Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.

In the large group of genetically undetermined infantile-onset mitochondrial encephalopathies, multiple defects of mitochondrial DNA-related respiratory-chain complexes constitute a frequent biochemical signature. In order to identify responsible genes, we used exome-next-generation sequencing in a selected cohort of patients with this biochemical signature. In an isolated patient, we found two mutant alleles for EARS2, the gene encoding mitochondrial glutamyl-tRNA synthetase. The brain magnetic resonance imaging of this patient was hallmarked by extensive symmetrical cerebral white matter abnormalities sparing the periventricular rim and symmetrical signal abnormalities of the thalami, midbrain, pons, medulla oblongata and cerebellar white matter. Proton magnetic resonance spectroscopy showed increased lactate. We matched this magnetic resonance imaging pattern with that of a cohort of 11 previously selected unrelated cases. We found mutations in the EARS2 gene in all. Subsequent detailed clinical and magnetic resonance imaging based phenotyping revealed two distinct groups: mild and severe. All 12 patients shared an infantile onset and rapidly progressive disease with severe magnetic resonance imaging abnormalities and increased lactate in body fluids and proton magnetic resonance spectroscopy. Patients in the 'mild' group partially recovered and regained milestones in the following years with striking magnetic resonance imaging improvement and declining lactate levels, whereas those of the 'severe' group were characterized by clinical stagnation, brain atrophy on magnetic resonance imaging and persistent lactate increases. This new neurological disease, early-onset leukoencephalopathy with thalamus and brainstem involvement and high lactate, is hallmarked by unique magnetic resonance imaging features, defined by a peculiar biphasic clinical course and caused by mutations in a single gene, EARS2, expanding the list of medically relevant defects of mitochondrial DNA translation.

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Backgroud: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, healthcare workers (HCWs) have been the workers most likely to contract the disease. Intensive focus is therefore needed on hospital strategies that minimize exposure and diffusion, confer protection and facilitate early detection and isolation of infected personnel. Methods: To evaluate the early impact of a structured risk-management for exposed COVID-19 HCWs and describe how their characteristics contributed to infection and diffusion. Socio-demographic and clinical data, aspects of the event-exposure (date, place, length and distance of exposure, use of PPE) and details of the contact person were collected. Results: The 2411 HCWs reported 2924 COVID-19 contacts. Among 830 HCWs who were at 'high or medium risk', 80 tested positive (9.6%). Physicians (OR=2.03), and non-medical services resulted in an increased open access www.lamedicinadellavoro.it covid-19 infection and diffusion 185

Interictal spike detection is a time-consuming, low-efficiency task, but is important to epilepsy diagnosis. Automated systems reported to date usually have their practical efficacy compromised by elevated rates of false-positive detections per minute, which are caused mainly by the influence of artifacts (such as noise activity and ocular movements) and by the adoption of single or simple approaches. This work describes the development of a hybrid system for automatic detection of spikes in long-term electroencephalogram (EEG), named System for Automatic Detection of Epileptiform Events in EEG (SADE(3)), which uses wavelet transform, neural networks and artificial intelligence procedures to recognize epileptic and to reject non-epileptic activity. The system's pre-processing stage filters the EEG epochs with the Coiflet wavelet function, which showed the closest correlation to epileptogenic (EPG) activity, in opposition to some other wavelet functions that did not correlate with these events. In contrast to current attempts using continuous wavelet transform, we chose to work with fast wavelet transform to reduce processing time and data volume. Detail components at appropriate decomposition levels were used to accentuate spikes, sharp waves, high-frequency noise activity and ocular artifacts. These four detailed components were used to train four specialized neural networks, designed to detect and classify the EPG and non-EPG events. An expert module analyzes the networks' outputs, together with multichannel and context information and concludes the detection. The system was evaluated with 126,000 EEG epochs, obtained from seven different patients during long-term monitoring, under diverse behavior and mental states. More than 6,721 spikes and sharp waves were previously identified by three experienced human electroencephalographers. In these tests, the SADE(3) system simultaneously achieved 70.9% sensitivity, 99.9% specificity and a rate of 0.13 false-positives per minute, indicating its usefulness and low vulnerability to artifact influence. After tests, the SADE(3) system showed itself to be able to process bipolar cortical EEG records, from long-term monitoring, up to 32 channels, without any data preparation or event positioning. At the same time, SADE(3) revealed a high capacity to reject non-epileptic paroxysms, robustness in relation to a variety of spike morphologies, flexibility in adjustment of performance rates and the capacity to actually save time during EEG reading. Furthermore, it can be adapted to other applications for pattern recognition, with simple adjustments.