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We performed a post-marketing study of patients with multiple sclerosis (MS) attending the outpatient service to evaluate the impact of interferon beta-1b (IFNbeta-1b) in the daily clinical setting. The absolute changes in relapse frequency and in the mean EDSS score over a three-year period were compared between 83 patients with relapsing remitting MS treated with IFNbeta-1b and 83 RRMS patients who did not take the drug. Annualized relapse frequency significantly decreased in patients undergoing therapy while no statistically significant changes in EDSS score were observed. These findings point out the role of post-marketing studies in evaluating the impact of approved drugs in the daily clinical setting in terms of safety and tolerability. Furthermore, our results confirm the positive effect of immunomodulatory treatment in decreasing the occurrence of inflammatory events.

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.

HLA-A, -B, -C, -DR, -DQ antigens were studied in 11 multiplex MS families, 11 single-case MS families and 100 healthy subjects. The HLA DR4 was the most frequent antigen in all MS patients (p = 0.015). When the antigenic frequency in index familial cases was compared with that in single cases, the DR4 antigen was found to be more frequent (p = 0.01) in familial cases only. Furthermore, when the DR4 antigen was excluded from the analysis, we observed an increase in DR2 (p = 0.11) only in the familial MS cases. These results can be compatible with a multifactorial hypothesis according to which the HLA genes have an important role in MS susceptibility in familial cases.

A standardized protocol was used for duplicate examination by two neurologists of the clinical history and neurological signs in 55 patients with reversible cerebral ischemia. One trained examiner from each of eight clinical centres involved in the Italian Cooperative Study on reversible cerebral ischemia participated in this research. Duplicate examination were compared in order to evaluate the percentage of agreement achieved in the responses. Several discrepancies relating to either historical data or neurological signs were detected. Possible causes of this disagreement are discussed. The inter-observer differences appear to be an important problem to be faced in cooperative studies on reversible ischemic attacks. The purpose of the study was to estimate these differences in the attempt to increase the degree of agreement by repeated training sessions and discussion between the different examiners. These efforts are needed to improve the quality of clinical investigations on reversible cerebral ischemia and to increase the validity of their results.

This study is based on 166 patients with definite multiple sclerosis (MS) residing in different Italian regions and on 332 parents and 326 siblings. Seven patients had a first-degree relative with a definite diagnosis. The comparison with a population age-matched for specific frequency of MS showed an increase of the disease among relatives. The increase in MS frequency among sibs is compared with that expected under an autosomal dominant, autosomal recessive or multifactorial model. The multifactorial hypothesis appears to better fit the data. The heritability index is calculated for each combination of relative and affected patient sex and compared with estimates of other European and American countries. The recurrence risk rates for male and female relatives have been computed for the more frequent family situations. Our results support the hypothesis of a multifactorial model of inheritance and provide risk figures to be used in genetic counseling.

Two cases of histopathologically documented Creutzfeldt-Jakob disease were observed in the same area of the province of Siena in 1974-1975. The transmission of the disease was obtained through brain homogenates and lymphnodes in one of the two cases. This confirms that the agent is present in other tissues besides the brain and underlines further the analogies between Creutzfeld-Jakob disease and scrapie.

A total of 462 patients (mean age 52 years) affected by reversible focal ischemic attacks (RIAs) were followed prospectively in 8 neurologic institutions in Italy for 4 years. All cases were evaluated with a cerebral angiography and 21% of angiograms were normal. At the end of the follow-up period the cumulated probability for death, stroke, cardiac event and new RIA was respectively 7%, 8%, 3% and 36%. The predictive value of the baseline characteristics of this series was evaluated by a multifactorial analysis which showed that RIA and stroke (specific cerebrovascular risk) were more likely to develop in patients with a history of more than one RIA and in those in whom multiple vascular territories were involved. Moreover, previous myocardial infarction, intermittent claudication, angina pectoris, time elapsed since the first attack, and duration and severity of the attack itself were independently associated with general cardiovascular risk (death, stroke and myocardial infarction). We conclude that predictive factors, and thus also pathogenetic mechanisms, may be different for general cardiovascular risk and specific cerebrovascular risk in RIA patients.

We conducted a case-control study of 116 patients with the clinical diagnosis of Alzheimer's 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 subject's 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 Down's syndrome.