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ObjectivesNigrostriatal dopaminergic denervation (NSDD) remains poorly characterized in cerebellar multiple system atrophy (MSA-C). We aimed to study NSDD progression in MSA-C and evaluate the capacity for [123I]-FP-CIT-SPECT and parkinsonism to differentiate MSA-C from idiopathic late-onset cerebellar ataxia (ILOCA).MethodsWe included 85 patients successively referred for sporadic late-onset cerebellar ataxia (SLOCA). Every 6 months, SARA, UPDRS-III, and SDFS scores were measured, and MSA-C diagnostic criteria were searched for. Striatal/occipital dopaminergic binding ratio was evaluated every year with [123I]-FP-CIT-scintigraphy.ResultsAfter a mean follow-up of 33.8 months, 33 patients had probable MSA-C, 8 possible MSA-C, and 44 ILOCA. SARA and UPDRS-III scores worsened faster in the probable MSA-C group (p < 0.01) compared with the ILOCA group. The baseline striatal/occipital ratio was lower (2.3 vs 2.97; p < 0.01) and more decreasing among patients with probable MSA-C (p < 0.01). Weighting dysautonomia and parkinsonism and/or NSDD as additional and principal criterion, respectively, in the possible MSA-C diagnostic criteria slightly improved their specificity (81.6% vs 76.9%) and sensitivity (77.8% vs 72.2%) to predict a final diagnosis of probable MSA-C.DiscussionRapid symptom worsening and NSDD existence and progression predict MSA-C among patients with SLOCA. Parkinsonism, NSDD, and dysautonomia should be considered equivalent for possible MSA-C diagnosis.

Objectives Administrative claims data are prone to underestimate the burden of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Methods We developed machine learning-based algorithms using historical claims data from cases with NTM-PD to predict patients with a high probability of having previously undiagnosed NTM-PD and to assess actual prevalence and incidence. Adults with incident NTM-PD were classified from a representative 5% sample of the German population covered by statutory health insurance during 2011–2016 by the International Classification of Diseases, 10th revision code A31.0. Pre-diagnosis characteristics (patient demographics, comorbidities, diagnostic and therapeutic procedures, and medications) were extracted and compared to that of a control group without NTM-PD to identify risk factors. Results Applying a random forest model (area under the curve 0.847; total error 19.4%) and a risk threshold of >99%, prevalence and incidence rates in 2016 increased 5-fold and 9-fold to 19 and 15 cases/100,000 population, respectively, for both coded and non-coded vs. coded cases alone. Conclusions The use of a machine learning-based algorithm applied to German statutory health insurance claims data predicted a considerable number of previously unreported NTM-PD cases with high probabilty.

Introduction L’histoire naturelle de l’atteinte des voies dopaminergiques nigro-striatale dans l’atrophie multisystematisee de type cerebelleuse (MSA) est mal connue. Objectifs Evaluer prospectivement l’evolution des syndromes cerebelleux et extrapyramidal ainsi que de la denervation dopaminergique par scintigraphie au FP-CIT (DaTscan) chez des patients presentant une MSA ou une ataxie sporadique tardive idiopathique (ILOCA). Patients et methodes Les scores UPDRS III, SARA, SDFS, ainsi que les criteres de MSA furent evalues prospectivement tout les 6 mois et les ratios striatum/occipital (rS/O) au DaTscan tout les ans sur une cohorte de 85 patients presentant des ataxies cerebelleuses sporadiques debutant apres 40 ans. Les patients developpant une MSA furent compares aux patients presentant une ILOCA (absence de diagnostic apres exploration exhaustive des causes acquises et genetique d’ataxies cerebelleuses et un suivi clinique d’au moins 2 ans). Resultats Trente-trois patients avaient une MSA probable (MSApr), 8 une MSA possible et 44 une ILOCA en fin d’etude. Bien que non differents en debut de maladie, les scores SARA, SDFS et UPDRS III s’aggravaient plus dans les groupes MSA ou MSApr que dans le groupe ILOCA (p Discussion Notre travail montre la grande precocite et evolutivite de l’atteinte nigro-striatale dans la MSA en comparaison des ILOCA. La valeur diagnostique du DaTscan au debut de la maladie etait comparable aux criteres de MSApr pris isolement, supportant l’inclusion de cet examen dans la revision des criteres de MSApr. La positivite du DaTscan precedait le diagnostic de 1,6 ans en moyenne, soulignant son interet pour un diagnostic precoce. Conclusion L’aggravation rapide des symptomes extrapyramidaux ainsi que l’existence et l’evolutivite d’une denervation dopaminergique au DaTscan predisent l’evolution vers une MSA probable chez des patients presentant une ataxie cerebelleuse tardive.

International audience; Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 \textmug/L), AOA2 (15-65 \textmug/L) and AT (\textgreater65 \textmug/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.

International audience; The management of sporadic late-onset cerebellar ataxias represents a very heterogeneous group of patients and remains a challenge for neurologist in clinical practice. We aimed at describing the different causes of sporadic late-onset cerebellar ataxias that were diagnosed following standardized, exhaustive investigations and the population characteristics according to the aetiologies as well as at evaluating the relevance of these investigations. All patients consecutively referred to our centre due to sporadic, progressive cerebellar ataxia occurring after 40~years of age were included in the prospective, observational study. 80 patients were included over a 2~year period. A diagnosis was established for 52 patients (65%) corresponding to 18 distinct causes, the most frequent being cerebellar variant of multiple system atrophy (n~=~29). The second most frequent cause was inherited diseases (including spinocerebellar ataxias, late-onset Friedreich's disease, SLC20A2 mutations, FXTAS, MELAS, and other mitochondrial diseases) (n~=~9), followed by immune-mediated or other acquired causes. The group of patient without diagnosis showed a slower worsening of ataxia (p~\textless~0.05) than patients with multiple system atrophy. Patients with later age at onset experienced faster progression of ataxia (p~=~0.001) and more frequently parkinsonism (p~\textless~0.05) than patients with earlier onset. Brain MRI, DaT scan, genetic analysis and to some extent muscle biopsy, thoracic-abdominal-pelvic tomodensitometry, and cerebrospinal fluid analysis were the most relevant investigations to explore sporadic late-onset cerebellar ataxia. Sporadic late-onset cerebellar ataxias should be exhaustively investigated to identify the underlying causes that are numerous, including inherited causes, but dominated by multiple system atrophy.

Road traffic accident (RTA)-related trauma remains a public health issue. The aim of this study was to determine the frequency, causes and human impact of motor vehicle-related RTA in Lubumbashi, Democratic Republic of Congo. A prospective cross-sectional study was conducted in the first semester of the year 2015 in which 288 drivers (144 RTA-causing drivers and 144 control drivers who have been declared not guilty by road safety agents) involved in 144 motor vehicle-related RTA were interviewed, and only data on all RTA involving two motor vehicles with at least four wheels were recorded and analyzed. Results showed a total of 144 RTA that involved two motor vehicles with four wheels occurring during the study period which affected 104 people, including 93 injury and 11 fatality cases. The mean age of RTA-causing drivers was 33.8 ± 7.4, whereas it was 35 ± 8.8 for control drivers. The majority of RTA-causing drivers (53.4 %) did not attend a driving school. Over speeding (32 %), distracted driving (22 %), overtaking (16 %) and careless driving/risky maneuver (15 %) and driving under the influence of alcohol (9 %) were the main causes of RTA occurrence. In addition, the absence of a valid driving license [aOR = 12.74 (±2.71); 95 % CI 3.877–41.916; p = 0.015], unfastened seat belt for the RTA-causing driver [aOR = 1.85 (±0.62); 95 % CI 1.306–6.661; p = 0.048] and presence of damages on RTA-causing vehicle [aOR = 33.56 (24.01); 95 % CI 1.429–78.352; p = 0.029] were associated with the occurrence of RTA-related fatality. This study showed a relatively high frequency of RTA occurring in Lubumbashi and suggests the necessity to reinforce road traffic regulation.

Introduction L’ataxie avec apraxie oculomotrice de type 1 (AOA1) est une ataxie cerebelleuse autosomique recessive. Elle associe ataxie, apraxie oculomotrice (AOM), polyneuropathie, hypoalbuminemie et hypercholesterolemie. Objectifs Notre objectif etait de mieux definir le spectre clinique et biologique d’AOA1 (notamment l’alpha-foetoproteine (AFP), augmentee dans d’autres ataxies recessives) et d’en etudier les correlations genotype-phenotype. Patients et methodes Nous avons retrospectivement etudie une grande serie mondiale de patients AOA1 diagnostiques au service de genetique du CHU de Strasbourg entre 2002 et 2014. Le diagnostic d’AOA1 du a des mutations dans le gene APTX codant pour l’aprataxine avait ete confirme chez 80 patients issus de 51 familles differentes : cinquante-sept nouveaux patients (dont 9 nouvelles mutations) et 23 deja publies. Resultats Parmi les patients, 2/3avaient une AOM, 93 % une polyneuropathie, 98 % une atrophie cerebelleuse. L’hypoalbuminemie etait observee chez 62 % et l’AFP etait elevee dans 41 % des cas (max 17 ng/ml). Le taux d’AFP etait plus eleve chez les AOA1 que chez les non ataxiques (p Discussion L’atrophie cerebelleuse et la polyneuropathie sont quasi constants dans notre serie. La mutation p.Trp279 * est de loin la mutation du gene APTX la plus frequente dans le monde. Les mutations faux sens d’APTX sont associees a un phenotype moins severe d’AOA1. L’AFP est legerement augmentee chez une proportion importante de patients AOA1. Conclusion Nous decrivons la plus grande serie de patients AOA1 jamais rapportee et montrons que l’AFP peut etre augmentee dans cette pathologie mais a un taux plus faible que dans l’ataxie telangectasie ou AOA2.

Introduction : L'objectif etait de comparer la prevalence de l'hypertension arterielle chez les meuniers dans la ville de Lubumbashi qui sont exposes d'une maniere permanente aux bruits des machines de transformation des cereales a la prevalence de l'hypertension arterielle chez un groupe des gardiens. Methodes : Quic'est une etude descriptive transversale qui a concerne 286 meuniers et 115 agents d'une entreprise de gardiennage. Apres un consentement eclaire, un auto questionnaire a ete administre aux enquetes et des mesures de poids, taille, et tension arterielle ont ete prises. Resultats : La prevalence de l'HTA chez les meuniers etait 49.3% et celle des gardes etait 20.9%, pour un ratio de prevalence de 2.4.significativement elevee par rapport aux controles (49.3% vs 20.9%) et le ratio de prevalence etait de 2.4 . Les facteurs de risque tels que: l'âge, l'indice de masse corporelle, l'anciennete, la duree de travail ont ete significativement eleves chez les meuniers par rapport aux gardiens. Conclusion : Nous avons trouve une prevalence elevee de l'HTA chez les meuniers. Nos resultats suggerent que cette prevalence est probablement due a l'environnement du milieu de travail des meuniers (bruits, vibration des machines) et ce dernier constitue un facteur de risque de l'hypertension arterielle. Key words : Hypertension arterielle, meuniers, bruits, environnement du milieu de travail

Introduction La prise en charge des ataxies cerebelleuses sporadiques tardives, du fait de leur nombre et de leur caractere heterogene, reste encore a ce jour un challenge diagnostique pour le clinicien. Objectifs L’objectif principal de cette etude est de decrire les principales etiologies des ataxies cerebelleuses tardives sporadiques, un objectif secondaire est d’etudier la pertinence des examens complementaires. Patients et methodes Tout patient presentant une ataxie cerebelleuse isolee ou non, apres 40 ans, sporadique et progressive a ete inclus dans une etude prospective, observationnelle et monocentrique au CHU de Strasbourg. Chaque patient a beneficie d’un examen clinique complet avec scores cliniques (SARA, UPDRS3, SDFS), recherche de dysautonomie et d’investigations complementaires multiples : analyses biologiques (metabolique, auto-immun), genetiques (SCA, FXTAS, FRDA), ponction lombaire, IRM cerebrale, DAT-scan, ENMG, entre autres. Resultats Sur une periode de 2 ans, nous avons inclut 80 patients. Un diagnostic a ete pose pour 52 d’entre eux (65 %) dont une majorite d’atrophie multi-systematisee (n = 29). Les 23 patients restant se repartissent en 17 etiologies variees et heterogenes, comprenant des causes genetiques hereditaires autosomiques ou recessives (n= 9), des causes auto-immunes ou toxiques, entre autres. L’IRM cerebrale, le DAT-Scan, la biopsie musculaire et l’analyse genetique ont ete les plus rentables pour orienter le diagnostic. Discussion Beaucoup d’inconnus persistent concernant ce type de pathologies et malgre un bilan pousse, 35 % des patients restent sans diagnostic. Elles necessitent un bilan pousse et standardise afin de potentialiser notre rentabilite diagnostique et notre prise en charge. Malgre leur caractere sporadique, 9 patients presentent une origine genetique qui ne doit donc pas etre negligee. Conclusion Les ataxies cerebelleuses sporadiques tardives necessitent des investigations poussees pour mieux identifier leurs causes qui sont multiples et heterogenes, souvent genetiques, mais dominees par l’atrophie multi-systematisee.

International audience; INTRODUCTION: Biobanks may play a pivotal role in lung cancer patients' management, research, and health policy. The Nancy "Centre of Biologic Resources" analyzed the evolving profiles of operated lung cancer patients and their management over 20 years. METHODS: A total of 1259 consecutive patients operated upon from 1988 till 2007 were included. Survival rates were statistically compared before and after 1997. The parameters associated with a significant improvement of survival were determined. RESULTS: After 1997, lung cancer was diagnosed at an earlier stage. For Squamous Cell Lung Cancer (SQCLC), stages IA increased from 5.4 to 19.5% and for Adenocarcinoma (ADC), stage IA increased from 9.9 to 24.7%. More women with stage I ADC were operated upon after 1997 (p = 0.01). More patients with Large Cell Lung Cancer were diagnosed recently. Recent patients received more adjuvant or neo-adjuvant chemotherapy (p < 0.001) and less radiotherapy (stage I SQCLC: p = 0.019, stage I ADC: p < 0.001). A longer overall patients' survival was observed after 1997 (chi test for SQLC and ADC independently p < or = 0.002). Among SQCLC long survivors, those at stage I-II, below 50 years, were more numerous. A longer survival was associated with early stage in ADC patients. Stage was the single constant factor for overall outcome. CONCLUSION: Overall and stage-adjusted survival of operated lung cancer patients has been improved in the last decade due mainly to earlier diagnosis. The generalized use of computed tomography scan, chemotherapy, and a collegial management improved patients' survival.

Squamous cell carcinoma (SCC) of the lung is a frequent and aggressive cancer type. Gene amplifications, a known activating mechanism of oncogenes, target the 3q26-qter region as one of the most frequently gained/amplified genomic sites in SCC of various types. Here, we used array comparative genomic hybridization to delineate the consensus region of 3q26.3 amplifications in lung SCC. Recurrent amplifications occur in 20% of lung SCC (136 tumors in total) and map to a core region of 2 Mb (Megabases) that encompasses SOX2, a transcription factor gene. Intense SOX2 immunostaining is frequent in nuclei of lung SCC, indicating potential active transcriptional regulation by SOX2. Analyses of the transcriptome of lung SCC, SOX2-overexpressing lung epithelial cells and embryonic stem cells (ESCs) reveal that SOX2 contributes to activate ESC-like phenotypes and provide clues pertaining to the deregulated genes involved in the malignant phenotype. In cell culture experiments, overexpression of SOX2 stimulates cellular migration and anchorage-independent growth while SOX2 knockdown impairs cell growth. Finally, SOX2 over-expression in non-tumorigenic human lung bronchial epithelial cells is tumorigenic in immunocompromised mice. These results indicate that the SOX2 transcription factor, a major regulator of stem cell function, is also an oncogene and a driver gene for the recurrent 3q26.33 amplifications in lung SCC.