Giovanni Pracucci

Sex Differences in the Clinical Presentation, Resource Use, and 3-Month Outcome of Acute Stroke in Europe: Data From a Multicenter Multinational Hospital-Based Registry

Background and Purpose— The information on the existence of sex differences in management of stroke patients is scarce. We evaluated whether sex differences may influence clinical presentation, resource use, and outcome of stroke in a European multicenter study. Methods— In a European Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin Scale). Results— Overall, 2239 patients were males and 2260 females. Compared with males, female patients were significantly older (mean age 74.5±12.5 versus 69.2±12.1 years), more frequently institutionalized before stroke, and with a worse prestroke Rankin score (all values P <0.001). History of hypertension (P =0.007) and atrial fibrillation (P <0.001) were significantly more frequent in female stroke patients, as were coma (P <0.001), paralysis (P <0.001), aphasia (P =0.001), swallowing problems (P =0.005), and urinary incontinence (P <0.001) in the acute phase. Brain imaging, Doppler examination, echocardiogram, and angiography were significantly less frequently performed in female than male patients (all values P <0.001). The frequency of carotid surgery was also significantly lower in female patients (P <0.001). At the 3-month follow-up, after controlling for all baseline and clinical variables, female sex was a significant predictor of disability (odds ratio [OR], 1.41; 95% CI 1.10 to 1.81) and handicap (OR, 1.46; 95% CI 1.14 to 1.86). No significant gender effect was observed on 3-month survival. Conclusions— Sex-specific differences existed in a large European study of hospital admissions for acute stroke. Both medical and sociodemographic factors may significantly influence stroke outcome. Knowledge of these determinants may positively impact quality of care.

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Characteristics, Outcome, and Care of Stroke Associated With Atrial Fibrillation in Europe Data From a Multicenter Multinational Hospital–Based Registry (The European Community Stroke Project)

Background and Purpose — The role of atrial fibrillation (AF) as a determinant of stroke outcome is not well established. Studies focusing on this topic relied on relatively small samples of patients, scarcely representative of the older age groups. We aimed at evaluating clinical characteristics, care, and outcome of stroke associated with AF in a large European sample. Methods — In a European Concerted Action involving 7 countries, 4462 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin scale). Results — AF was present in 803 patients (18.0%). AF patients, compared with those without AF, were older, were more frequently female, and more often had experienced a previous myocardial infarction; they were less often diabetics, alcohol consumers, and smokers (all P <0.001). At 3 months, 32.8% of the AF patients were dead compared with 19.9% of the non-AF patients (P <0.001). With control for baseline variables, AF increased by almost 50% the probability of remaining disabled (multivariate odds ratio 1.43, 95% CI 1.13 to 1.80) or handicapped (multivariate odds ratio 1.51, 95% CI 1.13 to 2.02). Before stroke, only 8.4% of AF patients were on anticoagulants. The chance of being anticoagulated was reduced by 4% per year of increasing age. AF patients underwent CT scan and other diagnostic procedures less frequently and received less physiotherapy or occupational therapy. Conclusions — Stroke associated with AF has a poor prognosis in terms of death and function. Prevention and care of stroke with AF is a major challenge for European health systems.

Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65–84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 ± 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

Objective To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes. Design Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints. Setting 11 European centres. Participants 639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy. Main outcome measure Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score ≥2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke. Results Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect. Conclusion The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.

Stroke in the Very Old Clinical Presentation and Determinants of 3-Month Functional Outcome: A European Perspective

BACKGROUND AND PURPOSEnThe oldest old represent the fastest-growing segment of the elderly population in developed countries. Knowledge of age-specific aspects of stroke is essential to establish diagnostic and therapeutic pathways and to set up prevention and rehabilitation programs. We sought to evaluate stroke features and functional outcome in patients aged >/=80 years compared with the younger age groups.nnnMETHODSnIn a European Union Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month disability (Barthel Index) and handicap (Rankin Scale).nnnRESULTSnOverall, 3141 patients (69.8%) were aged <80 years, and 1358 (30.2%) were aged >/=80 years. At baseline, female sex, prestroke institutionalization, and a worse prestroke Rankin score were significantly more frequent in the older patients, as were coma, paralysis, swallowing problems, and urinary incontinence in the acute phase (all P values <0.001). Brain imaging and other diagnostic tools were significantly less used in the older patients. Paralysis, swallowing problems, and incontinence during hospitalization independently predicted 3-month disability or handicap in both groups. For the older patients, prestroke institutionalization proved a further strong and independent determinant of 3-month disability (odds ratio, 2.33; 95% CI, 1.22 to 4.45) and handicap (odds ratio, 7.04; 95% CI, 1.62 to 30. 69).nnnCONCLUSIONSnIn the very old, both medical and sociodemographic factors may significantly influence stroke outcome, showing peculiar characteristics. Knowledge of these determinants may reduce the burden on health systems, improving quality of care.

Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.

Background: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. Methods: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1 ± 5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. Results: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. Conclusions: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.

Risk factors and outcome of subtypes of ischemic stroke. Data from a multicenter multinational hospital-based registry. The European Community Stroke Project

BACKGROUNDnInformation on determinants and prognosis of ischemic stroke subtypes is scarce. We aimed at evaluating risk factors, pathogenesis, treatment and outcome of different ischemic stroke subtypes.nnnMETHODSnIn a European Concerted Action involving seven countries, ischemic stroke subtypes defined according to the Oxfordshire Community Stroke Project (OCSP) were evaluated for demographics, baseline risk factors, resource use, 3-month survival, disability (Barthel Index) and handicap (Rankin Scale).nnnRESULTSnDuring the 12-month study period, cerebral infarction was diagnosed in 2740 patients with first-in-a-lifetime stroke (mean age 70.5+/-12.4 years, 53.4% males). OCSP classification was achieved in 2472 (90.2%). Of these, 26.7% were total anterior circulation infarctions (TACI), 29.9% partial anterior circulation infarctions (PACI), 16.7% posterior circulation infarctions (POCI) and 26.7% lacunar infarctions (LACI). In multivariate analysis, atrial fibrillation was predictive of TACI (odds ratio [OR], 1.61; 95% CI, 1.28-2.03), hypertension (OR, 1.38; 95% CI, 1.16-1.65) and myocardial infarction (OR, 1.42; 95% CI, 1.08-1.86) predictive of PACI, hypertension (OR, 1.25; 95% CI, 1.04-1.50) predictive of LACI. A negative association was observed between TACI and hypertension (OR, 0.51; 95% CI, 0.42-0.61). Discharge home was 50% less probable in TACI and PACI than in LACI patients. As compared to LACI, TACI significantly increased the risk of 3-month death (OR, 5.73; 95% CI, 3.91-8.41), disability (OR, 3.27; 95% CI, 2.30-4.66) and handicap (OR, 2.71; 95% CI, 1.91-3.85).nnnCONCLUSIONSnIschemic stroke subtypes have different risk factors profile, with consequences on pathogenesis and prognosis. Information on determinants of the clinical syndromes may impact on prevention and acute-phase interventions.

Incidence and Determinants of Poststroke Dementia as Defined by an Informant Interview Method in a Hospital-Based Stroke Registry

BACKGROUND AND PURPOSEnInconsistent information about incidence and determinants of poststroke dementia might be related to patient attrition, partly because of nonapplicability of formal neuropsychological testing to a large proportion of patients registered in a definite setting.nnnMETHODSnUsing a proxy-informant interview based on ICD-10 criteria, we determined dementia at stroke onset and 1 year after stroke in the 339 patients who survived, were available for follow-up, and were not demented at stroke onset of 635 patients entered over a 1-year period in a stroke registry taken at 2 community hospitals in Florence, Italy.nnnRESULTSnOf the 339 patients, 57 (16.8%) proved to have poststroke dementia. These patients were older, more frequently female, and more often (multivariate odds ratio, 2.35; 95% CI, 1.21 to 4.58) had atrial fibrillation than those without dementia. Aphasia and the clinical features expressing the severity of the stroke event in the acute phase predicted poststroke dementia.nnnCONCLUSIONSnIn a hospital-based nonselected series of stroke survivors, despite the use of a method with low sensitivity for defining dementia, our study confirms that dementia is a frequent sequela of stroke and is mainly predicted by stroke severity. Certain determinants could be controlled in the prestroke phase, thus reducing its risk.

Leukoaraiosis, intracerebral hemorrhage, and arterial hypertension.

To investigate whether the observed association of leukoaraiosis with intracerebral hemorrhage is direct or mediated by risk factors, we compared 116 patients with intracerebral hemorrhage confirmed by computed tomography and 155 controls without intracerebral hemorrhage, evaluating the prevalence of leukoaraiosis and vascular risk factors. Leukoaraiosis was observed in 21 (18%) of the 116 patients and in 12 (8%) of the 155 controls (p less than 0.01). Only two (6%) of the 31 patients with lobar hemorrhage had leukoaraiosis on computed tomograms, compared with 17 (24%) of the 71 patients with basal ganglionic hemorrhage (p less than 0.05). Leukoaraiosis was significantly correlated with intracerebral hemorrhage after controlling for age and sex by using multiple logistic regression analysis, while the correlation disappeared after controlling for hypertension. Our results indicate that leukoaraiosis is not an independent risk factor for intracerebral hemorrhage.