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

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes

Douze années de pose d’endoprothèses rectocoliques : résultats et suivi chez 204 patients

Objectifs : Les buts de cette étude étaient d’évaluer la faisabilité et l’efficacité à long terme de la mise en place d’endoprothèses métalliques ou plastiques pour des sténoses recto-coliques malignes ou bénignes dans la « vraie vie ». Patients et méthodes : De septembre 1994 à septembre 2006, 204 patients consécutifs (118 femmes, 86 hommes, âge moyen : 73,2 ans, extrêmes : 49-97 ans) présentant une obstruction rectocolique partielle ou complète, étaient traités par une ou plusieurs endoprothèses métalliques ou plastiques. Une pose d’endoprothèse était tentée pour 168 patients porteurs d’une sténose colique maligne en situation palliative, pour 17 malades porteurs également d’un cancer avant un geste chirurgical curatif, pour 19 patients présentant une sténose bénigne, mais contreindiqués pour la chirurgie en raison d’un état général trop altéré. La pose des prothèses était réalisée par voie endoscopique et radioscopique. Différents modèles de prothèses étaient utilisés, incluant les Enteral Wallstent, Wallflex, Colonic Z stent, Ultraflex precision, Choo Stent, Hanarostent et Polyflex. Les données sur l’efficacité de la procédure, les complications et le devenir des patients étaient collectées rétrospectivement à partir des médecins traitants qui ont suivi leurs patients jusqu’à leur décès. Résultats : La pose d’une endoprothèse était effectuée avec succès chez 154 patients en situation palliative (91,6 %), chez les 17 patients avant la chirurgie curative (100 %) et chez 15 malades porteurs d’une sténose bénigne (78 %). Une complication survenait pour 28 patients : perforation colique (n = 8) ; inefficacité (n = 8) ; ré-obstruction par matières fécales ou progression tumorale (n = 6) ; migration (n = 4) ; douleur abdominale sévère (n = 1). Une patiente décédait. Une deuxième endoprothèse était rendue nécessaire ultérieurement chez 6 malades. Conclusions : La pose d’une prothèse rectocolique par voie endoscopique est un traitement palliatif efficace en cas d’obstruction maligne. Ce traitement est également efficace avant un geste chirurgical curatif et pour certaines sténoses bénignes en l’absence d’alternatives thérapeutiques moins agressives

Bone marrow stromal cells spontaneously produce Flt3-ligand: Influence of ionizing radiations and cytokine stimulation

Purpose: To define the ability of human bone marrow (BM) stromal cells to produce fms-like tyrosine kinase 3 (Flt3)-ligand (FL), and the effect of irradiation, tumour necrosis factor-alpha (TNF[image omitted]) or tumour growth factor beta (TGF[image omitted]) on FL production. Material and methods: Primary BM stromal cell cultures were irradiated at 2-10 Gy or were stimulated with TNFα or TGFβ1. The presence of FL was tested in culture supernatants and in cell lysate. The presence of a membrane-bound form of FL and the level of gene expression were also tested. Results: Primary BM stromal cells spontaneously released FL. This production was increased by TNFα but not by TGFβ1 or by irradiation. Chemical induction of osteoblastic differentiation from BM stromal cells also induced an increase in FL release. Conclusions: Our results suggest that the observed increase in FL concentration after in vivo irradiation is an indirect effect. The possible implication of BM stromal cells in these mechanisms is discussed. © 2008 Informa UK Ltd

Endoscopic palliative treatment of malignant colorectal stenosis with metallic stents: results in 41 patients

But : la colostomie de décharge est la prise en charge thérapeutique admise de l'occlusion rectocolique d'origine tumorale. Le but de cette étude était d'évaluer la faisabilité et l'efficacité du traitement endoscopique des sténoses malignes colo-rectales par prothèses métalliques expansives chez des patients non opérables. Patients et méthodes: entre septembre 1994 et septembre 2002, 41 patients consécutifs (21 femmes, âge moyen de 69,5 ans, extrême 41-92 ans) présentant une occlusion colo-rectale d'origine néoplasique non opérable ont été traités de manière palliative par pose d'endoprothèse métallique auto-expansive. L'occlusion avait pour étiologie une atteinte tumorale colo-rectale primitive dans 32 cas et une atteinte carcinomateuse péritonéale compressive pour les 9 autres patients. Le niveau de l'occlusion était rectal dans 11 cas, sigmoïdien dans 26 cas, transverse colique dans 2 cas, à l'angle colique gauche dans un cas et à l'angle colique droit pour le dernier. Les prothèses utilisées étaient de type Enteral Wallstent®, Colonic Z stent®, Ultraflex precision® ou encore de type Choo stent®. Résultats: l'insertion prothétique était possible chez 37 patients (90,2 %) et permettait de manière constante la levée de l'occlusion. Huit de ces 37 patients présentaient un stent perméable après un suivi moyen de 23,5 semaines. L'évolution fut la suivante pour les 29 autres patients: 22 patients avaient une prothèse perméable au moment de leur décès, 2 prothèses étaient envahies par la tumeur nécessitant un second traitement endoscopique (insertion d'un second stent), 5 prothèses (14,7 %) avaient migré de manière spontanée sans récidive de l'occlusion et un stent avait été retiré pour un ténesme rectal à la suite de sa pose. Conclusion: l'insertion endoscopique de prothèses métalliques auto-expansives est un traitement efficace et bien toléré des sténoses malignes colo-rectales. La complication la plus fréquente est la migration survenant quel que soit le modèle de prothèse utilisé

Comparison of autologous cell therapy and granulocyte-colony stimulating factor (G-CSF) injection vs. G-CSF injection alone for the treatment of acute radiation syndrome in a non-human primate model

Purpose: To compare the efficacy of autologous cell therapy after irradiation combined with granulocyte-colony stimulating factor (G-CSF) injections with G-CSF treatment alone in a heterogeneous model of irradiation representative of an accidental situation. Material and Methods: Non-human primates were irradiated at 8.7 Gy whole-body dose with the right arm shielded to receive 4.8 Gy. The first group of animals received G-CSF (lenograstim) injections starting 6 h after irradiation, and a second group received a combination of G-CSF (lenograstim) injections and autologous expanded hematopoietic cells. Animals were followed up for blood cell counts, circulating progenitors, and bone marrow cellularity. Results: No significant differences were seen between the two treatment groups, whatever the parameter observed: time to leukocyte or platelet recovery and duration and severity of aplasia. Conclusion: Our results indicated that identical recovery kinetic was observed when irradiated animals are treated with G-CSF independently of the reinjection of ex vivo expanded autologous hematopoietic cells. Thus G-CSF injections might be chosen as a first-line therapeutic strategy in the treatment of accidental acute radiation victims. © 2005 Elsevier Inc

Effect of ondansetron, a 5-HT(3) receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study

Background and aims: There are no available effective therapies for fatigue associated with chronic hepatitis C (CHC). The serotonin antagonist ondansetron has been shown to be effective in the chronic fatigue syndrome. In this randomised, placebo controlled, double blind trial, we investigated the effect of orally administered ondansetron on fatigue in CHC. Methods: Thirty six patients with CHC were included if fatigue was their predominant symptom and they scored more than 4 on a visual analogue scale (0–10). During the study, fatigue and depression were measured on days 0, 15, 30, and 60 using a validated self report questionnaire (fatigue impact scale and Beck depression inventory). Patients were randomised to receive ondansetron tablets 4 mg twice daily or placebo for one month followed by an additional four weeks of observation. Results: Fatigue score was 85.4 (28.2) and 98.2 (26.9) in the ondansetron and placebo groups, respectively (NS). Ondansetron significantly reduced the fatigue score with more than 30% improvement on day 15 (57.1 (38.9); p<0.01), day 30 (54.5 (37.6); p<0.01), and day 60 (60.8 (37.3); p<0.01) whereas placebo did not. Overall, the reduction in fatigue was significantly higher with ondansetron compared with placebo (ANOVA for repeated measurements) for the whole follow up period (p = 0.03) or for the treatment period only (p = 0.04). Ondansetron also significantly reduced depression scores. Conclusions: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron had a significant positive effect on fatigue in CHC. These observations support the concept that fatigue involves serotoninergic pathways and may encourage further evaluations of the efficacy of ondansetron on fatigue in chronic liver diseases