Massimiliano Prencipe

Risk factors for clinically diagnosed Alzheimer's disease A case‐control study of an Italian population

We conducted a case-control study of 116 patients with the clinical diagnosis of Alzheimers disease (AD) in seven Italian centers. One hundred sixteen hospital controls and 97 population controls were matched by age, sex, and region of residence to the cases. A structured questionnaire was administered to the next-of-kin of cases and controls by trained interviewers to identify possible risk factors. Genetic, viral, toxic, immunologic, medical, surgical, and personality factors were investigated. Dementia among first- or second-degree relatives and advanced age of the mother at subjects birth (age over 40) were associated with AD. Head trauma was more frequent in cases than in either hospital or population controls, but the differences were not significant. Our data did not confirm the previously reported association with antecedent thyroid disease or family history of Downs syndrome.

Derangement of regional cerebral blood flow and of its regulatory mechanisms in acute cerebrovascular lesions

IT HAS LONG BEEN RECOGNIZED~ that cerebral anoxia produces, in addition to damage to nervous structures, a serious derangement of the mechanisms of regulation of cerebral vasomotility. A more detailed knowledge of the functional aspects of cerebral vascular pathology has been permitted by the availability of reliable methods of exploring quantitatively the circulation in discrete parts of the brain. Studies performed in patients with the radioactive inert gas regional clearance method proposed by Lassen and co-workers in 1963* have demonstrated that [ 11 the autoregulation (constancy of cerebral blood flow at different levels of perfusion pressure) is lost in many patients in the first days after an ischemic insult,”-5 [2] in the same group of patients6 the response to changes in arterial CO, tension may be regionally impaired (loss or delay of cerebral vasodilatation in response to hypercapnia had been previously demonstrated with the N 2 0 method7 and with radioalbumins), and [3] shortly after an acute brain infarction a cerebral reactive hyperemia with marked increase in blood flow (the “luxury perfusion” phenomenon) may occur.5~9,10 Experimental studies have confirmed the above observations,l1-15 whose physiological and possibly practical implications are of considerable importance. The present study further documents the

A prospective study of cerebral ischemia in the young. Analysis of pathogenic determinants. The National Research Council Study Group.

Background and Purpose The etiology of stroke in the young is different from that in older patients and remains unknown in almost one third of the cases. To gain further insight into both pathogenic and etiologic determinants, we prospectively studied a large number of consecutive young adults with focal cerebral ischemia. Methods Three hundred thirty-three patients aged 15–44 years with transient ischemic attack or ischemic stroke within the 8 weeks before hospital admission were recruited and investigated by using a standardized protocol of clinical evaluation, blood tests, electrocardiography, echocardiography, chest roentgenography, and brain computed tomography. Presumed etiology was diagnosed by prospectively applied criteria. Results Women predominated (61%) among patients under 35 years of age, mainly due to the frequency of cerebral ischemia related to oral contraceptive use, while men outnumbered women (60%) among patients over that age because of a higher prevalence of atherothrombotic disease. Potential cerebral embolism of cardiac origin was the presumed cause of stroke in 23.7%, but conventional sources of emboli were found only in 7.5% of cases. There was a low prevalence of atrial fibrillation among young patients with cerebral ischemia. Mitral valve prolapse was found in 8.4%, as expected, predominantly (71.4%) among the younger patients. The prevalence of stroke over transient ischemic attack was proportional to the likelihood of cardiac embolism. Acute alcohol intoxication was considered a precipitating factor in only three patients. The percentages of cerebral ischemia attributed to arterial dissection (0.3%), oral contraceptive use in women (8.1%), migraine (1.2%), and other associated medical diseases (1.5%) were lower than reported in recent clinical series. Conclusions Two different groups of pathogenic determinants predominate in younger women and in older men, supporting public health measures aimed at strict medical control of the recognized cerebrovascular risk factors.

Stroke, Disability, and Dementia Results of a Population Survey

BACKGROUND AND PURPOSE Stroke, disability, and dementia often coexist in elderly people. We assessed the prevalence and mutual association of these disorders in an elderly rural population. METHODS We carried out a door-to-door survey on all subjects aged 65 years or over (n=1032) living in a rural community. To evaluate the associations between stroke and disability and between stroke and dementia, we compared stroke patients with all stroke-free subjects by means of two multiple logistic regression analyses. Subsequently, we performed a case-control analysis by comparing each stroke patient with two age- and sex-matched population control subjects. RESULTS We identified 80 stroke patients. After the exclusion of five incident cases, the prevalence of stroke was 7.3% (95% confidence interval [CI], 5.7 to 8.9). Sixty-five percent of stroke survivors and 23% of stroke-free subjects were disabled (age- and sex-adjusted odds ratio [OR], 6.3; 95% CI, 3.7 to 10.9). Thirty percent of stroke survivors and 5.7% of stroke-free subjects were demented. The OR for dementia (stroke patients versus all stroke-free subjects) was 5.8 (95% CI, 3.1 to 10.8) and became 3.4 (95% CI, 1.5 to 8.0) in the case-control analysis. CONCLUSIONS In our population, the prevalence of stroke was higher than in previous studies. Stroke survivors were more disabled and more at risk for dementia than stroke-free subjects.

Long-term Prognosis After a Minor Stroke 10-Year Mortality and Major Stroke Recurrence Rates in a Hospital-Based Cohort

BACKGROUND AND PURPOSE Determinants of long-term outcome are not well defined in minor stroke patients. This study aims to evaluate which factors are independent long-term predictors of death and major stroke recurrence in a cohort of minor ischemic strokes. METHODS A cohort of 322 patients with first-ever minor ischemic strokes (mean age, 55 years; 89% were treated with antiplatelet or anticoagulant drugs) with minor (Rankin score=2) or no disability (Rankin score <2) were followed for 10 years, with only 6% lost to follow-up. Death and major stroke recurrence rates were evaluated by Kaplan-Meier analysis. Hazard ratios and 95% confidence intervals (CI) of factors with P<.1 at the log-rank test were evaluated by multivariate Cox analysis. RESULTS The 10-year mortality rate was 32%, with a relative risk of 1.7 (95% CI, 1.4 to 2.1) compared with the age- and sex-matched general population. The 10-year recurrence rate of major strokes was 14%. The hazard ratio (95% CI) of death was 1.1 (1.05 to 1.09) for age (1-year increments), 3.4 (2.2 to 5.2) for minor disability, 1.8 (1.1 to 3.1) for myocardial infarction (MI), 2.0 (1.1 to 3.7) for nonvalvular atrial fibrillation, and 1.8 (1.2 to 2.7) for hypercholesterolemia. The hazard ratio (95% CI) of major stroke recurrence was 2.8 (1.3 to 6.2) for recurrent minor strokes, 3.1 (1.9 to 4.6) for nonlacunar stroke, 2.9 (1.3 to 6.8) for MI, and 3.0 (1.4 to 6.4) for hypertension. CONCLUSIONS In minor ischemic strokes, age, minor disability, MI, nonvalvular atrial fibrillation, and hypercholesterolemia increase the risk of death; recurrent minor strokes, nonlacunar stroke, MI, and hypertension increase the risk of major stroke.

Altered response to rTMS in patients with Alzheimer's disease

OBJECTIVE In this study, we tested the excitability of cortical motor areas in patients with Alzheimers disease. Because repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability, possibly by inducing a short-term increase in synaptic efficacy, we used rTMS to investigate motor cortex excitability in patients with Alzheimers disease. METHODS We tested the changes in the size and threshold of motor evoked potential (MEP) and cortical silent period (CSP) duration evoked by focal rTMS delivered in 10 trains of 10 stimuli at 5Hz frequency and 120% rMth intensity in a group of patients with Alzheimers disease, and age-matched controls. In a further session, rTMS was also delivered at 1Hz frequency (trains of 10 stimuli, 120% rMth). RESULTS Whereas in control subjects, 5Hz-rTMS elicited normal MEPs that progressively increased in size during the train, in patients, it elicited MEPs that decreased in size. The increase in the duration of the CSP was similar in patients and healthy controls. One hertz rTMS left the MEP amplitude unchanged in patients and healthy controls. CONCLUSIONS The lack of MEP facilitation reflects an altered response to 5Hz-rTMS in patients with Alzheimers disease. SIGNIFICANCE Our rTMS findings strongly suggest an altered cortical plasticity in excitatory circuits within motor cortex in patients with Alzheimers disease.

Focal Cerebral Ischemia in Young Adults: A Collaborative Case-Control Study

Because there is uncertainty about the role of atherogenic and nonatherogenic risk factors for cerebral ischemia in the young, we carried out a multicenter, hospital-based, case-control study. 333 patients (15-44 years) with focal cerebral ischemia (transient ischemic attack or stroke within 8 weeks of admission) were eligible. 25 patients were excluded, according to the protocol. 308 cases were matched by age and gender to one hospital and one population control. Independent risk was shown by logistic conditional regression for migraine with aura [odds ratio (OR) = 14.8], smoking (OR = 3.7), alcohol (OR = 2.8), serum triglycerides (OR = 1.6), arrhythmias (OR = 9.5), mitral stenosis (OR = 56), coronary heart disease (OR = 4.3) and carotid stenosis or occlusion (OR = 41). Serum HDL-cholesterol had a relative protective effect (OR = 0.8). These data confirm the role of atherosclerosis and cardiac diseases as well as migraine with aura and alcohol consumption in the pathophysiology of cerebral ischemia in the young. More thorough prevention programs may contribute to earlier detection and control of all of these risk factors, but further investigations in patients with as yet unidentified risk factors are warranted because the above-mentioned factors do not account for the total risk of ischemic stroke in the young.

Diffusion-weighted magnetic resonance imaging in patients with partial status epilepticus

Purpose:  Diffusion‐weighted magnetic resonance imaging (DWI) is used to detect changes in the distribution of water molecules in regions affected by various pathologies. Like other conditions, ictal epileptic activity, such as status epilepticus (SE), can cause regional vasogenic/cytotoxic edema that reflects hemodynamic and metabolic changes. This study describes the electroclinical and neuroimaging findings in 10 patients with partial SE whose DWI evaluation disclosed periictal changes related to sustained epileptic activity.

Video-EEG Study of Psychogenic Nonepileptic Seizures: Differential Characteristics in Patients with and without Epilepsy

Summary:  Purpose: Psychogenic nonepileptic seizures (PNES) are episodes that may resemble epileptic seizures (ES) but are not associated with abnormal electrical discharges in the brain. Video‐EEG recording of a typical episode is considered the best diagnostic tool available. PNES are, however, also documented in patients with epilepsy (PNES/ES). The purpose of this study was to assess this comorbid population, focusing on the differences between patients with PNES/ES and patients with PNES alone.

The COX-2 G/C -765 polymorphism may modulate the occurrence of cerebrovascular ischemia.

In the atherosclerotic plaque, cycloxygenase-2 (COX-2) catalyzes prostaglandin E formation, which acts as a pro-atherogenic factor. A polymorphism, G/C −765, within the COX-2 promoter region modulates gene expression and the risk of cerebrovascular disease. We have evaluated the relation between COX-2 G/C −765 genotypes and the occurrence of cerebrovascular ischemia. We evaluated the COX-2 G/C −765 polymorphism in 110 consecutive patients with a documented history of acute ischemic cerebrovascular disease, in 110 age-matched and sex-matched subjects without such history, and in a general population (n = 324) from the same ethnical background. The frequency of the COX-2 −765C allele in patients [0.21; 95% confidence interval (CI), 0.16–0.26] was similar to those found in controls (0.28; 95% CI, 0.22–0.34) and in the general population (0.26; 95% CI, 0.23–0.29). Carriers of the CC genotype differed between patients (0.02; 95% CI, 0.00–0.05) and controls [0.10 (95% CI, 0.04–0.16), P = 0.019; odds ratio, 0.17 (95% CI, 0.04–0.79)] or the general population [0.08 (95% CI, 0.05–0.11), P = 0.023; odds ratio, 0.22 (95% CI, 0.05–0.95)]. In a multiple logistic regression analysis adjusted for confounding variables, smoking status (P < 0.001), atrial fibrillation (P = 0.004) and COX-2 G/C−765 polymorphism (P = 0.016) independently contributed to cerebrovascular ischemia, with CC carriers exhibiting a lower risk (odds ratio, 0.07; 95% CI, 0.01–0.61). Our data show an association between the COX-2 G/C−765 gene polymorphism and cerebrovascular ischemia, suggesting that the COX-2 gene is a susceptibility locus for the risk of cerebrovascular ischemic disease.