Predictors and indicators of disability and quality of life 4 years after a severe traumatic brain injury. A Structural Equation Modelling analysis from the PariS-TBI study

ObjectiveTo assess the predictors and indicators of disability and quality of life four years after a severe traumatic brain injury (TBI), using a Structural Equation Modelling (SEM). SEM is a multivariate approach permitting to take into account the complex inter-relationships between individual predictors, in order to disentangle factors which have a direct or indirect relationship with the dependant variable.MethodsThe Paris-TBI study is a longitudinal inception cohort study of 504 patients with severe TBI in the Parisian area [1]. Among 245 survivors, 147 patients were assessed four years post-injury. Two outcome measures were analysed separately using SEM: the Glasgow Outcome Scale-extended (GOS-E) [2], which is a global measure of disability after TBI, and the QOLIBRI, a disease-specific measure of quality of life after TBI [3]. Four groups of variable were entered in the model: demographics; injury severity; psychological and cognitive impairments; somatic impairments.ResultsThe GOS-E was directly significantly related to all four groups of variables (age, gender, severity of injury, psycho-cognitive and somatic impairments). Education duration had an indirect effect, mediated by psycho-cognitive impairments. In contrast, the QOLIBRI was only directly predicted by psycho-cognitive impairments. Age and somatic impairments had an indirect influence on the QOLIBRI, via psycho-cognitive impairments.Discussion/ConclusionDisability and quality of life were directly influenced by different factors. While disability appeared to result from an interaction of a wide range of factors, including demographics, injury severity, psycho-cognitive and somatic deficiencies, quality of life was solely directly related to psycho-cognitive factors. Other factors, such as age and somatic impairments only had an indirect effect

Platelet Serotonin Level Predicts Survival in Amyotrophic Lateral Sclerosis

International audienceBACKGROUND: Amyotrophic lateral sclerosis (ALS) is a life-threatening neurodegenerative disease involving upper and lower motor neurons loss. Clinical features are highly variable among patients and there are currently few known disease-modifying factors underlying this heterogeneity. Serotonin is involved in a range of functions altered in ALS, including motor neuron excitability and energy metabolism. However, whether serotoninergic activity represents a disease modifier of ALS natural history remains unknown. METHODOLOGY: Platelet and plasma unconjugated concentrations of serotonin and plasma 5-HIAA, the major serotonin metabolite, levels were measured using HPLC with coulometric detection in a cohort of 85 patients with ALS all followed-up until death and compared to a control group of 29 subjects. PRINCIPAL FINDINGS: Platelet serotonin levels were significantly decreased in ALS patients. Platelet serotonin levels did not correlate with disease duration but were positively correlated with survival of the patients. Univariate Cox model analysis showed a 57% decreased risk of death for patients with platelet serotonin levels in the normal range relative to patients with abnormally low platelet serotonin (p = 0.0195). This protective effect remained significant after adjustment with age, gender or site of onset in multivariate analysis. Plasma unconjugated serotonin and 5-HIAA levels were unchanged in ALS patients compared to controls and did not correlate with clinical parameters. CONCLUSIONS/SIGNIFICANCE: The positive correlation between platelet serotonin levels and survival strongly suggests that serotonin influences the course of ALS disease

Genetic Biomarkers for ALS Disease in Transgenic SOD1G93A Mice

The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1G93A mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1G93A mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1G93A mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies