ObjectiveTo characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype–phenotype correlation.MethodsWe analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations.ResultsChildhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype–phenotype correlation did not emerge.ConclusionCOL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.

Background There is lack of guidance on specific CT protocols for imaging patients with coronavirus disease 2019 (COVID-19) pneumonia. Purpose To assess international variations in CT utilization, protocols, and radiation doses in patients with COVID-19 pneumonia. Materials and Methods In this retrospective data collection study, the International Atomic Energy Agency (IAEA) coordinated a survey between May and July 2020 regarding CT utilization, protocols, and radiation doses from 62 healthcare sites in 34 countries across five continents for CT exams performed in COVID-19 pneumonia. The questionnaire obtained information on local prevalence, method of diagnosis, most frequent imaging, indications for CT, and specific policies on use of CT in COVID-19 pneumonia. Collected data included general information (patient age, weight, clinical indication), CT equipment (CT make and model, year of installation, number of detector rows), scan protocols (body region, scan phases, tube current and potential), and radiation dose descriptors (CT dose index (CTDI vol ) and dose length product (DLP)). Descriptive statistics and generalized estimating equations were performed. Results Data from 782 patients (median age (interquartile range) of 59(15) years) from 54 healthcare sites in 28 countries were evaluated. Less than one-half of the healthcare sites used CT for initial diagnosis of COVID-19 pneumonia and three-fourth used CT for assessing disease severity. CTDI vol varied based on CT vendors (7-11mGy, p<0.001), number of detector-rows (8-9mGy, p<0.001), year of CT installation (7-10mGy, p=0.006), and reconstruction techniques (7-10mGy, p=0.03). Multiphase chest CT exams performed in 20% of sites (11 of 54) were associated with higher DLP compared with single-phase chest CT exams performed in 80% (43 of 54 sites) (p=0.008). Conclusion CT use, scan protocols, and radiation doses in patients with COVID-19 pneumonia showed wide variation across healthcare sites within the same and different countries. Many patients were scanned multiple times and/or with multiphase CT scan protocols. See also the editorial by Lee .

The value of CBF velocity changes to predict poor outcome in asphyxiated infants is low 2-6 h after asphyxia, but increases by the age of 12 ho.

Epileptic encephalopathies represent a clinically and genetically heterogeneous group of disorders, majority of which are of unknown etiology. We used whole-exome sequencing of a parent-offspring trio to identify the cause of early infantile epileptic encephalopathy in a boy with neonatal seizures, movement disorders, and multiple congenital anomalies who died at the age of 17 months because of respiratory illness and identified a de novo heterozygous missense mutation (c.3979A>G; p.Ile1327Val) in SCN8A (voltage-gated sodium-channel type VIII alpha subunit) gene. The variant was confirmed in the proband with Sanger sequencing. Because the clinical phenotype associated with SCN8A mutations has previously been identified only in a few patients with or without epileptic seizures, these data together with our results suggest that mutations in SCN8A can lead to early infantile epileptic encephalopathy with a broad phenotypic spectrum. Additional investigations will be worthwhile to determine the prevalence and contribution of SCN8A mutations to epileptic encephalopathies.

Plasticity of language function after brain damage can depend on maturation of the brain. Children with left-hemisphere perinatal (n = 7) or childhood stroke (n = 5) and 12 controls were investigated using functional magnetic resonance imaging. The verb generation and the sentence comprehension tasks were employed to activate the expressive and receptive language areas, respectively. Weighted laterality indices were calculated and correlated with results assessed by neuropsychological test battery. Compared to controls, children with childhood stroke showed significantly lower mean scores for the expressive (P < .05) and receptive (P = .05) language tests. On functional magnetic resonance imaging they showed left-side cortical activation, as did controls. Perinatal stroke patients showed atypical right-side or bilateral language lateralization during both tasks. Negative correlation for stroke patients was found between scores for expressive language tests and laterality index during the verb generation task. (Re)organization of language function differs in children with perinatal and childhood stroke and correlates with neurocognitive performance.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation.

Objective. The purpose of this study was to evaluate the changes in Doppler blood flow velocity (BFV) in cerebral and visceral arteries during infancy. Methods. The BFV was measured in 37 healthy term neonates in the anterior cerebral artery (ACA), middle cerebral artery (MCA), basilar artery, internal carotid artery (ICA), celiac artery (CA), superior mesenteric artery (SMA), and renal artery (RA). Results. The mean BFV increased and the resistive index decreased (P < .05) in all cerebral arteries, SMA, and CA by the age of 12 to 23.9 hours and in the RA by the age of 24 to 35.9 hours compared with 2 to 11.9 hours. A further significant increase (P < .05) of the mean BFV occurred in all arteries except the ICA and CA by the age of 72 to 120 hours compared with 12 to 23.9 hours. By the age of 21 to 59 days, the mean BVF doubled in all investigated arteries compared with 2 to 11.9 hours, with a further significant increase (P < .05) by the age of 150 to 240 days in cerebral and renal arteries. There was no correlation between the mean blood pressure (BP) and mean BFV in the ACA and MCA. However, there was a positive correlation (r ≥ 0.5; P < .05) between the BP and BFV in the RA and SMA at the age of 12 to 23.9 hours. Conclusions. A significant increase in the cerebral and visceral BFV occurs normally throughout infancy, with the visceral BFV affected by BP changes during the first day of life. Key words: cerebral blood flow velocity; neonate; sonography; visceral blood flow velocity. oppler sonography is a noninvasive method that allows repeated and safe assessment of hemodynamics in neonatal units. Several studies have shown that a pulsed Doppler technique can be used to examine the pattern of blood flow velocity (BFV) in major vessels of the brain 1 as well as visceral organs 2 in neonates with good reproducibility. Several studies have followed the BFV in different cerebral 3-6 and visceral 7-11 arteries during cardiovascular adaptation of the neonate within the first week of life. These studies typically evaluated a single organ. A few cross-sectional studies have followed the changes of the cerebral BFV in neonates up to the first 20 days of life 12 and infants older than 30 days. 13,14 Cross-sectional studies of the BFV in renal arteries have also been performed in infants older than 30 days. 7,[15][16][17] To our knowledge there have been no studies looking at the normal preprandial splanchic BFV in infants older than 1 month.

In this national cohort, poor long-term neurodevelopmental outcome after perinatal ischemic stroke was seen irrespective of the vascular type or time of diagnosis of stroke. However, the spectrum of neurological deficits is different after perinatal AIS and PVI, with combined deficits more common among children following AIS.