Short and long-term impact of four sets of actions on acute ischemic stroke management in Rhône County, a population based before-and-after prospective study.

BACKGROUND: Optimizing access to recanalization therapies in acute ischemic stroke patients is crucial. Our aim was to measure the short and long term effectiveness, at the acute phase and 1 year after stroke, of four sets of actions implemented in the Rhône County. METHODS: The four multilevel actions were 1) increase in stroke units bed capacity and development of endovascular therapy; 2) improvement in knowledge and skills of healthcare providers involved in acute stroke management using a bottom-up approach; 3) development and implementation of new organizations (transportation routes, pre-notification, coordination by the emergency call center physician dispatcher); and 4) launch of regional public awareness campaigns in addition to national campaigns. A before-and-after study was conducted with two identical population-based cohort studies in 2006-7 and 2015-16 in all adult ischemic stroke patients admitted to any emergency department or stroke unit of the Rhône County. The primary outcome criterion was in-hospital management times, and the main secondary outcome criteria were access to reperfusion therapy (either intravenous thrombolysis or endovascular treatment) and pre-hospital management times in the short term, and 12-month prognosis measured by the modified Rankin Scale (mRS) in the long term. RESULTS: Between 2015-16 and 2006-7 periods ischemic stroke patients increased from 696 to 717, access to reperfusion therapy increased from 9 to 23% (p < 0.0001), calls to emergency call-center from 40 to 68% (p < 0.0001), first admission in stroke unit from 8 to 30% (p < 0.0001), and MRI within 24 h from 18 to 42% (p < 0.0001). Onset-to-reperfusion time significantly decreased from 3h16mn [2 h54-4 h05] to 2h35mn [2 h05-3 h19] (p < 0.0001), mainly related to a decrease in delay from admission to imaging. A significant decrease of disability was observed, as patients with mild disability (mRS [0-2]) at 12 months increased from 48 to 61% (p < 0.0001). Pre-hospital times, however, did not change significantly. CONCLUSIONS: We observed significant improvement in access to reperfusion therapy, mainly through a strong decrease of in-hospital management times, and in 12-month disability after the implementation of four sets of actions between 2006 and 2016 in the Rhône County. Reducing pre-hospital times remains a challenge.

Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?

Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling. One patient was adopted and among the other 19 patients, seven (37%) had inherited their duplication from their mother, including three mildly (XCI: 70/30, 63/37, 100/0 in blood and random in saliva), one moderately (XCI: random) and three severely (XCI: uninformative and 88/12) affected patients. After combining our data with data from the literature, we could not show a correlation between XCI in the blood or duplication size and the severity of the phenotype, or explain the presence of a phenotype in these females. These findings confirm that an abnormal phenotype, even severe, can be a rare event in females born to asymptomatic carrier mothers, making genetic counselling difficult in couples at risk in terms of prognosis, in particular in prenatal cases.