👤 Riley M Bove

To identify preoperative clinical predictive factors of postoperative speech changes in Parkinson's disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Demographic variables, neuroimaging data, and clinical characteristics were retrospectively collected from consecutive PD patients, before, 1 and 10-years after bilateral STN-DBS at the Grenoble University Hospital (France) from 1993 to 2015. Predictors of postoperative speech changes (demographic, clinical and MRI variables) were assessed with univariate and multivariate logistic regression analyses. We considered as "event" a worsening of speech subscore (UPDRS item 18; MDS-UPDRS item 3.1) in the postoperative on-stimulation/off-medication (1-year follow-up) or under chronic treatment (10-years follow-up) conditions compared with the preoperative off-medication condition. 324 PD patients (males: 196; disease duration at surgery: 11.10 [± 4.13] years; age at surgery: 56.25 [± 8.52] years) were included in the analysis. Overall, the speech item of the clinical rating did not change in 138 patients (42.6%), it improved in 113 patients (34.9%) and worsened in 73 patients (22.50%) 1-year after surgery. The preoperative off-medication speech item score and the degree of motor improvement after surgery in the med-off condition predicted the 1-year postoperative speech change. In the long-term subgroup (n=51) the preoperative percentage of daily time spent with fluctuations was associated with long-term speech worsening. Effects of STN-DBS on speech can substantially vary in PD patients. Predictors of short-term speech deterioration appears to be related to preoperative off-medication speech impairment and degree of motor improvement after surgery. Show less

Hypercholesterolemia is the main modifiable risk factor for atherosclerosis progression and cardiovascular disease (CVD) development. Its pharmacological management is usually based on the prescription of statins, that in some cases are not however fully effective to reach the desired Low-Density-Lipoproteins cholesterol (LDL-C) target, or are not tolerated by patients due to side effects. Areas covered: This manuscript summarizes the basic properties of the emerging new classes of lipid-lowering drugs such as ezetimibe, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, and Microsomal Triglyceride Transfer Protein (MTP) inhibitors, also citing new drugs in development. Our aim is to describe the main pharmacodynamic and pharmacokinetic characteristics, the available efficacy, tolerability and safety data obtained in randomized clinical trials where these drugs were tested. Expert opinion: Non-statin lipid-lowering drugs can be considered an excellent strategy to reduce the residual CV risk, also represented by non-target LDL-C values and high lipoprotein(a) serum levels. In particular, the approved PCSK9 inhibitors (Evolocumab and Alirocumab) have been very effective in optimizing plasma LDL-C values and reducing CV event risk. Show less

We have witnessed major successes in the development of effective immunomodulatory therapies capable of reducing adaptive immune-mediated myelin damage in MS over the last 30 years. However, until it is possible to prevent MS or initiate treatment before it has already caused lesions there is a need to repair myelin damage to prevent further axonal loss. The past decade has brought remarkable advances in our understanding of oligodendrocyte biology and the related search for remyelinating therapies in humans. In this review, we first outline the basic biology of central nervous system myelin and remyelination, including a discussion of the major identified pathways and targets that might help yield CNS remyelinating drugs. In conjunction, we provide an overview of techniques that have helped identify compounds capable of promoting oligodendrocyte precursor cell differentiation and myelination. This includes the methods for both initial in vitro screening and subsequent in vivo confirmation of the target. We then review methods proposed to quantify human remyelination in vivo, including visual evoked potentials and putative imaging modalities. As the remyelination era approaches, with the announcement of the first positive trial in remyelination, we are now tasked with answering new questions regarding patient-specific factors (e.g., age) that may influence the extent and optimal therapeutic window for remyelination. Show less