Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia.

Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.

Four-week experimental plus 1-week taper period using live high train low does not alter muscle glycogen content.

This study aimed to investigate the effects of a 4-week live high train low (LHTL; FiO2 ~ 13.5%), intervention, followed by a tapering phase, on muscle glycogen concentration. Fourteen physically active males (28 ± 6 years, 81.6 ± 15.4 kg, 179 ± 5.2 cm) were divided into a control group (CON; n = 5), and the group that performed the LHTL, which was exposed to hypoxia (LHTL; n = 9). The subjects trained using a one-legged knee extension exercise, which enabled four experimental conditions: leg training in hypoxia (TLHYP); leg control in hypoxia (CLHYP, n = 9); leg trained in normoxia (TLNOR, n = 5), and leg control in normoxia (CLNOR, n = 5). All participants performed 18 training sessions lasting between 20 and 45 min [80-200% of intensity corresponding to the time to exhaustion (TTE) reached in the graded exercise test]. Additionally, participants spent approximately 10 h day-1 in either a normobaric hypoxic environment (14.5% FiO2; ~ 3000 m) or a control condition (i.e., staying in similar tents on ~ 530 m). Thereafter, participants underwent a taper protocol consisting of six additional training sessions with a reduced training load. SpO2 was lower, and the hypoxic dose was higher in LHTL compared to CON (p < 0.001). After 4 weeks, glycogen had increased significantly only in the TLNOR and TLHYP groups and remained elevated after the taper (p < 0.016). Time to exhaustion in the LHTL increased after both the 4-week training period and the taper compared to the baseline (p < 0.001). Although the 4-week training promoted substantial increases in muscle glycogen content, TTE increased in LHTL condition.

Imaging Aspects of the Hippocampus.

The hippocampus is one of the most sophisticated structures in the brain, owing to its complex anatomy, intriguing functions, relationship with other structures, and relevant associated symptoms. Despite being a structure analyzed for centuries, its anatomy and physiology in the human body are still being extensively studied, as well as associated pathologic conditions and potential biomarkers. It can be affected by a broad group of diseases that can be classified as congenital, degenerative, infectious or inflammatory, neoplastic, vascular, or toxic-metabolic disease. The authors present the anatomy and close structures, function, and development of the hippocampus, as well as an original algorithm for imaging diagnosis. The algorithm includes pathologic conditions that typically affect the hippocampus and groups them into nodular (space occupying) and nonnodular pathologic conditions, serving as a guide to narrow the differential diagnosis. MRI is the imaging modality of choice for evaluation of the hippocampus, and CT and nuclear medicine also improve the analysis. The MRI differential diagnosis depends on anatomic recognition and careful characterization of associated imaging findings such as volumetric changes, diffusion restriction, cystic appearance, hyperintensity at T1-weighted imaging, enhancement, or calcification, which play a central role in diagnosis along with clinical findings. Some pathologic conditions arising from surrounding structures such as the amygdala are also important to recognize. Pathologic conditions of the hippocampus can be a challenge to diagnose because they usually manifest as similar clinical syndromes, so the imaging findings play a potential role in guiding the final diagnosis. Online supplemental material is available for this article. ©RSNA, 2022.

Urban critical infrastructure disruption after a radiological dispersive device event.

This study aims to evaluate the impacts of the activation of a hypothetical radiological dispersal device (RDD) on the urban critical infrastructure (health facilities and public transport). A densely populated urban region was chosen as a scenery. Additionally, the influence of local environmental factors in the post-detonation process was verified. The source term was Cs-137 due to its mobility in the environment and relative ease of access. The approach used for the evaluation of the consequences was a computer simulation by Gaussian modeling. The HotSpot Health Physics Codes software was applied in conjunction with the RESRAD-RDD software. The results suggest that there is a strong influence of the local atmospheric stability classes (Pasquill-Gifford classes) on both the total equivalent effective dose (TEDE) and soil contamination. Consequently, the impacts on critical urban infrastructure follow the same trend. The method used for comparing the simulated and reference limits was the proportional ratio. All calculated values for radioactive contamination were divided by the reference value adopted by the RESRAD-RDD model for urban critical infrastructure. The results indicate that the information compiled is useful to support the decision-making process, although it is not sufficient to provide care and support for longer periods than those considered in the initial response phase.

The vertical radiation dose profile and decision-making in a simulated urban event.

A radiological dispersal device (RDD) is built using an explosive device laced with radioactive materials. The RDD appears as a speculative radiological weapon with the aim of spreading radioactive material across an inhabited area. This study seeks to evaluate how the official decision-making process is influenced by the radiation vertical profile dose, using the hypothetical scenario of a simulated RDD detonation in a densely populated urban area. A simulated plume of strong radiation was generated from the explosion site, contaminating the surrounding area. Several atmospheric conditions impact on the contamination. However, this study focusses on the following main variables considered by HotSpot for a conservative simulation: (a) the atmospheric stability conditions (Pasquill-Gifford - PG classes); (b) the explosive power, and (c) the source-term. Gaussian modeling was used for its speed, and for its capacity to estimate the time-integrated atmospheric concentration of an aerosol at any point in 3D space. The simulation provided information about four main outcomes: (a) contamination plume area; (b) radiological risk dependency on PG classes; (c) total effective dose equivalent (TEDE) with a possible dependence on receptor height; and (d) potentially affected population's size. The findings suggest that a protocolled response from authorities should be implemented in order to effectively follow possible changes in the PG class. Which, in turn, may negatively impact the decision-making process.

Support to triage and public risk perception considering long-term response to a Cs-137 radiological dispersive device scenario.

A radiological dispersive device (RDD) spreads radioactive material, complicates the treatment of physical injuries, raises cancer risk, and induces disproportionate fear. Simulating such an event enables more effective and efficient utilization of the triage and treatment resources of staff, facilities, and space. Fast simulation can give detail on events in progress or future events. The resources for triage and treatment of contaminated trauma victims can differ for pure exposure individuals, while discouraging the "worried well" from presenting in the crisis phase by media announcement would relieve pressure on hospital facilities. The proposed methodology integrates capabilities from different platforms in a convergent way composed of three phases: (a) scenario simulation, (b) data generation, and (c) risk assessment for triage focused on follow-up epidemiological assessment. Simulations typically indicate that most of the affected population does not require immediate medical assistance. Medical triage for the few severely injured and the radiological triage to diminish the contamination with radioactivity will always be the priority. For this study, however, higher priorities should be given to individuals from radiological "warm" and "hot" zones as required by risk criteria. The proposed methodology could thus help to (a) filter and reduce the number of individuals to be attended, (b) optimize the prioritization of medical care,