Effets de la stimulation pallidale interne dans les dystonies-dyskinésies aux neuroleptiques, les dystonies primaires étendues non généralisées et les dystonies par anoxie néonatale

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Juvenile amyotrophic lateral sclerosis associated with biallelic c.757delG mutation of sorbitol dehydrogenase gene

International audienceMutation in the sorbitol dehydrogenase gene (SORD) has been recently described to cause axonal Charcot-Marie-Tooth disease (CMT), intermediate CMT, and distal hereditary motor neuropathy (dHMN). We herein report the case of a 24-year-old patient diagnosed with juvenile amyotrophic lateral sclerosis (JALS) who carried the homozygous c.757delG mutation in SORD. No other pathogenic variant in frequent JALS-causative genes was found. Our findings expand the phenotype related to SORD mutation, a new and potentially treatable genetic disease

Role of serotonergic 1A receptor dysfunction in depression associated with Parkinson's disease

International audienceDepression is frequent in Parkinson's disease, but its pathophysiology remains unclear. Two recent studies have investigated the role of serotonergic system at the presynaptic level. The objective of the present study was to use positron emission tomography and [18F]MPPF to investigate the role of postsynaptic serotonergic system dysfunction in the pathophysiology of depression in Parkinson's disease. Four parkinsonian patients with depression and 8 parkinsonian patients without depression were enrolled. Each patient underwent a scan using [18F]MPPF, a selective serotonin 1A receptor antagonist. Voxel‐by‐voxel statistical comparison of [18F]MPPF uptake of the 2 groups of parkinsonian patients and with 7 matched normal subjects was made using statistical parametric mapping (P uncorrected < .001). Compared with nondepressed parkinsonian patients, depressed patients exhibited reduced tracer uptake in the left hippocampus, the right insula, the left superior temporal cortex, and the orbitofrontal cortex. Compared with controls, nondepressed parkinsonian patients presented reduced [18F]MPPF uptake bilaterally in the inferior frontal cortex as well as in the right ventral striatum and insula. Compared with controls, [18F]MPPF uptake was decreased in depressed parkinsonian patients in the left dorsal anterior cingulate and orbitofrontal cortices, in the right hippocampic region, and in the temporal cortex. The present imaging study suggests that abnormalities in serotonin 1A receptor neurotransmission in the limbic system may be involved in the neural mechanisms underlying depression in patients with Parkinson's disease

Multicenter quality control of hepatitis C virus protease inhibitor resistance genotyping.

International audienceHepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents

Emerging resistance mutations in PI-naive patients failing an atazanavir-based regimen (ANRS multicentre observational study)

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Clinical characterisation of sensory neuropathy with anti-FGFR3 autoantibodies

Sensory neuropathies (SNs) are often classified as idiopathic even if immunological mechanisms can be suspected. Antibodies against the intracellular domain of the fibroblast growth factor receptor 3 (FGFR3) possibly identify a subgroup of SN affecting mostly the dorsal root ganglion (DRG). The aim of this study was to identify the frequency of anti-FGFR3 antibodies and the associated clinical pattern in a large cohort of patients with SN. A prospective, multicentric, European and Brazilian study included adults with pure SN. Serum anti-FGRF3 antibodies were analysed by ELISA. Detailed clinical and paraclinical data were collected for each anti-FGFR3-positive patient and as control for anti-FGFR3-negative patients from the same centres ('center-matched'). Sixty-five patients out of 426 (15%) had anti-FGFR3 antibodies, which were the only identified autoimmune markers in 43 patients (66%). The neuropathy was non-length dependent in 89% and classified as sensory neuronopathy in 64%, non-length-dependent small fibre neuropathy in 17% and other neuropathy in 19%. Specific clinical features occurred after 5-6 years of evolution including frequent paresthesia, predominant clinical and electrophysiological involvement of the lower limbs, and a less frequent mixed large and small fibre involvement. Brazilians had a higher frequency of anti-FGFR3 antibodies than Europeans (36% vs 13%, p<0.001), and a more frequent asymmetrical distribution of symptoms (OR 169, 95% CI 3.4 to 8424). Anti-FGFR3 antibodies occur in a subgroup of SN probably predominantly affecting the DRG. Differences between Europeans and Brazilians could suggest involvement of genetic or environmental factors9114957FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/01766-7; 2013/26410-0This study was supported by University hospital of Saint-Etienne (NCT02539329). CPM was funded by the German Research Foundation (DFG; MO 3240/1-1:1) during the study. MCFJ has a research grant on SNN funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/01766-7). ARMM is supported by PhD scholarship from FAPESP (2013/26410-0

Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

International audienceThe pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of 3-fold shift in 50% inhibitory concentration (IC50) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (P = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment

Predictors of Parenchymal Hematoma After Mechanical Thrombectomy

International audienceBackground and Purpose— Parenchymal hematoma (PH) is a rare but dreadful complication of acute ischemic stroke with unclear underlying mechanisms. We aimed to study the incidence and predictors of PH after mechanical thrombectomy. Methods— Data from a prospective observational multicenter registry was screened to identify acute ischemic stroke patients with an anterior circulation large vessel occlusion who underwent mechanical thrombectomy. Clinical, imaging, and procedural characteristics were used for the analysis, including brain imaging systematically performed at 24 hours. PH occurrence was assessed according to ECASS (European Collaborative Acute Stroke Study) criteria. Univariate and multivariable analyses were performed to identify predictors of PH. Results— A total of 1316 patients were included in the study. PH occurred in 153 out of 1316 patients (11.6%) and was associated with a lower rate of favorable outcome and increased mortality. On multivariable analysis, age (per 1 year increase, odds ratio [OR], 1.01; 95% CI, 1.00–1.03; P =0.05), current smoking (OR, 2.02; 95% CI, 1.32–3.09; P <0.01), admission Alberta Stroke Program Early CT Score (per a decrease of 1 point, OR, 1.70; 95% CI, 1.18–2.44; P <0.01), general anesthesia (OR, 1.98; 95% CI, 1.36–2.90; P <0.001), angiographic poor collaterals (OR, 2.13; 95% CI, 1.36–3.33; P <0.001) and embolization in new territory (OR, 2.94; 95% CI, 1.70–5.10; P <0.001) were identified as independent predictors of PH. Conclusions— PH occurred at a rate of 11.6% after mechanical thrombectomy, with high morbidity and mortality. Our study identified clinical, radiological, and procedural predictors of PH occurrence that can serve as the focus of future periprocedural management studies with the aim of reducing its occurrence. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03776877