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The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10−5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.

International audience; Stroke frequently causes deglutition disorders, leading to a decline in nutritional status and complications, and increasing mortality. Sub-Saharan data are scarce. The objectives of this study were to assess complications and mortality among hospitalized patients in Burkina Faso during the first two weeks after stroke, and to investigate associated factors. Patients with stroke were followed prospectively in Ouagadougou and Bobo-Dioulasso hospitals. Deglutition disorders and nutritional parameters were assessed at baseline (D0) and on Days 8 (D8) and 14 (D14). Complications and mortality were recorded up to D14. Factors associated with complications and mortality were investigated using multivariate analysis. Of the 222 patients included, 81.5% developed at least one complication, and mortality was 17.1%. At D0, D8, and D14, the rate of deglutition disorders was 37.4%, 28.4%, and 15.8%, respectively, and that of undernourishment 25.2%, 29.4%, and 31.0%, respectively. In multivariate analysis, only the presence of deglutition disorders was a risk factor for developing at least one complication (OR = 5.47, 95% CI 1.81–16.51). Factors predicting death were the presence of deglutition disorders at D0 (OR = 7.19, 95% CI 3.10–16.66), and at least one seizure during follow-up (OR = 3.69, 95% CI 1.63–8.36). After stroke, the rates of complications, death, and undernourishment were high compared to Western countries. Prevention and management of deglutition disorders, and specific follow-up of patients with seizures could reduce post-stroke mortality.

Background Toxoplasmic encephalitis in patients with AIDS is a life-threatening disease mostly due to reactivation of Toxoplasma gondii cysts in the brain. The main objective of this study was to evaluate the performance of real-time PCR assay in peripheral blood samples for the diagnosis of toxoplasmic encephalitis in AIDS patients in the French West Indies and Guiana. Methodology/Principal Findings Adult patients with HIV and suspicion of toxoplasmic encephalitis with start of specific antitoxoplasmic therapy were included in this study during 40 months. The real-time PCR assay targeting the 529 bp repeat region of T. gondii was performed in two different centers for all blood samples. A Neighbor-Joining tree was reconstructed from microsatellite data to examine the relationships between strains from human cases of toxoplasmosis in South America and the Caribbean. A total of 44 cases were validated by a committee of experts, including 36 cases with toxoplasmic encephalitis. The specificity of the PCR assay in blood samples was 100% but the sensitivity was only 25% with moderate agreement between the two centers. Altered level of consciousness and being born in the French West Indies and Guiana were the only two variables that were associated with significantly decreased risk of false negative results with the PCR assay. Conclusion/Significance Our results showed that PCR sensitivity in blood samples increased with severity of toxoplasmic encephalitis in AIDS patients. Geographic origin of patients was likely to influence PCR sensitivity but there was little evidence that it was caused by differences in T. gondii strains. Trial Registration ClinicalTrials.gov NCT00803621, Author Summary Diagnosis of toxoplasmic encephalitis (TE) in patients with AIDS is not straightforward because clinicians rely initially on an empiric diagnosis based on clinical and radiographic improvement to specific anti-Toxoplasma gondii therapy. There is therefore a need for biological tools to improve the diagnosis of TE, especially in tropical areas where this diagnosis is likely to be underestimated. The use of PCR testing in blood samples for the diagnosis of TE has been limited by its poor sensitivity in the studies conducted in Europe. In tropical South America, the results of PCR sensitivity in blood samples were controversial. Considering that T. gondii strains from tropical South America have substantial genetic and pathogenic differences with those from USA and Europe, it is therefore important to re-evaluate the performance of the PCR assay in blood samples for the diagnosis of TE in AIDS patients from this region. Our results showed that the only interest of PCR would be in the most severe forms of TE with altered consciousness because PCR is more likely to be positive. We also provided important genotyping data on T. gondii strains isolated in human cases of toxoplasmosis in the Caribbean and in South America.

Introduction La Trypanosomiase humaine africaine est une parasitose endemique dans certaines regions d’Afrique subsaharienne. Elle peut etre responsable d’atteinte encephalitique severe pouvant aller jusqu’au deces si elle n’est pas prise en charge a temps. Observation Nous rapportons ici le cas d’une jeune patiente de 21 ans originaire du Congo, arrivee en France recemment. Celle-ci a presente rapidement des troubles du comportement, de l’humeur, du sommeil et un syndrome confusionnel, pour lesquels elle a consulte aux urgences a plusieurs reprises. Un syndrome infectieux est apparu par la suite. La ponction lombaire retrouvait dans le LCR 225 elements. l’IRM cerebral retrouvait des hypersignaux diffus de la substance blanche bilateral, en sequence FLAIR, sus et sous tentoriels. La serologie positive dans le LCR a permis de porter le diagnostic de meningoencephalite a Trypanosoma brucei. La patiente a beneficie d’un traitement anti-infectieux par Eflornithine et Nifurtimox. L’evolution clinique a 6 mois mettait en evidence des sequelles neuro psychologiques avec une labilite thymique, un syndrome dysexecutif, et des troubles phasiques. L’IRM cerebral de controle montrait une nette regression des hypersignaux de la substance blanche. Discussion La description des cas de meningoencephalites a Trypanosomiases et notamment la description des lesions cerebrales a l’IRM est assez rare dans la litterature. Un diagnostic est possible avec de simples serologies et des traitements antibiotiques efficaces existent a la phase cerebrale. Cependant la meconnaissance de cette pathologie peut aboutir a un retard diagnostic et a une issue fatale. Conclusion La trypanosomiase humaine africaine peut se rencontrer dans nos hopitaux par les migrants ou les voyageurs. Un diagnostic precoce de la phase cerebrale pourrait permettre de limiter les sequelles neurologiques.

The MRI is often the initial exploration proposed to a patient presenting a confusion of memory. This examination has for purpose first to eliminate surgical differential diagnoses, such as a chronic hydrocephalus of the adult. It can then help in the differential diagnosis between the various insane syndromes, like Alzheimer's disease.

INTRODUCTION: Several neurological complications are associated with cerebral malaria (CM). However, few long-term data from childhood survivors have been published. METHODS: A cross-sectional study was carried out in Mali among children followed from 1999 to 2002 after serious and complicated malaria. Our aim was to evaluate the persistent neurological sequelae associated with CM. RESULTS: This study concerned 101 subjects who had had CM. Mean age was 5.6+/-3.6 years. Twenty-eight children presented persistent neurological sequelae (27.7p.cent). Among them eight (7.9p.cent) children had developed these sequelae just after CM and 20 (19.8p.cent) a few months later: headaches, mental retardation, speech delay, bucco-facial dyspraxia, diplegia and frontal syndrome (one case each), dystonia (two cases), epilepsy (five cases) and behavior and attention disorders (15 cases). CONCLUSIONS: In this study, we show that neurological signs due to CM can persist in the long run. Long-term follow-up and proper management after CM are essential.

Background Although initially considered safe when covering bifurcation sites, flow-diverting stents may provoke thrombosis of side branches that are covered during aneurysm treatment. Objective To understand the occurrence and clinical expression of side-branch remodeling in distal intracranial arterial sites after flow diverter deployment by means of correlation of imaging and clinical data. Methods We analyzed our prospectively collected data on a series of patients treated with flow diverters for intracranial aneurysms at bifurcation sites. From February 2011 to May 2013, 32 patients with 37 aneurysms (anterior communicating artery, 9 [24.3%]; anterior cerebral artery, 5 [13.5%]; middle cerebral artery, 19 (51.4%); terminal internal carotid artery, 4 [10.8%]) were treated. We divided aneurysms into 2 groups based on the side branches covered by the stent during treatment. Group A consisted of cases with side branches that supplied brain territories also receiving a direct collateral supply. Group B consisted of cases in which side branches supplied territories without direct collateral supply. The 2 groups were compared statistically. Results Total exclusion occurred in 97.3% of aneurysms at follow-up. Initial modified Rankin Scale (mRS) score was 0 to 1 for 29 patients (90.6%) and 2 for 3 patients (9.4%). New permanent neurological deficit was reported in 3 patients (9.4%). At the 6-month follow-up, the mRS score was 0 to 1 for 31 patients (96.8%) and 3 for 1 patient (3.2%). Although 78.5% of side branches in group A underwent narrowing or occlusion after 6 months, no new stroke was found on magnetic resonance imaging. Conclusion Symptomatic modifications of side branches after flow diverter treatment depend on the extent and type of collateral supply.

Background Multiplane transesophageal echocardiography (TEE) and helical computed tomography (CT) of the chest have been validated separately against aortography for the diagnosis of acute traumatic aortic injuries (ATAI). However, their respective diagnostic accuracy in identifying blunt traumatic cardiovascular lesions has not been compared. Methods During a 3-yr period, 110 consecutive patients with severe blunt chest trauma (age: 41 +/- 17 yr; injury severity score: 34 +/- 14) prospectively underwent TEE and chest CT as part of their initial evaluation. Results of both imaging methods were interpreted independently by experienced investigators and subsequently compared. All cases of subadventitial acute traumatic aortic injury were surgically confirmed. Results Seventeen patients had vascular injury and 11 had cardiac lesions. TEE and CT identified all subadventitial disruptions involving the aortic isthmus (n = 10) or the ascending aorta (n = 1) that necessitated surgical repair. In contrast, CT only depicted one disruption of the innominate artery. TEE detected injuries involving the intimal or medial layer, or both, of the aortic isthmus in four patients with apparently normal CT results who underwent successful conservative treatment. All cardiac injuries but two were identified only by TEE. Conclusions In patients with severe blunt chest trauma, TEE and CT have similar diagnostic accuracy for the identification of surgical acute traumatic aortic injuy. TEE also allows the diagnosis of associated cardiac injuries and is more sensitive than CT for the identification of intimal or medial lesions of the thoracic aorta.

International audience; Neurosurgery and Maxillofacial Surgery Departments of Limoges University Hospital Centre have developed a new concept of a custom made ceramic implant in hydroxyapatite (HA) for the reconstruction of large and complex craniofacial bone defects (more than 25 cm2). Materials and methods: The manufacturing process of the implants used a stereolithography technique that produces implants with three-dimensional shapes derived directly from the scan file of the patient's skull without moulding or machining. Eight patients received 8 implants between 2005 and 2008. Results: The surgical procedure is simple and fast. The post-operative follow-up was 12 months. No major complications (infection or fracture of the implant) were observed. The cosmetic result was considered satisfactory by both patients and surgeons. Conclusions: These new implants are well suited for reconstruction of large craniofacial bone defects (greater than 25 cm2) in adults and children over 8 years. 2012 European Association for Cranio-Maxillo-Facial Surgery.

Background and importance The goal of spinal dural arteriovenous fistula (DAVF) treatment is to permanently occlude the proximal draining vein and the fistula itself, which can be achieved by open surgery or endovascular treatment. The endovascular approach is currently the primary treatment, but it requires the presence of an access as close to the site of the fistula as possible. This case illustrates that the retrocorporeal artery may be an alternative option in case of previous embolization failure with proximal occlusion of the radicular arteries. Clinical presentation A 54-year-old man presented with an 18-month history of progressive paraparesis secondary to right L2 spinal DAVF. The first endovascular treatment failed to achieve occlusion of the fistula via the ipsilateral L2 and L3 radicular arteries. Given the proximal occlusion of these feeders during the first embolization, the dilated retrocorporeal arteries were approached via the contralateral L2 and L3 radicular arteries. Complete occlusion of the fistula was achieved with Onyx in a single session with progressive improvement of preoperative neurological deficit. Conclusion The retrocorporeal artery may provide a safe alternative approach to spinal DAVFs in cases in which a conventional endovascular approach failed, thus avoiding invasive surgical treatment.

Objective : To assess the value of routine transesophageal echocardiography (TEE) in diagnosing traumatic disruption of the aorta (TDA) in trauma patients presenting without enlarged mediastinum on chest x-ray films. Design : Prospective study. Material and Methods : TEE was routinely performed to exclude the presence of TDA in patients who sustained severe trauma secondary to abrupt deceleration collisions and presented with an upper mediastinum of fewer than 8 cm on supine chest x-ray films. Patients were divided into two groups according to the presence (group I) or absence (group II) of mediastinal hematoma diagnosed during TEE examination. Radiographic signs regarded as indicators of the presence of TDA were evaluated in both groups. Results : Among the 40 consecutive patients studied, TEE demonstrated two cases of TDA associated with a mediastinal hematoma that were confirmed by both aortography and surgery. One of the patients had a normal mediastinum on presentation chest x-ray films, and the other only exhibited a blurred aortic knob. Radiographic mediastinal abnormalities suggestive of TDA were observed in 13 patients, but chest x-ray films were unremarkable in 12 patients. Twenty patients had multiple rib fractures. The frequency of chest radiographic abnormalities was not significantly higher in group I (n = 6) when compared with group II patients (n = 34). TEE examination demonstrated a normal thoracic aorta in 35 patients and was nondiagnostic in 3 patients (normal aortography). Conclusion : TEE should be routinely performed in victims of violent deceleration collisions, even in patients presenting with apparently normal mediastinum on supine chest radiograph.

A comprehensive description of transesophageal echocardiographic (TEE) findings associated with traumatic aortic rupture (TAR) is still lacking. To correlate TEE and anatomic findings, a prospective study was conducted in 29 consecutive patients suffering from blunt chest trauma and suspected TAR. Confirmation of the diagnosis of TAR was obtained by either aortography, surgery, or necropsy in all patients. TEE studies were performed during the first day of admission using a monoplane probe. TEE studies and aortograms were reviewed by independent experienced observers. The diagnosis of subadventitial TAR was made in 9 patients and intimal tears in 2 patients (one confirmed and one missed by aortography). Subadventitial TAR appeared as an abnormal thick structure composed of intima and media, and mobile within the isthmus lumen. Color flow mapping revealed no differences in blood flow velocity on both sides of the disrupted aortic wall with turbulent flow surrounding the traumatic tear. Symmetric or asymmetric localized aortic enlargement reflecting the adventitia under tension was also noted. This type of lesion requires prompt surgical repair. In contrast. intimal aortic tears appeared as very mobile thin appendages of the aortic wall. Color flow mapping demonstrated a localized mosaic of colors reflecting blood flow turbulence around the intimal laceration, Aortic diameter remained unchanged, since the tear was too small and superficial to induce adventitial distention. Since these lesions appear to regress spontaneously, conservative management and TEE follow-up was undertaken. TEE failed to diagnose a two-millimeter long medial aortic rupture with integrity of the adventitia (demonstrated at necropsy). Aortography must be obtained when the TEE study is equivocal or when a laceration of the aortic arch and the brachiocephalic arteries is suspected. Conclusions In this study, transesophageal echocardiographic and anatomic findings in patients with traumatic aortic rupture were strongly correlated. In experienced hands, TEE can be considered as an accurate firstline imaging technique for the diagnosis and management of traumatic aortic rupture.