Extending the spectrum of AKT1 mosaicism - not just the Proteus syndrome

A five-year-old girl was referred to our department for evaluation of a pigmented birthmark on her right cheek, present unchanged since birth. There was no other past medical history of note and no family history of relevant problems. Cutaneous examination revealed a pigmented keratinocytic epidermal naevus following fine Blaschko's lines on the right cheek and neck (Figure 1), and a solitary café-au-lait macule of 1cm on the lower leg

New vascular classification of port-wine stains: improving prediction of Sturge-Weber risk

Background Facial port-wine stains (PWSs) are usually isolated findings; however, when associated with cerebral and ocular vascular malformations they form part of the classical triad of Sturge–Weber syndrome (SWS). Objectives To evaluate the associations between the phenotype of facial PWS and the diagnosis of SWS in a cohort with a high rate of SWS. Methods Records were reviewed of all 192 children with a facial PWS seen in 2011–13. Adverse outcome measures were clinical (seizures, abnormal neurodevelopment, glaucoma) and radiological [abnormal magnetic resonance imaging (MRI)], modelled by multivariate logistic regression. Results The best predictor of adverse outcomes was a PWS involving any part of the forehead, delineated at its inferior border by a line joining the outer canthus of the eye to the top of the ear, and including the upper eyelid. This involves all three divisions of the trigeminal nerve, but corresponds well to the embryonic vascular development of the face. Bilateral distribution was not an independently significant phenotypic feature. Abnormal MRI was a better predictor of all clinical adverse outcome measures than PWS distribution; however, for practical reasons guidelines based on clinical phenotype are proposed. Conclusions Facial PWS distribution appears to follow the embryonic vasculature of the face, rather than the trigeminal nerve. We propose that children with a PWS on any part of the ‘forehead’ should have an urgent ophthalmology review and a brain MRI. A prospective study has been established to test the validity of these guidelines

Classification of neurological abnormalities in children with congenital melanocytic naevus syndrome identifies magnetic resonance imaging as the best predictor of clinical outcome

Background: The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much wider variation in outcome. Objectives: To establish whether routine MRI of the CNS is a clinically relevant investigation in children with multiple CMN (more than one at birth), and to subclassify radiological abnormalities. Methods: Of 376 patients seen between 1991 and 2013, 289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has been more than one CMN at birth, independent of size and site of the largest naevus. Cutaneous phenotyping and radiological variables were combined in a multiple regression model of long-term outcome measures (abnormal neurodevelopment, seizures, requirement for neurosurgery). Results: Twenty-one per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the most significant predictor of all outcome measures. Abnormalities were subclassified into group 1 ‘intraparenchymal melanosis alone’ (n = 28) and group 2 ‘all other pathology’ (n = 18). Group 1 was not associated with malignancy or death during the study period, even when symptomatic with seizures or developmental delay, whereas group 2 showed a much more complex picture, requiring individual assessment. Conclusions: For screening for congenital neurological lesions a single MRI in multiple CMN is a clinically relevant strategy. Any child with a stepwise change in neurological/developmental symptoms or signs should have an MRI with contrast of the brain and spine to look for new CNS melanoma

An Autonomous Sailboat for Environment Monitoring

The marine environment is constantly at risk from coastal urbanization. The deterioration of coastal and marine environments is evidenced by the decline of mangroves and the biodiversity of such environments and increasing recurrences of algal and jellyfish blooms. There is a lack of environmental data especially in developing countries such as Malaysia to determine the sustainability and impact of the current development on coastal resources. We developed an autonomous sailboat that utilizes the Internet of things technology to collect and analyze ocean water quality data for local authorities to obtain insights into the sustainable development of coastal resources. The USV is equipped with sensors, microcontrollers, and a wireless communication module based on ZigBee standards to allow sending water quality data to a gateway located at the shore. The data collected by the USV will be processed by a cloud server and visualized through user applications

Developmental conduction aphasia after neonatal stroke

Objective Impairment of speech repetition following injury to the dorsal language stream is a feature of conduction aphasia, a well-described “disconnection syndrome” in adults. The impact of similar lesions sustained in infancy has not been established. Methods We compared language outcomes in term-born individuals with confirmed neonatal stroke (n = 30, age = 7–18 years, left-sided lesions in 21 cases) to matched controls (n = 40). Injury to the dorsal and/or ventral language streams was assessed using T1- and T2-weighted magnetic resonance imaging (MRI) and diffusion tractography. Language lateralization was determined using functional MRI. Results At the group level, left dorsal language stream injury was associated with selective speech repetition impairment for nonwords (p = 0.021) and sentences (p < 0.0001). The majority of children with significant repetition impairment had retained left hemisphere language representation, but right hemisphere dominance was correlated with minimal or absent repetition deficits. Post hoc analysis of the repetition-impaired group revealed additional language-associated deficits, but these were more subtle and variable. Interpretation We conclude that (1) despite the considerable plasticity of the infant brain, early dorsal language stream injury can result in specific and long-lasting problems with speech repetition that are similar to the syndrome of conduction aphasia seen in adults; and (2) language reorganization to the contralateral hemisphere has a protective effect. Ann Neurol 2018;83:664–675 Ann Neurol 2018;83:664–67

Starting a movement: An epidemiological audit into the distribution and determinants of Clostridium Difficele infection at an Australian tertiary hospital site

BackgroundThe emergence of hypervirulent strains of Clostridioides (Clostridium) difficile over the past few decades has cemented C. difficile infection (CDI) as the most common cause of nosocomial infectious diarrhoea within Australia. This report was initiated to better understand the burden of disease at the Bankstown-Lidcombe Hospital through analysis of CDI incidence, risk factors, and treatment.AimsThe specific objectives of this study were two-fold; 1) to determine the prevalence of hospitalised patients affected with CDI and 2) to identify risk factors for CDI in hospitalised patients.Methods A retrospective review of all consecutive CDI cases at the Bankstown-Lidcombe Hospital between 1 July 2014 and 31 December 2018 was performed. CDI incidence was calculated based on the number of CDI cases observed per 10,000 patient days. Annual incidence and predisposing antibiotics to CDI were compared via univariate analysis and Student t-tests. Treatment for CDI was compared using contingency analysis via Pearson’s chi-squared analysis. Results The CDI diagnoses ranged from 3.2–4.6 (as a proportion of 10,000 occupied bed days) throughout 2014 and 2018. There was a significant decrease in CDI associated with Macrolides between 2017 and 2018 (p=0.03). There was a significant rise in CDI associated with Beta lactamase inhibitors and Penicillins (e.g., Tazobactam/Piperacillin). The majority of CDI patients were treated with single therapy metronidazole during their hospital stays.ConclusionCDI risk minimisation presents a significant challenge to all hospital departments. This audit highlights the importance of antibiotic usage influencing in-patient CDI cases and the vital role of multidisciplinary teams (microbiologists, pathologists, physicians, surgeons and pharmacists) in managing and monitoring these patients

TRNT1 deficiency: clinical, biochemical and molecular genetic features

BACKGROUND: TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs). RESULTS: We investigated four patients from two families with infantile-onset cyclical, aseptic febrile episodes with vomiting and diarrhoea, global electrolyte imbalance during these episodes, sideroblastic anaemia, B lymphocyte immunodeficiency, retinitis pigmentosa, hepatosplenomegaly, exocrine pancreatic insufficiency and renal tubulopathy. Other clinical features found in children include sensorineural deafness, cerebellar atrophy, brittle hair, partial villous atrophy and nephrocalcinosis. Whole exome sequencing and bioinformatic filtering were utilised to identify recessive compound heterozygous TRNT1 mutations (missense mutation c.668T>C, p.Ile223Thr and a novel splice mutation c.342+5G>T) segregating with disease in the first family. The second family was found to have a homozygous TRNT1 mutation (c.569G>T), p.Arg190Ile, (previously published). We found normal mitochondrial translation products using passage matched controls and functional perturbation of 3' CCA addition to mitochondrial tRNAs (tRNA(Cys), tRNA(LeuUUR) and tRNA(His)) in fibroblasts from two patients, demonstrating a pathomechanism affecting the CCA addition to mt-tRNAs. Acute management of these patients included transfusion for anaemia, fluid and electrolyte replacement and immunoglobulin therapy. We also describe three-year follow-up findings after treatment by bone marrow transplantation in one patient, with resolution of fever and reversal of the abnormal metabolic profile. CONCLUSIONS: Our report highlights that TRNT1 mutations cause a spectrum of disease ranging from a childhood-onset complex disease with manifestations in most organs to an adult-onset isolated retinitis pigmentosa presentation. Systematic review of all TRNT1 cases and mutations reported to date revealed a distinctive phenotypic spectrum and metabolic and other investigative findings, which will facilitate rapid clinical recognition of future cases

Interhemispheric temporal lobe connectivity predicts language impairment in adolescents born preterm.

Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses showed that a combination of anatomical measures of temporal interhemispheric connectivity (through the splenium of the corpus callosum and anterior commissure) explained 57% of the variance in language abilities. This supports recent theories emphasizing the importance of interhemispheric connections for language, particularly in the developing brain