The delta brush, a well‐known characteristic waveform of the human preterm electroencephalogram, represents spontaneous electrical activity. Recent experimental animal model evidence suggests that ...delta brushes are not only spontaneous intrinsic activity but are also evoked by external sensory stimulation or spontaneous movement. They are also likely to reflect the activity of subplate neurons, which play an important role in early brain development and network organization. Here, evidence about delta brushes in human preterm electroencephalogram is provided along with future perspectives.
Objective To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology, and brain structure at ...hospital discharge; and developmental outcomes at 2 years of age. Study design In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at 2 years of age (n = 86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were: (1) medical factors throughout the hospitalization; (2) neurobehavior; and (3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). Results At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores ( P = .02; β = −0.52 CI −0.95, −0.10). At age 2 years, infants from private rooms had lower language scores ( P = .006; β = −8.3 CI −14.2, −2.4) and a trend toward lower motor scores ( P = .02; β = −6.3 CI −11.7, −0.99), which persisted after adjustment for potential confounders. Conclusion These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.
To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors ...and 2-year neurodevelopmental outcomes.
MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy.
Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW.
At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development.
Background: Uncertainty remains about the rate of specific psychiatric disorders and associated predictive factors for very preterm (VPT) children. The aims of this study were to document rates of ...psychiatric disorders in VPT children aged 7 years compared with term born children, and to examine potential predictive factors for psychiatric diagnoses in VPT children.
Methods: Participants were 177 VPT and 65 term born children. Perinatal medical data were collected, which included brain abnormalities detected using magnetic resonance imaging. The Infant‐Toddler Social‐Emotional Assessment (ITSEA) and Strengths and Difficulties Questionnaire (SDQ) were administered at 2 and 5 years respectively. At 7 years of age, the Developmental and Well‐being Assessment (DAWBA) was used to indicate psychiatric diagnoses.
Results: Compared with term born children, VPT children had three times the odds of meeting criteria for any psychiatric diagnosis at age 7 years (odds ratio 3.03; 95% confidence interval 1.23, 7.47, p = .02). The most common diagnoses were anxiety disorders (11% VPT, 8% term), attention‐deficit/hyperactivity disorder (10% VPT, 3% term) and autism spectrum disorder (4.5% VPT, 0% term). For VPT children, those with severe global brain abnormalities (p = .02), those who displayed social‐emotional problems at age 5 (p = .000) and those with higher social risk at age 7 (p = .001) were more likely to meet criteria for a psychiatric illness at age 7.
Conclusions: Compared with term born children, VPT children have higher rates of psychiatric diagnoses at early school age, predicted by neonatal brain abnormalities, prior social‐emotional problems and social factors.
Abstract
Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have ...set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.
Williams syndrome (WS) is a genetically based neurodevelopmental disorder characterized by intellectual disability and impaired visuospatial recognition. The aim of this study was to analyze the gait ...characteristics of WS children with impaired visuospatial recognition using a three-dimensional gait analysis (3DGA) to clarify the gait adaptation needed to compensate for it. 3DGA was performed in 8 WS children with impaired visuospatial recognition (mean age, 11.8 years) and 9 age-, sex-, height-, and weight-matched controls. Clinical data, fundamental motor tests, and gait variables while walking on a flat surface and walking up a mat were compared between the two groups, and the correlations between variables were analyzed in the WS children. WS children showed impairment of balance function without muscle weakness. In walking on a flat surface, the WS group showed reduced walking speed, short step length, increased variability of step length, increased knee flexion throughout the stance phase, increased horizontal pelvic range of motion (ROM), and a low Gait Deviation Index and a high Gait Profile Score, which are indices of gait quality. In walking up a mat, the WS group showed further reduced walking speed and decreased sagittal hip flexion and ankle dorsiflexion ROM in the swing phase. Impaired balance function was significantly correlated with increased variability of step length and decreased sagittal ankle dorsiflexion ROM in the swing phase. The detailed gait pattern of WS children with impaired visuospatial recognition was presented. These findings show that impaired visuospatial recognition and balance function contribute to gait adaptation.
3C/Ritscher-Schinzel syndrome is characterised by congenital cranio-cerebello-cardiac dysplasia, where
and
are accepted as the causative genes. In combination with the retromer or retriever complex, ...these genes play a role in endosomal membrane protein recycling. We aimed to identify the gene abnormality responsible for the pathogenicity in siblings with a 3C/Ritscher-Schinzel-like syndrome, displaying cranio-cerebello-cardiac dysplasia, coloboma, microphthalmia, chondrodysplasia punctata and complicated skeletal malformation.
Exome sequencing was performed to identify pathogenic variants. Cellular biological analyses and generation of knockout mice were carried out to elucidate the gene function and pathophysiological significance of the identified variants.
We identified compound heterozygous pathogenic variants (c.1097dup; p.Cys366Trpfs*28 and c.2755G>A; p.Ala919Thr) in the
gene, which encodes a core protein of the retriever complex. The identified missense variant lacked the ability to form the retriever complex, and the frameshift variant induced non-sense-mediated mRNA decay, thereby confirming biallelic loss of function of VPS35L. In addition,
knockout cells showed decreased autophagic function in nutrient-rich and starvation conditions, as well as following treatment with Torin 1. We also generated
mice and demonstrated that they were embryonic lethal at an early stage, between E7.5 and E10.5.
Our results suggest that biallelic loss-of-function variants in
underlies 3C/Ritscher-Schinzel-like syndrome. Furthermore, VPS35L is necessary for autophagic function and essential for early embryonic development. The data presented here provide a new insight into the critical role of the retriever complex in fetal development.
Objective
To assess hippocampal signal changes on diffusion‐weighted imaging (DWI) during the acute period after febrile status epilepticus (FSE) and to examine the relationship between DWI and ...subsequent epilepsy.
Methods
A prospective, multicenter study of children with a first episode of FSE was performed. The patients underwent magnetic resonance imaging (MRI) within 3 days of FSE, and signal intensity was evaluated on DWI. Electroencephalography studies within 3 days of FSE were also assessed. Nine to 13 years after FSE, information on subsequent epilepsy was obtained.
Results
Twenty‐two children with FSE were evaluated. DWI showed unilateral hippocampal hyperintensity in six patients (27%). Three of six patients with hippocampal hyperintensity had ipsilateral thalamic hyperintensity. On EEG within 3 days of FSE, five of six patients with hippocampal hyperintensity had ipsilateral focal slowing, spikes, or attenuation. Nine to 13 years later, the outcomes could be determined in five patients with hippocampal hyperintensity and in 10 without. All 5 patients with hippocampal hyperintensity had hippocampal atrophy and developed focal epilepsy, whereas only 1 of 10 patients without hippocampal hyperintensity developed epilepsy (P = 0.002). Ictal semiology was concordant with temporal lobe seizures in all patients. Ipsilateral temporal epileptiform abnormalities were seen on EEG in four of five at last follow‐up.
Significance
Acute DWI hippocampal hyperintensity was seen in 27% of patients with FSE. Acute DWI hyperintensity suggests cytotoxic edema caused by prolonged seizure activity. Hippocampal DWI hyperintensity is related to mesial temporal lobe epilepsy and can be a target of neuroprotective treatments to prevent the onset of epilepsy.
The authors recently reported a novel subsecond analysis method of analyzing EEG-functional MRI (fMRI) to improve the detection rate of epileptic focus. This study aims to validate the utility of ...this method for presurgical evaluation in pharmacoresistant focal epilepsy.
Among 13 patients with focal epilepsy undergoing presurgical examinations including simultaneous EEG-fMRI at 3T, 11 patients had interictal epileptiform discharges (IEDs) during fMRI. The authors used the sequence of topographic maps during the IEDs as a reference to obtain subsecond fMRI activation maps with the same temporal resolution as the EEG data, and constructed "spike-and-slow-wave-activation-summary" (SSWAS) maps that showed the activation frequency of voxels during IEDs. Clusters were defined by thresholding the SSWAS maps (voxel value > 10), and those containing voxels with the top 3 highest activation frequencies were considered significant. Significant hemodynamic responses using conventional event-related (ER) analysis and SSWAS maps were compared with the resection areas and surgical outcomes at 1 year after surgery.
Using ER analysis, 4 (36%) of 11 patients had significant hemodynamic responses. One of 4 patients had significant hemodynamic responses in the resection area and good surgical outcome. Using SSWAS maps, 10 (91%) of 11 patients had significant hemodynamic responses. Six of 10 patients had significant hemodynamic responses in the resection area, and 5 of the 6 patients achieved good surgical outcomes. The remaining 4 patients had significant hemodynamic responses distant from the resection area, and only 1 of the 4 patients achieved good surgical outcomes. The sensitivity, specificity, positive predictive value, and negative predictive value of SSWAS maps were 83.3%, 75.0%, 83.3%, and 75.0%, respectively.
This study demonstrated the clinical utility of SSWAS maps for presurgical evaluation of pharmacoresistant focal epilepsy. The findings indicated that subsecond EEG-fMRI analysis may help surgeons choose the resection areas that could lead to good surgical outcomes.
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