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Background: According to the literature, about one third of patients with brain ischemic symptoms lasting <24 hours, which are classified as TIAs according to the traditional "time-based" definition, show the presence of acute ischemic lesions at neuroimaging. Recent evidence has shown that the presence of acute ischemic lesions at neuroimaging may impact on the outcome of patients with transient ischemic symptoms treated with dual antiplatelet treatment (DAPT). This uncertainty is even more compelling in recent years as short-term DAPT has become the standard treatment for any non-cardioembolic TIA or minor ischemic stroke., Methods: This is a pre-specified subgroup analysis from a prospective multicenter real-world study (READAPT). The analysis included patients with time-based TIA - i.e. those with ischemic symptoms lasting <24 hours - who started DAPT. In the whole population, we assessed the presence of acute brain ischemic lesions at neuroimaging and their association with the ABCD2 score. To assess the impact of acute brain ischemic lesions on 90-day prognosis, we performed a propensity score matching of patients with and without those lesions. We adopted a primary effectiveness outcome which was a composite of new stroke/TIA events and death due to vascular causes at 90 days., Results: We included 517 patients - 324 (62.7%) male - with a median (interquartile range - IQR) age of 74 (IQR 65-81) years; 144 patients (27.9%) had acute brain ischemic lesions at neuroimaging. The proportion of patients with brain ischemic lesions did not vary according to the ABCD2 score. At follow-up, 4 patients with brain ischemic lesions (2.8%) and 21 patients without lesions (5.6%) reported the primary effectiveness outcome, which was similar between the groups before (p=0.178) and after matching (p=0.518)., Conclusions: In our population, patients with transient ischemic symptoms and acute ischemic lesions at brain MRI had a risk of recurrent ischemic events similar to those without lesions. The risk of recurrent ischemic events was low in both groups.

Background: Short-term dual antiplatelet treatment (DAPT) is superior to single antiplatelet treatment (SAPT) for secondary prevention in non-cardioembolic minor ischemic stroke and high-risk TIA. As the real-world use of DAPT is broader than in trials, it is important to clarify its benefit/risk profile in a diverse population., Methods: Post-hoc analysis of prospectively collected data from the READAPT cohort and 3 prospective stroke registries including patients with mild-to-moderate (National Institute of Health Stroke Scale [NIHSS] score 0-10) ischemic stroke receiving early DAPT or SAPT. The primary effectiveness outcome was 90-day return to pre-stroke neurological functioning using modified Rankin Scale (mRS) score. Secondary effectiveness outcomes were 90-day mRS shift, new ischemic stroke/TIA, vascular and all-cause death, 24-h early neurological improvement or deterioration. The safety outcome was 90-day intracranial hemorrhage., Results: We matched 1008 patients treated with DAPT and 1008 treated with SAPT. Compared to SAPT, patients treated with DAPT showed higher likelihood of 90-day primary effectiveness outcome (87.5% versus 84.4%, risk difference 3.1% [95%CI 0.1%-6.1%];p=0.047, risk ratio 1.03 [95%CI 1.01-1.07];p=0.043) and higher rate of 24-h early neurological improvement (25.3% versus 15.4%, risk difference 9.9% [95%CI 6.4%-13.4%];p<0.001, risk ratio 1.65 [95%CI 1.37-1.97];p<0.001). No differences were observed for other study outcomes. Subgroup analysis confirmed benefit of DAPT over SAPT for primary effectiveness outcome in patients with moderate stroke, those treated with intravenous thrombolysis and who received antiplatelet loading dose., Conclusions: Our findings suggest that DAPT use might be safe and more effective than SAPT even in the real-world and in patients who do not strictly fulfill criteria of landmark large clinical trials.

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.

Interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are proinflammatory cytokines which may be involved in the pathogenesis of MS. IFN-alpha counteracts many of the proinflammatory actions of IFN-gamma and TNF-alpha. We treated 20 patients with relapsing-remitting (RR) MS with 9 MIU of recombinant IFN-alpha-2a (rIFN-alpha) (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions at serial MRI occurred in 2/12 rIFN-alpha-treated and in 7/8 placebo-treated patients (P < 0.005). Only one new MRI lesion was detected in the rIFN-alpha group, while 27 new or enlarging lesions were detected in placebo group (P < 0.01). Baseline lymphocyte IFN-gamma (19.10 +/- 7.12 U ml-1) and TNF-alpha (18.05 +/- 5.34 pg ml-1) production significantly decreased to 3.03 +/- 0.66 (P < 0.04) (for IFN-gamma) and to 5.78 +/- 0.90 (P < 0.04) (for TNF-alpha) after rIFN-alpha treatment. IFN-gamma and TNF-alpha production was unchanged in the placebo group. rIFN-alpha was tolerated without drop-outs or serious side-effects, but fever, malaise, fatigue (interfering with daily activities in two patients) and leukopenia frequently occurred. High-dose chronic systemic rIFN-alpha might reduce clinical and MRI signs of disease activity in RRMS. The changes in cytokine production suggest that the effect is probably mediated by a down-regulation of proinflammatory cytokine.