[TIMMA: Ultrasonographic scale of carotid atherosclerosis by vascular neurologists]. / TIMMA : échelle échographique de la surcharge athéromateuse en carotide pratiquée par des neurologues vasculaires.

BACKGROUND: Carotid atherosclerosis is a powerful predictive factor of vascular risk at the individual patient level. Ultrasonography is a reference technique for the evaluation of this condition. However, its use in common practice remains difficult due to a lack of standardization and inter-operator variability. We present a new and simple technique for the assessment of carotid atherosclerosis; and evaluate the ability of vascular neurologists to obtain results consistent with those of an expert in vascular ultrasound. MATERIAL AND METHODS: The TIMMA scale is an acronym for the five classes of carotid atherosclerosis in French, VIMMA in English: very important, important, moderate, minimal and absent. Combined, the first two classes make up the group "significant atheroma" and the last three classes make up the group "no significant atheroma". This scale was evaluated in 38 patients (76 carotid arteries) suffering from ischemic stroke or transient ischemic attack by five operators who are competent in carotid echocardiography: one TIMMA-trained (40 hours of training) vascular neurologist physician (VNP), three VNPs informed on the measurement method (1 hour of information) and one specialized vascular physician (SVP) who was considered to be the reference examiner. We evaluated the concordance between the VNPs and the SVP in classifying patients, firstly into the significant or not atheroma group and, secondly, into the five TIMMA classes. RESULTS: The evaluation of the two-group clustering scale found a concordance between the informed VNPs and the SVP on 76 carotid arteries of 86% (kappa=0.7) and between the trained VNP and the SVP on 58 carotid arteries of 90% (kappa=0.8). The positive and negative predictive values for significant atheroma diagnosis were 100% and 81%, respectively, for the informed VNPs, and 100% and 80% for the trained VNP. The evaluation of the Five-Class Scale showed a concordance between the informed VNPs and the SVP of 46% (kappa=0.3), and between the trained VNP and the SVP of 74% (kappa=0.7). CONCLUSION: TIMMA allows VNPs who are competent in carotid ultrasonography to reproducibly identify subjects with significant carotid atheroma. The contribution of this scale to the determination of cardiovascular risk should be evaluated.

Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study.

BACKGROUND AND PURPOSE: To prospectively investigate causes of death and the circumstances surrounding death in 302 patients with amyotrophic lateral sclerosis (ALS). The functional status of patients immediately before death was also determined. METHODS: Information was obtained from neurologists at ALS centres, patients' files, and, when deaths occurred outside a medical facility, attending physicians. RESULTS: Most patients (63%) died in a medical facility. The most frequently reported cause of death was respiratory failure (77%), including terminal respiratory insufficiency (58%), pneumonia (14%), asphyxia due to a foreign body (3%) and pulmonary embolism (2%). Ten per cent of patients died from other causes: post-surgical or traumatic conditions (5%), cardiac causes (3.4%), suicide (1.3%) and sudden death of unknown origin (0.7%). The cause of death could not be determined in 13% of cases (6% inside a medical facility and 25% outside). At the time of death, only 55% of patients were receiving riluzole, 33% were undergoing non-invasive ventilation, 3% had a tracheotomy and 37% a gastrostomy. CONCLUSION: The information provided by this study helps to improve our understanding of the natural history of the disease and may help optimize the quality of care we can offer patients at the end of life.

Expression of X-chromosome linked inhibitor of apoptosis protein in mature Purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration.

Transgenic mice with overexpression of the caspase-inhibitor, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in Purkinje cell (PC) and in retinal bipolar cells (RBCs) were produced to study the regulation of cell death. Unexpectedly, an increased neurodegeneration was observed in the PCs in these L7-XIAP mice after the third postnatal week with the mice exhibiting severe ataxia. The loss of PCs was independent of Bax as shown by crossing the L7-XIAP mice with Bax gene-deleted mice. Electron microscopy revealed intact organelles in PCs but with the stacking of ER cisterns indicative of cell stress. Immunostaining for cell death proteins showed an increased phosphorylation of c-Jun in the PCs, suggesting an involvement in cell degeneration. Apart from PCs, the number of RBCs was decreased in adult retina in line with the expression pattern for the L7 promoter. The data show that overexpression of the anti-apoptotic protein XIAP in vulnerable neurons leads to enhanced cell death. The mechanisms underlying this neurodegeneration can be related to the effects of XIAP on cell stress and altered cell signaling.