Episodic Past, Future, and counterfactual thinking in Relapsing-Remitting Multiple sclerosis.

Multiple sclerosis (MS) is a progressive disease characterized by widespread white matter lesions in the brain and spinal cord. In addition to well-characterized motor deficits, MS results in cognitive impairments in several domains, notably in episodic autobiographical memory. Recent studies have also revealed that patients with MS exhibit deficits in episodic future thinking, i.e., our capacity to imagine possible events that may occur in our personal future. Both episodic memory and episodic future thinking have been shown to share cognitive and neural mechanisms with a related kind of hypothetical simulation known as episodic counterfactual thinking: our capacity to imagine alternative ways in which past personal events could have occurred but did not. However, the extent to which episodic counterfactual thinking is affected in MS is still unknown. The current study sought to explore this issue by comparing performance in mental simulation tasks involving either past, future or counterfactual thoughts in relapsing-remitting MS. Diffusion weighted imaging (DWI) measures were also extracted to determine whether changes in structural pathways connecting the brain's default mode network (DMN) would be associated with group differences in task performance. Relative to controls, patients showed marked reductions in the number of internal details across all mental simulations, but no differences in the number of external and semantic-based details. It was also found that, relative to controls, patients with relapsing-remitting MS reported reduced composition ratings for episodic simulations depicting counterfactual events, but not so for actual past or possible future episodes. Additionally, three DWI measures of white matter integrity-fractional anisotropy, radial diffusivity and streamline counts-showed reliable differences between patients with relapsing-remitting MS and matched healthy controls. Importantly, DWI measures associated with reduced white matter integrity in three association tracts on the DMN-the right superior longitudinal fasciculus, the left hippocampal portion of the cingulum and the left inferior longitudinal fasciculus-predicted reductions in the number of internal details during episodic counterfactual simulations. Taken together, these results help to illuminate impairments in episodic simulation in relapsing-remitting MS and show, for the first time, a differential association between white matter integrity and deficits in episodic counterfactual thinking in individuals with relapsing-remitting MS.

Practical Issues Concerning the Approval and Use of Biosimilar Drugs for the Treatment of Multiple Sclerosis in Latin America.

The use of biosimilar drugs for multiple sclerosis (MS) has become widespread in Latin America, with the goal of reducing costs of treatments, promoting the sustainability of healthcare systems, and improving patient access to these therapies. There is currently a need to define and comply with requirements to guarantee the efficacy, safety, and quality of these drugs. Thus, the objective of the present study was to compile up-to-date information from each Latin American country assessed on (a) approval of biosimilar drugs by regulatory agencies; (b) use of biosimilar drugs, pharmacovigilance plans, risk management; and (c) update in the knowledge on different molecules. To do so, a group of experts from Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Panama, Peru, Uruguay, and Venezuela met to discuss the current situation regarding good practices and risks associated with the use of biosimilar drugs in their respective countries. Regulation, risk management plans, and pharmacovigilance in the whole continent must guide the strategies on the commercialization and access of biosimilar drugs and copies of complex molecules. Current regulations must be implemented for the registration of biosimilar drug products and complex molecules. It is paramount to ensure that new products follow the best quality standards at all stages beyond being safe and efficient. Uncontrolled interchangeability between original biological and biosimilar should be avoided. Latin America requires the implementation and full use of strong pharmacovigilance programs. National and multinational clinical studies are required to demonstrate the similarity in safety, efficacy, and immunogenicity profiles of complex molecules, as well as biological and biosimilar products. Plain language summary available for this article.