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Morrow D.A.,Harvard University | Alberts M.J.,Southwestern University | Mohr J.P.,Columbia University | Ameriso S.F.,Raul Carrea Institute for Neurological Research FLENI | And 6 more authors.
Stroke | Year: 2013

Background and Purpose-Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the proteaseactivated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods-We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. Results-The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46-4.36). Conclusions-In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke. © 2013 American Heart Association, Inc. Source


Merello M.,Raul Carrea Institute for Neurological Research FLENI
Movement disorders : official journal of the Movement Disorder Society | Year: 2010

Gait festination (FE) can cause serious disability in Parkinson's disease (PD) patients. It is argued that the center of pressure position (COP) and body center of mass (COM) are possibly implicated in FE pathogenesis. The relationship between them remains unclear. The goal of this study was to determine spatiotemporal relationships between COM and COP in PD and to explore whether FE arises as a consequence of lack of physiological link between COP and COM during step stride. Twenty patients with idiopathic PD, in OFF state and 17-age-matched control subjects completed a 10-m walking protocol. PD patients were divided in two groups: those with FE and those without (NF). COM position, excursion, and its relationship with COP, as well as other kinematic parameters were analyzed. COM displacement along the horizontal and vertical plane was significantly lower in FE patients as was the maximum position on the movement direction axis compared with controls or NF patients. Significant difference in minimal COM position in FE patients was also observed. The percentage of stride time during which COM was situated ahead of COP along the movement axis in FE patients was significantly greater than for controls or NF patients. This would seem to indicate that FE patients are constantly attempting to align COP to COM, causing FE. The explanation might be that FE arises as a postural strategy to align COP within the area of COM displacement. Findings illustrate a putative role for postural strategies in the treatment of FE. 2010 Movement Disorder Society Source


Farez M.F.,Raul Carrea Institute for Neurological Research FLENI | Fiol M.P.,Raul Carrea Institute for Neurological Research FLENI | Gaitan M.I.,Raul Carrea Institute for Neurological Research FLENI | Quintana F.J.,Harvard University | Correale J.,Raul Carrea Institute for Neurological Research FLENI
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2014

Background Recently, salt has been shown to modulate the differentiation of human and mouse Th17 cells and mice that were fed a high-sodium diet were described to develop more aggressive courses of experimental autoimmune encephalomyelitis. However, the role of sodium intake in multiple sclerosis (MS) has not been addressed. We aimed to investigate the relationship between salt consumption and clinical and radiological disease activity in MS. Methods We conducted an observational study in which sodium intake was estimated from sodium excretion in urine samples from a cohort of 70 relapsing-remitting patients with MS who were followed for 2 years. The effect of sodium intake in MS disease activity was estimated using regression analysis. We then replicated our findings in a separate group of 52 patients with MS. Results We found a positive correlation between exacerbation rates and sodium intake in a multivariate model adjusted for age, gender, disease duration, smoking status, vitamin D levels, body mass index and treatment. We found an exacerbation rate that was 2.75-fold (95% CI 1.3 to 5.8) or 3.95-fold (95% CI 1.4 to 11.2) higher in patients with medium or high sodium intakes compared with the low-intake group. Additionally, individuals with high-sodium intake had a 3.4-fold greater chance of developing a new lesion on the MRI and on average had eight more T2 lesions on MRI. A similar relationship was found in the independent replication group. Conclusions Our results suggest that a higher sodium intake is associated with increased clinical and radiological disease activity in patients with MS. © 2014 by the BMJ Publishing Group Ltd. Source


Crivelli L.,Raul Carrea Institute for Neurological Research FLENI | Farez M.F.,Raul Carrea Institute for Neurological Research FLENI | Gonzalez C.D.,University of Buenos Aires | Fiol M.,Raul Carrea Institute for Neurological Research FLENI | And 3 more authors.
Journal of the International Neuropsychological Society | Year: 2012

The objective of this study is to assess attention in recently diagnosed relapsing-remitting multiple sclerosis patients. Twenty-seven patients with early multiple sclerosis and low clinical disability scores (EDSS<2) and 27 sex-, age-, and education-matched healthy controls underwent attention assessment using the Attentional Network Test, a computerized task designed to measure efficiency independently in 3 attentional networks (Alerting, Orienting and Executive Control). MS patients had significantly less efficiency in the Alerting network (p =.006). In contrast, in the Orienting and Executive Control networks, they did not differ from controls. A significant interaction between Alerting and Executive Control was also found in the MS patients (p =.007). Early relapsing-remitting multiple sclerosis particularly affects the Alerting domain of attention, whereas the Orienting and Executive Control domains are not affected. © 2012 INS. Published by Cambridge University Press. Source


Rossi M.,Raul Carrea Institute for Neurological Research FLENI | Merello M.,Raul Carrea Institute for Neurological Research FLENI | Perez-Lloret S.,Pontifical Catholic University of Argentina | Perez-Lloret S.,CONICET
Expert Opinion on Pharmacotherapy | Year: 2015

Introduction: Constipation is a frequent non-motor feature of Parkinson's disease (PD). It is the most common gastrointestinal symptom of the disease and it can precede motor symptoms by as much as 20 years. Constipation can produce discomfort and affect activities of daily living, productivity and quality of life, thus warranting early diagnosis and treatment.Areas covered: In this review, the safety and efficacy of traditional and novel strategies for constipation management will be discussed. A treatment algorithm for constipation in PD will be presented.Expert opinion: Polyethylene glycol and lubiprostone are first-line compounds recommended by evidence-based medicine guidelines for the treatment of constipation due to slow colonic transit in PD. Management of constipation secondary to defecatory dysfunction due to pelvic floor dyssynergia can be done by levodopa or apomorphine injections, botulinum toxin type A injection into the puborectalis muscle, and nonpharmacological interventions, like biofeedback therapy or functional magnetic stimulation, which showed some benefit in PD patients with constipation, but in general more extensive studies are warranted. © 2015 Informa UK, Ltd. Source

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