Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies

Ataxia with ocular motor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia (ARCA) associated with oculomotor apraxia, hypoalbuminaemia and hypercholesterolaemia. The gene APTX, which encodes aprataxin, has been identified recently. We studied a large series of 158 families with non-Friedreich progressive ARCA. We identified 14 patients (nine families) with five different missense or truncating mutations in the aprataxin gene (W279X, A198V, D267G, W279R, IVS5+1), four of which were new. We determined the relative frequency of AOA1 which is 5%. Mutation carriers underwent detailed neurological, neuropsychological, electrophysiological, oculographic and biological examinations, as well as brain imaging. The mean age at onset was 6.8 +/- 4.8 years (range 2-18 years). Cerebellar ataxia with cerebellar atrophy on MRI and severe axonal sensorimotor neuropathy were present in all patients. In contrast, oculomotor apraxia (86%), hypoalbuminaemia (83%) and hypercholesterolaemia (75%) were variable. Choreic movements were frequent at onset (79%), but disappeared in the course of the disease in most cases. However, a remarkably severe and persistent choreic phenotype was associated with one of the mutations (A198V). Cognitive impairment was always present. Ocular saccade initiation was normal, but their duration was increased by the succession of multiple hypometric saccades that could clinically be confused with 'slow saccades'. We emphasize the phenotypic variability over the course of the disease. Cerebellar ataxia and/or chorea predominate at onset, but later on they are often partially masked by severe neuropathy, which is the most typical symptom in young adults. The presence of chorea, sensorimotor neuropathy, oculomotor anomalies, biological abnormalities, cerebellar atrophy on MRI and absence of the Babinski sign can help to distinguish AOA1 from Friedreich's ataxia on a clinical basis. The frequency of chorea at onset suggests that this diagnosis should also be considered in children with chorea who do not carry the IT15 mutation responsible for Huntington's disease

Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes

PLASTIC DEFORMATION OF II-VI COMPOUNDS WITH SPHALERITE STRUCTURE : EXAMPLE ZnSe, ZnTe

Deux composés II-VI de structure cubique blende, le ZnSe (ao = 5,667 Å, facteur d'ionicité fi = 0 ,676) et le ZnTe (ao = 6,101 Å, fi = 0,546) ont été déformés plastiquement et les dislocations introduites ont été étudiées par MET. Les échantillons contenant une faible densité de dislocations ont été pré-déformés à 588 K pour le ZnSe et 430 K pour le ZnTe, puis déformés à 293 K pour les deux composés. Dans cette gamme de température, les paramètres d'activation montrent que le mécanisme de Peierls contrôle la déformation. Pour les deux composés, l'effet photoplastique est mis en évidence. Les dislocations glissiles sont étudiées par la méthode des faisceaux faibles. Les mesures de largeur de dissociation permettent de calculer l'énergie de défaut d'empilement. Comme pour les composés III-V la faible valeur de l'énergie de défaut d'empilement réduite peut être reliée au facteur d'ionicité.Two compounds with the sphalerite structure, ZnSe (ao = 5.667 Å, ionicity factor fi = 0.676) and Zn-Te (ao = 6.101 Å, fi = 0.546) have been plastically deformed and the induced dislocation substructure has been studied by TEM. The samples with low dislocation density have been pre-deformed at 588 K for ZnSe and at 430 K for ZnTe and then deformed at lower temperature, 293 K for the two compounds. The activation parameters show that in the temperature range, Peierls friction stresses control the deformation. For the two compounds, the photoplastic effect is evidenced. Using weak-beam electron microscopy the glide dislocations are studied. From the measured dissociation width the stacking fault energy is calculated. As for the III-V compounds the low value of the reduced stacking fault energy can be related to the bond ionicity

Effet électro-optique dans les cristaux de ZnSe

Nous avons préparé par une méthode de Piper et Polich modifiée des mono cristaux cubiques de ZnSe de bonne qualité optique et qui présentent un effet électro-optique linéaire. L'étude expérimentale de cet effet a permis de constater que le coefficient électro-optique r41 du ZnSe varie avec la longueur d'onde (0,5 μ < λ < 0,6 μ), mais que par contre l'intensité de la modulation optique semble indépendante de λ et ne dépend que du champ électrique appliqué au cristal

OBSERVATIONS OF STRUCTURAL DEFECTS IN FERRITES WITH SPINEL (Ni0.66Fe2.34O4) AND GARNET (Y3Fe5O12) STRUCTURES

On rend compte d'observations par topographie X et microscopie électronique de défauts de structure dans des monocristaux de ferrite bruts de croissance ou déformés plastiquement. Dans les échantillons de ferrite de nickel non déformés les dislocations ont des vecteurs de Burgers a/2 < 110 > et apparaissent en faible densité (103-104 cm-2). Cette densité reste faible dans les échantillons déformés de ferrite de nickel et de YIG. Dans le ferrite de Nickel des sous-joints de dislocations dissociés ainsi qu'une deuxième phase hexagonale peuvent apparaître après déformation selon la température de l'essai. Dans le YIG des dislocations de vecteurs de Burgers a/2 < 111 > et a < 001 > ont été caractérisées de même que des boucles coins de vecteur de Burgers a/2 < 111 >.Structural defects observed in ferrite single crystals from as-grown boules by X-Ray topography and from deformed specimens by electron microscopy are reported. In as-grown nickel ferrite a/2 < 110 > Burgers vectors of isolated dislocations are determined in a network with relatively low dislocation density (103-104 cm-2). It appears from observations of plastically deformed ferrite single crystals that resulting dislocation density is still low in both investigated specimens (nickel ferrite and YIG). In YIG it is shown that plastic deformation involves dislocations with both a < 001 > and a/2 < 111 > Burgers vectors ; dislocation loops with a/2 < 111 > Burgers vectors are also present. In nickel ferrite numerous slices with hexagonal structure together with simple stacking fault or sub-grain boundaries are found depending on test temperature, in this compound isolated dislocations always have a/2 < 110 > Burgers vectors and are often dissociated into two partials with collinear Burgers vectors