Efficacy of azathioprine on multiple sclerosis new brain lesions evaluated using magnetic resonance imaging.

BACKGROUND: Azathioprine is an immunosuppressive agent that reduces relapse rates in patients with multiple sclerosis (MS), but its efficacy in suppressing new brain lesions has never been evaluated. OBJECTIVE: To evaluate the efficacy of azathioprine therapy on new brain lesion suppression in MS. DESIGN: Open-label treatment vs baseline study. SETTING: Outpatient MS clinical center at a university hospital. PATIENTS: Fourteen patients with relapsing-remitting MS of short duration and at least 3 gadolinium-enhancing (Gd+) brain lesions observed within 6 months before treatment. INTERVENTION: Azathioprine, up to 3 mg/kg daily, individually adjusted according to blood lymphocyte number and the occurrence of adverse events. MAIN OUTCOME MEASURES: Brain Gd+ lesions evaluated by monthly magnetic resonance imaging for 6 months before and 6 months during treatment and new T2 lesions evaluated during the same periods and after an additional 6 months. RESULTS: The treatment reduced to 0 the median Gd+ lesion number and volume per magnetic resonance image (P<.001 for both), resulting in a Gd+ lesion number reduction of 50% or more in 12 of 14 patients (P<.01). An equivalent reduction in the new T2 lesion number was observed (P<.02); this activity also persisted during the additional treatment period evaluated using this outcome measure (P<.01). The median azathioprine dose administered (2.6-2.8 mg/kg daily) reduced the mean blood lymphocyte count to 57% of the baseline value. Adverse events were transient or reversible with dose adjustment. CONCLUSIONS: This study indicates for the first time that azathioprine, administered at lymphocyte-suppressing doses, is effective in reducing MS new brain inflammatory lesions and is well tolerated.

Stroke in an elderly population: incidence and impact on survival and daily function. The Italian Longitudinal Study on Aging.

BACKGROUND: Epidemiological data are essential to estimate the burden of stroke. We evaluated stroke incidence in older Italians and the effect of first-ever stroke on survival and activities of daily living (ADL). METHODS: The analysis was performed in the Italian Longitudinal Study on Aging (ILSA) sample, consisting of 5,632 individuals aged 65-84. The ILSA aims at major cardiovascular and neurological age-associated diseases. The baseline survey was performed in 1992 to detect prevalent diseases. The longitudinal examination started on September 1995 aiming at incidence, function and survival. RESULTS: Complete follow-up data were achieved for 77% of the baseline stroke-free cohort (4,164 persons; 50.9% males; mean age 74.5 +/- 5.7 years). Incidence for first-ever stroke was 9.51 (95% CI: 7.75-11.27) per 1,000 person years and 12.99 (95% CI: 10.99-14.98) including recurrent stroke (total incidence). Crude mortality was 49.2% among first stroke patients and 15% among persons without stroke. The first-ever stroke mortality risk ratio, adjusted for demographics and comorbidity, was 2.40 (95% CI: 1.62-3.54). In survivors, impairment of at least one ADL was present in 67.6% of first-ever stroke patients vs. 31.6% of individuals without stroke. The comorbidity-adjusted OR was 2.63 (95% CI: 1.20-5.78) in the total cohort, and 4.00 (95% CI: 1.39-11.46) in individuals without disability at baseline. CONCLUSIONS: The ILSA provides the first data on stroke incidence in Italy on a national basis. Overall, 153,000 new cases can be expected annually in the Italian elderly population. First-ever stroke still has a strong effect on survival and function of older persons.

Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study.

OBJECTIVES: To estimate the incidence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older Italians and evaluate the relationship of age, gender, and education to developing dementia. DESIGN: Cohort incidence study in the context of the Italian Longitudinal Study on Aging. SETTING: Population sample from eight Italian municipalities. PARTICIPANTS: A dementia-free cohort of 3,208 individuals (aged 65-84), individuated after a baseline evaluation performed in 1992 / 93, aimed at detecting prevalent cases. MEASUREMENTS: The dementia-free cohort was reexamined in 1995 to identify incident cases. The Mini-Mental State Examination (cutoff 23 / 24) was employed to screen for dementia. Trained neurologists evaluated the individuals who screened positive. Final diagnoses had to meet Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria for dementia, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and International Classification of Diseases, Tenth Revision criteria for VaD. RESULTS: Before the follow-up examination, 382 individuals had died (232 had reliable information). Of the 2,826 survivors, 2,266 completed the study. Overall, 127 new dementia cases were identified. Average incidence rates per 1,000 person-years were 12.47 (95% confidence interval (CI)=10.23-14.72) for dementia, 6.55 (95% CI=4.92-8.17) for AD, and 3.30 (95% CI=2.14-4.45) for VaD. Both AD and VaD showed age-dependent patterns. Education was protective against dementia and AD. Women carried a significantly higher risk of developing AD (hazard ratio=1.67, 95% CI=1.02-2.75), and men of developing VaD (hazard ratio=2.23, 95% CI=1.06-4.71). CONCLUSIONS: Incidence of dementia in Italy paralleled that in most industrialized countries. About 150,000 new cases per year are expected. A significant gender effect was evidenced for major dementia subtypes. The burden of VaD, especially in men, offers opportunities for prevention.

T-cell response to myelin basic protein and lipid-bound myelin basic protein in patients with multiple sclerosis and healthy donors.

An autoimmune T-cell response to myelin proteins is thought to be involved in the pathogenesis of multiple sclerosis (MS) and myelin basic protein (MBP) is the most widely studied potential target antigen. We investigated the T-cell response to MBP in MS patients and controls using two different molecular forms of the protein: the classical hydrophilic MBP (lipid-free MBP, LF-MBP) and a lipid-bound, native-like preparation of MBP isolated in a molecular form retaining the binding to all myelin lipids (lipid-bound-MBP, LB-MBP). Short term T-cell lines (TCL) were generated using either LF- or LB-MBP and tested for their reactivity to the in vitro stimulating antigen. No differences were detected between MS patients and healthy donors in the percentage of T-cell cultures responsive to the LF-MBP. In contrast, the number of LB-MBP reactive cultures was higher in MS patients than in controls. This difference was almost entirely due to the presence of high numbers of LB-MBP-specific TCL in MS patients which did not cross-react with LF-MBP and were not present in healthy subjects. LB-MBP may represent a novel antigen worth to be investigated in MS.