Impact of automatic tools for detecting new lesions on therapeutic strategies offered to patients with MS by neurologists.

BACKGROUND: Automatic tools for detecting new lesions in patients with MS between two MRI scans are now available to clinicians. They have been assessed from the radiologist's point of view, but their impact on the therapeutic strategies that neurologists offer their patients has not yet been documented. OBJECTIVES: To compare neurologist's decisions according to whether a lesion detection support system had been used and describe variability between neurologists on decision-making for the same clinical cases. METHODS: We submitted 28 clinical cases associated with pairs of MRI images and radiological reports (produced by the same radiologist without vs. with the help of a system to detect new lesions) to 10 neurologists who regularly follow patients with MS. They examined each clinical case twice (without vs. with support system) in two sessions several weeks apart, and their patient management decisions were recorded. RESULTS: There was considerable variability between neurologists on decision-making (both with and without support system). When the support system had been used, neurologists more often made changes to patient management (75 % vs. 68 % of cases, p = 0.01) and spent significantly less time analyzing the clinical cases (249 s vs. 216 s, p == 3.10-4). CONCLUSION: The use of a lesion detection support system has an impact not only on radiologists' reports, but also on neurologists' subsequent decision-making. This observation constitutes another strong argument for promoting the wider use of such systems in clinical routine. However, despite their use, there is still considerable variability in decision-making across neurologists, which should encourage us to refine the guidelines.

Tubular aggregate myopathy and Stormorken syndrome: Mutation spectrum and genotype/phenotype correlation.

Calcium (Ca2+ ) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca2+ entry, storage, and release. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling extracellular Ca2+ entry, and mainly relies on the accurate interplay between the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca2+ homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca2+ entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.