Irene Ciancarelli

Burden of first-ever ischemic stroke in the oldest old: Evidence from a population-based study

Objective: To evaluate the contribution of subjects 80 years old or older to the burden of ischemic stroke as compared with subjects younger than 80 years. Methods: All first-ever ischemic strokes occurring in a 5-year period (1994 to 1998) in the population-based L’Aquila registry were traced. Incidence, total health care utilization, disability, and mortality were assessed in patients 80 years old or older, and differences with those younger than 80 years were assessed by univariate and survival analyses. Results: One thousand three hundred sixteen of 3,594 first-ever ischemic strokes (36.6%) occurred in patients 80 years old or older, accounting on average for one-third of health care utilization. The crude annual incidence rate was 21.54 per 1,000 (95% CI 20.42 to 22.72). At the 1-year follow-up, 27.7% of patients had mild or no disability, 20.7% had severe disability, and 51.6% had died. With respect to patients under 80 years of age, older patients showed a higher proportion of women (61.3 vs 47.7%), atrial fibrillation (30.2 vs 20.7%), coronary heart disease (31.0 vs 23.4%), and peripheral arterial disease (14.6 vs 10.8%) and a lower proportion of cigarette smoking (15.3 vs 29.2%) and hypercholesterolemia (20.4 vs 29.4%). Thirty-day (34.6 vs 13.4%) and 1-year (51.6 vs 22.3%) mortality were higher in patients 80 years old or older than in those younger than 80, mostly in the presence of atrial fibrillation (hazard ratio [HR] was 1.39 for 30-day mortality and 1.37 for 1-year mortality) and diabetes mellitus (HR was 1.39 for 30-day mortality and 1.31 for 1-year mortality). Conclusion: The burden of ischemic stroke is high in subjects 80 years old or older, contributing about one-third of health care utilization and 59.8% of deaths within 30 days.

Stroke in young adults in the community-based L'Aquila registry: incidence and prognosis.

Background and Purpose— Stroke type in the young may influence the outcome and may have a dramatic impact on the quality of life in survivors. This study aimed to evaluate the incidence and prognosis of first-ever stroke in the young and to make comparisons with older patients within a well-defined population. Methods— All first-ever strokes occurring in the L’Aquila district, central Italy, were traced by active monitoring of inpatient and outpatient health services. Incidence rates were standardized to the 1996 European population according to the direct method. Long-term survival was estimated by the Kaplan-Meier method; outcome in survivors was evaluated by the modified Rankin scale. Results— Of 4353 patients who had a first-ever stroke, 89 patients <45 years of age (55 men and 34 women) (2%) were identified in a 5-year period. Mean age±SD was 36.1±8.1 years. Twenty patients (22.5%) had a subarachnoid hemorrhage, 18 (20.2%) an intracerebral hemorrhage, and 51 (57.3%) a cerebral infarction. The corresponding proportions in patients >45 years of age were 2.4%, 13.3%, and 83.1%. Neuroimaging studies of the brain detected 14 intracranial aneurysms and 6 arteriovenous malformations in 20 of 38 patients (52.6%) with either subarachnoid (n=17) or intracerebral (n=3) hemorrhage. The crude annual incidence rate was 10.18/100 000 (95% CI, 8.14 to 12.57) and 10.23/100 000 when standardized to the 1996 European population. The 30-day case-fatality rate was 11.2% (95% CI, 6.2 to 19.4). Patients with subarachnoid hemorrhage had the highest proportion of good recovery (60%), patients with intracerebral hemorrhage had the highest mortality (44%), and patients with cerebral infarction had the highest proportion of severe disability (47%). Conclusions— Stroke patients <45 years of age showed a disproportionate cumulative high prevalence (42.7%) of subarachnoid and intracerebral hemorrhage with respect to older patients (15.7%), mainly (52.6%) due to aneurysms and arteriovenous malformations. Therefore, screening procedures and preventive strategies in the young should also be addressed to subjects at risk of subarachnoid and intracerebral hemorrhage.

Urinary nitric oxide metabolites and lipid peroxidation by‐products in migraine

Enhanced endothelium nitric oxide (NO) and superoxide anion release may cause migraine through related cerebral blood flow changes. Thirty subjects suffering from migraine with and without aura and 20 healthy controls were investigated. Urine samples collected for 24 h during and after the migraine attack, and during the headache-free period, were assayed for urinary NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). During the headache-free period urinary NOx and TBARS levels were higher in migraine sufferers than in controls (NOx 0.77 ± 0.14 vs. 0.28 ± 0.15 mmol/mmol creatinine, P < 0.05; TBARS 0.40 ± 0.19 vs. 0.26 ± 0.13 μmol/mol creatinine, P < 0.05). Also, NOx excretion was higher during the headache-free period than during or after the migraine attack (P < 0.05). Urinary TBARS were increased during the attack with respect to the headache-free period (P < 0.05). No differences were observed in the same parameters between sufferers of migraine with and without aura. Urinary NOx and TBARS might be promising as markers of their systemic levels to evaluate the increased vulnerability to oxidative stress in migraine sufferers.

Proportion of Older People in the Community as a Predictor of Increasing Stroke Incidence

Objectives: To compare stroke incidence rates among comparable registries and to make correlations with aging of the resident populations. Methods: This correlation study included all comparable stroke registries maintained in industrialized countries (Italy, France, United Kingdom, Denmark, Norway, United States, and Australia). Eleven community-based stroke registries with similar high proportions of radiologically confirmed diagnoses based on standard definitions were identified. Incidence rates of first-ever stroke from the prospective L’Aquila registry and from the other registries were compared after age and sex standardization to the 1996 European population. The rates were then correlated with the proportion of individuals aged 65 and over in the corresponding resident populations by means of the Poisson regression analysis. Results: In the L’Aquila registry, the crude annual incidence of first-ever stroke was 281/100,000 (95% confidence interval 271–293) based on 2,515 patients included during a 3-year period. The rate standardized to the European population was 249/100,000. Standardized incidence ratios indicated a significant excess of first-ever strokes in the L’Aquila registry up to 51% with respect to most of the compared studies. A significant correlation was also found between crude (p < 0.0001) and standardized (p = 0.0012) stroke incidence rates and proportions of individuals aged 65 and over in the different populations. Conclusions: The L’Aquila experience suggests that any further aging of a population will increase the stroke occurrence for both the reasons of a direct and predictable effect of the growing proportion of elderly individuals within that population and a disproportionately increased stroke risk in the older age groups.

Helicobacter pylori infection and migraine.

The study is aimed to ascertain whether the Helicobacter pylori (Hp) infection is responsible for the vulnerability to oxidative stress observed in migraineurs. Hp sero-logical positivity was assessed by ELISA evaluation of specific IgA and IgG antibodies in 30 subjects (11 males and 19 females) suffering from migraine without aura during the headache-free period. The Hp infection was detected in 16.7% of migraineurs. Plasma accumulation of peroxidative substances (TBA-RS), an index of systemic oxidative status, was increased in migraineurs without Hp infection with respect to controls (P< 0.001), while no significant differences of TBA-RS were found in migraineurs with or without Hp infection. Unmodified values of plasma nitrite/nitrate concentrations, expression of systemic nitric oxide (NO), were obtained in migraineurs in comparison to controls indicating that Hp infection does not modify the plasma oxidative status and the systemic NO bioavailability of migraineurs. In conclusion, our results do not support any specific correlation between Hp infection and migraine.

Moderate consumption of red wine and human platelet responsiveness.

Available studies showed an inverse association between red wine consumption and prevalence of vascular risk factors in coronary hearth disease and stroke. Effects were mainly associated to wine antioxidant and antiaggregant properties. Actually, in vitro studies indicate a favourable effect of wine and/or of its non-alcoholic components in decreasing platelet sensitivity and aggregability. In a 4-week supplementation in 15 healthy male volunteers, we evaluated whether moderate red wine consumption might improve antioxidant defence mechanisms and promote positive modulation of inflammatory cytokines and cell adhesion molecules in relation to platelet responsiveness. We did not find any change of ADP- and collagen-induced platelet aggregation ex vivo, any change of biomarkers of oxidative stress, and any change of plasma lipid profile and haemostatic parameters, with the only exception of decreased fibrinogen levels (P<0.05). We also found an increase of mean platelet volume (P<0.05) without any significant modification of CD40 Ligand and P-selectin levels. Increased expressions of intercellular adhesion molecule-1, soluble E-selectin and interleukin-6 (P<0.05) were also observed. According to our findings increased circulating levels of inflammatory and endothelial cell activation markers may indicate a low-grade systemic inflammation and vascular activation that could be responsible for the lack of inhibition or of decreased platelet responsiveness, possibly because the plasmatic increase of wine antioxidant compounds is insufficient to improve endothelial function and to counteract the influence of ethanol on endothelial activation.

Relationship between biofeedback and oxidative stress in patients with chronic migraine

Chronic migraine (1.5.1) is burdened with headache-related disability. During noxious stimulation, changes of cerebral blood flow enhance the release of oxygen free radicals that react with nitric oxide (NO). We investigated the role of biofeedback in limiting migraine disability by influencing oxidative stress. Peroxides, NO and superoxide dismutase (SOD) were analysed in 20 female subjects with chronic migraine and in 20 female healthy controls before and after biofeedback sessions. NOx levels (23.7 ± 4.2 vs. 34.9 ± 4.6 μM; P < 0.05) and SOD activity (6.5 ± 1.0 vs. 8.0 ± 0.7 U/ml; P < 0.05) were lower in migraine sufferers before treatment than in healthy controls, whereas peroxide levels (145.8 ± 40.3 vs. 78.0 ± 20.0 μM; P < 0.05) were higher in migraine sufferers before treatment than in healthy controls. In migraine sufferers NOx levels (23.7 ± 4.2 vs. 31.3 ± 7.1 μM; P < 0.05) and SOD activity (6.5 ± 1.0 vs. 7.9 ± 0.9 U/ml; P < 0.05) were lower before than after treatment, whereas peroxide levels (145.8 ± 40.3 vs. 82.4 ± 21.1 μM; P < 0.05) were higher before than after treatment. SOD serum activity correlated positively with NOx serum levels and negatively with peroxide serum levels in healthy controls and in chronic migraine sufferers before and after biofeedback. The mean Migraine Disability Assessment Score before biofeedback sessions was higher than after treatment (36.9 ± 13.9 vs. 18.8 ± 10.4; P < 0.001). The effectiveness of biofeedback in limiting chronic migraine may be related to muscular relaxation associated with decreased oxidative stress accompanied by psychological well-being.

Evidence of redox unbalance in post-acute ischemic stroke patients.

Measurements of the redox balance after the ischemic stroke occurrence might be useful to monitor the outcome of patients who suffered an ischemic stroke in terms of stroke recurrence and other vascular events. For this purpose, fifteen patients (mean age 71.40±2.50 years) with a first-ever ischemic stroke were included in the study within 30 days of stroke onset. Stroke severity was evaluated according to the National Institutes of Health Stroke Scale (NIHSS). Redox balance was assessed by measuring plasma amount of total peroxidative by-products, nitrite/nitrate metabolites (NOx), as expression of nitric oxide (NO) plasma bioavailability, total plasma antioxidant capacity (TEAC), Cu/Zn Superoxide Dismutase (Cu/Zn SOD) activity, serum urate concentration and autoantibodies against ox-LDL (OLAB) serum level. Total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were also measured. Fifteen apparently healthy controls (mean age 70.28±2.03 years) were investigated to compare redox markers. Stroke patients had higher plasma values of total peroxidative by-products, NOx stable metabolites and of total cholesterol, triglycerides, and LDL-C than controls (P < 0.05). No differences in OLAB levels, Cu/Zn-SOD activity, serum urate concentration, and plasma HDL-C amount were found in stroke patients when compared to controls. Total plasma antioxidant capacity was lower in stroke patients than in controls. NOx values correlated positively with the NIHSS score in stroke patients (r=0.668; P=0.0065). The observed presence of redox unbalance in stroke patients could represent an early indicator of diffuse endothelial activation during which patients may be at increased risk of stroke recurrence and other vascular events.

Flunarizine Effects on Oxidative Stress in Migraine Patients

Prophylactic activity of flunarizine in migraine is attributed to its antioxidant properties and to the relief of cerebral vasospasm in which nitric oxide (NO) is involved. We investigated the antimigraine activity of flunarizine and its influence on NO and oxidative marker bioavailability in 25 subjects suffering from migraine without aura and in 25 healthy controls. Urinary samples collected before and after treatment with flunarizine (5 mg orally per day for 6 months) were assayed for NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). Urinary levels of NOx and TBARS were higher in migraine sufferers before treatment than in healthy controls. No differences were observed in NOx levels in migraine sufferers, before and after flunarizine treatment; urinary TBARS levels were decreased after flunarizine treatment (P < 0.05) and remained persistently higher than in healthy controls (P < 0.05). Our results suggest that flunarizine did not prevent NO-mediated vasodilatation, while it proved effective in limiting the oxidative reactions occurring in migraine sufferers.

Preventive non-pharmacological treatment and nitric oxide in chronic migraine.

In chronic migraine the central sensitisation and the changes of regional cerebral blood flow are mediated by nitric oxide (NO) and oxygen free radicals. Biofeedback is considered a preventive non–pharmacological treatment decreasing migraine attacks. We investigated whether biofeedback effectiveness is related to relaxation processes and its influence on oxidative stress. The Migraine Disability Assessment Score (MIDAS) and serum NO stable metabolites (NOx) were evaluated in 20 patients with chronic migraine before and at the end of biofeedback sessions. MIDAS score was lower after biofeedback than that reported before treatment. NOx serum levels were higher after biofeedback than those measured before starting treatment. Thus, the effectiveness of biofeedback is related to a muscular relaxation and to its influence on NO bioavailability in patients with chronic migraine.