Indication for molecular testing by multiplex ligation-dependent probe amplification in parkinsonism.

BACKGROUND AND PURPOSE: The monogenic forms of Parkinson's disease represent <10% of familial cases and a still lower frequency of sporadic cases. However, guidelines to orient genetic testing are lacking. The aim was to establish the interest of multiplex ligation-dependent probe amplification (MLPA) as a primary screening test and to propose clinical criteria to guide genetic diagnostic tests for patients with suspected Mendelian Parkinson's disease. METHODS: In all, 567 patients with parkinsonism from 547 unrelated families were recruited and two MLPAs were performed for each. All pathogenic G2019S variants in the LRRK2 gene were confirmed by Sanger sequencing and the PRKN gene was screened for a second mutation in the cases of one heterozygous structural variant in the PRKN gene. RESULTS: The performance of MLPA was 51/567 (9%) for the entire cohort and included 27 (4.8%) LRRK2 G2019S mutations, 19 (3.4%) PRKN mutations and five (0.9%) SNCA locus duplications. The variables significantly associated with a positive test in the total cohort were North African ancestry (p < 0.0001), female sex (p = 0.004) and younger age at onset (p < 0.0008). CONCLUSIONS: Retrospective analysis allowed us to refine our indication criteria: (i) North African ancestry, (ii) an age at onset <40 years or (iii) a familial history of parkinsonism with at least one affected first-degree relative. Our study highlights the interest of MLPA testing for other parkinsonism cases with a family history, especially for patients with dementia with Lewy bodies or a multiple-system-atrophy-like phenotype.

Biomechanical mechanisms and centre of pressure trajectory during planned gait termination.

AIM: Although gait initiation has been extensively studied, gait termination has received less attention. In particular, the trajectory of the centre of pressure (CoP) during gait termination, as well as the trajectory's determinants, has not yet been described. The purpose of the present study was to characterize the kinetic components of planned gait termination (including the CoP trajectory) with respect to the various gait events and centre of mass speed and trajectory. METHODS: Thirty healthy subjects were asked to walk along a test track and stop on a force platform while an optoelectronic system recorded temporal and spatial parameters. A total of 90 trials were analysed. RESULTS: Subjects needed two steps to stop on the force platform. The CoP trajectory during gait termination was composed of three phases. During the first phase, the CoP moved forward under the stance foot, which was in contact with the ground. The ground reaction forces exerted a sagittal braking action. The second phase showed a lateral CoP shift and was correlated with braking; this may correspond to anticipatory postural adjustments for gait termination. The third and last phase might correspond to compensatory adjustments before the stance phase. CONCLUSIONS: CoP trajectory is more complex during gait termination than during gait initiation. Gait termination comprises several specific sequences in the gait-stance transition. A better understanding of the kinetic parameters in gait termination should enable us to identify which kinetic parameters could be considered as risk factors for falls.

[Limbic encephalitis: a new paraneoplastic auto-immune manifestation associated with metastatic melanoma?]. / Encéphalite limbique : une nouvelle manifestation auto-immune paranéoplasique associée au mélanome métastatique ?

BACKGROUND: Several studies indicate an association between immune-related manifestations and prolonged survival in metastatic melanoma. Limbic encephalitis driven by immune-mediated disorders may also be observed during the course of certain cancers. PATIENTS AND METHODS: In November 2009, a 60-year-old woman followed up for metastatic melanoma since July 2005 developed rapidly progressive cognitive disorder. Clinical, biological, MRI and electroencephalogram abnormalities resulted in diagnosis of probably paraneoplastic limbic encephalitis in a context of immune-related manifestations although chemotoxicity could not be ruled out. Auto-immunity with hypothyroidism and thrombocytopenia were seen concomitantly. DISCUSSION: To the best of our knowledge, this is the first reported case of probably paraneoplastic limbic encephalitis associated with melanoma, a new example of an immune-related condition associated with prolonged survival in metastatic melanoma.

The multileaf collimator for fast neutron therapy at Louvain-la-Neuve.

The multileaf collimator of the fast neutron therapy facility at Louvain-la-Neuve is described, as well as some of the physics experiments performed in order to evaluate the attenuation of neutron beams in different materials and thus optimize the composition of the collimator leaves. The multileaf collimator consists of two sets of 22 leaves each, which can be moved independently. They are made of iron and their thickness is 95 cm. Seven borated polyethylene disks are located in the distal part of the leaves in order to absorb more efficiently the low-energy component of the neutron spectrum. The width of the leaves is 1 cm at their distal part. The leaves can move 11 cm outwards and 6 cm inwards from their reference position, and field sizes up to 25.7 x 24.8 cm, as well as irregular field shapes, can be obtained. The inner part of the leaves and their two sides are always focused on the target. The complete multileaf collimator can rotate around the beam axis, from -90 degrees to +90 degrees from the reference position. The width of the penumbra (80-20% isodoses) is 0.64 cm and 1.17 cm at the depth of the maximum buildup and at 10 cm in depth respectively, for a 10 x 10 cm field size. The collimator is adequate for the energy of the p(65)+Be neutron beam of Louvain-la-Neuve and has been adapted to the fixed vertical beam. It has been designed following the original plans of Scanditronix, adjusted and fully assembled at the workshop of the Centre de Recherches du Cyclotron (CRC). Systematic measurements were performed in order to optimize the design and the composition of the leaves. In particular the attenuations of the actual beam and of monoenergetic neutron beams were measured in different materials such as iron and polyethylene. Above (upstream) the multileaf collimator, a fixed pre-collimator (iron thickness 50 cm; section 1 x 1 m) defines a conical aperture aligned on the largest opening of the leaves. It contains the two transmission chambers and a 2 cm thick polyethylene layer used for hardening the beam.