Massimo Baldassarre

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.

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.

Cerebrovascular Reactivity Evaluated by Transcranial Doppler: Reproducibility of Different Methods

Transcranial Doppler is routinely used to assess the cerebrovascular reactivity, despite scarce information on its reproducibility. We evaluated the reproducibility of cerebrovascular reactivity measurements by this method utilizing different vasodilatory and vasoconstrictor stimuli. The cerebrovascular reactivity was measured in 45 healthy volunteers during hypercapnia induced by inhalation of a mixture of 5% CO2 and 95% O2, breath holding and rebreathing, and during hypocapnia induced by voluntary hyperventilation. Three sets of measurements were performed at times 0, 1, and 24 h to assess the within-observer short- and long-term reproducibility. The reproducibility was analyzed using the intraclass correlation coefficient. For the CO2 inhalation method, a good short-term (rI = 0.55; 95% CI = 0.39–0.68) and a good long-term (rI = 0.43; 95% CI = 0.25–0.59) reproducibility was found. For the breath-holding method a good short-term agreement was found (rI = 0.41; 95% CI = 0.22–0.57), while the long-term reproducibility was poor (rI = 0.17; 95% CI = –0.03–0.36). Rebreathing showed a fair (rI = 0.31; 95% CI = 0.11–0.48) short-term and a poor (rI = 0.17; 95% CI = –0.03–0.36) long-term reproducibility. For voluntary hyperventilation, the short-term reproducibility was good (rI = 0.53; 95% CI = 0.36–0.66), and the long- term reproducibility was fair (rI = 0.31; 95% CI = 0.11–0.48). In our study, CO2 inhalation and voluntary hyperventilation had the highest reproducibility and should be preferred when assessing cerebral vasoreactivity, especially in follow-up studies.

Sumatriptan and Cerebral Blood Flow Velocity Changes During Migraine Attacks

Transcranial Doppler studies on the effects of sumatriptan on cerebral hemodynamics have shown conflicting results. We evaluated blood flow velocity changes in 21 patients suffering from migraine with (n = 4) or without aura (n = 17) during a spontaneous attack, before and after treatment with sumatriptan. Flow velocity in the internal and external carotid, middle cerebral, and basilar arteries was measured by means of transcranial Doppler. During the attack, measurements were taken before subcutaneous sumatriptan injection, then after 30 minutes, 2 hours, and 24 hours. An additional measurement was taken 1 week later, in a headache‐free state. We found a significant reduction of flow velocity during the attack in the middle cerebral artery on both sides (P < 0.05). After sumatriptan administration, flow velocity increased in the internal carotid artery on both sides (P < 0.05) and in the middle cerebral artery on the headache side (P = 0.0001), but not in the external carotid and basilar arteries (P > 0.05). Flow velocity changes may reflect the vasodilation present at the onset of the migraine attack followed by vasoconstriction in the internal carotid and middle cerebral arteries after sumatriptan treatment. Since vasoconstriction occurs in responders and nonresponders to treatment, it is unlikely to be the primary mechanism by which sumatriptan relieves headache.

Prolongation of TCD-enhanced Doppler signal by continuous infusion of levovist

This study evaluated the effects of two different rates of infusion of echo-contrast agents (ECA) on signal enhancement. A total of 15 patients with insufficient Doppler signal due to inadequate transtemporal acoustic bone window were examined. Signal from the middle cerebral artery was recorded during the IV infusion of Levovist (300 mg/mL). Increment of signal enhancement in dB, time to signal enhancement appearance, time to clinically useful signal enhancement appearance, and duration of clinically useful signal enhancement were assessed during two infusions at the rate of 1 and 0.66 mL/min, respectively. Increment of signal enhancement was similar at the rate of 1 and 0.66 mL/min (p = 0.4). Mean time to signal enhancement appearance and mean time to clinically useful signal enhancement appearance were not significantly different with the two rates of infusion (p = 0.9 and p = 0.3, respectively). Mean duration of clinically useful signal enhancement was significantly higher with the infusion rate of 0.66 mL/min as compared to 1 mL/min (p < 0.0001). Levovist injected at the infusion rate of 0.66 mL/min prolonged the mean duration of signal enhancement, maintaining its effectiveness.

Chrononeuroendocrinology of Depression

The recent progress in neurobiology has redefined most of the classical concepts in the neurosciences. Not even the role of the neurotransmitters, from the study of which many data about the pathophysiology of the nervous system were drawn, has remained unchanged by the new considerations. In fact, their functions, previously believed to be transmission of biological messages from neuron to neuron or from neuron to a peripheral receptor, have been newly defined (Calne, 1979).