Serum Neurotrophin Profile in Systemic Sclerosis

International audienceBACKGROUND: Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts; they can modulate angiogenesis and sympathic vascular function. Thus, they can be implicated in the three pathogenic processes of systemic sclerosis (SSc). The aims of this study are to determine blood levels of Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to correlate them with clinical and biological data.METHODS: Serum samples were obtained from 55 SSc patients and 32 control subjects to measure NTs levels by ELISA and to determine their relationships with SSc profiles. FINDINGS: Serum NGF levels were higher in SSc patients (288.26 ± 170.34 pg/mL) than in control subjects (170.34 ± 50.8 pg/mL, p<0.001) and correlated with gammaglobulins levels and the presence of both anti-cardiolipin and anti-Scl-70 antibodies (p<0.05). In contrast, BDNF levels were lower in SSc patients than in controls (1121.9 ± 158.1 vs 1372.9 ± 190.9 pg/mL, p<0.0001), especially in pulmonary arterial hypertension and diffuse SSc as compared to limited forms (all p<0.05). NT-3 levels were similar in SSc and in the control group (2657.2 ± 2296 vs 2959.3 ± 2555 pg/mL, NS). BDNF levels correlated negatively with increased NGF levels in the SSc group (and not in controls). CONCLUSION: Low BDNF serum levels were not previously documented in SSc, particularly in the diffuse SSc subset and in patients with pulmonary hypertension or anti-Scl-70 antibodies. The negative correlation between NGF and BDNF levels observed in SSc and not in healthy controls could be implicated in sympathic vascular dysfunction in SSc

Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges

Ultra-fast recovery from right neglect after 'awake surgery' for slow-growing tumor invading the left parietal area

It is now possible to perform resections of slow-growing tumors in awake patients. Using direct electrical stimulation, real-time functional mapping of the brain can be used to prevent the resection of essential areas near the tumor. Simple clinical observations of patients with a resection of slow-growing tumors have demonstrated substantial recovery within a few days of such 'awake surgery'. The aim of this study was to investigate the kinetics of recovery following the resection of slow-growing tumors invading the left parietal area and to focus mainly on its rapidity. Two patients were assessed by standard line bisection tests and compared with eight healthy individuals. Independently of the pure nature of the symptoms, we report that the patients rapidly and substantially recovered from pronounced right neglect. They were tested 48 hours after the surgery and the recovery was significant for both patients after less than 4 hours. Strikingly, for one patient, recovery was ultra fast and substantial in the first practice session within less than 7 minutes: it occurred without verbal feedback and was substantially retained during the following testing session. Its rapidity suggests a process of unmasking redundant networks. With the slow growth of the lesion, the contralesional hemisphere is probably progressively prepared for rapid unmasking of homologue networks. These results have major clinical implications. For patients with an invading left-side tumor, it is now clear that line bisections are required before, during, and after awake surgery to: plan the surgery, control the quality of the resection, and also optimize the rehabilitation of the patien

Manual reaction times and brain dynamics after 'awake surgery' of slow-growing tumors invading the parietal area. A case report

Primary objectives: Awake surgeries of slow-growing tumours invading the brain and guided by direct electrical stimulation induce major brain reorganizations accompanied with slight impairments post-operatively. In most cases, these deficits are so slight after a few days that they are often not detectable on classical neuropsychological evaluations. Consequently, this study investigated whether simple visuo-manual reaction time paradigms would sign some level of functional asymmetries between both hemispheres. Importantly, the visual stimulus was located in the saggital plane in order to limit attentional biases and to focus mainly on the inter-hemispheric asymmetry. Methods and procedures: Three patients (aged 41, 59 and 59 years) after resections in parietal regions and a control group (age¼44, SD¼6.9) were compared during simple uni- and bimanual reaction times (RTs). Main outcomes and results: Longer RTs were observed for the contralesional compared to the ipsilesional hand in the unimanual condition. This asymmetry was reversed for the bimanual condition despite longer RTs. Conclusion and clinical implications: Reaction time paradigms are useful in these patients to monitor more precisely their functional deficits, especially their level of functional asymmetry, and to understand brain (re)organization following slowgrowing lesions

Delayed postural control during self-generated perturbations in the frail older adults

Alexandre Kubicki1&ndash;3, Fran&ccedil;ois Bonnetblanc1,2, Geoffroy Petrement3, Yves Ballay1,2, France Mourey2,4&sup1;UFR STAPS, Universit&eacute; de Bourgogne, Dijon, France; &sup2;Motricit&eacute; et Plasticit&eacute;, Institut National de la Sant&eacute; et de la Recherche M&eacute;dicale (INSERM), Dijon, France; &sup3;SARL Fovea Interactive, Campus Industriel &ndash; Espace Entreprises, Chalon sur Sa&ocirc;ne, France; 4UFR M&eacute;decine, Universit&eacute; de Bourgogne, Dijon, FrancePurpose: The aim of this study was to investigate the coordination between posture and movement in pathological aging (frailty) in comparison with normal aging, with the hypothesis that in pathological aging, postural control evolves towards a more reactive mode for which the perturbation induced by the movement is not anticipated and leads to delayed and late postural adjustments.Methods: Elderly subjects performed rapid focal arm-raising movements towards a target, from an upright standing position in two stimuli conditions: simple reaction time and choice reaction time (CRT). Hand and center of pressure (CoP) kinematics were compared between a control group and a frail group of the same age.Results: In frail individuals, the entire movement was impaired and slowed down. In addition, postural adjustments that classically precede and accompany the focal arm movement were delayed and reduced, especially in the CRT condition in which the motor prediction is more limited. Finally, a correlation between the time to CoP maximal velocity and the timed up-and-go score was observed.Conclusion: In these patients, it was concluded that the control of the CoP displacement evolved from a proactive mode in which the perturbation associated with the arm movement is anticipated toward a more reactive mode in which the perturbation is compensated by late and delayed adjustments.Keywords: frailty, anticipatory postural adjustments, backward disequilibriu

Pyoderma gangrenosum complicating Cogan's syndrome

Cogan's syndrome is a rare clinical entity defined by the association of a nonsyphilitic interstitial keratitis and vestibuloauditory dysfunction, typically Menière's disease-like; the condition has been reported in association with a variety of cutaneous diseases. We now report a case of pyoderma gangrenosum complicating Cogan's syndrome in a 57-year-old woman, which then healed dramatically, as more interestingly did the associated uveitis with minocycline therapy.Case ReportsJournal ArticleFLWINinfo:eu-repo/semantics/publishe

Functional reorganization of the attentional networks in low-grade glioma patients: A longitudinal study

Right brain damage often provokes deficits of visuospatial attention. Although the spatial attention networks have been widely investigated in stroke patients as well as in the healthy brain, little is known about the impact of slow growing lesions in the right hemisphere. We here present a longitudinal study of 20 patients who have been undergoing awake brain surgery with per-operative line bisection testing. Our aim was to investigate the impact of tumour presence and of tumour resection on the functional (re)organization of the attention networks. We assessed patients' performance on lateralized target detection, visual exploration and line bisection before surgery, and in the acute and post-acute operative phases after surgery. Clear evidence for transient neglect signs was observed in the acute post-operative phase, although full recovery had invariably occurred in all patients. The resection of the right angular gyrus was associated with transient neglect-like symptoms in all tasks, whereas resection of more anterior regions correlated with transient deficits only in visual exploration or detection (but not in line bisection). The attentional networks showed substantial functional recovery. This impressive pattern of recovery is discussed in terms of involvement of the contralateral left hemisphere and of preservation of long-range white matter pathways within the right hemisphere