D. Guidetti

Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.

BACKGROUND Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. METHODS After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events. CONCLUSIONS As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)

The spectrum of Notch3 mutations in 28 Italian CADASIL families

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cause of hereditary cerebrovascular disease. It results from mutations in the Notch3 gene, a large gene with 33 exons. A cluster of mutations around exons 3 and 4 was originally reported and limited scanning of these exons was suggested for the diagnosis in most cases. Objective: To report Notch3 mutation analysis in 28 unrelated Italian CADASIL families from central and south Italy. Results: The highest rate of mutations was found in exon 11 (21%) and only 18% of mutations were in exon 4. This may be related to the peculiar distribution of Notch3 mutations in the regions of origin of the families. Conclusions: The results suggest that limited scanning of exons 3 and 4 is inadvisable in CADASIL cases of Italian origin.

The neurologist in the emergency department. An Italian nationwide epidemiological survey

A nationwide survey has been undertaken to evaluate the resources and the activities of Italian hospital neurology units (NU) in the emergency setting. NU are widely disseminated throughout the entire country and 220 (84%) are located in hospitals with an emergency room (ER). Complete data about hospital setting, structural and functional characteristics of each NU and clinical activities were obtained from 159 (72.3%). Each NU has, on average, 25 beds (7% bedside monitoring), 7 neurologists and 17 nurses. A neuroscience department is present in 25% of the hospitals. The ER is the source of 71% of the 148,040 annual admissions and of 57% of the 577,279 annual neurological consultations. Stroke is the most common cause of admission (29%), followed by epilepsy/headache and transient ischaemic attacks. Head trauma prevails in hospitals with no neurosurgical units. Cerebrovascular disorders are the main cause of neurological consultations (28%), followed by headache (22%), dizziness (13%), head trauma (13%), impairment of consciousness (12%) and epilepsy (9%). Only 36% of NU have a 24-h/day, 7 days/week on-duty neurologist and 28% have a stroke unit. The burden of neurological activities is unrelated to the geographical area and hospital’s complexity (size, structural and functional context, ER organisation, presence of stroke units, neurosurgery units or 24/7 neurological service).

Relevance of Prehospital Stroke Code Activation for Acute Treatment Measures in Stroke Care: A Review

Background: The use of emergency services with prehospital stroke assessment and early notification to the treatment hospital (stroke code) is a crucial determinant of delay time for acute stroke treatment. We reviewed and summarized the literature on prehospital stroke code system implementation. Methods: Two databases were explored (last update June 20, 2011) with 3 key words (stroke code, stroke prehospital management and stroke prehospital services). Inclusion criteria were: randomized and quasirandomized controlled trials, cohort and case-control studies, and hospital- and emergency-based registers, with no year or language restrictions. We examined the reference lists of all included articles. All potentially relevant reports and abstracts were transcribed into a specifically designed data abstraction form. Results: Only 19 of the 680 studies which were initially retrieved, published from 1999 to 2011, fulfilled our inclusion criteria. One clinical trial was identified. Large differences in stroke code procedures and study designs within and across countries prohibited the pooling of the data. Most studies were carried out in urban areas. Assuming the rate of tissue-plasminogen activator treatment as the performance measure, most studies report a significant increase in the rate of treatment (increase between 3.2 and 16%) with only 1 study not reporting any increase. Conclusions: Despite its limitations, this review suggests that the use of prehospital stroke code is an important intervention to improve the accessibility of the benefits of thrombolysis, especially when implemented together with educational campaigns to optimize the awareness and behavior of patients and bystanders.

Previous infection and the risk of ischaemic stroke in Italy: the IN2 study

There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population.