chronological dynamic changes in cortico-subcortical imbalance of cerebral
           blood flow in a boy with CAPOS syndrome
    • Abstract: Publication date: Available online 20 March 2019Source: Brain and DevelopmentAuthor(s): Aya Hashimoto, Ichiro Kuki, Masataka Fukuoka, Kiyohiro Kim, Takeshi Inoue, Megumi Nukui, Shin Okazaki, Hisashi Kawawaki, Yuji Nakamura, Shinji SaitohAbstractBackgroundCerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS) syndrome is a known ATP1A3-related disorder, but little has been elucidated regarding its pathophysiology. We now report two new patients, a Japanese boy and his mother with a pathogenic mutation (c.2452G>A) in ATP1A3, who were diagnosed with CAPOS syndrome.MethodsAfter febrile illnesses at 7 months of age, and again at 22 months of age, the boy had a reduced level of consciousness, truncal ataxia and eye movement-disorders. The patient’s 32-year-old mother may have experienced an episode of acute encephalopathy in her childhood and sustained sensorineural hearing loss. In the present study, we demonstrated chronological dynamic changes in cerebral blood flow (CBF) in the son, using serial single-photon emission computed tomography (SPECT).ResultsThe serial CBF-SPECT findings using statistical methods showed progressive hyperperfusion in the frontal lobes, basal ganglia and thalamus, and hypoperfusion in the occipital and temporal lobes during the acute and subacute phases. Thereafter, the dynamic changes of CBF improved in the chronic but hypoperfusion in thalamus appeared to the chronic phase.ConclusionThe abnormal cortico-subcortical CBF may contribute to an acute encephalopathy-like condition in the acute stage of CAPOS syndrome. CAPOS syndrome is not often reported, and is possibly an under-recognized syndrome in clinically mild cases.
  • Infantile-onset spinocerebellar ataxia type 5 associated with a novel
           SPTBN2 mutation: A case report
    • Abstract: Publication date: Available online 18 March 2019Source: Brain and DevelopmentAuthor(s): Tomoko Mizuno, Ayako Kashimada, Toshihiro Nomura, Kengo Moriyama, Haruna Yokoyama, Setsuko Hasegawa, Masatoshi Takagi, Shuki MizutaniAbstractBackgroundSpinocerebellar ataxia type 5 (SCA5), a dominant spinocerebellar ataxia is caused by spectrin beta nonerythrocytic 2 gene (SPTBN2) mutation. It typically consists of a slow progressive cerebellar ataxia with an onset principally in adulthood. Here, we report on the first Japanese patient with infantile-onset SCA5 associated with a novel heterozygous SPTBN2 mutation.Case reportThe patient, a 6-year-old girl, developed delayed motor development and unsteady arm movement during infancy. She also showed gaze-evoked nystagmus, saccadic eye pursuit, dysarthria, dysmetria, intention tremor and mild intellectual disability. Brain MRI revealed moderate cerebellar atrophy and mild pontine atrophy. Comprehensive target capture sequencing to identify the causative gene identified a novel missense mutation in SPTBN2 (c.1309C
  • General movements: Longitudinal assessment better than cross-sectional
    • Abstract: Publication date: Available online 12 March 2019Source: Brain and DevelopmentAuthor(s): Lokesh Saini, Priyanka Madaan, M.R. Rudresh Naik
  • Reply to “Poor clinico-radiological correlation: A hallmark of acute
           flaccid myelitis”
    • Abstract: Publication date: Available online 11 March 2019Source: Brain and DevelopmentAuthor(s): Akihisa Okumura, Harushi Mori
  • Brain stem infarction in a 6-year-old boy with Down syndrome
    • Abstract: Publication date: Available online 8 March 2019Source: Brain and DevelopmentAuthor(s): Toru Imagi, Tomonaga Matsushita, Miyuki Matsushita, Yukako Yae, Takaoki Yokochi, Go Kawano, Yukihiro Akita, Keizo Ohbu, Toyojiro MatsuishiAbstractInfarct locations in children with arterial ischemic stroke have primarily been reported to be lobar or in the basal ganglia, and those in patients with Down syndrome (DS) and antiphospholipid syndrome (APS) are typically wide and multiple. No solitary brain stem infarctions have ever been reported in children with DS until now. Here, we report a case of brain stem infarction in a 6-year-old boy with DS who had no cardiac, renal, or intestinal complications. He exhibited ataxic gait and medial longitudinal fasciculus (MLF) symptoms at first presentation. Neuroimaging revealed a localized and isolated lesion in the midbrain. Although he did not satisfy the diagnostic criteria of APS, he showed persistently elevated levels of anticardiolipin antibody (21 U/mL; normal value
  • Rhinovirus-associated acute encephalitis/encephalopathy and cerebellitis
    • Abstract: Publication date: Available online 6 March 2019Source: Brain and DevelopmentAuthor(s): Kyoko Hazama, Takashi Shiihara, Hiroyuki Tsukagoshi, Takeshi Matsushige, Yuri Dowa, Mio WatanabeAbstractBackgroundRhinovirus is a common respiratory pathogen for children throughout the year; nevertheless, its central nervous system involvement is extremely rare, and only two cases have been reported to date: meningitis and sepsis-like illness.PatientA previously healthy 2-year-old Japanese boy developed fever, followed by seizures and lethargy. His cerebrospinal fluid cell count and protein level were slightly increased; brain magnetic resonance imaging showed abnormal intensities in the bilateral cerebellar dentate nuclei, which were prominent in diffusion-weighted images. After his consciousness disturbance improved, cerebellar dysfunction became apparent. He was treated symptomatically, without steroids or any other immunosuppressants. He almost recovered within a few months; however, cerebellar atrophy became evident on brain magnetic resonance imaging. Using acute specimens, human rhinovirus A was detected in his throat swab and cerebrospinal fluid.DiscussionAcute cerebellitis, in which cerebellar inflammation is predominant, is occasionally accompanied by cerebral symptoms, such as consciousness disturbance and seizures. As a causative pathogen, rotavirus is the most common; however, rhinovirus-associated acute encephalitis/encephalopathy and concurrent cerebellitis have not been reported before. Further research, using recent molecular techniques to detect various central nervous system pathogens, including rhinovirus, is needed to delineate the underlying pathophysiology.
  • Phenotype of a limb-girdle congenital myasthenic syndrome patient carrying
           a GFPT1 mutation
    • Abstract: Publication date: Available online 4 March 2019Source: Brain and DevelopmentAuthor(s): Chihiro Matsumoto, Madoka Mori-Yoshimura, Satoru Noguchi, Yukari Endo, Yasushi Oya, Miho Murata, Ichizo Nishino, Yuji TakahashiAbstractWe report a 38-year-old woman who presented with mild proximal dominant muscle weakness and fatigability that fluctuated during menstruation and treatment with ephedrine-containing medication. The patient had been diagnosed with “congenital myopathy with tubular aggregates” by muscle biopsy at age 19. Her revised diagnosis was congenital myasthenic syndrome (CMS) caused by a mutation in GFPT1 (2p13.3 [MIM 610542], c.722_723insG homozygote, CMS-GFPT1) based on a screening gene analysis. Muscle CT revealed diffuse atrophy of proximal and axial muscles focused on the vastus lateralis, hamstrings, medial gastrocnemius and soleus muscles. Oral administration of pyridostigmine bromide clearly ameliorated weakness and fatigability. This is the first reported case of CMS-GFPT1 in Japan. Since CMS symptoms are reactive to treatment, it is important for clinicians to make an accurate diagnosis at an early stage to improve patient QOL. Tubular aggregates in muscle biopsy and day-to-day fluctuations are important features of the disorder. Quantitative muscle strength measurement was effective for evaluating treatment efficacy.
  • Is the motor skills checklist appropriate for assessing children in
    • Abstract: Publication date: Available online 2 March 2019Source: Brain and DevelopmentAuthor(s): Yosuke Kita, Fumiko Ashizawa, Masumi InagakiAbstractPurposeMotor skill screening tools are essential for the early detection of developmental coordination disorder (DCD). The present study aimed to examine any cultural and rater effects on these tools. This then enabled us to judge the validity of the original cut-off values for identifying diagnosable children.MethodsA community sample survey was performed in Japan; 3852 children aged 6–9 years were recruited. Both parents and teachers evaluated the motor skills of their children using the Movement Assessment Battery for Children – Second Edition Checklist. The psychometric properties were evaluated and the scoring characteristics examined based on the type of rater and country of origin, as compared to data originally sampled in the UK.ResultsHigh reliability and validity of the Japanese samples were confirmed. The Japanese adults evaluated their children’s motor skills more rigorously than the Europeans. Additionally, there was a large disagreement between parent and teacher rating scores; the degree of agreement varied depending on the severity of motor deficits in the child.ConclusionThe first findings from a Japanese sample suggest that the assessment of motor skills in children is significantly affected by culture and rater. These cultural characteristics and rater biases strongly suggest that new cut-off values, reflecting country and rater type, be introduced for identifying children at risk of DCD.
  • Clinical time course of pediatric acute disseminated encephalomyelitis
    • Abstract: Publication date: Available online 2 March 2019Source: Brain and DevelopmentAuthor(s): Masahiro Nishiyama, Hiroaki Nagase, Kazumi Tomioka, Tsukasa Tanaka, Hiroshi Yamaguchi, Yusuke Ishida, Daisaku Toyoshima, Kyoko Fujita, Azusa Maruyama, Kaori Sasaki, Yoshinobu Oyazato, Taku Nakagawa, Yuichi Takami, Kandai Nozu, Noriyuki Nishimura, Ichiro Nakashima, Kazumoto IijimaAbstractThe detailed clinical time course in acute disseminated encephalomyelitis (ADEM) from initial symptoms, through exacerbation, to remission has not been widely reported. Hence, this study aimed to investigate the clinical time course of pediatric ADEM. This was a multicenter retrospective study based on registry data from medical chart reviews. The study included children who met the international consensus diagnostic criteria for ADEM. The patients comprised 18 boys and 6 girls, with a mean age of 5.5 ± 3.3 years at onset. From onset, the time until peak neurological symptoms, time until initial improvement, and time until full recovery was 3.1 ± 3.7 days, 6.0 ± 4.5 days, and 26 ± 34 days, respectively. Twenty-three (96%) patients were treated with high-dose methylprednisolone (mPSL) with a mean duration of 4.1 ± 4.0 days from onset. The condition of 15 patients (65%) improved within 3 days of high-dose mPSL initiation, whereas, that of four patients began to improve after>5 days of high-dose mPSL initiation. Only one patient (4%) did not achieve full recovery despite treatment with high-dose mPSL, intravenous immunoglobulin, and plasma exchange. This study presents the detailed clinical time course in pediatric ADEM in Japan. Progression of neurologic deficits typically lasts a few days, with initial improvement in 1 week leading to full recovery within 1 month.
  • Reversible splenial lesion syndrome in children with benign convulsions
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Lihua Jiang, Shanshan Mao, Jialu Xu, Feng GaoAbstractObjectiveTo assess the clinical and imaging features of reversible splenial lesion syndrome (RESLES) with benign convulsions associated with mild gastroenteritis (CwG) in children.Patients and methodsWe retrospectively reviewed the clinical course, blood and stool examinations, cerebrospinal fluid (CSF) examination, magnetic resonance imaging (MRI), electroencephalography (EEG) findings, therapy and prognosis of five children with RESLES associated with CwG.ResultsFive previously healthy patients, four girls and one boy, with mean age 26.4 ± 8.1 months, had clusters of general tonic-clonic or clonic seizures within the first two days of gastroenteritis. Rotavirus antigen was positive in the stool of one case. Interictal EEG was normal except in one case, which showed occipital slow wave. The initial MRI was performed within five days of onset, four patients had an isolated lesion in the splenium of the corpus callosum (SCC), and one patient had lesions extending outside the SCC that involved the genu of the corpus callosum. The follow-up MRI was performed 10–15 days after onset, and all lesions had completely disappeared. All patients were treated with antiviral, rehydration and anticonvulsant therapy in the acute phase. They had good prognosis and normal psychomotor development, with no neurological sequelae after 26–30 months of follow-up.ConclusionsCwG and RESLES can coexist in young children. The patients present with clusters of general tonic-clonic or clonic seizures in the acute phase. Brain MRI shows focal lesion in the SCC with high signal intensity on T2-weighted and FLAIR sequences. It has good prognosis and excessive treatment is not necessary.
  • Three Japanese patients with 3p13 microdeletions involving FOXP1
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Keiko Yamamoto-Shimojima, Nobuhiko Okamoto, Wataru Matsumura, Tetsuya Okazaki, Toshiyuki YamamotoAbstractBackgroundFOXP1 is known as the gene responsible for neurodevelopmental delay associated with language impairment. Broad clinical findings also include feeding difficulty, muscular hypotonia, and distinctive features. These findings are common between patients with loss-of-function mutations in FOXP1 and 3p13 microdeletion involving FOXP1. Thus, “FOXP1-related intellectual disability syndrome” is now recommended.MethodsAfter obtaining informed consent, chromosomal microarray testing was performed for patients with unknown etiology.ResultsWe identified three Japanese patients with 3p13 microdeletions involving FOXP1. One of the patients showed an additional 1q31.3q32.1 deletion as de novo, which was rather considered as a benign copy number variant.ConclusionThis is the first report of patients with 3p13 microdeletions from Japan. All patients showed growth delay, moderate to severe developmental delay, hearing loss, and distinctive facial features including prominent forehead and mid facial hypoplasia. In addition, “square shaped face” commonly observed in all three patients may be a characteristic finding undescribed previously. From the obtained findings, “FOXP1-related intellectual disability syndrome” was considered to be clinically recognizable.
  • Restless Legs Syndrome in NKX2-1-related chorea: An expansion of
           the disease spectrum
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): A. Iodice, M. Carecchio, G. Zorzi, B. Garavaglia, C. Spagnoli, G.G. Salerno, D. Frattini, N.E. Mencacci, F. Invernizzi, L. Veneziano, E. Mantuano, M. Angriman, C. FuscoAbstractBackgroundMolecular technologies are expanding our knowledge about genetic variability underlying early-onset non-progressive choreic syndromes. Focusing on NKX2-1-related chorea, the clinical phenotype and sleep related disorders have been only partially characterized.MethodsWe propose a retrospective and longitudinal observational study in 7 patients with non-progressive chorea due to NKX2-1 mutations. In all subjects sleep and awake EEG, brain MRI with study of pituitary gland, chest X-rays, endocrinological investigations were performed. Movement disorders, pattern of sleep and related disorders were investigated using structured clinical evaluation and several validated questionnaires.ResultsIn patients carrying NKX2-1 mutations, chorea was mainly distributed in the upper limbs and tended to improve with age. All patients presented clinical or subclinical hypothyroidism and delayed motor milestones. Three subjects had symptoms consistent with Restless Legs Syndrome (RLS) that improved with Levodopa.ConclusionsPatients with NKX2-1 gene mutations should be investigated for RLS, which, similarly to chorea, can sometimes be ameliorated by Levodopa.
  • Oxidant and antioxidant levels and DNA damage in tuberous sclerosis
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Mine Yuksel, Feyza Ustabas Kahraman, Sahbettin Selek, Omer Faruk Ozer, Akin IscanAbstractObjectiveThe pathogenesis of inherited diseases is thought to involve oxidative stress and the associated DNA damage, which are also implicated in many other conditions including cancer. Tuberous sclerosis is a genetic disease with autosomal dominant inheritance pattern that is characterized by the development of hamartomas in multiple organ systems. Oxidative stress and the related DNA damage are also likely to play a significant role in the pathogenesis of this condition. Thus, our study aimed to assess total oxidant-antioxidant level, oxidative stress index and DNA damage in patients diagnosed with tuberous sclerosis.MethodsThe study included 30 patients with tuberous sclerosis between the ages of 0 and 16 years. The control group consisted of 29 age-matched healthy children. Blood samples obtained from each subject were centrifuged to separate the sera. The Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) were measured in serum samples with a Thermo Scientific Multiscan plate reader (FC, 2011-06, USA) at wavelengths of 240 nm and 520 nm, respectively. The measured TAS and TOS values were used to calculate the Oxidative Stress Index (OSI). In addition, the Comet Assay Method was used to determine DNA damage in the samples. Data were analyzed using SPSS software.ResultsPatients with tuberous sclerosis complex (TSC) and controls were compared with respect to TAS, TOS, and OSI. TAS was significantly lower (p 
  • Abnormal cortical activation during silent reading in adolescents with
           autism spectrum disorder
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Rei Ogawa, Kuriko Kagitani-Shimono, Junko Matsuzaki, Junpei Tanigawa, Ryuzo Hanaie, Tomoka Yamamoto, Koji Tominaga, Masayuki Hirata, Ikuko Mohri, Masako TaniikeAbstractObjectiveAutism spectrum disorder (ASD) is a developmental disorder characterized by communication deficits and social difficulties, and individuals with ASD frequently exhibit varied levels of language abilities. However, the neurophysiological mechanisms underlying their language deficits remain unclear. To gain insight into the neurophysiological mechanisms of receptive language deficits, we assessed cortical activation patterns in adolescents with ASD during silent word-reading.MethodsWe used magnetoencephalography to measure cortical activation during a silent word-reading task in 14 adolescent boys with high-functioning ASD and 17 adolescent boys with typical development (TD).ResultsCompared with participants with TD, those with ASD exhibited significantly decreased cortical activation in the left middle temporal gyrus, left temporoparietal junction, bilateral superior temporal gyrus, left posterior insula, and right occipitotemporal gyrus, and increased activation in the right anterior insula. Participants with ASD also exhibited a lack of left-lateralization in the central sulcus and abnormal right-lateralization in the anterior insula area. Furthermore, in participants with ASD, we found that abnormal activation of the right central sulcus correlated significantly with lower visual word comprehension scores, and that decreased activation of the right anterior insula correlated significantly with the severity of social interaction difficulties.ConclusionOur findings suggest that atypical cortical activation and lateralization in the temporal-frontal area, which is associated with higher-order language processing functions, such as semantic analysis, may play a crucial role in visual word comprehension and social interaction difficulties in adolescents with ASD.
  • Correlation between human nervous system development and acquisition of
           fetal skills: An overview
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Elisa Borsani, Anna Maria Della Vedova, Rita Rezzani, Luigi Fabrizio Rodella, Carlo CristiniAbstractUnderstanding the association between fetal nervous system structure and functioning should be an important goal in neurodevelopmental sciences, especially when considering the emerging knowledge regarding the importance of prenatal onset. Intrauterine development of the human central nervous system consists of specific processes: neurogenesis, neuronal migration, synaptogenesis, and myelination. However, as extensively shown by the neurobehavioral studies in the last century, the development of the central nervous system involves both structure and functioning. It is now recognised that the developing motor and sensory systems are able to function long before they have completed their neural maturation and that the intrauterine experience contributes to neurobehavioral development. This review analyzes the recent literature, looking at the association between the human nervous system maturation and fetal behavior. This article will follow the development and skill acquisition of the anatomical nervous system across the three trimesters of the gestation period.
  • Announcements and reports
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s):
  • Acute encephalopathy with biphasic seizures and late reduced diffusion
           accompanied by Takotsubo cardiomyopathy
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Hiroshi Yamaguchi, Hiroaki Nagase, Shinobu Yoshida, Shoichi Tokumoto, Ken Hayashi, Daisaku Toyoshima, Hiroshi Kurosawa, Toshikatsu Tanaka, Azusa Maruyama, Kazumoto IijimaAbstractBackgroundAcute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and impaired consciousness. Takotsubo cardiomyopathy (TTC), which is typically triggered by psychological or physical stress, is characterized by transient myocardial dysfunction affecting the left ventricular apex. Recent reports have suggested that seizures can also trigger TTC. However, no cases of TTC accompanied by AESD have been reported.PatientA previously healthy 4-year-old girl was brought to a hospital with first-time febrile generalized tonic-clonic convulsions, which lasted approximately 40 min. After the seizure resolved, she was intubated due to respiratory deterioration. On the next day, her cardiac function deteriorated, and echocardiography revealed systolic apical ballooning of the left ventricle accompanied by hyperkinesis of the basal wall, which are typical in patients with TTC. Her condition gradually improved, and catecholamine support was tapered. However, 6 days after admission, she experienced a cluster of brief convulsions. Ten days after admission, head MRI revealed lesions with reduced diffusion throughout the cortex, except in the occipital lobe, as well as perirolandic sparing. Follow-up MRI 35 days after onset revealed whole-brain atrophy, following which she developed severe cognitive dysfunction.ConclusionsOur patient developed TTC accompanied by features of AESD. Our findings may thus provide insight into the development of TTC and prompt further studies regarding the relationship between prolonged seizures and TTC.
  • Severe anti-GAD antibody-associated encephalitis after stem cell
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Koki Nagai, Takanobu Maekawa, Hiroshi Terashima, Masaya Kubota, Akira IshiguroAbstractBackgroundGeneral features of anti-glutamic acid decarboxylase (GAD) antibody-associated limbic encephalitis are seizures, cognitive impairment, and imaging findings at the medial temporal lobes. We report a patient affected with remarkably severe anti-GAD antibody-positive encephalitis after hematopoietic stem cell transplantation (HSCT).Case ReportA 5-year-old girl received HSCT due to pineoblastoma. Thirteen months after HSCT, she showed seizure clustering and altered mental status. Her anti-GAD antibody level was high, 65,100 U/mL (reference range 
  • Successful corpus callosotomy for post-encephalopathic refractory epilepsy
           in a patient with MECP2 duplication syndrome
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Sotaro Kanai, Tohru Okanishi, Ayataka Fujimoto, Shinji Itamura, Shimpei Baba, Mitsuyo Nishimura, Kazuya Itomi, Hideo EnokiAbstractBackgroundPatients with MECP2 duplication syndrome present with distinct facial anomalies and clinical features such as global developmental delay, recurrent respiratory infections, and epileptic seizures. Approximately half of all patients develop epileptic seizures which are refractory in most cases despite active medical management. Furthermore, no previous reports have discussed the efficacy of surgical treatment for seizures in patients with MECP2 duplication syndrome.Case reportIn the present report, we describe a case of MECP2 duplication syndrome in a 15-year-old boy who developed epileptic seizures following influenza-associated acute encephalitis. His frequent epileptic spasms, tonic, atonic, and partial seizures were refractory to multiple antiepileptic medications. Electroencephalography revealed continuous diffuse epileptic discharge, resulting in regression. A total corpus callosotomy (CC) was performed at the age of 14 years and 7 months. His seizures markedly decreased following CC, although he continued to experience brief partial seizures approximately once per month. Post-operative examination revealed that his epileptic discharges had disappeared, and that his developmental state had returned to pre-encephalopathy levels.ConclusionOur findings indicate that CC may represent a valuable surgical option for children with medically refractory generalized seizures following acute encephalopathy, irrespective of genetic disorders such as MECP2 duplication syndrome.
  • Concentrations of various forms of vitamin B6 in ginkgo seed
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Tomomitsu Sado, Setsuko Nakata, Takahisa Tsuno, Masanori Sato, Yuka Misawa, Shoko Yamauchi, Yuji Inaba, Daisuke Kobayashi, Keiji WadaAbstractA 2-year-old girl required medical attention for a sudden onset of repetitive tonic-clonic convulsions after ingesting 20–30 ginkgo seeds. Concentrations of the major forms of circulating vitamin B6, pyridoxal-5′-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid, as well as the known ginkgo seed toxin 4′-O-methylpyridoxine (MPN) were measured in the serum and cerebrospinal fluid (CSF). PLP is an active form of vitamin B6 and necessary for γ-aminobutyric acid (GABA) production. High MPN concentrations were observed in both the serum and CSF. As the PLP to PL ratio was markedly decreased in serum and CSF examinations, we suspected the ratio to be important in GABA production. This case report provides novel information on the metabolism of vitamin B6 in humans as a result of ginkgo seed poisoning.
  • A case of early onset life-threatening epilepsy associated with a novel
           ATP1A3 gene variant
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Naoko Ishihara, Hidehito Inagaki, Misa Miyake, Yoshiki Kawamura, Tetsushi Yoshikawa, Hiroki KurahashiAbstractIntroductionMutations of the ATP1A3 gene are associated with a wide spectrum of neurological disorders including rapid onset dystonia-parkinsonism and alternating hemiplegia of childhood (AHC). The genotype-phenotype correlations in these cases remain unclear however. We here report a pediatric case of catastrophic early life epilepsy, respiratory failure, postnatal microcephaly, and severe developmental disability associated with a novel heterozygous ATP1A3 mutation.SubjectA boy with a normal birth to nonconsanguineous parents was transferred to the NICU due to postnatal respiratory failure at 2 days. He showed extreme hypotonia, episodic oculomotor abnormality and tachycardia, and frequent epileptic seizures. Mechanical ventilation was required but his epileptic seizures were intractable to multiple antiepileptic drugs, including extremely high doses of phenobarbital.Methods and ResultsWhole exome sequencing analysis of the case and his parents identified a de novo heterozygous mutation in the ATP1A3 gene (c.2736_2738CTTdel, p.Phe913del).DiscussionThe Phe913 residue in the ATP1α3 protein that is deleted in our case is highly conserved among vertebrates. Notably, an amino acid deletion in the same transmembrane domain of this protein, p.Val919del, has been reported previously in typical AHC cases, suggesting that p.Phe913del is a pathogenic mutation. Several reported cases with severe symptoms and very early onset epilepsy harbor ATP1α3 mutations at structural positions in this protein that differ from that of Phe913. Further functional studies are required to clarify the relationship between the loss of Phe913 and the very distinct resulting phenotype.
  • A case of dihydropyrimidinase deficiency incidentally detected by urine
           metabolome analysis
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Hiroki Tsuchiya, Tomoyuki Akiyama, Tomiko Kuhara, Yoko Nakajima, Morimasa Ohse, Hiroki Kurahashi, Takema Kato, Yasuhiro Maeda, Harumi Yoshinaga, Katsuhiro KobayashiAbstractDihydropyrimidinase deficiency is a rare autosomal recessive disease affecting the second step of pyrimidine degradation. It is caused by mutations in the DPYS gene. Only approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. We report a case of dihydropyrimidinase deficiency incidentally detected by urine metabolome analysis. Gas chromatography-mass spectrometry-based urine metabolomics demonstrated significant elevations of dihydrouracil and dihydrothymine, which were subsequently confirmed by a quantitative analysis using liquid chromatography-tandem mass spectrometry. Genetic testing of the DPYS gene revealed two mutations: a novel mutation (c.175G > T) and a previously reported mutation (c.1469G > A). Dihydropyrimidinase deficiency is probably underdiagnosed, considering its wide phenotypical variability, nonspecific neurological presentations, and an estimated prevalence of 2/20,000. As severe 5-fluorouracil-associated toxicity has been reported in patients and carriers of congenital pyrimidine metabolic disorders, urinary pyrimidine analysis should be considered for those who will undergo 5-fluorouracil treatment.
  • A novel mutation in the GATAD2B gene associated with severe
           intellectual disability
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Kimiko Ueda, Kumiko Yanagi, Tadashi Kaname, Nobuhiko OkamotoAbstractBackgroundThe human GATA zinc finger domain containing 2B (GATAD2B) encodes a subunit of the MeCP1-Mi-2/nucleosome remodeling and deacetylase complex, which is involved in chromatin modification and transcription. Recently, patients with severe intellectual disabilities and characteristic features associated with GATAD2B mutations have been identified.Case reportThe patient was a 4-year-old male with dysmorphic features, including frontal bossing, hypertelorism, epicanthal folds, down-slanting palpebral fissures, a flat nasal bridge, a high arched palate, and micrognathia. He spoke no meaningful words and exhibited severe intellectual disability. Hypermetropic astigmatism and mild spasticity of the lower extremities were noted. Whole-exome sequencing revealed a de novo missense mutation in GATAD2B (NM_020699:exon4:c.502C>T; p.(Glu168∗)).ConclusionWe report a novel GATAD2B mutation in a boy exhibiting bilateral leg spasticity and white matter abnormalities on brain magnetic resonance imaging.
  • Facial nerve palsy associated with atomoxetine-induced hypertension
    • Abstract: Publication date: March 2019Source: Brain and Development, Volume 41, Issue 3Author(s): Hironobu Kobayashi, Katsunori Fujii, Masayo Kobayashi, Naoki Saito, Kentaro Okunushi, Ryota Ebata, Tadashi Shiohama, Daisuke Sawada, Naoki ShimojoAbstractBackgroundPeripheral facial nerve palsy is characterized by unilateral facial paresis due to ipsilateral facial nerve dysfunction. Most cases are idiopathic; however, some have specific etiologies, such as herpesvirus infection, immunological disorders, and hypertension. Atomoxetine is a norepinephrine reuptake inhibitor that is used in the treatment of attention deficit hyperactivity disorder (ADHD). This drug is known to cause adverse effects, such as nausea, appetite loss, headache, insomnia, and hypertension.Case descriptionWe herein describe a case of sudden-onset right peripheral facial palsy in a 9-year-old Japanese boy. The patient’s systolic blood pressure was as high as 200 mmHg, and he was therefore admitted to our hospital for investigation. Extensive surveillance including blood examination; endocrinological testing; imaging studies such as computed tomography, magnetic resonance imaging, and renography; and renal biopsy did not reveal any abnormalities. The patient had ADHD and was under treatment with atomoxetine. We discontinued treatment with atomoxetine; the patient showed gradual improvement. His hypertension and facial palsy resolved. We therefore diagnosed the patient with peripheral facial palsy associated with atomoxetine-induced hypertension.ConclusionAlthough peripheral facial nerve palsy is usually benign and self-limiting, blood pressure should be monitored in children under treatment with atomoxetine and the possibility of drug-induced hypertension should be considered in order to prevent palsy associated with hypertension.
  • Serum carnitine levels of children with epilepsy: Related factors
           including valproate
    • Abstract: Publication date: Available online 28 February 2019Source: Brain and DevelopmentAuthor(s): Akihisa Okumura, Hirokazu Kurahashi, Hideyuki Iwayama, Shingo NumotoAbstractObjectiveThis study measured the serum carnitine levels in patients with epilepsy and determined the factors contributing to low carnitine levels.MethodsWe measured the serum carnitine levels in 94 consecutive patients with epilepsy, including the free carnitine (FC) and acylcarnitine fractions, using an enzyme cycling method. We defined a low FC as a serum FC level 
  • Causal connection between methamphetamine and neurotoxicity not
    • Abstract: Publication date: Available online 26 February 2019Source: Brain and DevelopmentAuthor(s): Christopher Medina-Kirchner, Ciara A. Torres
  • Acute encephalopathy with brain swelling
    • Abstract: Publication date: Available online 22 February 2019Source: Brain and DevelopmentAuthor(s): Priyanka Madaan, Lokesh Saini
  • The risk of hypoglycemia and the ketogenic diet for super-refractory
           status epilepticus patients
    • Abstract: Publication date: Available online 22 February 2019Source: Brain and DevelopmentAuthor(s): Klára Brožová, Jan Brož
  • Personality profile and health-related quality of life in adults with
           previous continuous spike-waves during slow sleep syndrome
    • Abstract: Publication date: Available online 20 February 2019Source: Brain and DevelopmentAuthor(s): Giovanna Lenci, Maria Grazia Calevo, Roberto Gaggero, Giulia Prato, Livia Pisciotta, Elisa De Grandis, Maria Margherita Mancardi, Maria Giuseppina Baglietto, Monica Vigano', Edvige VeneselliAbstractIntroductionEpilepsy with continuous spike-waves during slow sleep syndrome (CSWSS) is characterized by various seizure types, a characteristic EEG pattern and neuropsychological disorders. The main purpose of this study was to evaluate the long-term outcome of CSWSS occurred in childhood and to evaluate the variables that could influence the quality of social adaptation and the personality profile.Material and methodsThis is a prospective study on 24 young adults with previous CSWSS (median age 24.5 yrs) who were enrolled between January and July 2011 at the G. Gaslini Children’s Hospital, Genoa, Italy. Patients were divided into two groups: twelve with previous spike-wave index (SWI > 85%) defined as typical CSWSS (T-CSWSS) and twelve with previous SWI = 50–85% defined as atypical CSWSS (A-CSWSS). All the subjects were submitted to Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Psychological General Well-Being Index (PGWBI), and to a structured interview.ResultsA correlation was observed with the severity of EEG abnormalities expressed by the SWI and outcome. The T-CSWSS group showed a significantly lower perceived well-being. Similarly in the T-CSWSS group the percentage of MMPI-2 clinical scales with T-scores ≥65 was higher than in the A-CSWSS group. Finally, a significant lower schooling in the T-CSWSS group was observed.ConclusionThere seem to be two forms of the same disease, with similar onset and clinical evolution but a different outcome regarding the social and psychological conditions. The outcome of the social adaptation and of the personality consciousness was related with the severity of the EEG abnormalities: more favorable in patients with less intense SWI activity (A-CSWSS) compared those with a more severe EEG impairment (T-CSWSS).
  • Two unrelated girls with intellectual disability associated with a
           truncating mutation in the PPM1D penultimate exon
    • Abstract: Publication date: Available online 20 February 2019Source: Brain and DevelopmentAuthor(s): Yukiko Kuroda, Hiroaki Murakami, Takayuki Yokoi, Tatsuro Kumaki, Yumi Enomoto, Yoshinori Tsurusaki, Kenji KurosawaAbstractPPM1D truncating mutations in the last and penultimate exons of the gene have been associated with intellectual disability (ID) syndrome. Only 15 affected patients to-date have been reported with mild-to-severe ID, autistic behavior, anxiety and dysmorphic features. Here, we describe the clinical characteristics and underlying genetics of two unrelated girls with moderate developmental delay and dysmorphic features associated with novel mutations in PPM1D exon 5. The dysmorphic features demonstrated by these two patients are consistent with previously reported patients, including broad forehead, thin upper lip, brachydactyly, and hypoplastic nails. We identified a de novo PPM1D mutation in exon 5 of each patient (c.1250_1251insACCA p.V419Tfs*16 and c.1256_1257insCAAG p.S421Qfs*14) by panel sequencing for 4,813 disease-related genes. Both patients also had frameshift mutations (at different positions) that resulted in the same estimated termination codon at 434. These additional reports add to the growing literature on PPM1D-associated ID syndrome and help delineate the clinical phenotype and genetic basis.
  • Expert consensus on pharmacotherapy for tic disorders in Japan
    • Abstract: Publication date: Available online 19 February 2019Source: Brain and DevelopmentAuthor(s): Yu Hamamoto, Miyuki Fujio, Maiko Nonaka, Natsumi Matsuda, Toshiaki Kono, Yukiko KanoAbstractObjectiveWe aimed to clarify the current status of pharmacotherapy for tic disorders and comorbidities in Japan. We used a systematic survey to collate the consensus of Japanese experts and compare it with the recent international evidence.MethodsWe devised a questionnaire on pharmacotherapy for tics and comorbidities and sent it to Japanese experts on tic disorders. Based on the response to the first survey, we revised the questionnaire and conducted a second survey to determine the consensus among the experts on a 4-point Likert scale by the Delphi method.ResultsThe first survey revealed variability in preferred medications and dosages among the experts in Japan. However, we were able to build a general consensus on pharmacotherapy for tic disorders and comorbidities based on the second survey. Aripiprazole and risperidone were the first- and second-line medication for tic disorders, respectively. Agonists of α-2 adrenergic receptors were seldom prescribed. Fluvoxamine was the first-line medication for comorbid obsessive-compulsive disorder, and atomoxetine for comorbid attention deficit/hyperactivity disorder.ConclusionsThis study will help Japanese physicians choose medications for tic disorders more judiciously and will improve the quality of tic pharmacotherapy in Japan.
  • A case of confusional migraine with transient increased cerebral blood
    • Abstract: Publication date: Available online 14 February 2019Source: Brain and DevelopmentAuthor(s): Emiko Momoki, Tatsuo Fuchigami, Yuki Kasuga, Kaori Kimura, Wakako Ishii, Ayumi Fukuda, Yukihiko Fujita, Ichiro MoriokaAbstractBackgroundConfusional migraine is a rare type of migraine presenting as an acute confusional state. However, the mechanism of this confusional state remains unclear.Subject and methodsWe examined an 11-year-old girl with confusional migraine, using electroencephalography, brain magnetic resonance imaging, cerebrovascular magnetic resonance angiography, and single-photon emission computed tomography to investigate cerebral blood flow changes.ResultsOur findings revealed vessel narrowing in the left middle and posterior cerebral artery territory, indicating vasospasm and suggesting that the confusion was caused by hypoperfusion. However, abnormal increased cerebral blood flow in the left middle and posterior cerebral artery territory was observed during the non-confusional state.ConclusionThe recorded cerebral blood flow changes are similar to those associated with migraine attacks, gradually changing from abnormally low to abnormally high during the confusional and post-confusional state.
  • Poor clinico-radiological correlation: A hallmark of acute flaccid
    • Abstract: Publication date: Available online 13 February 2019Source: Brain and DevelopmentAuthor(s): Priyanka Madaan, Shivan Keshavan, Lokesh Saini
  • The association between brain morphological development and the quality of
           general movements
    • Abstract: Publication date: Available online 12 February 2019Source: Brain and DevelopmentAuthor(s): Tomoki Maeda, Hajime Iwata, Kazuhito Sekiguchi, Mizuho Takahashi, Kenji IharaAbstractAimTo clarify the morphologic characteristics of the brain, which are the foundation of the emergence of general movements (GMs) in very-low-birth-weight infants.Study designProspective cohort study. GMs were scored according to a semiquantitative scoring system: the GMs optimality score (GMOS) at preterm and term ages. Brain magnetic resonance imaging (MRI) at term-equivalent age was scored using a validated scoring system (MRI score). We examined the relationship between the two scores by multiple regression analysis with relevant clinical background.SubjectsWe included 50 very-low-birth-weight infants cared for at Oita University Hospital from August 2012 to August 2018 who underwent MRI and GMs assessment. Their median gestational age and birth weight were 29w2d and 1145 g, respectively.ResultsThe MRI score and systemic steroid administration were related to preterm GMOS, and the MRI score was related to term GMOS. The component cerebellum score and cortical grey matter score of the MRI score were associated with preterm GMOS, and the cerebellum and the cerebral white matter scores were associated with term GMOS.ConclusionThe quality of GMs was associated with brain morphological development. The co-evaluation of GMs and brain morphology leads to accurate developmental prediction.
  • Early enzyme replacement therapy enables a successful hematopoietic stem
           cell transplantation in mucopolysaccharidosis type IH: Divergent clinical
           outcomes in two Japanese siblings
    • Abstract: Publication date: Available online 10 February 2019Source: Brain and DevelopmentAuthor(s): Narutoshi Yamazaki, Motomichi Kosuga, Kazuhiro Kida, Go Takei, Yasuyuki Fukuhara, Hiroshi Matsumoto, Masayoshi Senda, Akihito Honda, Akira Ishiguro, Takashi Koike, Hiromasa Yabe, Torayuki OkuyamaAbstractMucopolysaccharidosis type IH (MPS IH, Hurler syndrome) is a progressive, multisystem autosomal recessive lysosomal storage disorder resulting in the consequent accumulation of glycosaminoglycans. It is well recognized that early hematopoietic stem cell transplantation (HSCT) prevents neurocognitive decline in MPS IH. We followed the divergent clinical course in two Japanese siblings with MPS IH. The elder sister (proband) received a diagnosis of MPS IH at 6 months old. At the time of this diagnosis enzyme replacement therapy (ERT) was not available in Japan. She developed severe and recurrent respiratory disease and died at 1 year 10 months of age. Her younger sister also received a diagnosis of MPS IH, but at 18 days of age, and started ERT at 34 days of age. ERT continued until 8 months of age and prevented the progression of somatic manifestations of MPS IH. She received HSCT at 9 months old. Five years after HSCT she had no symptoms of MPS IH except for mild signs of dysostosis multiplex and mild cardiac valvular disease. Her neurological function was generally preserved compared with her elder sister. The prognosis and quality of life differed significantly between the sisters. Therefore, early HSCT can preserve neurocognition by preventing the neurodegeneration from MPS IH. In addition, ERT initiated during the asymptomatic period prevented the patient from developing somatic manifestations and enabled successful HSCT in this case.
  • MELAS syndrome with m.4450 G > A mutation in mitochondrial
           tRNAMet gene
    • Abstract: Publication date: Available online 7 February 2019Source: Brain and DevelopmentAuthor(s): Mari Kuwajima, Masahide Goto, Koyuru Kurane, Hiroko Shimbo, Narumi Omika, Eriko F. Jimbo, Kazuhiro Muramatsu, Makiko Tajika, Masaru Shimura, Kei Murayama, Kenji Kurosawa, Takanori Yamagata, Hitoshi OsakaAbstractMutations in the mitochondrial tRNAMet gene have been reported in only five patients to date, all of whom presented with muscle weakness and exercise intolerance as signs of myopathy. We herein report the case of a 12-year-old girl with focal epilepsy since the age of eight years. At age 11, the patient developed sudden visual disturbances and headaches accompanied by recurrent, stroke-like episodes with lactic acidosis (pH 7.279, lactic acid 11.6 mmol/L). The patient frequently developed a delirious state, exhibited regression of intellectual ability. Brain magnetic resonance imaging revealed high-intensity signals on T2-weighted images of the left occipital lobe. Mitochondrial gene analysis revealed a heteroplasmic m.4450G > A mutation in the mitochondrial tRNAMet. The heteroplasmic rate of the m.4450G > A mutation in blood, skin, urinary sediment, hair, saliva, and nail samples were 20, 38, 59, 41, 27, and 35%, respectively. The patient’s fibroblast showed an approximately 53% reduction in the oxygen consumption rate, compared to a control, and decreased complex I and IV activities. Stroke-like episodes, lactic acidosis, encephalopathy with brain magnetic resonance imaging findings, and declined mitochondrial function were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. To our knowledge, the findings associated with this first patient with MELAS syndrome harboring the m.4450G > A mutation in mitochondrial tRNAMet expand the phenotypic spectrum of tRNAMet gene.
  • A case of Niemann-Pick disease type C with neonatal liver failure
           initially diagnosed as neonatal hemochromatosis
    • Abstract: Publication date: Available online 6 February 2019Source: Brain and DevelopmentAuthor(s): Tadayuki Kumagai, Hiroshi Terashima, Hajime Uchida, Akinari Fukuda, Mureo Kasahara, Motomichi Kosuga, Torayuki Okuyama, Tomoyuki Tsunoda, Ayano Inui, Tomoo Fujisawa, Aya Narita, Yoshikatsu Eto, Masaya KubotaAbstractBackgroundNiemann-Pick type C (NPC) is a lysosomal lipid storage disease with mutation of NPC1/NPC2 genes, which transport lipids in the endosome and lysosome, and various neurological symptoms. NPC patients also develop hepatosplenomegaly or liver disorder in the neonatal period, and 10% suffer severe liver failure. Neonatal hemochromatosis (NH) is a liver disorder characterized by hepatic and extrahepatic siderosis. Although the etiology of NH is unclear, recent reports suggest that the gestational alloimmune mechanism is the cause of NH. Herein, we report a Japanese NPC patient initially diagnosed as NH.Case reportA 5-day-old boy was transferred to our hospital with severe cholestatic liver failure. Congenital infections and metabolic screening were negative, and NH was suspected. However intra and extrahepatic siderosis were not found. As his liver deteriorated rapidly, liver transplantation was performed at 19 days old. The explanted liver showed cirrhosis, and strong C5b-9 complex staining of hepatocytes, so NH was diagnosed. From the age of one and a half years, he developed regression, vertical supranuclear gaze palsy and cataplexy. Fibroblast filipin staining was strong, blood oxysterol was high, and there were compound heterozygous mutations in NPC1,p.[(F288L)];[(K1206N)]. The patient was then diagnosed as NPC and started on miglustat.ConclusionNeonatal liver failure was initially diagnosed as NH. Later, the patient developed various neurological symptoms characteristic of NPC. Neurological follow-up of children who develop NH is required.
  • Methotrexate myelopathy
    • Abstract: Publication date: Available online 2 February 2019Source: Brain and DevelopmentAuthor(s): Priyanka Madaan, Lokesh Saini
  • Coexistence of a CAV3 mutation and a DMD deletion in a family with complex
           muscular diseases
    • Abstract: Publication date: Available online 2 February 2019Source: Brain and DevelopmentAuthor(s): Takuya Hiraide, Tsutomu Ogata, Seiji Watanabe, Mitsuko Nakashima, Tokiko Fukuda, Hirotomo SaitsuAbstractWhole-exome sequencing (WES) can comprehensively detect both pathogenic single nucleotide variants and copy number variants, enabling identification of a coexistence of two or more genetic etiologies. Here we report a family consisting of individuals with Becker muscular dystrophy and rippling muscle disease. The proband, a 12-year-old boy, was diagnosed with Becker muscular dystrophy with exon 45–55 DMD deletions at age 4. He had myalgia and muscle stiffness. Interestingly, percussion-induced muscle mounding (PIMM), which is a characteristic of rippling muscle disease, was also observed. The father also showed muscle stiffness, myalgia, fatigability, muscle rippling and PIMM. WES revealed a missense CAV3 mutation (NM_033337.2:c.80G>A) in the proband, the father, the oldest sister and the grandmother, who had an elevated serum creatine kinase (CK) level. The c.80G>A mutation was considered pathogenic according to ACMG guidelines. The second older sister, the mother and the paternal grandfather did not have the CAV3 mutation and had normal CK. Using two programs for copy number analysis with WES data, we successfully identified the DMD deletion in the proband, the older sister and the mother. We revealed the coexistence of the CAV3 mutation and the DMD deletion in a family with complex muscular diseases and confirmed the usefulness of WES for elucidating such etiology.
  • Disrupted cortico-ponto-cerebellar pathway in patients with
    • Abstract: Publication date: Available online 18 January 2019Source: Brain and DevelopmentAuthor(s): Mikako Enokizono, Noriko Sato, Miho Ota, Yoko Shigemoto, Emiko Morimoto, Masatoshi Oba, Daichi Sone, Yukio Kimura, Kenji Sugai, Masayuki Sasaki, Naoki Ikegaya, Masaki Iwasaki, Hiroshi MatsudaAbstractObjectiveCerebellar dysmaturation and injury is associated with a wide range of neuromotor, neurocognitive and behavioral disorders as well as with preterm birth. We used diffusion tensor MR imaging to investigate a disruption in structural cortico-ponto-cerebellar (CPC) connectivity in children with infantile-onset severe epilepsy.MethodsWe performed CPC tract reconstructions in 24 hemimegalencephaly (HME) patients, 28 West syndrome (WS) of unknown etiology patients, and 25 pediatric disease control subjects without a history of epilepsy nor brain abnormality on MRI. To identify the CPC tract, we placed a seeding ROI separately in each right and left cerebral peduncle. We evaluated the distribution patterns of the CPC tracts to the cerebellum and their correlation with clinical findings.ResultsIn control and WS of unknown etiology groups, both sides’ CPC tracts descended to bilateral hemispheres in 20 (80.0%) and 21 (75.0%); mixed (bilateral on one side and unilateral on the other side) in five (20.0%) and five (17.9%); and unilateral in zero (0.0%) and two (7.1%), respectively. However, in the HME, both sides’ CPC tracts descended to bilateral hemispheres in four (16.7%); mixed in 13 (54.1%); and unilateral in seven (29.2%). These CPC patterns differed significantly between the HME and other groups (p 
  • Nutritional status among women whose pregnancy outcome was afflicted with
           neural tube defects in Tigray region of Ethiopia
    • Abstract: Publication date: Available online 14 January 2019Source: Brain and DevelopmentAuthor(s): Abadi Leul Welderufael, Birhane Alem Berihu, Yibrah Berhe, Tony Magana, Selemawit Asfaw, kibrom Gebreselassie, Ezra Belay, Hayelom Kebede, Afework MulugetaAbstractBackgroundNutritional deficiency in pregnant women is a confirmed cause of neural tube defects (NTDs). Alongside to this background, We sought to determine the nutritional status and level of awareness on the issue of the NTDs as well as folic acid (FA) utilization among women who born infants with NTDs in Tigray region of Ethiopia.MethodA standard interviewer and a food frequency questionnaire was used to obtain information from mothers of cases with neural tube defects (n = 205) and their controls (n = 412). Demographic information, weekly food frequency consumption, information on awareness on the issue of the NTDs as well as folic acid (FA) use was collected.ResultThe mean age of the mothers of the cases and controls was 26.5 years (range 17–43 years) and 26.05 years (range 18–40 years), respectively. Approximately 92.2% (189/205) of the cases and 90.5% (373/412) control mothers do not know the term folic acid (FA). Notably, all participant mothers (100%) did not understand that NTDs are a serious health problem associated with inadequate intake of FA and none of them used FA prior to conception. Food frequency analysis revealed that except for cereals (p = 0.12) and milk products (p = 0.8), the proportion of the consumed food type within seven days recalls period showed a statistically significant difference (p 
  • Corrigendum to “Measuring in vivo cerebral maturation using age-related
           T2 relaxation times at 3 T” [Brain Dev. 40 (2018) 85–93]
    • Abstract: Publication date: Available online 12 January 2019Source: Brain and DevelopmentAuthor(s): Eva Bültmann, Loukia M. Spineli, Hans Hartmann, Heinrich Lanfermann
  • Electroencephalographic and epilepsy findings in mecp2 duplication
           syndrome. A family study
    • Abstract: Publication date: Available online 11 January 2019Source: Brain and DevelopmentAuthor(s): Federica Lotti, Ursula Geronzi, Salvatore GrossoAbstractMECP2 duplication syndrome (MECP2 DS) is an X-linked disorder characterized by early-onset hypotonia, poor speech development, recurrent respiratory infections, epilepsy and progressive spasticity. Epilepsy occurs in more than 50% of the affected patients. Generalized tonic-clonic seizures (GTCS) are the most common seizure-type described but atonic seizures, absences and myoclonic seizures have also been reported. Electroencephalographic (EEG) and seizure types occurring in MECP2 DS have been poorly investigated. Here we report on two male siblings carrying a maternally-inherited MECP2 duplication. Patients underwent several EEG recordings and long-lasting video-EEG monitoring. The most represented seizure types were myoclonic and atonic seizures. GTCS were rarely observed. In patients, we found a slowing of the background activity with multifocal paroxysmal activity, prominent on the frontal areas. In conclusion, our observations seem to suggest that MECP2 syndrome seem to have a peculiar epileptic pattern mainly characterized by the occurrence of myoclonic seizures, the recognition of which is important in order to undertake an appropriate treatment.
  • Phenotypic features of 1q41q42 microdeletion including WDR26 and FBXO28
           are clinically recognizable: The first case from Japan
    • Abstract: Publication date: Available online 8 January 2019Source: Brain and DevelopmentAuthor(s): Tomoe Yanagishita, Keiko Yamamoto-Shimojima, Sayaka Nakano, Testuya Sasaki, Hideo Shigematsu, Katsumi Imai, Toshiyuki YamamotoAbstract1q41q42 microdeletion syndrome has been established in 2007. Since then, more than 17 patients have been reported so far. The reported deletions showed random breakpoints and deletion regions are aligned as roof tiles. Patients with 1q41q42 microdeletion syndrome show intellectual disability, seizures, and distinctive features. Many genotype-phenotype correlation studies have been performed and some genes included in this region have been suggested as potential candidate genes. Recently, de novo variants in WDR26 and FBXO28 were identified in patients who showed consistent phenotypes with 1q41q42 microdeletion syndrome. Thus, both genes are now considered as the genes possibly responsible for 1q41q42 microdeletion syndrome. Here, the first case of a Japanese patient with a de novo 1q41q42 microdeletion is reported. Owing to the distinctive features, this syndrome would be clinically recognizable.
  • Recreational nitrous oxide abuse related subacute combined degeneration of
           the spinal cord in adolescents – A case series and literature review
    • Abstract: Publication date: Available online 2 January 2019Source: Brain and DevelopmentAuthor(s): Shih-Yun Lan, Cheng-Yen Kuo, Cheng-Che Chou, Shu-Sing Kong, Po-Cheng Hung, Hsin-Yu Tsai, Yi-Ching Chen, Jainn-Jim Lin, I-Jun Chou, Kuang-Lin Lin, PCHAN Study GroupAbstractBackgroundNitrous oxide (N2O) is a commonly used inhaled anesthetic in outpatient dental procedures. However, the increasing recreational use of N2O may result in vitamin B12 deficiency-related neurologic and psychiatric symptoms. The aim of this study was to demonstrate the clinical features of chronic N2O abuse in pediatric patients.MethodsPatients under 20 years of age who were diagnosed with N2O-induced subacute combined degeneration of the spinal cord from 2012 to 2018 were enrolled in this study. Clinical presentations, laboratory, imaging, ancillary studies, treatments and outcomes were analyzed.ResultsNine patients were included, all of whom presented with symptoms of myeloneuropathy including limb numbness, limb weakness or unsteady gait. Six patients had low or low-normal vitamin B12 (cyanocobalamin) levels. Eight patients had evidence of subacute combined degeneration of the spinal cord via neuroimaging studies. All of the patients received vitamin B12 supplementation as treatment. All had full recovery of muscle power within 2 months. Five patients had persistent sensory deficits.ConclusionChronic N2O abuse can cause permanent neurological damage if not treated promptly. Clinical staff should be aware of the various presentations of neurotoxicity related to N2O abuse.
  • Catch-up growth and behavioral development among preterm,
           small-for-gestational-age children: A nationwide Japanese population-based
    • Abstract: Publication date: Available online 2 January 2019Source: Brain and DevelopmentAuthor(s): Akihito Takeuchi, Takashi Yorifuji, Mariko Hattori, Kei Tamai, Kazue Nakamura, Makoto Nakamura, Misao Kageyama, Toshihide Kubo, Tatsuya Ogino, Katsuhiro Kobayashi, Hiroyuki DoiAbstractObjectiveTo examine the relationship between the catch-up growth of preterm, SGA children and their behavioral development.MethodsWe analyzed data from a large Japanese, nationwide, population-based, longitudinal survey that started in 2001. We restricted the study participants to preterm children with information on height at 2 years of age (n = 1667). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age above −2.0 standard deviations for chronological age. We then used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations of SGA/catch-up status with neurobehavioral development both at 5.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors.ResultsTwenty-six percent of preterm SGA infants failed to catch up. SGA children without catch-up growth were more likely to be unable to listen without fidgeting (OR 2.51, 95% CI: 1.06–5.93) and unable to focus on one task (OR 2.66, 95% CI: 1.09–6.48) compared with non-SGA children at 5.5 years of age. Furthermore, SGA children without catch-up growth were at significant risk for inattention at 8 years of age.ConclusionsSGA infants with poor postnatal growth were at risk for attention problems throughout preschool-age to school-age among preterm infants. Early detection and intervention for attention problems among these infants is warranted.
  • Serial MRI findings of acute flaccid myelitis during an outbreak of
           enterovirus D68 infection in Japan
    • Abstract: Publication date: Available online 26 December 2018Source: Brain and DevelopmentAuthor(s): Akihisa Okumura, Harushi Mori, Pin Fee Chong, Ryutaro Kira, Hiroyuki Torisu, Sawa Yasumoto, Hiroyuki Shimizu, Tsuguto Fujimoto, Keiko Tanaka-Taya, the Acute Flaccid Myelitis Collaborative Study InvestigatorsAbstractObjeciveTo clarify the neuroimaging findings of children with acute flaccid myelitis during an outbreak of EV-D68 infection.MethodsWe performed a detailed review of the spinal and cranial MRI results of 54 children with acute flaccid myelitis. We focused on the range of longitudinal lesions, the localization and appearance of lesions within a horizontal section, Gadolinium-enhancement, and changes over time.ResultsAll children had longitudinal spinal lesions involving central gray matter. Twenty-six children had lesions spanning the entire spine. Six of them had weakness in all limbs, whereas seven had weakness of only one limb. Thirty-eight children had lesions in both gray and white matter and limb weakness tended to be more severe in these children. During the acute period, spinal lesions showed bilateral ill-defined widespread T2 hyperintensity. During the subacute period, lesions were well defined and confined to the anterior horn. The distribution of limb weakness was correlated with the appearance of lesions during the subacute period. Gadolinium enhancement was performed in 37 children, and enhancement was seen in the cauda equina in 29 children. Enhancement was infrequent within 2 days after onset but was seen in almost all children thereafter. Twenty-two children had brainstem lesions continuous with spinal lesions.ConclusionExtensive longitudinal spinal lesions were characteristic in children with acute flaccid myelitis. Lesions were usually bilateral and widespread during the acute period, whereas localization to the anterior horn could become obvious. Although enhancement of the cauda equina was often observed, its appearance was sometimes delayed.
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