From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG)

Congenital disorders of glycosylation are a growing group of inborn errors of protein glycosylation. Cardiac involvement is frequently observed in the most common form, PMM2-CDG, especially hypertrophic cardiomyopathy. Dilated cardiomyopathy, however, has been only observed in a few CDG subtypes, usually with a lethal outcome. We report on cardiac pathology in nine patients from three unrelated Israeli families, diagnosed with dolichol kinase deficiency, due to novel, homozygous DK1 gene mutations. The cardiac symptoms varied from discrete, mild dilation to overt heart failure with death. Two children died unexpectedly with acute symptoms of heart failure before the diagnosis of DK1-CDG and heart transplantation could take place. Three other affected children with mild dilated cardiomyopathy at the time of the diagnosis deteriorated rapidly, two of them within days after an acute infection. They all went through successful heart transplantation; one died unexpectedly and 2 others are currently (after 1-5 years) clinically stable. The other 4 children diagnosed with mild dilated cardiomyopathy are doing well on supportive heart failure therapy. In most cases, the cardiac findings dominated the clinical picture, without central nervous system or multisystem involvement, which is unique in CDG syndrome. We suggest to test for DK1-CDG in patients with dilated cardiomyopathy. Patients with discrete cardiomyopathy may remain stable on supportive treatment while others deteriorate rapidly. Our paper is the first comprehensive study on the phenotype of DK1-CDG and the first successful organ transplantation in CDG syndrome.status: publishe

Externally provoked freezing of gait in open runways in advanced Parkinson's disease results from motor and mental collapse.

Contains fulltext : 70316.pdf (publisher's version ) (Closed access)Freezing of gait (FOG) in Parkinson's disease (PD) is defined as a sudden inability to maintain effective stepping movements. However, its pathophysiology remains unclear. The objectives are: (1) To assess the contribution of both spatial (walking speed, stride length) and temporal parameters (cadence, stride time) and their coefficients of variation to the genesis of FOG in PD. (2) To evaluate whether and how externally imposed modifications of self-determined gait would elicit FOG. We included ten patients with advanced PD, and with daily off drug FOG episodes. We focused on walking in an open runway. For each subject, we manipulated gait by externally imposing four changes in walking speed and four changes in cadence. FOG episodes, often with a long duration of more than 5-s, were observed mostly under conditions with a high imposed cadence. The steps that immediately preceded these episodes were mainly characterized by an increase in cadence and an increase in stride length variability. The results also underscore that FOG can be elicited in a laboratory setting when patients are placed under considerable strain, at least in advanced stages of PD. Patients were unable to adequately negotiate the extreme imposed cadence condition, and this resulted in frequent FOG episodes, even while walking in an open runway. Placing advanced PD patients into extreme imposed conditions leads to a motor wise and mental collapse response, culminating in FOG. Future work should establish the relevance of these findings for the more common forms of FOG, including brief episodes during turning or gait initiation

Modelling the plastic anisotropy of metals

peer reviewedThis work is an overview of available constitutive laws used in finite element codes to model elastoplastic metal anisotropy behaviour at a macroscopic level. It focuses on models with strong links with the phenomena occurring at microscopic level. Starting from macroscopic well-known models such as Hill or Barlat’s laws, the limits of these macroscopic phenomenological yield loci are defined, which helps to understand the current trends to develop micro-macro laws. The characteristics of micro-macro laws, where physical behaviour at the level of grains and crystals are taken into account to provide an average macroscopic answer are described. Some basic knowledge about crystal plasticity models is given for non-specialists, so every one can understand the microscopic models used to reach macroscopic values. The assumptions defining the transition between the microscopic and macroscopic scales are summarized: full constraint or relaxed Taylor’s model, self-consistent approach, homogenisation technique. Then, the two generic families of micromacro models are presented: macroscopic laws without yield locus where computations on discrete set of crystals provide the macroscopic material behaviour and macroscopic laws with macroscopic yield locus defined by microscopic computations. The models proposed by Anand, Dawson, Miehe, Geers, Kalidindi or Nakamachi belong to the first family when proposals by Montheillet, Lequeu, Darrieulat, Arminjon, Van Houtte, Habraken enter the second family. The characteristics of all these models are presented and commented. This paper enhances interests of each model and suggests possible future developments