Analysis of Fine Motor Skills in Essential Tremor: Combining Neuroimaging and Handwriting Biomarkers for Early Management

Essential tremor (ET) is a highly prevalent neurological disorder characterized by action-induced tremors involving the hand, voice, head, and/or face. Importantly, hand tremor is present in nearly all forms of ET, resulting in impaired fine motor skills and diminished quality of life. To advance early diagnostic approaches for ET, automated handwriting tasks and magnetic resonance imaging (MRI) offer an opportunity to develop early essential clinical biomarkers. In this study, we present a novel approach for the early clinical diagnosis and monitoring of ET based on integrating handwriting and neuroimaging analysis. We demonstrate how the analysis of fine motor skills, as measured by an automated Archimedes’ spiral task, is correlated with neuroimaging biomarkers for ET. Together, we present a novel modeling approach that can serve as a complementary and promising support tool for the clinical diagnosis of ET and a large range of tremors.This work was supported in part by the Universidad del País Vasco/Euskal Herriko Unibertsitatea, the University of Cambridge, PPG 17/51 and GIU 092/19, the Basque government (Saiotek SA-2010/00028, ELEKIN, Engineering and Society and Bioengineering Research Groups, GIC18/136, and ELKARTEK 18/99, 20/81), ‘‘Ministerio de Ciencia e Innovación’’ (SAF201677758R), FEDER funds, DomusVi Foundation (FP18/76), and the government of Gipuzkoa (HELENA, SABRINA, DG18/14-23, DG19/29, DG20/25 projects). This work is also based upon the work from COST Actions CA18106 and CA15225, supported by COST (European Cooperation in Science and Technology)

An improved formulation of the relativistic hydrodynamics equations in 2D Cartesian coordinates

A number of astrophysical scenarios possess and preserve an overall cylindrical symmetry also when undergoing a catastrophic and nonlinear evolution. Exploiting such a symmetry, these processes can be studied through numerical-relativity simulations at smaller computational costs and at considerably larger spatial resolutions. We here present a new flux-conservative formulation of the relativistic hydrodynamics equations in cylindrical coordinates. By rearranging those terms in the equations which are the sources of the largest numerical errors, the new formulation yields a global truncation error which is one or more orders of magnitude smaller than those of alternative and commonly used formulations. We illustrate this through a series of numerical tests involving the evolution of oscillating spherical and rotating stars, as well as shock-tube tests.Comment: 19 pages, 9 figure

The Einstein Toolkit: A Community Computational Infrastructure for Relativistic Astrophysics

We describe the Einstein Toolkit, a community-driven, freely accessible computational infrastructure intended for use in numerical relativity, relativistic astrophysics, and other applications. The Toolkit, developed by a collaboration involving researchers from multiple institutions around the world, combines a core set of components needed to simulate astrophysical objects such as black holes, compact objects, and collapsing stars, as well as a full suite of analysis tools. The Einstein Toolkit is currently based on the Cactus Framework for high-performance computing and the Carpet adaptive mesh refinement driver. It implements spacetime evolution via the BSSN evolution system and general-relativistic hydrodynamics in a finite-volume discretization. The toolkit is under continuous development and contains many new code components that have been publicly released for the first time and are described in this article. We discuss the motivation behind the release of the toolkit, the philosophy underlying its development, and the goals of the project. A summary of the implemented numerical techniques is included, as are results of numerical test covering a variety of sample astrophysical problems.Comment: 62 pages, 20 figure

Parkin and LRRK2/Dardarin Mutations in Early Onset Parkinson’s Disease in the Basque Country (Spain)

8 páginas, 2 tablas.We have performed a complete screening of the Parkin gene (PRKN2) and looked for p.Gly2019Ser (G2019S) and p.Arg1441Gly (R1441G) LRRK2/dardarin gene mutations in twenty seven patients with Parkinson’s disease (PD) with an age at onset younger than 50 years (EOPD), living in Gipuzkoa (Basque Country, Spain). Thirteen of them (48%) were PRKN2 mutation carriers. The c.255-256DelA mutation was the most frequent, followed by a deletion involving exons 3 and 4. A deletion involving exons 3 and 12 of the PRKN2 gene and R1441G LRRK2 mutation was found together in one PD patient. Four out of fourteen PRKN2 negative patients carried the p.G2019S mutation. Both PRKN2 mutation carriers and non-carriers presented frequently with family history (10 PRKN2 mutation carriers and 8 PRKN2 non-carriers); in fact, five patients without a known gene mutation had a first degree relative affected, suggesting another monogenic disease. PRKN2 carriers presented with a younger age at onset (36.7 vs. 41.7) and more benign disease progression. Indeed, those PD patients younger than forty who initially presented with unilateral tremor became shortly bilateral. Relatively, symmetric parkinsonism and slow disease progression carried more frequently PRKN2 mutations than patients with unilateral akinetic rigid parkinsonism and age at onset later than 40 years. As expected in a recessive disease, PRKN2 patients present more often with affected siblings and unaffected patients. The G2019S LRRK2 mutation, less prevalent than R1441G in our area, may be also a frequent cause of PD in EOPD (4 patients).Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (PI070660), Eusko Jaurlaritza (Osasun Saila) (2006111003), Gipuzkoako Foru Aldundia, Fundación de Investigación Médica Mutua Madrileña, Ilundain Fundazioa.Peer reviewe

Antiganglioside antibodies in acute self-limiting ataxic neuropathy: incidence and significance

Antidisialosyl antibodies have been previously associated to chronic and acute ataxic neuropathies. We studied the presence of these antibodies in nine patients with acute self-limiting ataxic neuropathy (ASLAN) using ELISA and TLC immunodetection. One patient showed serum IgG immunoreactivity against gangliosides GD3 and GQ1b. The patient's IgG was able to bind to the nodes of Ranvier on frozen human dorsal root. Our studies confirmed that antidisialosyl reactivity is associated to ataxic neuropathy and its specific binding to the dorsal root could explain the predominant sensory involvement. Nevertheless, the low incidence of this reactivity indicates that a different pathogenic mechanism should be involved in most ASLAN patients