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.

Real-life evidence of treatment with alemtuzumab in patients diagnosed with relapsing-remitting multiple sclerosis in Colombia.

BACKGROUND: Physical disability, cognitive impairment, depression, and fatigue are poorly understood in Latin American patients with multiple sclerosis following alemtuzumab infusion. OBJECTIVES: To describe Sustained changes in physical disability in an average 22-month follow-up period after alemtuzumab infusion, and which demographical or clinical variables modulate change in EDSS, and adverse events, changes in cognition, fatigue, and depressive symptoms after an average 15-month follow-up period. METHOD: Retrospective cohort observational study. Following the review of medical records, 23 patients with Relapsing Remitting Multiple Sclerosis treated with alemtuzumab were identified; of these, 17 had a baseline neuropsychological assessment and 12 had at least one follow-up neuropsychological assessment. RESULTS: Most of the patients presented a low level of physical disability, depression, fatigue, and cognitive impairment, which was more pronounced in the processing speed and visuospatial memory at baseline. Fifteen of 23 (65.2%) of patients showed disability improvement, 7 (30.1%) patients remained stable, and 1 (4.3%) patient worsened, and change was not influenced by age or baseline disability score. Twenty (87%) patients remained free of clinical relapses. Performance improved on the BVMT-R visual memory test, 9 (75%) remained stable or improved on the BICAMS, and 66.6% perceived decreased fatigue on the d-FIS. Adverse events occurred in 7 (30.1%) of patients, the most common were opportunistic infections in 2 (8.6%) patients, and one 29-year-old patient presented papillary thyroid carcinoma after infusion of the second course of alemtuzumab. CONCLUSIONS: Results suggest that treatment with alemtuzumab has a beneficial impact on disability, cognitive impairment, and perception of fatigue. The percentage and type of adverse events observed in the cohort are similar to those reported for other real-life studies.